FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Nielsen, S Frokiaer, J Marples, D Kwon, TH Agre, P Knepper, MA AF Nielsen, S Frokiaer, J Marples, D Kwon, TH Agre, P Knepper, MA TI Aquaporins in the kidney: From molecules to medicine SO PHYSIOLOGICAL REVIEWS LA English DT Review ID NEPHROGENIC DIABETES-INSIPIDUS; WATER CHANNEL EXPRESSION; MEDULLARY COLLECTING DUCT; TOAD URINARY-BLADDER; INTEGRAL MEMBRANE-PROTEIN; ACUTE-RENAL-FAILURE; VASOPRESSIN-INDUCED ANTIDIURESIS; INDUCED NEPHROTIC SYNDROME; FREEZE-FRACTURE ANALYSIS; INDUCED DOWN-REGULATION AB The discovery of aquaporin-1 (AQP1) answered the long-standing biophysical question of how water specifically crosses biological membranes. In the kidney, at least seven aquaporins are expressed at distinct sites. AQP1 is extremely abundant in the proximal tubule and descending thin limb and is essential for urinary concentration. AQP2 is exclusively expressed in the principal cells of the connecting tubule and collecting duct and is the predominant vasopressin-regulated water channel. AQP3 and AQP4 are both present in the basolateral plasma membrane of collecting duct principal cells and represent exit pathways for water reabsorbed apically via AQP2. Studies in patients and transgenic mice have demonstrated that both AQP2 and AQP3 are essential for urinary concentration. Three additional aquaporins are present in the kidney. AQP6 is present in intracellular vesicles in collecting duct intercalated cells, and AQP8 is present intracellularly at low abundance in proximal tubules and collecting duct principal cells, but the physiological function of these two channels remains undefined. AQP7 is abundant in the brush border of proximal tubule cells and is likely to be involved in proximal tubule water reabsorption. Body water balance is tightly regulated by vasopressin, and multiple studies now have underscored the essential roles of AQP2 in this. Vasopressin regulates acutely the water permeability of the kidney collecting duct by trafficking of AQP2 from intracellular vesicles to the apical plasma membrane. The long-term adaptational changes in body water balance are controlled in part by regulated changes in AQP2 and AQP3 expression levels. Lack of functional AQP2 is seen in primary forms of diabetes insipidus, and reduced expression and targeting are seen in several diseases associated with urinary concentrating defects such as acquired nephrogenic diabetes insipidus, postobstructive polyuria, as well as acute and chronic renal failure. In contrast, in conditions with water retention such as severe congestive heart failure, pregnancy, and syndrome of inappropriate antidiuretic hormone secretion, both AQP2 expression levels and apical plasma membrane targetting are increased, suggesting a role for AQP2 in the development of water retention. Continued analysis of the aquaporins is providing detailed molecular insight into the fundamental physiology and pathophysiology of water balance and water balance disorders. C1 Aarhus Univ, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Aarhus Univ, Inst Expt Clin Res, DK-8000 Aarhus, Denmark. Univ Leeds, Leeds, W Yorkshire, England. Dongguk Univ, Kyungju, South Korea. Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Inst Anat, Water & Salt Res Ctr, Bldg 233-244, DK-8000 Aarhus C, Denmark. RI chen, xuanlan/H-4158-2011 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 279 TC 674 Z9 732 U1 9 U2 122 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD JAN PY 2002 VL 82 IS 1 BP 205 EP 244 PG 40 WC Physiology SC Physiology GA 507KY UT WOS:000173028700007 PM 11773613 ER PT S AU Bjorklund, LM Isacson, O AF Bjorklund, LM Isacson, O BE Hofman, MA Boer, GJ Holtmaat, AJG VanSomeren, EJW Verhaagen, J Swaab, DF TI Regulation of dopamine cell type and transmitter function in fetal and stem cell transplantation for Parkinson's disease SO PLASTICITY IN THE ADULT BRAIN: FROM GENES TO NEUROTHERAPY SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 22nd International Summer School of Brain Research CY AUG 20-24, 2001 CL UNIV AMSTERDAM, AMSTERDAM, NETHERLANDS SP Netherlands Inst Brain Res, Royal Netherlands Acad Arts & Sci, Grad Sch Neurosci Amsterdam, Co Biologists Ltd, GlaxoSmithKline, Merck Sharp & Dohme, Netherlands Sco Advancement Nat Sci, Med & Surg, Noldus Informat Technol BV, Sanofi Synthelabo, Soc Exptl & Clin Neurosci, Solvay Pharmaceut, VandenHouten Fdn, World Precis Instruments Germany HO UNIV AMSTERDAM ID SUBSTANTIA-NIGRA; VENTRAL MESENCEPHALON; TYROSINE-HYDROXYLASE; POSTNATAL-DEVELOPMENT; EXCITOTOXIC LESIONS; HUNTINGTON DISEASE; GENE-EXPRESSION; 6-OHDA LESIONS; MESSENGER-RNA; PRIMATE MODEL C1 Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Labs, Belmont, MA 02478 USA. Harvard Univ, Sch Med, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02114 USA. RP Isacson, O (reprint author), Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Labs, 115 Mill St, Belmont, MA 02478 USA. FU NINDS NIH HHS [R01-NS-41263, R01-NS-30064, P50 NS39793] NR 74 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50981-X J9 PROG BRAIN RES PY 2002 VL 138 BP 411 EP 420 DI 10.1016/S0079-6123(02)38090-7 PG 10 WC Cell Biology; Genetics & Heredity; Neurosciences SC Cell Biology; Genetics & Heredity; Neurosciences & Neurology GA BV65W UT WOS:000179669700024 PM 12432781 ER PT J AU Nam, TG Sangaiah, R Gold, A Lacks, GD Nylander-French, LA French, JE AF Nam, TG Sangaiah, R Gold, A Lacks, GD Nylander-French, LA French, JE TI Synthesis of FMOC-protected S-arylcysteines and modified keratin sequence peptides as specific epitopes as immunogens SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article; Proceedings Paper CT 18th International Symposium on Polycyclic Aromatic Compounds CY SEP 09-13, 2001 CL UNIV CINCINNATI, CINCINNATI, OHIO SP Int Soc Polycycl Aromat Compounds HO UNIV CINCINNATI DE FMOC-protected modified cysteines; keratin adducts of arene oxides; protein adducts; S-arylcysteines ID BENZENE METABOLISM; LIVER-MICROSOMES; MICE; EXPOSURE; TOXICITY; LEUKEMIA; RATS AB The sulfhydryl group of cysteine residues is a site for the adduction of ultimate carcinogenic arene oxide metabolites to the proteins keratin I and keratin 10, dominant proteins of the squame. The putative cysteine adducts are: S-phenylcysteine from benzene oxide and S-(1-naphthyl)- and S-(2-naphthyl)cysteine from naphthalene-1,2-oxide. In developing ELISAs for monitoring dermal exposures, we have embarked on synthesis of adducted head sequences GGRFSS(C*)GG (keratin 1) and GGGG(C*)GGGGG (keratin 10) by 9-fluorenyl-methoxycarbonyl chemistry to use in raising epitope-specific antibodies. Synthesis of the FMOC-protected cysteines was based on addition of arylthiols to 2-acetamidoacrylic acid, to give S-arylmercapturic acids. Removal of the N-acetyl group was accomplished quantitatively by extended refluxing in 1:1 t-butanol/concentrated HCl. FMOC derivatization of the S-arylcysteines vas accomplished by a published procedure, modified because of the low solubility. The oligopeptides (C* = S-phenylcysteinyl residue) have been synthesized and characterized. C1 Univ N Carolina, Dept Environm Sci & Engn, Sch Publ Hlth, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Natl Inst Hlth, Res Triangle Pk, NC USA. RP Nam, TG (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Sch Publ Hlth, Chapel Hill, NC 27599 USA. NR 25 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 2002 VL 22 IS 3-4 BP 239 EP 248 DI 10.1080/10406630290026885 PG 10 WC Chemistry, Organic SC Chemistry GA 592QX UT WOS:000177949300005 ER PT J AU Sayer, JM Kroth, H Yagi, H Kalena, G Jerina, DM Ramos, LA Dipple, A Ponten, I Goodman, ME AF Sayer, JM Kroth, H Yagi, H Kalena, G Jerina, DM Ramos, LA Dipple, A Ponten, I Goodman, ME TI Mutational consequences on replication of M13 constructs containing isomeric diol epoxide adducts in E. Coli SO POLYCYCLIC AROMATIC COMPOUNDS LA English DT Article; Proceedings Paper CT 18th International Symposium on Polycyclic Aromatic Compounds CY SEP 09-13, 2001 CL UNIV CINCINNATI, CINCINNATI, OHIO SP Int Soc Polycycl Aromat Compounds HO UNIV CINCINNATI DE benzo[a]pyrene; benzo[c]phenanthrene; DNA adducts; Escherichia coli; M13; mutagenesis ID DEOXYADENOSINE ADDUCTS; DIHYDRODIOL EPOXIDES; 9,10-EPOXIDE ADDUCTS; M13MP7L2 CONSTRUCTS; HYDROXYL-GROUPS; CIS; OLIGONUCLEOTIDES; MUTAGENESIS; POSITION; VECTOR AB Eight isomeric dGuo and eight dAdo adducts resulting from cis and trans opening of each of the four optic-ally active diol epoxides (DEs) derived from benzo[a]pyrene (BaP) and benzo[c]phenanthrene (BcPh) were placed in each of two 16-mer DNA sequences to give 32 modified oligonucleotides, which were ligated into M13mp7L2 and allowed to replicate in SOS-induced Escherichia coli. The effects of parent hydrocarbon, adduct stereochemistry, and sequence context on mutagenic response are highly interdependent. BaP DE adducts are generally more mutagenic than the corresponding BcPh adducts. The mutational frequency is generally larger for cis- relative to trans-opened DE adducts of both dGuo and dAdo. In a similar toTA*Gsimilar to context, BcPh DE dAdo adducts (A*) with R configuration at the site of attachment to the adenine base produced very few substitution mutations when compared with adducts having S configuration. This configurational effect is not observed for BaP DE dAdo adducts, nor for BaP or BcPh dGuo adducts. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, Chem & Carcinogenesis Lab, Frederick, MD 21701 USA. Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA. RP Sayer, JM (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NR 24 TC 3 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1040-6638 J9 POLYCYCL AROMAT COMP JI Polycycl. Aromat. Compd. PY 2002 VL 22 IS 3-4 BP 871 EP 879 DI 10.1080/10406630290104022 PG 9 WC Chemistry, Organic SC Chemistry GA 592QX UT WOS:000177949300061 ER PT J AU Kloczkowski, A Ting, KL Jernigan, RL Garnier, J AF Kloczkowski, A Ting, KL Jernigan, RL Garnier, J TI Protein secondary structure prediction based on the GOR algorithm incorporating multiple sequence alignment information SO POLYMER LA English DT Article DE protein; GOR algorithm; secondary structure ID HOMOLOGOUS SEQUENCES; ACCURACY; FUTURE; IMPROVEMENT AB We have developed a new method for the prediction of the protein secondary structure from the amino acid sequence. The method is based on the most recent version (IV) of the standard GOR (J Mol Biol 120 (1978) 97) algorithm. A significant improvement is obtained by combining multiple sequence alignments with the GOR method. Additional improvement in the predictions is obtained by a simple correction of the results when helices or sheets are too short, or if helices and sheets are direct neighbors along the sequence (we require at least one residue of coil state between them). The imposition of the requirement that the prediction must be strong enough, i.e. that the difference between the probability of the predicted (most probable) state and the probability of the second most probable state must be larger than a certain minimum value also improves significantly secondary structure predictions. We have tested our method on 12 different proteins from the Protein Data Bank with known secondary structures. The average quality of the GOR prediction of the secondary structure for these 12 proteins without multiple sequence alignment was 63.4%. The multiple sequence alignments improve the average prediction to 71.9%. The correction for short helices and sheets and coil states separating sheets and helices improve further the average prediction to 74.4%. Setting the 10% minimum difference between the most probable and the second probable conformation leads to 77.0% accuracy of the prediction, while increasing this limit to 20% increases the average accuracy of the secondary structure prediction to 81.2%. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Natl Inst Hlth, Natl Canc Inst, Lab Expt & Computat Biol, Bethesda, MD 20892 USA. NIH, Analyt Biostat Sect, Math & Stat Comp Lab, CIT, Bethesda, MD 20892 USA. RP Kloczkowski, A (reprint author), Natl Inst Hlth, Natl Canc Inst, Lab Expt & Computat Biol, 12 S Dr,Bldg 12B,Rm B116, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012; Kloczkowski, Andrzej/B-9868-2012 NR 29 TC 15 Z9 15 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD JAN PY 2002 VL 43 IS 2 BP 441 EP 449 DI 10.1016/S0032-3861(01)00425-6 PG 9 WC Polymer Science SC Polymer Science GA 491MZ UT WOS:000172113500022 ER PT J AU Bagci, Z Jernigan, RL Bahar, I AF Bagci, Z Jernigan, RL Bahar, I TI Residue coordination in proteins conforms to the closest packing of spheres SO POLYMER LA English DT Article DE packing in proteins; face-centered-cubic lattice; uniform packing density ID SECONDARY STRUCTURE; GLOBULAR-PROTEINS; STATE MODELS; LATTICE; CHAINS; RESOLUTION; ACCURACY; REPRESENTATION; PROPENSITIES; MATHEMATICS AB Coarse-grained protein structures have the unusual property of manifesting a greater regularity than is evident when all atoms are considered. Here, we follow proteins at the level of one point per residue. We confirm that lattices with large coordination numbers provide better fits to protein structures. But, underlying these protein structures, there is an intrinsic geometry that closely resembles the face-centered-cubic (fcc) lattice, in so far as the coordination angles observed in clusters of near neighboring residues are concerned. While the fcc lattice has 12 neighbors, the coordination number about any given residue in a protein is usually smaller; however, the neighbors are not distributed in a uniform, less dense way, but rather in a clustered dense way, occupying positions closely approximating those of a distorted fcc packing. This packing geometry is a direct manifestation of the hydrophobic effect. Surprisingly, specific residues are clustered with similar angular geometry, whether on the interior or on the exterior of a protein. (C) 2001 Published by Elsevier Science Ltd. C1 Univ Pittsburgh, Sch Med, Ctr Computat Biol & Bioinformat, Pittsburgh, PA 15231 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15231 USA. Bogazici Univ, Dept Chem Engn, Istanbul, Turkey. Bogazici Univ, Ctr Polymer Res, Istanbul, Turkey. NIH, Natl Canc Inst, Div Basic Sci, Mol Struct Sect,Lab Expt & Computat Biol, Bethesda, MD 20892 USA. RP Bahar, I (reprint author), Univ Pittsburgh, Sch Med, Ctr Computat Biol & Bioinformat, Kaufmann Bldg,Suite 601,3471 5th Ave, Pittsburgh, PA 15231 USA. RI Jernigan, Robert/A-5421-2012; bagci, elife/B-9032-2012; Bagci, Elife/A-9660-2016 NR 37 TC 24 Z9 24 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0032-3861 J9 POLYMER JI Polymer PD JAN PY 2002 VL 43 IS 2 BP 451 EP 459 DI 10.1016/S0032-3861(01)00427-X PG 9 WC Polymer Science SC Polymer Science GA 491MZ UT WOS:000172113500023 ER PT J AU Klassen, AC Smith, ALM Meissner, HI Zabora, J Curbow, B Mandelblatt, J AF Klassen, AC Smith, ALM Meissner, HI Zabora, J Curbow, B Mandelblatt, J TI If we gave away mammograms, who would get them? A neighborhood evaluation of a no-cost breast cancer screening program SO PREVENTIVE MEDICINE LA English DT Article DE mammography; breast cancer screening; intervention; low income; evaluation ID CERVICAL-CANCER; UNDERSERVED WOMEN; MORTALITY AB Background. Low- and no-cost mammography programs have become a widespread strategy to increase access to breast cancer screening in low-income populations. However, rigorous evaluations of who remains unscreened in communities with these programs are lacking. We conducted a case-control study of African American older women in East Baltimore, Maryland, comparing attendees at a no-cost program to friends and neighbors not using no-cost venues. Methods. We recruited 288 women ages 50 and older, who attended a no-cost program at Johns Hopkins Hospital, to complete a 1(1/2) h home interview, answering semistructured and open-ended questions about cancer and health and a wide range of social and psychological items. For each case, we recruited one friend or neighbor, within 5 years of age, not receiving no-cost screening, to complete a similar control interview. Matched case-control analyses were used to compare program attendees to nonattendees within the target community. Results. Women using the no-cost program at least once were generally more poorly screened than their neighborhood control prior to the program, but had better recent screening history 3 years after the program began. In multivariate analyses, program attendees were more likely to have <$10,000 annual income (OR = 2.34, 95% CI 1.55,3.61), more likely to have had more children (OR = 1.13, 95% CI 1.04,1.24), and less likely to have health insurance (OR = 0.42, 95% CI 0.25,0.68). They were more likely to see a female primary care provider (OR = 1.82, 95% CI 1.24,2.70) and to see multiple providers (OR = 3.38,95% CI 1.52,8.60). Conclusions. Low-cost screening intervention programs reach women who might otherwise not receive screening. However, within target communities, improved partnerships with specific types of primary care providers could reach additional women. (C) 2002 American Health Foundation and Elsevier Science. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NCI, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. RP Klassen, AC (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 624 N Broadway,Room 745, Baltimore, MD 21205 USA. FU NCI NIH HHS [R01 CA66065] NR 27 TC 19 Z9 20 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN PY 2002 VL 34 IS 1 BP 13 EP 21 DI 10.1006/pmed.2001.0956 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 510YN UT WOS:000173235300003 PM 11749092 ER PT J AU Riecken, B Pfeiffer, R Ma, JL Jin, ML Li, JY Liu, WD Zhang, L Chang, YS Gail, MH You, WC AF Riecken, B Pfeiffer, R Ma, JL Jin, ML Li, JY Liu, WD Zhang, L Chang, YS Gail, MH You, WC TI No impact of repeated endoscopic screens on gastric cancer mortality in a prospectively followed Chinese population at high risk SO PREVENTIVE MEDICINE LA English DT Article DE stomach neoplasms; gastroscopy; mortality; China ID STOMACH-CANCER; LESIONS; JAPAN; DIAGNOSIS; PROGRAM; DESIGN AB Background. Gastric cancer (GC) is the leading cause of cancer deaths in China. Our study prospectively evaluated the impact of repeated endoscopic screens on GC mortality in a high-risk population in China. Methods. Between 1989 and 1999, a population-based gastroscopic screening was conducted in 4,394 residents of Linqu County, China, a region with the highest rates of GC worldwide. Residents ages 35 to 64 years received initial gastroscopies with biopsies in 1989. Repeated endoscopies were performed in 1994 and 1999. Cancer occurrences and deaths were actively monitored throughout the entire period until July 2000. Mortality from GC was compared with expected values based on mortality rates obtained for Linqu in the 1990-1992 Chinese Cancer Mortality Survey. Results. Between March 1989 and July 2000, 39,303 person-years were accumulated; 85 new GCs occurred, 29 (34.5%) were in early stage. Fifty-eight cases (68%) were identified at one of the screens. The number of observed deaths from GC (37) was close to the expected (36.8). The standardized mortality ratio was 1.01 (95% Cl 0.72-1.37) for the entire cohort, 1.13 (95% CI 0.77-1.57) for males, and 0.65 (95% C1 0.26-1.32) for females. Conclusions. Despite high population coverage with repeated screens, no reduction in GC mortality was observed in this high-risk population in China. C1 Peking Univ, Beijing Inst Canc Res, Beijing 100036, Peoples R China. Peking Univ, Sch Oncol, Beijing 100036, Peoples R China. Freiburg Univ Hosp, Dept Gastroenterol & Hepatol, Freiburg, Germany. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP You, WC (reprint author), Peking Univ, Beijing Inst Canc Res, 52 Fu Cheng Rd,Haidian Dist, Beijing 100036, Peoples R China. RI Pfeiffer, Ruth /F-4748-2011 FU NCI NIH HHS [N01-CP-05631, N01-CP-15620, N01-CP-21009, N01-CP-33041, N01-CP-95660] NR 24 TC 31 Z9 32 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN PY 2002 VL 34 IS 1 BP 22 EP 28 DI 10.1006/pmed.2001.0925 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 510YN UT WOS:000173235300004 PM 11749093 ER PT J AU Stoddard, AM Fox, SA Costanza, ME Lane, DS Andersen, MR Urban, N Lipkus, I Rimer, BK AF Stoddard, AM Fox, SA Costanza, ME Lane, DS Andersen, MR Urban, N Lipkus, I Rimer, BK CA NCI Breast Screening Consortium TI Effectiveness of telephone counseling for mammography: Results from five randomized trials SO PREVENTIVE MEDICINE LA English DT Article DE mammography; transtheoretical model; women's health; telephone counseling ID INCREASE MAMMOGRAPHY; PROMOTING MAMMOGRAPHY; SCREENING MAMMOGRAPHY; BREAST-CANCER; SELF-REPORTS; WOMEN; INTERVENTIONS; ACCURACY; BEHAVIOR; MODELS AB Background. Women over age 50 continue to be underscreened for breast cancer. The purpose of this report is to compare the effectiveness of a barrier-specific telephone counseling intervention across the five study sites of the Breast Cancer Screening Consortium (BCSC). Methods. Each of the BCSC projects was a randomized study of the effectiveness of telephone counseling (TC) in comparison to a control condition. Eligible underusers were identified and surveyed by telephone before and after the implementation of the interventions. Data from a total of 3,461 underusers were analyzed. We tested whether significantly more women randomized to TC than to control were regular mammography users at the follow-up survey. Data were analyzed separately by site. Results. Overall, TC was not significantly more effective than control in encouraging regular mammography. The pooled consortium-wide odds ratio was 1.08 (95% confidence interval: 0.91 to 1.27). Conclusions. TC has the potential to support maintenance of mammogram use. Modifications are needed to maximize this potential and additional methods should be used in conjunction with TC to reach women who are underusers of mammography. (C) 2002 American Health Foundation and Elsevier Science. C1 Univ Massachusetts, Amherst, MA 01003 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Seattle, WA 98195 USA. Duke Univ, Med Ctr, Durham, NC 27701 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RAND Corp, Santa Monica, CA 90406 USA. RP Stoddard, AM (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01-CA60129, R01-CA65880, R01-CA63782, R01-CA60131, R01-CA60130] NR 30 TC 23 Z9 23 U1 2 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD JAN PY 2002 VL 34 IS 1 BP 90 EP 99 DI 10.1006/pmed.2001.0960 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 510YN UT WOS:000173235300012 PM 11749101 ER PT B AU Sidorov, IA Hosack, DA Gee, D Yang, J Cam, MC Lempicki, RA Dimitrov, DS AF Sidorov, IA Hosack, DA Gee, D Yang, J Cam, MC Lempicki, RA Dimitrov, DS BE Caulfield, HJ Chen, SH Duro, R Honavar, V Kerre, EE Lu, M Romay, MG Shih, TK Ventura, D Wang, PP Yang, YY TI Oligonucleotide microarray data distribution and normalization SO PROCEEDINGS OF THE 6TH JOINT CONFERENCE ON INFORMATION SCIENCES LA English DT Proceedings Paper CT 6th Joint Conference on Information Sciences CY MAR 08-13, 2002 CL RES TRIANGLE PK, NC SP Assoc Intelligent Machinery, Informat Sci Journal, Duke Univ, Acad Affairs, Tamkang Univ, N Carolina Biotechnol Ctr, GalxoSmithKline, George Mason Univ ID GENE-EXPRESSION; DNA ARRAYS AB Variations in oligonucleotide microarray probe signals that result from, various factors, including differences in sample concentrations, can lead to major problems in the interpretation of data obtained from different experiments. Normalization of such signals is, typically performed by procedures involving division by a constant approximately determined by average signal intensities as, e.g., in the, Affymetrix software. Here we show. that Affymetrix oligonucleotide probe signal distributions can be fitted by using a superposition of two normal or two extreme distributions, and that by using such distributions we can normalize data with high accuracy (parametric algorithm). We also developed a second algorithm (non-parametric) based on ranking of signal intensifies which gave equal or better normalization than the parametric one. These approaches have been used for normalization of three sets of data obtained from cancer cell lines, peripheral blood mononuclear cells from patients with HIV infections, and cells from patients with diabetes. Both, parametric and nonparametric normalization procedures, were found to be superior when compared to the standard global normalization approach [1]. These results suggest that the new approaches may. be helpful for microarray data normalization especially for comparison of clinical data where interpatient differences can be large and difficult to avoid. C1 NCI, NIH, Frederick, MD 21702 USA. RP Sidorov, IA (reprint author), NCI, NIH, Frederick, MD 21702 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 6 TC 0 Z9 0 U1 0 U2 0 PU ASSOC INTELLIGENT MACHINERY PI DURHAM PA PO BOX 90291, DURHAM, NC 27708-0291 USA BN 0-9707890-1-7 PY 2002 BP 1219 EP 1222 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BV54W UT WOS:000179331800282 ER PT B AU Suranauwarat, S Taniguchi, H AF Suranauwarat, S Taniguchi, H BE Hamza, MH TI Improving a WWW server's response time using its execution behavior information in resource scheduling SO PROCEEDINGS OF THE IASTED INTERNATIONAL CONFERENCE ON COMMUNICATIONS, INTERNET, AND INFORMATION TECHNOLOGY LA English DT Proceedings Paper CT IASTED International Conference on Communications, Internet and Information Technology CY NOV 18-20, 2002 CL St Thomas, VI SP Int Assoc Sci & Technol Dev, IASTED, TC Informat Syst, IASTED, TC Telecommun, IASTED, TC Web, Internet & Multimedia DE operating systems support; WWW servers; resource scheduling; behavior AB With the phenomenal, continual growth in the number of the WAVW (World Wide Web) users has come an increase in the number of simultaneous requests a server must handle. As a result, users experience slower response times during periods of high demand. In other words, it takes a longer time for the first data to display on browsers. the text data stored in an HTML (HyperText Markup Language) file, to start displaying when servers are accessed by many requests simultaneously. This situation could be one in which it is most desirable to improve the response time and this can be achieved by scheduling resources more efficiently in operating systems. We have proposed a resource scheduling policy for improving response time of a WWW server. This policy gives preferential use of the resources such as a CPU resource (or I/O devices) to any process that is predicted based on its execution behavior information to be a server process handling an HTML file request. It does this by moving that process (or its I/O requests) to the head of the waiting queue where processes (or their I/O requests) are waiting for the desired resources to become available. In this paper, we present the experimental evaluation of our resource scheduling policy when applied to the allocation of a CPU resource and a disk drive. C1 NIDA, Sch Appl Stat, Bangkok 10240, Thailand. RP NIDA, Sch Appl Stat, Bangkok 10240, Thailand. NR 15 TC 0 Z9 0 U1 0 U2 0 PU ACTA PRESS PI CALGARY PA B6, STE 101, 2509 DIEPPE AVE SW, CALGARY, ALBERTA T3E 7J9, CANADA BN 0-88986-327-X PY 2002 BP 485 EP 491 PG 7 WC Computer Science, Information Systems; Computer Science, Software Engineering; Telecommunications SC Computer Science; Telecommunications GA BAB33 UT WOS:000221457100084 ER PT J AU Elkashef, AM Al-Barazi, H Venable, D Baker, I Hill, J Apud, J Wyatt, RJ AF Elkashef, AM Al-Barazi, H Venable, D Baker, I Hill, J Apud, J Wyatt, RJ TI Dopamine effect on the mitochondria potential in B lymphocytes of schizophrenic patients and normal controls SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE B lymphocytes; dopamine; flow cytometery; free radicals; mitochondria; schizophrenia ID FREE-RADICAL PATHOLOGY; METABOLISM; APOPTOSIS; DEATH AB Brain metabolic abnormalities and aberrant dopamine (DA) metabolism have been reported in patients with schizophrenia. The authors hypothesized that mitochondria is a primary target of damage by increased free radical generation secondary to increased DA metabolism by monoamine oxidase (MAO). Epstein-Barr virus (EBV) -transformed human B-lymphocytes cell lines derived from patients with schizophrenia and normal controls were incubated in the absence or presence of DA, hydrogen peroxide (H2O2), or rotenone (Rot). The cells were then stained with rhodamine 123 (Rh 123) and analyzed for uptake using flow cytometry. Compared with untreated cells, DA significantly decreased Rh 123 uptake by the mitochondria. This effect was similar to the control cells treated with H2O2 or Rot. Nevertheless, there were no differences in Rh 123 uptake between the cells of schizophrenic patients and normal controls. This study shows that DA can impair the mitochondria membrane potential but that mechanism may not be evident in schizophrenia, (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIDA, Clin Trials Branch, Bethesda, MD USA. NCI, Lab Pathol, Bethesda, MD USA. NIMH, Neuropsychiat Branch, Bethesda, MD USA. RP Elkashef, AM (reprint author), NJDA, DTR&D, Clin Med Branch, Rm 4123,MSC 9551,600 Execut Blvd, Bethesda, MD 20892 USA. NR 14 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD JAN PY 2002 VL 26 IS 1 BP 145 EP 148 DI 10.1016/S0278-5846(01)00239-1 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 506UU UT WOS:000172990800021 PM 11853105 ER PT J AU Sommer, L Rao, M AF Sommer, L Rao, M TI Neural stem cells and regulation of cell number SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; FIBROBLAST-GROWTH-FACTOR; NOTCH-3 INTRACELLULAR DOMAIN; DEVELOPING MOUSE NEOCORTEX; DEVELOPING CEREBRAL-CORTEX; CORTICAL PROGENITOR CELLS; ADULT MAMMALIAN BRAIN; SPINAL-CORD; SUBVENTRICULAR ZONE; NEUROEPITHELIAL CELLS AB Normal CNS development involves the sequential differentiation of multipotent stem cells. Alteration of the numbers of stem cells, their self-renewal ability, or their proliferative capacity will have major effects on the appropriate development of the nervous system. In this review, we discuss different mechanisms that regulate neural stem cell differentiation. Proliferation signals and cell cycle regulators may regulate cell kinetics or total number of cell divisions. Loss of trophic support and cytokine receptor activation may differentially contribute to the induction of cell death at specific stages of development. Signaling from differentiated progeny or asymmetric distribution of specific molecules may alter the self-renewal characteristics of stem cells. We conclude that the final decision of a cell to self-renew, differentiate or remain quiescent is dependent on an integration of multiple signaling pathways and at each instant will depend on cell density, metabolic state, ligand availability, type and levels of receptor expression, and downstream cross-talk between distinct signaling pathways. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NIA, Baltimore, MD 21224 USA. ETH Honggerberg HPM E38, Inst Cell Biol, Swiss Fed Inst Technol, CH-8093 Zurich, Switzerland. RP Rao, M (reprint author), NIA, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 201 TC 122 Z9 133 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JAN PY 2002 VL 66 IS 1 BP 1 EP 18 AR PII S0301-0082(01)00022-3 DI 10.1016/S0301-0082(01)00022-3 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 540VP UT WOS:000174951200001 PM 11897403 ER PT J AU Liu, H Chakravarty, D Maceyka, M Milstien, S Spiegel, S AF Liu, H Chakravarty, D Maceyka, M Milstien, S Spiegel, S TI Sphingosine kinases: A novel family of lipid kinases SO PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY, VOL 71 SE PROGRESS IN NUCLEIC ACID RESEARCH AND MOLECULAR BIOLOGY LA English DT Review ID MEDIATED CA2+ MOBILIZATION; PROGRAMMED CELL-DEATH; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; PROTEIN-KINASE; HEAT-STRESS; LYSOPHOSPHATIDIC ACID; HL-60 CELLS; SPHINGOLIPID METABOLISM C1 Virginia Commonwealth Univ, Dept Biochem, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Liu, H (reprint author), Virginia Commonwealth Univ, Dept Biochem, Med Coll Virginia Campus, Richmond, VA 23298 USA. RI Maceyka, Michael/B-9277-2008; OI Chakravarty, Debyani/0000-0001-8629-5732 FU NCI NIH HHS [CA61774]; NIGMS NIH HHS [GM43880] NR 85 TC 107 Z9 112 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0079-6603 J9 PROG NUCLEIC ACID RE PY 2002 VL 71 BP 493 EP 511 DI 10.1016/S0079-6603(02)71049-0 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU73V UT WOS:000176862700010 PM 12102559 ER PT J AU Hoskins, JR Sharma, S Sathyanarayana, BK Wickner, S AF Hoskins, JR Sharma, S Sathyanarayana, BK Wickner, S TI Clp ATPases and their role in protein unfolding and degradation SO PROTEIN FOLDING IN THE CELL SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID ATP-DEPENDENT PROTEASE; HEAT-SHOCK-PROTEIN; BACTERIOPHAGE-MU REPRESSOR; SENSITIVE FUSION PROTEIN; N-END RULE; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; MOLECULAR CHAPERONES; TERMINAL DOMAIN; SUBSTRATE-RECOGNITION C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hoskins, JR (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 105 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2002 VL 59 BP 413 EP 429 PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BT85N UT WOS:000174258400013 ER PT S AU Stratakis, CA AF Stratakis, CA BE Stratakis, CA ChoChung, YS TI Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit (PRKAR1A) in patients with the "Complex of spotty skin pigmentation, myxomas, endocrine overactivity, and schwannomas" (Carney complex) SO PROTEIN KINASE A AND HUMAN DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protein Kinase A and Human Disease CY SEP 10, 2001 CL NIH, BETHESDA, MARYLAND SP NICHHD HO NIH ID RI-ALPHA; CARDIAC MYXOMAS; LOCUS; MICE; CAMP AB Carney complex (CNC) is a familial multiple neoplasia syndrome associated with abnormal skin and mucosal pigmentation. The complex has features overlapping those of McCune-Albright syndrome (MAS) and the other multiple endocrine neoplasias (MENs). CNC is inherited as an autosomal dominant trait, and the responsible genes have been mapped by linkage analysis to loci at 2p16 and 17q22-24. Because of its unusual biochemical features (e.g., paradoxical responses to various endocrine signals) and its clinical similarities to MAS, genes implicated in cyclic nucleotide-dependent signaling, including GNAS1 (which is responsible for MAS), had been considered likely candidates for causing CNC. The gene encoding the protein kinase A (PKA) type I-alpha regulatory subunit (RIalpha), PRKAR1A, had been mapped to 17q22-24; loss-of-heterozygosity (LOH) analysis using polymorphic markers from this region revealed consistent changes in tumors from patients with CNC, including those from one family previously mapped to 17q22-24. Investigation of a polymorphic site within the 5' of the PRKAR1A gene showed segregation with the disease and retention of the allele bearing the disease gene in CNC tumors. Mutations of the PRKAR1A gene were also found to have occurred de novo in sporadic cases of CNC; no mutations were found in kindreds mapping to 2p16. Thus, genetic heterogeneity in CNC was confirmed; in total, 41% of all patients with CNC had mutations in the PRKAR1A gene. All mutations were frame-shifts, insertions, and deletions that led to nonsense mRNA and premature termination of the predicted peptide product. Functional studies in CNC tumors suggested that inactivating mutations of the PRKAR1A gene led to nonsense mRNA decay (the mutant peptide product was not present) and were associated with dysregulated PKA activity, increased responsiveness to CANT, and excess of type-II PKA activity. We conclude that the PRKAR1A gene, coding for the RIalpha subunit of PKA, a critical cellular component of a number of cyclic nucleotide-dependent signaling pathways, is mutated in a subset of patients with CNC. In their tumors, there is LOH of the normal allele, suggesting that normal RI-alpha may have tumor suppression function in the tissues affected by CNC. An excess of type-II PKA activity was present in affected tissues, which may be responsible for the apparent tumorigenicity of PRKAR1A mutations in endocrine tissues. C1 NICHD, Unit Genet & Endocrinol, DEB, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC1862, Bethesda, MD 20892 USA. NR 23 TC 38 Z9 38 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-412-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 968 BP 3 EP 21 PG 19 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BU83Q UT WOS:000177158100001 PM 12119264 ER PT S AU Cho-Chung, YS Nesterova, M Becker, KG Srivastava, R Park, YG Lee, YN Cho, YS Kim, MK Neary, C Cheadle, C AF Cho-Chung, YS Nesterova, M Becker, KG Srivastava, R Park, YG Lee, YN Cho, YS Kim, MK Neary, C Cheadle, C BE Stratakis, CA ChoChung, YS TI Dissecting the circuitry of protein kinase A and cAMP signaling in cancer genesis - Antisense, microarray, gene overexpression, and transcription factor decoy SO PROTEIN KINASE A AND HUMAN DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protein Kinase A and Human Disease CY SEP 10, 2001 CL NIH, BETHESDA, MARYLAND SP NICHHD HO NIH DE antisense; protein kinase A; cancer; growth inhibition; cDNA; microarrays; transcription factor decoy ID RI-ALPHA-SUBUNIT; CYCLIC-AMP ANALOGS; HL-60 LEUKEMIA-CELLS; REGULATORY SUBUNIT; CATALYTIC SUBUNIT; GROWTH ARREST; RESPONSE ELEMENT; BETA-SUBUNIT; TUMOR-GROWTH; MOLECULAR-CLONING AB Expression of the RIalpha subunit of the cAMP-dependent protein kinase type I (PKA-I) is enhanced in human cancer cell lines, in primary tumors, in transformed cells, and in cells upon stimulation of growth. Signaling via the cAMP pathway may be complex, and the biological effects of the pathway in normal cells may depend upon the physiological state of the cells. However, results of different experimental approaches such as antisense exposure, 8-Cl-cAMP treatment, and gene overexpression have shown that the inhibition of RIalpha/PKA-I exerts antitumor activity in a wide variety of tumor-derived cell lines examined in vitro and in vivo. cDNA microarrays have further shown that in a sequence-specific manner, RIalpha antisense induces alterations in the gene expression profile of cancer cells and tumors. The cluster of genes that define the "proliferation-transformation" signature are down-regulated, and those that define the "differentiation-reverse transformation" signature are up-regulated in antisense-treated cancer cells and tumors, but not in host livers, exhibiting the molecular portrait of the reverted (flat) phenotype of tumor cells. These results reveal a remarkable cellular regulation, elicited by the antisense RIalpha, superimposed on the regulation arising from the Watson-Crick base-pairing mechanism of action. Importantly, the blockade of both the PKA and PKC signaling pathways achieved with the C RE-transcription factor decoy inhibits tumor cell growth without harming normal cell growth. Thus, a complex circuitry of cAMP signaling comprises cAMP growth regulatory function, and deregulation of the effector molecule by this circuitry may underlie cancer genesis and tumor progression. C1 NCI, Cellular Biochem Sect, BRL, CCR,NIH, Bethesda, MD 20892 USA. NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, BRL, CCR,NIH, Bethesda, MD 20892 USA. OI Becker, Kevin/0000-0002-6794-6656 FU NCI NIH HHS [N02-BC-76212/C270012] NR 86 TC 38 Z9 40 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-412-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 968 BP 22 EP 36 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BU83Q UT WOS:000177158100002 PM 12119265 ER PT S AU Matyakhina, L Lenherr, SM Stratakis, CA AF Matyakhina, L Lenherr, SM Stratakis, CA BE Stratakis, CA ChoChung, YS TI Protein kinase A and chromosomal stability SO PROTEIN KINASE A AND HUMAN DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protein Kinase A and Human Disease CY SEP 10, 2001 CL NIH, BETHESDA, MARYLAND SP NICHHD HO NIH DE protein kinase A; regulatory subunits; chromosomes; tumor suppressor gene; genomic instability; cell cycle; mitosis; chromosomal stability ID POLO-LIKE KINASE; MICROTUBULE DYNAMICS; CYTOGENETIC HETEROGENEITY; GENETIC INSTABILITY; ANCHORING PROTEIN; CARNEY COMPLEX; CELL-CYCLE; CENTROSOME AMPLIFICATION; GENOMIC INSTABILITY; REGULATORY SUBUNIT AB All malignant human tumors contain chromosomal rearrangements. Among them, the majority of solid tumors show chromosomal instability, caused by abberations in chromosomal segregation during cell division. Chromosomal instability, defined as increased probability of formation of novel chromosomal mutations compared to that of normal or control cells, appears to be a feature of tumorigenesis in vivo and in vitro (in cancer cell lines). Several enzymatic kinases are involved in maintaining proper chromosomal segregation and regulating cell cycle progression. One such kinase, cAMP-dependent protein kinase A (PKA), has a functional role in many aspects of cell signaling, metabolism, and proliferation. In this review, we will discuss the potential participation of PKA in chromosomal stability. This role includes the association of PKA with the centrosome, microtubules, and the anaphase-promoting complex/ cyclosome (ACP/C), all key aspects of proper chromosomal segregation. C1 NICHD, UGEN, DEB, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, UGEN, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC1862, Bethesda, MD 20892 USA. OI Lenherr, Sara/0000-0002-4162-1546 NR 78 TC 18 Z9 19 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-412-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 968 BP 148 EP 157 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BU83Q UT WOS:000177158100011 PM 12119274 ER PT S AU Weinstein, LS Chen, M Liu, J AF Weinstein, LS Chen, M Liu, J BE Stratakis, CA ChoChung, YS TI Gs(alpha) mutations and imprinting defects in human disease SO PROTEIN KINASE A AND HUMAN DISEASE SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Protein Kinase A and Human Disease CY SEP 10, 2001 CL NIH, BETHESDA, MD SP NICHHD HO NIH DE G proteins; cAMP; Albright hereditary osteodystrophy; McCune-Albright syndrome; fibrous dysplasia; progressive osseous heteroplasia; genomic imprinting ID MCCUNE-ALBRIGHT-SYNDROME; STIMULATORY-G-PROTEIN; NUCLEOTIDE-BINDING PROTEIN; PSEUDOHYPOPARATHYROIDISM TYPE-IB; G(S)ALPHA GENE GNAS1; POLYOSTOTIC FIBROUS DYSPLASIA; ALPHA-SUBUNIT GENE; CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE RESPONSE; NONFUNCTIONING PITUITARY-TUMORS; GRADIENT GEL-ELECTROPHORESIS AB Gs is the ubiquitously expressed heterotrimeric G protein that couples receptors to the effector enzyme adenylyl cyclase and is required for receptor-stimulated intracellular cAMP generation. Activated receptors promote the exchange of GTP for GDP on the Gs alpha-subunit (Gs(alpha)), resulting in Gs activation; an intrinsic GTPase activity of Gs(alpha) deactivates Gs by hydrolyzing bound GTP to GDP. Mutations of Gs(alpha) residues involved in the GTPase reaction that lead to constitutive activation are present in endocrine tumors, fibrous dysplasia of bone, and McCune-Albright syndrome. Heterozygous loss-of-function mutations lead to Albright hereditary osteodystrophy (AHO), a disease characterized by short stature, obesity, and skeletal defects, and are sometimes associated with progressive osseous heteroplasia. Maternal transmission of Gs(alpha) mutations leads to AHO plus resistance to several hormones (e.g., parathyroid hormone) that activate Gs in their target tissues (pseudohypoparathyroidism type IA), while paternal transmission leads only to the AHO phenotype (pseudopseudohypoparathyroidism). Studies in both mice and humans demonstrate that Gs(alpha) is imprinted in a tissue-specific manner, being expressed primarily from the maternal allele in some tissues and biallelically expressed in most other tissues. This likely explains why multihormone resistance occurs only when Gs(alpha) mutations are inherited maternally. The Gs(alpha) gene GNAS1 has at least four alternative promoters and first exons, leading to the production of alternative gene products including Gs(alpha), XLalphas (a novel Gs(alpha) isoform expressed only from the paternal allele), and NESP55 (a chromogranin-like protein expressed only from the maternal allele). The fourth alternative promoter and first exon (exon 1A) located just upstream of the Gs(alpha) promoter is normally methylated on the maternal allele and is transcriptionally active on the paternal allele. In patients with parathyroid hormone resistance but without AHO (pseudohypoparathyroidism type 113), the exon IA promoter region is unmethylated and transcriptionally active on both alleles. This GNAS1 imprinting defect is predicted to decrease Gs(alpha) expression in tissues where Gs(alpha) is normally imprinted and therefore to lead to renal parathyroid hormone resistance. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov RI Weinstein, Lee/I-5575-2015; OI Weinstein, Lee/0000-0002-1899-5152 NR 248 TC 60 Z9 68 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-412-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 968 BP 173 EP 197 PG 25 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BU83Q UT WOS:000177158100013 PM 12119276 ER PT S AU Choi, WS Chahdi, A Kim, YM Fraundorfer, PF Beaven, MA AF Choi, WS Chahdi, A Kim, YM Fraundorfer, PF Beaven, MA BE Stratakis, CA ChoChung, YS TI Regulation of phospholipase D and secretion in mast cells by protein kinase A and other protein kinases SO PROTEIN KINASE A AND HUMAN DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protein Kinase A and Human Disease CY SEP 10, 2001 CL NIH, BETHESDA, MARYLAND SP NICHHD HO NIH DE phospholipase D; protein kinases; mast cells; exocytosis ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; BASOPHILIC RBL-2H3 CELLS; ADP-RIBOSYLATION FACTOR; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; DEPENDENT ACTIVATION; PLASMA-MEMBRANE; PHOSPHORYLATION; ALPHA; STIMULATION; EXOCYTOSIS AB Functions attributed to phospholipase (PL) D include the regulation of intracellular trafficking of Golgi-derived vesicles and secretion of granules from mast cells. We have reported that activation of PLD and secretion in a rat mast cell (RBL-2H3) line is substantially enhanced by cholera toxin, a known activator of protein kinase (PK) A. Here we review the evidence that (1) the synergistic interactions of cholera toxin and other pharmacological agents on mast cell secretion are attributable to the synergistic activation of PLD via PKA, CaM kinase II, and PKC and (2) both PLD1 and PLD2 participate in this process. For example, treatment with cholera toxin, thapsigargin, and phorbol 12-myristate 13-acetate (which activate PKA, CaM kinase H, and PKC, respectively) exhibit synergy in the stimulation of both PLD and secretion. These kinases and PLD are likely confined to membrane components, as similar synergistic interactions could be demonstrated in permeabilized cells. The regulation of PLD and secretion by these kinases is also apparent from studies of inhibitors of PKA and other kinases. Also, by overexpression of either PLD1 or PLD2 it is apparent that both isoforms respond to the same stimuli as endogenous PLD, although PLD1 is largely associated with secretory granules and PLD2 with plasma membrane. The studies reveal interesting differences in the regulation of the translocation of granules (regulated by PKA) and the fusion of these granules with the plasma membrane (regulated by Ca2+ and PKC). The pathological/physiological implications of the regulation of PLD by PKA require further evaluation in other cell systems. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Beaven, MA (reprint author), NHLBI, Immunol Lab, NIH, Room 8N109,Bldg 10, Bethesda, MD 20896 USA. NR 46 TC 22 Z9 22 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-412-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 968 BP 198 EP 212 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BU83Q UT WOS:000177158100014 PM 12119277 ER PT S AU Kirschner, LS AF Kirschner, LS BE Stratakis, CA ChoChung, YS TI Signaling pathways in adrenocortical cancer SO PROTEIN KINASE A AND HUMAN DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protein Kinase A and Human Disease CY SEP 10, 2001 CL NIH, BETHESDA, MARYLAND SP NICHHD HO NIH DE adrenal cancer; adrenocortical carcinoma; growth factors; signal transduction; G proteins; protein kinase A (PKA); mitogen-activated protein kinase (MAPK); ACTH receptor; p53; ras; insulin-like growth factor; EGF ID GROWTH-FACTOR-II; ADRENAL-CORTICAL CARCINOMA; ACTIVATED PROTEIN-KINASE; HUMAN ENDOCRINE TUMORS; CUSHINGS-SYNDROME; ANGIOTENSIN-II; LAPAROSCOPIC ADRENALECTOMY; ONCOGENIC MUTATIONS; CORTISOL SECRETION; HORMONE RECEPTORS AB Adrenocortical carcinoma is a rare tumor that carries a very poor prognosis. Despite efforts to develop new therapeutic regimens to treat this disease, surgery remains the mainstay of treatment. Laboratory studies of adrenocortical cancers have revealed a wide variety of signaling pathways that can be altered in these neoplasms. Although ACTH signaling through adenylyl cyclase and protein kinase A is important for normal adrenal cellular physiology, there is evidence to suggest that this pathway may inhibit the growth of adrenocortical tumors, and that inactivation of the ACTH receptor may promote tumor formation. Although multiple signal transduction pathways are essential for normal adrenal growth and hormone secretion, efforts to identify events required for neoplastic transformation have met with limited success. Alterations that have frequently been observed in adrenocortical carcinoma include up-regulation of the IGF-II system, as well as mutations in TP53 and RAS. Current studies aim to elucidate the mechanisms of tumor growth by studying proproliferative signaling pathways, such as those involving Akt/PKB and the mitogen-activated protein kinases (MAPKs). Although studies of single pathways have been helpful in guiding investigations, new tools to study the integration and multiplicity of signaling pathways hold the hope of improved understanding of the signaling pathway alterations in adrenocortical cancer. C1 NICHD, Unit Genet & Endocrinol, DEB, NIH, Bethesda, MD 20892 USA. RP Kirschner, LS (reprint author), Ohio State Univ, Div Endocrinol, 491D McCampbell Hall,1581 Dodd Dr, Columbus, OH 43210 USA. NR 106 TC 39 Z9 39 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-412-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 968 BP 222 EP 239 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BU83Q UT WOS:000177158100016 PM 12119279 ER PT S AU Bourdeau, I Stratakis, CA AF Bourdeau, I Stratakis, CA BE Stratakis, CA ChoChung, YS TI Cyclic AMP-dependent signaling aberrations in macronodular adrenal disease SO PROTEIN KINASE A AND HUMAN DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protein Kinase A and Human Disease CY SEP 10, 2001 CL NIH, BETHESDA, MARYLAND SP NICHHD HO NIH DE cyclic AMP; signaling; benign adrenal tumors; macronodular hyperplasia; GIP; GIPR ID GASTRIC-INHIBITORY POLYPEPTIDE; HUMAN ADRENOCORTICAL NEOPLASMS; MCCUNE-ALBRIGHT-SYNDROME; INDEPENDENT CUSHINGS-SYNDROME; MEMBRANE HORMONE RECEPTORS; ELEMENT-BINDING PROTEIN; STIMULATORY G-PROTEIN; STEROIDOGENIC ENZYMES; ACTIVATING MUTATIONS; ONCOGENIC MUTATIONS AB The adrenal glands are a major source of steroid hormone biosynthesis. In normal physiology, the pituitary hormone corticotropin (ACTH) regulates the secretion of glucocorticoids via its G protein-coupled receptor (ACTHR), the product of the MC2R gene. Aldosterone is another major product of the adrenal gland; its regulation is controlled mainly by the renin-angiotensin system, although ACTH plays a role, too, especially under certain pathological conditions. The adrenal gland also secretes lesser amounts of androgens and intermediate metabolites of all these steroids. Unregulated secretion of any of these hormones can be caused by tumors, adrenocortical adenomas or carcinomas, and/or bilateral (or, rarely, unilateral) hyperplasia. Cortisol-producing hyperplasia of the adrenal glands is caused by two distinct syndromes, both of which have been directly or indirectly associated with protein kinase A signaling: (i) primary pigmented nodular adrenocortical disease (PPNAD) (a micronodular form of bilateral adrenal hyperplasia), either isolated (rarely) or in the context of Carney complex, is caused (in most cases) by mutations of the PRKAR1A gene; and (ii) ACTH-independent macronodular adrenal hyperplasia (AIMAH), or massive macronodular adrenal disease (MMAD), has been associated with aberrant (ectopic) expression, and presumably regulation, of various G protein-coupled receptors. AIMAH is a rare, sporadic condition affecting predominantly middle-aged men and women with an almost equal ratio (the latter in contrast to other forms of endogenous Cushing's syndrome). Some familial cases of AIMAH have also been described, and it appears that the pathophysiological phenomena underlying AIMAH may be present in the far more common, sporadic adrenocortical tumors and, perhaps, in the nodular growth detected in the adrenal glands of the elderly in the general population. Thus, the study of ectopic receptor expression and cAMP-dependent PKA activity in AIMAH may have wider implications for adrenal and, indeed, endocrine tumorigenesis. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC1862, Bethesda, MD 20892 USA. RI Levesque, Isabelle/A-1899-2012 NR 114 TC 44 Z9 45 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-412-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 968 BP 240 EP 255 PG 16 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BU83Q UT WOS:000177158100017 PM 12119280 ER PT S AU Robinson-White, A Stratakis, CA AF Robinson-White, A Stratakis, CA BE Stratakis, CA ChoChung, YS TI Protein kinase A signaling - "Cross-talk" with other pathways in endocrine cells SO PROTEIN KINASE A AND HUMAN DISEASE SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Protein Kinase A and Human Disease CY SEP 10, 2001 CL NIH, BETHESDA, MARYLAND SP NICHHD HO NIH DE cyclic AMP; endocrine cell signaling; integration; mitogen-activated protein kinase (MAPK) ID Y1 ADRENOCORTICAL-CELLS; PANCREATIC BETA-CELL; ADENOSINE-MONOPHOSPHATE; TRANSCRIPTION FACTOR; GROWTH-INHIBITION; ACTIVATION; PHOSPHORYLATION; RAS; TRANSDUCTION; RECEPTOR AB Protein kinase A (PKA) signaling, in "classic" endocrine cell functioning, is known to mediate cAMP effects, generated through adenylate cyclase as a response to the activation of G protein-coupled receptors (GPCRs). This signaling system is highly versatile; its flexibility is supported by a number of adenylate cyclases, four PKA regulatory and three catalytic subunits, and several phosphodiesterases that close the negative feedback loop of cAMP generation, most molecules that are expressed in a tissue-specific manner. A central question, however, remains: how do the hundreds of GPCRs mediate their specific effects? Tissue specificity of the expression of the various components of the PKA system, albeit necessary, cannot be the only answer. It helps more to view PKA as a central hub that interacts with a variety of other signaling pathways in endocrine cells, not only mediating but also communicating cAMP effects to the mitogen-activated protein kinase (MAPK), protein kinase C and B (PKC and PKB/Akt, respectively). The net result of these complex interactions, evidence for which is reviewed in this chapter, is what we know as "cAMP effects." It is, perhaps, because of this complexity that investigations of PKA signaling in vivo and in vitro often give contradictory results and are difficult to interpret. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Unit Genet & Endocrinol, DEB, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC1862, Bethesda, MD 20892 USA. NR 44 TC 46 Z9 46 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-412-9 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 968 BP 256 EP 270 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BU83Q UT WOS:000177158100018 PM 12119281 ER PT S AU Carlson, BA Hatfield, DL AF Carlson, BA Hatfield, DL BE Sies, H Packer, L TI Transfer RNAs that insert selenocysteine SO PROTEIN SENSORS AND REACTIVE OXYGEN SPECIES, PT A, SELENOPROTEINS AND THIOREDOXIN SE Methods in Enzymology LA English DT Review ID SERINE TRANSFER-RNA; SELENOPROTEIN SYNTHESIS; MAMMALIAN-CELLS; SELENOPHOSPHATE SYNTHETASE; TRANSFER RNASEC; SECONDARY STRUCTURE; GENE; POPULATION; MOUSE; LIVER C1 NCI, Sect Mol Biol Selenium, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Carlson, BA (reprint author), NCI, Sect Mol Biol Selenium, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NR 47 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182248-6 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 347 BP 24 EP 39 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BT92J UT WOS:000174462200003 PM 11898413 ER PT J AU Kumaraswamy, E Korotkov, KV Diamond, AM Gladyshev, VN Hatfield, DL AF Kumaraswamy, E Korotkov, KV Diamond, AM Gladyshev, VN Hatfield, DL TI Genetic and functional analysis of mammalian Sep15 selenoprotein SO PROTEIN SENSORS AND REACTIVE OXYGEN SPECIES, PT A, SELENOPROTEINS AND THIOREDOXIN SE METHODS IN ENZYMOLOGY LA English DT Review ID ENDOPLASMIC-RETICULUM; GOLGI-APPARATUS; SELENOCYSTEINE; CANCER; SEQUENCE; PROTEIN; PURIFICATION; PREVENTION; CERAMIDE; CELLS C1 NCI, Basic Res Lab, NIH, Sect Mol Biol Selenium,Ctr Canc Res, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Illinois, Dept Human Nutr, Chicago, IL 60612 USA. RP Kumaraswamy, E (reprint author), NCI, Basic Res Lab, NIH, Sect Mol Biol Selenium,Ctr Canc Res, Bethesda, MD 20892 USA. RI Gladyshev, Vadim/A-9894-2013 FU NCI NIH HHS [CA080946] NR 26 TC 14 Z9 16 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 347 BP 187 EP 197 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BT92J UT WOS:000174462200015 PM 11898406 ER PT J AU Tamura, T Stadtman, TC AF Tamura, T Stadtman, TC TI Mammalian thioredoxin reductases SO PROTEIN SENSORS AND REACTIVE OXYGEN SPECIES, PT A, SELENOPROTEINS AND THIOREDOXIN SE METHODS IN ENZYMOLOGY LA English DT Review ID LUNG ADENOCARCINOMA CELLS; NF-KAPPA-B; DNA-BINDING; RAT-LIVER; SELENIUM; SELENOCYSTEINE; IDENTIFICATION; INHIBITION; CLONING; SELENOPROTEIN C1 Okayama Univ, Fac Agr, Dept Bioresources Chem, Okayama 7008530, Japan. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Tamura, T (reprint author), Okayama Univ, Fac Agr, Dept Bioresources Chem, Okayama 7008530, Japan. NR 27 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 347 BP 297 EP 306 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BT92J UT WOS:000174462200027 PM 11898419 ER PT J AU Davis, DA Newcomb, FM Moskovitz, J Fales, HM Levine, RL Yarchoan, R AF Davis, DA Newcomb, FM Moskovitz, J Fales, HM Levine, RL Yarchoan, R TI Reversible oxidation of HIV-2 protease SO PROTEIN SENSORS AND REACTIVE OXYGEN SPECIES, PT B, THIOL ENZYMES AND PROTEINS SE METHODS IN ENZYMOLOGY LA English DT Review ID METHIONINE SULFOXIDE REDUCTASE; IN-VITRO; RESIDUES; PROTEINS; ENZYME; REPAIR; VIVO C1 NCI, HIV AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Davis, DA (reprint author), NCI, HIV AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 19 TC 10 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 348 BP 249 EP 259 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BT92K UT WOS:000174462300024 PM 11885278 ER PT J AU Jones, MB Krutzsch, H Shu, HJ Zhao, YM Liotta, LA Kohn, EC Petricoin, EF AF Jones, MB Krutzsch, H Shu, HJ Zhao, YM Liotta, LA Kohn, EC Petricoin, EF TI Proteomic analysis and identification of new biomarkers and therapeutic targets for invasive ovarian cancer SO PROTEOMICS LA English DT Article; Proceedings Paper CT Meeting of the British-Electrophoresis-Society CY APR 04-06, 2001 CL YORK, ENGLAND SP British Electrophoresis Soc DE ovarian; microdissection; cancer; biomarkers; laser capture ID LASER CAPTURE MICRODISSECTION; HUMAN PROSTATE-CANCER; MASS-SPECTROMETRY; GLYOXALASE-I; CARCINOMA; PROTEIN; DIAGNOSIS; RECEPTORS; TUMORS; CELLS AB Epithelial ovarian cancer kills almost 16 000 women each year in part due to late stage of presentation and lack of reliable biomarkers for disease detection. CA-125, the currently accepted serum marker, alone lacks the sensitivity for early stage diagnosis, as only 50% of early stage cases are detected with this marker. Although more early stage cases may be detected by lysophosphatidic acid, this marker is also elevated in other cancers. One major objective of the NCI-FDA Tissue Proteomics Initiative has been to combine the technique of laser capture microdissection (LCM) of epithelial tumor cells in human tissue specimens with two-dimensional gel electrophoresis (2-D PAGE) to identify proteins that may serve as invasive ovarian cancer-specific biomarkers for early detection and/or new therapeutic targets. We performed 2-D PAGE on lysates from five microdissected ovarian tumors (three invasive ovarian cancers and two non-invasive, low malignant potential (LMP) ovarian tumors). We then compared silver stained 2-D gels created from microdissected lysates with SYPRO-Ruby stained 2-D PAGE profiles of the patient-matched undissected bulk tumor lysates from all five patients. Twenty-three proteins were consistently differentially expressed between both the LMP and three invasive ovarian tumors in the limited study set. Thirteen were uniquely present in all three of the invasive ovarian cancer cases and absent or under-expressed in the two LMP cases. Ten were uniquely present in the LMP cases but absent or under-expressed in all invasive ovarian cancer cases. Credentialing and preliminary target validation of the mass spectrometry identified proteins cut from the Ruby-red stained gels was performed by LCM coupled Western blot and reverse-phase array technology in a study set of six cases (the aforementioned five cases used in the 2-D PAGE profiling component of the study plus one additional LMP case). The analysis revealed that the 52 kDa FK506 binding protein, Rho G-protein dissociation inhibitor (RhoGDI), and glyoxalase I are found to be uniquely over-expressed in invasive human ovarian cancer when compared to the LMP form of this cancer. The direct comparison of LCM generated proteomic profiles of invasive vs. LMP ovarian cancer may more directly generate important markers for early detection and/or therapeutic targets unique to the invasive phenotype. C1 NCI, US FDA,Clin Prote Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD USA. Univ Texas, SW Med Sch, Dept Biochem & Pharmacol, Dallas, TX 75230 USA. NCI, US FDA, Clin Prote Program, Div Therapeut Prod,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), Bldg 29A Room 2B02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 222 Z9 251 U1 2 U2 12 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD JAN PY 2002 VL 2 IS 1 BP 76 EP 84 DI 10.1002/1615-9861(200201)2:1<76::AID-PROT76>3.3.CO;2-F PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 513BU UT WOS:000173358700010 PM 11788994 ER PT S AU Thayer, JF Ruiz-Padial, E AF Thayer, JF Ruiz-Padial, E BE Sivik, T Byrne, D Lipsitt, DR Christodoulou, GN Dienstfrey, H TI Neurovisceral integration in emotion and health SO PSYCHO-NEURO-ENDOCRINO-IMMUNOLOGY (PNEI): A COMMON LANGUAGE FOR THE WHOLE HUMAN BODY SE INTERNATIONAL CONGRESS SERIES LA English DT Proceedings Paper CT 16th World Congress on Psychosomatic Medicine CY AUG 24-29, 2001 CL GOTHENBURG, SWEDEN ID HEART-RATE-VARIABILITY; MODULATION; PERSPECTIVE; MECHANISMS; DEPRESSION; BEHAVIOR; ANXIETY; SYSTEM; CORTEX; EEG C1 NIA, GRC, LPC, Baltimore, MD 21224 USA. RP Thayer, JF (reprint author), NIA, GRC, LPC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 35 TC 0 Z9 1 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0531-5131 BN 0-444-50989-5 J9 INT CONGR SER PY 2002 VL 1241 BP 321 EP 327 DI 10.1016/S0531-5131(02)00648-9 PG 7 WC Neurosciences SC Neurosciences & Neurology GA BX04D UT WOS:000184043600046 ER PT J AU Majewska, MD Gordon, HW Thadani, P AF Majewska, MD Gordon, HW Thadani, P TI Stress and drug abuse - Preface SO PSYCHONEUROENDOCRINOLOGY LA English DT Editorial Material C1 NIDA, NIH, Div Treatment Res & Dev, Ctr Neurosci, Bethesda, MD 20892 USA. RP Majewska, MD (reprint author), NIDA, NIH, Div Treatment Res & Dev, Ctr Neurosci, Room 4123,6001 Execut Blvd, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN-FEB PY 2002 VL 27 IS 1-2 BP 1 EP 3 DI 10.1016/S0306-4530(01)00032-4 PG 3 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 518CQ UT WOS:000173649400001 ER PT J AU Majewska, MD AF Majewska, MD TI HPA axis and stimulant dependence: an enigmatic relationship SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE cocaine/stimulant abuse; HPA axis activation and dysfunction; humans; animal models; hemispheric laterality ID TRANSCRANIAL MAGNETIC STIMULATION; DEFICIT HYPERACTIVITY DISORDER; POSTTRAUMATIC-STRESS-DISORDER; PREFRONTAL CORTEX; SALIVARY CORTISOL; COCAINE ADDICTS; BOYS; NEUROENDOCRINE; DEPRESSION; RESPONSES AB Clinical and preclinical evidence links stress to drug dependence. Stress is accompanied by the rapid modification of brain and body physiology which leads to release of neuroactive hormones, including biogenic amines and adrenal steroids, which activate the same brain circuitry, as stimulant drugs, such as cocaine and amphetamines. Some preclinical studies showed that stress and elevated plasma concentrations of glucocorticoids increase acquisition and maintenance of stimulant use in rats, whereas other studies revealed that animals with inherently hypoactive HPA axis are more vulnerable to stimulant "abuse". In humans cocaine acutely activates the HPA axis, and in chronic cocaine abusers early abstinence is accompanied by alterations of the HPA axis function, with distinct patterns of hormonal changes characteristic for different subgroups of addicts. Some of these changes correspond to psychiatric comorbidities, which may be predictive of propensity to relapse. Hemispheric laterality plays a role in the stress-induced activation of the HPA axis, with right prefrontal cortex (PFC) having mostly stimulatory effects and the left, inhibitory effects. Brain-imaging studies showed preferential alteration of structure and function of the right cerebral hemisphere in cocaine addicts, Activation of the right PFC and inhibition of the left was noted in typical depressive disorders, and right hemispheric hypoactivity was reported in attention deficit hyperactivity and antisocial personality disorders, which are highly comorbid with stimulant dependence. Distinct patterns of hemispheric predominance or hypofunction between individuals may contribute to vulnerability or resilience to stimulant dependence. The nature and significance of the link between stress and activity of HPA axis, and vulnerability to drug dependence is not clear and deserves further study. Published by Elsevier Science Ltd. C1 NIDA, NIH, Div Treatment Res & Dev, Bethesda, MD 20892 USA. RP Majewska, MD (reprint author), NIDA, NIH, Div Treatment Res & Dev, 6001 Execut Blvd,Room 4123,MSC 9551, Bethesda, MD 20892 USA. NR 32 TC 39 Z9 39 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN-FEB PY 2002 VL 27 IS 1-2 BP 5 EP 12 DI 10.1016/S0306-4530(01)00033-6 PG 8 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 518CQ UT WOS:000173649400002 PM 11750767 ER PT J AU Buydens-Branchey, L Branchey, M Majewska, MD AF Buydens-Branchey, L Branchey, M Majewska, MD TI Perturbations of plasma cortisol and DHEA-S following discontinuation of cocaine use in cocaine addicts SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE cortisol; dehydroepiandrosterone (DHEA); cocaine; aggression ID GABA-A RECEPTOR; DEHYDROEPIANDROSTERONE-SULFATE; MAJOR DEPRESSION; PULSATILE SECRETION; ANTERIOR-PITUITARY; SALIVARY CORTISOL; HORMONES; AGE; MEN; CHLOROPHENYLPIPERAZINE AB Changes in plasma levels of cortisol and dchydroepiandrosterone sulfate (DHEA-S) following cocaine discontinuation were assessed in hospitalized chronic cocaine users. Measurements were performed after 6, 9, 18 and 21 days of abstinence. Repeated measures ANOVAs revealed significant time effects for cortisol (P<0.02) and DHEA-S (P<0.001). Changes in the two hormones did not follow the same course. Levels of cortisol. were highest on day 6 and then subsequently decreased, whereas DHEA-S levels were low on day 6 and highest on day 18. Repeated measures ANCOVAs were used to test the overall effects of total duration of cocaine use, daily or weekly cocaine amounts consumed, or frequency of use on cortisol secretion. Analyses revealed a significant effect of frequency of use only (P<0.04). More sustained cocaine use was associated with higher cortisol levels and less pronounced cortisol decline after discontinuation of cocaine use, but drug intake variables had no influence on DHEA-S. The effects of presence or absence of life-long histories of aggression were also assessed. Repeated measures ANOVAs revealed a near significant group x time interaction for cortisol, which declined more dramatically in aggressive addicts than in non-aggressive addicts after day 6. DHEA-S was consistently higher in aggressive cocaine addicts, although this effect did not reach statistical significance. There was a noticeable difference in the dynamics of normalization of adrenal hormones between the two groups, with DHEA-S/cortisol ratios rising more dramatically during cocaine abstinence in aggressive than in non-aggressive addicts. In conclusion, lingering neuroendocrine perturbations persist after discontinuation of cocaine use in addicts. Some of these changes could be associated with an increased relapse risk. Published by Elsevier Science Ltd. C1 New York Harbor Healthcare Syst, Brooklyn, NY 11209 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. NIDA, Bethesda, MD 20892 USA. RP Buydens-Branchey, L (reprint author), New York Harbor Healthcare Syst, Brooklyn Campus,800 Poly Pl, Brooklyn, NY 11209 USA. NR 45 TC 24 Z9 25 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN-FEB PY 2002 VL 27 IS 1-2 BP 83 EP 97 DI 10.1016/S0306-4530(01)00037-3 PG 15 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 518CQ UT WOS:000173649400006 PM 11750771 ER PT J AU Gordon, HW AF Gordon, HW TI Early environmental stress and biological vulnerability to drug abuse SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE stress; drug abuse; PTSD; brain development; trauma; adoption ID CORTICOTROPIN-RELEASING FACTOR; DOPAMINE-BETA-HYDROXYLASE; CHILDHOOD SEXUAL ABUSE; POSTTRAUMATIC-STRESS; HIPPOCAMPAL VOLUME; SUBSTANCE USE; TRAUMA HISTORY; DISORDER; BEHAVIOR; GENETICS AB It has long been believed that stress and drug abuse are related. Studies using animal models have repeatedly demonstrated that stressed animals more readily self-administer alcohol or other drugs. Similarly, human patients consistently report in clinical interviews that stress is one reason for taking drugs. There are also studies that document neurophysiological, neuroanatomical, neurochemical, and physiological changes to animals and humans who are stressed. Many of these changes occur within biological systems that are also affected by psychoactive drugs. Early response to stress also modifies neurodevelopment in permanent ways, and these neuroadaptations occur within the same neuronal systems which comprise the drug-reward circuit. But absent are studies in humans that link early stress and modifications of neurodevelopment with increased vulnerability to drug abuse. This article provides a glimpse of research relating stress to alteration of brain functions and to drug abuse, and points to the work of others in this volume for more details. We hope this attempt to understand how early stress affects the developing brain and increases vulnerability to drug abuse will lead to a new program of research in this emerging area. Published by Elsevier Science Ltd. C1 NIDA, Clin Neurobiol Branch, Div Treatment Res & Dev, Bethesda, MD 20892 USA. RP Gordon, HW (reprint author), NIDA, Clin Neurobiol Branch, Div Treatment Res & Dev, 6001 Execut Blvd,Room 4234, MSC 9559, Bethesda, MD 20892 USA. NR 37 TC 84 Z9 87 U1 3 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN-FEB PY 2002 VL 27 IS 1-2 BP 115 EP 126 DI 10.1016/S0306-4530(01)00039-7 PG 12 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 518CQ UT WOS:000173649400008 PM 11750773 ER PT J AU Byrne, G Suomi, SJ AF Byrne, G Suomi, SJ TI Cortisol reactivity and its relation to homecage behavior and personality ratings in tufted capuchin (Cebus apella) juveniles from birth to six years of age SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE Cebus; capuchin; cortisol; behavior; personality; reactivity ID MALE SOCIAL-BEHAVIOR; RHESUS-MONKEYS; WILD BABOONS; ENDOCRINE; RESPONSES; STYLES; EXPERIENCES; DOMINANCE; PATTERNS; CAPTURE AB Rank correlations between cortisol reactivity measures (baseline, 2 h stress peak and change from baseline) at 6 months and 1 year and (1) behaviors videotaped in the home cage and (2) subjectively judged personality ratings were examined in 36 juvenile tufted capuchins from birth to 6 years of age. High cortisol reactivity was associated with both lower levels of play and exploration in the home cage, and higher levels of proximity and contact with mothers. Animals with higher baseline cortisol played by themselves more, and played with other animals less, than did those with lower baselines. High cortisol reactivity, especially at 1 year of age, was also related to higher levels of dorsal carrying by mothers in the second year, when most infants are independent of mothers. Ratings on the personality traits, Aggressive, Confident, Curious, Effective and Opportunistic, were all negatively correlated with cortisol reactivity levels, while Apprehensive, Fearful, Insecure, Submissive and Tense were positively correlated with cortisol reactivity. In summary, there was a relationship between high physiological reactivity and inhibited, fearful behavior and temperament patterns not previously described in capuchins. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, Poolesville, MD 20837 USA. RP Byrne, G (reprint author), NICHHD, Comparat Ethol Lab, NIH, Anim Ctr, POB 529, Poolesville, MD 20837 USA. NR 28 TC 28 Z9 28 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN-FEB PY 2002 VL 27 IS 1-2 BP 139 EP 154 DI 10.1016/S0306-4530(01)00041-5 PG 16 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 518CQ UT WOS:000173649400010 PM 11750775 ER PT J AU Thadani, PV AF Thadani, PV TI The intersection of stress, drug abuse and development SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE abused drugs; brain; development; monoamines; HPA axis; stress; pregnancy; prenatal; postnatal ID PRENATAL COCAINE EXPOSURE; CORTICOTROPIN-RELEASING FACTOR; PITUITARY-ADRENAL RESPONSES; BRAIN-DEVELOPMENT; CORTICAL DEVELOPMENT; MATERNAL SEPARATION; ALCOHOL EXPOSURE; ETHANOL EXPOSURE; POSTNATAL STRESS; CEREBRAL-CORTEX AB Use or abuse of licit and illicit substances is often associated with environmental stress. Current clinical evidence clearly demonstrates neurobehavioral, somatic growth and developmental deficits in children born to drug-using mothers. However, the effects of environmental stress and its interaction with prenatal drug exposure on a child's development is unknown. Studies in pregnant animals under controlled conditions show drug-induced long-term alterations in brain structures and functions of the offspring. These cytoarchitecture alterations in the brain are often associated with perturbations in neurotransmitter systems that are intimately involved in the regulation of the stress responses. Similar abnormalities have been observed in the brains of animals exposed to other adverse exogenous (e.g., environmental stress) and/or endogenous (e.g., glucocorticoids) experiences during early life. The goal of this article is to: (1) provide evidence and a perspective that common neural systems are influenced during development both by perinatal drug exposure and early stress exposure; and (2) identify gaps and encourage new research examining the effects of early stress and perinatal drug exposure, in animal models, that would elucidate how stress- and drug-induced perturbations in neural systems influence later vulnerability to abused drugs in adult offspring. Published by Elsevier Science Ltd. C1 NIDA, Div Neurosci & Behav Res, Ctr Neurosci, Bethesda, MD 20892 USA. RP Thadani, PV (reprint author), NIDA, Div Neurosci & Behav Res, Ctr Neurosci, 6001 Execut Blvd,Room 4282,MSC 9555, Bethesda, MD 20892 USA. NR 71 TC 21 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD JAN-FEB PY 2002 VL 27 IS 1-2 BP 221 EP 230 DI 10.1016/S0306-4530(01)00046-4 PG 10 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 518CQ UT WOS:000173649400015 PM 11750780 ER PT J AU Chausmer, AL Katz, JL AF Chausmer, AL Katz, JL TI Comparison of interactions of D-1-like agonists, SKF 81297, SKF 82958 and A-77636, with cocaine: locomotor activity and drug discrimination studies in rodents SO PSYCHOPHARMACOLOGY LA English DT Article DE dopamine; D-1 dopamine receptors; cocaine; drug discrimination; locomotor activity; A-77636; SKF 81297; SKF 82958; drug interactions ID DOPAMINE-RECEPTOR AGONISTS; C-FOS EXPRESSION; SQUIRREL-MONKEYS; ROTATIONAL BEHAVIOR; ADENYLYL-CYCLASE; PHARMACOLOGICAL CHARACTERIZATION; STIMULUS PROPERTIES; D2-LIKE AGONISTS; RHESUS-MONKEYS; D-1 AB Rationale: Recent data suggest that dopamine (DA) D-1-like receptor full agonists may be potential pharmacotherapeutic agents for treating cocaine abuse. The structurally novel isochroman D-1-like agonist, A-77636, has not been well characterized and may prove to be useful as such an agent. Objectives: The interactions of cocaine and A-77636 were compared to those obtained with the better investigated benzazepine D-1-like dopamine agonists, SKF 82958 and SKF 81297. The alterations in the locomotor stimulant and discriminative-stimulus effects of cocaine by the full D-1-like dopamine receptor agonists were investigated across a full range of doses in order to characterize their interactions. Methods: Drug-naive Swiss-Webster mice were pretreated with SKF 81297, SKF 82958 or A-77636 (1-10 mg/kg) and cocaine (5-56 mg/kg) prior to a 30-min period in which locomotor activity was assessed. Rats were trained on a fixed ratio 20 (FR20) schedule to discriminate IP saline from cocaine (10 mg/kg) injections. Cocaine alone (1-10 mg/kg) and with either A-77636 (0.56-1.7 mg/kg), SKF 82958 (0.01-0.1 mg/kg) or SKF 81297 (0.1-0.56) were injected IP 5 min prior to a 15-min test session. Results: Cocaine maximally stimulated activity at 20-40 mg/kg with higher and lower doses stimulating activity less. Each D-1-like agonist produced a dose-related decrease in cocaine-induced locomotor activity and lowered its maximal rate. Each of the D-1-like agonists partially substituted for cocaine, with maximal substitution approximating 49, 35, and 24% for SKF 81297, SKF 82958, and A-77636, respectively. SKF 82958 significantly shifted the cocaine dose-effect curve approximately 3-fold to the left. With SKF 81297, there was a trend towards a leftward shift of cocaine dose effects, however the change was not statistically significant. In contrast to the other two D-1-like agonists, A-77636 either did not affect the cocaine dose-effect curve or shifted it to the right. Conclusions: All three agonists produced similar effects on cocaine-induced locomotor activity, however the discriminative-stimulus effects of cocaine were affected differently by the D-1 agonists. These results suggest fundamental differences in the actions of these D-1 agonists. Because A-77636 consistently attenuated the present effects of cocaine, it may prove more useful than the others as a pharmacotherapy to treat cocaine abuse. C1 NIH, Natl Inst Drug Abuse, Intramural Res Program, Med Discovery Res Branch, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), NIH, Natl Inst Drug Abuse, Intramural Res Program, Med Discovery Res Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 58 TC 21 Z9 21 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JAN PY 2002 VL 159 IS 2 BP 145 EP 153 DI 10.1007/s002130100896 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 516GP UT WOS:000173545800005 PM 11862342 ER PT J AU Baas, JMP Bocker, KBE Kenemans, JL Verbaten, MN AF Baas, JMP Bocker, KBE Kenemans, JL Verbaten, MN TI Attentional selection of threat cues and targets SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Utrecht, NL-3508 TC Utrecht, Netherlands. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S20 EP S20 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700075 ER PT J AU Baas, JMP Bocker, KBE Kenemans, JL Verbaten, MN AF Baas, JMP Bocker, KBE Kenemans, JL Verbaten, MN TI Effects of threat measured with startle and event-related potentials SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Utrecht, NL-3508 TC Utrecht, Netherlands. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S10 EP S10 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700036 ER PT J AU Blair, J AF Blair, J TI Reduced responses to threat but not to social inappropriateness in boys with psychopathic tendencies SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S16 EP S16 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700059 ER PT J AU Grillon, C AF Grillon, C TI Startle, anxiety, context, and predictability SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S6 EP S6 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700017 ER PT J AU Hagemann, D Sollers, JJ Naumann, E Hewig, J Seifert, J Bartussek, D Thayer, JF AF Hagemann, D Sollers, JJ Naumann, E Hewig, J Seifert, J Bartussek, D Thayer, JF TI Heart rate variability during the presentation of emotional films SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Trier, D-54286 Trier, Germany. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S39 EP S39 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700153 ER PT J AU Knutson, B Fong, GW Bennett, SM Adams, CM Hommer, D AF Knutson, B Fong, GW Bennett, SM Adams, CM Hommer, D TI FMRI characterization of a region of medial prefrontal cortex that tracks rewarding outcomes SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIAAA, Rockville, MD 20852 USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S4 EP S4 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700009 ER PT J AU Merritt, MM Abernethy, DR Evans, MK Solders, JJ Zonderman, AB Thayer, JF AF Merritt, MM Abernethy, DR Evans, MK Solders, JJ Zonderman, AB Thayer, JF TI Cardiovascular reactivity to perception of affect among older African-american adults SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S9 EP S9 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700031 ER PT J AU Monk, CS Grillon, C McClure, EB Nelson, ER Ernst, M Baas, JMP Charney, DS Pine, DS AF Monk, CS Grillon, C McClure, EB Nelson, ER Ernst, M Baas, JMP Charney, DS Pine, DS TI Neuroimaging methods for the study of threat in children SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. RI Monk, Christopher/J-1805-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S10 EP S10 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700034 ER PT J AU Ruiz-Padial, E Mata-Martin, JL Thayer, JF Vila, J AF Ruiz-Padial, E Mata-Martin, JL Thayer, JF Vila, J TI Nonconscious startle modulation by phobic stimuli SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Jaen, Jaen, Spain. Univ Granada, E-18071 Granada, Spain. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S72 EP S72 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700284 ER PT J AU Ruiz-Padial, E Vila, J Sollers, JJ Thayer, JF AF Ruiz-Padial, E Vila, J Sollers, JJ Thayer, JF TI The relationship between strain gauge measures of respiration and those derived via autoregressive spectral analysis SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Jaen, Jaen, Spain. Univ Granada, E-18071 Granada, Spain. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S72 EP S72 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700285 ER PT J AU Ruiz-Padial, E Vila, J Thayer, JF AF Ruiz-Padial, E Vila, J Thayer, JF TI Emotion modulated startle and defense responses to nonconsciously presented stimuli in small-animal phobics SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 Univ Jaen, Jaen, Spain. Univ Granada, E-18071 Granada, Spain. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S12 EP S12 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700044 ER PT J AU Smith, K Milstein, J Baas, J Grillon, C AF Smith, K Milstein, J Baas, J Grillon, C TI Effects of predictable and unpredictable shocks on fear-potentiated startle SO PSYCHOPHYSIOLOGY LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0048-5772 EI 1469-8986 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PY 2002 VL 39 SU 1 BP S78 EP S78 PG 1 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 592LT UT WOS:000177939700307 ER PT J AU Manuck, SB Kaufmann, P AF Manuck, SB Kaufmann, P TI Symposium synopsis: Genetically informed research in cardiovascular risk - Quantitative and molecular applications SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2002 VL 64 IS 1 MA 2 BP 86 EP 86 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 520BM UT WOS:000173760200018 ER PT J AU Blumenthal, JA DeBusk, RF Kaufmann, PG Powell, LH Saab, PG Schneiderman, N AF Blumenthal, JA DeBusk, RF Kaufmann, PG Powell, LH Saab, PG Schneiderman, N TI The enhancing recovery in Coronary Heart Disease (ENRICHD) trial: Results and implications. SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, ABPP, Durham, NC 27706 USA. Stanford Cardiac Rehabil Program, Palo Alto, CA USA. NHLBI, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Miami, Dept Psychol, Coral Gables, FL 33124 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2002 VL 64 IS 1 MA 12 BP 97 EP 98 PG 2 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 520BM UT WOS:000173760200066 ER PT J AU Lutgendorf, SK Russell, D Harris, T Wallace, R AF Lutgendorf, SK Russell, D Harris, T Wallace, R TI Religious participation and IL-6 predict survival in older adults SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Epidemiol, Iowa City, IA USA. RI Russell, Daniel/A-7559-2013 OI Russell, Daniel/0000-0003-2264-861X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2002 VL 64 IS 1 MA 54 BP 108 EP 108 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 520BM UT WOS:000173760200112 ER PT J AU Johnson, BH Hansen, AL Sollers, JJ Murison, R Julian, JF AF Johnson, BH Hansen, AL Sollers, JJ Murison, R Julian, JF TI Heart rate variability is inversely related to cortisol reactivity during cognitive stress SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. Univ Bergen, Psychol Serv, Bergen, Norway. NIA, Lab Personality & Cognit, Baltimore, MD 21224 USA. NR 0 TC 3 Z9 3 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2002 VL 64 IS 1 MA 148 BP 128 EP 128 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 520BM UT WOS:000173760200206 ER PT J AU Ruiz-Padial, E Sollers, JJ Vila, J Thayer, JF AF Ruiz-Padial, E Sollers, JJ Vila, J Thayer, JF TI Emotion modulated startle magnitude covaries with heart rate variability SO PSYCHOSOMATIC MEDICINE LA English DT Meeting Abstract C1 Univ Granada, Granada, Spain. NIA, Lab Personality & Cognit, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD JAN-FEB PY 2002 VL 64 IS 1 MA 151 BP 129 EP 129 PG 1 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 520BM UT WOS:000173760200209 ER PT J AU Jones, DJ Mills, AR Francis, HL AF Jones, DJ Mills, AR Francis, HL TI Drug use, HIV/AIDS, and health outcomes among racial and ethnic populations - Introduction SO PUBLIC HEALTH REPORTS LA English DT Editorial Material C1 NIDA, Ctr AIDS & Other Med Consequences Drug Abuse, NIH, Bethesda, MD USA. NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD USA. RP Jones, DJ (reprint author), NIDA, Ctr AIDS & Other Med Consequences Drug Abuse, NIH, Bethesda, MD USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PY 2002 VL 117 IS 3 SU 1 BP S3 EP S7 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 619DU UT WOS:000179459700002 ER PT J AU Krewski, D Lubin, JH Samet, JM Hopke, PK James, AC Brand, KP AF Krewski, D Lubin, JH Samet, JM Hopke, PK James, AC Brand, KP TI Projection of residential radon lung cancer risks: The BEIR VI risk models SO RADIATION PROTECTION DOSIMETRY LA English DT Letter ID EXPOSURE; MINERS; HOMES C1 Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON K1N 6N5, Canada. NCI, Biostat Branch, Rockville, MD 20852 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. Clarkson Univ, Dept Chem Engn, Potsdam, NY 13699 USA. ACJ & Associates, Richland, WA 99352 USA. RP Krewski, D (reprint author), Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON K1N 6N5, Canada. RI Hopke, Philip/C-6020-2008 OI Hopke, Philip/0000-0003-2367-9661 NR 17 TC 4 Z9 4 U1 0 U2 4 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD TN23 1YW, KENT, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2002 VL 102 IS 4 BP 371 EP 373 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 627TW UT WOS:000179953100012 PM 12474949 ER PT J AU Huston, AL Justus, BL Falkenstein, PL Miller, RW Ning, H Altemus, R AF Huston, AL Justus, BL Falkenstein, PL Miller, RW Ning, H Altemus, R TI Optically stimulated luminescent glass optical fibre dosemeter SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT 13th International Conference on Solid State Dosimetry CY JUL 09-13, 2001 CL ATHENS, GREECE ID DOPED FUSED QUARTZ; DOSIMETRY; THERMOLUMINESCENCE AB An optical fibre radiation dosemeter has been developed that utilises optically stimulated luminescence and scintillation to provide independent, remote, real-time dose measurements. The radiation sensitive element consists of a I ifim long, 0.4 turn diameter piece of copper- ion-doped fused quartz that is attached to a 1m length of commercial optical fibre. The dose-meter probe is 0.6 nun in diameter and is flexible enough to be used in standard medical catheters for internal radiation dose measurements. A four-channel dosemeter system has been built and characterised Under conditions typical of a radiotherapy environment. The device exhibits a linear response over the range of doses from 0.01 Gy to 10 Gy. The dosenieter responds identically to both electrons and photons in the range from 4 to 20 MV and the calibration was retained to within +/-2% over a period of 4 weeks. The fibre dosemeter has been used successfully to verify doses received by three patients receiving radiotherapy treatments. C1 USN, Res Lab, Div Opt Sci, Washington, DC 20375 USA. NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, DCT,NIH, Bethesda, MD 20892 USA. RP Huston, AL (reprint author), USN, Res Lab, Div Opt Sci, Code 5611, Washington, DC 20375 USA. NR 6 TC 16 Z9 16 U1 0 U2 3 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD TN23 1YW, KENT, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2002 VL 101 IS 1-4 BP 23 EP 26 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 609JM UT WOS:000178899900002 PM 12382700 ER PT J AU Skopec, M Price, JL Guardala, N Loew, M Moscovitch, M AF Skopec, M Price, JL Guardala, N Loew, M Moscovitch, M TI Glow curve analysis applied to the discrimination of X ray versus proton irradiation SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT 13th International Conference on Solid State Dosimetry CY JUL 09-13, 2001 CL ATHENS, GREECE AB Three types of thermoluminescence dosemeters (TLDs): LiF:Mg,Ti (TLD-100). CaF2:Tm (TLD-300), and alpha- Al2O3:C (TLD-500), were investigated for their glow curve response to separate X ray and proton irradiations. The glow Curve structure for each individual TLD's exposure to the X ray and proton irradiations was analysed and compared. Distinguishable differences between the glow curve structure characteristic of each type of radiation were observed. The proton TLD-100 glow curve has revealed a complex high-temperature peak structure that was used for the proton/X ray discrimination algorithm. Proton irradiation of TLD-300 resulted in an apparent switch in the relative heights of peaks 3 and 5 as compared to X ray. In TLD-500, proton irradiation produced a more subtle difference in the glow curve with an increase in the ratio between high- and low-temperature peaks. Results demonstrate promising differences in glow curve structure present allowing for discrimination between X ray and proton radiation field exposures. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. USN, Ctr Surface Warfare, Carderock, MD USA. George Washington Univ, Washington, DC 20052 USA. Georgetown Univ, Washington, DC 20057 USA. RP Skopec, M (reprint author), NIH, Dept Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 3 Z9 3 U1 0 U2 1 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD TN23 1YW, KENT, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2002 VL 101 IS 1-4 BP 99 EP 102 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 609JM UT WOS:000178899900016 PM 12382714 ER PT J AU Li, W Friedland, W Jacob, P Paretzke, HG Panyutin, I Neumann, RD AF Li, W Friedland, W Jacob, P Paretzke, HG Panyutin, I Neumann, RD TI Simulation of I-125 induced DNA strand breaks in a CAP-DNA complex SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT 13th Symposium on Microdosimetry CY MAY 27-JUN 01, 2001 CL STRESA, ITALY ID MONTE-CARLO SIMULATION; SYNTHETIC OLIGODEOXYNUCLEOTIDE; LIQUID WATER; DECAY; IRRADIATION; MODELS AB The E. coli catabolite gene activator protein (CAP)-DNA complex with I-125 located at the position of the H5 atom of the cytosine near the centre was incorporated into the PARTRAC track structure code. DNA strand breaks due to irradiation were calculated by track structure and radical attack simulations strand breaks due to neutralisation of the highly charged Te-125 ion were derived from a semi-empirical distribution. According to the calculations, the neutralisation effect dominates the strand breakage frequency at 2 bases away front the I-125 decay site on both strands. The first breakage distribution counted from a P-32 labelled end on the strand with I-125 agreed well with experimental data. but on the opposite strand. the calculated distribution is more concentrated around the decay site and its yield is about 20% larger than the measured data. C1 GSF, Natl Res Ctr Environm & Hlth, Inst Radiat Protect, D-85764 Neuherberg, Germany. NIH, Dept Nucl Med, Bethesda, MD 20892 USA. RP Li, W (reprint author), GSF, Natl Res Ctr Environm & Hlth, Inst Radiat Protect, D-85764 Neuherberg, Germany. RI Li, Weibo/M-7475-2013 FU PHS HHS [265-MM-918 31] NR 17 TC 2 Z9 2 U1 0 U2 0 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD TN23 1YW, KENT, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2002 VL 99 IS 1-4 BP 109 EP 112 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 580RV UT WOS:000177249400020 PM 12194260 ER PT J AU Miller, AC Luo, L Chin, WK Director-Myska, AE Prasanna, PGS Blakely, WF AF Miller, AC Luo, L Chin, WK Director-Myska, AE Prasanna, PGS Blakely, WF TI Proto-oncogene expression: A predictive assay for radiation biodosimetry applications SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT 13th Symposium on Microdosimetry CY MAY 27-JUN 01, 2001 CL STRESA, ITALY ID IONIZING-RADIATION; PERIPHERAL-BLOOD; GENE-EXPRESSION; MESSENGER-RNA; GAMMA-RAYS; CELLS; MODULATION; INDUCTION; EXPOSURE; PROTOONCOGENE AB Using a model system of in vitro human peripheral blood lymphocytes. the effect of low-dose (0,25 to 1,50 Gy) 250-kV(p) X ray radiation (1 Gy.min(-1)) on the expression of several proto-oncogenes was examined (c-Haras, c-src, c-met, c-jun, c-fos, and c-myc) and beta-actin from 0.25 to 17 h post-radiation, RNA was extracted from cells harvested at various times after exposure and examined for levels of particular mRNAs by northern blot hybridisation. A progressive time- and dose-dependent increase in mRNA levels was observed for c-Haras mRNA, while the other proto-oncogenes (c-src, c-met, c-fos. c-jun and c-myc) examined were variable during the same time period. beta-actin levels were initially decreased but at 17 h post-radiation had returned to control levels. A comparison of the rate of c-Haras transcription at 5 and 17 h post-irradiation revealed that c-Harus transcription was higher Lit 5 h than at 17 h. These findings suggest that the level of specific proto-oncogene expression, particularly c-Haras may be useful early diagnostic molecular biomarkers for biodosimetry applications. The use of real-time PCR technologies to quantify gene expression changes will also be discussed. C1 Armed Forces Radiobiol Res Inst, Appl Cellular Radiobiol Dept, Bethesda, MD 20889 USA. NCI, Mol Pharmacol Branch, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. RP Miller, AC (reprint author), Armed Forces Radiobiol Res Inst, Appl Cellular Radiobiol Dept, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 32 TC 14 Z9 14 U1 0 U2 0 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD TN23 1YW, KENT, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2002 VL 99 IS 1-4 BP 295 EP 302 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 580RV UT WOS:000177249400067 PM 12194311 ER PT J AU Hendee, WR Chien, S Maynard, CD Dean, DJ AF Hendee, WR Chien, S Maynard, CD Dean, DJ TI The National Institute of Biomedical Imaging and Bioengineering: History, status, and potential impact SO RADIOLOGY LA English DT Review DE radiology and radiologists; radiology and radiologists, research; radiology and radiologists, socioeconomic issues AB In December 2000, President Clinton signed legislation establishing the National Institute of Biomedical Imaging and Bioengineering (NIBIB). This action was the result of a multidecade effort of the biomedical imaging and engineering communities to gain increased recognition for biomedical imaging and engineering research within the National Institutes of Health and to enhance the impact of these disciplines on the health and well-being of people worldwide. Beginning in January 2001, several activities were initiated to form NIBIB into a real asset for researchers in biomedical imaging and engineering. These activities reflect a recognition that research in biomedical imaging and bioengineering has the potential of positively Influencing research in many other biomedical disciplines, as well as directly affecting the welfare of people everywhere. This potential impact is discussed in this report, together with the history and present status of the formation of NIBIB. C1 Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA. Univ Calif San Diego, Dept Bioengn & Med, San Diego, CA 92103 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA. RP Hendee, WR (reprint author), Med Coll Wisconsin, Dept Radiol, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. NR 12 TC 16 Z9 17 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2002 VL 222 IS 1 BP 12 EP 18 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 504YW UT WOS:000172884800004 PM 11756699 ER PT J AU Pearson, KM Pannell, LK Fales, HM AF Pearson, KM Pannell, LK Fales, HM TI Intramolecular cross-linking experiments on cytochrome c and ribonuclease A using an isotope multiplet method SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID MASS-SPECTROMETRY; ESCHERICHIA-COLI; RIBOSOMAL-SUBUNIT; PROTEIN; IDENTIFICATION; CROSSLINKING AB Mass spectral analysis of tryptic digests of cross-linked proteins offers considerable promise as a simple technique to probe protein structure and study protein-protein interactions. We describe the use of a 1:1 mixture of isotopically labeled and unlabeled cross-linkers, disuccinimidyladipate (DSA) and dimethyladipimidate (DMA), to enhance visualization of cross-linked peptides in a tryptic digest. Optimized intramolecular reactions of cytochrome c and ribonuclease A (RNase A) with DSA yielded an average of two cross-links per protein molecule. After digestion of the crosslinked cytocbrome c with trypsin and analysis by liquid chromatography/mass spectrometry (LC/MS) and matrix-assisted laser desorption/ionization (MALDI), eight modified peptides, five crosslinked and two end-capped, were detected by virtue of their doublet character. An eighth modified peptide's identity remained ambiguous because of its inability to fragment. The lysine-lysine distance constraints obtained are discussed in the context of the known NMR and X-ray structures of cytochrome c. Analysis of cross-linked RNase A by LC/MS and MALDI yielded nine modified peptides, four of which were modified twice, as indicated by the isotopic triplets. Although seven of these peptides contained cross-links, few distance constraints were gained due to the fact that the cross-linked products were variations of modification of the same three lysine residues. Published in 2001 by John Wiley Sons, Ltd. C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Fales, HM (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA. NR 15 TC 86 Z9 88 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2002 VL 16 IS 3 BP 149 EP 159 DI 10.1002/rcm.554 PG 11 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 518EU UT WOS:000173654300001 PM 11803535 ER PT J AU Wierenga, SK Zocher, MJ Mirus, MM Conrads, TP Goshe, MB Veenstra, TD AF Wierenga, SK Zocher, MJ Mirus, MM Conrads, TP Goshe, MB Veenstra, TD TI A method to evaluate tryptic digestion efficiency for high-throughput proteome analyses SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Letter ID 2-DIMENSIONAL ELECTROPHORESIS; PROTEINS; IDENTIFICATION; GENOME C1 NCI, SAIC Frederick, Frederick, MD 21702 USA. Prosser High Sch, Prosser, WA 99350 USA. Pacific NW Natl Lab, Environm & Mol Sci Lab, Richland, WA 99352 USA. RP Veenstra, TD (reprint author), NCI, SAIC Frederick, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 10 TC 17 Z9 17 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2002 VL 16 IS 14 BP 1404 EP 1408 DI 10.1002/rcm.729 PG 5 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 574KD UT WOS:000176887500008 PM 12112621 ER PT J AU Sechi, S AF Sechi, S TI A method to identify and simultaneously determine the relative quantities of proteins isolated by gel electrophoresis SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID 2-DIMENSIONAL ELECTROPHORESIS; QUANTITATIVE-ANALYSIS; MASS-SPECTROMETRY; GLOBAL ANALYSIS; AFFINITY TAGS; PROTEOMICS; PEPTIDE; PREFRACTIONATION; IDENTIFICATION; ALKYLATION AB Gel electrophoresis is often used for the primary analysis and purification of proteins, and peptide mapping by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) is a widely used technique for the rapid identification of unknown proteins. The identification is usually obtained by digesting the protein with an enzyme and matching the masses of the proteolytic peptides with those of each protein in a sequence database. Another important aspect in many proteomic experiments is the determination of the relative protein quantities (e.g. comparison between control and altered states). Usually, this is obtained by comparing the spot intensities of two independent gels. This procedure is time-consuming and not very accurate. Recently, several methodologies using isotope labeling of proteins for quantitative proteomic studies have been introduced (e.g. using ICAT reagents or growing cells in isotopically enriched nutrients). However, none of these methodologies is foolproof and there is still the need for simple and inexpensive alternatives for determining the relative quantities of proteins. Previously, we showed that a mixture of acrylamide and deuterated acrylamide could be used as cysteine alkylating reagent prior to electrophoresis, improving the coverage and the confidence of the protein identification procedure (Sechi S, Chait BT. Anal. Chem. 1998; 70: 5150). Here we show that a similar approach can be used to obtain relative quantitation at the femtomole level of proteins isolated by gel electrophoresis. Deuterated acrylamide is used to alkylate the cysteines in one sample and regular acrylamide is used to alkylate the cysteines in the second sample. The two samples are then mixed together in a 1:1 ratio and the relative protein quantities are determined from the ion intensity ratios of the two cysteine-containing peptides isotopic envelopes (regular/deuterated). The analysis of several proteins mixed in different ratios is reported showing that this approach can reliably be used for protein identification and quantification. Briefly, a simple and inexpensive method for quantifying and simultaneously identifying proteins isolated by gel electrophoresis using MALDI-MS is presented. Published in 2002 by John Wiley Sons, Ltd. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Sechi, S (reprint author), NIDDKD, NIH, 6707 Democracy BlvdmRm 611, Bethesda, MD 20892 USA. NR 25 TC 58 Z9 62 U1 0 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2002 VL 16 IS 15 BP 1416 EP 1424 DI 10.1002/rcm.734 PG 9 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 578QX UT WOS:000177131400002 PM 12125017 ER PT S AU Hager, GL AF Hager, GL BE Cato, A Schacke, H Asadullah, K TI The dynamics of intranuclear movement and chromatin remodeling by the glucocorticoid receptor SO RECENT ADVANCES IN GLUCOCORTICOID RECEPTOR ACTION SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP LA English DT Proceedings Paper CT 40th Ernst-Schering-Research-Foundation Workshop CY OCT 31-NOV 02, 2001 CL BERLIN, GERMANY SP Ernst Schering Res Fdn ID TUMOR VIRUS PROMOTER; TRANSCRIPTION FACTORS; LIVING CELLS; IN-VIVO; MMTV PROMOTER; NUCLEOSOME; PROGESTERONE; TRAFFICKING; COMPLEXES; TEMPLATES C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Bldg 41,Room B602, Bethesda, MD 20892 USA. NR 31 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-43229-9 J9 E SCHERING RES FDN W PY 2002 VL 40 BP 111 EP 129 PG 19 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Immunology GA BV74Q UT WOS:000179942100008 ER PT S AU Schaaf, WJM Cidlowski, JA AF Schaaf, WJM Cidlowski, JA BE Cato, A Schacke, H Asadullah, K TI The glucocorticoid receptor beta-isoform: A perspective on its relevance in human health and disease SO RECENT ADVANCES IN GLUCOCORTICOID RECEPTOR ACTION SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP LA English DT Proceedings Paper CT 40th Ernst-Schering-Research-Foundation Workshop CY OCT 31-NOV 02, 2001 CL BERLIN, GERMANY SP Ernst Schering Res Fdn ID STEROID-HORMONE RECEPTORS; HEAT-SHOCK-PROTEIN; NF-KAPPA-B; RESPONSE ELEMENT; FUNCTIONAL ANTAGONISM; NUCLEAR-LOCALIZATION; MULTIPLE FUNCTIONS; GENE-EXPRESSION; DNA-BINDING; CROSS-TALK C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Schaaf, WJM (reprint author), NIEHS, Lab Signal Transduct, NIH, MD F307,111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. NR 63 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-43229-9 J9 E SCHERING RES FDN W PY 2002 VL 40 BP 197 EP 211 PG 15 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Immunology GA BV74Q UT WOS:000179942100012 ER PT S AU Mittelstadt, PR Galon, J Franchimont, D O'Shea, JJ Ashwell, JD AF Mittelstadt, PR Galon, J Franchimont, D O'Shea, JJ Ashwell, JD BE Cato, A Schacke, H Asadullah, K TI Glucocorticold-inducible genes that regulate T-cell function SO RECENT ADVANCES IN GLUCOCORTICOID RECEPTOR ACTION SE ERNST SCHERING RESEARCH FOUNDATION WORKSHOP LA English DT Proceedings Paper CT 40th Ernst-Schering-Research-Foundation Workshop CY OCT 31-NOV 02, 2001 CL BERLIN, GERMANY SP Ernst Schering Res Fdn ID NF-KAPPA-B; PROTEIN-PROTEIN-INTERACTION; RECEPTOR-ALPHA CHAIN; DNA-BINDING; HOMEOSTATIC PROLIFERATION; RESPONSE ELEMENT; DEFICIENT MICE; C-JUN; TRANSCRIPTIONAL ACTIVATION; LYMPHOID DEVELOPMENT C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Mittelstadt, PR (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NR 97 TC 2 Z9 2 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0947-6075 BN 3-540-43229-9 J9 E SCHERING RES FDN W PY 2002 VL 40 BP 319 EP 339 PG 21 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Immunology GA BV74Q UT WOS:000179942100018 ER PT J AU Eddy, EM AF Eddy, EM TI Male germ cell gene expression SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 57 SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Review ID MOUSE SPERMATOGENIC CELLS; FOLLICLE-STIMULATING-HORMONE; RAT SERTOLI CELLS; PHOSPHOGLYCERATE KINASE GENE; MESSENGER-RIBONUCLEIC-ACID; TESTIS-SPECIFIC PROMOTER; PORIN-BINDING DOMAIN; FIBROUS SHEATH; MANNOSE 6-PHOSPHATE; TRANSLATIONAL REGULATION AB Formation of the male gamete occurs in sequential mitotic, meiotic, and postmeiotic phases. Many germ cell-specific transcripts are produced during this process. Their expression is developmentally regulated and stage specific. Some of these transcripts are product of genes that are male germ cell-specific homologs of genes expressed in somatic cells, while some are expressed from unique genes unlike any others in the genome. Others are alternate transcripts derived from the same gene as transcripts in somatic cells but differing from them in size and/or overall sequence. They are generated during gene expression by using promoters and transcription factors that activate transcription at different start sites upstream or downstream of the usual site, by incorporation of alternate exons, by germ cell-specific splicing events, and by using alternate initiation sites for polyadenylation. Male germ cell development consists of an assortment of unique processes, including meiosis, genetic recombination, haploid gene expression, formation of the acrosome and flagellum, and remodeling and condensation of the chromatin. These processes are intricate, highly ordered, and require novel gene products and a precise and well-coordinated program of gene expression to occur. The regulation of gene expression in male germ cells occurs at three levels: intrinsic, interactive, and extrinsic. A highly conserved genetic program "intrinsic" to germ cells determines the sequence of events that underlies germ cell development. This has been underscored by recent studies showing that meiosis involves many genes that have been conserved during evolution from yeast to man. During meiosis and other processes unique to germ cells, the intrinsic program determines which genes are utilized and when they are expressed. In the postmeiotic phase, it coordinates the expression of genes whose products are responsible for constructing the sperm. The process of spermatogenesis occurs in overlapping wave,;, with cohorts of germ cells developing in synchrony. The intrinsic program operating within a particular germ cell requires information from and provides information to neighboring cells to achieve this coordination. Sertoli cells are crucial for this "interactive" process as well as for providing essential support for germ cell proliferation and progression through the phases of development. The interactive level of regulation is dependent on "extrinsic" influences, primarily testosterone and follicle-stimulating hormone (FSH). Studies during the last 4 years have established that FSH is not essential for germ cell development but instead serves an important supportive role for this process. While testosterone is essential for maintenance of spermatogenesis, it acts on Sertoli cells and peritubular cells and has indirect effects on germ cells. The extrinsic and interactive processes are extremely important for establishing and maintaining an optimum environment within which gametogenesis occurs. Nevertheless, an intrinsic evolutionarily conserved genetic program regulates male germ cell gene expression and development. C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 115 TC 278 Z9 306 U1 0 U2 10 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4410 USA SN 0079-9963 J9 RECENT PROG HORM RES PY 2002 VL 57 BP 103 EP 128 DI 10.1210/rp.57.1.103 PG 26 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BV77R UT WOS:000179991300005 PM 12017539 ER PT J AU Usdin, TB Bonner, TI Hoare, SRJ AF Usdin, TB Bonner, TI Hoare, SRJ TI The parathyroid hormone 2 (PTH2) receptor SO RECEPTORS & CHANNELS LA English DT Article DE parathyroid hormone; receptor; review; tuberoinfundibular peptide of 39 residues ID TUBEROINFUNDIBULAR PEPTIDE; 39 RESIDUES; CHROMOSOME 2Q33; LOOP REGIONS; LIGAND; RAT; AGONIST; PROTEIN; IDENTIFICATION; DETERMINANTS AB The human PTH2 receptor binds and is activated at high potency by PTH and by the recently discovered peptide tuberoinfundibular peptide of 39 residues (TIP39). Rat and zebrafish PTH2 receptors are more weakly activated by PTH, suggesting that may be the natural ligand for the PTH2 receptor. Unlike the PTH1 receptor, the PTH2 receptor interacts extremely weakly with parathyroid hormone-related peptide (PTHrP). The PTH2 receptor is strongly coupled to stimulation of cAMP accumulation, and more weakly, in a cell-specific manner to increases in intracellular calcium concentration. A variety of evidence supports the general model of receptor amino terminal sequences binding ligand carboxyl terminal sequences with high affinity, and ligand amino terminal sequences activating the receptor through interaction with the "juxtamembrane" portion of the receptor. The receptor is present at greatest levels in the nervous system. It is expressed in scattered cells in the cerebral cortex and basal ganglia and at relatively high abundance in the septum, midline thalamic nuclei, several hypothalamic nuclei, and the dorsal horn of the spinal cord. Peripherally, expression in pancreatic islet somatostatin cells is most dramatic. Functional hypotheses based on the receptor's distribution are being tested. Recent data support involvement in hypothalamic releasing-factor secretion and pain. C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. RP Usdin, TB (reprint author), NIMH, Genet Lab, Bldg 36 Room 3D06,36 Convent Dr, Bethesda, MD 20892 USA. NR 36 TC 28 Z9 28 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1060-6823 J9 RECEPTOR CHANNEL JI Recept. Channels PY 2002 VL 8 IS 3-4 SI SI BP 211 EP 218 DI 10.1080/10606820290005092 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 596LH UT WOS:000178166000008 PM 12529938 ER PT J AU Bilski, P Daub, ME Chignell, CF AF Bilski, P Daub, ME Chignell, CF TI Direct detection of singlet oxygen via its phosphorescence from cellular and fungal cultures SO REDOX CELL BIOLOGY AND GENETICS, PART A SE METHODS IN ENZYMOLOGY LA English DT Review ID MOLECULAR-OXYGEN; ROSE-BENGAL; CATIONIC SURFACTANT; CERCOSPORIN; YIELDS; PHOTOPROCESSES; PHOTOTOXICITY; DERIVATIVES; TEMPERATURE; SOLVENTS C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Bilski, P (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Strid, Ake/E-5309-2012 OI Strid, Ake/0000-0003-3315-8835 NR 19 TC 7 Z9 7 U1 0 U2 10 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 352 BP 41 EP 52 PN A PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU93G UT WOS:000177426500003 PM 12125368 ER PT J AU Mattson, MP AF Mattson, MP TI Involvement of superoxide in pathogenic action of mutations that cause Alzheimer's disease SO REDOX CELL BIOLOGY AND GENETICS, PART A SE METHODS IN ENZYMOLOGY LA English DT Review ID AMYLOID-PRECURSOR PROTEIN; AMYOTROPHIC-LATERAL-SCLEROSIS; OXIDATIVE STRESS; BETA-PEPTIDE; LIPID-PEROXIDATION; MUTANT PRESENILIN-1; HIPPOCAMPAL-NEURONS; CALCIUM HOMEOSTASIS; CORTICAL-NEURONS; MITOCHONDRIAL DYSFUNCTION C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 50 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 352 BP 455 EP 474 PN A PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU93G UT WOS:000177426500038 PM 12125371 ER PT J AU Sullivan, DM Levine, RL Finkel, T AF Sullivan, DM Levine, RL Finkel, T TI Detection and affinity puriflcation of oxidant-sensitive proteins using biotinylated glutathione ethyl ester SO REDOX CELL BIOLOGY AND GENETICS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID S-THIOLATION; TYROSINE PHOSPHATASES; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; REDOX REGULATION; DIETHYL ESTER; IDENTIFICATION; BIOCHEMISTRY; DISULFIDE; CELLS C1 NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Sullivan, DM (reprint author), NHLBI, Mol Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 26 TC 17 Z9 17 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 353 BP 101 EP 113 PN B PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU60C UT WOS:000176466500010 PM 12078486 ER PT J AU Felix, K Rockwood, LD Janz, S AF Felix, K Rockwood, LD Janz, S TI Transgenic shuttle vector assays for determining genetic differences in oxidative B cell mutagenesis in vivo SO REDOX CELL BIOLOGY AND GENETICS, PT B SE METHODS IN ENZYMOLOGY LA English DT Review ID ELEVATED MUTANT FREQUENCIES; IN-VIVO; PLASMACYTOMA DEVELOPMENT; POSITIVE SELECTION; COLOR MUTANTS; MICE; MOUSE; MUTATIONS; LACI; MODEL C1 NCI, Genet Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Felix, K (reprint author), NCI, Genet Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. NR 27 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 353 BP 434 EP 448 PN B PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BU60C UT WOS:000176466500037 PM 12078516 ER PT S AU Sipe, JD AF Sipe, JD BE Sipe, JD Kelley, CA McNicol, LA TI Tissue engineering and reparative medicine SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE bioreactors; biomaterials; bioscaffolds; cryopreservation; host remodeling AB Reparative medicine is a critical frontier in biomedical and clinical research. The National Institutes of Health Bioengineering Consortium (BECON) convened a symposium titled "Reparative Medicine: Growing Tissues and Organs," which was held on June 25 and 26, 2001 in Bethesda, Maryland. The relevant realms of cells, molecular signaling, extracellular matrix, engineering design principles, vascular assembly, bioreactors, storage and translation, and host remodeling and the immune response that are essential to tissue engineering were discussed. This overview of the scientific program summarizes the plenary talks, extended poster presentations and breakout session reports with an emphasis on scientific and technical hurdles that must be overcome to achieve the promise of restoring, replacing, or enhancing tissue and organ function that tissue engineering offers. C1 NIH, Ctr Sci Review, Bethesda, MD 20814 USA. RP Sipe, JD (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr, Bethesda, MD 20814 USA. NR 32 TC 83 Z9 83 U1 0 U2 8 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 1 EP 9 PG 9 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500001 PM 12081856 ER PT S AU McKay, R AF McKay, R BE Sipe, JD Kelley, CA McNicol, LA TI Building animals from stem cells SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE neurotrophins; glia; neural stem cells C1 NINDS, NIH, Bethesda, MD 20892 USA. RP McKay, R (reprint author), NINDS, NIH, Bldg 36,Room 5A29,36 Ctr Dr, Bethesda, MD 20892 USA. NR 1 TC 4 Z9 4 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 44 EP 44 PG 1 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500006 PM 12081861 ER PT S AU Faustman, DL Pedersen, RL Kim, SK Lemischka, IR McKay, RD AF Faustman, DL Pedersen, RL Kim, SK Lemischka, IR McKay, RD BE Sipe, JD Kelley, CA McNicol, LA TI Cells for repair - Breakout session summary SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Princeton Univ, Princeton, NJ 08544 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Faustman, DL (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 45 EP 47 PG 3 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500007 PM 12081862 ER PT S AU Osyczka, AM Noth, U Danielson, KG Tuan, RS AF Osyczka, AM Noth, U Danielson, KG Tuan, RS BE Sipe, JD Kelley, CA McNicol, LA TI Different osteochondral potential of clonal cell lines derived from adult human trabecular bone SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE adult human; trabecular bone; cell lines; osteoblasts; osteogenesis; chondrogenesis; adipogenesis; mesenchymal progenitors ID MESENCHYMAL STEM-CELLS; CHONDROGENIC DIFFERENTIATION; MORPHOGENETIC PROTEIN-2; IN-VITRO; MARROW; STIMULATION; PHENOTYPE AB Cells derived from human trabecular bones have been shown to have multipotential differentiation ability along osteogenic, chondrogenic, and adipogenic lineages. In this study, we have derived two clonal sublines of human trabecular bone cells by means of stable transduction with human papilloma virus E6/E7 genes. Our results showed that these clonal sublines differ in their osteochondral potential, but are equally adipogenic, indicative of the heterogeneous nature of the parental cell population. The availability of these cell lines should be useful for the analysis of the mechanisms regulating the differentiation of adult mesenchymal progenitor cells. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Univ Wurzburg, Dept Orthopaed Surg, Wurzburg, Germany. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, 50 South Dr,Bldg 50,Room 1503, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 71602]; NIAMS NIH HHS [AR 39740, AR 44501, AR 45181, R03 AR 47396]; NIDCR NIH HHS [DE 11327, DE 12864] NR 18 TC 20 Z9 21 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 73 EP 77 PG 5 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500015 PM 12081870 ER PT S AU Elisseeff, JH Lee, A Kleinman, HK Yamada, Y AF Elisseeff, JH Lee, A Kleinman, HK Yamada, Y BE Sipe, JD Kelley, CA McNicol, LA TI Biological response of chondrocytes to hydrogels SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE cartilage replacement; hydrogels; chondrocytes; bioscaffolds ID CARTILAGE AB Primary bovine chondrocytes were encapsulated in alginate and alginate combined with cartilage matrix extract, Cartrigel, for the purpose of cartilage tissue engineering. The cell constructs were incubated in vitro and gene expression of cartilage-specific extracellular matrix molecules was quantitated and localized with in situ hybridization with a decrease in expression observed in the alginate-Cartrigel constructs. Further understanding of cell response to scaffolds will allow rational design and development of hydrogels for cartilage tissue engineering. C1 Johns Hopkins Univ, Dept Biomed Engn, Whitaker Inst Biomed Engn, Baltimore, MD 21218 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev & Regenerat Branch, Bethesda, MD 20892 USA. RP Elisseeff, JH (reprint author), Johns Hopkins Univ, Dept Biomed Engn, Whitaker Inst Biomed Engn, 3400 N Charles St,Clark Hall, Baltimore, MD 21218 USA. NR 13 TC 32 Z9 34 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 118 EP 122 PG 5 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500023 PM 12081878 ER PT S AU Tuli, R Seghatoleslami, MR Tuli, S Howard, MS Danielson, KG Tuan, RS AF Tuli, R Seghatoleslami, MR Tuli, S Howard, MS Danielson, KG Tuan, RS BE Sipe, JD Kelley, CA McNicol, LA TI p38 MAP kinase regulation of AP-2 binding in TGF-beta 1-stimulated chondrogenesis of human trabecular bone-derived cells SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE mesenchymal progenitor cell; human trabecular bone; chondrogenesis; p38 mitogen-activated protein (MAP) kinase; activated protein-2 (AP-2) ID OSTEOPENIC DISORDERS; MARROW AB Collagenase-treated, explanted human trabecular-bone chips are an excellent source of osteoblast-like cells. We have recently shown the multiple differentiation potential of these cells; in addition to osteogenesis and adipogenesis, these cells also undergo chondrogenesis when maintained as high-density pellet cultures (250,000 cells/pellet) in a serum-free, chemically defined medium stimulated with TGF-beta1 (10 ng/mL). In this investigation, we have analyzed how transactivating nuclear transcription factors, specifically AP-2 and SP-1, may interact with common cis-acting elements found in the regulatory region of cartilage-specific genes as part of the signal transduction mechanism of TGF-beta1 and p38 during chondrogenesis of human trabecular bone-derived multipotential cells. Both TGF-beta1 stimulation and p38 MAP kinase activation affect the binding of AP-2 as well as SP-1 to oligonucleotides with sequence similarity to the overlapping AP-2/SP-1 sites found in the putative 52-bp immediate upstream regulatory region and the 5'-untranslated region of the human aggrecan gene. Electrophoretic mobility shift assays show that TGF-beta1 treatment of the bone-derived cells inhibits AP-2 DNA binding but enhances the DNA binding ability of SP-1. Additionally, treatment of these TGF-beta1-stimulated cells with p38 MAP kinase inhibitor, SB203580, rescued the AP-2 DNA binding but did not affect SP-1 DNA binding. These findings indicate that AP-2 DNA binding is the target of both TGF-beta1 and p38 MAP kinase signaling pathways and suggest a possible signal transduction cascade whereby TGF-beta1 induction of chondrogenesis involves the activation of p38 MAP kinase and the subsequent inhibition of DNA binding by AP-2, thereby preventing the transcriptional repression of the aggrecan gene. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, 50 South Dr,Bldg 50,Room 1503, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR 47396, AR 45181, AR 44501, AR 39740]; NIDCR NIH HHS [DE 12864] NR 10 TC 31 Z9 37 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 172 EP 177 PG 6 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500038 PM 12081893 ER PT S AU Koretsky, AP AF Koretsky, AP BE Sipe, JD Kelley, CA McNicol, LA TI Functional assessment of tissues with magnetic resonance imaging SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MD SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE magnetic resonance imaging; tissue function ID CONTRAST AGENT; MRI; PERFUSION C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Koretsky, AP (reprint author), NINDS, NIH, Bldg 10,Room B1S317,9000 Rockville Pike, Bethesda, MD 20892 USA. EM koretsky@ninds.nih.gov NR 13 TC 7 Z9 7 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 203 EP 205 PG 3 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500045 PM 12081900 ER PT S AU Guilak, F Kapur, R Sefton, MV Vandenburgh, HH Koretsky, AP Kriete, A O'Keefe, RJ AF Guilak, F Kapur, R Sefton, MV Vandenburgh, HH Koretsky, AP Kriete, A O'Keefe, RJ BE Sipe, JD Kelley, CA McNicol, LA TI Functional assessment of engineered tissues and elements of tissue design - Breakout session summary SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn C1 Duke Univ, Med Ctr, Durham, NC 27706 USA. Univ Toronto, Toronto, ON, Canada. Brown Univ, Sch Med, Providence, RI 02912 USA. NIH, Bethesda, MD USA. Univ Rochester, Rochester, NY 14627 USA. RP Guilak, F (reprint author), Duke Univ, Med Ctr, Durham, NC 27706 USA. OI Guilak, Farshid/0000-0001-7380-0330 NR 0 TC 6 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 207 EP 209 PG 3 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500047 PM 12081902 ER PT S AU Harlan, DM Karp, CL Matzinger, P Munn, DH Ransohoff, RM Metzger, DW AF Harlan, DM Karp, CL Matzinger, P Munn, DH Ransohoff, RM Metzger, DW BE Sipe, JD Kelley, CA McNicol, LA TI Immunological concerns with bioengineering approaches SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE bioengineered tissue; immune response ID SMALL-INTESTINAL SUBMUCOSA; RENAL-ALLOGRAFT REJECTION; INTRAHEPATIC ISLET ALLOGRAFTS; TOLL-LIKE RECEPTOR-4; LONG-TERM SURVIVAL; TRYPTOPHAN CATABOLISM; IMMUNE-RESPONSE; DENDRITIC CELLS; TRANSPLANTATION TOLERANCE; HUMANIZED ANTI-CD154 C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Childrens Hosp, Res Fdn, Cincinnati, OH USA. NIAID, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Augusta, GA 30912 USA. Cleveland Clin Fdn, Lerner Res Inst, Cleveland, OH USA. Albany Med Coll, Ctr Immunol & Microbial Dis, Albany, NY 12208 USA. RP Harlan, DM (reprint author), NIDDKD, NIH, Bldg 10,room 11S210,10 Ctr Dr, Bethesda, MD 20892 USA. OI Metzger, Dennis/0000-0002-8000-9907 NR 47 TC 9 Z9 9 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 323 EP 330 PG 8 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500075 PM 12081930 ER PT S AU Harlan, DM AF Harlan, DM BE Sipe, JD Kelley, CA McNicol, LA TI Islet cell allotransplantation as a model system for a bioengineering approach to reparative medicine - Immunological concerns SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE islet cell allotransplantation; type 1 diabetes ID DIABETES-MELLITUS; PANCREATIC-ISLETS; TRANSPLANTATION; ALLOGRAFTS C1 NIDDKD, NIH, Bethesda, MD 20892 USA. RP Harlan, DM (reprint author), NIDDKD, NIH, Bldg 10,Room 11S210,10 Ctr Dr, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 331 EP 334 PG 4 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500076 PM 12081931 ER PT S AU Matzinger, P AF Matzinger, P BE Sipe, JD Kelley, CA McNicol, LA TI An innate sense of danger SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn DE self and non-self; immune system ID DENDRITIC CELLS; TOLERANCE C1 NIAID, NIH, Bethesda, MD 20894 USA. RP Matzinger, P (reprint author), NIAID, NIH, Bldg 4,Room 111, Bethesda, MD 20894 USA. NR 5 TC 158 Z9 164 U1 1 U2 13 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 341 EP 342 PG 2 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500079 PM 12081934 ER PT S AU Harlan, DM Metzger, DW Karp, CL Matzinger, P Munn, DH Ransohoff, RM AF Harlan, DM Metzger, DW Karp, CL Matzinger, P Munn, DH Ransohoff, RM BE Sipe, JD Kelley, CA McNicol, LA TI Immune response to engineered tissues and cells - Breakout session summary SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn C1 NIDDK, NIH, Bethesda, MD 20892 USA. Albany Med Coll, Albany, NY 12208 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Med Coll Georgia, Augusta, GA 30912 USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Harlan, DM (reprint author), NIDDK, NIH, Bethesda, MD 20892 USA. OI Metzger, Dennis/0000-0002-8000-9907 NR 0 TC 1 Z9 1 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 350 EP 351 PG 2 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500082 PM 12081937 ER PT S AU Nerem, R Sage, H Kelley, CA McNicol, LA AF Nerem, R Sage, H Kelley, CA McNicol, LA BE Sipe, JD Kelley, CA McNicol, LA TI Symposium summary SO REPARATIVE MEDICINE: GROWING TISSUES AND ORGANS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Reparative Medicine - Growing Tissues and Organs CY JUN 25-26, 2001 CL BETHESDA, MARYLAND SP NIH Bioengn Consortium, Natl Eye Inst, NICHHD, Natl Inst Bioimaging & Biomed Engn C1 Georgia Inst Technol, Atlanta, GA 30332 USA. Hope Heart Inst, Seattle, WA 98104 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Nerem, R (reprint author), Georgia Inst Technol, Atlanta, GA 30332 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-382-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 961 BP 386 EP 389 PG 4 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Engineering; Science & Technology - Other Topics GA BU82Q UT WOS:000177134500089 PM 12081944 ER PT B AU Korach, KS Emmen, JMA Walker, VR Hewitt, SC Yates, MM Hall, JM Swope, DL Harrell, JC Couse, NF AF Korach, KS Emmen, JMA Walker, VR Hewitt, SC Yates, MM Hall, JM Swope, DL Harrell, JC Couse, NF BE Healy, DL Kovacs, GT McLachlan, R RodriguezArmas, O TI Animal models developed for analyzing the biological activity of estrogen receptors SO REPRODUCTIVE MEDICINE IN THE TWENTY-FIRST CENTURY LA English DT Proceedings Paper CT 17th World Congress on Fertility and Sterility CY NOV 25-30, 2001 CL MELBOURNE, AUSTRALIA SP Fertil Soc Australia ID MAMMARY-GLAND DEVELOPMENT; ALPHA-KNOCKOUT MOUSE; BETA ER-BETA; TARGETED DISRUPTION; REPRODUCTIVE PHENOTYPES; TISSUE DISTRIBUTION; SIGNALING PATHWAYS; OVARIAN PHENOTYPE; GROWTH-FACTOR; MICE C1 NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA. NR 37 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP LTD PI LANCASTER PA CASTERTON HALL, CARNFORTH, LANCASTER LA6 2LA, ENGLAND BN 1-84214-036-1 PY 2002 BP 261 EP 268 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA BT91R UT WOS:000174431300025 ER PT J AU Doerge, DR Twaddle, NC Churchwell, MI Chang, HC Newbold, RR Delclos, KB AF Doerge, DR Twaddle, NC Churchwell, MI Chang, HC Newbold, RR Delclos, KB TI Mass spectrometric determination of p-nonylphenol metabolism and disposition following oral administration to Sprague-Dawley rats SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE nonylphenol; mass spectrometry; toxicokinetics; alkylphenol ethoxylates ID TROUT ONCORHYNCHUS-MYKISS; TISSUE DISTRIBUTION; BISPHENOL-A; IN-VITRO; 4-NONYLPHENOL; OCTYLPHENOL; HEPATOCYTES; VIVO; DNA AB Isomers of 4-nonylphenol (NP), which are important industrial compounds and environmental breakdown products from widely used surfactants, have estrogenic activity in vitro and in vivo that has prompted interest in its potential for modulation of endocrine function in humans and wildlife. Mass spectrometry was used to quantify NP and metabolites in serum and endocrine-responsive tissues from dietary exposure in Sprague-Dawley rats. Tissue accumulation of NP aglycone was observed despite the predominance of glucuronidation in blood. Serum toxicokinetics of total NP, measured following gavage administration, showed rapid absorption and elimination (average half-times 0.8 and 3.5 h, respectively). NP was similarly administered by gavage to pregnant dams and total and aglycone NP were measured in clam serum and fetuses to show placental transfer into serum and brain. These data provide a basis for future correlations of biologic effects observed following dietary exposure in rats with those predicted from environmental exposures to humans. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Lab Toxicol,Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 32 TC 35 Z9 38 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 2002 VL 16 IS 1 BP 45 EP 56 AR PII S0890-6238(01)00198-8 DI 10.1016/S0890-6238(01)00198-8 PG 12 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 539UC UT WOS:000174888700007 PM 11934531 ER PT J AU Longart, M Buonanno, A AF Longart, M Buonanno, A TI Neuregulins: A family of factors with critical functions during nervous system development and in the cellular transformation and differentiation SO REVISTA DE NEUROLOGIA LA Spanish DT Review DE cancer; EGF domain; ErbB receptors; glia; herceptin; neuregulin; neuromuscular junction; neuron ID EPIDERMAL GROWTH-FACTOR; DIMINISHES AUTOIMMUNE DEMYELINATION; NICOTINIC ACETYLCHOLINE-RECEPTOR; CEREBELLAR GRANULE CELLS; ETS TRANSCRIPTION FACTOR; SCHWANN-CELLS; TYROSINE KINASE; BREAST-CANCER; EGF RECEPTOR; OLIGODENDROCYTE DEVELOPMENT AB Introduction. The neuregulins are a family of factors that perform important functions during the development of the nervous system, neuromuscular junction and heart. These factors are also involved in nervous system disorders, and in the generation and progression of tumors. Development. There are four genes and many isoforms which share a similar molecular structure. The neuregulins are differentially expressed and bind with different affinities to specific combinations of ErbB receptors. This level of complexity is directing numerous researching in order to understand the molecular mechanisms that regulate a specific pathway. Conclusion. Neuregulin-ErbB receptor complexes activate specific intracellular pathways that culminate in very different fates: differentiation or proliferation. C1 NICHHD, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NR 89 TC 3 Z9 3 U1 0 U2 0 PU REVISTA DE NEUROLOGIA PI BARCELONA PA C/O CESAR VIGUERA, EDITOR, APDO 94121, 08080 BARCELONA, SPAIN SN 0210-0010 J9 REV NEUROLOGIA JI Rev. Neurologia PD JAN 1 PY 2002 VL 34 IS 1 BP 91 EP 97 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 546JH UT WOS:000175270600011 PM 11988896 ER PT J AU Brule, F Marquet, R Rong, L Wainberg, MA Roques, BP Le Grice, SFJ Ehresmann, B Ehresmann, C AF Brule, F Marquet, R Rong, L Wainberg, MA Roques, BP Le Grice, SFJ Ehresmann, B Ehresmann, C TI Structural and functional properties of the HIV-1 RNA-tRN(3)(Lys) primer complex annealed by the nucleocapsid protein: Comparison with the heat-annealed complex SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE HIV-1; nucleocapsid protein; reverse transcription; tRNA annealing ID HUMAN-IMMUNODEFICIENCY-VIRUS; BINDING-SITE COMPLEMENTARY; TYPE-1 REVERSE TRANSCRIPTION; ACID-CHAPERONE ACTIVITY; TRANSFER-RNA; ZINC FINGERS; INITIATION; TRNA(3)(LYS); REPLICATION; ELONGATION AB The conversion of the single-stranded RNA genome into double-stranded DNA by virus-coded reverse transcriptase (RT) is an essential step of the retrovirus life cycle. In human immunodeficiency virus type 1 (HIV-1), RT uses the cellular tRNA(3)(Lys) to initiate the (-) strand DNA synthesis. Placement of the primer tRNA(3)(Lys) involves binding of its 3'-terminal 18 nt to a complementary region of genomic RNA termed PBS. However, the PBS sequence is not the unique determinant of primer usage and additional contacts are important. This placement is believed to be achieved in vivo by the nucleocapsid domain of Gag or by the mature protein NCp. Up to now, structural information essentially arose from heat-annealed primer-template complexes (Isel et al., J Mol Biol, 1995, 247:236-250; Isel et al., EMBO J, 1999, 18:1038-1048). Here, we investigated the formation of the primer-template complex mediated by NCp and compared structural and functional properties of heat- and NCp-annealed complexes. We showed that both heat- and NCp-mediated procedures allow comparable high yields of annealing. Then, we investigated structural features of both kinds of complexes by enzymatic probing, and we compared their relative efficiency in (-) strong stop DNA synthesis. We did not find any significant differences between these complexes, suggesting that information derived from the heat-annealed complex can be transposed to the NCp-mediated complex and most likely to complexes formed in vivo. C1 CNRS, Inst Biol Mol & Cellulaire, UPR 9002, F-67084 Strasbourg, France. McGill Univ, AIDS Ctr, Lady Davis Inst Med Res, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. CNRS, INSERM, Unite Rech & Format Sci Pharmacol & Biol, Unite Pharmacol Mol & Struct, F-75270 Paris, France. NCI, Resistance Mechanism Lab, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Ehresmann, C (reprint author), CNRS, Inst Biol Mol & Cellulaire, UPR 9002, 15 Rue Rene Descartes, F-67084 Strasbourg, France. NR 38 TC 33 Z9 33 U1 2 U2 2 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD JAN PY 2002 VL 8 IS 1 BP 8 EP 15 DI 10.1017/S1355838202010981 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 513KU UT WOS:000173378200002 PM 11873759 ER PT J AU Trawoger, R Kolobow, T Patroniti, N Forcier, K AF Trawoger, R Kolobow, T Patroniti, N Forcier, K TI Intratracheal pulmonary ventilation keeps tracheal tubes clean without impairing mucociliary transport SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article DE low tidal volume ventilation; tracheal gas insufflation; tracheal suctioning ID MUCOUS VELOCITY; ENDOTRACHEAL-TUBES; MUCUS; CLEARANCE; PRESSURE; AIRWAYS; MODEL AB Background. Intratracheal pulmonary ventilation (ITPV) is a form of tracheal gas insufflation through a reverse thrust catheter that facilitates expiration and enhances CO(2) removal. Tracheas of sheep mechanically ventilated for 3 days with gas delivered through the reverse-thrust catheter remained free of secretions, without suctioning. It was hypothesized that: 1) The expiratory flow from the lungs, combined with continuous cephalad flow from the reverse-thrust catheter keeps endotracheal tubes clean; and 2) tracheal mucus velocity is not impaired by ITPV. Methods: A model trachea connected to a test lung and to a ventilator, via an 8-mm endotracheal. tube, was used. Inspiratory and expiratory peak flow velocities and the movement of mucus in the model trachea and in the endotracheal tube were measured during conventional mechanical ventilation and ITPV. Tracheal mucus velocity was measured radiographically, using tantalum discs as markers, in seven intubated sheep ventilated for one hour with volume-controlled ventilation, and with ITPV. One millilitre Evans Blue dye was introduced into the trachea, to visualize mucus transport into the endotracheal tube. Results: Peak expiratory flow velocity exceeded peak inspiratory flow velocity by 100% during ITPV. During volume-controlled ventilation, flow velocities were equal. During ITPV, there was slow, then rapid cephalad movement of mucus in the model trachea, 0.5 cm distal to the tip of the endotracheal tube, the velocity increasing once mucus entered the endotracheal tube. During volume-controlled ventilation, no movement of mucus was found. Baseline tracheal mucus velocity was equal during volume-controlled ventilation and ITPV. Secretions stained with Evans Blue dye entered the endotracheal tube and were rapidly expelled from within the endotracheal tubes during ITPV; only traces of mucus were found in two sheep during volume-controlled ventilation. Conclusion: The enhanced expiratory flow during ITPV expels secretions from the endotracheal tube through entraining of mucus at the tip of the endotracheal tube. Tracheal mucus velocity is not influenced by ITPV. C1 NHLBI, Sect Pulm & Cardiac Assist Devices, PCCMB, NIH, Bethesda, MD 20892 USA. Univ Hosp Pediat, Innsbruck, Austria. RP Trawoger, R (reprint author), Univ Innsbruck, Klin Kinder & Jugendheilkunde, Neonatol Intens Stn, Anichstr 35, A-6020 Innsbruck, Austria. EM Rudolf.Trawoeger@uibk.ac.at RI Patroniti, Nicolo/K-6347-2016 OI Patroniti, Nicolo/0000-0003-3600-193X NR 17 TC 1 Z9 1 U1 1 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5513 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PY 2002 VL 62 IS 5 BP 351 EP 356 DI 10.1080/00365510260296500 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 600AH UT WOS:000178368100004 PM 12387580 ER PT J AU Stuhlman, MW Pianta, RC AF Stuhlman, MW Pianta, RC TI Teachers' narratives about their relationships with children: Associations with behavior in classrooms SO SCHOOL PSYCHOLOGY REVIEW LA English DT Article ID ATTACHMENT; SCHOOL; MODELS; TRANSMISSION; ADJUSTMENT; PERCEPTION; OUTCOMES AB Teachers" narratives concerning their relationships with children were elicited through semistructured interviews and examined in relation to teachers' characteristics and observations of teachers' behavior with children in the classroom. Fifty teachers in kindergarten (N=21) and first grade (N=29) were interviewed about their relationships with a specific child and their classrooms were observed for one-half day. Interviews were coded for seven constructs reflective of different aspects of their relationship with that specific child, including compliance, achievement, secure base, neutralizing of negative emotion, positive affect, and negative affect. Teachers' reports on the interview were significantly related to several aspects of observed child behavior toward them as well as observed teacher behavior toward the child. The feature of teachers' responses to interview questions most frequently associated with classroom behavior was expressed negative emotion. Associations between mentioning compliance and expressing negative affect during the interview and observed behavior remained significant even after controlling for the child's positive affect and self-reliance and teacher experience. Furthermore, among teachers with fewer years of experience, there was no relation between expressed negative emotion in relationship narratives and sensitivity in interactions with children. This was not the case for teachers with more experience. Results are discussed in terms of the importance of understanding salient elements of the relationship between teachers and students. Future directions (including the use of interviews about child-teacher relationships in consultation) are explored. C1 Univ Virginia, NICHD Study Early Child Care & Youth Dev, Charlottesville, VA 22903 USA. Univ Virginia, Curry Sch Educ, Program Clin Psychol, Charlottesville, VA USA. Univ Virginia, Curry Sch Educ, Program Sch Psychol, Charlottesville, VA USA. RP Pianta, RC (reprint author), Univ Virginia, NICHD Study Early Child Care & Youth Dev, POB 800784, Charlottesville, VA 22903 USA. OI Pianta, Robert/0000-0002-6280-8051 NR 36 TC 51 Z9 51 U1 5 U2 26 PU NATL ASSN SCHOOL PSYCHOLOGISTS PI BETHESDA PA 4340 EAST WEST HWY, STE 402, BETHESDA, MD 20814 USA SN 0279-6015 J9 SCHOOL PSYCHOL REV JI Sch. Psychol. Rev. PY 2002 VL 31 IS 2 BP 148 EP 163 PG 16 WC Psychology, Educational SC Psychology GA 572WJ UT WOS:000176797700002 ER PT S AU Yim, PJ Cebral, JR Weaver, A Lutz, R Vasbinder, GBC Choyke, PL AF Yim, PJ Cebral, JR Weaver, A Lutz, R Vasbinder, GBC Choyke, PL GP IEEE IEEE IEEE TI Measurement of pressure drops at arterial stenoses from MR imaging SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE renal artery disease; magnetic resonance imaging; computational fluid dynamics; particle image velocimetry AB Atherosclerotic disease of the renal arteries can reduce blood flow to the kidneys leading to disorders including hypertension and renal insufficiency. Patients who benefit from invasive revascularization procedures have significant pressure drops at the renal artery stenoses. A computational methodology is presented for measuring pressure drops at renal artery stenoses from magnetic resonance (MR) imaging. The methodology is comprised of a computational fluid dynamics (CFD) model of blood flow with realistic vessel shape and flow rates. Realistic vessel shape is derived from contrast-enhanced magnetic resonance angiography (MRA) with a deformable model. Flow rates are measured from phase-contrast MR respectively. The methodology was applied to the case of a patient with 30% stenosis of a renal artery. The finite element solution was obtained with a volumetric mesh of 106 elements. A physical flow-through model was constructed with similar shape, flow rates and fluid viscosity. The peak pressure drop measured by the CFD model was 60% greater than that measured from the physical flow-through model (33.8 mmHg and 21.1 mmHg respectively). The blood velocity vector field was obtained with particle image velocimetry (PIV) and will be used for improvement of the CFD model. C1 NIH, Imaging Sci Program, Bethesda, MD 20892 USA. RP Yim, PJ (reprint author), NIH, Imaging Sci Program, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 1029 EP 1030 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800497 ER PT S AU Hassan, M Hattery, D Chernomordik, V Aleman, K Wyvill, K Merced, F Little, R Yarchoan, R Gandjbakhche, AH AF Hassan, M Hattery, D Chernomordik, V Aleman, K Wyvill, K Merced, F Little, R Yarchoan, R Gandjbakhche, AH GP IEEE IEEE IEEE TI Non-invasive multi-modality technique to study angiogenesis associated with Kaposi's sarcoma SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE sarcoma; AIDS; multi-modality imaging; angiogenesis AB In this on going study, we are investigating the usefulness of thermography and laser Doppler imaging techniques to study vascularity and vascular changes associated with Kaposils sarcoma. Both techniques are useful for observing the lesions associated with Kaposi's sarcoma. A comparative image analysis of thermography, between the lesion and the contralateral, lesion free sites, shows that lesions are a different temperature than the contralateral side. Similar relationships are also observed in laser Doppler images. The present data supports further study of these imaging modalities to assess Kaposi's sarcoma. C1 Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD 20892 USA. RP Hassan, M (reprint author), Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 1139 EP 1140 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800550 ER PT S AU Basser, PJ AF Basser, PJ GP IEEE IEEE IEEE TI Diffusion-tensor MRI: Theory, experimental design, and data analysis SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE diffusion; tensor; MRI; DTI; DT-MRI ID B-MATRIX; SPECTROSCOPY; ECHO AB The MR measurement of the effective diffusion tensor of water, D, in tissues is described. The definition and physical interpretation of quantitative MR parameters derived from D, (e.g., Trace(D) and measures of diffusion anisotropy) are presented. An overview of DT-MRl data acquisition, experimental design, artifacts and post-processing issues is also provided. C1 NICHD, Sect Tissue Biophys & biomimet, NIH, Bethesda, MD USA. RP Basser, PJ (reprint author), NICHD, Sect Tissue Biophys & biomimet, NIH, Bethesda, MD USA. NR 10 TC 3 Z9 3 U1 0 U2 4 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 1165 EP 1166 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800563 ER PT S AU Smith, JC AF Smith, JC GP IEEE IEEE IEEE TI Generation of respiratory rhythm: Models and mechanisms SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE respiration; neurophysiology; pacemaker-network ID PRE-BOTZINGER COMPLEX; NEURAL MECHANISMS; PACEMAKER; NEURONS; GENESIS; PATTERN; MAMMALS AB We have developed a mechanistic computational model of mammalian respiratory rhythm and pattern generation-the hybrid pacemaker-network model-that represents a synthesis of cellular and network mechanisms derived from experimental studies with the mammalian nervous system in vitro and in vivo. This model can theoretically account for rhythm generation in different functional states of the respiratory network, ranging from the most reduced states in neonatal rodent in vitro brainstem slice preparations to the more intact adult system in vivo. In this presentation I will discuss results of simulation studies and experimental data that support this model. C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP Smith, JC (reprint author), NINDS, Neural Control Lab, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 1509 EP 1510 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194800739 ER PT S AU Hattery, D Hassan, M Chernomordik, V Mulshine, J Gandjbakhche, A AF Hattery, D Hassan, M Chernomordik, V Mulshine, J Gandjbakhche, A GP IEEE IEEE IEEE TI Measuring oral inflamination in vivo with diffuse reflectance spectroscopy SO SECOND JOINT EMBS-BMES CONFERENCE 2002, VOLS 1-3, CONFERENCE PROCEEDINGS: BIOENGINEERING - INTEGRATIVE METHODOLOGIES, NEW TECHNOLOGIES SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 24th Annual International Conference of the Engineering-in-Medicine-and-Biology-Society/Annual Fall Meeting of the Biomedical-Engineering-Society (EMBS 2002 BMES) CY OCT 23-26, 2002 CL HOUSTON, TX SP Engn Med & Biol Soc, Biomed Engn Soc, Natl Sci Fdn, Natl Inst Hlth, Natl Inst Biomed Imaging & Bioengn, Whitaker Fdn DE oral; spectroscopy; inflammation; diffuse-reflectance; leukoplakia; chemoprevention ID INFLAMMATION AB Inflammation of the oral epithelium has been shown to provide a promotional environment for evolving cancer cells. This has led to chemoprevention trials exploring the effectiveness of various anti-inflammatory drugs. These trials require quantitative assessment of epithelial inflammation which are traditionally provided by punch biopsy. To reduce patient discomfort and morbidity, we have developed a non-invasive alternative using diffuse reflectance spectroscopy. Though any optical system has the potential for probing near-surface structures, traditional methods of accounting for scattering of photons are generally invalid for typical epithelial thicknesses. We have developed a theory that is valid in this regime and our Monte Carlo simulations and phantom models of a two layered structure have validated our approach. We use a differential measure with accute sensitivity to small changes in layer scattering coefficients. Preliminary results from this work are encouraging and further development is planned to enable quantification of epithelial thickness in vivo. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Hattery, D (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-7612-9 J9 P ANN INT IEEE EMBS PY 2002 BP 2243 EP 2244 DI 10.1109/IEMBS.2002.1053262 PG 2 WC Computer Science, Artificial Intelligence; Engineering, Biomedical; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Instruments & Instrumentation; Radiology, Nuclear Medicine & Medical Imaging GA BV84T UT WOS:000180194801100 ER PT J AU Morf, CC Mischel, W AF Morf, Carolyn C. Mischel, Walter TI Introduction to Special Issue: Self-Concept, Self-Regulation, and Psychological Vulnerability SO SELF AND IDENTITY LA English DT Editorial Material C1 [Morf, Carolyn C.] NIMH, Bethesda, MD 20892 USA. [Mischel, Walter] Columbia Univ, New York, NY USA. RP Morf, CC (reprint author), NIMH, NIH, DNBS, 6001 Execut Blvd,Room 7S7211, Rockville, MD 20852 USA. EM cmorf@mail.nih.gov NR 0 TC 1 Z9 1 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1529-8868 EI 1529-8876 J9 SELF IDENTITY JI Self Identity PY 2002 VL 1 IS 2 BP 103 EP 104 DI 10.1080/152988602317319267 PG 2 WC Psychology, Social SC Psychology GA V40WB UT WOS:000209507600001 ER PT J AU Morf, CC Mischel, W AF Morf, Carolyn C. Mischel, Walter TI Epilogue: Self-Regulation, Vulnerability, and Implications for Mental Health SO SELF AND IDENTITY LA English DT Editorial Material C1 [Morf, Carolyn C.] NIMH, Bethesda, MD 20892 USA. [Mischel, Walter] Columbia Univ, New York, NY USA. RP Morf, CC (reprint author), NIMH, 6001 Execut Blvd,Room 7216,MSC 9651, Bethesda, MD 20892 USA. EM cmorf@mail.nih.gov NR 16 TC 0 Z9 0 U1 0 U2 0 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1529-8868 EI 1529-8876 J9 SELF IDENTITY JI Self Identity PY 2002 VL 1 IS 2 BP 191 EP 199 DI 10.1080/152988602317319384 PG 9 WC Psychology, Social SC Psychology GA V40WB UT WOS:000209507600013 ER PT J AU Barrett, J Childs, R AF Barrett, J Childs, R TI New directions in allogeneic stem cell transplantation SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Natl Heart Lung & Blood Inst, Hematol Branch, Stem Cell Allotransplantat Sect, NIH, Bethesda, MD USA. RP Barrett, J (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2002 VL 39 IS 1 BP 1 EP 2 DI 10.1053/shem.2002.30913 PG 2 WC Hematology SC Hematology GA 512AT UT WOS:000173299500001 PM 11799523 ER PT J AU Schmitz, N Barrett, J AF Schmitz, N Barrett, J TI Optimizing engraftment - Source and dose of stem cells SO SEMINARS IN HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; VERSUS-HOST DISEASE; BONE-MARROW TRANSPLANTATION; MOBILIZED PERIPHERAL-BLOOD; UMBILICAL-CORD BLOOD; HLA-IDENTICAL SIBLINGS; PROGENITOR-CELL; ALLOGENEIC BLOOD; UNRELATED DONORS; HEMATOLOGIC MALIGNANCIES C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Natl Heart Lung & Blood Inst, Hematol Branch, Stem Cell Transplant Unit, NIH, Bethesda, MD USA. RP Barrett, J (reprint author), NHLBI, Hematol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 87 TC 46 Z9 51 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2002 VL 39 IS 1 BP 3 EP 14 DI 10.1053/shem.2002.29245 PG 12 WC Hematology SC Hematology GA 512AT UT WOS:000173299500002 PM 11799524 ER PT J AU Childs, R Barrat, J AF Childs, R Barrat, J TI Nonmyeloablative stem cell transplantation for solid tumors: Expanding the application of allogeneic immunotherapy SO SEMINARS IN HEMATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; MINOR HISTOCOMPATIBILITY ANTIGENS; RESTRICTED TISSUE DISTRIBUTION; RELAPSED MULTIPLE-MYELOMA; HOST DISEASE; T-CELLS; MYELOABLATIVE THERAPY; CANCER-IMMUNOTHERAPY; BREAST-CANCER C1 NHLBI, Hematol Branch, Stem Transplant Unit, NIH, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Hematol Branch, Stem Transplant Unit, NIH, Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 58 TC 23 Z9 27 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 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2002 VL 39 IS 1 BP 63 EP 71 DI 10.1053/shem.2002.29257 PG 9 WC Hematology SC Hematology GA 512AT UT WOS:000173299500009 PM 11799531 ER PT S AU Burke, RE AF Burke, RE BE Gandevia, SC Proske, U Stuart, DG TI Some unresolved issues in motor unit research SO SENSORIMOTOR CONTROL OF MOVEMENT AND POSTURE SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT Conference on Neural Mechanisms of Sensorimotor Control CY SEP 03-06, 2001 CL CAIRNS, AUSTRALIA SP Prince Wales Med Res Inst, Sydney Univ, Monash Univ ID DEEP LUMBRICAL MUSCLE; MEDIAL GASTROCNEMIUS; FICTIVE LOCOMOTION; DECEREBRATE CAT; LENGTHENING CONTRACTIONS; SELECTIVE RECRUITMENT; ORDERLY RECRUITMENT; SYNAPTIC INPUT; MOTONEURONS; PATHWAYS AB The intrinsic properties of motoneurones, muscle units, and synaptic inputs exhibit correlated variations that subserve a wide range of functional demands. In large limb muscles, these correlations suggest distinct "types" of motor units, while in smaller, distal muscles their distributions are more continuous. The CNS mechanisms that control recruitment patterns are still unclear, particularly the organization of spinal interneurone circuits. We need new approaches to identify segmental interneurones by their inputs and output targets. However, functional circuitry is changeable, depending on the "state" of the system. Shifting alliances of interneurone groups can in principle produce virtually unlimited permutations of motor unit coactivation and suppression. Although such state-dependence plasticity is a challenge, it can also be a useful tool in unraveling interneurone organization. C1 NINDS, Neural Control Lab, NIH, Bethesda, MD 20092 USA. RP Burke, RE (reprint author), NINDS, Neural Control Lab, NIH, Bethesda, MD 20092 USA. NR 64 TC 7 Z9 7 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47285-6 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2002 VL 508 BP 171 EP 178 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BV02X UT WOS:000177650600020 PM 12171107 ER PT J AU Clark, KL Howell, MR Li, YZ Powers, T McKee, KT Quinn, TC Gaydos, JC Gaydos, CA AF Clark, KL Howell, MR Li, YZ Powers, T McKee, KT Quinn, TC Gaydos, JC Gaydos, CA TI Hospitalization rates in female US Army recruits associated with a screening program for Chlamydia trachomatis SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; PELVIC INFLAMMATORY DISEASE; PUBLIC-HEALTH; INFECTIONS; PREVENTION; MILITARY AB Background: A volunteer program to test non-healthcare-seeking women for genital Chlamydia trachomatis infection was instituted at the US Army's largest basic training center and evaluated for its effectiveness in reducing sequelae. Goal: To compare hospitalization rates between women with positive test results for C trachomatis and those with negative results, and between women tested and those not tested for C trachomatis. Study Design: For this study, 28,074 women who entered the Army in 1996 and 1997 were followed for hospitalizations through December 1998. Of these women, 7053 were tested for C trachomatis, and 21,021 were not screened. Hospital admissions were calculated per person-year, and adjusted relative risks were determined. Results: The overall prevalence of C trachomatis in the screened group was 9.1%. The relative risk of hospitalization for pelvic inflammatory disease in the screened cohort was 0.94 (95% Cl, 0.69-1.29), as compared with those not screened. The relative risk of hospitalization for any reason was 0.94 (95% Cl, 0.90-0.99). Among women screened, no difference was found in pelvic inflammatory disease hospitalizations between women with positive test results who were being treated for C trachomatis and those with negative test results. Conclusions: The investigated C trachomatis intervention program for female Army recruits was associated with a lower overall hospitalization rate in screened volunteers, as compared with unscreened women. The pelvic inflammatory disease hospitalization rate in women with C trachomatis who were screened and treated was similar to that observed in uninfected women. C1 Johns Hopkins Univ, Div Infect Dis, Baltimore, MD 21205 USA. Allied Technol Grp, Rockville, MD USA. Womack Army Med Ctr, Ft Bragg, NC USA. NIAID, NIH, Bethesda, MD 20892 USA. Dept Def Global Emerging Infect Surveillance & Re, Silver Spring, MD USA. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Div Infect Dis, Ross Res Bldg,Room 1159,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 14 TC 23 Z9 24 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JAN PY 2002 VL 29 IS 1 BP 1 EP 5 DI 10.1097/00007435-200201000-00001 PG 5 WC Infectious Diseases SC Infectious Diseases GA 511VT UT WOS:000173286800001 PM 11773871 ER PT J AU Lieberthal, W Fuhro, R Alam, H Rhee, P Szebeni, J Hechtman, HB Favuzza, J Veech, RL Valeri, CR AF Lieberthal, W Fuhro, R Alam, H Rhee, P Szebeni, J Hechtman, HB Favuzza, J Veech, RL Valeri, CR TI Comparison of the effects of a 50% exchange-transfusion with albumin, hetastarch, and modified hemoglobin solutions SO SHOCK LA English DT Article DE colloid; hypotension; vascular resistance; hematocrit; resuscitation ID CRITICALLY ILL PATIENTS; COMPLEMENT ACTIVATION; FLUID RESUSCITATION; VOLUME EXPANDERS; OXYGEN CARRIER; NITRIC-OXIDE; EFFICACY; RAT; CRYSTALLOIDS; HEMODILUTION AB We compared the hemodynamic effects of replacing 50% of the blood volume of anesthetized rats with an equal volume of five solutions: human serum albumin (HSA), hetastarch, unmodified hemoglobin, diaspirin-crosslinked hemoglobin, and o-raffinose-crosslinked hemgolobin. Control rats were exchange-transfused with their own blood. HSA and hetastarch caused a severe reduction in systemic vascular resistance (SVR), hypotension, and acute renal failure immediately after the exchange-transfusion. Unmodified and diaspirin-crosslinked hemoglobins caused comparable and severe increases in SVR, whereas vasoconstriction induced by o-raffinose-crosslinked hemoglobin was minimal. The increased SVR induced by all hemoglobin solutions resolved over a 2-day period as the hemoglobin was cleared from plasma. Body weight was monitored for 5 days after the exchange transfusion as a measure of the relative long-term efficacy of the exchange solutions tested and increased substantially in control rats (that received blood). Rats that received both crosslinked hemoglobin solutions gained a comparable amount of weight as the control group. By contrast rats that received HSA, hetastarch and unmodified hemoglobin failed to gain weight or lost weight over the same period. In summary: i) HSA and hetastarch are relatively ineffective as resuscitative fluids when administered after the loss of a large volume of blood; ii) diaspirin-crosslinked hemoglobin causes severe vasoconstriction, comparable in intensity to that induced by unmodified hemoglobin; iii) o-raffinose-crosslinked hemoglobin induces minimal vasoconstriction; iv) the vasoactive effects of all hemoglobin solutions are reversible. We conclude, that of all solutions tested, both the short- and long-term effects of an exchange-transfusion with whole blood are most closely reproduced by an exchange with o-raffinose-crosslinked hemoglobin. C1 Boston Univ, Med Ctr, Evans Dept Clin Res, Div Renal, Boston, MA USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Inst Res, Dept Membrane Biochem, Silver Spring, MD USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Membrane Biochem, Boston, MA 02115 USA. NIAAA, Unit Metab Control, LMBB, Rockville, MD 20852 USA. Boston Univ, Med Ctr, Naval Blood Res Lab, Boston, MA USA. RP Lieberthal, W (reprint author), Evans Biomed Res Ctr, Renal Sect, 5th Floor,Room 537,650 Albany St, Boston, MA 02118 USA. FU NHLBI NIH HHS [HL53031]; NIDDK NIH HHS [DK52898, DK375105] NR 39 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD JAN PY 2002 VL 17 IS 1 BP 61 EP 69 DI 10.1097/00024382-200201000-00011 PG 9 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 507ZF UT WOS:000173061000011 PM 11795671 ER PT B AU Skopec, M Price, JL Guardala, N Loew, M Moscovitch, M AF Skopec, M Price, JL Guardala, N Loew, M Moscovitch, M BE Horowitz, YS Oster, L TI Glow curve analysis applied to the discrimination of X ray versus proton irradiation SO SOLID STATE DOSIMETRY, PTS 1 AND 2, PROCEEDINGS LA English DT Proceedings Paper CT 13th International Conference on Solid State Dosimetry CY JUL 09-13, 2001 CL ATHENS, GREECE SP Ben Gurion Univ Negev, Bicron Radiat Measurements Products, Bubble Technol, Int Soild State Dosimetry Org, Landauer, Natl Aeronaut & Space Adm, Natl Space Biomed Res Inst, Nucl Technol Publishing AB Three types of thermoluminescence dosemeters (TLDs): LiF:Mg,Ti (TLD-100), CaF2:Tm (TLD-300), and alpha- Al2O3:C (TLD-500), were investigated for their glow curve response to separate X ray and proton irradiations. The glow curve structure for each individual TLD's exposure to the X ray and proton irradiations was analysed and compared. Distinguishable differences between the glow Curve structure characteristic of each type of radiation were observed. The proton TLD-100 glow curve has revealed a complex high-temperature peak structure that was used for the proton/X ray discrimination algorithm. Proton irradiation of TLD-300 resulted in an apparent switch in the relative heights of peaks 3 and 5 as compared to X ray. In TLD-500, proton irradiation produced a more subtle difference in the glow curve with an increase in the ratio between high- and low-temperature peaks. Results demonstrate promising differences in glow curve structure present allowing for discrimination between X ray and proton radiation field exposures. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. RP Skopec, M (reprint author), NIH, Dept Diagnost Radiol, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU RAMTRANS PUBLISHING PI ASHFORD PA PO BOX NO 7, ASHFORD TN23 1YW, KENT, ENGLAND BN 1-870965-73-6 PY 2002 BP A99 EP A102 PG 4 WC Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Instruments & Instrumentation; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA BV69W UT WOS:000179805700135 ER PT J AU Wu, CWH Kaas, JH AF Wu, CWH Kaas, JH TI The effects of long-standing limb loss on anatomical reorganization of the somatosensory afferents in the brainstem and spinal cord SO SOMATOSENSORY AND MOTOR RESEARCH LA English DT Article DE amputation; phantom limb; sprouting; primates ID EXTERNAL CUNEATE NUCLEUS; ADULT MACAQUE MONKEYS; PRIMARY MOTOR CORTEX; MASSIVE CORTICAL REORGANIZATION; TRANSGANGLIONIC TRANSPORT; SUBCORTICAL CONTRIBUTIONS; HORSERADISH-PEROXIDASE; FORELIMB DENERVATION; STEM CONTRIBUTIONS; MUSCLE AFFERENTS AB We examined the terminations of sensory afferents in the brainstem and spinal cord of squirrel monkeys and prosimian galagos 4-8 years after a therapeutic forelimb or hindlimb amputation within 2 months of birth. In each animal, the distributions of labeled sensory afferent terminations from remaining body parts proximal to the limb stump were much more extensive than in normal animals. These sprouted afferents extended into the portions of the dorsal horn of the spinal cord as well as the cuneate and external cuneate nuclei of the brainstem (forelimb amputees) or spinal Clarke's column (hindlimb amputee) related to the amputated limb. Such reorganization in sensory afferents along with reorganization of the motor efferents to muscles (Wu and Kaas, J Neurosci 19: 7679-7697, 1999, Neuron 28: 967-978, 2000) may provide a basis for mislocated phantom sensations of missing forelimb movements accompanying actual shoulder movements during cortical stimulation or movement imagery in patients with amputations. C1 Vanderbilt Univ, Dept Psychol, Nashville, TN 37240 USA. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Kaas, JH (reprint author), Vanderbilt Univ, Dept Psychol, 301 Wilson Hall, Nashville, TN 37240 USA. FU NINDS NIH HHS [NS 16446] NR 48 TC 26 Z9 26 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0899-0220 J9 SOMATOSENS MOT RES JI Somatosens. Mot. Res. PY 2002 VL 19 IS 2 BP 153 EP 163 DI 10.1080/0899022020133261 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 566QJ UT WOS:000176439500008 PM 12088390 ER PT J AU Neelapu, S Figg, WD Dahut, W Reed, E AF Neelapu, S Figg, WD Dahut, W Reed, E TI Leptomeningeal carcinomatosis in metastatic prostate cancer SO SOUTHERN MEDICAL JOURNAL LA English DT Letter C1 NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Neelapu, S (reprint author), NCI, Div Clin Sci, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 5 TC 2 Z9 2 U1 0 U2 0 PU SOUTHERN MEDICAL ASSN PI BIRMINGHAM PA 35 LAKESHORE DR PO BOX 190088, BIRMINGHAM, AL 35219 USA SN 0038-4348 J9 SOUTHERN MED J JI South.Med.J. PD JAN PY 2002 VL 95 IS 1 BP 107 EP 108 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 517EX UT WOS:000173599100020 PM 11827241 ER PT J AU Hsu, E Hung, C desJardins, R Foster, M Gilstrap, R Chao, L Gill, M Tatsumi, H Edelson, B Helm, N MacRae, A Kadowaki, N Yoshimura, N Takahashi, T Gary, P Lang, P Kranacs, K Shopbell, P Walker, G Wellnitz, D Gargione, F AF Hsu, E Hung, C desJardins, R Foster, M Gilstrap, R Chao, L Gill, M Tatsumi, H Edelson, B Helm, N MacRae, A Kadowaki, N Yoshimura, N Takahashi, T Gary, P Lang, P Kranacs, K Shopbell, P Walker, G Wellnitz, D Gargione, F TI Trans-Pacific HDR satellite communications experiment, Phase-2 results summary SO SPACE COMMUNICATIONS LA English DT Article; Proceedings Paper CT 7th Ka Band Utilization Conference CY SEP 26-28, 2001 CL GENOA, ITALY AB In 1993, a proposal at the Japan-US Science, Technology, and Space Applications Program (JUSTSAP) workshop led to a subsequent series of satellite communications experiments and demonstrations, under the title of Trans-Pacific High Data Rate Satellite Communications Experiments. The first phase of which was a joint collaboration between government and industry teams in the United States and Japan that successfully demonstrated distributed high definition video (HDV) post-production on a global scale using a combination of high data rate satellites and terrestrial fiber optic asynchronous transfer mode (ATM) networks. This was followed by the Phase-2 Internet Protocol (IP) based experiments and demonstrations [4-6] in tele-medicine and distance education, using another combination of two high data rate satellites and terrestrial fiber optic networks. The Visible Human tele-medicine and Remote Astronomy distance education demonstrations and their use of distributed systems technologies afforded an opportunity for people around the world to work together as a virtual team under one roof, using resources thousands of miles away as if they were next to each other. The visible human activity demonstrated global-scale interactive biomedical image segmentation, labeling, classification, and indexing using large images; the remote astronomy activity demonstrated collaborative observation and distance education at multiple locations around the globe and the transparent operations of distributed systems technologies over a combination of broadband satellites and terrestrial networks. The use of Internet Protocol related technologies allowed the general public to be an integral part of the exciting activities, helped to examine issues in constructing a global information infrastructure with broadband satellites, and afforded an opportunity to tap the research results from the (reliable) multicast and distributed systems communities. This paper summarizes the Phase-2 of Trans-Pacific series of experiments and demonstrations by an international team in Canada, Japan, and the United States. C1 CALTECH, Jet Prop Lab, Pasadena, CA 91109 USA. NASA, NASA Res & Educ Network, Incline Village, NV USA. Natl Lib Med, Bethesda, MD USA. Sapporo Med Univ, Sapporo, Hokkaido, Japan. George Washington Univ, Inst Appl Space Res, Washington, DC USA. Independent Adm Inst, Commun Res Lab, Tokyo, Japan. NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA. Univ Maryland, Baltimore, MD 21201 USA. Satellite Syst Consultant, Lawrenceville, NJ USA. RP Hsu, E (reprint author), CALTECH, Jet Prop Lab, 4800 Oak Grove Dr,Ms 300-123, Pasadena, CA 91109 USA. NR 10 TC 0 Z9 0 U1 1 U2 1 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0924-8625 J9 SPACE COMMUN JI Space Commun. PY 2002 VL 18 IS 1-2 SI SI BP 23 EP 30 PG 8 WC Engineering, Aerospace; Telecommunications SC Engineering; Telecommunications GA 618WF UT WOS:000179439700005 ER PT S AU Costes, S Barcellos-Hoff, MH AF Costes, S Barcellos-Hoff, MH BE Ijiri, K Slenzka, K Kronenberg, A TI Radiation quality and tissue-specific microenvironments following exposure to 1 GeV/amu Fe SO SPACE LIFE SCIENCES: BIOLOGICAL RESEARCH AND SPACE RADIATION SE ADVANCES IN SPACE RESEARCH LA English DT Article; Proceedings Paper CT F1 2/F1 3/F1 3/F2 2 and F2 6 Symposia of COSPAR Scientific Commission F, held at the 33rd COSPAR Scientific Assembly CY JUL, 2000 CL WARSAW, POLAND SP Comm Space Res, NASA ID TRACK STRUCTURE; MAMMARY-GLAND; LAMININ; EXPRESSION; BIOLOGY; MODELS; CELLS AB This paper summarizes quantitative in vivo laminin immunofluorescence analysis of mammary glands and skin epithelial structures from mice exposed to 1 GeV/amu Fe ions. Digital confocal microscopic images were quantified and linked to the rough "core-penumbra" Fe track physical description. Comparison to gamma-ray sparsely ionizing radiation suggested the core of the Fe track being responsible for a biological response only seen with energetic Fe particles. Conclusions for modeling in vivo responses to radiation were then implied. (C) 2002 COSPAR. Published by Elsevier Science Ltd. All rights reserved. C1 Natl Canc Inst, Frederick, MD 21702 USA. Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. RP Costes, S (reprint author), Natl Canc Inst, Ft Detrick,Bldg 538, Frederick, MD 21702 USA. RI Costes, Sylvain/D-2522-2013 OI Costes, Sylvain/0000-0002-8542-2389 NR 23 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0273-1177 J9 ADV SPACE RES PY 2002 VL 30 IS 4 BP 865 EP 870 AR PII S0273-1177(02)00410-6 DI 10.1016/S0273-1177(02)00410-6 PG 6 WC Engineering, Aerospace; Astronomy & Astrophysics; Geosciences, Multidisciplinary; Meteorology & Atmospheric Sciences SC Engineering; Astronomy & Astrophysics; Geology; Meteorology & Atmospheric Sciences GA BV67M UT WOS:000179730600024 PM 12530433 ER PT J AU Kerr, MK Afshari, CA Bennett, L Bushel, P Martinez, J Walker, NJ Churchill, GA AF Kerr, MK Afshari, CA Bennett, L Bushel, P Martinez, J Walker, NJ Churchill, GA TI Statistical analysis of a gene expression microarray experiment with replication SO STATISTICA SINICA LA English DT Article DE analysis of variance; bootstrap; cDNA microarray; gene expression; orthogonal design ID CELLS AB Common ratio-based approaches for analyzing gene expression microarray data do not provide a framework for handling replication, although replication is clearly desirable for these noisy data. In contrast, replication fits naturally into analysis of variance (ANOVA) methods. We use ANOVA to analyze data from a microarray experiment to compare gene expression in drug-treated and control cells lines. We discuss issues that commonly arise in the analysis of microarray data, and present practical solutions to some common problems. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NIEHS, Microarray Ctr, Res Triangle Pk, NC 27709 USA. NIEHS, Microarray Ctr, ITSS Contract, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Kerr, MK (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. RI Walker, Nigel/D-6583-2012; Kerr, Kathleen/A-2893-2013 OI Walker, Nigel/0000-0002-9111-6855; NR 12 TC 111 Z9 115 U1 0 U2 9 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JAN PY 2002 VL 12 IS 1 BP 203 EP 217 PG 15 WC Statistics & Probability SC Mathematics GA 530RM UT WOS:000174372800011 ER PT J AU Chen, GX Jaradat, SA Banerjee, N Tanaka, TS Ko, MSH Zhang, MQ AF Chen, GX Jaradat, SA Banerjee, N Tanaka, TS Ko, MSH Zhang, MQ TI Evaluation and comparison of clustering algorithms in analyzing es cell gene expression data SO STATISTICA SINICA LA English DT Article DE cluster analysis; gene expression; microarray; mouse embryonic stem cell ID TRANSCRIPTION FACTOR; PATTERNS; PROTEIN; DISPLAY; EMBRYO; OCT-4 AB Many clustering algorithms have been used to analyze microarray gene expression data. Given embryonic stein cell gene expression data, we applied several indices to evaluate the performance of clustering algorithms, including hierarchical clustering, k-means, PAM and SOM. The indices were homogeneity and separation scores, silhouette width, redundant score (based on redundant genes), and WADI? (testing the robustness of clustering results after small perturbation). The results showed that the ES cell dataset posed a challenge for cluster analysis in that the clusters generated by different methods were only partially consistent. Using this data set, we were able to evaluate the advantages and weaknesses of algorithms with respect to both internal and external quality measures. This study may provide a guideline on how to select suitable clustering algorithms and it may help raise issues in the extraction of meaningful biological information from microarray expression data. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Chen, GX (reprint author), Cold Spring Harbor Lab, 1 Bungtown Rood Hershey Bldg, Cold Spring Harbor, NY 11724 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 22 TC 68 Z9 76 U1 1 U2 6 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JAN PY 2002 VL 12 IS 1 BP 241 EP 262 PG 22 WC Statistics & Probability SC Mathematics GA 530RM UT WOS:000174372800013 ER PT J AU Kadereit, S Deeds, LS Haynesworth, SE Koc, ON Kozik, MM Szekely, E Daum-Woods, K Goetchius, GW Fu, PF Welniak, LA Murphy, WJ Laughlin, MJ AF Kadereit, S Deeds, LS Haynesworth, SE Koc, ON Kozik, MM Szekely, E Daum-Woods, K Goetchius, GW Fu, PF Welniak, LA Murphy, WJ Laughlin, MJ TI Expansion of LTC-ICs and maintenance of p21 and BCL-2 expression in cord blood CD34(+)/CD38(-) early progenitors cultured over human MSCs as a feeder layer SO STEM CELLS LA English DT Article DE UCB; expansion; hematopoietic progenitors; mesenchymal stem cells ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW STROMA; IN-VITRO; UNRELATED DONORS; PLACENTAL-BLOOD; VIVO; TRANSPLANTATION; RECIPIENTS; MICE; DIFFERENTIATION AB Allogeneic transplantation with umbilical cord blood (UCB) is limited in adult recipients by a low CD34(+) cell dose. Clinical trials incorporating cytokine-based UCB in vitro expansion have not demonstrated significant shortening of hematologic recovery despite substantial increases in CD34(+) cell dose, suggesting loss of stem cell function. To sustain stem cell function during cytokine-based in vitro expansion, a feeder layer of human mesenchymal stem cells (MSCs) was incorporated in an attempt to mimic the stem cell niche in the marrow microenvironment. UCB expansion on MSCs resulted in a 7.7-fold increase in total LTC-IC output and a 3.8-fold increase of total early CD34(+) progenitors (CD38(-)/HLA-DR-). Importantly, early CD34(+)/CD38(-)/HLA-DR- progenitors from cultures expanded on MSCs demonstrated higher cytoplasmic expression of the cell-cycle inhibitor, p21(cip1/waf1), and the antiapoptotic protein, BCL-2, compared with UCB expanded in cytokines alone, suggesting improved maintenance of stem cell function in the presence of MSCs. Moreover, the presence of MSCs did not elicit UCB lymphocyte activation. Taken together, these results strongly suggest that the addition of MSCs as a feeder layer provides improved conditions for expansion of early UCB CD34(+)/CD38(-)/HLA-DR- hematopoietic progenitors and may serve to inhibit their differentiation and rates of apoptosis during short-term in vitro expansion. C1 Case Western Reserve Univ, Univ Hosp Cleveland, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Biol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Univ Hosp Cleveland, NCI Comprehens Canc Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. NCI, SAIC, Frederick, MD 21701 USA. RP Laughlin, MJ (reprint author), Case Western Reserve Univ, Allogene Transplant Program, Univ Hosp Ireland Comprehens Canc Ctr, 11100 Euclid Ave, Cleveland, OH 44106 USA. NR 37 TC 86 Z9 102 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2002 VL 20 IS 6 BP 573 EP 582 DI 10.1634/stemcells.20-6-573 PG 10 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 626PU UT WOS:000179882400012 PM 12456965 ER PT B AU Pacak, K Tjurmina, O Palkovits, M Goldstein, DS Koch, CA Hoff, T Goldsmith, P Chrousos, GP AF Pacak, K Tjurmina, O Palkovits, M Goldstein, DS Koch, CA Hoff, T Goldsmith, P Chrousos, GP BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Chronic hypercortisolemia inhibits dopaminergic activity in the nucleus accumbens SO STRESS: NEURAL, ENDOCRINE AND MOLECULAR STUDIES LA English DT Proceedings Paper CT 7th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 28-JUL 03, 1999 CL SMOLENICE CASTLE, SLOVAKIA SP NICHHD, Catecholamine Fdn, Slovak Acad Sci, Nippon Zoki Pharmaceut Co Ltd, Wellcome Trust, Wakunaga Pharmaceut Co Ltd, Hoechst Marion Roussel AG, Ajinomoto Co Inc, Bristol Myers Squibb Pharmaceut Res Inst, Novartis Pharma Serv, Immunotech sro, Amersham Pharmacia Biotech, MGP sro, Clinalfa AG, Baxter Export Corp ID PARAVENTRICULAR NUCLEUS; CUSHINGS-SYNDROME; CONSCIOUS RATS; DEPRESSION; STRESS; RELEASE; SYSTEM; GLUCOCORTICOIDS; PSYCHOPATHOLOGY; CORTICOSTERONE C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RI Palkovits, Miklos/F-2707-2013 NR 32 TC 0 Z9 0 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 0-415-27220-3 PY 2002 BP 33 EP 36 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BU84W UT WOS:000177182800005 ER PT B AU Aguilera, G Lightman, SL Ma, XM AF Aguilera, G Lightman, SL Ma, XM BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Transcriptional and post-transcriptional regulation of corticotropin releasing hormone and vasopressin expression by stress and glucocorticoids SO STRESS: NEURAL, ENDOCRINE AND MOLECULAR STUDIES LA English DT Proceedings Paper CT 7th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 28-JUL 03, 1999 CL SMOLENICE CASTLE, SLOVAKIA SP NICHHD, Catecholamine Fdn, Slovak Acad Sci, Nippon Zoki Pharmaceut Co Ltd, Wellcome Trust, Wakunaga Pharmaceut Co Ltd, Hoechst Marion Roussel AG, Ajinomoto Co Inc, Bristol Myers Squibb Pharmaceut Res Inst, Novartis Pharma Serv, Immunotech sro, Amersham Pharmacia Biotech, MGP sro, Clinalfa AG, Baxter Export Corp ID MESSENGER-RIBONUCLEIC-ACID; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; PARVOCELLULAR NEUROSECRETORY NEURONS; HYPERTONIC SALINE INJECTION; ARGININE-VASOPRESSIN; IMMOBILIZATION STRESS; HETERONUCLEAR RNA; DIFFERENTIAL REGULATION; RECEPTOR REGULATION; REPEATED RESTRAINT C1 NICHHD, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA. NR 51 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 0-415-27220-3 PY 2002 BP 91 EP 97 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BU84W UT WOS:000177182800017 ER PT B AU Rabadan-Diehl, C Aguilera, G AF Rabadan-Diehl, C Aguilera, G BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Pituitary CRH and VP receptors and their role in corticotroph responsiveness during stress SO STRESS: NEURAL, ENDOCRINE AND MOLECULAR STUDIES LA English DT Proceedings Paper CT 7th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 28-JUL 03, 1999 CL SMOLENICE CASTLE, SLOVAKIA SP NICHHD, Catecholamine Fdn, Slovak Acad Sci, Nippon Zoki Pharmaceut Co Ltd, Wellcome Trust, Wakunaga Pharmaceut Co Ltd, Hoechst Marion Roussel AG, Ajinomoto Co Inc, Bristol Myers Squibb Pharmaceut Res Inst, Novartis Pharma Serv, Immunotech sro, Amersham Pharmacia Biotech, MGP sro, Clinalfa AG, Baxter Export Corp ID MESSENGER-RIBONUCLEIC-ACID; HORMONE-RECEPTOR; ADRENOCORTICOTROPIN SECRETION; VASOPRESSIN RECEPTORS; RAT PITUITARY; GLUCOCORTICOIDS; EXPRESSION; RESPONSES; ADRENALECTOMY; BRAIN C1 NICHHD, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA. RP Rabadan-Diehl, C (reprint author), NICHHD, Sect Endocrine Physiol, NIH, Bethesda, MD 20892 USA. NR 22 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 0-415-27220-3 PY 2002 BP 227 EP 231 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BU84W UT WOS:000177182800037 ER PT B AU Goldstein, DS Elman, I Frank, SM Lenders, JWM AF Goldstein, DS Elman, I Frank, SM Lenders, JWM BE McCarty, R Aguilera, G Sabban, EL Kvetnansky, R TI Stressor-specific activation of catecholaminergic systems: Clinical demonstrations SO STRESS: NEURAL, ENDOCRINE AND MOLECULAR STUDIES LA English DT Proceedings Paper CT 7th Symposium on Catecholamines and Other Neurotransmitters in Stress CY JUN 28-JUL 03, 1999 CL SMOLENICE CASTLE, SLOVAKIA SP NICHHD, Catecholamine Fdn, Slovak Acad Sci, Nippon Zoki Pharmaceut Co Ltd, Wellcome Trust, Wakunaga Pharmaceut Co Ltd, Hoechst Marion Roussel AG, Ajinomoto Co Inc, Bristol Myers Squibb Pharmaceut Res Inst, Novartis Pharma Serv, Immunotech sro, Amersham Pharmacia Biotech, MGP sro, Clinalfa AG, Baxter Export Corp C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 8 TC 1 Z9 1 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND BN 0-415-27220-3 PY 2002 BP 249 EP 253 PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA BU84W UT WOS:000177182800041 ER PT J AU Goldstein, DS McEwen, B AF Goldstein, David S. McEwen, Bruce TI Allostasis, Homeostats, and the Nature of Stress SO STRESS-THE INTERNATIONAL JOURNAL ON THE BIOLOGY OF STRESS LA English DT Article DE Stress; Distress; Allostasis; Homeostasis; Homeostat AB This essay continues discussion of a new formulation of homeostasis that uses the concepts of allostasis and homeostats. The new formulation moves beyond Cannon's concept of "homeostasis," which posits an ideal set of conditions for maintenance of the internal environment. The notion of allostasis recognizes that there is no single ideal set of steady-state conditions in life, and different stressors elicit different patterns of activation of the sympathetic nervous and adrenomedullary hormonal systems. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators-"homeostats." "Allostatic load" refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of a home temperature control system, the temperature can be maintained at any of a variety of levels (allostatic states) by multiple means (effectors), regulated by the thermostat (homeostat). Allostatic load and risks of system breakdown increase when, for example, the front door is left open in the winter. Applying these notions can aid in understanding how acute and chronic stress can exert adverse health consequences via allostatic load. C1 [Goldstein, David S.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. [McEwen, Bruce] Rockefeller Univ, New York, NY 10021 USA. RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10-6N252,10 Ctr Dr,MSC 1620, Bethesda, MD 20892 USA. EM goldsteind@ninds.nih.gov NR 18 TC 14 Z9 14 U1 1 U2 9 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1025-3890 J9 STRESS JI Stress PY 2002 VL 5 IS 1 BP 54 EP 57 DI 10.1080/10253890290012345 PG 4 WC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences SC Behavioral Sciences; Endocrinology & Metabolism; Neurosciences & Neurology GA V19RT UT WOS:000208090200007 ER PT J AU Havlik, RJ Foley, DJ Sayer, B Masaki, K White, L Launer, LJ AF Havlik, RJ Foley, DJ Sayer, B Masaki, K White, L Launer, LJ TI Variability in midlife systolic blood pressure is related to late-life brain white matter lesions - The Honolulu-Asia Aging Study SO STROKE LA English DT Article DE blood pressure; epidemiology; magnetic resonance imaging; risk factors; white matter ID CARDIOVASCULAR RISK-FACTORS; CORONARY HEART-DISEASE; JAPANESE-AMERICAN MEN; AGE; ATHEROSCLEROSIS; LEUKOARAIOSIS; HYPERTENSION; ASSOCIATION; MORTALITY; HAWAII AB Background and Purpose-Although white matter lesions (WMLs) on brain MRI in older persons are common, the mechanisms are unclear. Besides the associations with advanced age and high blood pressure (BP), variability in systolic BP (SBP) and the resulting changes in blood flow to the deep arteries of the brain may be contributing factors. Methods-Japanese-American men in Hawaii have participated in a long-term study of cardiovascular disease, including midlife BP measurements at 3 clinical examinations in the period from 1965 to 1974. In the period from 1991 to 1993, dementia status was added to the fourth examination, and a brain MRI was completed in a fifth examination, which was from 1994 to 1996, on a subset of 575 men, who averaged 82 years. WMLs and ventricular atrophy were determined as the upper fifth in a standardized semiquantitative measure. Excess SBP variability was defined as greater than average increases in BP measurements from up to 3 examinations over 6 years. Logistic regression was used for the association of this variability with WMLs and atrophy, controlling for age, apolipoprotein E4 status, dementia diagnosis, and history of stroke. Results-There were significant (2-fold) increased risks for WMLs among those with moderate and high SBP variability (third and fifth quintiles compared with the lowest quintile). Those in the highest SBP variability category (the fifth quintile) also had significantly more atrophy. Conclusions-These SBP variability-MRI relationships suggest that variation in SBP in midlife may be a contributing factor to the development of WMLs and ventricular atrophy in late life. C1 NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA. Kuakini Med Ctr, Honolulu, HI USA. Univ Hawaii, John A Burns Sch Med, Dept Med, Honolulu, HI 96822 USA. Social & Sci Syst, Bethesda, MD USA. RP Havlik, RJ (reprint author), NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Gateway Bldg,Suite 3C309, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [N01-AG-4-2149] NR 26 TC 72 Z9 73 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 BP 26 EP 30 DI 10.1161/hs0102.101890 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700007 PM 11779884 ER PT J AU Rodriguez, BL D'Agostino, R Abbott, RD Kagan, A Burchfiel, CM Yano, K Ross, GW Silbershatz, H Higgins, MW Popper, J Wolf, PA Curb, JD AF Rodriguez, BL D'Agostino, R Abbott, RD Kagan, A Burchfiel, CM Yano, K Ross, GW Silbershatz, H Higgins, MW Popper, J Wolf, PA Curb, JD TI Risk of hospitalized stroke in men enrolled in the Honolulu Heart Program and the Framingham Study - A comparison of incidence and risk factor effects SO STROKE LA English DT Article DE Asian-Americans; epidemiology; ethnic groups; risk factors; stroke; whites ID HAWAIIAN JAPANESE MEN; SERUM-CHOLESTEROL; THROMBOEMBOLIC STROKE; HEMORRHAGIC STROKE; DISEASE; CALIFORNIA; MORTALITY; COMMUNITY; AGE AB Background and Purpose-Risk of death due to stroke in Japan is more than double the risk in the United States. It remains unknown why some ethnic groups are more prone to stroke than others. Our purpose was to compare the 20-year incidence of hospitalized stroke between Japanese-American men in the Honolulu Heart Program and white men in the Framingham Study. Methods-This was a 20-year follow-up study beginning around 1965, a population-based study on the island of Oahu, Hawaii, and in Framingham, Mass. Participants were 7589 men in Honolulu and 1216 men in Framingham without prevalent coronary heart disease and stroke. Subjects were 45 to 68 years old when follow-up began. Main outcome measures were incident thromboembolic and hemorrhagic stroke. Results-Framingham men had a 40% excess of thromboembolic stroke compared with Honolulu men after adjustment for age and other risk factors (62/1000 versus 45/1000, respectively, P<0.001), whereas incidence of hemorrhagic stroke was nearly identical (14.8/1000). In both cohorts, each stroke type was consistently elevated in the presence of hypertension and cigarette smoking. Diabetes and body mass index increased the risk of thromboembolic stroke in both samples, and diabetes increased the risk of hemorrhagic events in Framingham. Alcohol intake and low total cholesterol were associated with hemorrhagic events in Honolulu but not in Framingham. Despite occasional differences in risk factor effects, none were significantly different between cohorts. Conclusions-The incidence of thromboembolic stroke requiring hospitalization is markedly less in Honolulu than in Framingham. The difference in stroke incidence rates observed cannot be explained by the traditional risk factors. Further studies are needed to identify factors that protect Japanese-American men in Honolulu from stroke. C1 Univ Hawaii Manoa, John A Burns Sch Med, Div Clin Epidemiol, Honolulu, HI 96822 USA. Univ Hawaii Manoa, John A Burns Sch Med, Div Geriatr Med, Honolulu, HI 96822 USA. Kuakini Med Ctr, Honolulu, HI USA. Dept Vet Affairs, Honolulu, HI USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. NHLBI, Jackson, MS USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Univ Virginia, Sch Med, Div Biostat & Epidemiol, Charlottesville, VA 22908 USA. RP Rodriguez, BL (reprint author), Hawaii Ctr Hlth Res, 846 S Hotel St,Suite 306, Honolulu, HI 96813 USA. FU NHLBI NIH HHS [N01-HC-38038, N01-HC-05102, UO1-HL-56274]; NIA NIH HHS [N01-AG-4-2149] NR 29 TC 107 Z9 112 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 BP 230 EP 236 DI 10.1161/hs0102.101081 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700044 PM 11779915 ER PT J AU Chalela, JA Ezzeddine, MA Calabrese, TM Latour, LL Baird, AE Luby, ML Warach, S AF Chalela, JA Ezzeddine, MA Calabrese, TM Latour, LL Baird, AE Luby, ML Warach, S TI Diffusion and perfusion changes two hours after intravenous rt-PA therapy: A preliminary report SO STROKE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA 82 BP 356 EP 357 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700155 ER PT J AU Hillis, AE Barker, PB Beauchamp, NJ Tuffiash, EC Wityk, RJ Cooper, O Metter, J AF Hillis, AE Barker, PB Beauchamp, NJ Tuffiash, EC Wityk, RJ Cooper, O Metter, J TI Aphasia and neglect associated with subcortical Infarcts can be explained by cortical hypoperfusion SO STROKE LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. RI Cooper, Odelia/G-1549-2016 OI Cooper, Odelia/0000-0001-5955-8242 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA 88 BP 358 EP 358 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700161 ER PT J AU Latour, LL Calabrese, TM Ezzeddine, MA Chalela, JA Luby, ML Warach, S AF Latour, LL Calabrese, TM Ezzeddine, MA Chalela, JA Luby, ML Warach, S TI Lesion probability mapping: Accounting for uncertainty in identifying lesions on MRI of acute stroke in humans SO STROKE LA English DT Meeting Abstract C1 NINCDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P9 BP 363 EP 363 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700189 ER PT J AU Chalela, JA Ezzeddine, MA Latour, LL Baird, AE Warach, S AF Chalela, JA Ezzeddine, MA Latour, LL Baird, AE Warach, S TI Cerebral microbleeds in potential thrombolysis candidates: A gradient-echo T2*imaging study SO STROKE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P30 BP 367 EP 367 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700209 ER PT J AU Ezzeddine, MA Chalela, JA Latour, LL Davis, LA Nyquist, PA Baird, AE Warach, S AF Ezzeddine, MA Chalela, JA Latour, LL Davis, LA Nyquist, PA Baird, AE Warach, S TI Thrombus detection in acute stroke patients using gradient echo magnetic resonance imaging SO STROKE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P32 BP 367 EP 367 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700211 ER PT J AU Nadareishvili, ZG McCarron, R Hamm, T Prat, E Martin, R Degraba, TJ AF Nadareishvili, ZG McCarron, R Hamm, T Prat, E Martin, R Degraba, TJ TI Predominant expression of proinflammatrory cytokines by carotid atherosclerotic plaque T cells SO STROKE LA English DT Meeting Abstract C1 NINCDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. NINCDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P84 BP 377 EP 377 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700263 ER PT J AU Chalela, JA Ezzeddine, MA Davis, LA Nyquist, PA Latour, LL Unipan, S Baird, AE Warach, S AF Chalela, JA Ezzeddine, MA Davis, LA Nyquist, PA Latour, LL Unipan, S Baird, AE Warach, S TI Myocardial ischemia in acute stroke patients; A troponin I study SO STROKE LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P120 BP 383 EP 383 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700299 ER PT J AU McCarron, RM Ohara, Y Golech, S Lenz, FA Bembry, J Spatz, M AF McCarron, RM Ohara, Y Golech, S Lenz, FA Bembry, J Spatz, M TI Human brain microvascular endothelium: Adrenergic modulation of ICAM-1 expression induced by TNF alpha SO STROKE LA English DT Meeting Abstract C1 Naval Med Res Ctr, Silver Spring, MD USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NINCDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2002 VL 33 IS 1 MA P247 BP 406 EP 406 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 509KV UT WOS:000173147700425 ER PT B AU Bezrukov, SM Kasianowicz, JJ AF Bezrukov, SM Kasianowicz, JJ BE Kasianowicz, JJ Kellermayer, MSZ Deamer, DW TI Dynamic partitioning of neutral polymers into a single ion channel SO STRUCTURE AND DYNAMICS OF CONFINED POLYMERS SE NATO SCIENCE SERIES, PARTNERSHIP SUB-SERIES 3: HIGH TECHNOLOGY LA English DT Proceedings Paper CT NATO Advanced Research Workshop on Biological, biophysical and Theoretical Aspects of Polymer Structure and Transport CY JUN 20-25, 1999 CL BIKAL, HUNGARY SP NATO DE polymer confinement; poly(ethylene glycol); PEG; PEO; structure-function ID PORE; FLUCTUATIONS; MEMBRANES; CONDUCTANCE; STATES AB Polymers partitioning into highly confined spaces can be studied using single nanometer-scale pores formed by protein ion channels. The ionic conductance of a channel depends on the state of occupancy of the pore by polymer and serves as a measure of polymer partitioning. Specifically, the movement of neutral polymer into the pore causes a reduction of the channel's conductance. The mean conductance is used to determine the polymer partition coefficient and the conductance fluctuations report the rates at which polymer exchanges between the bulk and the pore. Three theoretical approaches to describe the steric interaction of polymer and a single pore (hard spheres, random flight model, and scaling theory) fail to describe the partitioning of poly(ethylene glycol) into two structurally and chemically different ion channels (Staphylococcus aureus a-hemolysin and alamethicin). In particular, these theories cannot account for the sharp molecular weight dependence of the partition coefficient. C1 NICHD, LPSB, NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NICHD, LPSB, NIH, Bethesda, MD 20892 USA. NR 28 TC 6 Z9 6 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-0697-7 J9 NATO SCI S PRT 3 HI PY 2002 VL 87 BP 117 EP 130 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Polymer Science SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Polymer Science GA BU87Y UT WOS:000177287200007 ER PT J AU Kozel, NJ Robertson, EB Falkowski, CL AF Kozel, NJ Robertson, EB Falkowski, CL TI The community epidemiology work group approach SO SUBSTANCE USE & MISUSE LA English DT Article DE drug misuse; community; epidemiology; networks; surveillance; vulnerable populations AB "Drug abuse" provides many unique challenges to the research community. Some of these involve fundamental epidemiologic issues, such as measuring the extent of the problem, identifying and assessing changes in patterns and trends, detecting emerging "drugs of abuse", characterizing vulnerable populations and determining health and social consequences. A number of research methods are employed to address these issues. This paper describes one of these-a model in which ongoing surveillance of "drug abuse" is maintained through a network of community-based researchers, local officials, academics, and other interested and qualified members of the community. Timely, accurate, and cost-effective data can be generated through systematic collection and analysis of indirect indicators of "drug abuse" that are often routinely produced by a variety of community sources. This information, in turn, can be used to make informed public health policy decisions. The community-based network model has been implemented at the city, state, national, regional, and international levels, and a case is made that this type of program could be useful, as well, in understanding the dynamics of "drug abuse" in rural areas of the country. [Translations are provided in the International Abstracts Section of this issue]. C1 NIDA, Div Epidemiol Serv & Prevent Res, NIH, Rockville, MD USA. Hazelden Fdn, Butler Ctr Res, Center City, MN USA. RP Kozel, NJ (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, NIH, Rockville, MD USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2002 VL 37 IS 5-7 BP 783 EP 803 DI 10.1081/JA-120004283 PG 21 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 571YZ UT WOS:000176747900011 PM 12117070 ER PT J AU Hayashi, T Tsao, LI Su, TP AF Hayashi, T Tsao, LI Su, TP TI Antiapoptotic and cytotoxic properties of delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin in PC12 cells SO SYNAPSE LA English DT Article DE MAP kinase; DNA laddering; ERK; opioid; naltrexone; Fas; Fas ligand; DADLE; PD98059 ID ACTIVATED PROTEIN-KINASE; RAT PHEOCHROMOCYTOMA CELLS; MAPK SIGNALING PATHWAY; AVIAN CILIARY GANGLION; NERVE GROWTH-FACTOR; IN-VITRO; AGONIST ACTIVATION; RECEPTOR SUBTYPES; T-CELLS; APOPTOSIS AB The delta opioid peptide [D-Ala(2),D-Leu(5)]enkephalin (DADLE) has been shown to promote organ survival and to protect against methamphetamine-induced neurodegeneration. However, the cellular mechanisms of these actions of DADLE are not totally clear. We examined the action of DADLE in serum-deprived pheochromocytoma cells (PC12) and found that DADLE protected against cell death in those cells. However, the dose-response curves of the protective effects of DADLE are U-shaped as judged by three biochemical or morphological assays: the LDH release, the DNA laddering, and the apoptotic nuclei. It was found that femtomolar to picomolar concentrations of DADLE are antiapoptotic, whereas micormolar concentrations of DADLE are cytotoxic in PC12 cells. The protective effect of DADLE could be attenuated by a selective delta2 opioid antagonist and the cytotoxic action of DADLE was reduced by a selective mu opioid receptor antagonist. The treatment of cells with PD98059, a selective inhibitor of ERK kinase (MEK), or the transfection of cells with a dominant interfering form of MEK (MEK-KA97) blocked both the protective effect of DADLE and the ERK phosphorylation induced by DADLE. Cytotoxic concentrations of DADLE, on the other hand, caused an increase of Fas-ligand (FasL) in PC12 cells that was attenuated by a selective mu antagonist. Our results suggest, therefore, that endogenous opioid peptides may, at low concentrations, promote cell survival via the MEK-ERK pathway perhaps through delta2 opioid receptors, whereas they may kill cells at high concentrations via the activation of FasL through an as-yet unknown mechanism involving mu opioid receptors. (C) 2001 Wiley-Liss, Inc.(dagger). C1 NIDA, Cellular Pathobiol Unit, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Su, TP (reprint author), NIDA, Cellular Pathobiol Unit, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hayashi, Teruo/A-9690-2008 NR 47 TC 55 Z9 58 U1 0 U2 5 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 JAN PY 2002 VL 43 IS 1 BP 86 EP 94 DI 10.1002/syn.10019 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 502CK UT WOS:000172726000010 PM 11746737 ER PT J AU Donovan, PJ Smith, GT Riggs, CW Alexandrov, VA AF Donovan, PJ Smith, GT Riggs, CW Alexandrov, VA TI Effects of glucose on cloning efficiency and mutagenesis of fetal rat cells SO TERATOGENESIS CARCINOGENESIS AND MUTAGENESIS LA English DT Article DE genotoxicity; MNU; ENU; 6-thioguanine; gestation; in vivo/in vitro assay; transplacental ID CALORIE RESTRICTION; SOMATIC MUTATION; CANCER; CARCINOGENESIS; RISK; SENSITIVITY; FREQUENCY; CHILDHOOD; HAMSTER; FEMALE AB In a previous study, treatment of rats with 10% glucose in the drinking water, as fetuses during gestation and for 1.5 months after delivery, significantly enhanced tumor incidence that resulted from N-methyl-N-nitrosourea (MNU, 20mg/kg) given transplacentally on gestation day 21, with a 1.6-fold increase in overall tumor incidence. We investigated whether glucose would have an effect on MNU-induced mutation in fetal F-344 rat somatic cells as measured in an in vivo/in vitro assay. Rat fetuses were exposed transplacentally to MNU on gestation day 16 and to a 10% glucose solution from gestation day 7 to day 17. Cells were isolated on gestation day 17 for determination of cloning efficiency and for selection of 6-thioguanine (6-TG)-resistant HGPRT mutants. Cloning efficiency of the fetal cells exposed to MNU alone was 22.6 +/- 2.3% S.E., while that for cells from fetuses exposed to MNU+glucose was 27.5+/-1.6% S.E., which was a significant difference (P=0.018). This indicates an effect of glucose on cell proliferation and survival. MNU treatment significantly increased the mutation frequency of fetal cells from a spontaneous value of 0.4 x 10(-6) per viable cell to (8.8 +/- 1.8 S.E.,) x 10-6 (P=0.0087). The coexposure to MNU and glucose yielded a mutant frequency per plate of 0.62+/-0.05 S.E., which was a 1.5-fold increase compared to MNU alone (0.43+/-0.11 S.E., P=0.075. In summary, the data indicate that glucose during pregnancy increases proliferation/survival of fetal cells and possibly also mutation rate. Published 2002 Wiley-Liss, Inc.(dagger) C1 Natl Canc Inst Frederick, Lab Comparat Carcinogenesis, Ft Detrick, MD 21702 USA. NCI Federick, Data Management Serv Inc, Frederick, MD USA. NN Petrov Res Inst Oncol, St Petersburg, Russia. RP Donovan, PJ (reprint author), Natl Canc Inst Frederick, Lab Comparat Carcinogenesis, Bldg 538,Rm 205E, Ft Detrick, MD 21702 USA. FU NCI NIH HHS [N01-CO-46002] NR 20 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-3211 J9 TERATOGEN CARCIN MUT JI Teratogenesis Carcinog. Mutagen. PY 2002 VL 22 IS 5 BP 329 EP 334 DI 10.1002/tcm.10027 PG 6 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 589UQ UT WOS:000177779100002 PM 12210495 ER PT J AU Mohiddin, SA Fananapazir, L AF Mohiddin, SA Fananapazir, L TI Systolic compression of epicardial coronary and intramural arteries in children with hypertrophic cardiomyopathy SO TEXAS HEART INSTITUTE JOURNAL LA English DT Article; Proceedings Paper CT Symposium on Coronary Artery Anomalies - Morphogenesis, Morphology, Pathophysiology and Clinical Corelations CY FEB 28-MAR 01, 2002 CL TEXAS HEART INST, HOUSTON, TEXAS HO TEXAS HEART INST DE bridging; cardiomyopathy; hypertrophic; child; death; sudden; cardiac/etiology/prevention & control; coronary vessel/pathology; heart septum/physiopathology; human; mycardial ischemia; perforator arteries; thallium scintigraphy ID LEFT-VENTRICULAR HYPERTROPHY; POSITRON EMISSION TOMOGRAPHY; BLOOD-FLOW VELOCITY; MYOCARDIAL-ISCHEMIA; SUDDEN-DEATH; VASODILATOR RESERVE; PATIENT POPULATION; CARDIAC-ARREST; INFARCTION; BRIDGES AB It has been suggested that systolic compression of epicardial coronary arteries is an important cause of myocardial ischemia and sudden death in children with hypertrophic cardiomyopathy We examined the associations between sudden death, systolic coronary compression of intra- and epicardial arteries, myocardial perfusion abnormalities, and severity of hypertrophy in children with hypertrophic cardiomyopathy. We reviewed the angiograms from 57 children with hypertrophic cardiomyopathy for the presence of coronary and septal artery compression; coronary compression was present in 23 (40%). The left anterior descending artery was most often affected, and multiple sites were found in 4 children. Myocardial perfusion abnormalities were more frequently present in children with coronary compression than in those without (94% vs 47%, P = 0.002). Coronary compression was also associated with more severe septal hypertrophy and greater left ventricular outflow gradient. Septal branch compression was present in 65% of the children and was significantly associated with coronary compression, severity of septal hypertrophy, and outflow obstruction. Multivariate analysis showed that septal thickness and septal branch compression, but not coronary compression, were independent predictors of perfusion abnormalities. Coronary compression was not associated with symptom severity, ventricular tachycardia, or a worse prognosis. We conclude that compression of coronary arteries and their septal branches is common in children with hypertrophic cardiomyopathy and is related to the magnitude of left ventricular hypertrophy. Our findings suggest that coronary compression does not make an important contribution to myocardial ischemia in hypertrophic cardiomyopathy; however, left ventricular hypertrophy and compression of intramural arteries may contribute significantly. C1 NHLBI, Cardiol Branch, Inherited Cardiac Dis Sect, Bethesda, MD 20892 USA. RP Fananapazir, L (reprint author), NHLBI, Cardiol Branch, Inherited Cardiac Dis Sect, Bldg 10,Room 7B-15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 60 TC 15 Z9 16 U1 0 U2 0 PU TEXAS HEART INST PI HOUSTON PA PO BOX 20345, HOUSTON, TX 77225-0345 USA SN 0730-2347 J9 TEX HEART I J JI Tex. Heart Inst. J. PY 2002 VL 29 IS 4 BP 290 EP 298 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 621MF UT WOS:000179592600011 PM 12484613 ER PT J AU Parikh, S Ando, S Schneider, A Skarulis, MC Sarlis, NJ Yen, PM AF Parikh, S Ando, S Schneider, A Skarulis, MC Sarlis, NJ Yen, PM TI Resistance to thyroid hormone in a patient without thyroid hormone receptor mutations SO THYROID LA English DT Article ID RUBINSTEIN-TAYBI-SYNDROME; BETA; COREPRESSORS; FAMILIES; ALPHA; GENES AB Resistance to thyroid hormone (RTH) is a clinical syndrome characterized by elevated serum thyroid hormone (TH) levels, unsuppressed thyrotropin (TSH) levels, and tissue hyposensitivity to TH. In almost all cases, the genetic basis of RTH lies in mutation of one of the two TH receptor beta (TRbeta) alleles. Recently, patients from several families with phenotypic manifestations of RTH in the absence of TR mutations have been described. We report a case of a 31-year-old woman who presented with goiter, tachycardia, elevated TH levels, unsuppressed TSH, and "inappropriately normal" levels of peripheral TH action markers. In two separate clinical evaluations, the patient exhibited typical clinical and biochemical evidence for peripheral and pituitary RTH. Surprisingly, reverse transcriptase-polymerase chain reaction (RT-PCR) of full-length TRalpha and TRbeta mRNAs, and genomic PCR using primers flanking exons encoding the carboxy-terminal region of TRbeta failed to demonstrate mutations in the TRalpha or TRbeta genes. It is likely that defects in the regulation of TR genes or mutations in transcriptional cofactors involved in TR signaling account for this patient's phenotype. C1 NIDDKD, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Dept Intramural Res, NIH, Bethesda, MD 20892 USA. RP Yen, PM (reprint author), NIDDKD, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bldg 10,Room 8D12, Bethesda, MD 20892 USA. RI Schneider, Anja/F-5293-2010 NR 22 TC 11 Z9 11 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD JAN PY 2002 VL 12 IS 1 BP 81 EP 86 DI 10.1089/105072502753452011 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 516MK UT WOS:000173556900013 PM 11838736 ER PT J AU Feolo, M Ward, M Helmberg, W AF Feolo, M Ward, M Helmberg, W TI Putting HLA polymorphisms on the map SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 Natl Lib Med, Natl Inst Biotechnol Informat, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 2 EP 2 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300007 ER PT J AU Cullen, M Perfetto, S Klitz, W Nelson, G Carrington, M AF Cullen, M Perfetto, S Klitz, W Nelson, G Carrington, M TI Defining meiotic recombination across the human major histocompatibility complex SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NCI, SAIC, Frederick, MD 21701 USA. Gyeongsang Natl Univ, Chinju, South Korea. NCI, Rockville, MD USA. Univ Cambridge, Cambridge, England. Univ Calif Los Angeles, Los Angeles, CA USA. San Francisco City Clin Cohort, San Francisco, CA USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 3 EP 3 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300009 ER PT J AU Yuhki, N Beek, T O'Brien, SJ AF Yuhki, N Beek, T O'Brien, SJ TI Comparative genome organization of human, murine and feline MHC class II region SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NCI, Frederick, MD 21701 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 7 EP 7 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300023 ER PT J AU Martin, MP Carrington, M Wilson, M Trowsdale, J AF Martin, MP Carrington, M Wilson, M Trowsdale, J TI KIR genotyping and haplotype determination in CEPH SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NCI, SAIC Frederick, Frederick, MD 21701 USA. Univ Cambridge, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 9 EP 9 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300028 ER PT J AU Carrington, M Martin, MP Gao, XJ Nelson, G Lee, JH O'Brien, SJ Goedert, JJ Wilson, M Trowsdale, J Detels, R Buchbinder, S Hoots, K Vlahov, D AF Carrington, M Martin, MP Gao, XJ Nelson, G Lee, JH O'Brien, SJ Goedert, JJ Wilson, M Trowsdale, J Detels, R Buchbinder, S Hoots, K Vlahov, D TI Epistatic interaction between KIR3DS1 and HLA-B delays the progression to aids SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NCI, SAIC, Frederick, MD 21701 USA. Gyeongsang Natl Univ, Chinju, South Korea. NCI, Rockville, MD USA. Univ Cambridge, Cambridge, England. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. San Francisco City Clin Cohort, San Francisco, CA USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 34 EP 34 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300104 ER PT J AU Karacki, P Gao, X Nelson, G Jin, X Vlahov, D Goedert, J Kaslow, R Buchbinder, S Hoots, K O'Brien, S Carrington, M AF Karacki, P Gao, X Nelson, G Jin, X Vlahov, D Goedert, J Kaslow, R Buchbinder, S Hoots, K O'Brien, S Carrington, M TI HLA class I polymorphism influences the rate of progression to aids SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NCI, SAIC, IRSP, Frederick, MD 21701 USA. Univ Rochester, Rochester, NY 14627 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. NCI, DCEG, VEB, Rockville, MD USA. SFCC, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 34 EP 34 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300103 ER PT J AU Carrington, M Martin, M Nelson, G Gao, X Gladman, D Pellett, F Wade, J AF Carrington, M Martin, M Nelson, G Gao, X Gladman, D Pellett, F Wade, J TI Disease-associated susceptibility markers in the KIR and HLA class I loci for psoriatic arthritis SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NCI, SAIC Frederick, Frederick, MD 21701 USA. Univ Toronto, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 35 EP 35 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300106 ER PT J AU Gao, X Marti, D Karacki, P Vlahov, D Goedert, J Kaslow, R Buchbinder, S Hoots, K O'Brien, S Carrington, M AF Gao, X Marti, D Karacki, P Vlahov, D Goedert, J Kaslow, R Buchbinder, S Hoots, K O'Brien, S Carrington, M TI HLA class II polymorphism and AIDS progression SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NCI, SAIC, IRSP, Frederick, MD USA. Johns Hopkins Sch Hyg & Publ Hlth, Baltimore, MD USA. NCI, DCEG, VEB, Rockville, MD USA. Univ Alabama, Birmingham, AL USA. SFCC, San Francisco, CA USA. UT, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 67 EP 67 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300216 ER PT J AU Malkki, M Harding, A Carrington, M Petersdorf, E AF Malkki, M Harding, A Carrington, M Petersdorf, E TI Disparity for class I, III, II microsatellite markers in unrelated donor hematopoietic stem cell transplantation SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 Fred Hutchinson Canc Res Ctr, Seattle, WA USA. NCI, Frederick Canc Res & De Ctr, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 91 EP 91 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300298 ER PT J AU Wu, GG Deng, ZH Cheng, LH Wei, TL Li, Z Zhou, D Yang, CS Zhao, TM AF Wu, GG Deng, ZH Cheng, LH Wei, TL Li, Z Zhou, D Yang, CS Zhao, TM TI Stable inheritance of an HLA-A null allele, A*0253N, through three generations of a family SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 Shenzhen Inst Transfus Med, Shenzhen, Peoples R China. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 95 EP 95 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300311 ER PT J AU Yao, Z Witter, K Volgger, A Helmberg, W Albert, ED AF Yao, Z Witter, K Volgger, A Helmberg, W Albert, ED TI Sequencing of mica alleles for exon 5 SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 LMU, Kinderpoliklin, Munich, Germany. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 103 EP 103 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300335 ER PT J AU Riteau, B Barber, D Faure, M Long, EO AF Riteau, B Barber, D Faure, M Long, EO TI Signaling events in natural cytotoxicity SO TISSUE ANTIGENS LA English DT Meeting Abstract C1 NIAID, NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PY 2002 VL 59 SU 2 BP 105 EP 105 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 564JM UT WOS:000176311300342 ER PT J AU Boorman, GA Anderson, SP Casey, WM Brown, RH Crosby, LM Gottschalk, K Easton, M Ni, H Morgan, KT AF Boorman, GA Anderson, SP Casey, WM Brown, RH Crosby, LM Gottschalk, K Easton, M Ni, H Morgan, KT TI Toxicogenomics, drug discovery, and the pathologist SO TOXICOLOGIC PATHOLOGY LA English DT Article DE differential gene expression; genomics; proteomics; rodent studies; pathology; liver; research teams; microarray; toxicology; safety assessment ID REPRESENTATIONAL DIFFERENCE ANALYSIS; GENE-EXPRESSION PROFILES; MESSENGER-RNA; CDNA; IDENTIFICATION; ARRAYS; CELLS; BIOINFORMATICS; MICROARRAYS; TECHNOLOGY AB The field of toxicogenomics, which currently focuses on the application of large-scale differential gene expression (DGE) data to toxicology, is starting to influence drug discovery and development in the pharmaceutical industry. Toxicological pathologists, who play key roles in the development of therapeutic agents, have much to contribute to DGE studies, especially in the experimental design and interpretation phases. The intelligent application of DGE to drug discovery can reveal the potential for both desired (therapeutic) and undesired (toxic) responses. The pathologist's understanding of anatomic, physiologic, biochemical, immune, and other underlying factors that drive mechanisms of tissue responses to noxious agents turns a bewildering array of gene expression data into focused research programs. The latter process is critical for the successful application of DGE to toxicology. Pattern recognition is a useful first step, but mechanistically based DGE interpretation is where the long-term future of these new technologies lies. Pathologists trained to carry out such interpretations will become important members of the research teams needed to successfully apply these technologies to drug discovery and safety assessment. As a pathologist using DGE, you will need to learn to read DGE data in the same way you learned to read glass slides, patiently and with a desire to learn and, later, to teach. In return, you will gain a greater depth of understanding of cell and tissue function, both in health and disease. C1 NIEHS, Lab Expt Pathol, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. GlaxoSmithKline, Res Triangle Pk, NC 27709 USA. US EPA, NHEERL, Res Triangle Pk, NC 27711 USA. RP Boorman, GA (reprint author), NIEHS, Lab Expt Pathol, Environm Toxicol Program, POB 12233,MD B3-08,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 54 TC 34 Z9 34 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN 1 PY 2002 VL 30 IS 1 BP 15 EP 27 DI 10.1080/01926230252824671 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA 558ED UT WOS:000175952600005 PM 11890469 ER PT J AU Zhang, J Herman, EH Knapton, A Chadwick, DP Whitehurst, VE Koerner, JE Papoian, T Ferrans, VJ Sistare, FD AF Zhang, J Herman, EH Knapton, A Chadwick, DP Whitehurst, VE Koerner, JE Papoian, T Ferrans, VJ Sistare, FD TI SK&F 95654-induced acute cardiovascular toxicity in Sprague-Dawley rats - Histopathologic, electron microscopic, and immunohistochemical studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE myocardial necrosis and inflammation; drug-induced vasculitis; vasodilatation; endothelial cell activation; endothelial and smooth muscle cell apoptosis; intercellular adhesion molecule-1 (ICAM-1); von Willebrand factor; mast cell degranulation ID ENDOTHELIAL-CELL ACTIVATION; SMOOTH-MUSCLE CELLS; PHOSPHODIESTERASE INHIBITORS; ADHESION MOLECULES; MAST-CELLS; APOPTOSIS; DEATH; CARDIOTOXICITY; INFLAMMATION; NOMENCLATURE AB The characteristics and pathogenesis of the cardiovascular toxicity induced by the type III selective phosphodiesterase inhibitor SK&F 95654 were examined in 2 studies. Sprague-Dawley rats received either a single sc injection of 50, 100, or 200 mg/kg SK&F 95654 and were euthanized at 24 hours after administration of the drug (Study 1), or were given a single subcutaneous (sc) injection of 100 mg/kg SK&F 95654 and euthanized at 1, 2, 4, 6, 8, 12, 24 hours, or 2 weeks after treatment (Study 2). Control rats received either DMSO or saline. Myocardial lesions and vascular lesions of the mesentery, spleen, and pancreas were seen 24 hours after dosing with either 50, 100, or 200 mg/kg SK&F 95654. The frequency and severity of these lesions (evaluated after the 100 mg/kg dose) increased with time over a period of 1 to 24 hours. By 2 weeks, the lesions subsided. Cardiac lesions consisted of myocyte necrosis with hypercontraction bands, inflammatory cell infiltration, interstitial hemorrhage, and interstitial edema. Vascular lesions of the mesentery were most prominent and consisted of vasodilatation and inflammation in the small-sized vessels, arterial medial necrosis and hemorrhage, and venous thrombosis. The vascular lesions included: leukocyte adhesion to endothelial cells, transendothelial migration of leukocytes, and inflammatory cell infiltration into vessel walls. Affected vessels included arteries, terminal arterioles, capillaries, postcapillary venules, and veins. Apoptosis of endothelial and smooth muscle cells was detected in the mesenteric vasculature by both TUNEL assay and electron microscopy. Evidence of endothelial cell activation in the mesenteric arteries and veins was also observed by electron microscopy. Immunohistochemical staining detected enhanced endothelial cell expression of intercellular adhesion molecule-1 (ICAM-1) and von Willebrand factor (vWF) in the mesenteric arteries and veins. Mast cells were noted to be more prevalent in affected mesenteric tissue from drug-treated animals. The present findings suggest that apoptosis of endothelial and smooth muscle cells, activation of endothelial cells, recruitment of mast cells, and increased expression of adhesion molecules are important factors to the overall pathogenesis of SK&F 95654-induced vasculitis. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD910, Laurel, MD 20708 USA. US FDA, Ctr Drug Evaluat & Res, Div Pulm Drug Prod HFD570, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Div Cardiorenal Drug Prod HFD110, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Div Anesthet Crit Care & Addict Drug Prod HFD170, Rockville, MD 20857 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA HFD910, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 45 TC 37 Z9 37 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN 1 PY 2002 VL 30 IS 1 BP 28 EP 40 DI 10.1080/01926230252824680 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA 558ED UT WOS:000175952600006 PM 11890473 ER PT J AU Boorman, GA Haseman, JK Waters, MD Hardisty, JF Sills, RC AF Boorman, GA Haseman, JK Waters, MD Hardisty, JF Sills, RC TI Quality review procedures necessary for rodent pathology Databases and toxicogenomic studies: The National Toxicology Program experience SO TOXICOLOGIC PATHOLOGY LA English DT Article DE cancer; bioassay; rodent studies; F344 rat; B6C3F1 mouse; toxicology; toxicogenomics ID WORKING GROUP; B6C3F(1) MICE; CARCINOGENICITY; LESIONS; RATS; CHEMICALS; ANIMALS; IMPACT; UPDATE AB Accuracy of the pathology data is crucial since rodent studies often provide critical data used for setting human chemical exposure standards. Diagnoses represent a judgment on the expected biological behavior of a lesion and peer review can improve diagnostic accuracy and consistency. With the conduct of 500 2-year rodent studies, the National Toxicology Program (NTP) has refined its process for comprehensive review of the pathology data and diagnoses. We have found that careful judgment can improve and simplify the review, whereas simply applying a set review procedure may not assure study quality. The use of reviewing pathologists and pathology peer review groups is a very effective procedure to increase study quality with minimal time and cost. New genomic technology to assess differential gene expression is being used to predict morphological phenotypes such as necrosis, hyperplasia, and neoplasia. The challenge for pathologists is to provide uniform pathology phenotypes that can be correlated with the gene expression changes. The lessons learned in assuring data quality in standard rodent studies also applies to the emerging field of toxicogenomics. C1 NIEHS, Lab Expt Pathol, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Environm Dis & Med Program, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Ctr Toxicogenom, Environm Dis & Med Program, Res Triangle Pk, NC 27709 USA. Expt Pathol Labs Inc, Durham, NC 27713 USA. RP Boorman, GA (reprint author), NIEHS, Lab Expt Pathol, Environm Toxicol Program, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 26 TC 38 Z9 39 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN 1 PY 2002 VL 30 IS 1 BP 88 EP 92 DI 10.1080/01926230252824752 PG 5 WC Pathology; Toxicology SC Pathology; Toxicology GA 558ED UT WOS:000175952600013 PM 11890481 ER PT J AU Shackelford, C Long, G Wolf, J Okerberg, C Herbert, R AF Shackelford, C Long, G Wolf, J Okerberg, C Herbert, R TI Qualitative and quantitative analysis of nonneoplastic lesions in toxicology studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE thoroughness; thresholds; accuracy; consistency; semiquantitative; severity grades; image analysis; stereology ID PATHOLOGY AB A pathology report is written to convey information concerning the pathologic findings in a study. This type of report must be complete, accurate and communicate the relative importance of various findings in a study. The overall quality of the report is determined by three Quality Indicators: thoroughness, accuracy, and consistency. Thoroughness is the identification of every lesion present in a particular organ or tissue, including spontaneous background lesions. Experienced pathologists familiar with background lesions may disregard certain types of lesions or establish a threshold or a severity above which background lesions are diagnosed. Accuracy is the ability to make, and precisely communicate, correct diagnoses. Nomenclature of lesions is a matter of definition and experienced pathologists generally agree as to what terms are to be used. Consistency is the uniform use of a specific term to record a defined lesion and implies that the same diagnostic criteria are being followed for each type of diagnosis. The relative severity of nonneoplastic lesions can be recorded either semiquantitatively or quantitatively. Semiquantitative analysis involves the application of defined severity grades or ranges for specific lesions. Quantitative analysis (counts and measurements) can be performed manually or electronically, utilizing image analysis and stereological techniques to provide numerical values. When both qualitative and quantitative parameters are applied in preparation of a pathology report, the recorded pathology findings can be interpreted and put into perspective. The use of this approach assures a reader that the pathology report meets the highest standards. C1 Expt Pathol Labs Inc, Res Triangle Pk, NC 27709 USA. Eli Lilly & Co, Lilly Res Labs, Greenfield, IN 46140 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Shackelford, C (reprint author), Expt Pathol Labs Inc, POB 12766, Res Triangle Pk, NC 27709 USA. EM cshackelford@epl-inc.com NR 18 TC 98 Z9 99 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN 1 PY 2002 VL 30 IS 1 BP 93 EP 96 DI 10.1080/01926230252824761 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 558ED UT WOS:000175952600014 PM 11890482 ER PT J AU Hejtmancik, MR Ryan, MJ Toft, JD Persing, RL Kurtz, PJ Chhabra, RS AF Hejtmancik, MR Ryan, MJ Toft, JD Persing, RL Kurtz, PJ Chhabra, RS TI Hematological effects in F344 rats and B6C3F1 mice during the 13-week gavage toxicity study of methylene blue trihydrate SO TOXICOLOGICAL SCIENCES LA English DT Article DE methylene blue trihydrate; F344 rats; B6C3F1 mice; methemoglobin and Heinz body formation; splenomegaly; hematopoiesis ID PARA-CHLOROANILINE AB Methylene blue trihydrate is used widely as a dye and therapeutic agent. Methylene blue was administered by gavage to 30 animals/sex/dose group in a 0.5% aqueous methylcellulose suspension at doses of 0, 25, 50, 100, and 200 mg/kg. Blood samples from 10 animals/sex/dose group were collected at the end of study weeks 1, 6, and 13. Methylene blue treatment resulted in methemoglobin formation and oxidative damage to red blood cells, leading to a regenerative anemia and a variety of tissue and biochemical changes secondary to erythrocyte injury. An early change was a dose-related increase in methemoglobin, where the response of rats and mice was similar in magnitude. Mice appeared to be more sensitive than rats to the formation of Heinz bodies and the development of anemia that was characterized by a decrease in hemoglobin, hematocrit, and erythrocyte count. SpIenomegaly was apparent in all treated mice and in the 100 mg/kg (males only) and 200 mg/kg rats at necropsy. There was a dose-related increase in absolute and relative spleen weight for both species. Microscopic examination revealed increased splenic hematopoiesis in all mice treatment groups and in rats at the 50 mg/kg dose level and above. Splenic congestion and bone marrow hyperplasia were also observed in these rat-dose groups. Mice at the higher doses showed hematopoiesis in the liver and accumulation of hemosiderin in Kupffer cells. These gross and microscopic findings are consistent with the development of hemolytic anemia. A dose-related increase in the reticulocyte count during study weeks 6 and 13 suggested a compensatory response to anemia. C1 Battelle Mem Inst, Columbus, OH 43201 USA. NIEHS, Div Toxicol Res, Res Triangle Pk, NC 27709 USA. NIEHS, Testing Program, Res Triangle Pk, NC 27709 USA. RP Hejtmancik, MR (reprint author), Battelle Mem Inst, 505 King Ave, Columbus, OH 43201 USA. NR 17 TC 18 Z9 18 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2002 VL 65 IS 1 BP 126 EP 134 DI 10.1093/toxsci/65.1.126 PG 9 WC Toxicology SC Toxicology GA 508PJ UT WOS:000173097400015 PM 11752692 ER PT J AU Kuester, RK Waalkes, MP Goering, PL Fisher, BL McCuskey, RS Sipes, IG AF Kuester, RK Waalkes, MP Goering, PL Fisher, BL McCuskey, RS Sipes, IG TI Differential hepatotoxicity induced by cadmium in Fischer 344 and Sprague-Dawley rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE cadmium; liver; Sprague-Dawley; Fischer344; heat shock protein 72; metallothionein; Kupffer cell; endothelial cell ID KUPFFER CELLS; LIVER; METALLOTHIONEIN; CHLORIDE; MACROPHAGES; TOXICITY; NEPHROTOXICITY; METABOLISM; MECHANISMS; TOLERANCE AB A number of reports document that Fischer 344 (F344) rats are more susceptible to chemically induced liver injury than Sprague-Dawley (SD) rats. Cadmium (CdCl2), a hepatotoxicant that does not require bioactivation, was used to better define the biological events that are responsible for the differences in liver injury between F344 and SD rats. CdCl2 (3 mg/kg) produced hepatotoxicity in both rat strains, but the hepatic injury was 18-fold greater in F344 rats as assessed by plasma alanine aminotransferase (ALT) activity. This difference in toxicity was not observed when isolated hepatocytes were incubated with CdCl2 in vitro, indicating that other cell types contribute to Cd-induced hepatotoxicity in vivo. Indeed, the sieve plates of hepatic endothelial cells (EC) in F344 rats were damaged to a greater degree than EC in SD rats. Additionally, Kupffer cell (KC) inhibition reduced hepatotoxicity in both strains, suggesting that this cell type is involved in the progression of CdCl2-induced hepatotoxicity. Moreover, enhanced synthesis of heat shock protein 72 occurred earlier in the SD rat. Maximal levels of hepatic metallothionein (MT), a protein associated with cadmium tolerance, were greater in SD rats. These protective factors may limit CdCl2-induced hepatocellular injury in SD compared with F344 rats by reducing KC activation and the subsequent inflammatory response that allows for the progression of hepatic injury. C1 Univ Arizona, Dept Pharmacol & Toxicol, Ctr Toxicol, Tucson, AZ 85721 USA. NIEHS, NCI, Res Triangle Pk, NC 27709 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Sipes, IG (reprint author), Univ Arizona, Dept Pharmacol & Toxicol, Ctr Toxicol, POB 210297, Tucson, AZ 85721 USA. FU NIEHS NIH HHS [ES-06694] NR 39 TC 50 Z9 55 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2002 VL 65 IS 1 BP 151 EP 159 DI 10.1093/toxsci/65.1.151 PG 9 WC Toxicology SC Toxicology GA 508PJ UT WOS:000173097400017 PM 11752694 ER PT J AU Debski, B Milner, JA AF Debski, B Milner, JA TI Influence of dietary selenium and cytochrome P450 modifiers on liver selenium content and cytochrome P450 activity in rats SO TRACE ELEMENTS AND ELECTROLYTES LA English DT Article DE cytochroms; dietary selenium; pentobarbital; rat ID XENOBIOTIC-METABOLIZING ENZYMES; DEFICIENCY; INDUCTION; MODULATION; CANCER; WOMEN AB The current studies examined the influence of dietary selenium on cytochrome P450 in male Sprague-Dawley rats. Selenium concentration was determined using a gas chromatograph with electron capture (method of McCarthy et al. [1981]), glutathione peroxidase activity by the coupled assay of Paglia and Valentine and the concentration of cytochrome P-450 in microsomal fraction by the method of Omura and Sato [1964]. Increasing dietary Se from 0.01 to 2.0 ppm markedly increased hepatic Se content and elevated GPx activity. It was found that hepatic selenium concentrations were inversely correlated with body weight of rats. Higher concentration of Se was found in the cytosolic than the microsomal fraction of the liver. Se supplementation also increased liver cytochrome P450 activity. Pentobarbital treatment did not alter the concentration of Se in liver or its distribution between the cytosolic and microsomal fractions, but did markedly elevate P450 activity. Comparing with control animals rats given 3-methylcholanthrene had the highest amount of cytochrome P450c and slightly inreased concentration of cytochrome P450b. The rats treated with 3 -amino- 1,2,4-triazol possesed lower amount of hepatic cytochrome P-450b. Cytochrome P450 fraction differences between Se-adequate and Se-supplemented rats disappeared after treatment with pentobarbital, 3-MC, Aroclor 1254 or 3 -amino- 1,2,4-triazol. Induction of hepatic P-450b cytochrome by Se may explain, in part, its anticarcinogenic properties. Exposure to several cytochrome P450 modifiers can mask the promotion effects of selenium on cytochrome P450. C1 Agr Univ Warsaw, Fac Med Vet, Dept Physiol Sci, SGGW,Biochem Div, PL-02787 Warsaw, Poland. NCI, Nutr Sci Res Grp, Div Canc Prevent, Rockville, MD USA. RP Debski, B (reprint author), Agr Univ Warsaw, Fac Med Vet, Dept Physiol Sci, SGGW,Biochem Div, Nowoursynowwska 159, PL-02787 Warsaw, Poland. NR 37 TC 2 Z9 2 U1 1 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0174-7371 J9 TRACE ELEM ELECTROLY JI Trace Elem. Electrolytes PY 2002 VL 19 IS 4 BP 209 EP 214 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 608UQ UT WOS:000178865400009 ER PT J AU Rios, M Hue-Roye, K Oyen, R Miller, J Reid, ME AF Rios, M Hue-Roye, K Oyen, R Miller, J Reid, ME TI Insights into the Holley- and Joseph- phenotypes SO TRANSFUSION LA English DT Article ID BLOOD-GROUP ANTIGENS; GLYCOPROTEIN; HY; GY(A); JOA AB BACKGROUND: The Dombrock blood group system consists of two antithetical antigens (Do(a) and Do(b)) and three high-incidence antigens (Gregory [Gy(a)], Holley [Hy], and Joseph [Jo(a)]). Hy and Jo(a) have an unusual phenotypic relationship. All Hy- RBCs are Jo(a-), but not all Jo(a-) RBCs are Hy- The molecular background associated with Hy- and Jo(a-) phenotypes is reported. STUDY DESIGN AND METHODS: DNA from 18 probands with Gy(a+(w)) Hy- Jo(a-) RBCs (Hy- phenotype) and from 13 probands with Gy(a+) Hy+(w) Jo(a-) RBCs (Jo[a-] phenotype) was tested. RESULTS- Sequencing and PCR-RFLP revealed 323 G>T (Gly108Val) and 378 T>C (silent mutation) changes on a DOB background (H) associated with the Hy- samples. The sister of the original Hy- proband and the majority of samples had an additional mutation of 898 C>G (Leu300Val) (HY1); others had 898C (300Leu) (HY2). In the Jo(a-) phenotype, there is a 350 C>T (Thrl 17lle) and a 378 C>T (silent mutation) change on a DOA background (JO). CONCLUSION: The results provide an explanation for the variation in typing results in antibody producers. The ablation of jo(a) in the Hy- phenotype and the weakening of Hy in the Jo(a-) phenotype may be due to the close proximity of these antigens. The 898 C>G mutation, within the sequence motif for glycosylphosphatidylinositol linkage, may cause reduced efficiency of anchoring the protein to the RBC membrane, thereby weakening the expression of Gya and Dob. C1 New York Blood Ctr, Immunochem Lab, New York, NY 10021 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Reid, ME (reprint author), New York Blood Ctr, Immunochem Lab, 310 E 67th St, New York, NY 10021 USA. FU NHLBI NIH HHS [HL54459] NR 22 TC 21 Z9 23 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JAN PY 2002 VL 42 IS 1 BP 52 EP 58 DI 10.1046/j.1537-2995.2002.00004.x PG 7 WC Hematology SC Hematology GA 522TQ UT WOS:000173913400009 PM 11896313 ER PT J AU Logdberg, L Reid, ME Miller, JL AF Logdberg, L Reid, ME Miller, JL TI Cloning and genetic characterization of blood group carrier molecules and antigens SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID DECAY-ACCELERATING FACTOR; LEUKOCYTE ACTIVATION ANTIGEN; AMINO-ACID SEQUENCE; IMMUNOGLOBULIN SUPERFAMILY; GROUP GLYCOPROTEIN; MEMBRANE-PROTEIN; GROUP SYSTEM; NEGATIVE INDIVIDUALS; NUCLEOTIDE-SEQUENCE; GROUP POLYMORPHISM AB Based an the astounding pace of growth in the field of molecular biology over the last 2 decades, we are now able to consider the allogenicity of transfused blood products in genetic terms. In this sense, the allogenic barriers to the transfusion-based transplantation are defined by differences between those portions of the donor and recipient genomes that define the antigenicity and immune response to transfused cells. The genetic basis of the major histocompatibility complex barrier described earlier is because of well-characterized transcription from a polymorphic locus on chromosome 6 in nonerythroid cells. In contrast, the allo-barrier of ABO-matched RBC transfusion is the result of differences in over 2 dozen independent genes expressed during erythropoiesis that encode a wide variety of molecules important in membrane biology. Variability in the structure of those genes among separate donors often provides the molecular basis of many blood group antigens and phenotypes. This article reviews our current knowledge of the human blood group systems in genetic terms, focusing on strategies used to identify the relevant genes and their polymorphisms. Copyright (C) 2002 by W.B. Saunders Company. C1 Emery Univ, Dept Pathol, Transfus Med Program, Atlanta, GA USA. New York Blood Ctr, Immunochem Lab, New York, NY 10021 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Reid, ME (reprint author), New York Blood Ctr, Immunohematol Lab, 310 E 67th St, New York, NY 10021 USA. FU NHLBI NIH HHS [HL54459] NR 65 TC 8 Z9 10 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 2002 VL 16 IS 1 BP 1 EP 10 DI 10.1053/tmrv.2002.29347 PG 10 WC Hematology SC Hematology GA 511JL UT WOS:000173260800001 PM 11788925 ER PT J AU Stroncek, D AF Stroncek, D TI Neutrophil alloantigens SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID GAMMA RECEPTOR-III; ALLOIMMUNE NEONATAL NEUTROPENIA; POLYMERASE CHAIN-REACTION; SEQUENCE-SPECIFIC PRIMERS; ANTIGEN NB1; GENE-FREQUENCIES; GRANULOCYTE ANTIBODIES; MONOCLONAL-ANTIBODIES; FRENCH POPULATION; EXPRESSION AB Antibodies to neutrophil antigens can cause neonatal alloimmune neutropenia, autoimmune neutropenia, febrile transfusion reactions, and transfusion-related acute lung injury. Several neutrophil antigen systems have been described serologically, but only the human neutrophil antigen-1 (HNA-1) or NA and HNA-2 or NB systems have been well characterized biochemically and molecularly. HNA-1 antigens are located on FcgammaRlllb, CD16. HNA-2 antigens are located on 58- to 64-Kd glycoprotein, CD177, and are encoded by a gene on chromosome 19 that belongs to the Ly-6 family. The function of the CD177 is not known, but the CD177 gene is highly homologous to a gene overexpressed in neutrophils from patients with polycythemia rubra vera called PRV-1. New polymorphisms in these antigen systems are still being described, but the complete understanding of these neutrophil antigen systems has been slow because of the complexity of these genes. Copyright (C) 2002 by W.B. Saunders Company. C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Stroncek, D (reprint author), NIH, Dept Transfus Med, 10 Ctr Dr,MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 56 TC 21 Z9 25 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 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JAN PY 2002 VL 16 IS 1 BP 67 EP 75 DI 10.1053/tmrv.2002.29406 PG 9 WC Hematology SC Hematology GA 511JL UT WOS:000173260800007 PM 11788931 ER PT J AU Hurley, JH Anderson, DE Beach, B Canagarajah, B Ho, YSJ Jones, E Miller, G Misra, S Pearson, M Saidi, L Suer, S Trievel, R Tsujishita, Y AF Hurley, JH Anderson, DE Beach, B Canagarajah, B Ho, YSJ Jones, E Miller, G Misra, S Pearson, M Saidi, L Suer, S Trievel, R Tsujishita, Y TI Structural genomics and signaling domains SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Review ID GAF DOMAIN; VHS DOMAIN; PROTEINS; TUBBY; IDENTIFICATION; TRAFFICKING; GENE; STAR AB Many novel signal transduction domains are being identified in the wake of genome sequencing projects and improved sensitivity in homology-detection techniques. The functions of these domains are being discovered by hypothesis-driven experiments and structural genomics approaches. This article reviews the recent highlights of research on modular signaling domains, and the relative contributions and limitations of the various approaches being used. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. OI Misra, Saurav/0000-0002-1385-8554 NR 40 TC 17 Z9 18 U1 1 U2 1 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 JAN PY 2002 VL 27 IS 1 BP 48 EP 53 DI 10.1016/S0968-0004(01)02022-9 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 513GY UT WOS:000173370900013 PM 11796224 ER PT J AU Nabel, EG AF Nabel, EG TI The golden egg - Making good on discovery and translation SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Editorial Material C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, 10 Ctr Dr,Bldg 10,Room 8C103, Bethesda, MD 20892 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 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD JAN PY 2002 VL 12 IS 1 BP 3 EP 4 DI 10.1016/S1050-1738(01)00162-1 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 515WU UT WOS:000173520300002 PM 11796237 ER PT J AU Ross, KE Cohen-Fix, O AF Ross, KE Cohen-Fix, O TI Separase: a conserved protease separating more than just sisters SO TRENDS IN CELL BIOLOGY LA English DT Article ID CHROMATID SEPARATION; ANAPHASE; COHESIN; YEAST; CLEAVAGE; PROTEOLYSIS; CHROMOSOME; SPINDLE C1 NIDDK, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ross, KE (reprint author), NIDDK, Mol & Cellular Biol Lab, NIH, 8 Ctr Dr,Bldg 8 Room 319, Bethesda, MD 20892 USA. NR 21 TC 27 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD JAN PY 2002 VL 12 IS 1 BP 1 EP 3 DI 10.1016/S0962-8924(01)02202-4 PG 3 WC Cell Biology SC Cell Biology GA 504YG UT WOS:000172883400001 PM 11853993 ER PT J AU Hampton, RR Healy, SD Shettleworth, SJ Kamil, AC AF Hampton, RR Healy, SD Shettleworth, SJ Kamil, AC TI 'Neuroecologists' are not made of straw SO TRENDS IN COGNITIVE SCIENCES LA English DT Letter ID FOOD-STORING BIRDS; HIPPOCAMPUS; MEMORY C1 NIMH, Lab Neuropsychol, NIH, Bethesda, MD 20892 USA. Univ Edinburgh, ICAPB, Edinburgh EH9 3JT, Midlothian, Scotland. Univ Toronto, Dept Psychol, Toronto, ON M5S 1A1, Canada. Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA. RP Hampton, RR (reprint author), NIMH, Lab Neuropsychol, NIH, Bldg 49,Rm 1B-80, Bethesda, MD 20892 USA. RI Piper, Walter/B-7908-2009 NR 12 TC 26 Z9 27 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD JAN PY 2002 VL 6 IS 1 BP 6 EP 7 DI 10.1016/S1364-6613(00)01821-0 PG 2 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 510AM UT WOS:000173186600003 ER PT J AU Shah, BH AF Shah, BH TI Epidermal growth factor receptor transactivation in angiotensin II-induced signaling: role of cholesterol-rich microdomains SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID PHOSPHORYLATION; CAVEOLAE; CELLS AB Angiotensin II (Ang II), the major effector peptide of the renin-angiotensin system, stimulates growth and proliferation responses in vascular smooth muscle cells (VSMCs) and other target cells, in which Ang II-induced MAP kinase activation is predominantly mediated by transactivation of epidermal growth factor receptors (EGF-Rs). Recent studies indicate that cholesterol-rich microdomains such as caveolae and their structural protein, caveolin-1, have an important role in regulating the transactivation of EGF-R by Ang II. Cholesterol depletion abolishes Ang U-induced phosphorylation of both EGF-R and protein kinase B/Akt, but has no such effects after EGF stimulation. Activated EGF-R and tyrosine phosphorylated caveolin are localized in focal adhesions. This not only reveals a unique scaffolding role of caveolin in EGF-R transactivation by Ang II, but also shows that cholesterol-rich microdomains, in addition to focal adhesion sites, are important cellular compartments in the spatial and temporal organization of Ang II-induced AT(1)-R signaling in VSMCs. C1 NICHHD, ERRB, NIH, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHHD, ERRB, NIH, Bld 49 Rm 6A36, Bethesda, MD 20892 USA. NR 11 TC 15 Z9 15 U1 0 U2 2 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 JAN-FEB PY 2002 VL 13 IS 1 BP 1 EP 2 DI 10.1016/S1043-2760(01)00539-2 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 516WN UT WOS:000173579900001 PM 11750852 ER PT J AU Rogozin, IB Kunkel, TA Pavlov, YI AF Rogozin, IB Kunkel, TA Pavlov, YI TI Double-strand breaks in DNA during somatic hypermutation of Ig genes: cause or consequence? SO TRENDS IN IMMUNOLOGY LA English DT Letter ID IMMUNOGLOBULIN GENES C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Kunkel, TA (reprint author), NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NR 11 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD JAN PY 2002 VL 23 IS 1 BP 12 EP 13 DI 10.1016/S1471-4906(01)02112-3 PG 2 WC Immunology SC Immunology GA 510GR UT WOS:000173200800002 PM 11801448 ER PT J AU Neckers, L AF Neckers, L TI Hsp90 inhibitors as novel cancer chemotherapeutic agents SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID IMPORTANT BIOLOGIC ACTIVITIES; HEAT-SHOCK PROTEINS; GENE-PRODUCT P185; HUMAN TUMOR-CELLS; TYROSINE KINASE; IN-VIVO; BENZOQUINOID ANSAMYCINS; HETEROPROTEIN COMPLEX; MOLECULAR CHAPERONE; LEUKEMIA-CELLS AB Heat shock protein 90 (Hsp90) is a molecular chaperone whose association is required for the stability and function of multiple mutated, chimeric and over-expressed signaling proteins that promote the growth and/or survival of cancer cells. Hsp90 client proteins include mutated p53, Bcr-Abl, Raf-1, Akt, ErbB2 and hypoxia-inducible factor 1alpha (HIF-1alpha). Hsp90 inhibitors, by interacting specifically with a single molecular target, cause the destabilization and eventual degradation of Hsp90 client proteins, and they have shown promising antitumor activity in preclinical model systems. One Hsp90 inhibitor, 17-allylaminogeldanamycin (17AAG), is currently in phase I clinical trial. Because of the chemoprotective activity of several proteins that are Hsp90 clients, the combination of an Hsp90 inhibitor with a standard chemotherapeutic agent could dramatically increase the in vivo efficacy of the therapeutic agent. C1 NCI, Cell & Canc Biol Branch, NIH, Rockville, MD 20850 USA. RP Neckers, L (reprint author), NCI, Cell & Canc Biol Branch, NIH, 9610 Med Ctr Dr,Suite 300, Rockville, MD 20850 USA. NR 59 TC 356 Z9 384 U1 7 U2 25 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PY 2002 VL 8 IS 4 SU S BP S55 EP S61 DI 10.1016/S1471-4914(02)02316-X PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 539YB UT WOS:000174899700011 PM 11927289 ER PT J AU Sausville, EA AF Sausville, EA TI Complexities in the development of cyclin-dependent kinase inhibitor drugs SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID RNA-POLYMERASE-II; CARBOXYL-TERMINAL DOMAIN; FACTOR P-TEFB; CARCINOMA-CELLS; PROTEIN-KINASE; GROWTH-INHIBITION; IN-VITRO; FLAVOPIRIDOL; EXPRESSION; APOPTOSIS AB Abnormalities in the normal regulation of the cell cycle are a hallmark of neoplasia. Drugs directed against the cyclin-dependent kinases (CDKs), which govern the normal orderly progression through the cell cycle, have been proposed to address the pathogenic defect in tumors. Recently, CDK family members that do not regulate the cell cycle directly but instead influence transcription (CDK7, CDK8, and CDK9) and neuronal and secretory cell function (CDK5) have been described. Continued synthetic chemistry efforts have defined important new selective inhibitors of CDKs, and strategies directed at newly described CDK-related targets, such as transcription control, can now be envisaged. CDKs remain important and novel targets whose potential needs to be more fully explored, albeit in light of the newly emerging complexities of their cellular physiology. C1 NCI, Dev Therapeut Program, Rockville, MD 20852 USA. RP Sausville, EA (reprint author), NCI, Dev Therapeut Program, Execut Plaza N,Room 8018,6130 Execut Blvd, Rockville, MD 20852 USA. NR 54 TC 71 Z9 76 U1 0 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4914 J9 TRENDS MOL MED JI Trends Mol. Med PY 2002 VL 8 IS 4 SU S BP S32 EP S37 DI 10.1016/S1471-4914(02)02308-0 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 539YB UT WOS:000174899700007 PM 11927285 ER PT J AU Rathod, PK Ganesan, K Hayward, RE Bozdech, Z DeRisi, JL AF Rathod, PK Ganesan, K Hayward, RE Bozdech, Z DeRisi, JL TI DNA microarrays for malaria SO TRENDS IN PARASITOLOGY LA English DT Review ID PLASMODIUM-FALCIPARUM MALARIA; GENE-EXPRESSION PATTERNS; TRANSCRIPTIONAL PROGRAM; CHLOROQUINE RESISTANCE; CDNA MICROARRAYS; REGULATED GENES; GENOMIC-SCALE; IDENTIFICATION; PARASITES; RECOMBINATION AB DNA microarrays are a powerful tool for the analysis of RNA and DNA composition on a whole-genome scale. The first applications of this technology in parasitology are in place. This review examines the various approaches to Plasmodium transcript-profiling that are being adopted using DNA microarray analysis and discusses additional strategies for obtaining and collating information relevant to the search for drug and vaccine candidates in malaria. C1 Univ Washington, Dept Chem, Seattle, WA 98195 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA. RP Rathod, PK (reprint author), Univ Washington, Dept Chem, Seattle, WA 98195 USA. RI Bozdech, Zbynek/A-2205-2011 FU NIAID NIH HHS [AI26912, AI40956] NR 53 TC 46 Z9 47 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4922 J9 TRENDS PARASITOL JI Trends Parasitol. PD JAN PY 2002 VL 18 IS 1 BP 39 EP 45 DI 10.1016/S1471-4922(01)02153-5 PG 7 WC Parasitology SC Parasitology GA 510GU UT WOS:000173201000010 PM 11850013 ER PT J AU Slayden, RA Barry, CE AF Slayden, RA Barry, CE TI The role of KasA and KasB in the biosynthesis of meromycolic acids and isoniazid resistance in Mycobacterium tuberculosis SO TUBERCULOSIS LA English DT Article ID CARRIER PROTEIN SYNTHASE; FATTY-ACID; MYCOLIC ACIDS; CELL-WALL; POLYKETIDE SYNTHASES; CONDENSING ENZYMES; CONTROL MECHANISMS; ENOYL REDUCTASE; TRICLOSAN; INHIBITION AB Mycobacterium tuberculosis has two discrete beta-ketoacyl synthases encoded by kasA and kasB that are located in tandem within a five-gene operon that has been implicated in isoniazid-sensitivity and mycolic acid synthesis. We have developed an in vitro meromycolic acid synthase assay to elucidate the anabolic role of these enzymes. Overproduction of KasA and KasB individually and together in M. smegmatis enabled cell-free incorporation of [C-14] malonyl-CoA into lipids whose chain length was dependent upon the M. tuberculosis elongating enzyme used. KasA specifically elongated palmitoyl-CoA to monounsaturated fatty acids that averaged 40 carbons in length. Kas B hyperproduction in the presence of KasA produced longer chain multiunsaturated hydrocarbons averaging 54 carbons in length. These products comigrated with a synthetic standard of meromycolic acid and their production was sensitive to isoniazid, thiolactomycin, and triclosan. KasA mutations associated with isoniazid resistance produced an enzyme that had a diminished overall catalytic activity but conferred enhanced resistance to isoniazid. In vivo analysis confirmed that overexpression of each of the four mutant KasAs enhanced isoniazid resistance when compared to overexpression of wild-type KasA. These results suggest discrete anabolic roles for both KasA and KasB in mycolic acid synthesis and substantiate the involvement of KasA mutations in isoniazid resistance. (C) Published by Elsevier Science Ltd. C1 NIAID, Host Def Lab, Tuberculosis Res Sect, NIH, Rockville, MD 20852 USA. RP Barry, CE (reprint author), NIAID, Host Def Lab, Tuberculosis Res Sect, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Barry, III, Clifton/H-3839-2012; Slayden, Richard/O-8626-2016 OI Slayden, Richard/0000-0001-6857-7277 FU Intramural NIH HHS [Z01 AI000783-11] NR 51 TC 52 Z9 55 U1 0 U2 8 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PY 2002 VL 82 IS 4-5 BP 149 EP 160 DI 10.1054/tube.2002.0333 PG 12 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 623UB UT WOS:000179720300001 PM 12464486 ER PT S AU Baker, H AF Baker, H BE Trombka, JI Spears, DP Solomon, PH TI Small business grants at the National Cancer Institute and National Institutes of Health SO UNATTENDED RADIATION SENSOR SYSTEMS FOR REMOTE APPLICATIONS SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT Workshop on Unattended Radiation Sensor Systems for Remote Applications CY APR 15-17, 2002 CL WASHINGTON, D.C. SP NASA, Headquarters, NASA, Goddard Space Flight Ctr, USDE, US Dept Justice, US State, Nonproliferat & Arms Control Technol Working Grp AB Ten Federal Agencies set aside 2.5% of their external research budget for US small businesses-mainly for technology research and development, including radiation sensor system developments. Five agencies also set aside another 0.15% for the Small Business Technology Transfer Program, which is intended to facilitate technology transfers from research laboratories to public use through small businesses. The second largest of these agencies is the Department of Health and Human Services, and almost all of its extramural research funds flow through the 28 Institutes and Centers of the National Institutes of Health. For information, instructions, and application forms, visit the NIH website's Omnibus Solicitation for SBIR and STTR applications. The National Cancer Institute is the largest NIH research unit and SBIR/STTR participant. NCI also issues SBIR and STTR Program Announcements of its own that feature details modified to better support its initiatives and objectives in cancer prevention, detection, diagnosis, treatment, and monitoring. C1 NCI, Biomed Imaging Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Baker, H (reprint author), NCI, Biomed Imaging Program, Div Canc Treatment & Diag, NIH, 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 0094-243X BN 0-7354-0087-3 J9 AIP CONF PROC PY 2002 VL 632 BP 266 EP 276 PG 11 WC Astronomy & Astrophysics; Remote Sensing SC Astronomy & Astrophysics; Remote Sensing GA BV40F UT WOS:000178846200030 ER PT J AU Cude, KJ Montgomery, JS Price, DK Dixon, SC Kincaid, RL Kovacs, KF Venzon, DJ Liewehr, DJ Johnson, ME Reed, E Figg, WD AF Cude, KJ Montgomery, JS Price, DK Dixon, SC Kincaid, RL Kovacs, KF Venzon, DJ Liewehr, DJ Johnson, ME Reed, E Figg, WD TI The role of an androgen receptor polymorphism in the clinical outcome of patients with metastatic prostate cancer SO UROLOGIA INTERNATIONALIS LA English DT Article DE prostate cancer; androgen receptor; CAG trinucleotide repeat ID CAG REPEAT LENGTH; PHASE-II; GENE; SURAMIN; RISK; MEN; TRANSACTIVATION; ASSOCIATION; HYPERPLASIA; WITHDRAWAL AB The androgen receptor plays a major role in the development and function of normal and malignant prostate cells. Due to the relationship of the androgen receptor and prostatic growth, it has been proposed that polymorphisms within the androgen receptor may play a role in an individual's susceptibility to developing prostate cancer. An inverse relationship has been established between a highly polymorphic trinucleotide repeat located in the first exon of the androgen receptor and the transactivaton function of the receptor. Serum samples were collected from 131 patients with histologically confirmed adenocarcinoma of the prostate, DNA was isolated, and the polymorphic CAG repeat was amplified by PCR and sequenced. The CAG repeat lengths were then compared with age at diagnosis, age at time of study, baseline log(10) PSA, Gleason score, time from diagnosis to initiation of hormonal therapy, time to progression after androgen ablation, and overall survival time. No correlation was found between CAG length and time to progression or overall survival time, but a significant correlation was found between Gleason score and CAG length suggesting that shorter CAG lengths may predict a higher histological grade of prostate cancer. Copyright (C) 2002 S. Karger AG, Basel. C1 NCI, Med Branch, Dept Clin Sci, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Med Branch, Dept Clin Sci, NIH, Bldg 10 Rm 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 25 TC 15 Z9 15 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0042-1138 J9 UROL INT JI Urol.Int. PY 2002 VL 68 IS 1 BP 16 EP 23 DI 10.1159/000048412 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 516NA UT WOS:000173558300004 PM 11803263 ER PT J AU Kusek, JW Ahrens, A Burrows, PK Clarke, HS Foster, HE Hanson, K Jacobs, SC Kirkemo, A O'Berry, K Pavlik, VN AF Kusek, JW Ahrens, A Burrows, PK Clarke, HS Foster, HE Hanson, K Jacobs, SC Kirkemo, A O'Berry, K Pavlik, VN CA MTOPS Res Grp TI Recruitment for a clinical trial of drug treatment for benign prostatic hyperplasia SO UROLOGY LA English DT Article ID DOUBLE-BLIND; FINASTERIDE; PLACEBO; MULTICENTER; STRATEGIES; TERAZOSIN; EFFICACY; MEN; TAMSULOSIN; SYMPTOMS AB Objectives. To evaluate the effectiveness of various recruitment strategies for a 6-year multicenter clinical trial of medical therapy for benign prostatic hyperplasia, the Medical Therapy of Prostatic Symptoms Trial. Methods. How participants learned about the trial was obtained during initial contact with clinical centers and at the first screening visit. The yield of randomized participants from the initial contact and first screening visit was calculated for each of the recruitment techniques. Results. During a period of 28 months, 16,723 potential trial participants made an initial contact with the 17 clinical centers, and 2931 men were randomized. An average of four initial contacts were required for each first screen visit and six per randomized participant. Newspaper (29.9%) and mail (26.7%) were the two leading sources of randomized participants. Medical sources (9.6%), radio (8.8%), and newsletters (8.4%) were also important sources. All clinical centers achieved or exceeded their recruitment goals. Conclusions. Mass mail and newspaper were the most effective recruitment techniques to enlist the interest of men with urinary symptoms for a long-term trial of drug therapy for benign prostatic hyperplasia. UROLOGY 59: 63-67, 2002. (C) 2002, Elsevier Science Inc. C1 NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20817 USA. Univ Texas, SW Med Ctr, Dept Urol, Dallas, TX USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Emory Univ, Urol Clin, Atlanta, GA 30322 USA. Yale Univ, Dept Urol Surg, New Haven, CT USA. Mayo Clin & Mayo Fdn, Dept Urol, Rochester, MN 55905 USA. Univ Maryland, Med Syst, Div Urol, Baltimore, MD 21201 USA. Metropolitan Urol Specialists, St Paul, MN USA. Univ Iowa, Dept Urol, Iowa City, IA 52242 USA. Baylor Coll Med, Baylor Prostate Ctr, Houston, TX 77030 USA. RP Kusek, JW (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, NIH, Room 617,6707 Democracy Blvd, Bethesda, MD 20817 USA. NR 28 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD JAN PY 2002 VL 59 IS 1 BP 63 EP 67 DI 10.1016/S0090-4295(01)01454-6 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 513DP UT WOS:000173362900015 PM 11796283 ER PT S AU Gainer, H Yamashita, M Fields, RL House, SB Rusnak, M AF Gainer, H Yamashita, M Fields, RL House, SB Rusnak, M BE Poulain, D Oliet, S Theodosis, D TI The magnocellular neuronal phenotype: cell-specific gene expression in the hypothalamo-neurohypophysial system SO VASOPRESSIN AND OXYTOCIN: FROM GENES TO CLINICAL APPLICATIONS SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT World Congress on Neurohypophysial Hormones CY SEP 08-12, 2001 CL BORDEAUX, FRANCE DE oxytocin; vasopressin; cell-specific gene expression; magnocellular neuron; apoptosis; biolistics; neurosecretion ID ADENOASSOCIATED VIRUS VECTOR; MESSENGER RIBONUCLEIC-ACIDS; DNA-BINDING PROPERTIES; ZINC-FINGER PROTEIN; VASOPRESSIN NEURONS; SUPRAOPTIC NUCLEUS; OXYTOCIN GENES; HYPOTHALAMONEUROHYPOPHYSEAL SYSTEM; SUPRACHIASMATIC NUCLEUS; ARGININE-VASOPRESSIN AB The magnocellular oxytocin (OT) and vasopressin (VP) neurons of the hypothalamo-neurohypophysial system are exceptional cell biolotical models to study mechanisms of cell-specific gene expression and neurosecretion of neuropeptides in the central nervous system. Single cell differential gene expression experiments have further defined these phenotypes by identifying novel and distinct regulatory molecules in these neurons. Transgenic mouse studies have led to the intergenic region (IGR) hypothesis. which states that the DNA sequences between the OT- and VP-genes contain critical enhancer sites for their cell-specific expression, The recent cloning and sequencing of the human IGR, and its comparison with the mouse IGR sequence has identified conserved sequences as putative, cell-specific enhancer sites which are now being evaluated by biolistic transfections of organotypic hypothalamic cultures. With these data, it is possible to target the gene expression of specific molecules to magnocellular neurons both in vivo and in vitro, in order to perturb and/or visualize neurosecretory and other processes. C1 NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Mol Neurosci Sect, Neurochem Lab, NIH, Bldg 36,Room 4D04, Bethesda, MD 20892 USA. NR 82 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50982-8 J9 PROG BRAIN RES PY 2002 VL 139 BP 1 EP 14 PG 14 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Neurosciences & Neurology GA BV65X UT WOS:000179669800001 PM 12436922 ER PT S AU Ecelbarger, CA Murase, T Tian, Y Nielsen, S Knepper, MA Verbalis, JG AF Ecelbarger, CA Murase, T Tian, Y Nielsen, S Knepper, MA Verbalis, JG BE Poulain, D Oliet, S Theodosis, D TI Regulation of renal salt and water transporters during vasopressin escape SO VASOPRESSIN AND OXYTOCIN: FROM GENES TO CLINICAL APPLICATIONS SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT World Congress on Neurohypophysial Hormones CY SEP 08-12, 2001 CL BORDEAUX, FRANCE DE aquaporins; SIADH; thiazide-sensitive Na-Cl cotransporter; epithelial sodium channel; hyponatremia; bumetanide-sensitive Na-K-2Cl cotransporter ID ARGININE-VASOPRESSIN; RAT-KIDNEY; ANTIDIURETIC-HORMONE; HYPONATREMIA; SODIUM; DESMOPRESSIN; AQUAPORIN-2; MECHANISMS; MANAGEMENT; SECRETION AB Hyponatremia, defined as a serum sodium < 135 mmol/l, is one of the most commonly encountered and serious electrolyte disorders of clinical medicine. The predominant cause of hyponatremia is an inappropriate elevation of circulating vasopressin levels relative to serum osmolality or the 'syndrome of inappropriate antidiuretic hormone secretion' (SIADH). Fortunately, the degree of the hyponatremia is limited by a process that counters the water-retaining action of vasopressin, namely 'vasopressin escape'. Vasopressin escape is characterized by a sudden increase in urine volume with a decrease in urine osmolality independent of circulating vasopressin levels. Until recently, little was known about the molecular mechanisms underlying escape. In the 1980s, we developed an animal model for vasopressin escape in which male Sprague-Dawley rats were infused with dDAVP, a V2-receptor-selective agonist of vasopressin, while being fed a liquid diet. Rats drank a lot of water in order to get the calories they desired. Using this model, we demonstrated that the onset of vasopressin escape (increased urine volume coupled to decreased urine osmolality) coincided temporally with a marked decrease in renal aquaporin-2 water channel) protein and mRNA expression in renal collecting ducts. This protein reduction was reversible and correlated to decreased water permeability of the collecting duct. Studies examining the mechanisms underlying AQP2 decrease revealed a decrease in V2-receptor mRNA expression and binding, as well as a decrease in cyclic AMP production in response to acute-dDAVP challenge in collecting duct suspensions from these escape animals. Additional studies showed an increase in sodium transporters of the distal tubule. These changes, hypothetically, might help to attenuate the hyponatremia. Future studies are needed to fully elucidate systemic, intra-organ, and cellular signaling responsible for the physiological phenomenon of vasopressin escape. C1 Georgetown Univ, Dept Med, Div Endocrinol & Metab, Washington, DC 20007 USA. Nagoya Univ, Dept Internal Med 1, Nagoya, Aichi, Japan. Univ Aarhus, Dept Cell Biol, Aarhus, Denmark. NHLBI, Kidney & Electrolyte Metab Lab, Mihama Ku, Bethesda, MD 20892 USA. RP Ecelbarger, CA (reprint author), Georgetown Univ, Dept Med, Div Endocrinol & Metab, Bldg D,Room 232,4000 Reservoir Rd NW, Washington, DC 20007 USA. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NIDDK NIH HHS [K01 DK002672] NR 34 TC 8 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50982-8 J9 PROG BRAIN RES PY 2002 VL 139 BP 75 EP 84 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Neurosciences SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity; Neurosciences & Neurology GA BV65X UT WOS:000179669800006 PM 12436927 ER PT J AU Murphy, BR Coelingh, K AF Murphy, BR Coelingh, K TI Principles underlying the development and use of live attenuated cold-adapted influenza A and B virus vaccines SO VIRAL IMMUNOLOGY LA English DT Review ID WILD-TYPE VIRUS; ADULT SERONEGATIVE VOLUNTEERS; RANDOMIZED CONTROLLED TRIAL; SERUM ANTIBODY-RESPONSE; CHRONICALLY ILL ADULTS; A H1N1 VIRUSES; REASSORTANT VIRUS; YOUNG-CHILDREN; AVIAN-HUMAN; DOSE-RESPONSE C1 NIAID, Infect Dis Lab, Resp Viruses Sect, NIH, Bethesda, MD 20892 USA. MedImmune Vaccines Inc, Mt View, CA USA. RP Murphy, BR (reprint author), NIAID, Infect Dis Lab, Resp Viruses Sect, NIH, Bldg 50,Rm 6517,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. NR 102 TC 109 Z9 115 U1 0 U2 11 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PY 2002 VL 15 IS 2 BP 295 EP 323 DI 10.1089/08828240260066242 PG 29 WC Immunology; Virology SC Immunology; Virology GA 563QZ UT WOS:000176268200006 PM 12081014 ER PT J AU Newman, JT Surman, SR Riggs, JM Hansen, CT Collins, PL Murphy, BR Skiadopoulos, MH AF Newman, JT Surman, SR Riggs, JM Hansen, CT Collins, PL Murphy, BR Skiadopoulos, MH TI Sequence analysis of the Washington/1964 strain of human parainfluenza virus type 1 (HPIV1) and recovery and characterization of wild-type recombinant HPIV1 produced by reverse genetics SO VIRUS GENES LA English DT Article DE human parainfluenza viruses; murine parainfluenza virus; host range; nucleotide and amino acid sequence alignments; reverse genetics; vaccine virus ID RESPIRATORY SYNCYTIAL VIRUS; HEMAGGLUTININ-NEURAMINIDASE GLYCOPROTEINS; P/C MESSENGER-RNA; SENDAI-VIRUS; P-PROTEIN; FUSION GLYCOPROTEINS; CANDIDATE VACCINE; C-PROTEINS; V-PROTEIN; ANTIGENOMIC PROMOTERS AB A complete consensus sequence was determined for the genomic RNA of human parainfluenza virus type 1 (HPIV1) strain Washington/20993/1964 (HPIV1 WASH/64), a clinical isolate that previously was shown to be virulent in adults. The sequence exhibited a high degree of relatedness to both Sendai virus, a PIV1 virus recovered from mice, and human PIV3 (HPIV3) with regard to cis-acting regulatory regions and protein-coding sequences. This consensus sequence was used to generate a full-length antigenomic cDNA and to recover a recombinant wild-type HPIV1 (rHPIV1). Interestingly, the rHPIV1 could be rescued from full-length antigenomic rHPIV1 cDNA using HPIV3 support plasmids, HPIV1 support plasmids, or a mixture thereof. The replication of rHPIV1 in vitro and in the respiratory tract of hamsters was similar to that of its biologically derived parent virus. The similar biological properties of rHPIV1 and HPIV1 WASH/64 in vitro and in vivo, together with the previous demonstration of the virulence of this specific isolate in humans, authenticates the rHPIV1 sequence as that of a wild-type virus. This rHPIV1 can now be used to study the biological properties of HPIV1 and as a substrate to introduce attenuating mutations for the generation of live-attenuated HPIV1 vaccine candidates. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Newman, JT (reprint author), NIAID, NIH, Bldg 50,Room 6511,50 South Dr,MSC 8007, Bethesda, MD 20892 USA. FU NIAID NIH HHS [AI-000087, AI-000030] NR 71 TC 36 Z9 36 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0920-8569 J9 VIRUS GENES JI Virus Genes PD JAN PY 2002 VL 24 IS 1 BP 77 EP 92 DI 10.1023/A:1014042221888 PG 16 WC Genetics & Heredity; Virology SC Genetics & Heredity; Virology GA 518TX UT WOS:000173684900009 PM 11928991 ER PT S AU Okada, Y Tsuda, Y Bryant, SD Lazarus, LH AF Okada, Y Tsuda, Y Bryant, SD Lazarus, LH BE Litwack, W TI Endomorphins and related opioid peptides SO VITAMINS AND HORMONES - ADVANCES IN RESEARCH AND APPLICATIONS, VOL 65 SE Vitamins and Hormones LA English DT Review ID G-PROTEIN ACTIVATION; SPONTANEOUS-ALTERNATION PERFORMANCE; CENTRAL-NERVOUS-SYSTEM; HUMAN BRAIN CORTEX; GUINEA-PIG ILEUM; RAT SPINAL-CORD; GAMMA-S BINDING; MORPHINE-INDUCED ANALGESIA; ITCH-ASSOCIATED RESPONSE; RECEPTOR KNOCKOUT MICE C1 Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo 6512180, Japan. Kobe Gakuin Univ, High Technol Res Ctr, Kobe, Hyogo 6512180, Japan. NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. RP Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo 6512180, Japan. NR 155 TC 34 Z9 34 U1 0 U2 2 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 BN 0-12-709865-8 J9 VITAM HORM JI Vitam. Horm. PY 2002 VL 65 BP 257 EP 279 DI 10.1016/S0083-6729(02)65067-8 PG 23 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BV84V UT WOS:000180198600009 PM 12481550 ER PT J AU Barsony, J Prufer, K AF Barsony, J Prufer, K TI Vitamin D receptor and retinoid X receptor interactions in motion SO VITAMINS AND HORMONES - ADVANCES IN RESEARCH AND APPLICATIONS, VOL 65 SE VITAMINS AND HORMONES-ADVANCES IN RESEARCH AND APPLICATIONS LA English DT Review ID THYROID-HORMONE RECEPTOR; NUCLEAR EXPORT SIGNAL; PROLIFERATOR-ACTIVATED RECEPTOR; D-RESPONSIVE ELEMENT; KAPPA-B-ALPHA; LIGAND-BINDING DOMAIN; PROMOTER TRANSCRIPTION FACTOR; GREEN FLUORESCENT PROTEIN; HETERODIMERIC DNA-BINDING; CLASS-II TRANSACTIVATOR C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Barsony, J (reprint author), 8 Ctr Dr,Room 422, Bethesda, MD 20892 USA. NR 230 TC 33 Z9 34 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0083-6729 J9 VITAM HORM PY 2002 VL 65 BP 345 EP 376 DI 10.1016/S0083-6729(02)65071-X PG 34 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA BV84V UT WOS:000180198600013 PM 12481554 ER PT J AU Eisner, EJ Zook, EG Goodman, N Macario, E AF Eisner, EJ Zook, EG Goodman, N Macario, E TI Knowledge, attitudes, and behavior of women ages 65 and older on mammography screening and Medicare: Results of a national survey SO WOMEN & HEALTH LA English DT Article DE screening mammograms; Medicare; older women ID BREAST-CANCER; REIMBURSEMENT; BARRIERS; IMPACT; COST AB Background: Compared to younger women, women 65+ will experience the greatest increase in new breast cancer cases. In 199 1, Medicare began offering partial reimbursement for screening mammography every 2 years. Methods: In 1999, the National Cancer Institute (NCI) conducted a telephone survey on breast cancer, mammography, and Medicare reimbursement with a sample of households containing women ages 65+ using random-digit-dialing. Results were weighted to provide nationally representative estimates of U.S. women 65+. NCI compared 1999 results with similar data from a 1992 AARP survey. Results: Of the 814 women surveyed, 88% had had at least one mammogram in their lifetime; within this group, 80% had received their most recent mammogram 2 years ago or less. Only 57%, however, knew about recommendations to have a mammogram every 1-2 years. Approximately one-third indicated that they were not as concerned about getting breast cancer as when they were younger, and/or that women without risk factors could be less vigilant about mammograms. More than 75% were aware of Medicare coverage, but only 58% had used Medicare to help pay for their last mammogram. Minority women were almost twice as likely to be unaware of Medicare coverage. Recommendations: (1) Highlight that breast cancer risk increases with age (and does not decline in the absence of risk factors) and communicate the correct frequency for having mammograms; (2) expand primary care physicians' roles in promoting mammography screening for women 65+; and (3) provide Medicare coverage information to older women, particularly those not taking advantage of this benefit. (C) 2002 by The Haworth Press, Inc. All rights reserved. C1 NCI, Off Commun, Bethesda, MD 20892 USA. Advisory Board Co, Nursing Leadership Acad, Washington, DC USA. RP Goodman, N (reprint author), NCI, Off Commun, Bethesda, MD 20892 USA. NR 37 TC 9 Z9 10 U1 1 U2 1 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2002 VL 36 IS 4 BP 1 EP 18 DI 10.1300/J013v36n04_01 PG 18 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 636ZY UT WOS:000180488200001 PM 12555798 ER PT B AU Cannon, RO AF Cannon, RO BE Lobo, RA Crosignani, PG Paoletti, R Brusch, F TI Reducing cardiovascular risk in postmenopausal women: Estrogen or statins? SO WOMEN'S HEALTH AND MENOPAUSE: NEW STRATEGIES - IMPROVED QUALITY OF LIFE SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT 4th International Symposium on Womens Health and Menopause CY MAY 19-23, 2001 CL WASHINGTON, D.C. SP Giovanni Lorenzini Med Fdn ID C-REACTIVE PROTEIN; HORMONE-REPLACEMENT THERAPY; CORONARY-ARTERY ATHEROSCLEROSIS; AVERAGE CHOLESTEROL LEVELS; LOW-DENSITY LIPOPROTEINS; FOLLOW-UP; VENOUS THROMBOEMBOLISM; MYOCARDIAL-INFARCTION; SECONDARY PREVENTION; NURSES HEALTH C1 NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NIH, Bldg 10 Room 7B-15,10 Ctr Dr MSC 1650, Bethesda, MD 20892 USA. NR 52 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-7149-3 J9 MED SCI SYMP SER PY 2002 VL 17 BP 123 EP 130 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BV67F UT WOS:000179729400014 ER PT B AU Brinton, LA AF Brinton, LA BE Lobo, RA Crosignani, PG Paoletti, R Brusch, F TI Environmental factors related to cancers in postmenopausal women SO WOMEN'S HEALTH AND MENOPAUSE: NEW STRATEGIES - IMPROVED QUALITY OF LIFE SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT 4th International Symposium on Womens Health and Menopause CY MAY 19-23, 2001 CL WASHINGTON, D.C. SP Giovanni Lorenzini Med Fdn ID OCCUPATIONAL RISK-FACTORS; DONE MEAT INTAKE; BREAST-CANCER; ENDOMETRIAL CANCER; CIGARETTE-SMOKING; OVARIAN-CANCER; COLORECTAL-CANCER; UNITED-STATES; LUNG-CANCER; BODY-SIZE C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Brinton, LA (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Execut Plaza S,Rm 7068,MSC 7234, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 53 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-7149-3 J9 MED SCI SYMP SER PY 2002 VL 17 BP 181 EP 188 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BV67F UT WOS:000179729400022 ER PT B AU Rossouw, JE Collins, P Wenger, N Paoletti, R AF Rossouw, JE Collins, P Wenger, N Paoletti, R BE Lobo, RA Crosignani, PG Paoletti, R Brusch, F TI Cardiovascular disease in women SO WOMEN'S HEALTH AND MENOPAUSE: NEW STRATEGIES - IMPROVED QUALITY OF LIFE SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT 4th International Symposium on Womens Health and Menopause CY MAY 19-23, 2001 CL WASHINGTON, D.C. SP Giovanni Lorenzini Med Fdn ID HORMONE REPLACEMENT THERAPY; CORONARY HEART-DISEASE; POSTMENOPAUSAL WOMEN; CONTROLLED TRIAL; RISK; ATHEROSCLEROSIS; PROGRESSION; EVENTS C1 NHLBI, Womens Hlth Initiat, Rockledge Ctr 1, NIH, Bethesda, MD 20892 USA. RP Rossouw, JE (reprint author), NHLBI, Womens Hlth Initiat, Rockledge Ctr 1, NIH, 6705 Rockledge Dr,Suite 300,MSC 7966, Bethesda, MD 20892 USA. NR 21 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-7149-3 J9 MED SCI SYMP SER PY 2002 VL 17 BP 317 EP 321 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BV67F UT WOS:000179729400037 ER PT B AU Pinn, VW Legato, MJ Manson, JAE Goertz, C AF Pinn, VW Legato, MJ Manson, JAE Goertz, C BE Lobo, RA Crosignani, PG Paoletti, R Brusch, F TI Women's health and menopause in research and clinical practice: Session summary SO WOMEN'S HEALTH AND MENOPAUSE: NEW STRATEGIES - IMPROVED QUALITY OF LIFE SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT 4th International Symposium on Womens Health and Menopause CY MAY 19-23, 2001 CL WASHINGTON, D.C. SP Giovanni Lorenzini Med Fdn C1 NIH, Off Res Womens Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-7149-3 J9 MED SCI SYMP SER PY 2002 VL 17 BP 373 EP 375 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BV67F UT WOS:000179729400044 ER PT B AU Gordon, DJ AF Gordon, DJ BE Lobo, RA Crosignani, PG Paoletti, R Brusch, F TI Women and CHD: The case for prevention SO WOMEN'S HEALTH AND MENOPAUSE: NEW STRATEGIES - IMPROVED QUALITY OF LIFE SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT 4th International Symposium on Womens Health and Menopause CY MAY 19-23, 2001 CL WASHINGTON, D.C. SP Giovanni Lorenzini Med Fdn ID CORONARY HEART-DISEASE; HEALTHY POSTMENOPAUSAL WOMEN; HORMONE REPLACEMENT THERAPY; AVERAGE CHOLESTEROL LEVELS; C-REACTIVE PROTEIN; ESTROGEN REPLACEMENT; CONTROLLED TRIAL; RISK-FACTORS; ATHEROSCLEROSIS; PROGRESSION C1 NHLBI, Bethesda, MD 20892 USA. RP Gordon, DJ (reprint author), NHLBI, 6701 Rockledge Dr,Suite 9044, Bethesda, MD 20892 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-7149-3 J9 MED SCI SYMP SER PY 2002 VL 17 BP 377 EP 385 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BV67F UT WOS:000179729400045 ER PT B AU Pinn, VW Finnegan, LP Brett, KM Chong, Y Mark, S Keenan, N Fugh-Berman, A Kaczmarczyk, J Hunter, C Browne, D Wood, SF Hollinger, KA Miller, MA Chapman, KK Clancy, CM Gross, ML Lewis, CE Groff, JY McKeown, R Herman, C Pulley, L McCreath, H Cornell, C Richter, D AF Pinn, VW Finnegan, LP Brett, KM Chong, Y Mark, S Keenan, N Fugh-Berman, A Kaczmarczyk, J Hunter, C Browne, D Wood, SF Hollinger, KA Miller, MA Chapman, KK Clancy, CM Gross, ML Lewis, CE Groff, JY McKeown, R Herman, C Pulley, L McCreath, H Cornell, C Richter, D BE Lobo, RA Crosignani, PG Paoletti, R Brusch, F TI Selected US government sponsored women's health menopause initiatives: Session summary SO WOMEN'S HEALTH AND MENOPAUSE: NEW STRATEGIES - IMPROVED QUALITY OF LIFE SE MEDICAL SCIENCE SYMPOSIA SERIES LA English DT Proceedings Paper CT 4th International Symposium on Womens Health and Menopause CY MAY 19-23, 2001 CL WASHINGTON, D.C. SP Giovanni Lorenzini Med Fdn C1 NIH, Off Res Womens Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 1-4020-7149-3 J9 MED SCI SYMP SER PY 2002 VL 17 BP 393 EP 397 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA BV67F UT WOS:000179729400047 ER PT B AU Ikeyama, S Gorospe, M Holbrook, NJ AF Ikeyama, S Gorospe, M Holbrook, NJ BE Pasquier, C TI Oxidative stress response: Links to proliferation and aging SO XI BIENNIAL MEETING OF THE SOCIETY FOR FREE RADICAL RESEARCH INTERNATIONAL LA English DT Proceedings Paper CT 11th Biennial Meeting of the Society-for-Free-Radical-Research-International CY JUL 16-20, 2002 CL PARIS, FRANCE SP Soc Free Rad Res Int ID AGE-RELATED DECLINE; REDUCED ASSOCIATION; LIFE-SPAN; PROTEIN; RESTRICTION; HEPATOCYTES; RESISTANCE; LONGEVITY; RECEPTOR; SHC C1 NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Ikeyama, S (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY BN 88-323-2716-3 PY 2002 BP 199 EP 204 PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA BW55Z UT WOS:000182408200037 ER PT B AU Elkashef, A Walsh, R Li, S Montgomery, A Bloch, D Holmes, T Vocci, F AF Elkashef, A Walsh, R Li, S Montgomery, A Bloch, D Holmes, T Vocci, F GP MONDUZZI EDITORE MONDUZZI EDITORE TI HIV risk in drug dependent population SO XIV INTERNATIONAL AIDS CONFERENCE: SOCIAL SCIENCES LA English DT Proceedings Paper CT 14th International AIDS Conference CY JUL 07-12, 2002 CL BARCELONA, SPAIN SP Univ N Carolina, Gen Clin Res Ctr, UNC Ctr AIDS Res, Natl Inst Hlth, Swiss Natl AIDS Res Program, Bristol-Myers Squibb Co, Boehringer Ingelheim, GlaxoWellcome Res & Dev, HIV Antiviral Res ID COCAINE; USERS C1 NIDA, Div Treatment Res & Dev, NIH, Bethesda, MD 20892 USA. RP Elkashef, A (reprint author), NIDA, Div Treatment Res & Dev, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU MEDIMOND S R L PI 40128 BOLOGNA PA VIA MASERATI 5, 40128 BOLOGNA, 00000, ITALY PY 2002 BP 317 EP 323 PG 7 WC Public, Environmental & Occupational Health; Social Issues; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Social Issues; Biomedical Social Sciences GA BV85R UT WOS:000180241900065 ER PT J AU Dauter, Z Nagem, RAP AF Dauter, Z Nagem, RAP TI Direct way to anomalous scatterers SO ZEITSCHRIFT FUR KRISTALLOGRAPHIE LA English DT Article ID X-RAY DATA; MACROMOLECULAR STRUCTURES; ISOMORPHOUS REPLACEMENT; CRYSTAL-STRUCTURE; PROTEIN CRYSTALS; DIFFRACTION; CRYSTALLOGRAPHY; RESOLUTION; POSITION; SULFUR AB The first step in solving macromolecular crystal structures by multi- or single-wavelength anomalous diffraction methods is the location of the anomalous scatterers. This can be done by direct methods, using either Bijvoet differences within the single data set, or anomalous scattering amplitudes estimated from measurements at several wavelengths. The calculations suggest that Bijvoet differences are equally successful for this purpose as anomalous amplitudes, F(A), which theoretically should be more suitable. The calculation of F(A) values is susceptible to the accumulation of errors contained in the individual intensity measurements at several wavelengths and in the inaccurate estimation of the anomalous atomic scattering corrections, f' and f". Direct methods often give better results at resolution lower than the full extent of the diffraction data limit. This may be attributed to the enhanced accuracy of measurements of the strong, low resolution reflections and to more effective phase refinement and propagation through Sigma(2) relations. C1 Brookhaven Natl Lab, NCI, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. Univ Estadual Campinas, Lab Nacl Luz Sincrotron, CBME, BR-13084971 Campinas, SP, Brazil. Univ Estadual Campinas, Inst Fis Gleb Wataghin, BR-13084971 Campinas, SP, Brazil. RP Dauter, Z (reprint author), Brookhaven Natl Lab, NCI, Synchrotron Radiat Res Sect, Bldg 725A-X9, Upton, NY 11973 USA. EM dauter@bnl.gov RI Nagem, Ronaldo/K-3995-2012; Inst. of Physics, Gleb Wataghin/A-9780-2017 NR 24 TC 3 Z9 3 U1 0 U2 0 PU OLDENBOURG VERLAG PI MUNICH PA LEKTORAT MINT, POSTFACH 80 13 60, D-81613 MUNICH, GERMANY SN 0044-2968 J9 Z KRISTALLOGR JI Z. Kristall. PY 2002 VL 217 IS 12 BP 694 EP 702 DI 10.1524/zkri.217.12.694.20654 PG 9 WC Crystallography SC Crystallography GA 650WD UT WOS:000181285600009 ER PT J AU Shah, BH Rasheed, H Rahman, IH Shariff, AH Khan, FL Rahman, HB Hanif, S Saeed, SA AF Shah, BH Rasheed, H Rahman, IH Shariff, AH Khan, FL Rahman, HB Hanif, S Saeed, SA TI Molecular mechanisms involved in human platelet aggregation by synergistic interaction of platelet-activating factor and 5-hydroxytryptamine SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE platelet aggregation; PAF; 5-HT; MAP kinase; synergism ID PROTEIN-COUPLED RECEPTORS; PHOSPHATIDYLINOSITOL 3-KINASE; MAP KINASE; CALCIUM; PATHWAYS; PHOSPHOLIPASE; ADRENALINE; SEROTONIN; HISTAMINE; INHIBITOR AB Our recent studies have shown that co-activation of G(q) and G(i) proteins by 5-hydroxytryptamine (5-HT) and adrenaline show synergism in human platelet aggregation. This study was conducted to examine the mechanism(s) of synergistic interaction of 5-HT and platelet activating factor (PAF) in human platelets. We show that PAF, but not 5-HT, increased platelet aggregation in a concentration-dependent manner. However, low concentrations of 5-HT (2 muM) potentiated platelet aggregation induced by subthreshold concentration of PAF (40 nM) indicating a synergistic interaction between the two agonists and this synergism was blocked by receptor antagonists to either 5-HT or PAR 5-HT also potentiated the effect of PAF on thromboxane A(2) (TXA(2)) formation and phosphorylation of extracellularly regulated mitogen-activated protein kinases (ERK1/2). The synergism of 5-HT and PAF in platelet aggregation was inhibited by calcium (Ca2+) channel blockers, verapamil and diltiazem, phospholipase C (PLC) inhibitor, U73122, cyclooxygenase (COX) inhibitor, indomethacin, and MEK inhibitor, PD98059. These data suggest that synergistic effect of 5-HT and PAF on human platelet aggregation involves activation of PLC/Ca2+, COX and MAP kinase pathways. C1 Aga Khan Univ, Dept Biol & Biomed Sci, Karachi 74800, Pakistan. NICHHD, ERRB, NIH, Bethesda, MD 20892 USA. NR 35 TC 8 Z9 8 U1 0 U2 1 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD DEC 31 PY 2001 VL 33 IS 4 BP 226 EP 233 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 509RN UT WOS:000173163600007 PM 11795484 ER PT J AU Jang, IK Lee, ZH Kim, HH Hill, JM Kim, JD Kwon, BS AF Jang, IK Lee, ZH Kim, HH Hill, JM Kim, JD Kwon, BS TI A novel leucine-rich repeat protein (LRR-1): Potential involvement in 4-1BB-mediated signal transduction SO MOLECULES AND CELLS LA English DT Article DE 4-1BB; JNK; leucine-rich repeat; NF-kappa B; TRAF2 ID TUMOR-NECROSIS-FACTOR; KAPPA-B ACTIVATION; FACTOR RECEPTOR FAMILY; CELL ANTIGEN 4-1BB; N-TERMINAL KINASE; T-CELL; ADENYLATE-CYCLASE; CYTOPLASMIC DOMAIN; RING FINGER; MEMBER AB 4-1BB, a member of the tumor necrosis factor receptor (TNFR) superfamily, is induced on CD4(+) and CD8(+) T cells upon engagement of the T cell receptor (TCR)/CD3 complex with the antigen bound to MHC. 4-1BB plays an important role in transmitting costimulatory signal during T cell activation. However, 4-1BB-mediatded signal transduction pathways have remained elusive. We conducted the yeast two-hybrid screening to identify intracellular signaling molecules that associate with 4-1BB. A novel leucine-rich repeat (LRR)-containing protein, herein named LRR-1, was found to specifically interact with the cytoplasmic domain of 4-1BB. Overexpression of LRR-1 suppressed the activation of NF-kappaB induced by 4-1BB or TNF receptor-associated factor (TRAF) 2. In addition, LRR-1 down-regulated JNK1 activity was induced by 4-1BB. These results indicate that LRR-1 negatively regulates the 4-1BB-mediated signaling cascades which result in the activation of NF-kappaB and JNK1. C1 Univ Ulsan, Immunomodulat Res Ctr, Ulsan 680749, South Korea. NIAID, NIH, Bethesda, MD 20892 USA. Chosun Univ, Natl Res Lab Bone Metab, Kwangju 501759, South Korea. Chosun Univ, Res Ctr Proteineous Mat, Kwangju 501759, South Korea. Louisiana State Univ, Hlth Sci Ctr, Dept Ophthalmol, New Orleans, LA 70112 USA. RP Kwon, BS (reprint author), Univ Ulsan, Immunomodulat Res Ctr, Ulsan 680749, South Korea. NR 43 TC 8 Z9 11 U1 0 U2 5 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD DEC 31 PY 2001 VL 12 IS 3 BP 304 EP 312 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 509VB UT WOS:000173169400005 ER PT J AU Kwon, TK Park, JW Buchholz, MA Nordin, AA AF Kwon, TK Park, JW Buchholz, MA Nordin, AA TI The expression and characterization of cyclin-dependent kinase 6 during the activation of murine G(0) T-cells SO MOLECULES AND CELLS LA English DT Article DE cdk6; cell cycle; D-type cyclin; T lymphocytes ID PROTEIN-KINASE; G1 PHASE; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTOR; NEGATIVE REGULATORS; GENE-EXPRESSION; LYMPHOCYTES-T; PHOSPHORYLATION; PROGRESSION; INHIBITOR AB Recent evidence strongly suggest that the D type cyclins with cdk4 and cdk6 form holoenzymes that regulate cell cycle events earlier in G1 than cyclin E/cdk2 complexes which functions near the G1/S transition. In human T lymphocytes cdk6 has been shown to be the initial retinoblastoma protein kinase detectable at mid G1. Following activation of splenic derived murine G(0)T-cells, cdk6, cyclin D2 and D3 specific mRNAs were detected early in G1 and reached maximal levels prior to or near G1/S. The phosphorylation of retinoblastoma protein from T-cells was detected very early in G1 and was associated mainly with cdk6/cyclin D2 complexes which accounted for a minor portion of the total cellular cdk6 contained in the cytoplasmic fraction of T-cells and mostly in the catalytically inactive form. C1 Keimyung Univ, Sch Med, Dept Immunol, Taegu 700712, South Korea. NIA, Immunol Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Kwon, TK (reprint author), Keimyung Univ, Sch Med, Dept Immunol, Taegu 700712, South Korea. NR 45 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD DEC 31 PY 2001 VL 12 IS 3 BP 313 EP 320 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 509VB UT WOS:000173169400006 PM 11804329 ER PT J AU Ju, SK Park, JH Cho, EW You, KH Kim, KL AF Ju, SK Park, JH Cho, EW You, KH Kim, KL TI Specific detection of cell surface-displayed human melanocortin 4 receptors with antibodies generated in mice SO MOLECULES AND CELLS LA English DT Article DE antibody; flow Cytometry; immunization; melanocortin-4 receptor ID MONOCLONAL-ANTIBODY; FUSION PROTEINS; OBESITY; ANTAGONIST; MUTATION AB The melanocortin-4 receptor (MC-4R) is a 7-transmembrane protein, which is involved in the central regulation of appetite and obesity. Despite the great interest in this protein, tools for detecting this molecule (as expressed on the cell surface in its native state) have been unavailable. Radioactive- or otherwise labeled ligands showed low receptor specificity to this particular melanocortin receptor isotype. Also, the antibodies were only available for epitopes that were displayed in the cytoplasm. To produce antibodies that enable the detection of this receptor (as expressed on the cell surface without disruption of the target cells), a candidate epitope was selected from the extracellular domains by a computer-aided analysis of the MC-4R secondary structure. This particular region was then recombinantly expressed in E. coli. Immunization of BALB/c mice with the recombinant proteins induced a specific immune reaction, which resulted in the production of MC-4R-specific antibodies. Enzyme-linked immunosorbent assays confirmed the specificity of these antibodies. To examine whether this tool also reacts with native cell surface-displayed MC-4R, HEK-293 cells were transfected with the human MC-4R cDNA. They were analyzed with these antibodies using Western blot and flow cytometry. Specificity and exclusion of cross-reactivity of these antibodies to other MC receptors were further confirmed by an immunofluorescence analysis of the HEK-293 cells that were transfected with other MC receptor isotypes. It is evident that with the availability of this tool, studies on the cell- and tissue-specificity, as well as the regulation mechanism of the MC-4 receptor, will be largely facilitated. C1 Chungnam Natl Univ, Coll Nat Sci, Dept Biol, Taejon 305764, South Korea. Korea Res Inst Biosci & Biotechnol, Prot Engn Lab, Taejon 305600, South Korea. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea. RP Kim, KL (reprint author), Chungnam Natl Univ, Coll Nat Sci, Dept Biol, Taejon 305764, South Korea. EM kimkl@skku.ac.kr RI Park, Jung Hyun /B-5712-2015 OI Park, Jung Hyun /0000-0002-9547-9055 NR 25 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD DEC 31 PY 2001 VL 12 IS 3 BP 321 EP 328 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 509VB UT WOS:000173169400007 PM 11804330 ER PT J AU Lee, G Kim, MG Yim, JB Hong, SH AF Lee, G Kim, MG Yim, JB Hong, SH TI Alternative transcriptional initiation and splicing of mouse Lamc2 message SO MOLECULES AND CELLS LA English DT Article DE alternative splicing; alternative transcriptional initiation; genomic structure; laminin 5; premature termination codon; promoter ID JUNCTIONAL EPIDERMOLYSIS-BULLOSA; HOMOZYGOUS NONSENSE MUTATION; THYMIC STROMAL CELLS; BETA-3 CHAIN GENE; EUKARYOTIC RIBOSOMES; LAMININ-B2 CHAIN; B2 CHAIN; EXPRESSION; CLONING; LAMB3 AB To investigate the mechanism of two forms of messages (5.1 and 2.4 kb) in mouse Lamc2, a gene encoding for the gamma2 chain of epithelial cell-specific laminin 5, we analyzed approximately 40 kb of genomic DNA containing the sequences from the first intron to the 23rd exon to the 3' untranscribed region. With the 5' rapid amplification of cDNA end (RACE) and primer extension technique using RNA from mouse kidney and thymic epithelial cells, we found that the smaller message starts at the 2895th base of the cDNA within the 19th exon. Upstream sequences of this alternative start site showed the promoter activity in the reporter assay with the secreted form of alkaline phosphatase (SEAP). We also identified a novel alternatively spliced exon (exon 19B) that includes two stop codons. These results revealed two possible additional open reading frame that are different from the previously described alternative human gamma2 peptide. Therefore, the mechanism for generating smaller message and the event of alternative splicing are quite distinct between mouse and human Lamc2, although genomic organization is highly conserved. The significance of the presence of alternative message is discussed. C1 Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. Seoul Natl Univ, Natl Creat Res Initiat Genet Reprogramming, Seoul 151742, South Korea. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Kim, MG (reprint author), Seoul Natl Univ, Inst Mol Biol & Genet, Seoul 151742, South Korea. NR 45 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD DEC 31 PY 2001 VL 12 IS 3 BP 380 EP 390 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 509VB UT WOS:000173169400016 PM 11804339 ER PT J AU Park, JH Kwon, HW Chung, HK Kim, IH Ahn, K Choi, EJ Pastan, I Choe, M AF Park, JH Kwon, HW Chung, HK Kim, IH Ahn, K Choi, EJ Pastan, I Choe, M TI A divalent recombinant immunotoxin formed by a disulfide bond between the extension peptide chains SO MOLECULES AND CELLS LA English DT Article DE antibody refolding; B3 antibody; [B3(Fab)-ext-PE38](2); cytotoxicity; divalent immunotoxin; Pseudomonas exotoxin A ID MONOCLONAL-ANTIBODY B3; PSEUDOMONAS EXOTOXIN; SINGLE-CHAIN; ANTITUMOR-ACTIVITY; FV FRAGMENT; COMPLETE REGRESSION; MUTANT FORM; CELLS; MICE; STABILIZATION AB Recombinant immunotoxin for the treatment of cancer was made by connecting toxins to 'carcinoma-specific' antibodies that selectively bind to cancer cells, then kills them without harming the normal cells. The divalent recombinant immunotoxin, [B3(Fab)-ext-PE38](2), is a derivative of B3(Fab)-PE38. B3(Fab)-PE38 was made by fusing the Fab domain of the monoclonal antibody (MAb) B3 to PE38, a truncated mutant form of Pseudomonas exotoxin (PE). In this study, B3(Fab)ext-PE38 was constructed, which has the hinge region of the B3(Fab)-PE38 extended with the peptide extension, G(4)C(G(4)S)(2), and connected to the C3 connector. The Cys residue of the extension peptide chain makes the disulfide bond between the two Fab domains. The extension sequence (ext) makes the dimerization of B3(Fab)-ext-PE38 easier to form the divalent immunotoxin, because it decreases the steric hindrance between the two PE38s. The constructed genes were expressed in E. coli as inclusion bodies. Polypeptides that were obtained from the inclusion body were refolded, and the active forms were purified. The ID50 values of the divalent molecule, [B3(Fab)-ext-PE38](2), were about 4 ng/ml on A431 cell lines, about 1 ng/ml on CRL1739 cell lines, and 5 ng/ml on MCF-7 cell lines. The [B3(Fab)-ext-PE38](2) showed about a 12-fold higher cytotoxicity on CRL1739 cell lines than B3(scFv)-PE40 did. C1 Korea Univ, Grad Sch Biotechnol, Seoul 136701, South Korea. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Choe, M (reprint author), Korea Univ, Grad Sch Biotechnol, Seoul 136701, South Korea. NR 27 TC 7 Z9 7 U1 0 U2 2 PU SPRINGER-VERLAG SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD DEC 31 PY 2001 VL 12 IS 3 BP 398 EP 402 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 509VB UT WOS:000173169400018 PM 11804341 ER PT J AU Phillips, ML Medford, N Senior, C Bullmore, ET Suckling, J Brammer, MJ Andrew, C Sierra, M Williams, SCR David, AS AF Phillips, ML Medford, N Senior, C Bullmore, ET Suckling, J Brammer, MJ Andrew, C Sierra, M Williams, SCR David, AS TI Depersonalization disorder: thinking without feeling SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE depersonalized; emotion; functional magnetic resonance imaging ID DIFFERENTIAL NEURAL RESPONSE; OBSESSIVE-COMPULSIVE DISORDER; GENERIC BRAIN ACTIVATION; CEREBRAL BLOOD-FLOW; FACIAL EXPRESSIONS; VISUAL-CORTEX; EMOTION; DISSOCIATION; CONNECTIONS; DISGUST AB Patients with depersonalization disorder (DP) experience a detachment from their own senses and surrounding events, as if they were outside observers. A particularly common symptom is emotional detachment from the surroundings. Using functional magnetic resonance imaging (fMRI), we compared neural responses to emotionally salient stimuli in DP patients, and in psychiatric and healthy control subjects. Six patients with DP, 10 with obsessive-compulsive disorder (OCD), and six volunteers were scanned whilst viewing standardized pictures of aversive and neutral scenes, matched for visual complexity. Pictures were then rated for emotional content. Both control groups rated aversive pictures as much more emotive, and demonstrated in response to these scenes significantly greater activation in regions important for disgust perception, the insula and occipito-temporal cortex, than DP patients (covarying for age, years of education and total extent of brain activation). In DP patients, aversive scenes activated the right ventral prefrontal cortex. The insula was activated only by neutral scenes in this group. Our findings indicate that a core phenomenon of depersonalization - absent subjective experience of emotion - is associated with reduced neural responses in emotion-sensitive regions, and increased responses in regions associated with emotion regulation. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Inst Psychiat, Depersonalizat Res Unit, London SE5 8AF, England. Inst Psychiat, Div Psychol Med, London SE5 8AF, England. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Cambridge CB2 2QQ, England. Inst Psychiat, Brain Image Anal Unit, London SE5 8AF, England. RP Phillips, ML (reprint author), Inst Psychiat, Depersonalizat Res Unit, 103 Denmark Hill, London SE5 8AF, England. RI Williams, Steve/D-6979-2011; Brammer, Michael/B-7128-2012; David, Anthony/C-1315-2011; Bullmore, Edward/C-1706-2012 OI Williams, Steve/0000-0003-4299-1941; Brammer, Michael/0000-0001-9800-2052; David, Anthony/0000-0003-0967-774X; Bullmore, Edward/0000-0002-8955-8283 NR 51 TC 99 Z9 100 U1 12 U2 22 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 DEC 30 PY 2001 VL 108 IS 3 BP 145 EP 160 DI 10.1016/S0925-4927(01)00119-6 PG 16 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 516EV UT WOS:000173539900001 PM 11756013 ER PT J AU Persico, MG Liguori, GL Parisi, S D'Andrea, D Salomon, DS Minchiotti, G AF Persico, MG Liguori, GL Parisi, S D'Andrea, D Salomon, DS Minchiotti, G TI Cripto in tumors and embryo development SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review DE growth factor; tumor; mammary gland; mouse embryo development; glycosylphosphatidylinositol anchor ID GROWTH-FACTOR FAMILY; DIFFERENTIAL IMMUNOHISTOCHEMICAL DETECTION; MAMMARY EPITHELIAL-CELLS; HUMAN BREAST CARCINOMAS; FACTOR-RELATED PROTEINS; EARLY MOUSE DEVELOPMENT; FACTOR-RELATED PEPTIDES; FACTOR-ALPHA; TYROSINE PHOSPHORYLATION; COLORECTAL CARCINOMAS C1 CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy. NCI, Tumor Growth Factor Sect, Basic Res Lab, NIH, Bethesda, MD 20982 USA. RP Persico, MG (reprint author), CNR, Int Inst Genet & Biophys, Via G Marconi 12, I-80125 Naples, Italy. RI Liguori, Giovanna/N-8136-2015 OI Liguori, Giovanna/0000-0002-7239-3224 NR 58 TC 14 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD DEC 28 PY 2001 VL 1552 IS 2 BP 87 EP 93 DI 10.1016/S0304-419X(01)00039-7 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA 520NU UT WOS:000173788600003 PM 11825688 ER PT J AU Takebayashi, Y Nakayama, K Kanzaki, A Miyashita, H Ogura, O Mori, S Mutoh, M Miyazaki, K Fukumoto, M Pommier, Y AF Takebayashi, Y Nakayama, K Kanzaki, A Miyashita, H Ogura, O Mori, S Mutoh, M Miyazaki, K Fukumoto, M Pommier, Y TI Loss of heterozygosity of nucleotide excision repair factors in sporadic ovarian, colon and lung carcinomas: implication for their roles of carcinogenesis in human solid tumors SO CANCER LETTERS LA English DT Article DE carcinogenesis; genome; nucleotide excision repair; loss of heterozygosity ID MICROSATELLITE INSTABILITY; MALIGNANT-TISSUES; BLADDER-CANCER; CELL CARCINOMA; GENE; EXPRESSION; CHROMOSOME-9; MUTATIONS; REGIONS AB The deficiencies of nucleotide excision repair (NER) factors are genetic diseases, xeroderma pigmentosum (XP) increasing risk of developing cancer on sun-exposed areas of the skin. However, the abnormality of NTR factors in human sporadic carcinoma remains unclear. Loss of heterozygosity (LOH) analysis for the XP, XPA, XPB, XPC, XPD, XPE, XPF, XPG and the transcription-coupled repair factor, Cockayne syndrome B (CSB) revealed that NER factors were abnormal in 62.1% of ovarian tumors (18/29), 16.7% of colon (2/12) and 22.2% lung (2/9) carcinomas. Furthermore, 13.8% of ovarian, 8.3% of colon and 22% of lung carcinomas exhibited LOH for NER factors without LOH for tumor suppressor genes such as p53, FH1T, APC, BRCA1, BRCA2 and DCC. Although both microsatellite instability and LOH of NER factors were observed in some cases, there was no strong association between them in the present study. These observations raise the possibility that alterations of NER factors may be frequent in human sporadic carcinomas. Further study should be needed to find the direct evidence of NER gene abnormalities in human sporadic carcinoma tissues. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Tohoku Univ, Inst Dev Aging & Canc, Dept Pathol, Aoba Ku, Sendai, Miyagi 9808575, Japan. Ogura Mem Hosp, Kagoshima, Japan. Tohoku Univ, Grad Sch Dent, Dept Oral & Maxillofacial Surg, Aoba Ku, Sendai, Miyagi 9808575, Japan. Toray Industries Ltd, Pharmaceut Res Labs, Kamakura, Kanagawa 2488555, Japan. Shimane Med Univ, Dept Obstet & Gynecol, Izumo, Shimane 6938501, Japan. NIH, NCI, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Takebayashi, Y (reprint author), Tohoku Univ, Inst Dev Aging & Canc, Dept Pathol, Aoba Ku, 4-1 Seiryomachi, Sendai, Miyagi 9808575, Japan. NR 29 TC 51 Z9 54 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 28 PY 2001 VL 174 IS 2 BP 115 EP 125 DI 10.1016/S0304-3835(01)00690-5 PG 11 WC Oncology SC Oncology GA 494AH UT WOS:000172255500002 PM 11689286 ER PT J AU Habas, R Kato, Y He, X AF Habas, R Kato, Y He, X TI Wnt/Frizzled activation of Rho regulates vertebrate gastrulation and requires a novel formin homology protein Daam1 SO CELL LA English DT Article ID CONVERGENT EXTENSION MOVEMENTS; SIGNALING PATHWAYS; PLANAR POLARITY; CELL-ADHESION; XENOPUS DEVELOPMENT; ACTIN CYTOSKELETON; HUMAN NEUTROPHILS; TISSUE POLARITY; MAMMALIAN-CELLS; DROSOPHILA EYE AB Wnt signaling via the Frizzled (Fz) receptor controls cell polarity and movement during development, but the molecular nature of Wnt/Fz polarity signal transduction remains poorly defined. Here we report that in human cells and during Xenopus embryogenesis, Wnt/Fz signaling activates the small GTPase Rho, a key regulator of cytoskeleton architecture. Wnt/Fz activation of Rho requires the cytoplasmic protein Dishevelled (Dvl) and a novel Formin homology protein Daam1. Daam1 binds to both DvI and Rho, and mediates Wnt-induced DvI-Rho complex formation. Inhibition or depletion of Daam1 prevents Wnt/Fz activation of Rho and of Xenopus gastrulation, but not of beta -catenin signaling. Our study illustrates a molecular pathway from Wnt/Fz signaling to Rho activation in cell polarity signal transduction. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol,Div Neurosci, Boston, MA 02115 USA. NICHHD, Genet Mol Lab, Bethesda, MD 20892 USA. RP He, X (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dept Neurol,Div Neurosci, Boston, MA 02115 USA. NR 61 TC 476 Z9 482 U1 1 U2 10 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 28 PY 2001 VL 107 IS 7 BP 843 EP 854 DI 10.1016/S0092-8674(01)00614-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 507JQ UT WOS:000173024200006 PM 11779461 ER PT J AU Lukashev, D Caldwell, C Ohta, A Chen, P Sitkovsky, M AF Lukashev, D Caldwell, C Ohta, A Chen, P Sitkovsky, M TI Differential regulation of two alternatively spliced isoforms of hypoxia-inducible factor-1 alpha in activated T lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; MESSENGER-RNA EXPRESSION; FACTOR 1-ALPHA; FACTOR GENE; TRANSCRIPTIONAL REGULATION; DEGRADATION DOMAIN; O-2 HOMEOSTASIS; FACTOR-I; CELLS; RECEPTOR AB Cell adaptation to hypoxia is partially accomplished by hypoxia-inducible transcription factor-1 (HIF-1). Here we report the hypoxia-independent up-regulation of HIF-1alpha subunit in antigen receptor-activated T cells. This is explained by a selective up-regulation of alternatively spliced mRNA isoform I.1 that encodes the HIF-1alpha protein without the first 12 N-terminal amino acids. We show that both short (I.1) and long (I.2) HIF-1alpha isoforms display similar DNA binding and transcriptional activities. Major differences were observed between these two HIF-1alpha isoforms in their expression patterns with respect to the resting and activated T lymphocytes in hypoxic and normoxic conditions. The T cell antigen receptor (TCR)-triggered activation of normal ex vivo T cells and differentiated T cells results in up-regulation of expression of I.1 isoform of HIF-1alpha mRNA without an effect on constitutive I.2 HIF-1alpha mRNA expression. The accumulation of I.1 HIF-1alpha mRNA isoform in T lymphocytes is also demonstrated during cytokine-mediated inflammation in vivo, suggesting a physiological role of short HIF-1alpha isoform in activated lymphocytes. The TCR-triggered, protein kinase C and Ca2+/calcineurin-mediated HIF-1alpha I.1 mRNA induction is protein synthesis-independent, suggesting that the HIF-1alpha I.1 gene is expressed as an immediate early response gene. Therefore, these data predict a different physiological role of short and long isoforms of HIF-1alpha in resting and activated cells. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sitkovsky, M (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Rm 11N311, Bethesda, MD 20892 USA. RI Lukashev, Dmitriy/F-8133-2010; OI Caldwell, Charles/0000-0003-1692-4550 NR 61 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 48754 EP 48763 DI 10.1074/jbc.M104782200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100020 PM 11602577 ER PT J AU Choi, S Kim, HJ Ko, YS Jeong, SW Kim, YI Simonds, WF Oh, JW Nah, SY AF Choi, S Kim, HJ Ko, YS Jeong, SW Kim, YI Simonds, WF Oh, JW Nah, SY TI G alpha(q/11) coupled to mammalian phospholipase C beta 3-like enzyme mediates the ginsenoside effect on Ca2+-activated Cl- current in the Xenopus oocyte SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADRENAL CHROMAFFIN CELLS; CA2+ CHANNELS; G-PROTEIN; CATECHOLAMINE SECRETION; ALPHA-SUBUNIT; BETA; RECEPTOR; ACTIVATION AB Recently we demonstrated that ginsenosides, the active ingredients of Panax ginseng, enhanced Ca2+-activated Cl- current in the Xenopus oocyte through a signal transduction mechanism involving the activation of pertussis toxin-insensitive G protein and phospholipase C (PLC). However, it has not yet been determined precisely which G protein subunit(s) and which PLC isoform(s) participate in the ginsenoside signaling. To provide answers to these questions, we investigated the changes in ginsenoside effect on the Cl- current after intraoocyte injections of the cRNAs coding various G protein subunits, a regulator of G protein signaling (RGS2), and Gbetagamma-binding proteins. In addition, we examined which of mammalian PLCbeta1-3 antibodies injected into the oocyte inhibited the action of ginsenosides on the Cl- current. Injection of Galpha(q) or Galpha(11) cRNA increased the basal Cl- current recorded 48 h after, and it further prevented ginsenosides from enhancing the Cl- current, whereas Galpha(12) and Galpha(oA) cRNA injection had no significant effect. The changes following Galpha(q) cRNA injection were prevented when Gbeta(1)gamma(2) and Galpha(q) subunits were co-expressed by simultaneous injection of the cRNAs coding these subunits. Injection of cRNA coding Galpha(q)Q209L, a constitutively active mutant that does not bind to Gbetagamma, produced effects similar to those of Galpha(q) cRNA injection. The effects of Galpha(q)Q209L cRNA injection, however, were not prevented by co-injection of Gbeta(1)gamma(2) cRNA. Injection of the cRNA coding RGS2, which interacts most selectively with Galpha(q/11) among various identified RGS isoforms and stimulates the hydrolysis of GTP to GDP in active GTP-bound Galpha subunit, resulted in a severe attenuation of ginsenoside effect on the Cl- current. Finally, antibodies against PLCbeta3, but not -beta1 and -beta2, markedly attenuated the ginsenoside effect examined at 3-h postinjection. These results suggest that Galpha(q/11), coupled to mammalian PLC beta3-like enzyme mediates ginsenoside effect on Ca2+-activated Cl- current in the Xenopus oocyte. C1 Chonnam Natl Univ, Coll Vet Med, Natl Res Lab Study Ginseng Signal Transduct, Kwangju 500757, South Korea. Chonnam Natl Univ, Coll Vet Med, Dept Physiol, Kwangju 500757, South Korea. Korea Univ, Coll Med, Dept Physiol, Seoul 136701, South Korea. Korea Univ, Coll Med, Neurosci Res Inst, Seoul 136701, South Korea. Yonsei Univ, Wonju Coll Med, Dept Physiol, Seoul 136701, South Korea. NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA. Univ Alabama, Dept Cell Biol, Birmingham, AL 35294 USA. RP Nah, SY (reprint author), Chonnam Natl Univ, Coll Vet Med, Natl Res Lab Study Ginseng Signal Transduct, Kwangju 500757, South Korea. NR 23 TC 30 Z9 31 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 48797 EP 48802 DI 10.1074/jbc.M104346200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100025 PM 11673455 ER PT J AU Ishima, R Ghirlando, R Tozser, J Gronenborn, AM Torchia, DA Louis, JM AF Ishima, R Ghirlando, R Tozser, J Gronenborn, AM Torchia, DA Louis, JM TI Folded monomer of HIV-1 protease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRIPLE-RESONANCE NMR; RETROVIRAL PROTEASES; HUMAN-IMMUNODEFICIENCY; DRUG-RESISTANCE; INHIBITORS; KINETICS; SPECTROSCOPY; PROTEINASES; FLEXIBILITY; RELAXATION AB The mature human immunodeficiency virus type 1 protease rapidly folds into an enzymatically active stable dimer, exhibiting an intricate interplay between structure formation and dimerization. We now show by NMR and sedimentation equilibrium studies that a mutant protease containing the R87K substitution (PRR87K) within the highly conserved Gly(86)-Arg(87)-Asn(88) sequence forms a monomer with a fold similar to a single subunit of the dimer. However, binding of the inhibitor DMP323 to PRR87K produces a stable dimer complex. Based on the crystal structure and our NMR results, we postulate that loss of specific interactions involving the side chain of Arg(87) destabilizes PRR87K by perturbing the inner C-terminal beta-sheet (residues 96-99 from each monomer), a region that is sandwiched between the two beta-strands formed by the N-terminal residues (residues 1-4) in the mature protease. We systematically examined the folding, dimerization, and catalytic activities of mutant proteases comprising deletions of either one of the terminal regions (residues 1-4 or 96-99) or both. Although both N- and C-terminal P-strands were found to contribute to dimer stability, our results indicate that the inner C-terminal strands are absolutely essential for dimer formation. Knowledge of the monomer fold and regions critical for dimerization may aid in the rational design of novel inhibitors of the protease to overcome the problem of drug resistance. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDCR, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. RP Louis, JM (reprint author), NIDDK, Phys Chem Lab, NIH, Rm 411,Bldg 5, Bethesda, MD 20892 USA. EM jmlouis@helix.nih.gov RI Tozser, Jozsef/A-7840-2008; Ghirlando, Rodolfo/A-8880-2009; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729; Gronenborn, Angela M/0000-0001-9072-3525 NR 34 TC 71 Z9 71 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 49110 EP 49116 DI 10.1074/jbc.M108136200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100065 PM 11598128 ER PT J AU Wang, JH Guan, E Roderiquez, G Calvert, V Alvarez, R Norcross, MA AF Wang, JH Guan, E Roderiquez, G Calvert, V Alvarez, R Norcross, MA TI Role of tyrosine phosphorylation in ligand-independent sequestration of CXCR4 in human primary monocytes-macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; FOCAL ADHESION KINASE; HEMATOPOIETIC PROGENITOR CELLS; CHEMOKINE RECEPTOR CXCR4; HUMAN T-LYMPHOCYTES; SIGNAL-TRANSDUCTION; HIV-1 INFECTION; CCR5 EXPRESSION; BETA-ARRESTIN; BETA(2)-ADRENERGIC RECEPTOR AB The chemokine stromal cell-derived factor (SDF)-1 and its receptor, CXCR4, play important roles in human immunodeficiency virus type 1 (HIV-1) pathophysiology, leukocyte trafficking, inflammation, hematopoiesis, embryogenesis, angiogenesis, and cancer metastasis. The effects of cytokines on the regulation of CXCR4 function were investigated in human primary monocytes-macrophages. The expression of functional CXCR4 on the cell surface was demonstrated by the detection of ligand-in-induced Ca2+ mobilization, chemotaxis, and ligand-induced receptor endocytosis. Surface CXCR4 expression was down-regulated by cytokines interleukin-4 (IL-4), IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and up-regulated by IL-10 and transforming growth factor-beta1. Down-regulation was mediated post-translationally, in the absence of protein degradation, through an endocytotic mechanism. In contrast to SDF-1alpha-induced CXCR4 endocytosis, cytokine-induced endocytosis of this receptor was independent of actin filament polymerization. GM-CSF increased the expression of G protein-coupled receptor kinase 3 (GRK3), beta-arrestin-1, Pyk2, and focal adhesion kinase (FAK). Cytokine treatment also increased the total and tyrosine-specific phosphorylation of CXCR4 as well as the phosphorylation of FAK on tyrosine 397. It also induced the formation of GRK3.CXCR4 or FAK.CXCR4 complexes. Infection of macrophages by primary R5X4 and X4 isolates of HIV-1 was inhibited by IL-4, IL-13, and GM-CSF, an effect that was associated with down-regulation of surface CXCR4 expression. These data indicate that ligand-dependent and ligand-independent endocytoses of CXCR4 are mediated by different mechanisms. Cytokine-induced endocytosis of chemokine receptors may be of therapeutic value in HIV-1 infection, inflammation, tumor metastasis, and defective hematopoiesis. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Lab Gene Regulat, Bethesda, MD 20892 USA. RP Norcross, MA (reprint author), US FDA, NIH,Ctr Biol Evaluat & Res, Div Therapeut Prot, Lab Gene Regulat, Bldg 29B,Rm 4E12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 67 TC 58 Z9 59 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 49236 EP 49243 DI 10.1074/jbc.M108523200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100081 PM 11668182 ER PT J AU Protchenko, O Ferea, T Rashford, J Tiedeman, J Brown, PO Botstein, D Philpott, CC AF Protchenko, O Ferea, T Rashford, J Tiedeman, J Brown, PO Botstein, D Philpott, CC TI Three cell wall mannoproteins facilitate the uptake of iron in Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR CHARACTERIZATION; TRANSCRIPTIONAL CONTROL; FERRIC REDUCTASE; FET3 GENE; YEAST; TRANSPORT; COPPER; IDENTIFICATION; SIDEROPHORES; PROTEIN AB Analysis of iron-regulated gene expression in Saccharomyces cerevisiae using cDNA microarrays has identified three putative cell wall proteins that are directly regulated by Aft1p, the major iron-dependent transcription factor in yeast. FIT1, FIT2, and FIT3 (for facilitator of iron transport) were more highly expressed in strains grown in low concentrations of iron and in strains in which AFT1-1(up), a constitutively active allele of AFT1, was expressed. Northern blot analysis confirmed that FIT1, FIT2, and FIT3 mRNA transcript levels were increased 60-230-fold in response to iron deprivation in an Aft1p-dependent manner. Fit1p was localized exclusively to the cell wall by indirect immunofluorescence. Deletion of the FIT genes, individually or in combination, resulted in diminished uptake of iron bound to the siderophores ferrioxamine B and ferrichrome, without diminishing the uptake of ferric iron salts, or the siderophores triacetylfusarinine C and enterobactin. FIT-deletion strains exhibited increased expression of Aft1p target genes as measured by a FET3-lacZ reporter gene or by Arn1p Western blotting, indicating that cells respond to the absence of FIT genes by up-regulating systems of iron uptake. Aft1p activation in FIT-deleted strains occurred when either ferrichrome or ferric salts were used as sources of iron during growth, suggesting that the FIT genes enhance uptake of iron from both sources. Enzymatic digestion of the cell wall resulted in the release of significant amounts of iron from cells, and the relative quantity of iron released was reduced in FIT-deletion strains. Fit1p, Fit2p, and Fit3p may function by increasing the amount of iron associated with the cell wall and periplasmic space. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Howard Hughes Med Inst, Stanford, CA 94305 USA. RP NIDDK, Liver Dis Sect, NIH, Bldg 10,Rm 9B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM carolinep@intra.niddk.nih.gov NR 44 TC 95 Z9 101 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 28 PY 2001 VL 276 IS 52 BP 49244 EP 49250 DI 10.1074/jbc.M109220200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 522XK UT WOS:000173922100082 PM 11673473 ER PT J AU Di Palma, F Pellegrino, R Noben-Trauth, K AF Di Palma, F Pellegrino, R Noben-Trauth, K TI Genomic structure, alternative splice forms and normal and mutant alleles of cadherin 23 (Cdh23) SO GENE LA English DT Article DE waltzer; deafness; Usher syndrome type 1D; age-related hearing loss ID CELL-ADHESION; IDENTIFICATION; CALCIUM; MORPHOGENESIS; SUPERFAMILY AB Cadherins are components of adherens junctions and play critical roles during embryogenesis and organogenesis. They interact through the formation of anti-parallel dimers to mediate cell adhesion, migration and compaction. We recently showed that cadherins also play important roles in the inner ear; mutations in cadherin 23 (Cdh23) disrupt stereocilia organization on hair cells leading to deafness and vestibular dysfunction in waltzer mice. Here we extend our initial study on the structure and function of Cdh23. The mouse Cdh23 locus is comprised of two 5'-untranslated exons and 69 coding exons; together they cover a genomic distance of at least 350 kb. Amino acid sequence alignments and secondary structure prediction suggest that Cdh23 ectodomains adopt a conformation similar to the classic cadherins. Nucleotide sequence analysis of six alleles of waltzer reveals a strong correlation between loss of function mutations and the deafness/ waltzing phenotype. A Cdh23 transcript with a spliced exon 68 is the predominantly expressed isoform in the organ of Corti. Age-related hearing loss (Ahl) is a non-syndromic trait in common inbred strains of mice associated with the Ahl locus on chromosome 10. Sequence comparison of Cdh23 between C57BL/6J and CAST/Ei identified ten amino acid polymorphisms. In the 5'- and 3'-untranslated regions we detected 11 single nucleotide polymorphisms. None of these sequence changes correlate with the Ahl phenotype. Our results provide the necessary framework for further characterization of Cdh23-related hearing loss in mice. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, Rockville, MD 20850 USA. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, Mol Biol Lab, NIH, 5 Res Court, Rockville, MD 20850 USA. FU NIDCD NIH HHS [DC00036-02] NR 28 TC 51 Z9 53 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 27 PY 2001 VL 281 IS 1-2 BP 31 EP 41 DI 10.1016/S0378-1119(01)00761-2 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 516UB UT WOS:000173574200004 PM 11750125 ER PT J AU Lyons, SE Shue, BC Lei, L Oates, AC Zon, LI Liu, PP AF Lyons, SE Shue, BC Lei, L Oates, AC Zon, LI Liu, PP TI Molecular cloning, genetic mapping, and expression analysis of four zebrafish c/ebp genes SO GENE LA English DT Article DE Danio rerio; hematopoietic; CCAAT/enhancer binding protein; liver; adipocyte ID CCAAT/ENHANCER-BINDING-PROTEIN; LEUCINE ZIPPER; ALPHA; TRANSCRIPTION; MICE; GENOME; MACROPHAGES; DEFICIENT; COMMON; FAMILY AB The CCAAT/enhancer binding protein family (C/EBP) are transcription factors that play integral roles in the development and function of many organ systems, including hematopoietic cells, adipose tissues, and liver. We have identified and characterized putative zebrafish orthologs of mammalian C/EBP alpha, beta, gamma, and delta using low-stringency hybridization screening and computer searches of the GenBank EST database. c/ebpa and g were mapped within 1 cM of each other on linkage group (LG) 7, syntenic with human CEBPA and G genes on chromosome 19. c/ebpb was mapped to LG8, and c/ebpd was mapped to LG24, on the same LG as a recently identified unique c/ebp in zebrafish, c/ebp1. The mapping of these genes established new syntenic relationships between LG8 and human chromosome 20, extended existing synteny between LG7 and human chromosome 19, and confirmed the synteny between LG24 and human chromosome 8. In addition, these syntenies between zebrafish and human chromosomes are also conserved in the mouse genome. To characterize the expression of these genes, RNA in situ hybridization in embryos of wild type and a hematopoietic mutant, cloche, was performed. The results showed that zebrafish c/ebpa, b, g, and d were expressed in many embryonic tissues. c/ebpa and b were expressed in a subset of hematopoietic cells in a region consistent with myeloid expression. In addition, there was expression of c/ebpa and b in the liver and c/ebpa, b, and d in regions of the gastrointestinal tract. The expression of the c/ebps may serve as important markers for analysis of myelopoiesis, hepatic development, and other developmental processes in the future. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Liu, PP (reprint author), NHGRI, NIH, 49 Convent Dr,Room 3A18, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 28 TC 47 Z9 47 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 27 PY 2001 VL 281 IS 1-2 BP 43 EP 51 DI 10.1016/S0378-1119(01)00774-0 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 516UB UT WOS:000173574200005 PM 11750126 ER PT J AU Dalakas, MC Fujii, M Li, M Lutfi, B Kyhos, J McElroy, B AF Dalakas, MC Fujii, M Li, M Lutfi, B Kyhos, J McElroy, B TI High-dose intravenous immune globulin for stiff-person syndrome SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID GLUTAMIC-ACID DECARBOXYLASE; DIABETES-MELLITUS; AUTOANTIBODIES; IMMUNOGLOBULIN; DISEASES; THERAPY AB Background Stiff-person syndrome is a disabling central nervous system disorder with no satisfactory treatment that is characterized by muscle rigidity, episodic muscle spasms, high titers of antibodies against glutamic acid decarboxylase (GAD65), and a frequent association with autoimmune disorders. Because stiff-person syndrome is most likely immune-mediated, we evaluated the efficacy of intravenous immune globulin. Methods We assigned 16 patients who had stiff-person syndrome and anti-GAD65 antibodies, in random order, to receive intravenous immune globulin or placebo for three months, followed by a one-month washout period and then by three months of therapy with the alternative agent. Efficacy was judged by improvements in scores on the distribution-of-stiffness index and heightened-sensitivity scale from base line (month 1) to the second and third month of each treatment phase. Direct and carryover effects of treatment were compared in the two groups. Results Among patients who received immune globulin first, stiffness scores decreased significantly (P=0.02) and heightened-sensitivity scores decreased substantially during immune globulin therapy but rebounded during placebo administration. In contrast, the scores in the group that received placebo first remained constant during placebo administration but dropped significantly during immune globulin therapy (P=0.01). When the data were analyzed for a direct and a first-order carryover effect, there was a significant difference in stiffness scores (P=0.01 and P<0.001, respectively) between the immune globulin and placebo groups, and immune globulin therapy had a significant direct treatment effect on sensitivity scores (P=0.03). Eleven patients who received immune globulin became able to walk more easily or without assistance, their frequency of falls decreased, and they were able to perform work-related or household tasks. The duration of the beneficial effects of immune globulin varied from six weeks to one year. Anti-GAD65 antibody titers declined after immune globulin therapy but not after placebo administration. Conclusions Intravenous immune globulin is a well-tolerated and effective, albeit costly, therapy for patients with stiff-person syndrome and anti-GAD65 antibodies. (N Engl J Med 2001;345:1870-6.) Copyright (C) 2001 Massachusetts Medical Society. C1 NINCDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINCDS, Neuromuscular Dis Sect, NIH, Bldg 10,Rm 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 30 TC 169 Z9 173 U1 0 U2 8 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 27 PY 2001 VL 345 IS 26 BP 1870 EP 1876 DI 10.1056/NEJMoa01167 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 505TY UT WOS:000172932700002 PM 11756577 ER PT J AU Botkin, JR Clayton, E Nelson, R Wilfond, B Munger, MA AF Botkin, JR Clayton, E Nelson, R Wilfond, B Munger, MA TI Salmeterol and inhaled corticosteroids in patients with persistent asthma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. Univ Utah, Dept Med Eth, Salt Lake City, UT USA. Vanderbilt Univ, Dept Pediat, Nashville, TN USA. Childrens Hosp Philadelphia, Dept Anesthesia, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. NHGRI, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Utah, Dept Pharm Practice, Salt Lake City, UT 84112 USA. RP Botkin, JR (reprint author), Univ Utah, Dept Pediat, Salt Lake City, UT 84112 USA. NR 4 TC 2 Z9 2 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 DEC 26 PY 2001 VL 286 IS 24 BP 3075 EP 3075 DI 10.1001/jama.286.24.3075 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 505QM UT WOS:000172927100013 PM 11754662 ER PT J AU Miller, FG Shorr, AF AF Miller, FG Shorr, AF TI Salmeterol and inhaled corticosteroids in patients with persistent asthma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Pulm & Crit Care Med, Washington, DC 20307 USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 26 PY 2001 VL 286 IS 24 BP 3075 EP 3076 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 505QM UT WOS:000172927100014 PM 11754663 ER PT J AU Zametkin, AJ Alter, MR Yemini, T AF Zametkin, AJ Alter, MR Yemini, T TI Suicide in teenagers - Assessment, management, and prevention SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID TRYPTOPHAN-HYDROXYLASE GENE; ADOLESCENT SUICIDE; DEPRESSED-PATIENTS; MAJOR DEPRESSION; POLYMORPHISM; BEHAVIOR; ATTEMPTERS; VICTIMS; FAMILY; AUGMENTATION AB Adolescents who kill themselves invariably have an underlying psychiatric disorder. Biological markers are not yet clinically useful for identifying adolescents at risk, and there is a paucity of research data on the effectiveness of behavioral intervention for suicidal teenagers. A case of a 16-year-old scholar and athlete is presented to illustrate how multiple risk factors and a family diathesis often go undetected, resulting in tragic consequences. Psychiatric, familial, genetic, and social risk factors of adolescent suicide are reviewed, and the efficacy of lithium and antidepressant pharmacotherapy in reducing suicide rates is discussed. The importance of screening adolescent patients for depression is emphasized. Although teenage suicide is rare and hard to predict, identifying and treating adolescents at risk is essential to further reduce teenage suicide. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. US PHS, Washington, DC 20201 USA. RP Zametkin, AJ (reprint author), NIMH, Mood & Anxiety Disorders Program, 3N238 Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 24 Z9 25 U1 7 U2 11 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 DEC 26 PY 2001 VL 286 IS 24 BP 3120 EP 3125 DI 10.1001/jama.286.24.3120 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 505QM UT WOS:000172927100030 PM 11754678 ER PT J AU Cohen, RM Small, C Lalonde, F Friz, J Sunderland, T AF Cohen, RM Small, C Lalonde, F Friz, J Sunderland, T TI Effect of apolipoprotein E genotype on hippocampal volume loss in aging healthy women SO NEUROLOGY LA English DT Article ID TEMPORAL-LOBE ATROPHY; MILD COGNITIVE IMPAIRMENT; EARLY ALZHEIMERS-DISEASE; E EPSILON-4 ALLELE; ENTORHINAL CORTEX; MEMORY; DEMENTIA; MRI; RISK; AMYGDALA AB Objective: To determine whether the presence of a single epsilon4 allele of the APOE gene is associated with an increased rate of hippocampal volume loss or decline in cognition in healthy women in their sixth decade of life. Methods: Nine APOE-epsilon4 allele-negative (mean age +/- SD, 60.6 +/- 10.2 years) and 16 APOE-epsilon4 allele-positive (mean age +/- SD 55.1 +/- 6.0 years) healthy women underwent neurocognitive testing and MRI at the time of entry into the study (baseline) and 2 years later. Neurocognitive testing consisted of the Buschke-Fuld Free Recall, verbal fluency tests, the Rey Figure Test, the Wechsler Memory Scale-Revised, and the Wechsler Adult Intelligence Survey-Revised Block Design. Hippocampal volume determinations were based on manual outlining of sagittal slices aided by axial, coronal, and three-dimensional views of high-resolution 124-slice whole-brain scans; the scans were obtained with a 1.5-tesla scanner using a T1-weighted three-dimensional gradient echo sequence with RF spoiling (TR/TE/flip angle, 24 msec/3 msec/30 degrees). Results: The percent change in hippocampal volume per year was greater in the A-POE-epsilon4 allele-positive group (mean +/- SD, 2.32 +/- 1.75%) than in the APOE-epsilon4 allele-negative group (mean +/- SD, 0.77 +/- 1.02%; t = 2.41; p < 0.03, two-tailed test). There were no significant differences between the two groups in terms of any of the cognitive measures, and hippocampal volume loss was not correlated with changes in any of the above-mentioned cognitive measures. Conclusions: The presence of a single APOE-epsilon4 allele is associated with an increased rate of hippocampal volume loss in healthy women in their sixth decade of life that is not related to any detectable memory changes. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Cohen, RM (reprint author), NIH, Geriatr Psychiat Branch, Bldg 10,Room 3N218,10 Ctr Dr,MSC 1274, Bethesda, MD 20892 USA. NR 50 TC 108 Z9 110 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 26 PY 2001 VL 57 IS 12 BP 2223 EP 2228 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 505BP UT WOS:000172891500013 PM 11756601 ER PT J AU Wlodawer, A Li, M Gustchina, A Dauter, Z Uchida, K Oyama, H Goldfarb, NE Dunn, BM Oda, K AF Wlodawer, A Li, M Gustchina, A Dauter, Z Uchida, K Oyama, H Goldfarb, NE Dunn, BM Oda, K TI Inhibitor complexes of the Pseudomonas serine-carboxyl proteinase SO BIOCHEMISTRY LA English DT Article ID SUBSTRATE-SPECIFICITY; SUBSITE PREFERENCES; TRANSITION-STATE; SUBTILISIN; IDENTIFICATION; PURIFICATION; KUMAMOLYSIN; PROKARYOTES; REFINEMENT; MECHANISM AB Crystal structures of the serine-carboxyl proteinase from Pseudomonas sp. 101 (PSCP), complexed with a number of inhibitors, have been solved and refined at high- to atomic-level resolution. All of these inhibitors (tyrostatin, pseudo-tyrostatin, AcIPF, AcIAF, and chymostatin, as well as previously studied iodotyrostatin and pseudo-iodotyrostatin) make covalent bonds to the active site Ser287 through their aldehyde moieties, while their side chains occupy subsites S1-S4 of the enzyme. The mode of binding of the inhibitors is almost identical for their P1 and P2 side chains, while significant differences are observed for P3 and P4 (if present). Kinetic parameters for the binding of these nanomolar inhibitors to PSCP have been established and correlated with the observed mode of binding. The preferences of this enzyme for a larger side chain in P2 as well as Tyr or Phe in P1 are explained by the size, shape, and characteristics of the S2 and S1 regions of the protein structure, respectively. Networks of hydrogen bonds involving glutamic and aspartic acids have been analyzed for the atomic-resolution structure of the native enzyme. PSCP contains a calcium-binding site that consists of Asp328, Asp348, three amide carbonyl groups, and a water molecule, in almost perfect octahedral coordination. The presence of Ca2+ cation is necessary for the activity of the enzyme. C1 NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Upton, NY 11973 USA. Brookhaven Natl Lab, NSLS, Upton, NY 11973 USA. Teikyo Univ, Sch Sci & Engn, Dept Biosci, Utsunomiya, Tochigi 3208551, Japan. Kyoto Inst Technol, Fac Text Sci, Dept Appl Biol, Sakyo Ku, Kyoto 6068585, Japan. Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000]; NIAID NIH HHS [AI28571]; NIDDK NIH HHS [DK18865] NR 32 TC 43 Z9 44 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 25 PY 2001 VL 40 IS 51 BP 15602 EP 15611 DI 10.1021/bi011817n PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 509NF UT WOS:000173153300017 PM 11747435 ER PT J AU Fetsch, PA Steinberg, SM Riker, AI Marincola, FM Abati, A AF Fetsch, PA Steinberg, SM Riker, AI Marincola, FM Abati, A TI Melanoma antigen expression in serial fine-needle aspiration samples in patients with metastatic malignant melanoma participating in immunotherapy clinical trials - A preliminary look SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GEORGIA SP US & Canadian Acad Pathol DE melanoma; immunotherapy; MART-1; HMB-45; immunocytochemistry; fine-needle aspiration ID CYTOLYTIC T-LYMPHOCYTES; TUMOR-INFILTRATING LYMPHOCYTES; HLA-A2 MELANOMAS; IN-VIVO; GENE; MART-1; IDENTIFICATION; VACCINATION; VITILIGO; HMB-45 AB BACKGROUND. MART-1 and gp100 currently are utilized as targets in immunotherapy protocols for metastatic malignant melanoma (MMM). Enrollment of patients into ongoing peptide vaccination trials at the National Cancer Institute includes immunophenotyping of samples of metastatic lesions obtained by fine-needle aspiration (FNA). As therapy progresses, immunocytochemistry is performed on serial FNAs of metastatic lesions to monitor changes in antigen expression during treatment. It is theorized that antigen expression of melanoma cells may be diminished because of selective immunodestruction of tumor cells, or perhaps intentionally, to escape immunosurveillance. METHODS. Thirty-eight lesions from 33 patients were serially monitored for the expression of gp100 (clone HMB-45) and MART-1 (clone M2-7C10), using an avidin-biotin peroxidase technique. The staining intensity of tumor cells was scored on a scale of 0 to 3+, with the proportion of positive cells categorized as less than 25%, 25-50%, 50-75%, and greater than 75%. All lesions were examined within approximately 2 months after the start of peptide vaccination, providing a consistent timepoint for analysis. RESULTS. Using the Wilcoxon signed rank test, the authors found that there were no significant changes from baseline compared with 2 months later for quantitative antigen expression of HMB-45 or MART-1. However, there was a trend toward a decline in staining intensity of tumor cells for HMB-45. CONCLUSIONS. preliminary results evaluating antigen expression during selective immunotherapy indicate a trend in the decline of staining intensity of tumor cells to HMB-45. Thus, although other studies have shown that peptide-based immunotherapy results in immune selection, this does not hinder the diagnostic utility of antibodies to HMB-45 and MART-1 in FNA samples of MMM. Cancer (Cancer Cytopathol) 2001;93:409-14. (C) 2001 American Cancer Society. C1 NCI, Cytopathol Sect, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Abati, A (reprint author), NCI, Cytopathol Sect, NIH, Bldg 10,Room 2A19, Bethesda, MD 20892 USA. RI Riker, Adam/A-6065-2011 NR 23 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 2001 VL 93 IS 6 BP 409 EP 414 DI 10.1002/cncr.10138 PG 6 WC Oncology; Pathology SC Oncology; Pathology GA 504BZ UT WOS:000172838500008 PM 11748581 ER PT J AU Jimenez, MJG Balbin, M Alvarez, J Komori, T Bianco, P Holmbeck, K Birkedal-Hansen, H Lopez, JM Lopez-Otin, C AF Jimenez, MJG Balbin, M Alvarez, J Komori, T Bianco, P Holmbeck, K Birkedal-Hansen, H Lopez, JM Lopez-Otin, C TI A regulatory cascade involving retinoic acid, Cbfa1, and matrix metalloproteinases is coupled to the development of a process of perichondrial invasion and osteogenic differentiation during bone formation SO JOURNAL OF CELL BIOLOGY LA English DT Article DE arthritis; bone formation; cancer; metastasis; proteases ID ACTIVATED PROTEIN-KINASE; SMOOTH-MUSCLE CELLS; GROWTH-FACTOR-BETA; INTERSTITIAL COLLAGENASE; CHONDROCYTE MATURATION; PARATHYROID-HORMONE; BREAST CARCINOMAS; EXPRESSION; MMP-13; GENE AB Tissue-remodeling processes are largely mediated by members of the matrix metalloproteinase (MMP) family of endopeptidases whose expression is strictly controlled both spatially and temporally, In this article, we have examined the molecular mechanisms that could contribute to modulate the expression of MMPs like collagenase-3 and MT1-MMP during bone formation. We have found that all-trans retinoic acid (RA), which usually downregulates MMPs, strongly induces collagenase-3 expression in cultures of embryonic metatarsal cartilage rudiments and in chondrocytic cells. This effect is dose and time dependent, requires the de novo synthesis of proteins, and is mediated by RAR-RXR heterodimers. Analysis of the signal transduction mechanisms underlying the upregulating effect of RA on collagenase-3 expression demonstrated that this factor acts through a signaling pathway involving p38 mitogen-activated protein kinase. RA treatment of chondrocytic cells also induces the production of MT1-MMP, a membrane-bound metalloproteinase essential for skeletal formation, which participates in a proteolytic cascade with collagenase-3. The production of these MMPs is concomitant with the development of an RA-induced differentiation program characterized by formation of a mineralized bone matrix, downregulation of chondrocyte markers like type II collagen, and upregulation of osteoblastic markers such as osteocalcin. These effects are attenuated in metatarsal rudiments in which RA induces the invasion of perichondrial osteogenic cells from the perichondrium into the cartilage rudiment. RA treatment also resulted in the upregulation of Cbfa1, a transcription factor responsible for collagenase-3 and osteocalcin induction in osteoblastic cells. The dynamics of Cbfa1, MMPs, and osteocalcin expression is consistent with the fact that these genes could be part of a regulatory cascade initiated by RA and leading to the induction of Cbfa1, which in turn would upregulate the expression of some of their target genes like collagenase-3 and osteocalcin. C1 Univ Oviedo, Fac Med, Dept Bioquim & Biol Mol, Oviedo 33006, Spain. Univ Oviedo, Fac Med, Inst Univ Oncol, Oviedo 33006, Spain. Osaka Univ, Sch Med, Dept Mol Med, Suita, Osaka 5650871, Japan. Univ Roma La Sapienza, Dipartimento Med Sperimentale, I-00161 Rome, Italy. Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Lopez-Otin, C (reprint author), Univ Oviedo, Fac Med, Dept Bioquim & Biol Mol, Oviedo 33006, Spain. RI Balbin, Milagros/I-4206-2015; Lopez-Otin, Carlos/C-6657-2013 OI Lopez-Otin, Carlos/0000-0001-6964-1904 NR 57 TC 80 Z9 83 U1 2 U2 4 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 DEC 24 PY 2001 VL 155 IS 7 BP 1333 EP 1344 DI 10.1083/jcb.200106147 PG 12 WC Cell Biology SC Cell Biology GA 507JJ UT WOS:000173023500027 PM 11748248 ER PT J AU Bennett, AJ Sponberg, AC Graham, T Suomi, SJ Higley, JD DePetrillo, PB AF Bennett, AJ Sponberg, AC Graham, T Suomi, SJ Higley, JD DePetrillo, PB TI Initial ethanol exposure results in decreased heart rate variability in ethanol-naive rhesus monkeys SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ethanol; heart rate; dynamics, nonlinear ID NONHUMAN PRIMATE MODEL; 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; EXCESSIVE ALCOHOL-CONSUMPTION; DIMINISHED SOCIAL COMPETENCE; TIME-SERIES; FLUID; PERSONALITY; RESPONSES; DISEASE AB Ethanol's effects on heart rate variability may contribute to the increased cardiac disease and mortality observed far alcoholics. We assessed cardiac response to ethanol in seven previously ethanol-naive monkeys given a standard dose of ethanol, or saline. Ethanol exposure reduced cardiac signal complexity [mean +/- S.D, (ethanol: Hurst parameter = 0.39 +/- 0.02; saline: Hurst parameter = 0.32 +/- 0.06)] and increased the spectral exponent (ethanol: beta = 1.36 +/- 0.35; saline: beta = 1.12 +/- 0.35) when compared to saline, while heart rate itself was unaffected (saline: interbeat interval = 303.57 +/- 24.57; ethanol: interbeat interval = 308.14 +/- 20.45). Taken together with data that show autonomic disregulation in alcoholics, these findings provide further evidence of deleterious ethanol effects on cardiac signal dynamics. (C) 2001 Published by Elsevier Science B.V. C1 NIAAA, Clin Studies Lab, Primate Unit, Div Intramural Clin & Biochem Res, Poolesville, MD 20837 USA. NICHHD, Comparat Ethol Lab, Poolesville, MD 20837 USA. NIAAA, Clin Studies Lab, Unit Clin & Biochem Pharmacol, Div Intramural Clin & Biochem Res,NIH, Bethesda, MD 20892 USA. RP Bennett, AJ (reprint author), NIAAA, Clin Studies Lab, Primate Unit, Div Intramural Clin & Biochem Res, POB 529,Fisher Ave, Poolesville, MD 20837 USA. NR 21 TC 11 Z9 11 U1 1 U2 6 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 DEC 21 PY 2001 VL 433 IS 2-3 BP 169 EP 172 DI 10.1016/S0014-2999(01)01445-5 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 506VA UT WOS:000172991400006 PM 11755149 ER PT J AU Wang, J Boja, ES Tan, WH Tekle, E Fales, HM English, S Mieyal, JJ Chock, PB AF Wang, J Boja, ES Tan, WH Tekle, E Fales, HM English, S Mieyal, JJ Chock, PB TI Reversible glutathionylation regulates actin polymerization in A431 cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; HUMAN THIOLTRANSFERASE GLUTAREDOXIN; TYROSINE-PHOSPHATASE 1B; SIGNAL-TRANSDUCTION; S-THIOLATION; DISULFIDE; PHOSPHORYLATION; GENERATION; FILAMENTS; RECEPTOR AB In response to growth factor stimulation, many mammalian cells transiently generate reactive oxygen species (ROS) that lead to the elevation of tyrosine-phosphorylated and glutathionylated proteins. While investigating EGF-induced glutathionylation in A431 cells, paradoxically we found deglutathionylation of a major 42-kDa protein identified as actin. Mass spectrometric analysis revealed that the glutathionylation site is Cys-374. Deglutathionylation of the G-actin leads to about a 6-fold increase in the rate of polymerization. In vivo studies revealed a 12% increase in F-actin content 15 min after EGF treatment, and F-actin was found in the cell periphery suggesting that in response to growth factor, actin polymerization in vivo is regulated by a reversible glutathionylation mechanism. Deglutathionylation is most likely catalyzed by glutaredoxin (thioltranferase), because Cd(II), an inhibitor of glutaredoxin, inhibits intracellular actin deglutathionylation at 2 muM, comparable with its IC50 in vitro. Moreover, mass spectral analysis showed efficient transfer of GSH from immobilized S-glutathionylated actin to glutaredoxin. Overall, this study revealed a novel physiological relevance of actin polymerization regulated by reversible glutathionylation of the penultimate cysteine mediated by growth factor stimulation. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. RP Chock, PB (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Rm 2134,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. FU NIA NIH HHS [AG15885] NR 30 TC 212 Z9 219 U1 1 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 21 PY 2001 VL 276 IS 51 BP 47763 EP 47766 DI 10.1074/jbc.C100415200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505QL UT WOS:000172927000005 PM 11684673 ER PT J AU Lim, HM Kaneshige, M Zhao, L Zhang, XY Hanover, JA Cheng, SY AF Lim, HM Kaneshige, M Zhao, L Zhang, XY Hanover, JA Cheng, SY TI An isoform of branched-chain aminotransferase is a novel co-repressor for thyroid hormone nuclear receptors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTIONAL REPRESSION; HISTONE DEACETYLASE-3; MYC REGULATION; GENE; PROTEIN; TARGET; IDENTIFICATION; COREPRESSOR; INTERACTS; CLONING AB The functions of thyroid hormone receptors (TRs) are regulated by a host of co-regulatory proteins. Tissue-specific expression of these co-regulators leads to distinct expression patterns and regulation of thyroid hormone (T3) target genes in tissues. Previously we have found that human colon carcinoma RKO cells exhibit strong U-independent transcriptional activity. We therefore searched for co-regulatory proteins in RKO cells using a yeast two-hybrid system with the intact TR beta1 as bait. One of the three positive clones, designated as P3, was identified to be an isoform of human mitochondria branched-chain amino-transferase (BCATm). P3 was a spliced variant of BCATm with an internal 12-amino acid deletion near the carboxyl-terminal region and was abundantly expressed in RKO cells. The expressed protein localized both to the mitochondria and the nucleus of transfected CV1 cells. P3 physically interacted with TR beta1 in a T3-independent manner that led to the inhibition in binding of TRIM to thyroid hormone-responsive element. P3 not only enhanced the repressor activity of the unliganded TR but also repressed the ligand-dependent activation of TIL This repression was reversed by treatment of cells with trichostatin A, suggesting that in addition to the inhibition of DNA binding, the repression activity of P3 on TR may also be mediated by histone deacetylase activity. Thus, unlike the currently known corepressors, P3 is a novel ligand-independent co-repressor for TR. C1 NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Gene Regulat Sect, Mol Biol Lab, NIH, Bldg 37,Rm 2D-24,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 39 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 21 PY 2001 VL 276 IS 51 BP 48196 EP 48205 DI 10.1074/jbc.M104320200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505QL UT WOS:000172927000062 ER PT J AU Jian, XY Clark, WA Kowalak, J Markey, SP Simonds, WF Northup, JK AF Jian, XY Clark, WA Kowalak, J Markey, SP Simonds, WF Northup, JK TI GB gamma affinity for bovine rhodopsin is determined by the carboxyl-terminal sequences of the gamma subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; G-PROTEIN; ALPHA(2A)-ADRENERGIC RECEPTOR; ALPHA-SUBUNITS; INTRACELLULAR LOOP; SF9 CELLS; BINDING; TRANSDUCIN; MEMBRANES; PRENYLATION AB Two native beta gamma dimers, beta (1)gamma (1), and beta (1)gamma (2), display very different affinities for receptors. Since these gamma subunits differ in both primary structure and isoprenoid modification, we examined the relative contributions of each to G beta gamma interaction with receptors. We constructed baculoviruses encoding gamma (1) and gamma (2) subunits with altered CAAX (where A is an aliphatic amino acid) motifs to direct alternate or no prenylation of they chains and a set of gamma (1) and gamma (2) chimeras with the gamma (2) CAAX motif at the carboxyl terminus. All they constructs coexpressed with beta (1) in Sf9 cells yielded beta (1)gamma dimers, which were purified to near homogeneity, and their affinities for receptors and Ga were quantitatively determined. Whereas alteration of the isoprenoid of gamma (1) from farnesyl to geranylgeranyl and of gamma (2) from geranylgeranyl to farnesyl had no impact on the affinities of beta (1)gamma dimers for Gat, the non-prenylated beta (1)gamma (2) dimer had significantly diminished affinity. Altered prenylation resulted in a <2-fold decrease in affinity of the beta (1)gamma (2) dimer for rhodopsin and a <3-fold change for the beta (1)gamma (1), dimer. In each case with identical isoprenylation, the beta (1)gamma (2) dimer displayed significantly greater affinity for rhodopsin compared with the beta (1)gamma (1), dimer. Furthermore, dimers containing chimeric G gamma chains with identical geranylgeranyl modification displayed rhodopsin affinities largely determined by the carboxyl-terminal one-third of the protein. These results indicate that isoprenoid modification of the G gamma subunit is essential for binding to both G alpha and receptors. The isoprenoid type influences the binding affinity for receptors, but not for G alpha. Finally, the primary structure of the G gamma subunit provides a major contribution to receptor binding of G beta gamma, with the carboxyl-terminal sequence conferring receptor selectivity. C1 NIDCD, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Northup, JK (reprint author), NIDCD, Lab Cellular Biol, NIH, Rm 2A-11,5 Res Ct, Rockville, MD 20850 USA. NR 45 TC 21 Z9 21 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 21 PY 2001 VL 276 IS 51 BP 48518 EP 48525 DI 10.1074/jbc.M107129200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505QL UT WOS:000172927000105 PM 11602594 ER PT J AU Derrien, A Druey, KM AF Derrien, A Druey, KM TI RGS16 function is regulated by epidermal growth factor receptor-mediated tyrosine phosphorylation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEINS; COUPLED RECEPTORS; SIGNALING RGS; MAP KINASE; EXPRESSION; SRC; LYMPHOCYTES; MECHANISM; MEMBRANE; FEATURES AB G alpha (i)-coupled receptor stimulation results in epidermal growth factor receptor (EGFR) phosphorylation and MAPK activation. Regulators of G protein signaling (RGS proteins) inhibit G protein-dependent signal transduction by accelerating Ga. GTP hydrolysis, shortening the duration of G protein effector stimulation. RGS16 contains two conserved tyrosine residues in the RGS box, Tyr(168) and Tyr(177), which are predicted sites of phosphorylation. RGS16 underwent phosphorylation in response to m2 muscarinic receptor or EGFR stimulation in HEK 293T or COS-7 cells, which required EGFR kinase activity. Mutational analysis suggested that RGS16 was phosphorylated on both tyrosine residues (Tyr(168) much greater than Tyr(177)) after EGF stimulation. RGS16 co-immunoprecipitated with EGFR, and the interaction did not require EGFR activation. Purified EGFR phosphorylated only recombinant RGS16 wild-type or Y177F in vitro, implying that EGFR-mediated phosphorylation depended on residue Tyr(168). Phosphorylated RGS16 demonstrated enhanced GTPase accelerating (GAP) activity on G alpha (i). Mutation of Tyr(168) to phenylalanine resulted in a 30% diminution in RGS16 GAP activity but completely eliminated its ability to regulate Gi-mediated MAPK activation or adenylyl cyclase inhibition in HEK 293T cells. In contrast, mutation of Tyr(177) to phenylalanine had no effect on RGS16 GAP activity but also abolished its regulation of Gi-mediated signal transduction in these cells. These data suggest that tyrosine phosphorylation regulates RGS16 function and that EGFR may potentially inhibit G alpha (i)-dependent MAPK activation in a feedback loop by enhancing RGS16 activity through tyrosine phosphorylation. C1 NIH, Mol Signal Transduct Sect, Lab Allerg Dis, Rockville, MD 20852 USA. RP Druey, KM (reprint author), NIH, Mol Signal Transduct Sect, Lab Allerg Dis, 12441 Parklawn Dr, Rockville, MD 20852 USA. NR 35 TC 36 Z9 39 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 21 PY 2001 VL 276 IS 51 BP 48532 EP 48538 DI 10.1074/jbc.M108862200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505QL UT WOS:000172927000107 PM 11602604 ER PT J AU Laposky, AD Homanics, GE Basile, A Mendelson, WB AF Laposky, AD Homanics, GE Basile, A Mendelson, WB TI Deletion of the GABA(A) receptor beta 3 subunit eliminates the hypnotic actions of oleamide in mice SO NEUROREPORT LA English DT Article DE GABA(A) receptor; GABA(A) receptor beta 3 subunit; mice; non-rapid eye movement sleep; oleamide; sleep latency ID CANNABINOID RECEPTORS; A RECEPTOR; SLEEP; CEREBRODIENE; BEHAVIOR; NEURONS; ACID AB Oleamide (OA) is an endogenous unsaturated fatty acid amide with demonstrated sleep promoting effects in rodents, The sleep enhancing actions of OA may be mediated through interactions with the GABAergic, serotonergic or cannabinergic receptor systems. In this study, we investigated the possible interaction of OA with the GABA(A) receptor by administering OA to mice with a targeted mutation of the GABA(A) receptor beta3 subunit (Gabarb3-/-). Peripherally administered OA significantly decreased sleep latency and wake time, while it increased non-rapid eye movement and total sleep times in wild-type (Gabarb3+/+) mice. OA failed to have any sleep-wake effect in Gabarb3-/-- mice. On 24 h baseline recordings, no differences between Gabarb3-/- and Gabarb3+/+ mice were observed, indicating that the lack of a pharmacological response to OA in the Gabarb3-/- animals was not secondary to disruptions in physiological. sleep. Therefore, one mechanism by which OA exerts its sleep effects may be through interactions with GABAA receptors containing the beta3 subunit. NeuroReport 12:4143-4147 (C) 2001 Lippincott Williams & Wilkins. C1 Northwestern Univ, Ctr Sleep & Circadian Biol, Evanston, IL 60208 USA. Univ Pittsburgh, Sch Med, Dept Anesthesiol Crit Care Med, Pittsburgh, PA 15261 USA. NIDDK, Neurosci Grp, Bioorgan Chem Lab, NIH, Bethesda, MD USA. RP Laposky, AD (reprint author), Northwestern Univ, Ctr Sleep & Circadian Biol, Hogan Hall Room 2-160,2153 N Campus Dr, Evanston, IL 60208 USA. FU NHLBI NIH HHS [K07 HL03640]; NIAAA NIH HHS [AA14022]; NIDA NIH HHS [1R01DA10682-01]; NIGMS NIH HHS [GM52035] NR 25 TC 37 Z9 37 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 21 PY 2001 VL 12 IS 18 BP 4143 EP 4147 DI 10.1097/00001756-200112210-00056 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 502LT UT WOS:000172745600067 PM 11742254 ER PT J AU Richmond, B AF Richmond, B TI Neuroscience - Information coding SO SCIENCE LA English DT Editorial Material ID CORTEX; DISCHARGE; NEURONS; SIGNALS C1 NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Richmond, B (reprint author), NIMH, Neuropsychol Lab, Bldg 9, Bethesda, MD 20892 USA. NR 11 TC 4 Z9 4 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 21 PY 2001 VL 294 IS 5551 BP 2493 EP 2494 DI 10.1126/science.1067928 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 505QU UT WOS:000172927700039 PM 11752563 ER PT J AU Durell, SR Guy, HR AF Durell, Stewart R. Guy, H. Robert TI A family of putative K(ir) potassium channels in prokaryotes SO BMC EVOLUTIONARY BIOLOGY LA English DT Article AB Background: Prior to this report, members of the inward rectifier family, or Kir, have been found only in eukaryotes. Like most K(+) channels, the pore-forming part of the protein is formed by four identical, or closely related, subunits. Each subunit contains a transmembrane M1-P-M2 motif that is followed by a relatively large C-terminus region unique to Kir's. Results: In searching unfinished microbial genomes for K(+) channels, we identified five sequences in the prokaryote Burkholderia pseudomallei, Burkholderia cepacia, Burkholderia fungorum LB400, Magentospirillum magnetotacticum, and Nostoc Punctiforme genomes that code for proteins whose closest relatives in current sequence databases are eukaryote Kir's. The sequence similarity includes the C-terminus portion of Kir's, for which there are no other close homologs in current prokaryote sequences. Sequences of the pore-forming P and M2 segments of these proteins, which we call KirBac, is intermediate between those of eukaryotic Kir's and several other K(+) channel families. Conclusions: Although KirBac's are more closely related to Kir's than to other families of K(+) channels, the intermediate nature of their pore-forming P and M2 segments suggests that they resemble an ancestral precursor to the eukaryotic Kir's. The similarity of KirBac to the bacterial KcsA channel, whose transmembrane structure has been solved, helps align Kir's with KcsA. KirBac's may assist in solving the three-dimensional structure of a member of the Kir family since bacterial membrane proteins are more easily expressed in the quantities necessary for crystallography. C1 [Durell, Stewart R.; Guy, H. Robert] NCI, Mol Struct Sect, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Guy, HR (reprint author), NCI, Mol Struct Sect, Lab Expt & Computat Biol, NIH, 12 South Dr, Bethesda, MD 20892 USA. EM Durell@helix.nih.gov; bg4y@nih.gov NR 26 TC 38 Z9 40 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD DEC 20 PY 2001 VL 1 AR 14 DI 10.1186/1471-2148-1-14 PG 9 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA V13CN UT WOS:000207645000001 PM 11806753 ER PT J AU Choi, SH Kim, JE Lee, YC Jang, YJ Pastan, I Choe, MH AF Choi, SH Kim, JE Lee, YC Jang, YJ Pastan, I Choe, MH TI A divalent immunotoxin formed by the disulfide bond between hinge regions of Fab domain SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY LA English DT Article DE divalent immunotoxin; [B3(FabH1)-PE38](2); B3 antibody; pseudomonas exotoxin A; antibody refolding ID SINGLE-CHAIN FV; BACTERIAL INCLUSION-BODIES; MONOCLONAL-ANTIBODY B3; PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; RECOMBINANT IMMUNOTOXIN; COMPLETE REGRESSION; ESCHERICHIA-COLI; FUSION PROTEIN; CELL LYMPHOMA AB Recombinant immunotoxins are hybrid cytotoxic proteins designed to selectively kill cancer cells. A divalent immunotoxins, [B3(FabH1)-PE38](2), was constructed by recombining Fab domain of B3 antibody as a cell-targeting domain and Pseudomonas exotoxin A (PE) as a cytotoxic domain. Monoclonal antibody, B3, is the murine antibody (IgG1 kappa) directed against Lewis(Y)-related carbohydrate antigens, which are abundant on the surface of many carcinomas. Fab fragment of this antibody was used in this study with the modified hinge sequence where last two cysteines out of three were mutated to serine. PE is a 66 kDa bacterial toxin that kills eukaryotic cells by inhibiting protein synthesis with ADP ribosylation of ribosomal elongation factor 2 (EF2). Fc region of B3 antibody was substituted with the truncated form of PE (38 kDa, PE38) on DNA level. [B3(FabH1)-PE38](2) was formed by disulfide bond between cysteines in the modified hinge region of B3(FabH1)-PE38. Each polypeptide for recombinant immunotoxins was overexpressed in Escherichia coli and collected as inclusion bodies. Each inclusion body was solubilized and refolded, and cytotoxic effects were measured. Divalent immunotoxins, [B3(FabH1)-PE38](2), had ID50 values of about 10 ng/mL on A431 cell lines and about 4 ng/mL on CRL1739 cell lines. Control immunotoxins, B3(scFv)-PE40, had ID50 values of about 28 ng/mL on A431 cell lines and about 41 ng/mL on CRL1739 cell lines. Divalent immunotoxins, [B3(FabH1)-PE38](2), had higher cytotoxic effects than B3(scFv)-PE40 control immunotoxins. C1 Korea Univ, Grad Sch Biotechnol, Seoul 136701, South Korea. Ajou Univ, Sch Med, Inst Med Sci, Immunol Lab, Suwon 442749, South Korea. NCI, NIH, Div Basic Sci, Mol Biol Lab, Bethesda, MD 20892 USA. RP Choe, MH (reprint author), Korea Univ, Grad Sch Biotechnol, Seoul 136701, South Korea. EM choemh@korea.ac.kr NR 35 TC 6 Z9 6 U1 1 U2 4 PU KOREAN CHEMICAL SOC PI SEOUL PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 0253-2964 J9 B KOREAN CHEM SOC JI Bull. Korean Chem. Soc. PD DEC 20 PY 2001 VL 22 IS 12 BP 1361 EP 1365 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 507XA UT WOS:000173055500019 ER PT J AU Ohta, A Sitkovsky, M AF Ohta, A Sitkovsky, M TI Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage SO NATURE LA English DT Article ID T-CELL ACTIVATION; A(2A) RECEPTOR; RELEASE; INHIBITOR; HEPATITIS; ARTHRITIS; ISCHEMIA AB Inappropriate or prolonged inflammation is the main cause of many diseases(1); for this reason it is important to understand the physiological mechanisms that terminate inflammation in vivo(2). Agonists for several G(s)-protein-coupled receptors(3), including cell-surface adenosine purinergic receptors(4-7), can increase levels of immunosuppressive cyclic AMP in immune cells(8-15); however, it was unknown whether any of these receptors regulates inflammation in vivo. Here we show that A2a adenosine receptors have a non-redundant role in the attenuation of inflammation and tissue damage in vivo. Sub-threshold doses of an inflammatory stimulus(16,17) that caused minimal tissue damage in wild-type mice were sufficient to induce extensive tissue damage, more prolonged and higher levels of pro-inflammatory cytokines, and death of male animals deficient in the A2a adenosine receptor. Similar observations were made in studies of three different models of inflammation and liver damage as well as during bacterial endotoxin-induced septic shock. We suggest that A2a adenosine receptors are a critical part of the physiological negative feedback mechanism for limitation and termination of both tissue-specific and systemic inflammatory responses. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sitkovsky, M (reprint author), NIAID, Immunol Lab, NIH, 10 Ctr Dr,Room 10-11N311, Bethesda, MD 20892 USA. NR 30 TC 658 Z9 680 U1 1 U2 32 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 20 PY 2001 VL 414 IS 6866 BP 916 EP 920 DI 10.1038/414916a PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 503RB UT WOS:000172813300048 PM 11780065 ER PT J AU Folkers, GK Fauci, AS AF Folkers, GK Fauci, AS TI Neglected diseases of global importance - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Folkers, GK (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 19 PY 2001 VL 286 IS 23 BP 2943 EP 2944 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 502VY UT WOS:000172764500021 ER PT J AU Plaut, M AF Plaut, M TI Immune-based, targeted therapy for allergic diseases SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID ANTI-IGE ANTIBODY; RHINITIS; ASTHMA C1 NIAID, Allerg Mech Sect, NIH, Bethesda, MD 20817 USA. RP Plaut, M (reprint author), NIAID, Allerg Mech Sect, NIH, 6700-B Rockledge Dr,Room 5146,MSC-7640, Bethesda, MD 20817 USA. NR 26 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 19 PY 2001 VL 286 IS 23 BP 3005 EP 3006 DI 10.1001/jama.286.23.3005 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 502VY UT WOS:000172764500035 PM 11743844 ER PT J AU Kaye, FJ AF Kaye, FJ TI Publishing negative data: beta-tubulin mutations in lung cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GENE; POLYMORPHISM; PSEUDOGENE; RESISTANT C1 Natl Naval Med Res Inst, Bethesda, MD 20889 USA. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Kaye, FJ (reprint author), Natl Naval Med Res Inst, Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM fkaye@helix.nih.gov RI kaye, frederic/E-2437-2011 NR 16 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 19 PY 2001 VL 93 IS 24 BP 1832 EP 1833 DI 10.1093/jnci/93.24.1832 PG 2 WC Oncology SC Oncology GA 503AB UT WOS:000172774000002 PM 11752001 ER PT J AU Harlan, LC Potosky, A Gilliland, FD Hoffman, R Albertsen, PC Hamilton, AS Eley, JW Stanford, JL Stephenson, RA AF Harlan, LC Potosky, A Gilliland, FD Hoffman, R Albertsen, PC Hamilton, AS Eley, JW Stanford, JL Stephenson, RA TI Factors associated with initial therapy for clinically localized prostate cancer: Prostate cancer outcomes study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID QUALITY-OF-LIFE; DATA-BASE REPORT; RADICAL PROSTATECTOMY; AFRICAN-AMERICAN; SEXUAL FUNCTION; GLEASON SCORE; LUNG-CANCER; CARCINOMA; AGE; MEN AB Background: Because of the lack of results from randomized clinical trials comparing the efficacy of aggressive therapies with that of more conservative therapies for clinically localized prostate cancer, men and their physicians may select treatments based on other criteria. We examined the association of sociodemographic and clinical characteristics with four management options: radical prostatectomy, radiation therapy, hormonal therapy, and watchful waiting. Methods: We studied 3073 participants of the Prostate Cancer Outcomes Study diagnosed from October 1, 1994, through October 31, 1995, with clinically localized disease (T1 or T2). Participants completed a baseline survey, and diagnostic and treatment information was abstracted from medical records. Multiple logistic regression analysis identified factors associated with initial treatment. All statistical tests were two-sided. Results: Patients with clinically localized disease received the following treatments: radical prostatectomy (47.6%), radiation therapy (23.4%), hormonal therapy (10.5%), or watchful waiting (18.5%). Men aged 75 years or older more often received conservative treatment (i.e., hormonal therapy alone or watchful waiting; 57.9% of men aged 75-79 years and 82.1% of men aged 80 years and older) than aggressive treatment (i.e., radical prostatectomy or radiation therapy) (for all age groups, P less than or equal to .001). After adjustment for age, clinical stage, baseline prostate-specific antigen level, and histologic grade, the following factors were associated with conservative treatment: history of a heart attack, being unmarried, geographic region, poor pretreatment bladder control, and impotence. In men younger than 60 years, use of aggressive treatment was similar by race/ethnicity (adjusted percentages = 85.5%, 88.1%, and 85.3% for white, African-American, and Hispanic men, respectively). However, among men 60 years old and older, African-American men underwent aggressive treatment less often than did white men or Hispanic men (adjusted percentages for men aged 60-64 years = 67.1%, 84.7%, and 79.2%, respectively; 65-74 years = 64.8%, 73.4%, and 79.5%, respectively; and 75 years old and older = 25.2%, 45.7%, and 36.6%, respectively). Conclusions: The association of nonclinical factors with treatment suggests that, in the absence of definitive information regarding treatment effectiveness, men diagnosed with prostate cancer should be better informed of the risks and benefits of all treatment options. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Dept Vet Affairs Med Ctr, Albuquerque, NM USA. New Mexico Tumor Registry, Albuquerque, NM USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. Emory Univ, Atlanta, GA 30322 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Utah, Salt Lake City, UT USA. RP Harlan, LC (reprint author), NIH, Execut Plaza N,Suite 4005,6130 Execut Blvd,MSC 73, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01PC67000, N01PC67006, N01PC67005, N01PC67007, N01PC67009, N01PC67010] NR 34 TC 127 Z9 130 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 19 PY 2001 VL 93 IS 24 BP 1864 EP 1871 DI 10.1093/jnci/93.24.1864 PG 8 WC Oncology SC Oncology GA 503AB UT WOS:000172774000010 PM 11752011 ER PT J AU Chen, KH Srivastava, DK Wilson, SH AF Chen, KH Srivastava, DK Wilson, SH TI Relationship between base excision repair capacity and DNA alkylating agent sensitivity in mouse monocytes SO MUTATION RESEARCH-DNA REPAIR LA English DT Article DE base excision repair; DNA polymerase beta; interferon-gamma; mouse monocytes; DNA alkylation; cytotoxicity ID INTERFERON-GAMMA; POLYMERASE-BETA; UP-REGULATION; EXPRESSION; RECEPTOR; MACROPHAGES; CELLS; LIPOPOLYSACCHARIDE; DIFFERENTIATION; ALPHA AB Base excision repair (BER) capacity and the level of DNA polymerase (beta -pol) are higher in mouse monocyte cell extracts when cells are treated with oxidative stress-inducing agents. Consistent with this, such treated cells are more resistant to the cytotoxic effects of methyl methanesulfonate (MMS), which produces DNA damage considered to be repaired by the BER pathway. In contrast to the up-regulation of BER in oxidatively stressed cells, cells treated with the cytok-me interferon-gamma (IFN-gamma) are down-regulated in both BER capacity of the cell extract and level of beta -pol. We find that cells treated with IFN-gamma are more sensitive to MMS than untreated cells. These results demonstrate concordance between beta -pol level, BER capacity and cellular sensitivity to a DNA methylation-inducing agent. The results suggest that BER is a significant defense mechanism in mouse monocytes against the cytotoxic effects of methylated DNA. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), Univ Texas, Med Branch, Sealy Ctr Mol Sci, Galveston, TX 77555 USA. FU NIEHS NIH HHS [ES06492, ES06839] NR 21 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0921-8777 J9 MUTAT RES-DNA REPAIR JI Mutat. Res.-DNA Repair PD DEC 19 PY 2001 VL 487 IS 3-4 BP 121 EP 126 DI 10.1016/S0921-8777(01)00110-0 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 503QA UT WOS:000172808100005 PM 11738938 ER PT J AU Lemaitre, R Garcia-Gomez, J von Sternberg, R Campos, NH AF Lemaitre, R Garcia-Gomez, J von Sternberg, R Campos, NH TI A new genus and a new species of crab of the family Goneplacidae MacCleay, 1838 (Crustacea : Decapoda : Brachyura) from the tropical western Atlantic SO PROCEEDINGS OF THE BIOLOGICAL SOCIETY OF WASHINGTON LA English DT Article AB A new monotypic genus, Nancyplax, and a new species, N. vossi, of the family Goneplacidae MacLeay, are described from the southern Caribbean and northeastern coast of South America. Characters derived from male pleopods 1 and 2, and male abdomen-sternoabdominal cavity, allow Nancyplax to be assigned to the Euryplacinae Stimpson. The carapace in N. vossi, however, strongly resembles in overall conformation some species in the Carcinoplacinae H. Milne Edwards. In addition, N. vossi has a well developed stridulatory organ, a feature shared with only one other euryplacine species, some carcinoplacines, and some species in the Goneplacinae MacLeay. The mosaic habitus of Nancyplax precludes resolution of relationships with other euryplacine genera. Morphological similarities of N. vossi with species of Carcinoplax H. Milne Edwards, Psopheticus Wood-Mason, Psopheticoides Sakai, and Tri-zocarcinus Rathbun, are summarized. C1 Univ Miami, Rosenstiel Sch Marine & Atmospher Sci, Div Marine Biol & Fisheries, Miami, FL 33149 USA. Natl Museum Nat Hist, Dept Systemat Biol, Smithsonian Inst, Washington, DC 20560 USA. RP Lemaitre, R (reprint author), Natl Ctr Biotechnol Informat, Taxonomy Project, GenBank, NIH, Bldg 45,Rm 6An 18D-30, Bethesda, MD USA. NR 36 TC 3 Z9 3 U1 0 U2 1 PU BIOL SOC WASHINGTON PI WASHINGTON PA NAT MUSEUM NAT HIST SMITHSONIAN INST, WASHINGTON, DC 20560 USA SN 0006-324X J9 P BIOL SOC WASH JI Proc. Biol. Soc. Wash. PD DEC 19 PY 2001 VL 114 IS 4 BP 951 EP 963 PG 13 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 506AP UT WOS:000172948000013 ER PT J AU Vollmer, WM Sacks, FM Ard, J Appel, LJ Bray, GA Simons-Aaorton, DG Conlin, PR Svetkey, LP Erlinger, TP Moore, TJ Karanja, N AF Vollmer, WM Sacks, FM Ard, J Appel, LJ Bray, GA Simons-Aaorton, DG Conlin, PR Svetkey, LP Erlinger, TP Moore, TJ Karanja, N CA DASH Sodium Trial Collaborative Re TI Effects of diet and sodium intake on blood pressure: Subgroup analysis of the DASH-Sodium Trial SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; SALT SENSITIVITY; NATIONAL-HEALTH; CLINICAL-TRIAL; URINARY SODIUM; HYPERTENSION; REDUCTION; RISK; PATTERNS; ASSOCIATION AB Background: initial findings from the Dietary Approaches to Stop Hypertension (DASH)-Sodium Trial demonstrated that reduction of sodium intake in two different diets decreased blood pressure in participants with and without hypertension. Objective: To determine effects on blood pressure of reduced sodium intake and the DASH diet in additional subgroups. Design: Randomized feeding study. Setting: Four clinical centers and a coordinating center. Participants: 412 adults with untreated systolic blood pressure of 120 to 160 mm Hg and diastolic blood pressure of 80 to 95 mm Hg. Intervention: Participants followed the DASH diet or a control (typical U.S.) diet for three consecutive 30-day feeding periods, during which sodium intake (50, 100, and 150 mmol/d at 2100 kcal) varied according to a randomly assigned sequence. Body weight was maintained. Measurements: Systolic and diastolic blood pressure. Results: In all subgroups, the DASH diet and reduced sodium intake were each associated with significant decreases in blood pressure; these two factors combined produced the greatest reductions. Among nonhypertensive participants who received the control diet, lower (vs. higher) sodium intake decreased blood pressure by 7.0/3.8 mm Hg in those older than 45 years of age (P < 0.001) and by 3.7/1.5 mm Hg in those 45 years of age or younger (P < 0.05). Conclusion: The DASH diet plus reduced sodium intake is recommended to control blood pressure in diverse subgroups. C1 Ctr Hlth Res, Portland, OR 97227 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Boston Univ, Med Ctr, Boston, MA USA. Duke Univ, Med Ctr, Durham, NC USA. Johns Hopkins Univ, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. RP Vollmer, WM (reprint author), Ctr Hlth Res, 3800 N Interstate Ave, Portland, OR 97227 USA. EM william.vollmer@kpchr.org FU NCRR NIH HHS [M01-RR00722, M01-RR02635]; NHLBI NIH HHS [HL03857-01, U01-HL 57173, U01-HL57114, U01-HL57139, U01-HL57156, U01-HL57190] NR 36 TC 246 Z9 262 U1 1 U2 15 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 18 PY 2001 VL 135 IS 12 BP 1019 EP 1028 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 502TW UT WOS:000172759700001 PM 11747380 ER PT J AU Leveille, SG Ling, S Hochberg, MC Resnick, HE Bandeen-Roche, KJ Won, A Guralnik, JM AF Leveille, SG Ling, S Hochberg, MC Resnick, HE Bandeen-Roche, KJ Won, A Guralnik, JM TI Widespread musculoskeletal pain and the progression of disability in older disabled women SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID OSTEO-ARTHRITIS; GENERAL-POPULATION; OSTEOARTHRITIS; KNEE; PREVALENCE; HEALTH; HIP; FIBROMYALGIA; ASSOCIATION; COMMUNITY AB Background: Widespread musculoskeletal pain is a poorly understood but common problem in older adults. Little is known about the progression of disability related to this condition. Objective: To determine whether widespread musculoskeletal pain increases the risk for worsening disability in older women with disabilities. Design: Prospective cohort study. Setting: The Women's Health and Aging Study. Participants: 1002 community-dwelling women 65 years of age or older with disability. Measurements: Widespread musculoskeletal pain was defined as pain in the upper and lower extremities and axial pain with moderate or severe pain in at least one of the three regions. Worsening disability was defined as progression from no or mild difficulty to severe difficulty or inability to perform activities of daily living (ADLs), walk one-quarter mile, or lift 10 lbs. Results: At baseline, 24% of participants had widespread pain and 25% had no pain or only mild pain in a single site. Women with widespread pain were 2.5 to 3.5 times more likely to have severe difficulty with ADLs, walking, or lifting at baseline compared with women who had no or mild pain. In women without severe difficulty initially, widespread pain nearly doubled the risk for progression to severe difficulty in each of the tasks, after adjustment for age, body mass index, comorbid illness, and other confounders. Conclusion: Widespread musculoskeletal pain is frequent among community-dwelling older women with disability and appears to predict the progression of disability. Efforts to better understand the cause of this pain and its treatment might reduce the overall burden of disability. C1 Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Maryland Vet Affairs Hlth Care Syst, Baltimore, MD USA. NIA, Bethesda, MD 20892 USA. RP Leveille, SG (reprint author), Hebrew Rehabil Ctr Aged, Res & Training Inst, 1200 Ctr St, Boston, MA 02131 USA. FU NIA NIH HHS [N01-AG12112] NR 34 TC 114 Z9 116 U1 1 U2 3 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 18 PY 2001 VL 135 IS 12 BP 1038 EP 1046 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 502TW UT WOS:000172759700003 PM 11747382 ER PT J AU Li, JL Harrison, RJ Reszka, AP Brosh, RM Bohr, VA Neidle, S Hickson, ID AF Li, JL Harrison, RJ Reszka, AP Brosh, RM Bohr, VA Neidle, S Hickson, ID TI Inhibition of the Bloom's and Werner's syndrome helicases by G-quadruplex interacting ligands SO BIOCHEMISTRY LA English DT Article ID SYNDROME GENE-PRODUCT; ROTHMUND-THOMSON-SYNDROME; HUMAN TELOMERASE INHIBITION; DNA HELICASE; SYNDROME PROTEIN; DRUG DESIGN; HOLLIDAY JUNCTIONS; HUMAN-CELLS; IN-VIVO; RECQ AB G-Quadruplex DNAs are folded, non-Watson-Crick structures that can form within guanine-rich DNA sequences such as telomeric repeats. Previous studies have identified a series of trisubstituted acridine derivatives that are potent and selective ligands for G-quadruplex DNA. These ligands have been shown previously to inhibit the activity of telomerase, the specialized reverse transcriptase that regulates telomere length. The RecQ family of DNA helicases, which includes the Bloom's (BLM) and Werner's (WRN) syndrome gene products, are apparently unique among cellular helicases in their ability to efficiently disrupt G-quadruplex DNA. This property may be relevant to telomere maintenance, since it is known that the sole budding yeast RecQ helicase, Sgs1p, is required for a telomerase-independent telomere lengthening pathway reminiscent of the "ALT" pathway in human cells. Here, we show that trisubstituted acridine ligands are potent inhibitors of the helicase activity of the BLM and WRN proteins on both G-quadruplex and B-form DNA substrates. Inhibition of helicase activity is associated with both a reduction in the level of binding of the helicase to G-quadruplex DNA and a reduction in the degree to which the G-quadruplex DNA can support DNA-dependent ATPase activity. We discuss these results in the context of the possible utility of trisubstituted acridines as antitumor agents for the disruption of both telomerase-dependent and telomerase-independent telomere maintenance. C1 Univ Oxford, John Radcliffe Hosp, Imperial Canc Res Fund Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England. Inst Canc Res, Chester Beatty Labs, CRC, Biomol Struct Unit, London SW3 6JB, England. NIA, Mol Genet Lab, NIH, Baltimore, MD 21224 USA. RP Hickson, ID (reprint author), Univ Oxford, John Radcliffe Hosp, Imperial Canc Res Fund Labs, Weatherall Inst Mol Med, Oxford OX3 9DS, England. NR 60 TC 76 Z9 78 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 18 PY 2001 VL 40 IS 50 BP 15194 EP 15202 DI 10.1021/bi011067h PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502BL UT WOS:000172723800015 PM 11735402 ER PT J AU Nomizu, M Yokoyama, F Suzuki, N Okazaki, I Nishi, N Ponce, ML Kleinman, HK Yamamoto, Y Nakagawa, S Mayumi, T AF Nomizu, M Yokoyama, F Suzuki, N Okazaki, I Nishi, N Ponce, ML Kleinman, HK Yamamoto, Y Nakagawa, S Mayumi, T TI Identification of homologous biologically active sites on the N-terminal domain of laminin alpha chains SO BIOCHEMISTRY LA English DT Article ID CELL-BINDING SEQUENCES; BASEMENT-MEMBRANE; SYNTHETIC PEPTIDES; GLOBULAR DOMAIN; ALPHA-2-BETA-1 INTEGRINS; MOLECULAR-CLONING; NEURITE OUTGROWTH; GAMMA-1 CHAIN; BETA-1 CHAIN; SHORT ARM AB Laminin, a multifunctional glycoprotein of the basement membrane, consists of three different subunits alpha, beta, and gamma chains. To date, five different alpha chains have been identified. N-terminal domain VI in the al chain has various biological activities. Here we screened biologically active sequences on domain VI of the laminin alpha2, alpha3, and alpha5 chains using a large number of overlapping peptides. HT-1080 human fibrosarcoma cell attachment to the peptides was evaluated using peptide-coated plastic plates and peptide-conjugated Sepharose beads. We identified four cell adhesive sequences from laminin alpha2 chain domain VI, two sequences from the alpha3 chain and two sequences from the laminin alpha5 chain. Sequences homologous to A13 (RQVFQVAYIIIKA, alpha1 chain 121-133) on all the alpha chains (FQIAYVIVKA, alpha2 chain 130-139; GQLFHVAYILIKF, alpha3 chain 96-108; FHVAYVLIKA, alpha5 chain 74-83) showed strong cell attachment activity. A5-16 (LENGEIVVSLVNGR, alpha5 chain 147-160) showed the strongest cell attachment activity in the plate assay, and the homologous peptide in the alpha3 chain promoted similar strong cell attachment activity. A5-16 and its homologous peptide in the alpha2 chain promoted moderate cell attachment while the homologous peptide to A5-16 in the alpha1 chain did not show activity. A2-7 (SPSIKNGVEYHYV, alpha2 chain 108-120) showed cell attachment activity only in the plate assay, but homologous sequences in the alpha1, alpha3, and alpha5 chains did not promote activity. A2-7 promoted endothelial cell sprouting from aortic rings in vitro and melanoma colonization to murine lungs in vivo. However, none of the homologous peptides of A2-7 promoted experimental pulmonary metastasis by B16-BL6 melanoma cells. These results indicate that there are chain-specific active sites in domain VI of the laminin a chains, some of which contain conserved activities. C1 Hokkaido Univ, Grad Sch Environm Earth Sci, Kita Ku, Sapporo, Hokkaido 0600810, Japan. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka 5650871, Japan. RP Nomizu, M (reprint author), Hokkaido Univ, Grad Sch Environm Earth Sci, Kita Ku, Kita 10 Nishi 5, Sapporo, Hokkaido 0600810, Japan. NR 42 TC 14 Z9 14 U1 1 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 DEC 18 PY 2001 VL 40 IS 50 BP 15310 EP 15317 DI 10.1021/bi011552c PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502BL UT WOS:000172723800026 PM 11735413 ER PT J AU Miura, Y Hanada, K Jones, TLZ AF Miura, Y Hanada, K Jones, TLZ TI G(s) signaling is intact after disruption of lipid rafts SO BIOCHEMISTRY LA English DT Article ID GPI-ANCHORED PROTEINS; HETEROTRIMERIC G-PROTEINS; BETA-ADRENERGIC-RECEPTOR; T-CELL ACTIVATION; PLASMA-MEMBRANE; ADENYLYL-CYCLASE; DETERGENT INSOLUBILITY; CHOLESTEROL; DOMAINS; TRANSDUCTION AB Membrane microdomains enriched in cholesterol and sphingolipids modulate a number of signal transduction pathways and provide a residence for heterotrimeric G proteins, their receptors, and their effectors. We investigated whether signaling through GS was dependent on these membrane domains, characterized by their resistance to detergents, by depleting cells of cholesterol and sphingolipids. For cholesterol depletion, rat salivary epithelial A5 cells were cultured under low-cholesterol conditions, and then treated with the cholesterol chelator methyl-beta -cyclodextrin. For sphingolipid depletion, LY-B cells, a mutant CHO cell line that is unable to synthesize sphingolipids, were incubated under low-sphingolipid conditions. Depletion of cholesterol or sphingolipid led to a loss or decrease, respectively, in the amount of G alpha (s) from the detergent-resistant membranes without any change in the cellular or membrane-bound amounts of G alpha (s). The cAMP accumulation in response to a receptor agonist was intact and the level slightly increased in cells depleted of cholesterol or sphingolipids compared to that in control cells. These results indicate that localization of G alpha (s) to detergent-resistant membranes was not required for G(s) signaling. Analysis of the role of lipid rafts on the kinetics of protein associations in the membrane suggests that compartmentalization in lipid rafts may be more effective in inhibiting protein interactions and, depending on the pathway, ultimately inhibit or promote signaling. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Infect Dis, Dept Biochem & Cell Biol, Shinjuku Ku, Tokyo 1628640, Japan. RP Jones, TLZ (reprint author), NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NR 53 TC 39 Z9 39 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 18 PY 2001 VL 40 IS 50 BP 15418 EP 15423 DI 10.1021/bi015574a PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502BL UT WOS:000172723800039 PM 11735426 ER PT J AU Friso, S Jacques, PF Rosenberg, ID Selhub, J Wilson, PWF AF Friso, S Jacques, PF Rosenberg, ID Selhub, J Wilson, PWF TI Lack of association of increased C-reactive protein and total plasma homocysteine - Response SO CIRCULATION LA English DT Letter ID DISEASE C1 Tufts Univ, Res Ctr Aging, Jean Mayer US Dept Agr Human Nutr, Boston, MA USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Friso, S (reprint author), Tufts Univ, Res Ctr Aging, Jean Mayer US Dept Agr Human Nutr, Boston, MA USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 18 PY 2001 VL 104 IS 25 BP E164 EP E164 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 505GD UT WOS:000172904300014 ER PT J AU Lim, HM Lee, HJ Roy, S Adhya, S AF Lim, HM Lee, HJ Roy, S Adhya, S TI A "master" in base unpairing during isomerization of a promoter upon RNA polymerase binding SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID OPEN COMPLEX-FORMATION; AROMATIC-AMINO-ACIDS; AMP RECEPTOR PROTEIN; LAMBDA-PR PROMOTER; ESCHERICHIA-COLI; GALACTOSE OPERON; TRANSCRIPTION INITIATION; BACILLUS-SUBTILIS; CYCLIC-AMP; OVERLAPPING PROMOTERS AB Isomerization of a closed to open complex of a promoter upon RNA polymerase binding involves base unpairing at the -10 region. After potassium permanganate sensitivity of unpaired thymine residues, we studied base unpairing at the -10 region during isomerization upon RNA polymerase binding at the P1 and P3 promoters of the gal operon. Substitution of adenine by 2-amino purine (2-AP) at the invariable A-T base pair at the -11 position of P1 and P3 prevented unpairing not only at that position but also at the other downstream positions, suggesting a "master" role of the adenine base at -11 of the template strand in overall base unpairing. 2-AP at -11 did not inhibit the formation of RNA polymerase-promoter complex and subsequent isomerization of the polymerase. Substitution of adenine by 2-AP at several other positions did not affect thymine unpairing. Changing the position of the amino group from CIS in adenine to C2 in 2-AP is mutational only at the master switch position, - 11. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Chungnam Natl Univ, Coll Nat Sci, Dept Biol, Taejon 305764, South Korea. Bose Inst, Dept Biophys, Kolkata 700054, W Bengal, India. RP Adhya, S (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Room 2E16,37 Convent Dr, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov NR 39 TC 48 Z9 48 U1 1 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 DEC 18 PY 2001 VL 98 IS 26 BP 14849 EP 14852 DI 10.1073/pnas.261517398 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800023 PM 11734629 ER PT J AU Center, RJ Schuck, P Leapman, RD Arthur, LO Earl, PL Moss, B Lebowitz, J AF Center, RJ Schuck, P Leapman, RD Arthur, LO Earl, PL Moss, B Lebowitz, J TI Oligomeric structure of virion-associated and soluble forms of the simian immunodeficiency virus envelope protein in the prefusion activated conformation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CRYSTAL-STRUCTURE; MEMBRANE-FUSION; ASSEMBLY DOMAIN; TYPE-1; GLYCOPROTEIN; ECTODOMAIN; GP41; RESOLUTION; MASS; HEMAGGLUTININ AB The envelope proteins (env) of simian immunodeficiency virus (SIV) and HIV type I assemble to form noncovalently associated oligomers in the endoplasmic reticulum. After cleavage in a Golgi compartment, oligomeric env complexes are transported to the surface of infected cells, where incorporation into budding virions can occur. Difficulties in obtaining adequate quantities of virions retaining env, as well as the unstable nature and hydrophobicity of the oligomer, may account for the absence of previous biophysical studies to determine the oligomeric valency of membrane-associated env. The aim of this study was to evaluate the oligomeric state of SIV env before membrane-fusion activation. Virion-associated env, obtained by crosslinking and detergent extraction, and noncrosslinked secreted env ectodomain (recombinant gp140) were purified by lentil-lectin chromatography and gel filtration as single predominant species. Sedimentation equilibrium-derived mass values for both forms of SIV env were close to those predicted for trimeric assemblies. Determination of the mass of individual molecules by scanning transmission electron microscopy confirmed that SIV virion-associated env and gp140 formed largely homogeneous populations of trimers. Furthermore, a triangular or tri-lobed morphology was clearly visualized in a subset of the trimers. C1 NIH, Off Res Serv, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA. AIDS Vaccine Program, SAIC, NCI, Frederick, MD 21702 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Lebowitz, J (reprint author), NIH, Off Res Serv, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. OI Schuck, Peter/0000-0002-8859-6966 NR 35 TC 40 Z9 40 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2001 VL 98 IS 26 BP 14877 EP 14882 DI 10.1073/pnas.261573898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800028 PM 11752436 ER PT J AU Kaneshige, M Suzuki, H Kaneshige, K Cheng, J Wimbrow, H Barlow, C Willingham, MC Cheng, SY AF Kaneshige, M Suzuki, H Kaneshige, K Cheng, J Wimbrow, H Barlow, C Willingham, MC Cheng, SY TI A targeted dominant negative mutation of the thyroid hormone alpha 1 receptor causes increased mortality, infertility, and dwarfism in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LIGAND-BINDING; RESISTANCE; ERBA; GENE; GROWTH AB Mutations in the thyroid hormone receptor beta (TR beta) gene result in resistance to thyroid hormone. However, it is unknown whether mutations in the TR alpha gene could lead to a similar disease. To address this question, we prepared mutant mice by targeting mutant thyroid hormone receptor kindred PV (PV) mutation to the TRa gene locus by means of homologous recombination (TR alpha 1PV mice). The PV mutation was derived from a patient with severe resistance to thyroid hormone that has a frameshift of the C-terminal 14 aa of TR beta1. We knocked in the same PV mutation to the corresponding TRa gene locus to compare the phenotypes of TR alpha1(PV/+) mice with those of TR beta (PV/+) mice. TR alpha1(PV/+) mice were viable, indicating that the mutation of the TRa gene is not embryonic lethal. In drastic contrast to the TR beta (PV/+) mice, which do not exhibit a growth abnormality, TR alpha1(PV/+) mice were dwarfs. These dwarfs exhibited increased mortality and reduced fertility. In contrast to TR beta (PV/+) mice, which have a hyperactive thyroid, TR alpha1(PV/+) mice exhibited mild thyroid failure. The in vivo pattern of abnormal regulation of T3 target genes in TR alpha1(PV/+) mice was unique from those of TR beta (PV/+) mice. The distinct phenotypes exhibited by TR alpha1(PV/+) and Tr beta (PV/+) mice indicate that the in vivo functions of TR mutants are isoform-dependent. The TR alpha1(PV/+) mice may be used as a tool to uncover human diseases associated with mutations in the TR alpha gene and, furthermore, to understand the molecular mechanisms by which TR isoforms exert their biological activities. C1 NHGRI, Mol Biol Lab, Natl Canc Inst, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Frederick Canc Res & Dev Facil, Frederick, MD 21702 USA. Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. RP Cheng, SY (reprint author), NHGRI, Mol Biol Lab, Natl Canc Inst, NIH, Bethesda, MD 20892 USA. NR 21 TC 107 Z9 109 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 DEC 18 PY 2001 VL 98 IS 26 BP 15095 EP 15100 DI 10.1073/pnas.261565798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800065 PM 11734632 ER PT J AU Lighvani, AA Frucht, DM Jankovic, D Yamane, H Aliberti, J Hissong, BD Nguyen, BV Gadina, M Sher, A Paul, WE O'Shea, JJ AF Lighvani, AA Frucht, DM Jankovic, D Yamane, H Aliberti, J Hissong, BD Nguyen, BV Gadina, M Sher, A Paul, WE O'Shea, JJ TI T-bet is rapidly induced by interferon-gamma in lymphoid and myeloid cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE T helper 1; transcription factor; Stat ID TRANSCRIPTION FACTOR; DENDRITIC CELLS; TH2 CELLS; RESPONSES; INTERLEUKIN-12; STAT4; MICE; LYMPHOCYTES; GATA-3; IL-4 AB Differentiation of naive CD4(+) T cells into IFN-gamma -producing T helper 1 (T(H)1) cells is pivotal for protective immune responses against intracellular pathogens. T-bet, a recently discovered member of the T-box transcription factor family, has been reported to play a critical role in this process, promoting IFN-gamma production. Although terminal TH1 differentiation occurs over days, we now show that challenge of mice with a prototypical TH11-inclucing stimulus, Toxoplasma gondii soluble extract, rapidly induced IFN-gamma and T-bet; T-bet induction was substantially lower in IFN-rdeficient mice. Naive T cells expressed little T-bet, but this transcription factor was induced markedly by the combination of IFN-gamma and cognate antigen. Human myeloid antigen-presenting cells showed T-bet induction after IFN-gamma stimulation alone, and this induction was antagonized by IL-4 and granulocyte/macrophage colony-stimulating factor. Although T-bet was induced rapidly and directly by IFN-gamma it was not induced by IFN-alpha lipopolysaccharide, or IL-1, indicating that this action of IFN-gamma was specific. Moreover, T-bet induction was dependent on Stat1 but not Stat4. These data argue for a model in which IFN-gamma gene regulation involves an autocrine loop, whereby the cytokine regulates a transcription factor that promotes its own production. These findings substantially alter the current view of T-bet in IFN-gamma regulation and promotion of cell-mediated immune responses. C1 US FDA, Ctr Biol Evaluat & Res, Cell Biol Lab, Bethesda, MD 20892 USA. NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Cell Biol Lab, Bldg 29B,Room 3NN22,HFM-558, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 22 TC 448 Z9 470 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2001 VL 98 IS 26 BP 15137 EP 15142 DI 10.1073/pnas.261570598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800072 PM 11752460 ER PT J AU Dybul, M Chun, TW Yoder, C Hidalgo, B Belson, M Hertogs, K Larder, B Dewar, RL Fox, CH Hallahan, CW Justement, JS Migueles, SA Metcalf, JA Davey, RT Daucher, M Pandya, P Baseler, M Ward, DJ Fauci, AS AF Dybul, M Chun, TW Yoder, C Hidalgo, B Belson, M Hertogs, K Larder, B Dewar, RL Fox, CH Hallahan, CW Justement, JS Migueles, SA Metcalf, JA Davey, RT Daucher, M Pandya, P Baseler, M Ward, DJ Fauci, AS TI Short-cycle structured intermittent treatment of chronic HIV infection with highly active antiretroviral therapy: Effects on virologic, immunologic, and toxicity parameters SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BLOOD MONONUCLEAR-CELLS; CD4(+) T-CELLS; PROTEASE INHIBITORS; VIRAL SUPPRESSION; RISK-FACTORS; RESISTANCE; INDIVIDUALS; HYPERLIPIDEMIA; INTERRUPTION; REPLICATION AB Although continuous highly active antiretroviral therapy (HAART) is effective for many HIV-infected patients, it can be toxic and prohibitive in cost. By decreasing the total amount of time patients receive medications, intermittent HAART could reduce toxicity and cost. Therefore, we initiated a pilot study in which 10 HIV-infected individuals receiving effective therapy that resulted in levels of HIV RNA < 50 copies per ml of plasma and CD4(+) T cell counts > 300 cells per mm(3) of whole blood received repeated cycles of 7 days on HAART followed by 7 days off of HAART. Patients maintained suppression of plasma viremia for 32-68 weeks. There was no significant increase in HIV proviral DNA or replication-competent HIV in peripheral CD4(+) T cells or HIV RNA in peripheral blood or lymph node mononuclear cells. There was no significant change in CD4(+) T cell counts, no significant increase in CD4(+) or CD8(+) T cells expressing activation markers or producing IFN-gamma in response to HIV, no increase in CD4(+) T cell proliferation to p24 antigen, and no evidence for the development of resistance to HAART medications. There was a significant decrease in serum cholesterol and triglyceride levels. Thus, in this proof-of-concept study, short-cycle intermittent HAART maintained suppression of plasma viremia as well as HIV replication in reservoir sites while preserving CD4(+) T cell counts. In addition, there was a decrease in serum cholesterol and triglyceride levels. Intermittent therapy may be an important strategy to reduce cost and toxicity for HIV-infected individuals. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. VIRCO, B-2800 Mechelen, Belgium. Sci Applicat Int Corp, Frederick, MD 21701 USA. Mol Histol Labs, Rockville, MD 20886 USA. Dupont Circle Phys Grp, Washington, DC 20009 USA. RP Dybul, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11N204, Bethesda, MD 20892 USA. NR 36 TC 108 Z9 111 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 DEC 18 PY 2001 VL 98 IS 26 BP 15161 EP 15166 DI 10.1073/pnas.261568398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800076 PM 11734634 ER PT J AU McCampbell, A Taye, AA Whitty, L Penney, E Steffan, JS Fischbeck, KH AF McCampbell, A Taye, AA Whitty, L Penney, E Steffan, JS Fischbeck, KH TI Histone deacetylase inhibitors reduce polyglutamine toxicity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CREB-BINDING-PROTEIN; SPINOCEREBELLAR ATAXIA TYPE-7; EXPANDED ANDROGEN RECEPTOR; BULBAR MUSCULAR-ATROPHY; MACHADO-JOSEPH-DISEASE; NUCLEAR-LOCALIZATION; HUNTINGTONS-DISEASE; CASPASE CLEAVAGE; GENE-PRODUCT; CAG REPEAT AB Polyglutamine diseases include at least nine neurodegenerative disorders, each caused by a CAG repeat expansion in a different gene. Accumulation of mutant polyglutamine-containing proteins occurs in patients, and evidence from cell culture and animal experiments suggests the nucleus as a site of pathogenesis. To understand the consequences of nuclear accumulation, we created a cell culture system with nuclear-targeted polyglutamine. In our system, cell death can be mitigated by overexpression of full-length cAMP response element binding protein (CREB)-binding protein (CBP) or its aminoterminal portion alone. CBP is one of several histone acetyltransferases sequestered by polyglutamine inclusions. We found histone acetylation to be reduced in cells expressing mutant polyglutamine. Reversal of this hypoacetylation, which can be achieved either by overexpression of CBP or its amino terminus or by treatment with deacetylase inhibitors, reduced cell loss. These findings suggest that nuclear accumulation of polyglutamine can lead to altered protein acetylation in neurons and indicate a novel therapeutic strategy for polyglutamine disease. C1 NINCDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92697 USA. RP Fischbeck, KH (reprint author), NINCDS, Neurogenet Branch, NIH, Bldg 10,room 3B14,10 Ctr Dr, Bethesda, MD 20892 USA. NR 53 TC 171 Z9 176 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 DEC 18 PY 2001 VL 98 IS 26 BP 15179 EP 15184 DI 10.1073/pnas.261400698 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800079 PM 11742087 ER PT J AU Nacht, M Dracheva, T Gao, YH Fujii, T Chen, YD Player, A Akmaev, V Cook, B Dufault, M Zhang, M Zhang, W Guo, MZ Curran, J Han, S Sidransky, D Buetow, K Madden, SL Jen, J AF Nacht, M Dracheva, T Gao, YH Fujii, T Chen, YD Player, A Akmaev, V Cook, B Dufault, M Zhang, M Zhang, W Guo, MZ Curran, J Han, S Sidransky, D Buetow, K Madden, SL Jen, J TI Molecular characteristics of non-small cell lung cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GENE-EXPRESSION PROFILES; PROGNOSTIC-SIGNIFICANCE; SERIAL ANALYSIS; BREAST-CANCER; DNA-DAMAGE; C-MYC; P53; IDENTIFICATION; POLYMORPHISMS; CARCINOMA AB We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers. Separation of normal and tumor, as well as histopathological subtypes, was evident by using the 3,921 most abundant transcript tags. This distinction remained when only 115 highly differentially expressed tags were used. Furthermore, these 115 transcript tags clustered into groups suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, whereas squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21(WAF1/CIP1) and 14-3-3 sigma were consistently underexpressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression patterns observed by SAGE were consistent with results obtained by quantitative real-time PCR or cDNA array analyses by using a total of 43 lung tumor and normal samples. Thus, although derived from only a few tissue libraries, gene expression profiles obtained by using SAGE most likely represent an unbiased yet distinctive molecular signature for the most common forms of human lung cancer. C1 Genzyme Corp, Mol Oncol, Framingham, MA 01701 USA. NCI, Lab Populat Genet, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Ctr Human Genome Res, Bethesda, MD 20892 USA. Johns Hopkins Med Sch, Dept Otolaryngol & Oncol, Div Head & Neck Canc Res, Baltimore, MD 21205 USA. BioChain Inst Inc, Hayward, CA 94545 USA. RP Madden, SL (reprint author), Genzyme Corp, Mol Oncol, POB 9322, Framingham, MA 01701 USA. EM steve.madden@genzyme.com; jenj@mail.nih.gov RI Fujii, Takeshi/D-5877-2014 OI Fujii, Takeshi/0000-0001-7237-1183 FU NCI NIH HHS [CA58184, CA84986, P50 CA058184, U01 CA084986] NR 53 TC 108 Z9 110 U1 1 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 DEC 18 PY 2001 VL 98 IS 26 BP 15203 EP 15208 DI 10.1073/pnas.261414598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800083 PM 11752463 ER PT J AU Aslan, M Ryan, TM Adler, B Townes, TM Parks, DA Thompson, JA Tousson, A Gladwin, MT Patel, RP Tarpey, MM Batinic-Haberle, I White, CR Freeman, BA AF Aslan, M Ryan, TM Adler, B Townes, TM Parks, DA Thompson, JA Tousson, A Gladwin, MT Patel, RP Tarpey, MM Batinic-Haberle, I White, CR Freeman, BA TI Oxygen radical inhibition of nitric oxide-dependent vascular function in sickle cell disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRANSGENIC MOUSE MODEL; ACUTE CHEST SYNDROME; XANTHINE-OXIDASE; LIPID-PEROXIDATION; POTENTIAL ROLE; PEROXYNITRITE; SUPEROXIDE; ANEMIA; ENDOTHELIUM; TISSUE AB Plasma xanthine oxidase (XO) activity was defined as a source of enhanced vascular superoxide (O-2(.-)) and hydrogen peroxide (H2O2) production in both sickle cell disease (SCD) patients and knockout-transgenic SCID mice. There was a significant increase in the plasma XO activity of SCD patients that was similarly reflected in the SCD mouse model. Western blot and enzymatic analysis of liver tissue from SCID mice revealed decreased XO content. Hematoxylin and eosin staining of liver tissue of knockout-transgenic SCD mice indicated extensive hepatocellular injury that was accompanied by increased plasma content of the liver enzyme alanine aminotransferase. Immunincytochemical and enzymatic analysis of XO in thoracic aorta and liver tissue of SCD mice showed increased vessel wall and decreased liver XO, with XO concentrated on and in vascular luminal cells. Steady-state rates of vascular O-2(.-) production, as indicated by coelenterazine chemiluminescence, were significantly increased, and nitric oxide ((NO)-N-.)-dependent vasorelaxation of aortic ring segments was severely impaired in SCD mice, implying oxidative inactivation of (NO)-N-.. Pretreatment of aortic vessels with the superoxide dismutase mimetic manganese 5,10,15,20-tetrakis(N-ethylpyridinium-2-yl)porphyrin markedly decreased O-2(.-) levels and significantly restored acetylcholine-dependent relaxation, whereas catalase had no effect. These data reveal that episodes of intrahepatic hypoxia-reoxygenation associated with SCD can induce the release of XO into the circulation from the liver. This circulating XO can then bind avidly to vessel luminal cells and impair vascular function by creating an oxidative milieu and catalytically consuming (NO)-N-. via O-2(.-)-dependent mechanisms. C1 Univ Alabama, Dept Anesthesiol, Birmingham, AL 35233 USA. Univ Alabama, Dept Biochem & Mol Genet, Birmingham, AL 35233 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35233 USA. Univ Alabama, Dept Med, Birmingham, AL 35233 USA. Univ Alabama, Dept Surg, Birmingham, AL 35233 USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35233 USA. Univ Alabama, Imaging Facil, Birmingham, AL 35233 USA. Univ Alabama, Comprehens Sickle Cell Dis Ctr, Birmingham, AL 35233 USA. NIDDK, Dept Crit Care Med, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Freeman, BA (reprint author), Univ Alabama, Dept Anesthesiol, Birmingham, AL 35233 USA. RI Freeman, Bruce/H-9342-2012; Aslan, Mutay/C-7566-2016; OI Aslan, Mutay/0000-0002-0660-971X; Patel, Rakesh/0000-0002-1526-4303 FU NHLBI NIH HHS [R01 HL058115, P6-HL58418, R01 HL064937, R01-HL58115, R01-HL64937] NR 65 TC 221 Z9 225 U1 1 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 18 PY 2001 VL 98 IS 26 BP 15215 EP 15220 DI 10.1073/pnas.221292098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800085 PM 11752464 ER PT J AU Emerson, SU Zhang, M Meng, XJ Nguyen, H St Claire, M Govindarajan, S Huang, YK Purcell, RH AF Emerson, SU Zhang, M Meng, XJ Nguyen, H St Claire, M Govindarajan, S Huang, YK Purcell, RH TI Recombinant hepatitis E virus genomes infectious for primates: Importance of capping and discovery of a cis-reactive element SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CDNA CLONE; MOLECULAR-CLONING; PROTOTYPE STRAIN; INSECT CELLS; C VIRUS; HEV; RNA; TRANSCRIPTS; ANTIBODY; MONKEYS AB Hepatitis E virus recombinant genomes transcribed in vitro from two cDNA clones differing by two nucleotides were infectious for chimpanzees. However, one cDNA clone encoded a virus that was attenuated for chimpanzees and unable to infect rhesus monkeys. The second cDNA clone encoded a virus that infected both chimpanzees and rhesus monkeys and caused acute hepatitis in both. One mutation differentiating the two clones identified a cis-reactive element that appeared to overlap the 3' end of the capsid gene and part of the 3' noncoding region. Capping of the RNA transcripts was essential for infectivity. C1 NIAID, Mol Hepatitis & Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. Rancho Los Amigos Med Ctr, Liver Res & Educ Fdn, Downey, CA 90242 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Virginia Polytech Inst & State Univ, Dept Biomed Sci & Pathobiol, Ctr Mol Med & Infect Dis, Blacksburg, VA 20461 USA. NCI, Canc Res Ctr, Frederick, MD 21702 USA. RP Emerson, SU (reprint author), NIAID, Mol Hepatitis & Hepatitis Viruses Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Meng, X.J./B-8769-2009 OI Meng, X.J./0000-0002-2739-1334 FU NIAID NIH HHS [1-AO-02733, N01AO02733] NR 26 TC 70 Z9 76 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 DEC 18 PY 2001 VL 98 IS 26 BP 15270 EP 15275 DI 10.1073/pnas.251555098 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800095 PM 11742081 ER PT J AU Winther-Larsen, HC Hegge, FT Wolfgang, M Hayes, SF van Putten, JPM Koomey, M AF Winther-Larsen, HC Hegge, FT Wolfgang, M Hayes, SF van Putten, JPM Koomey, M TI Neisseria gonorrhoeae PilV, a type IV pilus-associated protein essential to human epithelial cell adherence SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TWITCHING MOTILITY; NATURAL TRANSFORMATION; COLONIZATION FACTOR; MEDIATED ADHERENCE; ESCHERICHIA-COLI; MENINGITIDIS; BIOGENESIS; ADHESION; SEQUENCE; BINDING AB Type IV pili (Tfp) of Neisseria gonorrhoeae, the Gram-negative etiologic agent of gonorrhea, facilitate colonization of the human host. Tfp are assumed to play a key role in the initial adherence to human epithelial cells by virtue of the associated adhesin protein PilC. To examine the structural and functional basis for adherence in more detail, we identified potential genes encoding polypeptides sharing structural similarities to PilE (the Tfp subunit) within the N. gonorrhoeae genome sequence database. We show here that a fiber subunit-like protein, termed PilV, is essential to organelle-associated adherence but dispensable for Tfp biogenesis and other pilus-related phenotypes, including autoagglutination, competence for natural transformation, and twitching motility. The adherence defect in pilV mutants cannot be attributed to reduced levels of piliation, defects in fiber anchoring to the bacterial cell surface, or to unstable pilus expression related to organelle retraction. PilV is expressed at low levels relative to PilE and copurifies with Tfp fibers in a PilC-dependent fashion. Purified Tfp from pilV mutants contain PilC adhesin at reduced levels. Taken together, these data support a model in which PilV functions in adherence by promoting the functional display of PilC in the context of the pilus fiber. C1 Biotechnol Ctr Oslo, N-0316 Oslo, Norway. Univ Oslo, Inst Pharm, Dept Microbiol, N-0316 Oslo, Norway. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. NIAID, Rocky Mt Labs, Microscopy Branch, NIH, Hamilton, MT 59840 USA. Univ Utrecht, Dept Infect Dis & Immunol, NL-3584 CL Utrecht, Netherlands. RP Koomey, M (reprint author), Biotechnol Ctr Oslo, N-0316 Oslo, Norway. OI van Putten, Jos/0000-0002-4126-8172 FU NIAID NIH HHS [AI 27837] NR 31 TC 82 Z9 82 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 DEC 18 PY 2001 VL 98 IS 26 BP 15276 EP 15281 DI 10.1073/pnas.261574998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 504GK UT WOS:000172848800096 PM 11752467 ER PT J AU Aghaiypour, K Wlodawer, A Lubkowski, J AF Aghaiypour, K Wlodawer, A Lubkowski, J TI Do bacterial L-asparaginases utilize a catalytic triad Thr-Tyr-Glu? SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY LA English DT Article DE bacterial L-asparaginase; enzymatic mechanism; X-ray crystallography; suicide inhibitor ID ESCHERICHIA-COLI ASPARAGINASE; 7A GLUTAMINASE-ASPARAGINASE; CRYSTAL-STRUCTURE; ACTIVE-SITE; PURIFICATION; SUCCINOGENES; PROGRAM; MUTANT; ACID AB The structures of Erwinia chrysanthemi L-asparaginase (ErA) complexed with the L- and D-stereoisomers of the suicide inhibitor, 6-diazo-5-oxy-norleucine, have been solved using X-ray crystallography and refined with data extending to 1.7 Angstrom. The distances between the C alpha atoms of the inhibitor molecules and the hydroxyl oxygen atoms of Thr-15 and Tyr-29 (1.20 and 1.60 Angstrom, respectively) clearly indicate the presence of covalent bonds between these moieties, confirming the nucleophilic role of Thr-15 during the first stage of enzymatic reactions and also indicating direct involvement of Tyr-29. The factors responsible for activating Tyr-29 remain unclear, although some structural changes around Ser-254', Asp-96, and Glu-63, common to both complexes, suggest that those residues play a function. The role of Glu-289' as the activator of Tyr-29, previously postulated for the closely related Pseudomonas 7A L-glutaminase-asparaginase, is not confirmed in this study, due to the lack of interactions between these residues in these complexes and in holoenzymes. The results reported here are consistent with previous reports that mutants of Escherichia coli L-asparaginase lacking Glu-289 remain catalytically active and prove the catalytic roles of both Thr-15 and Tyr-29, while still leaving open the question of the exact mechanism resulting in the unusual chemical properties of these residues. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Lubkowski, J (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. NR 38 TC 27 Z9 29 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4838 J9 BBA-PROTEIN STRUCT M JI Biochim. Biophys. Acta-Protein Struct. Molec. Enzym. PD DEC 17 PY 2001 VL 1550 IS 2 BP 117 EP 128 DI 10.1016/S0167-4838(01)00270-9 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 506ZP UT WOS:000173001900002 PM 11755201 ER PT J AU Cao, JJ Husbands, SM Kopajtic, T Katz, JL Newman, AH AF Cao, JJ Husbands, SM Kopajtic, T Katz, JL Newman, AH TI [3-cis-3,5-dimethyl-(1-piperazinyl)alkyl]-bis-(4 '-fluorophenyl)amine analogues as novel probes for the dopamine transporter SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID SIGMA-RECEPTOR LIGANDS; REUPTAKE INHIBITORS; 1-<2-ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES GBR-12935; MONOAMINE TRANSPORTERS; COCAINE; POTENT; 1-<2-(DIPHENYLMETHOXY)ETHYL>-4-(3-PHENYLPROPYL)PIPERAZINES; ATTENUATE; AFFINITY; SITES AB in a continuing effort to identify novel probes with which to study the dopamine transporter (DAT), we discovered that the a receptor antagonist, rimcazole, binds with moderate affinity (K-i=224 nM) to the DAT, The results from previous SAR studies suggested that substitution of the carbazole ring system of rimcazole with bis-(4'-fluorophenyl)amine might improve binding affinity and selectivity for the DAT. Thus, a novel series of [3-cis-3.5-dimethyl-(1-piperazinyl)alkyl]bis-(4'-fluorophenyl)amines were synthesized. The most potent compound in this series (9b) displaced [H-3]WIN 35.428 binding in rat caudate-putamen (K-i = 17.6 nM) with comparable affinity to GBR 12909. Despite high-affinity binding at DAT. and structural similarity to GBR 12909, preliminary studies suggest 9b behaves more like rimeazole than GBR 12909 and does not demonstrate cocaine-like psychostimulant behavior in mice. (C) 2001 Published by Elsevier Science Ltd. C1 NIDA, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Psychobiol Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Newman, AH (reprint author), NIDA, Med Chem Sect, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Husbands, Stephen/D-5926-2011; OI Katz, Jonathan/0000-0002-1068-1159; Husbands, Stephen/0000-0002-9928-6322 NR 30 TC 10 Z9 11 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 17 PY 2001 VL 11 IS 24 BP 3169 EP 3173 DI 10.1016/S0960-894X(01)00662-X PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 498FD UT WOS:000172498400019 PM 11720867 ER PT J AU Park, K Han, E Paulsson, J Chattoraj, DK AF Park, K Han, E Paulsson, J Chattoraj, DK TI Origin pairing ('handcuffing') as a mode of negative control of P1 plasmid copy number SO EMBO JOURNAL LA English DT Article DE DNA looping; DNA replication; DNA supercoiling; plasmid; replication control ID ESCHERICHIA-COLI; INITIATOR PROTEIN; DNA-REPLICATION; BINDING-SITES; SEQUESTRATION; REQUIREMENTS; CHROMOSOME; STABILITY; REPLICON; MUTANTS AB In one family of bacterial plasmids, multiple initiator binding sites, called iterons, are used for initiation of plasmid replication as well as for the control of plasmid copy number. Iterons can also pair in vitro via the bound initiators. This pairing, called handcuffing, has been suggested to cause steric hindrance to initiation and thereby control the copy number. To test this hypothesis, we have compared copy numbers of isogenic miniP1 plasmid monomer and dimer. The dimer copy number was only one-quarter that of the monomer, suggesting that the higher local concentration of origins in the dinner facilitated their pairing. Physical evidence consistent with iteron-mediated pairing of origins preferentially in the dimer was obtained in vivo. Thus, origin handcuffing can be a mechanism to control P1 plasmid replication. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. RP Chattoraj, DK (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 50 TC 35 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 17 PY 2001 VL 20 IS 24 BP 7323 EP 7332 DI 10.1093/emboj/20.24.7323 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 507UY UT WOS:000173050700038 PM 11743008 ER PT J AU Wang, JY Ling, H Yang, W Craigie, R AF Wang, JY Ling, H Yang, W Craigie, R TI Structure of a two-domain fragment of HIV-1 integrase: implications for domain organization in the intact protein SO EMBO JOURNAL LA English DT Article DE crystal structure; HIV-1; integrase; transposon Tn5 ID IMMUNODEFICIENCY-VIRUS TYPE-1; PHOTO-CROSS-LINKING; CARBOXYL-TERMINAL DOMAINS; DNA-BINDING DOMAIN; CATALYTIC DOMAIN; RETROVIRAL INTEGRATION; CRYSTAL-STRUCTURE; ACTIVE-SITE; IN-VITRO; COMPLEX AB Retroviral integrase, an essential enzyme for replication of human immunodeficiency virus type-1 (HIV-1) and other retroviruses, contains three structurally distinct domains, an N-terminal domain, the catalytic core and a C-terminal domain. To elucidate their spatial arrangement, we have solved the structure of a fragment of HIV-1 integrase comprising the N-terminal and catalytic core domains. This structure reveals a dimer interface between the N-terminal domains different from that observed for the isolated domain. It also complements the previously determined structure of the C-terminal two domains of HIV-1 integrase; superposition of the conserved catalytic core of the two structures results in a plausible full-length integrase dimer. Furthermore, an integrase tetramer formed by crystal lattice contacts bears structural resemblance to a related bacterial transposase, Tn5, and exhibits positively charged channels suitable for DNA binding. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Craigie, R (reprint author), NIDDK, Mol Biol Lab, NIH, 5 Ctr Dr MSC 0560, Bethesda, MD 20892 USA. RI Ling, Hong/E-3729-2010; Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 50 TC 257 Z9 268 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 17 PY 2001 VL 20 IS 24 BP 7333 EP 7343 DI 10.1093/emboj/20.24.7333 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 507UY UT WOS:000173050700039 PM 11743009 ER PT J AU Kovacs, JA Lempicki, RA Sidorov, IA Adelsberger, JW Herpin, B Metcalf, JA Sereti, I Polis, MA Davey, RT Tavel, J Falloon, J Stevens, R Lambert, L Dewar, R Schwartzentruber, DJ Anver, MR Baseler, MW Masur, H Dimitrov, DS Lane, HC AF Kovacs, JA Lempicki, RA Sidorov, IA Adelsberger, JW Herpin, B Metcalf, JA Sereti, I Polis, MA Davey, RT Tavel, J Falloon, J Stevens, R Lambert, L Dewar, R Schwartzentruber, DJ Anver, MR Baseler, MW Masur, H Dimitrov, DS Lane, HC TI Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE AIDS; bromodeoxyuridine; CD4T lymphocyte proliferation; CD8T lymphocyte proliferation; highly active antiretroviral therapy ID ACTIVE ANTIRETROVIRAL THERAPY; IMMUNODEFICIENCY-VIRUS TYPE-1; CELL TURNOVER; DIAGNOSTIC-TOOL; DNA-REPLICATION; RAPID TURNOVER; NO EVIDENCE; INFECTION; CD4(+); PROLIFERATION AB We examined the effects of human immunodeficiency virus infection on the turnover of CD4 and CD8 T lymphocytes in 17 HIV-infected patients by 30 min in vivo pulse labeling with bromodeoxyuridine (BrdU). The percentage of labeled CD4 and CD8 T lymphocytes was initially higher in lymph nodes than in blood. Labeled cells equilibrated between the two compartments within 24 h. Based on mathematical modeling of the dynamics of BrdU-labeled cells in the blood, we identified rapidly and slowly proliferating subpopulations of CD4 and CD8 T lymphocytes, The percentage, but not the decay rate, of labeled CD4 or CD8 cells in the rapidly proliferating pool correlated significantly with plasma HIV RNA levels for both CD4 (r = 0.77, P < 0.001) and CD8 (r = 0.81, P < 0.001) T cells. In six patients there was a geometric mean decrease of greater than 2 logs in HIV levels within 2 to 6 ino after the initiation of highly active antiretroviral therapy; this was associated with a significant decrease in the percentage (but not the decay rate) of labeled cells in the rapidly proliferating pool for both CD4 (P = 0.03) and CD8 (P < 0.001) T lymphocytes. Neither plasma viral levels nor therapy had an effect on the decay rate constants or the percentage of labeled cells in the slowly proliferating Pool. Monocyte production was inversely related to viral load (r = -0.56, P = 0.003) and increased with therapy (P = 0.01). These findings demonstrate that HIV does not impair CD4 T cell production but does increase CD4 and CD8 lymphocyte proliferation and death by inducing entry into a rapidly proliferating subpopulation of cells. C1 NIAID, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, DBS, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Space Applicat Int Corp, Frederick, MD 21702 USA. RP Kovacs, JA (reprint author), NIAID, Dept Crit Care Med, Ctr Clin, NIH, Bldg 10,Rm 7D43,MSC 1662, Bethesda, MD 20892 USA. RI Lempicki, Richard/E-1844-2012; OI Lempicki, Richard/0000-0002-7059-409X; Polis, Michael/0000-0002-9151-2268; Sidorov, Igor/0000-0001-6519-4983 FU PHS HHS [N01-C0-56000] NR 31 TC 169 Z9 171 U1 1 U2 4 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 DEC 17 PY 2001 VL 194 IS 12 BP 1731 EP 1741 DI 10.1084/jem.194.12.1731 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 505BJ UT WOS:000172890900005 PM 11748275 ER PT J AU Kawakami, K Kawakami, M Snoy, PJ Husain, SR Puri, RK AF Kawakami, K Kawakami, M Snoy, PJ Husain, SR Puri, RK TI In vivo overexpression of IL-13 receptor alpha 2 chain inhibits tumorigenicity of human breast and pancreatic tumors in immunodeficient mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE tumor antigen; neutrophil infiltration; tumorigenesis; IL-8; cytokine receptor ID CELL CARCINOMA-CELLS; AFFINITY INTERLEUKIN-4 RECEPTORS; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; CANCER-CELLS; (IL)-13 BINDING; SARCOMA-CELLS; EXPRESSION; CLONING AB Interleukin 13 receptor alpha2 (IL-13R alpha2) chain is highly expressed on some tumor cell lines and primary cell cultures. This receptor chain plays an important role in ligand binding and internalization. To determine the functional significance of overexpression of this chain, we stably transfected IL-13R alpha2 chain in human breast (MDA-MB-231) and pancreatic (PANC-1) cancer cell lines that naturally do not express this chain. There was no difference in growth between vector only transfected and IL-13R alpha2 chain transfected cells in vitro. However, surprisingly, in immunodeficient mice, tumorigenicity was profoundly inhibited in IL-13R alpha2 chain overexpressing tumors. Because breast tumors that grew later showed loss of IL-13R alpha2 gene expression, lack of tumorigenicity correlated positively with IL-13R alpha2 chain expression. Inflammatory cells including neutrophils and macrophages were identified in IL-13R alpha2 overexpressing regressing tumors and neutrophils were found to produce IL-13. IL-13 showed a modest antitumor activity to IL-13R alpha2 chain overexpressing tumors in vitro and in vivo. Furthermore, IL-13Ra2 chain overexpressing tumors constitutively produced IL-8 that has been shown to have antitumor effect. These results establish a novel function of a cytokine receptor chain and further suggest that the presence of this chain on tumor cells by itself may play a key role in tumorigenicity. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Vet Serv, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, MSC 4555,29 Lincoln Dr,Rm 2NN10,NIH Bldg 29B, Bethesda, MD 20892 USA. NR 50 TC 63 Z9 69 U1 0 U2 3 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 DEC 17 PY 2001 VL 194 IS 12 BP 1743 EP 1754 DI 10.1084/jem.194.12.1743 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 505BJ UT WOS:000172890900006 PM 11748276 ER PT J AU Schuler, T Kammertoens, T Preiss, S Debs, P Noben-Trauth, N Blankenstein, T AF Schuler, T Kammertoens, T Preiss, S Debs, P Noben-Trauth, N Blankenstein, T TI Generation of tumor-associated cytotoxic T lymphocytes requires interleukin 4 from CD8(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE tumor vaccination; cytotoxic T lymphocytes; interleukin 4; interleukin 4 (receptor)-deficient mice; cross-priming ID MHC CLASS-I; DENDRITIC CELLS; SELF-ANTIGENS; HELPER; MICE; IMMUNITY; VIVO; RESPONSES; CYTOKINES; INDUCE AB Activation of tumor-associated CD8(+) cytotoxic T lymphocytes (CTLs) often requires antigen representation, e.g., by dendritic cells (DCs), and CD4(+) T cell help. Previously, we showed that CTL-mediated tumor immunity required interleukin 4 (IL-4) during the immunization but not effector phase. To determine the source and target cells of IL-4, we performed adoptive T cell transfers using CD4(+) and CD8(+) T cells from IL-4(-/-) and IL-4R(-/-) mice and analyzed CTL generation. Even though necessary for CTL generation, CD4(+). T cells did not need to express IL-4 or IL-4R. Surprisingly, CTL generation required IL-4 but not IL-4R expression by CD8(+) T cells. As IL-4 (a) was expressed by naive CD8(+) T cells within 24 h after antigen encounter, (b) IL-4 induced DC maturation, and (c) CTL development was impaired in T cell-reconstituted IL-4P(-/-) mice, CD8(+) T cell-derived IL-4 appears to act on DCs. We conclude that CD4(+) and CD8(+) T cells provide different signals for DC activation during CTL generation. C1 Free Univ Berlin, Inst Immunol, D-12200 Berlin, Germany. NIH, Immunol Lab, Rockville, MD 20582 USA. Max Delbruck Ctr Mol Med, D-13092 Berlin, Germany. RP Schuler, T (reprint author), Max Delbruck Ctr Mol Med, Rober Rossle Str 10, D-13092 Berlin, Germany. NR 42 TC 51 Z9 51 U1 0 U2 2 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 DEC 17 PY 2001 VL 194 IS 12 BP 1767 EP 1775 DI 10.1084/jem.194.12.1767 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 505BJ UT WOS:000172890900008 PM 11748278 ER PT J AU Davis, RE Brown, KD Siebenlist, U Staudt, LM AF Davis, RE Brown, KD Siebenlist, U Staudt, LM TI Constitutive nuclear factor kappa B activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE gene expression profiling; signal transduction; I kappa B kinase; microarray; apoptosis ID HODGKIN/REED-STERNBERG CELLS; BRUTONS TYROSINE KINASE; INDUCED APOPTOSIS; GENE-EXPRESSION; MEDIATED TRANSFORMATION; TRANSCRIPTION FACTORS; REL PROTOONCOGENE; ANTIGEN RECEPTOR; UP-REGULATION; IKK-BETA AB Gene expression profiling has revealed that diffuse large B cell lymphoma (DLBCL) consists of at least two distinct diseases. Patients with one DLBCL subtype, termed activated B cell-like (ABC) DLBCL, have a distinctly inferior prognosis. An untapped potential of gene expression profiling is its ability to identify pathogenic signaling pathways in cancer that are amenable to therapeutic attack. The gene expression profiles of ABC DLBCLs were notable for the high expression of target genes of the nuclear factor (NF)-kappaB transcription factors, raising the possibility that constitutive activity of the NF-kappaB pathway may contribute to the poor prognosis of these patients. Two cell line models of ABC DLBCL had high nuclear NF-kappaB DNA binding activity, constitutive I kappaB kinase (IKK) activity, and rapid I kappaB alpha degradation that was not seen in cell lines representing the other DLBCL subtype, germinal center B-like (GCB) DLBCL. Retroviral transduction of a super-repressor form Of I kappaB alpha or dominant negative forms of IKK beta was toxic to ABC DLBCL cells but not GCB DLBCL cells. DNA content analysis showed that NF-kappaB inhibition caused both cell death and G1-phase growth arrest. These findings establish the NF-kappaB pathway as a new molecular target for drug development in the most clinically intractable subtype of DLBCL and demonstrate that the two DLBCL subtypes defined by gene expression profiling utilize distinct pathogenetic mechanisms. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, NCI Bldg 10,Rm VN114,9000 Rockville Pike, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov NR 71 TC 617 Z9 643 U1 2 U2 11 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 DEC 17 PY 2001 VL 194 IS 12 BP 1861 EP 1874 DI 10.1084/jem.194.12.1861 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 505BJ UT WOS:000172890900016 PM 11748286 ER PT J AU Lapidus, LJ Eaton, WA Hofrichter, J AF Lapidus, LJ Eaton, WA Hofrichter, J TI Dynamics of intramolecular contact formation in polypeptides: Distance dependence of quenching rates in a room-temperature glass SO PHYSICAL REVIEW LETTERS LA English DT Article ID ELECTRON-TRANSFER; CYTOCHROME-C; FREE-ENERGY; PROTEIN; MECHANISMS; PERSPECTIVE; TRYPTOPHAN; CHEMISTRY; KINETICS; MODEL AB Quenching of the triplet state of tryptophan by cysteine is an important new tool for measuring the rate of forming a specific contact between amino acids in a polypeptide chain. To determine the length scale associated with this contact, tryptophan was embedded in a room-temperature glass containing a high concentration of cysteine. The decay of the triplet population is extended in time, consistent with a rate coefficient that decreases exponentially with distance. Solving the diffusion equation with this distant-dependent rate reproduces the observed bimolecular rates in water and shows that quenching at low viscosities takes place less than or similar to1 Angstrom from van der Waals contact between the tryptophan and cysteine. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Lapidus, LJ (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. NR 32 TC 46 Z9 46 U1 0 U2 9 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD DEC 17 PY 2001 VL 87 IS 25 AR 258101 DI 10.1103/PhysRevLett.87.258101 PG 4 WC Physics, Multidisciplinary SC Physics GA 504PZ UT WOS:000172866200060 PM 11736610 ER PT J AU O'Farrell, C Murphy, DD Petrucelli, L Singleton, AB Hussey, J Farrer, M Hardy, J Dickson, DW Cookson, MR AF O'Farrell, C Murphy, DD Petrucelli, L Singleton, AB Hussey, J Farrer, M Hardy, J Dickson, DW Cookson, MR TI Transfected synphilin-1 forms cytoplasmic inclusions in HEK293 cells SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Parkinson's disease; Green fluorescent protein; protein-protein interaction; synuclein ID ALPHA-SYNUCLEIN; LEWY BODIES; PARKINSONS-DISEASE; IN-VITRO; NEURONS; UBIQUITIN; PROTEINS; MUTATION; DEATH; MICE AB The discovery of mutations in the gene for alpha -synuclein in familial Parkinson's disease (PD) has led to an increased interest in this pre-synaptic protein. Synphilin-1, a potential synuclein-binding protein, was cloned using yeast two-hybrid assays. The function of synphilin-1 is currently unknown, although it has been reported to be present along with alpha -synuclein in Lewy bodies in PD. In the present study, we monitored synphilin-1 aggregation directly using fusion proteins of synphilin-1 and green fluorescent protein (EGFP). Transfection of synphilin-EGFP fusion proteins formed cytoplasmic inclusions in HEK293 cells. Although these inclusions overlapped with the distribution of alpha -synuclein, they were unlike Lewy bodies in that they were not eosinophilic, and instead were membrane-bound, lipid-rich cytoplasmic inclusions. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Mayo Clin Jacksonville, Dept Neurosci, Neurogenet Lab, Jacksonville, FL 32224 USA. Mayo Clin Jacksonville, Neuropathol Lab, Jacksonville, FL 32224 USA. NINCDS, Ctr Neurosci, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), Mayo Clin Jacksonville, Dept Neurosci, Neurogenet Lab, Birdsall Bldg,4500 San Pablo Rd, Jacksonville, FL 32224 USA. RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; OI Dickson, Dennis W/0000-0001-7189-7917 NR 16 TC 23 Z9 23 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 16 PY 2001 VL 97 IS 1 BP 94 EP 102 DI 10.1016/S0169-328X(01)00292-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 507HR UT WOS:000173021400012 ER PT J AU Leon-Sarmiento, FE Prada, LJ AF Leon-Sarmiento, FE Prada, LJ TI Babinski's reflex, yes; Babinski's sign, no; Pseudobabinski never! SO REVISTA DE NEUROLOGIA LA French DT Letter C1 NIH, Med Neurol Branch, Bethesda, MD 20892 USA. Univ Ind Santander, Dept Med Interna & Ciencias Basicas, Santander, Spain. Inst Nacl Med Legal & Ciencias Forences, Epidemiol Grp Clin Forense, Bogota, Colombia. NR 15 TC 3 Z9 3 U1 0 U2 1 PU REVISTA DE NEUROLOGIA PI BARCELONA PA C/O CESAR VIGUERA, EDITOR, APDO 94121, 08080 BARCELONA, SPAIN SN 0210-0010 J9 REV NEUROLOGIA JI Rev. Neurologia PD DEC 16 PY 2001 VL 33 IS 12 BP 1200 EP 1200 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 509RP UT WOS:000173163700020 PM 11785062 ER PT J AU Subar, AF Thompson, FE Kipnis, V Midthune, D Hurwitz, P McNutt, S McIntosh, A Rosenfeld, S AF Subar, AF Thompson, FE Kipnis, V Midthune, D Hurwitz, P McNutt, S McIntosh, A Rosenfeld, S TI Comparative validation of the Block, Willett, and National Cancer Institute food frequency questionnaires - The eating at America's table study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diet; epidemiologic methods; food habits; nutrition assessment; nutrition surveys; questionnaires ID DIETARY MEASUREMENT ERROR; DOUBLY LABELED WATER; ENERGY-EXPENDITURE; WOMEN; RECORDS; REPRODUCIBILITY; VALIDITY; HISTORY; OBESE; MEN AB Researchers at the National Cancer Institute developed a new cognitively based food frequency questionnaire (FFQ), the Diet History Questionnaire (DHQ). The Eating at America's Table Study sought to validate and compare the DHQ with the Block and Willett FFQs. Of 1,640 men and women recruited to participate from a nationally representative sample in 1997, 1,301 completed four telephone 24-hour recalls, one in each season. Participants were randomized to receive either a DHQ and Block FFQ or a DHQ and Willett FFQ. With a standard measurement error model, correlations for energy between estimated truth and the DHQ, Block FFQ, and Willett FFQ, respectively, were 0.48, 0.45, and 0.18 for women and 0.49, 0.45, and 0.21 for men. For 26 nutrients, correlations and attenuation coefficients were somewhat higher for the DHQ versus the Block FFQ, and both were better than the Willett FFQ in models unadjusted for energy. Energy adjustment increased correlations and attenuation coefficients for the Willett FFQ dramatically and for the DHQ and Block FFQ instruments modestly. The DHQ performed best overall. These data show that the DHQ and the Block FFQ are better at estimating absolute intakes than is the Willett FFQ but that, after energy adjustment, all three are more comparable for purposes of assessing diet-disease risk. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. RP Subar, AF (reprint author), 6130 Execut Blvd,MSC 7344,EPN 4005, Rockville, MD 20852 USA. NR 38 TC 619 Z9 624 U1 4 U2 40 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2001 VL 154 IS 12 BP 1089 EP 1099 DI 10.1093/aje/154.12.1089 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 505GL UT WOS:000172905000002 PM 11744511 ER PT J AU Subar, AF Thompson, FE Kipnis, V AF Subar, AF Thompson, FE Kipnis, V TI Subar et al. respond to "A further look at dietary questionnaire validation" and "Another perspective on food frequency questionnaires" SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Subar, AF (reprint author), 6130 Execut Blvd,MSC 7344,EPN 4005, Bethesda, MD 20892 USA. NR 6 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2001 VL 154 IS 12 BP 1105 EP 1106 DI 10.1093/aje/154.12.1105 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 505GL UT WOS:000172905000005 ER PT J AU Schatzkin, A Subar, AF Thompson, FE Harlan, LC Tangrea, J Hollenbeck, AR Hurwitz, PE Coyle, L Schussler, N Michaud, DS Freedman, LS Brown, CC Midthune, D Kipnis, V AF Schatzkin, A Subar, AF Thompson, FE Harlan, LC Tangrea, J Hollenbeck, AR Hurwitz, PE Coyle, L Schussler, N Michaud, DS Freedman, LS Brown, CC Midthune, D Kipnis, V TI Design and serendipity in establishing a large cohort with wide dietary intake distributions - The National Institutes of Health-American Association of Retired Persons Diet and Health Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE cohort studies; dietary fats; dietary fiber; fruit; meat; neoplasms; questionnaires; vegetables ID FOOD-FREQUENCY QUESTIONNAIRES; BREAST-CANCER; RECALL; BIAS AB In 1995-1996, the authors mailed a food frequency questionnaire to 3.5 million American Association of Retired Persons members who were aged 50-69 years and who resided in one of six states or two metropolitan areas with high-quality cancer registries. In establishing a cohort of 567,169 persons (340,148 men and 227,021 women), the authors were fortunate in that a less-than-anticipated baseline response rate (threatening inadequate numbers of respondents in the intake extremes) was offset by both a shifting and a widening of the intake distributions among those who provided satisfactory data. Reported median intakes for the first and fifth intake quintiles, respectively, were 20.4 and 40.1 (men) and 20.1 and 40.0 (women) percent calories from fat, 10.3 and 32.0 (men) and 8.7 and 28.7 (women) g per day of dietary fiber, 3.1 and 11.6 (men) and 2.8 and 11.3 (women) servings per day of fruits and vegetables, and 20.7 and 156.8 (men) and 10.5 and 97.0 (women) g per day of red meat. After 5 years of follow-up, the cohort is expected to yield nearly 4,000 breast cancers, more than 10,000 prostate cancers, more than 4,000 colorectal cancers, and more than 900 pancreatic cancers. The large size and wide intake range of the cohort will provide ample power for examining a number of important diet and cancer hypotheses. C1 NCI, Bethesda, MD 20892 USA. Amer Assoc Retired Persons, Washington, DC USA. WESTAT Corp, Rockville, MD 20850 USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Schatzkin, A (reprint author), NCI, 6120 Execut Blvd,EPS 7032, Bethesda, MD 20892 USA. RI Michaud, Dominique/I-5231-2014 NR 16 TC 333 Z9 333 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD DEC 15 PY 2001 VL 154 IS 12 BP 1119 EP 1125 DI 10.1093/aje/154.12.1119 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 505GL UT WOS:000172905000008 PM 11744517 ER PT J AU Devereux, RB Jones, EC Roman, MJ Howard, BV Fabsitz, RR Liu, JE Palmieri, V Welty, TK Lee, ET AF Devereux, RB Jones, EC Roman, MJ Howard, BV Fabsitz, RR Liu, JE Palmieri, V Welty, TK Lee, ET TI Prevalence and correlates of mitral valve prolapse in a population-based sample of American Indians: the strong heart study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID PRESSURE-OVERLOAD HYPERTROPHY; LEFT-VENTRICULAR MASS; CARDIOVASCULAR-DISEASE; RISK-FACTORS; M-MODE; INFECTIVE ENDOCARDITIS; ARTERIAL-HYPERTENSION; COLLAGEN GENES; VOLUME; REGURGITATION AB PURPOSE: Mitral valve prolapse is heritable and occurs frequently in the general population despite associations with mitral regurgitation and infective endocarditis, suggesting that selective advantages might be associated with mitral valve prolapse. SUBJECTS AND METHODS: Clinical examination and 2-dimensional and color Doppler echocardiography were performed in 3340 American Indian participants in the Strong Heart Study. RESULTS: Mitral valve prolapse (clear-cut billowing of one or both mitral leaflets across the mitral anular plane in 2-dimensional parasternal long-axis recordings or >2-mm late systolic posterior displacement of mitral leaflets by M mode) occurred in 37 (1.8%) of 2077 women and 20 (1.6%) of 1263 men (P 0.88); 32 (3.5%) of 907 patients with normal glucose tolerance, 11 (2.3%) of 486 patients with impaired glucose tolerance, and 13 (0.7%) of 1735 patients with diabetes (P <0.0001). Participants with mitral valve prolapse had lower mean ( +/- SD) body mass index (28 5 kg/m(2) vs. 31 +/- 6 kg/m(2), p = 0.001) and blood pressure (124/71 +/- 19/10 mm Hg vs. 130/75 +/- 21/10 mm Hg, P <0.05), as well as lower levels of fasting glucose, triglycerides, serum creatinine, and log urine albumin/creatinine ratio (all P <0.001), than did those without mitral valve prolapse, although all subjects were similar in age (60 +/- 8 years). Participants with mitral valve prolapse had lower ventricular septal (0.87 +/- 0.08 cm vs. 0.93 +/- 0.13 cm) and posterior wall thicknesses (0.82 +/- 0.08 cm vs. 0.87 +/- 0.10 cm), mass (38 +/- 7 g/m(2.7) vs. 42 +/- 11 g/m(2.7)), and relative wall thickness (0.33 +/- 0.04 vs. 0.35 +/- 0.05), and increased stress-corrected midwall shortening (all P <0.01). Mitral valve prolapse was associated with a higher prevalence of mild (16 of 57 [28%] vs. 614 of 3283 [19%]) and more severe mitral regurgitation (5 of 57 [9%] vs. 48 of 3283 [1%], P <0.0001). Regression analyses showed prolapse was associated with low ventricular relative wall thickness, high midwall function, and low urine albumin/creatinine ratio, independent of age, sex, body mass index, and diabetes. CONCLUSIONS: Mitral valve prolapse is fairly common and is strongly associated with mitral regurgitation in the general population. However, it is also associated with lower body weight, blood pressure, and prevalence of diabetes; a more favorable metabolic profile and ventricular geometry; and better myocardial and renal function. Am J Med. 2001;111:679-685. (C) 2001 by Excerpta Medica, Inc. C1 Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Med,Div Cardiol, New York, NY 10021 USA. MedStar Res Inst, Washington, DC USA. NHLBI, Bethesda, MD 20892 USA. Aberdeen Area Tribal Chairmens Hlth Board, Rapid City, SD USA. Univ Oklahoma, Hlth Sci Ctr, Sch Publ Hlth, Oklahoma City, OK USA. RP Devereux, RB (reprint author), Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Med,Div Cardiol, Box 222,525 E 68th St, New York, NY 10021 USA. FU NCRR NIH HHS [M01RR0047-34]; NHLBI NIH HHS [U01-HL41642, U01-HL41654, U01-HL41652] NR 49 TC 40 Z9 43 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2001 VL 111 IS 9 BP 679 EP 685 AR PII S0002-9343(01)00981-0 DI 10.1016/S0002-9343(01)00981-0 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 539CC UT WOS:000174851300001 PM 11747846 ER PT J AU Steinmuller, L Cibelli, G Moll, JR Vinson, C Thiel, G AF Steinmuller, L Cibelli, G Moll, JR Vinson, C Thiel, G TI Regulation and composition of activator protein 1 (AP-1) transcription factors controlling collagenase and c-Jun promoter activities SO BIOCHEMICAL JOURNAL LA English DT Article DE ATF2; ATF4; c-Fos; MEKK1 ID CAMP RESPONSE ELEMENT; I GENE PROMOTER; DNA-BINDING; HETERODIMER FORMATION; LEUCINE ZIPPER; FOS PROTEIN; KINASES; INDUCTION; CREB; JNK AB The activator protein 1 (AP-1) transcription factor is composed of heterodimers of the Fos/activating transcription factor (ATF) and Jun subfamilies of basic-region leucine-zipper (B-ZIP) proteins. In order to determine the identities of individual B-ZIP proteins in various AP-1 complexes we tested the effect of dominant-negative mutants to the B-ZIP proteins c-Fos, ATF2, ATF4 and CCAAT-enhancer-binding protein (C/EBP) on the activities of the collagenase and c-Jun promoters. These dominant-negative mutants inhibit DNA binding of wild-type B-ZIP proteins in a leucine-zipper-dependent fashion. Transcription of a collagenase promoter/reporter gene was induced in HepG2 hepatoma cells by expression of c-Fos and c-Jun, administration of PMA ('TPA') or by expression of a truncated form of MEK (mitogen-activated/extracellular-signal-regulated kinase kinase) kinase-1, MEKK1 Delta. In all cases, the dominant-negative mutants A-Fos and A-ATF2 decreased collagenase promoter activity. However, A-ATF4 and A-C/EBP had no effect. A-Fos and A-ATF2 also reduced MEKK1 Delta -induced stimulation of the c-Jun promoter. In contrast, constitutive c-Jun promoter activity was blocked solely by A-ATF2, strongly suggesting that ATF2 and/or an ATF2-dimerizing protein are of major importance for c-Jun transcription in unstimulated cells. These results demonstrate that AP-1 transcription factors of different compositions control c-jun gene transcription in resting or stimulated cells. C1 Univ Saarland, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. Univ Bari, Fac Med, Dept Pharmacol & Human Physiol, I-70124 Bari, Italy. NCI, Met Lab, NIH, Bethesda, MD 20892 USA. RP Thiel, G (reprint author), Univ Saarland, Dept Med Biochem & Mol Biol, Bldg 44, D-66421 Homburg, Germany. NR 36 TC 49 Z9 49 U1 1 U2 4 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 15 PY 2001 VL 360 BP 599 EP 607 DI 10.1042/0264-6021:3600599 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 505YT UT WOS:000172943700010 PM 11736649 ER PT J AU Weinstein, LS AF Weinstein, LS TI The role of tissue-specific imprinting as a source of phenotypic heterogeneity in human disease SO BIOLOGICAL PSYCHIATRY LA English DT Article DE genomic imprinting; uniparental disomy; DNA methylation; Prader-Willi syndrome; Angelman syndrome; pseudohypoparathyroidism ID BECKWITH-WIEDEMANN-SYNDROME; PSEUDOHYPOPARATHYROIDISM TYPE IB; MATERNAL-BEHAVIOR; GENE; BRAIN; CHROMOSOME; PROTEIN; LOCUS; RESISTANCE; DISORDERS AB Genomic imprinting is an epigenetic phenomenon affecting a small number of genes that leads to expression from only one parental allele. Several imprinted genes are important for neurologic development and function and several neurobehavioral disorders are caused by genetic defects involving imprinted genes. For some genes, the imprinting is tissue specific, leading to biallelic expression in some tissues and monoallelic expression in other tissues. Defects involving these genes may produce one restricted phenotype due to loss of expression of the gene product in tissues where the gene is imprinted and, in some instances, a second phenotype due to haploinsufficiency of the gene product in tissues where it is biallelically expressed. Biol Psychiatry 2001;50:927-931 (C) 2001 Society of Biological Psychiatry. C1 NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Weinstein, LS (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. RI Weinstein, Lee/I-5575-2015; OI Weinstein, Lee/0000-0002-1899-5152 NR 30 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2001 VL 50 IS 12 BP 927 EP 931 DI 10.1016/S0006-3223(01)01295-1 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 504DD UT WOS:000172841300001 PM 11750888 ER PT J AU Storek, J Joseph, A Espino, G Dawson, MA Douek, DC Sullivan, KM Flowers, MED Martin, P Mathioudakis, G Nash, RA Storb, R Appelbaum, FR Maloney, DG AF Storek, J Joseph, A Espino, G Dawson, MA Douek, DC Sullivan, KM Flowers, MED Martin, P Mathioudakis, G Nash, RA Storb, R Appelbaum, FR Maloney, DG TI Immunity of patients surviving 20 to 30 years after allogeneic or syngeneic bone marrow transplantation SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; SEVERE COMBINED IMMUNODEFICIENCY; VERSUS-HOST DISEASE; T-CELLS; TETANUS ANTITOXIN; IMMUNOGLOBULIN-G; LATE INFECTIONS; THYMIC FUNCTION; CHRONIC GRAFT; B-CELL AB The duration of immunodeficiency following marrow transplantation is not known. Questionnaires were used to study the infection rates in 72 patients surviving 20 to 30 years after marrow grafting. Furthermore, in 33 of the 72 patients and in 16 donors (siblings who originally donated the marrow) leukocyte subsets were assessed by flow cytometry. T-cell receptor excision circles (TRECs), markers of T cells generated de novo, were quantitated by real-time polymerase chain reaction. Immunoglobulin G(2) (IgG(2)) and antigen-specific IgG levels were determined by enzyme-linked immunosorbent assay. Infections diagnosed 15 years after transplantation occurred rarely. The average rate was 0.07 infections per patient-year (one infection every 14 years), excluding respiratory tract infections, gastroenteritis, lip sores, and hepatitis C. The counts of circulating monocytes, natural killer cells, B cells, CD4 T cells, and CD8 T cells in the patients were not lower than in the donors. The counts of TREC+ CD4 T cells in transplant recipients younger than age 18 years (at the time of transplantation) were not different from the counts in their donors. In contrast, the counts of TREC+ CD4 T cells were lower in transplant recipients age 18 years or older, even in those with no history of clinical extensive chronic graft-versus-host disease, compared with their donors. The levels of total IgG(2) and specific IgG against Haemophilus, influenzae and Streptococcus pneumoniae were similar in patients and donors. Overall, the immunity of patients surviving 20 to 30 years after transplantation is normal or near normal. Patients who received transplants in adulthood have a clinically insignificant deficiency of de novo-generated CD4 T cells, suggesting that in these patients the posttransplantation thymic insufficiency may not be fully reversible. (C) 2001 by The American Society of Hematology. C1 FHCRC, Seattle, WA 98109 USA. Univ Washington, Seattle, WA 98195 USA. NCI, Med Branch, Vaccine Res Ctr, NIAID,HIH, Bethesda, MD USA. NCI, Med Branch, Dept Expt Transplantat & Immunol, HIH, Bethesda, MD USA. RP Storek, J (reprint author), FHCRC, D1-100,1100 Fairview Ave N, Seattle, WA 98109 USA. FU NCI NIH HHS [CA18821, CA15704, CA18029, CA68496]; NHLBI NIH HHS [HL36444]; NIAID NIH HHS [AI46108] NR 68 TC 81 Z9 83 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 DEC 15 PY 2001 VL 98 IS 13 BP 3505 EP 3512 DI 10.1182/blood.V98.13.3505 PG 8 WC Hematology SC Hematology GA 500AX UT WOS:000172604700001 PM 11739150 ER PT J AU Maciejewski, JP Follmann, D Nakamura, R Saunthararajah, Y Rivera, CE Simonis, T Brown, KE Barrett, JA Young, NS AF Maciejewski, JP Follmann, D Nakamura, R Saunthararajah, Y Rivera, CE Simonis, T Brown, KE Barrett, JA 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 Article ID DEPENDENT APLASTIC-ANEMIA; T-CELL REPERTOIRE; CLASS-II; INDUCED AGRANULOCYTOSIS; HLA ASSOCIATIONS; BONE-MARROW; SUSCEPTIBILITY; DISEASE; CYCLOSPORINE; ANTIGEN AB Many autoimmune diseases are associated with HLA alleles, and such a relationship also has been reported for aplastic anemia (AA). AA and paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and glycophosphoinositol (GPI)-anchored protein (AP)-deficient cells can be found in many patients with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA alleles was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PNH. Tests of proportions were used to compare allelic frequencies. For patients with a PNH clone (defined by the presence of GPI-AP-deficient granulocytes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58% versus 28%; z = 4.05). The increased presence of HILA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/PNH (56%) than in AA without a PNH clone (37%; z = 3.36). Analysis of a second cohort of patients with bone marrow failure treated with immunosuppression showed that HLA-DR2 was associated with a hematologic response (50% of responders versus 34% of nonresponders; z = 2.69). Both the presence of HLA-DR2 and the PNH clone were independent predictors of response but the size of PNH clone did not correlate with improvement in blood count. The results suggest that clonal expansion of GPI-AP-deficient cells is linked to HLA and likely related to an immune mechanism. (C) 2001 by The American Society of Hematology. C1 NIH, Hematol Branch, Clin Ctr, Hematol Sect,Dept Lab Med, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD USA. HLA Lab, Dept Transfus Med, Bethesda, MD USA. RP Maciejewski, JP (reprint author), NIH, Hematol Branch, Clin Ctr, Hematol Sect,Dept Lab Med, Bldg 10,Rm 7C108, Bethesda, MD 20892 USA. NR 40 TC 84 Z9 93 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 DEC 15 PY 2001 VL 98 IS 13 BP 3513 EP 3519 DI 10.1182/blood.V98.13.3513 PG 7 WC Hematology SC Hematology GA 500AX UT WOS:000172604700002 PM 11739151 ER PT J AU Mahieux, R Pise-Masison, C Gessain, A Brady, JN Olivier, R Perret, E Misteli, T Nicot, C AF Mahieux, R Pise-Masison, C Gessain, A Brady, JN Olivier, R Perret, E Misteli, T Nicot, C TI Arsenic trioxide induces apoptosis in human T-cell leukemia virus type 1-and type 2-infected cells by a caspase-3-dependent mechanism involving Bcl-2 cleavage SO BLOOD LA English DT Article ID NF-KAPPA-B; ACUTE PROMYELOCYTIC LEUKEMIA; I-TRANSFORMED-CELLS; HTLV-1 TAX PROTEIN; GENE-EXPRESSION; GROWTH-INHIBITION; 1-INFECTED CELLS; DOWN-REGULATION; RETINOIC ACIDS; DNA-REPAIR AB Treatment of patients with adult T-cell leukemia-lymphoma (ATLL) using conventional chemotherapy has limited benefit because human T-cell leukemia virus type 1 (HTLV-1) cells are resistant to most apoptosis-inducing agents. The recent report that arsenic trioxide induces apoptosis in HTLV-1-transformed cells prompted investigation of the mechanism of action of this drug in HTLV-1 and HTLV-2 interleukin-2-independent T cells and in HTLV-1-immortalized cells or in ex vivo ATLL samples. Fluorescence-activated cell sorter analysis, fluorescence microscopy, and measures of mitochondrial membrane potential (Delta Psim) demonstrated that arsenic trioxide alone was sufficient to induce programmed cell death in all HTLV-1 and -2 cells tested and in ATLL patient samples. I kappaB-alpha phosphorylation strongly decreased, and NF-kappaB translocation to the nucleus was abrogated. Expression of the antiapoptotic protein Bcl-X-L, whose promoter is NF-kappaB dependent, was down-regulated. The collapse of Delta Psim and the release of cytochrome c to the cytosol resulted in the activation of caspase-3, as demonstrated by the cleavage of PARR A specific caspase-3 Inhibitor (Ac-DEVD-CHO) could reverse this phenotype. The antiapoptotic factor Bcl-2 was then cleaved, converting ft to a Sax-like death effector. These results demonstrated that arsenic trioxide Induces apoptosis In HTLV-1- and -2-infected cells through activation of the caspase pathway. (C) 2001 by The American Society of Hematology. C1 Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, F-75724 Paris 15, France. Inst Pasteur, Unite Oncol Virale, F-75724 Paris, France. NCI, Virus Tumor Biol Sect, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Mahieux, R (reprint author), Inst Pasteur, Unite Epidemiol & Physiopathol Virus Oncogenes, 28 Rue Dr Roux, F-75724 Paris 15, France. NR 61 TC 78 Z9 86 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 DEC 15 PY 2001 VL 98 IS 13 BP 3762 EP 3769 DI 10.1182/blood.V98.13.3762 PG 8 WC Hematology SC Hematology GA 500AX UT WOS:000172604700035 PM 11739184 ER PT J AU Allander, SV Nupponen, NN Ringner, M Hostetter, G Maher, GW Goldberger, N Chen, YD Carpten, J Elkahloun, AG Meltzer, PS AF Allander, SV Nupponen, NN Ringner, M Hostetter, G Maher, GW Goldberger, N Chen, YD Carpten, J Elkahloun, AG Meltzer, PS TI Gastrointestinal stromal tumors with KIT mutations exhibit a remarkably homogeneous gene expression profile SO CANCER RESEARCH LA English DT Article ID MOLECULAR CLASSIFICATION; TYROSINE KINASE; CANCER; AMPLIFICATION; CELLS AB Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the digestive tract, are believed to arise from the interstitial cells of Cajal. GISTs are characterized by mutations in the proto-oncogene KIT that lead to constitutive activation of its tyrosine kinase activity. The tyrosine kinase inhibitor STI571, active against the BCR-ABI. fusion protein in chronic myeloid leukemia, was recently shown to be highly effective in GISTs. We used 13,826-element cDNA microarrays to define the expression patterns of 13 KIT mutation-positive GISTs and compared them with the expression profiles of a group of spindle cell tumors from locations outside the gastrointestinal tract. Our results showed a remarkably distinct and uniform expression profile for all of the GISTs. In particular, hierarchical clustering of a subset of 113 cDNAs placed all of the GIST samples into one branch, with a Pearson correlation >0.91. This homogeneity suggests that the molecular pathogenesis of a GIST results from expansion of a clone that has acquired an activating mutation in KIT without the extreme genetic instability found in the common epithelial cancers. The results provide insight into the histogenesis of GIST and the clinical behavior of this therapeutically responsive tumor. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. RI Ringner, Markus/G-3641-2011 OI Ringner, Markus/0000-0001-5469-8940 NR 27 TC 140 Z9 142 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 DEC 15 PY 2001 VL 61 IS 24 BP 8624 EP 8628 PG 5 WC Oncology SC Oncology GA 505CU UT WOS:000172894500004 PM 11751374 ER PT J AU Huhn, M Sasse, S Tur, MK Matthey, B Schinkothe, T Rybak, SM Barth, S Engert, A AF Huhn, M Sasse, S Tur, MK Matthey, B Schinkothe, T Rybak, SM Barth, S Engert, A TI Human angiogenin fused to human CD30 ligand (Ang-CD30L) exhibits specific cytotoxicity against CD30-positive lymphoma SO CANCER RESEARCH LA English DT Article ID REFRACTORY HODGKINS LYMPHOMA; A-CHAIN IMMUNOTOXIN; CELLS IN-VITRO; RECOMBINANT IMMUNOTOXIN; SCID MICE; ANTI-CD30 IMMUNOTOXIN; MONOCLONAL-ANTIBODIES; ANTITUMOR-ACTIVITY; TUMOR-CELLS; PHASE-I AB A number of different immunotoxins composed of cell-specific targeting structures coupled to plant or bacterial toxins have increasingly been evaluated for immunotherapy. Because these foreign proteins are highly immunogenic in humans, we have developed a new CD30 ligand-based fusion toxin (Ang-CD30L) using the human RNase angiogenin. The completely human fusion gene was inserted into a pET-based expression plasmid. Transformed Escherichia coli BL21(DE3) were grown under osmotic stress conditions in the presence of compatible solutes. After isopropyl beta -D-thiogalactoside induction, the M-r 37,000 His(10)-tagged Ang-CD30L was directed into the periplasmic space and functionally purified by a combination of metal ion affinity followed by enterokinase cleavage of the His(10)-Tag and molecular size chromatography. The characteristics of the recombinant protein were assessed by ELISA, flow cytometry, and toxicity assays showing specific activity against CD30(+) Hodgkin-derived cells. Specific binding activity of Ang-CD30L was verified by competition with anti-CD30 monoclonal antibody Ki-4 and commercially available CD30L-CD8 chimeric protein. Ang-CD30L showed RNase activity in vitro. The human recombinant immunotoxin showed significant toxicity toward several CD30-positive cell lines (HDLM-2, L1236, KM-H2, and L540Cy) and exhibited highest cytotoxicity against L540 cells (IC50 = 8 ng/ml) as determined by cell proliferation assays. CD30 specificity was confirmed by competitive toxicity assays. This is the first report on the specific cytotoxicity of a recombinant completely human fusion toxin with possibly largely reduced immunogenicity for the treatment of CD30-positive malignancies. C1 Fraunhofer IME, Dept Pharmaceut Prod Dev, D-52074 Aachen, Germany. Univ Hosp Cologne, Dept Internal Med 1, Lab Immunotherapy, D-50931 Cologne, Germany. NCI, Frederick Canc Res & Dev Ctr, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA. RP Barth, S (reprint author), Fraunhofer IME, Dept Pharmaceut Prod Dev, Worringer Weg 1, D-52074 Aachen, Germany. RI Barth, Stefan/F-7301-2012 OI Barth, Stefan/0000-0001-9589-653X NR 43 TC 62 Z9 66 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2001 VL 61 IS 24 BP 8737 EP 8742 PG 6 WC Oncology SC Oncology GA 505CU UT WOS:000172894500023 PM 11751393 ER PT J AU McCart, JA Ward, JM Lee, J Hu, Y Alexander, HR Libutti, SK Moss, B Bartlett, DL AF McCart, JA Ward, JM Lee, J Hu, Y Alexander, HR Libutti, SK Moss, B Bartlett, DL TI Systemic cancer therapy with a tumor-selective vaccinia virus mutant lacking thymidine kinase and vaccinia growth factor genes SO CANCER RESEARCH LA English DT Article ID PURINE NUCLEOSIDE PHOSPHORYLASE; IN-VIVO; CARCINOEMBRYONIC ANTIGEN; TRANSGENE EXPRESSION; RECOMBINANT; VECTOR; ADENOVIRUS; IMMUNOGENICITY; ANGIOGENESIS; POXVIRUSES AB We have demonstrated previously the oncolytic effects of a systemically delivered, replicating vaccinia virus. To enhance the tumor specificity of this vector, we have developed a combined thymidine kinase-deleted (TK-) and vaccinia growth factor-deleted (VGF-) vaccinia virus and investigated its properties in vitro and in vivo. The gene for enhanced green fluorescent protein (EGFP) was inserted into the TK locus of a VGF- vaccinia virus by homologous recombination creating a double-deleted mutant vaccinia virus (vvDD-GFP). Infection of resting and dividing NIH3T3 cells with vvDD-GFP yielded reduced viral recovery compared with wild-type (WT), TK-, or VGF- viruses from resting cultures but equivalent virus recovery from dividing cultures. Eight days after nude mice were injected i.p. with 10(7) plaque-forming units (pfu) of WT, TK-, VGF-, or vvDD-GFP vaccinia virus, tissues and tumor were harvested for viral titer determination. No virus was recovered from the brains of mice injected with vvDD-GFP compared with the other viruses, which ranged from 130 to 28,000 pfu/mg protein; however, equivalent amounts were recovered from tumor. There was no toxicity from vvDD-GFP because nude mice receiving 10(8) pfu of IP vvDD-GFP lived > 100 days, whereas mice receiving WT, VGF-, or TK- virus had median survivals of only 6, 17, and 29 days, respectively. Similar results were seen when 10(9) pfu of vvDD-GFP were given. Nude mice bearing s.c. murine colon adenocarcinoma (MC38) had significant tumor regression after treatment with 109 pfu of systemic (i.p.) vvDD-GFP compared with control (mean tumor size, 180.71 +/- 35.26 mm(3) versus 2796.79 +/- 573.20 mm(3) 12 days after injection of virus). Our data demonstrate that a TK- and VGF- mutant vaccinia virus is significantly attenuated in resting cells in vitro and demonstrates tumor-specific replication in vivo. It is a promising vector for use in tumor-directed gene therapy, given its enhanced safety profile, tumor selectivity, and the oncolytic effects after systemic delivery. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Off Lab Anim Resources, Ft Detrick, MD 21702 USA. RP Bartlett, DL (reprint author), Univ Pittsburgh, Kauffman Med Bldg,Suite 300,3471 5th Ave, Pittsburgh, PA 15213 USA. NR 61 TC 205 Z9 211 U1 3 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2001 VL 61 IS 24 BP 8751 EP 8757 PG 7 WC Oncology SC Oncology GA 505CU UT WOS:000172894500025 PM 11751395 ER PT J AU Zimonjic, D Brooks, MW Popescu, N Weinberg, RA Hahn, WC AF Zimonjic, D Brooks, MW Popescu, N Weinberg, RA Hahn, WC TI Derivation of human tumor cells in vitro without widespread genomic instability SO CANCER RESEARCH LA English DT Article ID LARGE T-ANTIGEN; EPITHELIAL-CELLS; MICROSATELLITE INSTABILITY; COLORECTAL-CANCER; TRANSFORMATION; ANEUPLOIDY; DNA; KERATINOCYTES; CHROMOSOMES; EXPRESSION AB The majority of adult human epithelial cancers exhibit evidence of genetic instability, and it is widely believed that the genetic instability manifested by aneuploidy or microsatellite instability plays an essential role in the genesis of these tumors. Indeed, most experimental models of cancer also show evidence of genomic instability. The resulting genetic chaos, which has widespread effects on many genes throughout the genome, confounds attempts to determine the precise cohort of genetic changes that are required for the transformation of normal human cells to a tumorigenic state. Here we show that genetic transformation of human kidney epithelial cells can occur in the absence of extensive aneuploidy, chromosomal translocations, and microsatellite instability. These observations demonstrate that the in vitro oncogenic transformation of human cells can proceed without widespread genomic instability. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. NCI, Mol Cytogenet Sect, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20815 USA. RP Hahn, WC (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. EM william_hahn@dfci.harvard.edu FU NCI NIH HHS [K01 CA94223, R01 CA78461] NR 39 TC 83 Z9 83 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2001 VL 61 IS 24 BP 8838 EP 8844 PG 7 WC Oncology SC Oncology GA 505CU UT WOS:000172894500036 PM 11751406 ER PT J AU Conze, D Weiss, L Regen, PS Bhushan, A Weaver, D Johnson, P Rincon, M AF Conze, D Weiss, L Regen, PS Bhushan, A Weaver, D Johnson, P Rincon, M TI Autocrine production of interleukin 6 causes multidrug resistance in breast cancer cells SO CANCER RESEARCH LA English DT Article ID RECOMBINANT HUMAN INTERLEUKIN-6; TRANSCRIPTION FACTOR NF-IL6; PHASE-I TRIAL; P-GLYCOPROTEIN; GENE-EXPRESSION; MDR1 GENE; PROGNOSTIC-SIGNIFICANCE; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; PROTEIN-KINASES AB It has been shown that serum levels of interleukin (IL)-6 are elevated in patients with various types of cancer. However, the exact source of IL-6 in these patients and its role in tumor progression remain unclear. Here we demonstrate that the autocrine production of IL-6 by tumor cells promotes resistance of the cells to chemotherapy, a novel function of IL-6 in cancer biology. Breast cancer cells that are sensitive to drug treatment do not express IL-6, whereas high levels of IL-6 are produced by multidrug-resistant breast cancer cells. Expression of the IL-6 gene in drug-sensitive breast cancer cells increases their resistance to drug treatment by activating the CCAAT enhancer-binding protein family of transcription factors and inducing mdr1 gene expression. Thus, the autocrine production of IL-6 by tumor cells is an important factor in determining the susceptibility or resistance of these cells to drug treatment. Because tumors from some breast cancer patients contain IL-6-producing cells, it is possible that IL-6 could potentially be used as a prognostic factor for chemotherapy resistance. C1 Univ Vermont, Dept Med, Immunobiol Sect, Burlington, VT 05405 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Idaho State Univ, Coll Pharm, Dept Pharmaceut Sci, Pocatello, ID 83209 USA. NCI, Eukaryot Transcript Regulat Sect, Regulat Cell Growth Lab, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. RP Rincon, M (reprint author), Univ Vermont, Dept Med, Immunobiol Sect, Given Med Bldg D-305, Burlington, VT 05405 USA. RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 NR 84 TC 137 Z9 144 U1 3 U2 9 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 DEC 15 PY 2001 VL 61 IS 24 BP 8851 EP 8858 PG 8 WC Oncology SC Oncology GA 505CU UT WOS:000172894500038 PM 11751408 ER PT J AU Hunter, KW Broman, KW Le Voyer, T Lukes, L Cozma, D Debies, MT Rouse, J Welch, DR AF Hunter, KW Broman, KW Le Voyer, T Lukes, L Cozma, D Debies, MT Rouse, J Welch, DR TI Predisposition to efficient mammary tumor metastatic progression is linked to the breast cancer metastasis suppressor gene Brms1 SO CANCER RESEARCH LA English DT Article ID QUANTITATIVE TRAIT LOCI; AUTOCRINE MOTILITY FACTOR; LYMPH-NODE METASTASIS; INBRED MOUSE STRAINS; LUNG-CANCER; EXTRACELLULAR-MATRIX; MELANOMA METASTASIS; MALIGNANT-MELANOMA; ACTIVATION; CARCINOMA AB Tumor metastasis is one of the most important clinical aspects of neoplastic disease because patient mortality is frequently attributable to disseminated rather than primary tumors. However, it still is not possible to definitively distinguish those individuals at high risk for disseminated disease, who would benefit from aggressive adjuvant therapy, from the low-risk patients who might be spared the side effects of additional anticancer therapy. To identify factors that predispose toward metastatic disease, we have used a genetic approach. Using a highly metastatic model of mammary cancer, we identified previously inbred mouse strains (DBA/ 2J, NZB/B1NJ, and I/LnJ) that harbor genetic factors that significantly suppress metastatic efficiency. In this study, we report the results of four experiments to localize the genetic map locations of the metastasis efficiency modifier genes. One statistically significant locus was identified on proximal Chr 19 designated Mtes1. Secondary candidate intervals were detected on Chrs 6, 9, 13, and 17. Interestingly, Mtes1 colocalizes with the murine orthologue of the human breast cancer metastasis suppressor gene Brms1, suggesting that allelic variants of Brms1 might be responsible for the metastasis suppression observed. C1 NCI, Lab Populat Genet, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA. Penn State Univ, Coll Med, Jake Gittlen Canc Res Inst, Hershey, PA 17033 USA. RP Hunter, KW (reprint author), NCI, Lab Populat Genet, Div Canc Epidemiol & Genet, NIH, 41-D702,41 Ctr Dr, Bethesda, MD 20892 USA. RI Welch, Danny/B-7310-2009 OI Welch, Danny/0000-0002-1951-4947 FU NCI NIH HHS [R01 CA88728] NR 49 TC 85 Z9 89 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 DEC 15 PY 2001 VL 61 IS 24 BP 8866 EP 8872 PG 7 WC Oncology SC Oncology GA 505CU UT WOS:000172894500040 PM 11751410 ER PT J AU Olive, PL Aquino-Parsons, C MacPhail, SH Liao, SY Raleigh, JA Lerman, MI Stanbridge, EJ AF Olive, PL Aquino-Parsons, C MacPhail, SH Liao, SY Raleigh, JA Lerman, MI Stanbridge, EJ TI Carbonic anhydrase 9 as an endogenous marker for hypoxic cells in cervical cancer SO CANCER RESEARCH LA English DT Article ID TUMOR HYPOXIA; DIAGNOSTIC BIOMARKER; PIMONIDAZOLE BINDING; COMET ASSAY; BLOOD-FLOW; EXPRESSION; CARCINOMA; PROTEIN; UBIQUITINATION; RADIATION AB The presence of radiation-resistant hypoxic cells in some solid tumors is known to predict for relapse after radiotherapy. Use of an endogenous marker of hypoxia would be a convenient alternative to current methods that measure tumor oxygenation, provided the marker could be shown to reliably identify viable, radiation-resistant, hypoxic cells. Carbonic anhydrase 9 (CA9) is a transmembrane protein overexpressed in a wide variety of tumor types and induced by hypoxia. Using a monoclonal antibody and cell sorting, CA9-positive cells in SiHa cervical carcinoma xenografts growing in immunodeficient mice were found to be clonogenic, resistant to killing by ionizing radiation, and preferentially able to bind the hypoxia marker pimonidazole. CA9 and pimonidazole immunostaining were compared in formalin-fixed sections from tumors of 18 patients undergoing treatment for cancer of the cervix. Excellent colocalization was observed, although the area of the tumor section that bound anti-CA9 antibodies represented double the number of cells that bound anti-pimonidazole antibodies. Occasional regions staining with pimonidazole but not CA9 could be indicative of transient changes in tumor perfusion. Results support the hypothesis that CA9 is a useful endogenous marker of tumor hypoxia. C1 British Columbia Canc Res Ctr, Dept Med Biophys, Vancouver, BC V5Z 1L3, Canada. British Columbia Canc Agcy, Vancouver, BC V5Z 1L3, Canada. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Olive, PL (reprint author), British Columbia Canc Res Ctr, Dept Med Biophys, 601 W 10th Ave, Vancouver, BC V5Z 1L3, Canada. FU NCI NIH HHS [CA-19401, CA-37879, CA-50995] NR 29 TC 135 Z9 137 U1 1 U2 7 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2001 VL 61 IS 24 BP 8924 EP 8929 PG 6 WC Oncology SC Oncology GA 505CU UT WOS:000172894500048 PM 11751418 ER PT J AU Dionne, SO Smith, MH Marincola, FM Lake, DF AF Dionne, SO Smith, MH Marincola, FM Lake, DF TI Antigen presentation of a modified tumor-derived peptide by tumor infiltrating lymphocytes SO CELLULAR IMMUNOLOGY LA English DT Article DE gp100; peptide presentation; antigen presenting cells; HLA; tumor infiltrating lymphocytes ID CYTOTOXIC T-CELLS; METASTATIC MELANOMA; SELF-PRESENTATION; IMMUNE-EVASION; EXPRESSION; VACCINE; GP100; LYSIS; RESPONSES; CANCER AB CD8(+) T-lymphocytes recognize peptides in the context of major histocompatibility complex (MHC) class I antigens. Upon activation, these cells differentiate into effector cytotoxic T lymphocytes (CTL) and no longer require formal antigen presentation by professional antigen presenting cells (APC). Subsequently, any cell expressing MHC class I/cognate peptide can stimulate CTL. Using TIL specific for a melanoma antigen-derived peptide, IMDQVPFSV (g209 2M), we sought to determine whether these CTL could present peptide to each other. Our findings demonstrate that peptide presentation of the g209 2M peptide epitope by TIL is comparable to conventional methods of using T2 cells as APC. We report here that CTL are capable of self-presentation of antigenic peptide to neighboring CTL resulting in IFN-gamma secretion, proliferation, and lysis of peptide-loaded CTL. These results demonstrate that human TIL possess both APC functions as well as cytotoxic functions and that this phenomenon could influence CTL activity elicited by immunotherapy. (C) 2001 Elsevier Science (USA). C1 Univ Arizona, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. Univ Arizona, Dept Biochem, Tucson, AZ 85724 USA. NCI, Div Clin Sci, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Lake, DF (reprint author), Univ Arizona, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. FU NIAID NIH HHS [AI43480-01A2] NR 29 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 2001 VL 214 IS 2 BP 139 EP 144 DI 10.1006/cimm.2001.1893 PG 6 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 551FQ UT WOS:000175549600004 PM 12088412 ER PT J AU Nanki, T Lipsky, PE AF Nanki, T Lipsky, PE TI Stimulation of T-cell activation by CXCL12/stromal cell derived factor-1 involves a G-protein mediated signaling pathway SO CELLULAR IMMUNOLOGY LA English DT Article DE human; T lymphocytes; chemokine; stromal cell derived factor-1 ID CHEMOKINE RECEPTOR CXCR4; LYMPHOCYTES; KINASE; CHEMOTAXIS; ACCUMULATION; TRANSDUCTION; POLARIZATION; CORECEPTORS; EXPRESSION; INDUCTION AB Recently we found that CXCL12/SDF-1 is a costimulator of peripheral CD4(+) T cells. In this study, we report that CXCL12 alone induced expression of activation markers by peripheral CD4(+) memory T cells and costimulated activation marker expression by anti-CD3 stimulated peripheral CD4(+) naive and CD4(+) memory T cells as well as by peripheral CD8(+) T cells. The stimulation by CXCL12 was inhibited by Pertussis Toxin (PTX), but not by anti-CD25 mAb. CXCL12 also induced enhancement of IL-2 production and proliferation by anti-CD3 stimulated CD4(+) memory T cells, but not by CD4(+) naive T cells. PTX inhibited the enhancement of IL-2 production and proliferation, whereas anti-CD25 mAb inhibited proliferation, but not IL-2 production. Thus, CXCL12 upregulated T-cell activation, and a G-coupled protein mediated signaling pathway was necessary for stimulation of T cells by CXCL12. C1 Natl Inst Arthritis & Musculoskeletal & Skin Dis, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), Natl Inst Arthritis & Musculoskeletal & Skin Dis, Bldg 10 Rm 9N228 10 Ctr Dr MSC 1820, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR-39169] NR 33 TC 17 Z9 17 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 2001 VL 214 IS 2 BP 145 EP 154 DI 10.1006/cimm.2001.1890 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 551FQ UT WOS:000175549600005 PM 12088413 ER PT J AU Xu, H Izon, DJ Loftin, C Spain, LM AF Xu, H Izon, DJ Loftin, C Spain, LM TI The COX-2 inhibitor NS-398 causes T-cell developmental disruptions independent of COX-2 enzyme inhibition SO CELLULAR IMMUNOLOGY LA English DT Article DE thymus; cellular differentiation; transgenic/knockout; lipid mediators ID COLON-CANCER CELLS; PROSTAGLANDIN E-2; SYNTHASE CYCLOOXYGENASE; DUCTUS-ARTERIOSUS; GENE-EXPRESSION; DENDRITIC CELLS; BLOOD-PRESSURE; UP-REGULATION; MICE LACKING; KAPPA-B AB Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the function of cyclooxygenases, COX-1 and COX-2, which catalyze the first step in the synthesis of inflammatory mediators (PGE(2)). We sought to understand the roles of cyclooxygenases and NSAIDs in T-cell development. Our data show no significant defects in T-cell development in fetal thymic organ cultures of mice disrupted in both or either COX genes or in mice disrupted in either EP-1 or EP-2 receptor genes. On the other hand, NSAIDs reproducibly caused thymocyte developmental defects. However, the specific effects of the COX-2 inhibitors were not correlated with their potency for inhibition of COX-2 activity. We focused on the NS-398 COX-2 inhibitor and showed that its effects could not be reversed by exogenous PGE(2). Furthermore, NS-398 was inhibitory even when its target, COX-2, was absent. These data show that the T-cell developmental effects of NS-398 are COX-2 and PGE(2) independent. (C) 2001 Elsevier Science (USA). C1 Amer Red Cross, Jerome H Holland Lab Biomed Res, Rockville, MD 20855 USA. NIEHS, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. RP Spain, LM (reprint author), Amer Red Cross, Jerome H Holland Lab Biomed Res, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. FU NIAID NIH HHS [AI49807] NR 53 TC 11 Z9 11 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD DEC 15 PY 2001 VL 214 IS 2 BP 184 EP 193 DI 10.1006/cimm.2001.1891 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 551FQ UT WOS:000175549600009 PM 12088417 ER PT J AU Goldenthal, KL Falk, LA Ball, L Geber, A AF Goldenthal, KL Falk, LA Ball, L Geber, A TI Prelicensure evaluation of combination vaccines SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID CONJUGATE VACCINE; CLINICAL-TRIALS; IMMUNOGENICITY; SAFETY; ISSUES; POLYSACCHARIDE; INFANTS; POTENCY AB There is considerable public health interest in licensing safe and effective combination vaccines. Because combination vaccines may progress rapidly from phase 1 to a pivotal phase 2 immunogenicity trial, a rigorous approach to address product issues early in development is warranted. Clinical studies to evaluate the safety, immunogenicity, and (when necessary) clinical end point efficacy of combination vaccines should be randomized and well controlled in most cases. A large phase 3 safety study (i.e., a study that enrolls thousands of vaccinees) should be included in the development plan if a phase 3 (clinical end point) efficacy trial will not be conducted. Often, the new combination vaccine under development contains immunogens that have all been previously licensed, have demonstrated efficacy in earlier clinical trials, or both. For such products, comparative immunogenicity data may be sufficient to support efficacy. When applicable, clinical data to support simultaneous administration with other relevant vaccines should be obtained. Given the complexity of combination vaccine development, early consultation with United States Food and Drug Administration can be invaluable. C1 US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. RP Goldenthal, KL (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, HFM-475,1401 Rockville Pike, Rockville, MD 20852 USA. NR 46 TC 9 Z9 9 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2001 VL 33 SU 4 BP S267 EP S273 DI 10.1086/322561 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 494QB UT WOS:000172293300002 PM 11709758 ER PT J AU Roederer, M AF Roederer, M TI Compensation is not dependent on signal intensity or on number of parameters SO CYTOMETRY LA English DT Letter ID FLUORESCENCE C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIH, Vaccine Res Ctr, Bldg 10, Bethesda, MD 20892 USA. RI Roederer, Mario/G-1887-2011 NR 6 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD DEC 15 PY 2001 VL 46 IS 6 BP 357 EP 357 DI 10.1002/cyto.10008 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 506DT UT WOS:000172955100006 PM 11754206 ER PT J AU Hellsten, E Evans, JP Bernard, DJ Janne, PA Nussbaum, RL AF Hellsten, E Evans, JP Bernard, DJ Janne, PA Nussbaum, RL TI Disrupted sperm function and fertilin beta processing in mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b SO DEVELOPMENTAL BIOLOGY LA English DT Article DE phosphoinositide; inositol polyphosphate 5-phosphatase; fertilization; sperm; epididymis; fertilin beta ID MALE-INFERTILITY; MOUSE FERTILIN; TYROSINE PHOSPHORYLATION; SEQUENCE-ANALYSIS; EPIDIDYMAL SPERM; CRE RECOMBINASE; ZONA-PELLUCIDA; ALPHA; MATURATION; ROLES AB Inpp5b is an ubiquitously expressed type 11 inositol polyphosphate 5-phosphatase. We have disrupted the Inpp5b gene in mice and found that homozygous mutant males are infertile. Here we examine the causes for the infertility in detail. We demonstrate that sperm from Inpp5b(-/-) males have reduced motility and reduced ability to fertilize eggs, although capacitation and acrosome exocytosis appear to be normal. In addition, fertilin 13, a sperm surface protein involved in sperm-egg membrane interactions that is normally proteolytically processed during sperm transit through the epididymis, showed reduced levels of processing in the Inpp5b(-/-) animals. Inpp5b was expressed in the Sertoli cells and epididymis and at low levels in the developing germ cells; however, mice lacking Inpp5b in spermatids and not in other cell types generated by conditional gene targeting, were fully fertile. The abnormalities in mutant sperm function and maturation appear to arise from defects in the functioning of Sertoli and epididymal epithelial cells. Our results directly demonstrate a previously unknown role for phosphoinositides in normal sperm maturation beyond their previously characterized involvement in the acrosome reaction. Inpp5b(-/-) mice provide an excellent model to study the role of Sertoli and epididymal epithelial cells in the differentiation and maturation of sperm. (C) 2001 Elsevier Science. C1 Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Div Reprod Biol, Baltimore, MD 21205 USA. Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Nussbaum, RL (reprint author), Natl Human Genome Res Inst, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD 37696] NR 51 TC 27 Z9 28 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD DEC 15 PY 2001 VL 240 IS 2 BP 641 EP 653 DI 10.1006/dbio.2001.0476 PG 13 WC Developmental Biology SC Developmental Biology GA 510PK UT WOS:000173216300025 PM 11784089 ER PT J AU Wheeler, MD Kono, H Yin, M Nakagami, M Uesugi, T Arteel, GE Gabele, E Rusyn, I Yamashina, S Froh, M Adachi, Y Iimuro, Y Bradford, BU Smutney, OM Connor, HD Mason, RP Goyert, SM Peters, JM Gonzalez, FJ Samulski, RJ Thurman, RG AF Wheeler, MD Kono, H Yin, M Nakagami, M Uesugi, T Arteel, GE Gabele, E Rusyn, I Yamashina, S Froh, M Adachi, Y Iimuro, Y Bradford, BU Smutney, OM Connor, HD Mason, RP Goyert, SM Peters, JM Gonzalez, FJ Samulski, RJ Thurman, RG TI The role of Kupffer cell oxidant production in early ethanol-induced liver disease SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE adenovirus; superoxide dismutase; TNF alpha; NADPH oxidase; knockout mice; free radicals ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; NADPH OXIDASE; FREE-RADICALS; ALCOHOL; INJURY; RAT; GLUTATHIONE; ACTIVATION; SUPEROXIDE AB Considerable evidence for a role of Kupffer cells in alcoholic liver disease has accumulated and they have recently been shown to be a predominant source of free radicals. Several approaches including pharmacological agents, knockout trice. and viral gene transfer have been used to fill critical gaps in understanding key mechanisms by which Kupffer cell activation, oxidant formation and cytokine production lead to liver damage and subsequent pathogenesis. This review highlights new data in support of the hypothesis that Kupffer cell, play a pivotal role in hepatotoxicity due to ethanol by producing oxidants via NADPH oxidise. (C) 2001 Elsevier Science Inc. C1 Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pharmacol, Gene Therapy Ctr, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. New York Med Coll, New York, NY USA. NCI, Bethesda, MD 20892 USA. RP Wheeler, MD (reprint author), Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, CB 7365,Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. RI Peters, Jeffrey/D-8847-2011; Rusyn, Ivan/S-2426-2016 NR 43 TC 153 Z9 163 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD DEC 15 PY 2001 VL 31 IS 12 BP 1544 EP 1549 DI 10.1016/S0891-5849(01)00748-1 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 503JX UT WOS:000172796300006 PM 11744328 ER PT J AU Fisher, GH Wellen, SL Klimstra, D Lenczowski, JM Tichelaar, JW Lizak, MJ Whitsett, JA Koretsky, A Varmus, HE AF Fisher, GH Wellen, SL Klimstra, D Lenczowski, JM Tichelaar, JW Lizak, MJ Whitsett, JA Koretsky, A Varmus, HE TI Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes SO GENES & DEVELOPMENT LA English DT Article DE lung cancer; K-Ras; tetracycline; p53; Ink4A; apoptosis ID ONCOGENIC RAS; IN-VIVO; CANCER; P53; MICE; GROWTH; CELLS; ACTIVATION; DEATH; PROLIFERATION AB To investigate the role of an activated K-Ras gene in the initiation and maintenance of lung adenocarcinomas, we developed transgenic mice that express murine K-Ras4b(G12D) under the control of doxycycline in type II pneumocytes. Focal proliferative lesions of alveolar type II pneumocytes were observed as early as seven days after induction with doxycycline; after two months of induction, the lungs contained adenomas and adenocarcinomas, with focal invasion of the pleura at later stages. Removal of doxycycline caused a rapid fan in levels of mutant K-Ras RNA and concomitant apoptotic regression of both the early proliferative lesions and the tumors. Tumor burden was dramatically decreased by three days after withdrawal, and tumors were undetectable after one month. When similar experiments were performed with animals deficient in either the p53 gene or the Ink4A/Arf locus, tumors arose more quickly (within one month of exposure to doxycycline) and displayed more obvious histological features of malignancy; nevertheless, these tumors also regressed rapidly when the inducer was removed, implying that continued production of mutant K-Ras is necessary to maintain the viability of tumor cells in the absence as well as the presence of tumor suppressor genes. We also show that the appearance and regression of these pulmonary tumors can be readily monitored in anesthetized transgenic animals by magnetic resonance imaging. C1 NCI, Varmus Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Cell Biol, New York, NY 10021 USA. Cincinnati Childrens Hosp, Cincinnati, OH 45229 USA. Natl Inst Neurol Disorders & Stroke, MRI Res Facil & Mouse Imaging Facil, NIH, Bethesda, MD 20892 USA. RP Varmus, HE (reprint author), NCI, Varmus Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RI Tichelaar, Jay/B-9148-2011; Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 NR 45 TC 360 Z9 373 U1 0 U2 15 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 2001 VL 15 IS 24 BP 3249 EP 3262 DI 10.1101/gad.947701 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 504WP UT WOS:000172879200004 PM 11751631 ER PT J AU Sukhodolets, MV Cabrera, JE Zhi, HJ Jin, DJ AF Sukhodolets, MV Cabrera, JE Zhi, HJ Jin, DJ TI RapA, a bacterial homolog of SWI2/SNF2, stimulates RNA polymerase recycling in transcription SO GENES & DEVELOPMENT LA English DT Article DE RapA; SWI2/SNF2 homolog; transcriptional activation; RNA polymerase recycling; remodeling posttranscription complexes ID PROTEIN-DNA INTERACTIONS; RHO-INDEPENDENT TERMINATORS; ESCHERICHIA-COLI; SUPERCOILED DNA; CLEAVAGE FACTORS; IONIC CONDITIONS; GENE-EXPRESSION; IN-VITRO; INITIATION; FAMILY AB We report that RapA, an Escherichia coli RNA polymerase (RNAP)-associated homolog of SW12/SNF2, is capable of dramatic activation of RNA synthesis. The RapA-mediated transcriptional activation in vitro depends on supercoiled DNA and high salt concentrations, a condition that is likely to render the DNA superhelix tightly compacted. Moreover, RapA activates transcription by stimulating RNAP recycling. Mutational analyses indicate that the ATPase activity of RapA is essential for its function as a transcriptional activator, and a rapA null mutant exhibits a growth defect on nutrient plates containing high salt concentrations in vivo. Thus, RapA acts as a general transcription factor and an integral component of the transcription machinery. The mode of action of RapA in remodeling posttranscription or posttermination complexes is discussed. C1 NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. RP Jin, DJ (reprint author), NCI, Lab Mol Biol, NIH, Bethesda, MD 20892 USA. NR 47 TC 37 Z9 38 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 2001 VL 15 IS 24 BP 3330 EP 3341 DI 10.1101/gad.936701 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 504WP UT WOS:000172879200011 PM 11751638 ER PT J AU Srivastava, AK Durmowicz, MC Hartung, AJ Hudson, J Ouzts, LV Donovan, DM Cui, CY Schlessinger, D AF Srivastava, AK Durmowicz, MC Hartung, AJ Hudson, J Ouzts, LV Donovan, DM Cui, CY Schlessinger, D TI Ectodysplasin-A1 is sufficient to rescue both hair growth and sweat glands in Tabby mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID HYPOHIDROTIC ECTODERMAL DYSPLASIA; FOLLICLE INDUCTION; FACTOR RECEPTOR; HUMAN HOMOLOG; MOUSE; PROTEIN; GENE; MUTATIONS; DIFFERENTIATION; ENCODES AB Mutations in the human ectodysplasin-A (EDA) are responsible for the most common form of the ectodermal dysplasia and the defective orthologous gene in mice produces the tabby phenotype, suggesting its vital role in the development of hair, sweat glands and teeth. Among several EDA splice isoforms, the most common and the longest EDA splice isoforms, EDA-A1 and EDA-A2, differing by only two amino acids, activate NF-kappaB-promoted transcription by binding to distinct receptors, EDAR and XEDAR. The extent to which any particular isoform is sufficient for the formation of hair, sweat glands or teeth has remained unclear. Here we report that transgenic expression of the mouse EDA-A1 isoform in tabby (EDA-less) males rescued development of several skin appendages. The transgenic tabby mice showed almost complete restoration of hair growth, dermal ridges, sweat glands and molars. The number of hair follicles in the transgenic mice is the same as in wild-type; though the development of follicles and associated glands varies from indistinguishable from wild-type to smaller and/or only partially formed. These results suggest that the other EDA isoforms may not be absolutely required for skin appendage formation, but consistent with distinctive temporal and spatial expression of the EDA-A2 isoform, are likely required for appropriate timing and completeness of development. Our data provide the first direct physiological evidence that EDA-A1 is a key regulator of hair follicle and sweat gland initiation; its soluble ligand form could aid in deriving therapeutic reagents for conditions affecting hair and sweat gland formation. C1 Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. NIA, Genet Lab, Baltimore, MD 21224 USA. RP Srivastava, AK (reprint author), Greenwood Genet Ctr, JC Self Res Inst Human Genet, Greenwood, SC 29646 USA. NR 39 TC 59 Z9 61 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2001 VL 10 IS 26 BP 2973 EP 2981 DI 10.1093/hmg/10.26.2973 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 504RU UT WOS:000172870300002 PM 11751679 ER PT J AU Esteller, M Fraga, MF Guo, MZ Garcia-Foncillas, J Hedenfalk, I Godwin, AK Trojan, J Vaurs-Barriere, C Bignon, YJ Ramus, S Benitez, J Caldes, T Akiyama, Y Yuasa, Y Launonen, V Canal, MJ Rodriguez, R Capella, G Peinado, MA Borg, A Aaltonen, LA Ponder, BA Baylin, SB Herman, JG AF Esteller, M Fraga, MF Guo, MZ Garcia-Foncillas, J Hedenfalk, I Godwin, AK Trojan, J Vaurs-Barriere, C Bignon, YJ Ramus, S Benitez, J Caldes, T Akiyama, Y Yuasa, Y Launonen, V Canal, MJ Rodriguez, R Capella, G Peinado, MA Borg, A Aaltonen, LA Ponder, BA Baylin, SB Herman, JG TI DNA methylation patterns in hereditary human cancers mimic sporadic tumorigenesis SO HUMAN MOLECULAR GENETICS LA English DT Article ID NONPOLYPOSIS COLORECTAL-CANCER; PEUTZ-JEGHERS-SYNDROME; SERINE THREONINE KINASE; AND/OR OVARIAN-CANCER; PROMOTER HYPERMETHYLATION; BREAST-CANCER; MOLECULAR ANALYSIS; COLON TUMORS; BRCA1 GENE; INACTIVATION AB Cancer cells have aberrant patterns of DNA methylation including hypermethylation of gene promoter CpG islands and global demethylation of the genome. Genes that cause familial cancer, as well as other genes, can be silenced by promoter hypermethylation in sporadic tumors, but the methylation of these genes in tumors from kindreds with inherited cancer syndromes has not been well characterized. Here, we examine CpG island methylation of 10 genes (hMLH1, BRCA1, APC, LKB1, CDH1, p16(INK4a), p14(ARF), MGMT, GSTP1 and RAR beta2) and 5-methylcytosine DNA content, in inherited (n = 342) and non-inherited (n = 215) breast and colorectal cancers. Our results show that singly retained alleles of germline mutated genes are never hypermethylated in inherited tumors. However, this epigenetic change is a frequent second 'hit', associated with the wild-type copy of these genes in inherited tumors where both alleles are retained. Global hypomethylation was similar between sporadic and hereditary cases, but distinct differences existed in patterns of methylation at non-familial genes. This study demonstrates that hereditary cancers 'mimic' the DNA methylation patterns present in the sporadic tumors. C1 Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. Ctr Nacl Invest Oncol, Mol Pathol Program, Canc Epigenet Lab, Madrid, Spain. Ctr Nacl Invest Oncol, Mol Pathol Program, Human Genet Lab, Madrid, Spain. Univ Navarra, Clin Univ Pamplona, Lab Biotechnol & Genom, E-31080 Pamplona, Spain. Fox Chase Canc Ctr, Mol Genet Lab, Philadelphia, PA 19111 USA. Univ Frankfurt, Dept Internal Med, D-6000 Frankfurt, Germany. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Ctr Jean Perrin, Oncol Mol Lab, Clermont Ferrand, France. Tokyo Med & Dent Univ, Sch Med, Dept Mol Oncol, Tokyo 113, Japan. Hosp Clin San Carlos, Mol Oncol Lab, Madrid, Spain. Sch Biol, Dept Biochem, Oviedo, Spain. Inst Recerca Oncol, Barcelona, Catalonia, Spain. Inst Catala Oncol, Barcelona, Catalonia, Spain. Lund Univ, Dept Oncol, Lund, Sweden. Univ Helsinki, Haartman Inst, Dept Med Genet, Helsinki, Finland. Addenbrookes Hosp, Cambridge Inst Med Res, Cambridge, England. RP Herman, JG (reprint author), Johns Hopkins Oncol Ctr, Room 543,1650 Orleans St, Baltimore, MD 21231 USA. RI Susan, Ramus/C-1607-2008; Garcia-Foncillas, Jesus/E-6857-2010; Peinado, Miguel A./A-5591-2008; Canal, Maria Jesus/L-1005-2014; Aaltonen, Lauri/A-5375-2010; Esteller, Manel/L-5956-2014; OI Peinado, Miguel A./0000-0002-4090-793X; Canal, Maria Jesus/0000-0002-1639-9672; Aaltonen, Lauri/0000-0001-6839-4286; Esteller, Manel/0000-0003-4490-6093; Ramus, Susan/0000-0003-0005-7798 NR 41 TC 296 Z9 310 U1 9 U2 22 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2001 VL 10 IS 26 BP 3001 EP 3007 DI 10.1093/hmg/10.26.3001 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 504RU UT WOS:000172870300005 PM 11751682 ER PT J AU Chiba-Falek, O Nussbaum, RL AF Chiba-Falek, O Nussbaum, RL TI Effect of allelic variation at the NACP-Rep1 repeat upstream of the alpha-synuclein gene (SNCA) on transcription in a cell culture luciferase reporter system SO HUMAN MOLECULAR GENETICS LA English DT Article ID SPORADIC PARKINSONS-DISEASE; DNA-FORMING SEQUENCES; HANDED Z-DNA; ALZHEIMERS-DISEASE; PROMOTER REGION; SUBUNIT GENE; HUMAN GENOME; LEWY BODIES; POLYMORPHISM; EXPRESSION AB Mutations in the alpha -synuclein gene (SNCA) have been implicated in familial Parkinson's disease (PD) while certain polymorphic alleles at a microsatellite repeat, NACP-Rep1, located similar to 10 kb upstream of the gene, have been associated with sporadic PD. In order to study the regulation of the human alpha -synuclein gene, we performed a deletion analysis of 10.7 kb upstream of the translational start site, using the luciferase reporter assay in 293T cells and the neuroblastoma cell line SH-SY5Y. The shortest fragment, 400 bp upstream of the transcriptional start site, was sufficient for transcription in both cell lines. The other constructs led to variable expression levels, with some showing maximum expression and others showing nearly complete extinction of expression. An 880 bp fragment located similar to 10 kb upstream of the gene and containing the NACP-Rep1 polymorphism, was shown to be necessary for normal expression. Additional analysis of the NACP-Rep1 locus and surrounding DNA suggested that two domains flanking the repeat interact to enhance expression while the repeat acts as a negative modulator. Next, we measured the activity of the entire 10.7 kb upstream region in the luciferase reporter assay when each of our different NACP-Rep1 alleles were present. The expression levels varied very significantly among the different alleles over a 3-fold range in the SH-SY5Y cells but showed little or no significant variation in the 293T cells. Given that even small changes in alpha -synuclein expression may, over many decades, predispose to PD, the association of different NACP-Rep1 alleles with PD may be a consequence of polymorphic differences in transcriptional regulation of alpha -synuclein expression resulting from different NACP-Rep1 alleles. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA. NR 31 TC 143 Z9 146 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD DEC 15 PY 2001 VL 10 IS 26 BP 3101 EP 3109 DI 10.1093/hmg/10.26.3101 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 504RU UT WOS:000172870300015 PM 11751692 ER PT J AU Vaillant, B Chiaramonte, MG Cheever, AW Soloway, PD Wynn, TA AF Vaillant, B Chiaramonte, MG Cheever, AW Soloway, PD Wynn, TA TI Regulation of hepatic fibrosis and extracellular matrix genes by the Th response: New insight into the role of tissue inhibitors of matrix metalloproteinases SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE SCHISTOSOMIASIS-MANSONI; IN-VITRO; GRANULOMATOUS RESPONSE; CYTOKINE PRODUCTION; PROGELATINASE-A; DOWN-MODULATION; STELLATE CELLS; LIVER FIBROSIS; GELATINASE-B; EXPRESSION AB Hepatic fibrosis is the hallmark of Schistosoma mansoni infection and often results in portal hypertension and bleeding from esophageal varices. The fibrotic process is highly dependent on type 2 cytokines, yet their role in the regulation of extracellular matrix remodeling genes remains largely unknown. Here, we examined the expression of matrix metalloproteases (MMP) -2, -3, -9, -12, and -13 and their inhibitors, tissue inhibitor of metalloproteases (TIMP) -1, -2, and -3, in the livers of infected mice and correlated their expression profiles with fibrosis and type 2 cytokine production. Expression of MMP-2, -3, -9, -12, and -13 and of TIMP-1 and -2 mRNA rapidly increased at the onset of egg laying in infected mice, while TIMP-3 was unchanged. Because TIMP are presumed to be important regulators of the extracellular matrix, and their expression correlated with the development of fibrosis, we studied their role in fibrogenesis by infecting TIMP-1- and TIMP-2-deficient mice. Strikingly, our data revealed no role for TIMP-1 or -2 in the fibrotic pathology induced by S. mansoni eggs. Because of these findings, we infected IL-10/IFN-gamma -deficient mice that develop an exaggerated fibrotic response to determine whether changes in type 2 cytokine dominance influence the pattern of MMP and TIMP expression. Fibrosis and type 2 cytokine production correlated with increased MMP-2/MMP-9 vs TIMP-1/TIMP-2 expression. These data, in addition to our knockout studies, demonstrate that TIMP-1/TIMP-2 play no essential role in fibrogenesis in schistosomiasis. Indeed, our findings suggest that inhibiting profibrotic cytokines or specific MMP may be a more effective strategy to ameliorate fibrotic pathology. C1 NIAID, Schistosomiasis Immunol & Pathol Unit, Immunobiol Sect, Lab Parasit Dis,NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. Roswell Pk Canc Inst, Dept Mol & Cellular Biol, Buffalo, NY 14263 USA. RP Wynn, TA (reprint author), NIAID, Schistosomiasis Immunol & Pathol Unit, Immunobiol Sect, Lab Parasit Dis,NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 66 TC 87 Z9 95 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2001 VL 167 IS 12 BP 7017 EP 7026 PG 10 WC Immunology SC Immunology GA 500ER UT WOS:000172613400041 PM 11739522 ER PT J AU Hel, Z Tsai, WP Thornton, A Nacsa, J Giuliani, L Tryniszewska, E Poudyal, M Venzon, D Wang, XC Altman, J Watkins, DI Lu, WH von Gegerfelt, A Felber, BK Tartaglia, J Pavlakis, GN Franchini, G AF Hel, Z Tsai, WP Thornton, A Nacsa, J Giuliani, L Tryniszewska, E Poudyal, M Venzon, D Wang, XC Altman, J Watkins, DI Lu, WH von Gegerfelt, A Felber, BK Tartaglia, J Pavlakis, GN Franchini, G TI Potentiation of simian immunodeficiency virus (SIV)-speciific CD4(+) and CD8(+) T cell responses by a DNA-SIV and NYVAC-SIV prime/boost regimen SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFECTED RHESUS-MONKEYS; PERIPHERAL-BLOOD LYMPHOCYTES; VACCINIA VIRUS; IMMUNE-RESPONSES; IN-VIVO; PROTECTIVE EFFICACY; ANTIRETROVIRAL TREATMENT; ESCAPE VARIANTS; HIV-1 INFECTION; MACAQUES AB T cell-mediated immune responses play an important role in the containment of HIV-1 replication. Therefore, an effective vaccine against HIV-1 should be able to elicit high frequencies of virus-specific CD8(+) and CD4(+) T cells. The highly attenuated poxvirus-based vaccine candidate, NYVAC-SIV-gag-pol-env (NYVAC-SIV-gpe), has been shown to induce and/or expand SIV-specific CD4(+) and CD8(+) T cell responses in both naive and infected macaques. In this study, the immunogenicity of NYVAC-SIV-gpe alone was compared with a combination regimen where printing with an optimized DNA-SIV-gag-env vaccine candidate was followed by a NYVAC-SIV-gpe boost. In macaques immunized with the prime-boost regimen, the extent and durability of CD8(+) T cell response to an immunodominant SIV gag epitope was increased and these animals recognized a broader array of subdominant SIV epitopes in the cytolytic assay. In addition, the prime-boost regimen significantly enhanced the proliferative responses to both SIV gag and env proteins. Thus, the combination of these vaccine modalities may represent a valuable strategy in the development of a vaccine for HIV. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Emory Univ, Vaccine Ctr Yerkes, Atlanta, GA 30329 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53715 USA. Aventis Pasteur, Toronto, ON, Canada. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41 Lib Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; OI Hel, Zdenek/0000-0002-4923-4794 NR 71 TC 69 Z9 71 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2001 VL 167 IS 12 BP 7180 EP 7191 PG 12 WC Immunology SC Immunology GA 500ER UT WOS:000172613400060 PM 11739541 ER PT J AU Domachowske, JB Bonville, CA Ali-Ahmad, D Dyer, KD Easton, AJ Rosenberg, HF AF Domachowske, JB Bonville, CA Ali-Ahmad, D Dyer, KD Easton, AJ Rosenberg, HF TI Glucocorticoid administration accelerates mortality of pneumovirus-infected mice SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; RANDOMIZED CONTROLLED TRIAL; NITRIC-OXIDE; NEBULIZED BUDESONIDE; ORAL DEXAMETHASONE; EPITHELIAL-CELLS; PNEUMONIA VIRUS; HOST-DEFENSE; BRONCHIOLITIS; EOSINOPHILIA AB The use of glucocorticoids for the treatment of symptoms associated with respiratory syncytial virus (RSV) infection has been questioned. To evaluate the sequelae of glucocorticoid administration in the setting of pneumovirus infection in vivo, hydrocortisone was administered to mice infected with pneumonia virus of mice (PVM), a pneumovirus and natural rodent pathogen that is closely related to RSV and replicates the signs and symptoms of severe human RSV infection. Results showed that hydrocortisone spared the pulmonary neutrophilia but resulted in ablation of the pulmonary eosinophilia, despite continued production of the relevant chemoattractant, macrophage inflammatory protein-1 alpha. Hydrocortisone also led to diminished production of inducible nitric oxide synthase and accumulation of reactive nitrogen species in lung tissue and bronchoalveolar lavage fluid and diminished lymphocyte recruitment. PVM-infected mice responded to hydrocortisone with enhanced viral replication and accelerated mortality. These results suggest several mechanisms to explain why glucocorticoid therapy may be of limited benefit in the overall picture of pneumovirus infection. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Univ Warwick, Coventry CV4 7AL, W Midlands, England. SUNY Upstate Med Univ, Dept Pediat, Div Infect Dis, Syracuse, NY USA. RP Rosenberg, HF (reprint author), NIAID, Host Def Lab, NIH, 10-11N104,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 46 TC 29 Z9 29 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2001 VL 184 IS 12 BP 1518 EP 1523 DI 10.1086/324664 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 498ZW UT WOS:000172545000003 PM 11740726 ER PT J AU Uhm, CS Neuhuber, B Lowe, B Crocker, V Daniels, MP AF Uhm, CS Neuhuber, B Lowe, B Crocker, V Daniels, MP TI Synapse-forming axons and recombinant agrin induce microprocess formation on myotubes SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuromuscular junction; synapse formation; acetylcholine receptor; cell adhesion; cell motility; neuronal polarity ID ACETYLCHOLINE-RECEPTOR CLUSTERS; CELL-ADHESION MOLECULE; CULTURED MUSCLE-CELLS; SPINAL-CORD NEURONS; NEUROMUSCULAR-JUNCTION; PERICELLULAR PROTEOLYSIS; DENDRITIC FILOPODIA; EMBRYONIC MUSCLE; DEFICIENT MICE; GROWTH-FACTOR AB We examined cell-surface behavior at nerve-muscle contacts during synaptogenesis in cocultures of rat ventral spinal cord (VSC) neurons and myotubes. Developing synapses in 1-d-old cocultures were identified by the presence of axon-induced acetylcholine receptor (AChR) aggregation. Identified regions were then examined by transmission and scanning electron microscopy. The myotube surface near contacts with axons that induced AChR aggregation typically displayed ruffles, microvilli, and filopodia (microprocesses), indicating motility of the myotube surface. At some of these contact sites microprocesses were wrapped around the axon, resulting in the partial or total "submersion" of the axon within the myotube contours. Sites of myotube contact with somata and dendrites of the same neurons showed much less evidence of motility and surface interaction than sites of contact with axons. Moreover, the distance between opposed membranes of axons and myotubes was smaller than between dendrites or somata and myotubes, suggesting stronger adhesion of axons. These results suggest polarized expression of molecules involved in the induction of microprocess formation and adhesion in developing VSC neurons. We therefore tested the ability of agrin, which is preferentially secreted by axons, to induce microprocess formation in myotubes. Addition of recombinant C-terminal agrin to culture medium resulted in formation of microprocesses within 3 hr. Myotubes transfected with full-length rat agrin constructs displayed numerous filopodia, as revealed by fluorescence microscopy. The results suggest that the induction of muscle cell surface motility may be linked to the signaling processes that trigger the initial formation of the neuromuscular junction. C1 NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. NINCDS, Electron Microscopy Facil, NIH, Bethesda, MD 20892 USA. Korea Univ, Coll Med, Dept Anat, Seoul 136705, South Korea. Korea Univ, Coll Med, Inst Med Genet, Seoul 136705, South Korea. RP Daniels, MP (reprint author), NHLBI, Cell Biol Lab, NIH, 50 South Dr,Room 3318,MSC 8017, Bethesda, MD 20892 USA. NR 60 TC 30 Z9 30 U1 1 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2001 VL 21 IS 24 BP 9678 EP 9689 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 500XW UT WOS:000172654800019 PM 11739577 ER PT J AU Rusch, A Ng, L Goodyear, R Oliver, D Lisoukov, I Vennstrom, B Richardson, G Kelley, MW Forrest, D AF Rusch, A Ng, L Goodyear, R Oliver, D Lisoukov, I Vennstrom, B Richardson, G Kelley, MW Forrest, D TI Retardation of cochlear maturation and impaired hair cell function caused by deletion of all known thyroid hormone receptors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cochlea; development; tectorial membrane; hair cell; thyroid hormone receptor; transcription factor ID TYPE-2 IODOTHYRONINE DEIODINASE; INNER-EAR DEVELOPMENT; HEARING-LOSS; POSTNATAL-DEVELOPMENT; TECTORIAL MEMBRANE; AUDITORY FUNCTION; GENE-EXPRESSION; MOTOR PROTEIN; ALPHA; BETA AB The deafness caused by early onset hypothyroidism indicates that thyroid hormone is essential for the development of hearing. We investigated the underlying roles of the TR alpha1 and TR beta thyroid hormone receptors in the auditory system using receptor-deficient mice. TR alpha1 and TR beta, which act as hormone-activated transcription factors, are encoded by the Thra and Thrb genes, respectively, and both are expressed in the developing cochlea. TR beta is required for hearing because TR beta -deficient (Thrb(tm1/tm1)) mice have a defective auditory-evoked brainstem response and retarded expression of a potassium current (I-K,I-f) in the cochlear inner hair cells. Here, we show that although TR alpha1 is individually dispensable, TR alpha1 and TR beta synergistically control an extended array of functions in postnatal cochlear development. Compared with Thrb(tm1/tm1) mice, the deletion of all TRs in Thra(tm1/tm1)Thrb(tm1/tm1) mice produces exacerbated and novel phenotypes, including delayed differentiation of the sensory epithelium, malformation of the tectorial membrane, impairment of electromechanical transduction in outer hair cells, and a low endocochlear potential. The induction of I-K,I-f in inner hair cells was not markedly more retarded than in Thrb(tm1/tm1) mice, suggesting that this feature of hair cell maturation is primarily TR beta -dependent. These results indicate that distinct pathways mediated by TR beta alone or by TR beta and TR alpha1 together facilitate control over an extended range of functions during the maturation of the cochlea. C1 Univ Tubingen, Inst Physiol, D-72076 Tubingen, Germany. Univ Tubingen, Hals Nasen Ohren Klin, Sekt Sensor Biophys, D-72076 Tubingen, Germany. Univ Sussex, Sch Biol Sci, Brighton BN1 9QG, E Sussex, England. Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden. NIDCD, NIH, Rockville, MD 20850 USA. CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. RP Forrest, D (reprint author), CUNY Mt Sinai Sch Med, Dept Human Genet, Box 1498,1425 Madison Ave, New York, NY 10029 USA. RI Oliver, Dominik/F-5845-2013 FU NIDCD NIH HHS [DC 03441] NR 56 TC 84 Z9 85 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2001 VL 21 IS 24 BP 9792 EP 9800 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 500XW UT WOS:000172654800029 PM 11739587 ER PT J AU Biesecker, LG Rosenberg, MJ Vacha, S Turner, JT Cohen, MM AF Biesecker, LG Rosenberg, MJ Vacha, S Turner, JT Cohen, MM TI PTEN mutations and Proteus syndrome SO LANCET LA English DT Letter C1 NHGRI, NIH, Bethesda, MD 20892 USA. Dalhousie Univ, Halifax, NS, Canada. RP Biesecker, LG (reprint author), NHGRI, NIH, Bldg 49,Room 4A80,31 Ctr Dr, Bethesda, MD 20892 USA. NR 5 TC 29 Z9 29 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 15 PY 2001 VL 358 IS 9298 BP 2079 EP 2079 DI 10.1016/S0140-6736(01)07109-4 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 502BB UT WOS:000172722800037 PM 11755638 ER PT J AU Karmakar, P Natarajan, AT Poddar, RK Dasgupta, UB AF Karmakar, P Natarajan, AT Poddar, RK Dasgupta, UB TI Induction of apoptosis by Phenothiazine derivatives in V79 cells SO TOXICOLOGY LETTERS LA English DT Article DE phenothiazines; apoptosis; cell cycle; p53 ID DNA-DAMAGE; CHLORPROMAZINE; P53; TRIFLUOPERAZINE; CALMODULIN; EXPRESSION; PROTEIN AB Phenothiazine derivatives chlorpromazine (cpz) and trifluoperazine (tfp) were found to induce apoptosis, abnormal cell cycle and expression of p53 in Chinese hamster lung fibroblast V79 cells. Both the drugs can induce apoptosis when cells are treated with drug at a concentration of 10 mug/ml within 4 h, as detected by propidium. iodide staining and DNA fragmentation analysis, Flow cytometric analysis revealed that the apoptotic response is mediated by a loss of Gt population of cells. In Western blot analysis, p21 is induced and p53 is accompanied by additional bands. Also indirect immunolabeling of single cells revealed that p21 is accumulated from cytoplasm into nucleus after the drug treatment and the intensities of p53 increased. Our findings demonstrate for the first time that phenothiazine derivatives, in addition to their cytotoxic effects, could induce apoptosis, an observation that has important clinical implications. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Dept Biophys Mol Biol & Genet, Kolkata 700009, W Bengal, India. Leiden Univ, Dept Genet Radiat Genet & Chem Mutagenesis, NL-2300 RA Leiden, Netherlands. RP Karmakar, P (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM karmakarp@grc.nia.nih.gov NR 30 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD DEC 15 PY 2001 VL 125 IS 1-3 BP 19 EP 28 DI 10.1016/S0378-4274(01)00411-8 PG 10 WC Toxicology SC Toxicology GA 498UX UT WOS:000172529800003 PM 11701219 ER PT J AU Xu, H Arnaud, F Tadaki, DK Burkly, LC Harlan, DM Kirk, AD AF Xu, H Arnaud, F Tadaki, DK Burkly, LC Harlan, DM Kirk, AD TI Human platelets activate porcine endothelial cells through a CD154-dependent pathway SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 1st Joint Meeting of the American-Society-of-Transplantation/American-Society-of-Transplant-Surge ons CY MAY 13-17, 2000 CL CHICAGO, ILLINOIS SP Amer Soc Transplantat, Amer Transplant Surgeons ID XENOGRAFT REJECTION; CD40; SURVIVAL; LIGAND AB Background. Delayed xenograft rejection is associated with endothelial cell activation, platelet sequestration, and subsequent thrombosis. We evaluated whether human platelets could directly activate porcine endothelium (PEC), and if so, whether this was mediated by an interaction between platelet-bound CD154 and PEC CD40. Methods. Platelet activation was achieved by thrombin exposure and confirmed by evaluation of up-regulated CD62P and CD154. Co-incubation of platelets or D1.1 cells with PEC was performed, and PEC activation was evaluated by up-regulation of CD62E. Results. Co-incubation of resting platelets that lacked significant expression of CD62P and were void of CD154 did not activate PEC. In contrast, thrombin-activated human platelets expressing considerable amounts of both CD62P and CD154 induced PEC activation. This activation could be completely inhibited by coincubation with a humanized monoclonal antibody directed at human CD154 (hu5c8). Similarly, human D1.1 cells expressing CD154 were shown to activate PEC in a CD154-dependent manner. Conclusion. Human CD154 expressed on activated human platelets or on T cells interacts with CD40 expressed on PEC leading to PEC activation. This interaction can be inhibited by a monoclonal antibody directed against CD154, suggesting that an interaction between human CD154 and PEC CD40 is at least in part responsible for PEC activation seen in delayed xenograft rejection. These data strengthen the rationale for the use of CD154-directed therapy in discordant xenotransplantation. C1 NIDDK, Navy Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. Biogen Inc, Cambridge, MA 02142 USA. RP Xu, H (reprint author), NIDDK, Navy Transplantat & Autoimmun Branch, Room 11S-219,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 FU NIAID NIH HHS [AI43900-01] NR 10 TC 21 Z9 24 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2001 VL 72 IS 11 BP 1858 EP 1861 DI 10.1097/00007890-200112150-00029 PG 4 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 504ET UT WOS:000172844900029 PM 11740405 ER PT J AU Balint, E Vousden, KH AF Balint, E Vousden, KH TI Activation and activities of the p53 tumour suppressor protein SO BRITISH JOURNAL OF CANCER LA English DT Review ID CELL-CYCLE ARREST; WILD-TYPE P53; LI-FRAUMENI-SYNDROME; RING-FINGER DOMAIN; NF-KAPPA-B; RIBONUCLEOTIDE REDUCTASE GENE; AUTOREGULATORY FEEDBACK LOOP; UBIQUITIN LIGASE ACTIVITY; P53-MEDIATED G(1) ARREST; HUMAN CANCER-CELLS AB The p53 tumour suppressor protein inhibits malignant progression by mediating cell cycle arrest, apoptosis or repair following cellular stress. One of the major regulators of p53 function is the MDM2 protein, and multiple forms of cellular stress activate p53 by inhibiting the MDM2-mediated degradation of p53. Mutations in p53, or disruption of the pathways that allow activation of p53, seem to be a general feature of all cancers. Here we review recent advances in our understanding of the pathways that regulate p53 and the pathways that are induced by p53, as well as their implications for cancer therapy. (C) 2001 Cancer Research Campaign. C1 NCI Frederick, Frederick, MD 21702 USA. RP Balint, E (reprint author), NCI Frederick, Bldg 560,Room 22-96,1050 Boyles St, Frederick, MD 21702 USA. RI Balint, Eva/B-8695-2008 NR 215 TC 192 Z9 210 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD DEC 14 PY 2001 VL 85 IS 12 BP 1813 EP 1823 DI 10.1054/bjoc.2001.2128 PG 11 WC Oncology SC Oncology GA 513HT UT WOS:000173373000001 PM 11747320 ER PT J AU Driggers, PH Segars, JH Rubino, DM AF Driggers, PH Segars, JH Rubino, DM TI The proto-oneoprotein Brx activates estrogen receptor beta by a p38 mitogen-activated protein kinase pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAP KINASE; BREAST-CANCER; GROWTH-FACTOR; DBL FAMILY; C-JUN; STRESS; CELLS; PHOSPHORYLATION; DIFFERENTIATION; TRANSFORMATION AB The estrogen receptors (ERs) are ligand-inducible transcription factors that play key roles in the control of growth and differentiation in reproductive tissues. We showed that the novel Dbl family proto-oncoprotein Brx enhances ligand-dependent activity of ER alpha via a Cdc42-dependent pathway. Brx also significantly enhances ligand-dependent activity of ER beta. This enhancement is not affected by inhibition of p44/42 mitogen-activated protein kinase (MAPK) activation by PD98059. However, addition of the p38 MAPK inhibitor SB202190 abrogates the enhancement of ER beta activity by Brx, showing that p38 MAPK activity is required for the enhancement of ER beta function by Brx. In COS-7 cells, transfection of Brx leads to activation of endogenous p38 MAPK activity. Co-expression of the beta2 isoform of human p38 MAPK and a constitutively active form of the p38 MAPK kinase MKK6 (MKK6-EE) synergistically augments ligand-dependent activity of ER beta. Our findings suggest that p38 MAPKs may be important regulators of ER beta activity. C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. US Mil Canc Inst, Bethesda, MD 20814 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Driggers, PH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. FU Intramural NIH HHS [Z99 HD999999] NR 38 TC 35 Z9 37 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 46792 EP 46797 DI 10.1074/jbc.M106927200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500017 PM 11579095 ER PT J AU Sinal, CJ Yoon, M Gonzalez, FJ AF Sinal, CJ Yoon, M Gonzalez, FJ TI Antagonism of the actions of peroxisome proliferator-activated receptor-alpha by bile acids SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHOLESTEROL 7-ALPHA-HYDROXYLASE GENE; ORPHAN NUCLEAR RECEPTOR; RESPONSIVE ELEMENT UPSTREAM; FATTY-ACIDS; PPAR-ALPHA; HORMONE-RECEPTOR; LIPOPROTEIN METABOLISM; TARGETED DISRUPTION; ADAPTIVE RESPONSE; LIPID-METABOLISM AB The peroxisome proliferator-activated receptor-a (PPAR alpha) is a ligand-activated transcription factor that regulates the expression of a number of genes critical for fatty acid beta -oxidation. Because a number of substrates and intermediates of this metabolic pathway serve as ligand activators of this receptor, homeostatic control of fatty acid metabolism is achieved. Evidence also exists for PPAR alpha -dependent regulation of genes encoding critical enzymes of bile acid biosynthesis. To determine whether the primary products of bile acid biosynthesis, cholic acid and chenodeoxycholic acid, were capable of modulating PPAR alpha function, a variety of in vivo and in vitro approaches were utilized. Feeding a bile acid-enriched diet significantly reduced the degree of hepatomegaly and induction of target genes encoding enzymes of fatty acid beta -oxidation caused by treatment with the potent PPAR alpha ligand Wyeth-14,643. Convergent data from mechanistic studies indicate that bile acids interfere with transactivation by PPAR alpha at least in part by impairing the recruitment of transcriptional coactivators. The results of this study provide the first evidence in favor of the existence of compounds, normally found within the body, that are capable of antagonizing the physiological actions of PPAR alpha. The impact of PPAR alpha antagonism by endogenous bile acids is likely to be limited under normal conditions and to have only minimal effects on bile acid homeostasis. However, during certain pathophysiological states where intracellular bile acid concentrations are elevated, meaningful effects on PPAR alpha -dependent target gene regulation are possible. C1 NCI, Div Basic Sci, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Div Basic Sci, Lab Metab, NIH, Bldg 10,Rm 3E24, Bethesda, MD 20892 USA. NR 66 TC 45 Z9 46 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 47154 EP 47162 DI 10.1074/jbc.M107000200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500066 PM 11606578 ER PT J AU Ganguly, S Mummaneni, P Steinbach, PJ Klein, DC Coon, SL AF Ganguly, S Mummaneni, P Steinbach, PJ Klein, DC Coon, SL TI Characterization of the Saccharomyces cerevisiae homolog of the melatonin rhythm enzyme arylalkylamine N-acetyltransferase (EC 2.3.1.87) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR-FORCE FIELD; DROSOPHILA-MELANOGASTER; CATALYTIC MECHANISM; ANGSTROM RESOLUTION; PINEAL-GLAND; MMFF94; PROTEIN; CLONING; GEOMETRIES; DYNAMICS AB Arylalkylamine N-acetyltransferase (AANAT, serotonin N-acetyltransferase, EC 2.3.1.87) plays a unique transduction role in vertebrate physiology by converting information about day and night into a hormonal signal: melatonin. Only vertebrate members of the AANAT family have been functionally characterized. Here a putative AANAT from Saccharomyces cerevisiae (scAANAT) was studied to determine whether it possessed the catalytic activity of the vertebrate enzyme. scAANAT is 47% similar to ovine AANAT, but lacks the regulatory N- and C-terminal flanking regions conserved in all vertebrate AANATs. It was found to have enzyme activity generally typical for AANAT family members, although the substrate preference pattern was somewhat broader, the specific activity was lower, and the pH optimum was higher. Deletion of scAANAT reduced arylalkylamine acetylation by S. cerevisiae extracts, indicating that scAANAT contributes significantly to this process. The scAANAT sequence conformed to the three-dimensional structure of ovine AANAT catalytic core; however, an important structural element (loop 1) was found to be shorter and to lack a proline involved in substrate binding. These differences could explain the lower specific activity of scAANAT, because of the importance of loop 1 in catalysis. Data base analysis revealed the presence of putative AANATs in other fungi but not in the nearly complete genomes of Drosophila melanogaster or Caenorhabditis elegans. These studies indicate that the catalytic and kinetic characteristics of fungal and vertebrate enzymes can be considered to be generally similar, although some differences exist that appear to be linked to changes in one structural element. Perhaps the most striking difference is that fungal AANATs lack the regulatory domains of the vertebrate enzyme, which appear to be essential for the regulatory role the enzyme plays in photochemical transduction. C1 NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Ctr Mol Modeling, Bethesda, MD 20892 USA. RP Klein, DC (reprint author), NICHHD, Dev Neurobiol Lab, Sect Neuroendocrinol, NIH, 49 Convent Dr,MSC 4480,Bldg 49,Rm 6A-82, Bethesda, MD 20892 USA. NR 36 TC 34 Z9 35 U1 0 U2 12 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 47239 EP 47247 DI 10.1074/jbc.M107222200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500077 PM 11559708 ER PT J AU Buslepp, J Zhao, R Donnini, D Loftus, D Saad, M Appella, E Collins, EJ AF Buslepp, J Zhao, R Donnini, D Loftus, D Saad, M Appella, E Collins, EJ TI T cell activity correlates with oligomeric peptide-major histocompatibility complex binding on T cell surface SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MHC CLASS-II; MAXIMUM-LIKELIHOOD; ANTAGONIST LIGANDS; CRYSTAL-STRUCTURE; RECEPTOR-BINDING; TCR; MOLECULES; REFINEMENT; ACTIVATION; ANTIGEN AB Recognition of virally infected cells by CD8(+) T cells requires differentiation between self and nonself peptide-class I major histocompatibility complexes (pMHC). Recognition of foreign pMHC by host T cells is a major factor in the rejection of transplanted organs from the same species (allotransplant) or different species (xenotransplant). AHIII12.2 is a murine T cell clone that recognizes the xenogeneic (human) class I NMC HLA-A2.1 molecule (A2) and the syngeneic murine class I MHC H-2 D-b molecule (D-b). Recognition of both A2 and D-b are peptide-dependent, and the sequences of the peptides recognized have been determined. Alterations in the antigenic peptides bound to A2 cause large changes in AHIII12.2 T cell responsiveness. Crystal structures of three representative peptides (agonist, null, and antagonist) bound to A2 partially explain the changes in AHIII12.2 responsiveness. Using class I pMHC octamers, a strong correlation is seen between T cell activity and the affinity of pMHC complexes for the T cell receptor. However, contrary to previous studies, we see similar half-lives for the pMHC multimers bound to the AHIII12.2 cell surface. C1 Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Collins, EJ (reprint author), Univ N Carolina, Dept Microbiol & Immunol, CB 7290,804 ME Jones Bldg, Chapel Hill, NC 27599 USA. OI SAAD, Mohamed/0000-0003-0458-5942 NR 47 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 47320 EP 47328 DI 10.1074/jbc.M109231200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500087 PM 11584024 ER PT J AU Brzeska, H Young, R Tan, C Szczepanowska, J Korn, ED AF Brzeska, H Young, R Tan, C Szczepanowska, J Korn, ED TI Calmodulin-binding and autoinhibitory domains of Acanthamoeba myosin I heavy chain kinase, a p21-activated kinase (PAK) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE; CATALYTIC DOMAIN; SUBSTRATE-SPECIFICITY; RAC GTPASES; ACTIVATION; CDC42; PHOSPHORYLATION; IDENTIFICATION; SEQUENCE; FAMILY AB The sequence homology between Acanthamoeba myosin I heavy chain kinase (MIHCK) and other p21-activated kinases (PAKs) is relatively low, including only the catalytic domain and a short PAK N-terminal motif (PAN), and even these regions are not highly homologous. In this paper, we report the expression in insect cells of full-length, fully regulated Acanthamoeba MIHCK and further characterize the regulation of this PAK by Rac, calmodulin, and autoinhibition. We map the autoinhibitory region of MIHCK to its PAN region and show that the PAN region inhibits autophosphorylation and kinase activity of unphosphorylated full-length MIHCK and its expressed catalytic domain but has very little effect on either when they are phosphorylated. These properties are similar to those reported for mammalian PAK1. Unlike PAK1, MIHCK is activated by Rac only in the presence of phospholipid. However, peptides containing the PAN region of MIHCK bind Rac in the absence of lipid, and Rac binding reverses the inhibition of the MIHCK catalytic domain by PAN peptides. Our data suggest that a region N-terminal to PAN is required for optimal binding of Rac. Also unlike mammalian PAK, phospholipid stimulation of Acanthamoeba MIHCK and Dictyostelium MIHCK) (which is also a PAK) is inhibited by Ca2+-calmodulin. In contrast to Dictyostelium MIHCK, however, Ca2+-calmodulin also inhibits Rac-induced activity of Acanthamoeba MIHCK. The basic region N-terminal to PAN is essential for calmodulin binding. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Rm 2517,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Korn, Edward/F-9929-2012 NR 41 TC 5 Z9 6 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 47468 EP 47473 DI 10.1074/jbc.M108957200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500103 PM 11579107 ER PT J AU Hui, YQ Yang, GC Galczenski, H Figueroa, DJ Austin, CP Copeland, NG Gilbert, DJ Jenkins, NA Funk, CD AF Hui, YQ Yang, GC Galczenski, H Figueroa, DJ Austin, CP Copeland, NG Gilbert, DJ Jenkins, NA Funk, CD TI The murine cysteinyl leukotriene 2 (CysLT(2)) receptor - cDNA and genomic cloning, alternative splicing, and in vitro characterization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOLECULAR-CLONING; HUMAN LUNG; RELEASE; AGONIST; TISSUE AB Two classes of cysteinyl leukotriene receptor, CysLT(1) and CysLT(2), have been identified and pharmacologically characterized in human tissues. Although the CysLT(1) receptor mediates the proinflammatory effects of leukotrienes in human asthma, the physiological roles of CysLT(2) receptor are not defined, and a suitable mouse model would be useful in delineating function. We report here the molecular cloning and characterization of the mouse CysLT2 receptor (mCysLT(2)R) from heart tissue. mCysLT(2)R cDNA encodes a protein of 309 amino acids, truncated at both ends compared with the human ortholog (hCysLT(2)R). The gene resides on the central region of mouse chromosome 14 and is composed of 6 exons with the entire coding region located in the last exon. Two W-untranslated region splice variants were identified with the short form lacking exon 3 as the predominant transcript. Although the overall expression of mCysLT2R is very low, the highest expression was detected in spleen, thymus, and adrenal gland by ribonuclease protection assay, and discrete sites of expression in heart were observed by in situ hybridization. Intracellular calcium mobilization in response to cysteinyl leukotriene administration was detected in human embryonic kidney 293T cells transfected with recombinant mCysLT2R with a rank order of potency leukotriene C-4 (LTC4) = LTD4 > > LTE4. [H-3]LTD4 binding to membranes expressing mCysLT2R could be effectively competed by LTC, and LTD, and only partially inhibited by LTE4 and BAYu9773. The identification of mCysLT2R will be useful for establishing CysLT(2)R-deficient mice and determining novel leukotriene functions. C1 Univ Penn, Ctr Expt Therapeut, Dept Pharmacol, Philadelphia, PA 19104 USA. Merck & Co Inc, Dept Pharmacol, W Point, PA 19486 USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Funk, CD (reprint author), Univ Penn, Ctr Expt Therapeut, Dept Pharmacol, Rm 814 BRBII-3,421 Curie Blvd, Philadelphia, PA 19104 USA. RI Funk, Colin/A-9518-2010 FU NHLBI NIH HHS [HL 58464] NR 26 TC 59 Z9 62 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 47489 EP 47495 DI 10.1074/jbc.M107556200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500106 PM 11591709 ER PT J AU Gao, Y Xing, J Streuli, M Leto, TL Zheng, Y AF Gao, Y Xing, J Streuli, M Leto, TL Zheng, Y TI Trp(56) of Rac1 specifies interaction with a subset of guanine nucleotide exchange factors SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DBL HOMOLOGY DOMAIN; CRYSTAL-STRUCTURE; RHO-GTPASES; ONCOGENIC DBL; GTP ANALOG; FAMILY; TRIO; PROTEIN; ACTIVATION; KINASE AB Signaling specificity of Rho GTPase pathways is achieved in part by selective interaction between members of the Dbl family guanine nucleotide exchange factors (GEFs) and their Rho GTPase substrates. For example, Trio, GEF-H1, and Tiam1 are a subset of GEFs that specifically activate Rac1 but not the closely related Cdc42. The Rac1 specificity of these GEFs appears to be governed by Rac1-GEF binding interaction. To understand the detailed mechanism underlying the GEF specificity issue, we have analyzed a panel of chimeras made between Rac1 and Cdc42 and examined a series of point mutants of Racl made at the switch I, switch II, and beta (2)/beta (3) regions for their ability to interact with and to be activated by the GEFs. The results reveal that Rac1 residues of both the switch I and switch II regions are involved in GEF docking and GEF-mediated nucleotide disruption, because mutation of Asp(38), Asn(39), Gln(61), Tyr(64), or Arg(66)/Leu(67) into Ala results in the loss of GEF binding, whereas mutation at Tyr(32), Asp(65), or Leu(70)/ Ser(71) leads to the loss of GEF catalysis while retaining the binding capability. The region between amino acids 53-72 of Rac1 is required for specific recognition and activation by the GEFs, and Trp(56) in beta (3), appears to be the critical determinant. Introduction of Trp(56) to Cdc42 renders it fully responsive to the Rac-specific GEF in vitro and in cells. Further, a polypeptide derived from the beta (3) region of Rac1 including the Trp,56 residue serves as a specific inhibitor for Rac1 interaction with the GEFs. Taken together, these results indicate that Trp-56 is the necessary and sufficient determinant of Rac1 for discrimination by the subset of Rac1-specific GEFs and suggest that a compound mimicking Trp 56 action could be explored as an interfering reagent specifically targeting Rac1 activation. C1 Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Zheng, Y (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA. EM yzheng@utmem.edu RI Xing, Jinchuan/A-2489-2012; Zheng, Yi/J-7235-2015 OI Zheng, Yi/0000-0001-7089-6074 FU NIGMS NIH HHS [GM 53943, GM 60523] NR 41 TC 63 Z9 63 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 14 PY 2001 VL 276 IS 50 BP 47530 EP 47541 DI 10.1074/jbc.M108865200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 502XR UT WOS:000172768500112 PM 11595749 ER PT J AU Murphy, WJ Eizirik, E O'Brien, SJ Madsen, O Scally, M Douady, CJ Teeling, E Ryder, OA Stanhope, MJ de Jong, WW Springer, MS AF Murphy, WJ Eizirik, E O'Brien, SJ Madsen, O Scally, M Douady, CJ Teeling, E Ryder, OA Stanhope, MJ de Jong, WW Springer, MS TI Resolution of the early placental mammal radiation using Bayesian phylogenetics SO SCIENCE LA English DT Article ID EVOLUTION; SEQUENCES; TREES AB Molecular phylogenetic studies have resolved placental. mammals into four major groups, but have not established the full hierarchy of interordinal relationships, including the position of the root. The latter is critical for understanding the early biogeographic history of placentals. We investigated placental phylogeny using Bayesian and maximum-likelihood methods and a 16.4-kilobase molecular data set. Interordinal. relationships are almost entirely resolved. The basal split is between Afrotheria and other placentals, at about 103 million years, and may be accounted for by the separation of South America and Africa in the Cretaceous. Crown-group Eutheria may have their most recent common ancestry in the Southern Hemisphere (Gondwana). C1 Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Univ Nijmegen, Dept Biochem, Nijmegen, Netherlands. Queens Univ Belfast, Belfast, Antrim, North Ireland. Zool Soc San Diego, Ctr Reprod Endangered Species, San Diego, CA 92112 USA. Glaxo SmithKline, Collegeville, PA 19426 USA. Inst Systemat & Populat Biol, Amsterdam, Netherlands. RP O'Brien, SJ (reprint author), Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA. RI Madsen, Ole/E-3730-2012; Eizirik, Eduardo/K-8034-2012; Douady, Christophe/N-1357-2014 OI Madsen, Ole/0000-0001-8082-7881; Eizirik, Eduardo/0000-0002-9658-0999; NR 29 TC 844 Z9 887 U1 8 U2 100 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 14 PY 2001 VL 294 IS 5550 BP 2348 EP 2351 DI 10.1126/science.1067179 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 503TT UT WOS:000172817200045 PM 11743200 ER PT J AU Li, Q Li, T Wu, JG AF Li, Q Li, T Wu, JG TI Luminescence of europium(III) and terbium(III) complexes incorporated in poly(vinyl pyrrolidone) matrix SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID POLYMER WAVE-GUIDES; LANTHANIDE COMPLEXES; OPTICAL-PROPERTIES; EMISSION; EU(III); PROTEIN; EU3+; TB3+; ND3+ AB Lanthanide complexes of europium and terbium ions with hydrogen phthalate [Eu(Hphth)(3) and Tb(Hphth)(3), respectively, Hphth = hydrogen phthalate] were incorporated into poly(vinyl pyrrolidone) (PVP) matrix. Transmission electron microscopy (TEM) results showed that the lanthanide complexes, with a mean diameter about 8.0 nm, were dispersed homogeneously in the PVP matrix. The excitation of the Ln(Hphth)(3)-PVP system by UV light resulted in a ligand-to-metal energy transfer and the emission spectra of the complexes displayed characteristic luminescence of the central ions. PVP significantly affected the strength of the hypersensitive transitions (D-5(0) --> F-7(2) for EU3+, and D-5(4) --> F-7(5) for Tb3+) of the complexes. For the mixed complexes containing both EU3+ and Tb3+ as central ions, the luminescent intensity was strongly dependent upon the ratio of the lanthanide ions. Trace amount of EU3+ quenched the luminescence of the Tb3+, whereas the presence of Tb3+ enhanced the luminescence of the EU3+, thus demonstrating an important feature of energy transfer from terbium to europium in the mixed complexes. C1 Peking Univ, Coll Chem & Mol Engn, Beijing 100871, Peoples R China. RP Li, T (reprint author), NIH, Bldg 10,Rm 10D08,10 Ctr Dr, Bethesda, MD 20892 USA. NR 22 TC 156 Z9 166 U1 5 U2 19 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 13 PY 2001 VL 105 IS 49 BP 12293 EP 12296 DI 10.1021/jp012922+ PG 4 WC Chemistry, Physical SC Chemistry GA 502CY UT WOS:000172727200011 ER PT J AU Binder, H Gawrisch, K AF Binder, H Gawrisch, K TI Effect of unsaturated lipid chains on dimensions, molecular order and hydration of membranes SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID INFRARED DICHROISM INVESTIGATIONS; ACYL-CHAIN; DOCOSAHEXAENOIC ACID; PHASE-BEHAVIOR; X-RAY; PHOSPHOLIPID-BILAYERS; LAMELLAR STRUCTURES; MAGNETIC-RESONANCE; LECITHIN BILAYERS; PROTEIN FUNCTION AB We conducted infrared linear dichroism and X-ray measurements to characterize membranes of sn-1 chain perdeuterated, polyunsaturated 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (18:0-22:6 omega3 PC, SDPC-d35) and of monounsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (16:0-18:1 PC, POPC-d31) as a function of hydration and temperature. Our novel approach is to use IR order parameters of C-H and C-D vibrations of both sn-1 and sn-2 chains for a separate estimation of the mean length and effective cross sectional area of the saturated and unsaturated chains in the bilayers, In the gel phase, the thickness of the hydrophobic core of SDPC bilayers exceeded the thickness of POPC bilayers, because the polyunsaturated chains adopted an extended conformation. However, in the fluid phase, the hydrophobic thickness of SDPC membranes, with the longer 18:0 and 22:6 acyl chains, was almost equal to the thickness of the 16:0-18:1 chains in POPC membranes. The isothermal compressibility modulus of the docosahexaenoyl chains was smaller than the modulus of the stearoyl chains of SDPC, whereas the palmitoyl and oleoyl chains of POPC are similarly compressible. Analysis in terms of a simple polymer brush model showed that unsaturation increases chain flexibility and chain mean area in lipid membranes. Temperature dependent measurements indicated that polyunsaturation decreased the sensitivity of the bilayer to temperature changes. The study of lipid hydration-sensitive spectral parameters suggested that this tendency may be at least partially explained by a weakening of water binding to polar moieties of polyunsaturated lipids with increasing temperature. Although the influence of hydrocarbon chain polyunsaturation on hydration of phosphate groups and the entire lipid was minor, we observed a modification of lipid carbonyl group hydration. Hydration properties and phase behavior of SDPC suggest an influence from polyunsaturation on the lateral pressure profile across the bilayer. C1 Univ Leipzig, Inst Med Phys & Biophys, D-04103 Leipzig, Germany. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Binder, H (reprint author), Univ Leipzig, Inst Med Phys & Biophys, Liebigstr 27, D-04103 Leipzig, Germany. NR 67 TC 66 Z9 66 U1 4 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5647 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 13 PY 2001 VL 105 IS 49 BP 12378 EP 12390 DI 10.1021/jp010118h PG 13 WC Chemistry, Physical SC Chemistry GA 502CY UT WOS:000172727200021 ER PT J AU Fuller, RK Gordis, E AF Fuller, RK Gordis, E TI Naltrexone treatment for alcohol dependence. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIAL; THERAPY C1 NIAAA, Bethesda, MD 20892 USA. RP Fuller, RK (reprint author), NIAAA, Bethesda, MD 20892 USA. NR 16 TC 18 Z9 19 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 13 PY 2001 VL 345 IS 24 BP 1770 EP 1771 DI 10.1056/NEJM200112133452411 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 500YK UT WOS:000172656100010 PM 11742054 ER PT J AU Winterhalter, M Hilty, C Bezrukov, SM Nardin, C Meier, W Fournier, D AF Winterhalter, M Hilty, C Bezrukov, SM Nardin, C Meier, W Fournier, D TI Controlling membrane permeability with bacterial porins: application to encapsulated enzymes SO TALANTA LA English DT Article; Proceedings Paper CT 2nd France-Israel Workshop on Biosensors and Biochips CY DEC 11-16, 2000 CL GRENOBLE, FRANCE DE biosensor; nanocapsule; protein stabilisation; single molecule detection; bacterial porins ID TRIBLOCK COPOLYMER VESICLES; SUGAR TRANSLOCATION; LIPID-MEMBRANES; OUTER-MEMBRANE; CHANNELS; MALTOPORIN; ACETYLCHOLINESTERASE; TRANSPORT; LEVEL; PORE AB Recent achievements of membrane protein science allow easy protein modification by genetic engineering and, for some proteins, their production in large quantities. We regard these features as the basic requirements for applications of membrane proteins in materials science. Here, we demonstrate a possible application of membrane proteins, inserting porins from the outer cell wall of Escherichia coli into the walls of liposomes. Encapsulation of enzymes into liposomes or polymer nanocapsules protects them against proteases and denaturation. Functional reconstitution of porins into the capsule shell allows to control the rate and selectivity of substrate permeation, and thus to control the enzyme reaction kinetics. We suggest that this technique can prove to be useful in the area of biosensors, providing enzymatic stability while keeping the functionality or even enhancing the sensitivity by substrate preselection. Another application of this kind of stabilisation is in the field of single enzyme activity recording. (C) 2001 Elsevier Science B.V. All rights reserved. C1 CNRS, Inst Pharmacol & Biol Struct, UMR CNRS 5089, F-31077 Toulouse, France. NICHHD, NIH, Bethesda, MD 20892 USA. St Petersburg Nucl Phys Inst, Gatchina 188350, Russia. CNRS, UMR5068, F-31062 Toulouse, France. RP Winterhalter, M (reprint author), CNRS, Inst Pharmacol & Biol Struct, UMR CNRS 5089, 205 Rte de Narbonne, F-31077 Toulouse, France. RI Hilty, Christian/C-1892-2015 OI Hilty, Christian/0000-0003-2539-2568 NR 23 TC 41 Z9 41 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 J9 TALANTA JI Talanta PD DEC 13 PY 2001 VL 55 IS 5 BP 965 EP 971 DI 10.1016/S0039-9140(01)00494-5 PG 7 WC Chemistry, Analytical SC Chemistry GA 502HL UT WOS:000172737900011 PM 18968447 ER PT J AU Zhang, F Jetten, AM AF Zhang, F Jetten, AM TI Genomic structure of the gene encoding the human GLI-related, Kruppel-like zinc finger protein GLIS2 SO GENE LA English DT Article DE Kruppel-like zinc finger proteins; GLI; ZIC; kidney; genome ID HEDGEHOG-PATCHED-GLI; CELL LINEAGE; TSC2 GENE; FAMILY; EXPRESSION; DISEASE; MEMBER; IDENTIFICATION; TRANSCRIPTION; REPRESSION AB In this study, we describe the sequence and genomic structure of the human GLIS2 gene, encoding a new member of the Kruppel-like zinc finger protein family. GLIS2 is a relatively proline-rich, basic protein of 55.7 kDa in size. It contains five tandem Cys(2)-His(2) zinc finger motifs consisting of the consensus sequence X-Cys-X-2.4-Cys-X-12.15-HiS-X-3.4-His-X. The sequence of the zinc finger domain exhibits highest homology with those of members of the GLI and ZIC subfamilies of Kruppel-like proteins. The zinc finger domain of GLIS2 exhibits highest (58%) homology with that of GLI-1. The human GLIS2 gene consists of six exons and five introns, and spans more than 7.5 kb. Primer extension identified several putative transcription initiation sites. GLIS2 mRNA is most abundantly expressed in human kidney suggesting a role in the regulation of certain kidney functions. The GLIS2 gene maps to human chromosome 16p13.3, a locus implicated in several human kidney diseases. The sequence and structure of human GLIS2 will be useful tools to study the regulation of GLIS2 and its potential role in human disease. (C) 2001 Published by Elsevier Science B.V. C1 NIEHS, Div Intramural Res, Cell Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. RP Jetten, AM (reprint author), NIEHS, Div Intramural Res, Cell Biol Sect, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. OI Jetten, Anton/0000-0003-0954-4445 NR 33 TC 20 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD DEC 12 PY 2001 VL 280 IS 1-2 BP 49 EP 57 DI 10.1016/S0378-1119(01)00764-8 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 509QD UT WOS:000173160400006 PM 11738817 ER PT J AU Patel, SC Levine, SR Tilley, BC Grotta, JC Lu, M Frankel, M Haley, EC Brott, TG Broderick, JP Horowitz, S Lyden, PD Lewandowski, CA Marler, JR Welch, KMA AF Patel, SC Levine, SR Tilley, BC Grotta, JC Lu, M Frankel, M Haley, EC Brott, TG Broderick, JP Horowitz, S Lyden, PD Lewandowski, CA Marler, JR Welch, KMA CA Natl Inst Neurological Disorders TI Lack of clinical significance of early ischemic changes on computed tomography in acute stroke SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MIDDLE CEREBRAL-ARTERY; RANDOMIZED CONTROLLED TRIAL; THROMBOLYTIC THERAPY; CT FINDINGS; PLASMINOGEN-ACTIVATOR; PA STROKE; INFARCTION; ALTEPLASE; RELIABILITY; VARIABILITY AB Context The prevalence and clinical significance of early ischemic changes (EICs) on baseline computed tomography (CT) scan of the head obtained within 3 hours of ischemic stroke are not established. Objective To determine the frequency and significance of EIC on baseline head CT scans in the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA (recombinant tissue plasminogen activator) Stroke Trial. Design and Setting The original study, a randomized controlled trial, took place from January 1991 through October 1994 at 43 sites, during which CT images were obtained within 3 hours of symptom onset and prior to the initiation of rt-PA or placebo. For the current analysis, detailed reevaluation was undertaken after October 1994 of all baseline head CT scans with clinical data available pretreatment (blinded to treatment arm). Patients Of 624 patients enrolled in the trial, baseline CT scans were retrieved and reviewed for 616 (99%). Main Outcome Measures Frequency of EICs on baseline CT scans; association of EIC With other baseline variables; effect of EICs on deterioration at 24 hours (greater than or equal to4 points increase from the baseline National Institutes of Health Stroke Scale [NIHSS] score); clinical outcome (measured by 4 clinical scales) at 3 months, CT lesion volume at 3 months, death at 90 days; and symptomatic intracranial hemorrhage (ICH) within 36 hours of treatment. Results The prevalence of EIC on baseline CT in the combined rt-PA and placebo groups was 31% (n = 194). The EIC was significantly associated with baseline NIHSS score (p=0.23; P<.001) and time from stroke onset to baseline CT scan (p=0.11; P=.007). After adjusting for baseline variables, there was no EIC X treatment interaction detected for any clinical outcome, including deterioration at 24 hours, 4 clinical scales, lesion volume, and death at 90 days (P.25), implying that EIC is unlikely to affect response to rt-PA treatment. After adjusting for NIHSS score (an independent predictor of ICH), no EIC association with symptomatic ICH at 36 hours was detected in the group treated with rt-PA (P greater than or equal to .22). Conclusions Our analysis suggests that EICs are prevalent within 3 hours of stroke onset and correlate with stroke severity. However, EICs are not independently associated with increased risk of adverse outcome after rt-PA treatment. Patients treated with rt-PA did better whether or not they had EICs, suggesting that EICs on CT scan are not critical to the decision to treat otherwise eligible patients with rt-PA within 3 hours of stroke onset. C1 Henry Ford Hosp & Hlth Sci Ctr, Div Neuroradiol, Detroit, MI 48202 USA. Mt Sinai Sch Med, New York, NY USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Texas, Med Ctr, Houston, TX USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. Mayo Clin, Jacksonville, FL 32224 USA. Univ Cincinnati, Cincinnati, OH USA. Univ Missouri, Columbia, MO USA. Univ Calif San Diego, Stroke Ctr, San Diego, CA 92103 USA. NINCDS, NIH, Bethesda, MD 20892 USA. Univ Kansas, Sch Med, Kansas City, KS USA. RP Patel, SC (reprint author), Henry Ford Hosp & Hlth Sci Ctr, Div Neuroradiol, 2799 W Grand Blvd,K-3, Detroit, MI 48202 USA. NR 39 TC 228 Z9 233 U1 1 U2 5 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 DEC 12 PY 2001 VL 286 IS 22 BP 2830 EP 2838 DI 10.1001/jama.286.22.2830 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 500YC UT WOS:000172655400031 PM 11735758 ER PT J AU Gaemers, S Bax, A AF Gaemers, S Bax, A TI Morphology of three lyotropic liquid crystalline biological NMR media studied by translational diffusion anisotropy SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; RESIDUAL DIPOLAR COUPLINGS; PROTEIN-STRUCTURE DETERMINATION; ORIENTED PHOSPHOLIPID MICELLES; HIGH-RESOLUTION NMR; SELF-DIFFUSION; INDUCED ALIGNMENT; LAMELLAR PHASE; NEMATIC PHASE; WATER-SYSTEM AB The morphologies of three dilute liquid crystalline phases, which are widely used for biological NMR spectroscopy, are investigated by the study of tracer self-diffusion. The aqueous liquid crystalline media investigated include the common phospholipid bicelle medium, a phase consisting of a mixture of pentaethyleneglycol mono dodecyl ether and hexanol, and a medium containing cetylpyridinium bromide and hexanol. Threonine and water were used as tracer molecules for probing the aqueous environment, and tetramethylsilane (TMS) was for probing the lipophilic environment. Pulsed field gradient NMR was used to measure tracer self-diffusion rates in three orthogonal directions. Although results for the water-soluble tracers in bicelle media do not contradict the widely accepted disk-shaped bicelle model, the high TMS diffusion rate observed in the bilayer plane requires extensive transient edge-to-edge contacts of such disks. This morphology is essentially that of a heavily perforated lamellar bilayer phase and explains why this medium remains liquid crystalline well below the Onsager limit for disk-shaped nematogens. Below 25 degreesC, a bicelle mixture consisting of dimyristoyl phosphatidyl choline and dihexanoyl phosphatidyl choline remains isotropic, but tracer diffusion obstruction indicates that the particles are significantly oblate. The diffusion anisotropy in the penta(ethyleneglycol) mono dodecyl ether liquid crystals confirms the previously proposed alpha -lamellar phase. However, weak inhibition of aqueous-phase self-diffusion in the z direction points to the presence of bridge- or caplike obstructions, and the bilayers appear slightly permeable to water. If the previously proposed concentric cylinder superstructure of bilayers applies, the diffusion data indicate that the most outer cylinder must have a diameter greater than 50 mum. The tracer self-diffusion data for the cetylpyridinium bromide/hexanol medium is only compatible with a planar alpha -lamellar phase, with its local director orthogonal to the magnetic field, and a very large domain size over which the director remains parallel. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 126, Bethesda, MD 20892 USA. NR 78 TC 119 Z9 121 U1 1 U2 12 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 DEC 12 PY 2001 VL 123 IS 49 BP 12343 EP 12352 DI 10.1021/ja011967l PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 500UL UT WOS:000172645100027 PM 11734036 ER PT J AU Shankar, P Schlom, J Hodge, JW AF Shankar, P Schlom, J Hodge, JW TI Enhanced activation of rhesus T cells by vectors encoding a triad of costimulatory molecules (B7-1, ICAM-1, LFA-3) SO VACCINE LA English DT Article DE costimulation; rhesus macaque; vaccinia; fowlpox; B7-1; LFA-3; ICAM-1; TRICOM ID RECOMBINANT VACCINIA VIRUS; MALARIA DNA VACCINE; IMMUNE-RESPONSES; ANTITUMOR IMMUNITY; PROTECTIVE EFFICACY; NONHUMAN-PRIMATES; TUMOR-IMMUNITY; LYMPHOCYTES-T; INDUCTION; IMMUNIZATION AB Since the rhesus is often used as a "gatekeeper" model for the evaluation of malaria and simian immunodeficiency virus (SIV)/HIV vaccines, the identification of strategies to enhance the, activation of rhesus T cells would potentially aid in the generation of more potent vaccines directed against these infectious agents. Several molecules normally found on the surface of professional human APCs are capable of providing the second signals critical for T cell activation: B7-1 (CD80), ICAM-1 (CD54), and LFA-3 (CD58). With the exception of B7, T cell costimulatory molecules in the rhesus have not been identified. We have recently designed and characterized both recombinant vaccinia. and recombinant avipox vectors. containing the transgenes for a triad of human T cell costimulatory molecules (B7-1, ICAM-1, LFA-3; designated TRICOM). Here, we demonstrate the enhanced activation of rhesus T cells stimulated with rhesus APCs infected with TRICOM vectors in the presence of signal 1. Infection with TRICOM vectors led to significant improvement of APC capabilities in terms of reduction of the amount of signal 1 needed to activate naive T cells, and reduction in the amount of APCs required to activate T cells using a constant amount of signal 1. Antibody blocking studies demonstrated that each of the three costimulatory molecule transgenes contributed to the enhanced proliferation of T cells. TRICOM-enhanced T cell activation was shown to correspond to increases in type 1 cytokines and a reduced level of apoptosis. TRICOM-infected autologous B cells from rhesus immunized with either an SIV vaccine or a malaria vaccine stimulated significantly greater levels of IFN-gamma in response to specific peptide than stimulation with uninfected autologous B cells or B cells infected with wild-type vector. The ability to augment immune responses using poxvirus-based vaccines containing multiple costimulatory molecule transgenes can now be addressed in the rhesus macaque model. Published by Elsevier Science Ltd. C1 NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Ctr Canc Res, Tumor Immunol & Biol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 8B09, Bethesda, MD 20892 USA. RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 51 TC 19 Z9 19 U1 0 U2 1 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 DEC 12 PY 2001 VL 20 IS 5-6 BP 744 EP 755 DI 10.1016/S0264-410X(01)00409-1 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 504TJ UT WOS:000172871700013 PM 11738738 ER PT J AU Hisaeda, H Collins, WE Saul, A Stowers, AW AF Hisaeda, H Collins, WE Saul, A Stowers, AW TI Antibodies to Plasmodium vivax transmission-blocking vaccine candidate antigens Pvs25 and Pvs28 do not show synergism SO VACCINE LA English DT Article DE Plasmodium vivax; transmission-blocking vaccine; Pvs25 and Pvs28 ID SURFACE PROTEIN; FALCIPARUM; MALARIA; PFS25; TARGET; STAGE; TRANSFORMATION; ZYGOTES; BERGHEI; GALLINACEUM AB Transmission-blocking vaccines against malaria parasites target molecules expressed by sexual stage parasites to elicit antibodies that prevent the infection of the mosquito vector. Pvs25 and Pvs28, expressed on the surface of ookinetes, are potential candidates for such a vaccine and induce antibodies that block the infectivity of Plasmodium vivax in immunized animals. To improve the ability to induce transmission-blocking antibodies, Pvs25 and Pvs28 were produced as a single fusion protein by the yeast Saccharomyces cerevisiae. Mice immunized with a low dose of the chimeric molecule (Pvs25-28) developed higher antibody responses compared with mice immunized with either Pvs25 or Pvs28. In membrane feeding assays, both anti-Pvs25-28 and anti-Pvs25 antisera had similarly potent transmission-blocking activities (and both were much greater than anti-Pvs28). Furthermore, serum from mice simultaneously immunized with both Pvs25 and Pvs28, or serum mixtures of anti-Pvs25 alone and anti-Pvs28 alone did not enhance the efficacy over anti-Pvs25 serum alone, demonstrating that there is no synergism in the ability to block transmission of P. vivax between anti-Pvs25 and anti-Pvs28 antibodies. Published by Elsevier Science Ltd. C1 NIAID, Malaria Vaccine Dev Unit, NIH, Rockville, MD 20852 USA. Univ Tokushima, Sch Med, Dept Parasitol & Immunol, Tokushima 7708503, Japan. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Sci Resources Program, Div Parasit Dis & Anim Resources Branch, Chamblee, GA 30341 USA. RP Stowers, AW (reprint author), NIAID, Malaria Vaccine Dev Unit, NIH, 5640 Fisher Lane, Rockville, MD 20852 USA. RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 23 TC 16 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 DEC 12 PY 2001 VL 20 IS 5-6 BP 763 EP 770 DI 10.1016/S0264-410X(01)00402-9 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 504TJ UT WOS:000172871700015 PM 11738740 ER PT J AU Moriya, O Matsui, M Osorio, M Miyazawa, H Rice, CM Feinstone, SM Leppla, SH Keith, JM Akatsuka, T AF Moriya, O Matsui, M Osorio, M Miyazawa, H Rice, CM Feinstone, SM Leppla, SH Keith, JM Akatsuka, T TI Induction of hepatitis C virus-specific cytotoxic T lymphocytes in mice by immunization with dendritic cells treated with an anthrax toxin fusion protein SO VACCINE LA English DT Article DE anthrax toxin; cytotoxic T lymphocytes; hepatitis C virus ID MAJOR HISTOCOMPATIBILITY COMPLEX; PROTECTIVE ANTIGEN; MEDIATED DELIVERY; DIPHTHERIA-TOXIN; LETHAL FACTOR; IN-VIVO; PEPTIDES; CORE; RECOGNITION; MOLECULES AB As a novel and safe vaccine strategy, the anthrax toxin-mediated antigen delivery system composed of lethal factor (LF) fusion protein and protective antigen (PA) has been studied to prime hepatitis C virus (HCV) core-specific cytotoxic T lymphocytes (CTLs) in vivo. The core epitope fused to LF (LF-core) tocrether with PA induces a negligible core-specific CTL response in mice, whereas core-specific CTL are effectively primed in mice by injecting dendritic cells (DCs) treated in vitro with LF-core and PA. These findings imply that LF fusion protein plus PA in combination with dendritic cells may be useful for a novel T cell vaccine against HCV infection. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Saitama Med Sch, Dept Microbiol, Moroyama, Saitama 3500495, Japan. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Virol & Infect Dis, New York, NY 10021 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Akatsuka, T (reprint author), Saitama Med Sch, Dept Microbiol, Moroyama, Saitama 3500495, Japan. NR 39 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 12 PY 2001 VL 20 IS 5-6 BP 789 EP 796 DI 10.1016/S0264-410X(01)00407-8 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 504TJ UT WOS:000172871700017 PM 11738742 ER PT J AU Lodmell, DL Parnell, MJ Bailey, JR Ewalt, LC Hanlon, CA AF Lodmell, DL Parnell, MJ Bailey, JR Ewalt, LC Hanlon, CA TI One-time gene gun or intramuscular rabies DNA vaccination of non-human primates: comparison of neutralizing antibody responses and protection against rabies virus 1 year after vaccination SO VACCINE LA English DT Article DE rabies virus; DNA vaccine; protection; neutralizing antibody ID SURGICAL STRESS; RHESUS MACAQUES; MICE; IMMUNIZATION; RECOVERY; IMMUNITY; CELLS; DOGS; INFECTION; EXPOSURE AB We have previously shown that Macaca fascicularis (Cynomologus) monkeys receiving a primary and either one or two booster rabies DNA vaccinations are protected against rabies virus. In this study, we determined whether monkeys that had been vaccinated only once via gene gun or intramuscularly (i.m.) with different concentrations of DNA would be protected against rabies virus challenge. Neutralizing antibody responses were assayed for I year before the monkeys were challenged. Neutralizing antibody was detected at least 50 days earlier in gene gun vaccinated as compared to i.m. vaccinated animals. Prior to viral challenge, all (6/6, 100%) gene gun vaccinated animals, but only 3/6 (50%) i.m. vaccinated animals seroconverted In general, antibody titers of the gene gun vaccinated animals were higher than the titers of the i.m. vaccinated animals. There was no correlation between the concentration of DNA used for vaccination, the neutralizing antibody responses elicited and protection against viral challenge. Seven days after viral challenge, a rapid and strong anamnestic antibody response Was elicited in 100% of the gene gun vaccinated monkeys and in four i.m. vaccinated monkeys. Neutralizing antibody remained undetectable in two i.m. vaccinated monkeys. Overall, 60% (3/5) of the gene gun vaccinated animals and 87% (5/6) of the i.m. vaccinated monkeys survived viral challenge. This study is the first, to our knowledge, to show long-term protection of non-human primates against a human viral pathogen using a DNA vaccination protocol that did not include a booster immunization. Published by Elsevier, Science Ltd. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Rabies Sect,Viral & Rickettsial Zoonoses Branch, Atlanta, GA 30333 USA. RP Lodmell, DL (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 44 TC 28 Z9 30 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 12 PY 2001 VL 20 IS 5-6 BP 838 EP 844 DI 10.1016/S0264-410X(01)00392-9 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 504TJ UT WOS:000172871700022 PM 11738747 ER PT J AU Zhang, MD Emerson, SU Nguyen, H Engle, RE Govindarajan, S Gerin, JL Purcell, RH AF Zhang, MD Emerson, SU Nguyen, H Engle, RE Govindarajan, S Gerin, JL Purcell, RH TI Immunogenicity and protective efficacy of a vaccine prepared from 53 kDa truncated hepatitis E virus capsid protein expressed in insect cells SO VACCINE LA English DT Article DE hepatitis E; vaccine; HEV ORF2; 53 kDa protein; 56 kDa protein ID CYNOMOLGUS MONKEYS; IDENTIFICATION; HEV AB Hepatitis E virus (HEV) is an enterically transmitted virus that causes acute hepatitis. Expression of recombinant HEV capsid protein in insect cells results in two major proteolytically-processed products of 56 and 53 kDa which consist of amino acids (aa) 112-607 and 112-578, respectively. The only neutralization epitope identified to date is located at least partially between amino acids 578 and 607 meaning it should be present only in the 56 and not in the 53 kDa protein. Previously, it was shown that vaccination with the 56 kDa protein greatly reduced virus shedding and protected Rhesus monkeys from hepatitis E when challenged with a high intravenous dose of homologous or heterologous HEV. To evaluate the immunogenicity and protective efficacy of the 53 kDa protein, we vaccinated Rhesus monkeys with this protein and challenged them with a high or low dose of homologous virus. Vaccination with the 53 kDa protein greatly reduced virus shedding but did not protect against hepatitis following the high dose challenge. Virus was not detected in the vaccinated animals following the low dose challenge, suggesting that sterilizing immunity may have been achieved. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, Mol Hepatitis Sect, NIH, Bethesda, MD 20892 USA. Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA USA. Georgetown Univ, Sch Med, Dept Microbiol, Div Mol Virol & Immunol, Rockville, MD USA. RP Purcell, RH (reprint author), NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NR 10 TC 38 Z9 45 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 DEC 12 PY 2001 VL 20 IS 5-6 BP 853 EP 857 DI 10.1016/S0264-410X(01)00399-1 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 504TJ UT WOS:000172871700024 PM 11738749 ER PT J AU Pitisuttithum, P Cohen, MB Phonrat, B Suthisarnsuntorn, U Bussaratid, V Desakorn, V Phumratanaprapin, W Singhasivanon, P Looareesuwan, S Schiff, GM Ivanoff, B Lang, D AF Pitisuttithum, P Cohen, MB Phonrat, B Suthisarnsuntorn, U Bussaratid, V Desakorn, V Phumratanaprapin, W Singhasivanon, P Looareesuwan, S Schiff, GM Ivanoff, B Lang, D TI A human volunteer challenge model using frozen bacteria of the new epidemic serotype, V. cholerae O139 in Thai volunteers SO VACCINE LA English DT Article DE diarrhea; dose-escalation; antitoxin; vibriocidal serology ID NORTH-AMERICAN VOLUNTEERS; VIBRIO; VACCINE; EFFICACY; BENGAL; TOXIN AB A total of 35 volunteers were recruited for an IRB-approved inpatient dose-escalation challenge. The goal was to identify a. dose that produced an observed cholera attack rate greater than or equal to 80% and an illness of sufficient severity during the defined study period such that the model would be useful for determining vaccine protection. Volunteers were challenged in groups of 5 with V cholerae O139 that had been reconstituted immediately before use. Only 2 out of 5 volunteers who received the lowest dose (4.3 x 10(4) cfu) had diarrhea. As the inoculum size increased, the attack rate of diarrhea increased to 3-4 of 5 volunteers. At the highest dose tested, approximately 5 x 10(7) cfu, the attack rate was 73%. We recommend the use of frozen V Cholera O139 in a human experimental challenge model to assess cholera vaccine efficacy (VE) in a cholera endemic area but with 4 days observation period before initiation of tetracycline to allow assessment of severity. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Mahidol Univ, Fac Trop Med, Vaccine Trial Ctr, Bangkok, Thailand. Univ Cincinnati, Childrens Hosp Med Ctr, Div Pediat Gastroenterol & Nutr, Cincinnati, OH USA. Univ Cincinnati, Childrens Hosp Med Ctr, Gamble VTEU, Cincinnati, OH USA. WHO, CH-1211 Geneva, Switzerland. NIAID, NIH, Bethesda, MD 20892 USA. RP Pitisuttithum, P (reprint author), Mahidol Univ, Fac Trop Med, Vaccine Trial Ctr, 420-6 Rajvithi Rd, Bangkok, Thailand. OI Cohen, Mitchell/0000-0002-4412-350X FU NIAID NIH HHS [AI-45252] NR 14 TC 6 Z9 6 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 12 PY 2001 VL 20 IS 5-6 BP 920 EP 925 DI 10.1016/S0264-410X(01)00381-4 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 504TJ UT WOS:000172871700033 PM 11738758 ER PT J AU Zhang, RQ Elzey, B Williams, G Lu, S Law, DJ Horowits, R AF Zhang, RQ Elzey, B Williams, G Lu, S Law, DJ Horowits, R TI Ultrastructural and biochemical localization of N-RAP at the interface between myofibrils and intercalated disks in the mouse heart SO BIOCHEMISTRY LA English DT Article ID F-ACTIN-BINDING; CULTURED CHICK CARDIOMYOCYTES; NEBULIN-RELATED PROTEIN; CELL-CELL ADHESION; ALPHA-ACTININ; STRIATED-MUSCLE; INTRAMOLECULAR ASSOCIATION; MYOTENDINOUS JUNCTIONS; VINCULIN-BINDING; SKELETAL-MUSCLE AB N-RAP is a recently discovered muscle-specific protein found at cardiac intercalated disks. Double immunogold labeling of mouse cardiac muscle reveals that vinculin is located immediately adjacent to the fascia adherens region of the intercalated disk membrane, while N-RAP extends similar to 100 nm further toward the interior of the cell. We partially purified cardiac intercalated disks using low- and high-salt extractions followed by density gradient centrifugation. Immunoblots show that this preparation is highly enriched in desmin and junctional proteins, including N-RAP, talin, vinculin, beta1-integrin, N-cadherin, and connexin 43. Electron microscopy and immunolabeling demonstrate that N-RAP and vinculin are associated with the large fragments of intercalated disks that are present in this preparation, which also contains numerous membrane vesicles. Detergent treatment of the partially purified intercalated disks removed the membrane vesicles and extracted vinculin and beta1-integrin. Further separation on a sucrose gradient removed residual actin and myosin and yielded a fraction morphologically similar to fasciae adherentes that was highly enriched in N-RAP, N-cadherin, connexin 43, talin, desmin, and alpha -actinin. The finding that N-RAP copurifies with detergent-extracted intercalated disk fragments even though beta -integrin and vinculin have been completely removed suggests that N-RAP association with the adherens junction region is mediated by the cadherin system. Consistent with this hypothesis, we found that recombinant N-RAP fragments bind alpha -actinin in a gel overlay assay. In addition, immunofluorescence shows that N-RAP remains bound at the ends of isolated, detergent-treated cardiac myofibrils. These results demonstrate that N-RAP remains tightly bound to myofibrils and fasciae adherentes during biochemical purification and may be a key constituent in the mechanical link between these two structures. C1 NIAMSD, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Missouri, Div Cell Biol & Biophys, Kansas City, MO 64110 USA. RP Horowits, R (reprint author), NIAMSD, Muscle Biol Lab, NIH, Bldg 6,Room 408,MSC 2751, Bethesda, MD 20892 USA. EM horowits@helix.nih.gov NR 50 TC 23 Z9 23 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 11 PY 2001 VL 40 IS 49 BP 14898 EP 14906 DI 10.1021/bi0107445 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 500CJ UT WOS:000172608100020 ER PT J AU Zuzak, KJ Schaeberle, MD Gladwin, MT Cannon, RO Levin, IW AF Zuzak, KJ Schaeberle, MD Gladwin, MT Cannon, RO Levin, IW TI Noninvasive determination of spatially resolved and time-resolved tissue perfusion in humans during nitric oxide inhibition and inhalation by use of a visible-reflectance hyperspectral imaging technique SO CIRCULATION LA English DT Article DE peripheral vascular disease; blood flow; nitric oxide; hemoglobin; imaging ID DEPENDENT DIABETES-MELLITUS; OXYGEN-SATURATION; SPECTROSCOPY; INVIVO; MICROCIRCULATION; VASODILATION; MICROSCOPY; DISEASE AB Background-Vascular disease is commonly associated with reduced local synthesis of nitric oxide (NO) and impaired tissue perfusion. We introduce a novel noninvasive, visible-reflectance, hyperspectral imaging technique for quantifying the percentage of hemoglobin existing as oxyhemoglobin (HbO(2)) as an index of skin tissue perfusion. Methods and Results-To simulate vascular endothelial dysfunction. N-G-monomethyl-L-arginine (L-NMMA) was infused into the brachial arteries of 9 healthy subjects for 5 minutes to inhibit forearm NO synthesis, first with the subject breathing room air and subsequently during NO inhalation at 80 ppm for I hour. Blood flow was measured by venous occlusion plethysmography, and the percentage of HbO(2) perfusing skin tissue was imaged noninvasively with a visible-reflectance hyperspectral technique. L-NMMA reduced blood flow by 31.7 +/-4.9% and percentage of HbO(2) by 6.5 +/-0.1 (P=0.002 and P <0.001 versus baseline. respectively). With subjects inhaling NO, blood flow fell during L-NMMA infusion by only 10.9 +/-7.3%, and the percentage of HbO(2) decreased by 3.6 +/-0.1 (P=0.007 and P <0.001, respectively, versus room air L-NMMA responses). Conclusions-Visible-reflectance hyperspectral imaging demonstrates (1) a significant decline in the percentage of HbO(2) in skin tissue when blood flow is reduced after inhibition of forearm NO synthesis and (2) restoration of HbO(2) toward basal values with improved blood flow during inhalation of NO. This imaging method may provide an effective approach Cor time-resolved noninvasive monitoring of skin hemoglobin oxygen saturation and assessment of responses to therapeutic interventions in patients with vascular disease. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Natl Heart & Lung Inst, Dept Crit Care Med, NIH, Bethesda, MD USA. Natl Heart & Lung Inst, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD USA. Natl Heart & Lung Inst, Cardiol Branch, NIH, Bethesda, MD USA. RP Levin, IW (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 5,Room B1-32,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 57 Z9 57 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 11 PY 2001 VL 104 IS 24 BP 2905 EP 2910 DI 10.1161/hc4901.100525 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 501TC UT WOS:000172701300024 PM 11739304 ER PT J AU Ma, H Baumann, CT Li, HW Strahl, BD Rice, R Jelinek, MA Aswad, DW Allis, CD Hager, GL Stallcup, MR AF Ma, H Baumann, CT Li, HW Strahl, BD Rice, R Jelinek, MA Aswad, DW Allis, CD Hager, GL Stallcup, MR TI Hormone-dependent, CARM1-directed, arginine-specific methylation of histone H3 on a steroid-regulated promoter SO CURRENT BIOLOGY LA English DT Article ID IN-VIVO; RECEPTORS; EXCHANGE AB Activation of gene transcription involves chromatin remodeling by coactivator proteins that are recruited by DNA-bound transcription factors. Local modification of chromatin structure at specific gene promoters by ATP-dependent processes and by posttranslational modifications of histone N-terminal tails provides access to RNA polymerase II and its accompanying transcription initiation complex [1, 2]. While the roles of lysine acetylation, serine phosphorylation, and lysine methylation of histones in chromatin remodeling are beginning to emerge [2-5], low levels of arginine methylation of histones have only recently been documented [4, 6-9], and its physiological role is unknown. The coactivator CARM1 methylates histone H3 at Arg17 and Arg26 in vitro [7] and cooperates synergistically with p160-type coactivators; (e.g., GRIP1, SRC-1, ACTR) and coactivators with histone acetyltransferase activity (e.g., p300, CBP) to enhance gene activation by steroid and nuclear hormone receptors (NR) in transient transfection assays [10, 11]. In the current study, CARM1 cooperated with GRIP1 to enhance steroid hormone-dependent activation of stably integrated mouse mammary tumor virus (MMTV) promoters, and this coactivator function required the methyltransferase activity of CARM1. Chromatin immunoprecipitation assays and immunofluorescence studies indicated that CARM1 and the CARM1-methylated form of histone H3 specifically associated with a large tandem array of MMTV promoters in a hormone-dependent manner. Thus, arginine-specific histone methylation by CARM1 is an important part of the transcriptional activation process. C1 Univ So Calif, Dept Pathol, Los Angeles, CA 90089 USA. Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. Univ Calif Irvine, Dept Biochem & Mol Biol, Irvine, CA 92697 USA. Upstate Biotechnol, Lake Placid, NY 12946 USA. RP Stallcup, MR (reprint author), Univ So Calif, Dept Pathol, HMR 301,2011 Zonal Ave, Los Angeles, CA 90089 USA. RI Strahl, Brian/C-7601-2012 OI Strahl, Brian/0000-0002-4947-6259 FU NIDDK NIH HHS [DK55274]; NIGMS NIH HHS [GM20039, GM53512]; NINDS NIH HHS [NS17269] NR 17 TC 153 Z9 156 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 11 PY 2001 VL 11 IS 24 BP 1981 EP 1985 DI 10.1016/S0960-9822(01)00600-5 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 502QR UT WOS:000172754700028 PM 11747826 ER PT J AU Morgen, K Martin, R Stone, RD Grafman, J Kadom, N McFarland, HF Marques, A AF Morgen, K Martin, R Stone, RD Grafman, J Kadom, N McFarland, HF Marques, A TI FLAIR and magnetization transfer imaging of patients with post-treatment Lyme disease syndrome SO NEUROLOGY LA English DT Article ID MULTIPLE-SCLEROSIS; BORRELIA-BURGDORFERI; NEUROBORRELIOSIS; RESONANCE; LESIONS; BRAIN; IDENTIFICATION; MANIFESTATIONS; ENCEPHALOPATHY; INVOLVEMENT AB Objective: To determine patterns of abnormalities on cerebral MRI that may characterize subgroups of patients with post-treatment Lyme disease syndrome (PTLDS) and to help identify pathomechanisms of disease. Methods: The authors analyzed the distribution of cerebral lesions in a cohort of 27 patients with PTLDS. A subgroup of eight patients with PTLDS was further studied using whole-brain magnetization transfer ratio measures to identify abnormalities not seen on T2-weighted images. Results: Four patients had focal neurologic deficits, relapsing-remitting disease, and lesions in a distribution typical of MS. Twenty-three patients presented with nonfocal symptoms such as fatigue, subjective memory deficits, and mood disturbance. Twelve of these patients had normal MRI, including the more sensitive fluid-attenuated inversion recovery sequence, 10 had primarily punctate and subcortical lesions, and one patient had multiple periventricular lesions. Conclusions: In a portion of patients with post-treatment Lyme disease syndrome, white-matter hyperintensities tend to occur in subcortical arteriolar watershed areas and are not specific. Magnetization transfer ratio analysis did not provide evidence for structural abnormalities of the brain parenchyma in patients with nonfocal disease. C1 NINCDS, Neuroimmunol Branch, Cellular Immunol Sect, Bethesda, MD 20892 USA. NINCDS, Cognit Neurosci Sect, Bethesda, MD 20892 USA. NIDA, NIH, Bethesda, MD 20892 USA. Univ Giessen, Dept Neurol, Giessen, Germany. RP Martin, R (reprint author), NINCDS, Neuroimmunol Branch, Cellular Immunol Sect, Bldg 10,Room 5B16,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 30 TC 22 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 11 PY 2001 VL 57 IS 11 BP 1980 EP 1985 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 500AP UT WOS:000172603900008 PM 11739813 ER PT J AU Kim, YB Lee, MK Han, DP Cho, MW AF Kim, YB Lee, MK Han, DP Cho, MW TI Development of a safe and rapid neutralization assay using murine leukemia virus pseudotyped with HIV type 1 envelope glycoprotein lacking the cytoplasmic domain SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; PBL-SCID MICE; HIV-1/SIV CHIMERIC VIRUS; MEDIATED NEUTRALIZATION; PASSIVE-IMMUNIZATION; CORECEPTOR USAGE; VACCINIA VIRUS; RNA-POLYMERASE; FAB FRAGMENTS AB Neutralizing antibody (NAb) is a critical component of an immune system that can potentially provide sterilizing protection against human immunodeficiency virus type 1 (HIV-1). Therefore, an in vitro assay that can rapidly, safely, and accurately evaluate the NAb response vaccine candidates elicit, especially against a large number of HIV-1 variants, would be highly valuable. It has been demonstrated that HIV-1 envelope glycoprotein lacking the cytoplasmic domain can pseudotype murine leukemia virus encoding the beta -galactosidase gene and that this pseudovirus can specifically, infect CD4(+) cells (Schnierle BS, Stitz J, Bosch V, et al.: Proc Natl Acad Sci USA 1997;94:8640-8645). Because the pseudovirus is not biohazardous and because the infection can be quantitatively determined within 2 days, we examined the feasibility of using the pseudovirus for high-throughput neutralization assays for HIV-1. We have generated viruses pseudotyped with gp140 of six different HIV-1 isolates (LAI, RF, Bal, AD8, 89.6, and DH12). All six pseudoviruses were infectious and exhibited expected coreceptor usage phenotype in HOS-CD4 cells expressing either CCR5 or CXCR4. More importantly, the neutralization sensitivity profile of these pseudoviruses was virtually identical to that observed from more conventional neutralization assays using either HIV-1 or SHIV. All pseudoviruses could be neutralized by broadly reactive human monoclonal antibody IgG1 b12. Our results indicate that the pseudoviruses are ideal for high-throughput evaluation of immune sera for their capacity to broadly neutralize a large number of HIV-1 isolates. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Cho, MW (reprint author), NIAID, Mol Microbiol Lab, NIH, 9000 Rockville Pike,Bldg 4,Room 339, Bethesda, MD 20892 USA. NR 49 TC 18 Z9 20 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD DEC 10 PY 2001 VL 17 IS 18 BP 1715 EP 1724 DI 10.1089/08892220152741414 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 507VF UT WOS:000173051400004 PM 11788023 ER PT J AU Chiou, S Yoo, J Loh, KC Guzman, RC Gopinath, GR Rajkumar, L Chou, YC Yang, J Popescu, NC Nandi, S AF Chiou, S Yoo, J Loh, KC Guzman, RC Gopinath, GR Rajkumar, L Chou, YC Yang, J Popescu, NC Nandi, S TI Identification of rat mammary tumor-1 gene (RMT-1), which is highly expressed in rat mammary tumors SO CANCER LETTERS LA English DT Article DE rat mammary tumour-1 gene; identification; expression patterns ID IN-SITU HYBRIDIZATION; BREAST-CANCER; GROWTH-FACTOR; CARCINOGENESIS; ESTROGEN; GLAND; TUMORIGENESIS; REFRACTORINESS; PREVENTION; INDUCTION AB Full-term pregnancy early in life results in a permanent reduction in lifetime breast cancer risk in women. Parous rats and mice are also refractory to chemical carcinogenesis. Therefore, investigation of the differences between mammary glands from virgin and parous rats would provide valuable information regarding the protective effects of early full-term pregnancy. In this report, we examined the gene expression patterns in mammary glands from virgin and parous Lewis rats. Using differential display technology, a novel 4.2 kb cDNA, designated rat mammary tumor-1 (RMT-1) was isolated. Northern blot analysis of RMT-1 showed that RMT-1 expression was higher in the pre-pubertal and pubertal stages during rat mammary gland development while it was down-regulated in mammary glands from mature virgin and parous rats. RMT-1 expression was highest in rat mammary cancers compared with either the mammary glands of virgin or parous rats. At the Northern blot sensitivity level, RMT-1 expression was found only in the mammary gland. Northern blot analysis also showed that the expression of this gene was found in 74% of N-methyl-nitrosourea (MNU)-induced mammary cancers while it was not found in MNU-induced cancers from other organs. The examination of the RMT-1 gene structure revealed that it consists of five exons spanning 5.9 kb. Using fluorescence in situ hybridization, the gene was localized on rat chromosome 1 band q 43-51. The present data show that there is a correlation between high RMT-1 expression and rat mammary carcinogenesis or decreased RMT-1 expression and parity associated refractoriness to chemically induced mammary carcinogenesis. However, whether or not RMT-1 gene has a functional role in these processes remains to be investigated. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Chiou, S (reprint author), Univ Calif Berkeley, Canc Res Lab, Berkeley, CA 94720 USA. FU NCI NIH HHS [CA-78253, CA-72598] NR 38 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 10 PY 2001 VL 174 IS 1 BP 45 EP 55 DI 10.1016/S0304-3835(01)00668-1 PG 11 WC Oncology SC Oncology GA 491PQ UT WOS:000172117700005 PM 11675151 ER PT J AU Wheeler, MD Katuna, M Smutney, OM Froh, M Dikalova, A Mason, RP Samulski, RJ Thurman, RG AF Wheeler, MD Katuna, M Smutney, OM Froh, M Dikalova, A Mason, RP Samulski, RJ Thurman, RG TI Comparison of the effect of adenoviral delivery of three superoxide dismutase genes against hepatic ischemia-reperfusion injury SO HUMAN GENE THERAPY LA English DT Article ID PERFUSED-RAT-LIVER; TUMOR-NECROSIS-FACTOR; KAPPA-B ACTIVATION; KUPFFER CELLS; NITRIC-OXIDE; XANTHINE-OXIDASE; INDUCED APOPTOSIS; CYTOCHROME-C; TRANSPLANTATION; MITOCHONDRIA AB The purpose of this study was to investigate the effectiveness of superoxide dismutase (SOD) overexpression in an acute model of hepatic oxidative stress. Oxidative stress was established using a warm ischemia-reperfusion model, where nearly 70% of the liver was made hypoxic by clamping the hepatic artery and a branch of the portal vein for I hr followed by restoration of blood flow. Animals were infected i.v. with 1 x 10(9) plaque-forming units (PFU) of adenovirus containing the transgene for cytosolic Cu/Zn-SOD (Ad.SOD1), mitochondrial Mn-SOD (Ad.SOD2), extracellular Cu/Zn-SOD (Ad.SOD3), or the bacterial reporter gene for beta -galactosidase (Ad.lacZ) 3 days prior to experiments. Ad.SOD1 and Ad.SOD2 caused a three-fold increase in SOD expression and activity in liver compared to Ad.lacZ-treated control animals. Intravenous administration of Ad.SOD3 increased SOD activity slightly in serum but not in liver. Increases in serum transaminases and pathology due to ischemia-reperfusion were blunted by Ad.SOD1 and Ad.SOD2; however, extracellular SOD had no significant effect. Moreover, lipid-derived free radical adducts (a(N) = 15.65 G and a(beta)(H) = 2.78 G) were increased by ischemia-reperfusion. This effect was blunted by about 60% in Ad.SOD1- and Ad.SOD2-infected animals, but was unaffected by Ad.SOD3. However, when high doses of Ad.SOD3 (3 x 10(10) PFU) were administered. serum SOD activity was elevated three-fold and was protective against hepatic ischemia-reperfusion injury under these conditions. These data demonstrate that adenoviral delivery of superoxide dismutase can effectively reduce hepatic oxidative stress. C1 Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Alcohol Studies, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Wheeler, MD (reprint author), Univ N Carolina, Dept Pharmacol, CB 7365 Mary Ellen Jones Bldg, Chapel Hill, NC 27599 USA. EM wheelmi@med.unc.edu NR 52 TC 50 Z9 51 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 10 PY 2001 VL 12 IS 18 BP 2167 EP 2177 DI 10.1089/10430340152710513 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 505FP UT WOS:000172903000002 PM 11779401 ER PT J AU Zheng, CY Hoque, ATMS Braddon, VR Baum, BJ O'Connell, BC AF Zheng, CY Hoque, ATMS Braddon, VR Baum, BJ O'Connell, BC TI Evaluation of salivary gland acinar and ductal cell-specific promoters in vivo with recombinant adenoviral vectors SO HUMAN GENE THERAPY LA English DT Article ID MEDIATED GENE-TRANSFER; TISSUE-SPECIFIC EXPRESSION; HUMAN AMYLASE GENES; KALLIKREIN GENE; TRANSGENIC MICE; IN-VIVO; ACTIN PSEUDOGENE; SECRETION; LOCALIZATION; KININOGEN AB Adenoviral vectors efficiently deliver exogenous genes to salivary glands. There are two general epithelial cell types, with very different functions, in salivary glands-acinar and ductal. To determine if gene expression can be restricted in vivo to either general cell type using a relatively cell/tissue-specific promoter in conjunction with adenovirus-mediated gene transfer, we tested the human amylase and kallikrein promoters. For initial studies the sensitive reporter gene luciferase was used in two adenoviral constructs. The adenovirus AdAMY-Inc contains the human salivary gland amylase promoter (-1003 to +2)(AMY1C) and AdKALL-luc contains the human tissue kallikein promoter (-315 to -1)(KLK1). The adenovirus AdKALL-hAQP1 was also used to test a therapeutic gene, human aquaporin-1 (hAQP1), potentially of importance in treating surviving ductal cells in irradiation-damaged glands. Luciferase expression after AdAMY-luc delivery in vivo directly to the parotid, submandibular, and sublingual glands, as well as to the lungs, and intravenously via the femoral vein, was restricted to the three salivary glands and the pancreas. AdKALL-luc delivery via the same routes resulted in a more general distribution of luciferase expression, although greatest luciferase activity was seen in salivary glands and lung. Luciferase activity after AdAMY-luc delivery was proportionally greater (similar to 14-fold) in acinar cells, whereas luciferase activity after AdKALL-luc delivery was proportionally greater (similar to9-fold) in ductal cells. The expression of hAQP1 after AdKALL-hAQP1 gene transfer was mainly observed in ductal cells in vivo. AdKALL-hAQP1 was as useful as AdCMV-hAQP1 in increasing salivary flow rates of irradiated rats. This study demonstrates that adenoviral vectors containing the relatively cell/tissue-specific AMY1C or KLK1 promoters may be useful for targeting therapeutic gene expression in salivary glands. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. RP Zheng, CY (reprint author), NIDCR, GTTB, NIH, 9000 Rockville Pike,Bldg 10,1N113,MSC 1190, Bethesda, MD 20892 USA. OI O'Connell, Brian/0000-0003-4529-7664 NR 40 TC 20 Z9 23 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD DEC 10 PY 2001 VL 12 IS 18 BP 2215 EP 2223 DI 10.1089/10430340152710559 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 505FP UT WOS:000172903000006 PM 11779405 ER PT J AU Franzen, R Tanner, SL Dashiell, SM Rottkamp, CA Hammer, JA Quarles, RH AF Franzen, R Tanner, SL Dashiell, SM Rottkamp, CA Hammer, JA Quarles, RH TI Microtubule-associated protein 1B: a neuronal binding partner for myelin-associated glycoprotein SO JOURNAL OF CELL BIOLOGY LA English DT Article DE axons; cytoskeleton; microtubule-associated proteins; myelin-associated glycoprotein; neuroglia ID NERVOUS-SYSTEM; ADHESION MOLECULES; MAP1B EXPRESSION; SCHWANN-CELLS; AXONS; MICE; ABNORMALITIES; FAMILY AB Myelin-associated glycoprotein (MAG) is expressed in periaxonal membranes of myelinating glia where it is believed to function in glia-axon interactions by binding to a component of the axolemma. Experiments involving Western blot overlay and coimmunoprecipitation demonstrated that MAG binds to a phosphorylated neuronal isoform of microtubule-associated protein 1B (MAP1B) expressed in dorsal root ganglion neurons (DRGNs) and axolemma-enriched fractions from myelinated axons of brain, but not to the isoform of MAP1B expressed by glial cells. The expression of some MAP1B as a neuronal plasma membrane glycoprotein (Tanner, S.L., R. Franzen, H. Jaffe, and R.H. Quarles. 2000. J. Neurochem. 75:553-562.), further documented here by its immunostaining without cell permeabilization, is consistent with it being a binding partner for MAG on the axonal surface. Binding sites for a MAG-Fc chimera on DRGN's colocalized with MAP1B on neuronal varicosities, and MAG and MAP1B also colocalized in the periaxonal region of myelinated axons. In addition, expression of the phosphorylated isoform of MAP1B was increased significantly when DRGNs were cocultured with MAG-transfected COS cells. The interaction of MAG with MAP1B is relevant to the known role of MAG in affecting the cytoskeletal structure and stability of myelinated axons. C1 NINCDS, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Quarles, RH (reprint author), NINCDS, Mol & Cellular Neurobiol Lab, NIH, Bldg 49,Rm 2A28,49 Convent Dr,MSC 4440, Bethesda, MD 20892 USA. NR 28 TC 49 Z9 49 U1 0 U2 0 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 DEC 10 PY 2001 VL 155 IS 6 BP 893 EP 898 DI 10.1083/jcb.200108137 PG 6 WC Cell Biology SC Cell Biology GA 502EF UT WOS:000172730200004 PM 11733546 ER PT J AU Sarabi, A Hoffer, BJ Olson, L Morales, M AF Sarabi, A Hoffer, BJ Olson, L Morales, M TI GFR alpha-1 mRNA in dopaminergic and nondopaminergic neurons in the substantia nigra and ventral tegmental area SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE GDNF; interneurons; calcium-binding proteins; gamma-aminobutyric acid; glutamic acid decarboxylase; Parkinson's disease ID CALCIUM-BINDING PROTEINS; C-RET PROTOONCOGENE; NEUROTROPHIC-FACTOR; PARKINSONS-DISEASE; IN-VIVO; GABAERGIC NEURONS; TYROSINE KINASE; SURVIVAL FACTOR; BASAL GANGLIA; RAT-BRAIN AB Glial cell line-derived neurotrophic factor (GDNF) is a survival factor for several types of neurons, including dopaminergic (DAergic) neurons. GDNF binds with high affinity to the GDNF family receptor alpha -1 (GFR alpha -1), which is highly expressed in the midbrain. Using anatomical and lesion techniques, we demonstrated that GFR alpha -1 was expressed in DAergic and non-DAergic neurons in the rat midbrain. Immunohistochemical characterization of GFR alpha -1-expressing neurons indicated that most of the neurons that were immunopositive for the DAergic marker tyrosine hydroxylase (TH) expressed GFR alpha -1 in the substantia nigra pars compacta (SNC). In contrast, fewer TH-containing neurons expressed GFR alpha -1 in the substantia nigra pars reticulata (SNR) and the ventral tegmental area (VTA). Depletion of GFR alpha -1/TH neurons was observed in the SNC following treatment with the neurotoxin 6-hydroxydopamine (6-OHDA); however, GFR alpha -1 expression remained in some neurons located in the SNR. The gamma -aminobutyric acid (GABA)ergic nature of GFR alpha -1-expressing neurons located in the SNR, which were resistant to (6-hydroxydopamine) 6-OHDA, was established by their expression of glutamic acid decarboxylase (GAD; the synthesizing enzyme for GABA). Further analysis indicated that coexpression of GFR alpha -1 and GAD varied in a rostrocaudal gradient in the SNR, substantia nigra pars lateralis (SNL), and VTA. Midbrain DAergic and GABAergic neurons have been previously classified according to their Ca2+ binding protein (CaBP) content; thus, we also sought to investigate the proportion of midbrain GFR alpha -1-expressing neurons containing parvalbumin (PV), calbindin (CB), and calretinin (CR) in the midbrain. Although GFR alpha -1 expression was found mainly in CB- and CR-immunoreactive neurons, it was rarely observed in PV-immunolabeled neurons. Analysis of the proportion of GFR alpha -1-expressing neurons for each CaBP subpopulation indicated the coexistence of GFR alpha -1 with CR in the VTA and all subdivisions of the SN; double-labeled GFR alpha -1/CR neurons were distributed in the SNC, SNR, SNL, and VTA. GFR alpha -1/CB neurons were also detected in the SNC, SNL, and VTA. Expression of GFR alpha -1 in DAergic and non-DAergic neurons in the rat SN and VTA suggests that GDNF, via GFR alpha -1, might modulate DAergic and GABAergic functions in the nigrostriatal, mesolimbic, and nigrothalamic circuits of the adult rat. J. Comp. Neurol. 441:106-117, 2001. Published 2001 Wiley-Liss, Inc.dagger C1 NIDA, Baltimore, MD 21224 USA. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. RP Morales, M (reprint author), NIDA, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 56 TC 45 Z9 46 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 10 PY 2001 VL 441 IS 2 BP 106 EP 117 DI 10.1002/cne.1400 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 489YV UT WOS:000172021500002 PM 11745638 ER PT J AU Boulanger, A Liu, SY Yu, S Redmond, T AF Boulanger, A Liu, SY Yu, S Redmond, T TI Sequence and structure of the mouse gene for RPE65 SO MOLECULAR VISION LA English DT Article ID RETINAL-PIGMENT EPITHELIUM; CONGENITAL AMAUROSIS; MICROSOMAL PROTEIN; VISUAL CYCLE; IN-VITRO; MUTATIONS; EXPRESSION; DYSTROPHY AB Purpose: To determine the genomic organization of the mouse gene for the retinal pigment epithelium (RPE) specific protein RPE65. Methods: A genomic clone containing the entire Rpe65 gene was isolated from a mouse genomic P1 library. Fragments of this clone were subcloned and sequenced by automated fluorescent dideoxy DNA sequencing and analyzed. Direct sequencing of PCR amplification products was used to complete the structure. Primer extension analysis was used to determine the transcription start site. Results: Southern hybridization of restriction digests of mouse genomic DNA reveals a likely single autosomal gene for Rpe65 with no evidence of pseudogenes. Sequence analysis of the mouse P1 clone for Rpe65 and fragments thereof reveals 14 exons distributed over 27 kbp. The transcription start site is located 57 bp upstream of the initiation codon. The protein encoded by the mouse Rpe65 gene is highly conserved when compared with RPE65s from other species. Conclusions: RPE65 is a highly conserved protein and it appears that the genes for the mouse and human RPE65s, at least, are also conserved in overall structure. C1 NEI, LRCMB, NIH, Bethesda, MD 20892 USA. RP Redmond, T (reprint author), NEI, LRCMB, NIH, Bldg 6,Room 339,6 Ctr Dr,MSC 2740, Bethesda, MD 20892 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 18 TC 9 Z9 12 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD DEC 10 PY 2001 VL 7 IS 40 BP 283 EP 287 PG 5 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 501HQ UT WOS:000172679600001 PM 11740468 ER PT J AU Zubenko, GS Zubenko, WN Spiker, DG Giles, DE Kaplan, BB AF Zubenko, GS Zubenko, WN Spiker, DG Giles, DE Kaplan, BB TI Malignancy of recurrent, early-onset major depression: A family study SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE major depression; recurrent mood disorders; comorbidity; mortality; family and genetic studies ID CORONARY-ARTERY DISEASE; ALZHEIMERS-DISEASE; AFFECTIVE-DISORDERS; PSYCHIATRIC-DISORDERS; RISK-FACTORS; UNIPOLAR DEPRESSION; SUSCEPTIBILITY LOCI; HISTORY; ILLNESS; TWIN AB Coordinated efforts to identify susceptibility genes for unipolar major depressive disorder (MDD) and related disorders are now underway. These studies have focused on recurrent, early-onset MDD (RE-MDD), the most heritable form of this disorder. The goal of this study was to characterize the burden of MDD and other mood disorders, comorbid mental disorders, and excess mortality in RE-MDD families. A total of 81 families were identified through probands over the age of 18, who met criteria for recurrent (greater than or equal to2 episodes), early-onset (less than or equal to 25 years), nonpsychotic, unipolar MDD (RE-MDD), and included 407 first-degree relatives and 835 extended relatives. Psychiatric diagnoses for probands and their family members who provided blood samples were formulated from structured personal interviews, structured family history assessments, and available medical records. The remaining family members who participated and those who were deceased were evaluated through the family history method augmented by available medical records. Best estimate diagnoses were made during a consensus conference according to established diagnostic criteria. Approximately half of the first-degree relatives and a quarter of extended relatives of RE-MDD probands suffered from at least one mood disorder, typically MDD. As commonly observed for other oligogenic, multifactorial disorders, the severity of MMD reflected by age at onset and number of episodes attenuated with increasing familial/genetic distance from the proband. A substantial fraction of RE-MDD probands and their first-degree relatives met diagnostic criteria for additional psychiatric disorders that include prominent disturbances of mood. The deceased relatives of RE-MDD probands died at a median age that was 8 years earlier than for the local population; over 40% died before reaching age 65. These differences in mortality statistics resulted from a shift toward younger ages at death across the lifespan, including a fivefold increase in the proportion of individuals who died in the first year of life. Several-fold increases in the proportion of deaths by suicide, homicide, and liver disease were observed among the relatives of RE-MDD probands. However, the rank order of the three most common causes of death-heart disease, cancer, and stroke-remained unchanged and differences in the proportions of deaths from the remaining causes were small. RE-MDD is a strongly familial condition with a high rate of psychiatric comorbidity, whose malignant effects have a significant negative impact on the health and longevity of patients and their family members. (C) 2001 Wiley-Liss, Inc. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15261 USA. Carnegie Mellon Univ, Mellon Coll Sci, Dept Biol Sci, Pittsburgh, PA 15213 USA. Univ Rochester, Sch Med, Dept Psychiat, Rochester, NY 14642 USA. Univ Rochester, Sch Med, Dept Neurol, Rochester, NY 14642 USA. NIMH, Intramural Res Program, Bethesda, MD 20892 USA. RP Zubenko, GS (reprint author), WPIC,Room E1230,3811 Ohara St, Pittsburgh, PA 15213 USA. FU NIMH NIH HHS [MH39531, MH30915, MH48969, MH00540] NR 66 TC 56 Z9 57 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 8 PY 2001 VL 105 IS 8 BP 690 EP 699 DI 10.1002/ajmg.1554 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 497TE UT WOS:000172470900007 PM 11803516 ER PT J AU Tentler, D Brandberg, G Betancur, C Gillberg, C Anneren, G Orsmark, C Green, ED Carlsson, B Dahl, N AF Tentler, D Brandberg, G Betancur, C Gillberg, C Anneren, G Orsmark, C Green, ED Carlsson, B Dahl, N TI A balanced reciprocal translocation t(5;7)(q14;q32) associated with autistic disorder: Molecular analysis of the chromosome 7 breakpoint SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE autism; balanced reciprocal translocation; 7q31-q32; breakpoint mapping ID IDENTIFICATION; HYBRIDIZATION; TWIN; 7Q31 AB Autism is a neuropsychiatric disorder characterized by impairments in social interaction, restricted and stereotypic pattern of interest with onset by 3 years of age. The results of genetic linkage studied for autistic disorder (AD) have suggested a susceptibility locus for the disease on the long arm of chromosome 7. We report a girl with AD and a balanced reciprocal translocation t(5;7)(q14;q32). The mother carries the translocation but do not express the disease. Fluorescent in situ hybridization (FISH) analysis with chromosome 7-specific YAC clones showed that the breakpoint coincides with the candidate region for AD. We identified a PAC clone that spans the translocation breakpoint and the breakpoint was mapped to a 2 kb region. Mutation screening of the genes SSBP and T2R3 located just centromeric to the breakpoint was performed in a set of 29 unrelated autistic sibling pairs who shared at least one chromosome 7 haplotype. We found no sequence variations, which predict amino acid alterations. Two single nucleotide polymorphisms were identified in the T2R3 gene, and associations between allele variants and AD in our population were not found. The methylation pattern of different chromosome 7 regions in the patient's genomic DNA appears normal. Here we report the clinical presentation of the patient with AD and the characterization of the genomic organization across the breakpoint at 7q32. The precise localization of the breakpoint on 7q32 may be relevant for further linkage studies and molecular analysis of AD in this region. Published 2001 Wiley-Liss, Inc.(dagger). C1 Univ Uppsala, Rudbeck Lab, Clin Genet Unit, Dept Genet & Pathol, S-75185 Uppsala, Sweden. Falun Cty Hosp, Falun, Sweden. Fac Med Creteil, INSERM, U513, Paris, France. Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. NHGRI, NIH, Bethesda, MD 20892 USA. RP Tentler, D (reprint author), Univ Uppsala, Rudbeck Lab, Clin Genet Unit, Dept Genet & Pathol, S-75185 Uppsala, Sweden. NR 20 TC 14 Z9 14 U1 2 U2 5 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 DEC 8 PY 2001 VL 105 IS 8 BP 729 EP 736 DI 10.1002/ajmg.1607 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 497TE UT WOS:000172470900012 PM 11803521 ER PT J AU Gejman, PV Sanders, AR Badner, JA Cao, QH Zhang, J AF Gejman, PV Sanders, AR Badner, JA Cao, QH Zhang, J TI Linkage analysis of schizophrenia to chromosome 15 SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE genetic mapping; nonparametric; dominant; recessive; P50 auditory-evoked response ID CHRNA7 GENE REGION; NEUROPHYSIOLOGICAL DEFICIT; SCHIZOAFFECTIVE DISORDER; SUSCEPTIBILITY LOCUS; CONTROLLED FAMILY; COMPLEX TRAITS; NO EVIDENCE; MARKERS; TRANSMISSION; MODELS AB We have mapped a sample of 68 families consisting of one or more affected sibling pairs with schizophrenia or schizoaffective disorder with 20 markers spanning all of chromosome 15 to investigate whether there is a locus on chromosome 15 that confers an increased susceptibility to schizophrenia using parametric and nonparametric linkage analyses. Allele sharing identical by descent and multipoint maximum likelihood score (MLS) statistics were employed. Results show excess allele sharing for multiple markers in 15q11.2-q25, a chromosomal region previously found linked to a decrease in the normal inhibition of the P50 auditory-evoked response to the second of paired stimuli, a decrease associated with schizophrenia. Excess allele sharing was found for markers spanning about 48 cM in 15q11.2q25 (D15S1002-D15S1023). The greatest single point allele sharing was found at D15S659 (62.6%). The multipoint MLS scores were greater than 1.0 in the 30-52 cM interval delimited by ACTC and D15S150, with a maximum value of 2.0 with GENE-HUNTER PLUS near D15S1039. (C) 2001 Wiley-Liss, Inc. C1 Univ Chicago, Jules F Knapp Res Ctr, Dept Psychiat, Schizophrenia Genet Res Program, Chicago, IL 60637 USA. NIMH, Unit Mol Clin Invest, Clin Neurogenet Branch, Bethesda, MD 20892 USA. RP Gejman, PV (reprint author), Univ Chicago, Jules F Knapp Res Ctr, Dept Psychiat, Schizophrenia Genet Res Program, 924 E 57th St,Room R-010, Chicago, IL 60637 USA. NR 32 TC 45 Z9 46 U1 2 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 8 PY 2001 VL 105 IS 8 BP 789 EP 793 DI 10.1002/ajmg.1552 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 497TE UT WOS:000172470900023 PM 11803532 ER PT J AU El-Osta, A Wolffe, AP AF El-Osta, A Wolffe, AP TI Analysis of chromatin-immunopurified MeCP2-associated fragments SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HISTONE DEACETYLASE; MECP2; DNA; METHYLATION; SITES AB As molecular biologists, we are continuing to unravel the interactions by which DNA binding proteins mediate the expression of genes. The chromatin immunoprecipitation (ChIP) technique provides us with an exquisite tool to investigate the interplay between chromatin structure and its role in regulating transcription, replication, and recombination in vivo. We describe a robust assay used to identify the molecular determinants associated with chromatin. In this article we illustrate the ChIP technique and use the transcriptionally silent-hypermethylated multidrug resistance (MDR1) gene as the platform for methyl-CpG binding protein 2 (MeCP2) localization on chromatin. Driven by the hypothesis that repression is strongly dependent on the methylation profile of the endogenous promoter, we demonstrate that MDR1 is targeted by MeCP2. Methylated MDR1 chromatin is highly enriched with McCP2 and is in striking contrast to localization observed in cells in which MDR1 is transcriptionally active. In a distinct model system we discuss experimental methods used to immunopurify the MeCP2 repressor complex on chromatin and quantify protein-DNA association by competitive PCR approach. (C) 2001 Elsevier Science. C1 Peter MacCallum Canc Inst, Sir Donald & Lady Trescowthick Res Labs, Melbourne, Vic 3002, Australia. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. Sangamo BioSci Inc, Point, Point Richmond Tech Ctr, Richmond, CA 94804 USA. RP El-Osta, A (reprint author), Peter MacCallum Canc Inst, Sir Donald & Lady Trescowthick Res Labs, St Andrews Pl, Melbourne, Vic 3002, Australia. NR 11 TC 20 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 7 PY 2001 VL 289 IS 3 BP 733 EP 737 DI 10.1006/bbrc.2001.6023 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 502PH UT WOS:000172751600015 PM 11726209 ER PT J AU Wang, XY Cen, XB Lu, L AF Wang, XY Cen, XB Lu, L TI Noradrenaline in the bed nucleus of the stria terminalis is critical for stress-induced reactivation of morphine-conditioned place preference in rats SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE noradrenaline; clonidine; 6-hydroxydopamine; opiate dependence; conditioned place preference; relapse; stress; bed nucleus of the stria terminalis; locus coeruleus ID CORTICOTROPIN-RELEASING FACTOR; INDUCED RELAPSE; OPIATE WITHDRAWAL; LOCUS-COERULEUS; MOLECULAR MECHANISMS; BASAL FOREBRAIN; COCAINE-SEEKING; HEROIN-SEEKING; DRUG-ABUSE; CORTICOSTERONE AB The effect of noradrenaline in the bed nucleus of the stria terminalis and locus coeruleus on maintenance and reactivation of morphine-conditioned place preference induced by footshock stress was investigated in rats. After receiving alternate injection of morphine (10 mg/kg) and saline for 6 consecutive days, the rats spent more time in the drug-paired compartment (morphine-conditioned place preference) on day 7. These animals did not show morphine-conditioned place preference on day 37 following sham-footshock once every 3 days from days 8 to 36 (28 days drug-free). However, 15 min of intermittent footshock once every 3 days could induce the maintenance of morphine-conditioned place preference on day 37 with significantly more time spent in the drug-paired compartment than on day 0. Microinjection of the alpha (2)-adrenoceptor agonist, clonidine (0.1 or 1 mug), into the locus coeruleus 30 min before footshock did not affect stress-induced maintenance of conditioned place preference. However, infusions of clonidine (I mug) into the bed nucleus of the stria terminalis significantly attenuated the maintenance of conditioned place preference induced by footshock stress. In another experiment, after a 21-day extinction of morphine-conditioned place preference, a single footshock could reactivate the morphine place preference that was significantly blocked by pretreatment with infusion of clonidine (0.1 or 1 mug) into the bed nucleus of the stria terminalis but not the locus coeruleus. Reactivation of morphine-conditioned place preference elicited by footshock stress was significantly inhibited by 6-hydroxydopamine-induced lesions in the ventral noradrenergic bundle, most of the norepinephrine input to the bed nucleus of the stria terminalis arising from caudal brain stem noradrenergic cell groups. In contrast, chemical lesions of the dorsal noradrenergic bundle that arises from the locus coeruleus had no such effects. These findings suggest that noradrenergic neurons in locus coeruleus are not involved in stress-induced reinstatement of drug-seeking and further clearly demonstrate that noradrenaline in the bed nucleus of the stria terminalis plays a critical role in mediating this effect. Comprehension of the neurochemical events underlying the stress-induced and the bed nucleus of the stria terminalis-mediated reinstatement of drug-seeking may, therefore, throw more light on the biological bases of drug dependence and addictive behavior. (C) 2001 Published by Elsevier Science B.V. C1 W China Univ Med Sci, Ctr Med Expt, Chengdu 640041, Peoples R China. Shanghai Med Univ, Natl Lab Med Neurobiol, Shanghai 200032, Peoples R China. Kailuan Mental Hlth Ctr, Tangshan 063001, Peoples R China. RP Lu, L (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 45 TC 82 Z9 84 U1 0 U2 5 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 DEC 7 PY 2001 VL 432 IS 2-3 BP 153 EP 161 DI 10.1016/S0014-2999(01)01487-X PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 503AA UT WOS:000172773900006 PM 11740951 ER PT J AU Mackem, S Baumann, CT Hager, GL AF Mackem, S Baumann, CT Hager, GL TI A glucocorticoid/retinoic acid receptor chimera that displays cytoplasmic/nuclear translocation in response to retinoic acid - A real time sensing assay for nuclear receptor ligands SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FLUORESCENT PROTEIN CHIMERA; THYROID-HORMONE RECEPTOR; BINDING DOMAIN; LIVING CELLS; PROGESTERONE-RECEPTOR; CRYSTAL-STRUCTURE; ESTROGEN-RECEPTOR; STEROID-BINDING; HSP90; LOCALIZATION AB Members of the nuclear receptor superfamily play key roles in a host of physiologic and pathologic processes from embryogenesis to cancer. Some members, including the retinoic acid receptor (RAR), are activated by ligand binding but are unaffected in their subcellular distribution, which is predominantly nuclear. In contrast, several members of the steroid receptor family, including the glucocorticoid receptor, are cytoplasmic and only translocate to the nucleus after ligand binding. We have constructed chimeras between RAR and glucocorticoid receptor that selectively respond to RAR agonists but display cytoplasmic localization in the absence of ligand. These chimeric receptors manifest both nuclear translocation and gene activation functions in response to physiological concentrations of PLAR ligands. The ability to achieve regulated subcellular trafficking with a heterologous ligand binding domain has implications both for current models of receptor translocation and for structural-functional conservation of ligand binding domains broadly across the receptor superfamily. When coupled to the green fluorescent protein, chimeric receptors offer a powerful new tool to 1) study mechanisms of steroid receptor translocation, 2) detect dynamic and graded distributions of ligands in complex microenvironments such as embryos, and 3) screen for novel ligands of "orphan" receptors in vivo. C1 NCI, Lab Receptor Biol & Gene Express, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Canc Res Ctr, NIH, Bldg 41,Rm B602, Bethesda, MD 20892 USA. NR 34 TC 21 Z9 21 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 DEC 7 PY 2001 VL 276 IS 49 BP 45501 EP 45504 DI 10.1074/jbc.C100269200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100002 PM 11585812 ER PT J AU Schofield, MJ Brownewell, FE Nayak, S Du, CW Kool, ET Hsieh, P AF Schofield, MJ Brownewell, FE Nayak, S Du, CW Kool, ET Hsieh, P TI The Phe-X-Glu DNA binding motif of MutS - The role of hydrogen bonding in mismatch recognition SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CEREVISIAE MSH2-MSH6 COMPLEX; REPAIR PROTEIN MUTS; HETERODUPLEX DNA; HMUTS-ALPHA; MSH6; REPLICATION; MUTATION; SUBUNIT; ANALOGS; CANCER AB The crystal structures of MutS protein from Thermus aquaticus and Escherichia coli in a complex with a mismatch-containing DNA duplex reveal that the Glu residue in a conserved Phe-X-Glu motif participates in a hydrogen-bonded contact with either an unpaired thymidine or the thymidine of a G-T base-base mismatch. Here, the role of hydrogen bonding in mismatch recognition by MutS is assessed. The relative affinities of MutS for DNA duplexes containing nonpolar shape mimics of A and T, 4-methylbenzimidazole (Z), and difluoro-toluene (F), respectively, that lack hydrogen bonding donors and acceptors, are determined in gel mobility shift assays. The results provide support for an induced fit mode of mismatch binding in which duplexes destabilized by mismatches are preferred substrates for kinking by MutS. Hydrogen bonding between the O is an element of2 group of Glu and the mismatched base contributes only marginally to mismatch recognition and is significantly less important than the aromatic ring stack with the conserved Phe residue. A MutS protein in which Ala is substituted for Glu(38) is shown to be defective for mismatch repair in vivo. DNA binding studies reveal a novel role for the conserved Glu residue in the establishment of mismatch discrimination by MutS. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Chem, Stanford, CA 94305 USA. RP Hsieh, P (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 10,Rm 9D06, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [R01 GM52956] NR 27 TC 72 Z9 73 U1 2 U2 9 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 DEC 7 PY 2001 VL 276 IS 49 BP 45505 EP 45508 DI 10.1074/jbc.C100449200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100003 PM 11602569 ER PT J AU Sturgeon, BE Glover, RE Chen, YR Burka, LT Mason, RP AF Sturgeon, BE Glover, RE Chen, YR Burka, LT Mason, RP TI Tyrosine iminoxyl radical formation from tyrosyl radical/nitric oxide and nitrosotyrosine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-SPIN-RESONANCE; PHOTOSYSTEM-II; RIBONUCLEOTIDE REDUCTASE; NITRIC-OXIDE; ESCHERICHIA-COLI; HORSERADISH-PEROXIDASE; ANACYSTIS-NIDULANS; MODEL COMPOUNDS; DNA PHOTOLYASE; OXYGEN AB The quenching of the Y-D tyrosyl radical in photosystem II by nitric oxide was reported to result from the formation of a weak tyrosyl radical-nitric oxide complex (Petrouleas, V., and Diner, B. A (1990) Biochim. Biophys. Acta 1015, 131-140). This radical/radical reaction is expected to generate an electron spin resonance (ESR)silent 3-nitrosocyclohexadienone species that can reversibly regenerate the tyrosyl radical and nitric oxide or undergo rearrangement to form 3-nitrosotyrosine. It has been proposed that 3-nitrosotyrosine can be oxidized by one electron to form the tyrosine iminoxyl radical (>C=N-O). This proposal was put forth as a result of ESR detection of the iminoxyl radical intermediate when photosystem II was exposed to nitric oxide (Sanakis, Y., Goussias, C., Mason, R. P., and Petrouleas, V. (1997) Biochemistry 36, 1411-1417). A similar iminoxyl radical was detected in prostaglandin H synthase-2 (Gunther, M. R., Hsi, L. C., Curtis, J. F., Gierse, J. K., Marnett. L. J., Eling, T. E., and Mason, R. P. (1997) J. Biol. Chem., 272, 17086-17090). Although the iminoxyl radicals detected in the photosystem II and prostaglandin H synthase-2 systems strongly suggest a mechanism involving 3-nitrosotyrosine, the iminoxyl radical ESR spectrum was not unequivocally identified as originating from tyrosine. We report here the detection of the non-protein L-tyrosine iminoxyl radical generated by two methods: 1) peroxidase oxidation of synthetic 3-nitroso-N-acetyl-L-tyrosine and 2) peroxidase oxidation of free L-tyrosine in the presence of nitric oxide. A newly developed ESR technique that uses immobilized enzyme was used to perform the ESR experiments. Analysis of the high resolution ESR spectrum of the tyrosine iminoxyl radical generated from free tyrosine and nitric oxide reveals a 28.4-G isotropic nitrogen hyperfine coupling and a 2.2-G proton hyperfine coupling assigned to the proton originally ortho to the phenoxyl oxygen. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Sturgeon, BE (reprint author), NC Sch Sci & Math, 1219 Broad St, Durham, NC 27705 USA. NR 46 TC 26 Z9 26 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2001 VL 276 IS 49 BP 45516 EP 45521 DI 10.1074/jbc.M106835200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100006 PM 11551949 ER PT J AU Mimura, Y Sondermann, P Ghirlando, R Lund, J Young, SP Goodall, M Jefferis, R AF Mimura, Y Sondermann, P Ghirlando, R Lund, J Young, SP Goodall, M Jefferis, R TI Role of oligosaccharide residues of IgG1-Fc in Fc gamma RIIb binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IGG-FC; CRYSTAL-STRUCTURE; CARBOHYDRATE STRUCTURE; PROTEIN INTERACTIONS; EFFECTOR FUNCTIONS; INTERACTION SITES; RECEPTOR IIB; ANTIBODY; GLYCOSYLATION; CELLS AB Engagement of Fc gamma receptors (Fc gamma Rs) with the Fe region of IgG elicits immune responses by leukocytes. The recent crystal structure of Fc gamma RIII in complex with IgG-Fc has provided details of molecular interactions between these components (Sondermann, P., Huber, R., Oosthuizen, V., and Jacob, U. (2000) Nature 406, 267-273). One of the most intriguing issues is that glycosylation of IgG-Fc is essential for the recognition by Fc gamma Rs although the carbohydrate moieties are on the periphery of the Fc gamma RIII-Fc interface. To better understand the role of Fe glycosylation in Fc gammaR binding we prepared homogeneous glycoforms of IgG-Fc (Cri) and investigated the interactions with a soluble form of Fc gamma RIIb (sFc gamma RIIb). A 1:1 complex stoichiometry was observed in solution at 30 degreesC (K-d, 0.94 muM; DeltaG, - 8.4 kcal mol(-1); DeltaH, -6.5 kcal mol(-1); T DeltaS, 1.9 kcal mol(-1); DeltaC(p), -160 cal mol(-1) K-1). Removal of terminal galactose residues did not alter the thermodynamic parameters significantly. Outer-arm GlcNAc residues contributed significantly to thermal stability of the C(H)2 domains but only slightly to sFc gamma RIIb binding. Truncation of 1,3- and 1,6-arm mannose residues generates a linear trisaccharide core structure and resulted in a significantly decreased affinity, a less exothermic DeltaH, and a more negative DeltaC(p) for sFc gamma RIIb binding, which may result from a conformational change coupled to complex formation. Deglycosylation of the C(H)2 domains abrogated sFc gamma RIIb binding and resulted in the lowest thermal stability accompanied with noncooperative unfolding. These results suggest that truncation of the oligosaccharides of IgG-Fc causes disorder and a closed disposition of the two C(H)2 domains, impairing sFc gamma RIIb binding. C1 Univ Birmingham, Sch Med, Div Immun & Infect, Birmingham B15 2TT, W Midlands, England. Max Planck Inst Biochem, Abt Strukturforsch, D-82152 Martinsried, Germany. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mimura, Y (reprint author), Univ Oxford, Dept Biochem, Glycobiol Inst, S Parks Rd, Oxford OX1 3QU, England. RI Ghirlando, Rodolfo/A-8880-2009; Young, Stephen P/A-7380-2008 OI Young, Stephen P/0000-0002-6355-3361 NR 50 TC 147 Z9 150 U1 2 U2 9 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 DEC 7 PY 2001 VL 276 IS 49 BP 45539 EP 45547 DI 10.1074/jbc.M107478200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100009 PM 11567028 ER PT J AU Martelli, MP Boomer, J Bu, M Bierer, BE AF Martelli, MP Boomer, J Bu, M Bierer, BE TI T cell regulation of p62(dok) (Dok1) association with Crk-L SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; NATURAL-KILLER-CELLS; TYROSINE PHOSPHORYLATION; ANTIGEN-RECEPTOR; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAIN; BCR-ABL; ZETA-CHAIN; CD2 STIMULATION; DOCKING PROTEIN AB In addition to engagement of the T cell receptor-CD3 complex, T lymphocytes can be activated by a variety of cell surface molecules including the similar to 50-kDa surface receptor CD2. While the majority of biochemical signaling elements are triggered by either CD2 or TcR-CD3 receptors, a small number of proteins are engaged by only one receptor. Recently, p62(dok) (Dok1), a member of the Dok family of adapter molecules, has been reported to be activated by CD2 and not by C133 engagement. Here we have examined the role of p62(dok) in CD2-dependent signaling in Jurkat T cells. As previously reported, we find that ligation of the CD2 molecule by mitogenic pairs of anti-CD2 mAbs led to phosphorylation of p62(dok). While CD2-induced p62(dok) tyrosine phosphorylation was independent of both the p36/38 membrane adapter protein linker of activated T cells (LAT) and the ZAP70/Syk family of kinases, it was dependent upon the Src family of kinases including Lck and Fyn. We find further that CD2 engagement induced the association of tyrosine-phosphorylated p62(dok) to Crk-L. The CD2-dependent association of p62(dok) to Crk-L was independent of expression of the ZAP70/Syk family of kinases. Of note, while T cell receptor-CD3 engagement did not induce either p62(dok) phosphorylation or Crk-L association in Jurkat T cells, it did inhibit CD2-dependent p62 (dok)-Crk-L complexes; this TcR-CD3-mediated regulation was dependent upon ZAP70 kinase activity. Our data suggest that phosphorylation of p62(dok) and its interaction with other signaling proteins may depend upon integrated signals emanating from the CD2 receptor, utilizing a ZAP70/LAT-independent pathway, and the TcR-CD3 receptor, which is ZAP70/Syk-dependent. C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, Bldg 10,Rm 6C208,10 Ctr Dr, Bethesda, MD 20892 USA. RI Martelli, Maria Paola/I-5618-2012 NR 85 TC 16 Z9 17 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2001 VL 276 IS 49 BP 45654 EP 45661 DI 10.1074/jbc.M105777200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100023 PM 11553620 ER PT J AU Strachan, GD Rallapalli, R Pucci, B Lafond, TP Hall, DJ AF Strachan, GD Rallapalli, R Pucci, B Lafond, TP Hall, DJ TI A transcriptionally inactive E2F-1 targets the MDM family of proteins for proteolytic degradation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUSCEPTIBILITY GENE-PRODUCT; CELL-GROWTH CONTROL; RETINOBLASTOMA PROTEIN; P53-BINDING PROTEIN; P53; APOPTOSIS; ONCOPROTEIN; PATHWAY; DOMAIN; P73 AB E2F-1-activated transcription promotes cell cycle progression and apoptosis. These functions are regulated by several factors including the E2F-1-binding protein MDM2 and the retinoblastoma protein pRb. Using a yeast two-hybrid screen we have identified the MDM2-related protein, MDMX as an E2F-1-binding protein. In these studies we find that coexpression of MDMX with E2F-1 results in degradation of the MDMX protein. Although this proteolytic degradation can be blocked by the protease inhibitors bafilomycin A(1), N-acetyl-Leu-Leu-Norleu-AL, and N-acetyl-Leu-Leu-Met-AL, MDMX degradation is not inhibited by lactacystin, suggesting that degradation occurs by a proteasome-independent mechanism. Using an E2F-1 deletion mutant (E2F-1(180-437)) we show that E2F-1-targeted degradation of MDMX does not require the E2F-1 DNA binding domain and therefore is independent of E2F-1-driven transcription. We also find that this transcriptionally inactive E2F-1 mutant is capable of degrading the MDMX-related protein MDM2 and the MDMX isoform MDMX-S. Mapping of the E2F-1 C terminus reveals that neither a previously characterized C-terminal MDM2 binding domain nor the pRb binding domain on E2F-1 is required for MDMX and MDM2 degradation. C1 Thomas Jefferson Univ, Dept Orthoped Surg, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Biochem & Mol Pharmacol, Philadelphia, PA 19107 USA. RP Hall, DJ (reprint author), NIAMS, Cartilage Biol & Orthoped Branch, NIH, Bldg 13,Rm 3W17,13 S Dr,MSC 5755, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA67032] NR 46 TC 14 Z9 14 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 DEC 7 PY 2001 VL 276 IS 49 BP 45677 EP 45685 DI 10.1074/jbc.M103765200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100026 PM 11568180 ER PT J AU Tuo, J Muftuoglu, M Chen, C Jaruga, P Selzer, RR Brosh, RM Rodriguez, H Dizdaroglu, M Bohr, VA AF Tuo, J Muftuoglu, M Chen, C Jaruga, P Selzer, RR Brosh, RM Rodriguez, H Dizdaroglu, M Bohr, VA TI The Cockayne Syndrome group B gene product is involved in general genome base excision repair of 8-hydroxyguanine in DNA SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION-COUPLED REPAIR; CYCLOBUTANE PYRIMIDINE DIMERS; SITE-DIRECTED MUTAGENESIS; AQUEOUS-SOLUTION; SYNDROME CELLS; ACTIVE GENES; XERODERMA-PIGMENTOSUM; PREFERENTIAL REPAIR; PUTATIVE HELICASES; DEFECTIVE REPAIR AB Cockayne Syndrome (CS) is a human genetic disorder with two complementation groups, CS-A and CS-B. The CSB gene product is involved in transcription-coupled repair of DNA damage but may participate in other pathways of DNA metabolism. The present study investigated the role of different conserved helicase motifs of CSB in base excision repair. Stably transformed human cell lines with site-directed CSB mutations in different motifs within its putative helicase domain were established. We find that CSB null and helicase motif V and VI mutants had greater sensitivity than wild type cells to gamma -radiation. Whole cell extracts from CSB null and motif V/VI mutants had lower activity of 8-hydroxyguanie incision in DNA than wild type cells. Also, 8-hydroxyguanine accumulated more in CSB null and motif VI mutant cells than in wild type cells after exposure to gamma -radiation. We conclude that a deficiency in general genome base excision repair of selective modified DNA base(s) might contribute to CS pathogenesis. Furthermore, whereas the disruption of helicase motifs V or VI results in a CSB phenotype, mutations in other helicase motifs do not cause this effect. The biological functions of CSB in different DNA repair pathways may be mediated by distinct functional motifs of the protein. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. NIST, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. RP NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM vbohr@nih.gov RI Jaruga, Pawel/M-4378-2015 NR 55 TC 106 Z9 108 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2001 VL 276 IS 49 BP 45772 EP 45779 DI 10.1074/jbc.M107888200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100038 PM 11581270 ER PT J AU Lukong, KE Seyrantepe, V Landry, K Trudel, S Ahmad, A Gahl, WA Lefrancois, S Morales, CR Pshezhetsky, AV AF Lukong, KE Seyrantepe, V Landry, K Trudel, S Ahmad, A Gahl, WA Lefrancois, S Morales, CR Pshezhetsky, AV TI Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYMPHOCYTE-ASSOCIATED MOLECULE-4; FACTOR-II RECEPTOR; BETA-GALACTOSIDASE; RAPID INTERNALIZATION; CATHEPSIN-A; T-CELLS; TRANSFERRIN RECEPTOR; ACID-PHOSPHATASE; NEURAMINIDASE; MEMBRANE AB Sialidase (neuraminidase), encoded by the neu-1 gene in the major histocompatibility complex locus catalyzes the intralysosomal degradation of sialylated glycoconjugates. Inherited deficiency of sialidase results in sialidosis or galactosialidosis, both severe metabolic disorders associated with lysosomal storage of oligosaccharides and glycopeptides. Sialidase also plays an important role in cellular signaling and is specifically required for the production of cytokine interleukin-4 by activated T lymphocytes. In these cells, neu-1-encoded sialidase activity is increased on the cell surface, suggesting that a specific mechanism regulates sorting of this enzyme to the plasma membrane. We investigated that mechanism by first showing that sialidase contains the internalization signal found in lysosomal membrane proteins targeted to endosomes via clathrin-coated pits. The signal consists of a C-terminal tetrapeptide (412)YGTL(415), with Tyr(412) and Leu(415) essential for endocytosis of the enzyme. We further demonstrated that redistribution of sialidase from lysosomes to the cell surface of activated lymphocytes is accompanied by increased reactivity of the enzyme with anti-phosphotyrosine antibodies. We speculate that phosphorylation of Tyr(412) results in inhibition of sialidase internalization in activated lymphocytes. C1 Hop St Justine, Serv Genet Med, Montreal, PQ H3T 1C5, Canada. Univ Montreal, Dept Pediat, Montreal, PQ H3T 1C5, Canada. McGill Univ, Dept Anat & Cell Biol, Montreal, PQ H3A 2B2, Canada. NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Pshezhetsky, AV (reprint author), Hop St Justine, Serv Genet Med, 3175 Cote St Catherine, Montreal, PQ H3T 1C5, Canada. RI Morales, Carlos/H-1055-2011; OI A, Pshezhetsky/0000-0002-6612-1062 NR 54 TC 63 Z9 66 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2001 VL 276 IS 49 BP 46172 EP 46181 DI 10.1074/jbc.M104547200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100093 PM 11571282 ER PT J AU Drotschmann, K Yang, W Brownewell, FE Kool, ET Kunkel, TA AF Drotschmann, K Yang, W Brownewell, FE Kool, ET Kunkel, TA TI Asymmetric recognition of DNA local distortion - Structure-based functional studies of eukaryotic Msh2-Msh6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REPAIR PROTEIN MUTS; MISMATCH REPAIR; HMUTS-ALPHA; ATPASE ACTIVITY; BINDING; HMSH6; COMPLEXES; MUTATION; SUBUNIT; MSH6 AB Crystal structures of bacterial MutS homodimers bound to mismatched DNA reveal asymmetric interactions of the two subunits with DNA. A phenylalanine and glutamate of one subunit make mismatched base-specific interactions, and residues of both subunits contact the DNA backbone surrounding the mismatched base, but asymmetrically. A number of amino acids in MutS that contact the DNA are conserved in the eukaryotic Msh2-Msh6 heterodimer. We report here that yeast strains with amino acids substituted for residues inferred to interact with the DNA backbone or mismatched base have elevated spontaneous mutation rates consistent with defective mismatch repair. Purified Msh2-Msh6 with substitutions in the conserved Phe(337) and Glu(339) in Msh6 thought to stack or hydrogen bond, respectively, with the mismatched base do have reduced DNA binding affinity but normal ATPase activity. Moreover, wild-type Msh2-Msh6 binds with lower affinity to mismatches with thymine replaced by difluorotoluene, which lacks the ability to hydrogen bond. The results suggest that yeast Msh2-Msh6 interacts asymmetrically with the DNA through base-specific stacking and hydrogen bonding interactions and backbone contacts. The importance of these contacts decreases with increasing distance from the mismatch, implying that interactions at and near the mismatch are important for binding in a kinked DNA conformation. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Chem, Stanford, CA 94305 USA. RP Kunkel, TA (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 FU NIGMS NIH HHS [GM52956] NR 29 TC 53 Z9 55 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 7 PY 2001 VL 276 IS 49 BP 46225 EP 46229 DI 10.1074/jbc.C100450200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100100 PM 11641390 ER PT J AU Miura, K Miyazawa, S Furuta, S Mitsushita, J Kamijo, K Ishida, H Miki, T Suzukawa, K Resau, J Copeland, TD Kamata, T AF Miura, K Miyazawa, S Furuta, S Mitsushita, J Kamijo, K Ishida, H Miki, T Suzukawa, K Resau, J Copeland, TD Kamata, T TI The Sos1-Rac1 signaling - Possible involvement of a vacuolar H+ -ATPase E subunit SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CLATHRIN-MEDIATED ENDOCYTOSIS; NUCLEOTIDE EXCHANGE FACTOR; PROTON ATPASE; RAS; RECEPTOR; GENE; RAC1; TRANSDUCTION; DOMAIN; CDC42 AB We have purified and identified a 32-kDa protein interacting with the Dbl oncogene homology domain of mSos1(Sos-DH) from rat brains by glutathione S-transferase-Sos-DH affinity chromatography. Peptide sequencing revealed that the protein is identical to a positive regulatory E subunit (V-ATPase E) of a vacuolar H+-ATPase, which is responsible for acidification of endosome and alkalinization of intracellular pH. The interaction between V-ATPase E and Sos-DH was confirmed by yeast two-hybrid assay. A coimmunoprecipitation assay demonstrated that a V-ATPase E protein physiologically bound to mSos1, and the protein was colocalized with mSos1 in the cytoplasm, as determined by immunohistochemistry. mSos1 was found in the early endosome fraction together with V-ATPase E and Rac1, suggesting the functional involvement of mSos1/V-ATPase E complexes in the Rac1 activity at endosomes. Overexpression of V-ATPase E in COS cells enhanced the ability of mSos1 to promote the guanine nucleotide exchange activity for Rac1 and stimulated the kinase activity of Jun kinase, a downstream target of Rac1. Thus, the data indicate that V-ATPase E may participate in the regulation of the mSos1-dependent Rac1 signaling pathway involved in growth factor receptor-mediated cell growth control. C1 Shinshu Univ, Sch Med, Dept Mol Biol & Biochem, Matsumoto, Nagano 3908621, Japan. Sci Applicat Int Corp, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Adv BioSci Labs, NIH, Frederick, MD 21702 USA. NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP Kamata, T (reprint author), Shinshu Univ, Sch Med, Dept Mol Biol & Biochem, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan. RI Mitsushita, Junji/D-7688-2016 OI Mitsushita, Junji/0000-0001-9402-4318 NR 35 TC 24 Z9 24 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 DEC 7 PY 2001 VL 276 IS 49 BP 46276 EP 46283 DI 10.1074/jbc.M102387200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100107 PM 11560919 ER PT J AU Kim, RH Flanders, KC Reffey, SB Anderson, LA Duckett, CS Perkins, ND Roberts, AB AF Kim, RH Flanders, KC Reffey, SB Anderson, LA Duckett, CS Perkins, ND Roberts, AB TI SNIP1 inhibits NF-kappa B signaling by competing for its binding to the C/H1 domain of CBP/p300 transcriptional Co-activators SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TGF-BETA; MOLECULAR-CLONING; COACTIVATOR P300; GENE-EXPRESSION; MICE LACKING; GROWTH; PROTEIN; CBP; AP-1; TRANSACTIVATION AB SNIP1 is a 396-amino acid nuclear protein shown to be an inhibitor of the TGF-beta signal transduction. pathway and to be important in suppressing transcriptional activation dependent on the co-activators CBP and p300. In this report we show that SNIP1 potently inhibits the activity of NF-kappaB, which binds the C/H1 domain of CBP/p300, but does not interfere with the activity of transcription factors such as p53, which bind to other domains of p300, or factors such as VP16, which are independent of these co-activators. Inhibition of NF-kappaB activity is a function of the N-terminal domain of SNIP1 and involves competition of SNIP1 and the NF-kappaB subunit, RelA/p65, for binding to p300, similar to the mechanism of inhibition of Smad signaling by SNIP1. Immunohistochemical staining shows that expression of SNIP1 is strictly regulated in development and that it colocalizes, in certain tissues, with nuclear staining for RelA/p65 and for p300, suggesting that they may regulate NF-kappaB activity in vivo in a spatially and temporally controlled manner. These data led us to suggest that SNIP1 may be an inhibitor of multiple transcriptional pathways that require the C/H1 domain of CBP/p300. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. Univ Dundee, Dept Biochem, Div Gene Regulat & Express, Dundee DD1 5EH, Scotland. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Rm C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 54 TC 39 Z9 40 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 DEC 7 PY 2001 VL 276 IS 49 BP 46297 EP 46304 DI 10.1074/jbc.M103819200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100110 PM 11567019 ER PT J AU Liu, XH Collier, RJ Youle, RJ AF Liu, XH Collier, RJ Youle, RJ TI Inhibition of axotomy-induced neuronal apoptosis by extracellular delivery of a Bcl-XL fusion protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINAL GANGLION-CELLS; NERVE GROWTH-FACTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; MICE OVEREXPRESSING BCL-2; TOXIN-MEDIATED DELIVERY; TRANSGENIC MICE; ANTHRAX TOXIN; LETHAL FACTOR; IN-VIVO; PROTECTIVE ANTIGEN AB Bcl-2 and Bcl-XL prevent neuronal apoptosis during development, neurodegenerative disease, and trauma. To test a new anti-apoptosis strategy for neuroprotection, we engineered nontoxic components of anthrax toxin into a Bcl-XL delivery system. Delivery of Bcl-XL by this system prevented apoptosis of cultured rat cerebellar granule cells and macrophages, and the prevention depended on both the Bcl-XL and the anthrax toxin receptor binding/translocation moieties. Furthermore, neuronal death in vivo in a retinal ganglion cell model of axotomy-induced apoptosis was inhibited by administration of this fusion protein. Thus, Bcl-XL protein can he delivered into cells from the medium or interstitial space, offering a new way to block apoptosis upstream of many caspases and the mitochondria dysfunction phase of apoptosis. C1 NINCDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Youle, RJ (reprint author), NINCDS, Biochem Sect, Surg Neurol Branch, NIH, Bldg 10,Rm 5D-37,MSC 1414,10 Ctr Dr, Bethesda, MD 20892 USA. OI Collier, R John/0000-0002-2427-4239 NR 72 TC 30 Z9 32 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 DEC 7 PY 2001 VL 276 IS 49 BP 46326 EP 46332 DI 10.1074/jbc.M108930200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100114 PM 11574549 ER PT J AU Zhang, Z Yu, Y Musser, JM Palzkill, T AF Zhang, Z Yu, Y Musser, JM Palzkill, T TI Amino acid sequence determinants of extended spectrum cephalosporin hydrolysis by the class CP99 beta-lactamase. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PENICILLIN-BINDING PROTEINS; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; CRYSTAL-STRUCTURE; KLEBSIELLA-PNEUMONIAE; SUBSTRATE-SPECIFICITY; PSEUDOMONAS-AERUGINOSA; AMPC CEPHALOSPORINASE; MOLECULAR EVOLUTION; AEROMONAS-SOBRIA AB Class C beta -lactamases are commonly encoded on the chromosome of Gram-negative bacterial species. Mutations leading to increased expression of these enzymes are a common cause of resistance to many cephalosporins including extended spectrum cephalosporins. Recent reports of plasmid- and integrin-encoded class C beta -lactamases are a cause for concern because these enzymes are likely to spread horizontally to susceptible strains. Because of their increasing clinical significance, it is critical to identify the determinants of catalysis and substrate specificity of these enzymes. For this purpose, the codons of a set of 21 amino acid residues that encompass the active site region of the P99 beta -lactamase were individually randomized to create libraries containing all possible amino acid substitutions. The amino acid sequence requirements for the hydrolysis of ceftazidime, an extended spectrum cephalosporin commonly used to treat serious infections, were determined by selecting resistant mutants from each of the 21 libraries. DNA sequencing identified the residue positions that are critical for ceftazidime hydrolysis. In addition, it was found that certain amino acid substitutions in the omega -loop region of the P99 enzyme result in increased ceftazidime hydrolysis suggesting the loop is an important determinant of substrate specificity. C1 Baylor Coll Med, Struct & Computat Biol & Mol Biophys Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Palzkill, T (reprint author), Baylor Coll Med, Struct & Computat Biol & Mol Biophys Program, Houston, TX 77030 USA. FU NIAID NIH HHS [AI32956] NR 59 TC 27 Z9 27 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 DEC 7 PY 2001 VL 276 IS 49 BP 46568 EP 46574 DI 10.1074/jbc.M102757200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 499LR UT WOS:000172573100143 PM 11591698 ER PT J AU Sasaki, T Gohring, W Mann, K Brakebusch, C Yamada, Y Fassler, R Timpl, R AF Sasaki, T Gohring, W Mann, K Brakebusch, C Yamada, Y Fassler, R Timpl, R TI Short arm region of laminin-5 gamma 2 chain: Structure, mechanism of processing and binding to heparin and proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE basement membranes; disulfide isomerase; laminin-5; ligand binding; recombinant protein ID EGF-LIKE MOTIF; EPIDERMOLYSIS-BULLOSA; DISULFIDE-ISOMERASE; NIDOGEN BINDING; ALPHA-DYSTROGLYCAN; EPIDERMAL JUNCTION; CELL-MIGRATION; GROWTH-FACTOR; GENE LAMC2; B2 CHAIN AB Laminin-5 is a typical component of several epithelial tissues and contains a unique gamma2 chain which can be proteolytically processed by BMP-1. This occurs in the N-terminal half of the gamma2 chain (606 residues), which consists of two rod-like tandem arrays of LE modules, LE1-3 and LE4-6, that flank a globular L4m module containing the cleavage site. Recombinant analysis of L4m, which includes an additional imperfect LE module essential for proper folding, demonstrated an unusual pattern of disulfide bonding. These connectivities prevented the release of gamma2LE1-3L4 m after BMP-1 cleavage which required in addition disulfide reshuffling by isomerases. The liberated segment bound through its L4 m module to heparin, nidogen-1, fibulin-1 and fibulin-2. A further heparin/sulfatide-binding site could be attributed to some arginine residues in module LE1. The gamma2LE4-6 segment remaining in processed laminin-5 showed only a strong binding to fibulin-2. Immunological studies showed a similar partial processing in cell culture and tissues and the persistence of the released fragment in tissues. This indicated that both N-terminal regions of the gamma2 chain may have a function in vivo. (C) 2001 Academic Press. C1 Max Planck Inst Biochem, D-82152 Martinsried, Germany. Lund Univ, Dept Expt Pathol, S-22185 Lund, Sweden. NIDCR, NIH, Bethesda, MD USA. RP Timpl, R (reprint author), Max Planck Inst Biochem, D-82152 Martinsried, Germany. RI Mann, Karlheinz/C-4254-2008 NR 45 TC 81 Z9 84 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 7 PY 2001 VL 314 IS 4 BP 751 EP 763 DI 10.1006/jmbi.2001.5176 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 514YV UT WOS:000173469400010 PM 11733994 ER PT J AU Wedekind, JE Trame, CB Dorywalska, M Koehl, P Raschke, TM McKee, M FitzGerald, D Collier, RJ McKay, DB AF Wedekind, JE Trame, CB Dorywalska, M Koehl, P Raschke, TM McKee, M FitzGerald, D Collier, RJ McKay, DB TI Refined crystallographic structure of Pseudomonas aeruginosa exotoxin A and its implications for the molecular mechanism of toxicity SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE exotoxin; Pseudomonas aeruginosa toxicity; crystal structure; furin; pH-induced conformational change ID RECEPTOR-BINDING DOMAIN; HEAT-LABILE ENTEROTOXIN; ELECTRON-DENSITY MAPS; CRYSTAL-STRUCTURE; DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; RETROGRADE TRANSPORT; CHOLERA-TOXIN; ENDOPLASMIC-RETICULUM; PROTEIN STRUCTURES AB Exotoxin A of Pseudomonas aeruginosa asserts its cellular toxicity through ADP-ribosylation of translation elongation factor 2, predicated on binding to specific cell surface receptors and intracellular trafficking via a complex pathway that ultimately results in translocation of an enzymatic activity into the cytoplasm. In early work, the crystallographic structure of exotoxin A was determined to 3.0 Angstrom resolution, revealing a tertiary fold having three distinct structural domains; subsequent work has shown that the domains are individually responsible for the receptor binding, (domain 1), transmembrane targeting (domain II), and ADP-ribosyl transferase (domain III) activities, respectively. Here, we report the structures, of wild-type and W281A mutant toxin proteins at pH 8.0, refined with data to 1.62 Angstrom and 1.45 Angstrom resolution, respectively. The refined models clarify several ionic interactions within structural domains I and II that may modulate an obligatory conformational change that is induced by low pH. Proteolytic cleavage by furin is also obligatory for toxicity; the W281A mutant protein is substantially more susceptible to cleavage than the wild-type toxin. The tertiary structures of the furin cleavage sites of the wild-type and W281 mutant toxins are similar; however, the mutant toxin has significantly higher B-factors around the cleavage site, suggesting that the greater susceptibility to furin cleavage is due to increased local disorder/flexibility at the site, rather than to differences in static tertiary structure. Comparison of the refined structures of full-length toxin, which lacks ADP-ribosyl transferase activity, to that of the enzymatic domain alone reveals a salt bridge between Arg467 of the catalytic domain and Glu348 of domain II that restrains the substrate binding cleft in a conformation that precludes NAD(+) binding. The refined structures of exotoxin A provide precise models for the design and interpretation of further studies of the mechanism of intoxication. (C) 2001 Academic Press. C1 Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. NCI, Mol Biol Lab, Div Canc Biol, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Stanford Univ, Sch Med, Dept Biol Struct, Stanford, CA 94305 USA. EM Dave.McKay@Stanford.edu RI Koehl, Patrice/K-5708-2013; OI Koehl, Patrice/0000-0002-0908-068X; Collier, R John/0000-0002-2427-4239 FU NIGMS NIH HHS [GM-39928] NR 61 TC 55 Z9 61 U1 2 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD DEC 7 PY 2001 VL 314 IS 4 BP 823 EP 837 DI 10.1006/jmbi.2001.5195 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 514YV UT WOS:000173469400016 PM 11734000 ER PT J AU Lee, J Han, KC Kang, JH Pearce, LL Lewin, NE Yan, SQ Benzaria, S Nicklaus, MC Blumberg, PM Marquez, VE AF Lee, J Han, KC Kang, JH Pearce, LL Lewin, NE Yan, SQ Benzaria, S Nicklaus, MC Blumberg, PM Marquez, VE TI Conformationally constrained analogues of diacylglycerol. 18. The incorporation of a hydroxamate moiety into diacylglycerol-lactones reduces lipophilicity and helps discriminate between sn-1 and sn-2 binding modes to protein kinase c (PK-C). Implications for isozyme specificity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Letter ID GREEN FLUORESCENT PROTEIN; PHORBOL ESTER; LIVING CELLS; LIGANDS AB An approach to reduce the log P in a series of diacylglycerol (DAG)-lactones known for their high binding affinity for protein kinase C (PK-C) is presented. Branched alkyl groups with reduced lipophilicity were selected and combined with the replacement of the ester or lactone oxygens by NH or NOH groups. Compound 6a with an isosteric N-hydroxyl amide arm represents the most potent and least lipophilic DAG analogue known to date. C1 Seoul Natl Univ, Coll Pharm, Med Chem Lab, Kwanak Ku, Seoul 151742, South Korea. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Med Chem Lab, Kwanak Ku, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr; marquezv@dc37a.nci.nih.gov RI Nicklaus, Marc/N-4183-2014 NR 13 TC 12 Z9 12 U1 0 U2 2 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 DEC 6 PY 2001 VL 44 IS 25 BP 4309 EP 4312 DI 10.1021/jm0103965 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 498DK UT WOS:000172494400001 PM 11728178 ER PT J AU Enyedy, IJ Ling, Y Nacro, K Tomita, Y Wu, XH Cao, YY Guo, RB Li, BH Zhu, XF Huang, Y Long, YQ Roller, PP Yang, DJ Wang, SM AF Enyedy, IJ Ling, Y Nacro, K Tomita, Y Wu, XH Cao, YY Guo, RB Li, BH Zhu, XF Huang, Y Long, YQ Roller, PP Yang, DJ Wang, SM TI Discovery of small-molecule inhibitors of bcl-2 through structure-based computer screening SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTISENSE THERAPY; ESCHERICHIA-COLI; PROTEIN FAMILY; TUMOR-CELLS; APOPTOSIS; CANCER; DATABASE; BCL-X(L); SYSTEM; NMR AB Bcl-2 belongs to a growing family of proteins which regulates programmed cell death (apoptosis). Overexpression of Bcl-2 has been observed in 70% of breast cancer, 30-60% of prostate cancer, 80% of B-cell lymphomas, 90% of colorectal adenocarcinomas, and many other forms of cancer. Thereby, Bcl-2 is an attractive new anti-cancer target. Herein, we describe the discovery of novel classes of small-molecule inhibitors targeted at the BH3 binding pocket in Bcl-2. The three-dimensional (3D) structure of Bcl-2 has been modeled on the basis of a high-resolution NMR solution structure of Bcl-X-L, which shares a high sequence homology with Bcl-2. A structure-based computer screening approach has been employed to search the National Cancer Institute 3D database of 206 876 organic compounds to identify potential Bcl-2 small-molecule inhibitors that bind to the BH3 binding site of Bcl-2. These potential Bcl-2 small-molecule inhibitors were first tested in an in vitro binding assay for their potency in inhibition of the binding of a Bak BH3 peptide to Bcl-2. Thirty-five potential inhibitors were tested in this binding assay, and seven of them were found to have a binding affinity (IC50 value) from 1.6 to 14.0 muM. The anti-proliferative activity of these seven active compounds has been tested using a human myeloid leukemia cell line, HL-60, which expresses the highest level of Bcl-2 protein among all the cancer cell lines examined. Compound 6 was the most potent compound and had an IC50 value of 4 muM in inhibition of cell growth using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Five other compounds had moderate activity in inhibition of cell growth. Compound 6 was further evaluated for its ability to induce apoptosis in cancer cells. It was found that 6 induces apoptosis in cancer cells with high Bcl-2 expression and its potency correlates with the Bcl-2 expression level in cancer cells. Furthermore, using NMR methods, we conclusively demonstrated that 6 binds to the BH3 binding site in Bcl-XL. Our results showed that small-molecule inhibitors of Bcl-2 such as 6 modulate the biological function of Bcl-2, and induce apoptosis in cancer cells with high Bcl-2 expression, while they have little effect on cancer cells with low or undetectable levels of Bcl-2 expression. Therefore, compound 6 can be used as a valuable pharmacological tool to elucidate the function of Bcl-2 and also serves as a novel lead compound for further design and optimization. Our results suggest that the structure-based computer screening strategy employed in the study is effective for identifying novel, structurally diverse, nonpeptide small-molecule inhibitors that target the BH3 binding site of Bcl-2. C1 Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Struct Biol & Canc Drug Discovery Program, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA. NCI, Med Chem Lab, FCRDC, Frederick, MD 21702 USA. RP Wang, SM (reprint author), Georgetown Univ, Med Ctr, Lombardi Canc Ctr, Struct Biol & Canc Drug Discovery Program, 3970 Reservoir Rd, Washington, DC 20007 USA. EM yangd@georgetown.edu RI Wang, Shaomeng/E-9686-2010 FU NCI NIH HHS [P50CA058185] NR 43 TC 251 Z9 265 U1 1 U2 24 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 DEC 6 PY 2001 VL 44 IS 25 BP 4313 EP 4324 DI 10.1021/jm010016f PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 498DK UT WOS:000172494400002 PM 11728179 ER PT J AU Zou, MF Kopajtic, T Katz, JL Wirtz, S Justice, JB Newman, AH AF Zou, MF Kopajtic, T Katz, JL Wirtz, S Justice, JB Newman, AH TI Novel tropane-based irreversible ligands for the dopamine transporter SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID N-SUBSTITUTED 3-ALPHA-TROPANE; COCAINE RECOGNITION SITES; 3-ALPHA-(DIPHENYLMETHOXY)TROPANE ANALOGS; NOREPINEPHRINE TRANSPORTERS; UPTAKE INHIBITORS; ADDICTIVE DRUGS; BINDING; POTENT; DOMAINS; ABUSE AB 3 alpha-(Diphenylmethoxy)tropane (benztropine) and its analogues are tropane ring-containing dopamine uptake inhibitors that display binding and behavioral profiles that are distinct from cocaine. We previously prepared a benztropine-based photoaffinity label [I-125]-(N-[4-(4'-azido-3'-iodophenyl)butyl]-3 alpha-[bis(4'-fluorophenyl)methoxy]tropane, [I-125] 1, that covalently attached to the 1-2 transmembrane spanning region of the dopamine transporter (DAT). This was in contrast to the 4-7 transmembrane spanning region labeled by a cocaine-based photoaffinity label, [I-125] 2 (RTI 82). To characterize further these different binding domains, photoaffinity ligands that had the 4'-azido-3'-iodophenyl substituent extended from the same position on the tropane ring were desirable. Thus, identification of the optimal alkyl linker between this substituent and the tropane nitrogen in the benztropine series was investigated to ultimately prepare the identical N-substituted analogue of 2. In this pursuit, the N-[4-(4'-azido-3'-iodophenyl)propyl] analogue of 3 alpha-[bis(4'-fluorophenyl)methoxy]tropane (9a) was synthesized as well as two isothiocyanate analogues that do not require photoactivation (10a,b) for irreversible binding. The synthesis of these target compounds was achieved using a modification of the strategy developed for 1. Evaluation of these compounds for displacing [H-3]WIN 35 428 binding at DAT in rat caudate putamen revealed that the 4'-azido-3'-iodophenylbutyl substituent, found in 1, provided optimal binding affinity and was chosen to replace the N-CH3 group on 2. Both the 4'-azido-3'-iodophenyl- and the 4'-isothiocyanatophenylbutyl analogues of 2 (25 and 26, respectively) were synthesized. Both products bound to DAT with comparable potency (IC50 = 30 nM) to RTI 82 (2). In addition, compound 26 demonstrated wash-resistant displacement of [H-3]WIN 35 428 in HEK 293 cells stably transfected with hDAT. These ligands will provide important tools for further characterizing the binding domains for tropane-based dopamine uptake inhibitors at the DAT. C1 Natl Inst Drug Abuse, Intramural Res Program, Med Chem Sect, Baltimore, MD 21131 USA. Natl Inst Drug Abuse, Intramural Res Program, Psychobiol Sect, Baltimore, MD 21131 USA. Emory Univ, Dept Chem, Atlanta, GA 30322 USA. RP Newman, AH (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Med Chem Sect, Baltimore, MD 21131 USA. EM anewman@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA11176, DA00179] NR 32 TC 29 Z9 29 U1 2 U2 7 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 DEC 6 PY 2001 VL 44 IS 25 BP 4453 EP 4461 DI 10.1021/jm0101904 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 498DK UT WOS:000172494400013 PM 11728190 ER PT J AU Petersen, S Casellas, R Reina-San-Martin, B Chen, HT Difilippantonio, MJ Wilson, PC Hanitsch, L Celeste, A Muramatsu, M Pilch, DR Redon, C Ried, T Bonner, WM Honjo, T Nussenzweig, MC Nussenzweig, A AF Petersen, S Casellas, R Reina-San-Martin, B Chen, HT Difilippantonio, MJ Wilson, PC Hanitsch, L Celeste, A Muramatsu, M Pilch, DR Redon, C Ried, T Bonner, WM Honjo, T Nussenzweig, MC Nussenzweig, A TI AID is required to initiate Nbs1/gamma-H2AX focus formation and mutations at sites of class switching SO NATURE LA English DT Article ID DOUBLE-STRAND BREAKS; CYTIDINE DEAMINASE AID; HEAVY-CHAIN SWITCH; SOMATIC HYPERMUTATION; B-CELLS; IMMUNOGLOBULIN GENES; DNA-DAMAGE; RECOMBINATION; REPAIR; SEQUENCES AB Class switch recombination (CSR) is a region-specific DNA recombination reaction that replaces one immunoglobulin heavy-chain constant region (CH) gene with another. This enables a single variable (V) region gene to be used in conjunction with different downstream CH genes, each having a unique biological activity. The molecular mechanisms that mediate CSR have not been defined, but activation-induced cytidine deaminase (AID), a putative RNA-editing enzyme, is required for this reaction(1). Here we report that the Nijmegen breakage syndrome protein (Nbs1) and phosphorylated H2A histone family member X (gamma -H2AX, also known as gamma -H2afx), which facilitate DNA double-strand break (DSB) repair(2-4), form nuclear foci at the CH region in the G1 phase of the cell cycle in cells undergoing CSR, and that switching is impaired in H2AX(-/-) mice. Localization of Nbs1 and gamma -H2AX to the IgH locus during CSR is dependent on AID. In addition, AID is required for induction of switch region (S mu)-specific DNA lesions that precede CSR. These results place AID function upstream of the DNA modifications that initiate CSR. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Howard Hughes Med Inst, New York, NY 10021 USA. Kyoto Univ, Grad Sch Med, Dept Med Chem, Kyoto 6068501, Japan. RP Nussenzweig, A (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Muramatsu, Masamichi/C-4339-2015; Reina-San-Martin, Bernardo/I-9484-2016; Honjo, Tasuku/N-4470-2016 OI Muramatsu, Masamichi/0000-0002-0153-3533; Reina-San-Martin, Bernardo/0000-0003-2083-6166; FU Intramural NIH HHS [Z99 CA999999] NR 30 TC 372 Z9 382 U1 0 U2 7 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 6 PY 2001 VL 414 IS 6864 BP 660 EP 665 DI 10.1038/414660a PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 498WB UT WOS:000172535600053 PM 11740565 ER PT J AU Becerra, L Breiter, HC Wise, R Gonzalez, RG Borsook, D AF Becerra, L Breiter, HC Wise, R Gonzalez, RG Borsook, D TI Reward circuitry activation by noxious thermal stimuli SO NEURON LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; NUCLEUS-ACCUMBENS NEURONS; HUMAN BRAIN; PREFRONTAL CORTEX; ELECTROPHYSIOLOGICAL EVIDENCE; PERIAQUEDUCTAL GRAY; PAIN PERCEPTION; SOMATOSENSORY CORTEX; ORBITOFRONTAL CORTEX AB Using functional magnetic resonance imaging (fMRI), we observed that noxious thermal stimuli (46 degreesC) produce significant signal change in putative reward circuitry as well as in classic pain circuitry. Increases in signal were observed in the sublenticular extended amygdala of the basal forebrain (SLEA) and the ventral tegmentum/periaqueductal gray (VT/PAG), while foci of increased signal and decreased signal were observed in the ventral striatum and nucleus accumbens (NAc). Early and late phases were observed for signals in most brain regions, with early activation in reward related regions such as the SLEA, VT/PAG, and ventral striatum, In contrast, structures associated with somatosensory perception, including SI somatosensory cortex, thalamus, and insula, showed delayed activation. These data support the notion that there may be a shared neural system for evaluation of aversive and rewarding stimuli. C1 Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Boston, MA 02129 USA. Massachusetts Gen Hosp, Motivat & Emot Neurosci Ctr, Boston, MA 02129 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02129 USA. NIDA, NIH, Baltimore, MD 21224 USA. RP Borsook, D (reprint author), Massachusetts Gen Hosp, Ctr Funct Pain Neuroimaging & Therapy Res, Boston, MA 02129 USA. RI Wise, Roy/A-6465-2012 FU PHS HHS [00265, 01258, 034626, 09467, 13650] NR 121 TC 298 Z9 299 U1 1 U2 34 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 6 PY 2001 VL 32 IS 5 BP 927 EP 946 DI 10.1016/S0896-6273(01)00533-5 PG 20 WC Neurosciences SC Neurosciences & Neurology GA 501RW UT WOS:000172700700017 PM 11738036 ER PT J AU Modan, B Wacholder, S AF Modan, B Wacholder, S CA Natl Israeli Ovarian Canc Study Gr TI Ovarian cancer, oral contraceptives, and BRCA mutations - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NCI, Bethesda, MD 20892 USA. RP Modan, B (reprint author), Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 DEC 6 PY 2001 VL 345 IS 23 BP 1707 EP 1707 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 498NH UT WOS:000172517200013 ER PT J AU Woodson, K Lanza, E Tangrea, JA Albert, PS Slattery, M Pinsky, J Caan, B Paskett, E Iber, F Kikendall, IW Lance, P Shike, M Weissfeld, J Schatzkin, A AF Woodson, K Lanza, E Tangrea, JA Albert, PS Slattery, M Pinsky, J Caan, B Paskett, E Iber, F Kikendall, IW Lance, P Shike, M Weissfeld, J Schatzkin, A TI Hormone replacement therapy and colorectal adenoma recurrence among women in the polyp prevention trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID VITAMIN-D-RECEPTOR; LARGE-BOWEL CANCER; COLON-CANCER; REPRODUCTIVE HISTORY; ESTROGEN-RECEPTOR; MICROSATELLITE INSTABILITY; PROGESTERONE RECEPTORS; CALCIUM-ABSORPTION; EXOGENOUS HORMONES; UNITED-STATES AB Background: Epidemiologic studies have suggested that estrogen may protect against the development of colorectal cancers and adenomatous polyps. We conducted a prospective study to evaluate the association between hormone replacement therapy (HRT) and adenoma recurrence among perimenopausal and postmenopausal women participating in the Polyp Prevention Trial, a randomized dietary intervention study of individuals with colorectal adenomas. Methods: We used a questionnaire and interviews to collect detailed information, at baseline and at each of four annual study visits, from 620 women regarding hormone use, menopausal status, diet, alcohol consumption, and other risk factors. Adenoma recurrence was ascertained by complete colonoscopy at baseline and after 1 and 4 years. Logistic regression models were used to evaluate the association between hormone use and adenoma recurrence after adjusting for intervention group and for age and body mass index at baseline. All statistical tests were two-sided. Results: Adenomas recurred in 200 women. There was no overall association between adenoma recurrence and either overall hormone use (odds ratio [OR] = 1.01; 95% confidence interval [CI] = 0.70 to 1.45), combined estrogen and progestin use (OR = 0.94; 95% CI = 0.57 to 1.56), or unopposed estrogen use (OR = 1.04; 95% CI = 0.68 to 1.59). HRT use was associated with a reduction in risk for recurrence of distal adenomas (OR = 0.56; 95% CI = 0.32 to 1.00) and a statistically nonsignificant increase in risk for recurrence of proximal adenomas (OR = 1.39; 95% CI = 0.85 to 2.26). We observed a statistically significant interaction between the HRT-adenoma recurrence association and age (P = .02). HRT was associated with a 40% reduced risk of adenoma recurrence among women older than 62 years (OR = 0.58; 95% CI = 0.35 to 0.97) but with an increased risk among women younger than 62 years (OR = 1.99; 95 % CI = 1.11 to 3.55). Conclusions: HRT was not associated with a reduced risk for overall adenoma recurrence in this trial cohort, although there was a suggestion of an age interaction. The effect of age on the association needs to be confirmed in other adenoma recurrence trials. C1 NCI, Canc Prevent Studies Branch, Div Clin Sci, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Natl Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. Westat Corp, Rockville, MD USA. Kaiser Fdn, Res Inst, Oakland, CA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Edward Hines Jr Hosp, Dept Vet Affairs Med Ctr, Hines, IL USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Woodson, K (reprint author), NIH, 6006 Execut Blvd,MSC 7058, Bethesda, MD 20892 USA. NR 42 TC 35 Z9 35 U1 0 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 5 PY 2001 VL 93 IS 23 BP 1799 EP 1805 DI 10.1093/jnci/93.23.1799 PG 7 WC Oncology SC Oncology GA 498DN UT WOS:000172494700010 PM 11734596 ER PT J AU Goldstein, DS Li, ST Kopin, IJ AF Goldstein, DS Li, ST Kopin, IJ TI Sympathetic neurocirculatory failure in Parkinson disease: Evidence for an etiologic role of alpha-synuclein SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA NS003034-07, ZIA NS003125-01, Z99 NS999999] NR 5 TC 11 Z9 11 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 4 PY 2001 VL 135 IS 11 BP 1010 EP 1011 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 498PN UT WOS:000172520000021 PM 11730415 ER PT J AU Carmeliet, E Fozzard, HA Hiraoka, M Janse, MJ Ogawa, S Roden, DM Rosen, MR Rudy, Y Schwartz, PJ Matteo, PS Antzelevitch, C Boyden, PA Catterall, WA Fishman, GI George, AL Izumo, S Jalife, J January, CT Kleber, AG Marban, E Marks, AR Spooner, PM Waldo, AL Weiss, JM Zipes, DLP AF Carmeliet, E Fozzard, HA Hiraoka, M Janse, MJ Ogawa, S Roden, DM Rosen, MR Rudy, Y Schwartz, PJ Matteo, PS Antzelevitch, C Boyden, PA Catterall, WA Fishman, GI George, AL Izumo, S Jalife, J January, CT Kleber, AG Marban, E Marks, AR Spooner, PM Waldo, AL Weiss, JM Zipes, DLP CA Sicilian Gambit TI New approaches to antiarrhythmic therapy, part I - Emerging therapeutic applications of the cell biology of cardiac arrhythmias SO CIRCULATION LA English DT Article; Proceedings Paper CT 4th Sicilian Gambit Meeting CY OCT 15-19, 2000 CL CAPE COD, MASSACHUSETTS DE molecular biology; gene therapy; genes; electrophysiology; pharmacology ID LEFT-VENTRICULAR DYSFUNCTION; LONG-QT SYNDROME; SUSTAINED ATRIAL-FIBRILLATION; SIGNAL-TRANSDUCTION PATHWAYS; TRANSIENT OUTWARD CURRENT; RENIN-ANGIOTENSIN SYSTEM; GERMAN-SHEPHERD DOGS; MYOCARDIAL-INFARCTION; SLOW CONDUCTION; HEART-FAILURE AB Cardiac arrhythmias complicate many diseases affecting the heart and circulation, and they incorporate a multiplicity of underlying mechanisms. The evolution of scientific knowledge has made the complex changes produced by cardiovascular disease sufficiently understood at the organ, cellular, and molecular levels such that there is a diversity of therapeutic targets for pharmacological therapy and/or prevention. Moreover, the approach of rational drug design in mechanism-specific and disease-specific fashions facilitates the targeting of therapy using the methods of molecular, structural, and translational biology. Additional approaches, using similar drug design strategies but based on gene therapy and transcriptional and translational modification, are on the horizon. Hence, there is reason to be optimistic regarding the design, testing, and clinical availability of novel antiarrhythmic therapies. C1 Columbia Univ, Coll Phys & Surg, Ctr Mol Therapeut, Dept Pharmacol, New York, NY 10032 USA. Katholieke Univ Leuven, B-3001 Louvain, Belgium. Univ Illinois, Chicago, IL 60680 USA. Tokyo Med & Dent Univ, Tokyo 1138549, Japan. Cardiovasc Res, Amsterdam, Netherlands. Keio Univ, Tokyo 160, Japan. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Policlin San Matteo, IRCCS, I-27100 Pavia, Italy. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Masonic Med Res Lab, Utica, NY USA. Univ Washington, Seattle, WA 98195 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. SUNY Syracuse, Syracuse, NY 13210 USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Bern, CH-3012 Bern, Switzerland. Johns Hopkins Univ, Baltimore, MD 21218 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Cardiovasc Res Lab, Los Angeles, CA 90024 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. RP Rosen, MR (reprint author), Columbia Univ, Coll Phys & Surg, Ctr Mol Therapeut, Dept Pharmacol, 630 W 168 St,H7W-321, New York, NY 10032 USA. RI Schwartz, Peter/J-4267-2016; Jalife, Jose/L-4833-2015 OI Schwartz, Peter/0000-0003-0367-1048; Jalife, Jose/0000-0003-0080-3500 NR 128 TC 20 Z9 22 U1 0 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 4 PY 2001 VL 104 IS 23 BP 2865 EP 2873 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 499NN UT WOS:000172577400022 ER PT J AU Knutson, B Fong, GW Adams, CM Varner, JL Hommer, D AF Knutson, B Fong, GW Adams, CM Varner, JL Hommer, D TI Dissociation of reward anticipation and outcome with event-related fMRI SO NEUROREPORT LA English DT Article DE reward; anticipation; outcome; nucleus accumbens; ventromedial frontal cortex; fMRI; human ID BRAIN ACTIVITY; DOPAMINE; VISUALIZATION; ACTIVATION; RESPONSES; SYSTEMS AB Reward processing involves both appetitive and consummatory phases. We sought to examine whether reward anticipation vs outcomes would recruit different regions of ventral forebrain circuitry using event-related fMRI. Nine healthy volunteers participated in a monetary incentive delays task in which they either responded to a cued target for monetary reward, responded to a cued target for no reward, or did not respond to a cued target during scanning. Multiple regression analyses indicated that while anticipation of reward Ys non-reward activated foci in the ventral striatum, reward vs non-reward outcomes activated foci in the ventromedial frontal cortex. These findings suggest that reward anticipation band outcomes may differentially recruit distinct regions that lie along the trajectory of ascending dopamine projections. NeuroReport 12:3683-3687 (C) 2001 Lippincott Williams & Wilkins. C1 NIAAA, NIH, Bethesda, MD 20892 USA. Dept Psychol, Stanford, CA 94305 USA. RP Knutson, B (reprint author), NIAAA, NIH, 10 Ctr Dr,Bldg 10,Rm 6S240, Bethesda, MD 20892 USA. OI Knutson, Brian/0000-0002-7669-426X NR 17 TC 656 Z9 667 U1 6 U2 61 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 4 PY 2001 VL 12 IS 17 BP 3683 EP 3687 DI 10.1097/00001756-200112040-00016 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 496LL UT WOS:000172397000012 PM 11726774 ER PT J AU Hamiche, A Kang, JG Dennis, C Xiao, H Wu, C AF Hamiche, A Kang, JG Dennis, C Xiao, H Wu, C TI Histone tails modulate nucleosome mobility and regulate ATP-dependent nucleosome sliding by NURF SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHROMATIN-REMODELING COMPLEX; TRANSCRIPTION FACTOR-BINDING; SWI/SNF COMPLEX; CORE PARTICLE; N-TERMINI; IN-VITRO; SACCHAROMYCES-CEREVISIAE; LINKER HISTONES; IONIC-STRENGTH; POSITIVE ROLE AB Nucleosome Remodeling Factor (NURF) is an ATP-dependent nucleosome remodeling complex that alters chromatin structure by catalyzing nucleosome sliding, thereby exposing DNA sequences previously associated with nucleosomes. We systematically studied how the unstructured N-terminal residues of core histories (the N-terminal histone tails) influence nucleosome sliding. We used bacterially expressed Drosophila histories to reconstitute hybrid nucleosomes lacking one or more histone N-terminal tails. Unexpectedly, we found that removal of the N-terminal tail of histone H2B promoted uncatalyzed nucleosome sliding during native gel electrophoresis. Uncatalyzed nucleosome mobility was enhanced by additional removal of other histone tails but was not affected by hyperacetylation of core histories by p300. In addition, we found that the N-terminal tail of the histone H4 is specifically required for ATP-dependent catalysis of nucleosome sliding by NURF. Alanine scanning mutagenesis demonstrated that H4 residues 16-KRHR-19 are critical for the induction of nucleosome mobility, revealing a histone tail motif that regulates NURF activity. An exchange of histone tails between H4 and H3 impaired NURF-induced sliding of the mutant nucleosome, indicating that the location of the KRHR motif in relation to global nucleosome structure is functionally important. Our results provide functions for the N-terminal histone tails in regulating the mobility of nucleosomes. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bldg 37,Room 6068, Bethesda, MD 20892 USA. NR 81 TC 109 Z9 111 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 4 PY 2001 VL 98 IS 25 BP 14316 EP 14321 DI 10.1073/pnas.251421398 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 499NH UT WOS:000172576900026 PM 11724935 ER PT J AU Fang, SY Ferrone, M Yang, CH Jensen, JP Tiwari, S Weissman, AM AF Fang, SY Ferrone, M Yang, CH Jensen, JP Tiwari, S Weissman, AM TI The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL ANTIGEN RECEPTOR; SACCHAROMYCES-CEREVISIAE; NG108-15 CELLS; PROTEASOME; SURFACE; IDENTIFICATION; ENZYME; UBC7; ER; TRANSLOCATION AB gp78, also known as the tumor autocrine motility factor receptor, is a transmembrane protein whose expression is correlated with tumor metastasis. We establish that gp78 is a RING finger-dependent ubiquitin protein ligase (E3) of the endoplasmic reticulum (ER). Consistent with this, gp78 specifically recruits MmUBC7, a ubiquitin-conjugating enzyme (E2) implicated in ER-associated degradation (ERAD), through a region distinct from the RING finger. gp78 can target itself for proteasomal degradation in a RING finger- and MmUBC7-dependent manner. Importantly, gp78 can also mediate degradation of CD3-delta, a well-characterized ERAD substrate. In contrast, gp78 lacking an intact RING finger or its multiple membrane-spanning domains stabilizes CD3-delta. gp78 has thus been found to be an example of a mammalian cellular E3 intrinsic to the ER, suggesting a potential link between ubiquitylation, ERAD, and metastasis. C1 NCI, Regulat & Prot Funct Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Weissman, AM (reprint author), NCI, Regulat & Prot Funct Lab, Ctr Canc Res, Bldg 10,Room 1B34,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Fang, Shengyun/H-3802-2011 NR 47 TC 261 Z9 269 U1 1 U2 13 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 DEC 4 PY 2001 VL 98 IS 25 BP 14422 EP 14427 DI 10.1073/pnas.251401598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 499NH UT WOS:000172576900044 PM 11724934 ER PT J AU Azimi, N Nagai, M Jacobson, S Waldmann, TA AF Azimi, N Nagai, M Jacobson, S Waldmann, TA TI IL-15 plays a major role in the persistence of tax-specific CD8 cells in HAM/TSP patients SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS TYPE-I; MYELOPATHY/TROPICAL SPASTIC PARAPARESIS; CYTOTOXIC LYMPHOCYTES-T; KAPPA-B SITE; CEREBROSPINAL-FLUID; NATURAL-KILLER; NEUROLOGICAL DISEASE; GENE-EXPRESSION; TRANSGENIC MICE; ALPHA-CHAIN AB IL-15 is a critical cytokine for the maintenance of memory-phenotype CD8 cells in mice. Here, we investigated the role of IL-15 in the neurological disease termed human T cell lymphotropic virus I-associated myelopathy/tropical spastic paraparesis (HAM;TSP). The high number of viral-specific CD8 cells in these patients is associated with inflammatory responses in the central nervous system. Because IL-15 is overexpressed in these patients, we asked whether IL-15 contributes to the persistence of human T cell lymphotropic virus I viral-specific CD8 cells. Using ex vivo cultures of HAM/TSP peripheral blood mononuclear cells, we demonstrated that in the majority of patients examined here blocking IL-15 action resulted in a decrease in the number of viral-specific CD8 cells. This decrease was caused by both inhibition of proliferation and induction of apoptosis in these cells. The data indicate that IL-15 plays a major role in the maintenance of viral-specific CD8 cells in HAM/ TSP. C1 NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NINCDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Azimi, N (reprint author), NCI, Metab Branch, Ctr Canc Res, NIH, 10 Ctr Dr 1374, Bethesda, MD 20892 USA. EM nazli@helix.nih.gov NR 43 TC 45 Z9 47 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 DEC 4 PY 2001 VL 98 IS 25 BP 14559 EP 14564 DI 10.1073/pnas.251540598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 499NH UT WOS:000172576900068 PM 11717409 ER PT J AU Boroojerdi, B Battaglia, F Muellbacher, W Cohen, LG AF Boroojerdi, B Battaglia, F Muellbacher, W Cohen, LG TI Mechanisms underlying rapid experience-dependent plasticity in the human visual cortex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG-TERM POTENTIATION; TRANSCRANIAL MAGNETIC STIMULATION; METHYL-D-ASPARTATE; MOTOR CORTEX; FUNCTIONAL REORGANIZATION; MUSCARINIC RECEPTORS; SYNAPTIC PLASTICITY; NMDA RECEPTORS; NERVE INJURY; SCOPOLAMINE AB Visual deprivation induces a rapid increase in visual cortex excitability that may result in better consolidation of spatial memory in animals and in lower visual recognition thresholds in humans. gamma -Aminobutyric acid (GABA)ergic, N-methyl-D-aspartate (NMDA), and cholinergic receptors are thought to be involved in visual cortex plasticity in animal studies. Here, we used a pharmacological approach and found that lorazepam (which enhances GABAA receptor function by acting as a positive allosteric modulator), dextrometorphan (NMDA receptor antagonist), and scopolamine (muscarinic receptor antagonist) blocked rapid plastic changes associated with light deprivation. These findings suggest the involvement of GABA, NMDA, and cholinergic receptors in rapid experience-dependent plasticity in the human visual cortex. C1 NINCDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Univ Klinikum Aachen, Neurol Klin, D-52074 Aachen, Germany. RP Cohen, LG (reprint author), NINCDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NR 58 TC 44 Z9 44 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 4 PY 2001 VL 98 IS 25 BP 14698 EP 14701 DI 10.1073/pnas.251357198 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 499NH UT WOS:000172576900091 PM 11734655 ER PT J AU Priola, SA Lawson, VA AF Priola, SA Lawson, VA TI Glycosylation influences cross-species formation of protease-resistant prion protein SO EMBO JOURNAL LA English DT Article DE glycosylation; prion protein; PrP; scrapie ID ASPARAGINE-LINKED GLYCOSYLATION; NEUROBLASTOMA-CELLS; SCRAPIE ISOFORM; TRANSGENIC MICE; SPONGIFORM ENCEPHALOPATHY; CULTURED-CELLS; HAMSTER PRP; CONVERSION; SEQUENCE; STRAINS AB A key event in the transmissible spongiform encephalopathies (TSEs) is the formation of aggregated and protease-resistant prion protein, PrP-res, from a normally soluble, protease-sensitive and glycosylated precursor, PrP-sen. While amino acid sequence similarity between PrP-sen and PrP-res influences both PrP-res formation and cross-species transmission of infectivity, the influence of co- or post-translational modifications to PrP-sen is unknown. Here we report that, if PrP-sen and PrP-res are derived from different species, PrP-sen glycosylation can significantly affect PrP-res formation. Glycosylation affected PrP-res formation by influencing the amount of PrP-sen bound to PrP-res, while the amino acid sequence of PrP-sen influenced the amount of PrP-res generated in the post-binding conversion step. Our results show that in addition to amino acid sequence, co- or post-translational modifications to PrP-sen influence PrP-res formation in vitro. In vivo, these modifications might contribute to the resistance to infection associated with transmission of TSE infectivity across species barriers. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Priola, SA (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM spriola@nih.gov OI Lawson, Victoria/0000-0002-7362-7176 NR 41 TC 61 Z9 64 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 3 PY 2001 VL 20 IS 23 BP 6692 EP 6699 DI 10.1093/emboj/20.23.6692 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 500LM UT WOS:000172629100014 PM 11726505 ER PT J AU Lu, Y Qi, HY Hyndman, JB Ulbrandt, ND Teplyakov, A Tomasevic, N Bernstein, HD AF Lu, Y Qi, HY Hyndman, JB Ulbrandt, ND Teplyakov, A Tomasevic, N Bernstein, HD TI Evidence for a novel GTPase priming step in the SRP protein targeting pathway SO EMBO JOURNAL LA English DT Article DE GTPase; protein targeting; SRP; SRP receptor ID SIGNAL-RECOGNITION PARTICLE; GUANINE-NUCLEOTIDE-BINDING; ESCHERICHIA-COLI; MEMBRANE-PROTEINS; SEQUENCE BINDING; 54-KDA SUBUNIT; NG DOMAIN; FTSY; RNA; RECEPTOR AB Protein targeting by the signal recognition particle (SRP) pathway requires the interaction of two homologous GTPases that reciprocally regulate each other's GTPase activity, the SRP signal peptide-binding subunit (SRP54) and the SRP receptor alpha -subunit (SR alpha). The GTPase domain of both proteins abuts a unique 'N domain' that appears to facilitate external ligand binding. To examine the relationship between the unusual regulation and unique architecture of the SRP pathway GTPases, we mutated an invariant glycine in Escherichia coli SRP54 and SR alpha orthologs ('Ffh' and 'FtsY', respectively) that resides at the N-GTPase domain interface. A G257A mutation in Ffh produced a lethal phenotype. The mutation did not significantly affect Ffh function, but severely reduced interaction with FtsY. Likewise, mutation of FtsY Gly455 produced growth defects and inhibited interaction with Ffh. The data suggest that Ffh and FtsY interact only in a 'primed' conformation which requires interdomain communication. Based on these results, we propose that the distinctive features of the SRP pathway, GTPases evolved to ensure that SRP and the SR engage external ligands before interacting with each other. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bldg 10,Room 9D-20, Bethesda, MD 20892 USA. NR 43 TC 38 Z9 40 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 3 PY 2001 VL 20 IS 23 BP 6724 EP 6734 DI 10.1093/emboj/20.23.6724 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 500LM UT WOS:000172629100017 PM 11726508 ER PT J AU Mizuuchi, M Mizuuchi, K AF Mizuuchi, M Mizuuchi, K TI Conformational isomerization in phage Mu transpososome assembly: effects of the transpositional enhancer and of MuB SO EMBO JOURNAL LA English DT Article DE DNA-protein complex; DNA transposition; enhancer element; transposase ID DNA TRANSPOSITION; BACTERIOPHAGE-MU; STRAND-TRANSFER; B-PROTEIN; INVITRO TRANSPOSITION; RELATIVE ORIENTATION; TARGET IMMUNITY; A-PROTEIN; COMPLEX; CLEAVAGE AB Initiation of phage Mu DNA transposition requires assembly of higher order protein-DNA complexes called Mu transpososomes containing the two Mu DNA ends and MuA transposase tetramer. Mu transpososome assembly is highly regulated and involves multiple DNA sites for transposase binding, including a transpositional enhancer called the internal activation sequence (IAS). In addition, a number of protein cofactors participate, including the target DNA activator MuB ATPase. We investigated the impact of the assembly cofactors on the kinetics of transpososome assembly with the aim of deciphering the reaction steps that are influenced by the cofactors. The transpositional enhancer IAS appears to have little impact on the initial pairing of the two Mu end segments bound by MuA. Instead, it accelerates the post-synaptic conformational step(s) that converts the reversible complex to the stable transpososome. The transpososome assembly stimulation by MuB does not require its stable DNA binding activity, which appears critical for directing transposition to sites distant from the donor transposon. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Mizuuchi, K (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 35 TC 11 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 3 PY 2001 VL 20 IS 23 BP 6927 EP 6935 DI 10.1093/emboj/20.23.6927 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 500LM UT WOS:000172629100037 PM 11726528 ER PT J AU Rosenwald, A Alizadeh, AA Widhopf, G Simon, R Davis, RE Yu, X Yang, LM Pickeral, OK Rassenti, LZ Powell, J Botstein, D Byrd, JC Grever, MR Cheson, BD Chiorazzi, N Wilson, WH Kipps, TJ Brown, PO Staudt, LM AF Rosenwald, A Alizadeh, AA Widhopf, G Simon, R Davis, RE Yu, X Yang, LM Pickeral, OK Rassenti, LZ Powell, J Botstein, D Byrd, JC Grever, MR Cheson, BD Chiorazzi, N Wilson, WH Kipps, TJ Brown, PO Staudt, LM TI Relation of gene expression phenotype to immunoglobulin mutation genotype in B cell chronic lymphocytic leukemia SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE cDNA microarrays; gene expression profiling; leukemia; lymphocytic; chronic ID TYROSINE KINASES; AUTOANTIBODIES; PROTEIN; ACTIVATION; LYMPHOMA; RECEPTOR; CANCER; SYK AB The most common human leukemia is B cell chronic lymphocytic leukemia (CLL), a malignancy of mature B cells with a characteristic clinical presentation but a variable clinical course. The rearranged immunoglobulin (Ig) genes of CLL cells may be either germ-line in sequence or somatically mutated. Lack of Ig mutations defined a distinctly worse prognostic group of CLL patients raising the possibility that CLL comprises two distinct diseases. Using genomic-scale gene expression profiling, we show that CLL is characterized by a common gene expression "signature," irrespective of Ig mutational status, suggesting that CLL cases share a common mechanism of transformation and/or cell of origin. Nonetheless, the expression of hundreds of other genes correlated with the Ig mutational status, including many genes that are modulated in expression during mitogenic B cell receptor signaling. These genes were used to build a CLL subtype predictor that may help in the clinical classification of patients with this disease. C1 NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NIH, Bioinformat & Mol Anal Sect, CBEL, CIT, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Med, Washington, DC 20307 USA. Ohio State Univ, Dept Internal Med, Columbus, OH 43214 USA. NCI, CTEP, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. N Shore Long Isl Jewish Res Inst, Manhasset, NY 11030 USA. NCI, Med Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, Bldg 10,Rm 4N114, Bethesda, MD 20892 USA. OI Alizadeh, Arash Ash/0000-0002-5153-5625 FU NCI NIH HHS [R01 CA 87956, R01 CA081554, R01 CA087956, R01 CA 81554] NR 29 TC 717 Z9 737 U1 0 U2 17 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 DEC 3 PY 2001 VL 194 IS 11 BP 1639 EP 1647 DI 10.1084/jem.194.11.1639 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 500ZX UT WOS:000172659500009 PM 11733578 ER PT J AU Frost, P Barrientos, RM Makino, S Wong, ML Sternberg, EM AF Frost, P Barrientos, RM Makino, S Wong, ML Sternberg, EM TI IL-1 receptor type I gene expression in the amygdala of inflammatory susceptible Lewis and inflammatory resistant Fischer rats SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE IL-1 receptor type I; amygdala; Lewis rat; Fischer rat; HPA axis ID CORTICOTROPIN-RELEASING HORMONE; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; INTERLEUKIN-1 RECEPTOR; CORTICOSTERONE RESPONSES; BRAIN; PITUITARY; STRESS; LOCALIZATION AB Lewis (LEW/N) and Fischer (F344/N) rats have different responses to inflammatory and behavioral stressors due to differences in hypothalamus-pituitary-adrenal (HPA) axis function. For example, LEW/N rats are more sensitive to restraint, inflammation and experimentally induced autoimmunity due to decreased HPA activity. The HPA axis response to peripheral inflammation is mediated, at least in part, by IL- 1beta and its receptor, IL-1 type 1 (IL- IRI). Here, we studied the distribution of IL- 1RI mRNA in the brains of LEW/N and F344/N rats, and demonstrated that IL-IRI mRNA expression has significantly increased in the basolateral nucleus (BLA) of the amygdala of LEW/N rats. These findings suggest that strain-specific HPA axis responses may be mediated by extrahypothalamic pathways. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Inst Neuropsychiat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Brain Res Inst, Gonda Ctr 3357A, Los Angeles, CA 90095 USA. NIMH, NIH, Bethesda, MD 20892 USA. Kobe Univ, Sch Med, Dept Internal Med 2, Kobe, Hyogo 650, Japan. RP Univ Calif Los Angeles, Inst Neuropsychiat, 695 Charles Young Dr S, Los Angeles, CA 90095 USA. EM mali@ucla.edu RI Wong, Ma-Li/D-7903-2011; Barrientos, Ruth/E-3244-2013; OI Barrientos, Ruth/0000-0001-7224-4109; Frost, Patrick/0000-0003-3348-5983 FU NCCIH NIH HHS [P 50 AT00151-0] NR 34 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 EI 1872-8421 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC 3 PY 2001 VL 121 IS 1-2 BP 32 EP 39 DI 10.1016/S0165-5728(01)00440-4 PG 8 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 508NJ UT WOS:000173095100005 PM 11730937 ER PT J AU Whitney, LW Ludwin, SK McFarland, HF Biddison, WE AF Whitney, LW Ludwin, SK McFarland, HF Biddison, WE TI Microarray analysis of gene expression in multiple sclerosis and EAE identifies 5-lipoxygenase as a component of inflammatory lesions SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE multiple sclerosis; gene expression; 5-lipoxygenase ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; UP-REGULATION; LEUKOTRIENES; RECEPTOR; VULNERABILITY; SUPPRESSION; INHIBITION; PROMOTER; SCREEN AB Multiple sclerosis (MS) is a demyelinating disease of the central nervous system characterized by lesions that are areas of blood-brain barrier breakdown, inflammation and myelin damage. To identify genes that contribute to lesion pathology, we have compared gene expression in MS lesions and in brains of mice with experimental allergic encephalomyelitis (EAE) with that in normal white matter. Gene expression was analyzed by cDNA microarrays consisting of 2798 human genes. One of the genes found to be upregulated in both MS lesions and EA-E brains was 5-lipoxygenase (5-LO), a key enzyme in the biosynthesis of the proinflammatory leukotrienes. The presence of 5-LO in MS lesions was confirmed by immunohistochemistry and indicated that 5-LO was primarily contained within macrophages. Although these findings are not specific for MS, they identify a potentially important component of pro-inflammatory activity in the demyelinating process in MS and suggest a possible target for anti-inflammatory therapy in MS. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NINCDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. RP Biddison, WE (reprint author), NINCDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10-Rm 5B-16, Bethesda, MD 20892 USA. NR 41 TC 101 Z9 106 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD DEC 3 PY 2001 VL 121 IS 1-2 BP 40 EP 48 DI 10.1016/S0165-5728(01)00438-6 PG 9 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 508NJ UT WOS:000173095100006 PM 11730938 ER PT J AU Gu, YJ Reshetnikova, L Li, Y Yan, H Singh, SV Ji, XH AF Gu, YJ Reshetnikova, L Li, Y Yan, H Singh, SV Ji, XH TI Crystallization and preliminary X-ray diffraction analysis of shikimate kinase from Mycobacterium tuberculosis in complex with MgADP SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PATHWAY; ACID AB Shikimate kinase (SK) from Mycobacterium tuberculosis (Mt) was overexpressed in Escherichia coli, purified and cocrystallized with MgADP in hanging drops using the vapor-diffusion procedure with PEG 4000 and 2-propanol as precipitants at pH 7.5. The crystal of MtSK-MgADP, which diffracted to 2.2 Angstrom resolution, belonged to space group P3(2)21 or P3(1)21, with unit-cell parameters a=b=64.01, c=92.41 Angstrom. There was one MtSK molecule in the asymmetric unit. Molecular-replacement trials with the crystal structure of SK from Erwinia chrysanthemi (PDB code 1shk) and adenylate kinase (PDB code 1ake) as search models were not successful. Heavy-atom derivative screening is in progress. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Inst Canc, Pittsburgh, PA 15261 USA. RP Ji, XH (reprint author), NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM jix@ncifcrf.gov RI Gu, Yijun/B-6017-2012; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 FU NCI NIH HHS [CA55589, R01 CA76348]; NIGMS NIH HHS [GM51901] NR 12 TC 9 Z9 12 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD DEC PY 2001 VL 57 BP 1870 EP 1871 DI 10.1107/S0907444901014032 PN 12 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 495CE UT WOS:000172322000015 PM 11717501 ER PT J AU Pawlosky, RJ Bacher, J Salem, N AF Pawlosky, RJ Bacher, J Salem, N TI Ethanol consumption alters electroretinograms and depletes neural tissues of docosahexaenoic acid in rhesus monkeys: Nutritional consequences of a low n-3 fatty acid diet SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE electroretinogram; amblyopia; retina; brain; docosahexaenoic acid ID TOBACCO-ALCOHOL AMBLYOPIA; LIPID-PEROXIDATION; OXIDATIVE STRESS; RAT-BRAIN; INDUCTION; METABOLISM; CELLS; DEFICIENCY; RHODOPSIN; GLUTAMATE AB Background: Alcohol amblyopia is a rare neuropathy characterized by the development of blurred vision and a reduction in visual acuity. Further diagnostic details of this condition have shown abnormalities in the electroretinogram (ERG) that include an increase in implicit times in the a- and b-waves and a depression of h-wave amplitude. Methods: Periodically, the ERGs and the fatty acyl composition of nervous tissue were analyzed from alcohol-consuming rhesus monkeys (Macaca mulatta) (mean consumption 2.6 g kg/day over a 5-year period) and controls that were maintained on a nutritionally sufficient diet that had low, yet adequate, amounts of linoleic acid but very low a-linolenic acid. Results: Animals consuming alcohol had increased a- and b-wave implicit times and decreased b-wave amplitudes in their electroretinograms compared with those of the dietary control group at 2.5 and 5 years, The fatty acyl composition of brain specimens obtained by surgical biopsy at baseline, 2.5 years, and 5 years demonstrated that docosahexaenoic acid (DHA) had decreased in both groups (if animals compared with baseline values. In the brains of the alcohol-treated animals, DHA was even further decreased (2.5 years: - 20%: 5 years: - 33%) compared with the diet controls. In the retinas of the alcohol-consuming animals at 5 years, there was a similar decrease in DHA (-35%) compared with controls. Generally, the n-6 fatty acid, docosapentaenoic acid (DPAn-6) increased in these tissues, apparently compensating for the loss of DHA. Conclusions: A reciprocal change in the DHA/DPAn-6 ratio is known to be associated with abnormal electroretinograms in a number of species. Thus, a marginal intake of n-3 fatty acids in some alcohol abusers may. in part, be responsible for the biochemical changes that underlie the diminished retinal function associated with the visual abnormalities observed in alcohol-amblyopic patients. C1 ARS, Food Composit Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD 20705 USA. NIH, Off Res Serv, Vet Resources Program, Beltsville, MD USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. RP Pawlosky, RJ (reprint author), ARS, Food Composit Lab, Beltsville Human Nutr Res Ctr, USDA, Bldg 161,10300 Baltimore Ave, Beltsville, MD 20705 USA. NR 46 TC 37 Z9 42 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2001 VL 25 IS 12 BP 1758 EP 1765 DI 10.1111/j.1530-0277.2001.tb02187.x PG 8 WC Substance Abuse SC Substance Abuse GA 505XD UT WOS:000172940100009 PM 11781509 ER PT J AU Ahmed, S Shapiro, EP O'Connor, FE Fleg, JL AF Ahmed, S Shapiro, EP O'Connor, FE Fleg, JL TI Effect of normative aging on midwall left ventricular systolic performance SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ECHOCARDIOGRAPHIC MEASUREMENTS; HYPERTENSION; HYPERTROPHY; HEART; AGE; GEOMETRY; DISEASE AB To determine whether aging is accompanied by a reduction in left ventricular resting midwall systolic performance despite normal endocardial systolic function, we evaluated endocardial and midwall mechanics by echocardiography in 330 healthy adults with blood pressures < 160/95 nun Hg. In both sexes, midwall left ventricular fractional shortening varied inversely with end-systolic wall stress, but no differences in this relation were observed between subgroups that were older versus younger than the median age (48 years in women and 50 years in men). C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Johns Hopkins Bayview Med Ctr, Bethesda, MD USA. RP Fleg, JL (reprint author), NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 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 DEC 1 PY 2001 VL 88 IS 11 BP 1330 EP + DI 10.1016/S0002-9149(01)02103-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 499NF UT WOS:000172576700025 PM 11728370 ER PT J AU Mahady, GB Matsuura, H Pendland, SL AF Mahady, GB Matsuura, H Pendland, SL TI Allixin, a phytoalexin from garlic, inhibits the growth of Helicobacter pylori in vitro SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID GASTRIC-CANCER C1 Univ Illinois, UIC, NIH,Program Collaborat Res Pharmaceut Sci, Ctr Bot Dietary Supplement Res, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL USA. RP Mahady, GB (reprint author), Univ Illinois, UIC, NIH,Program Collaborat Res Pharmaceut Sci, Ctr Bot Dietary Supplement Res, MC 877,Room 310,833 S Wood St, Chicago, IL 60612 USA. FU NCCIH NIH HHS [R21 AT000412-01] NR 6 TC 13 Z9 13 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD DEC PY 2001 VL 96 IS 12 BP 3454 EP 3455 DI 10.1016/S0002-9270(01)03913-2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 502WV UT WOS:000172766500051 PM 11774979 ER PT J AU Anikster, Y Kleta, R Shaag, A Gahl, WA Elpeleg, O AF Anikster, Y Kleta, R Shaag, A Gahl, WA Elpeleg, O TI Type III 3-methylglutaconic aciduria (optic atrophy plus syndrome, or Costeff optic atrophy syndrome): Identification of the OPA3 gene and its founder mutation in Iraqi Jews SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CARDIOMYOPATHY; PEROXISOMES; DEFICIENCY; PROTEIN AB Type III 3-methylglutaconic aciduria (MGA) (MIM 258501) is a neuro-ophthalmologic syndrome that consists of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. Urinary excretion of 3-methylglutaconic acid and of 3-methylglutaric acid is increased. The disorder has been reported in 40 patients of Iraqi Jewish origin, allowing the mapping of the disease to chromosome 19q13.2-q13.3, by linkage analysis. To isolate the causative gene, OPA3, we sequenced four genes within the critical interval and identified, in the intronic sequence of a gene corresponding to cDNA clone FLJ22187, a point mutation that segregated with the type III MGA phenotype. The FLJ22187-cDNA clone, which we identified as the OPA3 gene, consists of two exons and encodes a peptide of 179 amino acid residues. Northern blot analysis revealed a primary transcript of similar to5.0 kb that was ubiquitously expressed, most prominently in skeletal muscle and kidney. Within the brain, the cerebral cortex, the medulla, the cerebellum, and the frontal lobe, compared to other parts of the brain, had slightly increased expression. The intronic G -->C mutation abolished mRNA expression in fibroblasts from affected patients and was detected in 8 of 85 anonymous Israeli individuals of Iraqi Jewish origin. Milder mutations in OPA3 should be sought in patients with optic atrophy with later onset, even in the absence of additional neurological abnormalities. C1 Hebrew Univ Jerusalem, Fac Med, Shaare Zedek Med Ctr, Metab Dis Unit, IL-91031 Jerusalem, Israel. NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Elpeleg, O (reprint author), Hebrew Univ Jerusalem, Fac Med, Shaare Zedek Med Ctr, Metab Dis Unit, IL-91031 Jerusalem, Israel. NR 24 TC 105 Z9 107 U1 0 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2001 VL 69 IS 6 BP 1218 EP 1224 DI 10.1086/324651 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 491AY UT WOS:000172086900006 PM 11668429 ER PT J AU Uhl, GR Liu, QR Walther, D Hess, J Naiman, D AF Uhl, GR Liu, QR Walther, D Hess, J Naiman, D TI Polysubstance abuse-vulnerability genes: Genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID NEUROTROPHIC FACTOR; ALCOHOL DEPENDENCE; SUBSTANCE-ABUSE; DRUG-ABUSE; ENVIRONMENTAL-INFLUENCES; LINKAGE DISEQUILIBRIUM; LOCOMOTOR-ACTIVITY; FEMALE TWINS; RAT-BRAIN; BDNF-GENE AB Strong genetic contributions to drug abuse vulnerability are well documented, but few chromosomal locations for human drug-abuse vulnerability alleles have been confirmed. We now identify chromosomal markers whose alleles distinguish drug abusers from control individuals in each of two samples, on the basis of pooled-sample microarray and association analyses. Reproducibly positive chromosomal regions defined by these markers in conjunction with previous results were especially unlikely to have been identified by chance. Positive markers identify the alcohol dehydrogenase (ADH) locus, flank the brain-derived neurotropic factor (BDNF) locus, and mark seven other regions previously linked to vulnerability to nicotine or alcohol abuse. These data support polygenic contributions of common allelic variants to polysubstance abuse vulnerability. C1 NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD USA. Johns Hopkins Univ, Dept Math Sci, Baltimore, MD 21218 USA. RP Uhl, GR (reprint author), Box 5180, Baltimore, MD 21224 USA. RI Naiman, Daniel/A-3304-2010; Liu, Qing-Rong/A-3059-2012 OI Naiman, Daniel/0000-0001-6504-9081; Liu, Qing-Rong/0000-0001-8477-6452 NR 49 TC 179 Z9 181 U1 5 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2001 VL 69 IS 6 BP 1290 EP 1300 DI 10.1086/324467 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 491AY UT WOS:000172086900014 PM 11704927 ER PT J AU Cocco, P Rice, CH Chen, JQ McCawley, MA McLaughlin, JK Dosemeci, M AF Cocco, P Rice, CH Chen, JQ McCawley, MA McLaughlin, JK Dosemeci, M TI Lung cancer risk, silica exposure, and silicosis in Chinese mines and pottery factories: The modifying role of other workplace lung carcinogens SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE silica; silicosis; lung cancer; arsenic; PAH; cadmium; nickel; radon-daughters ID NESTED CASE-CONTROL; CRYSTALLINE SILICA; WORKERS; MORTALITY; COHORT; QUARTZ; DUST AB Background Aims of our study were to explore whether and to what extent exposure to other lung carcinogens, or staging and clinical features of silicosis modify or confound the association between silica and lung cancer Methods We used data from a nested case-control study, conducted in the late 1980s in 29 Chinese mines and potteries (10 tungsten mines, 6 copper and iron mines, 4 tin mines, 8 pottery factories, and I clay mine), that included 316 lung cancer cases and 1,356 controls, matched by decade of birth and facility type. The previous analysis of these data presented results by type of mine or factory. Results In our study, pooling all 29 Chinese work sites, lung cancer risk showed a modest association with silica exposure. Risk did not vary after excluding subjects with silicosis or adjusting the risk estimates by radiological staging of silicosis. Strong correlation among exposures prevented a detailed evaluation of the role of individual exposures. However, lung cancer risk was for the most part absent when concomitant exposure to other workplace lung carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), nickel or radon-daughters, was considered The cross classification of lung cancer risk by categories of exposure to respirable silica and total respirable dust did not show an independent effect of total respirable dust. Silicosis showed a modest association with lung cancer, which did not vary by severity of radiological staging, or by radiological evidence of disease progression, or by level of silica exposure. However, among silicotic subjects, lung cancer risk was significantly elevated only when exposure to cadmium and PAH had occurred Conclusions Our results suggest that, among silica-exposed Chinese workers, numerous occupational and non-occupational risk factors interact in a complex fashion to modify lung cancer risk. Future epidemiological studies on silica and lung cancer should incorporate detailed information on exposure to other workplace lung carcinogens, total respirable dust, and on surface size and age of silica particles to understand whether and to what extent they affect the carcinogenic potential of silica. (C) 2001 Wiley-Liss, Inc. C1 Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Ist Med Lavoro, I-09124 Cagliari, Italy. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Tongji Med Univ, Dept Labor Hlth & Occupat Dis, Wuhan, Peoples R China. NIOSH, Morgantown, WV USA. Int Epidemiol Inst, Rockville, MD USA. RP Cocco, P (reprint author), Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, Ist Med Lavoro, Via San Giorgio 12, I-09124 Cagliari, Italy. NR 31 TC 28 Z9 30 U1 2 U2 13 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 2001 VL 40 IS 6 BP 674 EP 682 DI 10.1002/ajim.10022 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 497XG UT WOS:000172480300007 PM 11757044 ER PT J AU Francomano, CA Ho, NC AF Francomano, CA Ho, NC TI Latest developments in skeletal dysplasias SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Editorial Material ID NEURAL CREST; MUTATIONS; PSEUDOACHONDROPLASIA; GENE C1 NIA, Sect Human Genet & Integrat Med, Genet Lab, NIH,IRP, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Francomano, CA (reprint author), NIA, Sect Human Genet & Integrat Med, Genet Lab, NIH,IRP, Room 4A,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM francomanocl@grc.nia.nih.gov NR 19 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD WIN PY 2001 VL 106 IS 4 BP 241 EP 243 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 518KY UT WOS:000173668500001 ER PT J AU Arikawa-Hirasawa, E Wilcox, WR Yamada, Y AF Arikawa-Hirasawa, E Wilcox, WR Yamada, Y TI Dyssegmental dysplasia, Silverman-Handmaker type: Unexpected role of perlecan in cartilage development SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE dyssegmental dysplasia; Silverman-Handmaker type (DDSH); perlecan; functional null mutations; chondrodysplasia; Schwartz-Jampel syndrome (SJS) ID GROWTH-FACTOR; BASEMENT-MEMBRANES; PROTEOGLYCAN; RECEPTOR AB Dyssegmental dysplasia, Silverman-Handmaker type (DDSH), is a lethal autosomal recessive form of dwarfism with characteristic anisospondylic micromelia. The remarkable similarities in the radiographic, clinical, and chondroosseous morphology of DDSH patients to those of perlecan-null mice led to the identification of mutations in the perlecan gene (HSPG2) of DDSH. Perlecan, a large heparan sulfate proteoglycan, is expressed in various tissues and is a component of all basement membrane extracellular matrices. A chondrodysplasia phenotype caused by the loss of perlecan was unexpected, because cartilage does not have basement membranes. Insertion and splicing mutations in HSPG2 of DDSH were found that were predicted to create a premature termination codon. Immunostaining and biochemical analysis revealed that the mutant perlecan molecules were unstable and not secreted into the extracellular matrix. These results indicate that DDSH is caused by functional null mutations of HSPG2 and that perlecan is essential for cartilage development. (C) 2002 Wiley-Liss, Inc. C1 NIDCR, Mol Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Yamada, Y (reprint author), NIDCR, Mol Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 405,30 Convent Dr, Bethesda, MD 20892 USA. NR 14 TC 40 Z9 41 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD WIN PY 2001 VL 106 IS 4 BP 254 EP 257 DI 10.1002/ajmg.10229 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 518KY UT WOS:000173668500004 PM 11891676 ER PT J AU Jia, LB Ho, NC Park, SS Powell, J Francomano, CA AF Jia, LB Ho, NC Park, SS Powell, J Francomano, CA TI Comprehensive resource: Skeletal gene database SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE skeletal gene database; gene expression analysis; data mining AB The Skeletal Gene Database (SGD) is an integrated resource that provides comprehensive information about bone-related genes, mRNA, and proteins expressed in human and mouse, with rich links to numerous other electronic tools. SGD contains expressed sequence tag (EST) data from all the skeletal-related cDNA libraries that are available to the public. It supplies the query/data access analytic tools for users to search and compare each gene expressed in skeletal tissue(s). The results derived from EST tissue expression profiling will allow users to get the data on the mRNA copy numbers of each gene expressed in each tissue and its normalized value. From the SGD, researchers can obtain information regarding the name, symbol, size, exon/intron number, chromosomal location, LocusLink, and related disease (if any is known) of each gene. This electronic compendium also furnishes information on the protein of the corresponding gene including the protein size (amino acid number and molecular weight). It provides swift and ready access to other useful databases including OMIM, UniGene and PUBMED. The data will be updated regularly in step with current and future research, thereby providing what we hope will serve as a highly useful source of information and a powerful analytic tool to the scientific community. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NIH, Bioinformat & Mol Anal Sect, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD USA. NIA, Genet Lab, Bethesda, MD 20892 USA. RP Jia, LB (reprint author), NHGRI, Med Genet Branch, NIH, 10-10C101,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 6 TC 4 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 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD WIN PY 2001 VL 106 IS 4 BP 275 EP 281 DI 10.1002/ajmg.10227.abs PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 518KY UT WOS:000173668500007 PM 11891679 ER PT J AU Bingham, R AF Bingham, R TI Waiting SO AMERICAN JOURNAL OF NURSING LA English DT Article C1 Georgetown Univ Hosp, Washington, DC 20007 USA. Fairfax Hosp, Falls Church, VA 22046 USA. RP Bingham, R (reprint author), NINR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-936X J9 AM J NURS JI Am. J. Nurs. PD DEC PY 2001 VL 101 IS 12 BP 55 EP 55 PG 1 WC Nursing SC Nursing GA 529AD UT WOS:000174277100040 ER PT J AU Agbaria, R Bashiri, A Furman, B Rubin, M Al-Athamen, K Marquez, V Ford, H Kelley, J Johns, D Mazor, M AF Agbaria, R Bashiri, A Furman, B Rubin, M Al-Athamen, K Marquez, V Ford, H Kelley, J Johns, D Mazor, M TI Metabolic activation of 2 '-beta-fluoro-2 ',3 '-dideoxyadenosine and 2'-fluoro-2'-deoxyadenosine in maternal and fetal peripheral mononuclear cells at term gestation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Soroka Univ, Med Ctr, Beer Sheva, Israel. NCI, NIH, Med Chem Lab, Frederick, MD 21701 USA. Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 422 BP S195 EP S195 DI 10.1016/S0002-9378(01)80454-3 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000419 ER PT J AU Allen, R Rosenbaum, T Ghidini, A Spong, C AF Allen, R Rosenbaum, T Ghidini, A Spong, C TI Which variables predict neonatal asphyxia in cases of shoulder dystocia with permanent neurologic damage? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. RDA, Baltimore, MD USA. Georgetown Univ, Washington, DC USA. NICHHD, NIH, PPB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 269 BP S154 EP S154 DI 10.1016/S0002-9378(01)80302-1 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000268 ER PT J AU Ananth, G Smulian, J Wilcox, A AF Ananth, G Smulian, J Wilcox, A TI Neonatal mortality in relation to fetal size and gestational duration in the US: The effect of placenta previa SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, St Peters Univ Hosp, New Brunswick, NJ USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 288 BP S159 EP S159 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000287 ER PT J AU Bernstein, H Kinter, A Chun, TW Jackson, R Hallahan, C Fauci, A AF Bernstein, H Kinter, A Chun, TW Jackson, R Hallahan, C Fauci, A TI The effect of elective c-section, preterm labor and chorioamnionitis on fetal lymphocyte activation and susceptibility to HIV infection SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Gynecol & Obstet, Div Maternal Fetal Med, Baltimore, MD USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 395 BP S189 EP S189 DI 10.1016/S0002-9378(01)80427-0 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000392 ER PT J AU Bloom, SL AF Bloom, SL CA NICHD MFMU Network TI MFMU Cesarean Registry: Decision to incision times and infant outcome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 145 BP S121 EP S121 DI 10.1016/S0002-9378(01)80180-0 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000147 ER PT J AU Bukowski, R Zhang, J Gardosi, J Saade, G AF Bukowski, R Zhang, J Gardosi, J Saade, G TI Fetal growth potential as a predictor of neonatal morbidity SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Nottingham, Nottingham NG7 2RD, England. NICHHD, NI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 608 BP S245 EP S245 DI 10.1016/S0002-9378(01)80641-4 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000602 ER PT J AU Bukowski, R Zhang, J Olson, G Gardosi, J Saade, G AF Bukowski, R Zhang, J Olson, G Gardosi, J Saade, G TI Hypertension in pregnancy and impairment of fetal growth potential SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NICHHD, Bethesda, MD 20892 USA. Univ Texas, Med Ctr, Galveston, TX 77555 USA. Univ Nottingham, Nottingham NG7 2RD, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 342 BP S175 EP S175 DI 10.1016/S0002-9378(01)80373-2 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000339 ER PT J AU Bytautiene, E Vedernikov, Y Saade, G Romero, R Garfield, R AF Bytautiene, E Vedernikov, Y Saade, G Romero, R Garfield, R TI Histamine effects differ in phasicaly and tonicaly contracted pregnant human uterine tissue SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NICHHD, Perinatol Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 209 BP S139 EP S139 DI 10.1016/S0002-9378(01)80244-1 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000210 ER PT J AU Bytautiene, E Vedernikov, Y Saade, G Romero, R Garfield, R AF Bytautiene, E Vedernikov, Y Saade, G Romero, R Garfield, R TI Cyclooxygenase and lipoxygenase involvement in increased uterine contractility due to endogenous mast cell degranulation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NICHHD, Perinatol Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 45 BP S90 EP S90 DI 10.1016/S0002-9378(01)80080-6 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000047 ER PT J AU Bytautiente, GE Vedernikov, Y Saade, G Romero, R Garfield, R AF Bytautiente, GE Vedernikov, Y Saade, G Romero, R Garfield, R TI Effect of endogenous mast cell degranulation on uterine and cervical contractility in pregnant mice lacking a functional 5-lipoxygenase gene SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NICHHD, Perinatol Res Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 490 BP S215 EP S215 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000485 ER PT J AU Chaiworapongsa, T Edwin, S Kim, JC Kim, YM Conoscenti, G Yoon, BH Romero, R AF Chaiworapongsa, T Edwin, S Kim, JC Kim, YM Conoscenti, G Yoon, BH Romero, R TI Pro-inflammatory and anti-inflammatory cytokine profile in pregnant women with pyelonephritis SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, Perinatol Res Branch, Detroit, MI USA. Seoul Natl Univ, Seoul, South Korea. NICHHD, Perinatol Res Branch, NIH, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 339 BP S174 EP S174 DI 10.1016/S0002-9378(01)80370-7 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000336 ER PT J AU Chames, M AF Chames, M CA NICHD MFMU Network TI Spontaneous and indicated preterm deliveries are increased in twins vs singletons SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHD MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 114 BP S113 EP S113 DI 10.1016/S0002-9378(01)80149-6 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000116 ER PT J AU Davis, R AF Davis, R CA NICHD MFMU Network TI The MFMU Cesarean Registry: Primary cesarean deliveries are increased in private patients SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 146 BP S121 EP S121 DI 10.1016/S0002-9378(01)80181-2 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000148 ER PT J AU Ghidini, A Spong, C Pezzullo, J AF Ghidini, A Spong, C Pezzullo, J TI Is a lecithin/sphyngomyelin (L/S) ratio >= 3 the best predictor of presence of phosphatidylglycerol (PG) in diabetic women? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 556 BP S232 EP S232 DI 10.1016/S0002-9378(01)80589-5 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000551 ER PT J AU Ghidini, A Allen, R Rosenbaum, T Spong, C AF Ghidini, A Allen, R Rosenbaum, T Spong, C TI Does operative vaginal delivery worsen the outcome of permanent brachial plexus injury? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. Johns Hopkins Univ, Baltimore, MD USA. RDA, Baltimore, MD USA. NICHHD, NIH, PPB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 169 BP S127 EP S127 DI 10.1016/S0002-9378(01)80204-0 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000170 ER PT J AU Goepfert, A AF Goepfert, A TI The MFMU cesarean registry: Infectious morbidity following primary cesarean section (C/S) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, MFMU Network, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 410 BP S192 EP S192 DI 10.1016/S0002-9378(01)80442-7 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000407 ER PT J AU Gomez, R Nien, JK Sepulveda, G Carstens, M Medina, L Gonzalez, R Rojas, I Chaiworapongsa, T Romero, R AF Gomez, R Nien, JK Sepulveda, G Carstens, M Medina, L Gonzalez, R Rojas, I Chaiworapongsa, T Romero, R TI Antibiotic treatment of patients with preterm PROM does not eradicate intra-amniotic infection or prevent the development of intra-amniotic inflammation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Pontificia Univ Catolica Chile, Dept Ob Gin, Hosp Dr Sotero del Rio, CEDIP, Santiago, Chile. NIH, Perinatol Res Branch, Detroit, MI USA. Perinatol Res Branch, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 222 BP S142 EP S142 DI 10.1016/S0002-9378(01)80255-6 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000221 ER PT J AU Hitti, J Nugent, R Gardella, C Hillier, S Eschenbach, D AF Hitti, J Nugent, R Gardella, C Hillier, S Eschenbach, D TI Lower genital tract infection, racial group and risk of preterm delivery of a low birthweight infant SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NICHHD, Bethesda, MD USA. Magee Womens Hosp, Pittsburgh, PA 15213 USA. NR 0 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 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 413 BP S193 EP S193 DI 10.1016/S0002-9378(01)80446-4 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000410 ER PT J AU Hnat, M AF Hnat, M CA NICHD MFMU Network TI Preterm rupture of membranes at 24-32 weeks: Recent vaginal bleeding and perinatal outcome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 221 BP S142 EP S142 DI 10.1016/S0002-9378(01)80254-4 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000220 ER PT J AU Levine, R Qian, C Yu, K England, L Beste, L Chaiworapongsa, T Edwin, S Romero, R AF Levine, R Qian, C Yu, K England, L Beste, L Chaiworapongsa, T Edwin, S Romero, R CA CPEP Study Grp TI C-reactive protein not elevated in preeclamptic pregnancy at 9-20 weeks: The inflammation hypothesis fails a test SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. Allied Technol Grp, Rockville, MD USA. NICHHD, Stat Branch, Bethesda, MD 20892 USA. NICHHD, Perinatol Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 15 BP S75 EP S75 DI 10.1016/S0002-9378(01)80025-9 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000017 ER PT J AU Malone, FD Ball, RH Nyberg, DA Gross, SJ Comstock, CH Saade, GR Eddleman, KA Craigo, SD Timor, IE Carr, SR Hobbins, JC Dukes, KA De la Cruz, F D'Alton, ME AF Malone, FD Ball, RH Nyberg, DA Gross, SJ Comstock, CH Saade, GR Eddleman, KA Craigo, SD Timor, IE Carr, SR Hobbins, JC Dukes, KA De la Cruz, F D'Alton, ME TI First trimester cystic hygroma - A population based screening study (The FASTER Trial) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. Univ Utah, Med Ctr, Salt Lake City, UT USA. Swedish Med Ctr, Seattle, WA USA. Montefiore Med Ctr, Bronx, NY 10467 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. NYU, Med Ctr, New York, NY 10016 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. DM STAT, Boston, MA USA. NICHHD, Bethesda, MD 20892 USA. RI Malone, Fergal/D-6233-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 65 BP S99 EP S99 DI 10.1016/S0002-9378(01)80100-9 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000067 ER PT J AU Poggi, S Allen, R Ghidini, A Rosenbaum, T Spong, C AF Poggi, S Allen, R Ghidini, A Rosenbaum, T Spong, C TI Does upper extremity fracture predict degree of neurologic injury in patients with permanent injury? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. Johns Hopkins Univ, Baltimore, MD USA. RDA, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 271 BP S154 EP S154 DI 10.1016/S0002-9378(01)80304-5 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000270 ER PT J AU Poggi, S Vink, J Hill, J Brenneman, D Pinhasov, A Gozes, I Spong, K AF Poggi, S Vink, J Hill, J Brenneman, D Pinhasov, A Gozes, I Spong, K TI Differential expression of embryonic and maternal activity dependent neuroprotective protein (ADNP) during development SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Georgetown Univ, Washington, DC USA. NICHHD, NIH, SDMP, LDN,PPB, Bethesda, MD USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 48 BP S91 EP S91 DI 10.1016/S0002-9378(01)80083-1 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000050 ER PT J AU Ramsey, P Shinetugs, B Goldenberg, R AF Ramsey, P Shinetugs, B Goldenberg, R TI The Preterm Prediction Study: Elevated vaginal prolactin levels at 22-24 weeks gestation are associated with spontaneous preterm delivery in asymptomatic women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, MFMU Network, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 240 BP S146 EP S146 DI 10.1016/S0002-9378(01)80273-8 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000239 ER PT J AU Ramsey, P Shinetugs, B Goldenberg, R AF Ramsey, P Shinetugs, B Goldenberg, R TI The Preterm Prediction Study: Vaginal matrix metalloproteinase-9 (MMP-9) levels and spontaneous preterm delivery in asymptomatic women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 241 BP S147 EP S147 DI 10.1016/S0002-9378(01)80274-X PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000240 ER PT J AU Romero, R Chaiworapongsa, T Gomez, R Bo, HY Maymon, E Berry, S AF Romero, R Chaiworapongsa, T Gomez, R Bo, HY Maymon, E Berry, S TI Does the human fetus rupture the membranes in preterm PROM? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, Perinatol Res Branch, NIH, Detroit, MI USA. Seoul Natl Univ, Seoul, South Korea. Soroka Univ Med Ctr, Beer Sheva, Israel. Wayne State Univ, Detroit, MI USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 5 BP S71 EP S71 DI 10.1016/S0002-9378(01)80015-6 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000007 ER PT J AU Shellhaas, C AF Shellhaas, C CA NICHD MFMU Network TI The MFMU Cesarean Registry: Cesarean hysterectomy - Its indications, morbidities, and mortality SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, MFMU Network, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 155 BP S123 EP S123 DI 10.1016/S0002-9378(01)80191-5 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000157 ER PT J AU Spong, C Vink, J Auth, J Gozes, I Brenneman, D AF Spong, C Vink, J Auth, J Gozes, I Brenneman, D TI Oral prenatal treatment with peptides increases adult performance in a learning paradigm SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, LDN & PPB, SDMP, NIH, Bethesda, MD USA. NICHHD, LDN, SDMP, NIH, Bethesda, MD USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 597 BP S243 EP S243 DI 10.1016/S0002-9378(01)80629-3 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000591 ER PT J AU Swain, M AF Swain, M TI Ultrasound measured cervical length, (UMCL) is inversely associated with maternal height SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, MFMU Network, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 287 BP S158 EP S158 DI 10.1016/S0002-9378(01)80320-3 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000286 ER PT J AU Vergani, P Ghidini, A Spong, C Andreotti, C Roncaglia, N Arreghini, A Zagarella, A AF Vergani, P Ghidini, A Spong, C Andreotti, C Roncaglia, N Arreghini, A Zagarella, A TI Uterine artery Doppler in small for gestational age (SGA) fetuses at >= 34 weeks predicts neonatal outcome SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 Univ Milan, Monza, Italy. Georgetown Univ, Washington, DC USA. NIH, Bethesda, MD 20892 USA. RI Vergani, Patrizia/H-4580-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 670 BP S261 EP S261 DI 10.1016/S0002-9378(01)80704-3 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000664 ER PT J AU Zhang, J Meikle, S Grainger, D Trumble, A AF Zhang, J Meikle, S Grainger, D Trumble, A TI Multifetal pregnancy in older gravidas and perinatal outcomes SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, NI, Bethesda, MD 20892 USA. NICHHD, Ctr Res Mother & Children, Bethesda, MD USA. Univ Kansas, Wichita, KS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 281 BP S157 EP S157 DI 10.1016/S0002-9378(01)80314-8 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000280 ER PT J AU Zhang, J Troendle, J Yancey, M AF Zhang, J Troendle, J Yancey, M TI Reassessing the labor curve SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Meeting Abstract C1 NICHHD, NI, Bethesda, MD 20892 USA. Tripler Army Med Ctr, Honolulu, HI 96859 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2001 VL 185 IS 6 SU S MA 6 BP S71 EP S71 DI 10.1016/S0002-9378(01)80016-8 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 505PK UT WOS:000172921000008 ER PT J AU Moke, PS Turpin, AH Beck, RW Holmes, JM Repka, MX Birch, EE Hertle, RW Kraker, RT Miller, JM Johnson, CA AF Moke, PS Turpin, AH Beck, RW Holmes, JM Repka, MX Birch, EE Hertle, RW Kraker, RT Miller, JM Johnson, CA TI Computerized method of visual acuity testing: Adaptation of the amblyopia treatment study visual acuity testing protocol SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article AB - PURPOSE: To report a computerized method for deter, mining visual acuity in children using the Amblyopia Treatment Study visual acuity testing protocol. - METHODS: A computerized visual acuity tester was developed that uses a programmed handheld device that uses the Palm operating system (Palm, Inc, Santa Clara, California). The handheld device communicates with a personal computer running a Linux operating system and 17-inch monitor. At a test distance of 3 m, single letters can be displayed from 20/800 to 20/12. A C program on the handheld device runs the Amblyopia Treatment Study visual acuity testing protocol. Using this method, visual acuity was tested in both the right and left eyes, and then the testing was repeated in 156 children age 3 to 7 years at four clinical sites. - RESULTS: Test-retest reliability was high (r = .92 and 0.95 for and right and left eyes, respectively), with 88% of right eye retests and 94% of left eye retests within 0.1 logarithm of minimal angle of resolution (logMAR) units of the initial test. The 95% confidence interval for an acuity score was calculated to be the score +/- 0.13 logMAR units. For a change between two acuity scores, the 95% confidence interval was the difference +/- 0.19 logMAR units. - CONCLUSIONS: We have developed a computerized method for measurement of visual acuity. Automation of the Amblyopia Treatment Study visual acuity testing protocol is an effective method of testing visual acuity in children 3 to 7 years of age. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Jaeb Ctr Hlth Res, Tampa, FL 33613 USA. Curtin Univ Technol, Bentley, WA 6102, Australia. Mayo Clin, Rochester, MN USA. Johns Hopkins Univ, Baltimore, MD USA. Retina Fdn SW, Dallas, TX USA. NEI, Bethesda, MD 20892 USA. Univ Arizona, Tucson, AZ USA. Devers Eye Inst, Portland, OR USA. RP Moke, PS (reprint author), Jaeb Ctr Hlth Res, 3010 E 138th Ave,Suite 9, Tampa, FL 33613 USA. FU NEI NIH HHS [EY 11155, EY 11751, EY 13095] NR 5 TC 141 Z9 143 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2001 VL 132 IS 6 BP 903 EP 909 DI 10.1016/S0002-9394(01)01256-9 PG 7 WC Ophthalmology SC Ophthalmology GA 498JT UT WOS:000172506900014 PM 11730656 ER PT J AU Saramaki, O Willi, N Bratt, O Gasser, TC Koivisto, P Nupponen, NN Bubendorf, L Visakorpi, T AF Saramaki, O Willi, N Bratt, O Gasser, TC Koivisto, P Nupponen, NN Bubendorf, L Visakorpi, T TI Amplification of EIF3S3 gene is associated with advanced stage in prostate cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; ALLELIC IMBALANCE; BREAST-CANCER; MESSENGER-RNA; PROTEIN; INITIATION-FACTOR-3; TRANSFORMATION; CHROMOSOME-8; PROGRESSION; CARCINOMAS AB Gain of the long arm of chromosome 8 (8q) is one of the most common gains found in the advanced prostate cancer by comparative genomic hybridization. We have previously identified a putative target gene for the 8q gain, EIF3S3, that encodes a p40 subunit of eukaryotic translation initiation factor 3 (eIF3). Here, we studied the frequency of the EIF3S3 amplification in different stages of prostate cancer and co-amplification of EIF3S3 and oncogene MYC. In addition, prognostic utility of the EIF3S3 copy number alteration was evaluated. The analyses were done with fluorescence in situ hybridization and tissue microarray technology. High-level amplification of EIF3S3 was found in 11 of 125 (9%) of pT1/pT2 tumors, 12 of 44 (27%) of pT3/pT4 tumors, and 8 of 37 (22%) of lymph node metastases as well as in 26 of 78 (33%) and 15 of 30 (50%) of hormone refractory locally recurrent tumors and metastases, respectively. The amplification was associated with high Gleason score (P < 0.001). One of the 79 tumors with EIF3S3 amplification had only two copies of MYC, whereas all tumors with amplification of MYC had also amplification of EIF3S3 indicating common co-amplification of the genes. Gain of EIF3S3 was associated with poor cancer-specific survival in incidentally found prostate carcinomas (P = 0.023). In the analyses of prostatectomy-treated patients, the amplification was not statistically significantly associated with progression-free time. In conclusion, amplification of EIF3S3 gene is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease. C1 Tampere Univ Hosp, Canc Genet Lab, Inst Med Technol, Tampere, Finland. Tampere Univ Hosp, Dept Clin Genet, Tampere, Finland. Univ Basel, Inst Pathol, Basel, Switzerland. Univ Basel, Urol Clin BS BL, Basel, Switzerland. Helsingborg Hosp, Dept Surg, Helsingborg, Sweden. NHGRI, Canc Genet Branch, NIH, Bethesda, MD USA. RP Visakorpi, T (reprint author), Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland. RI Bubendorfl, Lukas/H-5880-2011 NR 29 TC 76 Z9 84 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2001 VL 159 IS 6 BP 2089 EP 2094 DI 10.1016/S0002-9440(10)63060-X PG 6 WC Pathology SC Pathology GA 497LR UT WOS:000172457400014 PM 11733359 ER PT J AU Kumaki, F Matsui, K Kawai, T Ozeki, Y Yu, ZX Ferrans, VJ Travis, WD AF Kumaki, F Matsui, K Kawai, T Ozeki, Y Yu, ZX Ferrans, VJ Travis, WD TI Expression of matrix metalloproteinases in invasive pulmonary adenocarcinoma with bronchioloalveolar component and atypical adenomatous hyperplasia SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PERIPHERAL LUNG; GELATINASE-A; TISSUE INHIBITOR; SCAR CARCINOMA; TUMOR-CELLS; MT-MMP; METASTASIS; CANCERS; ACTIVATION; PRECURSOR AB To investigate the association between the expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) and the clinicopathological features in lepidic and invasive components of adenocarcinoma of the lung, we performed immunostaining for type IV collagen, various MMPs, and TIMPs in 27 cases of invasive adenocarcinomas and 5 cases of atypical adenomatous hyperplasia of alveolar epithelial cells (AAH). Mean extent of lepidic growth was 61% and the survival was significantly better in cases with 50% or more lepidic component. The preservation of type IV collagen in lepidic areas correlated inversely with lymphatic or vascular invasion (P = 0.02 and 0.002, respectively). Five-year survival was reduced in cases showing destruction of type IV collagen (P = 0.004) or expression of MMP-2 (P = 0.008) in lepidic areas. MMP-2 co-localized with MT-1-MMP (its activating enzyme) and TIMP-2 in neoplastic cells. Reactivity for other MMPs and TIMPs did not correlate with destruction of type IV collagen or prognosis. Type IV collagen was preserved in all cases of AAH. MMP-2, but not MT-1-MMP, was expressed in two of the five cases of AAH. immunostaining for type TV collagen MMP-2 is useful in evaluating the prognosis of the lung. C1 Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Natl Def Med Coll, Dept Pathol, Tokorozawa, Saitama, Japan. Natl Def Med Coll, Dept Thorac Surg, Tokorozawa, Saitama, Japan. Natl Inst Hlth, NHLBI, Pathol Sect, Bethesda, MD USA. RP Travis, WD (reprint author), Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, 6825 16th St NW,Dist Columbia, Washington, DC 20306 USA. NR 36 TC 41 Z9 44 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2001 VL 159 IS 6 BP 2125 EP 2135 DI 10.1016/S0002-9440(10)63064-7 PG 11 WC Pathology SC Pathology GA 497LR UT WOS:000172457400018 PM 11733363 ER PT J AU Torhorst, J Bucher, C Kononen, J Haas, P Zuber, M Kochli, OR Mross, F Dieterich, H Moch, H Mihatsch, M Kallioniemi, OP Sauter, G AF Torhorst, J Bucher, C Kononen, J Haas, P Zuber, M Kochli, OR Mross, F Dieterich, H Moch, H Mihatsch, M Kallioniemi, OP Sauter, G TI Tissue microarrays for rapid linking of molecular changes to clinical endpoints SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HUMAN-BREAST CANCER; P53 PROTEIN EXPRESSION; RENAL-CELL CARCINOMA; HER-2 NEU ONCOGENE; TERM FOLLOW-UP; RECEPTOR ASSAYS; HETEROGENEITY; ESTROGEN; PROGNOSIS; SURVIVAL AB Advances in genomics and proteomics are dramatically increasing the need to evaluate large numbers of molecular targets for their diagnostic, predictive or prognostic value in clinical oncology. Conventional molecular pathology techniques are often tedious, time-consuming, and require a lot of tissue, thereby limiting both the number of tissues and the number of targets that can be evaluated. Here, we demonstrate the power of our recently described tissue microarray (TMA) technology in analyzing prognostic markers in a series of 553 breast carcinomas. Four independent TMAs were constructed by acquiring 0.6 nun biopsies from one central and from three peripheral regions of each of the formalin-fixed paraffin embedded tumors. Immunostaining of TMA sections and conventional "large" sections were performed for two well-established prognostic markers, estrogen receptor (ER) and progesterone receptor (PR), as well as for p53, another frequently examined protein for which the data on prognostic utility in breast cancer are less unequivocal. Compared with conventional large section analysis, a single sample from each tumor identified about 95% of the information for ER, 75 to 81% for PR, and 70 to 74% for p53. However, all 12 TMA analyses (three antibodies on four different arrays) yielded as significant or more significant associations with tumor-specific survival than large section analyses (p < 0.0015 for each of the 12 comparisons). A single sample from each tumor was sufficient to identify associations between molecular alterations and clinical outcome. It is concluded that, contrary to expectations, tissue heterogeneity did not negatively influence the predictive power of the TMA results. TMA technology will be of substantial value in rapidly translating genomic and proteomics information to clinical-applications. C1 Frauenklin, Rheinfelden, Germany. Kreiskrankenhauses, Lorrach, Germany. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Basel, Dept Surg, Basel, Switzerland. Univ Basel, Inst Pathol, Basel, Switzerland. RP Sauter, G (reprint author), Univ Hosp, Inst Pathol, Schonbeinstr 40, CH-4003 Basel, Switzerland. RI bucher, christoph/A-2520-2008; Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 27 TC 377 Z9 391 U1 2 U2 16 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2001 VL 159 IS 6 BP 2249 EP 2256 DI 10.1016/S0002-9440(10)63075-1 PG 8 WC Pathology SC Pathology GA 497LR UT WOS:000172457400029 PM 11733374 ER PT J AU Fuhrer, MJ AF Fuhrer, MJ TI Federal agency management practices for prioritizing and funding rehabilitation-related research SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE rehabilitation research; federal agencies; priorities; funding ID NIH AB This article focuses on the processes by which priorities are established and research is funded by three organizational entities that finance the preponderance of this country's rehabilitation-related research: the National Institute on Disability and Rehabilitation Research, the National Center for Medical Rehabilitation Research (the focal point of rehabilitation research at the National Institutes of Health), and the National Institutes of Health in aggregate (i.e., the several institutes that support rehabilitation-related research), Two perspectives are emphasized: the stakeholders' opportunities to influence deliberations at key steps in setting priorities and reaching funding decisions and the extent to which these management practices are explicitly conceptualized, transparent, and evidence-based. Those perspectives are brought to bear on three pivotal considerations: the agencies' commitment to directed vs. nondirected research, the role they assign to strategic planning, and their approach to reviewing applications for funding. C1 NICHHD, NIH, Bethesda, MD USA. RP Fuhrer, MJ (reprint author), 13 Kings Valley Ct, Damascus, MD 20872 USA. NR 12 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD DEC PY 2001 VL 80 IS 12 BP 926 EP 934 DI 10.1097/00002060-200112000-00010 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 495TW UT WOS:000172357300009 PM 11821676 ER PT J AU Marcell, TJ Harman, SM Urban, RJ Metz, DD Rodgers, BD Blackman, MR AF Marcell, TJ Harman, SM Urban, RJ Metz, DD Rodgers, BD Blackman, MR TI Comparison of GH, IGF-I, and testosterone with mRNA of receptors and myostatin in skeletal muscle in older men SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE androgens; reverse transcription-polymerase chain reaction; gene expression; elderly; protein metabolism ID GROWTH-FACTOR-I; MESSENGER-RNA EXPRESSION; CATABOLIC RESPONSE; PROTEIN-SYNTHESIS; HORMONE GH; SARCOPENIA; MASS; OXANDROLONE; RAT AB Growth hormone (GH), insulin-like growth factor I (IGF-I), and testosterone (T) are important mediators of muscle protein synthesis, and thus muscle mass, all of which decline with age. We hypothesized that circulating hormones would be related to the transcriptional levels of their respective receptors and that this expression would be negatively related to expression of the myostatin gene. We therefore determined content of mRNA transcripts (by RT-PCR) for GH receptor (GHR), IGF-I, androgen receptor (AR), and myostatin in skeletal muscle biopsy samples from 27 healthy men >65 yr of age. There were no significant relationships between age, lean body mass, or percent body fat and transcript levels of GHR, IGF-I, AR, or myostatin. Moreover, there were no significant correlations of serum GH, IGF-I, or T with their corresponding target mRNA levels (GHR, intramuscular IGF-I, or AR) in skeletal muscle. However, GHR was negatively correlated (r = -0.60, P = 0.001) with myostatin mRNA levels. The lack of apparent relationships of muscle transcripts with their respective ligands in healthy older adults suggests that age-related deficits in both GH and T may lead to an increase in myostatin expression and a disassociation in autocrine IGF-I effects on muscle protein synthesis, both of which could contribute to age-related sarcopenia. C1 NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Div Endocrinol & Metab, Baltimore, MD 21224 USA. Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77555 USA. RP Marcell, TJ (reprint author), Kronos Longev Res Inst, 4455 E Camelback Rd,Ste B135, Phoenix, AZ 85018 USA. FU NCRR NIH HHS [MO-1-RR-02719]; NIA NIH HHS [T32-AG-00250-01A1, R0-1 AG-11002-5] NR 31 TC 57 Z9 58 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD DEC PY 2001 VL 281 IS 6 BP E1159 EP E1164 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 490JA UT WOS:000172047700007 PM 11701429 ER PT J AU Fenton, WS Dickerson, F Boronow, J Hibbeln, JR Knable, M AF Fenton, WS Dickerson, F Boronow, J Hibbeln, JR Knable, M TI A placebo-controlled trial of omega-3 fatty acid (ethyl eicosapentaenoic acid) supplementation for residual symptoms and cognitive impairment in schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB objective: This study determined if augmentation of neuroleptics with 3 g/day of ethyl eicosapentaenoic acid (EPA) improves symptoms and cognition in patients with schizophrenia or schizoaffective disorder. Method: Eighty-seven patients meeting criteria for schizophrenia or schizoaffective disorder who had residual symptoms despite neuroleptic treatment were randomly assigned to receive either 3 g/day of ethyl EPA (N=43) or placebo (N=44) in a 16-week, double-blind supplementation trial. Assessments were performed at baseline and at weeks 1, 2, 4, 8, 12, and 16; a cognitive battery was administered at baseline and at week 16. Results: No differences were found between groups in positive or negative symptoms, mood, cognition, or global impression ratings. Results were similar for the intention-to-treat (N=87) and completer (N=75) groups. Conclusions: For schizophrenia patients treated with 3 g/day of ethyl EPA, improvement in residual symptoms and cognitive impairment was no greater than for schizophrenia patients treated with placebo. C1 NIMH, Bethesda, MD 20892 USA. Sheppard & Enoch Pratt Hosp, Towson, MD USA. NIAAA, Rockville, MD 20852 USA. Stanley Fdn Res Programs, Bethesda, MD USA. RP Fenton, WS (reprint author), NIMH, 6001 Execut Blvd,Rm 6217,MSC 9621, Bethesda, MD 20892 USA. NR 12 TC 153 Z9 158 U1 0 U2 12 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2001 VL 158 IS 12 BP 2071 EP 2074 DI 10.1176/appi.ajp.158.12.2071 PG 4 WC Psychiatry SC Psychiatry GA 497JQ UT WOS:000172452100024 PM 11729030 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI Untitled SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 Natl Lib Med, Hist Med Div, NIH, Bethesda, MD 20894 USA. Univ Rochester, Dept Hist, Rochester, NY 14642 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14642 USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2001 VL 91 IS 12 BP 1919 EP 1919 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 496TF UT WOS:000172412100004 ER PT J AU Fee, E Brown, TM Lazarus, J Theerman, P AF Fee, E Brown, TM Lazarus, J Theerman, P TI The influenza pandemic of 1918 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 Natl Lib Med, Hist Med Div, Nihon Univ, Bethesda, MD 20894 USA. Univ Rochester, Dept Hist, Rochester, NY 14627 USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY 14627 USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 2 TC 4 Z9 5 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2001 VL 91 IS 12 BP 1953 EP 1953 DI 10.2105/AJPH.91.12.1953 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 496TF UT WOS:000172412100016 PM 11726373 ER PT J AU Olden, K Guthrie, J Newton, S AF Olden, K Guthrie, J Newton, S TI A bold new direction for environmental health research SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material ID GENOME PROJECT AB The biotechnology revolution has opened new opportunities for addressing current inadequacies in decision making regarding environmental health. Strategic investments need to be made (1) to develop high-throughput technologies that could accelerate toxicity testing and generate a mechanistic understanding of toxicity, (2) to incorporate individual susceptibility into risk assessments, and (3) to establish a rational basis for testing and regulatory decision making. New initiatives of the National Institute of Environmental Health Sciences, including the Environmental Genome Project and the Toxicogenomics Center, are discussed. C1 NIEHS, Off Planning & Evaluat, Res Triangle Pk, NC 27709 USA. Natl Toxicol Program, Res Triangle Pk, NC USA. RP Olden, K (reprint author), NIEHS, Off Planning & Evaluat, POB 12233, Res Triangle Pk, NC 27709 USA. NR 8 TC 26 Z9 26 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2001 VL 91 IS 12 BP 1964 EP 1967 DI 10.2105/AJPH.91.12.1964 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 496TF UT WOS:000172412100018 PM 11726375 ER PT J AU Minter, KR Gladwin, MT AF Minter, KR Gladwin, MT TI Pulmonary complications of sickle cell anemia - A need for increased recognition, treatment, and research SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID ACUTE CHEST SYNDROME; CHRONIC LUNG-DISEASE; FAT-EMBOLISM; ERYTHROCYTE-MEMBRANES; THALASSEMIA MAJOR; NITRIC-OXIDE; HYPERTENSION; HEMOGLOBIN; MORTALITY; DEATH C1 NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 62 TC 49 Z9 52 U1 0 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2001 VL 164 IS 11 BP 2016 EP 2019 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 504CA UT WOS:000172838600003 PM 11739128 ER PT J AU Avol, EL Gauderman, WJ Tan, SM London, SJ Peters, JM AF Avol, EL Gauderman, WJ Tan, SM London, SJ Peters, JM TI Respiratory effects of relocating to areas of differing air pollution levels SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE air pollution; respiratory system; growth and development ID SOUTHERN CALIFORNIA COMMUNITIES; PULMONARY-FUNCTION; LUNG-FUNCTION; VENTILATORY FUNCTION; INHALABLE PARTICLES; DAILY MORTALITY; CHILDREN; HEALTH; SYMPTOMS; EXPOSURE AB We studied 110 children (59 boys and 51 girls, who were 10 yr of age at enrollment and 15 yr of age at follow-up) who had moved from communities participating in a 10-yr prospective study of respiratory health (The Children's Health Study [CHS]) to determine whether changes in air quality caused by relocation were associated with changes in annual lung function growth rates. The subjects were given health questionnaires and underwent spirometry in their homes across six western states, according to a protocol identical to evaluations performed annually on the CHS cohort in school. Changes in annual average exposure to particulate matter with a mean diameter of 10 mum (PM10) were associated with differences in annual lung function growth rates for FEV1, maximal mid-expiratory flow, and peak expiratory flow rate. As a group, subjects who had moved to areas of lower PM10 showed increased growth in lung function and subjects who moved to communities with a higher PM10 showed decreased growth in lung function. A stronger trend was found for subjects who had migrated at least 3 yr before the follow-up visit than for those who had moved in the previous 1 to 2 yr. We conclude that changes in air pollution exposure during adolescent growth years have a measurable and potentially important effect on lung function growth and performance. C1 Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Avol, EL (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, 1540 Alcazar St,Suite 236, Los Angeles, CA 90033 USA. RI Osborne, Nicholas/N-4915-2015; OI Osborne, Nicholas/0000-0002-6700-2284; London, Stephanie/0000-0003-4911-5290 FU NIEHS NIH HHS [5 P30 ES07048] NR 32 TC 136 Z9 141 U1 2 U2 13 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2001 VL 164 IS 11 BP 2067 EP 2072 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 504CA UT WOS:000172838600011 PM 11739136 ER PT J AU Hagaman, DD Okayama, Y D'Ambrosio, C Prussin, C Gilfillan, AM Metcalfe, DD AF Hagaman, DD Okayama, Y D'Ambrosio, C Prussin, C Gilfillan, AM Metcalfe, DD TI Secretion of interleukin-1 receptor antagonist from human mast cells after immunoglobulin E-mediated activation and after segmental antigen challenge SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID ASTHMATIC BRONCHIAL EPITHELIUM; PROINFLAMMATORY CYTOKINES; GUINEA-PIGS; IL-1; EXPRESSION; MODULATION; POPULATION; INHIBITION; IL-1-BETA; HEPARIN AB Mast cells produce substances with antiinflammatory properties in addition to their capacity to release proinflammatory mediators. To further probe the antiinflammatory aspect of mast-cell function we investigated the ability of human mast cells (huMCs) to produce interleukin (IL)-1 receptor antagonist (IL-1ra) in response to high-affinity Fc receptor for immunoglobulin E (FcepsilonRI) aggregation, and examined IL-1ra in bronchoalveolar lavage fluid (BALF) to determine whether it might be of mast-cell origin. Using a ribonuclease protection assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA), IL-1ra message and protein were found to be constitutively expressed in cultured huMCs. Upon stimulation through FcepsilonRI, IL-1ra message was upregulated in huMCs and IL-1ra protein secreted from cultured huMCs and isolated human lung mast cells. By immunoblot analysis, huMCs were found to produce the 17-kD form of IL-1ra and the presence of IL-1ra in human lung mast cells was confirmed by immunohistochemistry. In BALF obtained from allergic asthmatic subjects, IL-1ra production increased after specific antigen challenge, with the 17-kD isoform of IL-1ra predominating. These findings demonstrate that huMCs produce and release IL-1ra after FcepsilonRI aggregation, which may contribute to a local inhibition of IL-1-dependent effects on inflammation in the lung. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Okayama, Y (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C206,10 Ctr Dr MSC 1881, Bethesda, MD 20892 USA. OI Prussin, Calman/0000-0002-3917-3326 NR 32 TC 12 Z9 13 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2001 VL 25 IS 6 BP 685 EP 691 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 505MD UT WOS:000172915800006 PM 11726393 ER PT J AU Booth, BW Adler, KB Bonner, JC Tournier, F Martin, LD AF Booth, BW Adler, KB Bonner, JC Tournier, F Martin, LD TI Interleukin-13 induces proliferation of human airway epithelial cells in vitro via a mechanism mediated by transforming growth factor-alpha SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID FACTOR-RECEPTOR; IN-VITRO; EGF-RECEPTOR; EXPRESSION; INJURY; RATS; ASTHMA; LUNG AB Remodeling of the airways, as occurs in asthmatic patients, is associated with the continual presence of inflammatory mediators and Th2 cytokines, especially interleukin (IL)-13, during cycles of epithelial injury and repair. In this study, we examined the effect of IL-13 on well-differentiated normal human bronchial epithelial (NHBE) cells maintained in air-liquid interface culture. IL-13 induced proliferation of NHBE cells after 24 h exposure, as reflected by [H-3]thymidine uptake and cell counts. The effects of IL-13 were mediated through the epidermal growth factor receptor (EGFR), as proliferation was attenuated by AG1478, an EGFR tyrosine kinase inhibitor. Proliferation appeared to be mediated by transforming growth factor (TGF)-alpha, a potent ligand for EGFR, which was released rapidly from NHBE cells in response to IL-13. Neutralizing antibody to TGF-alpha, but not antibodies against other potentially important growth factors (EGF, heparin binding epidermal growth factor-like growth factor [HB-EGF], platelet-derived growth factor [PDGF]), inhibited the mitogenic response to IL-13. This study provides the first experimental evidence that IL-13 can initiate a proliferative response of human airway epithelium in the absence of inflammatory cells or other cell types. The results are consistent with a mechanism whereby IL-13 induces release of TGF-alpha from the epithelial cells, which in turn binds via an autocrine/paracrine-type action to the EGFR, initiating proliferation. IL-13-induced airway remodeling in vivo may involve this epithelium-driven response. C1 N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, Raleigh, NC 27606 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Paris 07, Lab Cytophysiol & Toxicol Cellulaire, Paris, France. RP Martin, LD (reprint author), N Carolina State Univ, Coll Vet Med, Dept Anat Physiol Sci & Radiol, Raleigh, NC 27606 USA. FU NHLBI NIH HHS [HL36982, HL66236] NR 31 TC 81 Z9 83 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2001 VL 25 IS 6 BP 739 EP 743 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 505MD UT WOS:000172915800013 PM 11726400 ER PT J AU Buccholz, DR Espira, A Barber, P Hayes, TB AF Buccholz, DR Espira, A Barber, P Hayes, TB TI Juvenile patterns and sexual dichromatism in the endemic African reedfrog family, Hyperoliidae SO AMERICAN ZOOLOGIST LA English DT Meeting Abstract C1 Univ Oxford, Oxford OX1 2JD, England. Harvard Univ, Cambridge, MA 02138 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. NICHHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 0003-1569 J9 AM ZOOL JI Am. Zool. PD DEC PY 2001 VL 41 IS 6 BP 1400 EP 1400 PG 1 WC Zoology SC Zoology GA 529NX UT WOS:000174306500087 ER PT J AU Frazier, M Huey, RB Berrigan, D AF Frazier, M Huey, RB Berrigan, D TI Thermal dependence of Darwinian fitness in insects: Biogeographic patterns. SO AMERICAN ZOOLOGIST LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 0003-1569 J9 AM ZOOL JI Am. Zool. PD DEC PY 2001 VL 41 IS 6 BP 1446 EP 1447 PG 2 WC Zoology SC Zoology GA 529NX UT WOS:000174306500241 ER PT J AU Piermarini, PM Verlander-Reed, JV Royaux, IE Evans, DH AF Piermarini, PM Verlander-Reed, JV Royaux, IE Evans, DH TI Immunochemical evidence for pendrin in the gills of the euryhaline Atlantic stingray (Dasyatis sabina): implications for ionic and acid/base regulation. SO AMERICAN ZOOLOGIST LA English DT Meeting Abstract C1 Univ Florida, Gainesville, FL 32611 USA. NHGRI, Genome Technol Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SOC INTEGRATIVE COMPARATIVE BIOLOGY PI MCLEAN PA 1313 DOLLEY MADISON BLVD, NO 402, MCLEAN, VA 22101 USA SN 0003-1569 J9 AM ZOOL JI Am. Zool. PD DEC PY 2001 VL 41 IS 6 BP 1556 EP 1556 PG 1 WC Zoology SC Zoology GA 529NX UT WOS:000174306500606 ER PT J AU Sipe, JD Cohen, AS AF Sipe, JD Cohen, AS TI History of the amyloid fibril, amyloid symposia and amyloid journal SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Editorial Material C1 NIH, Ctr Sci Review, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Amyloid Program, Boston, MA 02118 USA. RP Sipe, JD (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr,Room 4106,MSC 7814, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD DEC PY 2001 VL 8 SU 2 BP 9 EP 10 PG 2 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 509ED UT WOS:000173132100004 ER PT J AU Sipe, JD Schreiber, BM AF Sipe, JD Schreiber, BM TI Serum amyloid A, conformation, catabolism and cholesterol implications for amyloid A fibril formation SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article; Proceedings Paper CT 9th International Symposium on Amyloidosis CY JUL 15-21, 2001 CL BUDAPEST, HUNGARY SP Neurochem Inc, Prototech Inc C1 NIH, Bethesda, MD 20814 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. RP Sipe, JD (reprint author), NIH, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD DEC PY 2001 VL 8 SU 2 BP 29 EP 30 PG 2 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 509ED UT WOS:000173132100027 ER PT J AU Kumon, Y Suehiro, T Hosokawa, T Ikeda, Y Sipe, JD Hashimoto, K AF Kumon, Y Suehiro, T Hosokawa, T Ikeda, Y Sipe, JD Hashimoto, K TI Acute-phase serum amyloid A (A-SAA) is chemotactic for cultured human aortic smooth muscle cells SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Meeting Abstract C1 Kochi Med Sch, Dept Internal Med 2, Kochi, Japan. NIH, Ctr Sci Review, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD DEC PY 2001 VL 8 SU 2 BP 34 EP 34 PG 1 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 509ED UT WOS:000173132100034 ER PT J AU Weller, MG Zeck, A Eikenberg, A Nagata, S Ueno, Y Niessner, R AF Weller, MG Zeck, A Eikenberg, A Nagata, S Ueno, Y Niessner, R TI Development of a direct competitive microcystin immunoassay of broad specificity SO ANALYTICAL SCIENCES LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; BLUE-GREEN-ALGAE; ENZYME-IMMUNOASSAY; NITROAROMATIC RESIDUES; POLYCLONAL ANTIBODIES; INCREASED SENSITIVITY; TRIAZINE HERBICIDES; QUANTIFICATION; REACTIVITY; NODULARIN C1 Tech Univ Munich, Inst Hydrochem, D-81377 Munich, Germany. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Yashio Inst Environm Sci, Tokyo 1620812, Japan. RP Weller, MG (reprint author), Tech Univ Munich, Inst Hydrochem, Marchioninistr 17, D-81377 Munich, Germany. RI Weller, Michael G./B-5015-2008; Niessner, Reinhard/D-1502-2010 OI Weller, Michael G./0000-0003-2767-2029; NR 33 TC 19 Z9 19 U1 1 U2 12 PU JAPAN SOC ANALYTICAL CHEMISTRY PI TOKYO PA 26-2 NISHIGOTANDA 1 CHOME SHINAGAWA-KU, TOKYO, 141, JAPAN SN 0910-6340 J9 ANAL SCI JI Anal. Sci. PD DEC PY 2001 VL 17 IS 12 BP 1445 EP 1448 DI 10.2116/analsci.17.1445 PG 4 WC Chemistry, Analytical SC Chemistry GA 505XF UT WOS:000172940300015 PM 11783797 ER PT J AU Nagai, M Yamano, Y Brennan, MB Mora, CA Jacobson, S AF Nagai, M Yamano, Y Brennan, MB Mora, CA Jacobson, S TI Increased HTLV-I proviral load and preferential expansion of HTLV-I Tax-specific CD8(+) T cells in cerebrospinal fluid from patients with HAM/TSP SO ANNALS OF NEUROLOGY LA English DT Article ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; ACTIVATED LYMPHOCYTES-T; PERIPHERAL-BLOOD; MYELOPATHY; PROTEIN; INTEGRATION; ANTIBODIES; DNA AB To date, high human T-cell lymphotropic virus type I proviral load in patients with human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis has been reported and is thought to be related to the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. However, the proviral load in cerebrospinal. fluid has not been well investigated. We measured human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells from human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis patients using real-time quantitative polymerase chain reaction (TaqMan). Human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells were significantly higher than that of the matched peripheral blood mononuclear cells, and a high ratio of human T-cell lymphotropic virus type I proviral load in cerebrospinal fluid cells to peripheral blood mononuclear cells were observed in patients with short duration of illness. Human T-cell lymphotropic virus type I Tax-specific CD8(+) T cells, as detected by peptide-loaded HLA tetramers, accumulated in cerebrospinal fluid compared with that in peripheral blood mononuclear cells, while the frequency of cytomegalovirus-specific CD8(+) T cells in cerebrospinal fluid was reduced. These observations suggest that accumulation of both human T-cell lymphotropic virus type I-infected cells and preferential expansion of human T-cell lymphotropic virus type I-specific CD8(+) cells in cerebrospinal fluid may play a role in the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. C1 NINCDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Jacobson, S (reprint author), NINCDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 23 TC 75 Z9 75 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2001 VL 50 IS 6 BP 807 EP 812 DI 10.1002/ana.10065 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 496RV UT WOS:000172410900018 PM 11761481 ER PT J AU Csako, G McGriff, NJ Rotman-Pikielny, P Sarlis, NJ Pucino, F AF Csako, G McGriff, NJ Rotman-Pikielny, P Sarlis, NJ Pucino, F TI Exaggerated levothyroxine malabsorption due to calcium carbonate supplementation in gastrointestinal disorders SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE calcium carbonate; levothyroxine; malabsorption ID INTESTINAL ADSORPTION; THYROID-HORMONE; CELIAC-DISEASE; L-THYROXINE; HYPOTHYROIDISM; SUCRALFATE; ANTIBODIES; ABSORPTION; EFFICACY; THERAPY AB OBJECTIVE: To describe a patient with primary hypothyroidism in whom ingestion of levothyroxine with calcium carbonate led to markedly elevated serum thyrotropin concentrations. CASE SUMMARY: A 61-year-old white woman with primary hypothyroidism, systemic lupus erythematosus, celiac disease, and history of Whipple resection for pancreatic cancer was euthyroid with levothyroxine 175-188 mug/d. After taking a high dose of calcium carbonate (1250 mg three times daily) with levothyroxine, she developed biochemical evidence of hypothyroidism (thyrotropin up to 41.4 mU/L) while remaining clinically euthyroid. Delaying calcium carbonate administration by four hours returned her serum thyrotropin to a borderline high concentration (5.7 mU/L) within a month. Serum concentrations of unbound and total thyroxine and triiodothyronine tended to decrease, but remained borderline low to normal while the patient concomitantly received levothyroxine and calcium carbonate. DISCUSSION: Concomitant administration of levothyroxine and calcium carbonate often results in levothyroxine malabsorption. While in most patients the clinical consequences of this interaction, even with prolonged exposure, are relatively small, overt hypothyroidism may develop in patients with preexisting malabsorption disorders. However, as the current case illustrates, the clinical manifestations of the initial levothyroxine deficit may not always be apparent and, of all usual laboratory thyroid function tests, only thyrotropin measurement will reliably uncover the exaggerated levothyroxine malabsorption. CONCLUSIONS: Decreased absorption of levothyroxine when given with calcium carbonate may be particularly pronounced in patients with preexisting malabsorption disorders. Once recognized, a change in drug administration schedule usually minimizes or eliminates this interaction. C1 NIH, Dept Lab Med, Ctr Clin, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Sci, Dept Pharm Practice & Adm, Philadelphia, PA USA. NIH, Dept Pharm, Ambulatory Care Clin Pharm Team, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD USA. RP Csako, G (reprint author), NIH, Dept Lab Med, Ctr Clin, Warren G Magnuson Clin Ctr, Bldg 10,Rm 2C-407, Bethesda, MD 20892 USA. NR 30 TC 13 Z9 13 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD DEC PY 2001 VL 35 IS 12 BP 1578 EP 1583 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 505VP UT WOS:000172936500015 PM 11793625 ER PT J AU Zogakis, TG Bartlett, DL Libutti, SK Liewehr, DJ Steinberg, SM Fraker, DL Alexander, HR AF Zogakis, TG Bartlett, DL Libutti, SK Liewehr, DJ Steinberg, SM Fraker, DL Alexander, HR TI Factors affecting survival after complete response to isolated limb perfusion in patients with in-transit melanoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 54th Annual Meeting of the Society-of-Surgical-Oncology CY MAR 15-18, 2001 CL WASHINGTON, D.C. SP Soc Surg Oncol DE isolated perfusion; melanoma; tumor necrosis factor; hyperthermia; melphalan ID TUMOR-NECROSIS-FACTOR; MALIGNANT-MELANOMA; PROGNOSTIC FACTORS; INTERFERON-GAMMA; EXTREMITY; MELPHALAN; DISSECTION AB Background: Isolated limb perfusion (ILP) results in complete response (CR) rates of 60% to 90% in patients with regionally advanced melanoma. Survival after a CR may be influenced by various factors, particularly out-of-field disease in iliac lymph nodes (ILN) identified during lower-extremity ILP. We examined clinical and pathological parameters, including ILN status and outcome, for patients with in-transit melanoma who had a CR to ILP. Methods: From May 1992 to July 1997, 50 patients (16 men and 34 women; median age, 57 years) with stage IIIA or IIIAB melanoma had a CR to a 90-minute hyperthermic iliac ILP with melphalan (10 mg/L limb volume, n=20) or melphalan and tumor necrosis factor (4-6 mg +/- 200 mug interferon; n=30). Clinical and pathological parameters were analyzed by univariate and Cox proportional hazards models to determine which were associated with survival or in-field recurrence. Results: The median in-field recurrence-free survival in the cohort of 50 patients after a CR to U-P was 1.4 years, and the actuarial 5-year in-field recurrence-free survival was 30%. By univariate analysis, there was a trend for improved outcome with female sex and stage IIIA (vs. IIIAB) at initial diagnosis was associated with improved survival after a CR to ILP (P=.056 and .012, respectively). Eleven (22%) of 50 patients had positive ILNs identified and resected at ILP. The probability of overall in-field recurrence was 70% after 4 years, and there was no difference between those with or without positive ILNs; median time to in-field recurrence was 13 and 19 months, respectively (P=.62). Similarly, overall survival was not influenced by positive ILN status (median [months]: +ILN, 69 vs. -ILN, 58; P=.68). Of note, Cox models identified that the risk of death was significantly greater in those with a history of prior systemic therapy (hazard ratio: 2.67 [95% confidence interval, 1.17-6.11]; P=.02) and those with an in-transit lesion size greater than or equal to1.4 cm(2) (hazard ratio, 3.12 [95% confidence interval, 1.30-7.5]; P=.011). When these two variables were combined, there was a highly significant association with shortened survival (P=.002 by log-rank test). Conclusions: These data indicate that for patients undergoing ILP and in whom positive ILNs are found and resected, ILP is justified. In addition, patients who have a CR after ILP and have a history of prior treatment or larger lesions should be considered for adjuvant systemic therapy. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B07,10 Ctr Dr, Bethesda, MD 20892 USA. NR 20 TC 30 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2001 VL 8 IS 10 BP 771 EP 778 DI 10.1245/aso.2001.8.10.771 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 500ZD UT WOS:000172657800008 PM 11776490 ER PT J AU Libutti, SK Alexander, HR Choyke, P Bartlett, DL Bacharach, SL Whatley, M Jousse, F Eckelman, WC Kranda, K Neumann, RD Carrasquillo, JA AF Libutti, SK Alexander, HR Choyke, P Bartlett, DL Bacharach, SL Whatley, M Jousse, F Eckelman, WC Kranda, K Neumann, RD Carrasquillo, JA TI A prospective study of 2-[F-18] fluoro-2-deoxy-D-glucose/positron emission tomography scan, Tc-99m-labeled arcitumomab (CEA-scan), and blind second-look laparotomy for detecting colon cancer recurrence in patients with increasing carcinoembryonic antigen levels SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE carcinoembryonic antigen; positron emission tomography; FDG; colon cancer recurrence; radioimmunoscintigraphy ID ISOLATED HEPATIC PERFUSION; TUMOR-NECROSIS-FACTOR; DIRECTED 2ND-LOOK SURGERY; COLORECTAL-CANCER; FDG-PET; MONOCLONAL-ANTIBODY; RECTAL-CARCINOMA; LIVER RESECTION; IMMUNOSCINTIGRAPHY; METASTASES AB Background: An increasing carcinoembryonic antigen (CEA) level in the absence of disease on imaging studies can present a diagnostic challenge. We evaluated 2-[F-18] fluoro-2-deoxy-D-glucose and positron emission tomography (FDG-PET) scan and CEA scan before second-look laparotomy as a means of localizing recurrent colorectal cancer. Methods: Patients underwent computed tomography scan, bone scan, colonoscopy, and magnetic resonance imaging, and those without evidence of disease or resectable disease in the abdomen had FDG-PET and CEA scans. At second-look laparotomy, a surgeon blinded to the results of the FDG-PET and CEA scans performed an exploration and mapped findings. A second surgeon, with knowledge of the FDG-PET and CEA scans, then explored the patient; all lesions were biopsied or resected for pathology. Results: In 28 patients explored, disease was found at operation in 26 (94%). Ten had unresectable disease. FDG-PET scans predicted unresectable disease in 90% of patients. CEA scans failed to predict unresectable disease in any patient, In 16 patients found to have resectable disease or disease that could be treated with regional therapy, FDG-PET scan predicted this in 81% and CEA scan in 13%. Conclusions: FDG-PET scan can predict those patients who would likely benefit from a laparotomy. If the FDG-PET scan indicates resectable disease, laparotomy can be considered. However, if the findings predict unresectable disease or the absence of disease, the patient should pursue systemic therapy or continued observation. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Positron Emiss Tomog, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10,Room 3C428, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 38 TC 46 Z9 50 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD DEC PY 2001 VL 8 IS 10 BP 779 EP 786 DI 10.1245/aso.2001.8.10.779 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 500ZD UT WOS:000172657800009 PM 11776491 ER PT J AU Chiou, CC Mavrogiorgos, N Tillem, E Hector, R Walsh, TJ AF Chiou, CC Mavrogiorgos, N Tillem, E Hector, R Walsh, TJ TI Synergy, pharmacodynamics, and time-sequenced ultrastructural changes of the interaction between nikkomycin Z and the echinocandin FK463 against Aspergillus fumigatus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LIPOPEPTIDE ANTIFUNGAL AGENT; CANDIDA-ALBICANS; IMPORTANT FUNGI; PAPULACANDIN-B; MOUSE MODELS; PROTOPLASTS; EFFICACY; SYNTHASE AB We investigated the potential synergy between two cell wall-active agents, the echinocandin FK463 (FK) and the chitin synthase inhibitor nikkomycin Z (NZ), against 16 isolates of filamentous fungi. Susceptibility testing was performed with a broth macrodilution procedure by NCCLS methods. The median minimal effective concentration (MEC) of FK against all Aspergillus species was 0.25 mug/ml (range, 0.05 to 0.5 mug/ml). For Fusarium solani and Rhizopus oryzae, MECs of FK were > 512 mug/ml. The median MEC of NZ against Aspergillus fumigatus was 32 mug/ml (range, 8 to 64 mug/ml), and that against R. oryzae was 0.5 mug/ml (range, 0.06 to 2 mug/ml); however, for the other Aspergillus species, as well as F. solani, MECs were > 512 mug/ml. A checkerboard inhibitory assay demonstrated synergy against A. fumigatus (median fractional inhibitory concentration index = 0.312 [range, 0.15 to 0.475]). The effect was additive to indifferent against R. oryzae and indifferent against other Aspergillus spp. and F. solani. We further investigated the pharmacodynamics of hyphal damage by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and examined the time-sequenced changes in hyphal ultrastructure. Significant synergistic hyphal damage was demonstrated with the combination of NZ (2 to 32 mug/ml) and FK (0.03 to 0.5 mug/ml) over a wide range of concentrations (P < 0.001). The synergistic effect was most pronounced after 12 h of incubation and was sustained through 24 h. Time-sequenced light and electron microscopic studies demonstrated that structural alterations of hyphae were profound, with marked transformation of hyphae to blastospore-like structures, in the presence of FK plus NZ, while fungi treated with a single drug showed partial recovery at 24 h. The methods used in this study may be applicable to elucidating the activity and interaction of other cell wall-active agents. In summary, these two cell wall-targeted antifungal agents, FK and NZ, showed marked time-dependent in vitro synergistic activity against A. fumigatus. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Vet Gen Hosp, Dept Pediat, Kaohsiung, Taiwan. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N-240, Bethesda, MD 20892 USA. NR 18 TC 82 Z9 85 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2001 VL 45 IS 12 BP 3310 EP 3321 DI 10.1128/AAC.45.12.3310-3321.2001 PG 12 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 494UT UT WOS:000172304800005 PM 11709302 ER PT J AU Groll, AH Mickiene, D Petraitis, V Petraitiene, R Ibrahim, KH Piscitelli, SC Bekersky, I Walsh, TJ AF Groll, AH Mickiene, D Petraitis, V Petraitiene, R Ibrahim, KH Piscitelli, SC Bekersky, I Walsh, TJ TI Compartmental pharmacokinetics and tissue distribution of the antifungal echinocandin lipopeptide micafungin (FK463) in rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID EXPERIMENTAL DISSEMINATED CANDIDIASIS; ALBICANS INFECTION; IMPORTANT FUNGI; MOUSE MODELS; EFFICACY; AGENT; ASPERGILLOSIS; INHIBITOR; LY303366; SYNTHASE AB The plasma pharmacokinetics and tissue distribution of the novel antifungal echinocandin-like lipopeptide micafungin (FK463) were investigated in healthy rabbits. Cohorts of three animals each received micafungin at 0.5, 1, and 2 mg/kg of body weight intravenously once daily for a total of 8 days. Serial plasma samples were collected on days I and 7, and tissue samples were obtained 30 min after the eighth dose. Drug concentrations were determined by validated high-performance liquid chromatographic methods. Plasma drug concentration data were fit to a two-compartment pharmacokinetic model, and pharmacokinetic parameters were estimated using weighted nonlinear least-square regression analysis. Micafungin demonstrated linear plasma pharmacokinetics without changes in total clearance and dose-normalized area under the concentration-time curve from 0 It to infinity. After administration of single doses to the rabbits, mean peak plasma drug concentrations ranged from 7.62 mug/ml at 0.5 mg/kg to 16.8 mug/ml at 2 mg/kg, the area under the concentration-time curve from 0 to 24 h ranged from 5.66 to 21.79 mug.h/ml, the apparent volume of distribution at steady state ranged from 0.296 to 0.343 liter/kg, and the elimination half-life ranged from 2.97 to 3.20 h, respectively. No significant changes in pharmacokinetic parameters and no accumulation was noted after multiple dosing. Mean tissue micafungin concentrations 30 min after the last of eight daily doses were highest in the lung (2.26 to 11.76 mug/g), liver (2.05 to 8.82 mug/g), spleen (1.87 to 9.05 mug/g), and kidney (1.40 to 6.12 mug/g). While micafungin was not detectable in cerebrospinal fluid, the concentration in brain tissue ranged from 0.08 to 0.18 mug/g. These findings indicate linear disposition of micafungin at dosages of 0.5 to 2 mg/kg and achievement of potentially therapeutic drug concentrations in plasma and tissues that are common sites of invasive fungal infections. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Pharmacokinet Res Lab, Bethesda, MD 20892 USA. Fujisawa Healthcare USA, Deerfield, IL USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 72 Z9 78 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2001 VL 45 IS 12 BP 3322 EP 3327 DI 10.1128/AAC.45.12.3322-3327.2001 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 494UT UT WOS:000172304800006 PM 11709303 ER PT J AU Walsh, TJ Goodman, JL Pappas, P Bekersky, I Buell, DN Roden, M Barrett, J Anaissie, EJ AF Walsh, TJ Goodman, JL Pappas, P Bekersky, I Buell, DN Roden, M Barrett, J Anaissie, EJ TI Safety, tolerance, and pharmacokinetics of high-dose liposomal amphotericin B (AmBisome) in patients infected with Aspergillus species and other filamentous fungi: Maximum tolerated dose study SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PULMONARY ASPERGILLOSIS; NEUTROPENIC PATIENTS; LIPID COMPLEX; INVASIVE ASPERGILLOSIS; ANTIFUNGAL ACTIVITY; CANDIDA-ALBICANS; LEUKOPENIC MICE; RECENT PROGRESS; FORMULATION; TOXICITY AB We conducted a phase I-II study of the safety, tolerance, and plasma pharmacokinetics of liposomal amphotericin B (L-AMB; AmBisome) in order to determine its maximally tolerated dosage (MTD) in patients with infections due to Aspergillus spp. and other filamentous fungi. Dosage cohorts consisted of 7.5, 10.0, 12.5, and 15.0 mg/kg of body weight/day; a total of 44 patients were enrolled, of which 21 had a proven or probable infection (13 aspergillosis, 5 zygomycosis, 3 fusariosis). The MTD of L-AMB was at least 15 mg/kg/day. Infusion-related reactions of fever occurred in 8 (19%) and chills and/or rigors occurred in 5 (12%) of 43 patients. Three patients developed a syndrome of substernal chest tightness, dyspnea, and flank pain, which was relieved by diphenhydramine. Serum creatinine increased two times above baseline in 32% of the patients, but this was not dose related. Hepatotoxicity developed in one patient. Steady-state plasma pharmacokinetics were achieved by day 7. The maximum concentration of drug in plasma (C-max) of L-AMB in the dosage cohorts of 7.5, 10.0, 12.5, and 15.0 mg/kg/day changed to 76, 120, 116, and 105 mug/ml, respectively, and the mean area under the concentration-time curve at 24 h (AUC(24)) changed to 692, 1,062, 860, and 554 mug . h/ml, respectively, while mean CL changed to 23, 18, 16, and 25 ml/h/kg, respectively. These data indicate that L-AMB follows dose-related changes in disposition processing (e.g., clearance) at dosages of greater than or equal to7.5 mg/kg/day. Because several extremely ill patients had early death, success was determined for both the modified intent-to-treat and evaluable (7 days of therapy) populations. Response rates (defined as complete response and partial response) were similar for proven and probable infections. Response and stabilization, respectively, were achieved in 36 and 16% of the patients in the modified intent-to-treat population (n = 43) and in 52 and 13% of the patients in the 7-day evaluable population (n = 31). These findings indicate that L-AMB at dosages as high as 15 mg/kg/day follows nonlinear saturation-like kinetics, is well tolerated, and can provide effective therapy for aspergillosis and other filamentous fungal infections. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Div Infect Dis, Minneapolis, MN 55455 USA. Fujisawa Healthcare Inc, Deerfield, IL USA. Univ Alabama, Div Infect Dis, Birmingham, AL USA. Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 49 TC 212 Z9 219 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD DEC PY 2001 VL 45 IS 12 BP 3487 EP 3496 DI 10.1128/AAC.45.12.3487-3496.2001 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 494UT UT WOS:000172304800032 PM 11709329 ER PT J AU Garcia, RG Brank, AS Christman, JK Marquez, VE Eritja, R AF Garcia, RG Brank, AS Christman, JK Marquez, VE Eritja, R TI Synthesis of oligonucleotide inhibitors of DNA (cytosine-C5) methyltransferase containing 5-azacytosine residues at specific sites SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article ID 5-AZA-2'-DEOXYCYTIDINE DECITABINE; PROTECTING GROUPS; CPG SITES; 5-AZACYTIDINE; 5,6-DIHYDRO-5-AZACYTOSINE; METHYLATION; OLIGODEOXYNUCLEOTIDES; DIFFERENTIATION; DERIVATIVES; NUCLEOSIDES AB The incorporation of 5-azacytosine residues into DNA causes potent inhibition of DNA (Cytosine-C5) methyltransferases. The synthesis of oligodeoxyribonucleotides incorporating single or multiple 5-aza-2'-deoxycytidine residues at precise sites was undertaken to generate an array of sequences containing the reactive 5-azacytosine base as specific target sites for enzymatic methylation. Preparation of these modified oligonucleotides requires the use of 2-(p-nitrophenyl)ethyloxycarbonyl (NPEOC) groups for the protection of exocyclic amino functions. These groups are removed under mild conditions, thus avoiding conventional protocols that are detrimental to the integrity of the 5-azacytosine ring. C1 CSIC, Inst Biol Mol Barcelona, E-08034 Barcelona, Spain. European Mol Biol Lab, D-69117 Heidelberg, Germany. Univ Nebraska, Ctr Med, Dept Biochem & Mol Biol, Omaha, NE 69198 USA. Univ Nebraska, Ctr Med, UNMC Eppley Canc Ctr, Omaha, NE 69198 USA. Natl Canc Inst, Ctr Canc Res, Lab Med Chem, Frederick, MD 21702 USA. RP Eritja, R (reprint author), CSIC, Inst Biol Mol Barcelona, Jordi Girona 18-26, E-08034 Barcelona, Spain. RI eritja, ramon/B-5613-2008 OI eritja, ramon/0000-0001-5383-9334 NR 33 TC 10 Z9 10 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD DEC PY 2001 VL 11 IS 6 BP 369 EP 378 DI 10.1089/108729001753411335 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 516MM UT WOS:000173557100003 ER PT J AU Middaugh, SJ Haythornthwaite, JA Thompson, B Hill, R Brown, KM Freedman, RR Attanasio, V Jacob, RG Scheier, M Smith, EA AF Middaugh, SJ Haythornthwaite, JA Thompson, B Hill, R Brown, KM Freedman, RR Attanasio, V Jacob, RG Scheier, M Smith, EA TI The Raynaud's treatment study: Biofeedback protocols and acquisition of temperature biofeedback skills SO APPLIED PSYCHOPHYSIOLOGY AND BIOFEEDBACK LA English DT Article DE Raynaud's phenomenon; temperature biofeedback; EMG biofeedback; biofeedback therapy; normal subjects ID BEHAVIORAL TREATMENT; FOLLOW-UP; DISEASE; STRESS AB The Raynaud's Treatment Study (RTS) compared temperature biofeedback training and a behavioral control procedure (frontalis EMG biofeedback) with nifedipine-XL and a medication placebo for treatment of primary Raynaud's phenomenon (RP) in a large (N = 313) multicenter trial. The present study describes the RTS biofeedback protocols and presents data oil the acquisition of digital skin temperature and frontalis EMG responses in the RTS. The findings point to substantial problems with acquisition of physiological self-regulation skills in the RTS. Only 34.6% of the Temperature Biofeedback group (N = 81) and 55.4% of the EMG Biofeedback group (N = 74) successfully learned the desired physiological response. hi contrast, 67.4% of a Normal Temperature Biofeedback group (N = 46) learned hand warming. Multivariate analysis found that coping strategies, anxiety, gender, and clinic site predicted acquisition of hand-warming skills whereas variables related to RP disease severity did not. Physiological data showed vasoconstriction in response to the onset of biofeedback and also found that performance in the initial sessions was critical for successful acquisition. These findings indicate that attention to the emotional and cognitive aspects of biofeedback training, and a degree of success in the initial biofeedback sessions, are important for acquisition. C1 Med Univ S Carolina, Dept Anesthesiol & Perioperat Surg, Charleston, SC 29425 USA. Johns Hopkins Univ, Baltimore, MD USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Natl Heart Lung & Blood Inst, Bethesda, MD USA. Wayne State Univ, Detroit, MI USA. UMDNJ, New Jersey Med Sch, Newark, NJ USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RP Middaugh, SJ (reprint author), Med Univ S Carolina, Dept Anesthesiol & Perioperat Surg, 165 Ashley Ave,Suite 525,POB Box 250912, Charleston, SC 29425 USA. FU NHLBI NIH HHS [N01-HC-35127] NR 53 TC 14 Z9 14 U1 1 U2 3 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-0586 J9 APPL PSYCHOPHYS BIOF JI Appl. Psychophysiol. Biofeedback PD DEC PY 2001 VL 26 IS 4 BP 251 EP 278 DI 10.1023/A:1013182519331 PG 28 WC Psychology, Clinical SC Psychology GA 510TP UT WOS:000173223600001 PM 11802676 ER PT J AU Bhargava, R Fernandez, DC Schaeberle, MD Levin, IW AF Bhargava, R Fernandez, DC Schaeberle, MD Levin, IW TI Theory and application of gain ranging to Fourier transform infrared spectroscopic Imaging SO APPLIED SPECTROSCOPY LA English DT Article DE FT-IR; spectroscopy; step-scan; imaging; hyperspectral; gain ranging; signal; noise; signal-to-noise ratio; quantitative; prostate; carcinoma ID PLANE ARRAY DETECTOR; MICROSCOPY; TISSUES; VISUALIZATION; SPECTROMETER; CEREBELLUM; SYSTEMS; NOISE AB Gain ranging is incorporated into the data acquisition and processing protocol for a Fourier transform infrared (FT-IR) imaging spectrometer employing a focal plane array (FPA) detector. A model for predicting the signal, noise, and signal-to-noise ratio (SNR) for an FPA in terms of the dynamic range of the analog-to-digital converter (ADC) is presented. Conventional gain ranging theory, modified to account for variation of noise with gain by incorporating a linear model for noise prediction, is shown to provide excellent agreement with observed values for the SNR advantage afforded by gain ranging. SNR improvement, as affected by collection parameters, was shown to be limited by the noise characteristics of the FPA detector. The advantages of gain ranging were demonstrated by spectroscopic imaging of a thin section of human prostate tissue. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. OI Bhargava, Rohit/0000-0001-7360-994X NR 29 TC 12 Z9 12 U1 0 U2 1 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD DEC PY 2001 VL 55 IS 12 BP 1580 EP 1589 DI 10.1366/0003702011954143 PG 10 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 509WD UT WOS:000173172000010 ER PT J AU Wehr, TA Duncan, WC Sher, L Aeschbach, D Schwartz, PJ Turner, EH Postolache, TT Rosenthal, NE AF Wehr, TA Duncan, WC Sher, L Aeschbach, D Schwartz, PJ Turner, EH Postolache, TT Rosenthal, NE TI A circadian signal of change of season in patients with seasonal affective disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID WINTER DEPRESSION; LIGHT TREATMENT; PLASMA MELATONIN; CONTROLLED TRIAL; SYRIAN-HAMSTERS; BRIGHT LIGHT; PHOTOPERIOD; SUMMER; MECHANISMS; EXCRETION AB Background: In animals, the circadian pacemaker regulates seasonal changes in behavior by transmitting a signal of day length to other sites in the organism. The signal is expressed reciprocally in the duration of nocturnal melatonin secretion, which is longer in winter than in summer. We investigated whether such a signal could mediate the effects of change of season on patients with seasonal affective disorder. Methods: The duration of melatonin secretion in constant dim light was measured in winter and in summer in 55 patients and 55 matched healthy volunteers. Levels of melatonin were measured in plasma samples that were obtained every 30 minutes for 24 hours in each season. Results: Patients and volunteers responded differently to change of season. In patients, the duration of the nocturnal period of active melatonin secretion was longer in winter than in Summer (9.0 +/-1.3 vs 8.4 +/-1.3 hours; P=.001) but in healthy volunteers there was no change (9.0 +/-1.6 vs 8.9 +/-1.2 hours; P=.5). Conclusions: The results show that patients with seasonal affective disorder generate a biological signal of change of season that is absent in healthy volunteers and that is similar to the signal that mammals use to regulate seasonal changes in their behavior. While not proving causality, this finding is consistent with the hypothesis that neural circuits that mediate the effects of seasonal changes in day length on mammalian behavior mediate effects of season and light treatment on seasonal affective disorder. C1 NIMH, Intramural Res Program, Sect Biol Rhythms Mood, Bethesda, MD 20892 USA. NIMH, Intramural Res Program, Anxiety Disorders Program, Bethesda, MD 20892 USA. Columbia Univ, Psychiat Inst, New York, NY USA. Vet Adm Med Ctr, Cincinnati, OH USA. RP Wehr, TA (reprint author), NIMH, Intramural Res Program, Sect Biol Rhythms Mood, 10-3S231,10 Ctr Dr MSC1390, Bethesda, MD 20892 USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 42 TC 121 Z9 122 U1 3 U2 14 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2001 VL 58 IS 12 BP 1108 EP 1114 DI 10.1001/archpsyc.58.12.1108 PG 7 WC Psychiatry SC Psychiatry GA 499TG UT WOS:000172586000001 PM 11735838 ER PT J AU Zarate, CA Patel, J AF Zarate, CA Patel, J TI Sudden cardiac death and antipsychotic drugs - Do we know enough? SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Editorial Material ID MAJOR DEPRESSIVE DISORDER; CORONARY-ARTERY DISEASE; TORSADES-DE-POINTES; MYOCARDIAL-INFARCTION; INTERVAL ABNORMALITIES; PSYCHIATRIC-PATIENTS; QT PROLONGATION; MORTALITY; THERAPY; AGENTS C1 NIMH, Mood Disorders Res Unit, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Zarate, CA (reprint author), NIMH, Mood Disorders Res Unit, Mood & Anxiety Disorders Program, 9000 Rockville Pike,Bldg 10 Unit 3 W,Rm 3S250, Bethesda, MD 20892 USA. NR 42 TC 37 Z9 37 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2001 VL 58 IS 12 BP 1168 EP 1171 DI 10.1001/archpsyc.58.12.1168 PG 4 WC Psychiatry SC Psychiatry GA 499TG UT WOS:000172586000009 PM 11735846 ER PT J AU Nyska, A Moomaw, CR Lomnitski, L Chan, PC AF Nyska, A Moomaw, CR Lomnitski, L Chan, PC TI Glutathione S-transferase Pi expression in forestomach carcinogenesis process induced by gavage-administered 2,4-hexadienal in the F344 rat SO ARCHIVES OF TOXICOLOGY LA English DT Article DE basal cell hyperplasia; F344 rat; glutathione-S-transferase-Pi; 2,4-hexadienal; stomach ID BASAL-CELL HYPERPLASIA; OXIDATIVE DNA-DAMAGE; DIGESTIVE-TRACT; PROSTATIC CARCINOGENESIS; BUTYLATED HYDROXYANISOLE; BRUSSELS-SPROUTS; NEOPLASIA; IMMUNOHISTOCHEMISTRY; PERSISTENCE; ISOENZYMES AB 2,4-Hexadienal (2,4-Hx), an unsaturated aldehyde formed by in vivo and in vitro peroxidation of unsaturated lipid induced, in National Toxicology Program (NTP) gavage studies of F344 rats, forestomach hyperplasia in 13-week and 2-year exposures and squamous papilloma and carcinoma in 2-year studies. Hyperplasia was characterized by thickening of all layers of epithelium with particularly prominent proliferation of the basal cells. The present investigation describes the nature and potential significance of glutathione-S-transferase-Pi (GST-Pi) immunoexpression of normal forestornach epithelium, compared to that of 2,4-Hx-related basal cell hyperplasia and squamous cell papilloma and carcinoma. Paraffin-embedded forestomachs from these NTP studies were used to investigate possible correlations between the carcinogenic process and expression of GST-Pi, a physiological metabolic barrier and an inducible phase 11 detoxifying enzyme suggested to decrease the responsiveness of reactive oxygen species (ROS) and organic electrophilic compounds. The amount of immunopositive staining was graded on a scale of 0 (no staining) to 4 (marked staining). The simple basal epithelium of control rats showed strong immunopositivity. In cases or basal cell hyperplasia from the 13-week and 2-year Studies, these cells usually expressed strong immunopositivity for GST-Pi (grade 3 to 4). In the 2-year treated animals only, occasional focal reduction (grade 0 to 2) in immunoreactivity for GST-Pi was noted. In papillomas and squamous cell carcinomas, a wide range of GST-Pi expression was observed, perhaps indicating irregularities in its induction or change in the phenotype of these cells compared to normal or hyperplastic ones. Reduced expression of GST-Pi by the foci of basal cell hyperplasia and in tumor cells may suggest changes in cellular protection from oxidative or electrophilic DNA damage, these changes may result in genetic alterations and be the precursor to clonal expansion. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. Bar Ilan Univ, Inst Life Sci, IL-52900 Ramat Gan, Israel. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, NIH, MD B3-06,POB 12233, Res Triangle Pk, NC 27709 USA. NR 37 TC 9 Z9 9 U1 1 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD DEC PY 2001 VL 75 IS 10 BP 618 EP 624 DI 10.1007/s002040100278 PG 7 WC Toxicology SC Toxicology GA 509VX UT WOS:000173171400009 PM 11808924 ER PT J AU Dorner, T Lipsky, PE AF Dorner, T Lipsky, PE TI Immunoglobulin variable-region gene usage in systemic autoimmune diseases SO ARTHRITIS AND RHEUMATISM LA English DT Review ID ANTI-DNA ANTIBODIES; B-CELL REPERTOIRE; V-H GENES; NUCLEOTIDE-SEQUENCE ANALYSIS; HEAVY-CHAIN REPERTOIRE; J-LAMBDA REPERTOIRE; LUPUS-ERYTHEMATOSUS; SOMATIC HYPERMUTATION; SJOGRENS-SYNDROME; SELECTIVE INFLUENCES C1 Univ Hosp Charite, Dept Med, D-10098 Berlin, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Dorner, T (reprint author), Univ Hosp Charite, Dept Med, Schumannstr 20-21, D-10098 Berlin, Germany. FU NIAID NIH HHS [AI-31229] NR 115 TC 31 Z9 33 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2001 VL 44 IS 12 BP 2715 EP 2727 DI 10.1002/1529-0131(200112)44:12<2715::AID-ART458>3.0.CO;2-L PG 13 WC Rheumatology SC Rheumatology GA 500PA UT WOS:000172634900003 PM 11762931 ER PT J AU Chen, W Srinivasan, SR Elkasabany, A Ellsworth, DL Boerwinkle, E Berenson, GS AF Chen, W Srinivasan, SR Elkasabany, A Ellsworth, DL Boerwinkle, E Berenson, GS TI Influence of lipoprotein lipase serine 447 stop polymorphism on tracking of triglycerides and HDL cholesterol from childhood to adulthood and familial risk of coronary artery disease: the Bogalusa Heart Study SO ATHEROSCLEROSIS LA English DT Article DE lipoprotein lipase S447X polymorphism; lipoproteins; tracking; coronary disease ID APOLIPOPROTEIN-E POLYMORPHISM; SYSTOLIC BLOOD-PRESSURE; SERUM-LIPIDS; DENSITY LIPOPROTEINS; GENE; ATHEROSCLEROSIS; METABOLISM; TRUNCATION; VARIANTS; MALES AB The effects of the lipoprotein lipase (LPL) Serine 447 Stop (S447X) polymorphism on high-density lipoprotein cholesterol (HDLC) and triglycerides (TG) have been demonstrated. However, little is known about its effect on the tracking of HDLC and TG over time and familial risk of coronary artery disease (CAD). This aspect was examined in black and white individuals (n = 829) aged 5-18 year at baseline, followed on average 18.8 yr. The frequency of the X447 allele was lower in Blacks than Whites (0.043 vs 0.087, P = 0.002). Carriers vs noncarriers of the X447 allele had lower TG (99.3 vs 122.1 mg/dl, P < 0.01) and higher HDLC (51.1 vs 49.7 mg/dl, P < 0.05) in adulthood, but not in childhood. The trends in genotype-specific means of childhood and adulthood levels of HDLC and TG in sex or race subgroups were similar to those in the total sample. With respect to tracking over time, of those in the bottom quartile of HDLC in childhood, 46.1% of the noncarriers vs 23.1% of the carriers remained in this lowest quartile into adulthood (P = 0.03); corresponding values for the top quartile of HDLC were 37.5% for the noncarriers vs 57.1% for the carriers (P = 0.03). Although TG tended to track better among the carriers in the bottom quartile and among the noncarriers in the top quartile, this trend was not significant. Carriers showed lower prevalence of parental history of CAD than noncarriers (6.9% vs 14.1%, P = 0.02) independently of lipoprotein variables, adiposity, blood pressure, age, sex and race. Thus, the X447 allele of the LPL gene is associated with an increase in HDLC and a decrease in TG in adults, tracking of HDLC since childhood, and a lower family history of CAD. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Tulane Sch Publ Hlth & Trop Med, Ctr Cardiovasc Hlth, Dept Epidemiol, New Orleans, LA 70112 USA. NHLBI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA. Univ Texas, Houston Hlth Sci Ctr, Inst Mol Med, Ctr Human Genet, Houston, TX USA. RP Berenson, GS (reprint author), Tulane Sch Publ Hlth & Trop Med, Ctr Cardiovasc Hlth, Dept Epidemiol, 1440 Canal St,Suite 2140, New Orleans, LA 70112 USA. FU NHLBI NIH HHS [HL-38844]; NIA NIH HHS [AG-16592] NR 38 TC 34 Z9 37 U1 0 U2 3 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2001 VL 159 IS 2 BP 367 EP 373 DI 10.1016/S0021-9150(01)00508-1 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 504YZ UT WOS:000172885100013 PM 11730816 ER PT J AU Galluzzi, JR Cupples, LA Otvos, JD Wilson, PWF Schaefer, EJ Ordovas, JM AF Galluzzi, JR Cupples, LA Otvos, JD Wilson, PWF Schaefer, EJ Ordovas, JM TI Association of the A/T54 polymorphism in the intestinal fatty acid binding protein with variations in plasma lipids in The Framingham Offspring Study SO ATHEROSCLEROSIS LA English DT Article DE FABP2; cholesterol; polymorphism; Framingham ID CORONARY-ARTERY DISEASE; INSULIN-RESISTANCE; CHOLESTEROL ABSORPTION; ABORIGINAL CANADIANS; OBESE SUBJECTS; HEART-DISEASE; GENE; LIPOPROTEIN; VARIANTS; CODON-54 AB We investigated the potential role of the genetic variation at the intestinal fatty acid binding protein gene (FABP2) in influencing lipid levels in a representative sample of the Framingham Offspring Study participants (n = 1930). In men, the T54 allele was associated with significantly higher LDL-cholesterol (3.47 +/- 0.83 vs 3.36 +/- 0.83 mmol/l; P < 0.047), and ApoB (1.04 +/- 0.23 vs 1.01 +/- 0.24 g/l; P < 0.020) after adjustment for familial relationship, age, BMI, smoking, alcohol intake and the use of beta-blockers compared with the A54 allele. This relationship with ApoB continued to be significant after adjustment for APOE genotype (P < 0.034). In women, the T54 allele was associated with significantly higher total-cholesterol (5.32 +/- 1.01 vs 5.17 +/- 0.98 mmol/l; P < 0.049) and LDL-cholesterol (3.31 +/- 0.93 vs 3.18 +/- 0.85 mmol/l; P < 0.023) after adjustment for covariates and menopausal status, estrogen therapy and APOE genotype. In men, the T54 allele was associated with significantly higher levels of small VLDL and lower levels of large HDL. Moreover, there was no significant relationship between FABP2 alleles and lipoprotein diameter or the prevalence of coronary heart disease in both genders. Our data are consistent with the T54 IFABP increasing the flux of lipids through the enterocyte leading to an increase in chylomicron secretion. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Tufts Univ, Lipid Metab Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. N Carolina State Univ, Dept Biochem, Raleigh, NC 27695 USA. NHLBI, Framingham Heart Study, Framingham, MA 01701 USA. RP Galluzzi, JR (reprint author), Tufts Univ, Lipid Metab Lab, Jean Mayer USDA Human Nutr Res Ctr Aging, 711 Washington St, Boston, MA 02111 USA. OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL54776] NR 50 TC 33 Z9 38 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2001 VL 159 IS 2 BP 417 EP 424 DI 10.1016/S0021-9150(01)00517-2 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 504YZ UT WOS:000172885100019 PM 11730822 ER PT J AU Craft, RM Tseng, AH McNiel, DM Furness, MS Rice, KC AF Craft, RM Tseng, AH McNiel, DM Furness, MS Rice, KC TI Receptor-selective antagonism of opioid antinociception in female versus male rats SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE gender; analgesia; mu receptors; kappa receptors; delta receptors; rat ID SEX-RELATED DIFFERENCES; MU-OPIATE RECEPTOR; MORPHINE ANALGESIA; BETA-FUNALTREXAMINE; BRAIN-REGIONS; KAPPA; BINDING; AGONIST; GENDER; EFFICACY AB This study was conducted to determine whether sex differences in opioid antinociception may be explained by sex differences in opioid receptor activation. The time course, dose-effect and selectivity of antagonists that have been previously shown to be relatively mu (beta -funaltrexamine, beta -FNA), kappa (norbinaltorphimine, norBNI), or delta (naltrindole, NTI) receptor selective in male animals were compared in female and male Sprague-Dawley rats using a 52 degreesC hotplate test. In both sexes, beta -FNA (10 or 20 mug intracerebroventricularly [i.c.v.]) dose-dependently blocked the antinociceptive effects of fentanyl (0.056 mg/kg subcutaneously); antagonism was observed 24 h after beta -FNA, and diminished within 7-14 days. In both sexes, norBNI (1 ou 10 mug i.c.v.) dose-dependently blocked the antinociceptive effects of U69,593 (1.0 mg/kg subcutaneously); antagonism was maximal by 1-3 days post-norBNI and lasted longer than 56 days. NTI (1 or 10 mug i.c.v.) dose-dependently blocked the antinociceptive effects of [D-Pen(2), D-Pen(5)]enkephalin (DPDPE, 100 nmol i.c.v.) in both sexes; however, the duration of action of NTI was shorter in females than in males. The antinociceptive effects of the mu receptor-preferring agonists fentanyl, morphine and buprenorphine were significantly and dose-dependently antagonized by beta -FNA, but not by norBNI or NTI, in both: sexes. beta -FNA antagonism was significantly greater in females compared with males given morphine, but not fentanyl:or buprenorphine. The antinociceptive effects of the kappa receptor-preferring agonists U69,593 and U50,488 were significantly and dose-dependently antagonized by norBNI; U50,488 but not U69,593 was also: antagonized to a lesser extent by NTI I and beta -FNA, in both sexes. The antinociceptive effect of the delta receptor-preferring agonist SNC 80 was significantly antagonized by NTI, but not by norBNI or beta -FNA, in both sexes. The sex difference in beta -FNA antagonism of morphine suggests that there may be sex differences in functional mu opioid receptor reserve or signal transduction; however, the lack of consistency across all mu agonists weakens this hypothesis. Overall, the opioids tested had very similar receptor selectivity in male and female subjects. (C) 2001 Lippincott Williams & Wilkins. C1 Washington State Univ, Dept Psychol, Pullman, WA 99164 USA. Washington State Univ, Grad Program Pharmacol Toxicol, Pullman, WA 99164 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Craft, RM (reprint author), Washington State Univ, Dept Psychol, POB 644820, Pullman, WA 99164 USA. EM craft@wsu.edu FU NIDA NIH HHS [DA10284] NR 55 TC 31 Z9 31 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD DEC PY 2001 VL 12 IS 8 BP 591 EP 602 PG 12 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 506PL UT WOS:000172980900003 PM 11856896 ER PT J AU Battiwalla, M Barrett, J AF Battiwalla, M Barrett, J TI Allogeneic transplantation using non-myeloablative transplant regimens SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY LA English DT Article DE non-myeloablative stem cell transplants; graft-versus-tumour effect; mixed chimerism; adoptive immunotherapy; lymphocytes; stem cell transplantation conditioning ID BONE-MARROW TRANSPLANTATION; STEM-CELL TRANSPLANTATION; VERSUS-HOST DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; TOTAL-BODY IRRADIATION; MIXED HEMATOPOIETIC CHIMERISM; CYTOTOXIC T-LYMPHOCYTES; SEVERE APLASTIC-ANEMIA; IN-VIVO AB Reduced intensity (non-myeloablative) stem cell transplant (NST) preparative regimens are being increasingly used to exploit the curative potential of allogeneic stem cell transplantation without the morbidity and mortality associated with conventional transplantation. Growing confidence in the power of the allogeneic graft-versus-malignancy (GVM) effect makes such an approach attractive. Lower intensity transplants increase the degree of mixed chimerism, both in T cell and myeloid cell lineages. Currently a variety of NST treatment approaches are being developed and in this chapter their safety profile and the immunological characteristics of the mixed chimeric state are described. Results of NST in specific disease categories are still limited but the NST approach appears to have promise in the treatment of both haematological and non-haematological malignancies because of the benefit of low toxicity coupled with a strong graft-versus-malignancy effect. NST regimens are also being explored in high-risk patients with non-malignant disorders. However, at present, there is insufficient data to determine whether NST should replace standard myeloablative transplants in specific disease groups. With their low toxicity, NST are well placed as platforms for future developments in transplant immunology to avoid GVHD and enhance the allograft effect against malignant diseases. C1 NHLBI, Stem Cell Allotransplantat Sect, Haematol Branch, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Haematol Branch, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 79 TC 7 Z9 9 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6926 J9 BEST PRACT RES CL HA JI Best Pract. Res. Clin. Haematol. PD DEC PY 2001 VL 14 IS 4 BP 701 EP 722 DI 10.1053/beha.2001.0168 PG 22 WC Hematology SC Hematology GA 515AE UT WOS:000173472600004 PM 11924917 ER PT J AU Poruchynsky, MS Giannakakou, P Ward, Y Bulinski, JC Telford, WG Robey, RW Fojo, T AF Poruchynsky, MS Giannakakou, P Ward, Y Bulinski, JC Telford, WG Robey, RW Fojo, T TI Accompanying protein alterations in malignant cells with a microtubule-polymerizing drug-resistance phenotype and a primary resistance mechanism SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE drug-resistance; mutation; microtubules; Mcl-1; MAP4; cell death ID OVARIAN-CANCER CELLS; SIGNAL-TRANSDUCTION; TUBULIN MUTATIONS; MITOTIC SPINDLE; BCL-2 FAMILY; IN-VITRO; BAX GENE; MAP4; PHOSPHORYLATION; DYNAMICS AB Microtubules (MTs) are cytoskeletal components whose structural integrity is mandatory for the execution of many basic cell functions. Utilizing parental and drug-resistant ovarian carcinoma cell lines that have acquired point mutations in beta -tubulin and p53, we studied the level of expression and modification of proteins involved in apoptosis and NIT integrity. Extending previous results, we demonstrated phosphorylation of pro-survival Bcl-x(L) in an epothilone-A resistant cell line, correlating it with drug sensitivity to tubulin-active compounds. Furthermore, Mcl-1 protein turned over more rapidly following exposure to tubulin-modifying agents, the stability of Mcl-1 protein paralleling the drug sensitivity profile of the paclitaxel or epothilone-A resistant cell lines. The observed decreases in Mcl-1 were not a consequence of G(2)M arrest, as determined by flow cytometry analysis, which showed prominent levels of Mcl-1 in the absence of any drug treatment in populations enriched in mitotic cells. We also observed that a paclitaxel-resistant cell line expressed Bax at a much lower level than the sensitive parental line [A2780(1A9)], consistent with its mutant p53 status. MT-associated protein-4 (MAP4), whose phosphorylation during specific phases of the cell cycle reduces its MT-polymerizing and -stabilizing capabilities, was phosphorylated in response to drug challenge without a change in expression. Phosphorylation of MAP4 correlated with sensitivity to tubulin-binding drugs and with a dissociation from MTs. We propose that the tubulin mutations, which result in a compromised paclitaxel:tubulin or epothilone:tubulin interaction and paclitaxel or epothilone resistance, indirectly inhibit downstream events that lead to cell death, and this, in turn, may contribute to the drug-resistance phenotype. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NCI, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Poruchynsky, MS (reprint author), NCI, NIH, Ctr Canc Res, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Giannakakou, Paraskevi/0000-0001-7378-262X NR 45 TC 40 Z9 42 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD DEC 1 PY 2001 VL 62 IS 11 BP 1469 EP 1480 DI 10.1016/S0006-2952(01)00804-8 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 500NV UT WOS:000172634400005 PM 11728383 ER PT J AU Li, LP Weinberg, CR Darden, TA Pedersen, LG AF Li, LP Weinberg, CR Darden, TA Pedersen, LG TI Gene selection for sample classification based on gene expression data: study of sensitivity to choice of parameters of the GA/KNN method SO BIOINFORMATICS LA English DT Article ID CLUSTERING ANALYSIS; PATTERNS AB Motivation: We recently introduced a multivariate approach that selects a subset of predictive genes jointly for sample classification based on expression data. We tested the algorithm on colon and leukemia data sets. As an extension to our earlier work, we systematically examine the sensitivity, reproducibility and stability of gene selection/sample classification to the choice of parameters of the algorithm. Methods: Our approach combines a Genetic Algorithm (GA) and the k-Nearest Neighbor (KNN) method to identify genes that can jointly discriminate between different classes of samples (e.g. normal versus tumor). The GA/KNN method is a stochastic supervised pattern recognition method. The genes identified are subsequently used to classify independent test set samples. Results: The GA/KNN method is capable of selecting a subset of predictive genes from a large noisy data set for sample classification. It is a multivariate approach that can capture the correlated structure in the data. We find that for a given data set gene selection is highly repeatable in independent runs using the GA/KNN method. In general, however, gene selection may be less robust than classification. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Struct Biol, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Li, LP (reprint author), NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 FU NHLBI NIH HHS [HL-06350] NR 16 TC 339 Z9 370 U1 3 U2 24 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD DEC PY 2001 VL 17 IS 12 BP 1131 EP 1142 DI 10.1093/bioinformatics/17.12.1131 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 507UW UT WOS:000173050500006 PM 11751221 ER PT J AU Weinberger, DR Egan, MF Bertolino, A Callicott, JH Mattay, VS Lipska, BK Berman, KF Goldberg, TE AF Weinberger, DR Egan, MF Bertolino, A Callicott, JH Mattay, VS Lipska, BK Berman, KF Goldberg, TE TI Prefrontal neurons and the genetics of schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Meeting on New Perspectives on the Neurobiology of Schizophrenia and the Role of Atypical Antipsychotics CY NOV, 2000 CL KEY WEST, FL DE neurobiology; prefrontal cortex; schizophrenia; genetics; COMT ID CEREBRAL-BLOOD-FLOW; CATECHOL-O-METHYLTRANSFERASE; CARD SORTING TEST; MAGNETIC-RESONANCE-SPECTROSCOPY; MONOZYGOTIC TWINS DISCORDANT; POSITRON-EMISSION-TOMOGRAPHY; N-ACETYLASPARTATE MEASURES; VENTRAL TEGMENTAL AREA; ATTENUATED FRONTAL ACTIVATION; NEUROLEPTIC-NAIVE PATIENTS AB This article reviews prefrontal cortical biology as it relates to pathophysiology and genetic rash for schizophrenia. Studies of prefrontal neurocognition and functional neuroimaging of prefrontal information processing consistently reveal abnormalities in patients with schizophrenia. Abnormalities of prefrontal information processing also are found in unaffected individuals who are genetically at risk for schizophrenia, suggesting that genetic polymorphisms affecting prefrontal function may be susceptibility alleles for schizophrenia. One such candidate is a functional polymorphism in the catechol-o-methyl transferase (COMT) gene that markedly affects enzyme activity and that appears to uniquely, impact prefrontal dopamine. The COMT genotype predicts performance on prefrontal executive cognition and working memory tasks. Functional magnetic resonance imaging confirms that COMT genotype affects prefrontal physiology during working memory. Family-based association studies have revealed excessive transmission to schizophrenic offspring of the allele (val) related to poorer prefrontal function. These various data provide convergent evidence that the COMT val allele increases risk for schizophrenia by virtue of its effect on dopamine-mediated prefrontal information processing-the first plausible mechanism for a genetic effect on normal human cognition and risk for mental illness. (C) 2001 Society of Biological Psychiatry. C1 NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Weinberger, DR (reprint author), NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, 10 Ctr Dr,4S235, Bethesda, MD 20892 USA. RI Callicott, Joseph/C-9102-2009; Bertolino, Alessandro/O-6352-2016; Lipska, Barbara/E-4569-2017 OI Callicott, Joseph/0000-0003-1298-3334; Bertolino, Alessandro/0000-0002-1251-1380; NR 214 TC 502 Z9 514 U1 9 U2 51 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 1 PY 2001 VL 50 IS 11 BP 825 EP 844 DI 10.1016/S0006-3223(01)01252-5 PG 20 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 502WN UT WOS:000172765900002 PM 11743939 ER PT J AU Hild, SA Reel, JR Larner, JM Blye, RP AF Hild, SA Reel, JR Larner, JM Blye, RP TI Disruption of spermatogenesis and Sertoli cell structure and function by the indenopyridine CDB-4022 in rats SO BIOLOGY OF REPRODUCTION LA English DT Article DE inhibin; Leydig cells; male reproductive tract; Sertoli cells; spermatogenesis ID N-PENTYL PHTHALATE; INHIBIN-B; SEMINIFEROUS EPITHELIUM; TESTICULAR ATROPHY; FAS SYSTEM; ADULT-RAT; APOPTOSIS; TESTIS; INJURY; EXPRESSION AB The present studies were undertaken to determine the testicular cell type(s) affected by the antispermatogenic indenopyridine CDB-4022. At the oral threshold dose (2.5 mg/kg), CDB-4022 induced infertility in all males. CDB-4022 did not alter (P > 0.05) Leydig cell function as assessed by circulating testosterone, seminal vesicle, and ventral prostate weights or body weight gain compared to controls. Conversely, CDB-4022 reduced (P < 0.05) testicular weight, spermatid head counts, and percentage of seminiferous tubules undergoing spermatogenesis. In a second study, adult male rats received a maximally effective oral dose of CDB-4022 (12.5 mg/kg), dipentylphthalate (DPP; 2200 mg/kg; a Sertoli cell toxicant), or vehicle and were necropsied 3, 6, or 12 h after dosing to determine acute effects. Serum inhibin B levels were suppressed (P < 0.05) by 6 h after CDB-4022 or DPP treatment, but epididymal androgen-binding protein (ABP) levels were not altered (P > 0.05), compared to controls. CDB-4022 and DPP increased (P < 0.05) the percentage of tubules with apoptotic germ cells, particularly differentiating spermatogonia and spermatocytes, by 12 h after dosing. Microscopic examination of the testis indicated a greater degree of vacuolation in Sertoli cells and initial signs of apical germ cell sloughing/shedding by 3 or 12 h after CDB-4022 or DPP treatment, respectively. In a third study, prepubertal male rats were treated with vehicle, 12.5 mg/kg of CDB-4022, or 2200 mg/kg of DPP, and the efferent ducts of the right testis were ligated 23 h before necropsy. Seminiferous tubule fluid secretion (difference in weight of testes), serum inhibin B levels, and ABP levels in the unligated epididymis were reduced (P < 0.05) at 24 and 48 h after dosing in CDB-4022- and DPP-treated rats compared to controls. Collectively, these data suggest that CDB-4022 disrupts spermatogenesis by inducing apoptosis in early stage germ cells via a direct action on the Sertoli cell. C1 BIOQUAL Inc, Rockville, MD 20850 USA. NICHHD, Contracept & Reprod Hlth Branch, Rockville, MD 20852 USA. RP Hild, SA (reprint author), BIOQUAL Inc, 9600 Med Ctr Dr, Rockville, MD 20850 USA. FU NICHD NIH HHS [N01-HD-6-3289] NR 48 TC 26 Z9 28 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD DEC PY 2001 VL 65 IS 6 BP 1771 EP 1779 PG 9 WC Reproductive Biology SC Reproductive Biology GA 495AX UT WOS:000172319000020 PM 11717140 ER PT J AU Dunson, DB AF Dunson, DB TI Bayesian modeling of the level and duration of fertility in the menstrual cycle SO BIOMETRICS LA English DT Article DE Bayesian analysis; conception probability; fecundability; fertile interval; intercourse diaries; menstrual cycle; order restrictions; ovulation ID POSTERIOR DISTRIBUTIONS; MARKOV-CHAINS; CONCEPTION; OVULATION; INTERCOURSE; PROBABILITY; SURVIVAL; BABY; SEX AB Time to pregnancy studies that identify ovulation days and collect daily intercourse data can be used to estimate the day-specific probabilities of conception given intercourse on a single day relative to ovulation. In this article, a Bayesian semiparametric model is described for flexibly characterizing covariate effects and heterogeneity among couples in daily fecundability. The proposed model is characterized by the timing of the most fertile day of the cycle relative to ovulation, by the probability of conception due to intercourse on the most fertile day, and by the ratios of the daily conception probabilities for other days of the cycle relative to this peak probability. The ratios are assumed to be increasing in time to the peak and decreasing thereafter. Generalized linear mixed models are used to incorporate covariate and couple-specific effects on the peak probability and on the day-specific ratios. A Markov chain Monte Carlo algorithm is described for posterior estimation, and the methods are illustrated through application to caffeine data from a North Carolina pregnancy study. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233 MD A3-03, Res Triangle Pk, NC 27709 USA. NR 31 TC 24 Z9 24 U1 0 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2001 VL 57 IS 4 BP 1067 EP 1073 DI 10.1111/j.0006-341X.2001.01067.x PG 7 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 540XU UT WOS:000174956800009 PM 11764245 ER PT J AU Fay, MP Graubard, BI AF Fay, MP Graubard, BI TI Small-sample adjustments for Wald-type tests using sandwich estimators SO BIOMETRICS LA English DT Article DE conditional logistic regression; Cox proportional hazards model; generalized estimating equations; robust Wald statistics; sandwich estimator; small sample size ID GENERALIZED ESTIMATING EQUATIONS; REGRESSION; MODELS AB The sandwich estimator of variance may be used to create robust Wald-type tests from estimating equations that are sums of K independent or approximately independent terms. For example, for repeated measures data on K individuals, each term relates to a different individual. These tests applied to a parameter may have greater than nominal size if K is small, or more generally if the parameter to be tested is essentially estimated from a small number of terms in the estimating equation. We offer some practical modifications to these robust Wald-type tests, which asymptotically approach the usual robust Wald-type tests. We show that one of these modifications provides exact coverage for a simple ease and examine by simulation the modifications applied to the generalized estimating equations of Liang and Zeger (1986), conditional logistic regression, and the Cox proportional hazard model. C1 NCI, Bethesda, MD 20892 USA. RP Fay, MP (reprint author), NCI, 6116 Execut Blvd,Suite 504,MSC 8317,EPS Room 8032, Bethesda, MD 20892 USA. RI Fay, Michael/A-2974-2008; OI Fay, Michael P./0000-0002-8643-9625 NR 15 TC 64 Z9 65 U1 2 U2 6 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2001 VL 57 IS 4 BP 1198 EP + DI 10.1111/j.0006-341X.2001.01198.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 540XU UT WOS:000174956800025 PM 11764261 ER PT J AU Peddada, SD Prescott, KE Conaway, M AF Peddada, SD Prescott, KE Conaway, M TI Tests for order restrictions in binary data SO BIOMETRICS LA English DT Article DE binomial distribution; bootstrap methodology; Cochran-Armitage trend test; downturn order; National Toxicology Program; nodal parameter; ordered alternatives; poly-3 trend test; simple order; simple tree order; umbrella order ID GENERALIZED LINEAR-MODELS; CARCINOGENICITY; HYPOTHESES; BOOTSTRAP; SUBJECT AB In this article, a general procedure is presented for testing for equality of k independent binary response probabilities against any given ordered alternative. The proposed methodology is based on an estimation procedure developed in Hwang and Peddada (1994, Annals of Statistics 22, 67-93) and can be used for a very broad class of order restrictions. The procedure is illustrated through application to two data sets that correspond to three commonly encountered order restrictions: simple tree order, simple order, and down turn order. C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. Pfizer Ltd, Sandwich CT13 9NJ, Kent, England. Univ Virginia, Div Biostat, Charlottesville, VA 22903 USA. RP Peddada, SD (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RI Peddada, Shyamal/D-1278-2012 NR 28 TC 20 Z9 21 U1 1 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2001 VL 57 IS 4 BP 1219 EP 1227 DI 10.1111/j.0006-341X.2001.01219.x PG 9 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 540XU UT WOS:000174956800027 PM 11764263 ER PT J AU Pfeiffer, RM Gail, MH Pee, D AF Pfeiffer, RM Gail, MH Pee, D TI Inference for covariates that accounts for ascertainment and random genetic effects in family studies SO BIOMETRIKA LA English DT Article DE ascertainment correction; conditional logistic regression; correlated binary data; family study; misspecified model; nested random effects model ID NASOPHARYNGEAL CARCINOMA; BINARY DATA; MODELS; EFFICIENCY AB Family studies to identify disease-related genes often collect families with multiple cases. If environmental exposures or other measured covariates are also important, they should be incorporated into these genetic analyses to control for confounding and increase statistical power. We propose a two-level mixed effects model that allows us to estimate environmental effects while accounting for varying genetic correlations among family members and adjusting for ascertainment by conditioning on the number of cases in the family. We describe a conditional maximum likelihood analysis based on this model. When genetic effects are negligible, this conditional likelihood reduces to standard conditional logistic regression. We show that the simpler conditional logistic regression typically yields biased estimators of exposure effects, and we describe conditions under which the conditional logistic approach has little or no bias. C1 NCI, Bethesda, MD 20892 USA. Informat Management Serv Inc, Rockville, MD 20852 USA. RP Pfeiffer, RM (reprint author), NCI, Bethesda, MD 20892 USA. RI Pfeiffer, Ruth /F-4748-2011 NR 16 TC 26 Z9 26 U1 0 U2 6 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 2001 VL 88 IS 4 BP 933 EP 948 DI 10.1093/biomet/88.4.933 PG 16 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 498YT UT WOS:000172541700003 ER PT J AU Hoffman, EB Sen, PK Weinberg, CR AF Hoffman, EB Sen, PK Weinberg, CR TI Within-cluster resampling SO BIOMETRIKA LA English DT Article DE clustered binary data; generalised estimating equations; generalised linear model; marginal model; nonignorable cluster size; resampling; within-cluster correlation ID GENERALIZED LINEAR-MODELS; LONGITUDINAL DATA AB Within-cluster resampling is proposed as a new method for analysing clustered data. Although the focus of this paper is clustered binary data, the within-cluster resampling asymptotic theory is general for many types of clustered data. Within-cluster resampling is a simple but computationally intensive estimation method. Its main advantage over other marginal analysis methods, such as generalised estimating equations (Liang & Zeger, 1986; Zeger & Liang, 1986) is that it remains valid when the risk for the outcome of interest is related to the cluster size, which we term nonignorable cluster size. We present theory for the asymptotic normality and provide a consistent variance estimator for the within-cluster resampling estimator. Simulations and an example are developed that assess the finite-sample behaviour of the new method and show that when both methods are valid its performance is similar to that of generalised estimating equations. C1 Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Hoffman, EB (reprint author), 7 Janson Court, Westport, CT 06880 USA. NR 14 TC 105 Z9 105 U1 2 U2 8 PU BIOMETRIKA TRUST PI LONDON PA UNIV COLLEGE LONDON GOWER ST-BIOMETRIKA OFFICE, LONDON, ENGLAND WC1E 6BT SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 2001 VL 88 IS 4 BP 1121 EP 1134 DI 10.1093/biomet/88.4.1121 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 498YT UT WOS:000172541700015 ER PT J AU Royt, PW Honeychuck, RV Ravich, V Ponnaluri, P Pannell, LK Buyer, JS Chandhoke, V Stalick, WM DeSesso, LC Donohue, S Ghei, R Relyea, JD Ruiz, R AF Royt, PW Honeychuck, RV Ravich, V Ponnaluri, P Pannell, LK Buyer, JS Chandhoke, V Stalick, WM DeSesso, LC Donohue, S Ghei, R Relyea, JD Ruiz, R TI 4-hydroxy-2-nonylquinoline: A novel iron chelator isolated from a bacterial cell membrane SO BIOORGANIC CHEMISTRY LA English DT Article DE 4-hydroxy-2-nonylquinoline; iron chelator; pseudan; Pseudomonas aeruginosa; siderophore; iron metabolism; iron transport AB The membrane associated iron chelator of Pseudomonas aeruginosa has been extracted from membranes of iron-rich cells with ethanol and purified by reverse phase HPLC. Using C-13 NMR and FAB mass spectroscopy, the structure of the chelator has been determined to be 4-hydroxy-2-nonylquinoline. This compound has been previously isolated and named pseudan IX, a name which we use here. We synthesized pseudan IX and show that the spectral properties of the synthesized compound and the purified compound are nearly identical. Also purified from the ethanol extract of membranes is 4-hydroxy-2-heptylquinoline, i.e., pseudan VII. Bacterially purified pseudan IX binds iron as indicated by the incorporation of radiolabeled iron into the chelator and by the formation of pink micelles in a concentrated ethanol extract. The formation of pink micelles upon addition of iron to the synthesized compound indicates that it binds iron. (C) 2001 Elsevier Science (USA). C1 George Mason Univ, Dept Biol, Fairfax, VA 22030 USA. George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. George Mason Univ, Shared Res Instrumentat Facil, Fairfax, VA 22030 USA. NIDDK, Struct Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA. USDA, Sustainable Agr Syst Lab, Beltsville, MD 20705 USA. RP Royt, PW (reprint author), George Mason Univ, Dept Biol, Fairfax, VA 22030 USA. OI Buyer, Jeffrey/0000-0003-2098-0547 NR 11 TC 14 Z9 14 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD DEC PY 2001 VL 29 IS 6 BP 387 EP 397 DI 10.1006/bioo.2001.1225 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 524WR UT WOS:000174036300005 PM 11846436 ER PT J AU Tolstorukov, MY Ivanov, VI Malenkov, GG Jernigan, RL Zhurkin, VB AF Tolstorukov, MY Ivanov, VI Malenkov, GG Jernigan, RL Zhurkin, VB TI Sequence-dependent B <-> A transition in DNA evaluated with dimeric and trimeric scales SO BIOPHYSICAL JOURNAL LA English DT Article ID B-DNA; A-FORM; CONFORMATIONAL PREFERENCES; MOLECULAR-DYNAMICS; NUCLEIC-ACIDS; COMPLEXES; CRYSTAL; RESOLUTION; STABILIZATION; EQUILIBRIUM AB Experimental data on the sequence-dependent B-A conformational transition in 24 oligo- and polymeric duplexes yield optimal dimeric and trimeric scales for this transition. The 10 sequence dimers and the 32 trimers of the DNA duplex were characterized by the free energy differences between the B and A forms in water solution. In general, the trimeric scale describes the sequence-dependent DNA conformational propensities more accurately than the dimeric scale, which is likely related to the trimeric model accounting for the two interfaces between adjacent base pairs on both sides (rather than only one interface in the dimeric model). The exceptional preference of the B form for the AA:TT dimers and AAN:NTT trimers is consistent with the cooperative interactions in both grooves. In the minor groove, this is the hydration spine that stabilizes adenine runs in B form. In the major groove, these are hydrophobic interactions between the thymine methyls and the sugar methylene groups from the preceding nucleotides, occurring in B form. This interpretation is in accord with the key role played by hydration in the B-A transition in DNA. Importantly, our trimeric scale is consistent with the relative occurrences of the DNA trimers in A form in protein-DNA cocrystals. Thus, we suggest that the B/A scales developed here can be used for analyzing genome sequences in search for A-philic motifs, putatively operative in the protein-DNA recognition. C1 NCI, Lab Computat & Expt Biol, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, WA Engelhardt Inst Mol Biol, Moscow 119991, Russia. Russian Acad Sci, Inst Phys Chem, Moscow 119991, Russia. RP Zhurkin, VB (reprint author), NCI, Lab Computat & Expt Biol, NIH, Bldg 12B,Rm B116,12 S Dr, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 59 TC 39 Z9 40 U1 0 U2 11 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2001 VL 81 IS 6 BP 3409 EP 3421 PG 13 WC Biophysics SC Biophysics GA 496QQ UT WOS:000172407800034 PM 11721003 ER PT J AU Shi, S Robey, PG Gronthos, S AF Shi, S Robey, PG Gronthos, S TI Comparison of human dental pulp and bone marrow stromal stem cells by cDNA microarray analysis SO BONE LA English DT Article DE dental pulp stem cells (DPSCs); bone marrow stromal stem cells (BMSSCs) cDNA microarray; osteohlast; odontoblast ID EXTRACELLULAR-MATRIX PROTEINS; RECEPTOR TYROSINE KINASES; FACTOR-BINDING-PROTEINS; GROWTH-FACTOR; TOOTH DEVELOPMENT; IN-VIVO; OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; BECKWITH-WIEDEMANN; TUMOR-SUPPRESSOR AB We compared the gene expression profiles of human dental pulp stern cells (DPSCs) and bone marrow stromal stern cells (BMSSCs) as representative populations of odontoprogenitor and osteoprogenitor cells, respectively. Total RNA from primary cultures was reverse-transcribed to generate cDNA probes and then hybridized with the Research Genetics human gene microarray filter GF211. The microarrays were analyzed using the PATHWAYS software package. Human DPSCs and BMSSCs were found to have a similar level of gene expression for more than 4000 known human genes. A few differentially expressed genes, including collagen type XVIII alpha1, insulin-like growth factor-2 (IGF-2), discordin domain tyrosine kinase 2, NAD(P)H menadione oxidoreductase, homolog 2 of Drosophila large disk, and cyclin-dependent kinase 6 were highly expressed in DPSCs, whereas insulin-like growth factor binding protein-7 (IGFBP-7), and collagen type I alpha2 were more highly expressed in BMSSCs. Furthermore, we confirmed the differential expression of these genes by semiquantitative polymerase chain reaction (PCR) and northern blot hybridization. The protein expression patterns for both IGF-2 and IGFBP-7 correlated with the differential mRNA levels seen between DPSCs and BMSSCs. This report describes the gene expression patterns of two distinct precursor populations associated with mineralized tissue, and provides a basis for further characterization of the functional roles for many of these genes in the development of dentin and bone. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Gronthos, S (reprint author), NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Room 228,Bldg 30,30 Convent Dr,MSC-4320, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 72 TC 186 Z9 198 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD DEC PY 2001 VL 29 IS 6 BP 532 EP 539 DI 10.1016/S8756-3282(01)00612-3 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 502HG UT WOS:000172737500007 PM 11728923 ER PT J AU Buka, SL Tsuang, MT Torrey, EF Klebanoff, MA Wagner, RL Yolken, RH AF Buka, SL Tsuang, MT Torrey, EF Klebanoff, MA Wagner, RL Yolken, RH TI Maternal cytokine levels during pregnancy and adult psychosis SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Article DE schizophrenia; psychosis; pregnancy; maternal infections; cytokines; tumor necrosis factor alpha (TNF-alpha); National Collaborative Perinatal Project; enzyme immunoassay ID NECROSIS-FACTOR-ALPHA; BIPOLAR DISORDER; TNF-ALPHA; FOLLOW-UP; SCHIZOPHRENIA; INFECTIONS; CHORIOAMNIONITIS; INTERLEUKIN-6; COMPLICATIONS; ASSOCIATION AB We investigated levels of maternal cytokines in late pregnancy in relation to the subsequent development of adult schizophrenia and other psychoses in their offspring. The sample included the mothers of 27 adults with schizophrenia and other psychotic illnesses and 50 matched unaffected controls from the Providence cohort of the Collaborative Perinatal Project. Serum samples were analyzed for interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2), interleukin 6 (IL-6), interleukin 8 (IL-8), and tumor necrosis factor alpha (TNF-alpha) by enzyme immunoassay. Maternal levels of TNF-alpha were significantly elevated among the case series (t=2.22, p=.04), with evidence of increasing odds of psychosis in relation to higher cytokine levels. We did not find significant differences between case and control mothers in the serum levels of IL-1, IL-2, IL-6 or IL-8. These data support previous clinical investigations reporting maternal infections during pregnancy as a potential risk factor for psychotic illness among offspring. (C) 2001 Elsevier Science. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Stanley Res Lab, Bethesda, MD 20814 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Rhode Isl Psychiat Res & Training Ctr, Providence, RI 02912 USA. Johns Hopkins Sch Med, Stanley Div Dev Neurovirol, Baltimore, MD USA. RP Buka, SL (reprint author), Harvard Univ, Sch Publ Hlth, 667 Huntington Ave, Boston, MA 02115 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 NR 40 TC 158 Z9 165 U1 3 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD DEC PY 2001 VL 15 IS 4 BP 411 EP 420 DI 10.1006/brbi.2001.0644 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 505HB UT WOS:000172906400009 PM 11782107 ER PT J AU Maciejewski, JP Rivera, C Kook, H Dunn, D Young, NS AF Maciejewski, JP Rivera, C Kook, H Dunn, D Young, NS TI Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myelodysplasia; haemolysis; pancytopenia; haematopoiesis; clonality; bone marrow ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; ACQUIRED APLASTIC-ANEMIA; PIG-A GENE; SOMATIC MUTATIONS; PATHOPHYSIOLOGY; CELLS; PNH AB Because of the Insensitivity of the Ham test, paroxysmal nocturnal haemoglobinuria (PNH) has been inaccurately viewed as a late clonal complication of aplastic anaemia (AA). To clarify the relationship between PNH and marrow failure, we tested for the presence of glycosylphosphatidyl-anchored protein-deficient (GPI-AP) granulocytes in large cohorts of patients with AA, myelodysplasia (MDS), and pure haemolytic PNH. A PNH clone was detected in 32% of new AA patients and 18% of MDS patients. In serial studies, this proportion did not change up to 15 years after diagnosis, suggesting that expansion of aberrant cells is an early event (i.e. prior to initial presentation). For all patients with a PNH clone, on average 14% of PNH granulocytes were found on presentation and 37% at 10 years. Patients with PNH but without cytopenia showed higher percentages of GPI-AP-deficient cells than did those with the AA/PNH syndrome. After immunosuppression, there was no change in the contribution of PNH clone to blood production, arguing against the 'immune-escape' theory in PNH. Clinically, a high proportion of GPI-AP-deficient cells correlated with marrow hypercellularity. GPI-AP-deficient cells were similarly present in patients with and without karyotypic abnormalities. Our results indicate that the GPI-AP-deficient clones show quantitative and kinetic differences between classic haemolytic PNH and PNH with marrow failure, in which the evolution rate is low later in the course of the disease. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), Taussig Canc Ctr R40, 9500 Euclid Ave, Cleveland, OH 44195 USA. NR 26 TC 68 Z9 74 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2001 VL 115 IS 4 BP 1015 EP 1022 DI 10.1046/j.1365-2141.2001.03191.x PG 8 WC Hematology SC Hematology GA 509GD UT WOS:000173137200045 PM 11843844 ER PT J AU Teigen, PM AF Teigen, PM TI William Osler, again SO BULLETIN OF THE HISTORY OF MEDICINE LA English DT Article ID BIOETHICS C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. RP Teigen, PM (reprint author), Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4319 USA SN 0007-5140 J9 B HIST MED JI Bull. Hist. Med. PD WIN PY 2001 VL 75 IS 4 BP 745 EP 755 DI 10.1353/bhm.2001.0197 PG 11 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 499CC UT WOS:000172552600005 PM 11740126 ER PT J AU Rowland, AS Umbach, DM Catoe, KE Stallone, L Long, S Rabiner, D Naftel, AJ Panke, D Faulk, R Sandler, DP AF Rowland, AS Umbach, DM Catoe, KE Stallone, L Long, S Rabiner, D Naftel, AJ Panke, D Faulk, R Sandler, DP TI Studying the epidemiology of attention-deficit hyperactivity disorder: Screening method and pilot results SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE attention-deficit hyperactivity disorder; methods; epidemiology; stimulant medication; prevalence; psychiatric disorders; children ID OF-ONSET CRITERION; COUNTY-WIDE SAMPLE; IV FIELD TRIALS; DEFICIT/HYPERACTIVITY-DISORDER; DIAGNOSTIC-CRITERIA; CHILDREN; ADOLESCENTS; PREVALENCE; ADULTS; HEALTH AB Objective: As part of a larger epidemiologic study of risk factors for attention-deficit hyeractivity disorder (ADHD), this pilot study combined parent and teacher information to estimate ADHD prevalence among elementary school children in a North Carolina county The methods developed for this study and the pitfalls we encountered illustrate the challenges involved in conducting population-based studies of ADHD. Methods: We employed 2-stage screening using DSM-IV criteria. Teachers completed behaviour-rating scales for all children. We then administered a structured telephone interview to parents of potential cases. We screened 362 of 424 (85%) children in grades I to 5 it? 4 schools. Results: According to parent reports, 43 children (12%) had previously, been diagnosed with ADHD by a health professional. Thirty-four children (9%) were taking ADHD medication. Foro-six children (12.7%) met study case criteria for ADHD, based on combined teacher and parent reports. Of the 46 cases, 18 (39%) had not been previously identified. Eight previously diagnosed children, however, did not meet case criteria. After we adjusted for nonresponse, the estimated prevalence was 16% (95%CI, 12% to 20%). Conclusions: These data suggest that the DSM-IV prevalence of ADHD has been substantially underestimated, although the true prevalence in this population may be less than the 16% estimated here. Population-based studies of ADHD are feasible and may provide important information about practice and treatment patterns in community settings, as well as a broader understanding of the etiology and life course of this common disorder. C1 Westat Corp, CODA, Durham, NC USA. Duke Univ, Ctr Child & Family Policy, Durham, NC USA. Univ N Carolina, Sch Med, Dept Psychiat, Div Child & Adolescent Psychiat, Chapel Hill, NC USA. Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC USA. RP Rowland, AS (reprint author), Univ New Mexico, Ctr Hlth Sci, Dept Family & Community Med, MPH Program, 2400 Tucker NE, Albuquerque, NM 87131 USA. OI Sandler, Dale/0000-0002-6776-0018 NR 42 TC 47 Z9 52 U1 3 U2 6 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 260-441 MACLAREN ST, OTTAWA, ONTARIO K2H 2P3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD DEC PY 2001 VL 46 IS 10 BP 931 EP 940 PG 10 WC Psychiatry SC Psychiatry GA 508QH UT WOS:000173099800005 PM 11816314 ER PT J AU Toretsky, JA Steinberg, SM Thakar, M Counts, D Pironis, B Parente, C Eskenazi, A Helman, L Wexler, LH AF Toretsky, JA Steinberg, SM Thakar, M Counts, D Pironis, B Parente, C Eskenazi, A Helman, L Wexler, LH TI Insulin-like growth factor type 1 (IGF-1) and IGF binding protein-3 in patients with ewing sarcoma family of tumors SO CANCER LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Clinical-Oncologists CY MAY 13-18, 1999 CL ATLANTA, GEORGIA SP Amer Soc Clin Oncol DE insulin-like growth factor-1 (IGF-1); ewing sarcoma family of tumors; IGFBP-3; predictive markers ID FACTOR-I RECEPTOR; PROTEASE ACTIVITY; APOPTOSIS; CHILDHOOD; LEUKEMIA; RISK AB Background. Ewing sarcoma family of tumors (ESFTs) are the second most common bone tumor, that most often affects persons ages 3-40 years. The ESFTs rely on signaling through the insulin-like growth factor-1 receptor (IGF-1R) for growth and transformation. The current studies were performed to determine the levels of IGF-1 and IGF binding protein-3 (IGFBP-3) in patients with ESFT. The authors then performed an exploratory analysis to evaluate whether IGF parameters could differentiate event free or overall survival in ESFT patients. Methods. The authors measured serum levels of IGF-1 and IGFBP-3 by using a radioimmuno assay from 111 patients with ESFT with a median follow-up of 13 years from diagnosis. Results. The IGF-1 levels were lower among patients with metastatic disease to the bones or the bone marrow compared with patients without metastasis to these 2 sites (p2=0.021 and 0.0038, respectively). IGFBP-3 is known to sequester IGF-1; the ratios of IGFBP-3 to IGF-1 were evaluated. Patients with metastatic disease to any site had higher IGFBP-3 to IGF-1 ratios than patients with localized disease (p2=0.0067). There was a trend toward increased survival in patients with localized disease who had high IGFBP-3 to IGF-1 levels. Metastatic patients showed a similar trend. Conclusions. Levels of IGF-1 and IGFBP-3 in ESFT patients can identify patients with the most widespread disease. The IGFBP-3 to IGF-l ratio in patients with either localized or metastatic disease identified patients with a trend toward increased survival. Further prospective evaluation with higher patient numbers might show a prognostic role for the IGFBP-3 to IGF-l ratio in patients with ESFT. Cancer 2001;92:2941-7. (C) 2001 American Cancer Society. C1 Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. Program Mol Biol, Baltimore, MD USA. Greenebaum Canc Ctr, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Toretsky, JA (reprint author), 22 S Greene St,Room N5E16, Baltimore, MD 21201 USA. FU NCI NIH HHS [CA8804] NR 23 TC 39 Z9 41 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2001 VL 92 IS 11 BP 2941 EP 2947 DI 10.1002/1097-0142(20011201)92:11<2941::AID-CNCR10072>3.0.CO;2-C PG 7 WC Oncology SC Oncology GA 494XD UT WOS:000172310400026 PM 11753970 ER PT J AU Nupponen, NN Carpten, JD AF Nupponen, NN Carpten, JD TI Prostate cancer susceptibility genes: Many studies, many results, no answers SO CANCER AND METASTASIS REVIEWS LA English DT Review DE hereditary; prostate cancer; predisposition; mutation ID ANDROGEN-RECEPTOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENES; LINKAGE ANALYSIS; FAMILY HISTORY; CHROMOSOME 1Q; E-CADHERIN; P73 GENE; STEROID 5-ALPHA-REDUCTASE; GERMLINE MUTATIONS AB Since the first report of a genome-wide scan for hereditary prostate cancer (HPCA hereinafter) in 1996, several publications have presented data implicating various chromosomal regions by linkage analysis without any consequential identifications of the target genes. The most intensive attention has been focused on chromosome 1, and it has been proposed to contain at least three sub-chromosomal regions (HPC1, PCAP, CAPB) harboring putative prostate cancer susceptibility genes. Nevertheless, one susceptibility gene, ELAC2/HPC2 at chromosome 17, has now been identified. Yet it seems to have a questionable role in prostate cancer predisposition. HPCA susceptibility loci have become undeniable archenemies of prostate cancer investigators, as the results of candidate gene analyses have been bewilderingly inconclusive. Predisposition to prostate cancer is most likely to be caused by several genes, different models of Mendelian inheritance, incomplete penetrance and varying population ethnicity frequencies. We will review the current state of the HPCA field and discuss the difficulties associated with identifying prostate cancer susceptibility genes. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Carpten, JD (reprint author), NHGRI, Canc Genet Branch, NIH, 50 S Dr, Bethesda, MD 20892 USA. NR 99 TC 18 Z9 19 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 2001 VL 20 IS 3-4 BP 155 EP 164 DI 10.1023/A:1015557308033 PG 10 WC Oncology SC Oncology GA 554RW UT WOS:000175751800004 PM 12085959 ER PT J AU Soga, S Sharma, SV Shiotsu, Y Shimizu, M Tahara, H Yamaguchi, K Ikuina, Y Murakata, C Tamaoki, T Kurebayashi, J Schulte, TW Neckers, LM Akinaga, S AF Soga, S Sharma, SV Shiotsu, Y Shimizu, M Tahara, H Yamaguchi, K Ikuina, Y Murakata, C Tamaoki, T Kurebayashi, J Schulte, TW Neckers, LM Akinaga, S TI Stereospecific antitumor activity of radicicol oxime derivatives SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE radicicol; erbB2; Hsp90; apoptosis; breast cancer ID BREAST-CANCER CELLS; HEAT-SHOCK-PROTEIN; ESTROGEN-RECEPTOR; MOLECULAR CHAPERONES; IN-VIVO; SIGNAL-TRANSDUCTION; SELECTIVE DEPLETION; HSP90 COMPLEX; WILD-TYPE; GELDANAMYCIN AB Purpose: Radicicol is a novel hsp90 antagonist, distinct from the chemically unrelated benzoquinone ansamycin compounds, geldanamycin and herbimycin. Both geldanamycin and radicicol bind in the aminoterminal nucleotide-binding pocket of hsp90, destabilizing the hsp90 client proteins, many of which are essential for tumor cell growth. We describe here antitumor activity of a novel oxime derivative of radicicol, KF58333. We also investigated the mechanism of antitumor activity of KF58333 in comparison with its oxime isomer KF58332. Methods: Antiproliferative activities were determined in a panel of breast cancer cell lines in vitro. We also examined inhibition of hsp90 function and apoptosis induction in erbB2-overexpressing human breast carcinoma KPL-4 cells in vitro. Direct binding activity to hsp90 was assessed by hsp90-binding assays using geldanamycin or radicicol beads. In animal studies, we investigated plasma concentrations of these compounds after i.v. injection in BALB/c mice and antitumor activity against KPL-4 cells transplanted into nude mice. Inhibition of hsp90 function and induction of apoptosis in vivo were investigated using tumor specimens from drug-treated animals. Results: KF58333 showed potent antiproliferative activity against all breast cancer cell lines tested in vitro, and was more potent than its stereoisomer KF58332. These results are consistent with the ability of KF58333 to deplete hsp90 client proteins and the induction of apoptosis in KPL-4 cells in vitro. Interestingly, KF58333, but not KF58332, showed significant in vivo antitumor activity accompanied by induction of apoptosis in KPL-4 human breast cancer xenografts. Although the plasma concentrations of these compounds were equivalent, KF58333, but not KF58332, depleted hsp90 client proteins such as erbB2, raf-1 and Akt in the tumor specimen recovered from nude mice. Conclusions: These results suggest that inhibition of hsp90 function, which causes depletion of hsp90 client proteins in tumor, contributes to the antitumor activity of KF58333, and that the stereochemistry of the oxime moiety is important for the biological activity of radicicol oxime derivatives. C1 Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, Nagaizumi, Shizuoka 4118731, Japan. Kawasaki Med Univ, Dept Breast & Thyroid Surg, Kurashiki, Okayama 7010192, Japan. NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Kyowa Hakko Kogyo Co Ltd, Tokyo Res Labs, Tokyo 1948533, Japan. RP Akinaga, S (reprint author), Kyowa Hakko Kogyo Co Ltd, Pharmaceut Res Inst, 1188 Nagaizumi Cho, Nagaizumi, Shizuoka 4118731, Japan. NR 39 TC 42 Z9 44 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 2001 VL 48 IS 6 BP 435 EP 445 DI 10.1007/s002800100373 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 510DW UT WOS:000173194300003 PM 11800023 ER PT J AU Garte, S Gaspari, L Alexandrie, AK Ambrosone, C Autrup, H Autrup, JL Baranova, H Bathum, L Benhamou, S Boffetta, P Bouchardy, C Breskvar, K Brockmoller, J Cascorbi, I Clapper, ML Coutelle, C Daly, A Dell'Omo, M Dolzan, V Dresler, CM Fryer, A Haugen, A Hein, DW Hildesheim, A Hirvonen, A Hsieh, LL Ingelman-Sundberg, M Kalina, I Kang, DH Kihara, M Kiyohara, C Kremers, P Lazarus, P Le Marchand, L Lechner, MC van Lieshout, EMM London, S Manni, JJ Maugard, CM Morita, S Nazar-Stewart, V Noda, K Oda, Y Parl, FF Pastorelli, R Persson, I Peters, WHM Rannug, A Rebbeck, T Risch, A Roelandt, L Romkes, M Ryberg, D Salagovic, J Schoket, B Seidegard, J Shields, PG Sim, E Sinnet, D Strange, RC Stucker, I Sugimura, H To-Figueras, J Vineis, P Yu, MC Taioli, E AF Garte, S Gaspari, L Alexandrie, AK Ambrosone, C Autrup, H Autrup, JL Baranova, H Bathum, L Benhamou, S Boffetta, P Bouchardy, C Breskvar, K Brockmoller, J Cascorbi, I Clapper, ML Coutelle, C Daly, A Dell'Omo, M Dolzan, V Dresler, CM Fryer, A Haugen, A Hein, DW Hildesheim, A Hirvonen, A Hsieh, LL Ingelman-Sundberg, M Kalina, I Kang, DH Kihara, M Kiyohara, C Kremers, P Lazarus, P Le Marchand, L Lechner, MC van Lieshout, EMM London, S Manni, JJ Maugard, CM Morita, S Nazar-Stewart, V Noda, K Oda, Y Parl, FF Pastorelli, R Persson, I Peters, WHM Rannug, A Rebbeck, T Risch, A Roelandt, L Romkes, M Ryberg, D Salagovic, J Schoket, B Seidegard, J Shields, PG Sim, E Sinnet, D Strange, RC Stucker, I Sugimura, H To-Figueras, J Vineis, P Yu, MC Taioli, E TI Metabolic gene polymorphism frequencies in control populations SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GLUTATHIONE-S-TRANSFERASE; LUNG-CANCER RISK; ARYLAMINE N-ACETYLTRANSFERASES; MICROSOMAL EPOXIDE HYDROLASE; TOBACCO-RELATED CANCERS; AFRICAN-AMERICANS; BREAST-CANCER; BLADDER-CANCER; CYTOCHROME-P450 ENZYMES; GSTT1 POLYMORPHISMS AB Using the International Project on Genetic Susceptibility to Environmental Carcinogens (GSEC) database containing information on over 15,000 control (noncancer) subjects, the allele and genotype frequencies for many of the more commonly studied metabolic genes (CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1, NAT2, GSTP, and EPHX) in the human population were determined. Major and significant differences in these frequencies were observed between Caucasians (n = 12,525), Asians (n = 2,136), and Africans and African Americans (n = 996), and some, but much less, heterogeneity was observed within Caucasian populations from different countries. No differences in allele frequencies were seen by age, sex, or type of controls (hospital patients versus population controls). No examples of linkage disequilibrium between the different loci were detected based on comparison of observed and expected frequencies for combinations of specific alleles. C1 Univ Med & Dent New Jersey, EOHSI, Piscataway, NJ 08854 USA. Genet Res Inst, Milan, Italy. Karolinska Inst, Stockholm, Sweden. Natl Toxicol Program, Jefferson, AR USA. Univ Aarhus, Aarhus, Denmark. Univ Auvergne, Clermont Ferrand, France. Odense Univ Hosp, DK-5000 Odense, Denmark. INSERM, Villejuif, France. IARC, Lyon, France. Univ Ljubljana, Ljubljana, Slovenia. Humboldt Univ, Univ Klinikum Charite, Berlin, Germany. Ernst Moritz Arndt Univ Greifswald, Greifswald, Germany. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Bordeaux 2, F-33076 Bordeaux, France. Newcastle Univ, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Ist Med Lavoro, Perugia, Italy. Keele Univ, Keele, Staffs, England. Natl Inst Occupat Hlth, Oslo, Norway. Univ Louisville, Louisville, KY 40292 USA. NCI, Rockville, MD USA. Finnish Inst Occupat Hlth, Helsinki, Finland. Chang Gung Univ, Tao Yuan, Taiwan. Safarik Univ, Kosice, Slovakia. Seoul Natl Univ, Coll Med, Seoul, South Korea. Kyoto Univ, Sch Publ Hlth, Kyoto, Japan. Kyushu Univ, Fukuoka 812, Japan. Inst Pathol Liege Belgium, Liege, Belgium. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ Lisbon, P-1699 Lisbon, Portugal. Univ Nijmegen Hosp, NL-6500 HB Nijmegen, Netherlands. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Hosp Maastricht, Maastricht, Netherlands. Ctr Rene Gauducheau, F-44035 Nantes, France. Yao Municipal Hosp, Osaka, Japan. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Kanazawa Univ, Kanazawa, Ishikawa 920, Japan. Vanderbilt Univ, Nashville, TN USA. Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Univ Pittsburgh, Pittsburgh, PA USA. Natl Inst Environm Hlth, Budapest, Hungary. Lund Univ, Lund, Sweden. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ Oxford, Oxford, England. Hop St Justine, Montreal, PQ H3T 1C5, Canada. Hamamatsu Univ Sch Med, Shizuoka, Japan. Hosp Clin Barcelona, Barcelona, Spain. Univ Turin, Turin, Italy. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Osped Maggiore, IRCCS, Direz Sci, Milan, Italy. RP Garte, S (reprint author), Univ Med & Dent New Jersey, EOHSI, 170 Frelinghuysen Rd, Piscataway, NJ 08854 USA. RI Hein, David/A-9707-2008; Cascorbi, Ingolf/A-4519-2009; Shields, Peter/I-1644-2012; Kang, Dae Hee/E-8631-2012; Peters, W.H.M./L-4572-2015; Benhamou, Simone/K-6554-2015; dell'Omo, Marco/K-8649-2016; Osborne, Nicholas/N-4915-2015; Risch, Angela/H-2669-2013; OI dell'Omo, Marco/0000-0002-6476-9893; Osborne, Nicholas/0000-0002-6700-2284; Risch, Angela/0000-0002-8026-5505; London, Stephanie/0000-0003-4911-5290 FU NCI NIH HHS [R01 CA034627, R01 CA034627-16] NR 79 TC 624 Z9 649 U1 4 U2 27 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2001 VL 10 IS 12 BP 1239 EP 1248 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 507JF UT WOS:000173023100002 PM 11751440 ER PT J AU Vineis, P Marinelli, D Autrup, H Brockmoller, J Cascorbi, I Daly, AK Golka, K Okkels, H Risch, A Rothman, N Sim, E Taioli, E AF Vineis, P Marinelli, D Autrup, H Brockmoller, J Cascorbi, I Daly, AK Golka, K Okkels, H Risch, A Rothman, N Sim, E Taioli, E TI Current smoking, occupation, N-acetyltransferase-2 and bladder cancer: A pooled analysis of genotype-based studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID GENE-ENVIRONMENT INTERACTION; N-ACETYLTRANSFERASE; CIGARETTE-SMOKING; DNA-ADDUCTS; RISK; ACETYLATION; METAANALYSIS; NAT2; SUSCEPTIBILITY; POLYMORPHISMS AB The aim of this study was to investigate the association of NAT2 gene polymorphism with bladder cancer using the data derived from the International Project on Genetic Susceptibility to Environmental Carcinogens. Four case control studies conducted in four European countries, plus two case series, one from England and one from Germany, for a total of 1530 cases and 731 controls (all Caucasian) were included. The interaction between NAT2 and bladder cancer considering smoking habits and occupational exposure was studied. There was a significant association between NAT2 and bladder cancer (odds ratio: 1.42, 95% confidence interval: 1.14-1.77), with a slightly significant heterogeneity among studies. However, heterogeneity disappeared when smokers were divided into current and ex-smokers. The risk of cancer was elevated in smokers and occupationally exposed subjects, with the highest risk among slow acetylators. The increase in risk was limited, in fact, to current smokers (odds ratio = 1.74, 95% confidence interval: 0.96-3.15). This analysis confirms that the NAT2 genotype is a risk factor for bladder cancer by interacting with smoking or occupational exposures. Our observation suggests that NAT2 is not a risk factors per se but modulates the effect of carcinogens contained in tobacco smoke (probably arylamines) or associated with occupational exposures. C1 Osped Policlin, IRCCS, I-20122 Milan, Italy. Univ Turin, CPO Piemonte, I-10126 Turin, Italy. Inst Sci Interchange Fdn, I-10126 Turin, Italy. Univ Milan, I-20122 Milan, Italy. Aarhus Univ, DK-8000 Aarhus C, Denmark. Univ Berlin, D-10098 Berlin, Germany. Univ Greifswald, D-17487 Greifswald, Germany. Univ Newcastle Upon Tyne, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. Inst Arbeitsphysiol, D-44139 Dortmund, Germany. Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany. NCI, Bethesda, MD 20892 USA. Univ Oxford, Oxford OX1 3QT, England. RP Taioli, E (reprint author), Osped Policlin, IRCCS, I-20122 Milan, Italy. RI Cascorbi, Ingolf/A-4519-2009; Daly, Ann/H-3144-2011; Risch, Angela/H-2669-2013 OI Daly, Ann/0000-0002-7321-0629; Risch, Angela/0000-0002-8026-5505 NR 24 TC 91 Z9 93 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2001 VL 10 IS 12 BP 1249 EP 1252 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 507JF UT WOS:000173023100003 PM 11751441 ER PT J AU Stucker, I Boffetta, P Antilla, S Benhamou, S Hirvonen, A London, S Taioli, E AF Stucker, I Boffetta, P Antilla, S Benhamou, S Hirvonen, A London, S Taioli, E TI Lack of interaction between asbestos exposure and glutathione S-transferase M1 and T1 genotypes in lung carcinogenesis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COKE-OVEN WORKERS; CANCER RISK; GENETIC-POLYMORPHISM; CEMENT WORKERS; ADDUCT LEVELS; DNA-ADDUCTS; GSTM1; MU; SMOKING; THETA AB An interaction between occupational carcinogens and genetic susceptibility factors in determining individual lung cancer risk is biologically plausible, but the interpretation of available studies are limited by the small number of exposed subjects. We selected from the international database on Genetic Susceptibility and Environmental Carcinogens the studies of lung cancer that included information on metabolic polymorphisms and occupational exposures. Adequate data were available for asbestos exposure and GSTM1 (five studies) and GSTT1 (three studies) polymorphisms. For GSTM1, the pooled analysis included 651 cases and 983 controls. The odds ratio (OR) of lung cancer was 2.0 [95% confidence interval (CI) 1.4-2.7] for asbestos exposure and 1.1 (95% CI 0.9-1.4) for GSTM1-null genotype. The OR of interaction between asbestos and GSTM1 polymorphism was 1.1 (95% CI 0.6-2.1) based on 54 cases and 53 controls who were asbestos exposed and GSTM1 null. The case-only approach, which was based on 869 lung cancer cases and had an 80% power to detect an OR of interaction of 1.56, also provided lack of evidence of interaction. The analysis of possible interaction between GSTT1 polymorphism and asbestos exposure in relation to lung cancer was based on 619 cases. The prevalence OR of GSTT1-null genotype and asbestos exposure was 1.1 (95% CI 0.6-2.0). Our results do not support the hypothesis that the risk of lung cancer after asbestos exposure differs according to GSTM1 genotype. The low statistical power of the pooled analysis for GSTT1 genotypes hampered any firm conclusion. No adequate data were available to assess other interactions between occupational exposures and metabolic polymorphisms. C1 INSERM, U170, F-94807 Villejuif, France. Int Agcy Res Canc, F-69008 Lyon, France. Finnish Inst Occupat Hlth, FIN-00250 Helsinki, Finland. INSERM, U351, F-94805 Villejuif, France. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Milan, Osped Policlin, IRCCS, I-20122 Milan, Italy. RP Stucker, I (reprint author), INSERM, U170, 16 Av Paul Vaillant Couturier, F-94807 Villejuif, France. RI Benhamou, Simone/K-6554-2015; OI London, Stephanie/0000-0003-4911-5290 NR 34 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2001 VL 10 IS 12 BP 1253 EP 1258 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 507JF UT WOS:000173023100004 PM 11751442 ER PT J AU Peters, U McGlynn, KA Chatterjee, N Gunter, E Garcia-Closas, M Rothman, N Sinha, R AF Peters, U McGlynn, KA Chatterjee, N Gunter, E Garcia-Closas, M Rothman, N Sinha, R TI Vitamin D, calcium, and vitamin D receptor polymorphism in colorectal adenomas SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BONE-MINERAL DENSITY; EPITHELIAL-CELL PROLIFERATION; TRANSLATION INITIATION SITE; DIETARY CALCIUM; COLON-CANCER; PROSTATE-CANCER; BREAST-CANCER; 1,25-DIHYDROXYVITAMIN D-3; GENE POLYMORPHISM; RECTAL-CANCER AB Experimental studies suggest that vitamin D and calcium protect against cancer by reducing proliferation and inducing differentiation. The effects of vitamin D and calcium may be mediated by the vitamin D receptor (VDR), which is encoded by the VDR gene. The present study investigated whether calcium intake and serum vitamin D, as an integrated measure of intake and endogenous production, were associated with risk of colorectal adenoma, known precursors of invasive colorectal cancer. In addition, the interrelation among vitamin D, calcium, and FokI polymorphism of the VDR gene was investigated. Persons (239) with histologically confirmed colorectal adenomas and 228 control individuals without colorectal adenomas confirmed by sigmoidoscopy were enrolled in this case control study conducted at the National Naval Medical Center, Bethesda, MD. We observed an inverse association of serum 25-OH vitamin D [25-(OH)D] with colorectal adenoma. With each 10 ng/ml increase of serum 25-(OH)D, the risk of colorectal adenoma decreased by 26% (odds ratio 0.74, 95% confidence interval 0.60-0.92). The results provided limited evidence for a weak association between calcium intake and colorectal adenoma (odds ratio 0.97, 95% confidence interval 0.93-1.01 per each 100-mg calcium intake). However, the inverse association of serum 25-(OH)D with colorectal adenoma is suggested to be stronger in subjects with calcium intake above the median (P for multiplicative interaction 0.13). The VDR FokI polymorphism was not significantly associated with colorectal adenoma and did not modify the effect of vitamin D or calcium. In conclusion, the study results suggested a protective effect for vitamin D on colorectal adenoma. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. RP Peters, U (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS, Bethesda, MD 20892 USA. RI Garcia-Closas, Montserrat /F-3871-2015; Sinha, Rashmi/G-7446-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Sinha, Rashmi/0000-0002-2466-7462 NR 71 TC 119 Z9 121 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2001 VL 10 IS 12 BP 1267 EP 1274 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 507JF UT WOS:000173023100006 PM 11751444 ER PT J AU Garte, S Boffetta, P Caporaso, N Vineis, P AF Garte, S Boffetta, P Caporaso, N Vineis, P TI Metabolic gene allele nomenclature SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Letter ID CANCER SUSCEPTIBILITY; CYP GENES; POLYMORPHISM; EPIDEMIOLOGY C1 Genet Res Inst, I-20135 Milan, Italy. Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA. Int Agcy Res Canc, F-69372 Lyon, France. NCI, Bethesda, MD 20892 USA. Univ Turin, I-10126 Turin, Italy. RP Garte, S (reprint author), Genet Res Inst, I-20135 Milan, Italy. NR 11 TC 17 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2001 VL 10 IS 12 BP 1305 EP 1306 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 507JF UT WOS:000173023100013 PM 11751451 ER PT J AU Gottesman, MM Oppenheim, A Rund, D Kimchi-Sarfaty, C AF Gottesman, MM Oppenheim, A Rund, D Kimchi-Sarfaty, C TI Gene transfer using SV40 vectors packaged in vitro SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Hadassah Univ Hosp, IL-91010 Jerusalem, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD DEC PY 2001 VL 8 SU 2 MA O72 BP S22 EP S22 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 501YR UT WOS:000172714100073 ER PT J AU Kimchi-Sarfaty, C Garfield, S Arora, M Cruz, CO Oppenheim, A Rund, D Gottesman, MM AF Kimchi-Sarfaty, C Garfield, S Arora, M Cruz, CO Oppenheim, A Rund, D Gottesman, MM TI SV40 in vitro packaging-mediated transfer of MDR1 and GFP genes into hematopoietic cells SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Hadassah Univ Hosp, IL-91010 Jerusalem, Israel. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD DEC PY 2001 VL 8 SU 2 MA PD47 BP S14 EP S15 PG 2 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 501YR UT WOS:000172714100048 ER PT J AU Thorsen, F Afione, S Kotin, R Lonning, PE Oyvind, EP Bjerkvig, R Hoover, F AF Thorsen, F Afione, S Kotin, R Lonning, PE Oyvind, EP Bjerkvig, R Hoover, F TI Adeno-associated viral vector 2, 4 and 5 transduction efficiency in breast carcinoma- and glioma-derived cell lines and spheroids derived from human glioblastomas SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Univ Bergen, N-5020 Bergen, Norway. Haukeland Hosp, Dept Oncol, Onk Forsk Lab, N-5021 Bergen, Norway. NIH, Lab Biochem Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD DEC PY 2001 VL 8 SU 2 MA PD51 BP S15 EP S16 PG 2 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 501YR UT WOS:000172714100052 ER PT J AU Tisdale, JF AF Tisdale, JF TI Optimization of hematopoietic stem cell gene transfer methods using the non-human primate competitive repopulation model: recent progress toward clinical application SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD DEC PY 2001 VL 8 SU 2 MA O73 BP S22 EP S22 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 501YR UT WOS:000172714100074 ER PT J AU Sondak, VK Meltzer, PS Trent, JM AF Sondak, VK Meltzer, PS Trent, JM TI Application of molecular cytogenetic techniques in a case study of human cutaneous metastatic melanoma SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN-MALIGNANT MELANOMA; KINASE-4 INHIBITOR GENE; CHROMOSOME MICRODISSECTION; FAMILIAL MELANOMA; PAINTING PROBES; TUMOR PROGRESSION; RAPID GENERATION; GROWTH-FACTOR; SOLID TUMORS AB Consistent structural chromosome rearrangements have rarely been identified in adult solid tumors. The introduction of advanced molecular cytogenetic techniques has provided new ways of analyzing highly complex karyotypes commonly encountered in these malignancies. This study describes a detailed molecular cytogenetic analysis of a sporadic human cutaneous melanoma biopsy, M92-047, using a combination of G-banding, fluorescence in situ hybridization (FISH), chromosome microdissection, and comparative genomic hybridization (CGH). G-banding revealed that this tumor was composed primarily of closely related near-diploid and near-tetraploid cell subpopulations containing several clonal numerical and structural chromosome alterations. Fluorescence in situ hybridization using whole chromosome painting probes and chromosome arm painting probes, was employed to verify the rearranged chromosomes; dic(l; 4), der(8)t(1;8), and der(15)t(6:15), whereas marker chromosomes dic(8;1;16), der(12)t(9;12), and der(17)t(13;17) were discerned by chromosome microdissection and subsequent reverse in situ hybridization (rev ish) analysis. Comparative genomic hybridization illustrated DNA copy number changes in good agreement with the karyotypic analysis. Although this line exhibits recurrent alterations representative of melanoma, two unique breakpoints-1p13 and 8p21-were identified in two different rearranged chromosomes, suggesting potentially important regions for further dissection by molecular genetic techniques. This report demonstrates the advantages of combining multiple techniques in order to obtain a detailed description of cytogenetic changes in melanoma. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Trent, JM (reprint author), NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NR 50 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD DEC PY 2001 VL 131 IS 2 BP 97 EP 103 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 505MT UT WOS:000172917100001 ER PT J AU Peters, J Loud, J Dimond, E Jenkins, J AF Peters, J Loud, J Dimond, E Jenkins, J TI Cancer genetics fundamentals SO CANCER NURSING LA English DT Review DE carcinogenesis; cancer genetics; neoplasm; cell cycle; apoptosis; angiogenesis; genetic counseling ID NONPOLYPOSIS COLORECTAL-CANCER; DNA MISMATCH REPAIR; COLON-CANCER; TELOMERASE ACTIVITY; MUTATOR PHENOTYPE; HEREDITARY; MUTATIONS; HOMOLOG; RETINOBLASTOMA; TUMORIGENESIS AB It is often said that cancer is genetic. What exactly does that mean? This article is our answer to that question at the turn of the millennium. We present models of carcinogenesis, review basic cancer genetics terminology, and explain some of the fundamental genetic changes common to all types of cancer. These are organized into 6 sections of (1) self-sufficiency in growth signals, (2) insensitivity to growth-inhibitory signals, (3) evasion of programmed cell death, (4) limitless replicative potential, (5) sustained angiogenesis, and (6) tissue invasion and metastases. Underlying all of these changes are the even more fundamental enabling factors of genetic instability on both the chromosomal and the gene level. Finally, we look toward the future in a field where the future is now!. C1 NCI, CGB, DCEG, NIH, Rockville, MD 20852 USA. NCI, Natl Naval Med Ctr, Bethesda, MD 20892 USA. RP Peters, J (reprint author), NCI, CGB, DCEG, NIH, 6120 Execut Blvd,EPS 7021, Rockville, MD 20852 USA. NR 114 TC 6 Z9 7 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0162-220X J9 CANCER NURS JI Cancer Nurs. PD DEC PY 2001 VL 24 IS 6 BP 446 EP 461 DI 10.1097/00002820-200112000-00005 PG 16 WC Oncology; Nursing SC Oncology; Nursing GA 499ER UT WOS:000172558500004 PM 11762507 ER PT J AU Sohn, OS Fiala, ES Requeijo, SP Weisburger, JH Gonzalez, FJ AF Sohn, OS Fiala, ES Requeijo, SP Weisburger, JH Gonzalez, FJ TI Differential effects of CYP2E1 status on the metabolic activation of the colon carcinogens azoxymethane and methylazoxymethanol SO CANCER RESEARCH LA English DT Article ID PUTATIVE PRENEOPLASTIC LESIONS; ALCOHOL-DEHYDROGENASE; N-NITROSODIMETHYLAMINE; RAT-LIVER; NITROSAMINE METABOLISM; MOLECULAR-BASIS; DEER MOUSE; F344 RAT; MICE; OXIDATION AB Methylazoxymethanol (MAM) and its chemical and metabolic precursor, azoxymethane (AOM), both strong colon carcinogens in rodents, can be metabolically activated by CYP2E1 in vitro. Using CYP2E1-null mice, we found that CYP2E1 deficiency differentially affects the activation of AOM and MAM, as reflected in DNA guanine alkylation in the colon and in the formation of colonic aberrant crypt foci (ACF). Male and female inbred 129/SV wild-type (WT) and CYP2E1-null (null) mice were treated with 189 mu mol/kg of either AOM or methylazoxymethyl acetate (MAMAc), and 7-methylguanine (7-MeG) and O-6-methylguanine (O-6-MeG) were measured in the DNAs of various organs. The levels of O-6-MeG (as pmol/nmol guanine) in the liver, colon, kidney, and lung of male null mice treated with AOM were 87, 48, 70, and 43% lower, respectively, than in AOM-treated WT mice. In null mice treated with MAMAc, the DNA O-6-MeG levels were lower by 38% in the liver but were higher by 368,146, and 194% in the colon, kidney, and lung, respectively, compared with the same organs of WT mice treated in the same way. Determination of ACF revealed that although AOM-induced ACF formation was significantly lower in the null group than in the WT group, MAMAc-induced ACF formation was significantly higher in the null group than in the WT group. These results demonstrate an important role for CYP2E1 in the in vivo activation of AOM and MAM and suggest that agents that modify CYP2E1 activity at the tumor initiation stage might either enhance or inhibit colon carcinogenesis, depending on whether AOM or MAMAc is used as the carcinogen. The mechanism of this effect is discussed. C1 Amer Hlth Fdn, Valhalla, NY 10595 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Fiala, ES (reprint author), Amer Hlth Fdn, 1 Dana Rd, Valhalla, NY 10595 USA. EM efiala@ahf.org FU NCI NIH HHS [CA46589] NR 54 TC 70 Z9 71 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2001 VL 61 IS 23 BP 8435 EP 8440 PG 6 WC Oncology SC Oncology GA 499WX UT WOS:000172594600018 PM 11731424 ER PT J AU Hatoum, A El-Sabban, ME Khoury, J Yuspa, SH Darwiche, N AF Hatoum, A El-Sabban, ME Khoury, J Yuspa, SH Darwiche, N TI Overexpression of retinoic acid receptors alpha and gamma into neoplastic epidermal cells causes retinoic acid-induced growth arrest and apoptosis SO CARCINOGENESIS LA English DT Article ID PROTEIN-KINASE-C; CARCINOMA-CELLS; MOUSE SKIN; HIGH-RISK; TERMINAL DIFFERENTIATION; SQUAMOUS DIFFERENTIATION; MALIGNANT CONVERSION; HUMAN KERATINOCYTES; CANCER CELLS; RAR-ALPHA AB Retinoids are essential for normal epidermal differentiation and are used for the prevention and treatment of numerous skin disorders and cancers in humans. In previous studies, we have shown that retinoic acid receptors (RARs) -alpha and -gamma are down-regulated during skin tumor progression. The transduction of v-ras(Ha) into primary mouse keratinocytes is sufficient to reduce both RARalpha and RARgamma protein levels as well as inhibit their transactivation functions. Our primary objective is to investigate the roles that RARalpha and RARgamma play in keratinocyte tumor cell proliferation. Through retroviral gene transduction, we overexpressed RARalpha or RARgamma into neoplastic mouse epidermal cells with down-regulated endogenous RAR proteins. Following all-trans retinoic acid (RA) treatment, RARalpha- and RARgamma-transduced cell lines exhibit a progressive, dose-dependent growth inhibition relative to the control LXSN cell lines. Further characterization of RAR-transduced cells following RA treatment reveals that both RARalpha and RARgamma cause a decrease in S-phase population, while only RARalpha causes a simultaneous G(0)/G(1) block as evidenced by reduced [H-3]-thymidine incorporation and flow cytometric analysis of DNA content. Following RA treatment, both receptors cause an early, transient increase in the cyclin-dependent kinase inhibitor (CDKI) p21 proteins, while only RARalpha causes a simultaneous sharp, brief increase in the CDKI p16 protein. A later decrease in cyclin D-1 protein is also evident in RARalpha- and RARgamma-transduced cells. Chromatin condensation and PARP cleavage are observed in both RARalpha- and RARgamma-transduced cells indicating an RA-induced apoptosis that may be caspase dependent. Furthermore, both receptors cause a late upregulation and apparent cleavage of the squamous differentiation marker protein kinase C (PKC)-eta. These results suggest that RARalpha and RARgamma enhance growth suppression and apoptosis of neoplastic epidermal keratinocytes. This growth inhibitory effect of both retinoid receptors in neoplastic keratinocytes may be achieved through distinct as well as overlapping mechanisms of cell cycle control. C1 Amer Univ Beirut, Dept Biol, Beirut, Lebanon. Amer Univ Beirut, Dept Biochem, Beirut, Lebanon. Amer Univ Beirut, Dept Human Morphol, Beirut, Lebanon. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Darwiche, N (reprint author), Amer Univ Beirut, Dept Biol, POB 11-0236, Beirut, Lebanon. OI Darwiche, Nadine/0000-0002-1862-5426 NR 56 TC 31 Z9 32 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2001 VL 22 IS 12 BP 1955 EP 1963 DI 10.1093/carcin/22.12.1955 PG 9 WC Oncology SC Oncology GA 510NX UT WOS:000173215100006 PM 11751425 ER PT J AU Walker, CL Cesen-Cummings, K Houle, C Baird, D Barrett, JC Davis, B AF Walker, CL Cesen-Cummings, K Houle, C Baird, D Barrett, JC Davis, B TI Protective effect of pregnancy for development of uterine leiomyoma SO CARCINOGENESIS LA English DT Article ID REPRODUCTIVE-TRACT LEIOMYOMATA; ESTROGEN-RECEPTOR MODULATORS; BREAST-CANCER; PREMENOPAUSAL WOMEN; ENDOMETRIAL CANCER; RODENT MODEL; RISK-FACTORS; RAT; EPIDEMIOLOGY; PROLACTIN AB Many factors that can modulate the risk of developing uterine leiomyoma have been identified, including parity. Epidemiological data on decreased risk of developing this disease has been subject to different interpretations regarding whether pregnancy per se is protective or, as leiomyomas are a major cause of infertility, women that develop these tumors are less fertile and thus have lower pregnancy rates. We have utilized an animal model genetically predisposed to uterine leiomyoma to investigate the potential protective effect of pregnancy on the risk of developing this disease. Female Eker rats that carry a mutation in the tuberous sclerosis 2 (Tsc-2) tumor suppressor gene develop uterine leiomyoma with a frequency of 65% when nulliparous. These animals were bred with intact or vasectomized males and tumor incidence determined after a single pregnancy (to confirm fertility) or multiple pregnancies over the lifetime of the animals. Females with multiple litters displayed a dramatic shift in tumor incidence and presentation. Tumor incidence decreased from 71% in single litter females to 10% in females that had multiple litters (average: five litters/animal). Interestingly, females bred with vasectomized males also exhibited a reduced tumor incidence of 41%, suggesting that the hormonal changes associated with early stages of pregnancy that occur in pseudopregnant females may have contributed to the protective effect of pregnancy. C1 Univ Texas, MD Anderson Canc Ctr, Div Sci Pk Res, Smithville, TX 78957 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Walker, CL (reprint author), Univ Texas, MD Anderson Canc Ctr, Div Sci Pk Res, Pk Rd 1C, Smithville, TX 78957 USA. OI Baird, Donna/0000-0002-5544-2653 FU NCI NIH HHS [CA 16672]; NIEHS NIH HHS [ES 07784, ES 08263] NR 37 TC 32 Z9 34 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2001 VL 22 IS 12 BP 2049 EP 2052 DI 10.1093/carcin/22.12.2049 PG 4 WC Oncology SC Oncology GA 510NX UT WOS:000173215100019 PM 11751438 ER PT J AU Carmeliet, E Fozzard, HA Hiraoka, M Janse, MJ Ogawa, S Roden, DM Rosen, MR Rudy, Y Schwartz, PJ Matteo, PS Antzelevitch, C Boyden, PA Catterall, WA Fishman, GI George, AL Izumo, S Jalife, J January, CT Kleber, AG Marban, E Marks, AR Spooner, PM Waldo, AL Weiss, JM Zipes, DP AF Carmeliet, E Fozzard, HA Hiraoka, M Janse, MJ Ogawa, S Roden, DM Rosen, MR Rudy, Y Schwartz, PJ Matteo, PS Antzelevitch, C Boyden, PA Catterall, WA Fishman, GI George, AL Izumo, S Jalife, J January, CT Kleber, AG Marban, E Marks, AR Spooner, PM Waldo, AL Weiss, JM Zipes, DP CA Sicilian Gambit TI New approaches to antiarrhythmic therapy: emerging therapeutic applications of the cell biology of cardiac arrhythmias SO CARDIOVASCULAR RESEARCH LA English DT Review DE antiarrhythmic agents; gene therapy; genes ID LONG-QT SYNDROME; LEFT-VENTRICULAR DYSFUNCTION; SIGNAL-TRANSDUCTION PATHWAYS; TRANSIENT OUTWARD CURRENT; RENIN-ANGIOTENSIN SYSTEM; GERMAN-SHEPHERD DOGS; ATRIAL-FIBRILLATION; POTASSIUM CHANNEL; HEART-FAILURE; MYOCARDIAL-INFARCTION AB Cardiac arrhythmias complicate many diseases affecting the heart and the circulation, and incorporate a multiplicity of underlying mechanisms. The evolution of scientific knowledge has made the complex changes produced by cardiovascular disease sufficiently understood at the organ, cellular, and molecular levels such that there is a diversity of therapeutic targets for pharmacological therapy and/or prevention. Moreover, the approach of rational drug design in mechanism-specific and disease-specific fashion facilitates targeting of therapy via the methods of molecular, structural and translational biology. Additional approaches, employing similar drug design strategies but based on gene therapy and transcriptional and translational modification are on the horizon. Hence, there is reason to be optimistic regarding the design, testing and clinical availability of novel antiarrhythmic therapies. Condensed Abstract: The evolution of scientific knowledge has made the effects of cardiovascular disease sufficiently understood at the organ, cellular, and molecular levels such that there is a diversity of therapeutic tat-gets for pharmacological therapy and/or prevention. Moreover, the approach of rational drug design facilitates targeting of therapy via the methods of molecular, structural and translational biology. Additional approaches, employing similar drug design strategies but based on gene therapy and transcriptional and translational modification arc on the horizon. Hence, there is reason to be optimistic regarding the design, testing and clinical availability of novel antiarrhythmic therapies. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Katholieke Univ Leuven, Louvain, Belgium. Univ Chicago, Chicago, IL 60637 USA. Tokyo Med & Dent Univ, Tokyo, Japan. Cardiovasc Res, Amsterdam, Netherlands. Keio Univ, Tokyo, Japan. Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Columbia Univ, New York, NY USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. IRCCS, Policlin S Matteo, Pavia, Italy. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Masonic Med Res Lab, Utica, NY USA. Univ Washington, Seattle, WA 98195 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. SUNY Syracuse, Syracuse, NY USA. Univ Wisconsin, Madison, WI USA. Univ Bern, Bern, Switzerland. Johns Hopkins Univ, Baltimore, MD USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Cardiovasc Res Lab, Los Angeles, CA USA. Krannert Cardiovasc Res Inst, Indianapolis, IN USA. Columbia Univ, Coll Phys & Surg, Dept Pharmacol, Ctr Mol Therapeut, New York, NY 10032 USA. RP Rosen, MR (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pharmacol, Ctr Mol Therapeut, 630 W 168 St,PH7W-321, New York, NY 10032 USA. EM mrr1@columbia.edu RI Schwartz, Peter/J-4267-2016; Jalife, Jose/L-4833-2015; OI Schwartz, Peter/0000-0003-0367-1048; Jalife, Jose/0000-0003-0080-3500; Antzelevitch, Charles/0000-0001-5215-4667; Zipes, Douglas/0000-0001-7141-6829; Antzelevitch, Charles/0000-0001-7349-1582 NR 169 TC 10 Z9 10 U1 0 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD DEC PY 2001 VL 52 IS 3 BP 345 EP 360 AR PII S0008-6363(01)00465-5 PG 16 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 542HV UT WOS:000175038200002 ER PT J AU Mimnaugh, EG Kayastha, G McGovern, NB Hwang, SG Marcu, MG Trepel, J Cai, SY Marchesi, VT Neckers, L AF Mimnaugh, EG Kayastha, G McGovern, NB Hwang, SG Marcu, MG Trepel, J Cai, SY Marchesi, VT Neckers, L TI Caspase-dependent deubiquitination of monoubiquitinated nucleosomal histone H2A induced by diverse apoptogenic stimuli SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE ubiquitin; histones; nucleosomes; caspases; deubiquitination; apoptosis ID UBIQUITIN-PROTEIN LIGASE; CHROMATIN CONDENSATION; PROTEASOME INHIBITORS; POLYACRYLAMIDE GELS; CARCINOMA CELLS; APOPTOSIS; DISAPPEARANCE; PHOSPHORYLATION; TRANSCRIPTION; ACCUMULATION AB Enzymatic deubiquitination of mono-ubiquitinated nucleosomal histone H2A (uH2A) and H2B (uH2B) is closely associated with mitotic chromatin condensation, although the function of this histone modification in cell division remains ambiguous. Here we show that rapid and extensive deubiquitination of nucleosomal uH2A occurs in Jurkat cells undergoing apoptosis initiated by anti-Fas activating antibody, staurosporine, etoposide, doxorubicin and the proteasome inhibitor, N-acetyl-leucyl-leucyl-norlucinal. These diverse apoptosis inducers also promoted the accumulation of slowly migrating, high molecular weight ubiquitinated proteins and depleted the cellular pool of unconjugated ubiquitin. In apoptotic cells, ubiquitin was cleaved from uH2A subsequent to the appearance of plasma membrane blebbing, and deubiquitination of uH2A closely coincided with the onset of nuclear pyknosis and chromatin condensation. Nucleosomal uH2A deubiquitination, poly (ADP-ribose)polymerase (PARP) cleavage and chromatin condensation were prevented in cells challenged with apoptosis inducers by pretreatment with the pan-caspase inhibitor, zVAD-fmk, or by over-expressing antiapoptotic Bcl-xL protein. These results implicate a connection between caspase cascade activation and nucleosomal uH2A deubiquitination. Transient transfection of 293 cells with the gene encoding Ubp-M, a human deubiquitinating enzyme, promoted uH2A deubiquitination, while an inactive mutated Ubp-M enzyme did not. However, Ubp-M-promoted deubiquitination of uH2A was insufficient to initiate apoptosis in these cells. We conclude that uH2A deubiquitination is a downstream consequence of procaspase activation and that Unscheduled cleavage of ubiquitin from uH2A is a consistent feature of the execution phase of apoptosis rather than a determining or initiating apoptogenic event, Nucleosomal uH2A deubiquitination may function as a cellular sensor of stress in situations like apoptosis through which cells attempt to preserve genomic integrity. C1 NCI, Canc Res Ctr, Tumor Cell Biol Sect, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr,Cell Signaling & Oncogenesis Sect, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06536 USA. RP Mimnaugh, EG (reprint author), NCI, Med Branch, Tumor Cell Biol Sect, NIH, Key W Ctr,Suite 300,9610 Med Ctr Dr, Rockville, MD 20850 USA. RI cai, shaobin/A-6635-2016 NR 46 TC 42 Z9 45 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD DEC PY 2001 VL 8 IS 12 BP 1182 EP 1196 DI 10.1038/sj.cdd.4400924 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 502GL UT WOS:000172735300007 PM 11753566 ER PT J AU Shan, L Rouhani, SA Schut, HAJ Snyderwine, EG AF Shan, L Rouhani, SA Schut, HAJ Snyderwine, EG TI 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) modulates lactogenic hormone-mediated differentiation and gene expression in HC11 mouse mammary epithelial cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID BETA-CASEIN GENE; SPRAGUE-DAWLEY RATS; TYROSINE PHOSPHORYLATION; GLAND DEVELOPMENT; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; BREAST-CANCER; DNA-ADDUCTS; COOKED MEAT; TRANSCRIPTION; ACTIVATION AB 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen in cooked meat. Using the HC11 mouse mammary epithelial cell line, a well-characterized model for hormone-mediated differentiation, we examined whether PhIP altered the expression of genes regulated by lactogenic hormones dexamethasone, insulin, and prolactin (DIP). When HC11-Lux cells (stably transfected with a beta-casein promoter luciferase construct) were cultured in DIP-containing medium, PhIP (100 muM) enhanced luciferase activity 11-fold over that observed in DIP medium alone. The effect of PhIP on augmenting luciferase activity was observed only when lactogenic hormones were included in the medium. Expression of the endogenous beta-casein gene was also higher in HC11 cells treated with PhIP in hormone-enriched medium. With the increased expression of beta-casein gene, the level of phospho-signal transducer and activator of transcription 5A (phospho-STAT5A), the transcription factor regulating beta-casein gene expression, was elevated in PhIP-exposed HC11 cells. AG490, a Janus kinase 2 (JAK2)-specific inhibitor, blocked the effect of PhIP on beta-casein gene expression. PhIP-treated cells also showed higher expression of Bcl-2 and lower expression of Bax, consistent with a possible antiapoptotic action of PhIP. The findings indicate that PhIP modulates lactogenic hormone-mediated gene expression in mammary epithelia cells, apparently via enhanced phosphorylation of STAT5A. The findings have implications for a novel mechanism of action of the mammary gland carcinogen PhIP. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. Med Coll Ohio, Dept Pathol, Toledo, OH 43614 USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, Div Basic Sci,NIH, Bldg 37,Room 3C28, Bethesda, MD 20892 USA. EM elizabeth_snyderwine@nih.gov NR 43 TC 8 Z9 8 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD DEC PY 2001 VL 12 IS 12 BP 649 EP 656 PG 8 WC Cell Biology SC Cell Biology GA 511WZ UT WOS:000173289700008 PM 11751460 ER PT J AU Shi, YB Fu, LZ Hsia, SCV Tomita, A Buchholz, D AF Shi, YB Fu, LZ Hsia, SCV Tomita, A Buchholz, D TI Thyroid hormone regulation of apoptotic tissue remodeling during anuran metamorphosis SO CELL RESEARCH LA English DT Review DE Xenopus laevis; thyroid hormone receptor; extracellular matrix; apoptosis ID PROGRAMMED CELL-DEATH; TADPOLE TAIL REGRESSION; EXTRACELLULAR-MATRIX; XENOPUS-LAEVIS; RECEPTOR SUPERFAMILY; EPIDERMAL-CELLS; C-ELEGANS; FAMILY; BCL-2; EXPRESSION AB Anuran metamorphosis involves systematic transformations of individual organs in a thyroid hormone (TH)-dependent manner. Morphological and cellular studies have shown that the removal of larval organs/tissues such the tail and the tadpole intestinal epithelium is through programmed cell death or apoptosis. Recent molecular investigations suggest that TH regulates metamorphosis by regulating target gene expression through thyroid hormone receptors (TRs), which are DNA-binding transcription factors. Cloning and characterization of TH response genes show that diverse groups of early response genes are induced by TH. The products of these TH response genes are believed to directly or indirectly affect the expression and/or functions of cell death genes, which are conserved at both sequence and function levels in different animal species. A major challenge for future research lies at determining the signaling pathways leading to the activation of apoptotic processes and whether different death genes are involved in the regulation of apoptosis in different tissues/organs to effect tissue-specific transformations. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Shi, YB (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. NR 55 TC 32 Z9 34 U1 0 U2 0 PU SCIENCE CHINA PRESS PI BEIJING PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD DEC PY 2001 VL 11 IS 4 BP 245 EP 252 DI 10.1038/sj.cr.7290093 PG 8 WC Cell Biology SC Cell Biology GA 507YL UT WOS:000173058800001 PM 11787769 ER PT J AU Saavedra, JM AF Saavedra, JM TI Neuroscience in Israel at 2001 - Foreword SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD DEC PY 2001 VL 21 IS 6 BP 553 EP 554 AR UNSP 0272-4340/01/1200-0553/0 DI 10.1023/A:1015149732579 PG 2 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 555PV UT WOS:000175803200001 ER PT J AU Hanan, E Priola, SA Solomon, B AF Hanan, E Priola, SA Solomon, B TI Antiaggregating antibody raised against human PrP 106-126 recognizes pathological and normal isoforms of the whole prion protein SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE monoclonal antibody; prion protein; PrP 106-126; immunomodulation ID EPITOPE; RESIDUES-106-126; PEPTIDE-106-126; FRAGMENT; PEPTIDES AB Antibodies to the prion protein (PrP) have been critical to the neuropathological and biochemical characterization of PrP-related degenerative diseases in humans and animals. Although PrP is highly conserved evolutionarily, there is some sequence divergence among species; as a consequence, anti-PrP antibodies have a wide spectrum of reactivity when challenged with PrP from diverse species. We have produced an antibody [monoclonal antibody (mAb) 2-40] raised against a synthetic peptide corresponding to residues (106-126 of human PrP and have characterized it by epitope mapping, Western immunoblot analysis, and immunohistochemistry. The antibody recognizes not only human PrP isoforms but also pathological PrP from all species tested (i.e., sheep, hamsters, and mice). Together with the fact that it recognizes the whole PrP in both cellular and scrapie isoforms, mAb 2-40 may be helpful in studying conformational changes of the PrP, as well as establishing a possible connection between human and animal diseases. C1 Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, Fac Life Sci, IL-69978 Tel Aviv, Israel. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Solomon, B (reprint author), Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, Fac Life Sci, IL-69978 Tel Aviv, Israel. NR 22 TC 13 Z9 17 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD DEC PY 2001 VL 21 IS 6 BP 693 EP 703 AR UNSP 0272-4340/01/1200-0693/0 DI 10.1023/A:1015199904354 PG 11 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 555PV UT WOS:000175803200011 PM 12043842 ER PT J AU Reilly, TP Brady, JN Marchick, MR Bourdi, M George, JW Radonovich, MF Pise-Masison, CA Pohl, LR AF Reilly, TP Brady, JN Marchick, MR Bourdi, M George, JW Radonovich, MF Pise-Masison, CA Pohl, LR TI A protective role for cyclooxygenase-2 in drug-induced liver injury in mice SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article; Proceedings Paper CT 40th Annual Meeting of the Society-of-Toxicology CY MAR 24-29, 2001 CL SAN FRANCISCO, CALIFORNIA SP Soc Toxicol ID SHOCK-PROTEIN INDUCTION; COVALENT BINDING; EPITHELIAL-CELLS; GENE DISRUPTION; KAPPA-B; ACETAMINOPHEN; TOXICITY; MOUSE; PROSTAGLANDINS; HEPATOTOXICITY AB Despite the utility of cyclooxygenase (COX) inhibition as an antiinflammatory strategy, prostaglandin (PG) products of COX-1 and -2 provide important regulatory functions in some pathophysiological states. Scattered reports suggest that COX inhibition may also promote adverse drug events. Here we demonstrate a protective role for endogenous COX-derived products in a murine model of acetaminophen (APAP)-induced acute liver injury. A single hepatotoxic dose caused the selective induction of COX-2 mRNA and increased PGD2 and PGE2 levels within the livers of COX+/+ male mice suggesting a role for COX-2 in this model of liver injury. APAP-induced hepatotoxicity and lethality were markedly greater in COX-2(-/-) and (-/+) mice in which normal PG responsiveness is altered. The significantly increased toxicity linked to COX-2 deficiency could be mimicked using the selective COX-2 inhibitory drug, celecoxib, in COX+/+ mice and was not due to alterations in drug-protein adduct formation, a surrogate for bioactivation and toxicity. Microarray analyses indicated that increased injury associated with COX-2 deficiency coincided, most notably, with a profoundly impaired induction of heat shock proteins in COX-2(-/+) mice suggesting that PGs may act as critical endogenous stress signals following drug insult. These findings suggest that COX-2-derived mediators serve an important hepato-protective function and that COX inhibition may contribute to the risk of drug-induced liver injury, possibly through both nonimmunological and immunological pathways. C1 NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Reilly, TP (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH, 9000 Rockville Pike,Bldg 10,Room 8N110, Bethesda, MD 20892 USA. NR 59 TC 89 Z9 95 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2001 VL 14 IS 12 BP 1620 EP 1628 DI 10.1021/tx0155505 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 505UV UT WOS:000172934700008 PM 11743745 ER PT J AU Berard, AM Clerc, M Brewer, B Santamarina-Fojo, S AF Berard, AM Clerc, M Brewer, B Santamarina-Fojo, S TI A normal rate of cellular cholesterol removal can be mediated by plasma from a patient with familial lecithin-cholesterol acyltransferase (LCAT) deficiency SO CLINICA CHIMICA ACTA LA English DT Article DE reverse cholesterol transport; familial lecithin-cholesterol acyltransferase deficiency; DNA sequence analysis; site-directed mutagenesis; transfection; cholesterol efflux ID SITE-DIRECTED MUTAGENESIS; FISH-EYE DISEASE; GENE; TRANSPORT; MUTATIONS; ENZYME AB Lecithin-cholesterol acyltransferase (LCAT) is the major enzyme involved in the esterification of cholesterol in circulating plasma lipoproteins. In the present study, we describe the molecular defects in the LCAT gene and in lipoprotein metabolism of a 34-year-old patient presenting with features of classic familial LCAT deficiency. DNA sequencing revealed two separate point mutations in exon 3 of the patient's LCAT gene: a C to A substitution converting Tyr(83) to a Stop and a C to T transition converting an Arg(99) to a Cys. Digestion of patient PCR-amplified DNA with the restriction enzymes AccI and AciI established that the patient was a compound heterozygote for both mutations. In vitro expression of LCAT (Arg(99) --> Cys) in human embryonic kidney-293 cells demonstrated reduced expression, as well as reduced secretion and/or increased intracellular degradation of the mutant enzyme with significantly decreased alpha -LCAT specific activity, thus, establishing the functional significance of the LCAT (Arg(99) --> Cys) mutation. The plasma cholesterol esterification rate (CER, 2 +/- 0.3 nmol/ml/h), alpha -LCAT activity (2.9 +/- 0.1 nmol/ml/h) and LCAT concentration (0.3 +/- 0.1 mug/ml) were 2.9%, 2.3% and 6.1% that of normal subjects, respectively. Analysis of the patient's plasma lipid profile revealed reduced plasma concentrations of total cholesterol (111 +/- 0.5 mg/dl), HDL cholesterol (1.6 +/- 0.2 mg/dl), apolipoprotein (apo) A-I (52 +/- 4 mg/dl) and apo A-II (11 +/- 0.5 mg/dl). Nevertheless, for the first time, we demonstrate that the LCAT-deficient plasma is as efficient as control plasma in cholesterol efflux experiments performed with [H-3]-cholesterol loaded fibroblasts. This result could explain the absence of premature atherosclerosis in this LCAT-deficient patient. Published by Elsevier Science B.V. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Bordeaux 2, Lab Biochim & Biol Mol, F-33076 Bordeaux, France. RP Berard, AM (reprint author), Hop Haut Leveque, Ctr Hosp Reg Bordeaux, Ave Magellan, F-33600 Pessac, France. NR 26 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD DEC PY 2001 VL 314 IS 1-2 BP 131 EP 139 DI 10.1016/S0009-8981(01)00689-1 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 505VQ UT WOS:000172936600014 PM 11718688 ER PT J AU Goldstein, DS AF Goldstein, DS TI Cardiac sympathetic neuroimaging to distinguish multiple system atrophy from Parkinson disease SO CLINICAL AUTONOMIC RESEARCH LA English DT Editorial Material ID METAIODOBENZYLGUANIDINE MYOCARDIAL SCINTIGRAPHY; I-123 MIBG UPTAKE; ORTHOSTATIC HYPOTENSION; AUTONOMIC FAILURE; DIFFERENTIATION; DENERVATION; DYSFUNCTION; HEART C1 NINCDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Goldstein, DS (reprint author), NINCDS, Clin Neurocardiol Sect, NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. NR 21 TC 8 Z9 8 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0959-9851 J9 CLIN AUTON RES JI Clin. Auton. Res. PD DEC PY 2001 VL 11 IS 6 BP 341 EP 342 DI 10.1007/BF02292764 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 507YN UT WOS:000173059100003 PM 11794713 ER PT J AU Fedarko, NS Jain, A Karadag, A Van Eman, MR Fisher, LW AF Fedarko, NS Jain, A Karadag, A Van Eman, MR Fisher, LW TI Elevated serum bone sialoprotein and osteopontin in colon, breast, prostate, and lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID EPITHELIAL-CELLS; MATRIX PROTEINS; THYROID-CANCER; EXPRESSION; PROGRESSION; METASTASES; CARCINOMAS; SURVIVAL; PLASMA; MARKER AB Purpose: Histological studies have shown that the two sialoproteins, bone sialoprotein (BSP) and osteopontin (OPN), are induced in multiple types of cancer. We have recently found that these proteins are bound in serum to complement factor H and that the complex must be disrupted to generate free protein to measure their total levels. We hypothesized that measuring total BSP and OPN levels would provide informative markers for the detection of cancer. Experimental Design: As a proof of concept study, serum from patients with diagnosed breast, colon, lung, or prostate cancer (n = 20 for each type) as well as normal serum (n = 77) were analyzed using competitive ELISAs developed for BSP and OPN. Sensitivity, specificity, as well as positive and negative predictive values were determined for each sialoprotein and cancer type. The relationship between sensitivity and specificity was profiled by receiver operating characteristic curves. Results and Conclusions: Determined values for serum BSP in ng/ml were 285 +/- 19 for prostate, 373 +/- 19 for colon, 318 +/- 18 for breast, 155 +/- 11 for lung cancer sera, and 154 +/- 13 for normal sera. Values of OPN in ng/ml were 653 +/- 39 for prostate, 449 +/- 22 for colon, 814 +/- 53 for breast, 724 +/- 33 for lung, and 439 +/- 30 for normal sera. The assays provide a high degree of sensitivity and specificity that enables the detection of colon, breast, prostate, and lung cancer. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Geriatr, Baltimore, MD 21224 USA. Natl Inst Dent & Craniofacial Res, Matrix Biochem Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Fedarko, NS (reprint author), Room 5B-79 JHAAC,5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. FU NCI NIH HHS [CA 83711] NR 32 TC 262 Z9 279 U1 0 U2 7 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 2001 VL 7 IS 12 BP 4060 EP 4066 PG 7 WC Oncology SC Oncology GA 505UK UT WOS:000172933800029 PM 11751502 ER PT J AU Anaissie, EJ Kuchar, RT Rex, JH Francesconi, A Kasai, M Muller, FMC Lozano-Chiu, M Summerbell, RC Dignani, MC Chanock, SJ Walsh, TJ AF Anaissie, EJ Kuchar, RT Rex, JH Francesconi, A Kasai, M Muller, FMC Lozano-Chiu, M Summerbell, RC Dignani, MC Chanock, SJ Walsh, TJ TI Fusariosis associated with pathogenic Fusarium species colonization of a hospital water system: A new paradigm for the epidemiology of opportunistic mold infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID AMPLIFIED POLYMORPHIC DNA; LEGIONNAIRES-DISEASE; CANDIDA-ALBICANS; STRAINS; FUNGI AB We sought the reservoir of Fusarium species in a hospital with cases of known fusarial infections. Cultures of samples from patients and the environment were performed and evaluated for relatedness by use of molecular methods. Fusarium species was recovered from 162 (57%) of 283 water system samples. Of 92 sink drains tested, 72 (88%) yielded Fusarium solani; 12 (16%) of 71 sink faucet aerators and 2 (8%) of 26 shower heads yielded Fusarium oxysporum. Fusarium solani was isolated from the hospital water tank. Aerosolization of Fusarium species was documented after running the showers. Molecular biotyping revealed multiple distinct genotypes among the isolates from the environment and patients. Eight of 20 patients with F. solani infections had isolates with a molecular match with either an environmental isolate (n=2) or another patient isolate (n=6). The time interval between the 2 matched patient-environment isolates pairs was 5 and 11 months, and 2, 4, and 5.5 years for the 3 patient-patient isolate pairs. The water distribution system of a hospital was identified as a reservoir of Fusarium species. C1 Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma & Transplantat Res Ctr, Sect Support Care & Oncol Emergencies, Little Rock, AR 72205 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. Univ Texas, Sch Med, Ctr Infect Dis, Houston, TX 77030 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Cent Bur Schimmelcultures, Utrecht, Netherlands. RP Anaissie, EJ (reprint author), Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma & Transplantat Res Ctr, Sect Support Care & Oncol Emergencies, 4301 W Markham,Mail Slot 776, Little Rock, AR 72205 USA. OI Dignani, Maria Cecilia/0000-0002-7446-6183 NR 19 TC 168 Z9 174 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2001 VL 33 IS 11 BP 1871 EP 1878 DI 10.1086/324501 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 489NX UT WOS:000171998800011 PM 11692299 ER PT J AU Wheat, LJ Connolly, P Smedema, M Brizendine, E Hafner, R AF Wheat, LJ Connolly, P Smedema, M Brizendine, E Hafner, R CA AIDS Clin Trials Grp Mycoses Study Grp Natl Inst Allerg TI Emergence of resistance to fluconazole as a cause of failure during treatment of histoplasmosis in patients with acquired immunodeficiency disease syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID AMPHOTERICIN-B; ITRACONAZOLE; AIDS AB In sequential clinical trials of treatment for histoplasmosis in patients with acquired immunodeficiency syndrome, therapy with fluconazole failed in a higher proportion of patients than did therapy with itraconazole. To determine the cause for failure with fluconazole, antifungal susceptibility testing that used modified National Committee on Clinical Laboratory Standards procedures was performed on all baseline and failure isolates. Failure occurred more frequently in patients with baseline isolates with fluconazole minimum inhibitory concentrations (MICs) greater than or equal to5 mug/mL versus lower MICs; 29% versus 3%, respectively. There was at least a 4-fold increase in fluconazole MIC in the isolates from 10 (59%) of 17 patients for whom paired pretreatment and failure or relapse isolates were available. Cross-resistance to itraconazole was not seen. In conclusion, fluconazole is less active than itraconazole for Histoplasma capsulatum and induces resistance during therapy, which accounted for treatment failure in some patients. C1 Histoplasmosis Reference Lab, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Vet Affairs Med Ctr, Indianapolis, IN USA. NIAID, Div AIDS, Rockville, MD USA. RP Wheat, LJ (reprint author), Histoplasmosis Reference Lab, 1001 W 10th St,OPW 430, Indianapolis, IN 46202 USA. FU NIAID NIH HHS [AI 25859, N01-AI65296] NR 8 TC 37 Z9 41 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2001 VL 33 IS 11 BP 1910 EP 1913 DI 10.1086/323781 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 489NX UT WOS:000171998800017 PM 11692303 ER PT J AU Mermel, LA Farr, BM Sherertz, RJ Raad, II O'Grady, N Harris, JS Craven, D AF Mermel, LA Farr, BM Sherertz, RJ Raad, II O'Grady, N Harris, JS Craven, D TI Issues in the management of intravascular catheter-related infections - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID CANDIDEMIA C1 Brown Univ, Sch Med, Div Infect Dis, Providence, RI 02912 USA. Univ Virginia, Div Infect Dis, Charlottesville, VA USA. Wake Forest Univ, Sch Med, Infect Dis Sect, Winston Salem, NC 27109 USA. Univ Texas, MD Anderson Canc Ctr, Dept Internal Med Specialties, Houston, TX 77030 USA. NIH, Crit Care Dept, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Sec Pediat Infect Dis, Boston, MA 02118 USA. Boston Univ, Sch Med, Burlington, MA USA. Boston Univ, Sch Publ Hlth, Lahey Clin, Burlington, MA USA. RP Craven, D (reprint author), Lahey Clin Fdn, Dept Internal Med, Div Infect Dis, 41 Mall Rd, Burlington, MA 01805 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2001 VL 33 IS 11 BP 1949 EP 1951 DI 10.1086/323562 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 489NX UT WOS:000171998800026 ER PT J AU McNeil, DE Linehan, WM Glenn, GM AF McNeil, DE Linehan, WM Glenn, GM TI Comorbid genetic diseases, von Hippel-Lindau disease and spinocerebellar ataxia type 2, confounding the diagnosis of cerebellar dysfunction in an adolescent SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE von Hippel-Lindau disease; spinocerebellar ataxia; type 2; cerebellum; neurodegenerative disease ID TRINUCLEOTIDE REPEAT; IDENTIFICATION; EXPANSION; FEATURES; CLONING AB The authors report a 15-year-old female who presented with difficulties in ambulation as well as difficulties with balance and penmanship. She had a known genetic risk of von Hippel-Lindau (VHL; MIM 193300) disease. with a unique VHL mutation, but had no tumors of the brain or spine to explain her symptoms. Laboratory analysis of peripheral blood lymphocytes was targeted at genetic loci associated with ataxic disorders. Allelic expansion of the ataxin-2 gene was identified. Spinocerebellar ataxia type 2 (SCA2) was diagnosed as a comorbid genetic condition in this patient. Published by Elsevier Science B.V. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Glenn, GM (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, NCI NIH EPS Room 7108,6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD DEC PY 2001 VL 103 IS 4 BP 216 EP 219 DI 10.1016/S0303-8467(01)00153-6 PG 4 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 508VK UT WOS:000173110300004 PM 11714564 ER PT J AU Abernethy, DR AF Abernethy, DR TI QTc prolongation and drugs - Reply SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Letter C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Abernethy, DR (reprint author), NIA, Gerontol Res Ctr, 4940 Eastern Ave, Baltimore, MD 21224 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD DEC PY 2001 VL 70 IS 6 BP 568 EP 568 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 507JA UT WOS:000173022500012 ER PT J AU McCoy, JP Keren, DF AF McCoy, JP Keren, DF TI New applications of flow cytometry - Preface SO CLINICS IN LABORATORY MEDICINE LA English DT Editorial Material C1 NHLBI, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Warde Med Labs, Ann Arbor, MI 48108 USA. RP McCoy, JP (reprint author), NHLBI, Div Intramural Res, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD DEC PY 2001 VL 21 IS 4 BP XIII EP XIII PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 502ZQ UT WOS:000172773000001 ER PT J AU De Rosa, SC Roederer, M AF De Rosa, SC Roederer, M TI Eleven-color flow cytometry - A powerful tool for elucidation of the complex immune system SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID T-CELL SUBSETS; ACTIVE ANTIRETROVIRAL THERAPY; MYCOBACTERIUM-LEPRAE; CYTOKINE PROFILE; NAIVE; CD4(+); LEPROSY; ACTIVATION; POPULATION; DECREASE AB This article describes application of some of the most sophisticated flow technology currently available. Both basic and clinical research applications of this technology are illustrated, showing how a new picture of immune function arises that can simplify the understanding of immunopathogenesis of disease. Although the implementation of this technology in the clinic is still several years off, it can serve to identify important correlates of immune function that can be measured with today's technology. C1 NIAID, Immunol & Flow Cytometry Core, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, Immunol & Flow Cytometry Core, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. RI Roederer, Mario/G-1887-2011 NR 25 TC 31 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD DEC PY 2001 VL 21 IS 4 BP 697 EP + PG 17 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 502ZQ UT WOS:000172773000002 PM 11770282 ER PT J AU Hengel, RL Nicholson, JKA AF Hengel, RL Nicholson, JKA TI An update on the use of flow cytometry in HIV infection and AIDS SO CLINICS IN LABORATORY MEDICINE LA English DT Article ID T-CELLS; GATING LYMPHOCYTES; VIRUS-INFECTION; IMMUNODEFICIENCY; ACTIVATION; CD4; SUBSETS; SYSTEM; MEMORY; FLUORESCENCE AB This article reviews the routine use of flow cytometry in the clinical setting of HIV disease and updates it for recent advancements in technology. Nonroutine assays that have some evidence for routine clinical use are then addressed. Finally, assays in the research setting that hold promise for making their way into the clinic sometime soon are examined. C1 Georgetown Univ, Dept Med, Div Infect Dis, Washington, DC USA. NIAID, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Publ Hlth Serv, Atlanta, GA USA. RP Nicholson, JKA (reprint author), CDC, Mailstop C12,1600 Clifton Rd NE, Atlanta, GA 30333 USA. NR 36 TC 14 Z9 18 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 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD DEC PY 2001 VL 21 IS 4 BP 841 EP + PG 18 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 502ZQ UT WOS:000172773000011 PM 11770291 ER PT J AU Spong, CY AF Spong, CY TI Preterm premature rupture of the fetal membranes complicated by oligohydramnios SO CLINICS IN PERINATOLOGY LA English DT Article ID NEONATAL PULMONARY HYPOPLASIA; BREATHING MOVEMENTS; LUNG DEVELOPMENT; AMNIOTIC-FLUID; RISK-FACTORS; AMNIOINFUSION; GESTATION; MANAGEMENT; PREGNANCY; PREDICTOR AB Preterm premature rupture of the fetal membranes complicated by oligohydramnios may have significant impact and sequelae on pregnancy outcome. In this article the role of amniotic fluid in fetal development, especially lung development, is reviewed; complications resulting from oligohydramnios are outlined; and the evaluated therapeutics and management schemes are delineated. C1 NICHHD, Pregnancy & Perinatol Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. RP Spong, CY (reprint author), NICHHD, Pregnancy & Perinatol Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Room 4B03, Rockville, MD 20852 USA. NR 28 TC 2 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0095-5108 J9 CLIN PERINATOL JI Clin. Perinatol. PD DEC PY 2001 VL 28 IS 4 BP 753 EP + DI 10.1016/S0095-5108(03)00075-7 PG 8 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 495KN UT WOS:000172339900004 PM 11817187 ER PT J AU Counts, SE Perez, SE Kahl, U Bartfai, T Bowser, RP Deecher, DC Mash, DC Crawley, JN Mufson, EJ AF Counts, SE Perez, SE Kahl, U Bartfai, T Bowser, RP Deecher, DC Mash, DC Crawley, JN Mufson, EJ TI Galanin: Neurobiologic mechanisms and therapeutic potential for Alzheimer's disease SO CNS DRUG REVIEWS LA English DT Review DE Alzheimer's disease; galanin; galanin receptors ID RECEPTOR MESSENGER-RNA; RAT BASAL FOREBRAIN; TISSUE-SPECIFIC EXPRESSION; CENTRAL-NERVOUS-SYSTEM; CHOLINERGIC NEURONS; MOLECULAR-CLONING; PHARMACOLOGICAL CHARACTERIZATION; CHROMOSOMAL LOCALIZATION; VENTRAL HIPPOCAMPUS; ENTORHINAL CORTEX AB The neuropeptide galanin (GAL) is widely distributed in the mammalian CNS. Several lines of evidence suggest that GAL may play a critical role in cognitive processes such as memory and attention through an inhibitory modulation of cholinergic basal forebrain activity. Furthermore, GAL fibers hyperinnervate remaining cholinergic basal forebrain neurons in Alzheimer's disease (AD). This suggests that GAL activity impacts cholinergic dysfunction in advanced AD. Pharmacological and in vitro autoradiographic studies indicate the presence of heterogeneous populations of GAL receptor (GALR) sites in the basal forebrain which bind GAL with both high and low affinity. Interestingly, we have recently observed that GALR binding sites increase in the anterior basal forebrain in late-stage AD. Three G protein-coupled GALRs have been identified to date that signal through a diverse array of effector pathways in vitro, including adenylyl cyclase inhibition and phospholipase C activation. The repertoire and distribution of GALR expression in the basal forebrain remains unknown, as does the nature of GAL and GALR plasticity in the AD basal forebrain. Recently, GAL knockout and overexpressing transgenic mice have been generated to facilitate our understanding of GAL activity in basal forebrain function. GAL knockout mice result in fewer cholinergic basal forebrain neurons and memory deficits. On the other hand, mice overexpressing GAL display hyperinnervation of basal forebrain and memory deficits. These data highlight the need to explore further the putative mechanisms by which GAL signaling might be beneficial or deleterious for cholinergic cell survival and activity within basal forebrain. This information will be critical to understanding whether pharmacological manipulation of GALRs would be effective for the amelioration of cognitive deficits in AD. C1 Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA USA. Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA. Womens Hlth Res Inst, Radnor, PA USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL USA. NIMH, NIH, Sect Behav Neuropharmacol, Bethesda, MD USA. RP Mufson, EJ (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Neurol Sci, 2242 W Harrison St Suite 200, Chicago, IL 60612 USA. FU NIA NIH HHS [AG10668, AG09468, AG10161, AG14449, AG00257] NR 119 TC 33 Z9 34 U1 1 U2 1 PU NEVA PRESS PI BRANFORD PA P O BOX 347, BRANFORD, CT 06405 USA SN 1080-563X J9 CNS DRUG REV JI CNS Drug Rev. PD WIN PY 2001 VL 7 IS 4 BP 445 EP 470 PG 26 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 535VZ UT WOS:000174668200007 PM 11830760 ER PT J AU Li, LP Darden, TA Weinberg, CR Levine, AJ Pedersen, LG AF Li, LP Darden, TA Weinberg, CR Levine, AJ Pedersen, LG TI Gene assessment and sample classification for gene expression data using a genetic algorithm/k-nearest neighbor method SO COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING LA English DT Article DE pattern recognition; gene selection; high-dimensional; microarray ID INTERLEUKIN-8 EXPRESSION; CDNA MICROARRAYS; BREAST CANCERS; PATTERNS; GELSOLIN; PROTEIN; TUMOR; CELLS; GENOME; PREDICTION AB Recent tools that analyze microarray expression data have exploited correlation-based approaches such as clustering analysis. We describe a new method for assessing the importance of genes for sample classification based on expression data. Our approach combines a genetic algorithm (GA) and the k-nearest neighbor (KNN) method to identify genes that jointly can discriminate between two types of samples (e.g. normal vs. tumor). First, many such subsets of differentially expressed genes are obtained independently using the GA. Then, the overall frequency with which genes were selected is used to deduce the relative importance of genes for sample classification. Sample heterogeneity is accommodated; that is, the method should be robust against the existence of distinct subtypes. We applied GA/KNN to expression data from normal versus tumor tissue from human colon. Two distinct clusters were observed when the 50 most frequently selected genes were used to classify all of the samples in the data sets studied and the majority of samples were classified correctly. Identification of a set of differentially expressed genes could aid in tumor diagnosis and could also serve to identify disease subtypes that may benefit from distinct clinical approaches to treatment. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NIOSH, Exposure Assessment Branch, Hlth Effects Lab Div, Morgantown, WV 26505 USA. Rockefeller Univ, Off President, New York, NY 10021 USA. Univ N Carolina, Dept Chem, Chapel Hill, NC 27599 USA. RP Li, LP (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 43 TC 98 Z9 102 U1 0 U2 11 PU BENTHAM SCIENCE PUBL LTD PI HILVERSUM PA PO BOX 1673, 1200 BR HILVERSUM, NETHERLANDS SN 1386-2073 J9 COMB CHEM HIGH T SCR JI Comb. Chem. High Throughput Screen PD DEC PY 2001 VL 4 IS 8 BP 727 EP 739 PG 13 WC Biochemical Research Methods; Chemistry, Applied; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 507FP UT WOS:000173016600010 PM 11894805 ER PT J AU Lu, Z Johnson, WE Menotti-Raymond, M Yuhki, N Martenson, JS Mainka, S Shi-Qiang, H Zhihe, Z Li, GH Pan, WS Mao, XR O'Brien, SJ AF Lu, Z Johnson, WE Menotti-Raymond, M Yuhki, N Martenson, JS Mainka, S Shi-Qiang, H Zhihe, Z Li, GH Pan, WS Mao, XR O'Brien, SJ TI Patterns of genetic diversity in remaining giant panda populations SO CONSERVATION BIOLOGY LA English DT Article ID MITOCHONDRIAL-DNA; FLORIDA PANTHER; TREES; MICROSATELLITES; SUBSTITUTIONS; AMPLIFICATION; CONSERVATION; CONCOLOR AB The giant panda (Ailuropoda melanoleuca) is among the more familiar symbols of species conservation. The protection of giant panda populations has been aided recently by the establishment of more and better-managed reserves in existing panda habitat located in six mountain ranges in western China. These remaining populations are becoming increasingly isolated from one another, however, leading to the concern that historic patterns of gene flow will be disrupted and that reduced population sizes will lead to diminished genetic variability. We analyzed four categories of molecular genetic markers (mtDNA restriction fragment length polymorphisms [RFLP], mtDNA control region sequences, nuclear multilocus DNA fingerprints, and microsatellite size variation) In giant pandas from three mountain populations (Qionglai, Minshan, and Qinling) to assess current levels of genetic diversity and to detect evidence of historic population subdivisions. Tbe three populations had moderate levels of genetic diversity compared with similarly studied carnivores for all four gene measures, with a slight but consistent reduction in variability apparent in the smaller Qinling population. That population also showed significant differentiation consistent with its isolation since historic times. From a strictly genetic perspective, the giant panda species and the three populations look promising insofar as they have retained a large amount of genetic diversity in each population, although evidence of recent population reduction-likely from habitat loss-is apparent. Ecological management to increase habitat, population expansion, and gene flow would seem an effective strategy to stabilize the decline of this endangered species. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Peking Univ, Wildlife Res Ctr, Beijing 100671, Peoples R China. Species Survival Commiss, CH-1196 Gland, Switzerland. Chengdu Res Base Giant Panda Breeding, Fu Tou Shan, Sichuan, Peoples R China. RP Lu, Z (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. RI Johnson, Warren/D-4149-2016 OI Johnson, Warren/0000-0002-5954-186X NR 53 TC 45 Z9 57 U1 7 U2 57 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0888-8892 J9 CONSERV BIOL JI Conserv. Biol. PD DEC PY 2001 VL 15 IS 6 BP 1596 EP 1607 DI 10.1046/j.1523-1739.2001.00086.x PG 12 WC Biodiversity Conservation; Ecology; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA 501PA UT WOS:000172692900021 ER PT J AU Kephart, DK Chinchilli, VM Hurd, SS Cherniack, RM AF Kephart, DK Chinchilli, VM Hurd, SS Cherniack, RM CA Asthma Clinical Res Network TI The organization of the Asthma Clinical Research Network: A multicenter multiprotocol clinical trials team SO CONTROLLED CLINICAL TRIALS LA English DT Article DE protocol review committee; data and safety monitoring board; steering committee; data coordinating center; clinical centers AB Asthma is an increasingly serious cause of morbidity and mortality in the United States, affecting approximately 12 million people, including men and women, children and adults, and all racial and ethnic groups. It is now recognized that asthma is a complex disease of Varied etiology triggered by a number of factors such as allergens, drugs, chemicals, exercise, cold dry air, infections, and emotions. Asthma is a chronic disease requiring multiple medications to treat and control symptoms as well as medications thought to control the underlying inflammation. Despite major advances in understanding the etiology and pathophysiology of asthma and the development of new therapeutic modalities, the prevalence, severity, and mortality from asthma have all increased over the past decades in all age groups. Hospitalizations for asthma have doubled in adults and increased fivefold for children over the past 20 years. Mortality appears to be particularly high in urban and rural minority populations. Asthma continues to place a heavy burden on patients and their families as well as the health-care system. In an attempt to respond to the need for well-designed clinical trials to allow rapid evaluation of new and existing therapeutic approaches for asthma and for dissemination of laboratory and clinical findings to the health-care community, the Division of Lung Diseases, National Heart, Lung, and Blood Institute, established the Asthma Clinical Research Network. (C) Elsevier Science Inc. 2001. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA 17033 USA. NIH, Bethesda, MD 20892 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. RP Chinchilli, VM (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Hlth Evaluat Sci, A210, Hershey, PA 17033 USA. FU NHLBI NIH HHS [U10HL51845] NR 0 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 2001 VL 22 IS 6 SU S BP 119S EP 125S DI 10.1016/S0197-2456(01)00161-1 PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 504AM UT WOS:000172834200002 PM 11728618 ER PT J AU Wright, JT Cushman, WC Davis, BR Barzilay, J Colon, P Egan, D Lucente, T Nwachuku, C Pressel, S Leenen, FHH Frolkis, J Letterer, R Walsh, S Tobin, JN Deger, GE AF Wright, JT Cushman, WC Davis, BR Barzilay, J Colon, P Egan, D Lucente, T Nwachuku, C Pressel, S Leenen, FHH Frolkis, J Letterer, R Walsh, S Tobin, JN Deger, GE CA ALLHAT Res Grp TI The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT): Clinical center recruitment experience SO CONTROLLED CLINICAL TRIALS LA English DT Article DE clinical trial; site recruitment; antihypertensive drug treatment; lipid-lowering drug treatment AB The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT ) is a randomized clinical outcome trial of antihypertensive and lipid-lowering therapy in a diverse population (including substantial numbers of women and minorities) of 42,419 high-risk hypertensives aged greater than or equal to 55 years with a planned mean follow-up of 6 years. In this paper, we describe our experience in the identification, recruitment, and selection of clinical centers for this large simple trial capable of meeting the recruitment goals outlined for ALLHAT, and we highlight factors associated with clincal center performance. Over 135,000 recruitment brochures were mailed to physicians. Requests for information and application packets were received from 9351 (6.8%) interested investigators. A total of 1053 completed applications were received and 909 sites (86%) were eventually approved to join the trial. Of the approved sites, 278 either later declined participation or were never activated, and 8 were closed within a year for lack of enrollment. The final 623 randomizing centers exceeded the trial's recruitment goal to enroll at least 40,000 participants into the trial, although the recruitment period was extended 1.5 years longer than planned. Fewer than a quarter of the sites (22.6%) were recruited from academic medical centers or Department of Veterans Affairs Medical Centers. More than half of the sites (54.7%) were private solo or group practices, which contributed 53% of randomized participants. Community health centers comprised about 8% of the ALLHAT sites and 2.9% were part of health maintenance organizations. More than 22% of the principal investigators reported that they had no previous clinical research experience. In summary, ALLHAT was successful in recruiting a diverse group of clinical centers to achieve its patient recruitment goals. (C) Elsevier Science Inc. 2001. C1 Case Western Reserve Univ, Div Hypertens, Clin Hypertens Program, Cleveland, OH 44106 USA. Memphis VAMC, Memphis, TN USA. Univ Texas, Houston, TX USA. Kaiser Permanente, Tucker, GA USA. Ctr Cardiovasc Caguas, Cuguas, PR USA. NHLBI, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Washington, Seattle, WA 98195 USA. Clin Directors Network Inc, New York, NY USA. Madrona Med Grp, Bellingham, WA USA. RP Wright, JT (reprint author), Case Western Reserve Univ, Div Hypertens, Clin Hypertens Program, 10900 Euclid Ave, Cleveland, OH 44106 USA. FU NHLBI NIH HHS [N01-HC-35130] NR 14 TC 25 Z9 25 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD DEC PY 2001 VL 22 IS 6 BP 659 EP 673 DI 10.1016/S0197-2456(01)00176-3 PG 15 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 502QF UT WOS:000172753700005 PM 11738122 ER EF