FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Bell, EM Hertz-Picciotto, I Beaumont, JJ AF Bell, EM Hertz-Picciotto, I Beaumont, JJ TI Pesticides and fetal death due to congenital abnormalities - The authors reply SO EPIDEMIOLOGY LA English DT Letter C1 Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Chapel Hill, NC 27515 USA. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Epidemiol & Prevent Med, Davis, CA 95616 USA. RP Bell, EM (reprint author), Univ N Carolina, Dept Epidemiol, Sch Publ Hlth, Chapel Hill, NC 27515 USA. NR 8 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2001 VL 12 IS 5 BP 594 EP 595 DI 10.1097/00001648-200109000-00033 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 465GJ UT WOS:000170581000033 ER PT J AU Bell, EM Hertz-Picciotto, I Beaumont, JJ AF Bell, EM Hertz-Picciotto, I Beaumont, JJ TI Pesticides and fetal death due to congenital anomalies: Implications of an erratum SO EPIDEMIOLOGY LA English DT Letter C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. NCI, Occupat Epidemiol Branch, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Epidemiol & Prevent Med, Davis, CA 95616 USA. RP Bell, EM (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27514 USA. NR 5 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD SEP PY 2001 VL 12 IS 5 BP 595 EP 596 DI 10.1097/00001648-200109000-00034 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 465GJ UT WOS:000170581000034 PM 11505188 ER PT J AU Spiecker, M Darius, H Friedl, H Soufi, M Schafer, J Zeldin, DC Liao, J Hankeln, T Schmidt, ER AF Spiecker, M Darius, H Friedl, H Soufi, M Schafer, J Zeldin, DC Liao, J Hankeln, T Schmidt, ER TI Expression of vascular antiinflammatory eicosanoids producing cytochrome P450 2J2 (CYP2J2) is reduced by promoter single nucleotide polymorphism SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 Ruhr Univ Bochum, St Josef Hosp, Dept Med 2, D-4630 Bochum, Germany. Univ Mainz, Dept Med 2, D-6500 Mainz, Germany. Univ Mainz, GENterprise, Dept Mol Genet, Mainz, Germany. Univ Marburg, Dept Med, Marburg, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. Harvard Univ, Sch Med, Dept Med, BWH, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2001 VL 22 SU S BP 151 EP 151 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 472MQ UT WOS:000170988300582 ER PT J AU Audelin, MC McNamara, JR D'Agostino, R Schaefer, EJ Wilson, PWF AF Audelin, MC McNamara, JR D'Agostino, R Schaefer, EJ Wilson, PWF TI Remnants lipoproteins and carotid atherosclerosis; results from the Framingham offspring study SO EUROPEAN HEART JOURNAL LA English DT Meeting Abstract C1 Tufts Univ, Lipid Metab Lab, Boston, MA 02111 USA. Boston Univ, Boston, MA 02215 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD SEP PY 2001 VL 22 SU S BP 257 EP 257 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 472MQ UT WOS:000170988300977 ER PT J AU Housseau, F Moorthy, A Langer, DA Robbins, PF Gonzales, MI Topalian, SL AF Housseau, F Moorthy, A Langer, DA Robbins, PF Gonzales, MI Topalian, SL TI N-linked carbohydrates in tyrosinase are required for its recognition by human MHC class II-restricted CD4(+) T cells SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE T lymphocyte; tumor immunity; antigen processing; MHC ID MELANOMA-CELLS; MOLECULAR-BASIS; ANTIGEN; GLYCOSYLATION; PEPTIDES; LYMPHOCYTES; PROTEIN; SPECIFICITY; INHIBITION; MUTATIONS AB Glycosylation of mammalian proteins is known to influence their intracellular trafficking, half life, and susceptibility to enzymatic degradation. Rare instances of natural T cell epitopes dependent upon glycosylation for recognition have been described. We report here on human CD4(+) T lymphocyte. cultures and clones from two melanoma patients that recognize the melanoma-associated Ag tyrosinase in the context of HLA-DR4 and -DR8. These T cells recognize tyrosinase, normally a heavily glycosylated molecule, when expressed constitutively in melanoma cells or in COS-7 transfectants pulsed as lysates onto autologous APC. However, these T cells fail to recognize tyrosinase expressed in bacteria, nor do they react with overlapping peptides covering full-length tyrosinase, suggesting a critical role for glycosylation in the processing and/or composition of the stimulatory epitopes. The requirement for glycosylation was demonstrated by the failure of tyrosinase-specific CD4(+) T cells to recognize tyrosinase synthesized in the presence of glycosylation inhibitors, or deglycosylated enzymatically. Site-directed mutagenesis of each of seven potential N-glycosylation sites showed that four sites were required to generate forms of tyrosinase that could be recognized by individual T cell clones. These data indicate that certain carbohydrate moieties are required for processing the tyrosinase peptides recognized by CD4(+) T cells. Posttranslational modifications of human tumor-associated proteins such as tyrosinase could be a critical factor for the development of antitumor immune responses. C1 NCI, Surg Branch, Inst Canc, NIH, Bethesda, MD 20892 USA. RP Topalian, SL (reprint author), NCI, Surg Branch, Inst Canc, NIH, 10-2B47, Bethesda, MD 20892 USA. NR 40 TC 10 Z9 11 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD SEP PY 2001 VL 31 IS 9 BP 2690 EP 2701 DI 10.1002/1521-4141(200109)31:9<2690::AID-IMMU2690>3.0.CO;2-8 PG 12 WC Immunology SC Immunology GA 474EH UT WOS:000171092400018 PM 11536167 ER PT J AU Junker, K Weirich, G Moravek, P Podhola, M Ilse, B Hartmann, A Schubert, J AF Junker, K Weirich, G Moravek, P Podhola, M Ilse, B Hartmann, A Schubert, J TI Familial and sporadic renal onconytomas - A comparative molecular-genetic analysis SO EUROPEAN UROLOGY LA English DT Article DE kidney cancer; oncogytoma; genetics; comparative genomic hybridization; familial oncocytoma ID COMPARATIVE GENOMIC HYBRIDIZATION; CELL CARCINOMAS; ONCOCYTOMA; TUMORS; CLASSIFICATION; CHROMOSOME-1; REGION AB Objectives: Genetic causes of sporadic and familial renal oncocytomas are not known. We analyzed these tumors genetically in order to detect tumor-specific chromosome alterations. Methods. DNA from 26 sporadic and 31 familial renal oncocytomas were screened by comparative genomic hybridization according to standard protocols including degenerate oligonucleotide-primed PCR. Results. Chromosome alterations were detected in 19/26 sporadic (73%) and in 4/31 familial. renal oncocytomas, (13%). Partial or complete losses of chromosome 1 were most frequently found in both sporadic (15/26) and familial tumors (2/4). Less frequently, loss of chromosome 14 (3/26) was, detected in sporadic renal oncocytomas as well as losses of 2p, 2q, 4q, 10 and 18 and gains of 1q and 17q in individual sporadic tumors. Inter-tumor variation of chromosome aberrations was prominent in 1 patient, where 1 tumor showed gains of chromosomes 5, 6q, 7, 10p, 12 and 13q, whereas the second, tumor exhibited gains of chromosomes 5 and 7 and loss of 10q. In contrast to sporadic renal oncocytomas, most familial tumors (87%) were devoid of chromosome instabilities. Conclusion: Our results demonstrate that partial or complete loss of chromosome 1 is the most common alteration in renal oncocytomas, sporadic and familial. However, chromosome changes are much rarer in familial than in sporadic renal oncocytomas. Copyright (C) 2001 S. Karger AG, Basel. C1 Univ Jena, Dept Urol, D-07743 Jena, Germany. Tech Univ Munich, Inst Pathol, D-8000 Munich, Germany. Inst Pathol, Regensburg, Germany. NCI, Frederick Canc Res & Dev Ctr, LIB, Frederick, MD 21702 USA. Charles Univ, Dept Urol, CS-50165 Hradec Kralove, Czech Republic. Charles Univ, Inst Pathol, CS-50165 Hradec Kralove, Czech Republic. RP Junker, K (reprint author), Univ Jena, Dept Urol, Lessingstr 1, D-07743 Jena, Germany. NR 27 TC 18 Z9 18 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0302-2838 J9 EUR UROL JI Eur. Urol. PD SEP PY 2001 VL 40 IS 3 BP 330 EP 336 DI 10.1159/000049795 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 491UF UT WOS:000172127800014 PM 11684851 ER PT J AU Ma, MC Devereux, TR Stockton, P Sun, KL Sills, RC Clayton, N Portier, M Flake, G AF Ma, MC Devereux, TR Stockton, P Sun, KL Sills, RC Clayton, N Portier, M Flake, G TI Loss of E-cadherin expression in gastric intestinal metaplasia and later stage p53 altered expression in gastric carcinogenesis SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE E-cadherin; intestinal metaplasia; p53; gastric carcinogenesis; Helicobacter pylori; hypermethylation; beta-catenin ID HELICOBACTER-PYLORI INFECTION; TRANSCRIPTION FACTOR LEF-1; GENE-MUTATIONS PROVIDE; NITRIC-OXIDE SYNTHASE; BETA-CATENIN; DNA HYPERMETHYLATION; COLORECTAL-CANCER; BREAST-CANCER; CELL-LINES; CARCINOMAS AB Gastric cancers are commonly subdivided into intestinal and diffuse subtypes on a morphologic basis, supported by corollary evidence of differences at the pathogenetic and molecular levels. Chronic atrophic gastritis with intestinal metaplasia is a common precursor lesion for the intestinal type of carcinoma. To identify early molecular changes, in this study we have examined 13 surgical specimens both for the expression of E-cadherin, p53 and beta -catenin by immunohistochemistry and for methylation of the CDHI promoter (E-cadherin) by bisulfite genomic sequencing of laser capture microdissected samples. Each specimen examined contained areas of normal (nonmetaplastic) gastric mucosa, as well as areas of intestinal metaplasia and/or carcinoma. Reduced or absent E-cadherin and partial to complete methylation of one to multiple CpG sites examined in the CDHI promoter were observed in all of the metaplasia samples. Thus, the methylation status of the CDHI promoter and expression of E-cadherin together provide strong evidence that loss of E-cadherin is an early event in intestinal type gastric carcinogenesis. In contrast, expression of p53, assumed to be mutant p53, was generally not detected (except for isolated cells) until the carcinoma stage in tissues from these patients. These results suggest that mutation of p53 is a late event in intestinal type gastric cancer. The level of beta -catenin expression did not appear to change between normal, metaplastic and carcinoma cells of intestinal type, and no nuclear staining was visible in any of the tissues. These results suggest that the Wnt signaling pathway is not upregulated in this type of cancer. C1 NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. China Med Univ, Dept Mol Genet, Shenyang, Peoples R China. RP Flake, G (reprint author), NIEHS, Lab Expt Pathol, NIH, MD B3-06,POB 12233, Res Triangle Pk, NC 27709 USA. NR 51 TC 6 Z9 7 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD SEP PY 2001 VL 53 IS 4 BP 237 EP 246 DI 10.1078/0940-2993-00190 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 480MC UT WOS:000171464300001 ER PT J AU Plum, LA Parada, LF Tsoulfas, P Clagett-Dame, M AF Plum, LA Parada, LF Tsoulfas, P Clagett-Dame, M TI Retinoic acid combined with neurotrophin-3 enhances the survival and neurite outgrowth of embryonic sympathetic neurons SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article DE neurotrophin-3; retinoic acid; nerve growth factor; TrkA; p75 (NTR); sympathetic neuron ID NERVE GROWTH-FACTOR; PROGRAMMED CELL-DEATH; CHICK WING BUD; FACTOR RECEPTOR; GENE-EXPRESSION; DORSAL-ROOT; IN-VIVO; EXTRACELLULAR DOMAIN; MOLECULAR-CLONING; TRK RECEPTORS AB Both nerve growth factor (NGF) and neurotrophin-3 (NT-3) are necessary for the survival of embryonic sympathetic neurons in vivo. All-trans retinoic acid (atRA) has been shown to promote neurite outgrowth and long-term survival of chick embryonic sympathetic neurons cultured in the presence of NGF. The present study shows that atRA can also potentiate the survival and neurite outgrowth-promoting activities of NT-3. This was accomplished by enhancing the survival of existing neurons, as cell proliferation was unaffected by exposure to atRA. atRA also enhanced neurite outgrowth of the NT-3-treated cells; however, the neurites appeared thicker and less branched than cells treated with atRA in combination with NGF. Using a quantitative PCR assay, trkA and p75(NTR) mRNAs, but not trkC mRNA, were increased (similar to1.5- to 2-fold) after 72 and 48 hr of exposure of the cultures to atRA, respectively. The atRA-induced increase in trkA mRNA may play a role in the enhanced survival of neurons cultured in the presence of either NGF or NT-3, as both neurotrophins have been shown to signal through this receptor. The time course of these mRNA changes would indicate that atRA does not regulate the neurotrophin receptor mRNA directly, rather, intervening gene transcription is required. Thus, during development, atRA may play a role in fine-tuning embryonic responsiveness to both NT-3 and NGF. C1 Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA. Univ Wisconsin, Interdepartmental Grad Program Nutr Sci, Madison, WI 53706 USA. Univ Texas, SW Med Ctr, Ctr Dev Biol, Dallas, TX 75235 USA. Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Clagett-Dame, M (reprint author), Univ Wisconsin, Dept Biochem, 433 Babcock Dr, Madison, WI 53706 USA. RI Parada, luis/B-9400-2014; OI Tsoulfas, Pantelis/0000-0003-1974-6366 NR 73 TC 28 Z9 28 U1 0 U2 0 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 0037-9727 J9 EXP BIOL MED JI Exp. Biol. Med. PD SEP PY 2001 VL 226 IS 8 BP 766 EP 775 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 466TM UT WOS:000170661900009 PM 11520943 ER PT J AU Luft, AR Kaelin-Lang, A Hauser, TK Cohen, LG Thakor, NV Hanley, DF AF Luft, AR Kaelin-Lang, A Hauser, TK Cohen, LG Thakor, NV Hanley, DF TI Transcranial magnetic stimulation in the rat SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE transcranial magnetic stimulation; corticospinal excitability; rat ID MOTOR-EVOKED-POTENTIALS; SPINAL-CORD; PROPOFOL; CORTEX; NEUROPLASTICITY; ANESTHESIA; PLASTICITY; RODENT AB Transcranial magnetic stimulation (TMS) allows for quantification of motor system excitability. While routinely used in humans, application in other species is rare and little is known about the characteristics of animal TMS. The unique features of TMS, i.e., predominantly interneuronal stimulation at low intensity and non-invasiveness, are particularly useful in evaluating injury and recovery in animal models. This study was conducted to characterize the rodent motor evoked potential to TMS (MEPTMS) and to develop a methodology for reproducible assessment of motor excitability in the rat. MEPTMS were compared with responses evoked by electrical stimulation of cervical spinal cord (MEPCES) and peripheral nerve. MEP were recorded by subcutaneous electrodes implanted bilaterally over the calf. Animals remained under propofol infusion and restrained in a stereotactic frame while TMS followed by CES measurements were obtained before and after 2 h of idle time. TMS was applied using a 5-cm-diameter figure-of-eight coil. MEPTMS had onset latencies of 6.7 +/-1.3 ms. Latencies decreased with higher stimulation intensity (r=-0.7, P<0.05). Two morphologies, MEPTMS.1 and MEPTMS.2, were distinguished by latency of the first negative peak (N1), overall shape, and amplitude. MEPTMS.2 were more frequent at higher stimulation intensity. While recruitment curves for MEPTMS.1 followed a sigmoid course, no supramaximal response was reached for MEPTMS,2. Mid-cervical spinal transection completely abolished any response to TMS. MEPCES showed a significantly shorter latency (5.290.24, P<0.0001). Two types of MEPCES resembling MEPTMS, 1 and 2 were observed. Neither MEPTMS nor MEPCES changed on repeat assessment after 2 h. This study demonstrates the feasibility and reproducibility of TMS in the rat. Sigmoid recruitment curves for MEPTMS, 1 suggest input-output properties similar to those of the human corticospinal system. Latency differences between CES and TMS point to a supraspinal origin of the MEPTMS. The two morphologies likely reflect different cortical or subcortical origins of MEPTMS. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21287 USA. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Univ Tubingen, Abt Neurol, D-72076 Tubingen, Germany. RP Luft, AR (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA. RI Thakor, Nitish/G-9110-2015 OI Thakor, Nitish/0000-0002-9981-9395 FU NINDS NIH HHS [R01-NS24282] NR 32 TC 51 Z9 60 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD SEP PY 2001 VL 140 IS 1 BP 112 EP 121 DI 10.1007/s002210100805 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 468HP UT WOS:000170752300012 PM 11500803 ER PT J AU Levine, RL Stadtman, ER AF Levine, RL Stadtman, ER TI Oxidative modification of proteins during aging SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE carbonyl; metal-catalyzed oxidation; oxidative modification; protein modification; protein turnover; site-specific modification ID METAL-CATALYZED OXIDATION; AGE-RELATED-CHANGES; LIFE-SPAN; DAMAGE; STRESS; RAT; ENZYME; SYNTHETASE; EXTENSION; OXYGEN AB Accumulating experimental evidence supports the proposal that many of the changes which occur during aging are a consequence of oxidative damage. Reactive oxygen species react with all three of the major cellular macromolecules, nucleic acids, lipids, and proteins. This minireview focuses on proteins as targets of oxidizing species during aging. Many of the reactions mediated by these oxidizing species result in the introduction of carbonyl groups into proteins. The steady-state level of carbonyl-bearing proteins increases exponentially during the last third of lifespan in animals ranging from C. elegans to man. Genetic and non-genetic manipulations which lengthen lifespan cause a decrease in the level of protein carbonyl while those which shorten lifespan increase the level. Oxidized proteins bearing carbonyl groups are generally dysfunctional, and in the last third of lifespan the content of these oxidized proteins rises to a level likely to cause substantial disruption of cellular function. Published by Elsevier Science Inc. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NIH, Bldg 50,Room 2351,MSC 0812, Bethesda, MD 20892 USA. RI Levine, Rodney/D-9885-2011 NR 37 TC 256 Z9 267 U1 0 U2 25 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD SEP PY 2001 VL 36 IS 9 SI SI BP 1495 EP 1502 DI 10.1016/S0531-5565(01)00135-8 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 482MV UT WOS:000171580700006 PM 11525872 ER PT J AU Chen, MT Morales, M Woodward, DJ Hoffer, BJ Janak, PH AF Chen, MT Morales, M Woodward, DJ Hoffer, BJ Janak, PH TI In vivo extracellular recording of striatal neurons in the awake rat following unilateral 6-hydroxydopamine lesions SO EXPERIMENTAL NEUROLOGY LA English DT Article DE basal ganglia; dorsal striatum; dopamine; Parkinson's disease; ensemble recording ID DOPAMINERGIC INHIBITION; ACETYLCHOLINE-RELEASE; NUCLEUS-ACCUMBENS; FIRING PATTERNS; GABA RELEASE; APOMORPHINE; AMPHETAMINE; MODEL; NEOSTRIATUM; SYSTEM AB The purpose of this study was to further understand the functional effects of dopaminergic input to the dorsal striatum and to compare the effects of dopaminergic lesions in awake and anesthetized animals. We examined the effects of unilateral 6-hydroxydopamine (6-OHDA) lesions of the ascending dopaminergic bundle on the firing properties of dorsal striatal neurons in the awake freely moving rat using chronically implanted microwire electrode arrays. We recorded extracellular activity of striatal neurons under baseline conditions and following the systemic injection of apomorphine in awake and anesthetized subjects. Firing rates were higher in the hemisphere ipsilateral to the 6-OHDA lesion compared to rates of neurons from the contralateral unlesioned hemisphere. Striatal firing rates from sham and no-surgery control rats were, in general, higher than those from the contralateral unlesioned striatum of experimental subjects. Apomorphine (0.05 mg/kg, se) normalized the differences in firing rates in lesioned animals by increasing firing of neurons within the contralateral unlesioned side, while simultaneously decreasing firing of neurons within the ipsilateral lesioned side. Mean firing rates were substantially higher in awake animals than in subjects anesthetized with chloral hydrate, perhaps reflecting anesthesia-induced decreases in excitatory input to striatal neurons. Chloral hydrate anesthesia decreased firing rates of neurons in the lesioned, unlesioned, and control striata to a similar degree, although absolute firing rates of neurons from the 6-OHDA-lesioned striata remained elevated over all other groups. Unilateral 6-OHDA lesions also altered the pattern of spike output in the awake animal as indicated by an increase in the number of bursts per minute following dopaminergic deafferentation. This and other burst parameters were altered by apomorphine. Our findings show that effects of dopaminergic deafferentation can be measured in the awake behaving animal; this model should prove useful for testing the behavioral and functional effects of experimental manipulations designed to reduce or reverse the effects of dopaminergic cell loss. In addition, these results suggest that the contralateral changes in striatal function which occur in the unilateral dopaminergic lesion model should be considered when evaluating experimental results. (C) 2001 Academic Press. C1 NIDA, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD USA. Vet Gen Hosp, Dept Neurosurg, Taipei, Taiwan. Natl Def Med Ctr, Grad Inst Med Sci, Taipei, Taiwan. Wake Forest Univ, Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC USA. Univ Calif Emeryville, Dept Neurol, Ernest Gallo Clin & Res Ctr, Emeryville, CA USA. RP Chen, MT (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, Baltimore, MD USA. OI Janak, Patricia/0000-0002-3333-9049 NR 32 TC 46 Z9 47 U1 2 U2 6 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD SEP PY 2001 VL 171 IS 1 BP 72 EP 83 DI 10.1006/exnr.2001.7730 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 472JX UT WOS:000170981500007 PM 11520122 ER PT J AU Fedchuk, AS Lozitsky, VP Dyachenko, NS Nosach, LN Povnitsa, O Zhovnovataya, VL Vanden Eynde, JJ Lozitskaya, RN Kamalov, GL Kryzhanovsky, D Kuzmin, VE Sausville, E AF Fedchuk, AS Lozitsky, VP Dyachenko, NS Nosach, LN Povnitsa, O Zhovnovataya, VL Vanden Eynde, JJ Lozitskaya, RN Kamalov, GL Kryzhanovsky, D Kuzmin, VE Sausville, E TI Anticancer and antiviral properties of macrocyclic pyridinophanes and their derivatives SO EXPERIMENTAL ONCOLOGY LA Russian DT Article DE macrocyclic pyridinophanes; Schiff bases; in vitro anticancer screening; antiviral activity AB The permanent search for new anticancer and antiviral substances is a high-priority task. Macrocyclic pyridinophanes (MCPs) attract much attention as promising compounds with high potential of pharmaco-biological properties. The results of the experimental study of anticancer and antiviral properties of newly synthesized MCP, their analogues and derivatives have been presented. Several compounds under study have been shown to possess strong anticancer (against human cancer cell lines) and antiviral (inhibition of adenovirus type 5 and influenza virus A/Hong Kong/1/ 68 reproduction) activity in vitro. Several MCP studied were shown to share anticancer and antiviral properties. The results obtained in experiment will be used for molecular topological QSAR model evaluation. C1 II Mechnikov Res Inst Virol & Epidemiol, UA-65110 Odessa, Ukraine. DK Zabolotny Microbiol & Virol Res Inst, Kiev, Ukraine. Univ Mons, B-7000 Mons, Belgium. AV Bogatskii Inst Phys & Chem, UA-270080 Odessa, Ukraine. II Mechniov Odessa State Univ, Odessa, Ukraine. NCI, Bethesda, MD 20892 USA. RP Fedchuk, AS (reprint author), II Mechnikov Res Inst Virol & Epidemiol, UA-65110 Odessa, Ukraine. NR 9 TC 1 Z9 1 U1 1 U2 2 PU INST EXP PATHOL ONCOL RADIOBIOL PI KIEV PA AKAD NAUK UKR SSR, UL VASILKOVSKAYA 45, KIEV 252022, UKRAINE SN 0204-3564 J9 EXP ONCOL JI Exp. Oncol. PD SEP PY 2001 VL 23 IS 3 BP 193 EP 196 PG 4 WC Oncology SC Oncology GA 483NV UT WOS:000171641900011 ER PT J AU Wang, E Panelli, MC Marincola, FM AF Wang, E Panelli, MC Marincola, FM TI The impact of genomics on the biotechnology industry SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Editorial Material ID CANCER C1 NIH, Ctr Clin, Immunogenet Lab, Dept Transfus Med, Bethesda, MD 20892 USA. RP Marincola, FM (reprint author), NIH, Ctr Clin, Immunogenet Lab, Dept Transfus Med, Bethesda, MD 20892 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD SEP PY 2001 VL 1 IS 5 BP 749 EP 751 DI 10.1517/14712598.1.5.749 PG 3 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 493YA UT WOS:000172250000001 PM 11728210 ER PT J AU Gallucci, S AF Gallucci, S TI Novel activators of dendritic cells as fundamental tools in immunotherapy SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE activators; adjuvants; danger signals; dendritic cells; vaccines; immunotherapy ID ANTIGEN-PRESENTING FUNCTION; HEAT-SHOCK-PROTEIN; TNF FAMILY MEMBER; IMMUNE-SYSTEM; IN-VITRO; CYTOKINE PRODUCTION; DOWN-REGULATION; CROSS-LINKING; KILLER-CELL; T-CELLS AB Dendritic cells (DCs) are pivotal players in the initiation and amplification of an immune response and the stimuli able to activate these cells to become professional antigen presenting cells (APCs) form an exciting new field in immunology. This article reviews patents from the last four years which claim new dendritic. cell activators and their use in immunotherapy. Some of these activators are endogenous signals, released by peripheral tissues upon stress or injury, and are responsible for the initiation of an immune response, while others are stimulatory ligands, expressed by activated immune cells, and are mediators of the amplification of the response. Furthermore, others are exogenous substances able to induce cellular stress, such as those released by invading pathogens. Many of these stimuli, which are shown to activate dendritic cells in vitro, are also proposed as adjuvants in vivo and protocols are disclosed in the patents for their use in immunotherapy. Prevention of infectious diseases, clearance of neoplasms and manipulation of immunological disorders are situations in which immunotherapeutic strategies hold promise of success. Among these strategies, both the traditional and new dendritic cell-based vaccines require adjuvants to enhance the immune response. Therefore, a better characterisation of the currently known dendritic cell activators, and the discovery of new ones, will lead to safer and more efficacious vaccines. C1 NIAID, NIH, Cellular & Mol Immunol Lab, Bethesda, MD 20892 USA. RP Gallucci, S (reprint author), NIAID, NIH, Cellular & Mol Immunol Lab, Bdg 4,Room 111, Bethesda, MD 20892 USA. NR 123 TC 0 Z9 0 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD SEP PY 2001 VL 11 IS 9 BP 1411 EP 1421 DI 10.1517/13543776.11.9.1411 PG 11 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 468WU UT WOS:000170781800004 ER PT J AU Hanover, JA AF Hanover, JA TI Glycan-dependent signaling: O-linked N-acetylglucosamine SO FASEB JOURNAL LA English DT Review DE O-GlcNAc; hexosaminidase C; diabetes mellitus; OGT ID NUCLEAR-PORE COMPLEX; HEXOSAMINE BIOSYNTHESIS PATHWAY; GLUCOSE-INDUCED DESENSITIZATION; PANCREATIC BETA-CELLS; RNA POLYMERASE-II; NOVYI ALPHA-TOXIN; LARGE T-ANTIGEN; GLCNAC TRANSFERASE; GLUTAMINE-FRUCTOSE-6-PHOSPHATE AMIDOTRANSFERASE; TETRATRICOPEPTIDE REPEATS AB The addition of O-linked N-acetylglucosamine (O-GlcNAc) to target proteins may serve as a signaling modification analogous to protein phosphorylation. Like phosphorylation, O-GlcNAc is a dynamic modification occurring in the nucleus and cytoplasm. Various analytical methods have been developed to detect O-GlcNAc and distinguish it from glycosylation in the endomembrane system. Many target molecules have been identified; these targets are typically components of supramolecular complexes such as transcription factors, nuclear pore proteins, or cytoskeletal components. The enzymes responsible for O-GlcNAc addition and removal are highly conserved molecules having molecular features consistent with a signaling role. The O-GlcNAc transferase and O-GlcNA case are likely to act in consort with kinases and phosphatases generating various isoforms of physiological substrates. These isoforms may differ in such properties as protein-protein interactions, protein stability, and enzymatic activity. Since O-GlcNAc plays a critical role in the regulation of signaling pathways of higher plants, the glycan modification is likely to perform similar signaling functions in mammalian cells. Glucose and amino acid metabolism generates hexosamine precursors that may be key regulators of a nutrient sensing pathway involving O-GlcNAc signaling. Altered O-linked GlcNAc metabolism may also occur in human diseases including neurodegenerative disorders, diabetes mellitus and cancer. C1 NIDDK, LCBB, NIH, Bethesda, MD 20892 USA. RP Hanover, JA (reprint author), NIDDK, LCBB, NIH, Bldg 8,Rm 402, Bethesda, MD 20892 USA. EM jah@helix.nih.gov NR 131 TC 204 Z9 208 U1 5 U2 23 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2001 VL 15 IS 11 BP 1865 EP 1876 DI 10.1096/fj.01-0094rev PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 478XE UT WOS:000171372700001 PM 11532966 ER PT J AU Kersten, S Mandard, S Escher, P Gonzalez, FJ Tafuri, S Desvergne, B Wahli, W AF Kersten, S Mandard, S Escher, P Gonzalez, FJ Tafuri, S Desvergne, B Wahli, W TI The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism SO FASEB JOURNAL LA English DT Article DE fasting; microarray; PPAR alpha; SABRE ID CYCLE ENZYME GENES; APOLIPOPROTEIN C-III; CHAIN FATTY-ACIDS; LIPOPROTEIN METABOLISM; ADAPTIVE RESPONSE; PPAR-ALPHA; EXPRESSION; INDUCTION; MICE; SUPPRESSION AB The peroxisome proliferator-activated receptor a is alpha ligand-activated transcription factor that plays an important role in the regulation of lipid homeostasis. PPAR alpha mediates the effects of fibrates, which are potent hypolipidemic drugs, on gene expression. To better understand the biological effects of fibrates and PPAR alpha, we searched for genes regulated by PPAR alpha using oligonucleotide microarray and subtractive hybridization. By comparing liver RNA from wild-type and PPAR alpha null mice, it was found that PPAR alpha decreases the mRNA expression of enzymes involved in the metabolism of amino acids. Further analysis by Northern blot revealed that PPAR alpha influences the expression of several genes involved in trans- and deamination of amino acids, and urea synthesis. Direct activation of PPAR alpha using the synthetic PPAR alpha ligand WY14643 decreased mRNA levels of these genes, suggesting that PPAR alpha is directly implicated in the regulation of their expression. Consistent with these data, plasma urea concentrations are modulated by PPAR alpha in vivo. It is concluded that in addition to oxidation of fatty acids, PPAR alpha also regulates metabolism of amino acids in liver, indicating that PPAR alpha is a key controller of intermediary metabolism during fasting. C1 Univ Lausanne, Inst Biol Anim, CH-1015 Lausanne, Switzerland. Pfizer Global Res & Dev, Ann Arbor Labs, Ann Arbor, MI 48105 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Kersten, S (reprint author), Univ Wageningen & Res Ctr, Nutr Metab & Genom Grp, POB 8129, NL-6700 EV Wageningen, Netherlands. EM sander.kersten@staff.nutepi.wau.nl RI Kersten, Sander/A-1116-2011; Wahli, Walter/B-1398-2009; Desvergne, Beatrice/C-8892-2016 OI Kersten, Sander/0000-0003-4488-7734; Wahli, Walter/0000-0002-5966-9089; Desvergne, Beatrice/0000-0001-5483-288X NR 32 TC 139 Z9 144 U1 1 U2 6 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2001 VL 15 IS 11 BP 1971 EP 1978 DI 10.1096/fj.01-0147com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 478XE UT WOS:000171372700012 PM 11532977 ER PT J AU Hoffmann, KF McCarty, TC Segal, DH Chiaramonte, M Hesse, M Davis, EM Cheever, AW Meltzer, PS Morse, HC Wynn, TA AF Hoffmann, KF McCarty, TC Segal, DH Chiaramonte, M Hesse, M Davis, EM Cheever, AW Meltzer, PS Morse, HC Wynn, TA TI Disease fingerprinting with cDNA microarrays reveals distinct gene expression profiles in lethal type-1 and type-2 cytokine-mediated inflammatory reactions SO FASEB JOURNAL LA English DT Article DE schistosomiasis; Th1/Th2; liver; mice; fibrosis ID SCHISTOSOMA-MANSONI EGGS; GRANULOMA-FORMATION; HEPATIC-FIBROSIS; TNF-ALPHA; MURINE SCHISTOSOMIASIS; INHIBITS APOPTOSIS; LIVER PATHOLOGY; DEFICIENT MICE; INFECTED MICE; IFN-GAMMA AB Development of polarized immune responses controls resistance and susceptibility to many microorganisms. However, studies of several infectious, allergic, and autoimmune diseases have shown that chronic type-1 and type-2 cytokine responses can also cause significant morbidity and mortality if left unchecked. We used mouse cDNA microarrays to molecularly phenotype the gene expression patterns that characterize two disparate but equally lethal forms of liver pathology that develop in Schistosoma mansoni infected mice polarized for type-1 and type-2 cytokine responses. Hierarchical clustering analysis identified at least three groups of genes associated with a polarized type-2 response and two linked with an extreme type-1 cytokine phenotype. Predictions about liver fibrosis, apoptosis, and granulocyte recruitment and activation generated by the microarray studies were confirmed later by traditional biological assays. The data show that cDNA microarrays are useful not only for determining coordinated gene expression profiles but are also highly effective for molecularly "fingerprinting" diseased tissues. Moreover, they illustrate the potential of genome-wide approaches for generating comprehensive views on the molecular and biochemical mechanisms regulating infectious disease pathogenesis. C1 NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. RP Wynn, TA (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011; OI Morse, Herbert/0000-0002-9331-3705 NR 62 TC 70 Z9 73 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2001 VL 15 IS 11 BP 2545 EP + DI 10.1096/fj.01-0306fje PG 23 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 478XE UT WOS:000171372700027 PM 11641263 ER PT J AU Kim, WH Hong, F Jaruga, B Hu, ZY Fan, SJ Liang, TJ Gao, B AF Kim, WH Hong, F Jaruga, B Hu, ZY Fan, SJ Liang, TJ Gao, B TI Additive activation of hepatic NF-kappa B by ethanol and HBX or HCV core protein: involvement of TNF-alpha receptor I-independent and -dependent mechanisms SO FASEB JOURNAL LA English DT Article DE CYP2E1; ethanol metabolism; hepatitis; nuclear factor-kappa B; liver ID TUMOR-NECROSIS-FACTOR; ALCOHOLIC LIVER-DISEASE; C VIRUS-INFECTION; SIGNAL-TRANSDUCTION PATHWAY; TRANSCRIPTION FACTORS; INTERFERON THERAPY; X-PROTEIN; REGENERATING LIVER; LIPID-PEROXIDATION; HEPG2 CELLS AB Alcohol consumption and viral hepatitis infection synergistically accelerate liver injury, but the underlying mechanism is not fully understood. Here we have examined the effects of ethanol on hepatitis B protein X (HBX)- or hepatitis C core protein (HCV core protein)- mediated activation of NF-kappaB, a critical signal in hepatic injury, regeneration, and tumor transformation. Acute ethanol or acetaldehyde exposure potentiates HBX or HCV core protein activation of NF-kappaB in primary mouse hepatocytes. Such potentiation can be abolished by blocking ethanol metabolism or overexpression of dominant negative NF-kappaB inducing kinase (NIK), I kappaB kinase (IKK), or I kappaB. Moreover, pertussis toxin attenuates NF-kappaB activation induced by acetaldehyde but not by HBX or HCV core protein, whereas HBX or HCV core protein-mediated activation of NF-kappaB is abolished completely in tumor necrosis factor receptor 1 (TNFR1) (-/-) hepatocytes. Finally, chronic ethanol consumption induces hepatic CYP2E1 protein expression and potentiates HBX or HCV core protein activation of NF-kappaB in the liver. These findings suggest that ethanol activates hepatic NF-kappaB via its metabolism and that HBX or HCV core protein activates hepatic NF-kappaB via TNFR1. With the essential role of TNFR1 in alcoholic liver injury, targeting TNFR1 by hepatitis viral proteins could contribute to cooperative effects of alcohol consumption and viral hepatitis on liver disease. C1 NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Long Isl Jewish Med Ctr, Albert Einstein Coll Med, New Hyde Pk, NY 11042 USA. RP Gao, B (reprint author), NIAAA, Sect Liver Biol, Lab Physiol Studies, NIH, Pk Bldg,Room 120,12420 Parklawn Dr,MSC 8115, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov NR 76 TC 56 Z9 60 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD SEP PY 2001 VL 15 IS 11 BP 2551 EP + DI 10.1096/fj.00-01-0217fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 478XE UT WOS:000171372700023 PM 11641261 ER PT J AU Cisar, M Rose, S Reid, E Murdock, CM Nieman, L Segars, LH AF Cisar, M Rose, S Reid, E Murdock, CM Nieman, L Segars, LH TI Pseudo-isolated FSH deficiency caused by inhibin beta-secreting ovarian tumors: report of three cases. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol, Bethesda, MD 20892 USA. NIH, Pediat & Reprod Endocrinol, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA P157 BP S164 EP S165 DI 10.1016/S0015-0282(01)02485-2 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900450 ER PT J AU Hearns-Stokes, RM Mayers, C Segars, JH Stratton, P Gustafsson, J Nieman, L AF Hearns-Stokes, RM Mayers, C Segars, JH Stratton, P Gustafsson, J Nieman, L TI Estrogen receptor beta is expressed in human endometrium and levels of expression vary during the menstrual cycle. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol, Reisterstown, MD USA. NIH, Pediat & Reprod Endocrinol Branch, Reisterstown, MD USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. NIH, Combined Fed Program Reprod Endocrinol, Bethesda, MD 20892 USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Karolinska Inst, Huddinge, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA P307 BP S212 EP S213 DI 10.1016/S0015-0282(01)02635-8 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900595 ER PT J AU Jensen, JT Schwinof, K Zelinski-Wooten, M Conti, M DePaolo, LV Stouffer, RL AF Jensen, JT Schwinof, K Zelinski-Wooten, M Conti, M DePaolo, LV Stouffer, RL TI In vitro exposure to inhibitors of phosphodiesterase (PDE) 3, but not PDE 4, prevent spontaneous resumption of meiosis in rhesus macaque oocytes. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Beaverton, OR USA. Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Stanford Univ, Sch Med, Dept Obstet & Gynecol, Div Reprod Biol, Stanford, CA USA. NICHHD, Reprod Sci Branch, Populat Res Ctr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA O43 BP S17 EP S17 DI 10.1016/S0015-0282(01)02061-1 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900044 ER PT J AU Levi, AJ Alvero, RJ Leondires, MP Murdock, CM Segars, JH Armstrong, AY AF Levi, AJ Alvero, RJ Leondires, MP Murdock, CM Segars, JH Armstrong, AY TI Subcutaneous versus intramuscular administration of hMG with FSH during ART cycles: A retrospective crossover study. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol & Pediat &, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA P365 BP S233 EP S233 DI 10.1016/S0015-0282(01)02693-0 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900653 ER PT J AU Levi, AJ Leondires, MP Segars, JH McKeeby, JL Scott, LA Alvero, RJ AF Levi, AJ Leondires, MP Segars, JH McKeeby, JL Scott, LA Alvero, RJ TI Analysis of 50 frozen blastocyst transfers: pregnancy in prior fresh ART cycles does not predict outcome. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol, Bethesda, MD 20892 USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, ART Inst Washington Inc, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA P35 BP S123 EP S123 DI 10.1016/S0015-0282(01)02361-5 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900329 ER PT J AU McKeeby, JL Scott, LA Leondires, MP Alvero, RJ AF McKeeby, JL Scott, LA Leondires, MP Alvero, RJ TI Human pronuclear morphology is independent of maternal age and day 3 FSH in assisted reproductive technology (ART). SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol, Bethesda, MD USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. ART Inst Washington Inc, Walter Reed Army Med Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA P474 BP S270 EP S270 DI 10.1016/S0015-0282(01)02809-6 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900760 ER PT J AU McKeeby, JL Leondires, MP Alvero, RJ AF McKeeby, JL Leondires, MP Alvero, RJ TI Comparison of oocyte maturation in microdose follicular-phase and luteal-phase gonadotropin-releasing hormone agonist (GnRH-a) ovarian stimulation protocols. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol, Washington, DC USA. NIH, Pediat & Reprod Endocrinol Branch, Washington, DC USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA P189 BP S175 EP S176 DI 10.1016/S0015-0282(01)02517-1 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900482 ER PT J AU McKeeby, JL Leondires, MP Segars, JH Scott, LA Alvero, RJ Miller, BT AF McKeeby, JL Leondires, MP Segars, JH Scott, LA Alvero, RJ Miller, BT TI High order multiple gestations (HOM) are significantly reduced by the implementation of extended culture system and blastocyst transfer (BT) in an ART program. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol, Bethesda, MD 20892 USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Combined Fed Program Reprod Endocrinol, Washington, DC USA. NIH, Pediat & Reprod Endocrinol Branch, Washington, DC USA. Walter Reed Army Med Ctr, ART Inst Washington Inc, Washington, DC 20307 USA. Reprod Med Assoc New Jersey, Morristown, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA O33 BP S13 EP S13 DI 10.1016/S0015-0282(01)02051-9 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900034 ER PT J AU Murdock, CM McKeeby, JL Segars, JH Alvero, RJ Leondires, MP AF Murdock, CM McKeeby, JL Segars, JH Alvero, RJ Leondires, MP TI Endogenous luteinizing hormone is not increased during a GnRH-a microdose flare protocol. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol, Bethesda, MD USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA P184 BP S174 EP S174 DI 10.1016/S0015-0282(01)02512-2 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900477 ER PT J AU Murdock, CM Segars, JH Levi, AJ Armstrong, AY Leondires, MP AF Murdock, CM Segars, JH Levi, AJ Armstrong, AY Leondires, MP TI Miscarriage rates following day five blastocyst transfers are equivalent to day three embryo transfers. SO FERTILITY AND STERILITY LA English DT Meeting Abstract C1 NIH, Combined Fed Program Reprod Endocrinol, Bethesda, MD USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD SEP PY 2001 VL 76 IS 3 SU 3 MA P103 BP S147 EP S147 DI 10.1016/S0015-0282(01)02431-1 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 470HA UT WOS:000170863900396 ER PT J AU Sartorelli, V Puri, PL AF Sartorelli, V Puri, PL TI The link between chromatin structure, protein acetylation and cellular differentiation SO FRONTIERS IN BIOSCIENCE LA English DT Review DE chromatin remodeling; acetylation; acetyltransferases; deacetylases; cell differentiation; human diseases; review ID HELIX-LOOP-HELIX; TRANSCRIPTION FACTOR GATA-1; CREB-BINDING-PROTEIN; RUBINSTEIN-TAYBI-SYNDROME; NEURONAL INTRANUCLEAR INCLUSIONS; SKELETAL-MUSCLE DIFFERENTIATION; HISTONE ACETYLTRANSFERASES P300; ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ADENOVIRAL ONCOPROTEIN E1A AB Chromatin remodeling and protein acetylation control gene expression and consequently regulate cellular growth and differentiation. Here we review the role of individual chromatin remodeling factors, acetyltransferases and deacetylases in the establishment and maintenance of different cell lineages and in the genesis of some human diseases. C1 NIAMSD, Muscle Biol Lab, Muscle Gene Express Grp, IRP,NIH, Bethesda, MD 20892 USA. Salk Inst Biol Studies, Peptide Biol Lab, La Jolla, CA 92093 USA. Univ Roma La Sapienza, Fdn A Cesalpino, I-00161 Rome, Italy. RP Sartorelli, V (reprint author), NIAMSD, Muscle Biol Lab, Muscle Gene Express Grp, IRP,NIH, Bethesda, MD 20892 USA. NR 294 TC 19 Z9 19 U1 2 U2 5 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD SEP PY 2001 VL 6 BP D1024 EP D1047 DI 10.2741/Sartorel PG 24 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 469GK UT WOS:000170806000003 PM 11532612 ER PT J AU Okada, T Shah, M Higginbotham, JN Li, Q Wildner, O Walbridge, S Oldfield, E Blaese, RM Ramsey, WJ AF Okada, T Shah, M Higginbotham, JN Li, Q Wildner, O Walbridge, S Oldfield, E Blaese, RM Ramsey, WJ TI AV.TK-mediated killing of subcutaneous tumors in situ results in effective immunization against established secondary intracranial tumor deposits SO GENE THERAPY LA English DT Article DE glioma; cancer vaccine; in situ; adenovirus; HSVtk ID HERPES-SIMPLEX VIRUS; MALIGNANT BRAIN-TUMORS; VECTOR PRODUCER CELLS; KINASE GENE-THERAPY; MHC CLASS-I; ANTITUMOR IMMUNITY; HSV-TK; RETROVIRAL VECTORS; ADENOVIRAL VECTOR; GLIOMA-CELLS AB Gene transfer vectors expressing herpes simplex thymidine kinase (HSVtk), in addition to direct killing of tumor cells, often have an associated local 'bystander effect' mediated by metabolic coupling of tumor cells. A systemic antitumor effect mediated by the immune system, termed the distant bystander effect, has also been reported. We have observed the development of cytotoxic T-lymphocyte (CTL) populations and long-lasting antitumor immunity following treatment of subcutaneous tumors with an adenoviral vector expressing HSVtk (AV.TK) and ganciclovir (GCV) in rat glioma model. This vaccination effect seen with AV.TK/GCV treatment of subcutaneous tumor could even abrogate or retard growth of previously established secondary intracranial tumors. C1 NHGRI, Clin Gene Therapy Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Internal Med, Houston, TX 77030 USA. RP Okada, T (reprint author), Jichi Med Sch, Ctr Mol Med, Div Genet Therapeut, 3311-1 Yakushiji Minami Kawachi, Kawachi, Tochigi 3290498, Japan. NR 56 TC 27 Z9 27 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 2001 VL 8 IS 17 BP 1315 EP 1322 DI 10.1038/sj.gt.3301526 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 468HC UT WOS:000170751200005 PM 11571568 ER PT J AU Evans, JT Cravens, P Gatlin, J Kelly, PF Lipsky, PE Garcia, JV AF Evans, JT Cravens, P Gatlin, J Kelly, PF Lipsky, PE Garcia, JV TI Pre-clinical evaluation of an in vitro selection protocol for the enrichment of transduced CD34(+) cell-derived human dendritic cells SO GENE THERAPY LA English DT Article DE dendritic cells; DHFR selection; gene therapy; lentivirus vectors; MLV vectors; immunotherapy ID MEDIATED GENE-TRANSFER; CYTOTOXIC T-LYMPHOCYTES; RESISTANT BONE-MARROW; CORD-BLOOD; STEM-CELLS; DIHYDROFOLATE-REDUCTASE; HEMATOPOIETIC STEM; ANTITUMOR IMMUNITY; TRANSFER VECTORS; MICE AB The efficient genetic modification of CD34(+) cell-derived dendritic cells (DC) will provide a significant. advancement towards the development of immunotherapy protocols for cancer, autoimmune disorders and infectious diseases. Recent reports have described the transduction of CD34(+) cells via retrovirus- and lentivirus-based gene transfer vectors and subsequent differentiation into functional DC. Since there is significant apprehension regarding the clinical uses of HIV-based vectors, in this report, we compare a murine leukemia virus (MLV)- and a human immunodeficiency virus (HIV)-based bicistronic vector for gene transfer into human CD34(+) cells and subsequent differentiation into mature DC. Each vector expressed both EGFP and the dominant selectable marker DHFRL22Y allowing for the enrichment of marked cells in the presence of the antifolate drug trimetrexate (TMTX). Both MLV-based and HIV-based vectors efficiently transduced cytokine mobilized human peripheral blood CD34(+) cells. However, in vitro expansion and differentiation in the presence of GM-CSF, TNF-alpha, Flt-3L, SCF and IL-4 resulted in a reduction in the percentage of DC expressing the transgene. Selection with TMTX during differentiation increased the percentage of marked DC, resulting in up to 79% (MLV vector) and up to 94% (lentivirus-vector) transduced cells expressing EGFP without loss of DC phenotype. Thus, MLV-based vectors and in vitro selection of transduced human DC show great promise for immunotherapy protocols. C1 Univ Texas, SW Med Ctr, Dept Internal Med, Div Infect Dis Y9 206, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Harold C Simmons Arthrit Res Ctr, Dept Internal Med, Dallas, TX 75390 USA. St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. NIAMSD, Autoimmunol Branch, Bethesda, MD 20892 USA. RP Garcia, JV (reprint author), Univ Texas, SW Med Ctr, Dept Internal Med, Div Infect Dis Y9 206, Dallas, TX 75390 USA. FU NCI NIH HHS [CA-82055, 5T32CA09082]; NIAID NIH HHS [AI-39416] NR 43 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD SEP PY 2001 VL 8 IS 18 BP 1427 EP 1435 DI 10.1038/sj.gt.3301530 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 468YE UT WOS:000170785100009 PM 11571583 ER PT J AU Zheng, YL Herr, AM Jacobson, BA Ferrin, LJ AF Zheng, YL Herr, AM Jacobson, BA Ferrin, LJ TI High-density allelotype of the commonly studied gastric cancer cell lines SO GENES CHROMOSOMES & CANCER LA English DT Article ID IN-SITU HYBRIDIZATION; II RECEPTOR GENE; COMPARATIVE GENOMIC HYBRIDIZATION; MICROSATELLITE INSTABILITY; DIFFERENTIATED ADENOCARCINOMA; BARRETT-ESOPHAGUS; STOMACH-CANCER; ALLELIC LOSS; TGF-BETA; C-MET AB Gastric cancer is one of the leading causes of death from cancer throughout the world, and studies to elucidate the genetic defects found in this type of cancer are growing in number. Increasingly sophisticated techniques and the sequencing of the human genome have had an impact on the scope of such studies. While the use of tumor specimens remains popular, more emphasis is being placed on cell lines as model systems where specific data can be directly combined with results from other studies. This article describes a genetic survey of the most widely used gastric adenocarcinoma cell lines. The allelotype at 351 polymorphic loci in 14 cell lines was obtained, and the results from the 4,900 polymerase chain reactions are displayed. In addition to confirming loss of heterozygosity on chromosome arms 6p, 7q, 17p, and 18, additional deletions on arm Sp and the pericentromeric regions of chromosomes I and 10 were detected. Areas that might contain homozygous deletions or amplifications also were mapped. The rate of microsatellite instability was quantified and shown to vary greatly among the different cell lines. Most important, this study serves as a genetic scaffold for the integration of past and future studies on the nature of the genetic defects in gastric cancer. (C) 2001 Wiley-Liss, Inc. C1 Univ Minnesota, Div Gastroenterol, Minneapolis, MN 55455 USA. NCI, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Ferrin, LJ (reprint author), Univ Minnesota, Div Gastroenterol, Mayo Mail Code 36,420 Delaware St SE, Minneapolis, MN 55455 USA. NR 65 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD SEP PY 2001 VL 32 IS 1 BP 67 EP 81 DI 10.1002/gcc.1168 PG 15 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 461DE UT WOS:000170349000009 PM 11477663 ER PT J AU Kar, S Adhya, S AF Kar, S Adhya, S TI Recruitment of HU by piggyback: a special role of GalR in repressosome assembly SO GENES & DEVELOPMENT LA English DT Article DE transcription repression; DNA looping; protein-protein interaction; HU mutants ID HISTONE-LIKE PROTEINS; ESCHERICHIA-COLI; DNA-BINDING; HOMOLOGOUS RECOMBINATION; TRANSCRIPTION FACTORS; COMPLEX; PROMOTE; HMG1; INTERACTS; INVITRO AB In Gal repressosome assembly, a DNA loop is formed by the interaction of two GalR, bound to two distal operators, and the binding of the histone-like protein, HU, to an architecturally critical position on DNA to facilitate the GalR-GalR interaction. We show that GalR piggybacks HU to the critical position on the DNA through a specific GalR-HU interaction. This is the first example of HU making a specific contact with another protein. The GaIR-HU contact that results in cooperative binding of the two proteins to DNA may be transient and absent in the final repressosome structure. A sequence-independent DNA-binding protein being recruited to an architectural site on DNA through a specific association with a regulatory protein may be a common mode for assembly of complex nucleoprotein structures. C1 NCI, Dept Mol Biol, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Dept Mol Biol, NIH, Bethesda, MD 20892 USA. NR 37 TC 36 Z9 36 U1 0 U2 1 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 SEP 1 PY 2001 VL 15 IS 17 BP 2273 EP 2281 DI 10.1101/gad.920301 PG 9 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 470GT UT WOS:000170863100010 PM 11544184 ER PT J AU Chatterjee, N Shih, J Hartge, P Brody, L Tucker, M Wacholder, S AF Chatterjee, N Shih, J Hartge, P Brody, L Tucker, M Wacholder, S TI Association and aggregation analysis using kin-cohort designs with applications to genotype and family history data from the Washington Ashkenazi Study SO GENETIC EPIDEMIOLOGY LA English DT Article DE copula models; marginal likelihood; semiparametric estimation; residual familial aggregation; penetrance ID BREAST-CANCER RISK; LINKAGE ANALYSIS; OVARIAN-CANCER; BRCA1; PENETRANCE; MUTATIONS; CARRIERS; DISEASE; AGE AB When a rare inherited mutation in a disease gene, such as BRCA1, is found through extensive study of high-risk families, it is critical to estimate not only age-specific penetrance of the disease associated with the mutation, but also the residual effect of family history once the mutation is taken into account. The kin-cohort design, a cross-sectional survey of a suitable population that collects DNA and family history data, provides an efficient alternative to cohort or case-control designs for estimating age-specific penetrance in a population not selected because of high familial risk. In this report, we develop a method for analyzing kin-cohort data that simultaneously estimate the age-specific cumulative risk of the disease among the carriers and non-carriers of the mutations and the gene-adjusted residual familial aggregation or correlation of the disease. We employ a semiparametric modeling approach, where the marginal cumulative risks corresponding to the carriers and non-carriers are treated non-parametrically and the residual familial aggregation is described parametrically by a class of bivariate failure time models known as copula models. A simple and robust two-stage method is developed for estimation. We apply the method to data from the Washington Ashkenazi Study [Struewing et al., 1997, N Engl J Med 336:1401-1408] to study the residual effect of family history on the risk of breast cancer among non-carriers and carriers of specific BRCA1/BRCA2 germline mutations. We find that positive history of a single first-degree relative significantly increases risk of the non-carriers (RR = 2.0, 95% CI = 1.6-2.6) but has little or no effect on the carriers. (C) 2001 Wiley-Liss, Inc. C1 Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. NHLBI, Off Biostat Res, Rockville, MD USA. NHGRI, Lab Gene Transfer, Bethesda, MD 20892 USA. RP Chatterjee, N (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 8038, Rockville, MD 20852 USA. NR 22 TC 11 Z9 11 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD SEP PY 2001 VL 21 IS 2 BP 123 EP 138 DI 10.1002/gepi.1022 PG 16 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 465FA UT WOS:000170577900003 PM 11507721 ER PT J AU Burke, W Coughlin, SS Lee, NC Weed, DL Khoury, MJ AF Burke, W Coughlin, SS Lee, NC Weed, DL Khoury, MJ TI Application of population screening principles to genetic screening for adult-onset conditions SO GENETIC TESTING LA English DT Article ID FACTOR-V LEIDEN; BREAST-CANCER SUSCEPTIBILITY; PUBLIC-HEALTH PERSPECTIVES; HUMAN GENOME PROJECT; LONG-TERM SURVIVAL; FOLLOW-UP CARE; HEREDITARY HEMOCHROMATOSIS; INFORMED CONSENT; OVARIAN-CANCER; HUNTINGTONS-DISEASE AB Recent advances in molecular genetics have highlighted the potential use of genetic testing to screen for adult-onset chronic diseases. Several issues must be addressed, however, before such tests can be recommended for population-based prevention programs. These issues include the adequacy of the scientific evidence, the balance of risks and benefits, the need for counseling and informed consent, and the costs and resources required. Ongoing assessment of the screening program and quality assurance of laboratory testing are also needed. This paper considers the application of general principles for mass screening to genetic testing for susceptibility to adult-onset chronic diseases. Evaluation of proposals for genetic screening in context of these principles reveals that needed evidence is often absent, particularly with respect to the predictive value of tests, efficacy of interventions, and social consequences of testing. The principles of population screening are developed into a framework for public health policy on genetic screening that has three stages: assessment of the screening test and interventions for those who test positive, including assessment of risks and costs, policy development, and program evaluation. Essential elements are identified, including evaluation of evidence and processes for consensus development and program evaluation. The proposed framework for public health policymaking outlined in this commentary, when combined with future efforts that involve an authoritative consensus process, may be useful for the evaluation and planning of genetic screening programs aimed at reducing morbidity and mortality from adult-onset chronic diseases. C1 Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Canc Prevent & Control, Atlanta, GA 30341 USA. NCI, Div Canc Prevent, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Off Genet & Dis Prevent, Atlanta, GA 30341 USA. RP Burke, W (reprint author), Univ Washington, Dept Med Hist & Eth, Box 357120,1959 NE Pacific,Room A204, Seattle, WA 98195 USA. NR 97 TC 40 Z9 41 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1090-6576 J9 GENET TEST JI Genet. Test. PD FAL PY 2001 VL 5 IS 3 BP 201 EP 211 DI 10.1089/10906570152742245 PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 509FW UT WOS:000173136500005 PM 11788085 ER PT J AU Pavlov, YI Shcherbakova, PV Kunkel, TA AF Pavlov, YI Shcherbakova, PV Kunkel, TA TI In vivo consequences of putative active site mutations in yeast DNA polymerases alpha, epsilon, delta, and zeta SO GENETICS LA English DT Article ID I KLENOW FRAGMENT; STRAND-BREAK REPAIR; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; MISMATCH REPAIR; REPLICATION FIDELITY; EMBRYONIC LETHALITY; CRYSTAL-STRUCTURE; INDUCED MUTAGENESIS; THYMINE DIMER AB Several amino acids in the active site of family A DNA polymerases contribute to accurate DNA synthesis. For two of these residues, family B DNA polymerases have conserved tyrosine residues in regions II and III that are suggested to have similar functions. Here we replaced each tyrosine with alanine in the catalytic subunits of yeast DNA polymerases alpha, delta, epsilon, and zeta and examined the consequences in vivo. Strains with the tyrosine substitution in the conserved SL/MYPS/N motif in region It in Pol delta or Pol epsilon are inviable. Strains with same substitution in Rev3, the catalytic subunit of Pol zeta, are nearly UV immutable, suggesting severe loss of function. A strain with this substitution in Pol alpha (pol1-Y869A) is viable, but it exhibits slow growth, sensitivity to hydroxyurea, and a spontaneous mutator phenotype for frameshifts and base substitutions. The pol1-Y869A/pol1-Y869A diploid exhibits aberrant growth. Thus, this tyrosine is critical for the function of all four eukaryotic family B DNA polymerases. Strains with a tyrosine substitution in the conserved NS/VxYG motif in region III in Pol alpha, delta, or -epsilon are viable and a strain with the homologous substitution in Rev3 is UV mutable. The Pola mutant has no obvious phenotype. The Pol epsilon (pol.2-17831A) mutant is slightly sensitive to hydroxyurea and is a semidominant mutator for spontaneous base substitutions and frameshifts. The Pol delta mutant (Pol3-Y708A) grows slowly, is sensitive to hydroxy-urea and methyl methanesulfonate, and is a strong base substitution and frameshift, mutator. The pol3-Y708A/pol3-Y708A diploid grows slowly and aberrantly. Mutation rates in the Pol alpha, -delta, and -epsilon mutant strains are increased in a locus-specific manner by inactivation of PMS1-dependent DNA mismatch repair, suggesting that the mutator effects are due to reduced fidelity of chromosomal DNA replication. This could result directly from relaxed base selectivity of the mutant polymerases due to the amino acid changes in the polymerase active site. In addition, the alanine substitutions may impair catalytic function to allow a different polymerase to compete at the replication fork. This is supported by the observation that the pol3-Y708A mutation is recessive and its mutator effect is partially, suppressed by disruption of the REV3 gene. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. St Petersburg Univ, Dept Genet, St Petersburg 199034, Russia. RP Pavlov, YI (reprint author), NIEHS, Mol Genet Lab, Bldg 101,Rm 332,POB 12233, Res Triangle Pk, NC 27709 USA. NR 69 TC 74 Z9 74 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD SEP PY 2001 VL 159 IS 1 BP 47 EP 64 PG 18 WC Genetics & Heredity SC Genetics & Heredity GA 476WV UT WOS:000171252500005 PM 11560886 ER PT J AU Piao, Y Ko, NT Lim, MK Ko, MSH AF Piao, Y Ko, NT Lim, MK Ko, MSH TI Construction of long-transcript enriched cDNA libraries from submicrogram amounts of total RNAs by a universal PCR amplification method SO GENOME RESEARCH LA English DT Article ID CAP-TRAPPER; DNA; EXPRESSION; CELLS; GENES AB Here we report a novel design of linker primer that allows one to differentially amplify long tracts (average 3.0 kb with size ranges of 1-7 kb) or short DNAs (average 1.5 kb with size ranges of 0.5-3 kb) from a complex mixture. The method allows one to generate cDNA libraries enriched for long transcripts without size selection of insert DNAs. One representative library from newborn kidney includes 70% of clones bearing ATG start codons. A comparable library has been generated from 20 mouse blastocysts, containing only similar to 40 ng of total RNA. This universal PCR amplification scheme can provide a route to isolate very large cDNAs, even if they are expressed at very low levels. C1 NIA, Genet Lab, Dev Genom & Aging Sect, NIH, Baltimore, MD 21224 USA. RP Ko, MSH (reprint author), NIA, Genet Lab, Dev Genom & Aging Sect, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 21 TC 19 Z9 22 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD SEP PY 2001 VL 11 IS 9 BP 1553 EP 1558 DI 10.1101/gr.185501 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 470HG UT WOS:000170864600012 PM 11544199 ER PT J AU Davids, MS Crawford, E Weremowicz, S Morton, CC Copeland, NG Gilbert, DJ Jenkins, NA Phelan, MC Comb, MJ Melnick, MB AF Davids, MS Crawford, E Weremowicz, S Morton, CC Copeland, NG Gilbert, DJ Jenkins, NA Phelan, MC Comb, MJ Melnick, MB TI STK25 is a candidate gene for pseudopseudohypoparathyroidism SO GENOMICS LA English DT Article ID ALBRIGHT HEREDITARY OSTEODYSTROPHY; GNAS1 AB We determined the chromosomal location of the mouse gene Stk25, encoding a member of the Ste20/PAK family of serine/threonine kinases, by interspecific backcross analysis. We mapped Stk25 to the central region of mouse chromosome 1 linked to Chrng (formerly Acrg) and En1. This central region of mouse chromosome 1 shares a region of homology with the long arm of human chromosome 2, suggesting that the human homologue of Stk25 would also map to 2q. We proved this prediction of syntenic homology correct by mapping human STK25 to 2q37. Deletion of the 2q37 region has been implicated in the expression of pseudopseudohypoparathyroidism (PPHP), a disease which shares features of the Albright hereditary osteodystrophy (AHO) phenotype. To investigate a pathogenetic relationship between STK25 and PPHP, we carried out fluorescence in situ hybridization (FISH) using an STK25 gene probe and chromosomes from PPHP patients characterized as having small deletions near the distal end of 2q. PPHP patient DNA showed no hybridization to STK25 genomic DNA, indicating that STK25 is contained within the deleted.,, in conjunction with chromosomal region. This finding previous studies demonstrating the role of Ste20/PAK kinases in heterotrimeric G protein signaling, suggests that STK25 is a positional candidate gene for PPHP. C1 Cell Signaling Technol, Beverly, MA 01915 USA. Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. TC Thompson Childrens Hosp, Chattanooga, TN 37403 USA. RP Melnick, MB (reprint author), Cell Signaling Technol, Beverly, MA 01915 USA. NR 9 TC 9 Z9 11 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2001 VL 77 IS 1-2 BP 2 EP 4 DI 10.1006/geno.2001.6605 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 469GU UT WOS:000170806800002 PM 11543625 ER PT J AU Ayres, JA Shum, L Akarsu, AN Dashner, R Takahashi, K Ikura, T Slavkin, HC Nuckolls, GH AF Ayres, JA Shum, L Akarsu, AN Dashner, R Takahashi, K Ikura, T Slavkin, HC Nuckolls, GH TI DACH: Genomic characterization, evaluation as a candidate for postaxial polydactyly type A2, and developmental expression pattern of the mouse homologue SO GENOMICS LA English DT Article DE DACH; dachshund; transcription factor; chromosome 13q22; limb; kidney; ear; eye; postaxial polydactyly; mutation analysis ID DROSOPHILA EYES ABSENT; BRANCHIOOTORENAL BOR SYNDROME; DACHSHUND GENES; NEURAL PLATE; FAMILY; PAX-6; LIMB; TRANSLOCATION; MUTATIONS; ANTERIOR AB The gene DACH is a human homologue of Drosophila melanogaster dachshund (dac), which encodes a nuclear factor essential for determining cell fates in the eye, leg, and nervous system of the fly. To investigate possible connections between DACH and inherited developmental disorders, we have characterized the human DACH genomic structure and investigated the tissue and cellular distribution of the mouse DACH1 protein during development. DACH spans 400 kb and is encoded by 12 exons. The predominant DACH transcript is 5.2 kb and encodes a 706-amino-acid protein with an observed molecular weight of 97 kDa. DACH mRNA was defected in multiple adult human tissues including kidney and heart. The mouse DACH1 protein was immunolocalized to specific cell types within the developing kidneys, eyes, cochleae, and limb buds. Data suggest genetic linkage of the limb bud patterning defect postaxial polydactyly type A (designated PAP-A2, MIM 602085) to a 28-cM interval on chromosome 13 that includes DACH. However, mutation analysis of DACH in this PAP-A2 pedigree revealed no sequence differences in the coding region, splice sites, or proximal promoter region. The data presented will allow for the analysis of DACH as a candidate for other developmental disorders affecting the limbs, kidneys, eyes, ears, and other sites of DACH expression. C1 NIAMS, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. Hacettepe Univ, Dept Pediat, Basic & Appl Res Ctr, Gene Mapping Lab, Ankara, Turkey. RP Nuckolls, GH (reprint author), NIAMS, Craniofacial Dev Sect, NIH, Bethesda, MD 20892 USA. RI Akarsu, Nurten/E-9758-2013 OI Akarsu, Nurten/0000-0001-5432-0032 FU NIAMS NIH HHS [Z01-AR41114] NR 50 TC 21 Z9 23 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2001 VL 77 IS 1-2 BP 18 EP 26 DI 10.1006/geno.2001.6618 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 469GU UT WOS:000170806800005 PM 11543628 ER PT J AU Zeng, CJ Kouprina, N Zhu, B Cairo, A Hoek, M Cross, G Osoegawa, K Larionov, V de Jong, P AF Zeng, CJ Kouprina, N Zhu, B Cairo, A Hoek, M Cross, G Osoegawa, K Larionov, V de Jong, P TI Large-insert BAC/YAC libraries for selective re-isolation of genomic regions by homologous recombination in yeast SO GENOMICS LA English DT Article DE BAC and YAC libraries; human pathogens; TAR cloning; gene isolation ID HUMAN DNA; ARTIFICIAL CHROMOSOMES; TRYPANOSOMA-BRUCEI; CLONING; PROPAGATION; FRAGMENTS; VECTOR; TRANSFORMATION; INTEGRITY; YACS AB We constructed representative large-insert bacterial artificial chromosome (BAC) libraries of two human pathogens (Trypanosoma brucei and Giardia lamblia) using a new hybrid vector, pTARBAC1, containing a yeast artificial chromosome (YAC) cassette (a yeast selectable marker and a centromere). The cassette allows transferring of BACs into yeast for their further modification. Furthermore, the new hybrid vector provides the opportunity to re-isolate each DNA insert without construction of a new library of random clones. Digestion of a BAC DNA by an endonuclease that has no recognition site in the vector, but which deletes most of the internal insert sequence and leaves the unique flanking sequences, converts a BAC into a TAR vector, thus allowing direct gene isolation. Cotransformation of a TAR vector and genomic DNA into yeast spheroplasts, and subsequent recombination between the TAR vector's flanking ends and a specific genomic fragment, allows rescue of the fragment as a circular YAC/BAC molecule. Here we prove a new cloning strategy by re-isolation of randomly chosen genomic fragments of different size from T. brucei cloned in BACs. We conclude that genomic regions of unicellular eukaryotes can be easily re-isolated using this technique, which provides an opportunity to study evolution of these genomes and the role of genome instability in pathogenicity. C1 Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Rockefeller Univ, Mol Parasitol Lab, New York, NY 10021 USA. RP de Jong, P (reprint author), Childrens Hosp Oakland, BACPAC Resources, 747-52nd St, Oakland, CA 94609 USA. RI Cross, George/B-7444-2011 OI Cross, George/0000-0003-1374-6955 NR 19 TC 18 Z9 19 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP PY 2001 VL 77 IS 1-2 BP 27 EP 34 DI 10.1006/gene.2001.6616 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 469GU UT WOS:000170806800006 PM 11543629 ER PT J AU Burton, SL Randel, L Titlow, K Emanuel, EJ AF Burton, SL Randel, L Titlow, K Emanuel, EJ TI The ethics of pharmaceutical benefit management SO HEALTH AFFAIRS LA English DT Article ID RESPIRATORY-TRACT INFECTIONS; CARE; CAPITATION; PHYSICIANS; BRONCHITIS; COLDS; TRUST AB Efforts to limit pharmacy costs raise both ethical and economic considerations. Six values should inform pharmacy benefit management: (1) accepting resource constraints; (2) helping the sick; (3) protecting the worst off; (4) respecting autonomy; (5) sustaining trust; and (6) promoting inclusive decision making. Direct controls, such as formularies, step therapy, and prior authorization, can focus limited resources on the sick and worst off. However, direct controls limit autonomy and are administratively burdensome. controls, such as physician capitation, tiered copayments, and drug benefit caps, align physicians' and patients' interests with resource constraints, respect autonomy, and are administratively efficient. Unfortunately, they deter use based on cost, not medical need; they do not focus cuts on unnecessary or marginal drug use or focus resources on the sick. Budget caps are the least defensible, while tiered copays and physician capitation can be justified if implemented with safeguards. Formularies and step therapy are ethically justifiable if they can be efficiently instituted. C1 Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20057 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 27 TC 9 Z9 9 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD SEP-OCT PY 2001 VL 20 IS 5 BP 150 EP 163 DI 10.1377/hlthaff.20.5.150 PG 14 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 470GP UT WOS:000170862800014 PM 11558699 ER PT J AU Celentano, DD DiIorio, C Hartwell, T Kelly, J Magana, R Maibach, E O'Leary, A Pequegnat, W Rotheram-Borus, MJ Schilling, R Amsel, J El-Bassel, N Ferreira-Pinto, JB Gleghom, A Ivanoff, A Jemmott, JB Jemmott, LS Martin, R Miller, S Murphy, D Raffaelli, M Rompalo, AM Schlenger, W Sikkema, K Somlai, A Alford, K Allende-Ramos, C Hackl, K Kuklinski, M Langabeer, KA Lee, MB Lopez, E Nava, P Parra, M Pranke, J Reid, H Sharpe-Potter, J Witte, S Villasenor, Y Wight, RG Hansen, N LaVange, L McFadden, D Perritt, R Poole, WK Gaydos, C Quinn, TC Mitnick, L Roberts, S Stover, E Bellack, AS Coates, T Crano, WD Francis, D Green, SB Moras, K AF Celentano, DD DiIorio, C Hartwell, T Kelly, J Magana, R Maibach, E O'Leary, A Pequegnat, W Rotheram-Borus, MJ Schilling, R Amsel, J El-Bassel, N Ferreira-Pinto, JB Gleghom, A Ivanoff, A Jemmott, JB Jemmott, LS Martin, R Miller, S Murphy, D Raffaelli, M Rompalo, AM Schlenger, W Sikkema, K Somlai, A Alford, K Allende-Ramos, C Hackl, K Kuklinski, M Langabeer, KA Lee, MB Lopez, E Nava, P Parra, M Pranke, J Reid, H Sharpe-Potter, J Witte, S Villasenor, Y Wight, RG Hansen, N LaVange, L McFadden, D Perritt, R Poole, WK Gaydos, C Quinn, TC Mitnick, L Roberts, S Stover, E Bellack, AS Coates, T Crano, WD Francis, D Green, SB Moras, K CA Natl Inst Mental Hlth Multisite HI TI Social-cognitive theory mediators of behavior change in the National Institute of Mental Health Multisite HIV Prevention Trial SO HEALTH PSYCHOLOGY LA English DT Article; Proceedings Paper CT 12th World AIDS Conference CY JUN 28-JUL 03, 1998 CL GENEVA, SWITZERLAND DE HIV prevention intervention; social-cognitive theory; mediation analysis ID RISK-REDUCTION; SELF-EFFICACY; WOMEN; INTERVENTION; DISEASES AB The National Institute of Mental Health Multisite HIV Prevention Trial was a trial of an intervention to reduce sexual HIV risk behaviors among 3,706 low-income at-risk men and women at 7 U.S. research sites. The intervention, based on social-cognitive theory and designed to influence behavior change by improving expected outcomes of condom use and increasing knowledge, skills, and self-efficacy to execute safer sex behaviors, was effective relative to a control condition in reducing sexual risk behavior. At 3 months after completion of the intervention, measures of these potential mediators were higher in the intervention than in the control condition. Although the effect of the intervention on sexual risk behavior was significantly reduced when the variables were controlled statistically, supporting the hypothesis of their mediation of the intervention effect, most of the effect remained unexplained, indicating the influence of unmeasured factors on outcome. C1 NIMH, Multisite HIV Prevent Trial Grp, NIH, Rockville, MD 20857 USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, Bethesda, MD 20892 USA. Univ Houston, Houston, TX 77004 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Maryland, Data Safety & Monitoring Board, College Pk, MD 20742 USA. Johns Hopkins Univ, Sch Med, Core Lab, Baltimore, MD 21218 USA. Univ Arizona, Tucson, AZ 85721 USA. NIMH, Res Suppport Off, Bethesda, MD 20892 USA. Res Triangle Inst, Data Coordinating Ctr, Res Triangle Pk, NC 27709 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif Irvine, Irvine, CA 92717 USA. Columbia Univ, New York, NY 10027 USA. Emory Univ, Atlanta, GA 30322 USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Princeton Univ, Princeton, NJ 08544 USA. Emory Univ, Atlanta, GA 30322 USA. RP O'Leary, A (reprint author), CDCP, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, 1600 Clifton Rd,MS E-37, Atlanta, GA 30333 USA. RI Gaydos, Charlotte/E-9937-2010; Potter, Jennifer/C-6720-2008 OI Potter, Jennifer/0000-0002-7250-4422 NR 33 TC 42 Z9 42 U1 6 U2 15 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD SEP PY 2001 VL 20 IS 5 BP 369 EP 376 DI 10.1037//0278-6133.20.5.369 PG 8 WC Psychology, Clinical; Psychology SC Psychology GA 471KY UT WOS:000170929600007 ER PT J AU Seeff, LB Lindsay, KL Bacon, BR Kresina, TF Hoofnagle, JH AF Seeff, LB Lindsay, KL Bacon, BR Kresina, TF Hoofnagle, JH TI Complementary and alternative medicine in chronic liver disease SO HEPATOLOGY LA English DT Article ID CHRONIC HEPATITIS-C; SHO-SAIKO-TO; RANDOMIZED CONTROLLED TRIAL; HERBAL MEDICINE; B VIRUS; HEPATOCELLULAR-CARCINOMA; UNITED-STATES; DOUBLE-BLIND; CIRRHOSIS; RATS C1 NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA USA. St Louis Univ, Sch Med, St Louis, MO 63103 USA. RP Seeff, LB (reprint author), NIDDK, NIH, Bldg 31,Room 9A, Bethesda, MD 20892 USA. NR 81 TC 137 Z9 140 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD SEP PY 2001 VL 34 IS 3 BP 595 EP 603 DI 10.1053/jhep.2001.27445 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 467AW UT WOS:000170679200021 PM 11526548 ER PT J AU Walbert, T Jirikowski, GF Prufer, K AF Walbert, T Jirikowski, GF Prufer, K TI Distribution of 1,25-dihydroxyvitamin D3 receptor immunoreactivity in the limbic system of the rat SO HORMONE AND METABOLIC RESEARCH LA English DT Article DE steroid; 1,25-dihydroxyvitamin D3; limbic system; rat; vitamin D receptor ID NERVE GROWTH-FACTOR; FACTOR MESSENGER-RNA; VITAMIN-D RECEPTORS; ALZHEIMERS-DISEASE; TARGET-CELLS; D-3 RECEPTOR; BRAIN; HIPPOCAMPUS; INDUCTION; NEURONS AB We used immunocytochemistry to obtain a complete cellular and subcellular mapping of the 1,25-dihydroxyvitamin D3 receptor protein (VDR) in the rat limbic system. We observed specific VDR immunostaining in the nucleus as well as in the perinuclear cytoplasm of neuronal cells. The limbic system consists of a variety of neuronal structures, and is known to have influence on memory, behavior, emotions and reproduction. In the hippocampal formation, we found strong nuclear staining as well as less distinguished cytoplasmic VDR staining in CA1, CA3 and CA4. The CA2 area showed a unique cytoplasmic predominance of VDR. The amygdala was found to exhibit specific patterns of VDR distribution in the various regions of the nucleus. We observed distinct differences of VDR localization within the limbic preoptic areas of the hypothalamus. Further parts of the brain we analyzed included the mammillary bodies, the indusium griseum and the cingulate cortex. The subcellular distribution of VDR in regions of the limbic system suggests a specific functional role of the receptor protein and indicates a role for calcitriol as a neuroactive steroid. C1 Univ Jena, Inst Anat Anat 2, D-6900 Jena, Germany. NIDDK, NIH, LCBB, Bethesda, MD USA. RP Jirikowski, GF (reprint author), Klinikum FSU, Inst Anat 2, Teichgraben 7, D-07743 Jena, Germany. NR 41 TC 47 Z9 49 U1 1 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD SEP PY 2001 VL 33 IS 9 BP 525 EP 531 DI 10.1055/s-2001-17210 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 479DF UT WOS:000171388100003 PM 11561211 ER PT J AU Kang, E Giri, N Wu, T Sellers, S Kirby, M Hanazono, Y Tisdale, J Dunbar, CE AF Kang, E Giri, N Wu, T Sellers, S Kirby, M Hanazono, Y Tisdale, J Dunbar, CE TI In vivo persistence of retrovirally transduced murine long-term repopulating cells is not limited by expression of foreign gene products in the fully or minimally myeloablated setting SO HUMAN GENE THERAPY LA English DT Article ID HEMATOPOIETIC STEM-CELLS; CHRONIC GRANULOMATOUS-DISEASE; GREEN FLUORESCENT PROTEIN; BONE-MARROW CELLS; IN-VIVO; PERIPHERAL-BLOOD; PROGENITOR CELLS; GLUCOCEREBROSIDASE GENE; NONHUMAN-PRIMATES; IMMUNE-RESPONSES AB Many nonmalignant hematologic disorders could potentially be treated by genetic correction of as few as 5-10% of target lineage cells. However, immune system clearance of cells expressing gene products perceived as foreign could be limiting. There is evidence that tolerance to foreign proteins can result when myeloablative conditioning is used, but this limits the overall applicability of such techniques. Therefore, we sought to evaluate the engraftment of hematopoietic stem cells carrying a foreign transgene after low-dose irradiation by comparing in vivo survival of murine long-term repopulating cells (LTRC) transduced with either a retroviral vector expressing the bacterial neomycin phosphotransferase gene (neo) or a vector containing neo gene sequences but modified to prevent protein expression (nonexpression). First, marrow cells from congenic donors were transduced with either vector and transplanted into recipients treated with standard dose irradiation of 800 rads. High-level engraftment and gene marking resulted, without differences in the marking levels or pattern of persistence of the cells between cells transduced with either vector. Low-dose irradiation at 100 rads was tested using higher cell doses. Marking levels as high as 10% overall were obtained, again with no differences between mice receiving cells transduced with the neo versus the nonexpression vectors. To investigate a potentially more immunogenic protein, marrow cells were transduced with a vector containing the green fluorescent protein (GFP) gene, and their persistence was studied in recipient mice receiving 100 rads. Stable GFP expression in 5-10% of circulating cells was observed long term. We conclude that even with very low dose conditioning, engraftment by genetically modified LTRC cells at clinically significant levels can be achieved without evidence for clearance of cells known to be expressing immunogenic proteins. C1 NHLBI, NIH, Hematol Branch, Mol Hematopoiesis Sect, Bethesda, MD 20892 USA. NIDDKD, Mol Clin Hematol Branch, Bethesda, MD 20892 USA. Jichi Med Sch, Ctr Mol Med, Div Genet Therapeut, Tochigi, Japan. RP Dunbar, CE (reprint author), NHLBI, NIH, Hematol Branch, Mol Hematopoiesis Sect, Bldg 10,Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 30 Z9 30 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD SEP PY 2001 VL 12 IS 13 BP 1663 EP 1672 DI 10.1089/10430340152528156 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 468PT UT WOS:000170766400006 PM 11535169 ER PT J AU Rosenberg, MJ Killoran, C Dziadzio, L Chang, S Stone, DL Meck, J Aughton, D Bird, LM Bodurtha, J Cassidy, SB Graham, JM Grix, A Guttmacher, AE Hudgins, L Kozma, C Michaelis, RC Pauli, R Peters, KF Rosenbaum, KN Tifft, CJ Wargowski, D Williams, MS Biesecker, LG AF Rosenberg, MJ Killoran, C Dziadzio, L Chang, S Stone, DL Meck, J Aughton, D Bird, LM Bodurtha, J Cassidy, SB Graham, JM Grix, A Guttmacher, AE Hudgins, L Kozma, C Michaelis, RC Pauli, R Peters, KF Rosenbaum, KN Tifft, CJ Wargowski, D Williams, MS Biesecker, LG TI Scanning for telomeric deletions and duplications and uniparental disomy using genetic markers in 120 children with malformations SO HUMAN GENETICS LA English DT Article ID UNEXPLAINED MENTAL-RETARDATION; CHROMOSOMAL-ABNORMALITIES; REARRANGEMENTS; PHENOTYPE AB We screened 120 children with sporadic multiple congenital anomalies and either growth or mental retardation for uniparental disomy (UPD) or subtelomeric deletions. The screening used short tandem repeat polymorphisms (STRP) from the subtelomeric regions of 41 chromosome arms. Uninformative marker results were reanalyzed by using the next available marker on that chromosome arm. In total, approximately 25,000 genotypes were generated and analyzed for this study. Subtelomeric deletions of 1 Mb in size were excluded for 27 of 40 chromosome arms. Among the 120 subjects none was found to have UPD, but five subjects (4%, 95% confidence interval 1-9%) were found to have a deletion or duplication of one or more chromosome arms. We conclude that UPD is not a frequent cause of undiagnosed multiple congenital anomaly syndrome. In addition, we determined that 9p and 7q harbor chromosome length variations in the normal population. We conclude that subtelomeric marker analysis is effective for the detection of subtelomeric duplications and deletions, although it is labor intensive. Given a detection rate that is similar to prior studies and the large workload imposed by STRPs, we conclude that STRPs are an effective, but impractical, approach to the determination of segmental aneusomy given current technology. C1 NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA. Georgetown Univ, Washington, DC 20007 USA. William Beaumont Hosp, Royal Oak, MI 48073 USA. Univ Calif San Diego, Childrens Hosp & Hlth Ctr, San Diego, CA 92123 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Univ Calif Irvine, Orange, CA 92868 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Kaiser Permanente, Sacramento, CA 95815 USA. Stanford Univ, Stanford, CA 94305 USA. Greenwood Genet Ctr, Greenwood, SC 29646 USA. Univ Wisconsin, Med Ctr, Madison, WI 53705 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Gundersen Lutheran Med Ctr, La Crosse, WI 54601 USA. RP Rosenberg, MJ (reprint author), NHGRI, Genet Dis Res Branch, 49 Convent Dr, Bethesda, MD 20892 USA. RI Chang, Susie/E-2870-2011; OI Williams, Marc/0000-0001-6165-8701 NR 22 TC 41 Z9 41 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 2001 VL 109 IS 3 BP 311 EP 318 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 483UY UT WOS:000171655300010 PM 11702212 ER PT J AU Fumagalli, A Ferrari, M Soriani, N Gessi, A Foglieni, B Martina, E Manitto, MP Brancato, R Dean, M Allikmets, R Cremonesi, L AF Fumagalli, A Ferrari, M Soriani, N Gessi, A Foglieni, B Martina, E Manitto, MP Brancato, R Dean, M Allikmets, R Cremonesi, L TI Mutational scanning of the ABCR gene with double-gradient denaturing-gradient gel electrophoresis (DG-DGGE) in Italian Stargardt disease patients SO HUMAN GENETICS LA English DT Article ID MACULAR DEGENERATION; FUNDUS-FLAVIMACULATUS; TRANSPORTER GENE; RETINITIS-PIGMENTOSA; DYSTROPHY; MAPS; IDENTIFICATION; PHENOTYPE; ALLOWS; LOCUS AB Mutations in the retina-specific ABC transporter (ABCR) gene are responsible for autosomal recessive Stargardt disease (arSTGD). Mutation detection efficiency in ABCR in arSTGD patients ranges between 30% and 66% in previously published studies, because of high allelic heterogeneity and technical limitations of the employed methods. Conditions were developed to screen the ABCR gene by double-gradient denaturing-gradient gel electrophoresis. The efficacy of this method was evaluated by analysis of DNA samples with previously characterized ABCR mutations. This approach was applied to mutation detection in 44 Italian arSTGD patients corresponding to 36 independent genomes, in order to assess the nature and frequency of the ABCR mutations in this ethnic group. In 34 of 36 (94.4%) STGD patients, 37 sequence changes were identified, including 26 missense, six frameshift, three splicing, and two nonsense variations. Among these, 20 had not been previously described. Several polymorphisms were detected in affected individuals and in matched controls. Our findings extend the spectrum of mutations identified in STGD patients and suggest the existence of a subset of molecular defects specific to the Italian population. The identification of at least two disease-associated mutations in four healthy control individuals indicates a higher than expected carrier frequency of variant ABCR alleles in the general population. Genotype-phenotype analysis in our series showed a possible correlation between the nature and location of some mutations and specific ophthalmoscopic features of STGD disease. C1 Univ Hosp San Raffaele, Unit Genet & Mol Diagnost, I-20132 Milan, Italy. Univ Hosp San Raffaele, Dept Ophthalmol & Visual Sci, I-20132 Milan, Italy. NCI, Lab Genom Divers, FCRDC, Frederick, MD 21702 USA. Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. RP Cremonesi, L (reprint author), Univ Hosp San Raffaele, Unit Genet & Mol Diagnost, Via Olgettina 58-60, I-20132 Milan, Italy. RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 42 TC 33 Z9 33 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD SEP PY 2001 VL 109 IS 3 BP 326 EP 338 DI 10.1007/s004390100583 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 483UY UT WOS:000171655300012 PM 11702214 ER PT J AU Sutton-Tyrrell, K Newman, A Simonsick, EM Havlik, R Pahor, M Lakatta, E Spurgeon, H Vaitkevicius, P AF Sutton-Tyrrell, K Newman, A Simonsick, EM Havlik, R Pahor, M Lakatta, E Spurgeon, H Vaitkevicius, P CA Hlth ABC Investigators TI Aortic stiffness is associated with visceral adiposity in older adults enrolled in the study of health, aging, and body composition SO HYPERTENSION LA English DT Article DE vascular stiffness; central obesity; aging; insulin resistance; pulse wave velocity ID PULSE-WAVE VELOCITY; CARDIOVASCULAR RISK; ARTERIAL DISTENSIBILITY; HYPERTENSION; OBESITY; PRESSURE; GLUCOSE; YOUNG; FAT AB The central arteries stiffen with age, causing hemodynamic alterations that have been associated with cardiovascular events. Changes in body fat with age may be related to aortic stiffening. The association between vascular stiffness and body fat was evaluated in 2488 older adults (mean age, 74 years; 52% female; 40% black) enrolled in the Study of Health, Aging, and Body Composition (Health ABC), a prospective study of changes in weight and body composition. Clinical sites were located in Pittsburgh, Pa, and Memphis, Tenn. Aortic pulse wave velocity was used as an indirect measure of aortic stiffness. A faster pulse wave velocity indicates a stiffer aorta. Body fat measures were evaluated with dual energy x-ray absorptiometry and computed tomography. Independent of age and blood pressure, pulse wave velocity was positively associated with weight, abdominal circumference, abdominal subcutaneous fat, abdominal visceral fat, thigh fat area, and total fat (P<0.001 for all). The strongest association was with abdominal visceral fat. Elevated pulse wave velocity was also positively associated with history of diabetes and higher levels of glucose, insulin, and hemoglobin Alc (P<0.001 for all). In multivariate analysis, independent positive associations with pulse wave velocity were found for age, systolic blood pressure, heart rate, abdominal visceral fat, smoking, hemoglobin Alc, and history of hypertension. The association between pulse wave velocity and abdominal visceral fat was consistent across tertiles of body weight. Among older adults, higher levels of visceral fat are associated with greater aortic stiffness as measured by pulse wave velocity. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN USA. Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Sutton-Tyrrell, K (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2102, N01-AG-6-2103, N01-AG-6-2106] NR 29 TC 195 Z9 199 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2001 VL 38 IS 3 BP 429 EP 433 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 476KR UT WOS:000171226700024 PM 11566917 ER PT J AU Brooks, HL Beutler, KT Allred, AJ Coffman, TM Knepper, MA AF Brooks, HL Beutler, KT Allred, AJ Coffman, TM Knepper, MA TI Targeted proteomic analysis of AT1a receptor knockout mice to identify renal Na transporters regulated by angiotensin II SO HYPERTENSION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Duke Univ, VA Med Ctr, Durham, NC 27706 USA. Durham VA Med Ctr, Durham, NC USA. Duke Univ, Durham, NC 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2001 VL 38 IS 3 MA 25 BP 476 EP 476 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 476KR UT WOS:000171226700059 ER PT J AU Averill, DB Anderson, RA Strawn, WB Andrews, CA Ferrario, CM AF Averill, DB Anderson, RA Strawn, WB Andrews, CA Ferrario, CM TI ACE inhibition reverses hypertension of congenic mRen-2/Lewis rats SO HYPERTENSION LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2001 VL 38 IS 3 MA P34 BP 495 EP 495 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 476KR UT WOS:000171226700159 ER PT J AU Terris, JM Pamnani, MB Schooley, DF Wang, XY Beutler, KT Knepper, MA AF Terris, JM Pamnani, MB Schooley, DF Wang, XY Beutler, KT Knepper, MA TI Identification of renal sodium transporters and channels upregulated in a model of renin-dependent hypertension: The Goldblatt 2-kidney, one-clip rat SO HYPERTENSION LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2001 VL 38 IS 3 MA P46 BP 497 EP 497 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 476KR UT WOS:000171226700171 ER PT J AU Nielsen, J Beutler, KT Kwon, TH Nielsen, S Knepper, MA AF Nielsen, J Beutler, KT Kwon, TH Nielsen, S Knepper, MA TI Identification of spironolactone-sensitive and spironolactone-insensitive actions of aldosterone in kidney SO HYPERTENSION LA English DT Meeting Abstract C1 NHLBI, Bethesda, MD 20892 USA. Univ Aarhus, DK-8000 Aarhus C, Denmark. 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2001 VL 38 IS 3 MA P47 BP 498 EP 498 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 476KR UT WOS:000171226700172 ER PT J AU Bukoski, RD Batkai, S Jarai, Z Wang, YL Jackson, WF Kunos, G AF Bukoski, RD Batkai, S Jarai, Z Wang, YL Jackson, WF Kunos, G TI The CB1 receptor antagonist SR141716A inhibits Ca2+-induced relaxation in CB1 receptor deficient mice. Possible role for a non-classial cannabinoid receptor? SO HYPERTENSION LA English DT Meeting Abstract C1 N Carolina Cent Univ, Durham, NC USA. NIAAA, Bethesda, MD USA. Western Michigan Univ, Kalamazoo, MI 49008 USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2001 VL 38 IS 3 MA P107 BP 509 EP 509 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 476KR UT WOS:000171226700232 ER PT J AU Turban, SI Wang, XY Masilamani, S Knepper, MA AF Turban, SI Wang, XY Masilamani, S Knepper, MA TI Effects of angiotensin II and dietary NaCl intake on the abundance of the thiazide-sensitive Na-Cl cotransporter in the kidney. SO HYPERTENSION 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 0194-911X J9 HYPERTENSION JI Hypertension PD SEP PY 2001 VL 38 IS 3 MA P185 BP 523 EP 523 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 476KR UT WOS:000171226700309 ER PT J AU Staudt, LM Flavell, RA AF Staudt, LM Flavell, RA TI Genomics, genetics, and genes of the immune system SO IMMUNITY LA English DT Editorial Material C1 NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Yale Univ, Immunobiol Sect, Howard Hughes Med Inst, Sch Med, New Haven, CT 06520 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2001 VL 15 IS 3 SI SI BP 335 EP 336 DI 10.1016/S1074-7613(01)00204-7 PG 2 WC Immunology SC Immunology GA 476DW UT WOS:000171211800001 PM 11567624 ER PT J AU Shaffer, AL Rosenwald, A Hurt, EM Giltnane, JM Lam, LT Pickeral, OK Staudt, LM AF Shaffer, AL Rosenwald, A Hurt, EM Giltnane, JM Lam, LT Pickeral, OK Staudt, LM TI Signatures of the immune response SO IMMUNITY LA English DT Review ID NF-KAPPA-B; GERMINAL-CENTER FORMATION; GENE-EXPRESSION PATTERNS; DOUBLE-STRAND BREAKS; TRANSCRIPTION FACTORS; SOMATIC HYPERMUTATION; IMMUNOGLOBULIN GENES; ACTIN CYTOSKELETON; CDNA MICROARRAY; CELLS AB A compendium of global gene expression measurements from DNA microarray analysis of immune cells identifies gene expression signatures defining various lineages, differentiation stages, and signaling pathways. Germinal center (GC) B cells represent a discrete stage of differentiation with a unique gene expression signature. This includes genes involved in proliferation, as evidenced by high expression of G2/M phase regulators and low expression of ribosomal and metabolic genes that are transcriptional targets of c-myc. GC B cells also lack expression of the NF-kappaB signature genes, which may favor apoptosis. Finally, the transcriptional repression signature of BCL-6 reveals how this factor can prevent terminal differentiation of B cells and cause B cell lymphomas. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, NIH, 9000 Rockville Pike Blvd 10,Room 4N114, Bethesda, MD 20892 USA. RI Giltnane, Jennifer/D-2584-2013 NR 57 TC 241 Z9 243 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD SEP PY 2001 VL 15 IS 3 SI SI BP 375 EP 385 DI 10.1016/S1074-7613(01)00194-7 PG 11 WC Immunology SC Immunology GA 476DW UT WOS:000171211800005 PM 11567628 ER PT J AU Modi, WS Bergeron, J Sanford, M AF Modi, WS Bergeron, J Sanford, M TI The human MIP-1 beta chemokine is encoded by two paralogous genes, ACT-2 and LAG-1 SO IMMUNOGENETICS LA English DT Article DE macrophage inflammatory protein-1 beta; immune activation gene; lymphocyte activation gene; ACT-2; LAG-1 ID MACROPHAGE INFLAMMATORY PROTEIN-1-BETA; ACTIVATION GENE; GRO GENES; CYTOKINE; EXPRESSION; CLONING; FAMILY; IDENTIFICATION; RESOLUTION; BINDING AB Human macrophage inflammatory protein-1 beta (MIP-1 beta) is an M-r 8,000 acidic protein that is upregulated upon stimulation in monocytes, T cells, and other lymphocytes. This protein belongs to the CC chemokine subfamily and directs the migration of specific subsets of leukocytes. The first molecular clone was isolated in 1988, and ever since there has been confusion regarding the exact number of genes encoding this and closely related proteins. PCR primers were designed from two genomic GenBank entries to conduct single-strand conformational polymorphism analysis, sequence analysis, and PCR-RFLP, and we conclude that previously isolated clones referred to as MIP-1 beta are derived from two genes, originally called ACT-2 and LAG-1. The two proteins share a common length and are identical at 89 of 92 amino acids. The first two amino acid differences, V12M and L20P, occur in the signal peptide, while the third, G70S, is in the mature protein, Within the transcribed region, the genes differ at 25 of 662 nucleotides. A survey of the NCBI expressed sequence tag database reveals that both genes are expressed in a variety of tissues, and five clones representing LAG-1 transcripts are alternatively spliced, with the 115-bp exon 2 omitted. Database searches for putative orthologues in other species revealed that the rabbit protein is about 80% similar to the two human proteins, while those of rat and mouse are 70-75% similar. Comparative sequence analysis of the human and animal proteins indicates substantially higher rates of protein evolution in the two rodents compared to human and rabbit. C1 NCI, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Lab Genomic Divers, Frederick, MD 21702 USA. RP Modi, WS (reprint author), NCI, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 26 TC 17 Z9 18 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD SEP PY 2001 VL 53 IS 7 BP 543 EP 549 DI 10.1007/s002510100366 PG 7 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 494KX UT WOS:000172282500002 PM 11685466 ER PT J AU Mehta, IK Wang, J Roland, J Margulies, DH Yokoyama, WM AF Mehta, IK Wang, J Roland, J Margulies, DH Yokoyama, WM TI Ly49A allelic variation and MHC class I specificity SO IMMUNOGENETICS LA English DT Article DE natural killer cell; cell surface molecule; allele; polymorphism; multigene family ID NATURAL-KILLER-CELLS; IL-2-ACTIVATED NK CELLS; RAT MONOCLONAL-ANTIBODIES; INHIBITORY RECEPTOR LY49A; LY-49 MULTIGENE FAMILY; GENE-COMPLEX; TYROSINE PHOSPHATASE; MEMBRANE-PROTEINS; NK1.1 ANTIGEN; EXPRESSION AB The Ly49 family of natural killer (NK) cell receptors is encoded by a polygenic genetic locus. Allelic forms have been described and their expression appears to be regulated. The best-characterized Ly49 molecule, the C57BL/6 form of Ly49A, is an NK cell inhibitory receptor that binds H2D(d). To determine whether differences between Ly49a alleles may have functional consequences, allelic variants of Ly49a were cloned from several inbred mouse strains. Stable transfectants expressing each Ly49a allelic variant were generated and tested for reactivity with a panel of monoclonal antibodies (mAbs A1, JR9.318, YE1/32, and YE1/48) that recognize the C57BL/6 form of Ly49A. Binding to H2Dd was also assessed using fluorescently labeled H2D(d) tetramers. Furthermore, cytotoxicity assays were performed using anti-Ly49A mAb-separated interleukin-2-activated NK cells. We show that despite binding to fluorescently labeled H2Dd tetramers, the Ly49A(+) NK cells from representative mouse strains displayed significantly different degrees of inhibition with H2D(d) targets. These results can be interpreted in the li-ht of recent structural data on the Ly49A-H2D(d) complex. Thus, the Ly49 family displays functionally significant allelic polymorphism which adds to the repertoire of NK cell receptors. C1 Washington Univ, Sch Med, Immunol Program & Rheumatol Div, Dept Med,Ctr Arthritis & Related Dis, St Louis, MO 63110 USA. Howard Hughes Med Inst, St Louis, MO 63110 USA. NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Dept Immunol, CNRS, URA 1961,Unite Immunochim Analytique, F-75724 Paris, France. RP Yokoyama, WM (reprint author), Washington Univ, Sch Med, Immunol Program & Rheumatol Div, Dept Med,Ctr Arthritis & Related Dis, Box 8045,660 S Euclid Ave, St Louis, MO 63110 USA. RI Margulies, David/H-7089-2013; OI Margulies, David/0000-0001-8530-7375 NR 58 TC 27 Z9 27 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD SEP PY 2001 VL 53 IS 7 BP 572 EP 583 DI 10.1007/s002510100355 PG 12 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 494KX UT WOS:000172282500006 PM 11685470 ER PT J AU Ding, LN Shevach, EM AF Ding, LN Shevach, EM TI Inhibition of the function of the Fc gamma RIIB by a monoclonal antibody to thymic shared antigen-1, a Ly-6 family antigen SO IMMUNOLOGY LA English DT Article ID T-CELL ACTIVATION; IL-2 PRODUCTION; NEGATIVE REGULATION; CD40 LIGAND; B-CELLS; RECEPTOR; IDENTIFICATION; LYMPHOCYTES; EXPRESSION; INDUCTION AB Thymic shared antigen-1 (TSA-1) is a member of the Ly-6 family of glycosyl-phosphatidylinositol (GPI)-linked proteins. While it has been proposed that TSA-1 may play a role in thymic development, a physiological ligand for this antigen has not been identified. Here we report that a monoclonal antibody (mAb) to TSA-1, generated by ininaunizing a hamster with CD40 ligand (CD40L) -activated B cells, interferes with the function of Fc gamma RIIB on splenic B cells and the B-cell lymphoma cell line, M12, by binding to TSA on the same cells. The interaction of anti-TSA with Fc gamma RIIB resulted in an inhibition of the ability of the Fc gamma RIIB to cross-link and/or aggregate soluble anti-CD3 or soluble anti-C beta T-cell receptor (TCR), leading to an inhibition of induction of expression of CD25 and CD69, interleukin (IL)-2 production and proliferation of naive T cells. Cross-blocking studies with mAbs strongly suggested that a physical association exists between TSA-1 and the Fc gamma RIIB on the surface of activated B cells and favour the view that a functional intermolecular association exists between these two distinct membrane antigens. C1 US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Ding, LN (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res,HFM 315, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 45 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD SEP PY 2001 VL 104 IS 1 BP 28 EP 36 DI 10.1046/j.1365-2567.2001.01275.x PG 9 WC Immunology SC Immunology GA 481CA UT WOS:000171501300005 PM 11576217 ER PT J AU Elmore, E Luc, TT Steele, VE Redpath, JL AF Elmore, E Luc, TT Steele, VE Redpath, JL TI Comparative tissue-specific toxicities of 20 cancer preventive agents using cultured cells from 8 different normal human epithelia SO IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH LA English DT Article ID DNA POLYMERASE-DELTA; AUXILIARY PROTEIN; NUCLEAR ANTIGEN; CYTOTOXICITY; PCNA AB Comparative toxicity was determined for twenty potential chemopreventive agents in the Human Epithelial Cell Cytotoxicity (HECC) Assay using epithelial cell cultures from eight different tissues including: skin, kidney, breast, bronchus, cervix, prostate, oral cavity, and liver. The endpoints assessed were inhibition of: growth at 3 and 5 days; mitochondrial function; and proliferating cell nuclear antigen or albumin expression. Difluoromethylornithine (DFMO), s-allyleysteine, dehydroepiandrosterone (DHEA) analogue 8543, l-selenomethionine, and vitamin E acetate were not toxic or only produced mild toxicity with all endpoints in all eight cell types. N-acetyl-l-cysteine, calcium chloride, DHEA, genistein, ibuprofen, indole-3-carbinol, 4-hydroxyphenylretinamide (4-HPR), oltipraz, piroxicam, phenylethyl isothiocyanate, 9-cis-retinoic acid, and p-xylylselenocyanate each showed at least a 10-fold decrease in their TC50 (toxic Concentration that inhibited growth by 50%) for at least one endpoint with one or more cell types. For some agents such as DHEA and piroxicam, the TC50S for growth inhibition were 10-fold lower after 5 days compared with 3 days. Unique tissue-specific toxicity was observed for each toxic agent suggesting that tissue-specific effects are the rule rather than the exception. The HECC Assay is effective in identifying tissue-specific toxicity for chemopreventive agents and may help to identify potential toxicity problems in phase I human clinical trials. C1 Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA. NCI, Chemoprevent Agent Dev Grp, DCP, NIH, Bethesda, MD 20892 USA. RP Elmore, E (reprint author), Univ Calif Irvine, Dept Radiat Oncol, B149, Irvine, CA 92697 USA. FU NCI NIH HHS [N01 CN 75118] NR 18 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 1097-9336 J9 IN VITRO MOL TOXICOL JI In Vitro Mol. Toxicol.-J. Basic Appl. Res. PD FAL PY 2001 VL 14 IS 3 BP 191 EP 207 PG 17 WC Toxicology SC Toxicology GA 513GQ UT WOS:000173369900006 PM 11846992 ER PT J AU McAleer, MF Tuan, RS AF McAleer, MF Tuan, RS TI Metallothionein protects against severe oxidative stress-induced apoptosis of human trophoblastic cells SO IN VITRO & MOLECULAR TOXICOLOGY-A JOURNAL OF BASIC AND APPLIED RESEARCH LA English DT Article ID HYDROGEN-PEROXIDE; EPITHELIAL-CELLS; FREE-RADICALS; CADMIUM; DIETHYLSTILBESTROL; METABOLISM; PLACENTA; GENE; LOCALIZATION; SENSITIVITY AB Oxidative stress induces cellular apoptosis. Many agents producing intracellular oxidative stress, including H2O2 and steroid hormones, have also been found to induce metallothionein (MT) expression. Recently, MT has been recognized as potentially having antioxidant activity. This action may be essential for survival of terminally differentiated cells subject to oxidative stress, such as syncytiotrophoblasts, placental cells producing pregnancy hormones and forming the maternal-fetal barrier. We previously demonstrated an inverse relationship between basal MT expression and apoptotic incidence in the trophoblastic cell line, JEG-3. Using JEG-3 cells transfected with MT in sense or antisense orientation, we have examined here the effect of altered basal MT levels on trophoblastic function and apoptosis following treatment with H2O2 or diethylstilbestrol (DES). Induction of MT mRNA was observed In control and transfected JEG-3 cells following exposure to severe oxidative stress. Changes in the localization of MT protein, however, were apparent after a low oxidative stress challenge. Exposure to H2O2 resulted in a dose-dependent decrease in human chorionic gonadotropin secretion in an JEG-3 cultures regardless of basal MT expression, whereas no change was detected following DES treatment. With respect to apoptosis, a significant protective effect was observed proportional to the basal MT level. These results suggest that although MT does not ameliorate oxidative stress-induced perturbation of some trophoblastic functions, its expression is critical for protection of these cells from severe oxidative stress-induced apoptosis. MT thus appears to act as an anti-apoptotic antioxidant in trophoblastic cells. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. RP McAleer, MF (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bldg 13,3W17,MSC 5755,13 South Dr, Bethesda, MD 20892 USA. NR 56 TC 18 Z9 20 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1097-9336 J9 IN VITRO MOL TOXICOL JI In Vitro Mol. Toxicol.-J. Basic Appl. Res. PD FAL PY 2001 VL 14 IS 3 BP 219 EP 231 PG 13 WC Toxicology SC Toxicology GA 513GQ UT WOS:000173369900008 ER PT J AU Carroll, JA El-Hage, N Miller, JC Babb, K Stevenson, B AF Carroll, JA El-Hage, N Miller, JC Babb, K Stevenson, B TI Borrelia burgdorferi RevA antigen is a surface-exposed outer membrane protein whose expression is regulated in response to environmental temperature and pH SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; MONOCLONAL-ANTIBODY; IN-VITRO; DIFFERENTIAL EXPRESSION; ERP PROTEINS; GENE FAMILY; STRAIN B31; TICK BITE; LIPOPROTEINS; OSPC AB Borrelia burgdorferi, the causative agent of Lyme disease, produces RevA protein during the early stages of mammalian infection. B. burgdorferi apparently uses temperature as a cue to its location, producing proteins required for infection of warm-blooded animals at temperatures corresponding to host body temperature, but does not produce such virulence factors at cooler, ambient temperatures. We have observed that B. burgdorferi regulates expression of RevA in response to temperature, with the protein being synthesized by bacteria cultivated at 34 degreesC but not by those grown at 23 degreesC. Tissues encountered by B. burgdorferi during its infectious cycle vary in their pH values, and the level of RevA expression was also found to be dependent upon pH of the culture medium. The cellular localization of RevA was also analyzed. Borrelial inner and outer membranes were purified by isopycnic centrifugation, and membrane fractions were conclusively identified by immunoblot analysis using antibodies raised against the integral inner membrane protein MotB and outer membrane-associated Erp lipoproteins. Immunoblot analyses indicated that RevA is located in the B. burgdorferi outer membrane. These analyses also demonstrated that an earlier report (H. A. Bledsoe et al., Infect. Immun. 176:7447-7455, 1994) had misidentified such B. burgdorferi membrane fractions. RevA was further demonstrated to be exposed to the external environment, where it could facilitate interactions with host tissues. C1 NIAID, Microscopy Branch, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Univ Kentucky, Coll Med, Dept Microbiol & Immunol, Lexington, KY 40536 USA. RP Stevenson, B (reprint author), NIAID, Microscopy Branch, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. FU NIAID NIH HHS [R01 AI044254, AI44254, R56 AI044254] NR 64 TC 41 Z9 41 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2001 VL 69 IS 9 BP 5286 EP 5293 DI 10.1128/IAI.69.9.5286-5293.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000010 PM 11500397 ER PT J AU Scharf, O Agranovich, I Lee, K Eller, NL Levy, L Inman, J Scott, DE Golding, B AF Scharf, O Agranovich, I Lee, K Eller, NL Levy, L Inman, J Scott, DE Golding, B TI Ontogeny of Th1 memory responses against a Brucella abortus conjugate SO INFECTION AND IMMUNITY LA English DT Article ID CYTOKINE GENE-EXPRESSION; STIMULATORY FACTOR-I; CD4+ T-CELLS; IFN-GAMMA; INTERFERON-GAMMA; IMMUNE-RESPONSES; IGE RESPONSES; TYPE-1; SELECTION; ANTIBODY AB Protective immune responses to intracellular pathogens such as Brucella abortus are characteristically Th1-like. Recently we demonstrated that heat-killed B. abortus (HKBa), a strong Th1 stimulus, conjugated to ovalbumin (HKBA-OVA), but not B. abortus alone, can alter the antigen-specific cytokine profile from Th2- to Th1-like. In this report we study the ability of a single injection of B. abortus to switch a Th2 to a Th1 response in immature mice. One-day- and 1-week-old mice were given a single injection of B. abortus in the absence or presence of OVA, and at maturity mice were challenged with an allergenic preparation, OVA with alum (OVA-A). B. abortus given without OVA did not diminish the subsequent Th2 response in either age group. In contrast, mice receiving a single injection of B. abortus-OVA at the age of 1 week, but not those injected at the age of 1 day, had reversal of the ratio of OVA-specific Th1 to Th2 cells and decreased immunoglobulin E levels after allergen challenge as adults. Within 6 h both 1-day- and 1-week-old mice expressed interleukin-12 p40 mRNA following either B. abortus or B. abortus-OVA administration. However, only the 1-week-old mice exhibited increased expression of gamma interferon (IFN-gamma) mRNA. The absence of the early IFN-gamma response in 1-day-old mice may explain their inability to generate a Th1 memory response. These results suggest that at early stages of immune development, responses to intracellular bacteria may be Th2- rather than Th1-like. Furthermore, they suggest that the first encounter with antigen evokes either a Th1- or a Th2-like response which becomes imprinted, so that subsequent memory responses conform to the original Th bias. This has implications for protection against infectious agents and development of allergic responses. C1 US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Golding, B (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Ctr Biol Evaluat & Res, Bldg 29,Rm 232,8800 Rockville Pike, Bethesda, MD 20892 USA. EM golding@cber.fda.gov NR 25 TC 5 Z9 5 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2001 VL 69 IS 9 BP 5417 EP 5422 DI 10.1128/IAI.69.9.5417-5422.2001 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000025 PM 11500412 ER PT J AU Rogers, WO Baird, JK Kumar, A Tine, JA Weiss, W Aguiar, JC Gowda, K Gwadz, R Kumar, S Gold, M Hoffman, SL AF Rogers, WO Baird, JK Kumar, A Tine, JA Weiss, W Aguiar, JC Gowda, K Gwadz, R Kumar, S Gold, M Hoffman, SL TI Multistage multiantigen heterologous prime boost vaccine for Plasmodium knowlesi malaria provides partial protection in rhesus macaques SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; CYTOTOXIC T-LYMPHOCYTES; DNA VACCINE; CIRCUMSPOROZOITE PROTEIN; AOTUS MONKEYS; PLASMID DNA; IMMUNIZATION; RECOMBINANT; ANTIGEN; IMMUNOGENICITY AB A nonhuman primate model for malaria vaccine development allowing reliable, stringent sporozoite challenge and evaluation of both cellular and antibody responses is needed. We therefore constructed a multicomponent, multistage DNA vaccine for the simian malaria species Plasmodium knowlesi including two preerythrocytic-stage antigens, the circumsporozoite protein (PkCSP) and sporozoite surface protein 2 (PkSSP2), and two blood stage antigens, apical merozoite antigen I (PkAMA1) and merozoite surface protein I (PkMSP1p42), as well as recombinant canarypox viruses encoding the four antigens (ALVAC-4). The DNA vaccine plasmids expressed the corresponding antigens in vitro and induced antiparasite antibodies in mice. Groups of four rhesus monkeys received three doses of a mixture of the four DNA vaccine plasmids and a plasmid encoding rhesus granulocyte-monocyte colony-stimulating factor, followed by boosting with a single dose of ALVAC-4. Three groups received the priming DNA doses by different routes, either by intramuscular needle injection, by intramuscular injection with a needleless injection device, the Biojector, or by a combination of intramuscular and intradermal routes by Biojector. Animals immunized by any route developed antibody responses against sporozoites and infected erythrocytes and against a recombinant PkCSP protein, as well as gamma interferon-secreting T-cell responses against peptides from PkCSP. Following challenge with 100 P. knowlesi sporozoites, 1 of 12 experimental monkeys was completely protected and the mean parasitemia in the remaining monkeys was significantly lower than that in 4 control monkeys. This model will be important in preclinical vaccine development. C1 USN, Malaria Program, Med Res Ctr, Silver Spring, MD 20910 USA. Virogenet Corp, Troy, NY 12180 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20889 USA. Armed Forces Radiobiol Res Inst, Bethesda, MD 20889 USA. RP Rogers, WO (reprint author), USN, Malaria Program, Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. NR 36 TC 58 Z9 60 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2001 VL 69 IS 9 BP 5565 EP 5572 DI 10.1128/IAI.69.9.5565-5572.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000043 PM 11500430 ER PT J AU Schwebach, JR Casadevall, A Schneerson, R Dai, ZD Wang, XJ Robbins, JB Glatman-Freedman, A AF Schwebach, JR Casadevall, A Schneerson, R Dai, ZD Wang, XJ Robbins, JB Glatman-Freedman, A TI Expression of a Mycobacterium tuberculosis arabinomannan antigen in vitro and in vivo SO INFECTION AND IMMUNITY LA English DT Article ID CRYPTOCOCCAL POLYSACCHARIDE; MONOCLONAL-ANTIBODIES; ORGAN DISTRIBUTION; SPOT ASSAY; LIPOARABINOMANNAN; IDENTIFICATION; MACROPHAGES; INFECTION; DETERGENT; VIRULENT AB The outermost layer of Mycobacterium tuberculosis contains two major polysaccharides, arabinomannan (AM) and glucan (GC). We studied the in vitro and in vivo expression of an M. tuberculosis AM antigen using monoclonal antibody (MAb) 9d8 (2a), an isotype-switched variant of the immunoglobulin G3 (IgG3) MAb 9d8. MAb 9d8 had been previously shown to bind M. tuberculosis AM and the M. tuberculosis surface. Our in vitro experiments showed that MAb 9d8(2a) hound strongly to whole-cell M. tuberculosis Erdman but not to the CDC 1551 strain grown in medium for an extended period. However, AM antigen was detected in the culture supernatant of both strains, and its concentration increased in a time-dependent manner. The detection of AM antigen from both strains was decreased in the presence of Tween 80. In mice infected with M. tuberculosis Erdman, AM antigen accumulated in organ homogenates concomitant to an increase in bacterial organ burden and an increase in IgG and IgM titer to AM. These results (i) indicate that the surface expression of AM during in vitro growth changes with culture age, is strain dependent, and is affected by the presence of Tween 80 in the culture media; (ii) show that AM is produced by bacteria growth in vivo; and (iii) demonstrate that the amount of in vivo-detected AM can be dependent on the number of bacteria in the infected organ. C1 Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Med, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Pediat, Childrens Hosp Montefiore, Bronx, NY 10461 USA. Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA. NICHHD, NIH, Bethesda, MD 20892 USA. NIH, Biotechnol Unit, Bethesda, MD 20892 USA. RP Glatman-Freedman, A (reprint author), 702 Golding Bldg,1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NCI NIH HHS [CA13330, P30 CA013330]; NHLBI NIH HHS [HL59842, R01 HL059842]; NIAID NIH HHS [AI33142, AI333774, N01-AI-75320, R01 AI033142, R01 AI033774, R37 AI033142]; PHS HHS [T32A107501, 1K08A101691] NR 35 TC 26 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2001 VL 69 IS 9 BP 5671 EP 5678 DI 10.1128/IAI.69.9.5671-5678.2001 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000056 PM 11500443 ER PT J AU Palmer, RJ Kazmerzak, K Hansen, MC Kolenbrander, PE AF Palmer, RJ Kazmerzak, K Hansen, MC Kolenbrander, PE TI Mutualism versus independence: Strategies of mixed-species oral biofilms in vitro using saliva as the sole nutrient source SO INFECTION AND IMMUNITY LA English DT Article ID ACTINOMYCES-VISCOSUS T14V; STREPTOCOCCUS-SANGUIS; SPATIAL-ORGANIZATION; TYPE-1 FIMBRIAE; BACTERIA; COAGGREGATION; COMMUNITY; GROWTH; PLAQUE; IDENTIFICATION AB During initial dental plaque formation, the ability of a species to grow when others cannot would be advantageous, and enhanced growth through interspecies and intergeneric cooperation could be critical. These characteristics were investigated in three coaggregating early colonizers of the tooth surface (Streptococcus gordonii DL1, Streptococcus oralis 34, and Actinomyces naeslundii T14V). Area coverage and cell cluster size measurements showed that attachment of A. naeslundii and of S. gordonii to glass flowcells was enhanced by a salivary conditioning film, whereas attachment of S. oralis was hindered. Growth experiments using saliva as the sole carbon and nitrogen source showed that A. naeslundii was unable to grow either in planktonic culture or as a biofilm, whereas S. gordonii grew under both conditions. S. oralis grew planktonically, but to a much lower maximum cell density than did S. gordonii; S. oralis did not grow reproducibly as a biofilm. Thus, only S. gordonii possessed all traits advantageous for growth as a solitary and independent resident of the tooth. Two-species biofilm experiments analyzed by laser confocal microscopy showed that neither S. oralis nor A. naeslundii grew when coaggregated pairwise with S. gordonii. However, both S. oralis and A. naeslundii showed luxuriant, interdigitated growth when paired together in coaggregated microcolonies. Thus, the S. oralis-A. naeslundii pair formed a mutualistic relationship, potentially contact dependent, that allows each to grow where neither could survive alone. S. gordonii, in contrast, neither was hindered by nor benefited from the presence of either of the other strains. The formation of mutually beneficial interactions within the developing biofilm may be essential for certain initial colonizers to be retained during early plaque development, whereas other initial colonizers may be unaffected by neighboring cells on the substratum. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Tech Univ Denmark, Bioctr, DTU, DK-2800 Lyngby, Denmark. RP Kolenbrander, PE (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. NR 39 TC 139 Z9 145 U1 2 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2001 VL 69 IS 9 BP 5794 EP 5804 DI 10.1128/IAI.69.9.5794-5804.2001 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000070 PM 11500457 ER PT J AU Semnani, RT Sabzevari, H Iyer, R Nutman, TB AF Semnani, RT Sabzevari, H Iyer, R Nutman, TB TI Filarial antigens impair the function of human dendritic cells during differentiation SO INFECTION AND IMMUNITY LA English DT Article ID CD4(+) T-CELLS; HUMAN LYMPHATIC FILARIASIS; LEVEL IL-12 PRODUCTION; GROWTH-FACTOR-BETA; CYTOKINE PRODUCTION; IFN-GAMMA; IN-VITRO; COSTIMULATORY MOLECULES; PRESENTING CELLS; HELMINTH ANTIGENS AB The antigen-specific T-cell unresponsiveness seen in lymphatic filariasis is mediated, in part, by diminished antigen-presenting cell function and is most specific for microfilariae (MF), the parasite stage found in large numbers in the peripheral circulation. We investigated the effect of MF antigen (MFAg) on dendritic cells (DC) in both their differentiation process from monocyte precursors and also after they have developed into DC. When MFAg was added to cultures of monocytes during their; differentiation process to immature DC, the production of interleukin 12 (IL-12) p40, p70 protein, and IL-10 was significantly (P < 0.03) inhibited in response to Staphylococcus aureus Cowan (SAC) and SAC-gamma interferon (IFN-) (60% to 80% inhibition). IL-10 was also inhibited (P = 0.04) in response to CD40 ligand-IFN-gamma. Moreover, MFAg inhibited the mRNA expression of IL-12 p40 and IL-10 as assessed by RNA protection assays. This effect was antigen specific, as another parasite antigen (soluble Toxoplasma gondii antigen) did not inhibit the production of these cytokines. This effect was also not a result of diminished cell viability nor of an alteration in surface expression of most costimulatory surface molecules, including major histocompatibility complex class I and class II. In contrast to exposure throughout the differentiation process, MFAg added to immature DC had no effect on DC cytokine expression. Although NIF-differentiated DC were capable of inducing an allogeneic mixed lymphocyte reaction, they did so to a significantly lesser degree than DC without antigen exposure. These data collectively suggest that once DC are differentiated from their precursor cells, they become resistant to changes by MFAg. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Tumor Immunol, NIH, Bethesda, MD 20892 USA. RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-126, Bethesda, MD 20892 USA. NR 58 TC 44 Z9 47 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2001 VL 69 IS 9 BP 5813 EP 5822 DI 10.1128/IAI.69.9.5813-5822.2001 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000072 PM 11500459 ER PT J AU Carabeo, RA Hackstadt, T AF Carabeo, RA Hackstadt, T TI Isolation and characterization of a mutant Chinese hamster ovary cell line that is resistant to Chlamydia trachomatis infection at a novel step in the attachment process SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; EUKARYOTIC CELLS; EPITHELIAL-CELLS; HELA-CELLS; HOST-CELLS; INCLUSION; PSITTACI; PURIFICATION; MECHANISM; ORGANISMS AB Host factors involved in Chlamydia trachomatis pathogenesis were investigated by random chemical mu. tagenesis of Chinese hamster ovary (CHO-KI) cells followed by selection for clones resistant to chlamydial infection. A clonal mutant cell line, D4.1-3, refractory to infection by the C. trachomatis L2 serovar was isolated. The D4.1-3 cell line appears to be lacking in a previously undescribed temperature-dependent and heparin-resistant binding step that occurs subsequent to engagement of cell surface heparan sulfate by L2 elementary bodies. This novel binding step differentiates the lymphogranuloma venereum (LGV) serovar from other serovars and may contribute the different pathologies associated with LGV and non-LGV strains. C1 NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Intracellular Parasites Lab, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. NR 30 TC 40 Z9 40 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD SEP PY 2001 VL 69 IS 9 BP 5899 EP 5904 DI 10.1128/IAI.69.9.5899-5904.2001 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 464PB UT WOS:000170540000082 PM 11500469 ER PT J AU Greim, H Borm, P Schins, R Donaldson, K Driscoll, K Hartwig, A Kuempel, E Oberdorster, G Speit, G AF Greim, H Borm, P Schins, R Donaldson, K Driscoll, K Hartwig, A Kuempel, E Oberdorster, G Speit, G TI Toxicity of fibers and particles - Report of the Workshop Held in Munich, Germany, 26-27 October 2000 SO INHALATION TOXICOLOGY LA English DT Article ID ALVEOLAR EPITHELIAL-CELLS; POORLY SOLUBLE PARTICLES; CARCINOGENIC CHEMICALS; TISSUE RESPONSES; CLASSIFICATION; RETENTION; EXPOSURE; CLEARANCE; DUST; AREA C1 Tech Univ Munich, Inst Toxikol & Umwelthyg, D-85354 Freising Weihenstephan, Germany. Univ Dusseldorf, Med Inst Umwelthyg, Abt Faser & Partikel Toxikol, Dusseldorf, Germany. Napier Univ, Biomed Res Grp, Edinburgh EH14 1DJ, Midlothian, Scotland. Procter & Gamble Co, Human Safety Dept, Cincinnati, OH USA. Univ Karlsruhe, Inst Lebensmittelchem & Toxikol, Karlsruhe, Germany. NIOSH, Risk Evaluat Branch, Cincinnati, OH 45226 USA. Univ Rochester, Dept Environm Med, NIEHS, Environm Hlth Sci Ctr, Rochester, NY USA. RP Greim, H (reprint author), Tech Univ Munich, Inst Toxikol & Umwelthyg, Hohenbachernstr 15-17, D-85354 Freising Weihenstephan, Germany. NR 42 TC 51 Z9 55 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD SEP PY 2001 VL 13 IS 9 BP 737 EP 754 DI 10.1080/089583701316941285 PG 18 WC Toxicology SC Toxicology GA 469JP UT WOS:000170811000001 PM 11498804 ER PT J AU Davison, KK Susman, EJ AF Davison, KK Susman, EJ TI Are hormone levels and cognitive ability related during early adolescence? SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID CREATIVE MUSICAL BEHAVIOR; SPATIAL ABILITY; SEX-DIFFERENCES; CEREBRAL LATERALIZATION; DIETHYLSTILBESTROL DES; TESTOSTERONE LEVELS; PRENATAL EXPOSURE; STEROID-HORMONES; META-ANALYSIS; PERFORMANCE AB The present study assessed the longstanding question of whether there is a relationship between sex hormones and cognitive ability in young adolescent girls and boys. Three "theories" of the relationship between hormone levels and cognition were identified from a broad literature base and were used to formulate hypotheses regarding the relationship between sex hormones and cognitive ability in early adolescents. Fifty-six boys, aged 10-14, and 52 girls, aged 9-14, completed two standardised spatial ability tests and one standardised test of verbal ability. Three blood samples, at 20-minute intervals, were obtained to determine levels of estradiol and testosterone, Data were collected on three occasions for all measures at 6-month intervals. A positive linear relationship between testosterone and spatial ability was identified for boys at each time of measurement for both measures of spatial ability (i.e., mental rotation and block design). For girls, a positive linear relationship was identified between testosterone and mental rotation only at time 3. In addition, longitudinal relationships were identified between change in testosterone levels and change in spatial ability for both girls and boys. The conclusion was that testosterone is related to cognitive functioning during pubertal development for boys and to a lesser extent for girls. C1 Penn State Univ, Dept Human Dev & Family Studies, University Pk, PA 16801 USA. NIMH, Bethesda, MD 20892 USA. NICHHD, Bethesda, MD 20892 USA. RP Davison, KK (reprint author), Penn State Univ, Dept Human Dev & Family Studies, S-110 Henderson Bldg, University Pk, PA 16801 USA. NR 59 TC 13 Z9 16 U1 2 U2 9 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD SEP PY 2001 VL 25 IS 5 BP 416 EP 428 PG 13 WC Psychology, Developmental SC Psychology GA 471CD UT WOS:000170908500002 ER PT J AU Tractenberg, RE Gamst, A Weiner, MF Koss, E Thomas, RG Teri, L Thal, L AF Tractenberg, RE Gamst, A Weiner, MF Koss, E Thomas, RG Teri, L Thal, L TI Frequency of behavioral symptoms characterizes agitation in Alzheimer's disease SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Alzheimer's disease; assessment; agitation; behavioral disturbance ID NURSING-HOME PLACEMENT; DEMENTIA; TRIAL; PLACEBO; HALOPERIDOL; PSYCHOSIS; SCALE AB This study describes two well-characterized groups of Alzheimer's disease (AD) patients with similar levels of cognitive functioning, but with different overall behavioral disturbance levels. We sought to determine the nature of this difference whether AD patients with higher levels of behavioral disturbance (n=148) differ from less disturbed AD patients (n=235) in terms of (a) the range of symptoms exhibited, (b) the frequency of occurrence of these symptoms, or (c) both of these. We defined and operationalized 'diversity of behaviors' and 'frequency' with respect to the item-level responses on the Cohen-Mansfield agitation inventory (CMAI). We found that, in these two samples of AD patients, differences occurred in the frequency of 10 out of 21 behaviors, rather than in a variety of endorsed behaviors. These 10 behaviors, observed at different frequencies in both groups, may be useful for monitoring change in studies of drugs or behavioral interventions for behavioral disturbance in persons with AD. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Univ Calif San Diego, Alzheimers Dis Cooperat Study, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Houston, TX USA. Univ Texas, SW Med Ctr, Dept Neurol, Houston, TX USA. NIA, Washington, DC USA. Univ Washington, Dept Psychosocial & Community Hlth, Washington, DC USA. RP Tractenberg, RE (reprint author), Univ Calif San Diego, Alzheimers Dis Cooperat Study, Mail Code 0949,9500 Gilman Dr, La Jolla, CA 92093 USA. OI Weiner, Myron/0000-0001-5682-4410 FU NIA NIH HHS [U01 AG010483, P50 AG005131, AG 10483] NR 22 TC 6 Z9 6 U1 2 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0885-6230 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD SEP PY 2001 VL 16 IS 9 BP 886 EP 891 DI 10.1002/gps.441 PG 6 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 476NF UT WOS:000171233000009 PM 11571769 ER PT J AU Schneider, GP Salcedo, R Welniak, LA Howard, OMZ Murphy, WJ AF Schneider, GP Salcedo, R Welniak, LA Howard, OMZ Murphy, WJ TI The diverse role of chemokines in tumor progression: Prospects for intervention (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Review DE anti-tumor; chemokine; monoclonal antibodies; angiogenesis ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HUMAN ENDOTHELIAL-CELLS; PLATELET FACTOR-IV; INTERFERON-INDUCIBLE PROTEIN-10; HUMAN-MALIGNANT MELANOMA; FIBROBLAST-GROWTH-FACTOR; PANCREATIC-CANCER CELLS; HUMAN COLON-CARCINOMA; ANGIOGENESIS IN-VIVO; HUMAN OVARIAN-CANCER AB Chemokines, proteins chemotactic for leukocytes and non-leukocytes, have been intensively studied for their role in tumor growth and metastasis. Recent work has shown that particular chemokines may have multiple effects on tumors including promoting growth, angiogenesis, metastasis, and suppression of the immune response to cancer, while other chemokines inhibit tumor mediated angiogenesis and promote anti-tumor immune responses. Increasing biological evidence supports the hypothesis that tumor-generated chemokines provide more than simply angiogenic signals. Tumor-derived chemokines may potentially act as inhibitors of anti-tumor immune responses as well as autocrine growth factors for the tumor. The complexity and redundancy of tumor chemokine expression suggests that a single chemokine target for tumor therapy may not be appropriate. Indeed, multiple target therapy including blockade of tumor enhancing chemokines while delivering or inducing the secretion of anti-tumor chemokines is the approach that currently holds the most promise. The role of chemokines in tumor biology as well as various means of blocking chemokines in cancer models in order to develop successful therapeutic strategies will be discussed. C1 NCI, SAIC Frederick, Mol Immunoregulat Lab, Frederick, MD 21702 USA. SAIC Frederick, IRSP, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), NCI, SAIC Frederick, Mol Immunoregulat Lab, Bldg 567 Rm 210, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-56000] NR 122 TC 7 Z9 9 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD SEP PY 2001 VL 8 IS 3 BP 235 EP 244 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 464HG UT WOS:000170526700001 PM 11494048 ER PT J AU Klabunde, CN Sancho-Garnier, H Broeders, M Thoresen, S Rodrigues, VJL Ballard-Barbash, R AF Klabunde, CN Sancho-Garnier, H Broeders, M Thoresen, S Rodrigues, VJL Ballard-Barbash, R TI Quality assurance for screening mammography data collection systems in 22 countries SO INTERNATIONAL JOURNAL OF TECHNOLOGY ASSESSMENT IN HEALTH CARE LA English DT Article DE mass screening; mammography; breast cancer; quality assurance; data collection ID BREAST-CANCER; PROGRAMS AB Objectives: To document the mammography data that are gathered by the organized screening programs participating in the International Breast Cancer Screening Network (IBSN), the nature of their procedures for data quality assurance, and the measures used to assess program performance and impact. Methods: A detailed questionnaire covering multiple aspects of quality assurance in screening mammography was mailed to IBSN representatives in 23 countries. Results: Countries collect a wealth of screening mammography data, much of it computerized. Most countries have designated staff for data quality assurance. All provide staff training, and most have documentation requirements for data collection. Nearly all have one or more procedures to maintain data confidentiality. Countries are heterogeneous in collecting and assessing data to monitor screening program performance and impact. Conclusions: Demonstrating that population-based screening mammography reduces breast cancer mortality requires collection of high-quality data on key aspects of the multi-step screening process. Assuring the quality of data collection systems for screening mammography programs is an important and evolving area for IBSN countries. C1 NCI, DCCPS, ARP, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. Epidaure CRLC, F-34298 Montpellier 5, France. Univ Nijmegen, Med Ctr, Dept Biostat & Epidemiol, NL-6500 HB Nijmegen, Netherlands. Canc Registry Norway, N-0310 Oslo, Norway. Portuguese League Canc, P-3000 Coimbra, Portugal. RP Klabunde, CN (reprint author), NCI, DCCPS, ARP, Hlth Serv & Econ Branch, EPN Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Broeders, Mireille/C-8820-2015 NR 23 TC 9 Z9 9 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0266-4623 J9 INT J TECHNOL ASSESS JI Int. J. Technol. Assess. Health Care PD FAL PY 2001 VL 17 IS 4 BP 528 EP 541 PG 14 WC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Medical Informatics GA 495FL UT WOS:000172329500008 PM 11758297 ER PT J AU Mashima, Y Suzuki, Y Sergeev, Y Ohtake, Y Tanino, T Kimura, I Miyata, H Aihara, M Tanihara, H Inatani, M Azuma, N Iwata, T Araie, A AF Mashima, Y Suzuki, Y Sergeev, Y Ohtake, Y Tanino, T Kimura, I Miyata, H Aihara, M Tanihara, H Inatani, M Azuma, N Iwata, T Araie, A TI Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID LOCUS; BUPHTHALMOS; 2P21; IDENTIFICATION; SEQUENCE; SUGGEST; REGION; GLC3A AB PURPOSE. To investigate CYP1B1 gene mutations in Japanese patients with primary congenital glaucoma (PCG). METHODS. Sixty-five unrelated Japanese patients with PCG were screened by PCR-single-strand conformational polymorphism (SSCP) analysis followed by direct sequencing. No patients were offspring of consanguineous marriages, a common occurrence among patients in previous reports. PCG haplotypes were constructed with intragenic polymorphisms in affected individuals. Three-dimensional atomic structures of human CYP1B1 and four mutant CYP1B1 sequences representing missense mutations were assembled using homology modeling and were regularized by an energy-minimization procedure. RESULTS.. Eleven novel mutations, including seven definite and four probable mutations, were detected in 13 (20%) of the 65 unrelated patients. Of the seven definite mutations, three were predicted to truncate the CYP1B1 open reading frame. The other four were missense mutations (Asp192Val, Ala330Phe, Val364Met, and Arg444Gln), all located in conserved core structures determining proper folding and heme-binding ability of cytochrome P450 molecules. Molecular modeling demonstrated that two of four mutations in positions 330 and 364 were structurally neutral, but Arg444Gln caused significant structural change. Of the four probable mutations, three were missense (Val198Ile, Val320Leu, and Glu499Gly); the other was a base substitution in the noncoding region of exon 1. CONCLUSIONS. The 11 varied CYP1B1 mutations found in 13 unrelated Japanese patients with sporadic occurrence of PCG represent an allelic heterogeneity and may be unique to a specific population. C1 Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, Tokyo 1608582, Japan. Univ Tokyo, Grad Sch Med, Dept Ophthalmol, Tokyo, Japan. NEI, NIH, Ophthalm Genet & Visual Sch Med, Bethesda, MD 20892 USA. Tenri Yorozu Hosp, Dept Ophthalmol, Nara, Japan. Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto, Japan. Natl Childrens Hosp, Dept Ophthalmol, Tokyo 154, Japan. Natl Tokyo Med Ctr, Natl Inst Sensory Organs, Tokyo, Japan. RP Mashima, Y (reprint author), Keio Univ, Sch Med, Dept Ophthalmol, Shinjuku Ku, 35 Shinanomachi, Tokyo 1608582, Japan. NR 29 TC 67 Z9 75 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2001 VL 42 IS 10 BP 2211 EP 2216 PG 6 WC Ophthalmology SC Ophthalmology GA 469FL UT WOS:000170803900010 PM 11527932 ER PT J AU Chin, MS Nagineni, CN Hooper, LC Detrick, B Hooks, JJ AF Chin, MS Nagineni, CN Hooper, LC Detrick, B Hooks, JJ TI Cyclooxygenase-2 gene expression and regulation in human retinal pigment epithelial cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SMOOTH-MUSCLE CELLS; NF-KAPPA-B; PROSTAGLANDIN ENDOPEROXIDE SYNTHASE-2; ACTIVATED PROTEIN-KINASE; IMMUNOCYTOCHEMICAL LOCALIZATION; TRANSCRIPTIONAL REGULATION; SIGNAL-TRANSDUCTION; GAMMA-INTERFERON; COX-2 EXPRESSION; BINDING PROTEINS AB PURPOSE. Cyclooxygenases (COX) orchestrate a variety of homeostatic processes and participate in various pathophysiological conditions. The retinal pigment epithelium (RPE) cell performs a variety of regulatory functions within the retina. The conditions under which COX-1 and COX-2 are expressed and upregulated in human RPE (HRPE) cells were determined. METHODS COX gene expression was examined using RT-PCR analysis of untreated HRPE cultures or cultures exposed to bacterial lipopolysaccharide or various cytokines. COX proteins were detected by immunohistochemistry and Western blot analysis. Prostaglandin (PG) production was analyzed by EIA, RESULTS. Examination of untreated RPE cells revealed the presence of COX-2 mRNA and the absence of COX-1 mRNA. Moreover, cytokine stimulation more readily enhanced COX-2 gene expression than COX-1 gene expression. IL-1 beta, the most potent inducer, of COX-2, also resulted in detection of COX-2 protein by immunocytochemical staining and Western blot analysis. There was a direct relationship between both the appearance and amount of COX-2 mRNA and protein synthesis and the degree of PG synthesis by RPE cells. Furthermore, COX inhibitors significantly decreased PG production. Pretreatment of RPE cells with a NF-kappaB inhibitor, PDTC, resulted in dose-dependent decrease in IL-1 beta -induced COX-2 gene expression and PG production. CONCLUSIONS. COX-2 was the predominant isoform of cyclooxygenase in untreated HRPE cells. When HRPE cells were treated with proinflammatory cytokines, COX-2 gene expression and synthesis of PGs were enhanced. NF-kappaB mediated the induction of COX-2 gene expression in HRPE cells. These studies indicate that RPE cells may participate in normal and pathologic retinal conditions through the induction of COX-2. C1 NEI, NIH, Lab Immunol, Virol & Immunol Sect, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. RP NEI, NIH, Lab Immunol, Virol & Immunol Sect, Bldg 10,10 Ctr Dr,Rm 6N228, Bethesda, MD 20892 USA. EM jjhooks@helix.nih.gov NR 74 TC 46 Z9 49 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD SEP PY 2001 VL 42 IS 10 BP 2338 EP 2346 PG 9 WC Ophthalmology SC Ophthalmology GA 469FL UT WOS:000170803900026 PM 11527948 ER PT J AU Matsumoto, Y Takano, H Nagao, S Fojo, T AF Matsumoto, Y Takano, H Nagao, S Fojo, T TI Altered topoisomerase II alpha and multidrug resistance-associated protein levels during drug selection: Adaptations to increasing drug pressure SO JAPANESE JOURNAL OF CANCER RESEARCH LA English DT Article DE topoisomerase; MRP; drug resistance; etoposide; mAMSA ID DNA TOPOISOMERASES; CELL-LINE; ETOPOSIDE; CANCER; PROLIFERATION; GENE AB To understand resistance to topoisomerase II inhibitors, we used four cancer cell lines (ZR-75B, MDA-MB-231, T47D, and MCF-7) and performed a single-step selection process to isolate 50 clones resistant to topoisomerase II inhibitors. Of these, 26 were isolated with VP-16 and 24 with mAMSA. Sixteen of these isolates (four from each cell line; two selected with VP-16 and two with mAMSA) were further exposed to higher drug concentrations. Characterization of the resistant sublines revealed the adaptation that occurs with increasing drug concentration during in-vitro selections. Reduced topoisomerase II alpha mRNA level was observed in the majority of the initial isolates. This reduction was accompanied by a decrease in topoisomerase II activity. Other isolates showed increased levels of multidrug resistance-associated protein (MRP). With advancing resistance, MRP expression was increased further, concomitantly with some recovery in topoisomerase II alpha expression and topoisomerase II activity. In these sublines, high levels of resistance were attained as a result of synergism between the reduced topoisomerase II alpha levels and MRP overexpression. These results extend previous studies demonstrating how cellular adaptation to increasing drug pressure utilizes more than one mechanism. Reduced expression of topoisomerase II alpha occurs early in the selection process. MRP overexpression can occur early or can help to confer high levels of resistance. In the latter case, MRP overexpression allows some recovery of topoisomerase II activity without loss of high drug resistance. C1 Kagawa Med Univ, Dept Neurol Surg, Miki, Kagawa 7610793, Japan. NCI, Med Branch, DCS, NIH, Bethesda, MD 20892 USA. RP Matsumoto, Y (reprint author), Kagawa Med Univ, Dept Neurol Surg, 1750-1 Ikenobe, Miki, Kagawa 7610793, Japan. NR 19 TC 6 Z9 6 U1 0 U2 0 PU BUSINESS CENTER ACADEMIC SOCIETIES JAPAN PI TOKYO PA 5-16-9 HONKOMAGOME, BUNKYO-KU, TOKYO, 113-8633, JAPAN SN 0910-5050 J9 JPN J CANCER RES JI Jpn. J. Cancer Res. PD SEP PY 2001 VL 92 IS 9 BP 968 EP 974 PG 7 WC Oncology SC Oncology GA 474LH UT WOS:000171108100009 PM 11572765 ER PT J AU Rogers, AS AF Rogers, AS TI HIV research in American youth SO JOURNAL OF ADOLESCENT HEALTH LA English DT Editorial Material ID AIDS; AGE C1 NICHHD, PAMAB, CRMC, Pediat Adolescent & Maternal AIDS Branch,NIH, Bethesda, MD 20892 USA. RP Rogers, AS (reprint author), NICHHD, PAMAB, CRMC, Pediat Adolescent & Maternal AIDS Branch,NIH, 6100 Execut Blvd,Rm 4B11,MSC 7510, Bethesda, MD 20892 USA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2001 VL 29 IS 3 SU S BP 1 EP 4 PG 4 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 467EA UT WOS:000170687300001 PM 11530298 ER PT J AU Futterman, DC Peralta, L Rudy, BJ Wolfson, S Guttmacher, S Rogers, AS AF Futterman, DC Peralta, L Rudy, BJ Wolfson, S Guttmacher, S Rogers, AS CA Adolescent Med HIV AIDS Res Networ TI The ACCESS (Adolescents Connected to Care, Evaluation, and Special Services) Project: Social marketing to promote HIV testing to adolescents, methods and first year results from a six city campaign SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescents; HIV social marketing; HIV counseling and testing ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED-DISEASES; PUBLIC-HEALTH; ACTIVE ADOLESCENTS; UNITED-STATES; PREVENTION; INFECTION; RISK; INTERVENTION; PHYSICIANS C1 Childrens Hosp Montefiore, Albert Einstein Coll Med, Dept Pediat, New York, NY USA. Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. Univ Penn, Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Dept Pediat, Philadelphia, PA 19104 USA. Sensei Masterful Hlth Commun, New York, NY USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. RP Futterman, DC (reprint author), Albert Einstein Coll Med, Dept Pediat, New York, NY USA. FU NICHD NIH HHS [UO1HD32833]; PHS HHS [6H76HA00045-081] NR 46 TC 21 Z9 21 U1 3 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2001 VL 29 IS 3 SU S BP 19 EP 29 DI 10.1016/S1054-139X(01)00290-7 PG 11 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 467EA UT WOS:000170687300003 PM 11530300 ER PT J AU Rogers, AS Miller, S Murphy, DA Tanney, M Fortune, T AF Rogers, AS Miller, S Murphy, DA Tanney, M Fortune, T TI The TREAT (Therapeutic Regimens Enhancing Adherence in Teens) Program: Theory and preliminary results SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescents; adherence; HIV therapy; stages of change model ID HIGH-RISK; ADOLESCENTS; VALIDATION; SMOKERS; MODEL C1 NICHHD, PAMAB, CRMC, Pediat Adolescent & Maternal AIDS Branch,NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Pediat, Baltimore, MD 21201 USA. Univ Calif Los Angeles, Dept Psychiat, Hlth Risk Reduct Projects, Los Angeles, CA 90025 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Motivat Educ Entertainment Inc, Philadelphia, PA USA. RP Rogers, AS (reprint author), NICHHD, PAMAB, CRMC, Pediat Adolescent & Maternal AIDS Branch,NIH, 6100 Execut Blvd,Rm 4B11,MSC 7510, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01-HD-3-3162] NR 21 TC 23 Z9 23 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2001 VL 29 IS 3 SU S BP 30 EP 38 DI 10.1016/S1054-139X(01)00289-0 PG 9 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 467EA UT WOS:000170687300004 PM 11530301 ER PT J AU Vermund, SH Wilson, CM Rogers, AS Partlow, C Moscicki, AB AF Vermund, SH Wilson, CM Rogers, AS Partlow, C Moscicki, AB TI Sexually transmitted infections among HIV infected and HIV uninfected high-risk youth in the REACH study SO JOURNAL OF ADOLESCENT HEALTH LA English DT Review DE HIV; acquired immunodeficiency syndrome (AIDS); adolescence; sexually transmitted diseases; syphilis; chlamydia; gonorrhea; trichomoniasis; papillomavirus ID HUMAN-IMMUNODEFICIENCY-VIRUS; CHLAMYDIA-TRACHOMATIS INFECTIONS; URBAN ADOLESCENT FEMALES; GENITAL-TRACT INFECTIONS; HUMAN-PAPILLOMAVIRUS; WOMEN; DISEASES; PREVENTION; TRANSMISSION; PREVALENCE AB Overview: This review presents the findings of published research in the Reaching for Excellence in Adolescent Care and Health (REACH) Project on sexually transmitted infections (STIs) within the context of the project's scientific agenda. Methods employed in the study for specimen collection, management, and laboratory analysis are presented. This review presents published analyses of cross-sectional data; longitudinal analyses are underway. In addition, baseline prevalence data on selected STIs and sexual risk profiles of the subjects in REACH are presented. High STI rates were evident in both human immunodeficiency virus (HIV) infected and uninfected youth of both genders regardless of sexual orientation. High infection rates at baseline suggest that prevention-oriented programs for risk reduction among adolescents should focus on both HIV infected and at-risk, uninfected youth. (C) Society for Adolescent Medicine, 2001. C1 Univ Alabama, Birmingham, AL 35294 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Vermund, SH (reprint author), Univ Alabama, BBRB 206,1530 3rd Ave S, Birmingham, AL 35294 USA. OI Vermund, Sten/0000-0001-7289-8698 NR 59 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2001 VL 29 IS 3 SU S BP 49 EP 56 DI 10.1016/S1054-139X(01)00296-8 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 467EA UT WOS:000170687300006 PM 11530303 ER PT J AU Belzer, M Rogers, AS Camarca, M Fuchs, D Peralta, L Tucker, D Durako, SJ AF Belzer, M Rogers, AS Camarca, M Fuchs, D Peralta, L Tucker, D Durako, SJ CA Adolescent Med HIV AIDS Res Networ TI Contraceptive choices in HIV infected and HIV at-risk adolescent females SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE acquired immunodeficiency syndrome (AIDS); HIV infected adolescents; adolescents; contraception; adherence ID ORAL-CONTRACEPTIVES; PREGNANCY; CONDOMS; WOMEN AB Purpose: To describe reported contraception use in HIV infected and HIV uninfected but at-risk female adolescents, and determine associations with the reported consistent use of effective contraception methods, including its association with pregnancy. Methods: HIV infected and at-risk female youth, aged 13-18 years, who were sexually active and reporting no intention to become pregnant, were included. Contraception use data from three consecutive visits (approximately 6 months apart) were used. Results: Ninety-four percent of HIV infected and 89% of at-risk subjects reported choosing a main contraception method with demonstrated efficacy when used consistently. Approximately 50% chose partner condoms. HIV infected youth were more likely to report 100% a partner condom use in the past 3 months (73% vs. 46%; OR 3.3; 95% CI: 1.7-5.6). At-risk youth were 2.5 times more likely than HIV infected subjects to report using nothing (95% CI: 1.1-5.8). Slightly more than half (56%) demonstrated the consistent reporting of effective methods (CREM) of contraception. In multivariate analysis, HIV infection (OR 4.0; 95% CI: 2.2-8.2) and AfricanAmerican race (OR 2.7; 95% CI: 1.1-6.6) were significantly associated with CREM. Subjects reporting inconsistent or unreliable contraception use had higher 1-year pregnancy rates than CREM subjects (32% vs. 14%; p =.002): Conclusions: Only half of HIV infected and at-risk youth reported using effective contraception consistently, despite its availability. Additionally, regardless of reported contraceptive use, the rates of unplanned pregnancy were unacceptably high. Society for Adolescent Medicine, 2001. C1 Univ So Calif, Childrens Hosp Los Angeles, Div Adolescent Med, Los Angeles, CA 90054 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. Univ Maryland, Baltimore, MD 21201 USA. RP Belzer, M (reprint author), Univ So Calif, Childrens Hosp Los Angeles, Div Adolescent Med, POB 54700,Mail Stop 2, Los Angeles, CA 90054 USA. NR 26 TC 22 Z9 22 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2001 VL 29 IS 3 SU S BP 93 EP 100 DI 10.1016/S1054-139X(01)00282-8 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 467EA UT WOS:000170687300012 PM 11530309 ER PT J AU Levin, L Henry-Reid, L Murphy, DA Peralta, L Sarr, M Ma, Y Rogers, AS AF Levin, L Henry-Reid, L Murphy, DA Peralta, L Sarr, M Ma, Y Rogers, AS CA Adolescent Med HIV AIDS Res Networ TI Incident pregnancy rates in HIV infected and HIV uninfected at-risk adolescents SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE adolescence; HIV; pregnancy ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; WOMEN; CHILDBEARING; PREVALENCE; KNOWLEDGE; TRENDS; ABUSE AB Purpose: To compare pregnancy incidence between HIV infected and HIV uninfected adolescents over a 3-year period and to characterize factors that differentiate pregnant from nonpregnant HIV infected females. Methods: Female adolescents enrolled in Reaching for Excellence in Adolescent Care and Health (REACH), a national cohort study, and nonpregnant at baseline comprised the sample (it = 345). Subject information on pregnancy, risk behavior, and psychosocial characteristics was obtained through interview, chart review, physical examination and laboratory data collected every 3 months. Incident pregnancy rate was analyzed using Cox proportional hazards modeling; the predictors of incident pregnancy were evaluated using repeated measures analysis. Results: Ninety-four pregnancies were identified over 3 years. No significant difference in pregnancy incidence was detected between HIV infected and uninfected females (20.6 and 28.4 per 100 person-years, respectively, p =.16). However, for adolescents with living children at entry, HIV infected females were significantly less likely to become pregnant than HIV uninfected (HR =.45; p =.03). Among HIV infected adolescents, significant predictors of incident pregnancy were older age (p =.01) and not using hormonal contraception (p =.00), whereas increased spiritual hope and passive problem-solving capacity were protective against pregnancy (p =.02, and .05, respectively). Multivariate analysis revealed pregnancy prior to study entry to be predictive for (OR = 3.0; 95% CI: 1.2-7.7), and increased spiritual hope to be protective (OR = .4; 95% CI:.2-.9) against incident pregnancy in HIV infected females without the hormonal contraceptive variable in the model. Conclusions: The pregnancy rate is high in this study population. Further research is needed into its determinants and attenuating factors, particularly the role of spiritual elements, to design better contraceptive services and reproduction-related education targeting high-risk youth. Society for Adolescent Medicine, 2001. C1 Mt Sinai Hosp, New York, NY 10029 USA. Cook Childrens Cty Hosp, Chicago, IL USA. Univ Calif Los Angeles, Dept Psychiat, Hlth Risk Reduct Projects, Los Angeles, CA 90024 USA. Univ Maryland, Baltimore, MD 21201 USA. Westat Corp, Rockville, MD USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Rockville, MD USA. RP Levin, L (reprint author), Mt Sinai Adolescent Hlth Ctr, 320 E 94th St, New York, NY 10128 USA. NR 36 TC 17 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD SEP PY 2001 VL 29 IS 3 SU S BP 101 EP 108 DI 10.1016/S1054-139X(01)00281-6 PG 8 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 467EA UT WOS:000170687300013 PM 11530310 ER PT J AU Lane, MA AF Lane, MA TI Retardation of aging by calorie restriction SO JOURNAL OF ANTI-AGING MEDICINE LA English DT Editorial Material C1 NIA, Nutrit & Mol Physiol Unit, Neurosci Lab, NIH, Baltimore, MD 21224 USA. RP Lane, MA (reprint author), NIA, Nutrit & Mol Physiol Unit, Neurosci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1094-5458 J9 J ANTI-AGING MED JI J. Anti-Aging Med. PD FAL PY 2001 VL 4 IS 3 BP 185 EP 185 DI 10.1089/109454501753249939 PG 1 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 495QM UT WOS:000172351900002 ER PT J AU Mattson, MP Duan, WZ Lee, J Guo, ZH Roth, GS Ingram, DK Lane, MA AF Mattson, MP Duan, WZ Lee, J Guo, ZH Roth, GS Ingram, DK Lane, MA TI Progress in the development of caloric restriction mimetic dietary supplements SO JOURNAL OF ANTI-AGING MEDICINE LA English DT Article ID PROTECTS HIPPOCAMPAL-NEURONS; CORTICAL SYNAPTIC TERMINALS; AMYLOID BETA-PEPTIDE; SACCHAROMYCES-CEREVISIAE; MITOCHONDRIAL-FUNCTION; GLUTAMATE TRANSPORT; PARKINSONS-DISEASE; BRAIN-DAMAGE; LIFE-SPAN; 2-DEOXY-D-GLUCOSE AB Caloric restriction (CR)-or reduced calorie intake with nutritional maintenance-can extend lifespan and increase resistance to age-related disease by mechanisms which likely involve reduced oxyradical production and cellular hormesis responses in which genes encoding cytoprotective proteins are upregulated. Recent studies suggest that several of the anti-aging effects of CR can be mimicked by giving animals compounds that reduce energy availability at the cellular level. Such CR mimetic compounds (e.g., 2-deoxy-D-glucose, phenformin and iodoacetate) have proven beneficial in experimental models of neurodegenerative disorders and cancer. CR mimetics appear to act via a hormesis-based mechanism in which cells upregulate heat-shock and other chaperone proteins, and growth factors. Although long-term effects of dietary supplementation with such CR mimetics remain to be determined, the initial findings reviewed here suggest a novel approach for the investigation of basic mechanisms of aging, for the possible extension of lifespan without CR, and for dealing with the rising tide of obesity in industrialized countries. C1 NIA, Neurosci Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012; Lee, Jaewon/N-9064-2013 NR 48 TC 14 Z9 16 U1 0 U2 5 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1094-5458 J9 J ANTI-AGING MED JI J. Anti-Aging Med. PD FAL PY 2001 VL 4 IS 3 BP 225 EP 232 DI 10.1089/109454501753249993 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 495QM UT WOS:000172351900008 ER PT J AU Zimmerman, SB Murphy, LD AF Zimmerman, SB Murphy, LD TI Release of compact nucleoids with characteristic shapes from Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID STABILIZE DNA FOLDS; SPERMIDINE NUCLEOIDS; LIGHT-MICROSCOPY; NALIDIXIC-ACID; PHASE-CONTRAST; CHROMOSOME; GYRASE; ENZYME AB The genomic DNA of bacteria is contained in one or a few compact bodies known as nucleoids. We describe a simple procedure that retains the general shape and compaction of nucleoids from Escherichia coli upon cell lysis and nucleoid release from the cell envelope. The procedure is a modification of that used for the preparation of spermidine nucleoids (nucleoids released in the presence of spermidine) (T. Kornberg, A. Lockwood, and A. Worcel, Proc. Natl. Acad. Sci. USA 71:3189-3193, 1974). Polylysine is added to prevent the normal decompaction of nucleoids which occurs upon cell lysis. Nucleoids retained their characteristic shapes in lysates of exponential-phase cells or in lysates of cells treated with chloramphenicol or nalidixate to alter nucleoid morphology. The notably unstable nucleoids of rifampin-treated cells were obtained in compact, stable form in such lysates. Nucleoids released in the presence of polylysine were easily processed and provided well-defined DNA fluorescence and phase-contrast images. Uniform populations of nucleoids retaining characteristic shapes could be isolated after formaldehyde fixation and heating with sodium dodecyl sulfate. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zimmerman, SB (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 328W, Bethesda, MD 20892 USA. NR 40 TC 17 Z9 17 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2001 VL 183 IS 17 BP 5041 EP 5049 DI 10.1128/JB.183.17.5041-5049.2001 PG 9 WC Microbiology SC Microbiology GA 461DG UT WOS:000170349200013 PM 11489856 ER PT J AU Yamamoto, H Serizawa, M Thompson, J Sekiguchi, J AF Yamamoto, H Serizawa, M Thompson, J Sekiguchi, J TI Regulation of the glv operon in Bacillus subtilis: YfiA (GlvR) is a positive regulator of the operon that is repressed through CcpA and cre SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SUCRASE-ISOMALTASE-MALTASE; PHOSPHOTRANSFERASE SYSTEM; CATABOLITE REPRESSION; FAMILY 4; FUSOBACTERIUM-MORTIFERUM; ESCHERICHIA-COLI; EXPRESSION; GENES; ASSIGNMENT; BACTERIA AB Maltose metabolism and the regulation of the glv operon of Bacillus subtilis, comprising three genes, glvA (6-phospho-alpha -glucosidase), yfiA (now designated glvR), and glvC (EIICB transport protein), were investigated. Maltose dissimilation was dependent primarily upon the glv operon, and insertional inactivation of either glvA, glvR, or glvC markedly inhibited growth on the disaccharide. A second system (MAIL) contributed to a minor extent to maltose metabolism. Northern blotting revealed two transcripts corresponding to a monocistronic mRNA of glvA and a polycistronic mRNA of glvA-glvR-glvC. Primer extension analysis showed that both transcripts started at the same base (G) located 26 by upstream of the 5' end of glvA. When glvR was placed under control of the spac promoter, expression of the glv operon was dependent upon the presence of isopropyl-beta -D-thiogalactopyranoside (IPTG). In regulatory studies, the promoter sequence of the glv operon was fused to lacZ and inserted into the amyE locus, and the resultant strain (AMGLV) was then transformed with a citrate-controlled glvR plasmid, pHYCM2VR. When cultured in Difco sporulation medium containing citrate, this transformant [AMGLV(pHYCM2VR)] expressed LacZ activity, but synthesis of LacZ was repressed by glucose. In an isogenic strain, [AMGLVCR(pHYCM2VR)], except for a mutation in the sequence of a catabolite-responsive element (ere), LacZ activity was expressed in the presence of citrate and glucose. Insertion of a citrate-controlled glvR plasmid at the amyE locus of ccpA(+) and ccpA mutant organisms yielded strains AMCMVR and AMCMVRCC, respectively. In the presence of both glucose and citrate, AMCMVR failed to express the glv operon, whereas under the same conditions high-level expression of both mRNA transcripts was found in strain AMCMVRCC. Collectively, our findings suggest that GlvR (the product of the glvR gene) is a positive regulator of the glv operon and that glucose exerts its effect via catabolite repression requiring both CcpA and cre. C1 Shinshu Univ, Fac Text Sci & Technol, Dept Appl Biol, Ueda, Nagano 3868567, Japan. NIDCR, Microbial Biochem & Genet Unit, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Sekiguchi, J (reprint author), Shinshu Univ, Fac Text Sci & Technol, Dept Appl Biol, 3-15-1 Tokida, Ueda, Nagano 3868567, Japan. RI Sekiguchi, Junichi/F-9963-2010 NR 36 TC 36 Z9 40 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD SEP PY 2001 VL 183 IS 17 BP 5110 EP 5121 DI 10.1128/JB.183.17.5110-5121.2001 PG 12 WC Microbiology SC Microbiology GA 461DG UT WOS:000170349200021 PM 11489864 ER PT J AU Riminucci, M Collins, MT Corsi, A Boyde, A Murphey, MD Wientroub, S Kuznetsov, SA Cherman, N Robey, PG Bianco, P AF Riminucci, M Collins, MT Corsi, A Boyde, A Murphey, MD Wientroub, S Kuznetsov, SA Cherman, N Robey, PG Bianco, P TI Gnathodiaphyseal dysplasia: A syndrome of fibro-osseous lesions of jawbones, bone fragility, and long bone bowing SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE gnathodiaphyseal dysplasia; fibrous dysplasia; craniofacial; craniognathic; bone fragility; fractures; bowing; fibro-osseous; ossifying fibroma; cemento-ossifying fibroma; psammomatoid bodies ID MCCUNE-ALBRIGHT-SYNDROME; OSSIFYING FIBROMA; OSTEOGENESIS IMPERFECTA; FIBROOSSEOUS LESIONS; MUTATIONS; CELLS; MICE; GENE AB We report an unusual generalized skeletal syndrome characterized by fibro-osseous lesions of the jawbones with a prominent psammomatoid body component, bone fragility, and bowing(sclerosis of tubular bones. The case fits with the emerging profile of a distinct syndrome with similarities to previously reported cases, some with an autosomal dominant inheritance and others sporadic. We suggest that the syndrome be named gnathodiaphyseal dysplasia. The patient had been diagnosed previously with polyostotic fibrous dysplasia (PFD) elsewhere, but further clinical evaluation, histopathological study, and mutation analysis excluded this diagnosis. In addition to providing a novel observation of an as yet poorly characterized syndrome, the case illustrates the need for stringent diagnostic criteria for Fl). The jaw lesions showed fibro-osseous features with the histopathological characteristics of cemento-ossifying fibroma, psammomatoid variant. This case emphasizes that the boundaries between genuine GNAS1 mutation-positive FD and other fibro-osseous lesions occurring in the jawbones should be kept sharply defined, contrary to a prevailing tendency in the literature. A detailed pathological study revealed previously unreported features of cemento-ossifying fibroma, including the participation of myofibroblasts and the occurrence of psammomatoid bodies and aberrant mineralization, within the walls of blood vessels. Transplantation of stromal cells grown from the lesion into immunocompromised mice resulted in a close mimicry of the native lesion, including the sporadic formation of psammomatoid bodies, suggesting an intrinsic abnormality of bone-forming cells. C1 Univ Aquila, Dept Expt Med, Div Pathol, I-67100 Laquila, Italy. Univ Roma La Sapienza, Dept Expt Med & Pathol, Div Pathol, Rome, Italy. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Univ Coll, Dept Anat & Dev Biol, London, England. Armed Forces Inst Pathol, Dept Radiol Pathol, Washington, DC 20306 USA. Uniformed Serv Univ Hlth Sci, Dept Radiol & Nucl Med, Bethesda, MD 20814 USA. Univ Maryland, Med Ctr, Dept Diagnost Radiol, Baltimore, MD 21201 USA. Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, Dept Pediat Orthoped Surg, IL-64239 Tel Aviv, Israel. RP Robey, PG (reprint author), 30 Convent Dr,MSC 4320, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU Telethon [E.1029] NR 29 TC 27 Z9 27 U1 0 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 IS 9 BP 1710 EP 1718 DI 10.1359/jbmr.2001.16.9.1710 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 465PR UT WOS:000170599600018 PM 11547842 ER PT J AU Akintoye, S Lee, J Chebli, C Booher, S Wientroub, S Bianco, P Robey, PG Collins, MT AF Akintoye, S Lee, J Chebli, C Booher, S Wientroub, S Bianco, P Robey, PG Collins, MT TI Markers of bone metabolism in fibrous dysplasia. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Tel Aviv Med Ctr & Sch Med, Dana Childrens Hosp, IL-64239 Tel Aviv, Israel. Univ Rome, Rome, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S422 EP S422 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709001195 ER PT J AU Barsony, J Prufer, K Segovis, C AF Barsony, J Prufer, K Segovis, C TI Shuttling vitamin D receptors transport the hormone into and out of the nucleus. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH, LCBB, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S184 EP S184 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000192 ER PT J AU Black, DM Rosen, C Greenspan, S Ensrud, K Bilezikian, J McGowan, J AF Black, DM Rosen, C Greenspan, S Ensrud, K Bilezikian, J McGowan, J TI PTH and bisphosphonates in the treatment of osteoporosis: The PTH and alendronate (PaTH) trial. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Maine, Bangor, ME USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Columbia Univ, New York, NY USA. NIAMS, Bethesda, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S287 EP S287 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000613 ER PT J AU Blunt, BA Fuerst, T Nevitt, M Lohman, T Schoeller, D Visser, M Harris, T Tylavsky, F AF Blunt, BA Fuerst, T Nevitt, M Lohman, T Schoeller, D Visser, M Harris, T Tylavsky, F TI Hologic QDR4500A: Recalibration of fat free mass measured by the QDR 4500A using the four compartment model. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Synarc Inc, San Francisco, CA USA. Univ Arizona, Tucson, AZ USA. Univ Wisconsin, Madison, WI USA. Vrije Univ Amsterdam, Amsterdam, Netherlands. NIH, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S341 EP S341 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000841 ER PT J AU Brown, SA Ontjes, DA Aris, RM Lester, GE Lark, RK Hensler, MB Blackwood, AD Caminiti, MJ AF Brown, SA Ontjes, DA Aris, RM Lester, GE Lark, RK Hensler, MB Blackwood, AD Caminiti, MJ TI Short-term calcitriol administration improves calcium homeostasis in adults with Cystic Fibrosis. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ N Carolina, Dept Endocrinol, Chapel Hill, NC 27515 USA. Univ N Carolina, Dept Pulmonol, Chapel Hill, NC 27515 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S223 EP S223 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000352 ER PT J AU Chen, X Allen, MR Bloomfield, SA Xu, T Young, MF AF Chen, X Allen, MR Bloomfield, SA Xu, T Young, MF TI Biglycan deficient mice have delayed bone formation after bone marrow ablation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, CSDB, Bethesda, MD USA. Texas A&M Univ, Dept Hlth & Kinesiol, College Stn, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S450 EP S450 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709001312 ER PT J AU Chiusaroli, R Juel, J Neff, L Sanjay, A Naramura, M Gu, H Horne, WC Baron, R AF Chiusaroli, R Juel, J Neff, L Sanjay, A Naramura, M Gu, H Horne, WC Baron, R TI Deletion of the genes encoding c-Cbl or Cbl-b alter the ability of osteoclasts to migrate during development, delaying resorption and ossification of cartilage in long bones. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S153 EP S153 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000069 ER PT J AU Fedarko, NS Jain, A Karadag, A Fisher, L AF Fedarko, NS Jain, A Karadag, A Fisher, L TI Bone sialoprotein binds to and modulates pro-matrix metalloproteinase-2 activity. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S142 EP S142 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000022 ER PT J AU Gafni, RI Cadet, ER McCarthy, EF McCray, DR Baron, J AF Gafni, RI Cadet, ER McCarthy, EF McCray, DR Baron, J TI Longitudinal growth of the cortex: Increased osteoblasts in the peripheral spongiosa causes coalescence of trabeculae to create new cortical bone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S486 EP S486 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709001464 ER PT J AU Gallardo-Williams, MT Maronpot, RR Turner, CH Johnson, CS Harris, MW Jayo, MJ Chapin, RE AF Gallardo-Williams, MT Maronpot, RR Turner, CH Johnson, CS Harris, MW Jayo, MJ Chapin, RE TI The effects of boron (boric acid) supplementation on bone histomorphometry and bone metabolism in aged female F-344 rats. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Expt Pathol Lab, Res Triangle Pk, NC 27709 USA. Indiana Univ, Dept Orthopaed Surg, Indianapolis, IN 46204 USA. Pathol Associates Inc, Advance, NC USA. DuPont Pharmaceut Co, Newark, DE USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S532 EP S532 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709001666 ER PT J AU Gronthos, S Robey, PG Boyde, A Shi, S AF Gronthos, S Robey, PG Boyde, A Shi, S TI Human dental pulp stem cells (DPSCs): Characterization and developmental potential. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH, NIDCR, Craniofacial & Skeletal Dis Branch, Bethesda, MD USA. UCL, Dept Anat & Dev Biol, London, England. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 4 Z9 4 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S265 EP S265 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000524 ER PT J AU Hausler, KD Horwood, NJ Uren, A Ellis, J Lengel, C Martin, TJ Rubin, JS Gillespie, MT AF Hausler, KD Horwood, NJ Uren, A Ellis, J Lengel, C Martin, TJ Rubin, JS Gillespie, MT TI Secreted Frizzled-related protein (sFRP-1) binds to RANKL to inhibit osteoclast formation. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 St Vincents Inst Med Res, Melbourne, Vic, Australia. NIH, NCI, Bethesda, MD 20892 USA. RI Horwood, Nicole/B-4351-2009 NR 0 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S153 EP S153 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000068 ER PT J AU Hoare, SRJ Usdin, TB AF Hoare, SRJ Usdin, TB TI A new high-affinity parathyroid hormone 1 receptor antagonist, mouse tuberoinfundibular peptide (7-39). SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH, NIMH, Genet Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S307 EP S307 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000698 ER PT J AU Holmbeck, K Bianco, P Chrysovergis, K Birkedal-Hansen, H AF Holmbeck, K Bianco, P Chrysovergis, K Birkedal-Hansen, H TI Development of the mouse cranium is a metamorphic process dependent on the matrix metalloproteinase MT1-MMP. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, Div Intramural Res, Bethesda, MD USA. Univ La Sapienza, Dipartimento Med Sperimentale & Patol Anat Patol, Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S452 EP S452 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709001322 ER PT J AU Horvath, C Falus, A Buzas, E Mester, A Nagy, A Fitzpatrick, L Barsony, J AF Horvath, C Falus, A Buzas, E Mester, A Nagy, A Fitzpatrick, L Barsony, J TI Targeted deletion of the histidine decarboxylase gene in mice increases bone formation and protects against ovariectomy-induced bone loss. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Semmelweis Univ, Dept Internal Med 1, H-1085 Budapest, Hungary. Semmelweis Univ, Dept Biol, Budapest, Hungary. Semmelweis Univ, Dept Radiol, H-1085 Budapest, Hungary. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. Mayo Clin, Dept Med, Rochester, MN USA. NIDDK, LCBB, NIH, Bethesda, MD 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 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S151 EP S151 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000058 ER PT J AU Karadag, A Riminucci, M Bianco, P Cherman, N Robey, PG Fisher, LW AF Karadag, A Riminucci, M Bianco, P Cherman, N Robey, PG Fisher, LW TI The use of protein nucleic acid (PNA) in the quantification of Arg201 mutations in FD/MAS and cancer. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, CSDB, NIH, Bethesda, MD USA. Univ Aquila, I-67100 Laquila, Italy. Univ Rome, Rome, Italy. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S418 EP S418 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709001176 ER PT J AU King, LM DeRubeis, AR Jia, L Francomano, C Robey, P AF King, LM DeRubeis, AR Jia, L Francomano, C Robey, P TI cDNA microarray analysis of human bone marrow stromal cell mRNA expression in response to dexamethasone. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, CSDB, NIH, Bethesda, MD USA. NHGRI, MGD, NIH, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S371 EP S371 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000971 ER PT J AU Kozloff, KM Frankenburg, EP Spurchise, MF Berwitz, C Forlino, A Marini, JC Goldstein, SA AF Kozloff, KM Frankenburg, EP Spurchise, MF Berwitz, C Forlino, A Marini, JC Goldstein, SA TI Postpubertal improvement in bone of knock-in mouse model (Brittle mouse) for osteogenesis imperfecta is due to fundamental alterations in bone material properties. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Michigan, Orthopaed Res Labs, Ann Arbor, MI 48109 USA. NICHHD, HDB, Sect Connect Tissue Disorders, Bethesda, MD USA. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S182 EP S182 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000182 ER PT J AU Kuznetsov, SA Cherman, N Lee, JS Collins, MT Robey, PG AF Kuznetsov, SA Cherman, N Lee, JS Collins, MT Robey, PG TI The concentration of marrow stromal precursor cells in skeletal and metabolic disorders. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDCR, CSDB, NIH, Bethesda, MD USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S419 EP S419 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709001183 ER PT J AU Robbins, J Hirsch, C Cauley, J Harris, T AF Robbins, J Hirsch, C Cauley, J Harris, T TI Association of weight with bone mineral density in older African Americans. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Univ Calif Davis, Sacramento, CA 95817 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S273 EP S273 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000556 ER PT J AU Shi, S Robey, PG Gronthos, S AF Shi, S Robey, PG Gronthos, S TI Adult human dental pulp stem cells (DPSCs) can differentiate into neural-like cells in vitro. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIH, Craniofacial & Skeletal Dis Branch, Bethesda, MD 20892 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S496 EP S496 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709001509 ER PT J AU Simonds, WF James-Newton, LA Agarwal, SK Yang, B Skarulis, MC Hendy, GN Marx, SJ AF Simonds, WF James-Newton, LA Agarwal, SK Yang, B Skarulis, MC Hendy, GN Marx, SJ TI Familial isolated hyperparathyroidism: Clinical and genetic characteristics of thirty-six kindreds. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 NIDDKD, Metab Dis Branch, Bethesda, MD 20892 USA. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Dept Physiol, Montreal, PQ, Canada. McGill Univ, Dept Human Genet, Montreal, PQ, Canada. NIDDKD, Div Intramural Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S156 EP S156 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000080 ER PT J AU Sjogren, K Mohan, S Sheng, HCM Liu, JL Blad, K Isaksson, O Tornell, J Ohlsson, C AF Sjogren, K Mohan, S Sheng, HCM Liu, JL Blad, K Isaksson, O Tornell, J Ohlsson, C TI Evidence that liver derived IGF-I exerts a minimal role in the regulation of peak BMD in mice. SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract C1 Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. Jerry L Pettis Mem Vet Adm Med Ctr, MDC, Loma Linda, CA 92354 USA. NIDDK, NIH, Bethesda, MD USA. Gothenburg Univ, S-41124 Gothenburg, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2001 VL 16 SU 1 BP S356 EP S356 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 467MU UT WOS:000170709000904 ER PT J AU Forrest, JL Drury, TF Horowitz, AM AF Forrest, JL Drury, TF Horowitz, AM TI US dental hygienists' knowledge and opinions related to providing oral cancer examinations SO JOURNAL OF CANCER EDUCATION LA English DT Article ID PHARYNGEAL CANCER; STATISTICS AB Background. Because U.S. dental hygienists play a significant role in providing prevention and early-detection services, it is important to describe and evaluate their oral cancer knowledge and opinions. Methods. A pretested survey, cover letter, and prepaid return envelope were mailed to 960 dental hygienists, followed by three complete follow-up mailings. Results. The respondents were not as knowledgeable about oral cancer risk factors and diagnostic procedures as hypothesized. Although the respondents were well informed about certain key aspects of oral cancer risk factors and diagnostic procedures, there were many aspects of these topics in which they were deficient and in some cases misinformed. Conclusions. Dental hygiene curricula should be updated and continuing education courses about oral cancer should be developed and implemented. C1 Univ So Calif, Natl Ctr Dent Hyg Res, Los Angeles, CA 90089 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Forrest, JL (reprint author), Univ So Calif, Natl Ctr Dent Hyg Res, 925 W 34th St,Room 4330, Los Angeles, CA 90089 USA. NR 24 TC 4 Z9 4 U1 1 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD FAL PY 2001 VL 16 IS 3 BP 150 EP 156 PG 7 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 482JB UT WOS:000171572100008 PM 11603878 ER PT J AU Hallstrom, AP Greene, HL Wilkoff, BL Zipes, DP Schron, E Ledingham, RB AF Hallstrom, AP Greene, HL Wilkoff, BL Zipes, DP Schron, E Ledingham, RB CA AVID Investigators TI Relationship between rehospitalization and future death in patients treated for potentially lethal arrhythmia SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE sudden death; fibrillation; heart failure; risk factors ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; SURROGATE ENDPOINTS; CLINICAL-TRIALS AB Introduction: It is generally considered that death is the only appropriate endpoint to evaluate interventions for preventing death; however, this belief may be based on the previous use of inappropriate or inadequate surrogates for death. The aim of this study was to evaluate whether rehospitalization following implementation of an intervention is a reasonable surrogate for death. Methods and Results: The time from discharge following intervention to rehospitalization was evaluated for 997 patients discharged after baseline hospitalization in the Antiarrhythmics Versus Implantable Defibrillators Trial. The relationship between rehospitalization for various reasons and subsequent death was compared in the two treatment arms to assess the adequacy of rehospitalization as a surrogate for death. Included were rehospitalization for: any reason, a cardiac problem, a noncardiac problem, new or worsened congestive heart failure (CHF), an acute coronary syndrome, and a cardiac procedure. For all of the reasons except cardiac procedure, rehospitalization was associated with a substantially increased hazard for subsequent death. Rehospitalization for new or worsened CHF was most closely (that is, temporally) related to subsequent death and was the only reason for rehospitalization, which fully explained the treatment effect of implantable cardiac defibrillators compared with antiarrhythmic drugs on death. Conclusion: Rehospitalization is a significant risk factor for subsequent death. However, only rehospitalization for new or worsened CHF appears to be a potential surrogate for death in the setting of antiarrhythmic interventions. C1 Univ Washington, Seattle, WA 98195 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Hallstrom, AP (reprint author), 1107 NE 45th St,Suite 505, Seattle, WA 98105 USA. EM aph@u.washington.edu OI Zipes, Douglas/0000-0001-7141-6829 FU PHS HHS [N01-11C-25117] NR 15 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1045-3873 EI 1540-8167 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD SEP PY 2001 VL 12 IS 9 BP 990 EP 995 DI 10.1046/j.1540-8167.2001.00990.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 470MF UT WOS:000170875200003 PM 11573708 ER PT J AU Kalinin, A Marekov, LN Steinert, PM AF Kalinin, A Marekov, LN Steinert, PM TI Assembly of the epidermal cornified cell envelope SO JOURNAL OF CELL SCIENCE LA English DT Article C1 NIAMS, Lab Skin Biol Branch, NIH, Bethesda, MD 20892 USA. RP Steinert, PM (reprint author), NIAMS, Lab Skin Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 108 Z9 112 U1 0 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 2001 VL 114 IS 17 BP 3069 EP 3070 PG 2 WC Cell Biology SC Cell Biology GA 477CT UT WOS:000171266100001 PM 11590230 ER PT J AU Whittard, JD Akiyama, SK AF Whittard, JD Akiyama, SK TI Positive regulation of cell-cell and cell-substrate adhesion by protein kinase A SO JOURNAL OF CELL SCIENCE LA English DT Article DE integrin activation; cell-cell adhesion; cAMP; PKA; F-actin; signal transduction ID CYCLIC-AMP; SIGNAL-TRANSDUCTION; ANCHORING PROTEINS; INTEGRIN FUNCTION; LIGAND-BINDING; CAMP; SUBUNIT; CYTOSKELETAL; ORGANIZATION; ACTIVATION AB Integrin receptor activation is an important regulatory mechanism for cell-substrate and cell-cell adhesion. In this study, we explore a signaling pathway activated by mAb 12G10, an antibody that can activate beta (1) integrins and induce integrin-mediated cell-cell and cell-substrate adhesion. We have found that the cAMP-dependent protein kinase (PKA) is required for both mAb 12G10-induced cell-cell and cell-substrate adhesion of HT-1080 cells. Binding of mAb 12G10 to beta (1) integrins stimulates an increase in intracellular cAMP levels and PKA activity, and a concomitant shift in the localization of the PKA type II regulatory subunits from the cytoplasm to areas where integrins expressing the 12G10 epitope are located. MAb 12G10-induced cell-cell adhesion was mimicked by a combination of clustering beta (1) integrins and elevating PKA activity with Sp-adenosine-3',5'-cyclic monophosphorothioate or forskolin. We also show that two processes required for HT-1080 cell-cell adhesion, integrin clustering and F-actin polymerization are both dependent on PKA. Taken together, our data suggest that PKA plays a key role in the signaling pathway, resulting from activation of beta (1) integrins, and that this enzyme may be required for upregulation of cell-substrate and cell-cell adhesion. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Akiyama, SK (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 42 TC 45 Z9 48 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 2001 VL 114 IS 18 BP 3265 EP 3272 PG 8 WC Cell Biology SC Cell Biology GA 481JW UT WOS:000171517000006 PM 11591815 ER PT J AU Nili, E Cojocaru, GS Kalma, Y Ginsberg, D Copeland, NG Gilbert, DJ Jenkns, NA Berger, R Shaklai, S Amariglio, N Brok-Simoni, F Simon, AJ Rechavi, G AF Nili, E Cojocaru, GS Kalma, Y Ginsberg, D Copeland, NG Gilbert, DJ Jenkns, NA Berger, R Shaklai, S Amariglio, N Brok-Simoni, F Simon, AJ Rechavi, G TI Nuclear membrane protein LAP2 beta mediates transcriptional repression alone and together with its binding partner GCL (germ-cell-less) SO JOURNAL OF CELL SCIENCE LA English DT Article DE GCL; germ-cell-less; LAP2; nuclear envelope; thymopoietin; transcription regulation ID LAMINA-ASSOCIATED POLYPEPTIDE-2; DREIFUSS MUSCULAR-DYSTROPHY; INTERMEDIATE FILAMENT PROTEINS; RETINOBLASTOMA GENE-PRODUCT; B-RECEPTOR; MOLECULAR-CLONING; ALSTROM-SYNDROME; PARTIAL LIPODYSTROPHY; GENOMIC ORGANIZATION; BTB/POZ DOMAIN AB LAP2 beta is an integral membrane protein of the nuclear envelope involved in chromatin and nuclear architecture. Using the yeast two-hybrid system, we have cloned a novel LAP2 beta -binding protein, mGCL, which contains a BTB/POZ domain and is the mouse homologue of the Drosophila germ-cell-less (GCL) protein. In Drosophila embryos, GCL was shown to be essential for germ cell formation and was localized to the nuclear envelope. Here, we show that, in mammalian cells, GCL is co-localized with LAP2 beta to the nuclear envelope. Nuclear fractionation studies reveal that mGCL acts as a nuclear matrix component and not as an integral protein of the nuclear envelope. Recently, mGCL was found to interact with the DP3 alpha component of the E2F transcription factor. This interaction reduced the transcriptional activity of the E2F-DP heterodimer, probably by anchoring the complex to the nuclear envelope. We demonstrate here that LAP2 beta is also capable of reducing the transcriptional activity of the E2F-DP complex and that it is more potent than mGCL in doing so. Co-expression of both LAP2 beta and mGCL with the E2F-DP complex resulted in a reduced transcriptional activity equal to that exerted by the pRb protein. C1 Chaim Sheba Med Ctr, Div Hematol, Pediat Hematooncol Dept, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Simon, AJ (reprint author), Chaim Sheba Med Ctr, Div Hematol, Pediat Hematooncol Dept, IL-52621 Tel Hashomer, Israel. NR 77 TC 146 Z9 159 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD SEP PY 2001 VL 114 IS 18 BP 3297 EP 3307 PG 11 WC Cell Biology SC Cell Biology GA 481JW UT WOS:000171517000009 PM 11591818 ER PT J AU Stratakis, CA Kirschner, LS Carney, JA AF Stratakis, CA Kirschner, LS Carney, JA TI Genetics of endocrine disease - Clinical and molecular features of the Carney complex: Diagnostic criteria and recommendations for patient evaluation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SPOTTY SKIN PIGMENTATION; PSAMMOMATOUS MELANOTIC SCHWANNOMA; AUTOSOMAL-DOMINANT TRANSMISSION; FAMILIAL CARDIAC MYXOMAS; ATRIAL-MYXOMA; REGULATORY SUBUNIT; CUSHING-SYNDROME; DUCTAL ADENOMA; NAME SYNDROME; OVERACTIVITY AB Carney complex is a multiple neoplasia syndrome featuring cardiac, endocrine, cutaneous, and neural tumors, as well as a variety of pigmented lesions of the skin and mucosae. Carney complex is inherited as an autosomal dominant trait and may simultaneously involve multiple endocrine glands, as in the classic multiple endocrine neoplasia syndromes 1 and 2. Carney complex also has some similarities to McCuneAlbright syndrome, a sporadic condition that is also characterized by multiple endocrine and nonendocrine tumors. Carney complex shares skin abnormalities and some nonendocrine tumors with the lentiginoses and certain of the hamartomatoses, particularly Peutz-Jeghers syndrome, with which it shares mucosal lentiginosis and an unusual gonadal tumor, large-cell calcifying Sertoli cell tumor. Careful clinical analysis has enabled positional cloning efforts to identify two chromosomal loci harboring potential candidate genes for Carney complex. Most recently, at the 17q22-24 locus, the tumor suppressor gene PRKAR1A, coding for the type 1 a regulatory subunit of PKA, was found to be mutated in approximately half of the known Carney complex kindreds. PRKAR1A acts a classic tumor suppressor gene as demonstrated by loss of heterozygosity at the 17q22-24 locus in tumors associated with the complex. The second locus, at chromosome 2p16, to which most (but not all) of the remaining kindreds map, is also involved in the molecular pathogenesis of Carney complex tumors, as demonstrated by multiple genetic changes at this locus, including loss of heterozygosity and copy number gain. Despite the known genetic heterogeneity in the disease, clinical analysis has not detected any corresponding phenotypic differences between patients with PRKAR1A mutations and those without. This article summarizes the clinical manifestations of Carney complex from a worldwide collection of affected patients and also presents revised diagnostic criteria for Carney complex. In light of the recent identification of mutations in the PRKAR1A gene, an estimate of penetrance and recommendations for genetic screening are provided. C1 NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55905 USA. RP Stratakis, CA (reprint author), NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr MSC 1862, Bethesda, MD 20892 USA. EM stratakc@ccl.nichd.nih.gov NR 42 TC 331 Z9 359 U1 1 U2 7 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2001 VL 86 IS 9 BP 4041 EP 4046 DI 10.1210/jc.86.9.4041 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 471WL UT WOS:000170951600001 PM 11549623 ER PT J AU Lindsay, RS Hanson, RL Roumain, J Ravussin, E Knowler, WC Tataranni, PA AF Lindsay, RS Hanson, RL Roumain, J Ravussin, E Knowler, WC Tataranni, PA TI Body mass index as a measure of adiposity in children and adolescents: Relationship to adiposity by dual energy X-ray absorptiometry and to cardiovascular risk factors SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FAT; OVERWEIGHT; OBESITY; GENDER; GIRLS; BLACK AB Body mass index is widely used as a measure of adiposity in adults, but its use in children and adolescents is controversial. We assessed body mass index as a measure of adiposity in children and adolescents between the ages of 5 and 20 yr examined as part of the NIH survey of health in the Pima Indian population. Body mass index (measured in 985 subjects and analyzed in 3 age groups: 5-9, 10-14, and 15-19 yr, in both sexes) was compared cross-sectionally to percent fat and fat mass derived from dual energy x-ray absorptiometry and to fasting and 2-h plasma glucose, systolic and diastolic blood pressures, cholesterol, high density lipoprotein cholesterol, fasting insulin, and triglycerides. Body mass index was strongly correlated in all age groups to both percent fat (r = 0.83-0.94; for each group, P < 0.0001) and fat mass (r = 0.96-0.98; P < 0.0001). The relationship of body mass index to percent fat was different in males and females; differences were more marked in older age groups. Body mass index, percent fat, and fat mass showed similar degrees of correlation to metabolic measures in childhood. Body mass index is strongly associated with measures of adiposity derived from dual energy x-ray absorptiometry. Both measures show similar associations with cardiovascular risk factors in Pima Indian children. C1 NIDDKD, NIH, Phoenix, AZ 85014 USA. RP Lindsay, RS (reprint author), 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rlindsay@mail.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 18 TC 96 Z9 101 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2001 VL 86 IS 9 BP 4061 EP 4067 DI 10.1210/jc.86.9.4061 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 471WL UT WOS:000170951600004 PM 11549626 ER PT J AU Krakoff, J Koch, CA Calis, KA Alexander, RH Nieman, LK AF Krakoff, J Koch, CA Calis, KA Alexander, RH Nieman, LK TI Use of a parenteral propylene glycol-containing etomidate preparation for the long-term management of ectopic Cushing's syndrome SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; DEXAMETHASONE SUPPRESSION TEST; CRITICALLY ILL PATIENTS; ADRENOCORTICAL FUNCTION; DIFFERENTIAL-DIAGNOSIS; CORTISOL; HYPERCORTISOLEMIA; PHARMACOKINETICS; ADRENALECTOMY; INFECTIONS AB Chronic severe hypercortisolism is associated with life-threatening infections, diabetes and a high surgical mortality rate. Oral medical therapy can inhibit steroidogenesis and reduce the risk of these complications. However, apart from a few reports using an ethyl alcohol formulation of the iv anesthetic etomidate, there is no well-tested parenteral steroidogenesis inhibitor. We used the propylene glycol preparation of etomidate available in the United States to control hypercortisolism in a 39-yr-old man with ectopic ACTH secretion who was unable to take oral medications. Etomidate was administered over a period of 5.5 months. We titrated the dose of etomidate daily using serum cortisol levels, to avoid steroid over replacement and allow for a response to ongoing stress. A reduced dose during a period of acute renal failure achieved adequate control of hypercortisolemia. Suppression of steroidogenesis persisted for at least 14 d and perhaps as long as 6 wk after cessation of the medication. Except for transient myoclonus, the patient tolerated this preparation well. Parenteral propylene glycol containing etomidate can be used safely for a prolonged period to reduce hypercortisolemia in patients unable to take oral medications. C1 NIDDKD, NIH, Phoenix, AZ 85014 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Clin Ctr Pharm, Bethesda, MD 20892 USA. RP Krakoff, J (reprint author), NIDDKD, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM jkrakoff@mail.nih.gov RI Koch, Christian/A-4699-2008; OI Koch, Christian/0000-0003-3127-5739; Koch, Christian/0000-0003-0678-1242 NR 35 TC 49 Z9 52 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2001 VL 86 IS 9 BP 4104 EP 4108 DI 10.1210/jc.86.9.4104 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 471WL UT WOS:000170951600011 PM 11549633 ER PT J AU Cappola, AR Bandeen-Roche, K Wand, GS Volpato, S Fried, LP AF Cappola, AR Bandeen-Roche, K Wand, GS Volpato, S Fried, LP TI Association of IGF-I levels with muscle strength and mobility in older women SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-3; 60 YEARS OLD; BODY-COMPOSITION; PHYSICAL-ACTIVITY; ELDERLY SUBJECTS; HORMONE; MEN; AGE; INSULIN-LIKE-GROWTH-FACTOR-1 AB The functional consequences of the age-associated decline in IGF-l are unknown. We hypothesized that low IGF-l levels in older women would be associated with poor muscle strength and mobility. We assessed this question in a population representative of the full spectrum of health in the community, obtaining serum IGF-l levels from women aged 70-79 yr, enrolled in the Women's Health and Aging Study I or II. Cross-sectional analyses were performed using 617 women with IGF-I levels drawn within 90 d of measurement of outcomes. After adjustment for age, there was an association between IGF-I and knee extensor strength (P = 0.004), but not anthropometry or other strength measures. We found a positive relationship between lGF-I levels and walking speed for IGF-I levels below 50 mug/liter (P < 0.001), but no relationship above this threshold. A decline in IGF-I level was associated with self-reported difficulty in mobility tasks. All findings were attenuated after multivariate adjustment. In summary, in a study population including frail and healthy older women, low IGF-I levels were associated with poor knee extensor muscle strength, slow walking speed, and self-reported difficulty with mobility tasks. These findings suggest a role for IGF-I in disability as well as a potential target population for interventions to raise IGF-I levels. C1 Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD 20892 USA. RP Cappola, AR (reprint author), Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, 660 W Redwood St,Room 495A, Baltimore, MD 21201 USA. EM acappola@medicine.umaryland.edu RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIA NIH HHS [N01-AG-1-2112, R01-AG-11703] NR 29 TC 110 Z9 114 U1 2 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2001 VL 86 IS 9 BP 4139 EP 4146 DI 10.1210/jc.86.9.4139 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 471WL UT WOS:000170951600017 PM 11549640 ER PT J AU Kohno, M Kawahito, Y Tsubouchi, Y Hashiramoto, A Yamada, R Inoue, KI Kusaka, Y Kubo, T Elenkov, IJ Chrousos, GP Kondo, M Sano, H AF Kohno, M Kawahito, Y Tsubouchi, Y Hashiramoto, A Yamada, R Inoue, KI Kusaka, Y Kubo, T Elenkov, IJ Chrousos, GP Kondo, M Sano, H TI Urocortin expression in synovium of patients with rheumatoid arthritis and osteoarthritis: Relation to inflammatory activity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; BLOOD MONONUCLEAR-CELLS; RAT SPINAL-CORD; BETA-ENDORPHIN; LEWIS RATS; ADRENOCORTICOTROPIC HORMONE; MESSENGER-RNA; GROWTH-FACTOR; FACTOR CRF AB Peripherally produced CRH acts as a local auto/paracrine proinflammatory agent. Urocortin is a new member of the CRH family that acts through the family of CRH receptors. In this study, we demonstrated that the expression of urocortin mRNA in synovia of patients with rheumatoid arthritis was greater than that of patients with osteoarthritis. Also, we detected urocortin and CRH receptor immunoreactivity in the synovial lining cell layer, subsynovial stromal cells, blood vessel endothelial cells, and mononuclear inflammatory cells from the joints of rheumatoid arthritis and osteoarthritis patients. The expression of immunoreactive urocortin was significantly greater in rheumatoid arthritis than ostcoarthritis (P<0.0001) and correlated with the extent of inflammatory infiltrate. CRH receptor immunoreactivity was strong in mononuclear inflammatory cells of rheumatoid arthritis synovia. Urocortin stimulated IL-1 and IL-6 secretion by human peripheral blood mononuclear cells in vitro. These findings suggest that, like CRH, urocortin is present in peripheral inflammatory sites, such as rheumatoid synovium, and acts as an immune-inflammatory mediator. C1 Kyoto Prefectural Univ Med, Dept Internal Med 1, Kamigyo Ku, Kyoto 6028566, Japan. Kyoto Prefectural Univ Med, Dept Orthoped, Kyoto 6028566, Japan. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. RP Sano, H (reprint author), Kyoto Prefectural Univ Med, Dept Internal Med 1, Kamigyo Ku, 465 Kajii Cho, Kyoto 6028566, Japan. EM hsano@koto.kpu-m.ac.jp NR 58 TC 69 Z9 70 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD SEP PY 2001 VL 86 IS 9 BP 4344 EP 4352 DI 10.1210/jc.86.9.4344 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 471WL UT WOS:000170951600048 PM 11549672 ER PT J AU Resnick, HE Shorr, RI Kuller, L Franse, L Harris, TB AF Resnick, HE Shorr, RI Kuller, L Franse, L Harris, TB TI Prevalence and clinical implications of American Diabetes Association-defined diabetes and other categories of glucose dysregulation in older adults: The Health, Aging and Body Composition Study SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE diabetes mellitus; epidemiology; aged; race; cardiovascular disease; lipids; obesity; glycated hemoglobin ID CARDIOVASCULAR-DISEASE; US ADULTS; MELLITUS; CLASSIFICATION; CRITERIA; RISK AB Using data on history of diabetes, fasting glucose (FG) and the oral glucose tolerance test (OGTT), the authors contrasted cardiovascular disease (CVD) risk factors (body mass index, blood pressure. lipids and glycated hemoglobin) in 3052 African-American and White adults aged 70-79 in mutually exclusive categories of diagnosed diabetes, undiagnosed diabetes defined by the American Diabetes Association (ADA), isolated post-challenge hyperglycemia (IPH:, FG < 126 mg/dL and 2 h post-OGTT 200 mg/dL), impaired fasting glucose (IFG; FG greater than or equal to 110 but < 126 mg/dL), and individuals who were non-diabetic by both ADA and World Health Organization (WHO) criteria (FG < 126 mg/dL and 2 h post-challenge glucose < 200 mg/dL). The prevalence of diagnosed diabetes, undiagnosed ADA diabetes and IPH were 15.2, 3.8 and 4.7%, respectively, with more diagnosed and undiagnosed ADA diabetes in African-Americans than Whites. Compared to mean glycated hemoglobin (HbA(1c)) among ADA/WHO non-diabetic individuals (6.0%), HbA(1c) was substantially higher in the diagnosed diabetes and undiagnosed ADA diabetes groups (8.0% and 7.7%), but not in the IPH group (6.3%). The diagnosed and undiagnosed ADA diabetic groups had worse CVD risk factor profiles than the ADA/WHO non-diabetic group. IPH subjects had elevated levels of some CVD risk factors, but differences were more modest than those for the diabetic groups. Among people with IPH, those who also had IFG had worse CVD profiles than those with IPH alone. Although the OGTT may identify additional adults with more CVD risk factors than normals, these differences appear to be clustered among those who also have IFG. (C) 2001 Elsevier Science Inc. All rights reserved. C1 MedStar Res Inst, Washington, DC 20010 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Pittsburgh, Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA. Vrije Univ Amsterdam, Inst Res Extramural Med, Amsterdam, Netherlands. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Resnick, HE (reprint author), MedStar Res Inst, 108 Irving St NW, Washington, DC 20010 USA. FU NIA NIH HHS [N01-AG-6-2106, N01-AG-6-2102, N01-AG-6-2103] NR 18 TC 35 Z9 37 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD SEP PY 2001 VL 54 IS 9 BP 869 EP 876 DI 10.1016/S0895-4356(01)00359-6 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 465RE UT WOS:000170603100002 PM 11520645 ER PT J AU Zeng, WH Maciejewski, JP Chen, GB Young, NS AF Zeng, WH Maciejewski, JP Chen, GB Young, NS TI Limited heterogeneity of T cell receptor BV usage in aplastic anemia SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VERSUS-HOST DISEASE; BONE-MARROW; RHEUMATOID-ARTHRITIS; HERPESVIRUS-SAIMIRI; CDR3 MOTIFS; IN-VIVO; REPERTOIRE; ANTIGEN; TCR; LYMPHOCYTES AB Immune mediation of aplastic anemia (AA) has been inferred from clinical responsiveness to immunosuppressive therapies and a large body of circumstantial laboratory evidence. However, neither the immune response nor the nature of the antigens recognized has been well characterized. We established a large number of CD4 and CD8 T cell clones from a patient with AA and analyzed their T cell receptor (TCR) usage. Most CD4 clones displayed BV5, whereas most CD8 clones displayed BV13. We found sequence identity for complementarity determining region 3 (CDR3) among a majority of CD4 clones; the same sequence was present in marrow lymphocytes from four other patients with AA but was not detected in controls. The dominant CD4 clone showed a Th1 secretion pattern, lysed autologous CD34 cells, and inhibited their hematopoietic colony formation. In three of four patients, successful immunosuppressive treatment led to marked decrease in clones beating the dominant CDR3 BV5 sequence. These results suggest surprisingly limited heterogeneity of the T cell repertoire in an individual patient and similarity at the molecular level of the likely pathological lymphocyte response among multiple patients with AA, consistent with recognition of limited numbers of antigens shared by individuals with the same HLA type in this disease. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Room 7C103900 Rockville Pike, Bethesda, MD 20892 USA. NR 46 TC 75 Z9 84 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2001 VL 108 IS 5 BP 765 EP 773 DI 10.1172/JCI12687 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 469MF UT WOS:000170818900019 PM 11544283 ER PT J AU Schiffer, M Bitzer, M Roberts, ISD Kopp, JB ten Dijke, P Mundel, P Bottinger, EP AF Schiffer, M Bitzer, M Roberts, ISD Kopp, JB ten Dijke, P Mundel, P Bottinger, EP TI Apoptosis in podocytes induced by TGF-beta and Smad7 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GROWTH-FACTOR-BETA; GLOMERULAR-DISEASES; TRANSGENIC MICE; CELL-LINES; PROTEIN; GLOMERULOSCLEROSIS; DIFFERENTIATION; IDENTIFICATION; PROGRESSION; INHIBITION AB Primary and secondary forms of focal segmental glomerulosclerosis (FSGS) are characterized by depletion of podocytes and constitute a central manifestation of chronic progressive glomerular diseases. Here we report that podocytes undergo apoptosis at early stages in the course of progressive glomerulosclerosis in TGF-beta1 transgenic mice. Apoptosis is associated with progressive depletion of podocytes and precedes mesangial expansion. Smad7 protein expression is strongly induced specifically in damaged podocytes of transgenic mice and in cultured murine podocytes treated with TGF-beta. TGF-beta1 and Smad7 each induce apoptosis in podocytes, and their coexpression has an additive effect. Activation of p38 MAP kinase and caspase-3 is required for TGF-beta -mediated apoptosis, but not for apoptosis induced by Smad7. Unlike TGF-beta, Smad7 inhibits nuclear translocation and transcriptional activity of the cell survival factor NF-kappaB. Our results suggest a novel functional role for Smad7 as amplifier of TGF-beta -induced apoptosis in podocytes and a new pathomechanism for podocyte depletion in progressive glomerulosclerosis. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Med, Div Nephrol, Bronx, NY 10461 USA. Univ Manchester, Dept Pathol Sci, Manchester, Lancs, England. NIDDKD, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Mol Genet, Bronx, NY 10467 USA. RP Bottinger, EP (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Med, Div Nephrol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. FU NIDDK NIH HHS [DK56077-01, R01 DK056077, R01 DK060043] NR 27 TC 383 Z9 422 U1 4 U2 17 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP PY 2001 VL 108 IS 6 BP 807 EP 816 DI 10.1172/JCI12367 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 473LB UT WOS:000171044500008 PM 11560950 ER PT J AU Van der Pol, B Martin, DH Schachter, J Quinn, TC Gaydos, CA Jones, RB Crotchfelt, K Moncada, J Jungkind, D Turner, B Peyton, C Kelly, JF Weiss, JB Rosenstraus, M AF Van der Pol, B Martin, DH Schachter, J Quinn, TC Gaydos, CA Jones, RB Crotchfelt, K Moncada, J Jungkind, D Turner, B Peyton, C Kelly, JF Weiss, JB Rosenstraus, M TI Enhancing the specificity of the COBAS AMPLICOR CT/NG test for Neisseria gonorrhoeae by retesting specimens with equivocal results SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID LIGASE CHAIN-REACTION; CHLAMYDIA-TRACHOMATIS; MULTICENTER EVALUATION; SWAB SPECIMENS; URINE; FEMALES; ASSAY AB The COBAS AMPLICOR CT/NG test for Neisseria gonorrhoeae cross-reacts with certain strains of nonpathogenic Neisseria species. In some strains, the target sequence is identical to that of N. gonorrhoeae, whereas other strains have a small number of mismatches within the regions recognized by the primers or probe used in the COBAS AMPLICOR NG test. These cross-reactive strains are occasionally present in urogenital specimens, causing false-positive results in the COBAS AMPLICOR NG test. Analysis of the data generated in a large multicenter clinical trial showed that 2.9% of the specimens gave signals between A(660)s of 0.2 and 3.5 but that one-half of these equivocal specimens did not contain N. gonorrhoeae. Most of these equivocal specimens were correctly classified as true positive or true negative by retesting in duplicate and defining a PCR-positive result as two of three results with an A(660) of greater than or equal to2.0. If specimens had been classified as positive or negative based on a single test result using a cutoff of an A(660) of 0.2, specificity would have ranged from 96.2 to 98.9% depending on specimen type, sex, and presence of symptoms. By employing the equivocal zone-retesting algorithm, specificity increased to 98.6 to 99.9% with little effect (0.1 to 4.9% decrease) on sensitivity in most specimen types, enabling the test to achieve a positive predictive value of at least 90% in populations with a prevalence of 4% or higher. In lower-prevalence populations, the test could be used to screen for presumptive infections that would have to be confirmed by an independent test. C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Louisiana State Univ, Baton Rouge, LA 70803 USA. City New Orleans Delgado Clin, New Orleans, LA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Roche Mol Syst, Pleasanton, CA USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. Thomas Jefferson Univ Hosp, Pittsburgh, PA USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. RP Rosenstraus, M (reprint author), Roche Mol Syst, 1080 US Highway 202 S, Somerville, NJ 08876 USA. RI Gaydos, Charlotte/E-9937-2010 NR 13 TC 43 Z9 43 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD SEP PY 2001 VL 39 IS 9 BP 3092 EP 3098 DI 10.1128/JCM.39.9.3092-3098.2001 PG 7 WC Microbiology SC Microbiology GA 469VV UT WOS:000170837500012 PM 11526134 ER PT J AU Potosky, AL Knopf, K Clegg, LX Albertsen, PC Stanford, JL Hamilton, AS Gilliland, FD Eley, JW Stephenson, RA Hoffman, RM AF Potosky, AL Knopf, K Clegg, LX Albertsen, PC Stanford, JL Hamilton, AS Gilliland, FD Eley, JW Stephenson, RA Hoffman, RM TI Quality-of-life outcomes after primary androgen deprivation therapy: Results from the prostate cancer outcomes study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SUPPRESSION; ORCHIECTOMY; RELIABILITY AB Purpose : To compare health-related quality-of-life outcomes after primary androgen deprivation (AD) therapy with orchiectomy versus luteinizing hormone-releasing hormone (LHRH) agonists for patients with prostate cancer. Patients and Methods: Men (n = 431) newly diagnosed with all stages of prostate cancer from six geographic regions who participated in the Prostate Cancer Outcomes Study and who received primary AD therapy but no other treatments within 12 months of initial diagnosis were included in a study of health outcomes. Comparisons were statistically adjusted for patient sociodemographic and clinical characteristics, timing of therapy, and use of combined androgen blockade. Results: More than half of the patients receiving primary AD therapy had been initially diagnosed with clinically localized prostate cancer. Among these patients, almost two thirds were at high risk of progression on the basis of prognostic factors. Sexual function outcomes were similar by treatment group both before and after implementation of AD therapy. LHRH patients reported more breast swelling than did orchiectomy patients (24.9% v 9.7%, P < .01). LHRH patients reported more physical discomfort and worry because of cancer or its treatment than did orchiectomy patients. LHRH patients assessed their overall health as fair or poor more frequently than did orchiectomy patients (35.4% v 28.1%, P = .01) and also were less likely to consider themselves free of prostate cancer after treatment. Conclusion: Most endocrine-related health outcomes are similar after surgical versus medical primary hormonal therapy. Stage at diagnosis had little effect on outcomes. These results provide representative information comparing surgical and medical AD therapy that may be used by physicians and patients to inform treatment decisions. (C) 2001 by American Society of Clinical Oncology. C1 NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ New Mexico, Hlth Sci Ctr, New Mexico Tumor Registry, Albuquerque, NM 87131 USA. Dept Vet Affairs Med Ctr, Med Serv, Albuquerque, NM USA. Emory Univ, Rollins Sch Publ Hlth, Georgia Ctr Canc Stat, Atlanta, GA 30322 USA. Univ Utah, Dept Surg, Div Urol, Salt Lake City, UT USA. RP Potosky, AL (reprint author), NCI, Appl Res Branch, Div Canc Control & Populat Sci, Execut Plaza N Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-PC-67010, N01-PC-67005, N01-CN-67009, N01-PC-67006, N01-PC-67000, N01-PC-67007] NR 23 TC 154 Z9 154 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD SEP 1 PY 2001 VL 19 IS 17 BP 3750 EP 3757 PG 8 WC Oncology SC Oncology GA 467WW UT WOS:000170727600008 PM 11533098 ER PT J AU Bekersky, I Fielding, RM Dressler, DE Kline, S Buell, DN Walsh, TJ AF Bekersky, I Fielding, RM Dressler, DE Kline, S Buell, DN Walsh, TJ TI Pharmacokinetics, excretion, and mass balance of C-14 after administration of C-14-cholesterol-labeled AmBisome to healthy volunteers SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID LIPOSOMAL AMPHOTERICIN-B; CHOLESTEROL-METABOLISM; UNILAMELLAR; SAFETY; HUMANS; LIPOPROTEINS; FORMULATION; PARAMETERS; CLEARANCE; TOXICITY AB Amphotericin B (AmB) in small unilamellar liposomes (AmBisome) provides higher plasma concentrations and greater safety than the conventional deoxycholate formulation. The authors compared the disposition of the liposome's drug and cholesterol components by measuring AmB and radioactivity in plasma, urine, and fences for 1 week after a single 2-hour infusion of C-14-cholesterol-labeled AmBisome (2 mg/kg, 1 mu Ci/kg) in healthy adults (4 males, 1 female). The plasma profile of C-14-cholesterol differed from that of AmB, locking an initial rapid disappearance phase, having a lower total clearance, and having a volume of distribution (0.13 L/kg) close to that of the plasma compartment. The biphasic disappearance and long plasma half-life (147 h) of C-14-cholesterol were similar to those of other low-clearance liposomes. This and the low clearance of C-14-cholesterol from the plasma compartment suggest that it served as a liposome marker. The plasma drug-lipid ratio fell during the study, showing that AmB was cleared from plasma more rapidly than cholesterol or liposomes and suggesting that the composition of the liposomes changed over time. C-14-radioactivity was recovered mainly in the feces (9.5% of dose), consistent with the catabolism of cholesterol to bile salts. Combined fecal and renal clearances were < 18% of total clearance, suggesting that most of the liposomal drug and lipid remained in the body 1 week after dosing. Thus, AmBisome remains in the circulation for an extended Period of time while releasing AmB, resulting in its markedly altered pharmacokinetic and safety profiles. (C) 2001 the American College of Clinical Pharmacology. C1 Fujisawa Healthcare Inc, Deerfield, IL 60015 USA. Biologist Serv, Boulder, CO USA. NCI, Immunocompromized Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Bekersky, I (reprint author), Fujisawa Healthcare Inc, 3 Pkwy N, Deerfield, IL 60015 USA. NR 27 TC 24 Z9 25 U1 1 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2001 VL 41 IS 9 BP 963 EP 971 DI 10.1177/00912700122010942 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 466TL UT WOS:000170661800006 PM 11549101 ER PT J AU Zhang, YT Goldszal, A Butman, J Choyke, P AF Zhang, YT Goldszal, A Butman, J Choyke, P TI Improving image contrast using principal component analysis for subsequent image segmentation SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE segmentation; contrast-to-noise ratio; principal component analysis ID BRAIN-TUMOR RESPONSE; MR-IMAGES; AUTOMATED SEGMENTATION; TISSUE SEGMENTATION; GRAY-MATTER AB This article presents a technique for improving MR image contrast by linearly combining multiple MR images with different tissue contrast. The weighting coefficients of the linear combination are derived using principal component analysis. The contrast-enhanced composite image is segmented subsequently using gray level-based ID segmentation methods. The technique reduces a multispectral image set to composite eigenimages and allows application of appropriate ID segmentation methods that do not have equivalent counterparts in multispectral methods. C1 NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Zhang, YT (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Rm 1C660, Bethesda, MD 20892 USA. RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 NR 24 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD SEP-OCT PY 2001 VL 25 IS 5 BP 817 EP 822 DI 10.1097/00004728-200109000-00024 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 473MH UT WOS:000171047700024 PM 11584246 ER PT J AU Martinez, A Pio, R Lopez, J Cuttitta, F AF Martinez, A Pio, R Lopez, J Cuttitta, F TI Expression of the adrenomedullin binding protein, complement factor H, in the pancreas and its physiological impact on insulin secretion SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID BETA-CELLS; GENE; LOCALIZATION; RESISTANCE; ACTIVATION; PEPTIDE AB Adrenomedullin (AM) is a ubiquitous peptide hormone which, among other functional roles, reduces insulin secretion in the pancreas. Recently we have described the interaction between AM and the complement regulator protein factor H, which results in mutual modulation of their respective functions. Here we identify the expression of factor H in the beta cells of the rat pancreatic islets by immunohistochemistry and multiple immunofluorescence followed by confocal microscopy. In addition, double immunogold staining under the electron microscope showed coexistence of insulin and factor H immunoreactivities within the same secretory granules; interestingly, factor H staining was found in the electron-lucent haloes whereas the insulin antibody labeled preferentially the dense cores. The existence of factor H mRNA in the pancreas was confirmed by RT-PCR and in situ hybridization. The function of factor H in the pancreas was investigated with an insulin secretion assay. Addition of factor H to freshly isolated islets in the presence of AM resulted in a further reduction in insulin secretion with a concomitant elevation of cAMP, suggesting that factor H increases AM function in glucose homeostasis. The expression of factor H in the pancreas may play other important roles such as protection against complement-mediated cell lysis. C1 NCI, Dept Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. Univ Autonoma Madrid, Dept Biol, Cell Biol Unit, Madrid, Spain. RP Martinez, A (reprint author), NCI, Dept Cell & Canc Biol, NIH, Bldg 10,Room 13N262,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Martinez, Alfredo/A-3077-2013; Pio, Ruben/F-5353-2017 OI Martinez, Alfredo/0000-0003-4882-4044; Pio, Ruben/0000-0002-6831-6111 FU NIDDK NIH HHS [DK41301] NR 26 TC 19 Z9 19 U1 0 U2 3 PU SOC ENDOCRINOLOGY PI BRISTOL PA 17/18 THE COURTYARD, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4NQ, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD SEP PY 2001 VL 170 IS 3 BP 503 EP 511 DI 10.1677/joe.0.1700503 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 472PB UT WOS:000170991700002 PM 11524230 ER PT J AU Engel, LS Seixas, NS Keifer, MC Longstreth, WT Checkoway, H AF Engel, LS Seixas, NS Keifer, MC Longstreth, WT Checkoway, H TI Validity study of self-reported pesticide exposure among orchardists SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE agriculture; occupational exposure; pesticides; recall; reproducibility of results; validity ID WORK HISTORIES; OCCUPATIONAL EXPOSURE; QUESTIONNAIRE; INTERVIEW; COHORT AB Self-reported work histories are often the only means of estimating occupational exposures in epidemiologic research. The objective of this study was to examine the accuracy of recall of historical pesticide use among orchardists. All 185 orchardists in this study had participated previously in a cohort study of men occupationally exposed to pesticides. In that study (1972 to 1976), subjects were interviewed annually and asked to list pesticides used since the last interview. In 1997, 265 of the 440 presumed-living orchardists from the original cohort were successfully recontacted and asked to complete a detailed questionnaire concerning their lifetime use of pesticides; 185 (69.8% of farmers successfully contacted) agreed. Considering the 1972-1976 data as the standard, sensitivity and specificity of recall were calculated for certain pesticides and pesticide categories. Sensitivity of recall was good to excellent (0.6-0.9) fur the broad categories of insecticides, herbicides, and fungicides, for heavily used chemical classes, such as organophosphates and organochlorines, and for commonly used pesticides; it was lower and more variable (0.1-0.6) for specific pesticides. Recall specificity was greatest (0.7-0.9) for the least used pesticides and chemical classes, such as dithiocarbamates and manganese-containing pesticides, and was generally modest for the rest (0.5-0.6). There was no evidence of selection bias between study participants and nonparticipants. In conclusion, recall accuracy was good for commonly used pesticides and pesticide categories. This level of recall accuracy is probably adequate for epidemiologic analyses of broad categories of pesticides, but is a limitation for detecting more specific associations. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Engel, LS (reprint author), NCI, Occupat Epidemol Branch, 6120 Execut Blvd,Room 8113, Bethesda, MD 20892 USA. FU NIEHS NIH HHS [ES07262]; PHS HHS [U07/CCU012926-02] NR 19 TC 31 Z9 32 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD SEP-OCT PY 2001 VL 11 IS 5 BP 359 EP 368 DI 10.1038/sj.jea.7500176 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 485VB UT WOS:000171783700003 PM 11687909 ER PT J AU Yamano, S Scott, DE Huang, LY Mikolajczyk, M Pillemer, SR Chiorini, JA Golding, B Baum, BJ AF Yamano, S Scott, DE Huang, LY Mikolajczyk, M Pillemer, SR Chiorini, JA Golding, B Baum, BJ TI Protection from experimental endotoxemia by a recombinant adeno-associated virus encoding interleukin 10 SO JOURNAL OF GENE MEDICINE LA English DT Article DE adeno-associated virus; cytokines; gene transfer; immunotherapy; immunoregulation ID TUMOR-NECROSIS-FACTOR; TERM GENE-TRANSFER; ADENOASSOCIATED VIRUS; SEPTIC SHOCK; IMMUNE-RESPONSES; IFN-GAMMA; VECTORS; MICE; MUSCLE; EXPRESSION AB Background Interleukin 10 (IL-10) is a homodimeric cytokine that shows considerable clinical promise. Adeno-associated virus (AAV) vectors appear increasingly useful for in vivo gene-transfer applications. Methods A recombinant AAV type 2 vector encoding human IL-10 (rAAVhIL10) was constructed by using an adenoviral-free, three-plasmid co-transfection. Cytokine production was measured by using an enzyme-linked immunosorbent assay. Endotoxic shock was induced by lipopolysaccharide (LPS) injection. Results As media from rAAVhIL10-infected COS cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout (KO) mice challenged with Brucella abortus, it was clear that vector-derived hIL-10 was biologically active in vitro. Intravenous or intramuscular administration of relatively modest levels of rAAVhIL10 (10(10) genomes) to IL-10 KO mice resulted in hIL-10 secretion into the bloodstream, which at 8, weeks, gave median serum levels of 0.9 and 0.45 pg/ml, respectively. Acute endotoxic shock led to a 33% mortality rate, and severe morbidity, in control IL-10 KO mice, whereas no mortality and little morbidity were seen in IL-10 KO mice given rAAVhIL10 7 weeks earlier. Conclusions The findings demonstrate that a modest dose of rAAVhIL10 administered in vivo provides long-term protection against LPS-induced endotoxic shock in a murine model. Thus, this vector may be useful for clinical applications requiring sustained IL-10 expression, for example in the treatment of several autoimmune diseases. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Yamano, S (reprint author), NIDCR, GTTB, NIH, 10 Ctr Dr,MSC 1190,Bldg 10,Room 1A01, Bethesda, MD 20892 USA. OI Yamano, Seiichi/0000-0003-2056-4359 NR 55 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD SEP-OCT PY 2001 VL 3 IS 5 BP 450 EP 457 DI 10.1002/jgm.213 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 479LZ UT WOS:000171407000005 PM 11601758 ER PT J AU Kobayashi, T Kida, Y Kaneko, T Pastan, I Kobayashi, K AF Kobayashi, T Kida, Y Kaneko, T Pastan, I Kobayashi, K TI Efficient ablation by immunotoxin-mediated cell targeting of the cell types that express human interleukin-2 receptor depending on the internal ribosome entry site SO JOURNAL OF GENE MEDICINE LA English DT Article DE cell targeting; internal ribosome entry site; recombinant immunotoxin; transgene expression ID RESISTANCE GENE MDR1; ENCEPHALOMYOCARDITIS VIRUS; TRANSGENIC MICE; IN-VIVO; RECOMBINANT IMMUNOTOXIN; RETROVIRAL COEXPRESSION; PSEUDOMONAS EXOTOXIN; CULTURED-CELLS; MESSENGER-RNA; TRANSLATION AB Background Immunotoxin-mediated cell targeting (IMCT) is a technique for conditional genetic ablation of specific cell types. IMCT provides a useful approach for generating animal models for human neurodegenerative disorders. The strategy of IMCT depends on the cytotoxic activity of anti-Tac-based recombinant immunotoxins that selectively target cells expressing the human interleukin-2 receptor alpha -subunit (IL-2R alpha). Transgenic mice were generated that express the IL-2R alpha under the control of an appropriate tissue specific gene promoter, and they were treated with the recombinant immunotoxins resulting in the ablation of the target cell types. To restrict the expression of IL-2R alpha transgene in the cell types of interest, it is useful to knock-in the IL-2R alpha expression cassette into the specific marker gene locus with gene targeting. Moreover, the knock-in of the IL-2R alpha cassette located downstream of an internal ribosome entry site (IRES) into the 3'-untranslated region of the marker gene enables IL-2R alpha expression in the restricted cell types while preserving the intact marker gene expression. However, there is a possibility that IRES-dependent expression of the receptor may be less efficient than cap-dependent expression. Methods and results The efficiency of IRES-dependent IL-2R alpha expression and immunotoxin responsiveness of the cells expressing the receptor were examined. The IL-2R alpha gene fused to green fluorescence protein (GFP) (IL-2R/GFP) was used as the target receptor. Embryonic stem cell clones were isolated that carry two types of bicistronic vectors in which the IL-2R/GFP fusion gene or the chloramphenicol acetyltransferase gene was connected upstream or downstream of IRES. The expression level of IL-2R/GFP protein in the cell clones was evaluated by GFP fluorescence detection and Western blot analysis. The IRES-dependent expression produced the same level of receptor protein as cap-dependent expression. The immunotoxin responsiveness of the cloned cells was evaluated by measuring the colony-forming efficiency in medium containing various amounts of a recombinant immunotoxin. The colony-forming efficiency of the cells expressing IL-2R/GFP through IRES-dependent expression was reduced together with increasing immunotoxin concentration in a similar dose-dependent manner to the cells expressing the receptor through cap-dependent expression. Conclusions The present results indicate that it is possible to effectively use the IRES-dependent expression system for IMCT. The system permits expression of the target receptor in selective cell types by introducing the IRES-driven expression cassette into the 3'-untranslated region of the marker gene locus. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Fukushima Med Univ, Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima 9601295, Japan. Kyoto Univ, Grad Sch Med, Dept Morphol Brain Sci, Kyoto 6068501, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Kobayashi, K (reprint author), Fukushima Med Univ, Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima 9601295, Japan. NR 33 TC 5 Z9 5 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD SEP-OCT PY 2001 VL 3 IS 5 BP 505 EP 510 DI 10.1002/jgm.208 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 479LZ UT WOS:000171407000011 PM 11601764 ER PT J AU Johnson, TR Fischer, JE Graham, BS AF Johnson, TR Fischer, JE Graham, BS TI Construction and characterization of recombinant vaccinia viruses co-expressing a respiratory syncytial virus protein and a cytokine SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTE; MEDIATED IMMUNE-RESPONSES; ATTACHMENT G-PROTEIN; G-GLYCOPROTEIN; IN-VIVO; PULMONARY EOSINOPHILIA; GAMMA-INTERFERON; INFLUENZA-VIRUS; APPROPRIATE RESPONSES; F-GLYCOPROTEIN AB Recombinant vaccinia viruses are well I-characterized tools that can be used to define novel approaches to vaccine formulation and delivery. While vector co-expression of immune mediators has enormous potential for optimizing the composition of vaccine-induced immune responses, the impact on antigen expression and vector antigenicity must also be considered. Co-expression of IL-4 increased vaccinia virus vector titres, while IFN-gamma co-expression reduced vaccinia virus replication in BALB/c mice and in C57BL/6 mice infected with some recombinant viruses. Protection against respiratory syncytial virus (RSV) challenge was similar in mice immunized with vaccinia virus expressing RSV G glycoprotein and IFN-gamma, even though the replication efficiency of the vector was diminished. These data demonstrate the ability of vector-expressed cytokine to influence the virulence of the vector and to direct the development of selected immune responses. This suggests that the co-expression of cytokines and other immunomodulators has the potential to improve the safety of vaccine vectors while improving the immunogenicity of vaccine antigens. C1 Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 2502,40 Convent Dr,MSC 3017, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R01-AI-33933, R01-AI-37216] NR 60 TC 17 Z9 17 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 2001 VL 82 BP 2107 EP 2116 PN 9 PG 10 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 467MF UT WOS:000170707800009 PM 11514719 ER PT J AU Sharpe, S Polyanskaya, N Dennis, M Sutter, G Hanke, T Erfle, V Hirsch, V Cranage, M AF Sharpe, S Polyanskaya, N Dennis, M Sutter, G Hanke, T Erfle, V Hirsch, V Cranage, M TI Induction of simian immunodeficiency virus (SIV)-specific CTL in rhesus macaques by vaccination with modified vaccinia virus Ankara expressing SIV transgenes: influence of pre-existing anti-vector immunity SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; RECOMBINANT VACCINIA; ENVELOPE GLYCOPROTEIN; IMMUNIZATION; PROTECTION; REPLICATION; CHALLENGE; INFECTION; MONKEYS; CELLS AB A major aim in AIDS vaccine development is the definition of strategies to stimulate strong and durable cytotoxic T lymphocyte (CTL) responses. Here we report that simian immunodeficiency virus (SIV)-specific CTL developed in 4/4 macaques following a single intramuscular injection of modified vaccinia virus Ankara (MVA) constructs expressing both structural and regulatory/ accessory genes of SIV. In two animals Nef-specific responses persisted, but other responses diminished and new responses were not revealed, following further vaccination. Vaccination of another two macaques, expressing Mamu A*O1 MHC class I, with MVA constructs containing nef and gag-pol under the control of the moderate strength natural vaccinia virus early/late promoter P7.5, again induced an early Nef-specific response, whereas responses to Gag remained undetectable. Anti-vector immunity induced by this immunization was shown to prevent the efficient stimulation of CTL directed to the cognate Gag epitope, p1 1C C-M, following vaccination with another MVA construct expressing SIV Gag-Pol under a strong synthetic vaccinia virus-specific promoter. In contrast, vaccination of a previously unexposed animal resulted in a SIV-specific CTL response widely disseminated in lymphoid tissues including lymph nodes associated with the rectal and genital routes of SIV entry. Thus, despite the highly attenuated nature of MVA, repeated immunization may elicit sufficient anti-vector immunity to limit the effectiveness of later vaccination. C1 Ctr Appl Microbiol & Res, CAMR, Salisbury SP4 0JG, Wilts, England. GSF Forschungszentrum Umwelt & Gesundheit GMBH, Inst Mol Virol, D-85764 Munich, Germany. Inst Mol Med, Human Immunol Unit, MRC, Oxford OX3 9DS, England. NIAID, Mol Microbiol Lab, Rockville, MD 20852 USA. RP Sharpe, S (reprint author), Ctr Appl Microbiol & Res, CAMR, Salisbury SP4 0JG, Wilts, England. NR 39 TC 59 Z9 59 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AE, BERKS, ENGLAND SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD SEP PY 2001 VL 82 BP 2215 EP 2223 PN 9 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 467MF UT WOS:000170707800022 PM 11514732 ER PT J AU Myslobodsky, M Lalonde, FM Hicks, L AF Myslobodsky, M Lalonde, FM Hicks, L TI Are patients with Parkinson's disease suicidal? SO JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY LA English DT Article; Proceedings Paper CT Neuroscience Meeting CY NOV, 2000 CL NEW ORLEANS, LOUISIANA ID SUPPLEMENTARY MOTOR AREA; UNILATERAL DOPAMINE DEFICIT; MORTALITY DATA; DEPRESSION; RISK; IMPULSIVITY; DISORDERS; CORTEX AB Using the National Center of Health Statistics' mortality statistics databases for 1991 through 1996 (12,430,473 deaths), we isolated 144,364 individuals 40 years of age or older with a primary diagnosis of Parkinson's disease (PD). Of these, 122 died by suicide. The rate of suicide in the general population was about 10 times higher than in patients with PD (0.8% compared with only 0.08%, respectively). These different rates of suicide cannot be attributed to differences in age, gender, race, education, or marital status. Compared with patients with suicidal PD, patients with PD who died from other causes manifested significantly lower rates of affective disorders. The referent population exhibited a higher rate of malignancy and a lower rate of depression. The findings suggest that marital status, mood disorder, and somatic comorbidity provide only a limited understanding of completed suicide. C1 NIMH, Geriatr Psychiat Branch, NIH, Bethesda, MD 20892 USA. Howard Univ, Dept Psychol, Washington, DC 20059 USA. NIMH, Cerebral Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Arts & Sci, Washington, DC USA. RP Lalonde, FM (reprint author), NIMH, Geriatr Psychiat Branch, NIH, 10 Ctr Dr,Room 3N228, Bethesda, MD 20892 USA. NR 45 TC 51 Z9 51 U1 0 U2 4 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 0891-9887 J9 J GERIATR PSYCH NEUR JI J. Geriatr. Psychiatry Neurol. PD FAL PY 2001 VL 14 IS 3 BP 120 EP 124 DI 10.1177/089198870101400304 PG 5 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 470WL UT WOS:000170894200003 PM 11563434 ER PT J AU Kreps, GL AF Kreps, GL TI Consumer/provider communication research: A personal plea to address issues of ecological validity, relational development, message diversity and situational constraints SO JOURNAL OF HEALTH PSYCHOLOGY LA English DT Editorial Material C1 NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Kreps, GL (reprint author), NCI, Hlth Commun & Informat Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4084,6130 Execut Blvd,MSC 736, Bethesda, MD 20892 USA. NR 17 TC 11 Z9 11 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 6 BONHILL STREET, LONDON EC2A 4PU, ENGLAND SN 1359-1053 J9 J HEALTH PSYCHOL JI J. Health Psychol. PD SEP PY 2001 VL 6 IS 5 BP 597 EP 601 PG 5 WC Psychology, Clinical SC Psychology GA 487FF UT WOS:000171862400011 PM 22049456 ER PT J AU Loreto, ELD Valente, VLD Zaha, A Silva, JC Kidwell, MG AF Loreto, ELD Valente, VLD Zaha, A Silva, JC Kidwell, MG TI Drosophila mediopunctata P elements: A new example of horizontal transfer SO JOURNAL OF HEREDITY LA English DT Article ID TRANSPOSABLE ELEMENTS; HOMOLOGOUS SEQUENCES; SPECIES GROUPS; MELANOGASTER; EVOLUTION; GENOME; IDENTIFICATION; WILLISTONI; BIFASCIATA; OBSCURA AB Sequences homologous to the P element of Drosophila melanogaster were previously identified in Drosophila mediopunctata, a member of the tripunctata group, subgenus Drosophila. We report here that the P element is present in about three to five copies in the D. mediopunctata genome. While one of the insertion sites appears to be fixed, others may be polymorphic, indicating relatively recent P element activity. Phylogenetic analysis revealed that the D. mediopunctata element belongs to the canonical subfamily of P elements and that divergence of the D. mediopunctata element from other members of this subfamily ranges from 2% to 5% at the nucleotide level. This is the first report of a canonical P element outside the subgenus Sophophora. Based primarily on the striking incongruence between P element and host species phylogenies, the presence of a canonical P element in D. mediopunctata is most likely explained by horizontal transfer between species. C1 Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA. Univ Fed Santa Maria, Dept Biol, BR-97105900 Santa Maria, RS, Brazil. Univ Fed Rio Grande Sul, Dept Mol Biol & Biotechnol, Porto Alegre, RS, Brazil. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD USA. RP Kidwell, MG (reprint author), Univ Arizona, Dept Ecol & Evolutionary Biol, Tucson, AZ 85721 USA. RI Valente, Vera/N-9031-2013 NR 29 TC 16 Z9 16 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD SEP-OCT PY 2001 VL 92 IS 5 BP 375 EP 381 DI 10.1093/jhered/92.5.375 PG 7 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 505PY UT WOS:000172925800001 PM 11773243 ER PT J AU Margalith, M Levy, E Rinaldo, CR Detels, R Phair, J Kaslow, R Saah, AJ Sarov, B AF Margalith, M Levy, E Rinaldo, CR Detels, R Phair, J Kaslow, R Saah, AJ Sarov, B TI HIV-1 IgA specific serum antibodies and disease progression during HIV-1 infection SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE HIV-1 IgA serum antibodies; viral load; CD4 cells ID HUMAN-IMMUNODEFICIENCY-VIRUS; HOMOSEXUAL MEN; SERONEGATIVE PARTNERS; PAROTID-SALIVA; BREAST-MILK; AIDS; SECRETIONS; TYPE-1; WOMEN; ANTIGENS AB Objective: To evaluate the role of serum human immunodeficiency virus type I immunoglobulin A (HIV-1 IgA) antibodies in the progression of HIV-1 infection in relation to viral load and CD4 cell counts. Methods: Sequential serum specimens were obtained from 218 homosexual men: 123 HIV-1 seropositives, 24 HIV-1 seroconverters, and 71 HIV-1 seronegatives. HIV-1 IgA antibodies were tested blindly by enzyme-linked immunosorbent assay and Western blot. T-lymphocyte subsets were measured by flow cytometry. Viral plasma load was determined by a sensitive branched DNA assay. Results: HIV-1 IgA antibodies with a titer greater than or equal to 50 were detected among 50% of the seroconverters, 27% of the HIV-1-seropositive asymptomatic subjects, 25% of lymphadenopathy, and 23% of HIV-1-related symptomatic subjects. Among patients with the acquired immune deficiency syndrome, the prevalence of virus-specific IgA antibodies (55%) was significantly higher (p < 0.03) as compared with the HIV-1-seropositive asymptomatic subjects, lymphadenopathy and HIV-1-related symptomatic patients, but not versus the seroconverters (p = 0.8). IgA antibodies to HIV-1 gP160 were the most prevalent among all subjects tested. A significant decrease in CD4 cell counts was observed after HIV-1 seroconversion. Viral load was slightly higher among the seroconverters who demonstrated higher (&GE;50) HIV-1 IgA levels. Conclusions: HIV-1 IgA serum antibodies did not predict the progression of the disease. Correlation between HIV-1 IgA antibodies titer, viral load, and CD4 cell counts was not detected. C1 Ben Gurion Univ Negev, Fac Hlth Sci, Dept Virol, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Epidemiol Unit, Beer Sheva, Israel. Johns Hopkins Sch Hyg & Publ Hlth, MACS, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Evanston, IL 60208 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Margalith, M (reprint author), Ben Gurion Univ Negev, Fac Hlth Sci, Dept Virol, POB 653, IL-84105 Beer Sheva, Israel. FU NCRR NIH HHS [5-M01-RR00052]; NIAID NIH HHS [UO1-AI-35040, UO1-AI-37984, UO1-AI-35042, UO1-AI-35041, UO1-AI-37613, UO1-AI-35043, UO1-AI-35039] NR 38 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD SEP-OCT PY 2001 VL 4 IS 5 BP 269 EP 277 PG 9 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 536RU UT WOS:000174716300005 PM 11907384 ER PT J AU Goldenberg, I Grossman, E Jacobson, KA Shneyvays, V Shainberg, A AF Goldenberg, I Grossman, E Jacobson, KA Shneyvays, V Shainberg, A TI Angiotensin II-induced apoptosis in rat cardiomyocyte culture: a possible role of AT(1) and AT(2) receptors SO JOURNAL OF HYPERTENSION LA English DT Article DE angiotensin II; AT(1) and AT(2) receptors; apoptosis; cardiomyocytes; Ca2+ concentration ID SPONTANEOUSLY HYPERTENSIVE RATS; MYOCYTE CELL-DEATH; CONVERTING-ENZYME; CARDIAC MYOCYTES; TYPE-2 RECEPTOR; HEART-FAILURE; IN-VITRO; HYPERTROPHY; DYSFUNCTION; ACTIVATION AB Objectives To investigate the mechanism of angiotensin II-induced apoptosis in cultured cardiomyocytes by determining which receptor subtype is involved, and what is the relationship between intracellular Ca2+ changes and apoptosis. Design and methods Neonatal rat cardiomyocytes were pretreated with either the AT(1) antagonist irbesartan or the AT(2) antagonist PD123319 before exposure to angiotensin Il. Apoptotis was evaluated using morphological technique, staining nuclei by Feulgen and Hoechst methods followed by image analysis and by in situ terminal deoxynucleotidyl transferase nick-end (TUNEL) labelling. TUNEL-positive cardiocytes were distinguished from other cells by double staining with a-sarcomeric actin. Intracellular Ca2+ changes were assessed by indo-1 fluorescence microscopy, and the effect of Ca2+ on angiotensin II-induced apoptosis was tested using the calcium channel blocker verapamil. Results Exposure to angiotensin II (110 nmol/l) resulted in cell replication and a three-fold increase in programmed cell death (P < 0.05). Pretreatment with either irbesartan (an AT(1) receptor antagonist, 100 nmol/l) or PD123319 (an AT(2) receptor antagonist, 1 mu mol/l) prevented the angiotensin II-induced apoptosis, indicating the presence of both AT(1) and AT(2) receptors on cardiomyocytes. Exposure of myocytes to angiotensin II caused an immediate and dose-dependent increase in the concentration of intracellular free Ca2+ that lasted 40-60 s. The effect was sustained in a Ca2+ free medium. Pretreatment of cells with irbesartan (100 nmol/l) and PD123319 (10 mu mol/l) blocked Ca2+ elevation. Pretreatment with verapamil (10 lamol/1) prevented angiotensin II-induced apoptosis. Conclusions Angiotensin II-induced apoptosis in rat cardiomyocytes is mediated through activation of both AT(1) and AT(2) receptors. The apoptotic mechanism is not related to the immediate angiotensin II-induced Ca2+ rise from intracellular stores. However, it is accompanied by cardiomyocyte proliferation and requires Ca2+ influx through L-type channel activity. (C) 2001 Lippincott Williams & Wilkins. C1 Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. Bar Ilan Univ, Fac Life Sci, Gonda Goldschmied Med Diagnost Res Ctr, Ramat Gan, Israel. NIH, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Grossman, E (reprint author), Chaim Sheba Med Ctr, IL-52621 Tel Hashomer, Israel. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 37 TC 44 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD SEP PY 2001 VL 19 IS 9 BP 1681 EP 1689 DI 10.1097/00004872-200109000-00022 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 469VP UT WOS:000170837000022 PM 11564990 ER PT J AU Ishii, KJ Suzuki, K Coban, C Takeshita, F Itoh, Y Matoba, H Kohn, LD Klinman, DM AF Ishii, KJ Suzuki, K Coban, C Takeshita, F Itoh, Y Matoba, H Kohn, LD Klinman, DM TI Genomic DNA released by dying cells induces the maturation of APCs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; DENDRITIC CELLS; BACTERIAL-DNA; CPG MOTIFS; IMMUNE-RECOGNITION; INNATE IMMUNITY; APOPTOTIC CELLS; ACTIVATION; TOLERANCE; NUCLEUS AB Mature APCs play a key role in the induction of Ag-specific immunity. This work examines whether genomic DNA released by dying cells provides a stimulus for APC maturation. Double-stranded but not single-stranded genomic DNA triggered APC to up-regulate expression of MHC class I/II and various costimulatory molecules. Functionally, dsDNA enhanced APC function in vitro and improved primary cellular and humoral immune responses in vivo. These effects were dependent on the length and concentration of the dsDNA but were independent of nucleotide sequence. The maturation of APC induced by dsDNA may promote host survival by improving immune surveillance at sites of tissue injury/infection. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A Rm 3 D 10, Bethesda, MD 20892 USA. EM Klinman@CBER.FDA.GOV RI Coban, Cevayir/B-2129-2012; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 36 TC 153 Z9 163 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 SEP 1 PY 2001 VL 167 IS 5 BP 2602 EP 2607 PG 6 WC Immunology SC Immunology GA 496JE UT WOS:000172391800023 PM 11509601 ER PT J AU Kuhns, DB Nelson, EL Alvord, WG Gallin, JI AF Kuhns, DB Nelson, EL Alvord, WG Gallin, JI TI Fibrinogen induces IL-8 synthesis in human neutrophils stimulated with formyl-methionyl-leucyl-phenylalanine or leukotriene B-4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; INFLAMMATORY RESPONSE; CHEMOTACTIC FACTOR; PEPTIDE RECEPTOR; HUMAN MONOCYTES; MODULATION; GENERATION; EXPRESSION; RELEASE AB Human exudative neutrophils have greatly increased stores of the neutrophil chemoattractant IL-8 compared with peripheral blood cells, but the mechanism for the increase is not defined. In this report, we show that treatment of peripheral blood neutrophils with the chemotactic peptide fMLP or with leukotriene B-4 or fibrinogen results in little increase in the production of IL-8 by peripheral blood neutrophils. However, a chemotactically active dose of fMLP (5 X 10(-9) M) or leukotriene B-4 (1 X 10(-7) M) in the presence of a physiological concentration (2 mg/ml) of fibrinogen results in a receptor-mediated, pertussis toxin-sensitive, synergistic 30-fold increase in IL-8 synthesis. The levels of IL-8 attained are comparable to those observed in exudative cells. Higher concentrations of fMLP (1 X 10(-7) M) are associated with reduced IL-8 protein synthesis without IL-8 degradation, indicating a sensitive regulatory mechanism for IL-8 production. Treatment of neutrophils with fibrinogen and fMLP resulted in minimal changes in the steady state levels of mRNA for macrophage inflammatory protein-1 alpha and -1 beta and monocyte chemoattractant protein-1. In contrast, in the presence of fibrinogen, the steady-state level of neutrophil IL-8 mRNA increased 8-fold with 5 X 10(-9) M fMLP but was not decreased with 1 X 10(-7) M fMLP, suggesting that neutrophils are specifically adapted to modulate neutrophil IL-8 synthesis through transcriptional and posttranscriptional mechanisms. The data indicate that fibrinogen can function not only as a substrate in the clotting cascade, but also as an important effector during the evolution of the innate immune response. C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. SAIC, Clin Serv Program, Frederick, MD 21702 USA. Natl Canc Inst, Data Management Serv, Frederick, MD 21702 USA. RP Gallin, JI (reprint author), NIAID, Host Def Lab, Bldg 10,Room 11N107, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 29 TC 40 Z9 42 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 1 PY 2001 VL 167 IS 5 BP 2869 EP 2878 PG 10 WC Immunology SC Immunology GA 496JE UT WOS:000172391800056 PM 11509634 ER PT J AU Mocellin, S Wang, E Marincola, FM AF Mocellin, S Wang, E Marincola, FM TI Cytokines and immune response in the tumor microenvironment SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE cytokine; tumor; immune response; immunotherapy ID GROWTH-FACTOR-BETA; RENAL-CELL CARCINOMA; CD8(+) T-CELLS; ANTIGEN-PRESENTING CELLS; NECROSIS-FACTOR-ALPHA; MHC CLASS-II; ACTIVE SPECIFIC IMMUNOTHERAPY; TRANSIT MELANOMA METASTASES; INTERFERON-GAMMA-PRODUCTION; COLONY-STIMULATING FACTOR AB Over the last few decades a wealth of evidence has been gathered on the potential role that the immune system (IS) can play in the fight against cancer. Together with cell surface adhesion molecules, cytokines (CKs) mediate the activities of IS cells. Therefore, CK kinetics may represent a mirror of the immunologic phenomena occurring in the tumor microenvironment, where immune and malignant cells interact. Yet, CKs are currently used in a clinical setting to polarize the immune response against cancer. Despite the large amount of information available on IS physiology. little is known about the role of CKs in modulating the effectiveness of immunotherapy clinical trials aimed at the treatment of patients with cancer. This underscores our relative ignorance about the complex cascade of events that lead to tumor rejection. Here, we review the properties of some CKs believed to be particularly relevant to tumor immunology (i.e.. interleukin [IL]-10, transforming growth factor-beta, interferon-gamma. IL-2, IL-4, and IL-12). We summarized the experience gained with these CKs in vitro, in animal models. and in human beings to illustrate the achievements, the controversies, and the challenges that characterize this fascinating field of oncology. In addition, we added a short section in which a broad view of CKs released in the tumor microenvironment is proposed to underline the variety of factors that contribute to the complexity of tumor-IS interactions. C1 NCI, Surg Branch, NIH, Bethesda, MD 20814 USA. NCI, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20814 USA. RP Marincola, FM (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B58,10 Ctr Dr, Bethesda, MD 20814 USA. NR 218 TC 147 Z9 150 U1 3 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD SEP-OCT PY 2001 VL 24 IS 5 BP 392 EP 407 DI 10.1097/00002371-200109000-00002 PG 16 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 488TQ UT WOS:000171952100002 PM 11696695 ER PT J AU Pikis, A Campos, JM Rodriguez, WJ Keith, JM AF Pikis, A Campos, JM Rodriguez, WJ Keith, JM TI Optochin resistance in Streptococcus pneumoniae: Mechanism, significance, and clinical implications SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Pediatric-Academic-Societies and American Academy of Pediatrics Joint Meeting CY MAY, 2000 CL BOSTON, MASSACHUSETTS SP Pediat Acad Soc ID F1F0 ATP SYNTHASE; ESCHERICHIA-COLI; SUBUNIT-C; ALPHA-SUBUNIT; DNA-PROBE; IDENTIFICATION; MUTATION; PNEUMOCOCCUS; WASHINGTON; ATPASES AB Traditionally, Streptococcus pneumoniae is identified in the laboratory by demonstrating susceptibility to optochin. Between 1992 and 1998, 4 pneumococcal isolates exhibiting optochin resistance were recovered from patients at Children's National Medical Center. Three of the 4 isolates consisted of mixed populations of optochin-resistant and -susceptible organisms. Both subpopulations had identical antibiograms, serotypes, and restriction fragment profiles. The other isolate was uniformly resistant to optochin. Resistant strains had MICs of optochin 4-30-fold higher than susceptible strains, belonged to different serotypes, and had dissimilar restriction fragment profiles, indicating clonal unrelatedness. Resistance arose from single point mutations in either the a-subunit (W206S) or the c-subunit (G20S, M23I, and A49T) of H+-ATPase. There is speculation of a possible association between exposure to antimalarial drugs and evolution of optochin resistance. alpha -Hemolytic streptococci resistant to optochin, particularly invasive isolates, should be tested for bile solubility or with an S. pneumoniae DNA probe before identification as viridans streptococci. C1 Natl Inst Dent & Craniofacial Res, Vaccine & therapeut Dev Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Infect Dis, Washington, DC 20010 USA. Childrens Natl Med Ctr, Dept Lab Med, Washington, DC 20010 USA. George Washington Univ, Med Ctr, Dept Pediat, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Microbiol Trop Med, Washington, DC 20037 USA. RP Pikis, A (reprint author), Natl Inst Dent & Craniofacial Res, Vaccine & therapeut Dev Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Rm 528,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. NR 37 TC 44 Z9 51 U1 0 U2 9 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 SEP 1 PY 2001 VL 184 IS 5 BP 582 EP 590 DI 10.1086/322803 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 462PR UT WOS:000170429400009 PM 11474432 ER PT J AU Sarangarajan, R Budev, A Zhao, Y Gahl, WA Boissy, RE AF Sarangarajan, R Budev, A Zhao, Y Gahl, WA Boissy, RE TI Abnormal translocation of tyrosinase and tyrosinase-related protein 1 in cutaneous melanocytes of Hermansky-Pudlak syndrome and in melanoma cells transfected with anti-sense HPS1 cDNA SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE albinism; hypopigmentation; trafficking ID VESICLE FORMATION; GENE; MELANOSOMES; MUTATIONS AB Hermansky-Pudlak syndrome is an autosomal recessive disorder characterized by oculocutaneous albinism, a bleeding disorder, and, in some patients, ceroid storage and progressive lung disease. Although Hermansky-Pudlak syndrome exhibits locus heterogeneity, most patients have mutations in the HPS1 gene. Melanocytes in the basal epithelial layer of skin from patients with different mutations in the HPS1 gene exhibited occasional large complexes containing dihydroxyphenylalanine-positive cisterna and 50 nm vesicles. To characterize the role of the HPS1 protein in cells, human HPS1 cDNA was transfected into pigmented SK-MEL-188 melanoma cells (M-188) in either the sense (S-188) or the antisense (A-188) orientation. Expression of the 79 kDa HPS1 protein (in M-188 and S-188 cells) or lack of expression (in A-188 cells) was confirmed by Western blotting using two HPS1-protein-specific polyclonal. antibodies. Significant reduction in expression of HPS1 protein in A-188 cells resulted in a significant decrease in tyrosinase activity and melanin content compared with M-188 and S-188 cells using an intact cell assay for tyrosinase. In contrast, tyrosinase activities in cell lysates of M-188, S-188, and A-188 cells were not significantly different. Knockout of HPS1 protein expression in A-188 cells caused both tyrosinase and tyrosinase-related protein 1 to be localized to large granular complexes in the cell cytosol and dendrites. Electron microscope analysis of the A-188 cells revealed that absence of HPS1 protein resulted in the deposition of dihydroxyphenylalanine reaction products (i.e., tyrosinase) confined to large membrane-bound structures with limiting membranes. We conclude that lack of HPS1 protein expression results in mistranslocation of tyrosinase and tyrosinase-related protein 1 to large granular complexes rather than melanosomes, compromising melanin synthesis. C1 Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH 45267 USA. NICHHD, NIH, Heritable Disorders Branch, Sect Human Biochem Genet, Bethesda, MD USA. RP Boissy, RE (reprint author), Univ Cincinnati, Coll Med, Dept Dermatol, POB 670592, Cincinnati, OH 45267 USA. NR 12 TC 16 Z9 17 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD SEP PY 2001 VL 117 IS 3 BP 641 EP 646 DI 10.1046/j.0022-202x.2001.01435.x PG 6 WC Dermatology SC Dermatology GA 473BJ UT WOS:000171019200011 PM 11564171 ER PT J AU Valencia, JC Matsui, K Bondy, C Zhou, J Rasmussen, A Cullen, K Yu, ZX Moss, J Ferrans, VJ AF Valencia, JC Matsui, K Bondy, C Zhou, J Rasmussen, A Cullen, K Yu, ZX Moss, J Ferrans, VJ TI Distribution and mRNA expression of insulin-like growth factor system in pulmonary lymphangioleiomyomatosis SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE pulmonary pathology lymphangioleiomyomatosis; immunohistochemistry; insulin-like growth factors; lung disease ID FACTOR-BINDING-PROTEINS; HUMAN BREAST-CANCER; IGF-II; GENE-EXPRESSION; DOWN-REGULATION; MESSENGER-RNA; RECEPTORS; LUNG; DIFFERENTIATION; PROLIFERATION AB Background. Insulin-like growth factors (IGF-1 and IGF-2), the IGF-1 receptor (IGF-1R), and IGF-binding proteins (IGFBPs) are involved in normal pulmonary development and in the pathogenesis of smooth muscle cell tumors. Methods: To evaluate the role of the IGF system in lymphangioleimnyomatosis (LAM), we used immunohistochemical and in situ hybridization techniques to characterize the expression of IGF-L IGF-2, IGF-IR, and IGFBP-2, -4, -5, and -6 in lung tissue from 18 LAM patients. Results: IGF-1, IGF-2, IGF-IR, IGFBP-1, IGFBP-2, IGFBP-4, IGFBP-5, and IGFBP-6 were expressed by LAM cells. Reactivity and mRNA expression for IGF-2 were observed in LAM cells and resembled that found in normal smooth muscle cells during pulmonary development as well as in smooth muscle cell tumors. IGFBP-2, IGFBP-4, and IGFBP-6 were associated with spindle-shaped LAM cells, whereas IGFBP-5 was associated mainly with epithelioid LAM cells. Conclusions: These findings suggest that the IGFBPs modulate the effects of the IGFs on LAM cells. Thus, the patterns of localization and expression of components of the IGF system in LAM strongly suggest that these agents are involved in the proliferation of LAM cells. C1 NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Ctr Med, Lombardi Canc Res Ctr, Washington, DC USA. RP Ferrans, VJ (reprint author), NHLBI, Pathol Sect, NIH, Bldg 10-N240,10 Ctr Dr,MSC-1518, Bethesda, MD 20892 USA. NR 38 TC 19 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD SEP PY 2001 VL 49 IS 5 BP 421 EP 433 DI 10.2310/6650.2001.33787 PG 13 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 464QQ UT WOS:000170543600007 PM 11523698 ER PT J AU Santamarina-Fojo, S Remaley, AT Neufeld, EB Brewer, HB AF Santamarina-Fojo, S Remaley, AT Neufeld, EB Brewer, HB TI Regulation and intracellular trafficking of the ABCA1 transporter SO JOURNAL OF LIPID RESEARCH LA English DT Article DE Tangier disease; HDL; ABC transporters ID APOLIPOPROTEIN-A-I; ATP-BINDING-CASSETTE; HIGH-DENSITY-LIPOPROTEINS; CELLULAR CHOLESTEROL; TANGIER-DISEASE; PLASMA-MEMBRANE; MOLECULAR-CLONING; APOA-I; EFFLUX; GENE AB The discovery of the role of the ATP-binding cassette transporter A1 (ABCA1) in mediating apolipoprotein A-I-mediated efflux has led to a dramatic increase in our knowledge of the molecular mechanisms involved in cholesterol efflux and cellular metabolism. In this review, we discuss several aspects of ABCA1 regulation including i) transcriptional regulation, il) substrate specificity and availability, iii) accessory proteins, iv) acceptor specificity and availability, and v) protein trafficking. The majority of studies of ABCA1 regulation to date have focused on the identification of promoter elements that determine ABCA1 gene transcription. Here we also review the potential functional role of ABCA1 in reverse cholesterol transport. Given the key role that ABCA1 plays in cholesterol homeostasis, it is likely that there are multiple mechanisms for controlling the overall transporter activity of ABCA1. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Santamarina-Fojo, S (reprint author), NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 64 TC 106 Z9 121 U1 0 U2 5 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2001 VL 42 IS 9 BP 1339 EP 1345 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468RZ UT WOS:000170773100001 PM 11518753 ER PT J AU Kruth, HS Ifrim, I Chang, J Addadi, L Perl-Treves, D Zhang, WY AF Kruth, HS Ifrim, I Chang, J Addadi, L Perl-Treves, D Zhang, WY TI Monoclonal antibody detection of plasma membrane cholesterol microdomains responsive to cholesterol trafficking SO JOURNAL OF LIPID RESEARCH LA English DT Article DE acyl-CoA : cholesterol acyltransferase; cholesterol efflux; macrophages; atherosclerosis; HDL; progesterone; ketoconazole; cyclodextrin; apoA-I; apoE; Niemann-Pick type C ID LOW-DENSITY LIPOPROTEIN; MONOCYTE-DERIVED MACROPHAGES; ACYL-COENZYME-A; HUMAN ATHEROSCLEROTIC LESIONS; NIEMANN-PICK DISEASE; CELLULAR CHOLESTEROL; INTRACELLULAR-TRANSPORT; UNESTERIFIED CHOLESTEROL; LYSOSOMAL CHOLESTEROL; CULTURED MACROPHAGES AB The hypothesis of lipid domains in cellular plasma membranes is well established. However, direct visualization of the domains has been difficult. Here we report direct visualization of plasma membrane cholesterol microdomains modulated by agents that affect cholesterol trafficking to and from the plasma membrane. The cholesterol microdomains were visualized with a monoclonal antibody that specifically detects ordered cholesterol arrays. These unique cholesterol microdomains were induced on macrophages and fibroblasts when they were enriched with cholesterol in the presence of an ACAT inhibitor, to block esterification of excess cellular cholesterol. Induction of the plasma membrane cholesterol microdomains could be blocked by agents that inhibit trafficking of cholesterol to the plasma membrane and by cholesterol acceptors that remove cholesterol from the plasma membrane. In addition, plasma membrane cholesterol microdomains did not develop in mutant Niemann-Pick type C fibroblasts, consistent with the defect in cholesterol trafficking reported for these cells. The induction of plasma membrane cholesterol microdomains on inhibition of ACAT helps explain how AC-AT inhibition promotes cholesterol efflux from cells in the presence of cholesterol acceptors such as HDL. The anti-cholesterol monoclonal antibody also detected extracellular cholesterol-containing particles that accumulated most prominently during cholesterol enrichment of less differentiated human monocyte-macrophages. For the first time, cholesterol microdomains have been visualized that function in cholesterol trafficking to and from the plasma membrane. C1 NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. RP Kruth, HS (reprint author), NHLBI, Sect Expt Atherosclerosis, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 60 TC 36 Z9 36 U1 0 U2 2 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD SEP PY 2001 VL 42 IS 9 BP 1492 EP 1500 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468RZ UT WOS:000170773100018 PM 11518770 ER PT J AU Hasan, KM Basser, PJ Parker, DL Alexander, AL AF Hasan, KM Basser, PJ Parker, DL Alexander, AL TI Analytical computation of the eigenvalues and eigenvectors in DT-MRI SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE analytical; diffusion tensor; eigenvalues; eigenvectors ID DIFFUSION-TENSOR; HUMAN BRAIN; ANISOTROPY; TRACKING; PATHWAYS; IMAGES AB In this paper a noniterative algorithm to be used for the analytical determination of the sorted eigenvalues and corresponding orthonormalized eigenvectors obtained by diffusion tensor magnetic resonance imaging (DT-MRI) is described. The algorithm uses the three invariants of the raw water spin self-diffusion tensor represented by a 3 x 3 positive definite matrix and certain mat functions that do not require iteration. The implementation requires a positive definite mask to preserve the physical meaning of the eigenvalues. This algorithm can increase the speed of eigenvalue/eigenvector calculations by a factor of 5-40 over standard iterative Jacobi or singular-value decomposition techniques. This approach may accelerate the computation of eigenvalues, eigenvalue-dependent metrics, and eigenvectors especially when having high-resolution measurements with large numbers of slices and large fields of view. (C) 2001 Academic Press. C1 Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53705 USA. Univ Wisconsin, WM Keck Lab Funct Brain Imaging & Behav, Madison, WI 53705 USA. NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Utah, Dept Radiol, Salt Lake City, UT 84132 USA. RP Hasan, KM (reprint author), Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA. RI Basser, Peter/H-5477-2011 FU NCI NIH HHS [P30 CA42014]; NIMH NIH HHS [R01 MH62015] NR 28 TC 93 Z9 94 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD SEP PY 2001 VL 152 IS 1 BP 41 EP 47 DI 10.1006/jmre.2001.2400 PG 7 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 472QD UT WOS:000170995700005 PM 11531362 ER PT J AU Luy, B Barchi, JJ Marino, JP AF Luy, B Barchi, JJ Marino, JP TI (SE)-E-3-E.COSY methods for the measurement of F-19 associated scalar and dipolar coupling constants SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE (SE)-E-3; E.COSY; fluorine; RNA; scalar couplings; residual dipolar couplings ID E.COSY-TYPE MEASUREMENT; NMR-SPECTROSCOPY; COHERENCE TRANSFER; SPIN SYSTEMS; RNA; HETERONUCLEAR; PROTEINS; POLARIZATION; INTERMEDIATE; TRANSITIONS AB A H-1-F-19 spin state selective excitation ((SE)-E-3) pulse sequence element has been applied in combination with IH homonuclear mixing to create E.COSY-type experiments designed to measure scalar J(HF2') and J(HH2') and residual dipolar D-HF2' and D-HH2' couplings in 2'-deoxy-2'-fluoro-sugars. The H-1-F-19 (SE)-E-3 pulse sequence element, which resembles a simple INEPT sequence, achieves spin-state-selective correlation between geminal H-1-F-19 spin pairs by linear combination of in-phase F-19 magnetization and anti-phase magnetization evolved from H-1. Since the (SE)-E-3 sequence converts both F-19 and H-1 steady-state polarization into observable coherences, an approximately twofold signal increase is observed for fully relaxed H-1-F-19 spin pairs with respect to a standard H-1 coupled F-19 1D experiment. The improved sensitivity and resolution afforded by the use of H-1-F-19 (SE)-E-3 E.COSY-type experiments for measuring couplings is demonstrated on the nucleoside 9-(2',3'-dideoxy-2'-fluoro-beta -D-threo-pentofuranosyl)adenine (beta -FddA) and on a selectively 2'-fluorine labeled 21mer RNA oligonucleotide. C1 Univ Maryland, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. NIST, Rockville, MD 20850 USA. NCI, Med Chem Lab, FCRDC, Frederick, MD 21702 USA. RP Marino, JP (reprint author), Univ Maryland, Ctr Adv Res Biotechnol, 9600 Gudelsky Dr, Rockville, MD 20850 USA. RI Luy, Burkhard/I-1918-2013; Barchi Jr., Joseph/N-3784-2014 OI Luy, Burkhard/0000-0001-9580-6397; FU NIGMS NIH HHS [GM 59107-01] NR 23 TC 21 Z9 21 U1 1 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD SEP PY 2001 VL 152 IS 1 BP 179 EP 184 DI 10.1006/jmre.2001.2386 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 472QD UT WOS:000170995700020 PM 11531377 ER PT J AU Weisz, A Andrzejewski, D Fales, HM Mandelbaum, A AF Weisz, A Andrzejewski, D Fales, HM Mandelbaum, A TI Structural assignment of isomeric 2-(2-quinolinyl)-1H-indene-1,3(2H)-dione mono- and disulfonic acids by liquid chromatography electrospray and atmospheric pressure chemical ionization tandem mass spectrometry SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE sulfonic acids; positional isomers; tandem mass spectrometry; regiospecific fragmentations; electrospray ionization; atmospheric pressure chemical ionization AB td2 C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. US FDA, Off Sci Anal & Support, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Technion Israel Inst Technol, Dept Chem, IL-32000 Haifa, Israel. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD SEP PY 2001 VL 36 IS 9 BP 1024 EP 1030 DI 10.1002/jms.205 PG 7 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 476MP UT WOS:000171231100004 PM 11599080 ER PT J AU Biesecker, B AF Biesecker, B TI Quality in the process of genetic counseling: an exploratory study of potential outcomes SO JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD SEP PY 2001 VL 38 SU 1 MA SP9 BP S14 EP S14 PG 1 WC Genetics & Heredity SC Genetics & Heredity GA 473NV UT WOS:000171051200010 ER PT J AU Rashid, MA Gustafson, KR Boyd, MR AF Rashid, MA Gustafson, KR Boyd, MR TI A new isoquinoline alkaloid from the marine sponge Haliclona species SO JOURNAL OF NATURAL PRODUCTS LA English DT Article AB Two isoquinoline alkaloids, including the new compound 1, were isolated from the cytotoxic fractions of an aqueous extract of the marine sponge Haliclona sp. The structures of these compounds were established as 1-hydroxymethyl-7-methoxyisoquinolin-6-ol (1) and mimosamycin (2) by conventional spectroscopic methods and by comparison with related compounds. Mimosamycin (2) was the principal cytotoxin with an IC50 of approximately 10 mug/mL against melanoma and ovarian human tumor cell lines. C1 NCI, Canc Res Ctr, Mol Targets Drug Discovery Program, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Canc Res Ctr, Mol Targets Drug Discovery Program, Bldg 1052,Room 121, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 11 TC 21 Z9 22 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD SEP PY 2001 VL 64 IS 9 BP 1249 EP 1250 DI 10.1021/np0102004 PG 2 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 479WR UT WOS:000171427100030 PM 11575970 ER PT J AU Chandross, KJ Mezey, E Guzik, A McKercher, S Maki, R Hudson, LD AF Chandross, KJ Mezey, E Guzik, A McKercher, S Maki, R Hudson, LD TI Adult mammalian bone marrow gives rise to cells that express neural antigens SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. Burnham Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 6 EP 6 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800017 ER PT J AU Ghiani, CA Gallo, V AF Ghiani, CA Gallo, V TI Cell cycle arrest and withdrawal are differentially regulated in oligodendrocyte progenitors SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NICHHD, LCMN, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Mental Retardat Res Ctr, NPI, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 28 EP 28 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800094 ER PT J AU Lapinska, J Szklarczyk, A Kaczmarek, L AF Lapinska, J Szklarczyk, A Kaczmarek, L TI Matrix metalloproteinase-9 and-2 activity changes during development of the rat visual cortex. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 M Nencki Inst Expt Biol, PL-02093 Warsaw, Poland. NINDS, LMB, NIH, Bethesda, MD 20892 USA. RI Kaczmarek, Leszek/B-6171-2008 OI Kaczmarek, Leszek/0000-0002-7207-3490 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 33 EP 33 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800111 ER PT J AU Barker, JL Maric, I Chang, YH Maric, D AF Barker, JL Maric, I Chang, YH Maric, D TI Neural stem cell progeny differentiating in vitro recapitulate lineage-restricted transmitter receptors and ion channels emerging in vivo SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 57 EP 57 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800200 ER PT J AU Nielsen, JA Hudson, LD Armstrong, RC AF Nielsen, JA Hudson, LD Armstrong, RC TI Nuclear organization in differentiating oligodendrocytes SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 57 EP 57 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800201 ER PT J AU Weiss, MD Dashiell, SM Pant, HC Quarles, RH AF Weiss, MD Dashiell, SM Pant, HC Quarles, RH TI Axonopathy in aging mice lacking myelin-associated glycoprotein SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 84 EP 84 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800299 ER PT J AU Barger, SW Basile, AS AF Barger, SW Basile, AS TI Role of the microglial cystine-glutathione system in neuroprotective antioxidant strategies: relevance to excitotoxicity and Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 107 EP 107 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800379 ER PT J AU Cohen, RI Maric, D Barker, J Hudson, LD AF Cohen, RI Maric, D Barker, J Hudson, LD TI Microarray analysis of developing oligodendrogia, neurons, and astrocytes reveal differential gene expression SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NINDS, NIH, LDN, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 119 EP 119 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800414 ER PT J AU Imam, SZ Itzhak, Y Cadet, JL Slikker, W Ali, SF AF Imam, SZ Itzhak, Y Cadet, JL Slikker, W Ali, SF TI Role of peroxynitrite and apoptosis related proteins, p53 and bcl-2, in methamphetamine-induced neurotoxicity SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33101 USA. NIDA, IRP, Mol Neuropsychiat Sect, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 129 EP 129 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800451 ER PT J AU Kim, SY Jeong, EJ Steinert, PM Jeitner, TM Blass, JP Cooper, AJL AF Kim, SY Jeong, EJ Steinert, PM Jeitner, TM Blass, JP Cooper, AJL TI Expression of transglutaminases 1, 2 and 3 in rat brain: cloning of rat brain transglutaminases 2 and 3 SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD USA. Cornell Univ, Weill Med Coll, Burke Med Res Inst, White Plains, NY USA. RI Cooper, Arthur/H-5171-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 137 EP 137 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800484 ER PT J AU Lahiri, DK Ge, Y Sambamurti, K Utsuki, T Greig, NH Farlow, MR AF Lahiri, DK Ge, Y Sambamurti, K Utsuki, T Greig, NH Farlow, MR TI A novel target for phenserine drug in regulating the translation of APP message SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Indianapolis, IN USA. Mayo Clin, Jacksonville, FL 32224 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 140 EP 140 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800495 ER PT J AU Qu, Y Chang, L Klaff, J Balbo, A Rapoport, RI AF Qu, Y Chang, L Klaff, J Balbo, A Rapoport, RI TI Imaging phospholipase A2 mediated signal transduction in response to a 5-HT2 agonist in brain of awake rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 144 EP 144 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800508 ER PT J AU Rapoport, SI Chang, MCJ Spector, AA AF Rapoport, SI Chang, MCJ Spector, AA TI In vivo quantification of rates of phospholipase A2-mediated release and metabolism of arachidonate acid in rat and human brain SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, NIH, Bethesda, MD 20892 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 144 EP 144 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800510 ER PT J AU Qu, Y Chang, L Klaff, J Balbo, A Rapoport, SI AF Qu, Y Chang, L Klaff, J Balbo, A Rapoport, SI TI In vivo neuroimaging on serotonin mediated phospholipase A2 signal transduction in awake rats: effect of methiothepin SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 152 EP 152 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800540 ER PT J AU Steinert, PM Jang, SI Jeong, EJ Kim, SY AF Steinert, PM Jang, SI Jeong, EJ Kim, SY TI Signaling of transglutaminase 1 by interferon-gamma is STAT-dependent in normal human muscle cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 166 EP 166 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800592 ER PT J AU Porcincula, LO Vinade, L Wofchuck, S Souza, DO AF Porcincula, LO Vinade, L Wofchuck, S Souza, DO TI Guanine-based purines inhibited [3H]glutamate and [3H]AMPA binding at the postsynaptic densities SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 UFRGS, ICBS, Dept Bioquim, Porto Alegre, RS, Brazil. NIH, Neurobiol Lab, Bethesda, MD 20892 USA. RI Souza, Diogo/J-8894-2014 OI Souza, Diogo/0000-0002-4322-0404 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 179 EP 179 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800644 ER PT J AU Mayne, M Chan, SL Holden, CP Geiger, JD Mattson, MP AF Mayne, M Chan, SL Holden, CP Geiger, JD Mattson, MP TI Presenilin-1 mutations increase levels of ryanodine receptors and calcium release in PC12 cells and cortical neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 Univ Manitoba, Fac Med, Dept Pharmacol & Therapeut, Winnipeg, MB R3E 0W3, Canada. Univ Kentucky, Sanders Brown Res Ctr Aging, Lexington, KY 40536 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 SU 1 BP 207 EP 207 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 469AF UT WOS:000170789800746 ER PT J AU Thanos, PK Volkow, ND Freimuth, P Umegaki, H Ikari, H Roth, G Ingram, DK Hitzemann, R AF Thanos, PK Volkow, ND Freimuth, P Umegaki, H Ikari, H Roth, G Ingram, DK Hitzemann, R TI Overexpression of dopamine D2 receptors reduces alcohol self-administration SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE adenovirus; alcoholism; animal model; drinking preference; gene therapy; nucleus accumbens ID MEDIATED GENE-TRANSFER; NUCLEUS-ACCUMBENS; RAT STRIATUM; ETHANOL REINFORCEMENT; ALLELIC ASSOCIATION; PREFERRING RATS; CONSUMPTION; INITIATION; PREFERENCE; DRINKING AB The mechanism(s) underlying predisposition to alcohol abuse are poorly understood but may involve brain dopamine system(s). Here we used an adenoviral vector to deliver the dopamine D2 receptor (DRD2) gene into the nucleus accumbens of rats, previously trained to self-administer alcohol, and to assess if DRD2 levels regulated alcohol preference and intake. We show that increases in DRD2 (52%) were associated with marked reductions in alcohol preference (43%), and alcohol intake (64%) of ethanol preferring rats, which recovered as the DRD2, returned to baseline levels. In addition, this DRD2 overexpression similarly produced significant reductions in ethanol nonpreferring rats, in both alcohol preference (16%) and alcohol intake (75%). This is the first evidence that overexpression of DRD2 reduces alcohol intake and suggests that high levels of DRD2 may be protective against alcohol abuse. C1 Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Nagoya Univ, Sch Med, Dept Geriatr, Aichi, Japan. NIA, Ctr Gerontol Res, Baltimore, MD 21224 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Bldg 490, Upton, NY 11973 USA. EM thanos@bnl.gov FU NIAAA NIH HHS [AA07574, AA11034] NR 56 TC 160 Z9 163 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 IS 5 BP 1094 EP 1103 DI 10.1046/j.1471-4159.2001.00492.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 467MG UT WOS:000170707900017 PM 11553683 ER PT J AU Colton, CA Gbadegesin, M Wink, DA Miranda, KM Espey, MG Vicini, S AF Colton, CA Gbadegesin, M Wink, DA Miranda, KM Espey, MG Vicini, S TI Nitroxyl anion regulation of the NMDA receptor SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Angeli's salt; glycine independent desensitization; hypoxia; nitroxyl anion; N-methyl-D-aspartate ID NITRIC-OXIDE SYNTHASE; GLUTAMATE-RECEPTOR; NR1 SUBUNIT; NO; DESENSITIZATION; NEUROTOXICITY; CYTOTOXICITY; CONVERSION; MODULATION; POLYAMINES AB Nitric oxide (NO) is an important regulator of NMDA channel function in the CNS. Recent findings suggest that nitroxyl anion (NO-) may also be generated by nitric oxide synthase, which catalyzes production of NO. Using recombinant NMDA receptors (NMDA-r) transfected into human embryonic kidney cells, our data demonstrate that the nitroxyl anion donor, Angeli's salt (AS; Na2N2O3) dramatically blocked glycine-independent desensitization in NMDA-r containing NR1-NR2A subunits. AS did not affect glycine-dependent desensitization, calcium dependent inactivation or glutamate affinity for the NMDA-r. This effect could be mimicked by treatment with DPTA, a metal chelator and was not evident under hypoxic conditions. In contrast, receptors containing the NR1-NR2B subunits demonstrated an approximate 25% reduction in whole cell currents in the presence of AS with no apparent change in desensitization. Our data suggest that the regulation of NMDA-r function by nitroxyl anion is distinctly different from NO and may result in different cellular outcomes compared with NO. C1 Duke Univ, Med Ctr, Div Neurol, Durham, NC 27710 USA. Georgetown Univ, Med Ctr, Interdisciplinary Program Neurosci, Washington, DC 20007 USA. NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Colton, CA (reprint author), Duke Univ, Med Ctr, Div Neurol, Bryan Res Bldg,Box 2900, Durham, NC 27710 USA. RI Miranda, Katrina/B-7823-2009 FU NIA NIH HHS [R03 AG16026]; NIMH NIH HHS [KO2MH01680, R01MH58946] NR 38 TC 40 Z9 40 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD SEP PY 2001 VL 78 IS 5 BP 1126 EP 1134 DI 10.1046/j.1471-4159.2001.00509.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 467MG UT WOS:000170707900020 PM 11553686 ER PT J AU Torres-Munoz, J Stockton, P Tacoronte, N Roberts, B Maronpot, RR Petito, CK AF Torres-Munoz, J Stockton, P Tacoronte, N Roberts, B Maronpot, RR Petito, CK TI Detection of HIV-1 gene sequences in hippocampal neurons isolated from postmortem AIDS brains by laser capture microdissection SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE hippocampus; HIV; HIV-associated dementia; HIV encephalitis; laser capture microdissection; polymerase chain reaction (PCR) ID HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE-CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; SITU HYBRIDIZATION; DEMENTIA COMPLEX; DNA EXTRACTION; NUCLEIC-ACIDS; NEURAL CELLS; FIXED TISSUE; INFECTION AB We employed laser capture microdissection to remove individual pyramidal neurons from the CA1, CA3, and CA4 regions of formalin-fixed, paraffin-embedded hippocampus from 8 AIDS brains and 2 HIV-1-seronegative normal brains. We amplified HIV-1 gag and nef gene sequences using separate, double round PCR reactions for each of the primer sets. In all 3 bippocampal regions, amplification efficiency was best with sequence length between 284 and 324 bp; HIV-1 nef gene sequences were more common than HIV-1 gag sequences; and rank order for percent positive amplification was CA3>CA4 >CA1 samples. These results are the first to detect HIV-1 gene sequences in microdissected human tissue. They indicate that brain neurons in vivo contain HIV-1 DNA sequences consistent with latent infection by this virus, and suggest that neurons display a selective vulnerability for HIV infection. Neuronal HIV infection could contribute to neuronal injury and death or act as a potential viral reservoir if reactivated. C1 Univ Miami, Sch Med, Dept Pathol R5, Miami, FL 33136 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. RP Petito, CK (reprint author), Univ Miami, Sch Med, Dept Pathol R5, 1550 NW 10th Ave ,PAP Bldg,Rm 417, Miami, FL 33136 USA. RI Torres-Munoz, Jorge/A-5179-2008 FU NICHD NIH HHS [N01-HD83284]; NINDS NIH HHS [R01 NS35331, R01 NS39177] NR 62 TC 78 Z9 79 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD SEP PY 2001 VL 60 IS 9 BP 885 EP 892 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 469WC UT WOS:000170838200007 PM 11556545 ER PT J AU Sommer, M Classen, J Cohen, LG Hallett, M AF Sommer, M Classen, J Cohen, LG Hallett, M TI Time course of determination of movement direction in the reaction time task in humans SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; NEURONAL POPULATION; MENTAL ROTATION; MOTOR PROGRAMS; REPRESENTATION; INHIBITION; COMMANDS; CORTEX; BRAIN AB The primary motor cortex produces motor commands that include encoding the direction of movement. Excitability of the motor cortex in the reaction time (RT) task can be assessed using transcranial magnetic stimulation (TMS). To elucidate the timing of the increase in cortical excitability and of the determination of movement direction before movement onset, we asked six right-handed, healthy subjects to either abduct or extend their right thumb after a go-signal indicated the appropriate direction. Between the go-signal and movement onset, single TMS pulses were delivered to the contralateral motor cortex. We recorded the direction of the TMS-induced thumb movement and the amplitude of motor-evoked potentials (MEPs) from the abductor pollicis brevis and extensor pollicis brevis muscles. Facilitation of MEPs from the prime mover, as early as 200 ms before the end of the reaction time, preceded facilitation of MEPs from the nonprime mover, and both preceded measurable directional change. Compared with a control condition in which no voluntary movement was required, the direction of the TMS-induced thumb movement started to change in the direction of the intended movement as early as 90 ms before the end of the RT, and maximum changes were seen shortly before the end of reaction time. Movement acceleration also increased with maxima shortly before the end of the RT. We conclude that in concentric movements a change of the movement direction encoded in the primary motor cortex occurs in the 200 ms prior to movement onset, which is as early as increased excitability itself can be detected. C1 NIH, NINDS, Med Neurol Branch, Human Motor Control Sect, Bethesda, MD 20892 USA. Univ Gottingen, Dept Clin Neurophysiol, D-37075 Gottingen, Germany. Univ Rostock, Dept Neurol, D-18147 Rostock, Germany. RP Hallett, M (reprint author), NIH, NINDS, Med Neurol Branch, Human Motor Control Sect, Bldg 10, Rm 5N226,10 Ctr Dr MSC1428, Bethesda, MD 20892 USA. RI Sommer, Martin/F-1503-2015 NR 16 TC 13 Z9 13 U1 2 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2001 VL 86 IS 3 BP 1195 EP 1201 PG 7 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 473DH UT WOS:000171024400014 PM 11535669 ER PT J AU Oz, M Kolaj, M Renaud, LP AF Oz, M Kolaj, M Renaud, LP TI Electrophysiological evidence for vasopressin V-1 receptors on neonatal motoneurons, premotor and other ventral horn neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID RAT SPINAL-CORD; PREPROVASOPRESSIN MESSENGER-RNA; CULTURED HIPPOCAMPAL-NEURONS; ARGININE-VASOPRESSIN; NEUROHYPOPHYSEAL PEPTIDES; CEREBROSPINAL-FLUID; MOTOR NUCLEI; PATHWAYS; CELLS; OXYTOCIN AB Prominent arginine-vasopressin (AVP) binding and AVP V-1 type receptors are expressed early in the developing rat spinal cord. We sought to characterize their influence, on neural excitability by using patch-clamp techniques to record AVP-induced responses from a population of motoneurons and interneurons in neonatal (5-18 days) rat spinal cord slices. Data were obtained from 58 thoracolumbar (T-7-L-5) motoneurons and 166 local interneurons. A majority (>90%) of neurons responded to bath applied AVP (10 nM to 3 muM) and (Phe(2), Orn(8))-vasotocin, a V-1 receptor agonist, but not V-2 or oxytocin receptor agonists. In voltage-clamp, postsynaptic responses in motoneurons were characterized by slowly rising, prolonged (7-10 min) and tetrodotoxin-resistant inward currents associated with a 25% reduction in a membrane potassium conductance that reversed near -100 mV. In interneurons, net AVP-induced inward currents displayed three patterns: decreasing membrane conductance with reversal near -100 mV, i.e., similar to that in motoneurons (24 cells), increasing conductance with reversal near -40 mV (21 cells); small reduction in conductance with no reversal within the current range tested (41 cells). A presynaptic component recorded in most neurons was evident as an increase in the frequency but not amplitude (in motoneurons) of inhibitory and excitatory postsynaptic currents (IPSCs and EPSCs), in large part due to AVP-induced firing in inhibitory (mainly glycinergic) and excitatory (glutamatergic) neurons synapsing on the recorded cells. An increase in frequency but not amplitude of miniature IPSCs and EPSCs also indicated an AVP enhancement of neurotransmitter release from axon terminals of inhibitory and excitatory interneurons. These observations provide support for a broad presynaptic and postsynaptic distribution of AVP V-1 type receptors and indicate that their activation can enhance the excitability of a majority of neurons in neonatal ventral spinal cord. C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD 21224 USA. Univ Ottawa, Ottawa Hlth Res Inst, Ottawa, ON K1Y 4E9, Canada. RP Renaud, LP (reprint author), Ottawa Hosp Civ Campus, 1053 Carling Ave, Ottawa, ON K1Y 4E9, Canada. RI Oz, Murat/E-2148-2012 NR 46 TC 21 Z9 21 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2001 VL 86 IS 3 BP 1202 EP 1210 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 473DH UT WOS:000171024400015 PM 11535670 ER PT J AU Kastner, S De Weerd, P Pinsk, MA Elizondo, MI Desimone, R Ungerleider, LG AF Kastner, S De Weerd, P Pinsk, MA Elizondo, MI Desimone, R Ungerleider, LG TI Modulation of sensory suppression: Implications for receptive field sizes in the human visual cortex SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INFERIOR TEMPORAL CORTEX; STRIATE CORTEX; EXTRASTRIATE CORTEX; FUNCTIONAL-ANALYSIS; CORTICAL AREAS; MACAQUE; NEURONS; RESPONSES; ATTENTION; MECHANISMS AB Neurophysiological studies in monkeys show that when multiple visual stimuli appear simultaneously in the visual field, they are not processed independently, but rather interact in a mutually suppressive way. This suggests that multiple stimuli compete for neural representation. Consistent with this notion, we have previously found in humans that functional magnetic resonance imaging (fMRI) signals in V1 and ventral extrastriate areas V2, V4, and TEO are smaller for simultaneously presented (i.e., competing) stimuli than for the same stimuli presented sequentially (i.e., not competing). Here we report that suppressive interactions between stimuli are also present in dorsal extrastriate areas V3A and MT, and we compare these interactions to those in areas V1 through TEO. To exclude the possibility that the differences in responses to simultaneously and sequentially presented stimuli were due to differences in the number of transient onsets, we tested for suppressive interactions in area V4, in an experiment that held constant the number of transient onsets. We found that the fMRI response to a stimulus in the upper visual field was suppressed by the presence of nearby stimuli in the lower visual field. Further, we excluded the possibility that the greater fMRI responses to sequential compared with simultaneous presentations were due to exogeneous attentional. cueing by having our subjects count T's or L's at fixation, an attentionally demanding task. Behavioral testing demonstrated that neither condition interfered with performance of the T/L task. Our previous findings suggested that suppressive interactions among nearby stimuli in areas V1 through TEO were scaled to the receptive field (RF) sizes of neurons in those areas. Here we tested this idea by parametrically varying the spatial separation among stimuli in the display. Display sizes ranged from 2 x 2 degrees to 7 X 7 degrees and were centered at 5.5 degrees eccentricity. Based on the effects of display size on the magnitude of suppressive interactions, we estimated that RF sizes at an eccentricity of 5.5 degrees were <2 in V1, 2-4 degrees in V2, 4-6 degrees in V4, larger than 7 degrees (but still confined to a quadrant) in TEO, and larger than 6 degrees (confined to a quadrant) in V3A. These estimates of RF sizes in human visual cortex are strikingly similar to those measured in physiological mapping studies in the homologous visual areas in monkeys. C1 Princeton Univ, Ctr Study Brain Mind & Behav, Dept Psychol, Princeton, NJ 08544 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. Univ Arizona, Dept Psychol, Coll Social & Behav Sci, Tucson, AZ 85721 USA. RP Kastner, S (reprint author), Princeton Univ, Ctr Study Brain Mind & Behav, Dept Psychol, Green Hall, Princeton, NJ 08544 USA. NR 52 TC 194 Z9 196 U1 1 U2 13 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2001 VL 86 IS 3 BP 1398 EP 1411 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 473DH UT WOS:000171024400031 PM 11535686 ER PT J AU Wenner, P O'Donovan, MJ AF Wenner, P O'Donovan, MJ TI Mechanisms that initiate spontaneous network activity in the developing chick spinal cord SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID DEVELOPING MAMMALIAN RETINA; EMBRYONIC CHICK; RAT MOTONEURONS; DEVELOPING HIPPOCAMPUS; SYNAPTIC TRANSMISSION; LOCOMOTOR-ACTIVITY; GANGLION-CELLS; MOTOR-ACTIVITY; VENTRAL ROOT; IN-VITRO AB Many developing networks exhibit a transient period of spontaneous activity that is believed to be important developmentally. Here we investigate the initiation of spontaneous episodes of rhythmic activity in the embryonic chick spinal cord. These episodes recur regularly and are separated by quiescent intervals of many minutes. We examined the role of motoneurons and their intraspinal synaptic targets (R-interneurons) in the initiation of these episodes. During the latter part of the inter-episode interval, we recorded spontaneous, transient ventral root depolarizations that were accompanied by small, spatially diffuse fluorescent signals from interneurons retrogradely labeled with a calcium-sensitive dye. A transient often could be resolved at episode onset and was accompanied by an intense pre-episode (similar to 500 ms) motoneuronal discharge (particularly in adductor and sartorius) but not by interneuronal discharge monitored from the ventrolateral funiculus (VLF). An important role for this pre-episode motoneuron discharge was suggested by the finding that electrical stimulation of motor axons, sufficient to activate R-interneurons, could trigger episodes prematurely. This effect was mediated through activation of R-interneurons because it was prevented by pharmacological blockade of either the cholinergic motoneuronal inputs to R-interneurons or the GABAergic outputs from R-interneurons to other interneurons. Whole-cell recording from R-interneurons and imaging of calcium dye-labeled interneurons established that R-interneuron cell bodies were located dorsomedial to the lateral motor column (R-interneuron region). This region became active before other labeled interneurons when an episode was triggered by motor axon stimulation. At the beginning of a spontaneous episode, whole-cell recordings revealed that R-interneurons fired a high-frequency burst of spikes and optical recordings demonstrated that the R-interneuron region became active before other labeled interneurons. In the presence of cholinergic blockade, however, episode initiation slowed and the inter-episode interval lengthened. In addition, optical activity recorded from the R-interneuron region no longer led that of other labeled interneurons. Instead the initial activity occurred bilaterally in the region medial to the motor column and encompassing the central canal. These findings are consistent with the hypothesis that transient depolarizations and firing in motoneurons, originating from random fluctuations of interneuronal synaptic activity, activate R-interneurons, which then trigger the recruitment of the rest of the spinal interneuronal network. This unusual function for R-interneurons is likely to arise because the output of these interneurons is functionally excitatory during development. C1 NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bethesda, MD 20892 USA. RP Wenner, P (reprint author), NINDS, Neural Control Lab, Sect Dev Neurobiol, NIH, Bldg 49,Rm 3A50,49 Convent Dr, Bethesda, MD 20892 USA. RI o'donovan, michael/A-2357-2015; OI o'donovan, michael/0000-0003-2487-7547; Wenner, Peter/0000-0002-7072-2194 NR 51 TC 72 Z9 72 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD SEP PY 2001 VL 86 IS 3 BP 1481 EP 1498 PG 18 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 473DH UT WOS:000171024400037 PM 11535692 ER PT J AU Coffey, CE Ratcliff, G Saxton, JA Bryan, RN Fried, LP Lucke, JE AF Coffey, CE Ratcliff, G Saxton, JA Bryan, RN Fried, LP Lucke, JE TI Cognitive correlates of human brain aging: A quantitative magnetic resonance imaging investigation SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID HIPPOCAMPAL-FORMATION SIZE; CARDIOVASCULAR HEALTH; MEMORY IMPAIRMENT; TEMPORAL-LOBE; COMPUTED-TOMOGRAPHY; ALZHEIMERS-DISEASE; TEST-PERFORMANCE; SEX-DIFFERENCES; ATROPHY; ABNORMALITIES AB The relations between age-related changes in brain structure and neuropsychological test performance in 320 elderly nonclinical volunteers (ages 66-90) were examined by using quantitative MRI data and measures of attention, information processing speed, language, memory, and visuospatial ability. Final path analyses revealed significant brain-behavior relationships for two of the six cognitive measures: the Trail Making Test part B and visual delayed memory. Poorer performance on Trails B was associated with smaller cerebral hemisphere volumes and larger volumes of peripheral CSF, lateral ventricles, and third ventricle. Poorer recall on visual delayed memory was associated with larger volumes of the lateral ventricles and third ventricle. The findings demonstrate a relationship between age-related changes in brain structure and an age-related decline in attention, psychomotor speed, and visual delayed memory. The neurobiological basis for this relationship requires further investigation. C1 Henry Ford Hlth Syst, Dept Psychiat, Detroit, MI 48202 USA. Henry Ford Hlth Syst, Dept Neurol, Detroit, MI 48202 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. HealthS Harmarville Rehabil Hosp, Pittsburgh, PA USA. NIH, Dept Radiol, Ctr Clin, Washington, DC USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA. RP Coffey, CE (reprint author), Henry Ford Hlth Syst, Dept Psychiat, 1 Ford Pl, Detroit, MI 48202 USA. RI Bryan, R. Nick/P-1661-2014 FU NIMH NIH HHS [MH46643] NR 54 TC 40 Z9 40 U1 0 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD FAL PY 2001 VL 13 IS 4 BP 471 EP 485 DI 10.1176/appi.neuropsych.13.4.471 PG 15 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 501VX UT WOS:000172707700004 PM 11748316 ER PT J AU Eshete, F Fields, RD AF Eshete, F Fields, RD TI Spike frequency decoding and autonomous activation of Ca2+-calmodulin-dependent protein kinase II in dorsal root ganglion neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Ca2+-calmodulin-dependent protein kinase II; autophosphorylation; Thr-286; frequency decoding; cytoplasmic calcium; extracellular calcium sensor; DRG neurons; CaMKII; LTP ID CALMODULIN-DEPENDENT KINASE; CAM KINASE; CA-2+ CALMODULIN; ELECTRICAL-ACTIVITY; HIPPOCAMPAL SLICES; ACTION-POTENTIALS; KINETIC-ANALYSIS; NEURAL IMPULSES; CALCIUM SIGNALS; AUTOPHOSPHORYLATION AB Autonomous activation of calcium-calmodulin kinase (CaMKII) has been proposed as a molecular mechanism for decoding Ca2+ spike frequencies resulting from action potential firing, but this has not been investigated in intact neurons. This was studied in mouse DRG neurons in culture using confocal measurements of [Ca2+](i) and biochemical measurements of CaMKII autophosphorylation and autonomous activity. Using electrical stimulation at different frequencies, we find that CaMKII autonomous activity reached near maximal levels after similar to 45 impulses, regardless of firing frequency (1-10 Hz), and autonomous activity declined with prolonged stimulation. Frequency-dependent activation of CaMKII was limited to spike frequencies in the range of 0.1-1 Hz, despite marked increases in [Ca2+](i) at higher frequencies (1-30 Hz). The high levels of autonomous activity measured before stimulation and the relatively long duration of Ca2+ spikes induced by action potentials (similar to 300 msec) are consistent with the lower frequency range of action potential decoding by CaMKII. The high autonomous activity under basal conditions was associated with extracellular [Ca2+], independently from changes in [Ca2+](i), and unrelated to synaptic or spontaneous impulse activity. CaMKII autonomous activity in response to brief bursts of action potentials correlated better with the frequency of Ca2+ transients than with the concentration of [Ca2+](i). In conclusion, CaMKII may decode frequency-modulated responses between 0.1 and 1 Hz in these neurons, but other mechanisms may be required to decode higher frequencies. Alternatively, CaMKII may mediate high-frequency responses in subcellular microdomains in which the enzyme is maintained at a low level of autonomous activity or the Ca2+ transients have faster kinetics. C1 NICHHD, Neurocytol & Physiol Unit, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHHD, Neurocytol & Physiol Unit, Lab Cellular & Synapt Neurophysiol, NIH, 49 Convent Dr,Bldg 49,Room 5A78, Bethesda, MD 20892 USA. NR 52 TC 66 Z9 66 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 1 PY 2001 VL 21 IS 17 BP 6694 EP 6705 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 467FC UT WOS:000170690900028 PM 11517259 ER PT J AU Ko, J Humbert, S Bronson, RT Takahashi, S Kulkarni, AB Li, E Tsai, LH AF Ko, J Humbert, S Bronson, RT Takahashi, S Kulkarni, AB Li, E Tsai, LH TI p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment SO JOURNAL OF NEUROSCIENCE LA English DT Article DE p35; p39; Cdk5; development; lamination; neuronal migration; Nudel; neurofilaments ID CDK5 ACTIVATOR P35; SONIC HEDGEHOG; NERVOUS-SYSTEM; CORTICAL DEVELOPMENT; REGULATORY SUBUNIT; LISSENCEPHALY GENE; INFERIOR OLIVE; P35(-/-) MICE; KDA SUBUNIT; NEUROFILAMENT AB Cyclin-dependent kinase 5 (Cdk5) plays a pivotal role in brain development and neuronal migration. Cdk5 is abundant in postmitotic, terminally differentiated neurons. The ability of Cdk5 to phosphorylate substrates is dependent on activation by its neuronal-specific activators p35 and p39. There exist striking differences in the phenotypic severity of Cdk5-deficient mice and p35-deficient mice. Cdk5-null mutants show a more severe disruption of lamination in the cerebral cortex, hippocampus, and cerebellum. In addition, Cdk5-null mice display perinatal lethality, whereas p35-null mice are viable. These discrepancies have been attributed to the function of other Cdk5 activators, such as p39. To understand the roles of p39 and p35, we created p39-null mice and p35/p39 compound-mutant mice. Interestingly, p39-null mice show no obvious detectable abnormalities, whereas p35(-/-)p39(-/-) double-null mutants are perinatal lethal. We show here that the p35(-/-)p39(-/-) mutants exhibit phenotypes identical to those of the Cdk5-null mutant mice. Other compound-mutant mice with intermediate phenotypes allow us to determine the distinct and redundant functions between p35 and p39. Our data strongly suggest that p35 and p39 are essential for Cdk5 activity during the development of the nervous system. Thus, p35 and p39 are likely to be the principal, if not the only, activators of Cdk5. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Ctr Univ Orsay, Inst Curie, CNRS, Unite Mixte Rech 146, F-91405 Orsay, France. Tufts Univ, Sch Vet Med, North Grafton, MA 01536 USA. Natl Inst Dent & Craniofacial Res, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiovasc Res Ctr,Dept Med, Charlestown, MA 02129 USA. RP Tsai, LH (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 200 Longwood Ave, Boston, MA 02215 USA. RI Humbert, Sandrine/S-2981-2016 FU NIGMS NIH HHS [GM53049] NR 64 TC 256 Z9 276 U1 2 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 SEP 1 PY 2001 VL 21 IS 17 BP 6758 EP 6771 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 467FC UT WOS:000170690900033 PM 11517264 ER PT J AU Persico, AM Mengual, E Moessner, R Hall, SF Revay, RS Sora, I Arellano, J DeFelipe, J Gimenez-Amaya, JM Conciatori, M Marino, R Baldi, A Cabib, S Pascucci, T Uhl, GR Murphy, DL Lesch, KP Keller, F AF Persico, AM Mengual, E Moessner, R Hall, SF Revay, RS Sora, I Arellano, J DeFelipe, J Gimenez-Amaya, JM Conciatori, M Marino, R Baldi, A Cabib, S Pascucci, T Uhl, GR Murphy, DL Lesch, KP Keller, F TI Barrel pattern formation requires serotonin uptake by thalamocortical afferents, and not vesicular monoamine release SO JOURNAL OF NEUROSCIENCE LA English DT Article DE barrel; homologous recombination; knock-out; monoamine; p-chlorophenylalanine; serotonin; serotonin transporter; vesicular monoamine transporter; GABA transporter; whisker ID MOUSE SOMATOSENSORY CORTEX; PRIMARY SENSORY AREAS; CRANIAL NEURAL CREST; SMOOTH-MUSCLE CELLS; CEREBRAL-CORTEX; DEVELOPING RAT; POSTNATAL-DEVELOPMENT; THALAMIC AFFERENTS; NEURITE OUTGROWTH; CORTICAL BARRELS AB Thalamocortical neurons innervating the barrel cortex in neonatal rodents transiently store serotonin (5-HT) in synaptic vesicles by expressing the plasma membrane serotonin transporter (5-HTT) and the vesicular monoamine transporter (VMAT2). 5-HTT knock-out (ko) mice reveal a nearly complete absence of 5-HT in the cerebral cortex by immunohistochemistry, and of barrels, both at P7 and adulthood. Quantitative electron microscopy reveals that 5-HTT ko affects neither the density of synapses nor the length of synaptic contacts in layer IV. VMAT2 ko mice, completely lacking activity-dependent vesicular release of monoamines including 5-HT, also show a complete lack of 5-HT in the cortex but display largely normal barrel fields, despite sometimes markedly reduced postnatal growth. Transient 5-HTT expression is thus required for barrel pattern formation, whereas activity-dependent vesicular 5-HT release is not. C1 Univ Campus Biomed, Neurosci Lab, I-00155 Rome, Italy. Univ Navarra, Fac Med, Dept Anat, Pamplona 31008, Spain. Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. CSIC, Inst Cajal, Madrid 28029, Spain. Univ Roma La Sapienza, Dept Psychol, I-00185 Rome, Italy. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Keller, F (reprint author), Univ Campus Biomed, Neurosci Lab, Via Longoni 83, I-00155 Rome, Italy. RI Lesch, Klaus-Peter/J-4906-2013; OI Lesch, Klaus-Peter/0000-0001-8348-153X; Pascucci, Tiziana/0000-0003-1520-7373; Hall, Frank/0000-0002-0822-4063; Baldi, Alfonso/0000-0002-8693-3842 NR 75 TC 144 Z9 146 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 SEP 1 PY 2001 VL 21 IS 17 BP 6862 EP 6873 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 467FC UT WOS:000170690900043 PM 11517274 ER PT J AU Riddell, C Carson, RE Carrasquillo, JA Libutti, SK Danforth, DN Whatley, M Bacharach, SL AF Riddell, C Carson, RE Carrasquillo, JA Libutti, SK Danforth, DN Whatley, M Bacharach, SL TI Noise reduction in oncology FDG PET images by iterative reconstruction: A quantitative assessment SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; iterative reconstruction; image noise; lesion detection ID LIKELIHOOD ESTIMATOR IMAGES; BODY PET; STATISTICAL RECONSTRUCTION; FILTERED BACKPROJECTION; EMISSION-TOMOGRAPHY; EM RECONSTRUCTION; ORDERED SUBSETS; ALGORITHM AB Tumor detection depends on the contrast between tumor activity and background activity and on the image noise in these 2 regions. The lower the image noise, the easier the tumor detection. Tumor activity contrast is determined by physiology. Noise, however, is affected by many factors, including the choice of reconstruction algorithm. Previous simulation and phantom measurements indicated that the ordered-subset expectation maximization (OSEM) algorithm may produce less noisy images than does the usual filtered backprojection (FBP) method, at equivalent resolution. To see if this prediction would hold in actual clinical situations, we quantified noise in clinical images reconstructed with both OSEM and FBP. Methods: Three patients (2 with colon cancer, 1 with breast cancer) were imaged with FDG PET using a "gated replicate" technique that permitted accurate measurement of noise at each pixel. Each static image was acquired as a gated image sequence, using a pulse generator with a 1 -s period, yielding 40 replicate images over the 10- to 15-min imaging time. The images were or were not precorrected for attenuation and were reconstructed with both FBP and OSEM at comparable resolution. From these data, images of pixel mean, SID, and signal-to-noise ratio (S/N) could be produced, reflecting only noise caused by the statistical fluctuations in the emission process. Results: Noise did not vary greatly over each FBP image, even when image intensity varied greatly from one region to the next, causing S/N to be worse in low-activity regions than in high-activity regions. In contrast, OSEM had high noise in hot regions and low noise in cold regions. OSEM had a much better S/N than did FBP in cold regions of the image, such as the lungs (in the attenuation-corrected images), where improvements in S/N averaged 160%. Improvements with OSEM were less dramatic in hotter areas such as the liver (averaging 25% improvement in the attenuation-corrected images). In very hot tumors, FBP actually produced higher S/Ns than did OSEM. Conclusion: We conclude that OSEM reconstruction can significantly reduce image noise, especially in relatively low-count regions. OSEM reconstruction failed to improve S/N in very hot tumors, in which S/N may already be adequate for tumor detection. C1 NIH, Bethesda, MD 20892 USA. RP Bacharach, SL (reprint author), NIH, Bldg 10,Room 1C401, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; Carson, Richard/H-3250-2011; OI Carson, Richard/0000-0002-9338-7966; Carrasquillo, Jorge/0000-0002-8513-5734 NR 20 TC 65 Z9 67 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 2001 VL 42 IS 9 BP 1316 EP 1323 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 469XH UT WOS:000170841000016 PM 11535719 ER PT J AU Carrasquillo, JA Whatley, M Dyer, V Figg, WD Dahut, W AF Carrasquillo, JA Whatley, M Dyer, V Figg, WD Dahut, W TI Alendronate does not interfere with Tc-99m-methylene diphosphonate bone scanning SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE prostate; bisphosphonate; Tc-99m-methylene diphosphonate; bone metastasis ID PAGETS-DISEASE; INTRAVENOUS PAMIDRONATE; BREAST-CANCER; SCINTIGRAPHY; BISPHOSPHONATE; PHARMACOKINETICS; THERAPY AB Several studies have found that administration of etidronate results in competitive interference with Tc-99m-labeled bone scanning reagents. In contrast, in other studies this problem was not encountered with other bisphosphonates. Methods: We prospectively studied 9 patients with hormone-refractory prostate cancer. Tc-99m-methylene diphosphonate (MDP) bone scanning was performed before they received alendronate, and scanning was repeated a mean of 16.6 d afterward, when the patients had been receiving 40 mg alendronate daily for a mean of 6 d. In addition, 7 patients who underwent delayed scanning when they had been receiving alendronate for a mean of 111 d were also restudied. Quantitative whole-body bone scanning was performed, and radioactivity deposited in the bone metastasis was determined using region-of-interest analysis. Results: A <6% increase in whole-body retention of Tc-99m-MDP was seen on the initial postalendronate scan compared with the baseline scan. No significant differences in activity were seen in the bone lesion evaluated on the baseline and initial postalendronate studies. The delayed postalendronate scan generally showed similar or higher tracer accumulation compared with the baseline scan. Conclusion: Alendronate did not competitively inhibit uptake of Tc-99m-MDP in the skeleton or tumor metastasis. Use of alendronate before bone scanning is unlikely to result in decreased detection of lesions or falsely decreased Tc-99m-MDP activity at metastatic bone tumor sites. C1 NCI, Warren G Magnuson Clin Ctr, Dept Nucl Med, NIH, Bethesda, MD 20892 USA. NCI, Med Branch, Clin Pharmacokinet Sect, NIH, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), Bldg 10,Room 1C496,10 Ctr Dr,MSC 1180, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; Figg Sr, William/M-2411-2016; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 20 TC 12 Z9 12 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD SEP PY 2001 VL 42 IS 9 BP 1359 EP 1363 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 469XH UT WOS:000170841000022 PM 11535725 ER PT J AU Moser-Veillon, PB Mangels, AR Vieira, NE Yergey, AL Patterson, KY Hill, AD Veillon, C AF Moser-Veillon, PB Mangels, AR Vieira, NE Yergey, AL Patterson, KY Hill, AD Veillon, C TI Calcium fractional absorption and metabolism assessed using stable isotopes differ between postpartum and never pregnant women SO JOURNAL OF NUTRITION LA English DT Article DE calcium; postpartum; lactation; fractional absorption; stable isotopes; humans ID BONE-MINERAL CONTENT; LACTATING WOMEN; URINARY CALCIUM; EFFICIENCY; EXCRETION; ZINC; HOMEOSTASIS; MAGNESIUM; KINETICS; DENSITY AB Determining the fractional absorption (FA) of calcium using the incorporation into urine of stable isotopes given intravenously (IV) and orally has become a routine procedure. We investigated the FA of calcium in two groups of (2-3 mo) postpartum women lactating (LACT) (n = 6) and nonlactating (PPNL) (n = 6), and in never pregnant (NP) women (n = 7). The women consumed a controlled diet containing 30-33 mmol/d calcium (Ca) for 21 d. On d 7 of the controlled diet, the women received 0.05 mmol Of Ca-42 IV and 0.25 mmol Ca-44 orally in milk. Urine samples (24-h) were collected for the next 14 d and morning blood samples were collected from fasting subjects before dosing and at 24 and 48 h after receiving the isotopes. Milk samples from the LACT women were collected from each feeding beginning 24 h before to 72 h after dosing. There were no significant differences in the FA of calcium as measured by stable isotope incorporation into urine (23.8 +/- 2.9%), serum (24.0 +/- 3.4%) or milk (23.6 +/- 3.6%) of LACT women. The fractional calcium absorption measured in urine of the postpartum women (LACT and PPNL, 23.8 +/- 2.9% and 25.0 +/- 3.3%, respectively) did not differ but was greater (P < 0.028) than that of the NP women (17.3 +/- 1.3%). The postpartum LACT and PPNL women had a reduced urinary excretion of calcium (P < 0.01) compared with the NP women. There was a significantly greater incorporation (P < 0.001) by LACT women of the oral isotope dose into milk than into urine. Calcium FA can be determined from incorporation of stable isotopes into breast milk and serum as well as urine. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. RP Moser-Veillon, PB (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. NR 30 TC 11 Z9 12 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD SEP PY 2001 VL 131 IS 9 BP 2295 EP 2299 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 471GT UT WOS:000170921000012 PM 11533269 ER PT J AU Strausberg, RL AF Strausberg, RL TI The Cancer Genome Anatomy Project: new resources for reading the molecular signatures of cancer SO JOURNAL OF PATHOLOGY LA English DT Review DE gene expression; polymorphisms; chromosomal aberrations; databases; genomics ID EXPRESSED SEQUENCE TAGS; GENE-EXPRESSION; SERIAL ANALYSIS; HUMAN BRAIN; DATABASE; GENERATION; DISCOVERY; ANTIGENS; PROSTATE; INDEX AB The Cancer Genome Anatomy Project (CGAP) has built informational, technological, and physical resources to interface genomics with basic and clinical cancer research. The CGAP web site (http://cgap.nci.nih.gov) provides informatics tools for in silico analysis of the CGAP datasets as well as information for accessing each of the CGAP resources. Published in 2001 by John Wiley & Sons, Ltd. C1 NCI, Bethesda, MD 20892 USA. RP Strausberg, RL (reprint author), NCI, Bethesda, MD 20892 USA. NR 36 TC 53 Z9 55 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD SEP PY 2001 VL 195 IS 1 BP 31 EP 40 DI 10.1002/1096-9896(200109)195:1<31::AID-PATH920>3.0.CO;2-W PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 475JK UT WOS:000171160100005 PM 11568889 ER PT J AU Montgomery, JS Price, DK Figg, WD AF Montgomery, JS Price, DK Figg, WD TI The androgen receptor gene and its influence on the development and progression of prostate cancer SO JOURNAL OF PATHOLOGY LA English DT Review DE prostate cancer; androgen receptor; CAG trinucleotide repeat; GGN trinucleotide repeat; gene amplification; somatic mutation ID BULBAR MUSCULAR-ATROPHY; EPIDERMAL GROWTH-FACTOR; IN-SITU HYBRIDIZATION; CAG REPEAT; CELL-LINES; TRINUCLEOTIDE REPEATS; MOLECULAR MECHANISMS; STEROID-HORMONES; LIGAND-BINDING; MUTATIONS AB Prostate adenocarcinoma has the highest incidence of any malignancy and is the second leading cause of cancer-related deaths in men in industrialized countries. The development and progression of prostate cancer are dependent on testosterone and dihydrotestosterone; the androgen receptor is the vehicle through which these androgens exert their regulation on prostate cellular proliferation and differentiation. As a result, much effort has been devoted to elucidating the role of the androgen receptor in prostate cancer. The CAG and GGN trinucleotide repeats in exon 1 of the androgen receptor gene have been linked to prostate cancer risk and progression in some studies. Also, androgen receptor gene amplification may be a mechanism of prostate cancer cell adaptation to hormonal therapy. In addition, androgen receptor somatic mutations can result in receptors that have altered binding specificity when compared with wild-type receptors and heightened affinity for hormones other than testosterone and dihydrotestosterone. Gene amplification and somatic mutations, coupled with the fact that various growth factors have been shown to stimulate androgen receptor activity independently of androgens, may enable prostate cancer cells to grow despite testicular-androgen ablation. Unfortunately, current medical therapy for metastatic prostate cancer is deficient, hormone-refractory prostate cancer is a major obstacle in treatment, and, as a result, prostate cancer mortality is still significant. Further study of the function of the androgen receptor will offer a better understanding of prostate cancer pathogenesis and progression, aiding the development of more effective treatments for this disease. C1 NCI, Canc Therapeut Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Canc Therapeut Branch, CCR, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 95 TC 72 Z9 77 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD SEP PY 2001 VL 195 IS 2 BP 138 EP 146 DI 10.1002/1096-9896(200109)195:2<138::AID-PATH961>3.0.CO;2-Y PG 9 WC Oncology; Pathology SC Oncology; Pathology GA 475JJ UT WOS:000171159900002 PM 11592091 ER PT J AU Rose, PS Ahn, NU Levy, HP Magid, D Davis, J Liberfarb, RM Sponseller, PD Francomano, CA AF Rose, PS Ahn, NU Levy, HP Magid, D Davis, J Liberfarb, RM Sponseller, PD Francomano, CA TI The hip in Stickler syndrome SO JOURNAL OF PEDIATRIC ORTHOPAEDICS LA English DT Article DE hereditary arthro-ophthalmopathy; Legg-Perthes disease; osteoarthritis; Protrusio acetabuli; slipped epiphysis; Stickler syndrome ID HEREDITARY ARTHRO-OPHTHALMOPATHY; II PROCOLLAGEN GENE; ARTHROOPHTHALMOPATHY; OSTEOARTHRITIS; MUTATION; MANIFESTATIONS; FAMILIES; LINKAGE; COL11A1 AB Stickler syndrome is an autosomal dominant connective tissue disorder with a prevalence similar to that of Marfan syndrome. No previous study has examined hip pain or abnormalities in a large series of patients with Stickler syndrome. The purpose of this study was to describe hip abnormalities and their correlation with age and chronic hip pain in a cohort of 51 patients followed at the National Institutes of Health. Ten percent of patients had protrusio acetabuli, 21% coxa valga, and 34% of adults had hip osteoarthritis. Sixty-three percent of all patients and 79% of adults had chronic hip pain. In additions 16% of adult patients had a history of femoral head failure during youth. Arthritic changes and adult age were associated with hip pain. In summary, hip abnormalities are commonly observed in Stickler syndrome. Young patients require careful evaluation of hip pain, and regular screening of children with Stickler syndrome may be indicated for early detection of hip complications. C1 NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Rose, PS (reprint author), Mayo Clin, Dept Orthoped Surg, 200 1st St SW, Rochester, MN 55905 USA. FU NHGRI NIH HHS [97-HG-0089] NR 47 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-6798 J9 J PEDIATR ORTHOPED JI J. Pediatr. Orthop. PD SEP-OCT PY 2001 VL 21 IS 5 BP 657 EP 663 DI 10.1097/00004694-200109000-00020 PG 7 WC Orthopedics; Pediatrics SC Orthopedics; Pediatrics GA 469VJ UT WOS:000170836500020 PM 11521037 ER PT J AU Wiener, LS Vasquez, MJP Battles, HB AF Wiener, LS Vasquez, MJP Battles, HB TI Brief report: Fathering a child living with HIV/AIDS: Psychosocial adjustment and parenting stress SO JOURNAL OF PEDIATRIC PSYCHOLOGY LA English DT Article DE fathers; HIV/AIDS; children; psychological distress; parenting stress; chronic illness ID SOCIAL NETWORKS; FAMILY; HIV; ADAPTATION; MOTHERS; RESPONSES AB Objective: To examine the psychosocial stressors experienced by fathers of children diagnosed with HIV/AIDS. Methods: Thirty-one fathers whose children (ages 6 to 19) were participating in pediatric HIV clinical trials completed self-report measures of parenting stress, psychological distress, and need for psychosocial services. Results: Over half of this sample experienced significantly elevated levels of both parenting stress and psychological distress compared to standardized norms. Ninety-seven percent of these men reported the need for services including gender-specific support groups, assistance with discipline, disease management, and assistance with planning for the future. Conclusions: Elevated levels of parenting stress and psychological distress in fathers of children living with HIV suggest the need for additional psychological intervention in this population. C1 NCI, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC 20052 USA. RP Wiener, LS (reprint author), NCI, 10-13N240,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 18 Z9 21 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-8693 J9 J PEDIATR PSYCHOL JI J. Pediatr. Psychol. PD SEP PY 2001 VL 26 IS 6 BP 353 EP 358 DI 10.1093/jpepsy/26.6.353 PG 6 WC Psychology, Developmental SC Psychology GA 469CQ UT WOS:000170796300004 PM 11490036 ER PT J AU Liu, B Qin, LY Yang, SB Wilson, BC Liu, YX Hong, JS AF Liu, B Qin, LY Yang, SB Wilson, BC Liu, YX Hong, JS TI Femtomolar concentrations of dynorphins protect rat mesencephalic dopaminergic neurons against inflammatory damage SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; CYCLASE-ACTIVATING POLYPEPTIDE; NITRIC-OXIDE; SUBSTANCE-P; ULTRALOW CONCENTRATIONS; RESPIRATORY BURST; OPIOID MODULATION; MOLECULAR-BIOLOGY; BASAL GANGLIA; MICROGLIA AB The hallmark of Parkinson's disease is the death of nigral dopaminergic neurons, and inflammation in the brain has been increasingly associated with the pathogenesis of this neurological disorder. Dynorphins are among the major opioid peptides in the striato-nigral pathway and are important in regulating dopaminergic neuronal activities. However, it is not clear whether dynorphins play a role in the survival of nigral dopaminergic neurons. We have recently demonstrated that lipopolysaccharide (LPS) activates the brain immune cells microglia, in vitro and in vivo, to release neurotoxic factors to degenerate dopaminergic neurons. The purpose of this study was to explore the neuroprotective effect of dynorphins in the inflammation-mediated degeneration of dopaminergic neurons in rat midbrain neuron-glia cultures. LPS-induced neurotoxicity was significantly reduced by treatment with ultra low concentrations (10(-13)-10(-15) M) of the kappa -Opioid receptor agonist dynorphin A (1-17) or the receptor binding ineffective [des-Tyr(1)]dynorphin A (2-17), but not by U50488, a synthetic kappa -receptor agonist. The glia-mediated neuroprotective effect of dynorphins was further supported by the finding that femtomolar concentrations of dynorphins did not prevent the killing of dopaminergic neurons by 6-hydroxydopamine. However, ultra low concentrations of dynorphins inhibited LPS-incluced production of superoxide. These results suggest a glia-mediated and conventional opioid receptor-unrelated mechanism of action for the neuroprotective effect of ultra low concentrations of dynorphins. Understanding the underlying mechanisms of action should further define the roles of dynorphins in the regulation of dopaminergic neurons and help devise novel strategies to combat neurodegenerative diseases. C1 NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Liu, B (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, MD F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM liu3@niehs.nih.gov RI liu, Bin/A-7695-2009 NR 52 TC 49 Z9 49 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2001 VL 298 IS 3 BP 1133 EP 1141 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 465MX UT WOS:000170593700034 PM 11504811 ER PT J AU Urani, A Roman, FJ Phan, VL Su, TP Maurice, T AF Urani, A Roman, FJ Phan, VL Su, TP Maurice, T TI The antidepressant-like effect induced by sigma 1-receptor agonists and neuroactive steroids in mice submitted to the forced swimming test SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID METHYL-D-ASPARTATE; INDUCED LEARNING IMPAIRMENT; RAT HIPPOCAMPAL SLICES; SIGMA(1) RECEPTOR; PREGNENOLONE-SULFATE; BEHAVIORAL DESPAIR; MAJOR DEPRESSION; DEHYDROEPIANDROSTERONE-SULFATE; NOREPINEPHRINE RELEASE; INTRACELLULAR CA2+ AB The interaction of neuroactive steroids with the sigma (1)-receptor was investigated in Swiss mice submitted to the forced swimming test. The sigma (1)-agonists igmesine and (+)-SKF-10,047 and the steroid dehydroepiandrosterone sulfate (DHEAS) showed some antidepressant-like activity by shortening the immobility time, these effects being blocked by the sigma (1)-antagonist BD1047 or progesterone. The sigma (1)-agonist PRE-084 or pregnenolone sulfate failed to affect the immobility time. In adrenalectomized/ castrated (AdX/CX) mice, the effects of igmesine and DHEAS were significantly potentiated, and PRE-084 or pregnenolone sulfate induced significant decreases of immobility time. The augmented effects in AdX/CX were fully blocked by BD1047. The effects of the classical antidepressants, desipramine or fluoxetine, were unchanged in AdX/CX mice. The effect of stress on the sigma (1)-receptor binding and neurosteroid levels was then examined in different brain structures, in terms of in vivo (+)-[H-3]SKF-10,047 binding to sigma (1)-sites and neurosteroids levels. In the hippocampus, but not in the cortex or cerebellum, inhibition of in vivo (+)-[H-3]SKF-10,047 binding was measured in parallel to the extent of progesterone levels according to the endocrine conditions. These data confirmed the antidepressant ability of sigma (1)-receptor agonists and revealed that the endogenous steroidal levels tonically interfere with the efficacy of the sigma (1)-system. It was observed that local modifications in progesterone levels are directly related to the changes of in vivo sigma (1)-binding. Such observations may be of major importance in view of the therapeutic use of selective sigma (1)-agonists in depression. C1 Inst Biol, INSERM, U336, Behav Neuropharmacol Grp, F-34060 Montpellier, France. NIDA, Cellular Pathol Unit, Intramural Res Program, NIH, Baltimore, MD USA. RP Maurice, T (reprint author), Inst Biol, INSERM, U336, Behav Neuropharmacol Grp, 4 Blvd Henri VI, F-34060 Montpellier, France. NR 55 TC 138 Z9 146 U1 1 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD SEP PY 2001 VL 298 IS 3 BP 1269 EP 1279 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 465MX UT WOS:000170593700053 PM 11504830 ER PT J AU Storey, NM O'Bryan, JP Armstrong, DL AF Storey, NM O'Bryan, JP Armstrong, DL TI Potassium channel stimulation by nuclear hormone family receptors through Rac-dependent signalling in a rat anterior pituitary cell line (GH4C1) SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Meeting Abstract CT Meeting of the Physiological-Society CY JUL 03-04, 2001 CL UNIV SHEFFIELD, SHEFFIELD, ENGLAND SP Physiolog Soc HO UNIV SHEFFIELD C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4221 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD SEP PY 2001 VL 535 SU S BP 7P EP 8P PG 2 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 606ZN UT WOS:000178766100010 ER PT J AU Njie, VPS Thomas, AC AF Njie, VPS Thomas, AC TI Quality issues in clinical research and the implications on health policy (QICRHP) SO JOURNAL OF PROFESSIONAL NURSING LA English DT Article DE quality; scientific misconduct; scientific integrity; health policy; clinical research/practice ID PROMOTING SCIENTIFIC INTEGRITY; BALANCING ETHICAL QUANDARIES; NURSING RESEARCH; MISCONDUCT; PUBLICATIONS; GUIDELINES; RIGOR AB Scientific (research) misconduct relating to fraudulent behaviors, plagiarism, and violations in research protocol is extant in the literature. These behaviors result in inadvertent infringement on subjects' rights, safety, and confidentiality, and can negatively impact the implementation of health policies. Funding agencies, legislators, regulators, clinicians, and scientists continue to subject researchers' work to scrutiny and in-depth analyses to evaluate its quality because of increased reports of scientific misconduct. Therefore, clinical researchers are motivated to restore and maintain credibility throughout clinical trials to regain public trust because of adverse publicity. Quality in clinical research addresses the study's integrity and merit, which has important practice and policy implications. Study integrity and merit encompass bot the scientific and ethical components of clinical re search studies. Researchers suggest using structured evaluation processes, educating, and mentoring aspiring scientists on scientific integrity to prevent scientific misconduct. In addressing these issues, this article explicates and provides a synthesized critique of quality issues in clinical research, analyzes its implications on health policy and clinical practice, and proposes a systematic framework to evaluate clinical research studies. Copyright (C) 2001 by W.B. Saunders Company. C1 NINR, Div Intramural Res, Hlth Promot Lab, NIH, Bethesda, MD 20892 USA. RP Njie, VPS (reprint author), Baltimore City Community Coll, 2901 Liberty Heights Ave, Baltimore, MD 21215 USA. OI Njie-Carr, Veronica/0000-0002-7197-502X NR 37 TC 1 Z9 1 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 8755-7223 J9 J PROF NURS JI J. Prof. Nurs. PD SEP-OCT PY 2001 VL 17 IS 5 BP 233 EP 242 DI 10.1053/jpnu.2001.26308 PG 10 WC Nursing SC Nursing GA 476FW UT WOS:000171216400008 PM 11559879 ER PT J AU Sher, L Matthews, JR Turner, EH Postolache, TT Katz, KS Rosenthal, NE AF Sher, L Matthews, JR Turner, EH Postolache, TT Katz, KS Rosenthal, NE TI Early response to light therapy partially predicts long-term antidepressant effects in patients with seasonal affective disorder SO JOURNAL OF PSYCHIATRY & NEUROSCIENCE LA English DT Article DE depression; mood disorders; phototherapy; seasonal affective disorder ID WINTER DEPRESSION; PHOTOTHERAPY AB Objective: To determine if the antidepressant effect of 1 hour of light therapy is predictive of the response after 1 and 2 weeks of treatment in patients with seasonal affective disorder (SAD). Patients: Twelve patients With SAD. Setting. National Institutes of Health Clinical Center, Bethesda, Md. Interventions: Light therapy for 2 weeks. Outcome measures: Scores on the Seasonal Affective Disorder Version of the Hamilton Depression Rating Scale (SIGH-SAD) on 4 occasions (before and after 1 hour of light therapy and after 1 and 2 weeks of therapy) in the Winter when the patients were depressed. Change on typical and atypical depressive scores at these time points were compared. Results: Improvement of atypical depressive symptoms after 1 hour of light therapy positively correlated with improvement after 2 weeks of therapy. Conclusion: In patients, with SAD, the early response to light therapy may predict some aspects of long-term response to light therapy, but these results should be treated with caution until replicated. C1 NIMH, Sect Biol Rhythms, Bethesda, MD 20892 USA. RP Sher, L (reprint author), Columbia Univ, Dept Psychiat, New York State Psychiat Inst, Dept Neurosci, 1051 Riverside Dr,Ste 2917,Box 42, New York, NY 10032 USA. RI Turner, Erick/A-4848-2008 OI Turner, Erick/0000-0002-3522-3357 NR 14 TC 9 Z9 9 U1 1 U2 2 PU CANADIAN MEDICAL ASSOCIATION PI OTTAWA PA 1867 ALTA VISTA DR, OTTAWA, ONTARIO K1G 3Y6, CANADA SN 1180-4882 J9 J PSYCHIATR NEUROSCI JI J. Psychiatry Neurosci. PD SEP PY 2001 VL 26 IS 4 BP 336 EP 338 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 477BY UT WOS:000171264300007 PM 11590974 ER PT J AU Zhang, PJ Beatty, A Milne, JLS Subramaniam, S AF Zhang, PJ Beatty, A Milne, JLS Subramaniam, S TI Automated data collection with a tecnai 12 electron microscope: Applications for molecular imaging by cryomicroscopy SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE high-resolution electron microscopy; electron crystallography; protein complexes; remote microscopy; high-throughput structure determination ID CCD CAMERA; 400 KV; CRYSTALLOGRAPHY; PERFORMANCE AB In high-resolution biological electron microscopy, the speed of collection of large numbers of high-quality micrographs is a rate-limiting step in the overall process of structure determination. Approaches to speed up data collection can be very useful, especially in "single-molecule" microscopy of large multiprotein and protein-nucleic acid complexes, where many thousands of individual molecular images need to be averaged to determine the three-dimensional structure. Toward this end, we report the development of automated low-dose image acquisition procedures on a Tecnai 12 electron microscope using the scripting functionality available on the microscope computer. At the lowest level of automation, the user is required to select regions of interest that are to be imaged. All subsequent steps of image acquisition are then carried out automatically to record high-resolution images on either film or CCD, at desired defocus values, under conditions that satisfy user-specified limits for drift rates of the specimen stage. At the highest level of automation, determination of the best grid squares and the best regions suitable for imaging are carried out automatically. A medium level of automation is also available in which the user can designate the most promising grid squares manually and leave the process of finding the best holes in those grid squares to the microscope computer. We also show that all steps subsequent to insertion of the specimen in the microscope can be carried out remotely by connecting to the microscope computer via the Internet. Both features are implemented using Windows NT and Web-based tools and provide tools for automated data collection on any Tecnai microscope from any location. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zhang, PJ (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NR 12 TC 33 Z9 33 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD SEP PY 2001 VL 135 IS 3 BP 251 EP 261 DI 10.1006/jsbi.2001.4404 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 502CA UT WOS:000172725100003 PM 11722165 ER PT J AU Durston, S Pol, HEH Casey, BJ Giedd, JN Buitelaar, JK van Engeland, H AF Durston, S Pol, HEH Casey, BJ Giedd, JN Buitelaar, JK van Engeland, H TI Anatomical MRI of the developing human brain: What have we learned? SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE brain; development; magnetic resonance imaging; review ID DEFICIT HYPERACTIVITY DISORDER; OBSESSIVE-COMPULSIVE DISORDER; MAGNETIC-RESONANCE IMAGES; NORMAL FETAL BRAIN; CORPUS-CALLOSUM; PSYCHIATRIC-DISORDERS; LONGITUDINAL MRI; TEMPORAL-LOBE; AGES 4-18; IN-VIVO AB Objective: To critically review and integrate the existing literature on magnetic resonance imaging (MRI) studies of the normally developing brain in childhood and adolescence and discuss the implications for clinical MRI studies. Method: Changes in regional brain volume with age and differences between the sexes are summarized from reports in refereed journal articles pertaining to MRI of the developing human brain. Results: White matter volume increases with age. Gray matter volumes increase during childhood and then decrease before adulthood. On average, boys have larger brains than girls; after correction for overall brain volume the caudate is relatively larger In girls, and the amygdala is relatively larger in boys. Differences are of clinical interest given gender-related differences in the age of onset, symptomatology, and prevalence noted for nearly all childhood-onset psychiatric disorders. Attention-deficit/hyperactivity disorder is frequently used as an example to demonstrate these points. Conclusions: Understanding the developmental trajectories of normal brain development and differences between the sexes is important for the interpretation of clinical imaging studies. C1 Univ Utrecht, Med Ctr, Dept Child & Adolescent Psychiat, NL-3584 CX Utrecht, Netherlands. NIMH, Bethesda, MD 20892 USA. Sackler Inst Dev Psychobiol, New York, NY USA. RP Durston, S (reprint author), Univ Utrecht, Med Ctr, Dept Child & Adolescent Psychiat, A01-468,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. RI Giedd, Jay/A-3080-2008; Buitelaar, Jan/E-4584-2012; Giedd, Jay/B-7302-2012; Hulshoff Pol, Hilleke/B-4795-2014; Giedd, Jay/J-9644-2015 OI Buitelaar, Jan/0000-0001-8288-7757; Giedd, Jay/0000-0003-0827-3460; Hulshoff Pol, Hilleke/0000-0002-2038-5281; Giedd, Jay/0000-0003-2002-8978 NR 59 TC 220 Z9 226 U1 5 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD SEP PY 2001 VL 40 IS 9 BP 1012 EP 1020 DI 10.1097/00004583-200109000-00009 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 467TF UT WOS:000170719300009 PM 11556624 ER PT J AU Albert, MR Klion, A Turner, ML AF Albert, MR Klion, A Turner, ML TI Pruritus and eosinophilia in a 14-year-old girl from Liberia SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID HYPERREACTIVE ONCHOCERCIASIS SOWDA; ONCHODERMATITIS SOWDA; IVERMECTIN TREATMENT; VOLVULUS INFECTION; DIAGNOSIS; DISEASE C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. Natl Inst Allergy & Infect Dis, Lab Parasit Dis, Bethesda, MD USA. RP Turner, ML (reprint author), NCI, Dermatol Branch, Bldg 10,Rm 12N238,10 Ctr Dr, Bethesda, MD 20892 USA. OI Klion, Amy/0000-0002-4986-5326 NR 15 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 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD SEP PY 2001 VL 45 IS 3 BP 435 EP 437 DI 10.1067/mjd.2001.116584 PG 3 WC Dermatology SC Dermatology GA 468TC UT WOS:000170773400012 PM 11511842 ER PT J AU Fananapazir, L Mohiddin, SA Shih, J AF Fananapazir, L Mohiddin, SA Shih, J TI Myocardial bridging of the left anterior descending coronary artery in children with hypertrophic cardiomyopathy - Reply SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID SUDDEN-DEATH; ISCHEMIA C1 NHLBI, Cardiol Branch, Electrophysiol & Inherited Heart Dis Sect, Bethesda, MD 20892 USA. RP Fananapazir, L (reprint author), NHLBI, Cardiol Branch, Electrophysiol & Inherited Heart Dis Sect, Bldg 10,Room 7B-15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD SEP PY 2001 VL 38 IS 3 BP 922 EP 922 DI 10.1016/S0735-1097(01)01462-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 469PG UT WOS:000170823600054 ER PT J AU Volpato, S Leveille, SG Corti, MC Harris, TB Guralnik, JM AF Volpato, S Leveille, SG Corti, MC Harris, TB Guralnik, JM TI The value of serum albumin and high-density lipoprotein cholesterol in defining mortality risk in older persons with low serum cholesterol SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE MeSH; low cholesterol; albumin; HDL-C; mortality; aging; frailty ID CORONARY HEART-DISEASE; CARDIOVASCULAR HEALTH; HYPOCHOLESTEROLEMIA; ASSOCIATION; POPULATION; FRAMINGHAM; HYPOALBUMINEMIA; INFLAMMATION; ADULTS; MEN AB OBJECTIVES: To investigate the relationship between low cholesterol and mortality in older persons to identify, using information collected at a single point in time, subgroups of persons with low and high mortality risk. DESIGN: Prospective cohort study with a median followup period of 4.9 years. SETTINGS: East Boston, Massachusetts; New Haven, Connecticut; and Iowa and Washington counties, Iowa. PARTICIPANTS: Four thousand one hundred twenty-eight participants (64% women) age 70 and older at baseline (mean 78.7 years, range 70-103); 393(9.5%) had low cholesterol, defined as less than or equal to 160 mg/dl. MEASUREMENTS: All-cause mortality and mortality not related to coronary heart disease and ischemic stroke. RESULTS: During the follow-up period there were 1,117 deaths. After adjustment for age and gender, persons with low cholesterol had significantly higher mortality than those with normal and high cholesterol. Among subjects with low cholesterol, those with albumin > 38 g/L had a Significant risk reduction compared with those with albumin less than or equal to 38 g/L (relative risk (RR) = 0.57; 95 % confidence interval (CI) = 0.41-0.79). Within the higher albumin group, high-density lipoprotein cholesterol (HDL-C) level further identified two subgroups of subjects with different risks; participants with HDL-C < 47 mg/dl had a 32% risk reduction (RR = 0.68; 95% CI = 0.47-0.99) and those with HDL-C greater than or equal to 47 mg/dl had a 62% risk reduction (RR = 0.38; 95% CI = 0.20-0.68), compared with the reference category; those with albumin less than or equal to 38 g/L and HDL-C < 47 mg/dl. CONCLUSIONS: Older persons with low cholesterol constitute a heterogeneous group with regard to health characteristics and mortality risk. Serum albumin and HDL-C can be routinely used in older patients with low cholesterol to distinguish three subgroups with different prognoses: (1) high risk (low albumin), (2) intermediate risk (high albumin and low HDL-Q, and (3) low risk (high albumin and high HDL-Q. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Hebrew Rehabil Ctr Aged Res & Training Inst, Boston, MA USA. Osped Camposampiero, Local Hlth Unit 15, Dept Geriatr, Padua, Italy. RP Volpato, S (reprint author), NIA, Epidemiol Demog & Biometry Program, 7201 Wisconsin Ave,Room 3C-309, Bethesda, MD 20892 USA. RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 NR 34 TC 71 Z9 75 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2001 VL 49 IS 9 BP 1142 EP 1147 DI 10.1046/j.1532-5415.2001.49229.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 474DR UT WOS:000171090700001 PM 11559371 ER PT J AU Fillenbaum, GG Landerman, LR Blazer, DG Saunders, AM Harris, TB Launer, LJ AF Fillenbaum, GG Landerman, LR Blazer, DG Saunders, AM Harris, TB Launer, LJ TI The relationship of APOE genotype to cognitive functioning in older African-American and Caucasian community residents SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE APOE epsilon 4; cognitive function; longitudinal; race ID APOLIPOPROTEIN-E GENOTYPE; ALZHEIMERS-DISEASE; APOE-EPSILON-4 ALLELE; ELDERLY POPULATION; E POLYMORPHISM; ASSOCIATION; DEMENTIA; DECLINE; RISK; EPSILON-4 AB OBJECTIVES: To determine whether cognitive decline associated with the apolipoprotein E (APOE) epsilon4 allele is different in older African Americans than it is in Caucasians. DESIGN: Performance on a brief screen of cognitive functioning was examined at baseline (N = 1,891), and 4 years later (N = 1,389) to determine the extent to which the presence of APOE epsilon4 affected level of and change in performance, and whether this differed as a function of race, age, initial score, and change in score. SETTING: Five adjacent counties in the Piedmont area of North Carolina. PARTICIPANTS: In 1986, a stratified random household sample of community residents age 65 and older (n = 4,162; 54% African-American, 45% Caucasian, 1% other race) formed the Duke Established Populations for Epidemiologic Studies of the Elderly. Of those available at the sixth annual wave, 76% were genotyped, with 1,891 providing baseline data on this wave, and the available survivors (n = 1,389) providing longitudinal data 4 years later. MEASUREMENTS: The Short Portable Mental Status Questionnaire (SPMSQ), a brief screen of cognitive functioning, was administered to all subjects on both occasions. We examined score at baseline and cognitive decline (i.e., increase of 2+ errors) at follow-up. Control measures included demographic characteristics, health behaviors, health and functional status, and medication use. APOE status was coded as epsilon4 present versus absent. RESULTS: APOE epsilon4 was significantly and uniquely related to lower score at baseline and significantly increased the odds of cognitive decline by 59%. There was no statistically significant interaction between APOE epsilon4 and age, race, initial SPMSQ score, or SPMSQ score at follow-up. CONCLUSION: APOE epsilon4 is modestly, if significantly, related to poorer cognitive functioning and to decline in cognitive functioning. No differences were found by age or race in this community representative sample.. C1 Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Div Neurol, Dept Med, Durham, NC 27710 USA. NIA, Epidemiol Demog & Biometry Program, NIH, Bethesda, MD USA. RP Fillenbaum, GG (reprint author), Duke Univ, Med Ctr, Ctr Study Aging & Human Dev, Dept Psychiat, Box 3003, Durham, NC 27710 USA. FU NIA NIH HHS [R01-AG17559, N01-AG-1-2102, R01-AG12765, R37 AG08937] NR 53 TC 47 Z9 48 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2001 VL 49 IS 9 BP 1148 EP 1155 DI 10.1046/j.1532-5415.2001.49230.x PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 474DR UT WOS:000171090700002 PM 11559372 ER PT J AU Walter-Ginzburg, A Guralnik, JM Blumstein, T Gindin, J Modan, B AF Walter-Ginzburg, A Guralnik, JM Blumstein, T Gindin, J Modan, B TI Assistance with personal care activities among the old-old in Israel: A national epidemiological study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE ADL; disability; ethnic differences; Israel; old-old ID LONG-TERM-CARE; FUNCTIONAL-CAPACITY; SOCIAL SUPPORT; ALAMEDA COUNTY; INFORMAL CARE; DISABILITY; HEALTH; AGE; POPULATIONS; PREDICTORS AB OBJECTIVES: The objectives of this study were to (1) estimate rates of difficulty, need for assistance, and receipt of assistance with activities of daily living (ADLs) among the old-old in Israel; (2) describe the, living arrangements of the dependent old-old; and (3) gain insight into the caregiving provided to the disabled members of this population. DESIGN. A random stratified sample of 1,820 subjects age 75 to 94 selected from the National Population Register (NPR), a complete listing of the Israeli population maintained by the Ministry of the Interior. The study sample consisted of Jews living in Israel on January 1, 1989, stratified by age (four 5-year age groups: 75-79, 80-84, 85-89, 90-94), sex, and place of birth (Europe-America, Middle East/North Africa, Israel). SETTING: National sample of old-old Jewish Israelis. PARTICIPANTS: One thousand eight hundred twenty Israelis age 75 to 94 who were living in the community or in institutions at the time of the baseline interview. MEASUREMENTS: Participants' disability status was classified in terms of difficulty, with, needing help with, and receiving help with any of five ADLs (washing/bathing, dressing, transferring, toileting, and eating). Only those receiving assistance from a person (as opposed to a device) were considered to be receiving help. The independent variables used included sociodemographic, health, and social network characteristics of the participants. C1 Tel Aviv Univ, Herczeg Inst Aging, IL-69978 Tel Aviv, Israel. Chaim Sheba Med Ctr, Dept Clin Epidemiol, IL-52621 Tel Hashomer, Israel. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Kaplan Hosp, Geriatr Inst Educ & Res, IL-76100 Rehovot, Israel. RP Walter-Ginzburg, A (reprint author), Mavoh Ganigar 4, IL-69359 Tel Aviv, Israel. FU NIA NIH HHS [R01 AGO5885] NR 58 TC 27 Z9 27 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2001 VL 49 IS 9 BP 1176 EP 1184 DI 10.1046/j.1532-5415.2001.49234.x PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 474DR UT WOS:000171090700006 PM 11559376 ER PT J AU Cricco, M Simonsick, EM Foley, DJ AF Cricco, M Simonsick, EM Foley, DJ TI The impact of insomnia on cognitive functioning in older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE insomnia; cognitive function; older; depressive symptoms ID JAPANESE-AMERICAN MEN; SLEEP DISORDERS; ELDERLY PERSONS; PERFORMANCE; IMPAIRMENT; DECLINE; ASSOCIATION; MORTALITY; DEMENTIA; WOMEN AB OBJECTIVES: To examine whether self-reported symptoms of insomnia independently increase risk of cognitive decline in older adults. DESIGN: Longitudinal cohort study. SETTING: The four sites of the Established Populations for Epidemiologic Studies of the Elderly. PARTICIPANTS: Six thousand four hundred forty-four community-dwelling men and women age 65 and older who had no more than one error on the Short Portable Mental Status Questionnaire (SPMSQ) at baseline and an in-person interview at the third annual follow-up (FU3). MEASUREMENTS: Insomnia was defined as report of trouble falling asleep or waking up too early most of the time. Cognitive decline was defined as two or more errors on the SPMSQ at FU3. Logistic regression was used to determine risk of cognitive decline associated with insomnia, controlling for demographic, behavioral, and health-related factors. Analyses were stratified by sex and depressed mood. RESULTS: Among nondepressed men, those reporting symptoms of insomnia at both baseline and FU3 had an adjusted odds ratio (OR) of 1.49 (95% CI = 1.03-2.14) for cognitive decline, relative to those with no insomnia at FU3. Men with insomnia at FU3 only were not at increased risk (OR = 1.16, 95% CI = 0.82-1.65). These relationships were not found in women. Men and women with depressive symptoms at FU3 were at increased risk for cognitive decline independent of insomnia. CONCLUSION: Chronic insomnia independently predicts incident cognitive decline in older men. More sensitive measures of cognitive performance may identify more subtle declines and may confirm whether insomnia is associated with cognitive decline in women. C1 Univ Iceland, Fac Med, Reykjavik, Iceland. NIA, Clin Invest Lab, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Cricco, M (reprint author), Skolavordustig 12, IS-101 Reykjavik, Iceland. FU NIA NIH HHS [AG-1-2102, N01-AG-02105, N01-AG-02106, N01-AG-02107] NR 35 TC 136 Z9 144 U1 2 U2 8 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD SEP PY 2001 VL 49 IS 9 BP 1185 EP 1189 DI 10.1046/j.1532-5415.2001.49235.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 474DR UT WOS:000171090700007 PM 11559377 ER PT J AU Wong, STC Koslow, SH AF Wong, STC Koslow, SH TI Human brain program research Progress in biomedical imaging/neuroscience, 2001 SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Editorial Material C1 Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94131 USA. Natl Inst Mental Hlth, Bethesda, MD USA. RP Wong, STC (reprint author), Univ Calif San Francisco, Dept Radiol, Box 0628,505 Parnassus Ave, San Francisco, CA 94131 USA. NR 7 TC 2 Z9 2 U1 2 U2 3 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD SEP-OCT PY 2001 VL 8 IS 5 BP 510 EP 511 PG 2 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 473GC UT WOS:000171031300009 PM 11522771 ER PT J AU Kim, YH Earm, JH Ma, TH Verkman, AS Knepper, MA Madsen, KM Kim, J AF Kim, YH Earm, JH Ma, TH Verkman, AS Knepper, MA Madsen, KM Kim, J TI Aquaporin-4 expression in adult and developing mouse and rat kidney SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID INSENSITIVE WATER CHANNEL; LOCALIZATION; MICE; IMMUNOLOCALIZATION; VASOPRESSIN; PHYSIOLOGY; MEMBRANES; SEGMENTS; PROTEIN; LACKING AB Aquaporin-4 (AQP4) is a member of the aquaporin water-channel family. AQP4 is expressed primarily in the brain, but it is also present in the collecting duct of the kidney, where it is located in the basolateral plasma membrane of principal cells and inner medullary collecting duct (IMCD) cells. Recent studies in the mouse also have reported the presence of AQP4 in the basolateral membrane of the proximal tubule. The purpose of this study was to establish the pattern of AQP4 expression during kidney development and in the adult kidney of both the mouse and the rat. Kidneys of adult and 3-, 7-, and 15-d-old mice and rats were preserved for immunohistochemistry and processed using a peroxidase pre-embedding technique. In both the mouse and the rat., strong basolateral immunostaining was observed in IMCD cells and principal cells in the medullary collecting duct at all ages examined. Labeling was weaker in the cortical collecting duct and the connecting tubule, and there was no labeling of connecting tubule cells in the mouse. In adult mouse kidney, strong AQP4 immunoreactivity was observed in the S3 segment of the proximal tubule. However, there was little or no labeling in the cortex or around the corticomedullary junction in 3- and 7-d-old mice. Between 7 and 15 d of age, distinct AQP4 immunoreactivity appeared in the S3 segment of the mouse proximal tubule concomitant with the differentiation of this segment of the nephron. Labeling of proximal tubules was never observed in the rat kidney. These results suggest that there are differences in transepithelial water transport between mouse and rat or that additional, not yet identified water channels exist in the rat proximal tubule. C1 Catholic Univ, Coll Med, Dept Anat, Seoul, South Korea. Univ Florida, Coll Med, Div Nephrol Hypertens & Transplantat, Gainesville, FL USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, Dept Physiol, San Francisco, CA 94143 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Madsen, KM (reprint author), Univ Florida, Div Nephrol, Box 100224, Gainesville, FL 32610 USA. FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 24 TC 17 Z9 17 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD SEP PY 2001 VL 12 IS 9 BP 1795 EP 1804 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 465QA UT WOS:000170600400001 PM 11518772 ER PT J AU Ito, T Nishimura, Y Saavedra, J AF Ito, T Nishimura, Y Saavedra, J TI Pre-treatment with candesartan protects from cerebral ischaemia SO JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM LA English DT Article DE renin angiotensin system; angiotensin receptors; genetic hypertension; stroke; brain injury ID ANGIOTENSIN-CONVERTING ENZYME; RECEPTOR ANTAGONIST CV-11974; BLOOD-FLOW AUTOREGULATION; HYPERTENSIVE RATS; AT(1) RECEPTORS; BRAIN; ISCHEMIA; INFARCTION; EXPRESSION; ENALAPRIL AB Angiotensin II (Ang II) regulates cerebral blood flow by stimulating cerebral vasoconstriction via AT,receptors. In adult spontaneously hypertensive rats (SHR), the cerebrovascular autoregulatory curve is shifted to the right, in the direction of higher blood pressures, an indication of excessive cerebrovascular vasoconstriction. A restricted capacity to dilate cerebral blood vessels may be responsible for the enhanced vulnerability to cerebrovascular ischaemia during hypertension. We found that chronic treatment with the AT(1)-receptor antagonist, candesartan, (0.5 mg/kg/day for 14 days, via osmotic minipumps implanted in the subcutaneous tissue) blocked Ang II binding to AT(1)-receptors in cerebral blood vessels and in brain areas involved in the regulation of cerebrovascular flow, and increased the ratio of lumen-wall area in the middle cerebral artery. Candesartan treatment normalised the lower part of the autoregulatory curve in SHR, and markedly decreased cerebral ischaemia as a consequence of middle cerebral artery occlusion with reperfusion. Protection from ischaemia is related to arterial remodelling, enhanced compensatory vasodilatation in the peripheral area of ischaemia, decreased reduction in cerebral blood flow following the occlusion of a major cerebral blood vessel, and protection from injury in the periphery of the lesion. Our results indicate that pre-treatment with AT(1)-antagonists such as candesartan could be of benefit in the prevention and treatment of brain ischaemia. C1 NIMH, Sect Pharmacol, NIH, Bethesda, MD 20892 USA. RP Saavedra, J (reprint author), NIMH, Sect Pharmacol, NIH, 10 Ctr Dr,Bldg 10,Rm 2D-57, Bethesda, MD 20892 USA. NR 29 TC 23 Z9 24 U1 0 U2 2 PU J R A A S LTD PI BIRMINGHAM PA EDGBASTON HOUSE, 3 DUCHESS PLACE, EDGBASTON, BIRMINGHAM B16 8NH, ENGLAND SN 1470-3203 J9 J RENIN-ANGIO-ALDO S JI J. Renin-Angiotensin-Aldosterone Syst. PD SEP PY 2001 VL 2 IS 3 BP 174 EP 179 DI 10.3317/jraas.2001.024 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 487XM UT WOS:000171904400005 PM 11881119 ER PT J AU Grady, PA Knebel, AR Draper, A AF Grady, PA Knebel, AR Draper, A TI End-of-life issues in AIDS: the research perspective SO JOURNAL OF THE ROYAL SOCIETY OF MEDICINE LA English DT Article ID PRIMARY-CARE CLINICIAN; HIV; COMMUNICATION; HOSPICE; QUALITY C1 NINR, NIH, Bethesda, MD 20892 USA. RP Knebel, AR (reprint author), NINR, NIH, 31 Ctr Dr,Room 5B-05, Bethesda, MD 20892 USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU ROYAL SOC MEDICINE PRESS LTD PI LONDON PA 1 WIMPOLE STREET, LONDON W1M 8AE, ENGLAND SN 0141-0768 J9 J ROY SOC MED JI J. R. Soc. Med. PD SEP PY 2001 VL 94 IS 9 BP 479 EP 482 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 472NY UT WOS:000170991400018 PM 11535756 ER PT J AU Bolling, SF Badhwar, V Schwartz, CF Oeltgen, PR Kilgore, K Su, TP AF Bolling, SF Badhwar, V Schwartz, CF Oeltgen, PR Kilgore, K Su, TP TI Opioids confer myocardial tolerance to ischemia: Interaction of delta opioid agonists and antagonists SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID AUTOPERFUSION MULTIORGAN PREPARATION; HIBERNATION INDUCTION TRIGGERS; MAJOR ORGANS; PRESERVATION; RECEPTORS; RAT; PROTECTION; DEPENDENCE AB Background: Mammalian hibernation biology is now known to be mediated by delta opioids. The altered myocellular physiology of hibernation closely parallels that of hypothermic ischemia used to protect the heart for cardiac surgery. Methods and Results: The present study examined the interaction of delta opioid agonists and antagonists on myocardial tolerance to ischemia. By means of a nonhibernating isolated rabbit heart model, functional and metabolic myocardial parameters were assessed during nonischemic baseline and postischemic recovery periods. Control hearts with standard cardioplegic protection alone were compared with those with cardioplegia plus preperfusion with a delta opioid agonist, a delta opioid antagonist, or both. All hearts were then subjected to 2 hours of global ischemia. Compared with cardioplegia alone, postischemic left ventricular developed pressure, coronary flows, and myocardial oxygen consumption were all increased with administration of delta opioid agonists and decreased below baseline with delta opioid antagonists. Functional recovery of left ventricular developed pressure was improved with opioids (control hearts: 36 +/- 3 nun Hg vs hearts with cardioplegia plus delta opioid agonist: 65 +/- 5 mm Hg, P <.01) and inhibited with antagonists (control hearts: 36 3 mm Hg vs hearts with cardioplegia plus delta opioid antagonist: 17 +/- 5 mm Hg, P <.05), rind true to form, the protective opioid effect was negated when combined with an antagonist (control hearts: 36 3 mm Hg vs hearts with cardioplegia plus delta opioid agonist and delta opioid antagonist: 42 +/- 4 mm Hg, P = not significant). Conclusions: This study demonstrates that cardiac tolerance to ischemia may be mediated by delta opioids. C1 Univ Michigan, Sect Cardiac Surg, Ann Arbor, MI USA. Univ Kentucky, Dept Pathol, Lexington, KY USA. Natl Inst Drug Abuse, Bethesda, MD USA. RP Bolling, SF (reprint author), Univ Michigan Hosp, Sect Cardiac Surg, 1500 E Med Ctr Dr,2120D Taubman Ctr,Box 0348, Ann Arbor, MI 48109 USA. FU NHLBI NIH HHS [HL58781-01A1] NR 29 TC 22 Z9 24 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD SEP PY 2001 VL 122 IS 3 BP 476 EP 481 DI 10.1067/mtc.2001.116203 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 473EM UT WOS:000171027100012 PM 11547297 ER PT J AU Alving, BM AF Alving, BM TI Diagnosis and management of patients with the antiphospholipid syndrome SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS LA English DT Article; Proceedings Paper CT 6th National Conference on Anticoagulant Therapy CY MAY 12, 2001 CL WASHINGTON, D.C. SP Anticoagulation Forum DE antiphospholipid syndrome; lupus anticoagulant; anticardiolipin antibodies ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RECURRENT PREGNANCY LOSS; ANTICARDIOLIPIN ANTIBODIES; THROMBOCYTOPENIC PURPURA; CLINICAL-SIGNIFICANCE; DOSE HEPARIN; ANTICOAGULANT; THROMBOSIS; TRIAL; ASSOCIATION AB The antiphospholipid syndrome is an autoimmune disorder characterized by venous or arterial thrombosis, recurrent pregnancy loss, and thrombocytopenia combined with laboratory tests that indicate the presence of antibodies against phospholipid-binding proteins. The antibodies are directed against a complex of phospholipid with a protein such as beta2-glycoprotein I (beta2-GPI) or prothrombin and are detected by means of phospholipid-dependent coagulation assays (known as assays for lupus anticoagulants) and by ELISAs that contain beta2-GPI and a phospholipid (e.g., cardiolipin). The antiphospholipid syndrome can be associated with other connective tissue disorders such as systemic lupus erythematosus or may be the only manifestation of an autoimmune disorder. Management of patients with this disorder usually includes anticoagulation, which has been found to reduce the rate of recurrence of venous and arterial thrombosis as well as the rate of fetal loss. C1 NHLBI, Div Blood Dis & Resources, NIH, Bethesda, MD 20892 USA. RP Alving, BM (reprint author), NHLBI, Div Blood Dis & Resources, NIH, 6701 Rockledge Dr,MSC 7950,Rockledge 2,10th Floor, Bethesda, MD 20892 USA. NR 24 TC 3 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0929-5305 J9 J THROMB THROMBOLYS JI J. Thromb. Thrombolysis PD SEP PY 2001 VL 12 IS 1 BP 89 EP 93 DI 10.1023/A:1012798713607 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 492KX UT WOS:000172168500013 PM 11711694 ER PT J AU Nam, JH Bukh, J Pucell, RH Emerson, SU AF Nam, JH Bukh, J Pucell, RH Emerson, SU TI High-level expression of hepatitis C virus (HCV) structural proteins by a chimeric HCV/BVDV genome propagated as a BVDV pseudotype SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE bovine viral diarrhea virus; hepatitis C virus; viral genome ID VIRAL DIARRHEA VIRUS; IN-VITRO INFECTION; CELL LINE; GLYCOPROTEIN COMPLEXES; MONOCLONAL-ANTIBODIES; REPLICATION; RNA; CHIMPANZEES; NEUTRALIZATION; HEPATOCYTES AB A chimeric cDNA genome was constructed in which the core, E1 and E2 genes of hepatitis C virus (HCV) replaced the core, E-rns, E1 and E2 genes of bovine viral diarrhea virus (BVDV). High levels of HCV structural proteins were expressed in a small number of human or bovine cells following transfection with chimeric RNA. However, in one cell line, bovine embryonic trachea cells [EBTr(A)], the number of cells expressing HCV proteins increased to greater than 70% following serial passage of culture medium. These cells were persistently infected with a non-cyto pathogenic BVDV helper virus. In these cells, the chimeric genome was packaged into infectious particles that accumulated in the culture medium at a titer as high as 10(7)-10(9) genome equivalents per mi. The virus particles were pseudotypes, because they were neutralized by anti-BVDV but not by anti-HCV. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Room 209 Bldg 7, Bethesda, MD 20892 USA. NR 28 TC 11 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD SEP PY 2001 VL 97 IS 1-2 BP 113 EP 123 DI 10.1016/S0166-0934(01)00339-1 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 467AG UT WOS:000170677900011 PM 11483222 ER PT J AU Nishigaki, K Thompson, D Hanson, C Yugawa, T Ruscetti, S AF Nishigaki, K Thompson, D Hanson, C Yugawa, T Ruscetti, S TI The envelope glycoprotein of Friend spleen focus-forming virus covalently interacts with and constitutively activates a truncated form of the receptor tyrosine kinase Stk SO JOURNAL OF VIROLOGY LA English DT Article ID MACROPHAGE-STIMULATING PROTEIN; COMPLETE NUCLEOTIDE-SEQUENCE; MURINE LEUKEMIA-VIRUS; ERYTHROPOIETIN RECEPTOR; ERYTHROLEUKEMIA VIRUS; ENDOPLASMIC-RETICULUM; SIGNAL-TRANSDUCTION; GENE-PRODUCT; CELLS; GROWTH AB The Friend spleen focus-forming virus (SFFV) encodes a unique envelope glycoprotein, gp55, which allows erythroid cells to proliferate and differentiate in the absence of erythropoietin (Epo). SFFV gp55 has been shown to interact with the Epo receptor complex, causing constitutive activation of various signal-transducing molecules. When injected into adult mice, SFFV induces a rapid erythroleukemia, with susceptibility being determined by the host gene Fv-2, which was recently shown to be identical to the gene encoding the receptor tyrosine kinase Stk/Ron. Susceptible, but not resistant, mice encode not only full-length Stk but also a truncated form of the kinase, sf-Stk, which may mediate the biological effects of SFFV infection. To determine whether expression of SFFV gp55 leads to the activation of sf-Stk, we expressed sf-Stk, with or without SFFV gp55, in hematopoietic cells expressing the Epo receptor. Our data indicate that sf-Stk interacts with SFFV gp55 as well as gp55(P), the biologically active form of the viral glycoprotein, forming disulfide-linked complexes. This covalent interaction, as well as noncovalent interactions with SFFV gp55, results in constitutive tyrosine phosphorylation of sf-Stk and its association with multiple tyrosine-phosphorylated signal-transducing molecules. In contrast, neither Epo stimulation in the absence of SFFV gp55 expression nor expression of a mutant of SFFV that cannot interact with sf-Stk was able to induce tyrosine phosphorylation of sf-Stk or its association with any signal-transducing molecules. Covalent interaction of sf-Stk with SFFV gp55 and constitutive tyrosine phosphorylation of sf-Stk can also be detected in an erythroleukemia cell line derived from an SFFV-infected mouse. Our results suggest that SFFV gp55 may mediate its biological effects in vivo by interacting with and activating a truncated form of the receptor tyrosine kinase Stk. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. RP Ruscetti, S (reprint author), NCI, Basic Res Lab, Bldg 469,Room 205, Frederick, MD 21702 USA. NR 50 TC 54 Z9 58 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2001 VL 75 IS 17 BP 7893 EP 7903 DI 10.1128/JVI.75.17.7893-7903.2001 PG 11 WC Virology SC Virology GA 461AZ UT WOS:000170343900013 PM 11483734 ER PT J AU Wang, KN Pesnicak, L Guancial, E Krause, PR Straus, SE AF Wang, KN Pesnicak, L Guancial, E Krause, PR Straus, SE TI The 2.2-kilobase latency-associated transcript of herpes simplex virus type 2 does not modulate viral replication, reactivation, or establishment of latency in transgenic mice SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; GENE MESSENGER-RNA; GENITAL HERPES; INFECTED MICE; STABLE INTRON; IN-VIVO; EXPRESSION; PROMOTER; NEURONS; REGION AB To better understand the mechanisms responsible for the observed effects of deletions in the promoter region of the latency-associated transcript (LAT) gene in impairing herpes simplex virus (HSV) reactivation, we generated mice transgenic for a 5.5-kb HSV type 2 (HSV-2) genomic fragment spanning the major LAT, along with the LAT promoter and flanking regions, in the C57BL/6 background. The mice expressed abundant 2.2-kb major LATs in trigeminal ganglia (TG) and other tissues. The effects of the transgene on HSV-2 infection, latency, and reactivation were assessed. When infected with wild-type (WT) HSV-2 or its LAT promoter deletion (LAT(-)) mutant, primary lung fibroblast lines established from normal C57BL/6 and transgenic mice supported virus growth equally well. The replication of these viruses in the mouse eye and their spread to TG and brains were similar. The quantities of latent viral DNA in TG of transgenic and normal mice, as determined by real-time PCR, were comparable. UV light-induced reactivation of the LAT- mutant from transgenic mice (0 to 7%) was no more frequent than that from normal mice (0 to 14%), while WT virus was reactivated from 13 to 54% of normal mice and 22 to 54% of transgenic mice. The cumulative data indicate that, when expressed transgenically, the HSV-2 major LAT cannot influence HSV-2 infection or latency and cannot complement the defect in reactivation of the LAT- mutant. These results imply that the phenotype of reduced reactivation associated with the LAT- mutant is related to a function encoded in the LAT promoter but not to the major LAT itself. C1 NCI, NIAID, NIH, Lab Clin Invest,Med Virol Sect, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res Food & Drug Adm, Div Viral Prod, Bethesda, MD 20892 USA. RP Wang, KN (reprint author), NCI, NIAID, NIH, Lab Clin Invest,Med Virol Sect, 10 Ctr Dr,Rm 11N228, Bethesda, MD 20892 USA. NR 29 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2001 VL 75 IS 17 BP 8166 EP 8172 DI 10.1128/JVI.75.17.8166-8172.2001 PG 7 WC Virology SC Virology GA 461AZ UT WOS:000170343900041 PM 11483762 ER PT J AU Pletnev, AG Bray, M Hanley, KA Speicher, J Elkins, R AF Pletnev, AG Bray, M Hanley, KA Speicher, J Elkins, R TI Tick-borne Langat/Mosquito-Borne dengue flavivirus chimera, a candidate live attenuated vaccine for protection against disease caused by members of the tick-borne encephalitis virus complex: Evaluation in rhesus monkeys and in mosquitoes SO JOURNAL OF VIROLOGY LA English DT Article ID HETEROLOGOUS CHALLENGE; JAPANESE ENCEPHALITIS; TYPE-4 VIRUSES; CONSTRUCTION; NEUROVIRULENCE; MICE; RECOMBINANT; MUTAGENESIS; REPLICATION; RESPONSES AB Langat virus (LGT), strain TP21, a naturally avirulent tick-borne flavivirus, was used to construct a chimeric candidate virus vaccine which contained LGT genes for premembrane (preM) and envelope (E) glycoprotein and all other sequences derived from dengue type 4 virus (DEN4). The live virus vaccine was developed to provide resistance to the highly virulent, closely related tick-borne flaviviruses that share protective E epitopes among themselves and with LGT. Toward that end the chimera, initially recovered in mosquito cells, was adapted to grow to high titer in qualified simian Vero cells. When inoculated intraperitoneally (i.p.), the Vero cell-adapted LGT TP21/DEN4 chimera remained completely attenuated for SCID mice. Significantly, the chimera protected immunocompetent mice against the most virulent tick-borne encephalitis virus (TBEV). Subsequently, rhesus monkeys were immunized in groups of 4 with 10(5) or 10(7) PFU of LGT strain TP21, with 105 PFU of DEN4, or with 10(3),10(5), or 10(7) PFU of the chimera. Each of the monkeys inoculated with DEN4 or LGT TP21 became viremic, and the duration of viremia ranged from 1 to 5 days. In contrast, viremia was detected in only 1 of 12 monkeys inoculated with the LGT TP21/DEN4 chimera; in this instance the level of viremia was at the limit of detection. All monkeys immunized with the chimera or LGT TP21 virus developed a moderate to high level of neutralizing antibodies against LGT TP21 as well as TBEV and were completely protected against subsequent LGT TP21 challenge, whereas monkeys previously immunized with DEN4 virus became viremic when challenged with LGT TP21. These observations suggest that the chimera is attenuated, immunogenic, and able to induce a protective immune response. Furthermore, passive transfer of serum from monkeys immunized with chimera conferred significant protection to mice subsequently challenged with 100 i.p. 50% lethal doses of the highly virulent TBEV. The issue of transmissibility of the chimera by mosquitoes was addressed by inoculating a nonhematophagous mosquito, Toxorhynchites splendens, intrathoracically with the chimera or its DEN4 or LGT parent. Neither the LGT TP21/DEN4 vaccine candidate nor the wild-type LGT TP21 virus was able to infect this mosquito species, which is highly permissive for dengue viruses. Certain properties of the chimera, notably its attenuation for monkeys, its immunogenicity, and its failure to infect a highly permissive mosquito host, make it a promising vaccine candidate for use in immunization against severe disease caused by many tick-borne flaviviruses. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. RP Pletnev, AG (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 7,Room 236,7 Ctr Dr,MSC 1740, Bethesda, MD 20892 USA. NR 39 TC 55 Z9 59 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2001 VL 75 IS 17 BP 8259 EP 8267 DI 10.1128/JVI.75.17.8259-8267.2001 PG 9 WC Virology SC Virology GA 461AZ UT WOS:000170343900050 PM 11483771 ER PT J AU Derse, D Hill, SA Lloyd, PA Chung, HK Morse, BA AF Derse, D Hill, SA Lloyd, PA Chung, HK Morse, BA TI Examining human T-lymphotropic virus type 1 infection and replication by cell-free infection with recombinant virus vectors SO JOURNAL OF VIROLOGY LA English DT Article ID LYMPHADENOPATHY-ASSOCIATED VIRUS; TROPICAL SPASTIC PARAPARESIS; BLOOD MONONUCLEAR-CELLS; HUMAN-ENDOTHELIAL CELLS; LEUKEMIA-VIRUS; PERIPHERAL-BLOOD; HTLV-I; SURFACE PHENOTYPE; LENTIVIRAL VECTOR; MOLECULAR CLONE AB A sensitive and quantitative cell-free infection assay, utilizing recombinant human T-cell leukemia virus type 1 (HTLV-1)-based vectors, was developed in order to analyze early events in the virus replication cycle. Previous difficulties with the low infectivity and restricted expression of the virus have prevented a clear understanding of these events. Virus stocks were generated by transfecting cells with three plasmids: (i) a packaging plasmid encoding HTLV-1 structural and regulatory proteins, (ii) an HTLV-1 transfer vector containing either firefly luciferase or enhanced yellow fluorescent protein genes, and (iii) an envelope expression plasmid. Single-round infections were initiated by exposing target cells to filtered supernatants and quantified by assaying for luciferase activity in cell extracts or by enumerating transduced cells by flow cytometry. Transduction was dependent on reverse transcription and integration of the recombinant virus genome, as shown by the effects of the reverse transcriptase inhibitor 3 ' -azido-3 ' -deoxythymidine (AZT) and by mutation of the integrase gene in the packaging vector, respectively. The 50% inhibitory concentration of AZT was determined to be 30 nM in this HTLV-1 replication system. The stability of HTLV-1 particles, pseudotyped with either vesicular stomatitis virus G protein or HTLV-1 envelope, was typical of retroviruses, exhibiting a half-life of approximately 3.5 h at 37 degreesC. The specific infectivity of recombinant HTLV-1 virions was at least 3 orders of magnitude lower than that of analogous HIV-1 particles, though both were pseudotyped with the same envelope. Thus, the low infectivity of HTLV-1 is determined in large part by properties of the core particle and by the efficiency of postentry processes. C1 NCI, Basic Res Lab, Frederick, MD 21702 USA. SAIC Frederick, Frederick, MD 21702 USA. RP Derse, D (reprint author), NCI, Basic Res Lab, Bldg 567, Frederick, MD 21702 USA. NR 38 TC 88 Z9 89 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2001 VL 75 IS 18 BP 8461 EP 8468 DI 10.1128/JVI.75.18.8461-8468.2001 PG 8 WC Virology SC Virology GA 464BL UT WOS:000170512800012 PM 11507191 ER PT J AU De Rosny, E Vassell, R Wingfield, PT Wild, CT Weiss, CD AF De Rosny, E Vassell, R Wingfield, PT Wild, CT Weiss, CD TI Peptides corresponding to the heptad repeat motifs in the transmembrane protein (gp41) of human immunodeficiency virus type 1 elicit antibodies to receptor-activated conformations of the envelope glycoprotein SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 GP41; SYNTHETIC PEPTIDE; ATOMIC-STRUCTURE; DOMAIN; INHIBITION; FUSION; RESIDUES AB Two heptad repeat regions in the ectodomain of the human immunodeficiency virus type 1 (HIV-1) transmembrane subunit (gp41) self-assemble into a six-helix bundle structure that is critical for virus entry. Immunizations with peptides corresponding to these regions generated antibodies specific to the receptor-activated conformations of gp41. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. Panacos Pharmaceut, Gaithersburg, MD USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines, HFM-466,NIH Bldg 29,Room 532,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 18 TC 48 Z9 48 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD SEP PY 2001 VL 75 IS 18 BP 8859 EP 8863 DI 10.1128/JVI.75.18.8859-8863.2001 PG 5 WC Virology SC Virology GA 464BL UT WOS:000170512800053 PM 11507232 ER PT J AU Edgar, JD Sapienza, CM Bidus, K Ludlow, CL AF Edgar, JD Sapienza, CM Bidus, K Ludlow, CL TI Acoustic measures of symptoms in abductor spasmodic dysphonia SO JOURNAL OF VOICE LA English DT Article DE abductor spasmodic dysphonia; voice disorders; acoustic analysis; percepted ratings ID BOTULINUM TOXIN INJECTION AB Speech of patients with abductor spasmodic dysphonia (ABSD) was analyzed using acoustic analyses to determine: (1) which acoustic measures differed from controls and were independent factors representing patients' voice control difficulties, and (2) whether acoustic measures related to blinded perceptual counts of the symptom frequency in the same patients. Patients' voice onset time for voiceless consonants in speech were significantly longer than the controls (p = 0.015). A principle components analysis identified three factors that accounted for 95% of the variance: the first factor included sentence and word duration, frequency shifts, and aperiodic instances; the second was phonatory breaks; and the third was voice onset time. Significant relationships with perceptual counts of symptoms were found for the measures of acoustic disruptions in sentences and sentence duration. Finally, a multiple regression demonstrated that the acoustic measures related well with the perceptual counts (r(2) = 0.84) with word duration most highly related and none of the other measures contributing once the effect of word duration was partialed out. The results indicate that some of the voice motor control deficits, namely aperiodicity, phonatory breaks, and frequency shifts, which occur in patients with ABSD, are similiar to those previously found in adductor spasmodic dysphonia. Results also indicate that acoustic measures of intermittent disruptions in speech, voice onset time, and speech duration are closely related to the perception of symptom frequency in the disorder. C1 Louisiana State Univ, Hlth Sci Ctr, Sch Allied Hlth Profess, Dept Commun Disorders, New Orleans, LA 70112 USA. Univ Florida, Dept Commun Sci & Disorders, Gainesville, FL USA. NINDS, Laryngeal & Speech Sect, NIH, Bethesda, MD 20892 USA. RP Edgar, JD (reprint author), Louisiana State Univ, Hlth Sci Ctr, Sch Allied Hlth Profess, Dept Commun Disorders, Room 9C-3,1900 Gravier St, New Orleans, LA 70112 USA. OI Ludlow, Christy/0000-0002-2015-6171 NR 17 TC 17 Z9 17 U1 0 U2 4 PU SINGULAR PUBLISHING GROUP INC PI SAN DIEGO PA 401 WEST A ST, STE 325, SAN DIEGO, CA 92101-7904 USA SN 0892-1997 J9 J VOICE JI J. Voice PD SEP PY 2001 VL 15 IS 3 BP 362 EP 372 DI 10.1016/S0892-1997(01)00038-8 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA 473PR UT WOS:000171055000006 PM 11575633 ER PT J AU Kwon, IS Oldaker, S Schrager, M Talbot, LA Fozard, JL Metter, EJ AF Kwon, IS Oldaker, S Schrager, M Talbot, LA Fozard, JL Metter, EJ TI Relationship between muscle strength and the time taken to complete a standardized walk-turn-walk test SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PHYSICAL ACTIVITIES; AGE-DIFFERENCES; GAIT; SPEED; WOMEN; MEN; OLD; DETERMINANTS; EXTREMITIES; DISABILITY AB We examined the effects of age and gender on the relationship between knee strength and walking time during a walk-turn-walk test in 176 male and 168 female generally healthy participants of the Baltimore Longitudinal Study of Aging who were aged 21-89 years. Subjects were timed as they walked 50 ft (15.24 m), turned around, and walked back to the starting point, both at a comfortable pace and as fast as possible, Isokinetic concentric knee extensor strength was measured at 30 degrees /s by using a Kin-Com dynamometer. Both comfortable and fast gait times increased with increasing age for both women and men, starting in middle age. An interaction was found between gender and age showing that older women are slower than older men at both paces. Gait time decreased linearly with increasing knee extensor strength, plateauing at higher strength levels (> 130 N m for comfortable gait, and 190 N in for fast gait). Most women occupied the linear part of the curve below the plateau. Adjustment for body size, age, physical activity, and particularly number of steps to complete the task removed the relationship between strength and gait time for the comfortable gait. Women took longer to complete the walk-turn-walk test than men at older ages, were on the linear part of the strength-gait time relationship, and used more steps to complete the task, all of which may contribute to their greater likelihood of frailty in later years. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. Florida Gerontol Res & Training Serv, Palm Harbor, FL USA. RP Metter, EJ (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Fozard, James Leonard/B-3660-2009 NR 38 TC 35 Z9 37 U1 0 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2001 VL 56 IS 9 BP B398 EP B404 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 468GK UT WOS:000170749600004 PM 11524441 ER PT J AU Korosi, J McIntosh, CHS Pederson, RA Demuth, HU Habener, JF Gingerich, R Egan, JM Elahi, D Meneilly, GS AF Korosi, J McIntosh, CHS Pederson, RA Demuth, HU Habener, JF Gingerich, R Egan, JM Elahi, D Meneilly, GS TI Effect of aging and diabetes on the enteroinsular axis SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID DIPEPTIDYL-PEPTIDASE-IV; DEPENDENT INSULINOTROPIC POLYPEPTIDE; GASTRIC-INHIBITORY POLYPEPTIDE; GLUCAGON-LIKE PEPTIDE-1; HUMAN SERUM; GLUCOSE-TOLERANCE; BETA-CELL; IN-VITRO; HYPOGLYCEMIA; DEGRADATION AB Background. The current studies were designed to examine the effect of aging and diabetes on the enteroinsular axis. Methods. Healthy young control subjects (n = 10 young, age 23 +/- 1 years; body mass index [BMI] 24 +/- 1 kg/m(2)), healthy elderly subjects (n = 10; age 80 +/- 2 years; BMI 26 +/- 1 kg/m(2)), and elderly patients with type 2 diabetes (n = 10, age 76 +/- 2 years; BMI 26 +/- 2 kg/m(2)) underwent a 3-hour oral glucose tolerance test (glucose dose 40 gm/m(2)). Results. Insulin responses were not different between young controls and elderly patients with diabetes but were significantly lower in elderly patients with diabetes and young controls than in elderly controls (young control: 178 +/- 27 pM: elderly control: 355 +/- 57 pM elderly diabetes: 177 +/- 30 pM; p < .05 elderly control vs young control and elderly diabetes). Total glucagon-like peptide 1 (GLP-1) responses were not significantly different between young and elderly control, and patients with diabetes (young control: 15 +/- 2 pM; old control: 8 +/- 2 pM; elderly diabetes: 12 +/- 3 pM; p = ns). Active GLP-1 responses were also not different between young and elderly controls and patients with diabetes (young control: 5 +/- 1 pM; old control: 6 +/- 1 pM; elderly diabetes: 7 +/- 1 pM; p = ns). However, the difference between total and active GLP levels was significantly greater in the young controls (young control: 10 +/- 2 pM: old control: 2 +/- 2 pM elderly diabetes: 4 +/- 2 pM; p < .05, young vs elderly). Glucose-dependent insulinotropic polypeptide responses were not different between young and elderly controls and between elderly controls and patients witl diabetes but were significantly higher in elderly patients with diabetes than in young controls (young control: 97 +/- 12 pM; elderly control: 121 +/- 16 pM; elderly diabetes: 173 +/- 27 pM; p < .05, young vs elderly diabetes). Glucagon responses were reduced in elderly controls but were similar in young controls and elderly patients with diabetes (young control: 15 +/- 1 pM; elderly control: 9 +/- 1 pK elderly diabetes: 16 +/- 1 pM: p < .01 elderly control vs young control and elderly diabetes). Dipeptidyl peptidase IV levels were lower in both elderly controls and patients with diabetes when compared with young controls (young control: 0.17 +/- 0.01 elderly control: 0.15 +/- 0.01; elderly diabetes 0.15 +/- 0.01 Delta OD/20 minutes; p < .05, elderly vs young). Conclusions. We conclude that normal aging and diabetes are associated with multiple changes in the enteroinsular axis. C1 Univ British Columbia, Dept Med, Vancouver, BC, Canada. Univ British Columbia, Dept Physiol, Vancouver, BC, Canada. Hans Kneoll Inst Nat Prod Res, Halle Saale, Germany. Harvard Univ, Dept Med, Boston, MA 02115 USA. Linco Res Inc, St Charles, MO USA. NIA, Lab Clin Physiol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Meneilly, GS (reprint author), Vancouver Hosp & Hlth Sci Ctr, Rm S 169,UBC Site 2211,Wesbrook Mall, Vancouver, BC V6T 2B5, Canada. NR 32 TC 26 Z9 26 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD SEP PY 2001 VL 56 IS 9 BP M575 EP M579 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 468GK UT WOS:000170749600014 PM 11524451 ER PT J AU Melzer, D Izmirlian, G Leveille, SG Guralnik, JM AF Melzer, D Izmirlian, G Leveille, SG Guralnik, JM TI Educational differences in the prevalence of mobility disability in old age: The dynamics of incidence, mortality, and recovery SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID SOCIOECONOMIC-STATUS; PHYSICAL FUNCTION; LIFE EXPECTANCY; HEALTH; POPULATION; RISK; PATTERNS; ACCOUNT; DECLINE; ADULTS AB Objectives. Older people with less education have substantially higher prevalence rates of mobility disability, This study aimed to establish the relative contributions of incidence, recovery rates, and death to prevalence differences in mobility disability associated with educational status. Methods. Data were from 3 sites of the Established Populations for Epidemiological Study of the Elderly, covering 8,871 people aged 65-84 years who were followed for up to 7 years. Participants were classified on years of education received and as disabled if they needed help or were unable to walk up or down stairs or walk half a mile. A Markov model computed relative risks, adjusting for the effects of repeated observations on the same individuals. Results. Differences between education groups in person-years lived with disability were large. The relative risk of incident disability in men with 0-7 years of education (vs. those with 12 or more years) was 1.65 (95% CI = 1.37-1.97) and in women was 1.70 (95% CI = 1.15-2.53). Both recovery risks and risks of death in those with disability were not significantly different across education groups in either gender. Discussion. Higher incidence of disability is the main contributor to the substantially higher prevalence of disability in older people of lower socioeconomic status. Efforts to reduce the disparity in disability rates by socioeconomic status in old age should focus mainly on preventing disability, because differences in the course of mobility disability after onset appear to play a limited role in the observed prevalence disparities. C1 NIA, Epidemiol Demog & Biometry Off, Bethesda, MD 20892 USA. RP Melzer, D (reprint author), Inst Publ Hlth, Forvie Site,Robinson Way, Cambridge CB2 2SR, England. NR 35 TC 58 Z9 59 U1 0 U2 6 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD SEP PY 2001 VL 56 IS 5 BP S294 EP S301 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 468GV UT WOS:000170750500012 PM 11522811 ER PT J AU Geissler, E Horkay, F Hecht, AM Deschamps, P d'Heres, SM AF Geissler, E Horkay, F Hecht, AM Deschamps, P d'Heres, SM TI Neutron scattering from elastomers gels SO KAUTSCHUK GUMMI KUNSTSTOFFE LA English DT Article DE polyisoprene; polydimethyl siloxane; small angle neutron scattering ID NETWORKS AB Small angle neutron scattering measurements are made on polyisoprene and polydimethylsiloxane (PDMS) solutions and gels. The polyisoprene solutions contain dense clusters of amorphous polymer whose volume fraction is of the order of 0.01 %. Unfilled uncross-linked PDMS solutions, however, show no long-range structure. Filled PDMS samples are also investigated using contrast variation by solvent deuteration to determine the polymer and filler structure factors. The surface area of the filler thus calculated demonstrates that less than 2 % of the free surface of the filler particles is in contact with polymer. The relationship between scattering results and swelling properties is discussed. C1 Univ Grenoble 1, UMR CNRS 5588, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. European Synchrotron Radiat Facil, F-38043 Grenoble, France. RP Geissler, E (reprint author), Univ Grenoble 1, UMR CNRS 5588, Spectrometrie Phys Lab, F-38402 St Martin Dheres, France. NR 15 TC 0 Z9 0 U1 1 U2 2 PU DR ALFRED HUTHIG VERLAG GMBH PI HEIDELBERG 1 PA POSTFACH 102869, W-69018 HEIDELBERG 1, GERMANY SN 0022-9520 J9 KAUT GUMMI KUNSTST JI Kautsch. Gummi Kunstst. PD SEP PY 2001 VL 54 IS 9 BP 446 EP + PG 5 WC Engineering, Chemical; Polymer Science SC Engineering; Polymer Science GA 481HJ UT WOS:000171513600002 ER PT J AU Kimmel, PL AF Kimmel, PL TI Depression in dialysis patients: Rubidium supplementation before other drugs and encouragement? Reply from the author SO KIDNEY INTERNATIONAL LA English DT Letter ID LOWER SERUM ZINC; MAJOR DEPRESSION; HEMODIALYSIS C1 NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Kimmel, PL (reprint author), NIDDK, Div Kidney Urol & Hematol Dis, NIH, Bethesda, MD 20892 USA. NR 11 TC 0 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD SEP PY 2001 VL 60 IS 3 BP 1201 EP 1202 DI 10.1046/j.1523-1755.2001.00920-2.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 466WA UT WOS:000170668100042 ER PT J AU Groll, AH Ritter, J Muller, FMC AF Groll, AH Ritter, J Muller, FMC TI Prevention of fungal infections in children and adolescents with cancer. SO KLINISCHE PADIATRIE LA German DT Review DE cancer; stem cell transplantation; mycoses; Candida; Aspergillus; prophylaxis; fluconazole; itraconazole; amphotericin; children ID BONE-MARROW TRANSPLANTATION; ITRACONAZOLE ORAL SOLUTION; LIPOSOMAL AMPHOTERICIN-B; PLACEBO-CONTROLLED TRIAL; INVASIVE PULMONARY ASPERGILLOSIS; SINGLE-CENTER EXPERIENCE; DEEP CANDIDA INFECTION; NEUTROPENIC PATIENTS; DOUBLE-BLIND; ANTIFUNGAL PROPHYLAXIS AB Opportunistic mycoses have emerged as important causes for morbidity and mortality in pediatric cancer patients, particularly in those with intensively treated hematological malignancies, allogeneic hematopoetic stem cell transplantation, and aplastic anemia. The incidence of invasive fungal infections in these settings may range from 10 to 25% despite empirical antifungal therapy with an overall case fatality rate of up to 50 and 75% depending on the organism. Preventive interventions are thus warranted, including but not limited to chemoprophylaxis with antifungal agents. Effective chemoprophylaxis of invasive Candida infections with a long-term benefit for overall survival has been demonstrated in patients with allogeneic bone marrow transplantation. However, its benefit in other high-risk populations is less well established, and a clearly effective approach to chemoprophylaxis for invasive Aspergillus infections has not been documented in appropriately designed clinical trials. This article reviews epidemiology and current approaches to chemoprophylaxis of opportunistic invasive fungal infections in children and adolescents with cancer and/or stem cell transplantation, and provides evidence-based guidelines for indications and modalities of antifungal prophylaxis and antifungal infection control measures in this population. C1 Univ Munster, Klin & Poliklin Kinderheilkunde Padiat Hamatol On, D-48129 Munster, Germany. NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Univ Munster, Klin & Poliklin Kinderheilkunde Padiat Hamatol On, Albert Schweitzer Str 33, D-48129 Munster, Germany. EM grolla@mail.nih.gov NR 184 TC 13 Z9 14 U1 0 U2 3 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0300-8630 EI 1439-3824 J9 KLIN PADIATR JI Klinische Padiatr. PD SEP PY 2001 VL 213 SI 1 BP A50 EP A68 DI 10.1055/s-2001-17502 PG 19 WC Pediatrics SC Pediatrics GA 476KF UT WOS:000171224800006 PM 11577364 ER PT J AU Groll, AH Ritter, J Muller, FMC AF Groll, AH Ritter, J Muller, FMC TI Guidelines for prevention of Pneumocystis carinii pneumonitis in children and adolescents with cancer. SO KLINISCHE PADIATRIE LA German DT Review DE cancer; children; mycoses; recommendations; Pneumocystis carinii; trimethoprim/sulfamethoxazole; pentamidine; dapsone; atovaquone ID HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW TRANSPLANTATION; HIV-POSITIVE PATIENTS; AEROSOLIZED PENTAMIDINE; TRIMETHOPRIM-SULFAMETHOXAZOLE; DAPSONE-PYRIMETHAMINE; PRIMARY PROPHYLAXIS; TOXOPLASMIC ENCEPHALITIS; DIHYDROFOLATE-REDUCTASE; INFECTED CHILDREN AB Pneumocystis carinii pneumonitis (PCP) is one of the most important opportunistic infections in children and adolescents with cancer. Its high frequency and a considerable mortality have led to primary chemoprophylaxis in patients with hematological malignancies and following allogeneic hematopoietic stem cell transplantation. Although less well characterized, patients with autologous stem cell transplantation and patients with dose-intensive chemotherapy for pediatric solid tumors may have a similarly high risk for PCP based on their profound T-cell depletion. For more than two decades, effective chemoprophylaxis for PCP has been available. Trimethoprim and sulfamethoxazole (TMP/SMX) is the prophylactic modality of first choice. The combination has been shown to be almost 100% efficacious in pediatric cancer patients at highest risk, and it is usually well tolerated in this setting. Secondary alternatives to TMP/SMX include oral dapsone, oral atovaquone, and aerosolized pentamidine-isethionate. These modalities are less effective than TMP/SMX, and have been evaluated predominantly in HIV-infected patients. This article reviews epidemiology and current approaches to chemoprophylaxis for PCP in children and adolescents with cancer and/or hematopoietic stem cell transplantation, and provides evidence-based guidelines for indications and modalities of PCP prophylaxis in this population. C1 Univ Munster, Klin & Poliklin Kinderheilkunde Padiatr Hamatol O, D-48129 Munster, Germany. NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. Univ Wurzburg, Kinderklin, D-8700 Wurzburg, Germany. RP Groll, AH (reprint author), Univ Munster, Klin & Poliklin Kinderheilkunde Padiatr Hamatol O, Albert Schweitzer Str 33, D-48129 Munster, Germany. NR 116 TC 10 Z9 10 U1 2 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0300-8630 J9 KLIN PADIATR JI Klinische Padiatr. PD SEP PY 2001 VL 213 SI 1 BP A38 EP A49 DI 10.1055/s-2001-17501 PG 12 WC Pediatrics SC Pediatrics GA 476KF UT WOS:000171224800005 PM 11577363 ER PT J AU Garnett, NL DeHaven, WR AF Garnett, NL DeHaven, WR TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 NIH, Lab Anim Welfare, Bethesda, MD 20892 USA. USDA, APHIS, Washington, DC USA. RP Garnett, NL (reprint author), NIH, Lab Anim Welfare, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD SEP PY 2001 VL 30 IS 8 BP 23 EP 23 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 468XA UT WOS:000170782400006 ER PT J AU Saif, MW Greenberg, BR AF Saif, MW Greenberg, BR TI Multiple myeloma and hairy cell leukemia: A rare association or coincidence? SO LEUKEMIA & LYMPHOMA LA English DT Article DE multiple myeloma; hairy cell leukemia; interferon; secondary neoplasm; transformation ID CHRONIC LYMPHOCYTIC-LEUKEMIA; RETICULOENDOTHELIOSIS; NEOPLASMS; DIAGNOSIS; FEATURES AB Hairy cell leukemia (HCL) and multiple myeloma (MM) are well-defined entities with distinctive clinical and pathological features. Although most cases of HCL and MM fit their classic descriptions, more recent studies have revealed that their clinical and morphological boundaries may not only overlap but a transformation of HCL into MM could also occur. We report another case of HCL followed by the development of MM after 9 years. He also developed hemarthrosis of his right ankle at the time of diagnosis of MM. PCR analysis of DNA extracted from the bone marrow aspirate was negative for the presence of a monoclonally rearranged immunoglobulin heavy chain gene. Immunophenoytping revealed no evidence of HCL. There are several possible explanations for the development of MM in HCL patients, such as the coexistence of separate disease entities or different clinical and morphologic phases of a single disease entity. An accurate diagnosis of HCL or MM is critical because of differences in their treatment. Hemarthrosis in this patient may also have been the first manifestation of MM, a feature of MM which has rarely been reported. C1 NCI, Med Branch, Natl Naval Med Ctr, Gaithersburg, MD 20889 USA. RP Saif, MW (reprint author), NCI, Med Branch, Natl Naval Med Ctr, Bldg 8,Room 5101,8902 Wisconsin Ave, Gaithersburg, MD 20889 USA. NR 39 TC 11 Z9 12 U1 0 U2 1 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PD SEP-OCT PY 2001 VL 42 IS 5 BP 1043 EP 1048 DI 10.3109/10428190109097724 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 467VD UT WOS:000170723700023 PM 11697621 ER PT J AU Jeffrey, BG Weisinger, HS Neuringer, M Mitchell, DC AF Jeffrey, BG Weisinger, HS Neuringer, M Mitchell, DC TI The role of docosahexaenoic acid in retinal function SO LIPIDS LA English DT Review ID POLYUNSATURATED FATTY-ACIDS; ROD OUTER SEGMENTS; A-WAVE; RAT RETINA; B-WAVE; RHESUS-MONKEYS; HUMAN ELECTRORETINOGRAM; ELECTRICAL RESPONSE; BINDING PROTEIN; CEREBRAL-CORTEX AB An important role for docosahexaenoic acid (DHA) within the retina is suggested by its high levels and active conservation in this tissue. Animals raised on n-3-deficient diets have large reductions in retinal DHA levels that are associated with altered retinal function as assessed by the electroretinogram (ERG). Despite two decades of research in this field, little is known about the mechanisms underlying altered retinal function in n-3-deficient animals. The focus of this review is on recent research that has sought to elucidate the role of DHA in retinal function, particularly within the rod photoreceptor outer segments where DHA is found at its highest concentration. An overview is also given of human infant studies that have examined whether a neonatal dietary supply of DHA is required for the normal development of retinal function. C1 Oregon Hlth & Sci Univ, Oregon Reg Primate Res Ctr, Beaverton, OR 97006 USA. Flinders Univ S Australia, Flinders Med Ctr, Dept Paediat & Child Hlth, Bedford Pk, SA 5042, Australia. Univ Melbourne, Royal Melbourne Inst Technol, Dept Food Sci, Melbourne, Vic 3000, Australia. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Neuringer, M (reprint author), Oregon Hlth & Sci Univ, Oregon Reg Primate Res Ctr, 505 NW 185th Ave, Beaverton, OR 97006 USA. FU NCRR NIH HHS [RR00163]; NIDDK NIH HHS [DK29930] NR 104 TC 75 Z9 78 U1 0 U2 13 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD SEP PY 2001 VL 36 IS 9 BP 859 EP 871 DI 10.1007/s11745-001-0796-3 PG 13 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 492RF UT WOS:000172180800001 PM 11724458 ER PT J AU Salem, N Litman, B Kim, HY Gawrisch, K AF Salem, N Litman, B Kim, HY Gawrisch, K TI Mechanisms of action of docosahexaenoic acid in the nervous system SO LIPIDS LA English DT Review ID POLYUNSATURATED FATTY-ACIDS; RAT PINEAL-GLAND; NOESY CROSS-RELAXATION; ALPHA-LINOLENIC ACID; GATED K+ CHANNELS; C6 GLIOMA-CELLS; TERM INFANTS; PRETERM INFANTS; VISUAL-ACUITY; HUMAN-MILK AB This review describes (from both the animal and human literature) the biological consequences of losses in nervous system docosahexaenoate (DHA). It then concentrates on biological mechanisms that may serve to explain changes in brain and retinal function. Brief consideration is given to actions. of DHA as a nonesterified fatty acid and as a docosanoid or other bioactive molecule. The role of DHA-phospholipids in regulating G-protein signaling is presented in the context of studies with rhodopsin. It is clear that the visual pigment responds to the degree of unsaturation of the membrane lipids. At the cell biological level, DHA is shown to have a protective role in a cell culture model of apoptosis in relation to its effects in increasing cellular photsphatidylserine (PS); also, the loss of DHA leads to a loss in PS. Thus, through its effects on PS, DHA may play an important role in the regulation of cell signaling and in cell proliferation. Finally, progress has been made recently in nuclear magnetic resonance studies to delineate differences in molecular structure and order in biomembranes due to subtle changes in the degree of phospholipid unsaturation. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Salem, N (reprint author), 12420 Parklawn Dr,Room 150, Rockville, MD 20852 USA. NR 148 TC 511 Z9 532 U1 12 U2 56 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD SEP PY 2001 VL 36 IS 9 BP 945 EP 959 DI 10.1007/s11745-001-0805-6 PG 15 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 492RF UT WOS:000172180800010 PM 11724467 ER PT J AU Kobayashi, H Sato, N Kawamoto, S Saga, T Hiraga, A Ishimori, T Konishi, J Togashi, K Brechbiel, MW AF Kobayashi, H Sato, N Kawamoto, S Saga, T Hiraga, A Ishimori, T Konishi, J Togashi, K Brechbiel, MW TI Novel intravascular macromolecular MRI contrast agent with generation-4 polyamidoamine dendrimer core: Accelerated renal excretion with coinjection of lysine SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic resonance imaging; angiography; lysine; contrast media; renal excretion ID MONOCLONAL-ANTIBODY FRAGMENTS; DISULFIDE-STABILIZED FV; GD-DTPA; GLOMERULAR-FILTRATION; ENHANCING AGENT; REDUCTION; RATS AB One of the major limitations to macromolecular MRI contrast agents (MRI-CAs) is their slow clearance and associated decreased excretion of gadolinium (Gd(III)). The effect of coinjecting lysine to accelerate renal excretion of a macromolecular MRI-CA (generation-4 PAMAM (TM) dendrimer (G4D-(1B4M-Gd)(64))) was investigated. The biodistribution and urine and fecal excretion in athymic mice was evaluated with and without lysine coinjection. 3D-dynamic-micro-MRI with G4D-(1B4M-Gd)(64) was obtained with and without lysine coinjection, and the serial signal intensity (SI) change in the blood and organs was evaluated. When lysine was coinjected, urinary excretion of G4D-(1B4M-Gd)(64) increased 5.4-fold compared to that without lysine, resulting in decreased renal accumulation of G4D(iB4M-Gd)(64) from 150% to 40% injected dose per gram (P < 0.001). On dynamic MRI with G4D-(iB4M-Gd)(64), when lysine was coinjected, the kidney-to-blood SI ratio was significantly lower than that obtained without lysine (P < 0.001). When lysine was coinjected, the G4D-(iB4M-Gd)(64) was excreted from the kidney intact. C1 Kyoto Univ, Grad Sch Med, Hitachi Med Co, Chaired Dept Diagnost & Intervent Imaging,Sakyo K, Kyoto 6068507, Japan. Kyoto Univ, Dept Nucl Med & Diagnost Imaging, Kyoto 6068507, Japan. Kyoto Univ, Dept Radiol, Kyoto 6068507, Japan. Otsu Municipal Hosp, Dept Radiol, Otsu, Shiga, Japan. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Kyoto Univ, Grad Sch Med, Hitachi Med Co, Chaired Dept Diagnost & Intervent Imaging,Sakyo K, 54 Kawahara Cho, Kyoto 6068507, Japan. NR 22 TC 37 Z9 38 U1 0 U2 6 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2001 VL 46 IS 3 BP 457 EP 464 DI 10.1002/mrm.1214 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 468CJ UT WOS:000170740300008 PM 11550236 ER PT J AU Aletras, AH Wen, H AF Aletras, AH Wen, H TI Mixed echo train acquisition displacement encoding with stimulated echoes: An optimized DENSE method for in vivo functional imaging of the human heart SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE cardiac; function; DENSE; meta-DENSE; STEAM; HARP; tagging; phase contrast; stimulated echoes; fast-DENSE; dual-echo DENSE; heart; PC; MRI; strain ID MRI; DIFFUSION; STRAIN; RARE AB Mixed echo train acquisition displacement encoding with stimulated echoes (meta-DENSE) is a phase-based displacement mapping technique suitable for imaging myocardial function. This method has been optimized for use with patients who have a history of myocardial infarction. The total scan time is 12-14 heartbeats for an in-plane resolution of 2.8 x 2.8 mm(2). Myocardial strain is mapped at this resolution with an accuracy of 2% strain in vivo. Compared to standard stimulated echo (STE) methods, both data acquisition speed and resolution are improved with inversion-recovery FID suppression and the meta-DENSE readout scheme. Data processing requires minimal user intervention and provides a rapid quantitative feedback on the MRI scanner for evaluating cardiac function. Published 2001 Wiley-Liss, Inc.(dagger) C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Aletras, AH (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10,Room B1D-416,MSC 1061, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010; OI Wen, Han/0000-0001-6844-2997; Aletras, Anthony/0000-0002-3786-3817 FU Intramural NIH HHS [ZIA HL004606-13] NR 19 TC 56 Z9 56 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2001 VL 46 IS 3 BP 523 EP 534 DI 10.1002/mrm.1223 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 468CJ UT WOS:000170740300017 PM 11550245 ER PT J AU Kobayashi, H Sato, N Kawamoto, S Saga, T Hiraga, A Ishimori, T Konishi, J Togashi, K Brechbiel, MW AF Kobayashi, H Sato, N Kawamoto, S Saga, T Hiraga, A Ishimori, T Konishi, J Togashi, K Brechbiel, MW TI 3D MR angiography of intratumoral vasculature using a novel macromolecular MR contrast agent SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE MRI; intratumoral vessels; MR angiography; angiogenesis; contrast agent ID MONOCLONAL-ANTIBODY; DENDRIMER; CANCER; ANGIOGENESIS; PERMEABILITY; THERAPEUTICS; FLEXIBILITY; THERAPY; FUTURE; MEDIA AB Noninvasive methods to visualize blood flow in the intratumoral vasculature have not previously been studied. In the present study, the use of a novel intravascular MR contrast agent with a generation-6 polyamidoamine dendrimer core (G6-(1B4M-Gd)(192); MW: 175kD) was investigated, and the vasculature in experimental tumors was visualized using 3D MR angiography (MRA). Xenografted tumors in nude mice of two different histologies-KT005 (human osteogenic sarcoma) and LS180 (human colon carcinoma)-were used to obtain 3D MRA using G6-(1B4M-Gd)(192) and Gd-DTPA. The contrast MR sectional images were correlated with the corresponding histological sections. The intratumoral vasculature in the KT005 tumor was clearly visualized by 3D MRA, which became more evident with the growth of the tumor xenograft. In contrast, the intratumoral vasculature in the LS180 tumor was sparser and much less developed than that in KT005 tumors. Blood vessels with a diameter as small as 100 mum based on histology were visualized using 0.033 mmol Gd/kg of G6-(1B4M-Gd)(192). In conclusion, intratumoral vasculature with a 100-mum diameter was visualized better using 3D MRA with G6-(1B4M-Gd)(192) than with Gd-DTPA. (C) 2001 Wiley-Liss, Inc. C1 Kyoto Univ, Grad Sch Med, Dept Diagnost & Intervent Radiol, Hitachi Med Co Chair, Kyoto 6068507, Japan. Kyoto Univ, Dept Nucl Med & Diagnost Imaging, Kyoto, Japan. Kyoto Univ, Dept Radiol, Kyoto, Japan. Otsu Municipal Hosp, Dept Radiol, Otsu, Shiga, Japan. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Diagnost & Intervent Radiol, Hitachi Med Co Chair, 54 Kawahara Cho, Kyoto 6068507, Japan. NR 25 TC 40 Z9 41 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD SEP PY 2001 VL 46 IS 3 BP 579 EP 585 DI 10.1002/mrm.1230 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 468CJ UT WOS:000170740300024 PM 11550252 ER PT J AU Lu, XY Gruia-Gray, J Copeland, NG Gilbert, DJ Jenkins, NA Londos, C Kimmel, AR AF Lu, XY Gruia-Gray, J Copeland, NG Gilbert, DJ Jenkins, NA Londos, C Kimmel, AR TI The murine perilipin gene: the lipid droplet-associated perilipins derive from tissue-specific, mRNA splice variants and define a gene family of ancient origin SO MAMMALIAN GENOME LA English DT Article ID DIFFERENTIATION-RELATED PROTEIN; HORMONE-SENSITIVE LIPASE; DEPENDENT DIABETES-MELLITUS; KINASE-II PHOSPHORYLATION; LIPOLYTIC STIMULATION; 3T3-L1 ADIPOCYTES; STORAGE DROPLETS; 15Q26 IDDM3; INSULIN; TRANSLOCATION AB The Perilipins are a family of intracellular neutral lipid droplet storage proteins that are responsive to acute protein kinase A-mediated, hormonal stimulation. Perilipin (Peri) expression appears to be limited to adipocytes and steroidogenic cells, in which intracellular neutral lipid hydrolysis is regulated by protein kinase A. We have isolated cDNA sets and overlapping genomic fragments of the murine Peri locus and mapped chromosomal location, transcription start sites, polyadenylylation sites, and intron/exon junctions. Data confirm that the Perilipins are encoded by a single-copy gene, with alternative and tissue-specific, mRNA splicing and polyadenylylation yielding four different protein species. The Perilipin proteins have identical similar to 22-kDa amino termini with distinct carboxyl terminal sequences of varying lengths. These genomic and transcriptional maps of murine. Perilipin are also essential for evaluating presumptive endogenous and targeted mutations within the locus. The N-terminal identity region of the Perilipins defines a sequence motif, which we term PAT, that is shared with the ADRP and TIP47 proteins; additionally, the PAT domain may represent a novel, conserved pattern for lipid storage droplet (LSD) proteins of vertebrates and invertebrates alike. Comparative genomics suggest the presence of related LSD genes in species as diverse as Drosophila and Dictyostelium. C1 NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mouse Canc Genet Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Kimmel, AR (reprint author), NIDDKD, Cellular & Dev Biol Lab, NIH, Bldg 50,Room 3351 MSC 8028, Bethesda, MD 20892 USA. NR 46 TC 130 Z9 142 U1 1 U2 13 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD SEP PY 2001 VL 12 IS 9 BP 741 EP 749 DI 10.1007/s00335-01-2055-5 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 468CG UT WOS:000170740100011 PM 11641724 ER PT J AU Slavkin, HC AF Slavkin, HC TI Enamel extracellular matrix mini-review SO MATRIX BIOLOGY LA English DT Editorial Material C1 NIAMSD, NIH, Craniofacial Dev Sect, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), Univ So Calif, Sch Dent, 925 W 34th St,Suite 203, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD SEP PY 2001 VL 20 IS 5-6 BP 271 EP 271 DI 10.1016/S0945-053X(01)00152-4 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 479JY UT WOS:000171402300001 ER PT J AU Donaldson, MS AF Donaldson, MS TI Continuity of care: A reconceptualization SO MEDICAL CARE RESEARCH AND REVIEW LA English DT Review ID GENERAL-PRACTITIONERS KNOWLEDGE; APPOINTMENT-KEEPING BEHAVIOR; PHYSICIAN-INDUCED DEMAND; MEDICAL-CARE; PATIENT SATISFACTION; PROVIDER CONTINUITY; REGULAR DOCTOR; HEALTH-CARE; AMBULATORY CARE; AGENCY PROBLEMS AB Although continuity of care is considered an essential feature of good health care, researchers have used and measured continuity in many different ways,and no clear conceptual framework links continuity to outcomes. This article offers a reconceptualization and definition of continuity based on agency theory. It posits that the value of continuity is to reduce agency loss by decreasing information asymmetry and increasing goal alignment. Three decades of empirical literature on continuity were examined to assess whether this model would provide greater clarity about continuity. Some authors measured improved information transfer, but more appeared to assume that continuity would lead to better information. Most authors appeared to have assumed that goal alignment was present and did not measure it. The model of continuity based on agency theory appears to provide a useful conceptual tool for health services research and policy. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Donaldson, MS (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 93 TC 38 Z9 38 U1 5 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1077-5587 J9 MED CARE RES REV JI Med. Care Res. Rev. PD SEP PY 2001 VL 58 IS 3 BP 255 EP 290 DI 10.1177/107755870105800301 PG 36 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 463KC UT WOS:000170474500001 PM 11523291 ER PT J AU Steinberg, MH Rodgers, GP AF Steinberg, MH Rodgers, GP TI Pharmacologic modulation of fetal hemoglobin SO MEDICINE LA English DT Review ID SICKLE-CELL-ANEMIA; GLOBIN GENE-EXPRESSION; RECOMBINANT-HUMAN-ERYTHROPOIETIN; ADULT ERYTHROID-CELLS; HB SC DISEASE; HYDROXYUREA THERAPY; BETA-THALASSEMIA; SODIUM-BUTYRATE; GAMMA-GLOBIN; IN-VIVO C1 Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. RP Steinberg, MH (reprint author), Room 211,88 E Newton St, Boston, MA 02118 USA. NR 178 TC 39 Z9 40 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD SEP PY 2001 VL 80 IS 5 BP 328 EP 344 DI 10.1097/00005792-200109000-00007 PG 17 WC Medicine, General & Internal SC General & Internal Medicine GA 473TN UT WOS:000171064300007 PM 11552087 ER PT J AU Mansoor, JK Eldridge, MW Yoneda, KY Schelegle, ES Wood, SC AF Mansoor, JK Eldridge, MW Yoneda, KY Schelegle, ES Wood, SC TI Role of airway receptors in altitude-induced dyspnea SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE pulmonary afferents; aerosolized tetracaine; c-fibers; hypoxia; exercise ID PULMONARY-EDEMA; BREATHLESSNESS; SENSATION; EXERCISE; ANESTHESIA; REFLEXES AB Purpose: The purpose of Us study was to examine the role of airway receptors in respiratory-related sensations after ascent to altitude. Methods: Ratings of respiratory-related sensations, perceived exertion and acute mountain sickness, heart rate, and peripheral oxygen saturation were recorded at rest and exercise in male and female subjects who had inhaled either aerosolized saline or saline with tetracaine after acute ascent to an altitude of 3500 m and after prolonged acclimatization of 18 d at altitudes between 4000 and 5000 m. Results: Tetracaine had no effect on respiratory-related sensations at altitude either at rest or during exercise, and male and female subjects experienced similar respiratory-related sensations. Sensations of rapid breathing were experienced at rest after acute exposure to 3500 ra as compared with sea level, but not after acclimatization to 5000 m. Sensations of rapid breathing, air hunger, and heavy breathing were experienced during exercise after acute and prolonged altitude exposure as compared with sea level, with a sensation of chest tightness experienced at 3500 m and a sensation of gasping experienced at 5000 m. Conclusion: These results suggest that airway afferents play no role in the respiratory-related sensations experienced by male and female subjects either during acute ascent to altitude or after prolonged acclimatization at altitude. C1 Univ Pacific, Sch Pharm & Hlth Sci, Phys Therapy Dept, Stockton, CA 95211 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ N Carolina, Ctr Environm Med & Lung Biol, Chapel Hill, NC USA. Univ Calif Davis, Sch Med, Div Pulm & Crit Care Med, Dept Med, Davis, CA 95616 USA. VA No Calif Hlth Care Syst, Dept Vet Affairs, Martinez, CA USA. Univ Calif Davis, Sch Vet Med, Dept Anat Cell Biol & Physiol, Davis, CA 95616 USA. Summa Hlth Syst Fdn, Akron, OH USA. RP Mansoor, JK (reprint author), Univ Pacific, Sch Pharm & Hlth Sci, Phys Therapy Dept, 3601 Pacific Ave, Stockton, CA 95211 USA. NR 22 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD SEP PY 2001 VL 33 IS 9 BP 1449 EP 1455 DI 10.1097/00005768-200109000-00005 PG 7 WC Sport Sciences SC Sport Sciences GA 470CY UT WOS:000170853900005 PM 11528331 ER PT J AU McHugh, RS Shevach, EM Thornton, AM AF McHugh, RS Shevach, EM Thornton, AM TI Control of organ-specific autoimmunity by immunoregulatory CD4+CD25+ T cells SO MICROBES AND INFECTION LA English DT Article DE autoimmunity; suppressor T cells; autoimmune gastritis ID ANTIGEN-PRESENTING CELLS; GROWTH-FACTOR-BETA; SELF-TOLERANCE; EFFECTOR FUNCTION; MICE; DISEASE; GASTRITIS; THYROIDITIS; INDUCTION; IDENTIFICATION AB CD4(+)CD25(+) T cells regulate the activity of autoreactive T cells. Depletion of these cells results in the development of a wide-spectrum of organ-specific autoimmune diseases. In vitro model systems have been developed to study the function of these potent suppressor cells. Following their activation via their T-cell receptor, they downregulate the responses of CD25(-) effectors by a T-T interaction. (C) 2001 Editions scientifiques et medicales Elsevier SAS. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 48 TC 46 Z9 47 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD SEP PY 2001 VL 3 IS 11 BP 919 EP 927 DI 10.1016/S1286-4579(01)01453-8 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 480FG UT WOS:000171450900007 PM 11564440 ER PT J AU Hase, CC Fedorova, ND Galperin, MY Dibrov, PA AF Hase, CC Fedorova, ND Galperin, MY Dibrov, PA TI Sodium ion cycle in bacterial pathogens: Evidence from cross-genome comparisons SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID NA+-TRANSLOCATING NADH; MARINE VIBRIO-ALGINOLYTICUS; COUPLED OXIDATIVE-PHOSPHORYLATION; METHYLMALONYL-COA DECARBOXYLASE; MULTIDRUG-RESISTANCE PUMPS; DEPENDENT CITRATE CARRIER; VIRULENCE GENE-EXPRESSION; PROTEIN SECRETION SYSTEMS; CYTOCHROME-C OXIDASES; AMINO-ACID-TRANSPORT AB Analysis of the bacterial genome sequences shows that many human and animal pathogens encode primary membrane Na+ pumps, Na+-transporting dicarboxylate decarboxylases or Na+-translocating NADH:ubiquinone oxidoreductase, and a number of Na+-dependent permeases. This indicates that these bacteria can utilize Na+ as a coupling ion instead of or in addition to the H+ cycle. This capability to use a Na+ cycle might be an important virulence factor for such pathogens as Vibrio, cholerae, Neisseria meningitidis, Salmonella enterica serovar Typhi, and Yersinia pestis. In Treponema pallidum, Chlamydia trachomatis, and Chlamydia pneumoniae, the Na+ gradient may well be the only energy source for secondary transport. A survey of preliminary genome sequences of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, and Treponema denticola indicates that these oral pathogens also rely on the Na+ cycle for at least part of their energy metabolism. The possible roles of the Na+ cycling in the energy metabolism and pathogenicity of these organisms are reviewed. The recent discovery of an effective natural antibiotic, korormicin, targeted against the Na+-translocating NADH:ubiquinone oxidoreductase, suggests a potential use of Na+ pumps as drug targets and/or vaccine candidates. The antimicrobial potential of other inhibitors of the Na cycle, such as monensin, Li+ and Ag+ ions, and amiloride derivatives, is discussed. C1 Univ Manitoba, Fac Sci, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Univ Manitoba, Fac Sci, Dept Microbiol, Rm 420,Buller Bldg, Winnipeg, MB R3T 2N2, Canada. EM dibrovp@ms.umanitoba.ca RI Galperin, Michael/B-5859-2013; Abrams, Natalie/F-4845-2011 OI Galperin, Michael/0000-0002-2265-5572; Abrams, Natalie/0000-0001-9698-2819 FU NCI NIH HHS [P30 CA021765] NR 227 TC 143 Z9 149 U1 2 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 EI 1098-5557 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD SEP PY 2001 VL 65 IS 3 BP 353 EP + DI 10.1128/MMBR.65.3.353-370.2001 PG 20 WC Microbiology SC Microbiology GA 470LY UT WOS:000170874500002 PM 11528000 ER PT J AU Overbaugh, J Miller, AD Eiden, MV AF Overbaugh, J Miller, AD Eiden, MV TI Receptors and entry cofactors for retroviruses include single and multiple transmembrane-spanning proteins as well as newly described glycophosphatidylinositol-anchored and secreted proteins SO MICROBIOLOGY AND MOLECULAR BIOLOGY REVIEWS LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; FELINE LEUKEMIA-VIRUS; AMINO-ACID TRANSPORTER; CELL-SURFACE RECEPTOR; ECOTROPIC MURINE RETROVIRUSES; GP120 ENVELOPE GLYCOPROTEIN; SARCOMA-ASSOCIATED VIRUS; MACROPHAGE-TROPIC HIV-1; N-LINKED GLYCOSYLATION; SPLEEN NECROSIS VIRUS AB In the past few years, many retrovirus receptors, coreceptors, and cofactors have been identified. These molecules are important for some aspects of viral entry, although in some cases it remains to be determined whether they are required for binding or postbinding stages in entry, such as fusion. There are certain common features to the molecules that many retroviruses use to gain entry into the cell. For example, the receptors for most mammalian oncoretroviruses are multiple membrane-spanning transport proteins. However, avian retroviruses use single-pass membrane proteins, and a sheep retrovirus uses a glycosylphosphatidylinositol-anchored molecule as its receptor. For some retroviruses, particularly the lentiviruses, two cell surface molecules are required for efficient entry. More recently, a soluble protein that is required for viral entry has been identified for a feline oncoretrovirus. In this review, we will focus on the various strategies used by mammalian retroviruses to gain entry into the cell. The choice of receptors will also be discussed in light of pressures that drive viral evolution and persistence. C1 Fred Hutchinson Canc Res Ctr, Div Human BIol, Seattle, WA 98109 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Overbaugh, J (reprint author), Fred Hutchinson Canc Res Ctr, Div Human BIol, 1100 Fairview Ave N,C3-168, Seattle, WA 98109 USA. OI Miller, Dusty/0000-0002-3736-3660 NR 200 TC 133 Z9 133 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1092-2172 J9 MICROBIOL MOL BIOL R JI Microbiol. Mol. Biol. Rev. PD SEP PY 2001 VL 65 IS 3 BP 371 EP + DI 10.1128/MMBR.65.3.371-389.2001 PG 20 WC Microbiology SC Microbiology GA 470LY UT WOS:000170874500003 PM 11528001 ER PT J AU Granholm, AC Helt, C Srivastava, N Backman, C Gerhardt, GA AF Granholm, AC Helt, C Srivastava, N Backman, C Gerhardt, GA TI Effects of age and GDNF on noradrenergic innervation of the hippocampal formation: Studies from intraocular grafts SO MICROSCOPY RESEARCH AND TECHNIQUE LA English DT Article DE noradrenergic neurons; locus coeruleus; glial cell line-derived neurotrophic factor; hippocampal formation; iris; aging; neuroplasticity; sprouting ID NEURONS IN-VIVO; LOCUS-COERULEUS; NEUROTROPHIC FACTOR; ALZHEIMERS-DISEASE; CEREBROSPINAL-FLUID; MESSENGER-RNA; RAT-BRAIN; PARKINSONS-DISEASE; NERVOUS SYSTEMS; NOREPINEPHRINE AB Recent studies have suggested that factors in the target tissue influence the degree of plasticity and regeneration following aging and/or specific insults. We have investigated whether young or aged targets differ in their noradrenergic innervation from fetal locus coeruleus (LC) neurons, and also if a specific growth factor, glial cell line-derived neurotrophic factor (GDNF) can affect this innervation pattern. Tissue pieces of fetal brainstem and young (3 months) or old (18 months) iris tissue were transplanted simultaneously into the anterior chamber of the eye of adult hosts. We found that aged iris transplants became innervated to a significantly lesser degree by the cografted LC neurons than young iris transplants. Fetal hippocampal tissue was then grafted to adult hosts, and a fetal brainstem graft containing LC neurons was placed adjacent to the first graft, either at 3 or 21 months post-grafting. Thus, old/young chimeras of the noradrenergic coeruleo-hippocampal pathway were created. Aged hippocampal grafts received a much less dense innervation from co-grafted LC neurons than young hippocampal grafts. Tyrosine hydroxylase-positive-immunoreactive innervation was only found in the outskirts of aged grafts, while the young hippocampal grafts contained an even innervation pattern. The innervation density of hippocampal grafts was significantly enhanced by GDNF treatment. These findings demonstrate that target-derived factors may regulate neuronal plasticity, and that the age of the target is more important for innervation properties than the age of the neuron innervating a particular target. Microsc. Res. Tech. 54:298-308, 2001. (C) 2001 Wiley-Liss, Inc. C1 Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Univ Rochester, Toxicol Grad Program, Rochester, NY USA. Univ Minnesota, Minneapolis, MN 55455 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Univ Kentucky, Dept Anat, Lexington, KY 40536 USA. Univ Kentucky, Dept Neurobiol, Lexington, KY 40536 USA. Univ Kentucky, Dept Neurol, Lexington, KY 40536 USA. RP Granholm, AC (reprint author), Med Univ S Carolina, Dept Physiol & Neurosci, 173 Ashley St, Charleston, SC 29425 USA. RI backman, cristina/C-1276-2013 FU NIA NIH HHS [AG12122, AG04418, R01 AG015239, AG15239, AG00796]; NIAAA NIH HHS [5T32AA07464-20]; NIMH NIH HHS [MH01245, MH49661] NR 60 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1059-910X J9 MICROSC RES TECHNIQ JI Microsc. Res. Tech. PD SEP 1 PY 2001 VL 54 IS 5 BP 298 EP 308 DI 10.1002/jemt.1142 PG 11 WC Anatomy & Morphology; Biology; Microscopy SC Anatomy & Morphology; Life Sciences & Biomedicine - Other Topics; Microscopy GA 468EL UT WOS:000170745100004 PM 11514986 ER PT J AU Danilkovitch-Miagkova, A Miagkov, A Skeel, A Nakaigawa, N Zbar, B Leonard, EJ AF Danilkovitch-Miagkova, A Miagkov, A Skeel, A Nakaigawa, N Zbar, B Leonard, EJ TI Oncogenic mutants of RON and MET receptor tyrosine kinases cause activation of the beta-catenin pathway SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Review ID HEPATOCYTE GROWTH-FACTOR; MACROPHAGE-STIMULATING PROTEIN; FACTOR SCATTER FACTOR; UBIQUITIN-PROTEASOME PATHWAY; PAPILLARY RENAL CARCINOMAS; EPITHELIAL-CELL MIGRATION; KAPPA-B-ALPHA; C-MET; HGF RECEPTOR; GENE-PRODUCT AB beta -Catenin is an oncogenic protein involved in regulation of cell-cell adhesion and gene expression. Accumulation of cellular beta -catenin occurs in many types of human cancers. Four mechanisms are known to cause increases in beta -catenin: mutations of beta -catenin, adenomatous polyposis coli, or axin genes and activation of Wnt signaling. We report a new cause of beta -catenin accumulation involving oncogenic mutants of RON and MET receptor tyrosine kinases (RTKs). Cells transfected with oncogenic RON or MET were characterized by beta -catenin tyrosine phosphorylation and accumulation; constitutive activation of a Tcf transcriptional factor; and increased levels of beta -catenin/Tcf target oncogene proteins c-myc and cyclin D1. Interference with the beta -catenin pathway reduced the transforming potential of mutated RON and MET. Activation of beta -catenin by oncogenic RON and MET constitutes a new pathway, which might lead to cell transformation by these and other mutant growth factor RTKs. C1 NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Neuromuscular Div, Baltimore, MD 21231 USA. RP Danilkovitch-Miagkova, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, Immunobiol Lab, Frederick, MD 21702 USA. NR 118 TC 104 Z9 106 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2001 VL 21 IS 17 BP 5857 EP 5868 DI 10.1128/MCB.21.17.5857-5868.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 461DP UT WOS:000170349900016 PM 11486025 ER PT J AU Wang, WG Yang, XL Cristofalo, VJ Holbrook, NJ Gorospe, M AF Wang, WG Yang, XL Cristofalo, VJ Holbrook, NJ Gorospe, M TI Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AU-RICH ELEMENT; HUMAN-DIPLOID FIBROBLASTS; FACTOR MESSENGER-RNA; ADULT MONONUCLEAR-CELLS; BINDING-PROTEIN; IN-VIVO; TRANSCRIPTION FACTORS; CELLULAR SENESCENCE; PROSTAGLANDIN A(2); DOWN-REGULATION AB Cellular aging is accompanied by alterations in gene expression patterns. Here, using two models of replicative senescence, we describe the influence of the RNA-binding protein HuR in regulating the expression of several genes whose expression decreases during senescence. We demonstrate that HuR levels, HuR binding to target mRNAs encoding proliferative genes, and the half-lives of such mRNAs are lower in senescent cells. Importantly, overexpression of HuR in senescent cells restored a "younger" phenotype, while a reduction in HuR expression accentuated the senescent phenotype. Our studies highlight a critical role for HuR during the process of replicative senescence. C1 NIA, Gerontol Res Ctr, IRP, Cellular & Mol Biol Lab,NIH, Baltimore, MD 21224 USA. Lankenau Inst Med Res, Wynnewood, PA 19096 USA. Thomas Jefferson Univ, Wynnewood, PA 19096 USA. RP Gorospe, M (reprint author), NIA, Gerontol Res Ctr, IRP, Cellular & Mol Biol Lab,NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 39 TC 104 Z9 106 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2001 VL 21 IS 17 BP 5889 EP 5898 DI 10.1128/MCB.21.17.5889-5898.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 461DP UT WOS:000170349900019 PM 11486028 ER PT J AU Ward, Y Wang, W Woodhouse, E Linnoila, I Liotta, L Kelly, K AF Ward, Y Wang, W Woodhouse, E Linnoila, I Liotta, L Kelly, K TI Signal pathways which promote invasion and metastasis: Critical and distinct contributions of extracellular signal-regulated kinase and Ral-specific guanine exchange factor pathways SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; PHOSPHOINOSITIDE 3-KINASES; DISSOCIATION STIMULATOR; PLASMINOGEN-ACTIVATOR; ONCOGENIC RAS; GROWTH-FACTOR; CELLS; TRANSFORMATION; EFFECTOR; TUMORIGENICITY AB Approximately 50% of metastatic tumors contain Ras mutations. Ras proteins can activate at least three downstream signaling cascades mediated by the Raf-MEK-extracellular signal-regulated kinase family, phosphatidylinositol-3 (P13) kinase, and Ral-specific guanine nucleotide exchange factors (RalGEFs). Here we investigated the contribution of RalGEF and ERK activation to the development of experimental metastasis in vivo and associated invasive properties in vitro. Each pathway contributes distinct properties to the metastatic phenotype. Following lateral tail vein injection, 3T3 cells transformed by constitutively active Raf or MEK produced lung metastasis that displayed circumscribed, noninfiltrating borders. In contrast, 3T3 cells transformed by Ras(12V,37G), a Ras effector mutant that activates RalGEF but not Raf or P13 kinase, formed aggressive, infiltrative metastasis. Dominant negative RalB inhibited Ras (12V,37G) -activated invasion and metastasis, demonstrating the necessity of the RalGEF pathway for a fully transformed phenotype. Moreover, 3T3 cells constitutively expressing a membrane-associated form of RalGEF (RalGDS-CAAX) formed invasive tumors as well, demonstrating that activation of a RalGEF pathway is sufficient to initiate the invasive phenotype. Despite the fact that Ras(12V,37G) expression does not elevate ERK activity, inhibition of this kinase by a conditionally expressed ERK phosphatase demonstrated that ERK activity was necessary for Ras (12V,37G)-transformed cells to express matrix-degrading activity in vitro and tissue invasiveness in vivo. Therefore, these experiments have revealed a hitherto-unknown but essential interaction of the RalGEF and ERK pathways to produce a malignant phenotype. The generality of the role of the RalGEF pathway in metastasis is supported by the finding that Ras(12V,37G) increased the invasiveness of epithelial cells as well as fibroblasts. C1 NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. RP Kelly, K (reprint author), Bldg 10,Room 3B43, Bethesda, MD 20892 USA. NR 46 TC 112 Z9 116 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2001 VL 21 IS 17 BP 5958 EP 5969 DI 10.1128/MCB.21.17.5958-5969.2001 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 461DP UT WOS:000170349900025 PM 11486034 ER PT J AU Iso, T Sartorelli, V Chung, G Shichinohe, T Kedes, L Hamamori, Y AF Iso, T Sartorelli, V Chung, G Shichinohe, T Kedes, L Hamamori, Y TI HERP, a new primary target of notch regulated by ligand binding SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HELIX BHLH PROTEINS; RBP-J-KAPPA; CELL DIFFERENTIATION; DROSOPHILA HAIRY; HEY GENES; SPLIT; EXPRESSION; ENHANCER; PATHWAY; HOMOLOG AB Notch signaling dictates cell fate and critically influences cell proliferation, differentiation, and apoptosis in metazoans. Ligand binding initiates the signal through regulated intramembrane proteolysis of a transmembrane Notch receptor which releases the signal-transducing Notch intracellular domain (NICD). The HES/E(spl) gene family is a primary target of Notch and thus far the only known Notch effector. A newly isolated HER-P family, a HES-related basic helix-loop-helix protein family, has been proposed as a potential target of Notch, based on its induction following NICD overexpression. However, NICD is physiologically maintained at an extremely low level that typically escapes detection, and therefore, nonregulated overexpression of NICD-as in transient transfection-has the potential of generating cellular responses of little physiological relevance. Indeed, a constitutively active NICD indiscriminately up-regulates expression of both HERP1 and HERP2 mRNAs. However, physiological Notch stimulation through ligand binding results in the selective induction of HERP2 but not HERP1 mRNA and causes only marginal up-regulation of HES1 mRNA. Importantly, HERP2 is an immediate target gene of Notch signaling since HERP2 mRNA expression is induced even in the absence of de novo protein synthesis. HERP2 mRNA induction is accompanied by specific expression of HERP2 protein in the nucleus. Furthermore, using RBP-jk-deficient cells, we show that an RBP-Jk protein, a transcription factor that directly activates HES/E(spl) transcription, also is essential for HERP2 mRNA expression and that expression of exogenous RBP-jk is sufficient to rescue HERP2 mRNA expression. These data establish that HERP2 is a novel primary target gene of Notch that, together with HES, may effect diverse biological activities of Notch. C1 Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90089 USA. NIAMS, Muscle Biol Lab, Muscle Gene Express Grp, IRP,NIH, Bethesda, MD 20892 USA. RP Hamamori, Y (reprint author), 2250 Alcazar St, Los Angeles, CA 90089 USA. RI SHICHINOHE, Toshiaki/A-4837-2012 NR 49 TC 140 Z9 145 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2001 VL 21 IS 17 BP 6071 EP 6079 DI 10.1128/MCB.21.17.6071-6079.2001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 461DP UT WOS:000170349900035 PM 11486044 ER PT J AU Iso, T Sartorelli, V Poizat, C Iezzi, S Wu, HY Chung, G Kedes, L Hamamori, Y AF Iso, T Sartorelli, V Poizat, C Iezzi, S Wu, HY Chung, G Kedes, L Hamamori, Y TI HERP, a novel heterodimer partner of HES/E(spl) in notch signaling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HELIX-LOOP-HELIX; HISTONE DEACETYLASE COMPLEX; TRANSCRIPTIONAL REPRESSION; DROSOPHILA HAIRY; BHLH PROTEINS; HEY GENES; N-COR; ENHANCER; SPLIT; DOMAIN AB HERP1 and -2 are members of a new basic helix-loop-helix (bHLH) protein family closely related to HES/E(spl), the only previously known Notch effector. Like that of HES, HERP mRNA expression is directly up-regulated by Notch ligand binding without de novo protein synthesis. HES and HERP are individually expressed in certain cells, but they are also coexpressed within single cells after Notch stimulation. Here, we show that HERP has intrinsic transcriptional repression activity. Transcriptional repression by HES/E(spl) entails the recruitment of the corepressor TLE/Groucho via a conserved WRPW motif, whereas unexpectedly the corresponding-but modified-tetrapeptide motif in HERP confers marginal repression. Rather, HERP uses its bHLH domain to recruit the mSin3 complex containing histone deacetylase HDAC1 and an additional corepressor, N-CoR, to mediate repression. HES and HER-P homodimers bind similar DNA sequences, but with distinct sequence preferences, and they repress transcription from specific DNA binding sites. Importantly, HES and HERP associate with each other in solution and form a stable HES-HERP heterodimer upon DNA binding. HES-HER-P heterodimers have both a greater DNA binding activity and a stronger repression activity than do the respective homodimers. Thus, Notch signaling relies on cooperation between HES and HERP, two transcriptional repressors with distinctive repression mechanisms which, either as homo- or as heterodimers, regulate target gene expression. C1 Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90089 USA. NIAMS, Muscle Biol Lab, Muscle Gene Express Grp, IRP,NIH, Bethesda, MD 20892 USA. RP Hamamori, Y (reprint author), 2250 Alcazar St, Los Angeles, CA 90089 USA. NR 50 TC 150 Z9 153 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD SEP PY 2001 VL 21 IS 17 BP 6080 EP 6089 DI 10.1128/MCB.21.17.6080-6089.2001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 461DP UT WOS:000170349900036 PM 11486045 ER PT J AU Lezin, GT Makarova, KV Velikodvorskaya, VV Zelentsova, ES Kechumyan, RR Kidwell, MG Koonin, EV Evgen'ev, MB AF Lezin, GT Makarova, KV Velikodvorskaya, VV Zelentsova, ES Kechumyan, RR Kidwell, MG Koonin, EV Evgen'ev, MB TI The structure and evolutionary role of the Penelope mobile element in the Drosophila virilis species group SO MOLECULAR BIOLOGY LA English DT Article DE mobile genetic element; retrotransposon; integrase; endonuclease; evolution; invasion; Drosophila virilis ID HYBRID DYSGENESIS SYNDROME; TRANSPOSABLE ELEMENTS; PHYLOGENIES; CHROMOSOMES; SEQUENCES; INVASION; FAMILY AB The mobile element Penelope is activated and mobilizes several other transposons in dysgenic crosses in Drosophila virilis. Its structure proved to be complex and to vary greatly in all examined species of the virilis group. Phylogenetic analysis of the reverse transcriptase (RT) domain assigned Penelope to a new branch, rather than to any known family, of LTR-lacking retroelements. Amino acid sequence analysis showed that the C-terminal domain of the Penelope polyprotein is an active endonuclease, which is related to intron-encoded endonucleases and to bacterial repair endonuclease UrvC, and may act as an integrase. Retroelements coding for a putative endonuclease that differs from typical integrase have not been known thus far. Phylogenetic analysis divided the Penelope copies from several virilis species into two subfamilies, one including virtually identical full-length copies, and the other comprising highly divergent defective copies. The results suggest both vertical and horizontal transfer of the element. Possibly, Penelope invasion recurred during evolution and contributed to genome rearrangement in the virilis species. Chromosome aberrations detected in D. virilis, which is now being invaded by Penelope, is direct evidence for this assumption. C1 Russian Acad Sci, Inst Cell Biophys, Pushchino 142292, Moscow Region, Russia. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 117984, Russia. RP Lezin, GT (reprint author), Russian Acad Sci, Inst Cell Biophys, Pushchino 142292, Moscow Region, Russia. NR 29 TC 0 Z9 0 U1 1 U2 2 PU MAIK NAUKA/INTERPERIODICA PI NEW YORK PA C/O KLUWER ACADEMIC-PLENUM PUBLISHERS, 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0026-8933 J9 MOL BIOL+ JI Mol. Biol. PD SEP-OCT PY 2001 VL 35 IS 5 BP 682 EP 690 DI 10.1023/A:1012370103209 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 488WB UT WOS:000171958700008 ER PT J AU Al-Haddad, AH Shonn, MA Redlich, B Blocker, A Burkhardt, JK Yu, H Hammer, JA Weiss, DG Steffen, W Griffiths, G Kuznetsov, SA AF Al-Haddad, AH Shonn, MA Redlich, B Blocker, A Burkhardt, JK Yu, H Hammer, JA Weiss, DG Steffen, W Griffiths, G Kuznetsov, SA TI Myosin va bound to phagosomes binds to F-actin and delays microtubule-dependent motility SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID J774 MACROPHAGES; PERITONEAL-MACROPHAGES; SQUID AXOPLASM; TRANSPORT; PHAGOCYTOSIS; MOVEMENT; MOTOR; BRAIN; PROTEINS; COMPLEX AB We established a light microscopy-based assay that reconstitutes the binding of phagosomes purified from mouse macrophages to preassembled F-actin in vitro. Both endogenous myosin Va from mouse macrophages and exogenous myosin Va from chicken brain stimulated the phagosome-F-actin interaction. Myosin Va association with phagosomes correlated with their ability to bind F-actin in an ATP-regulated manner and antibodies to myosin Va specifically blocked the ATP-sensitive phagosome binding to F-actin. The uptake and retrograde transport of phagosomes from the periphery to the center of cells in bone marrow macrophages was observed in both normal mice and mice homozygous for the dilute-lethal spontaneous mutation (myosin Va null). However, in dilute-lethal macrophages the accumulation of phagosomes in the perinuclear region occurred twofold faster than in normal macrophages. Motion analysis revealed saltatory phagosome movement with temporarily reversed direction in normal macrophages, whereas almost no reversals in direction were observed in dilute-lethal macrophages. These observations demonstrate that myosin Va. mediates phagosome binding to F-actin, resulting in a delay in microtubule-dependent retrograde phagosome movement toward the cell center. We propose an "antagonistic/cooperative mechanism" to explain the saltatory phagosome movement toward the cell center in normal macrophages. C1 Univ Rostock, FB Biowissensch, Inst Zellbiol & Biosyst Tech, D-18051 Rostock, Germany. European Mol Biol Lab, Heidelberg, Germany. Natl Univ Singapore, Inst Med, Clin Res Ctr, Singapore 117597, Singapore. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Kuznetsov, SA (reprint author), Univ Rostock, FB Biowissensch, Inst Zellbiol & Biosyst Tech, D-18051 Rostock, Germany. RI Yu, Hanry/C-1031-2013; Al-Haddad, Ahmed/N-4906-2016; Blocker, Ariel/Q-6617-2016; OI Yu, Hanry/0000-0002-0339-3685; Al-Haddad, Ahmed/0000-0002-9844-7868; Weiss, Dieter G./0000-0002-1789-2995 NR 57 TC 57 Z9 57 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 2001 VL 12 IS 9 BP 2742 EP 2755 PG 14 WC Cell Biology SC Cell Biology GA 472LQ UT WOS:000170985900016 PM 11553713 ER PT J AU Xiao, H Sandaltzopoulos, R Wang, HM Hamiche, A Ranallo, R Lee, KM Fu, DG Wu, C AF Xiao, H Sandaltzopoulos, R Wang, HM Hamiche, A Ranallo, R Lee, KM Fu, DG Wu, C TI Dual functions of largest NURF subunit NURF301 in nucleosome sliding and transcription factor interactions SO MOLECULAR CELL LA English DT Article ID CHROMATIN-REMODELING COMPLEX; GLUTAMINE-RICH DOMAIN; HISTONE-FOLD PROTEINS; YEAST SWI/SNF COMPLEX; DNA-BINDING DOMAIN; GAGA FACTOR; SACCHAROMYCES-CEREVISIAE; HIGH-AFFINITY; IN-VITRO; ISWI AB NURF is an ISWI complex of four proteins that uses the energy of ATP hydrolysis to catalyze nucleosome sliding. Three NURF components have been identified previously. We have cloned cDNA encoding the largest NURF subunit, revealing a 301 kDa polypeptide (NURF301) that shares structural motifs with ACF1. We have reconstituted full and partial NURF complexes from recombinant proteins and show that NURF301 and the ISWI ATPase are necessary and sufficient for accurate and efficient nucleosome sliding. An HMGA/HMGI(Y)-like domain of NURF301 that facilitates nucleosome sliding indicates the importance of DNA conformational changes in the sliding mechanism. NURF301 also shows interactions with sequence-specific transcription factors, providing a basis for targeted recruitment of the NURF complex to specific genes. 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. OI Fu, Dragony/0000-0002-8725-8658 NR 82 TC 149 Z9 152 U1 2 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD SEP PY 2001 VL 8 IS 3 BP 531 EP 543 DI 10.1016/S1097-2765(01)00345-8 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 476WJ UT WOS:000171251500009 PM 11583616 ER PT J AU Ando, S Sarlis, NJ Krishnan, J Feng, X Refetoff, S Zhang, MQ Oldfield, EH Yen, PM AF Ando, S Sarlis, NJ Krishnan, J Feng, X Refetoff, S Zhang, MQ Oldfield, EH Yen, PM TI Aberrant alternative splicing of thyroid hormone receptor in a TSH-secreting pituitary tumor is a mechanism for hormone resistance SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID HUMAN BREAST-CANCER; INSTITUTES-OF-HEALTH; MESSENGER-RNA; TRANSGENIC MICE; MOLECULAR-BASIS; HUMAN-DISEASE; BETA GENE; THYROTROPIN; EXPRESSION; MUTATIONS AB Patients with TSH-secreting pituitary tumors (TSHomas) have high serum TSH levels despite elevated thyroid hormone levels. The mechanism for this defect in the negative regulation of TSH secretion is not known. We performed RT-PCR to detect mutations in TR beta from a surgically resected TSHoma. Analyses of the RT-PGR products revealed a 135-bp deletion within the sixth exon that encodes the ligand-binding domain of TR beta2. This deletion was caused by alternative splicing of TR beta2 mRNA, as near-consensus splice sequences were found at the junction site and no deletion or mutations were detected in the tumoral genomic DNA. This TR beta variant (TR beta 2spl) lacked thyroid hormone binding and had impaired T-3-dependent negative regulation of both TSH beta and glycoprotein hormone alpha -subunit genes in cotransfection studies. Furthermore, TR beta 2spl showed dominant negative activity against the wild-type TR beta2. These findings strongly suggest that aberrant alternative splicing of TR beta2 mRNA generated an abnormal TR protein that accounted for the defective negative regulation of TSH in the TSHoma. This is the first example of aberrant alternative splicing of a nuclear hormone receptor causing hormonal dysregulation. This novel posttranscriptional mechanism for generating abnormal receptors may occur in other hormone-resistant states or tumors in which no receptor mutation is detected in genomic DNA. C1 NIDDK, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. RP Yen, PM (reprint author), NIDDK, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. FU NHGRI NIH HHS [HG-01696]; NIDDK NIH HHS [DK-15070] NR 58 TC 61 Z9 63 U1 0 U2 2 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4110 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD SEP PY 2001 VL 15 IS 9 BP 1529 EP 1538 DI 10.1210/me.15.9.1529 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 468CH UT WOS:000170740200006 PM 11518802 ER PT J AU Nwokoro, NA Wassif, CA Porter, FD AF Nwokoro, NA Wassif, CA Porter, FD TI Genetic disorders of cholesterol biosynthesis in mice and humans SO MOLECULAR GENETICS AND METABOLISM LA English DT Review ID LEMLI-OPITZ-SYNDROME; MEVALONATE KINASE-DEFICIENCY; PERIODIC FEVER SYNDROME; DOMINANT CHONDRODYSPLASIA PUNCTATA; DELTA-7-STEROL REDUCTASE GENE; CONRADI-HUNERMANN-SYNDROME; CULTURED SKIN FIBROBLASTS; EMOPAMIL-BINDING-PROTEIN; MATERNAL SERUM ESTRIOL; BARE PATCHES BPA AB Over the past few years, the number of identified inborn errors of cholesterol biosynthesis has increased significantly. The first inborn error of cholesterol biosynthesis to be characterized, in the mid 1980s, was mevalonic aciduria. In 1993, Irons et al. (1) (M. Irons, E. R. Elias, G. Salen, G. S. Tint, and A. K. Batta, Lancet 341:1414, 1993) reported that Smith-Lemli-Opitz syndrome, a classic autosomal recessive malformation syndrome, was due to an inborn error of cholesterol biosynthesis. This was the first inborn error of postsqualene cholesterol biosynthesis to be identified, and subsequently additional inborn errors of postsqualene cholesterol biosynthesis have been characterized to various extent. To date, eight inborn errors of cholesterol metabolism have been described in human patients or in mutant mice. The enzymatic steps impaired in these inborn errors of metabolism include mevolonate kinase (mevalonic aciduria as well as hyperimmunoglobulinemia D and periodic fever syndrome), squalene synthase (Ss-/- mouse), 3 beta -hydroxysteroid Delta (14)-reductase (hydrops-ectopic calcification-moth-eaten skeletal dysplasia), 3 beta -hydroxysteroid dehydrogenase (CHILD syndrome, bare patches mouse, and striated mouse), 3 beta -hydroxysteroid Delta (8),Delta (7)-isomerase (X-linked dominant chondrodysplasia punctata type 2, CHILD syndrome, and tattered mouse), 3 beta -hydroxysteroid Delta (24)-reductase (desmosterolosis) and 3 beta -hydroxysteroid Delta (7)-reductase (RSH/Smith-Lemli-Opitz syndrome and Dher7-/-mouse). Identification of the genetic and biochemical defects which give rise to these syndromes has provided the first step in understanding the pathophysiological processes which underlie these malformation syndromes. (C) 2001 Academic Press. C1 NICHHD, HDB, NIH, Bethesda, MD 20892 USA. RP Porter, FD (reprint author), NICHHD, HDB, NIH, Bldg 10,Room 9S241,10 Ctr Dr, Bethesda, MD 20892 USA. OI Wassif, Christopher/0000-0002-2524-1420 NR 105 TC 47 Z9 47 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2001 VL 74 IS 1-2 BP 105 EP 119 DI 10.1006/mgme.2001.3226 PG 15 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 480NW UT WOS:000171468700009 PM 11592808 ER PT J AU Huizing, M Anikster, Y White, JG Gahl, WA AF Huizing, M Anikster, Y White, JG Gahl, WA TI Characterization of the murine gene corresponding to human Hermansky-Pudlak syndrome type 3: Exclusion of the subtle gray (sut) locus SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE locus heterogeneity; mouse models; oculocutaneous albinism; storage pool deficiency; platelet dense bodies ID PALE EAR EP; PROTEIN COMPLEX; GRANULOMATOUS COLITIS; PULMONARY FIBROSIS; VESICLE FORMATION; AP-3 ADAPTER; HPS GENE; MOUSE; MUTATIONS; FORM AB Hermansky-Pudlak syndrome (HPS) consists of oculocutaneous albinism and a bleeding diathesis due to absent platelet dense bodies. In addition to exhibiting considerable phenotypic variation, this autosomal recessive disorder displays locus heterogeneity. One causative gene is HPS1, coding for a protein of unknown function and resulting in HPS-1 disease, common in northwest Puerto Rico. A second HPS-causing gene is ADTB3A, coding for the beta 3A subunit of adaptor complex-3 (AP-3, a coat protein complex) and resulting in HPS-2 disease. Each of these HPS subtypes has a murine counterpart, specifically pale ear for HPS-1 and pearl for HPS-2. Recently, the HPS3 gene, responsible for HPS-3 disease in a genetic isolate of central Puerto Rico, was isolated and characterized. Its location on human chromosome 3q24 suggested that the mouse model corresponding to HPS-3 disease might be subtle gray. To examine this possibility, we determined the mouse HPS3 sequence, its genomic organization, and its amino acid sequence, which shares 95.8% identity with the human protein. We demonstrated that the subtle gray mouse produces a normal size and amount of HPS3 mRNA and has an entirely normal sequence in every exon and intron/exon boundary. Furthermore, subtle gray exhibits a normal contingent of platelet dense bodies. Together, these data eliminate subtle gray as a murine model for HPS-3 disease and suggest that other mouse models be examined. (C) 2001 Academic Press. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. RP Gahl, WA (reprint author), NICHHD, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 37 TC 2 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD SEP-OCT PY 2001 VL 74 IS 1-2 BP 217 EP 225 DI 10.1006/mgme.2001.3233 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 480NW UT WOS:000171468700019 PM 11592818 ER PT J AU Hexham, JM Dudas, D Hugo, R Thompson, J King, V Dowling, C Neville, DM Digan, ME Lake, P AF Hexham, JM Dudas, D Hugo, R Thompson, J King, V Dowling, C Neville, DM Digan, ME Lake, P TI Influence of relative binding affinity on efficacy in a panel of anti-CD3 scFv immunotoxins SO MOLECULAR IMMUNOLOGY LA English DT Article DE immunotoxin; affinity; CD3; transplantation; tolerance; antibody engineering ID VERSUS-HOST DISEASE; T-CELL; DIPHTHERIA-TOXIN; PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY; FUSION PROTEINS; CLINICAL-TRIALS; TOLERANCE; LYMPHOCYTES; ANTIGEN AB The in vitro cell killing potency of an immunotoxin reflects the aggregate of several independent biochemical properties. These include antigen binding affinity: internalization rate, intracellular processing and intrinsic toxin domain potency. This study examines the influence of antigen binding affinity on potency in various immunotoxin fusion proteins where target antigen binding is mediated by single chain antibody variable region fragments (scFv). Firstly, the relationship between affinity and potency was examined in a panel of four scFv immunotoxins generated from different anti-CD3 monoclonal antibodies fused to the 38 kDa fragment of Pseudomonas aeruginosa exotoxin A (PE38). Of these four scFv-PE38 immunotoxins, the one derived from the anti-CD3 monoclonal antibody UCHT1 has highest cell killing potency. Analysis of these four scFv-PE38 immunotoxins indicated a correlation between antigen binding affinity and immunotoxin potency in the cell killing assay with the exception of the scFvPE38 immunotoxin derived from the antibody BC3. However this scFv appeared to suffer a greater drop in affinity ( similar to 100 x), relative to the parent Mab than did the other threo scFvs used in this study (2 - 10 x). secondly, the scFv(UCHT1)PE38 immunotoxin was then compared with a further panel of scFv(UCHT1)-derived immunotoxins including a divalent PE38 version and both monovalent and divalent Corynehacterium diphtheriae toxin (DT389) fusion proteins. When the scFv-UCHT1 domain was amino-terminally positioned relative to the toxin, as in the scFv(UCHT1)-PE38, an approximately 10-fold higher antigen-binding affinity was observed than with the C-terminal fusion, used in the DT389-scFv(UCHT1) molecule. Despite this lower antigen-binding activity, the DT389-scFv immunotoxin had a 60-fold higher potency in the T-cell-killing assay. Thirdly, a divalent form of the DT389-scFv construct. containing tandem scFv domains, had a 10-fold higher binding activity, which was exactly reflected in a 10-fold increase in potency. Therefore. when comparing immunotoxins in which scFvs from different antibodies are fused to the same toxin domain (DT or PE) a broad correlation appears to exist between binding affinity and immunotoxin potency. However. no correlation between affinity and potency appears to exist when different toxin domains are combined with the same scFv antibody domain. (C) 2001 Elsevier science Ltd. All rights reserved. C1 Novartis Pharmaceut, Transplantat Res, Summit, NJ 07901 USA. Penn State Univ, Fenske Lab, University Pk, PA 16802 USA. NIMH, Mol Biol Lab, Sect Biophys Chem, Bethesda, MD 20892 USA. RP Hexham, JM (reprint author), Novartis Pharmaceut, Transplantat Res, 556 Morris Ave, Summit, NJ 07901 USA. NR 32 TC 23 Z9 27 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD SEP PY 2001 VL 38 IS 5 BP 397 EP 408 DI 10.1016/S0161-5890(01)00070-0 PG 12 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 493XZ UT WOS:000172249900008 PM 11684296 ER PT J AU Mokkapati, SK de Henestrosa, ARF Bhagwat, AS AF Mokkapati, SK de Henestrosa, ARF Bhagwat, AS TI Escherichia coli DNA glycosylase Mug: a growth-regulated enzyme required for mutation avoidance in stationary-phase cells SO MOLECULAR MICROBIOLOGY LA English DT Article ID CYTOSINE METHYLTRANSFERASES; ADAPTIVE MUTATION; NONDIVIDING CELLS; OXIDATIVE STRESS; GENE-EXPRESSION; G/T MISMATCH; HELA-CELLS; HOT-SPOTS; IN-VIVO; URACIL AB The Escherichia coli DNA glycosylase Mug excises 3,N-4-ethenocytosines (epsilonC) and uracils from DNA, but its biological function is obscure. This is because epsilonC is not found in E. coli DNA, and uracil-DNA glycosylase (Ung), a distinct enzyme, is much more efficient at removing uracils from DNA than Mug. We find that Mug is overexpressed as cells enter stationary phase, and it is maintained at a fairly high level in resting cells. This is true of cells grown in rich or minimal media, and the principal regulation of mug is at the level of mRNA. Although the expression of mug is strongly dependent on the stationary-phase sigma factor, sigma (S), when cells are grown in minimal media, it shows only a modest dependence on sigma (S) when cells are grown in rich media. When mug cells are maintained in stationary phase for several days, they acquire many more mutations than their mug(+) counterparts. This is true in ung as well as ung(+) cells, and a majority of new mutations may not be C to T. Our results show that the biological role of Mug parallels its expression in cells. It is expressed poorly in exponentially growing cells and has no apparent role in mutation avoidance in these cells. In contrast, Mug is fairly abundant in stationary-phase cells and has an important anti-mutator role at this stage of cell growth. Thus, Mug joins a very small coterie of DNA repair enzymes whose principal function is to avoid mutations in stationary-phase cells. C1 Wayne State Univ, Dept Chem, Detroit, MI 48202 USA. NICHHD, Sect DNA Replicat Repair & Mutagenesis, Bethesda, MD 20892 USA. RP Bhagwat, AS (reprint author), Wayne State Univ, Dept Chem, 463 Chem Bldg, Detroit, MI 48202 USA. FU NIGMS NIH HHS [GM53273] NR 45 TC 17 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2001 VL 41 IS 5 BP 1101 EP 1111 DI 10.1046/j.1365-2958.2001.02559.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 477YQ UT WOS:000171314500013 PM 11555290 ER PT J AU Hiroi, N Wong, ML Licinio, J Park, C Young, M Gold, PW Chrousos, GP Bornstein, SR AF Hiroi, N Wong, ML Licinio, J Park, C Young, M Gold, PW Chrousos, GP Bornstein, SR TI Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls SO MOLECULAR PSYCHIATRY LA English DT Article DE CRH receptor; human tissues; pituitary; suicide ID IMPAIRED STRESS-RESPONSE; MAJOR DEPRESSION; MESSENGER-RNA; MICE LACKING; FACTOR CRF; RAT-BRAIN; ANTAGONIST; LOCALIZATION; CLONING; HORMONE-RECEPTOR-1 AB Corticotropin-releasing hormone (CRH) is a key neuroendocrine factor implementing endocrine, immune and behavioral responses to stress. CRH exerts its action through two major receptors, CRH-R1 and CRH-R2. Recently novel non-peptidic antagonists directed against CRH-R1 or CRH-R2 have been proposed as promising agents in the treatment of depression, anxiety and eating disorder. However, so far the CRH-receptor system has not been widely studied in humans. Therefore, we employed quantitative TaqMan PCR to analyze the expression and distribution of both CRH-R1 and CRH-R2 in human brain tissue and peripheral organs. Furthermore the expression of CRH receptors was analyzed for the first time in pituitaries of suicide victims by in situ hybridization and quantitative PCR. Our data demonstrated a different expression pattern in humans as compared to rodents. Both CRH-R1 and CRH-R2 were expressed in high amounts in the brain with the strongest expression in the pituitary. As described in rodents, however the CRH-R1 in human was the predominant receptor in the brain (82.7 +/- 11.0%), whilst CRH-R2 was the predominant receptor in peripheral organs (77.0 +/- 15.8%). There was a shift in the ratio of CRH-R1/R2 in the pituitaries of suicide victims. In conclusion, both CRH-R1 and GRH-R2 are widely expressed in human tissues with a distribution substantially different from rodents. Strong expression of both CRH-R1 and CRH-R2 in human pituitaries suggests that particularly under stress, activation of the HPA axis can be maintained through both receptors. C1 MNR Univ Dusseldorf, Dept Endocrinol, D-40001 Dusseldorf, Germany. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Inst Neuropsychiat, Lab Pharmacogenom, Los Angeles, CA 90095 USA. Univ Dusseldorf, Dept Endocrinol, D-4000 Dusseldorf, Germany. RP Bornstein, SR (reprint author), MNR Univ Dusseldorf, Dept Endocrinol, Mooren Str 5, D-40001 Dusseldorf, Germany. RI Wong, Ma-Li/D-7903-2011; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 FU NCCIH NIH HHS [P50 AT00151]; NHLBI NIH HHS [K30 HL04526]; NIDDK NIH HHS [R01 DK58851]; NIGMS NIH HHS [U01 GM61394] NR 38 TC 62 Z9 63 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2001 VL 6 IS 5 BP 540 EP 546 DI 10.1038/sj.mp.4000908 PG 7 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 461CG UT WOS:000170346900008 PM 11526468 ER PT J AU Butterweck, V Winterhoff, H Herkenham, M AF Butterweck, V Winterhoff, H Herkenham, M TI St John's wort, hypericin, and imipramine: a comparative analysis of mRNA levels in brain areas involved in HPA axis control following short-term and long-term administration in normal and stressed rats SO MOLECULAR PSYCHIATRY LA English DT Article DE antidepressant; hypothalamic-pituitary-adrenal; corticotropin-releasing hormone; paraventricular hypothalamic nucleus; norepinephrine; locus coeruleus; imipramine; Hypericum; in situ hybridization; gene expression regulation ID CORTICOTROPIN-RELEASING HORMONE; MESSENGER-RNA EXPRESSION; PITUITARY-ADRENOCORTICAL AXIS; GAMMA-AMINOBUTYRIC-ACID; FORCED SWIMMING TEST; TYROSINE-HYDROXYLASE; ANTIDEPRESSANT ACTIVITY; PARAVENTRICULAR NUCLEUS; ARGININE-VASOPRESSIN; MINERALOCORTICOID RECEPTOR AB Clinical studies demonstrate that the antidepressant efficacy of St John's wort (Hypericum) is comparable to that of tricyclic antidepressants such as imipramine. Onset of efficacy of these drugs occurs after several weeks of treatment. Therefore, we used in situ hybridization histochemistry to examine in rats the effects of short-term (2 weeks) and long-term (8 weeks) administration of imipramine, Hypericum extract, and hypericin (an active constituent of St John's wort) on the expression of genes that may be involved in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Imipramine (15 mg kg(-1)), Hypericum (500 mg kg(-1)), and hypericin (0.2 mg kg(-1)) given daily by gavage for 8 weeks but not for 2 weeks significantly decreased levels of corticotropin-releasing hormone (CRH) mRNA by 16-22% in the hypothalamic paraventricular nucleus (PVN) and serotonin 5-HT1A receptor mRNA by 11-17% in the hippocampus. Only imipramine decreased tyrosine hydroxylase (TH) mRNA levels in the locus coeruleus (by 23%), and only at 8 weeks. The similar delayed effects of the three compounds on gene transcription suggests a shared action on the centers that control HPA axis activity. A second study was performed to assess the effects of long-term imipramine and Hypericum administration on stress-induced changes in gene transcription in stress-responsive circuits. Repeated immobilization stress (2 h daily for 7 days) increased mRNA levels of CRH in the PVN, proopiomelanocortin (POMC) in the anterior pituitary, glutamic acid decarboxylase (GAD 65/67) in the bed nucleus of the stria terminalis (BST), cyclic AMP response element binding protein (CREB) in the hippocampus, and TH in the locus coeruleus. It decreased mRNA levels of 5-HT1A and brain-derived neurotrophic factor (BDNF) in the hippocampus. Long-term pretreatment with either imipramine or Hypericum reduced to control levels the stress-induced increases in gene transcription of GAD in the BST, CREB in the hippocampus, and POMC in the pituitary. The stress-induced increases in mRNA levels of CRH in the PVN and TH in the locus coeruleus were reduced by imipramine but not by Hypericum. The stress-induced decreases in BDNF and 5-HT1A mRNA levels were not prevented by either drug. Taken together, these data show: (1) that Hypericum and hypericin have delayed effects on HPA axis control centers similar to those of imipramine; and (2) that select stress-induced changes in gene transcription in particular brain areas can be prevented by long-term treatment with either the prototypic tricyclic antidepressant imipramine or the herbiceutical St John's wort. However, imipramine appears to be more effective in blocking stress effects on the HPA axis than the plant extract. C1 NIMH, Funct Neuroanat Sect, Bethesda, MD 20892 USA. Inst Pharmacol & Toxicol, D-48149 Munster, Germany. RP Herkenham, M (reprint author), NIMH, Funct Neuroanat Sect, NIMH Bldg 36,Rm 2D-15, Bethesda, MD 20892 USA. OI Herkenham, Miles/0000-0003-2228-4238 NR 79 TC 59 Z9 59 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2001 VL 6 IS 5 BP 547 EP 564 DI 10.1038/sj.mp.4000937 PG 18 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 461CG UT WOS:000170346900009 PM 11526469 ER PT J AU Akbarian, S Bates, B Liu, RJ Skirboll, SL Pejchal, T Coppola, V Sun, LD Fan, G Kucera, J Wilson, MA Tessarollo, L Kosofsky, BE Taylor, JR Bothwell, M Nestler, EJ Aghajanian, GK Jaenisch, R AF Akbarian, S Bates, B Liu, RJ Skirboll, SL Pejchal, T Coppola, V Sun, LD Fan, G Kucera, J Wilson, MA Tessarollo, L Kosofsky, BE Taylor, JR Bothwell, M Nestler, EJ Aghajanian, GK Jaenisch, R TI Neurotrophin-3 modulates noradrenergic neuron function and opiate withdrawal SO MOLECULAR PSYCHIATRY LA English DT Article DE locus coeruleus; morphine; addiction; norepinephrine; cre recombinase; pons; medulla ID MESSENGER-RNA EXPRESSION; LOCUS-COERULEUS; RAT-BRAIN; ANTEROGRADE TRANSPORT; TRANSGENIC MICE; NERVOUS-SYSTEM; PROTEIN-KINASE; NT-3; CERULEUS; TRKC AB Somatic symptoms and aversion of opiate withdrawal, regulated by noradrenergic signaling, were attenuated in mice with a CNS-wide conditional ablation of neurotrophin-3. This occurred in conjunction with altered cAMP-mediated excitation and reduced upregulation of tyrosine hydroxylase in A6 (locus coeruleus) without loss of neurons. Transgene-derived NT-3 expressed by noradrenergic neurons of conditional mutants restored opiate withdrawal symptoms. Endogenous NT-3 expression, strikingly absent in noradrenergic neurons of postnatal and adult brain, is present in afferent sources of the dorsal medulla and is upregulated after chronic morphine exposure in noradrenergic projection areas of the ventral forebrain. NT-3 expressed by noncatecholaminergic neurons may modulate opiate withdrawal and noradrenergic signalling. C1 Whitehead Inst, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA. NCI, Frederick, MD 21701 USA. MIT, Dept Biol, Cambridge, MA USA. Boston Univ, Dept Neurol, Boston, MA 02215 USA. RP Jaenisch, R (reprint author), Whitehead Inst, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Coppola, Vincenzo/E-2917-2011; OI Coppola, Vincenzo/0000-0001-6163-1779; Fan, Guoping/0000-0001-5235-6410 FU NCI NIH HHS [5-R35-CA44339]; NIDA NIH HHS [1-K08-DA00479] NR 50 TC 20 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD SEP PY 2001 VL 6 IS 5 BP 593 EP 604 DI 10.1038/sj.mp.4000897 PG 12 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 461CG UT WOS:000170346900014 PM 11526474 ER PT J AU Evidente, VGH Caviness, JN Adler, CH Gwinn-Hardy, KA Pratley, RE AF Evidente, VGH Caviness, JN Adler, CH Gwinn-Hardy, KA Pratley, RE TI Serum leptin concentrations and satiety in Parkinson's disease patients with and without weight loss SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; leptin; satiety; weight loss ID CEREBROSPINAL-FLUID; ANOREXIA-NERVOSA; PLASMA LEPTIN; DOPAMINE; OBESE AB We compared serum leptin and satiety measures in 18 Parkinson's disease (PD) patients with unintended weight loss (WL) and 18 PD patients whose weight was stable (WS). Mean serum leptin concentrations tended to be lower in WL than WS patients, but this did not reach statistical significance. Body mass index correlated with serum leptin concentrations. Ratings of hunger. satiety, fullness, and thirst did not differ between groups. However. the mean sensation of fullness before meals correlated with serum leptin in the entire cohort of patients, particularly in the WL group. ne results indicate that unintended weight loss in PD patients is unlikely to be due to abnormal serum leptin concentrations. (C) 2001 Movement Disorder Society. C1 Mayo Clin Scottsdale, Dept Neurol, Scottsdale, AZ 85259 USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Natl Inst Hlth, Phoenix, AZ USA. RP Caviness, JN (reprint author), Mayo Clin Scottsdale, Dept Neurol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. NR 15 TC 24 Z9 24 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD SEP PY 2001 VL 16 IS 5 BP 924 EP 927 DI 10.1002/mds.1165 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 484AA UT WOS:000171667000017 PM 11746624 ER PT J AU Schaaper, RM Dunn, RL AF Schaaper, RM Dunn, RL TI The antimutator phenotype of E-coli mud is only apparent and results from delayed appearance of mutants SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE antimutator; mud; purB; valine resistance ID ESCHERICHIA-COLI; DNA-REPLICATION; POLYMERASE; BACTERIOPHAGE-T4; MUTATIONS; FIDELITY; CLONING; K-12; GENE AB Antimutator strains are strains that have a lower mutation rate than the wild-type strain. We have reexamined the properties of one reported antimutator strain of Escherichia coli, termed mud [Mol. Gen. Genet. 153 (1977) 87]. This strain contains a temperature-sensitive mutation in the purB gene, leading to adenine -dependent growth at higher temperature. When grown at permissive or semi-permissive temperature in the absence of adenine it displays large reductions in the number of both spontaneous and mutagen-induced mutants (e.g. several hundred-fold for valine-resistant mutants). However. our studies show that strains containing the purB allele generate mutations at the same level as the wild-type strain, and that the apparent antimutator effect is the consequence of the delayed appearance of mutants on the selective plates. This delay likely results from the combined stress exerted by the adenine deficiency and the presence of the selective agent (i.e. valine). Published by Elsevier Science B.V. C1 NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 1 PY 2001 VL 480 SI SI BP 71 EP 75 DI 10.1016/S0027-5107(01)00170-1 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 467AK UT WOS:000170678200007 PM 11506800 ER PT J AU Bello-DeOcampo, D Kleinman, HK Webber, MM AF Bello-DeOcampo, D Kleinman, HK Webber, MM TI The role of alpha 6 beta 1 integrin and EGF in normal and malignant acinar morphogenesis of human prostatic epithelial cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE acinar morphogenesis; EGF; intergrins; prostate cancer; tumor progression ID EPIDERMAL GROWTH-FACTOR; BASEMENT-MEMBRANE; BREAST-CARCINOMA; ADULT; DIFFERENTIATION; EXPRESSION; INVASION; SURVIVAL; LINES AB Complex multiple interactions between cells and extracellular matrix occur during acinar morphogenesis involving integrin receptors and growth factors, Changes in these interactions occur during carcinogenesis as cells progress from a normal to a malignant, invasive phenotype. We have developed human prostatic epithelial cell lines of the same lineage, which represent multiple steps in carcinogenesis, similar to prostatic intraepithelial neoplasia and subsequent tumor progression. The non-tumorigenic, RWPE-1 and the tumorigenic WPE1-NB27 and WPE1-NB26 cell lines were used to examine their ability to undergo acinar morphogenesis in a 3-D cell culture model and its relationship to invasion, integrin expression and EGF presence. An inverse relationship between the degree of acinar formation and invasive ability was observed. The non-tumorigenic, non-invasive RWPE-1 and the low tumorigenic, low invasive, WPE1-NB27 cells show high and decreased acinar forming ability, respectively, while the more invasive WPE1-NB26 cells show a loss of acinar formation. While RWPE-1 acini show basal expression of alpha6 beta1 integrin, which correlates with their ability to polarize and form acini, WPE1-NB27 cells lack alpha6 but show basal, but weaker expression of beta1 integrin. beta1 WPE1-NB26 cells show loss alpha6 and abnormal, diffused beta1 integrin expression. A dose-dependent decrease in acinar formation was observed in RWPE-1 cells when cell proliferation was induced by EGF. Anti-functional antibody to EGF caused an increase in acinar formation in RWPE-1 cells. These results suggest that malignant cells lose the ability to undergo acinar morphogenesis and that the degree of this loss appears to be related to invasive ability, EGF levels and alterations in laminin-specific integrin expression. This model system mimics different steps in prostate carcinogenesis and has applications in the secondary and tertiary prevention of prostate cancer. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Michigan State Univ, Dept Zool & Med, E Lansing, MI 48824 USA. Natl Inst Dent & Craniofacial Res, Cell Biol Sect, NIH, Bethesda, MD USA. RP Webber, MM (reprint author), Michigan State Univ, Dept Zool & Med, S-350 Plant Biol Bldg, E Lansing, MI 48824 USA. NR 19 TC 25 Z9 25 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD SEP 1 PY 2001 VL 480 SI SI BP 209 EP 217 DI 10.1016/S0027-5107(01)00201-9 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 467AK UT WOS:000170678200022 PM 11506815 ER PT J AU Zhang, ZQ Wang, Y Vikis, HG Johnson, L Liu, GJ Li, J Anderson, MW Sills, RC Hong, HL Devereux, TR Jacks, T Guan, KL You, M AF Zhang, ZQ Wang, Y Vikis, HG Johnson, L Liu, GJ Li, J Anderson, MW Sills, RC Hong, HL Devereux, TR Jacks, T Guan, KL You, M TI Wildtype Kras2 can inhibit lung carcinogenesis in mice SO NATURE GENETICS LA English DT Article ID NEGATIVE RAS MUTANT; C-KI-RAS; GENE AMPLIFICATION; MALIGNANT TRANSFORMATION; PHEOCHROMOCYTOMA CELLS; TUMOR PROGRESSION; SARCOMA-VIRUSES; POINT MUTATION; N-RAS; MOUSE AB Although the ras genes have long been established as proto-oncogenes, the dominant role of activated ras in cell transformation has been questioned. Previous studies have shown frequent loss of the wildtype Kras2 allele in both mouse and human lung adenocarcinomas. To address the possible tumor suppressor role of wildtype Kras2 in lung tumorigenesis, we have carried out a lung tumor bioassay in heterozygous Kras2-deficient mice. Mice with a heterozygous Kras2 deficiency were highly susceptible to the chemical induction of lung tumors when compared to wildtype mice. Activating Kras2 mutations were detected in all chemically induced lung tumors obtained from both wildtype and heterozygous Kras2-deficient mice. Furthermore, wildtype Kras2 inhibited colony formation and tumor development by transformed NIH/3T3 cells and a mouse lung tumor cell line containing an activated Kras2 allele. Allelic loss of wildtype Kras2 was found in 67% to 100% of chemically induced mouse lung adenocarcinomas that harbor a mutant Kras2 allele. Finally, an inverse correlation between the level of wildtype Kras2 expression and extracellular signal-regulated kinase (ERK) activity was observed in these cells. These data strongly suggest that wildtype Kras2 has tumor suppressor activity and is frequently lost during lung tumor progression. C1 Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Sch Publ Hlth, Columbus, OH USA. Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA. MIT, Dept Biol, Cambridge, MA USA. MIT, Howard Hughes Med Inst, Cambridge, MA USA. Univ Cincinnati, Dept Environm Hlth, Cincinnati, OH USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Wang, Y (reprint author), Ohio State Univ, Ctr Comprehens Canc, Div Human Canc Genet, 420 W 12th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [R01CA58554, R01CA78797]; NIGMS NIH HHS [R01GM62694] NR 50 TC 188 Z9 189 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2001 VL 29 IS 1 BP 25 EP 33 DI 10.1038/ng721 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 468WN UT WOS:000170781300012 PM 11528387 ER PT J AU Parkinson, NJ Olsson, CL Hallows, JL McKee-Johnson, J Keogh, BP Noben-Trauth, K Kujawa, SG Tempel, BL AF Parkinson, NJ Olsson, CL Hallows, JL McKee-Johnson, J Keogh, BP Noben-Trauth, K Kujawa, SG Tempel, BL TI Mutant beta-spectrin 4 causes auditory and motor neuropathies in quivering mice SO NATURE GENETICS LA English DT Article ID CHANNEL; NEURONS; EXPRESSION AB The autosomal recessive mouse mutation quivering (qv), which arose spontaneously in 1953, produces progressive ataxia with hind limb paralysis, deafness and tremor(1). Six additional spontaneous alleles, qv(J), qv(2J), qv(3J), qv(4J) qv(ind) and qv(Ind2J), have been identified(2,3). Ear twitch responses (Preyer's reflex) to sound are absent in homozygous qv/qv mice, although cochlear morphology seems normal and cochlear potentials recorded at the round window are no different from those of control mice(4). However, responses from brainstem auditory nuclei show abnormal transmission of auditory information, indicating that, in contrast to the many known mutations causing deafness originating in the cochlea, deafness in qv is central in origin(4-6). Here we report that quivering mice carry loss-of-function mutations in the mouse beta -spectrin 4 gene (Spnb4) that cause alterations in ion channel localization in myelinated nerves; this provides a rationale for the auditory and motor neuropathies of these mice. C1 Univ Washington, Sch Med, Virginia Merrill Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Natl Inst Deafness & Other Commun Disorders, Neurogenet Sect, NIH, Rockville, MD USA. RP Tempel, BL (reprint author), Univ Washington, Sch Med, Virginia Merrill Bloedel Hearing Res Ctr, Seattle, WA 98195 USA. FU NIDCD NIH HHS [DC02739, DC00018, Z01DC00056-01, DC04661] NR 24 TC 75 Z9 76 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2001 VL 29 IS 1 BP 61 EP 65 DI 10.1038/ng710 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 468WN UT WOS:000170781300018 PM 11528393 ER PT J AU Seeliger, MW Grimm, C Stahlberg, F Friedburg, C Jaissle, G Zrenner, E Guo, H Reme, CE Humphries, P Hofmann, F Biel, M Fariss, RN Redmond, TM Wenzel, A AF Seeliger, MW Grimm, C Stahlberg, F Friedburg, C Jaissle, G Zrenner, E Guo, H Reme, CE Humphries, P Hofmann, F Biel, M Fariss, RN Redmond, TM Wenzel, A TI New views on RPE65 deficiency: the rod system is the source of vision in a mouse model of Leber congenital amaurosis SO NATURE GENETICS LA English DT Article ID RETINAL DYSTROPHY; CONE DYSTROPHY; ALPHA-SUBUNIT; MUTATIONS; PHOTORECEPTORS; CHANNEL; GENE; MICE AB Leber congenital amaurosis (LCA) is the most serious form of the autosomal recessive childhood-onset retinal dystrophies. Mutations in the gene encoding RPE65, a protein vital for regeneration of the visual pigment rhodopsin in the retinal pigment epithelium(1), account for 10-15% of LCA cases(2,3). Whereas previous studies of RPE65 deficiency in both animal models(1,4) and patients(5,6) attributed remaining visual function to cones, we show here that light-evoked retinal responses in fact originate from rods. For this purpose, we selectively impaired either rod or cone function in Rpe65(-/-) mice by generating double-mutant mice with models of pure cone function(7) (rhodopsin-deficient mice; Rho(-/-)) and pure rod function, (cyclic nucleotide-gated channel alpha3-deficient mice; Cnga3(-/-)). The electroretinograms (ERGs) of Rpe65(-/-) and Rpe65(-/-)Cnga3(-/-) mice were almost identical, whereas there was no assessable response in Rpe65(-/-)Rho(-/-) mice. Thus, we conclude that the rod system is the source of vision in RPE65 deficiency. Furthermore, we found that lack of RPE65 enables rods to mimic cone function by responding under normally cone-isolating lighting conditions. We propose as a mechanism decreased rod sensitivity due to a reduction in rhodopsin content to less than 1%. In general, the dissection of pathophysiological processes in animal models through the introduction of additional, selective mutations is a promising concept in functional genetics. C1 Univ Tubingen, Dept Ophthalmol, Retinal Electrodiagnost Res Grp, D-72074 Tubingen, Germany. Univ Zurich Hosp, Lab Retinal Cell Biol, CH-8091 Zurich, Switzerland. Swedish Univ Agr Sci, Fac Vet Med, Dept Med & Surg, S-75007 Uppsala, Sweden. Univ Dublin Trinity Coll, Dept Genet, Dublin 2, Ireland. Tech Univ Munich, Inst Pharmakol & Toxikol, D-8000 Munich, Germany. Univ Munich, Zentrum Pharmaforsch, Dept Pharm, D-80539 Munich, Germany. NEI, Lab Mechanisms Ocular Dis, Bethesda, MD 20892 USA. NEI, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. RP Seeliger, MW (reprint author), Univ Tubingen, Dept Ophthalmol, Retinal Electrodiagnost Res Grp, D-72074 Tubingen, Germany. RI Biel, Martin/G-1175-2014; OI Biel, Martin/0000-0002-9974-3052; Redmond, T. Michael/0000-0002-1813-5291 NR 26 TC 186 Z9 187 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD SEP PY 2001 VL 29 IS 1 BP 70 EP 74 DI 10.1038/ng712 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 468WN UT WOS:000170781300020 PM 11528395 ER PT J AU Martin, R Sturzebecher, CS McFarland, HF AF Martin, R Sturzebecher, CS McFarland, HF TI Immunotherapy of multiple sclerosis: Where are we? Where should we go? SO NATURE IMMUNOLOGY LA English DT Editorial Material ID ALTERED PEPTIDE LIGAND; AUTOIMMUNE ENCEPHALOMYELITIS; TRIAL; INDUCTION; DISEASES; LESIONS AB Differences in multiple sclerosis patient's disease and their responses to standard drugs indicate that today's therapies need to be more individualized. It is proposed that gene expression profiling in conjunction with magnetic resonance imaging be used to optimize future treatment approaches. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Schering AG, Clin Dev CNS, D-13342 Berlin, Germany. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr DR MSC 1400, Bethesda, MD 20892 USA. NR 23 TC 58 Z9 59 U1 0 U2 3 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD SEP PY 2001 VL 2 IS 9 BP 785 EP 788 DI 10.1038/ni0901-785 PG 4 WC Immunology SC Immunology GA 468WM UT WOS:000170781200011 PM 11526386 ER PT J AU Li, MX Jia, M Jiang, H Dunlap, V Nelson, PG AF Li, MX Jia, M Jiang, H Dunlap, V Nelson, PG TI Opposing actions of protein kinase A and C mediate Hebbian synaptic plasticity SO NATURE NEUROSCIENCE LA English DT Article ID NEUROMUSCULAR-JUNCTION; ACETYLCHOLINE-RECEPTOR; IN-VITRO; PHOSPHORYLATION; SITES C1 NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Henry Ford Hlth Sci Ctr, William T Gossett Neurol Labs, Detroit, MI 48202 USA. RP Nelson, PG (reprint author), NICHHD, Dev Neurobiol Lab, NIH, Bldg 49,Room 5A38, Bethesda, MD 20892 USA. NR 12 TC 20 Z9 20 U1 1 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD SEP PY 2001 VL 4 IS 9 BP 871 EP 872 DI 10.1038/nn0901-871 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 467JL UT WOS:000170698600010 PM 11528415 ER PT J AU Schnermann, J AF Schnermann, J TI Cyclooxygenase-2 and macula densa control of renin secretion SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Editorial Material DE angiotensin II; cyclooxygenase-2 ID DIETARY SALT INTAKE; ANGIOTENSIN-II; STIMULATED RENIN; RENAL-CORTEX; RENOVASCULAR HYPERTENSION; PROSTAGLANDIN SYNTHESIS; DIFFERENTIAL REGULATION; ARACHIDONIC-ACID; MESANGIAL CELLS; RAT-KIDNEY C1 NIDDK, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), NIDDK, NIH, Bldg 10,Room 4 D51,10 Ctr Dr MSC 1370, Bethesda, MD 20892 USA. NR 36 TC 22 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD SEP PY 2001 VL 16 IS 9 BP 1735 EP 1738 DI 10.1093/ndt/16.9.1735 PG 4 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 469NR UT WOS:000170822200001 PM 11522847 ER PT J AU Moffat, SD Zonderman, AB Resnick, SM AF Moffat, SD Zonderman, AB Resnick, SM TI Age differences in spatial memory in a virtual environment navigation task SO NEUROBIOLOGY OF AGING LA English DT Article DE navigation; hippocampus; age; spatial memory; route learning; virtual reality; maze; human ID HEAD-DIRECTION CELLS; HIPPOCAMPAL-FORMATION; PRIMATE HIPPOCAMPUS; ALZHEIMERS-DISEASE; COGNITIVE MAPS; PLACE CELLS; VIEW CELLS; MAZE; REAL; RATS AB The use of virtual environment (VE) technology to assess spatial navigation in humans has become increasingly common and provides an opportunity to quantify age-related deficits in human spatial navigation and promote a comparative approach to the neuroscience of cognitive aging. The purpose of the present study was to assess age differences in navigational behavior in a VE and to examine the relationship between this navigational measure and other more traditional measures of cognitive aging. Following pre-training, participants were confronted with a VE spatial learning task and completed a battery of cognitive tests. The VE consisted of a richly textured series of interconnected hallways, some leading to dead ends and others leading to a designated goal location in the environment. Compared to younger participants, older volunteers took longer to solve each trial, traversed a longer distance, and made significantly more spatial memory errors. After 5 learning trials, 86% of young and 24% of elderly volunteers were able to locate the goal without error. Performance on the VE navigation task was positively correlated with measures of mental rotation and verbal and visual memory. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Moffat, SD (reprint author), NIA, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Zonderman, Alan B/0000-0002-6523-4778 NR 63 TC 134 Z9 139 U1 6 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD SEP-OCT PY 2001 VL 22 IS 5 BP 787 EP 796 DI 10.1016/S0197-4580(01)00251-2 PG 10 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 492GU UT WOS:000172160700013 PM 11705638 ER PT J AU Kunos, G Batkai, S AF Kunos, G Batkai, S TI Novel physiologic functions of endocannabinoids as revealed through the use of mutant mice SO NEUROCHEMICAL RESEARCH LA English DT Article DE anandamide; 2-arachidonoyl glycerol; cannabinoid receptors ID RECEPTOR KNOCKOUT MICE; CANNABINOID CB1 RECEPTORS; FOOD-INTAKE; RAT-BRAIN; MOLECULAR CHARACTERIZATION; MESENTERIC VASODILATION; SELECTIVE ANTAGONIST; ENZYMATIC-SYNTHESIS; SR 141716A; ANANDAMIDE AB The presence in the mammalian brain of specific receptors for marijuana triggered a search for endogenous ligands, several of which have been recently identified. There has been growing interest in the possible physiological functions of endocannabinoids, and mutant mice that lack cannabinoid receptors have become an important tool in the search for such functions. To date, studies using CB1 knockout mice have supported the possible role of endocannabinoids in retrograde synaptic inhibition in the hippocampus, in long-term potentiation and memory, in the development of opiate dependence, and in the control of appetite and food intake. They also suggested the existence of as yet unidentified cannabinoid receptors in the cardiovascular and central nervous systems. The use of CB2 receptor knockout mice suggested a role for this receptor in macrophage-mediated helper T cell activation. Further studies will undoubtedly reveal many additional roles for this novel signaling system. C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Kunos, G (reprint author), NIAAA, NIH, 12420 Parklawn Dr,Rm 120,MSC-8115, Bethesda, MD 20892 USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 NR 66 TC 22 Z9 24 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD SEP PY 2001 VL 26 IS 8-9 BP 1015 EP 1021 DI 10.1023/A:1012301021419 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 487JK UT WOS:000171871800018 PM 11699929 ER PT J AU Chung, MK Worsley, KJ Paus, T Cherif, C Collins, DL Giedd, JN Rapoport, JL Evanst, AC AF Chung, MK Worsley, KJ Paus, T Cherif, C Collins, DL Giedd, JN Rapoport, JL Evanst, AC TI A unified statistical approach to deformation-based morphometry SO NEUROIMAGE LA English DT Article DE volume change; volumetry; brain growth; morphometry; atrophy; deformation; brain development ID HUMAN BRAIN-DEVELOPMENT; CORPUS-CALLOSUM; SEGMENTATION; ADOLESCENCE; ADULTHOOD; FIELDS; GROWTH; MRI AB We present a unified statistical framework for analyzing temporally varying brain morphology using the 3D displacement vector field from a nonlinear deformation required to register a subject's brain to an atlas brain. The unification comes from a single model for structural change, rather than two separate models, one for displacement and one for volume changes. The displacement velocity field rather than the displacement itself is used to set up a linear model to account for temporal variations. By introducing the rate of the Jacobian change of the deformation, the local volume change at each voxel can be computed and used to measure possible brain tissue growth or loss. We have applied this method to detecting regions of a morphological change in a group of children and adolescents. Using structural magnetic resonance images for 28 children and adolescents taken at different time intervals, we demonstrate how this method works. (C) 2001 Academic Press. C1 McGill Univ, Dept Math & Stat, Montreal, PQ, Canada. McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada. Ecole Polytech Fed Lausanne, Dept Math, Lausanne, Switzerland. NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. RP Chung, MK (reprint author), McGill Univ, Dept Math & Stat, Montreal, PQ, Canada. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 39 TC 213 Z9 213 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2001 VL 14 IS 3 BP 595 EP 606 DI 10.1006/nimg.2001.0862 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 467UT UT WOS:000170722700006 PM 11506533 ER PT J AU Immisch, I Waldvogel, D van Gelderen, P Hallett, M AF Immisch, I Waldvogel, D van Gelderen, P Hallett, M TI The role of the medial wall and its anatomical variations for bimanual antiphase and in-phase movements SO NEUROIMAGE LA English DT Article DE bimanual coordination; medial wall motor areas; supplementary motor area; cingulate motor area; paracingulate sulcus; functional MRI ID SUPPLEMENTARY MOTOR AREA; HUMAN-BRAIN; HUMAN CINGULATE; MONKEYS; CORTEX; COORDINATION; PARACINGULATE; SULCI; PERFORMANCE; ACTIVATION AB The medial wall of the frontal cortex is thought to play an important role for bimanual coordination. However, there is uncertainty regarding the exact neuroanatomical regions involved. We compared the activation patterns related to bimanual movements using functional magnetic resonance imaging in 12 healthy right-handed subjects, paying special attention to the anatomical variability of the frontal medial wall. The subjects performed unimanual right and left and bimanual antiphase and in-phase flexion and extension movements of the index finger. Activation of the right supplementary motor area (SMA) proper, right and left caudal cingulate motor area (CMA), and right and left premotor cortices was significantly stronger during bimanual antiphase than bimanual in-phase movements, indicating an important function of these areas with bimanual coordination. A frequent anatomical variation is the presence of the paracingulate sulcus (PCS), which might be an anatomical landmark to determine the location of activated areas. Seven subjects had a bilateral, three a unilateral right, and two a unilateral left PCS. Because the area around the PCS is functionally closer coupled to the CMA than to the SMA, activation found in the area around the PCS should be attributed to the CMA. With anatomical variations such as the presence of a PCS or a vertical branch of the cingulate sulcus, normalization and determination of the activation with the help of stereotaxic coordinates can cause an incorrect shift of CMA activation to the SMA. This might explain some of the discrepancies found in previous studies. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, In Vivo NMR Res Ctr, NIH, Bethesda, MD 20892 USA. RP Immisch, I (reprint author), NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NR 39 TC 75 Z9 75 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD SEP PY 2001 VL 14 IS 3 BP 674 EP 684 DI 10.1006/nimg.2001.0856 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 467UT UT WOS:000170722700013 PM 11506540 ER PT J AU Fukui, S Nawshiro, H Wada, K Shima, K Hallenbeck, JM AF Fukui, S Nawshiro, H Wada, K Shima, K Hallenbeck, JM TI A new method to catheterize a femoral artery in mice using a nylon suture as a 'guide wire' SO NEUROLOGICAL RESEARCH LA English DT Article DE catheterization; femoral artery; mice AB Mice are commonly used in laboratory experiments. Their femoral arteries are so tiny that catheterization is quite difficult. We describe a new method to catheterize the femoral artery in mice. The key feature of this new method is the use of a nylon suture as a 'guide wire'. The full catheterization system consists of two sizes of polyethylene tubes (PE-10, PE-50) and a 4-0 nylon suture. We have been able to repeatedly catheterize mouse femoral arteries (n = 57) successfully and easily with this new system. We believe that this new method can facilitate vascular catheterization in small animals such as mice. C1 Natl Def Med Coll, Dept Neurosurg, Tokorozawa, Saitama 3598513, Japan. NINDS, Stroke Branch, Bethesda, MD 20892 USA. RP Nawshiro, H (reprint author), Natl Def Med Coll, Dept Neurosurg, 3-2 Namiki, Tokorozawa, Saitama 3598513, Japan. NR 3 TC 1 Z9 1 U1 0 U2 1 PU FOREFRONT PUBL GROUP PI WILTON PA C/O MARY J RAWLINS, 5 RIVER RD, STE 113, WILTON, CT 06897 USA SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD SEP PY 2001 VL 23 IS 6 BP 655 EP 656 DI 10.1179/016164101101198974 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 466KM UT WOS:000170644800017 PM 11547938 ER PT J AU Sambuughin, N Nelson, TE Jankovic, J Xin, CL Meissner, G Mullakandov, M Ji, J Rosenberg, H Sivakumar, K Goldfarb, LG AF Sambuughin, N Nelson, TE Jankovic, J Xin, CL Meissner, G Mullakandov, M Ji, J Rosenberg, H Sivakumar, K Goldfarb, LG TI Identification and functional characterization of a novel ryanodine receptor mutation causing malignant hyperthermia in North American and South American families SO NEUROMUSCULAR DISORDERS LA English DT Article DE malignant hyperthermia; North American family; South American family; novel ryanodine receptor mutation; functional analysis of disease-causing; mutation ID CA2+ RELEASE CHANNEL; VITRO CONTRACTURE-TEST; DEPENDENT CALCIUM-CHANNEL; CENTRAL CORE DISEASE; SKELETAL-MUSCLE; SUSCEPTIBILITY LOCUS; RYR1 GENE; CHROMOSOME 19Q12-13.2; HALOTHANE; CAFFEINE AB Malignant hyperthermia is a pharmacogenetic disorder associated with mutations in Ca2+ regulatory proteins. It manifests as a hypermetabolic crisis triggered by commonly used anesthetics. Malignant hyperthermia susceptibility is a dominantly inherited predisposition to malignant hyperthermia that can be diagnosed by using caffeine/halothane contracture tests. In a multigenerational North American family with a severe form of malignant hyperthermia that has caused four deaths, a novel RYR1 A2350T missense mutation was identified in all individuals testing positive for malignant hyperthermia susceptibility. The same A2350T mutation was identified in an Argentinean family with two known fatal MH reactions. Functional analysis in HEK-293 cells revealed an altered Ca2+ dependence and increased caffeine sensitivity of the expressed mutant protein thus confirming the pathogenic potential of the RYR1 A2350T mutation. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NINCDS, NIH, Bethesda, MD 20892 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. Wake Forest Univ, Winston Salem, NC 27157 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA. BBI Biotech Res Labs, Gaithersburg, MD 20877 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. RP Goldfarb, LG (reprint author), NINCDS, NIH, Bldg 10,Room 4B37,10 Ctr Dr,MSC 1361, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR18687] NR 44 TC 33 Z9 35 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD SEP PY 2001 VL 11 IS 6-7 BP 530 EP 537 DI 10.1016/S0960-8966(01)00202-4 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 469NQ UT WOS:000170822100003 PM 11525881 ER PT J AU Zapata, A Witkin, JM Shippenberg, TS AF Zapata, A Witkin, JM Shippenberg, TS TI Selective D3 receptor agonist effects of (+)-PD 128907 on dialysate dopamine at low doses SO NEUROPHARMACOLOGY LA English DT Article DE D3 receptor; knock out mice; (+)-PD 128907; dopamine; no net flux microdialysis; ventral striatum ID WILD-TYPE MICE; D-3 RECEPTORS; IN-VIVO; D2 RECEPTORS; MUTANT MICE; LOCOMOTOR-ACTIVITY; DEFICIENT MICE; RAT-BRAIN; RELEASE; AUTORECEPTORS AB An involvement of the D3 dopamine receptor in the modulation of extracellular dopamine concentrations is suggested by pharmacological studies. However, recent studies using D3 receptor knock out mice indicated that several functions previously attributed to the D3 receptor are mediated by other receptor types. In the present study, we used the no-net flux microdialysis technique to characterize: (i) basal dopamine dynamics in the ventral striatum of D3 knock out and wild type mice and (ii) the effects of the putative D3-receptor selective agonist (+)-PD 128907. Neither the extracellular dopamine concentration nor the in vivo extraction fraction, an indirect measure of basal dopamine uptake, differed between D3 knock out and wild type mice. Moreover, no differences in potassium (60 mM) or cocaine (5 or 20 mg/kg i.p.) evoked dopamine concentrations were detected between the two genotypes. However, intra-striatal or systemic administration of doses of (+)-PD 128907 that failed to modify dopamine concentrations in knock out mice significantly decreased dialysate dopamine concentrations in the wild type. Comparison of the concentration-response curve for (+)-PD 128907 revealed IC25 values of 61 and 1327 nM in wild type and knock out mice, respectively, after intra-striatal infusions. Similar differences were obtained after systemic administration of the D3 preferring agonist (IC25 0.05 and 0.44 mg/kg i.p. in wild type and knock out mice, respectively). We conclude that the activation of the D3 receptor decreases extracellular dopamine levels and that, at sufficiently low doses, the effects of (+)-PD 128907 on extracellular dopamine are selectively mediated by the D3 receptor. Published by Elsevier Science Ltd. C1 NIDA, Integrat Neurosci Unit, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. RP Zapata, A (reprint author), NIDA, Integrat Neurosci Unit, Behav Neurosci Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 36 TC 55 Z9 55 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD SEP PY 2001 VL 41 IS 3 BP 351 EP 359 DI 10.1016/S0028-3908(01)00069-7 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 470RW UT WOS:000170885800008 PM 11522326 ER PT J AU Sokoloff, L AF Sokoloff, L TI Memorial for Seymour S. Kety - Introduction SO NEUROPSYCHOPHARMACOLOGY LA English DT Biographical-Item C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. RP Sokoloff, L (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Room 1A-07, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2001 VL 25 IS 3 BP 291 EP 293 DI 10.1016/S0893-133X(01)00274-3 PG 3 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 467JK UT WOS:000170698500001 ER PT J AU Ernst, M Heishman, SJ Spurgeon, L London, ED AF Ernst, M Heishman, SJ Spurgeon, L London, ED TI Smoking history and nicotine effects on cognitive performance SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE attention; working memory; nicotine withdrawal; abstinence; nicotine gum ID CIGARETTE-SMOKING; WITHDRAWAL SYNDROME; SMOKERS; SCALE; NONSMOKERS; TOLERANCE; INSTITUTE; MEMORY; 12-H; GUM AB This study examined the effects of abstinence from smoking, of smoking history, and of nicotine administration on visual attention (2-Letter Search Task), verbal information processing (Logical Reasoning Task), and working memory (N-Back Tasks). Fourteen smokers, 15 ex-smokers, and 9 never-smokers took part. All subjects participated in a training session (when smokers had been smoking ad libitum) and in two subsequent test sessions after administration of 4 mg nicotine gum or placebo, respectively. Smokers were 12-h abstinent when they received gum. An effect of acute nicotine administration (independent of smoking history) was seen only with respect to reaction time on the 2-Letter Search Task. Working memory performance was related to smoking history (smokers performed most poorly and never-smokers best). The Logical Reasoning Task showed no effects of either acute or chronic nicotine exposure. The findings indicate that nicotine may influence focusing of attention in smokers as well as nonsmokers, and that trait-like differences in some cognitive domains, such as working memory, may be either long-term effects or etiological factors related to smoking. (C) 2001 American College of Neuropsychopharmacology. Published by Elseiver Science Inc. All rights reserved. C1 NIDA, Brain Imaging Ctr, Baltimore, MD USA. NIDA, Clin Pharmacol & Therapeut Branch, Baltimore, MD USA. Univ Calif Los Angeles, Inst Neuropsychiat, NPI, Los Angeles, CA USA. RP Ernst, M (reprint author), NIMH, 1-B3-10,1 Ctr Dr,MSC 0135, Bethesda, MD 20892 USA. NR 35 TC 139 Z9 145 U1 5 U2 13 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2001 VL 25 IS 3 BP 313 EP 319 DI 10.1016/S0893-133X(01)00257-3 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 467JK UT WOS:000170698500005 PM 11522460 ER PT J AU Highfield, D Yap, J Grimm, JW Shalev, U Shaham, Y AF Highfield, D Yap, J Grimm, JW Shalev, U Shaham, Y TI Repeated lofexidine treatment attenuates stress-induced, but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE alpha-2 adrenoceptor agonists; cocaine; drug self-administration; extinction; heroin; reinstatement; relapse; stress ID EXTRACELLULAR DOPAMINE LEVELS; SELF-ADMINISTRATION BEHAVIOR; NUCLEUS-ACCUMBENS; NORADRENERGIC NEURONS; ADMINISTERED COCAINE; INTRAVENOUS COCAINE; CONDITIONED CHANGES; INDUCED RELAPSE; RHESUS-MONKEYS; ANIMAL-MODEL AB Alpha-2 adrenoceptor agonists (lofexidine, clonidine) are used to alleviate short-term opioid withdrawal in humans. In rats, acute injections of these agents attenuate stress-induced reinstatement of heroin and cocaine seeking at time points that are beyond the acute drug withdrawal phase. Here, we studied whether exposure to lofexidine would attenuate reinstatement of a heroin-cocaine mixture (speedball) seeking induced by exposure to stress or to drug-associated cues. Rats were trained to lever press for speedball for 10 days, and the drug-reinforced behavior was then extinguished for 11 days in the presence (Experiment 1) or the absence (Experiment 2) of the drug cues. Subsequently, rats were tested for reinstatement of drug seeking after exposure to intermittent footshock stress (5-15 min; Experiment 1) or the drug cues (Experiment 2). Starting on day 7 of training, rats received daily injections of saline or lofexidine (0.1 or 0.2 mg/kg). Repeated lofexidine treatment significantly attenuated footshock-induced reinstatement, but did not alter drug cues-induced reinstatement of speedball seeking. fit addition, lofexidine did not have a consistent effect on speedball self-administration and extinction behavior. Results extend previous reports with acute drug injections, indicating that lofexidine maintains its effect on stress-induced reinstatement after repeated treatment. The present data also suggest that the neurochemical events underlying stress- and drug cues-induced relapse are not identical. (C) 2001 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 NIDA, Behav Neurosci Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI shaham, yavin/G-1306-2014 NR 66 TC 51 Z9 55 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD SEP PY 2001 VL 25 IS 3 BP 320 EP 331 DI 10.1016/S0893-133X(01)00227-5 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 467JK UT WOS:000170698500006 PM 11522461 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 Remote optical fiber dosimetry SO NUCLEAR INSTRUMENTS & METHODS IN PHYSICS RESEARCH SECTION B-BEAM INTERACTIONS WITH MATERIALS AND ATOMS LA English DT Article; Proceedings Paper CT Summer School on Advanced Topics in Radiation Dosimetry CY JUL 03-07, 2001 CL ATHENS, GREECE SP St Gobain Crystals & Detectors ID DOPED FUSED QUARTZ; RADIATION; ABSORPTION; SILICA; GLASS; THERMOLUMINESCENCE; BANDS; GAMMA AB Optical fibers offer a unique capability for remote monitoring of radiation in difficult-to-access and/or hazardous locations. Optical fiber sensors can be located in radiation hazardous areas and optically interrogated from a safe distance. A variety of remote optical fiber radiation dosimetry methods have been developed. All of the methods take advantage of some form of radiation-induced change in the optical properties of materials such as: radiation-induced darkening due to defect formation in glasses, luminescence from native defects or radiation-induced defects, or population of metastable charge trapping centers. Optical attenuation techniques are used to measure radiation-induced darkening in fibers. Luminescence techniques include the direct measurement of scintillation or optical excitation of radiation-induced luminescent defects. Optical fiber radiation dosimeters have also been constructed using charge trapping materials that exhibit thermoluminescence or optically stimulated luminescence (OSL). (C) 2001 Published by Elsevier Science B.V. C1 USN, Res Lab, Div Opt Sci, Washington, DC 20375 USA. NCI, DCT, Radiat Oncol Branch, Radiat Oncol Sci Program,NIH, Bethesda, MD 20892 USA. RP Huston, AL (reprint author), USN, Res Lab, Div Opt Sci, Bldg A50,Code 5611,4555 Overlook Ave SW, Washington, DC 20375 USA. NR 34 TC 76 Z9 78 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-583X J9 NUCL INSTRUM METH B JI Nucl. Instrum. Methods Phys. Res. Sect. B-Beam Interact. Mater. Atoms PD SEP PY 2001 VL 184 IS 1-2 BP 55 EP 67 DI 10.1016/S0168-583X(01)00713-3 PG 13 WC Instruments & Instrumentation; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical; Physics, Nuclear SC Instruments & Instrumentation; Nuclear Science & Technology; Physics GA 478HN UT WOS:000171341100004 ER PT J AU Feng, NP Elberg, J Adler-Wailes, D Yanovski, JA AF Feng, NP Elberg, J Adler-Wailes, D Yanovski, JA TI Associations between polymorphisms of proopiomelanocortin gene and body composition in lean and obese children SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIH, Unit Growth & Obes, DEB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 53S EP 53S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300002 ER PT J AU Del Parigi, A Chen, K Salbe, AD Hill, J Wing, R Reiman, EM Tataranni, PA AF Del Parigi, A Chen, K Salbe, AD Hill, J Wing, R Reiman, EM Tataranni, PA TI Differences in the brain response to satiation in lean, obese and post-obese individuals SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIH, NIDDK, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 56S EP 56S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300016 ER PT J AU McDuffie, JR Christiansen, JD Riggs, P Sebring, N Rolls, BJ Yanovski, JA AF McDuffie, JR Christiansen, JD Riggs, P Sebring, N Rolls, BJ Yanovski, JA TI Effects of a low-fat diet and orlistat on the fat ratings or overweight adolescents SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIH, UGO, Bethesda, MD 20892 USA. RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 NR 0 TC 2 Z9 2 U1 1 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 69S EP 69S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300069 ER PT J AU McDuffie, JR Calis, K Booth, S Uwaifo, GI Yanovski, JA AF McDuffie, JR Calis, K Booth, S Uwaifo, GI Yanovski, JA TI Effect of orlistat on fat-soluble vitamins in obese adolescents SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Tufts Univ, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. NIH, Unit Growth & Obes, Bethesda, MD 20892 USA. NIH, Drug Informat Serv, Bethesda, MD 20892 USA. RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 NR 0 TC 2 Z9 2 U1 1 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 69S EP 69S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300067 ER PT J AU Rotimi, C Chen, G Kittles, R Parish-Gause, D Vosganian, G Furbert-Harris, P Amoah, A Acheampong, J Oli, J Osotimehin, B Johnson, T Dunston, G Collins, F AF Rotimi, C Chen, G Kittles, R Parish-Gause, D Vosganian, G Furbert-Harris, P Amoah, A Acheampong, J Oli, J Osotimehin, B Johnson, T Dunston, G Collins, F TI Evidence of linkage for BMI and fat mass on Chromosome 20 in West African affected sib-pairs with type 2 diabetes. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Howard Univ, Natl Human Genome Ctr, Washington, DC USA. Univ Ghana, Legon, Ghana. Univ Sci & Technol, Kumasi, Ghana. Univ Nigeria, Teaching Hosp, Nsukka, Nigeria. Univ Coll Hosp, Nsukka, Nigeria. Univ Lagos, Lagos, Nigeria. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 70S EP 70S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300073 ER PT J AU Stefan, N Vozarova, B Ravussin, E Tataranni, PA AF Stefan, N Vozarova, B Ravussin, E Tataranni, PA TI The Gln223Arg polymorphism of the leptin receptor is associated with higher subcutaneous abdominal adipose size and lower energy expenditure in Pima Indians SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 72S EP 72S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300079 ER PT J AU Salbe, AD Weyer, C Lindsay, RL Ravussin, E Tataranni, PA AF Salbe, AD Weyer, C Lindsay, RL Ravussin, E Tataranni, PA TI Physical activity energy expenditure and obesity in Pima Indian children: A 5-y prospective study. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIH, NIDDK, CDNS, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 78S EP 78S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300103 ER PT J AU Stefan, N Vozarova, B Weyer, C Funahashi, T Ravussin, E Tataranni, PA AF Stefan, N Vozarova, B Weyer, C Funahashi, T Ravussin, E Tataranni, PA TI Insure adiponectin levels are not associated with fat oxidation in humans SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, NIH, Phoenix, AZ USA. Amylin Pharmaceut Inc, San Diego, CA USA. Osaka Univ, Suita, Osaka, Japan. Pennington Biomed Res Ctr, Baton Rouge, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 81S EP 81S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300115 ER PT J AU Uwaifo, GI Nguyen, TT Russell, DL Nicholson, JC Keil, MF Goldhar, L Bonat, SH McDuffie, JR Yanovski, JA AF Uwaifo, GI Nguyen, TT Russell, DL Nicholson, JC Keil, MF Goldhar, L Bonat, SH McDuffie, JR Yanovski, JA TI Determinants of differences in insulin sensitivity, secretion and clearance of African American and Caucasian children SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIH, NICHD, DEB, Unit Growth & Obes, Bethesda, MD 20892 USA. RI Uwaifo, Gabriel/M-2361-2016 OI Uwaifo, Gabriel/0000-0002-6962-9304 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 84S EP 84S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300127 ER PT J AU Tanofsky-Kraff, M Yanovski, SZ Nguyen, TT McDuffie, J Wilfley, DE Yanovski, JA AF Tanofsky-Kraff, M Yanovski, SZ Nguyen, TT McDuffie, J Wilfley, DE Yanovski, JA TI Binge size and loss of control in children. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NICHHD, UGO, DEB, Bethesda, MD USA. NIDDK, DDDN, NIH, Bethesda, MD 20892 USA. San Diego State Univ, UCSD, Clin Psychol Program, San Diego, CA USA. Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 92S EP 92S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300161 ER PT J AU Visser, M Goodpaster, BH Kritchevsky, SB Newman, AB Nevitt, M Stamm, E Harris, TB AF Visser, M Goodpaster, BH Kritchevsky, SB Newman, AB Nevitt, M Stamm, E Harris, TB TI Total body fat and intramuscular fat in relation to mobility in older persons. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Vrije Univ Amsterdam, Amsterdam, Netherlands. Natl Inst Aging, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 94S EP 94S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300168 ER PT J AU Harris, T Visser, M Goodpaster, B Kritchevsky, S Newman, A Simonsick, E Pahor, M Nevitt, M Cummings, S Hubbard, V Everhart, J AF Harris, T Visser, M Goodpaster, B Kritchevsky, S Newman, A Simonsick, E Pahor, M Nevitt, M Cummings, S Hubbard, V Everhart, J TI Muscle fat: A new fat depot. Correlates in the health, aging and body composition study (Health ABC) SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIA, Lab Epidemiol Demography & Biometry, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 98S EP 98S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300185 ER PT J AU Madarnas, Y Fine, S Sawka, C Shepherd, L Tannock, T Tu, D Levine, M AF Madarnas, Y Fine, S Sawka, C Shepherd, L Tannock, T Tu, D Levine, M CA Natl Canc Inst Canada Clin Trials TI Body size, received dose-intensity and myelotoxicity of adjuvant chemotherapy in relation to outcome of premenopausal women with N-1 breast cancer: results from a National Cancer Institute of Canada randomized controlled trial. SO OBESITY RESEARCH LA English DT Meeting Abstract C1 Queens Univ, NCI, Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 151S EP 151S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300390 ER PT J AU Vozarova, B Metz, C Stefan, N Bucala, R Tataranni, PA AF Vozarova, B Metz, C Stefan, N Bucala, R Tataranni, PA TI Plasma concentrations of macrophage migration inhibitors factor (MIF) are associated with insulin resistance and are elevated in Pima Indians compared to Caucasians SO OBESITY RESEARCH LA English DT Meeting Abstract C1 NIDDK, CDNS, NIH, Phoenix, AZ USA. Pickower Inst, Manhasset, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI ROCHESTER PA C/O DR MICHAEL JENSEN, MAYO MEDICAL CENTER, MAYO CLIN 200 FIRST ST, SW, ROCHESTER, MN 55905 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD SEP PY 2001 VL 9 SU 3 BP 157S EP 157S PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 473YF UT WOS:000171076300414 ER PT J AU Engel, LS Checkoway, H Keifer, MC Seixas, NS Longstreth, WT Scott, KC Hudnell, K Anger, WK Camicioli, R AF Engel, LS Checkoway, H Keifer, MC Seixas, NS Longstreth, WT Scott, KC Hudnell, K Anger, WK Camicioli, R TI Parkinsonism and occupational exposure to pesticides SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE farmer; parkinsonism; pesticides ID ENVIRONMENTAL RISK-FACTORS; YOUNG-ONSET; DISEASE; PREVALENCE; SIGNS; EPIDEMIOLOGY; INTOXICATION; POPULATION; REGION; ISRAEL AB Objective-To examine the risk of parkinsonism related to lifetime occupational exposure to pesticides among a cohort of men, mostly orchardists, in Washington State. Methods-All 310 subjects in this study had previously participated in a cohort study of men occupationally exposed to pesticides. Subjects were given a structured neurological examination and completed a self administered questionnaire which elicited detailed information on pesticide (insecticide, herbicide, and fungicide) use throughout their working careers. Demographic characteristics were also sought. Subjects had a mean age of 69.6 years (range 49-96, SD 8.1). There were 238 (76.8%) subjects who reported some occupational exposure to pesticides, whereas 72 (23.2%) reported none. Parkinsonism was defined by the presence of two or more of rest tremor, rigidity, bradykinesia, and impairment of postural reflexes in subjects not on antiparkinsonian medication, or the presence of at least one sign if they were on such medication. Parkinson's disease was not studied explicitly because of the difficulty in distinguishing it from other parkinsonian syndromes. A generalised linear model was used to estimate prevalence ratios (PRs) for parkinsonism relative to history of farming, pesticide use, and use of well water. Results-A PR of 2.0 (95% confidence interval (95% CI) 1.0 to 4.2) was found for subjects in the highest tertile of years of exposure to pesticides; a similarly increased, non-significant, PR was found for the middle tertile (1.9 (95% CI 0.9 to 4.0)), although a trend test did not show a significant exposure-response relation. No increased risks were found associated with specific pesticides or pesticide classes, nor with a history of farming or use of well water. Conclusion-Parkinsonism may be associated with long term occupational exposure to pesticides, although no associations with specific pesticides could be detected. This finding is consistent with most of the publications on this topic. C1 Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Oregon Hlth & Sci Univ, Pacific NW Agr Safety & Hlth Ctr, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Environm Hlth, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Med, Occupat Med Program, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Environm Hlth, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Natl Hlth & Environm Effects Res Lab, Dept Neurol, Res Triangle Pk, NC 27711 USA. RP Engel, LS (reprint author), NCI, Occupat Epidemiol Branch, 6120 Execut Blvd,EPS 8113,MSC 7240, Bethesda, MD 20892 USA. EM engell@mail.nih.gov OI Camicioli, Richard/0000-0003-2977-8660 FU NIEHS NIH HHS [ES07262]; PHS HHS [U07/CCU012926-02] NR 41 TC 50 Z9 55 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD SEP PY 2001 VL 58 IS 9 BP 582 EP 589 DI 10.1136/oem.58.9.582 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 464UQ UT WOS:000170550500005 PM 11511745 ER PT J AU Freedman, M AF Freedman, M TI Amyotrophic lateral sclerosis and occupational exposure to 2,4-dichlorophenoxyacetic acid SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Letter ID MORTALITY C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Freedman, M (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 7 TC 4 Z9 5 U1 0 U2 1 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD SEP PY 2001 VL 58 IS 9 BP 609 EP 609 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 464UQ UT WOS:000170550500012 PM 11529236 ER PT J AU Colevas, AD West, PJ Cheson, BD AF Colevas, AD West, PJ Cheson, BD TI Clinical trials referral resource: Current clinical trials of epothilone B analog (BMS-247550) SO ONCOLOGY-NEW YORK LA English DT Article ID MICROTUBULE-STABILIZING AGENTS; TAXOL C1 NCI, Bethesda, MD 20892 USA. RP Colevas, AD (reprint author), NCI, Bethesda, MD 20892 USA. NR 12 TC 6 Z9 6 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD SEP PY 2001 VL 15 IS 9 BP 1168 EP + PG 5 WC Oncology SC Oncology GA 525LA UT WOS:000174070500015 PM 11589064 ER PT J AU Yaremchuk, K Dobie, RA AF Yaremchuk, K Dobie, RA TI Otologic injuries from airbag deployment SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID HEARING-LOSS; NOISE AB Airbags became available as an optional passive restraint system in motor vehicles in 1973. The National Highway Traffic Safety Administration mandated placement of driver and right passenger airbags in all passenger vehicles and light trucks beginning in model year 1997, An estimated 2.1 million airbags have been deployed from the late 1980s until the present. There have been several case reports of hearing loss after exposure to airbag deployments in drivers and passengers since 1995. Members of the American Academy of Otolaryngology-Head and Neck Surgery submitted case reports on 71 patients with otologic symptoms after airbag deployment. C1 Henry Ford Hlth Syst, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48202 USA. NIDCD, EPS, MSC 7180,Div Extramural Res, NIH, Bethesda, MD USA. RP Yaremchuk, K (reprint author), Henry Ford Hlth Syst, Dept Otolaryngol Head & Neck Surg, 2799 W Grand Blvd, Detroit, MI 48202 USA. OI dobie, robert/0000-0003-3833-1772 NR 25 TC 7 Z9 7 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD SEP PY 2001 VL 125 IS 3 BP 130 EP 134 DI 10.1067/mhn.2001.117872 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 473KM UT WOS:000171042900002 PM 11555742 ER PT J AU Cabot, PJ Carter, L Schafer, M Stein, C AF Cabot, PJ Carter, L Schafer, M Stein, C TI Methionine-enkephalin-and Dynorphin A-release from immune cells and control of inflammatory pain SO PAIN LA English DT Article DE opioid; analgesia; inflammation; peripheral; peptide; lymphocyte ID OPIOID RECEPTORS; INFLAMED TISSUE; BETA-ENDORPHIN; ANTINOCICEPTION; MECHANISMS; EMD-61753; AGONIST; RATS AB We have previously shown that beta -endorphin (END) is contained and released from memory-type T-cells within inflamed tissue and that it is capable to control pain (I Clin Invest 100(1) (1997) 142). Methionine-enkephalin (MET) and Dynorphin-A (DYN) are endogenous opioids with preference for delta- and kappa -opioid receptors, respectively. Both MET and DYN are produced and contained within immune cells. The goal of this study was to determine the release characteristics of MET and DYN in a rat model of localized hindpaw inflammation and to examine the antinociceptive role of MET and DYN in a Freund's adjuvant induced model of inflammatory pain. We found that corticotropin-releasing factor (CRF) can stimulate the release of both MET and DYN from lymphocytes. This release is dose-dependent and reversible by the selective CRF antagonist alpha -helical-CRF. Furthermore, CRF (1.5 ng) produces analgesia when injected into the inflamed paw, which is reversible by direct co-administration of antibodies to MET. Lymphocyte content of MET was 7.0 +/- 1.4 ng/million cells, whilst DYN content was similar to 30-fold lower. Both END and DYN, but not MET, were released by IL-1. Consistently, IL-1 produced peripheral analgesic effects which were not reversed by antibodies to MET. These results indicate that both MET and DYN play a role in peripheral analgesia but have different characteristics of release. These studies further support a role of the immune system in the control of inflammatory pain. This may be particularly important in patients suffering from compromised immune systems as with cancer and A-IDS. (C) 2001 International Association for the Study of Pain. Published by Elsevier Science B.V. All rights reserved. C1 NIDA, Behav Pharmacol & Genet Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21287 USA. Free Univ Berlin, Klinikum Benjamin Franklin, Klin Anaesthesiol & Operat Intensivmed, D-12200 Berlin, Germany. Univ Queensland, Sch Pharm, St Lucia, Qld 4072, Australia. RP Cabot, PJ (reprint author), NIDA, Behav Pharmacol & Genet Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RI Cabot, Peter/B-2424-2013; OI Cabot, Peter/0000-0003-1778-3753; Stein, Christoph/0000-0001-5240-6836 FU NINDS NIH HHS [R01 NS 32466] NR 18 TC 95 Z9 104 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD SEP PY 2001 VL 93 IS 3 BP 207 EP 212 DI 10.1016/S0304-3959(01)00322-0 PG 6 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 469HB UT WOS:000170807500002 PM 11514079 ER PT J AU Porto, AF Neva, FA Bittencourt, H Lisboa, W Thompson, R Alcantara, L Carvalho, EM AF Porto, AF Neva, FA Bittencourt, H Lisboa, W Thompson, R Alcantara, L Carvalho, EM TI HTLV-1 decreases Th2 type of immune response in patients with strongyloidiasis SO PARASITE IMMUNOLOGY LA English DT Article DE HTLV-1; strongyloidiasis; IgE; S. stercoralis ID T-CELL LEUKEMIA; INHIBITS CYTOKINE PRODUCTION; LYMPHOTROPIC VIRUS TYPE-1; STERCORALIS HYPERINFECTION; LYMPHOCYTES-T; INFECTION; MICE; ANTIBODY; CLONES; IL-10 AB Eosinophils, immunoglobilin (Ig)E and cytokines have important roles in defence mechanisms against helminths. In this study, the influence of HTLV-1 infection, characterized by a Th1 type of immune response, was evaluated on the cytokine pattern and parasitic specific IgE response in patients with strongyloidiasis. Patients were divided into four groups: strongyloidiasis without HTLV-1 infection, strongyloidiasis with HTLV-1, HTLV-1 without strongyloidiasis and controls without either helminth infection or HTLV-1. The cytokine profile was determined in supernatants of mononuclear cells stimulated with Strongyloides stercoralis crude antigen and the parasite specific IgE was measured by ELISA. Patients coinfected with HTLV-1 had higher levels of interfron (IFN)-gamma and interleukin (IL)-10 (P < 0.05) and lower levels of IL-5 and IgE (P < 0.05) than patients with strongyloidiasis without HTLV-1. There was an inverse relationship between IFN-gamma and IL-5 (P = 0.01; r(s) = - 0.37) and between IFN-gamma and parasite specific IgE (P = 0.01; r(s) = - 0.39), and a direct relationship between IFN-gamma and IL-10 (P = 0.04;, r(s) = 0.35). These data show that coinfection with HTLV-1 decreases IL-5 and IgE responses in patients with strongyloidiasis consistent with a relative switch from Th2 to Th1 response. Immunological responses such as these are important in the control of this helminthic infection. C1 Univ Fed Bahia, Hosp Univ Prof Edgard Santos, Serv Imunol, Lab Imunol, BR-40110160 Salvador, BA, Brazil. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Inst Gastroenterol & Hepatol, Salvador, BA, Brazil. Serv Transfusao Sangue, Salvador, BA, Brazil. Fundacao Oswaldo Cruz, Lab Avancado Saude Publ, Salvador, BA, Brazil. RP Carvalho, EM (reprint author), Univ Fed Bahia, Hosp Univ Prof Edgard Santos, Serv Imunol, Lab Imunol, 5 Andar,Rua Joao das Botas S-N Canela, BR-40110160 Salvador, BA, Brazil. FU NIAID NIH HHS [AI-30639] NR 40 TC 64 Z9 68 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0141-9838 J9 PARASITE IMMUNOL JI Parasite Immunol. PD SEP PY 2001 VL 23 IS 9 BP 503 EP 507 DI 10.1046/j.1365-3024.2001.00407.x PG 5 WC Immunology; Parasitology SC Immunology; Parasitology GA 473CL UT WOS:000171022000005 PM 11589779 ER PT J AU Longnecker, MP Rogan, WJ AF Longnecker, MP Rogan, WJ TI Persistent organic pollutants in children - Commentary SO PEDIATRIC RESEARCH LA English DT Editorial Material ID POLYCHLORINATED-BIPHENYLS PCBS; DICHLORODIPHENYL-TRICHLOROETHANE; HUMAN-MILK; DDT LEVELS; EXPOSURE; MOTHERS; ORGANOCHLORINE; DETERMINANTS; CONTAMINANTS; DIOXINS C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RI Rogan, Walter/I-6034-2012; OI Rogan, Walter/0000-0002-9302-0160; Longnecker, Matthew/0000-0001-6073-5322 NR 32 TC 14 Z9 16 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2001 VL 50 IS 3 BP 322 EP 323 DI 10.1203/00006450-200109000-00005 PG 2 WC Pediatrics SC Pediatrics GA 467YB UT WOS:000170730400003 PM 11518817 ER PT J AU Kuhn, L Coutsoudis, A Moodley, D Mngqundaniso, N Trabattoni, D Shearer, GM Clerici, M Coovadia, HM AF Kuhn, L Coutsoudis, A Moodley, D Mngqundaniso, N Trabattoni, D Shearer, GM Clerici, M Coovadia, HM TI Interferon-gamma and interleukin-10 production among HIV-1-Infected and uninfected infants of HIV-1-infected mothers SO PEDIATRIC RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-LYMPHOCYTE ACTIVITY; HIV-INFECTION; DISEASE PROGRESSION; VERTICAL TRANSMISSION; TYPE-1 TRANSMISSION; PROSPECTIVE COHORT; PERIPHERAL-BLOOD; CELL RESPONSES; CHILDREN BORN AB Immunologic consequences of exposure to HIV-1 in utero are still poorly understood. This study investigates relationships between type-l [interferon-gamma (IFN-gamma)] and type-2 (IL-10) cytokine production and maternal-infant HIV-1 transmission. Cord blood leukocytes from deliveries of 71 HIV-1-infected and 11 uninfected mothers were tested for in vitro IFN-gamma and IL-10 production after phytohemagglutinin (PHA) stimulation. The infants of these HIV-1-infected mothers were followed prospectively after birth to determine HIV vertical transmission, and IFN-gamma and IL-10 production was measured again at 6 mo. Median PHA-stimulated IFN-gamma production was 210 pg/mL in cord blood cells from infected and 73 pg/mL from uninfected mothers (p = 0.12), and median PHA-stimulated IL-10 production was 491 pg/mL in cord blood cells from infected and 161 pg/mL from uninfected mothers (p = 0.004). PHA-stimulated IFN-gamma and IL-10 production alone were not significantly associated with transmission, but relationships between the two cytokines differed among infected and uninfected infants of HIV-1-infected mothers. PRA-stimulated IFN-gamma and IL-10 production was positively correlated among infected (r = 0.7, p = 0.12 in cord blood and r = 0.66, p = 0.03 at 6 mo) but not uninfected infants, and stronger relative production of IFN-gamma to IL-10 was observed among exposed uninfected than among infected infants (p = 0.04). Exposure in utero to HIV-1 may augment production of IL-10 detectable in fetal cord blood. Stronger relative production of IFN-gamma to IL-10 in cord blood cells from infants of HIV-1-infected mothers may be associated with protection against perinatal HIV infection. C1 Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, New York, NY 10032 USA. Columbia Univ, Joseph H Mailman Sch Publ Hlth, Div Epidemiol, New York, NY 10032 USA. Univ KwaZulu Natal, Dept Paediat & Child Hlth, ZA-4001 Durban, South Africa. Univ Milan, Cattedra Immunol, I-20122 Milan, Italy. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Kuhn, L (reprint author), Columbia Univ, Coll Phys & Surg, Gertrude H Sergievsky Ctr, 630 W 168th St, New York, NY 10032 USA. EM lk24@columbia.edu RI Trabattoni, Daria/G-7424-2012 FU NICHD NIH HHS [HD36177] NR 33 TC 26 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0031-3998 EI 1530-0447 J9 PEDIATR RES JI Pediatr. Res. PD SEP PY 2001 VL 50 IS 3 BP 412 EP 416 DI 10.1203/00006450-200109000-00018 PG 5 WC Pediatrics SC Pediatrics GA 467YB UT WOS:000170730400016 PM 11518830 ER PT J AU Brenner, RA Simons-Morton, BG Bhaskar, B Das, A Clemens, JD AF Brenner, RA Simons-Morton, BG Bhaskar, B Das, A Clemens, JD CA NIH-DC Initiative Immunization Wor TI Prevalence and predictors of immunization among inner-city infants: A birth cohort study SO PEDIATRICS LA English DT Article DE immunizations; cohort studies; infant; vaccination; risk factors ID MISSED OPPORTUNITIES; RISK-FACTORS; DELAYED IMMUNIZATION; PRIMARY-CARE; CHILDREN; UNDERIMMUNIZATION; VACCINATION; BALTIMORE; COVERAGE AB Context. Although the proportion of US children who are appropriately immunized increased dramatically in the past decade, rates remain suboptimal among low-income, inner-city youth. Timely initiation of immunization is an important predictor of immunization status later in childhood; however, prospective studies identifying predictors of initiation are lacking. Objectives. The objectives of this study were to: 1) describe immunization patterns in a cohort of infants born to predominantly low-income, inner-city mothers; 2) identify determinants, as measured at birth, of immunization status at 3 and 7 months of age; and 3) identify determinants of continuation of immunization among those who initiate immunization by 3 months of age. Design. Prospective, birth cohort study. Methods. Maternal/infant dyads were systematically selected from 3 District of Columbia hospitals between August 1995 and September 1996. Three hundred sixty-nine mothers were interviewed shortly after delivery, at 3 to 7 months postpartum, and at 7 to 12 months postpartum. Medical records were reviewed at all reported sites of care for 324 (88%) infants. Vaccinations assessed included diphtheria, tetanus, and pertussis; polio; and Haemophilus influenzae type B. Multivariate logistic regression analyses were used to determine factors associated with immunization status of infants at 3 and 7 months of age. Results. At 3 months of age, 75% of infants were up-to-date (UTD) versus only 41% at 7 months. In adjusted analyses, baseline factors associated with being UTD at 3 months included enrollment in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) during pregnancy, intention to breastfeed, and presence of the infant's grandmother in the household. Infants were less likely to be UTD if their mothers perceived higher barriers to immunization. Baseline factors associated with being UTD at 7 months included lower birth order and maternal employment. Among the subset of infants who were UTD at 3 months, only 53% remained UTD at 7 months. Factors measured at the first follow-up interview that were associated with continuation of immunization at 7 months included maternal employment and lower perceived barriers. Conclusions. Immunization rates during the first 7 months of life were low in this inner-city population. Factors associated with immunization status that are potentially amenable to change included perceived barriers to immunization and enrollment in WIC during pregnancy. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Res Triangle Inst, Rockville, MD USA. Int Vaccine Inst, Seoul, South Korea. RP Brenner, RA (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617 FU NICHD NIH HHS [U18-HD30445, U18-HD30447, U18-HD30450, U18-HD30454, U18-HD30458, U18-HD31206, U18-HD31919] NR 35 TC 41 Z9 41 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD SEP PY 2001 VL 108 IS 3 BP 661 EP 670 DI 10.1542/peds.108.3.661 PG 10 WC Pediatrics SC Pediatrics GA 468WQ UT WOS:000170781500031 PM 11533333 ER PT J AU Manfredi, KP Vallurupalli, V Demidova, M Kindscher, K Pannell, LK AF Manfredi, KP Vallurupalli, V Demidova, M Kindscher, K Pannell, LK TI Isolation of an anti-HIV diprenylated bibenzyl from Glycyrrhiza lepidota SO PHYTOCHEMISTRY LA English DT Article DE Glycyrrhiza lepidota; Fabaceae; prenylated; glepidotin; HIV-1 AB The organic soluble extract from the leaves of Glycyrrhiza lepidota showed moderate activity in the US National Cancer Institute in vitro anti-HIV-1 bioassay, Chromatographic separation of this extract resulted in the identification of a new diprenylated bibenzyl as the compound responsible for the observed anti-viral activity. Extensive spectroscopic experiments provide the complete H-1 NMR and C-13 NMR spectral assignments to support the proposed structure. Known compounds glepidotin B and glepidotin A were also isolated from the extract and shown to be inactive in the anti-viral assay. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ No Iowa, Dept Chem, Cedar Falls, IA 50614 USA. Univ Kansas, Kansas Biol Survey, Lawrence, KS 66047 USA. NIDDK, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Manfredi, KP (reprint author), Univ No Iowa, Dept Chem, Cedar Falls, IA 50614 USA. NR 15 TC 28 Z9 29 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0031-9422 J9 PHYTOCHEMISTRY JI Phytochemistry PD SEP PY 2001 VL 58 IS 1 BP 153 EP 157 DI 10.1016/S0031-9422(01)00177-7 PG 5 WC Biochemistry & Molecular Biology; Plant Sciences SC Biochemistry & Molecular Biology; Plant Sciences GA 463ET UT WOS:000170464400018 PM 11524125 ER PT J AU Hiatt, RA Pasick, RJ Stewart, S Bloom, J Davis, P Gardiner, P Johnston, M Luce, J Schorr, K Brunner, W Stroud, F AF Hiatt, RA Pasick, RJ Stewart, S Bloom, J Davis, P Gardiner, P Johnston, M Luce, J Schorr, K Brunner, W Stroud, F TI Community-based cancer screening for underserved women: Design and baseline findings from the Breast and Cervical Cancer Intervention Study SO PREVENTIVE MEDICINE LA English DT Review DE behavior; cancer; breast neoplasms; cervix neoplasms; mass screening; intervention studies; minority; low-income; health surveys ID INCREASE MAMMOGRAPHY UTILIZATION; ELDERLY HISPANIC WOMEN; MEXICAN-AMERICAN WOMEN; LOW-INCOME; HEALTH-EDUCATION; BLACK-WOMEN; PAP SMEAR; MINORITY PARTICIPATION; PREVENTIVE SERVICES; COLORECTAL-CANCER AB Background. Underutilization of breast and cervical cancer screening has been observed in many ethnic groups and underserved populations. Effective community-based interventions are needed to eliminate disparities in screening rates and thus to improve prospects for survival Methods. The Breast and Cervical Cancer Intervention Study was a controlled trial of three interventions in the San Francisco Bay Area from 1993 to 1996: (1) community-based lay health worker outreach, (2) clinic-based provider training and reminder system; and (3) patient navigator for follow-up of abnormal screening results. Study design and a description of the interventions are reported along with baseline results of a household survey conducted in four languages among 1599 women, aged 40-75. Results. Seventy-six: percent of women ages 40 and over had had at least one mammogram, and most had had a clinical breast examination (88%) and Pap smear (89%). Rates were significantly lower for non-English-speaking Latinas and Chinese women (56 and 32%, respectively, for mammography), and maintenance screening (three mammograms in the past 5 years) varied from 7% (non-English-speaking Chinese) to 53% (Blacks). Pap smear screening in the past 3 years was low among non-English-spe-akin Latinas (72%) and markedly lower among non-English-speaking Chinese women (24%). The strongest predictors of screening behavior were having private health insurance and frequent use of medical services. Having a regular clinic and speaking English were also important. Race/ethnicity, education, household income, and employment status were, overall, not significant predictors of screening behavior. Conclusions. These baseline results support the importance of cancer screening interventions targeted to persons of foreign origin, particularly those less acculturated. (C) 2001 American Health Foundation and Academic Press. C1 No Calif Canc Ctr, Union City, CA 94587 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Contra Costa Cty Hlth Serv Dept, Martinez, CA 94553 USA. San Francisco Dept Publ Hlth, San Francisco, CA 94103 USA. RP Hiatt, RA (reprint author), NCI, NIH, DHHS, 6130 Execut Blvd,MSC 7339,EPN 6142, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA54605-05] NR 115 TC 128 Z9 131 U1 7 U2 24 PU ACADEMIC PRESS INC 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 SEP PY 2001 VL 33 IS 3 BP 190 EP 203 DI 10.1006/pmed.2001.0871 PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 467YD UT WOS:000170730600008 PM 11522160 ER PT J AU Marcus, AC Heimendinger, J Wolfe, P Fairclough, D Rimer, BK Morra, M Warnecke, R Himes, JH Darrow, SL Davis, SW Julesberg, K Slevin-Perocchia, R Steelman, M Wooldridge, J AF Marcus, AC Heimendinger, J Wolfe, P Fairclough, D Rimer, BK Morra, M Warnecke, R Himes, JH Darrow, SL Davis, SW Julesberg, K Slevin-Perocchia, R Steelman, M Wooldridge, J TI A randomized trial of a brief intervention to increase fruit and vegetable intake: A replication study among callers to the CIS SO PREVENTIVE MEDICINE LA English DT Review DE cancer prevention and control; diet; telephone information services; health education ID CANCER INFORMATION-SERVICE; 5-A-DAY PROMOTION PROGRAM; WORKING WELL TRIAL; TREATWELL 5-A-DAY; PHYSICAL-ACTIVITY; NUTRITION INTERVENTION; DIETARY BEHAVIOR; BASE-LINE; CARDIOVASCULAR HEALTH; EATING PATTERNS AB Background. Results are reported from a large randomized trial designed to increase fruit and vegetable consumption among callers to the National Cancer Institute's Cancer Information Service (CIS) (n = 1,717). Methods. CIS callers assigned to the intervention group (n = 861) received a brief proactive educational intervention over the telephone at the end of usual service, with two follow-up mailouts. Key educational messages and print material derived from the NCI 5 A Day for Better Health program were provided to intervention participants. Participants were interviewed by telephone at 4 weeks (n, = 1,307), 4 months (n 1,180), and 12 months for follow-up (n = 1,016). Results. Results obtained from a single-item measure of fruit and vegetable consumption indicate a significant intervention effect of 0.88 servings per day at 4 weeks follow-up (P < 0.001), 0.63 servings per day at 4 months follow-up (P < 0.001), and 0.43 servings per day at 12 months follow-up (P < 0.001). Using a 7-item food frequency measure, an intervention effect of 0.63 servings per day was obtained at 4 weeks follow-up (P < 0.001), compared with 0.39 servings per day at 4 months follow-up (P = 0.002) and 0.44 servings per day at 12 months follow-up (P = 0.002). A 24-h recall assessment included in the 4-month interviews also yielded a significant intervention effect of 0.67 servings per day (P = 0.015). The vast majority of callers (90%) endorsed the strategy of providing 5 A Day information proactively within the CIS. Conclusions. This brief educational intervention was associated with higher levels of self-reported fruit and vegetable intake at both short- and long-term followup. Additional research is recommended to test this or a similar intervention in diverse populations. <(c)> 2001 American Health Foundation and Academic Press. C1 AMC Canc Res Ctr, Denver, CO 80214 USA. Colorado Fdn Med Care, Aurora, CO 80014 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Morra Commun Inc, Milford, CT 06460 USA. Univ Illinois, Ctr Hlth Policy, Chicago, IL 60607 USA. Univ Illinois, Ctr Hlth Serv Res, Chicago, IL 60607 USA. Univ Minnesota, Nutr Coordinating Ctr, Minneapolis, MN 55454 USA. Haynes Int Inc, Buffalo, NY 14226 USA. No Calif Canc Ctr, Canc Informat Serv, Union City, CA 94587 USA. Univ Wisconsin, Ctr Comprehens Canc, Canc Informat Serv, Madison, WI 53711 USA. Mem Sloan Kettering Canc Ctr, Canc Informat Serv, New York, NY 10021 USA. W Virginia Univ, Mary Babb Canc Ctr, Morgantown, WV 26506 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98109 USA. RP Marcus, AC (reprint author), AMC Canc Res Ctr, 1600 Pierce St, Denver, CO 80214 USA. FU NCI NIH HHS [R01 CA5973, P01-CA57586] NR 101 TC 50 Z9 50 U1 4 U2 6 PU ACADEMIC PRESS INC 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 SEP PY 2001 VL 33 IS 3 BP 204 EP 216 DI 10.1006/pmed.2001.0873 PG 13 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 467YD UT WOS:000170730600009 PM 11522161 ER PT J AU Bashir, S Lipman, TO AF Bashir, S Lipman, TO TI Nutrition in gastroenterology and hepatology SO PRIMARY CARE LA English DT Article ID PROTEIN-CALORIE MALNUTRITION; INFLAMMATORY BOWEL-DISEASE; PLACEBO-CONTROLLED TRIAL; NURSING-HOME RESIDENTS; ACTIVE CROHNS-DISEASE; ENTERAL NUTRITION; GASTROINTESTINAL SYMPTOMS; VITAMIN-B-12 DEFICIENCY; CHRONIC-PANCREATITIS; DIETARY-SUPPLEMENTS AB Nutritional issues, sometimes obvious and sometimes not so obvious, confront the primary care practitioner on a daily basis. Understanding the multi-disciplinary nature of nutrition science and clinical nutrition and having a basic understanding of gastrointestinal tract digestive and absorptive physiology can only help sort out the many issues involved. The general practitioner needs a core understanding of the principles of nutrition assessment. C1 Dept Vet Affairs Med Ctr, GI Hepatol Nutr Sect 151W, Washington, DC 20422 USA. NIH, Bethesda, MD 20892 USA. RP Lipman, TO (reprint author), Dept Vet Affairs Med Ctr, GI Hepatol Nutr Sect 151W, 50 Irving St NW, Washington, DC 20422 USA. NR 63 TC 1 Z9 2 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 0095-4543 J9 PRIMARY CARE JI Primary Care PD SEP PY 2001 VL 28 IS 3 BP 629 EP + DI 10.1016/S0095-4543(05)70057-9 PG 18 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 474AE UT WOS:000171081500011 PM 11483448 ER PT J AU Olsson, P Bera, TK Essand, M Kumar, V Duray, P Vincent, J Lee, B Pastan, I AF Olsson, P Bera, TK Essand, M Kumar, V Duray, P Vincent, J Lee, B Pastan, I TI GDEP, a new gene differentially expressed in normal prostate and prostate cancer SO PROSTATE LA English DT Article DE EST database; RNA; LNCaP; 3 ' UTR; chromosome 4q21.1 ID TRANSCRIPT AB BACKGROUND. The database of human expressed sequence tags (dbEST) is a potential source for the identification of tissue specific genes. The database contains sequences that originate from cDNA libraries from different tissues cell types and tumors. METHODS. Computer based analysis identified a cluster of sequence homologous ESTs, containing ESTs derived only from human prostate cDNA libraries. The tissue specificity was examined by multiple tissue RNA dot blots and RT-FCR. The new RNA transcript was characterized using northern blot analysis, RACE-PCR, and a ribonuclease protection assay. RESULTS. We have identified a gene differentially expressed in prostate using EST database analysis and experimental studies. We name the gene GDEP for gene differentially expressed in prostate. The major GDEP transcript is about 520 bp long. GDEP RNA was detected in nine prostate tissue samples, four normal and five cancer. Expression in prostate epithelial cells was established by in situ hybridization. Weak expression was detected in the prostate cancer cell line LNCaP. In vitro transcription/ translation indicate that the RNA encodes a small 34 amino acid protein. The major transcript consists of two exons with one large intron (> 15 kb). The GDEP gene was mapped to chromosome 4q21.1 by radiation hybrid mapping. CONCLUSIONS. Our data proves that tissue specific genes can be identified by EST database mining. The prostate specificity of GDEP expression indicates that GDEP may be useful in the diagnosis or treatment of prostate cancer. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 12 TC 27 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0270-4137 J9 PROSTATE JI Prostate PD SEP 1 PY 2001 VL 48 IS 4 BP 231 EP 241 DI 10.1002/pros.1102 PG 11 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 470BP UT WOS:000170850800002 PM 11536302 ER PT J AU Jung, J Lee, B AF Jung, J Lee, B TI Circularly permuted proteins in the protein structure database SO PROTEIN SCIENCE LA English DT Article DE circular permutation; protein structure; structure alignment; gene duplication ID CONCANAVALIN-A; ALPHA/BETA-BARREL; PERMUTATION; DOMAIN; SEQUENCES; EVOLUTION; ALIGNMENT; ELEMENTS; AMINO; GENES AB Some proteins are homologous to others after their sequence is circularly permuted. A few such proteins have been recognized, mainly by sequence comparison, but also by comparing their three-dimensional structures. Here we report the result of a systematic search for all protein pairs in the SCOP 90% id domain database that become structurally superimposable when the sequence of one of the pairs is circularly permuted. Using a reasonable set of criteria, we find that 47% of all protein domains are superimposable to at least one other protein domain in the database after their sequence is circularly permuted. Many of these are symmetric proteins, which superimpose to another protein both with and without a circular permutation of the sequence. However, 412 of the total 3035 domains are nonsymmetric, and these become structurally superimposable to another protein only after a circular permutation of the sequence. These include most known and many previously undetected circularly permuted proteins with remote homology. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, B (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 4B15,37 Convent Dr MSC 4255, Bethesda, MD 20892 USA. NR 32 TC 50 Z9 52 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD SEP PY 2001 VL 10 IS 9 BP 1881 EP 1886 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 469NJ UT WOS:000170821500018 PM 11514678 ER PT J AU Tsai, CJ Ma, BY Sham, YY Kumar, S Nussinov, R AF Tsai, CJ Ma, BY Sham, YY Kumar, S Nussinov, R TI Structured disorder and conformational selection SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Review DE disorder; molten globule; stability; populations; folding binding; conformational selection ID MOLTEN GLOBULE STATE; ALPHA-LACTALBUMIN; FOLDING FUNNELS; LIMITED PROTEOLYSIS; ENERGY LANDSCAPES; BINDING CASCADES; PRO-DOMAIN; PROTEIN; STABILITY; SUBTILISIN AB Traditionally, molecular disorder has been viewed as local or global instability. Molecules or regions displaying disorder have been considered inherently unstructured. The term has been routinely applied to cases for which no atomic coordinates can be derived from crystallized molecules. Yet, even when it appears that the molecules are disordered, prevailing conformations exist, with population times higher than those of all alternate conformations. Disordered molecules are the outcome of rugged energy landscapes away from the native state around the bottom of the funnel. Ruggedness has a biological function, creating a distribution of structured conformers that bind via conformational selection, driving association and multimolecular complex formation, whether chain-linked in. folding or unlinked in binding. We classify disordered molecules into two types. The first type possesses a hydrophobic core. Here, even if the native conformation is unstable, it still has a large enough population time, enabling its experimental detection. In the second type, no such hydrophobic core exists. Hence, the native conformations of molecules belonging to this category have shorter population times, hindering their experimental detection. Although there is a continuum of distribution of hydrophobic cores in proteins, an empirical, statistically based hydrophobicity function may be used as a guideline for distinguishing the two disordered molecule types. Furthermore, the two types relate to steps in the protein folding reaction. With respect to protein design, this leads us to propose that engineering-optimized specific electrostatic interactions to avoid electrostatic repulsion would reduce the type I disordered state, driving the molten globule (MG) --> native (N) state. In contrast, for overcoming the type II disordered state, in addition to specific interactions, a stronger hydrophobic core is also indicated, leading to the denatured --> MG --> N state. Proteins 2001;44:418-427. (C) 2001 Wiley-Liss, Inc. C1 NCI, Intramural Res Support Program, Sci Applicat Int Corp, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Intramural Res Support Program, Sci Applicat Int Corp, Lab Expt & Computat Biol, Frederick Bldg 469,Room 151, Frederick, MD 21702 USA. RI Sham, Yuk/A-6472-2011; Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-56000] NR 52 TC 129 Z9 130 U1 1 U2 16 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD SEP 1 PY 2001 VL 44 IS 4 BP 418 EP 427 DI 10.1002/prot.1107 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 463LL UT WOS:000170477600003 PM 11484219 ER PT J AU Hoagwood, K Burns, BJ Kiser, L Ringeisen, H Schoenwald, SK AF Hoagwood, K Burns, BJ Kiser, L Ringeisen, H Schoenwald, SK TI Evidence-based practice in child and adolescent mental health services SO PSYCHIATRIC SERVICES LA English DT Article ID EMPIRICALLY SUPPORTED TREATMENTS; SERIOUS EMOTIONAL DISTURBANCE; GREAT SMOKY MOUNTAINS; PSYCHOSOCIAL INTERVENTIONS; PSYCHOTHERAPY-RESEARCH; MULTISYSTEMIC THERAPY; DEPRESSIVE DISORDER; JUVENILE-OFFENDERS; ALGORITHM PROJECT; RANDOMIZED TRIAL AB The authors review the status, strength, and quality of evidence-based practice in child and adolescent mental health services. The definitional criteria that have been applied to the evidence base differ considerably across treatments, and these definitions circumscribe the range, depth, and extensionality of the evidence. The authors describe major dimensions that differentiate evidence-based practices for children from those for adults and summarize the status of the scientific literature on a range of service practices. The readiness of the child and adolescent evidence base for large-scale dissemination should be viewed with healthy skepticism until studies of the fit between empirically based treatments and the context of service delivery have been undertaken. Acceleration of the pace at which evidence-based practices can be more readily disseminated will require new models of development of clinical services that consider the practice setting in which the service is ultimately to be delivered. C1 NIMH, Bethesda, MD 20817 USA. Duke Univ, Durham, NC USA. Univ Maryland, Baltimore, MD 21201 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Hoagwood, K (reprint author), NIMH, 6001 Execut Blvd, Bethesda, MD 20817 USA. NR 97 TC 282 Z9 283 U1 3 U2 21 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD SEP PY 2001 VL 52 IS 9 BP 1179 EP 1189 DI 10.1176/appi.ps.52.9.1179 PG 11 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 468XF UT WOS:000170782900007 PM 11533391 ER PT J AU Schoenwald, SK Hoagwood, K AF Schoenwald, SK Hoagwood, K TI Effectiveness, transportability, and dissemination of interventions: What matters when? SO PSYCHIATRIC SERVICES LA English DT Article ID ADOLESCENT PSYCHOTHERAPY; PROGRAM-DEVELOPMENT; SERVICES; FIDELITY; CHILD; OUTCOMES; MODEL AB The authors identify and define key aspects of the progression from research on the efficacy of a new intervention to its dissemination. They highlight the role of transportability questions that arise in that progression and illustrate key conceptual and design features that differentiate efficacy, effectiveness, and dissemination research. An ongoing study of the transportability of multisystemic therapy is used to illustrate independent and interdependent aspects of effectiveness, transportability; and dissemination studies. Variables relevant to the progression from treatment efficacy to dissemination include features of the intervention itself as well as variables pertaining to the practitioner, client, model of service delivery, organization, and service system. The authors provide examples of how some of these variables are relevant to the transportability of different types of interventions. They also discuss sample research questions, study designs, and challenges to be anticipated in the arena of transportability research. C1 Med Univ S Carolina, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Family Serv Res Ctr, Charleston, SC 29425 USA. NIMH, Child & Adolescent Serv Branch, Off Director, Bethesda, MD 20892 USA. RP Schoenwald, SK (reprint author), Med Univ S Carolina, Dept Psychiat & Behav Sci, 67 President St,Suite CPP,POB 250861, Charleston, SC 29425 USA. FU NIMH NIH HHS [MH-59138] NR 31 TC 371 Z9 372 U1 2 U2 12 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 1075-2730 J9 PSYCHIATR SERV JI Psychiatr. Serv. PD SEP PY 2001 VL 52 IS 9 BP 1190 EP 1197 DI 10.1176/appi.ps.52.9.1190 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 468XF UT WOS:000170782900008 PM 11533392 ER PT J AU Schooler, C Mulatu, MS AF Schooler, C Mulatu, MS TI The reciprocal effects of leisure time activities and intellectual functioning in older people: A longitudinal analysis SO PSYCHOLOGY AND AGING LA English DT Article ID RADICAL SOCIAL-CHANGE; ET-AL. 1999; ALZHEIMERS-DISEASE; SELF-DIRECTION; LIFE-STYLE; MEMORY; PERSONALITY; COMPLEXITY; WORK; INTELLIGENCE AB By using data from a representative longitudinal survey, the authors provide strong evidence that complex leisure time activities increase intellectual functioning for workers and nonworkers. Although the effects were relatively moderate, both the present article and its predecessor on the effects of paid work (C. Schooler, Mulatu, & Oates, 1999) showed that, even in old age, carrying out complex tasks has a positive effect on intellectual processes. In both cases, initially high levels of intellectual functioning led to high levels of environmental complexity, which in turn raised levels of intellectual functioning, thus providing a pathway contributing to the high correlation of intellectual functioning over a 20-year period in middle and late adulthood. The present findings indicate that even in old age carrying out substantively complex tasks builds the capacity to deal with the intellectual challenges such complex environments provide. C1 NIMH, Sect Socioenvironm Studies, Bethesda, MD 20892 USA. RP Schooler, C (reprint author), NIMH, Sect Socioenvironm Studies, Room B1A-14,Fed Bldg, Bethesda, MD 20892 USA. FU NIA NIH HHS [Y02 AG-1-0168] NR 51 TC 126 Z9 129 U1 3 U2 22 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0882-7974 J9 PSYCHOL AGING JI Psychol. Aging PD SEP PY 2001 VL 16 IS 3 BP 466 EP 482 DI 10.1037//0882-7974.16.3.466 PG 17 WC Gerontology; Psychology, Developmental SC Geriatrics & Gerontology; Psychology GA 468YX UT WOS:000170786700008 PM 11554524 ER PT J AU Carter, JA Herbst, JH Stoller, KB King, V Kidorf, MS Costa, PT Brooner, RK AF Carter, JA Herbst, JH Stoller, KB King, V Kidorf, MS Costa, PT Brooner, RK TI Short-term stability of NEO-PI-R personality trait scores in opioid-dependent outpatients SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS LA English DT Article ID 5-FACTOR MODEL; DIAGNOSES; INVENTORY; DISORDER; VALIDITY; ABUSERS; COCAINE AB The present study examined the short-term stability of personality trait scores from the Revised NEO Personality Inventory (NEO-PI-R) among 230 opioid-dependent outpatients. The NEO-PI-R is a 240-item empirically developed measure of the five-factor model of personality (Neuroticism, Extraversion, Openness, Agreeableness, and Conscientiousness). Participants completed the NEO-PI-R at admission and again approximately 19 weeks later. Results indicated fair to good stability for all NEO-PI-R factor domain scores, with coefficients ranging from .68 to .74. Stability of NEO-PI-R scores was decreased among potentially invalid response patterns but was not significantly affected by drug-positive versus drug-negative status at follow-up. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Carter, JA (reprint author), Johns Hopkins Univ, Bayview Med Ctr, Addict Treatment Serv, 4940 Eastern Ave,MFL East Tower,6th Floor, Baltimore, MD 21224 USA. OI Costa, Paul/0000-0003-4375-1712 FU NIDA NIH HHS [P50DAO9258, P50DAO5273] NR 23 TC 23 Z9 23 U1 0 U2 3 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0893-164X J9 PSYCHOL ADDICT BEHAV JI Psychol. Addict. Behav. PD SEP PY 2001 VL 15 IS 3 BP 255 EP 260 PG 6 WC Substance Abuse; Psychology, Multidisciplinary SC Substance Abuse; Psychology GA 471CT UT WOS:000170910500013 PM 11563805 ER PT J AU Grillon, C Ameli, R AF Grillon, C Ameli, R TI Conditioned inhibition of fear-potentiated startle and skin conductance in humans SO PSYCHOPHYSIOLOGY LA English DT Article DE startle; conditioning; conditioned inhibition; trait anxiety; humans ID POSTTRAUMATIC-STRESS-DISORDER; RELEVANT STIMULI; ELECTRODERMAL RESPONSES; AFFECTIVE MODULATION; PREPAREDNESS THEORY; REFLEX; EMOTION; ANXIETY; PHOBIAS; MODEL AB Conditioned inhibition of classical conditioning was investigated with the startle reflex and the skin conductance response (SCR) in humans using a serial presentation of the conditioned inhibitor (X) and of the conditioned stimulus (CS). The unconditioned stimulus (US) was a shock. During conditioning, participants were presented with two different reinforced CS (A, B) and with X preceding A (noted X --> A). During X --> A, A was not reinforced with the US. During the summation test, B, X --> B, and Y --> B were presented (Y was a new stimulus that tested the specificity of the inhibitory properties of X). B was not reinforced during the summation test. A, B, X, and Y were lights of different colors. Participants were divided into a low and a high anxious group based on the TPQ (C.R. Cloninger, 1987). In the low anxious group, conditioned startle potentiation and SCR responses to A were inhibited when X preceded A (noted A(XA)). This differential responding to A and AXA emerged earlier with the SCR than with startle. During the summation test, the inhibitory properties of X did not transfer to B. In the high anxious group, there was only a differential SCR to A and AXA. X did not inhibit startle potentiation to A. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. Hartford Hosp, Hartford, CT 06115 USA. RP Grillon, C (reprint author), NIMH, MADP, 1 Ctr Dr,Room B3-07,MSC 0135, Bethesda, MD 20892 USA. FU NIMH NIH HHS [R01 MH53618-01A2, R29 MH50720] NR 51 TC 49 Z9 52 U1 1 U2 8 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2001 VL 38 IS 5 BP 807 EP 815 DI 10.1017/S0048577201000294 PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 472GQ UT WOS:000170975800009 PM 11577904 ER PT J AU Hagemann, D Naumann, E Thayer, JF AF Hagemann, D Naumann, E Thayer, JF TI The quest for the EEG reference revisited: A glance from brain asymmetry research SO PSYCHOPHYSIOLOGY LA English DT Article DE electroencephalography; reference problem; topographical analysis; hemispheric lateralization ID AVERAGE REFERENCE; BIOLOGICAL SUBSTRATE; SCALP POTENTIALS; AFFECTIVE STYLE; DEPRESSION; SURFACE; RESPONSIVENESS; EXPECTANCY; DISORDERS; FREQUENCY AB Recent findings suggested that the choice of the EEG reference might be a critical issue for the study of anterior asymmetry in the alpha band. The present paper investigates the validity of different reference schemes for the measurement of alpha asymmetry. A 32-channel resting EEG was recorded with a common vertex reference (Cz), and transformed into computer-averaged ears (A1 + A2), average reference (AR), and current source density derivations. A correlation analysis of an alpha asymmetry measure between all derivation schemes indicated a poor convergent validity for anterior sites but an excellent convergent validity for posterior sites. Further analyses suggested the presence of substantial alpha activity at the various reference sites (Cz, Al + A2, AR), which might be similar in magnitude to anterior but smaller than posterior alpha. These findings suggest that the validity of a reference scheme is a function of the signal-to-noise ratio of the electrical activities at target and reference sites. The limitations of each reference scheme for the measurement of anterior alpha asymmetry are discussed. C1 Univ Trier, FB Psychol 1, D-54286 Trier, Germany. Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. NIA, Lab Personal & Cognit, Baltimore, MD 21224 USA. RP Naumann, E (reprint author), Univ Trier, FB Psychol 1, Univ Ring 15, D-54286 Trier, Germany. NR 62 TC 132 Z9 134 U1 4 U2 18 PU CAMBRIDGE UNIV PRESS PI PORT CHESTER PA 110 MIDLAND AVE, PORT CHESTER, NY 10573-9863 USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD SEP PY 2001 VL 38 IS 5 BP 847 EP 857 DI 10.1017/S0048577201001081 PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 472GQ UT WOS:000170975800013 PM 11577908 ER PT J AU Altemus, M Redwine, LS Leong, YM Frye, CA Porges, SW Carter, CS AF Altemus, M Redwine, LS Leong, YM Frye, CA Porges, SW Carter, CS TI Responses to laboratory psychosocial stress in postpartum women SO PSYCHOSOMATIC MEDICINE LA English DT Article DE stress; lactation; oxytocin; allopregnanolone; cortisol; vagal tone ID HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; PITUITARY-ADRENAL AXIS; LACTATING FEMALE RATS; PLASMA OXYTOCIN; SOCIAL SUPPORT; INDUCED ACTH; STIMULATION; BEHAVIOR; VIRGIN; NEUROSTEROIDS AB Objective: Lactation has been associated with attenuated hormonal responses to exercise stress in humans. This study was designed to determine the effect of lactation on hypothalamic-pituitary-adrenal axis, autonomic nervous system, and anxiety responses to psychological stress. Method: The Trier Social Stress Test was administered to 24 lactating women, 13 postpartum nonlactating women, and 14 healthy control women in the early follicular phase of the menstrual cycle. Lactating women were stressed at least 40 minutes after last feeding their infant. Results: ACTH, cortisol, heart rate, diastolic blood pressure, systolic blood pressure, and subjective anxiety ratings were all significantly increased in response to the psychological stress (all p < .0001). There were no differences among the three groups in any of these responses to the stress. However, postpartum nonlactating women did have a persistently higher systolic blood pressure and lower cardiac vagal tone than the lactating women and control subjects. In addition, the typical negative correlation between cardiac vagal tone and heart rate was consistently higher in lactating women than nonlactating postpartum women and controls, which suggests stronger vagal control of heart rate in lactating women. In addition, there was no change in oxytocin or allopregnanolone in response to the stress, and baseline oxytocin and allopregnanolone levels did not differ among the three groups. Conclusions: These results indicate that physiological and subjective responses to social stress are not attenuated in lactating women tested at least one hour after feeding their infant. However, enhanced vagal control of cardiac reactivity was observed in lactating women. In addition, postpartum women who did not lactate showed evidence of increased sympathetic and decreased parasympathetic nervous system tone. C1 Cornell Univ, Weill Med Coll, Dept Psychiat, New York, NY 10021 USA. VA San Diego Hlth Care Syst, San Diego, CA USA. NIMH, Intramural Res Program, Clin Sci Lab, Bethesda, MD 20892 USA. SUNY Albany, Dept Psychol, Albany, NY 12222 USA. Univ Illinois, Sch Med, Dept Psychiat, Chicago, IL USA. RP Altemus, M (reprint author), Cornell Univ, Weill Med Coll, Dept Psychiat, Box 244,1300 York Ave, New York, NY 10021 USA. OI Redwine, Laura/0000-0001-7633-2034 FU NIMH NIH HHS [K05-MH 01050] NR 53 TC 109 Z9 110 U1 1 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 SEP-OCT PY 2001 VL 63 IS 5 BP 814 EP 821 PG 8 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 475KQ UT WOS:000171163500015 PM 11573030 ER PT J AU Gerschenson, M Paik, CY Gaukler, EL Diwan, BA Poirier, MC AF Gerschenson, M Paik, CY Gaukler, EL Diwan, BA Poirier, MC TI Cisplatin exposure induces mitochondrial toxicity in pregnant rats and their fetuses SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE oxidative phosphorylation; mitochondria; DNA; fetus; electron microscopy; cis-diamminedicholorplatinum(II); DNA adduct; perinatal ID ACUTE-RENAL-FAILURE; INDUCED NEPHROTOXICITY; FETAL MITOCHONDRIAL; OVARIAN-CARCINOMA; PATAS MONKEYS; GENOMIC DNA; CELLS; CHEMOTHERAPY; TISSUES; DAMAGE AB High levels of cis-diamminedicholorplatinum II (cisplatin)-DNA adducts have previously been observed at term in mitochondrial DNA (mtDNA) from organs of pregnant rats, and from their offspring, after administration of a single injection of cisplatin 15 mg/kg body weight (bw) to the pregnant rat on day 18 of gestation. The consequences of such DNA damage may be clinically relevant as cisplatin is given to pregnant women discovered to have ovarian cancer during pregnancy. In this study, kidneys, livers, and brains of exposed pregnant rats and their offspring were examined for mitochondrial functional integrity. Consistent with previous literature, the most severe toxicity occurred in maternal kidney, where oxidative phosphorylation (OXPHOS) enzyme activities were significantly (similar to 50%) impaired for Complexes II, III, and IV, mtDNA levels in drug-exposed animals were higher than in the unexposed controls, and abnormal mitochondrial morphology was observed by transmission electron microscopy (TEM). In fetal kidneys and livers, cisplatin exposure did not alter mitochondrial morphology or mtDNA quantity, but specific activities of OXPHOS Complexes II and IV were significantly decreased. Fetal brain sustained no discernible mitochondrial toxicity. Therefore, cisplatin-induced mitochondrial toxicity in maternal rat kidney is severe, while damage to mitochondria in fetal kidney and liver, occurring as a result of the transplacental drug exposure, appears to be mild. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NCI, Carcinogen DNA Interact Sect, Div Basic Sci, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Intramural Res Support Program, Ft Detrick, MD 21702 USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, Div Basic Sci, NIH, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 35 TC 6 Z9 7 U1 1 U2 1 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 SEP-OCT PY 2001 VL 15 IS 5 BP 525 EP 531 DI 10.1016/S0890-6238(01)00156-3 PG 7 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 473PY UT WOS:000171055600006 PM 11780959 ER PT J AU Edskes, HK AF Edskes, HK TI Protein-based inheritance in Saccharomyces cerevisiae: [URE3] as a prion form of the nitrogen regulatory protein Ure2 SO RESEARCH IN MICROBIOLOGY LA English DT Review DE prion; Saccharomyces cerevisiae; [URE3] element; Ure2 nitrogen regulatory protein ID YEAST SUP35 PROTEIN; CATABOLITE REPRESSION; IN-VITRO; GLUTAMATE-DEHYDROGENASE; PSI+ PRION; TOR; PROPAGATION; GENE; ASSIMILATION; DETERMINANT AB The [URE3] element of the yeast Saccharomyces cerevisiae results from the presence of an altered form of the nitrogen regulatory protein Ure2. This altered form acts as an infectious protein (prion), Genes affecting [URE3] initiation and propagation should give valuable information about prion diseases as well as other conformational diseases. (C) 2001 Published by Editions scientifiques et medicales Elsevier SAS. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Edskes, HK (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bldg 8,Room 225,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA. NR 51 TC 3 Z9 3 U1 0 U2 4 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD SEP PY 2001 VL 152 IS 7 BP 605 EP 612 DI 10.1016/S0923-2508(01)01239-6 PG 8 WC Microbiology SC Microbiology GA 487QK UT WOS:000171886600002 PM 11605980 ER PT J AU Elvevag, B Weinstock, DM Akil, M Kleinman, JE Goldberg, TE AF Elvevag, B Weinstock, DM Akil, M Kleinman, JE Goldberg, TE TI A comparison of verbal fluency tasks in schizophrenic patients and normal controls SO SCHIZOPHRENIA RESEARCH LA English DT Article DE verbal fluency; schizophrenia ID SEMANTIC MEMORY; IMPAIRMENT; RETRIEVAL; THOUGHT AB Previous studies have reported significant impairment on verbal fluency tasks (semantic and letter) among schizophrenic subjects. However, the possibility of specific categorical deficits has not been adequately investigated. Nor have the effects of task duration, the stability between testing sessions, and the relationship between intelligence and performance on fluency been thoroughly studied. We performed a series of 3 min fluency tasks (semantic/syntactic and letter) to determine whether duration specific or category-specific differences exist between schizophrenic subjects and normal controls. Each subject was tested at three different times as a means of estimating word pool and assessing the stability of fluency output. Subjects were asked to generate exemplars from each of four semantic/syntactic categories (animals, tools, common nouns and verbs) and three letters (G, E and T). Data from 13 schizophrenic subjects and 15 sex-, age- and pre-morbid-IQ-matched control subjects revealed that patients' overall performance on both the semantic and letter fluency tasks was impaired. While differential impairment on specific semantic categories was noted between groups, no differential effects relating to task duration or testing session were present. Further, by comparing the number of novel words produced in the three testing sessions, we found the groups to be equivalent, a finding we take to suggest that schizophrenic patients' lexicon is intact. Covarying current IQ eliminated the group difference robustly for letter fluency, while only marginally for semantic fluency. Our data revealed the presence of impairment in semantic and letter fluency tasks in schizophrenic patients consistent with previous reports, and also that patients were differentially impaired on semantic categories. (C) 2001 Elsevier Science B.V. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Room 4S235,MSC 1379,Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 45 Z9 46 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP 1 PY 2001 VL 51 IS 2-3 BP 119 EP 126 DI 10.1016/S0920-9964(00)00053-0 PG 8 WC Psychiatry SC Psychiatry GA 470AB UT WOS:000170847300002 PM 11518632 ER PT J AU Dreher, JC Banquet, JP Allilaire, JF Paillere-Martinot, ML Dubois, B Burnod, Y AF Dreher, JC Banquet, JP Allilaire, JF Paillere-Martinot, ML Dubois, B Burnod, Y TI Temporal order and spatial memory in schizophrenia: a parametric study SO SCHIZOPHRENIA RESEARCH LA English DT Article DE frontal lobe; spatial working memory; executive processes; schizophrenia; encoding; retention; retrieval; rehearsal ID DORSOLATERAL PREFRONTAL CORTEX; MONOZYGOTIC TWINS DISCORDANT; FIRST-EPISODE SCHIZOPHRENIA; WORKING-MEMORY; FRONTAL-LOBE; DOPAMINE-RECEPTORS; NEGATIVE SYMPTOMS; DEFICITS; DYSFUNCTION; PERFORMANCE AB Spatial working memory has been shown to be impaired in schizophrenia. In contrast, memory for temporal order has been poorly studied in patients with schizophrenia. The aim of this study was to compare and to further characterize spatial working memory and sequence reproduction deficits in patients with schizophrenia under stable medication by manipulating cues (pattern versus sequence), delay, set-size and response type in various recall and recognition tasks. This allowed us to dissociate processes as encoding, retention and retrieval and to compare the performance of patients with schizophrenia to the performance of patients with prefrontal lesions, who have been previously tested in the same tasks. Our results show that increase of the set-size and of the delay decreased performance of both groups, and that these factors had larger detrimental effects in patients with schizophrenia than in controls. Furthermore, comparison between tasks revealed retention and retrieval deficits in schizophrenia. Finally, patients with schizophrenia showed impairments not only in recall but also in sequence recognition tasks with delay. This is in contrast to patients with prefrontal lesions, who have previously been shown to have intact recognition of sequences after a delay. These results suggest that the working memory deficit in schizophrenia cannot be restricted to a prefrontal dysfunction. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Paris 06, INSERM, U483, Paris, France. Hop La Pitie Salpetriere, Adult Psychiat Sect, Paris, France. Hop La Pitie Salpetriere, INSERM, U289, Paris, France. RP Dreher, JC (reprint author), NIMH, Unit Integrat Neuroimaging, Clin Brain Disorders Branch, Bldg 10,Room 4C-101,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 58 TC 21 Z9 21 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD SEP 1 PY 2001 VL 51 IS 2-3 BP 137 EP 147 DI 10.1016/S0920-9964(00)00151-1 PG 11 WC Psychiatry SC Psychiatry GA 470AB UT WOS:000170847300004 PM 11518634 ER PT J AU Nadareishvili, ZG Koziol, DE Szekely, B Ruetzler, C LaBiche, R McCarron, R DeGraba, TJ AF Nadareishvili, ZG Koziol, DE Szekely, B Ruetzler, C LaBiche, R McCarron, R DeGraba, TJ TI Increased CD8(+) T cells associated with Chlamydia pneumoniae in symptomatic carotid plaque SO STROKE LA English DT Article DE carotid artery diseases; Chlamydia pneumoniae; leukocytes; plaque ID HUMAN ATHEROSCLEROTIC PLAQUES; CORONARY HEART-DISEASE; INFECTION; ANTIGENS; ARTERY; STENOSIS; INFLAMMATION; LYMPHOCYTES; EXPRESSION; MOLECULES AB Background and Purpose-The presence of Chlamydia pneumoniae has been reported in carotid atheroma, but its causative effect in the activation of an atherosclerotic plaque to a prothrombotic state remains unproved. Antigen-mediated activation of T lymphocytes within plaque may represent a mechanism by which infection can result in plaque conversion. The goal of the present study was to characterize the T-cell subtype profile related to the presence of C pneumoniae in patients with symptomatic versus asymptomatic carotid atherosclerosis. Methods-We studied 14 plaques (5 symptomatic and 9 asymptomatic) positive for C pneumoniae confirmed by polymerase chain reaction and 14 plaques (6 symptomatic and 8 asymptomatic) from age- and stenosis-matched patients negative for C pneumoniae by polymerase chain reaction. T-cell subpopulations of T-helper. T-cytotoxic, and T-memory lymphocytes were identified through indirect enzyme immunohistochemistry with anti-CD3+, anti-CD4+, anti-CD8+, and anti-CD45RO+ monoclonal antibodies, respectively. Results are expressed as the number of positive cells per millimeter squared. Results-In the absence of C pneumoniae, symptomatic plaque,, had a modest but significant increase of CD3+ (89.6 versus 55.3, P = 0.013), CD4+ (57.3 versus 32.7, P = 0.01), and CD45RO+ (82.8 versus 43.7, P = 0.007), but not CD8+ T cells (28.5 versus 25.5, P = 0.245) compared with asymptomatic. However, in the presence of C pneumoniae, there was significant increase of all T-lymphocyte subtypes in symptomatic plaques, including CD8+ (76.8 versus 30.3, P = 0.03), CD3+ (192.1 versus 80.4, P = 0.004), CD4+ (111.9 versus 37.9, P = 0.003), and CD45RO+ (120.2 versus 72.9, P = 0.003) cells compared with asymptomatic plaques. With use of 2-way ANOVA, both the presence of chlamydia and symptoms were associated with significantly higher T-cell counts (P < 0.005 for all subtypes). Conclusions-Although all patients with symptomatic disease show a modest elevation in the concentration of intraplaque lymphocytes, a preferential increase in CD8+ class I-restricted T cells is observed in symptomatic carotid plaque positive for C pneumoniae. These data provide incentive to further explore the role of Chlamydia in the modification of immune-mediated mechanisms in active atherosclerotic plaque. C1 NINDS, NIH, Stroke Branch, Bethesda, MD 20892 USA. RP DeGraba, TJ (reprint author), NINDS, NIH, Stroke Branch, 36 Convent Dr,MSC 4128,Bldg 36,Room 4A-03, Bethesda, MD 20892 USA. FU FIC NIH HHS [1F05-TW-05469-01] NR 35 TC 24 Z9 27 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 SEP PY 2001 VL 32 IS 9 BP 1966 EP 1972 DI 10.1161/hs0901.095633 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 471KX UT WOS:000170929500006 PM 11546882 ER PT J AU Lev, MH Segal, AZ Farkas, J Hossain, ST Putman, C Hunter, GJ Budzik, R Harris, GJ Buonanno, FS Ezzeddine, MA Chang, YC Koroshetz, WJ Gonzalez, RG Schwamm, LH AF Lev, MH Segal, AZ Farkas, J Hossain, ST Putman, C Hunter, GJ Budzik, R Harris, GJ Buonanno, FS Ezzeddine, MA Chang, YC Koroshetz, WJ Gonzalez, RG Schwamm, LH TI Utility of perfusion-weighted CT imaging in acute middle cerebral artery stroke treated with intra-arterial thrombolysis - Prediction of final infarct volume and clinical outcome SO STROKE LA English DT Article DE cerebral ischemia; stroke; thrombolysis; tomography, perfusion-weighted ID ACUTE ISCHEMIC STROKE; COMPUTED-TOMOGRAPHY; HYPERACUTE STROKE; BLOOD-FLOW; THERAPY; ANGIOGRAPHY; BRAIN; VARIABILITY; VALIDATION; DIFFUSION AB Background and Purpose-The goal of this study was to evaluate the utility of perfusion-weighted CT (PWCT) in predicting final infarct volume and clinical outcome in patients with acute middle cerebral artery (MCA) stroke. Methods-Twenty-two consecutive patients with MCA stem occlusion who underwent intra-arterial thrombolysis within 6 hours of stroke onset had noncontrast CT and CT angiography with whole-brain PWCT imaging before treatment. Infarct volumes were computed from the initial PWCT and follow-up scans; clinical outcome was measured with the modified Rankin scale. Results-Initial PWCT lesion volumes correlated significantly with final infarct volume (P = 0.0002) and clinical outcome (P = 0.01). For the 10 patients with complete recanalization, the relationship between initial and final lesion volume was especially strong (R-2 = 0.94, P < 0.0001, slope of regression line = 0.92). For those without complete recanalization, there was progression of lesion volume on follow-up imaging (R-2 = 0.50, P = 0.01, slope of regression line = 1.61). All patients with either initial PWCT lesion volumes >100 mL or no recanalization had poor outcomes (Rankin scores, 4 to 6). Mean admission NIH Stroke Scale scores and mean lesion volumes in the poor outcome group were significantly different compared with the good or fair outcome (Rank-in scores, 0 to 3) group (21 +/- 4 versus 17 +/- 5, P = 0.05, and 106 +/- 79 versus 29 +/- 37 mL, P = 0.01). Patients with initial volumes <100 mL and partial or complete recanalization all had good (Rankin scores, 0 to 2) or fair (Rankin score, 3) outcomes. Conclusions-Lesion volumes on admission PWCT images approximate final infarct volume for patients with early complete recanalization of MCA stem occlusion. For those without complete recanalization, there is subsequent enlargement of lesion volume on follow-up. Initial PWCT lesion volumes also have predictive value; volumes >100 mL are associated with a poor clinical outcome. In these highly selected patients, initial PWCT lesion volume was a stronger predictor of clinical outcome than was initial NIH Stroke Scale score. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol GRB285, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Lev, MH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol GRB285, POB 9657, Boston, MA 02114 USA. OI Schwamm, Lee/0000-0003-0592-9145 FU NCRR NIH HHS [RR-13213]; NINDS NIH HHS [NS-34626] NR 32 TC 216 Z9 222 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2001 VL 32 IS 9 BP 2021 EP 2027 DI 10.1161/hs0901.095680 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 471KX UT WOS:000170929500017 PM 11546891 ER PT J AU Wang, Y Chang, CF Morales, M Chou, J Chen, HL Chiang, YH Lin, SZ Cadet, JL Deng, XL Wang, JY Chen, SY Kaplan, PL Hoffer, BJ AF Wang, Y Chang, CF Morales, M Chou, J Chen, HL Chiang, YH Lin, SZ Cadet, JL Deng, XL Wang, JY Chen, SY Kaplan, PL Hoffer, BJ TI Morphogenetic protein-6 reduces ischemia-induced brain damage in rats SO STROKE LA English DT Article DE apoptosis; bone morphogenetic proteins; cerebral ischemia; neuroprotection; rats ID MIDDLE CEREBRAL-ARTERY; NERVOUS-SYSTEM; IN-VIVO; EXPRESSION; INJURY; OCCLUSION; RECEPTORS; NEURONS; MODEL; ROLES AB Background and Purpose-Bone morphogenetic protein-6 (BMP6) and its receptors are expressed in adult and fetal brain. Receptors for BMP6 are upregulated in adult brain after injury, leading to the suggestion that BMP6 is involved in the physiological response to neuronal injury. The purpose of this study was to determine whether there was a neuroprotective effect of BMP6 in vivo and in vitro. Methods-Lactate dehydrogenase and microtubule-associated protein-2 (MAP-2) activities were used to determine the protective effect of BMP6 against H2O2 in primary cortical cultures. The neuroprotective effects of BMP6 were also studied in chloral hydrate-anesthetized rats. BMP6 or vehicle was injected into right cerebral cortex before transient right middle cerebral artery (MCA) ligation. Animals were killed for triphenyl-tetrazolium chloride staining, caspase-3 immunoreactivity and enzymatic assays, and TUNEL assay. A subgroup of animals were used for locornotor behavioral assays. Results-Application of H2O2 increased lactate dehydrogenase activity and decreased the density of MAP-2(+) neurons in culture. Both responses were attenuated by BMP6 pretreatment. Complementary in vivo studies showed that pretreatment with BMP6 increased motor performance and generated less cerebral infarction induced by MCA ligation/reperfusion in rats. Pretreatment with BMP6 did not alter cerebral blood flow or physiological parameters. There was decreased ischemia-induced caspase-3 immunoreactivity, caspase-3 enzymatic activity, and density of TUNEL-positive cells in ischemic cortex in BMP6-treated animals. Conclusions-BMP6 reduces ischemia/reperfusion injury, perhaps by attenuating molecular events underlying apoptosis. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Natl Def Med Ctr, Dept Physiol, Taipei, Taiwan. Natl Def Med Ctr, Tri Serv Gen Hosp, Taipei, Taiwan. Creat Biomol Inc, Boston, MA USA. RP Wang, Y (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 26 TC 53 Z9 63 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD SEP PY 2001 VL 32 IS 9 BP 2170 EP 2178 DI 10.1161/hs0901.095650 PG 9 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 471KX UT WOS:000170929500045 PM 11546913 ER PT J AU Beard, WA Wilson, SH AF Beard, WA Wilson, SH TI DNA lesion bypass polymerases open up SO STRUCTURE LA English DT Review ID THYMINE-THYMINE DIMER; CRYSTAL-STRUCTURES; ESCHERICHIA-COLI; NUCLEOTIDE INCORPORATION; GENE ENCODES; XERODERMA-PIGMENTOSUM; LARGE FRAGMENT; BETA; FIDELITY; ETA AB Structures of catalytic fragments of two DNA lesion bypass DNA polymerases, yeast DNA polymerase eta and an archeon DinB homolog, have recently been solved. These structures share several common architectural and structural features observed in other DNA polymerases, including a hand-like architecture with fingers, palm, and thumb subdomains. The new structures provide the first structural insights into DNA lesion bypass. The fingers and thumb are smaller than those in other DNA polymerases. Modeled substrates suggest that the fingers in the vicinity of the incoming nucleotide is closed, a conformation not previously observed for an unliganded polymerase. However, the template binding pocket appears to be more open, indicating that for DNA polymerase eta, a covalently linked thymine-thymine dinner could be accommodated. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 44 TC 19 Z9 19 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD SEP PY 2001 VL 9 IS 9 BP 759 EP 764 DI 10.1016/S0969-2126(01)00646-3 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 477KM UT WOS:000171282800002 PM 11566124 ER PT J AU French, J Storer, RD Donehower, LA AF French, J Storer, RD Donehower, LA TI The nature of the heterozygous Trp53 knockout model for identification of mutagenic carcinogens SO TOXICOLOGIC PATHOLOGY LA English DT Article DE p53 haploinsufficiency; risk assessment; C57BL/6 (N5) mouse; loss of heterozygosity ID P53-DEFICIENT MICE; RODENT CARCINOGENICITY; INDUCED TUMORIGENESIS; P53; CANCER; MOUSE; BIOASSAYS; TUMORS; PROGRESSION; MUTATIONS AB The heterozygous Trp53 null allele C57BL/6 (N5) mouse is susceptible to the rapid development of neoplasia by mutagenic carcinogens relative to control strains. This mouse model of chemical carcinogenesis demonstrates 1) dose-related rapid induction of tumors (26 wks), 2) multiple sites of carcinogen-specific tissue susceptibility, and 3) carcinogen-induced loss of heterozygosity involving the Trp53 wild-type allele or a p53 haploinsufficiency permitting mutation of other critical protooncogenes and/or inactivation of tumor suppressor genes driving tumorigenesis. Demonstration of mutation or loss of heterozygosity involving the Trp53 locus is consistent with a common finding in human cancers and supports extrapolation between rodents and humans. Using diverse experimental protocols, almost all mutagenic rodent carcinogens (including all mutagens that are carcinogenic to humans), but not nonmutagenic rodent carcinogens, induce tumors within 26 weeks of continuous exposure. These characteristics and results indicate that the mouse heterozygous for the Trp53 null allele may be of significant use for the prospective identification of mutagenic carcinogens of potential risk to human health. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Merck Res Labs, W Point, PA USA. Baylor Coll Med, Houston, TX 77030 USA. RP French, J (reprint author), NIEHS, NIH, POB 12233,MD F1-05, Res Triangle Pk, NC 27709 USA. NR 36 TC 44 Z9 46 U1 0 U2 3 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 SEP 1 PY 2001 VL 29 SU 1 BP 24 EP 29 DI 10.1080/019262301753178456 PG 6 WC Pathology; Toxicology SC Pathology; Toxicology GA 558DR UT WOS:000175951500005 PM 11695559 ER PT J AU Storer, RD French, JE Haseman, J Hajian, G LeGrand, EK Long, GG Mixson, LA Ochoa, R Sagartz, JE Soper, KA AF Storer, RD French, JE Haseman, J Hajian, G LeGrand, EK Long, GG Mixson, LA Ochoa, R Sagartz, JE Soper, KA TI p53(+/-) Hemizygous knockout mouse: Overview of available data SO TOXICOLOGIC PATHOLOGY LA English DT Article DE p53 defficient; bioassay; short-term; 26-weeks; alternatives; carcinogenicity; testing ID HETEROZYGOUS P53-DEFICIENT MICE; CARCINOGENICITY BIOASSAYS; INDUCED TUMORIGENESIS; P53; TUMORS; INDUCTION; CANCER; MODEL; PHARMACEUTICALS; DEFICIENT AB The performance of the p53(+/-) transgenic (knockout) mouse model was evaluated through review of the data from 31 short-term carcinogenicity studies with 21 compounds tested as part of the International Life Sciences Institute's (ILSI) Alternatives to Carcinogenicity Testing (ACT) project, together with data from other studies which used comparable protocols. As expected based on the hypothesis for the model, a significant number (12/16 or 75%) of the genotoxic human and/or rodent carcinogens tested were positive and the positive control, p-cresidine, gave reproducible responses across laboratories (18/19 studies positive in bladder). An immunosuppressive human carcinogen, cyclosporin A, was positive for lymphomas but produced a similar response in wild type mice. Two hormones that are human tumorigens, diethylstilbestrol and 17beta-estradiol, gave positive and equivocal results, respectively, in the pituitary with p53-deficient mice showing a greater incidence of proliferative lesions than wild type. None of the 22 nongenotoxic rodent carcinogens that have been tested produced a positive response but 2 compounds in this category, chloroform and diethylhexylphthalate, were judged equivocal based on effects in liver and kidney respectively. Four genotoxic noncarcinogens and 6 nongenotoxic, noncarcinogens were also negative. In total (excluding compounds with equivocal results), 42 of 48 compounds or 88% gave results that were concordant with expectations. The technical lessons learned from the ILSI ACT-sponsored testing in the p53(+/-) model are discussed. C1 Merck & Co Inc, Merck Res Labs, Dept Safety Assessment, W Point, PA 19486 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07083 USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. Eli Lilly & Co, Greenfield, IN 46140 USA. Pfizer Inc, Groton, CT 06340 USA. Monsanto Co, St Louis, MO 63141 USA. RP Storer, RD (reprint author), Merck & Co Inc, Merck Res Labs, Dept Safety Assessment, WP45-311, W Point, PA 19486 USA. NR 43 TC 73 Z9 73 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 SEP 1 PY 2001 VL 29 SU 1 BP 30 EP 50 DI 10.1080/019262301753178465 PG 21 WC Pathology; Toxicology SC Pathology; Toxicology GA 558DR UT WOS:000175951500006 PM 11695560 ER PT J AU Tennant, RW Stasiewicz, S Eastin, WC Mennear, JH Spalding, JW AF Tennant, RW Stasiewicz, S Eastin, WC Mennear, JH Spalding, JW TI The Tg.AC (v-Ha-ras) Transgenic mouse: Nature of the model SO TOXICOLOGIC PATHOLOGY LA English DT Article DE chemical carcinogens; alternative carcinogen bioassay; ras gene; transgenic mouse ID CENTER-DOT-AC; SKIN CARCINOGENESIS; MICE; BIOASSAYS; TUMORS; PHARMACEUTICALS; RESPONSIVENESS; MUTATIONS; LESIONS; RISK AB The Tg.AC (v-Ha-ras) transgenic mouse model provides a reporter phenotype of skin papillomas in response to either genotoxic or nongenotoxic carcinogens. In common with the conventional bioassay, the Tg. AC model responds to known human carcinogens and does not respond to noncarcinogens. It also does not respond to most chemicals that are positive in conventional bioassays principally at sites of high spontaneous tumor incidence. The mechanism of response of the Tg. AC model is related to the structure and genomic position of the transgene and the induction of transgene expression through specific mediated interactions between the chemicals and target cells in the skin. C1 NIEHS, Lab Environm Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Tennant, RW (reprint author), NIEHS, Lab Environm Carcinogenesis & Mutagenesis, 111 TW Alexander Dr,POB 12233 MD F1-05, Res Triangle Pk, NC 27709 USA. EM tennant@niehs.nih.gov NR 32 TC 27 Z9 27 U1 0 U2 2 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 SEP 1 PY 2001 VL 29 SU 1 BP 51 EP 59 DI 10.1080/019262301753178474 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 558DR UT WOS:000175951500007 PM 11695562 ER PT J AU Eastin, WC Mennear, JH Tennant, RW Stoll, RE Branstetter, DG Bucher, JR McCullough, B Binder, RL Spalding, JW Mahler, JF AF Eastin, WC Mennear, JH Tennant, RW Stoll, RE Branstetter, DG Bucher, JR McCullough, B Binder, RL Spalding, JW Mahler, JF TI Tg.AC genetically altered mouse: Assay working group overview of available data SO TOXICOLOGIC PATHOLOGY LA English DT Article DE Tg.AC mouse; hemizygous; homozygous; papilloma; short-term; 26-weeks; carcinogenicity; ras gene; transgenic mouse ID HA-RAS GENE; TRANSGENIC MICE; KERATINOCYTE DIFFERENTIATION; SKIN CARCINOGENESIS; SHORT-TERM; MODEL; EXPRESSION; BIOASSAYS; PROGRAM; OXYMETHOLONE AB In a Government/Industry/Academic partnership to evaluate alternative approaches to carcinogenicity testing, 21 pharmaceutical agents representing a variety of chemical and pharmacological classes and possessing known human and or rodent carcinogenic potential were selected for study in several rodent models. The studies from this partnership project, coordinated by the International Life Sciences Institute, provide additional data to better understand the models' limitations and sensitivity in identifying carcinogens. The results of these alternative model studies were reviewed by members of Assay Working Groups (AWG) composed of scientists from government and industry with expertise in toxicology, genetics, statistics, and pathology. The Tg.AC genetically manipulated mouse was one of the models selected for this project based on previous studies indicating that Tg.AC mice seem to respond to topical application of either mutagenic or nonmutagenic carcinogens with papilloma formation at the site of application. This communication describes the results and AWG interpretations of studies conducted on 14 chemicals administered by the topical and oral (gavage and/or diet) routes to Tg.AC genetically manipulated mice. Cyclosporin A, an immunosuppresant human carcinogen, ethinyl estradiol and diethylstilbestrol (human hormone carcinogens) and clofibrate, an hepatocarcinogenic peroxisome proliferator in rodents, were considered clearly positive in the topical studies. In the oral studies, ethinyl estradiol and diethylstilbestrol were negative, cyclosporin was considered equivocal, and results were not available for the clofibrate study. Of the 3 genotoxic human carcinogens (phenacetin, melphalan, and cyclophosphamide), phenacetin was negative by both the topical and oral routes. Melphalan and cyclophosphamide are, respectively, direct and indirect DNA alkylating agents and topical administration of both caused equivocal responses. With the exception of clofibrate, Tg.AC mice did not exhibit tumor responses to the rodent carcinogens that were putative human noncarcinogens, (di(2-ethylhexyl) phthalate, methapyraline HCl, phenobarbital Na, reserpine, sulfamethoxazole or WY-14643, or the nongenotoxic, noncarcinogen, sulfisoxazole) regardless of route of administration. Based on the observed responses in these studies, it was concluded by the AWG that the Tg.AC model was not overly sensitive and possesses utility as an adjunct to the battery of toxicity studies used to establish human carcinogenic risk. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Pharmacia & Upjohn Co, Kalamazoo, MI 49007 USA. Aventis Pharma, Collegeville, PA 19426 USA. Procter & Gamble Co, Cincinnati, OH 45217 USA. RP Eastin, WC (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27713 USA. NR 40 TC 27 Z9 30 U1 0 U2 1 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 SEP 1 PY 2001 VL 29 SU 1 BP 60 EP 80 DI 10.1080/019262301753178483 PG 21 WC Pathology; Toxicology SC Pathology; Toxicology GA 558DR UT WOS:000175951500008 PM 11695563 ER PT J AU Venkatachalam, S Tyner, SD Pickering, CR Boley, S Recio, L French, JE Donehower, LA AF Venkatachalam, S Tyner, SD Pickering, CR Boley, S Recio, L French, JE Donehower, LA TI Is p53 haploinsufficient for tumor suppression? Implications for the p53(+/-)mouse model in carcinogenicity testing SO TOXICOLOGIC PATHOLOGY LA English DT Article DE apoptosis; carcinogenicity testing; genotoxic carcinogens; knockout mice; loss of heterozygosity; mouse cancer model; tumor suppressor ID WILD-TYPE P53; P53-DEFICIENT MICE; TRANSGENIC MICE; IN-VIVO; CANCER; MOUSE; TUMORIGENESIS; BIOASSAYS; RADIATION; GENE AB The p53 tumor suppressor gene has been shown to be critical in preventing cancer in humans and mice. We have generated and extensively characterized p53-deficient mice lacking one (p53(+/-)) or both (p53(-/-)) p53 alleles. The p53-deficient mice are much more susceptible to an array of different tumor types than their wild-type (p53(+/+)) littermates. The enhanced tumor susceptibility of the p53(+/-) mice has made them one of several transgenic mouse models that are being considered as substitutes for standard 2-year rodent carcinogenicity assays. In order to fully exploit this model, it will be important to understand some of the basic biological and molecular mechanisms that underlie its enhanced tumor susceptibility. With this in mind, we have explored the fate of the remaining wild-type p53 allele in spontaneously arising p53(+/-) tumors and have shown that over half of these tumors retain an intact, functional wild-type p53 allele. This suggests that p53 is haploinsufficient for tumor suppression and that mere reduction in p53 dosage is sufficient to promote cancer formation. To support the idea that p53 is indeed a haploinsufficient tumor suppressor, we show here that normal p53(+/-) cells exhibit reduced parameters of growth control and stress response compared to their p53(+/+) counterparts. We hypothesize that the reduced p53 dosage in the p53(+/-) cells provides an environment more conducive to the development of further oncogenic lesions and the initiation of a tumor. Finally, we have assessed p53 loss of heterozygosity (LOH) in carcinogen-induced p53(+/-) tumors and have found that some agents induce tumors that almost invariably exhibit p53 LOH, whereas other agents induce tumors that often retain the wild-type p53 allele. Our preliminary data suggest that LOH is dependent on both the mechanism of genotoxicity of the agent utilized and the tissue type targeted. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Cell & Mol Biol Program, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Donehower, LA (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 33 TC 53 Z9 56 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 SEP 1 PY 2001 VL 29 SU 1 BP 147 EP 154 DI 10.1080/019262301753178555 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 558DR UT WOS:000175951500015 PM 11695551 ER PT J AU Williams, KD Dunnick, J Horton, J Greenwell, A Eldridge, SR Elwell, M Sills, RC AF Williams, KD Dunnick, J Horton, J Greenwell, A Eldridge, SR Elwell, M Sills, RC TI p-nitrobenzoic acid alpha(2u) nephropathy in 13-week studies is not associated with renal carcinogenesis in 2-year feed studies SO TOXICOLOGIC PATHOLOGY LA English DT Article DE p-nitrobenzoic acid; hyaline droplets; alpha(2u)-globulin; nephropathy; cell proliferation; renal neoplasms; kidney ID CELL NUCLEAR ANTIGEN; MALE-RAT KIDNEY; D-LIMONENE; ALPHA-2U-GLOBULIN; PROLIFERATION; MARKER AB The objective of this study was to characterize the renal toxicity and carcinogenicity of p-nitrobenzoic acid in F344 rats. Dose levels in 13-week and 2-year studies ranged from 630-10,000 ppm and 1,250-5,000 ppm, respectively. At 13 weeks, renal lesions included minimal to mild hyaline droplet accumulation in male rats and karyomegaly in male and female rats. At 2 years, renal lesions included proximal tubule epithelial cell hyperplasia in male rats and oncocytic hyperplasia in high-dose male and female rats, and a decreased severity of nephropathy in males and females. The hyaline droplets in renal tubular epithelial cells of male rats at 13 weeks were morphologically similar to those described in alpha(2u)-globulin nephropathy. Using immunohistochemical methods, alpha(2u)-globulin accumulation was associated with the hyaline droplets. In addition, at 13 weeks, cell proliferation as detected by PCNA immunohistochemistry was significantly increased in males exposed to 5,000 and 10,000 ppm when compared to controls. Cytotoxicity associated with alpha(2u)-globulin nephropathy such as single-cell necrosis of the P2 segment epithelium or accumulation of granular casts in the outer medulla did not occur in the 13-week study. In addition, chronic treatment related nephrotoxic lesions attributed to accumulation of alpha(2u)-globulin such as linear foci of mineralization within the renal papilla, hyperplasia of the renal pelvis urothelium and kidney tumors were not observed. Although there was histologic evidence of alpha(2u)-globulin accumulation in male rats at 13 weeks, the minimal severity of nephropathy suggests that the degree of cytotoxicity was below the threshold, which would contribute to the development of renal tumors at 2 years. C1 Natl Inst Environm Hlth Sci, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. Pathol Assoc Int, Frederick, MD 21701 USA. Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA. RP Sills, RC (reprint author), Natl Inst Environm Hlth Sci, Environm Toxicol Program, MD B3-08,111 Alexander Drive, Res Triangle Pk, NC 27709 USA. EM sills@niehs.nih.gov NR 21 TC 5 Z9 5 U1 1 U2 3 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 SEP-OCT PY 2001 VL 29 IS 5 BP 507 EP 513 DI 10.1080/019262301317226302 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 574KM UT WOS:000176888500002 PM 11695567 ER PT J AU Nold, JB Keenan, KP Nyska, A Cartwright, ME AF Nold, JB Keenan, KP Nyska, A Cartwright, ME TI Society of toxicologic pathology position paper: Diet as a variable in rodent toxicology and carcinogenicity studies SO TOXICOLOGIC PATHOLOGY LA English DT Article ID SPRAGUE-DAWLEY RATS; CALORIC RESTRICTION; BIOASSAY C1 Pathol Associates Inc, Durham, NC 27713 USA. Merck Res Labs, Dept Safety Assessment & Biometr, W Point, PA 19486 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Schering Plough Res Inst, Lafayette, NJ 07848 USA. RP Nold, JB (reprint author), Pathol Associates Inc, 4915 D Prospectus Drive, Durham, NC 27713 USA. NR 8 TC 13 Z9 13 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 SEP-OCT PY 2001 VL 29 IS 5 BP 585 EP 586 DI 10.1080/019262301317226393 PG 2 WC Pathology; Toxicology SC Pathology; Toxicology GA 574KM UT WOS:000176888500011 PM 11695576 ER PT J AU Laithwaite, JE Benn, SJ Marshall, WS FitzGerald, DJ LaMarre, J AF Laithwaite, JE Benn, SJ Marshall, WS FitzGerald, DJ LaMarre, J TI Divergent Pseudomonas exotoxin A sensitivity in normal and transformed liver cells is correlated with low-density lipoprotein receptor-related protein expression SO TOXICON LA English DT Article ID ALPHA(2)-MACROGLOBULIN RECEPTOR; DECREASED EXPRESSION; AERUGINOSA EXOTOXIN; ALPHA-2-MACROGLOBULIN; LRP; DEGRADATION; RESISTANCE; CHAPERONE; MECHANISM; BINDING AB Pseudomonas exotoxin A (PEA) is an extracellular virulence factor produced by the opportunistic human pathogen Pseudomonas aerguinosa. PEA intoxification begins when PEA binds to the low-density lipoprotein receptor-related protein (LRP). The liver is the primary target of systemic PEA, due largely to the high levels of functional LRP expressed by liver cells. Using a H-3-leucine incorporation assay to measure inhibition of protein synthesis we have demonstrated that normal (BNL CL.2) and transformed (BNL. 1ME A7R.1) liver cells exhibit divergent PEA sensitivity; with BNL 1ME A7R.1 cells demonstrating greater PEA sensitivity than their non-transformed counterparts. The receptor-associated protein, a LRP antagonist, decreased PEA toxicity in BNL 1ME A7R.1 cells, confirming the importance of the LRP in PEA intoxification in this cell type. Increased PEA sensitivity in BNL 1ME A7R.1 cells was associated with increased functional cell surface LRP expression, as measured by alpha (2)-macroglobulin binding and internalization studies, and increased LRP mRNA levels, as determined by Northern blot analysis. Interestingly, BNL CL.2 cells were more sensitive than BNL 1ME A7R.1 cells to conjugate and mutant PEA toxins that do not utilize the LRP for cellular entry. These data demonstrate that increased LRP expression is an important mechanism by which PEA sensitivity is increased in BNL 1ME A7R.1 transformed liver cells. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP LaMarre, J (reprint author), Univ Guelph, Dept Biomed Sci, Guelph, ON N1G 2W1, Canada. NR 32 TC 4 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD SEP PY 2001 VL 39 IS 9 BP 1283 EP 1290 DI 10.1016/S0041-0101(00)00260-9 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 446ND UT WOS:000169518600003 PM 11384715 ER PT J AU Busch, MP Glynn, SA Wu, Y McEntire, R Stramer, SL Operskalski, EA Murphy, EL Kleinman, SH AF Busch, MP Glynn, SA Wu, Y McEntire, R Stramer, SL Operskalski, EA Murphy, EL Kleinman, SH TI Demographic correlates of HCV viremia among HCV seropositive donors SO TRANSFUSION LA English DT Meeting Abstract C1 Pacific Blood Syst Inc, Ctr Blood, San Francisco, CA USA. Westat Corp, Rockville, MD USA. Amer Red Cross, Natl Confirmatory Lab, Gaithersburg, MD USA. Univ So Calif, Los Angeles, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Westat Corp, NHLBI Retrovirus Epidemiol Donor Study, Victoria, BC, Canada. NR 0 TC 2 Z9 2 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 SEP PY 2001 VL 41 IS 9 SU S BP 3S EP 3S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800010 ER PT J AU Rios, M Hue-Roye, K Oyen, R Miller, JL Reid, ME AF Rios, M Hue-Roye, K Oyen, R Miller, JL Reid, ME TI Molecular basis of the Joseph-negative phenotype SO TRANSFUSION LA English DT Meeting Abstract C1 New York Blood Ctr, New York, NY 10021 USA. NIDDK, Bethesda, MD USA. NR 0 TC 2 Z9 2 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 SEP PY 2001 VL 41 IS 9 SU S BP 14S EP 14S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800051 ER PT J AU Leitman, SF Browning, J Mason, G Yau, Y Conry-Cantilena, C Bolan, CD AF Leitman, SF Browning, J Mason, G Yau, Y Conry-Cantilena, C Bolan, CD TI Operational impact of using hemochromatosis (HH) subjects as allogeneic blood donors SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 21S EP 21S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800078 ER PT J AU Drew, W Alter, HJ Tegtmeier, GE Miner, RC Busch, MP AF Drew, W Alter, HJ Tegtmeier, GE Miner, RC Busch, MP TI Frequency and duration of plasma viremia in cytomegalovirus (CMV) seroconverters SO TRANSFUSION LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Community Blood Ctr Greater Kansas City, Kansas City, MO USA. Blood Ctr Pacific, San Francisco, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 22S EP 22S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800084 ER PT J AU Halverson, GR Schawalder, A Miller, JL Reid, ME AF Halverson, GR Schawalder, A Miller, JL Reid, ME TI Production of a monoclonal antibody shows the conservation of epitopes on the Dombrock glycoprotein in the great apes SO TRANSFUSION LA English DT Meeting Abstract C1 New York Blood Ctr, New York, NY 10021 USA. NIDDK, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 24S EP 24S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800091 ER PT J AU Leitman, SF Oblitas, JM Bolan, CD AF Leitman, SF Oblitas, JM Bolan, CD TI Crescendo angina during granulocytapheresis in a G-CSF-stimulated donor SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 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 SEP PY 2001 VL 41 IS 9 SU S BP 36S EP 36S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800134 ER PT J AU Stroncek, DF Matthews, C Leitman, SF AF Stroncek, DF Matthews, C Leitman, SF TI Same-day mobilization and collection of granulocytes SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 39S EP 39S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800147 ER PT J AU Bolan, CD Yau, YY Cecco, S Rehak, N Leitman, SF AF Bolan, CD Yau, YY Cecco, S Rehak, N Leitman, SF TI Influence of gender on citrate-related effects during large volume leukapheresis (LVL) SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 40S EP 41S PG 2 WC Hematology SC Hematology GA 472TV UT WOS:000171001800152 ER PT J AU Kissel, K Santoso, S Stroncek, DF Bux, J AF Kissel, K Santoso, S Stroncek, DF Bux, J TI Molecular basis of the human neutrophil alloantigen HNA-2a (NB1, CD177) SO TRANSFUSION LA English DT Meeting Abstract C1 Inst Clin Immunol & Transfus Med, Geissen, Germany. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 41S EP 41S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800153 ER PT J AU Bolan, CD Yau, YY Mason, G Browning, J Conry-Cantilena, C Leitman, SF AF Bolan, CD Yau, YY Mason, G Browning, J Conry-Cantilena, C Leitman, SF TI MCV-guided phlebotomy for hemochromatosis (HH) SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 72S EP 73S PG 2 WC Hematology SC Hematology GA 472TV UT WOS:000171001800273 ER PT J AU Wu, G Jin, S Deng, Z Zhao, T AF Wu, G Jin, S Deng, Z Zhao, T TI Studies of DO gene frequency in the Chinese Han and Uighur nationalities SO TRANSFUSION LA English DT Meeting Abstract C1 Shen Zhen InstTransfus Med, Shen Zhen, Peoples R China. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 102S EP 102S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800390 ER PT J AU Chambers, D Procter, J Muratova, O Cipolone, K Keister, D Shanks, D Magill, A Stroncek, DF AF Chambers, D Procter, J Muratova, O Cipolone, K Keister, D Shanks, D Magill, A Stroncek, DF TI Effects of in vitro Plasmodium falciparum exposure on RBC antigen expression SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, NIAID, Bethesda, MD 20892 USA. USAMC AFRMIS, Bangkok, Thailand. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 103S EP 104S PG 2 WC Hematology SC Hematology GA 472TV UT WOS:000171001800394 ER PT J AU Caruccio, L Cipolone, K Procter, JL Stroncek, D AF Caruccio, L Cipolone, K Procter, JL Stroncek, D TI A novel method using formamide for the elution of antibodies from erythrocytes SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 108S EP 109S PG 2 WC Hematology SC Hematology GA 472TV UT WOS:000171001800414 ER PT J AU Greco, V Cipolone, K Procter, J Stroncek, DF AF Greco, V Cipolone, K Procter, J Stroncek, DF TI Detection of antibodies in acid eluates with gel microcolumns SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 SU S BP 109S EP 109S PG 1 WC Hematology SC Hematology GA 472TV UT WOS:000171001800416 ER PT J AU Rios, M Hue-Roye, K Lee, AH Chiofolo, JT Miller, JL Reid, ME AF Rios, M Hue-Roye, K Lee, AH Chiofolo, JT Miller, JL Reid, ME TI DNA analysis for the Dombrock polymorphism SO TRANSFUSION LA English DT Article ID ANTI-DO(B) AB BACKGROUND: RBC typing for Do(a) and Do(b) is notoriously difficult, and inaccurate typing can predispose patients to hemolytic transfusion reactions. The DO1/DO2 polymorphism is associated with three nucleotide changes: 378 C >T, 624 T >C and 793 A >G. While the 378 C >T- and 624 T >C-containing codons are silent mutations. the 793 A >G polymorphism in codon 265 encodes asparagine for Do, and aspartic acid for Do(b). STUDY DESIGN AND METHODS: Described here are two PCR-RFLP assays, one using the Mnl I site associated with 624C (DO2) and the other altering two nucleotides within the sense primer, which allows recognition of 793G by the Eam 1105 I. RESULTS: The assays have been performed on over 100 samples for which the RBC typing of one or both antigens was known. Eight samples had been historically mistyped by hemagglutination. CONCLUSION: This RFLP assay provides a practical method for typing donor blood for Dombrock alleles. C1 New York Blood Ctr, Immunochem Lab, New York, NY 10021 USA. Winthrop Univ Hosp, Transfus Serv, Mineola, NY 11501 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 15 TC 21 Z9 22 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2001 VL 41 IS 9 BP 1143 EP 1146 DI 10.1046/j.1537-2995.2001.41091143.x PG 4 WC Hematology SC Hematology GA 472TD UT WOS:000171000300011 PM 11552072 ER PT J AU Bolan, CD Greer, SE Cecco, SA Oblitas, JM Rehak, NN Leitman, SF AF Bolan, CD Greer, SE Cecco, SA Oblitas, JM Rehak, NN Leitman, SF TI Comprehensive analysis of citrate effects during plateletpheresis in normal donors SO TRANSFUSION LA English DT Article ID THERAPEUTIC PLASMA-EXCHANGE; PARATHYROID-HORMONE; IONIZED CALCIUM; PLATELETAPHERESIS; INFUSION AB BACKGROUND: Although plateletpheresis procedures are generally well tolerated, the clinical and metabolic consequences associated with rapid infusion of up to 10 g of citrate are underappreciated, and a comprehensive description of these events is not available. STUDY DESIGN AND METHODS: Clinical and laboratory changes were studied in seven healthy donors undergoing three 90-minute plateletpheresis procedures each, at continuous, fixed citrate infusion rates of 1.1, 1.4, and 1.6 mg per kg per minute. RESULTS: Serum citrate levels increased markedly with increasing citrate infusion rates and did not achieve a stable plateau. As citrate infusion rates increased, the total volume processed and platelet yields also increased, but donor symptoms became more severe. Ionized calcium (iCa) and ionized magnesium (iMg) concentrations decreased markedly, by 33 and 39 percent below baseline, respectively, at a citrate rate of 1.6 mg per kg per minute. Intact parathyroid hormone levels were higher at 30 minutes than at later time points, despite progressive decreases in iCa and iMg. Urine citrate, calcium, magnesium, sodium, and potassium concentrations and urine pH values increased markedly during all procedures. CONCLUSION: Marked, progressive increases in serum citrate levels occur during plateletpheresis, accompanied by symptomatic decreases in iCa and iMg, with significantly increased renal excretion of calcium, magnesium, and citrate. C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. RP Bolan, CD (reprint author), NIH, Dept Transfus Med, Bldg 10,Room 1C711,10 Ctr Dr,MSC 1184, Bethesda, MD 20892 USA. NR 18 TC 42 Z9 47 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 SEP PY 2001 VL 41 IS 9 BP 1165 EP 1171 DI 10.1046/j.1537-2995.2001.41091165.x PG 7 WC Hematology SC Hematology GA 472TD UT WOS:000171000300015 PM 11552076 ER PT J AU Aravind, L AF Aravind, L TI DOMON: an ancient extracellular domain in dopamine beta-monooxygenase and other proteins SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID HYDROXYLASE GENE; EXPRESSION; INSIGHTS AB A previously uncharacterized 110-125 residue-long domain was identified both in the physiologically important enzyme dopamine P-monooxygenase and in several other secreted and transmembrane proteins such as SDR2 and CG-6. This domain was predicted to adopt an all-beta fold with seven or eight strands and might function as a module mediating a range of extracellular adhesive interactions. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NR 16 TC 26 Z9 26 U1 3 U2 9 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 SEP PY 2001 VL 26 IS 9 BP 524 EP 526 DI 10.1016/S0968-0004(01)01924-7 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 472GC UT WOS:000170974500003 PM 11551777 ER PT J AU Wolf, YI Kondrashov, FA Koonin, EV AF Wolf, YI Kondrashov, FA Koonin, EV TI Footprints of primordial introns on the eukaryotic genome: still no clear traces - Response SO TRENDS IN GENETICS LA English DT Letter ID PSI-BLAST C1 Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wolf, YI (reprint author), Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 10 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD SEP PY 2001 VL 17 IS 9 BP 499 EP 501 DI 10.1016/S0168-9525(01)02376-9 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 466TT UT WOS:000170662500004 PM 11721681 ER PT J AU Ohlsson, R Renkawitz, R Lobanenkov, V AF Ohlsson, R Renkawitz, R Lobanenkov, V TI CTCF is a uniquely versatile transcription regulator linked to epigenetics and disease SO TRENDS IN GENETICS LA English DT Review ID C-MYC GENE; PROTEIN PRECURSOR PROMOTER; ENHANCER-BLOCKING ACTIVITY; THYROID-HORMONE; ZINC FINGERS; FUNCTIONAL INTERACTION; IMPRINTED EXPRESSION; 5'-FLANKING SEQUENCE; DNA RECOGNITION; IGF2 EXPRESSION AB CTCF is an evolutionarily conserved zinc finger (ZF) phosphoprotein that binds through combinatorial use of its 11 ZFs to similar to 50 bp target sites that have remarkable sequence variation. Formation of different CTCF-DNA complexes, some of which are methylation-sensitive, results in distinct functions, including gene activation, repression, silencing and chromatin insulation. Disrupting the spectrum of target specificities by ZF mutations or by abnormal selective methylation of targets is associated with cancer, CTCF emerges, therefore, as a central player in networks linking expression domains with epigenetics and cell growth regulation. C1 Uppsala Univ, Dept Genet & Dev, Evolut Biol Ctr, S-75236 Uppsala, Sweden. Univ Giessen, Inst Genet, D-35392 Giessen, Germany. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Ohlsson, R (reprint author), Uppsala Univ, Dept Genet & Dev, Evolut Biol Ctr, Norbyvagen 18A, S-75236 Uppsala, Sweden. OI Lobanenkov, Victor/0000-0001-6665-3635 NR 69 TC 373 Z9 380 U1 3 U2 30 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD SEP PY 2001 VL 17 IS 9 BP 520 EP 527 DI 10.1016/S0168-9525(01)02366-6 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 466TT UT WOS:000170662500007 PM 11525835 ER PT J AU Slavotinek, AM Biesecker, LG AF Slavotinek, AM Biesecker, LG TI Unfolding the role of chaperones and chaperonins in human disease SO TRENDS IN GENETICS LA English DT Review ID BARDET-BIEDL-SYNDROME; ALPHA-B-CRYSTALLIN; MCKUSICK-KAUFMAN-SYNDROME; HEAT-SHOCK PROTEINS; MOLECULAR CHAPERONES; POLYGLUTAMINE DISEASE; AGGREGATE FORMATION; MISSENSE MUTATION; CELL-DEATH; IN-VIVO AB Molecular chaperones comprise several highly conserved families of related proteins, many of which are also heat shock proteins. Chaperone proteins are crucial for the maintenance of native protein conformation and recent research has demonstrated several mechanisms where defective chaperone proteins have pathogenic consequences. In this article, we describe the structure and function of chaperones in bacterial and eukaryotic cells, focusing on the chaperonin class of chaperones. We then summarize contemporary research concerning the role of these proteins in several human diseases, concentrating on the genes coding for chaperone and chaperonin proteins and the importance of chaperones in neurodegenerative diseases and as modifiers of amino acid substitution mutations in other proteins. C1 NHGRI, Med Genet Branch, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Slavotinek, AM (reprint author), NHGRI, Med Genet Branch, Genet Dis Res Branch, NIH, Bldg 49,Room 4B75,49 Convent Dr, Bethesda, MD 20892 USA. EM aslavoti@nhgri.nih.gov NR 65 TC 70 Z9 74 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD SEP PY 2001 VL 17 IS 9 BP 528 EP 535 DI 10.1016/S0168-9525(01)02413-1 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 466TT UT WOS:000170662500008 PM 11525836 ER PT J AU O'Brien, SJ Gao, XJ Carrington, M AF O'Brien, SJ Gao, XJ Carrington, M TI HLA and AIDS: a cautionary tale SO TRENDS IN MOLECULAR MEDICINE LA English DT Editorial Material ID T-CELLS; HIV-1; INFECTION; MOLECULES; RESPONSES; THERAPY; BW4 AB The human major histocompatibility complex HLA has been implicated repeatedly as a regulator of the outcome of HIV exposure and infection. A new study of long-term survivors who naturally depress HIV-1 replication and avoid the signs of AIDS for years after infection suggests that homozygosity for a group of HLA-B locus alleles termed Bw4 confers resistance, ostensibly by regulating natural killer cell-ligand interactions. However, close inspection of the accumulated evidence raises some questions and urges validation of the potential Bw4 effects in additional studies. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. NR 24 TC 152 Z9 156 U1 0 U2 2 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 PD SEP PY 2001 VL 7 IS 9 BP 379 EP 381 DI 10.1016/S1471-4914(01)02131-1 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 470VG UT WOS:000170891400001 PM 11530315 ER PT J AU Rudy, B McBain, CJ AF Rudy, B McBain, CJ TI Kv3 channels: voltage-gated K+ channels designed for high-frequency repetitive firing SO TRENDS IN NEUROSCIENCES LA English DT Review ID FAST-SPIKING INTERNEURONS; POTASSIUM-CHANNEL; DIFFERENTIAL EXPRESSION; PYRAMIDAL NEURONS; SUBUNIT KV3.1B; RAT-BRAIN; PHARMACOLOGICAL CHARACTERIZATION; NEOCORTICAL INTERNEURONS; CORTICAL-NEURONS; GLOBUS-PALLIDUS AB Analysis of the Kv3 subfamily of K+ channel subunits has lead to the discovery of a new class of neuronal voltage-gated K+ channels characterized by positively shifted voltage dependencies and very fast deactivation rates. These properties are adaptations that allow these channels to produce currents that can specifically enable fast repolarization of action potentials without compromising spike initiation or height. The short spike duration and the rapid deactivation of the Kv3 currents after spike repolarization maximize the quick recovery of resting conditions after an action potential. Several neurons in the mammalian CNS have incorporated into their repertoire of voltage-dependent conductances a relatively large number of Kv3 channels to enable repetitive firing at high frequencies- an ability that crucially depends on the special properties of Kv3 channels and their impact on excitability. C1 NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. NICHHD, Lab Cellular & Synapt Neurophysiol, Bethesda, MD 20892 USA. RP Rudy, B (reprint author), NYU, Sch Med, Dept Physiol & Neurosci, 550 1st Ave, New York, NY 10016 USA. FU NINDS NIH HHS [NS35215, NS30989] NR 77 TC 377 Z9 389 U1 5 U2 27 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD SEP PY 2001 VL 24 IS 9 BP 517 EP 526 DI 10.1016/S0166-2236(00)01892-0 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 466YX UT WOS:000170674700012 PM 11506885 ER PT J AU Stowers, AW Miller, LH AF Stowers, AW Miller, LH TI Are trials in New World monkeys on the critical path for blood-stage malaria vaccine development? SO TRENDS IN PARASITOLOGY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; PLASMODIUM-FALCIPARUM MALARIA; TERMINAL FRAGMENT; SYNTHETIC VACCINE; IMMUNE-RESPONSES; EFFICACY TRIAL; AOTUS MONKEYS; IMMUNOGENICITY; SAFETY; SPF66 AB The development of malaria blood-stage vaccines is gathering momentum: there are several new funding initiatives, one multiantigen formulation is currently being tested and at least one other blood-stage vaccine is expected to begin trials in 2001. However, there is no consensus over the best way to select which form of an antigen to take into clinical testing. There is thus a danger that less-effective vaccines might be tested in the field in the order of their availability, rather than merit. Here, we argue that first proving efficacy in the New World monkey challenge model would accelerate development. C1 NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. RP Stowers, AW (reprint author), NIAID, Malaria Vaccine Dev Unit, Parasit Dis Lab, NIH, Rockville, MD 20852 USA. NR 33 TC 35 Z9 35 U1 0 U2 1 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 SEP PY 2001 VL 17 IS 9 BP 415 EP 419 DI 10.1016/S1471-4922(01)02011-6 PG 5 WC Parasitology SC Parasitology GA 468JN UT WOS:000170754500006 PM 11530352 ER PT J AU Su, TP Hayashi, T AF Su, TP Hayashi, T TI Cocaine affects the dynamics of cytoskeletal proteins via sigma(1) receptors SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID BINDING; EXPRESSION; SITES AB Cytoskeletal proteins are important in protein trafficking, membrane protein clustering, dendrite growth and the morphological maintenance of neurons. Sigma, receptors are unique endoplasmic reticular (ER) proteins that bind (+)benzomorphans, neurosteroids and psychotropic drugs such as cocaine. Cocaine, via sigma, receptors, can cause the dissociation of a cytoskeletal adaptor protein ankyrin from inositol (1,4,5)-trisphosphate [Ins(1,4,5)P-3] receptors on the ER as a sigma(1)-receptor-ankyrin complex, which then translocates to the plasma membrane and nucleus. The dissociation of sigma(1)-receptor-ankyrin from Ins(1,4,5)P-3 receptors also increases the intracellular Ca2+ concentration ([Ca2+], which affects the activity of cytoskeletal proteins. Furthermore, cocaine might increase [Ca2+](i) via phospholipase C (PLC)-linked dopamine D1 receptors. We hypothesize that cocaine might cause life-long changes in neurons via cytoskeletal proteins by interacting with both D1 receptors and sigma, receptors. C1 NIDA, Cellular Pathobiol Unit, Cellular Neurobiol Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Su, TP (reprint author), NIDA, Cellular Pathobiol Unit, Cellular Neurobiol Res Branch, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hayashi, Teruo/A-9690-2008 NR 23 TC 30 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD SEP PY 2001 VL 22 IS 9 BP 456 EP 458 DI 10.1016/S0165-6147(00)01740-5 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 480QT UT WOS:000171474000008 PM 11543872 ER PT J AU Baldassarre, G Tucci, M Lembo, G Pacifico, FM Dono, R Lago, CT Barra, A Bianco, C Viglietto, G Salomon, D Persico, MG AF Baldassarre, G Tucci, M Lembo, G Pacifico, FM Dono, R Lago, CT Barra, A Bianco, C Viglietto, G Salomon, D Persico, MG TI A truncated form of teratocarcinoma-derived growth factor-1 (cripto-1) mRNA expressed in human colon carcinoma cell lines and tumors SO TUMOR BIOLOGY LA English DT Article DE teratocarcinoma-derived growth factor1/cripto-1 colon carcinomas; alternative transcription ID GENE; RECEPTOR; RNA; DIFFERENTIATION; PROTEIN; ACID; IDENTIFICATION; MORPHOGENESIS; GASTRULATION; TRANSLATION AB The human teratocarcinoma-derived growth factor (TDGF)-1 gene encodes a 188-amino acid protein, cripto-1. The TDGF-1 gene is overexpressed in the majority of human primary colorectal carcinomas and hepatic metastases, in breast carcinomas and in testicular nonseminoma germ cell embryonal carcinomas. In the human embryonal carcinoma cell line NTERA-2 clone D1, a 2-kb TDGF-1 mRNA transcript is expressed. The present study shows that a 1.7-kb mRNA transcript lacking the first two exons of the TDGF-1 gene is expressed in the human colon carcinoma cell line GEO. This shorter mRNA is the only TDGF-1 transcript that is present in the majority of primary human colorectal carcinomas and hepatic metastases and in adult human tissues such as the pancreas, heart, stomach, mammary gland, skeletal muscle, liver and placenta. In contrast, in the kidney, brain, testis, ovary and spleen, the longer 2-kb TDGF-1 mRNA transcript is expressed. The putative shorter protein starts at a CUG codon 129 nucleotides downstream of the starting AUG codon of the longer protein. These data indicate the potential for differential transcriptional regulation of the TDGF-1 gene in different normal and tumor tissues. Copyright (C) 2001 S. Karger AG, Basel. C1 CNR, Int Inst Genet & Biophys, I-80125 Naples, Italy. Fdn Pascale, Ist Studio & Cura Tumori, Naples, Italy. NCI, Tumor Growth Factor Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD USA. RP Persico, MG (reprint author), CNR, Int Inst Genet & Biophys, Via G Marconi 12, I-80125 Naples, Italy. RI DONO, ROSANNA/I-7821-2016; Baldassarre, Gustavo/K-1350-2016; OI Baldassarre, Gustavo/0000-0002-9750-8825; Pacifico, Francesco Maria/0000-0001-9563-3596; Lembo, Giuseppe/0000-0002-3510-223X NR 34 TC 12 Z9 15 U1 0 U2 6 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1010-4283 J9 TUMOR BIOL JI Tumor Biol. PD SEP-OCT PY 2001 VL 22 IS 5 BP 286 EP 293 DI 10.1159/000050629 PG 8 WC Oncology SC Oncology GA 474XX UT WOS:000171133100003 PM 11553858 ER PT J AU Tavani, A La Vecchia, C Brinton, LA McTiernan, A AF Tavani, A La Vecchia, C Brinton, LA McTiernan, A TI Hormone replacement therapy and risk of endometrial cancer SO TUMORI LA English DT Article; Proceedings Paper CT Meeting on Cervical and Endometrial Pathology Preventive Programme and Therapy CY MAY 25-26, 2001 CL FORLI, ITALY ID ESTROGEN REPLACEMENT; WOMEN C1 Ist Ric Farmacol Mario Negri, Milan, Italy. Univ Milan, Ist Stat Med & Biometria, I-20122 Milan, Italy. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Tavani, A (reprint author), Ist Ric Farmacol Mario Negri, Milan, Italy. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 19 TC 0 Z9 0 U1 0 U2 0 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD SEP-OCT PY 2001 VL 87 IS 5 BP S20 EP S21 PG 2 WC Oncology SC Oncology GA 502YQ UT WOS:000172770700036 PM 11765201 ER PT J AU Nagai, Y Helwegen, J Fleg, JL Beemer, MK Earley, CJ Metter, EJ AF Nagai, Y Helwegen, J Fleg, JL Beemer, MK Earley, CJ Metter, EJ TI Associations of aortic Windkessel function with age, gender and cardiovascular risk factors SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE Windkessel function; age; gender; risk factors; ultrasound ID COMMON CAROTID-ARTERY; STIFFNESS; DECREASE; PRESSURE AB Aortic Windkessel function is thought to represent a potential cardiovascular risk factor. As an indicator for the function, we have recently introduced the decay index (DI). DI is the coefficient of an exponential function applied to the postpeak portion of internal carotid artery Doppler waveform, and is inversely associated with the function. This study compares DI with age, gender and traditional cardiovascular risk factors in 220 apparently healthy volunteers (59 +/- 16 years). DI increased linearly with age (r=0.51, p<0.001), and was higher in women than in men at all ages (p<0.001). Also, DI was positively associated with systolic blood pressure (beta = 0.17,p<0.01) and diabetic medication ( = 0.14, p<0.05), independent of age ( = 0.49, p<0.0001), gender ( = 0.27,p<0.0001) and other traditional cardiovascular risk factors (model r(2) = 0.36). Based on the present results, the Windkessel function as assessed by DI declines with age and is lower in women. However, the associations with cardiovascular risk factors need to be established on a larger sample at higher cardiovascular risk. C1 Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut, Div Strokol, Suita, Osaka 5650871, Japan. NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Eindhoven Univ Technol, Dept Phys, Grp Phys Informat, NL-5600 MB Eindhoven, Netherlands. Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. RP Nagai, Y (reprint author), Osaka Univ, Grad Sch Med, Dept Internal Med & Therapeut, Div Strokol, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. NR 18 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD SEP PY 2001 VL 27 IS 9 BP 1207 EP 1210 DI 10.1016/S0301-5629(01)00445-8 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 481JF UT WOS:000171515600007 PM 11597361 ER PT J AU Coleman, CN AF Coleman, CN TI Urologic oncology: extraordinary opportunities for discovery - New initiatives in radiation oncology SO UROLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 1st Annual Midwinter Meeting of the Society-of-Urologic-Oncology CY DEC 01-02, 2000 CL BETHESDA, MARYLAND SP Soc Urol Oncol DE radiation oncology; molecular therapeutics; urologic oncology; radiation biology ID LOCALIZED PROSTATE-CANCER; GENES; TRIAL AB The discussion and debate over the "best" treatment for clinically localized prostate cancer will be an iterative process based on a combination of opinions and data. Success is a measure of both cancer control and quality of life such that in a disease with a long natural history, one must be very cautious about over-interpreting short- or medium-term results. As with many treatment approaches in the rapidly evolving world of medicine, outcomes improve over time so that retrospective studies are useful but of limited value due to changes in patient selection and therapeutic technique. Overly aggressive multimodality approaches will produce excellent short-term results such as PSA biochemical NED (bNED), yet these may be more costly in terms of toxicity and expense than necessary compared to uni-modality therapy. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NCI, Radiat Oncol Sci Program, ROB, Bethesda, MD 20892 USA. RP Coleman, CN (reprint author), NCI, Radiat Oncol Sci Program, ROB, Bldg 10,B3B69, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1078-1439 J9 UROL ONCOL JI Urol. Oncol. PD SEP-OCT PY 2001 VL 6 IS 5 BP 185 EP 188 DI 10.1016/S1078-1439(01)00139-9 PG 4 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 471GZ UT WOS:000170921600004 ER PT J AU Pautler, SE Linehan, WM Walther, MM AF Pautler, SE Linehan, WM Walther, MM TI Cytoreductive laparoscopic radical nephrectomy: the early experience SO UROLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 1st Annual Midwinter Meeting of the Society-of-Urologic-Oncology CY DEC 01-02, 2000 CL BETHESDA, MARYLAND SP Soc Urol Oncol DE laparoscopy; cytoreductive nephrectomy; renal cancer; immunotherapy ID RENAL-CELL CARCINOMA; SURGERY; INTERLEUKIN-2; THERAPY AB Laparoscopic radical nephrectomy is becoming increasingly utilized for localized renal tumors. We have applied this procedure to patients with metastatic disease for cytoreduction prior to systemic immunotherapy. Advantages of the laparoscopic approach include decreased parenteral narcotic requirement and decreased time to initiate systemic therapy. Herein, we describe the procedure with some technical pearls learned in our early experience. (C) 2001 Elsevier Science, Inc. All rights reserved. C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Walther, MM (reprint author), Bldg 10,Rm 2B47,10 Ctr Dr, Bethesda, MD 20892 USA. NR 17 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1078-1439 J9 UROL ONCOL JI Urol. Oncol. PD SEP-OCT PY 2001 VL 6 IS 5 BP 193 EP 195 DI 10.1016/S1078-1439(01)00138-7 PG 3 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 471GZ UT WOS:000170921600006 ER PT J AU Leach, FS AF Leach, FS TI Molecular genetics of urothelial malignancies: Mismatch repair genes as markers for detection and prognosis? SO UROLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 1st Annual Midwinter Meeting of the Society-of-Urologic-Oncology CY DEC 01-02, 2000 CL BETHESDA, MARYLAND SP Soc Urol Oncol DE mismatch repair; urothelial malignancy; cancer detection; prognosis ID NONPOLYPOSIS COLORECTAL-CANCER; TRANSITIONAL-CELL CARCINOMAS; BLADDER-CANCER; MICROSATELLITE INSTABILITY; COLON-CANCER; URINARY-BLADDER; ALTERED EXPRESSION; SOMATIC MUTATIONS; PROSTATE-CANCER; MUTS HOMOLOG AB Urothelial malignancies were diagnosed in over 50,000 men and women in the United States last year. The majority of these tumors are not muscle invasive and can be treated endoscopically with or without adjuvant intravesical therapy. Cystoscopy and cytology at regular and frequent intervals are essential since many patients experience tumor recurrence, progression or fail to respond to intravesical treatments. Cancer recurrence, progression and intravesical treatment failures can be associated with increased risk of developing metastatic disease if not promptly detected and aggressively treated. Markers that identify patients at increased risk for recurrence, progression and poor response to intravesical therapy would provide useful information in the management of patients with urothelial malignancies. Mismatch repair (MMR) genes are potential markers for detection and prognosis since their expression is linked to tumor predisposition, progression and resistance to chemotherapeutic agents. The molecular biology and biochemistry of MMR will be reviewed and the potential role of human MMR genes for detection, prognosis and treatment of urothelial malignancies will be discussed. (C) 2001 Elsevier Science, Inc. All rights reserved. C1 NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Leach, FS (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 2B47, Bethesda, MD 20892 USA. NR 65 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1078-1439 J9 UROL ONCOL JI Urol. Oncol. PD SEP-OCT PY 2001 VL 6 IS 5 BP 211 EP 219 DI 10.1016/S1078-1439(01)00144-2 PG 9 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 471GZ UT WOS:000170921600009 ER PT J AU Fang, JY Metter, EJ Landis, P Chan, DW Morrell, CH Carter, HB AF Fang, JY Metter, EJ Landis, P Chan, DW Morrell, CH Carter, HB TI Low levels of prostate-specific antigen predict long-term risk of prostate cancer: Results from the Baltimore Longitudinal Study of Aging SO UROLOGY LA English DT Article ID REFERENCE RANGES; MORTALITY; MEN; PREVENTION; POPULATION; FEATURES; TRENDS; UPDATE AB Objectives. To evaluate the relationship between low prostate-specific antigen (PSA) levels that are considered normal and the long-term risk of prostate cancer. Methods. The relative risk of, and cumulative probability of freedom from, prostate cancer by PSA level and age decade was evaluated in male participants of a longitudinal aging study, the Baltimore Longitudinal Study of Aging (National Institute on Aging). The relative risk was estimated from a Cox proportional hazards regression model for men aged 40 to 49.9 (n = 351) and 50 to 59.9 (n = 445). The disease-free probability was determined by Kaplan-Meier survival analysis. Results. The relative risk of prostate cancer for men aged 40 to 49.9 was 3.75 (range 1.6 to 8.6) when the PSA level was at or greater than the median (0.60 ng/mL) compared with men with PSA levels less than the median. This risk was similar for men aged 50 to 59.9 when comparing those with PSA levels greater than and less than the median (0.71 ng/mL). At 25 years, the cumulative probability of freedom from prostate cancer for men aged 40 to 49.9 was 89.6% (range 81% to 97%) and 71.6% (range 60% to 83%) when the PSA level was less than and greater than the median, respectively. The 25-year disease-free probability for men aged 50 to 59.9 was 83.6% (range 76% to 91%) and 58.9% (range 48% to 70%) when the PSA level was less than and greater than the median, respectively. Conclusions. The association between the baseline serum PSA level and the subsequent risk of prostate cancer suggests that the biologic events that predispose to prostate cancer begin early in middle age. Men who have baseline PSA levels that are "normal" but reflect a higher risk of prostate cancer may be the most appropriate candidates for future prevention trials. Those men with the lowest risk of prostate cancer on the basis of the baseline PSA measurements are unlikely to benefit from frequent PSA surveillance in an effort to detect prostate cancer early. UROLOGY 58: 411-416, 2001. (C) 2001, Elsevier Science Inc. C1 Johns Hopkins Univ, Sch Med,Dept Urol, Johns Hopkins Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med,Dept Pathol, Johns Hopkins Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. Loyola Coll, Baltimore, MD 21210 USA. RP Carter, HB (reprint author), Johns Hopkins Univ, Sch Med,Dept Urol, Johns Hopkins Hosp, James Buchanan Brady Urol Inst, 403 Marburg,600 N Wolfe St, Baltimore, MD 21287 USA. FU NCI NIH HHS [CA58236] NR 16 TC 117 Z9 119 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD SEP PY 2001 VL 58 IS 3 BP 411 EP 416 DI 10.1016/S0090-4295(01)01304-8 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 472HW UT WOS:000170978900021 PM 11549490 ER PT J AU Aarons, EJ Beddows, S Willingham, T Wu, LJ Koup, RA AF Aarons, EJ Beddows, S Willingham, T Wu, LJ Koup, RA TI Adaptation to blockade of human immunodeficiency virus type 1 entry imposed by the anti-CCR5 monoclonal antibody 2D7 SO VIROLOGY LA English DT Article DE HIV-1; CCR5; gp120; coreceptor; monoclonal antibody ID MACROPHAGE-TROPIC HIV-1; CHEMOKINE RECEPTOR GENE; CLINICAL COURSE; GP120 BINDING; CCR5 GENOTYPE; SOLUBLE CD4; IN-VITRO; V3 LOOP; INFECTION; NEUTRALIZATION AB The second extracellular loop (ECL2) domain of CC-chemokine receptor 5 (CCR5) has been proposed as a specific target site for therapeutic agents aimed at blocking CCR5-dependent entry by human immunodeficiency virus type I (HIV-1). We have adapted two CCR5-using HIV-1 isolates, prototypic JR-CSF, and a primary isolate, 11-121, to replicate in vitro in the presence of high concentrations of a monoclonal antibody (MAb 2D7) specific for the CCR5 ECL2 domain, The 75% inhibitory concentrations (IC75) for the two 2D7-adapted isolates were approximately 100-fold higher than those for corresponding control isolates passaged without the MAb. Adapted isolates did not acquire the ability to use CXCR4, CCR3, or CCR1. Env clones derived from MAb 2D7-adapted JR-CSF showed several gp120 mutations that were not found in any of the control JR-CSF clones. The in vitro observations suggest that CCR5-using HIV-1 strains might also be able to adapt In vivo to evade an ECL2-blocking therapeutic agent. (C) 2001 Academic Press. C1 Univ Texas, SW Med Ctr, Dept Med, Div Infect Dis, Dallas, TX 75390 USA. St Marys Hosp, Imperial Coll Sch Med, Dept GU Med & Communicable Dis, London W2 1PG, England. Millenium Pharmaceut Inc, Cambridge, MA 02139 USA. RP Koup, RA (reprint author), NIH, Immunol Lab, Vaccine Res Ctr, Bldg 40,Room 3502,40 Convent Dr, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R27-AI-35522, R21-AI-42630, R01-AI-42397] NR 59 TC 40 Z9 41 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2001 VL 287 IS 2 BP 382 EP 390 DI 10.1006/viro.2001.1046 PG 9 WC Virology SC Virology GA 471GY UT WOS:000170921500014 PM 11531415 ER PT J AU McDermott, DH Halcox, JPJ Schenke, WH Waclawiw, MA Merrell, MN Epstein, N Quyyumi, AA Murphy, PM AF McDermott, DH Halcox, JPJ Schenke, WH Waclawiw, MA Merrell, MN Epstein, N Quyyumi, AA Murphy, PM TI Association between polymorphism in the chemokine receptor CX3CR1 and coronary vascular endothelial dysfunction and atherosclerosis SO CIRCULATION RESEARCH LA English DT Article DE genetics; fractalkine; acetylcholine; inflammation; epidemiology ID NITRIC-OXIDE ACTIVITY; ARTERY DISEASE; HEART-DISEASE; RISK-FACTORS; REDUCES ATHEROSCLEROSIS; DELETION POLYMORPHISM; MYOCARDIAL-INFARCTION; DEFICIENT MICE; FRACTALKINE; CELLS AB Fractalkine, a chemokine expressed by inflamed endothelium, induces leukocyte adhesion and migration via the receptor CX3CR1, and the CX3CR1 polymorphism V249I affects receptor expression and function. Here we show that this polymorphism is an independent risk factor for atherosclerotic coronary artery disease (CAD). Genotyping of the CX3CR1-V249I polymorphism was performed in a cohort of 339 white individuals who underwent cardiac catheterization (n = 197 with and n = 142 without CAD, respectively). In 203 patients, intracoronary acetylcholine 15 mug/min) and sodium nitroprusside (20 mug/min) were administered to test endothelium-dependent and -independent coronary vascular function, respectively. Change in coronary vascular resistance (Delta CVR) was measured as an index of microvascular dilation. An association was observed between presence of the CX3CR1 1249 allele and reduced prevalence of CAD, independent of established CAD risk factors (odds ratio=0.54 [95% confidence interval, 0.30 to 0.96], P=0.03). Angiographic severity of CAD was also lower in these subjects (P=0.01). Furthermore, endothelium-dependent vasodilation was greater in these individuals compared with individuals homozygous for the CX3CR1-V249 allele (Delta CVR during acetylcholine = -46+/-3% versus -36+/-3%, respectively, P=0.02), whereas Delta CVR with sodium nitroprusside was similar in both groups (-55 +/- 2% versus -53 +/- 2%, P=0.45). The association between CX3CR1 genotype and endothelial function was independent of established risk factors and presence of CAD by multivariate analysis (P=0.02). Thus, the CX3CR1 1249 allele is associated with decreased risk of CAD and improved endothelium-dependent vasodilation. This suggests that CX3CR1 may be involved in the pathogenesis of CAD. C1 NIAID, Mol Signalling Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Mol Signalling Sect, Host Def Lab, NIH, Bldg 10,Room 11N113, Bethesda, MD 20892 USA. OI Halcox, Julian/0000-0001-6926-2947; McDermott, David/0000-0001-6978-0867 NR 53 TC 181 Z9 195 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD AUG 31 PY 2001 VL 89 IS 5 BP 401 EP 407 DI 10.1161/hh1701.095642 PG 7 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 471HD UT WOS:000170922000006 PM 11532900 ER PT J AU Petroff, MGV Egan, JM Wang, XL Sollott, SJ AF Petroff, MGV Egan, JM Wang, XL Sollott, SJ TI Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes SO CIRCULATION RESEARCH LA English DT Article DE cardiac myocytes; glucagon-like peptide-1; cAMP; calcium ID PROTEIN-KINASE-A; ARTERIAL BLOOD-PRESSURE; ADENYLYL-CYCLASE; CYCLIC-AMP; SARCOPLASMIC-RETICULUM; INSULIN-SECRETION; CYTOSOLIC CALCIUM; TWITCH RELAXATION; CA-2+ CURRENT; HEART-RATE AB The gut hormone, glucagon-like peptide-1 (GLP-1), which is secreted in nanomolar amounts in response to nutrients in the intestinal lumen, exerts cAMP/protein kinase A-mediated insulinotropic actions in target endocrine tissues, but its actions in heart cells are unknown. GLP-1 (10 nmol/L) increased intracellular cAMP (from 5.7+/-0.5 to 13.1 +/- 0.12 pmol/mg protein) in rat cardiac myocytes. The effects of cAMP-doubling concentrations of both GLP-1 and isoproterenol (ISO. 10 nmol/L) on contraction amplitude, intracellular Ca2+ transient (CaT), and pH(i) in indo-1 and seminaphthorhodafluor (SNARF)-1 loaded myocytes were compared. Whereas ISO caused a characteristic increase (above baseline) in contraction amplitude (160+/-34%) and CaT (70+/-5%), GLP-1 induced a significant decrease in contraction amplitude (-27+/-5%) with no change in the CaT after 20 minutes. Neither pertussis toxin treatment nor exposure to the cGMP-stimulated phosphodiesterase (PDE2) inhibitor erythro-9-(2-hydroxy-3-nonyl)adenine or the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine nor the phosphatase inhibitors okadaic acid or calyculin A unmasked an ISO-mimicking response of GLP-1. In SNARF-1-loaded myocytes, however, both ISO and GLP-1 caused an intracellular acidosis (Delta pH(i) -0.09+/-0.02 and -0.08+/-0.03, respectively). The specific GLP-1 antagonist exendin 9-39 and the cAMP inhibitory analog Rp-8CPT-cAMPS inhibited both the GLP-1-induced intracellular acidosis and the negative contractile effect. We conclude that in contrast to beta -adrenergic signaling, GLP-1 increases cAMP but fails to augment contraction, suggesting the existence of functionally distinct adenylyl cyclase/cAMP/protein kinase A compartments, possibly determined by unique receptor signaling microdomains that are not controlled by pertussis toxin-sensitive G proteins or by enhanced local PDE or phosphatase activation. Furthermore, GLP-1 elicits a cAMP-dependent modest negative inotropic effect produced by a decrease in myofilament-Ca2+ responsiveness probably resulting from intracellular acidification. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NIA, Diabet Sect, Gerontol Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA. Univ Nacl La Plata, Fac Ciencias Med, Ctr Invest Cardiovasc, La Plata, Buenos Aires, Argentina. RP Sollott, SJ (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Intramural Res Program,NIH, Box 13,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sollotts@grc.nia.nih.gov NR 47 TC 72 Z9 75 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 EI 1524-4571 J9 CIRC RES JI Circ.Res. PD AUG 31 PY 2001 VL 89 IS 5 BP 445 EP 452 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 471HD UT WOS:000170922000012 ER PT J AU Prasad, R Lavrik, OI Kim, SJ Kedar, P Yang, XP Vande Berg, BJ Wilson, SH AF Prasad, R Lavrik, OI Kim, SJ Kedar, P Yang, XP Vande Berg, BJ Wilson, SH TI DNA polymerase beta-mediated long patch base excision repair - Poly(ADP-ribose) polymerase-1 stimulates strand displacement DNA synthesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MAMMALIAN-CELLS; SITE; RECONSTITUTION; PROTEINS; BINDING; DOMAIN; FEN1; STEP; ATP AB Recently, photoaffinity labeling experiments with mouse cell extracts suggested that PARP-1 functions as a surveillance protein for a stalled DER intermediate. To further understand the role of PARP-1 in DER, we examined the DNA synthesis and flap excision steps in long patch DER using a reconstituted system containing a 34-base pair DER substrate and five purified human enzymes: uracil-DNA glycosylase, apurinic/apyrimidinic endonuclease, DNA polymerase beta, flap endonuclease-1 (FEN-1), and PARP-1. PARP-1 stimulates strand displacement DNA synthesis by DNA polymerase 13 in this system; this stimulation is dependent on the presence of FEN-1. PARP-1 and FEN-1, therefore, cooperate to activate long patch DER. The results are discussed in the context of a model for DER sub-pathway choice, illustrating a dual role for PARP-1 as a surveillance protein for a stalled DER intermediate and an activating factor for long patch DER DNA synthesis. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. RI Lavrik, Olga /G-4641-2013 NR 24 TC 136 Z9 141 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 31 PY 2001 VL 276 IS 35 BP 32411 EP 32414 DI 10.1074/jbc.C100292200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468EW UT WOS:000170746000006 PM 11440997 ER PT J AU Sheldon, LA Becker, M Smith, CL AF Sheldon, LA Becker, M Smith, CL TI Steroid hormone receptor-mediated histone deacetylation and transcription at the mouse mammary tumor virus promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUCOCORTICOID RECEPTOR; SODIUM-BUTYRATE; CYCLIC-AMP; ACETYLATION; CHROMATIN; NUCLEOSOME; INDUCTION; BINDING; GENES; DNA AB Acetylation of lysines in histones H3 and H4 N-terminal tails is associated with transcriptional activation and deacetylation with repression. Our studies with the mouse mammary tumor virus (MMTV) promoter in chromatin show significant levels of acetylation at promoter proximal and distal regions prior to transactivation. Upon activation with glucocorticoids or progestins, promoter proximal histones become deacetylated within the region of inducible nuclease hypersensitivity. The deacetylation lags behind the initiation of transcription, indicating a role in post-activation regulation. Our results indicate a novel mechanism by which target promoters are regulated by steroid receptors and chromatin modification machinery. C1 Dartmouth Coll Sch Med, Dept Physiol, Lebanon, NH 03756 USA. NCI, Lab Receptor Biol & Gene Express, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Sheldon, LA (reprint author), Dartmouth Coll Sch Med, Dept Physiol, 750W Borwell,1 Med Ctr Dr, Lebanon, NH 03756 USA. FU NIDDK NIH HHS [DK03535] NR 30 TC 35 Z9 36 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 AUG 31 PY 2001 VL 276 IS 35 BP 32423 EP 32426 DI 10.1074/jbc.C100315200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468EW UT WOS:000170746000009 PM 11448945 ER PT J AU Esposito, D Patel, P Stephens, RM Perez, P Chao, MV Kaplan, DR Hempstead, BL AF Esposito, D Patel, P Stephens, RM Perez, P Chao, MV Kaplan, DR Hempstead, BL TI The cytoplasmic and transmembrane domains of the p75 and Trk a receptors regulate high affinity binding to nerve growth factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NEUROTROPHIN RECEPTOR; SIGNAL-TRANSDUCTION; TYROSINE KINASE; LIGAND-BINDING; NGF BINDING; NEURONAL DIFFERENTIATION; CELL-DEATH; ACTIVATION; MODULATION; COMPLEX AB Ligand-induced receptor oligomerization is an established mechanism for receptor-tyrosine kinase activation. However, numerous receptor-tyrosine kinases are expressed in multicomponent complexes with other receptors that may signal independently or alter the binding characteristics of the receptor-tyrosine kinase. Nerve growth factor (NGF) interacts with two structurally unrelated receptors, the Trk A receptor-tyrosine kinase and p75, a tumor necrosis factor receptor family member. Each receptor binds independently to NGF with predominantly low affinity (K-d = 10(-9) M), but they produce high affinity binding sites (K-d = 10(-11) M) upon receptor co-expression. Here we provide evidence that the number of high affinity sites is regulated by the ratio of the two receptors and by specific domains of Trk A and p75. Co-expression of Trk A containing mutant transmembrane or cytoplasmic domains with p75 yielded reduced numbers of high affinity binding sites. Similarly, co-expression of mutant p75 containing altered transmembrane and cytoplasmic domains with Trk A also resulted in predominantly low affinity binding sites. Surprisingly, extracellular domain mutations of p75 that abolished NGF binding still generated high affinity binding with Trk A. These results indicate that the transmembrane and cytoplasmic domains of Trk A and p75 are responsible for high affinity site formation and suggest that p75 alters the conformation of Trk A to generate high affinity NGF binding. C1 Cornell Univ, Weill Med Coll, Div Hematol, New York, NY 10021 USA. McGill Univ, Montreal Neurol Inst, Montreal, PQ H3A 2T5, Canada. NYU, Sch Med, Skirball Inst Mol Med, New York, NY 10016 USA. Univ Salamanca, Inst Microbiol Bioquim, E-37008 Salamanca, Spain. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21701 USA. RP Hempstead, BL (reprint author), Cornell Univ, Weill Med Coll, Div Hematol, Rm C-606,1300 York Ave, New York, NY 10021 USA. RI Perez, Pilar/B-4948-2010 OI Perez, Pilar/0000-0003-3557-2247 FU NICHD NIH HHS [HD23315]; NINDS NIH HHS [NS21072, NS3027] NR 50 TC 146 Z9 151 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 31 PY 2001 VL 276 IS 35 BP 32687 EP 32695 DI 10.1074/jbc.M011674200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468EW UT WOS:000170746000043 PM 11435417 ER PT J AU Liu, XX Schrager, JA Lange, GD Marsh, JW AF Liu, XX Schrager, JA Lange, GD Marsh, JW TI HIV Nef-mediated cellular phenotypes are differentially expressed as a function of intracellular NEF concentrations SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GREEN FLUORESCENT PROTEIN; VIRUS TYPE-1 NEF; CD4 DOWN-REGULATION; CLASS-I MOLECULES; IMMUNODEFICIENCY-VIRUS; T-CELLS; DILEUCINE MOTIF; SURFACE CD4; MHC-I; GENE AB Nef is a regulatory protein encoded by the genome of both human and simian immunodeficiency virus. Its expression in T cells leads to CD4 and major histocompatibility complex class I modulation and either enhancement or suppression of T cell activation. How this viral protein achieves multiple and at times opposing activities has been unclear. Through direct measurements of Nef and the Nef-GFP fusion protein, we find that these events are mediated by different Nef concentrations. Relative to the intracellular concentration that down-modulates surface CD4, an order of magnitude increase in Nef-GFP expression is required for a comparable modulation of major histocompatibility complex class I, and a further 3-fold increase is necessary to suppress T cell activation. C1 NINDS, Instrumentat & Comp Sect, NIH, Bethesda, MD 20892 USA. RP Marsh, JW (reprint author), NIMH, Mol Biol Lab, Bldg 36,Rm 1B08,36 Convent Dr,MSC 4034, Bethesda, MD 20892 USA. NR 45 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 31 PY 2001 VL 276 IS 35 BP 32763 EP 32770 DI 10.1074/jbc.M101025200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468EW UT WOS:000170746000053 PM 11438519 ER PT J AU Wang, XW Tseng, A Ellis, NA Spillare, EA Linke, SP Robles, AI Seker, H Yang, Q Hu, P Beresten, S Bemmels, NA Garfield, S Harris, CC AF Wang, XW Tseng, A Ellis, NA Spillare, EA Linke, SP Robles, AI Seker, H Yang, Q Hu, P Beresten, S Bemmels, NA Garfield, S Harris, CC TI Functional interaction of p53 and BLM DNA helicase in apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BLOOM-SYNDROME CELLS; WERNERS-SYNDROME GENES; SYNDROME PROTEIN; P53-MEDIATED APOPTOSIS; PREMATURE SENESCENCE; GENOMIC INSTABILITY; IONIZING-RADIATION; NUCLEAR-STRUCTURE; ONCOGENIC RAS; CYCLE AB The Bloom syndrome (BS) protein, BLM, is a member of the RecQ DNA helicase family that also includes the Werner syndrome protein, WRN. Inherited mutations in these proteins are associated with cancer predisposition of these patients. We recently discovered that cells from Werner syndrome patients displayed a deficiency in p53-mediated apoptosis and WRN binds to p53. Here, we report that analogous to WRN, BLM also binds to p53 in vivo and in vitro, and the C-terminal domain of p53 is responsible for the interaction. p53-mediated apoptosis is defective in BS fibroblasts and can be rescued by expression of the normal BLM gene. Moreover, lymphoblastoid cell lines (LCLs) derived from BS donors are resistant to both gamma -radiation and doxorubicin-induced cell killing, and sensitivity can be restored by the stable expression of normal BLM. In contrast, BS cells have a normal Fas-mediated apoptosis, and in response to DNA damage normal accumulation of p53, normal induction of p53 responsive genes, and normal G(1)-S and G(2)-M Cell cycle arrest. BLM localizes to nuclear foci referred to as PAM nuclear bodies (NBs). Cells from Li-Fraumeni syndrome patients carrying p53 germline mutations and LCLs lacking a functional p53 have a decreased accumulation of BLM in NBs, whereas isogenic lines with functional p53 exhibit normal accumulation. Certain BLM mutants (C1055S or Delta 133-237) that have a reduced ability to localize to the NBs when expressed in normal cells can impair the localization of wild type BLM to NBs and block p53-mediated apoptosis, suggesting a dominant-negative effect. Taken together, our results indicate both a novel mechanism of p53 function by which p53 mediates nuclear trafficking of BLM to NBs and the cooperation of p53 and BLM to induce apoptosis. C1 NCI, LHC, NIH, Ctr Canc Res, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Lab Canc Susceptibil, Dept Human Genet, New York, NY 10021 USA. NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Harris, CC (reprint author), NCI, LHC, NIH, Ctr Canc Res, Bldg 37,Rm 2C05,MSC4255, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 FU NCI NIH HHS [R01 CA085867, R01 CA085867-01A2] NR 52 TC 108 Z9 110 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 AUG 31 PY 2001 VL 276 IS 35 BP 32948 EP 32955 DI 10.1074/jbc.M103298200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468EW UT WOS:000170746000077 PM 11399766 ER PT J AU Rubin, JS Day, RM Breckenridge, D Atabey, N Taylor, WG Stahl, SJ Wingfield, PT Kaufman, JD Schwall, R Bottaro, DP AF Rubin, JS Day, RM Breckenridge, D Atabey, N Taylor, WG Stahl, SJ Wingfield, PT Kaufman, JD Schwall, R Bottaro, DP TI Dissociation of heparan sulfate and receptor binding domains of hepatocyte growth factor reveals that heparan sulfate-c-Met interaction facilitates signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR SCATTER FACTOR; FACTOR ISOFORMS; PROTOONCOGENE PRODUCT; BIOLOGICAL-ACTIVITY; MITOGENIC ACTIVITY; CRYSTAL-STRUCTURE; EPITHELIAL-CELLS; NK1 FRAGMENT; DIMERIZATION; ACTIVATION AB Hepatocyte growth factor (HGF) is a secreted, heparan sulfate (HS) glycosaminoglycan-binding protein that stimulates mitogenesis, motogenesis, and morphogenesis in a wide array of cellular targets, including hepatocytes and other epithelial cells, melanocytes, endothelial cells, and hematopoietic cells. NK1 is an alternative HGF isoform that consists of the N-terminal (N) and first kringle (K1) domains of full-length HGF and stimulates all major HGF biological activities. Within NK1, the N domain retains the HS binding properties of full-length HGF and mediates HS-stimulated ligand oligomerization but lacks significant mitogenic or motogenic activity. In contrast, K1 does not bind HS, but it stimulates receptor and mitogen-activated protein kinase activation, mitogenesis, and motogenesis, demonstrating that structurally distinct and dissociable domains of HGF are the primary mediators of HS binding and receptor activation. Despite the absence of HS-K1 binding, K1 mitogenic activity in HS-negative cells is strictly dependent on added soluble heparin, whereas K1-stimulated motility is not. We also found that, like the receptors for fibroblast growth factors, the HGF receptor c-Met binds tightly to HS. These data suggest that HS can facilitate HGF signaling through interaction with c-Met that is independent of HGF-HS interaction and that the recruitment of specific intracellular effectors that mediate distinct HGF responses such as mitogenesis and motility is regulated by HS-c-Met interaction at the cell surface. C1 NCI, Cellular & Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NIAMS, Prot Express Lab, NIH, Bethesda, MD 20892 USA. Genentech Inc, Dept Mol Oncol, S San Francisco, CA 94080 USA. RP Bottaro, DP (reprint author), EntreMed Inc, 9640 Med Ctr Dr, Rockville, MD 20850 USA. RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 43 TC 64 Z9 65 U1 1 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 31 PY 2001 VL 276 IS 35 BP 32977 EP 32983 DI 10.1074/jbc.M105486200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468EW UT WOS:000170746000081 PM 11435444 ER PT J AU Ziebuhr, J Thiel, V Gorbalenya, AE AF Ziebuhr, J Thiel, V Gorbalenya, AE TI The autocatalytic release of a putative RNA virus transcription factor from its polyprotein precursor involves two paralogous papain-like proteases that cleave the same peptide bond SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INFECTIOUS-BRONCHITIS VIRUS; MULTIPLE SEQUENCE ALIGNMENT; EQUINE ARTERITIS VIRUS; MURINE CORONAVIRUS; CYSTEINE PROTEINASE; PROTEOLYTIC PRODUCTS; ENCODED PROTEINASES; 3C-LIKE PROTEINASE; STRAIN A59; IDENTIFICATION AB The largest replicative protein of coronaviruses is known as p195 in the avian infectious bronchitis virus (IBV) and p210 (p240) in the mouse hepatitis virus. It is autocatalytically released from the precursors pp1a and pp1ab by one zinc finger-containing papain-like protease (PLpro) in IBV and by two paralogous PLpros, PL1pro and PL2pro, in mouse hepatitis virus. The PL-pro-containing proteins have been recently implicated in the control of coronavirus subgenomic mRNA synthesis (transcription). By using comparative sequence analysis, we now show that the respective proteins of all sequenced coronaviruses are flanked by two conserved PLpro cleavage sites and share a complex (multi)domain organization with PL1pro being inactivated in IBV. Based upon these predictions, the processing of the human coronavirus 229E p195/p210 N terminus was studied in detail. First, an 87-kDa protein (p87), which is derived from a pp1a/pp1ab region immediately upstream of p195/p210, was identified in human coronavirus 229E-infected cells. Second, in vitro synthesized proteins representing different parts of pp1a were autocatalytically processed at the predicted site. Surprisingly, both PL1pro and PL2pro cleaved between p87 and p195/p210. The PL1pro-mediated cleavage was slow and significantly suppressed by a non-proteolytic activity of PL2pro. In contrast, PL2pro, whose proteolytic activity and specificity were established in this study, cleaved the same site efficiently in the presence of the upstream domains. Third, a correlation was observed between the overlapping substrate specificities and the parallel evolution of PL1pro and PL2pro. Collectively, our results imply that the p195/p210 autoprocessing mechanisms may be conserved among coronaviruses to an extent not appreciated previously, with PL2pro playing a major role. A large subset of coronaviruses may employ two proteases to cleave the same site(s) and thus regulate the expression of the viral genome in a unique way. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. Univ Wurzburg, Inst Immunol & Virol, D-97078 Wurzburg, Germany. RP Ziebuhr, J (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC, Adv Biomed Comp Ctr, 430 Miller Dr,Rm 228, Frederick, MD 21702 USA. RI Gorbalenya, Alexander/J-4818-2012 OI Gorbalenya, Alexander/0000-0002-4967-7341 FU NCI NIH HHS [N01-CO-56000] NR 56 TC 89 Z9 99 U1 1 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 AUG 31 PY 2001 VL 276 IS 35 BP 33220 EP 33232 DI 10.1074/jbc.M104097200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 468EW UT WOS:000170746000108 PM 11431476 ER PT J AU Sevilya, Z Loya, S Hughes, SH Hizi, A AF Sevilya, Z Loya, S Hughes, SH Hizi, A TI The ribonuclease H activity of the reverse transcriptases of human immunodeficiency viruses type 1 and type 2 is affected by the thumb subdomain of the small protein subunits SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1; HIV-2; reverse transcriptase; RNase H; chimeras ID MURINE LEUKEMIA-VIRUS; DNA-POLYMERASE-BETA; DOUBLE-STRANDED DNA; RNASE-H; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; MUTATIONAL ANALYSIS; NUCLEOSIDE ANALOGS; SELECTIVE MUTANTS AB Retroviral reverse transcriptases (RTs) have both DNA polymerase and ribonuclease H (RNase H) activities. The RTs of HIV-1 and HIV-2 are heterodimers of p66/p5l and p68/p54 subunits, respectively. The smaller subunit lacks the C-terminal segment of the larger subunit (which is the RNase H domain). The structure of the DNA polymerase domain of HIV-1 RT resembles a right hand (with fingers, palm and thumb subdomains), linked to the RNase H domain via the connection subdomain. The RNase H activity of the Rod strain of HIV-2 RT is about tenfold lower than that of HIV-1 RT, while the DNA polymerase activity of these RTs is similar. A chimeric RT in which residues 227-427 (which constitute a small part of the palm and the entire thumb and connection subdomains) of the Rod strain of HIV-2 RT were replaced by the corresponding segment from HIV-1 RT, has an RNase H activity as high as HIV-1 RT (despite the fact that the RNase H domain is derived from HIV-2 RT). We analyzed the RNase H activity of wild-type HIV-2 RT from the D-194 strain and compared it with this activity of the RT from the Rod strain of HIV-2 and HIV-1 RT. The level of this activity of both HIV-2 RT strains was low; suggesting that low RNase H activity is a general property of HIV-2 isolates. The in vitro RNase H digestion pattern of the three wild-type RTs was indistinguishable, despite the difference in the level of RNase H activity. We constructed new chimeric HIV-1/HIV-2 RTs, in which protein segments and/or subunits were exchanged. The DNA polymerase activity of the parental HIV-1 and HIV-2 RTs was similar; as expected, the specific activity of the polymerases of all the hybrid RTs were also similar. However, the RNase H specific activity of the chimeric RTs was either high (like HIV-1 RT) or low (like HIV-2 RT). The origin of the thumb subdomain in the small subunit of the chimeric RTs (residues 244-322) determines the level of the RNase H activity. The strand-transfer activity of the chimeric RTs is also affected by the thumb subdomain of the small subunit; transfer was much more efficient if this subdomain was derived from HIV-1 RT. The data can be explained from the three-dimensional structure of HIV-1 RT. The thumb of the smaller subunit contacts the RNase H domain; it is through these contacts that the thumb affects the level of the RNase H activity of RT. (C) 2001 Academic Press. C1 Tel Aviv Univ, Sackler Fac Med, Dept Cell Biol & Histol, IL-69978 Tel Aviv, Israel. NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Hizi, A (reprint author), Tel Aviv Univ, Sackler Fac Med, Dept Cell Biol & Histol, IL-69978 Tel Aviv, Israel. NR 41 TC 40 Z9 40 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 31 PY 2001 VL 311 IS 5 BP 957 EP 971 DI 10.1006/jmbi.2001.4904 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 469YG UT WOS:000170843200004 PM 11531332 ER PT J AU Garman, SC Sechi, S Kinet, JP Jardetzky, TS AF Garman, SC Sechi, S Kinet, JP Jardetzky, TS TI The analysis of the human high affinity IgE receptor Fc epsilon RI alpha from multiple crystal forms SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE IgE receptor; Fc receptor; glycoprotein; X-ray crystallography; protein-protein interactions ID PROTEIN-PROTEIN RECOGNITION; IMMUNOGLOBULIN-E-RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; STATISTICAL-ANALYSIS; ADHESION MOLECULES; GAMMA-RECEPTOR; BINDING-SITE; EXPRESSION; COMPLEX; GLYCOSYLATION AB We have solved the structure of the human high affinity IgE receptor, Fc epsilon RI alpha, in six different crystal forms, showing the structure in 15 different chemical environments. This database of structures shows no change in the overall shape of the molecule, as the angle between domains 1 and 2 (D1 and D2) varies little across the ensemble. However, the receptor has local conformational variability in the C' strand of D2 and in the BC loop of Dl. In every crystal form, a residue inserts between tryptophan residues 87 and 110, mimicking the position of a proline from the IgE ligand. The different crystal forms reveal a distribution of carbohydrates lining the front and back surfaces of the structure. An analysis of crystal contacts in the different forms indicates regions where the molecule interacts with other proteins, and reveals a potential new binding site distal to the IgE binding site. The results of this study point to new directions for the design of molecules to inhibit the interaction of Fc epsilon RI alpha with its natural ligand and thus to prevent a primary step in the allergic response. (C) 2001 Academic Press. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIA, NIH, Baltimore, MD 21224 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Garman, SC (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. EM garman@alpha.niaid.nih.gov NR 77 TC 40 Z9 41 U1 0 U2 3 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 31 PY 2001 VL 311 IS 5 BP 1049 EP 1062 DI 10.1006/jmbi.2001.4929 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 469YG UT WOS:000170843200011 PM 11531339 ER PT J AU Fugger, HN Kumar, A Lubahn, DB Korach, KS Foster, TC AF Fugger, HN Kumar, A Lubahn, DB Korach, KS Foster, TC TI Examination of estradiol effects on the rapid estradiol mediated increase in hippocampal synaptic transmission in estrogen receptor alpha knockout mice SO NEUROSCIENCE LETTERS LA English DT Article DE estrogen receptor alpha knockout; estradiol; hippocampus; synaptic; electrophysiology; mice; non-genomic ID KAINATE-INDUCED CURRENTS; BINDING-SITES; LONG-TERM; 17-BETA-ESTRADIOL; NEURONS; RAT; 17-ALPHA-ESTRADIOL AB Hippocampal slices from rats exhibit a rapid increase in basal synaptic transmission following 17 beta -estradiol (E-2) application. In the current study we examined the role of the classic genomic receptor, estrogen receptor alpha (ER alpha), in mediating E-2 effects on synaptic transmission. E-2 (100 pM) increased the extracellular synaptic response in hippocampal slices from gonadectomized male and female mice lacking a functional ER alpha knockout (ER alpha KO) and wild-type (WT) littermates. No sexually dimorphic differences were observed, however, the increase in the field potential was more pronounced in WT mice. ER antagonists did not block E-2 mediated growth of the synaptic response in ERaKO mice. The results suggest that the rapid effect of E-2 on synaptic transmission is not mediated by ER alpha, however, ER alpha appears to modulate non-genomic influences on synaptic transmission. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA. Univ Missouri, Dept Biochem, Columbia, MO 65211 USA. Univ Missouri, Dept Child Hlth, Columbia, MO 65211 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Foster, TC (reprint author), Univ Kentucky, Coll Med, Dept Mol & Biomed Pharmacol, Lexington, KY 40536 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NIA NIH HHS [AG/NS14979]; NIMH NIH HHS [MH59891, MH12075, R01 MH57759] NR 16 TC 34 Z9 35 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD AUG 31 PY 2001 VL 309 IS 3 BP 207 EP 209 DI 10.1016/S0304-3940(01)02083-3 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 468JU UT WOS:000170755000017 PM 11514077 ER PT J AU Poirot, E Chang, AHC Horton, D Kovac, P AF Poirot, E Chang, AHC Horton, D Kovac, P TI Synthetic explorations towards 3-deoxy-3-fluoro derivatives of D-perosamine SO CARBOHYDRATE RESEARCH LA English DT Article DE 3-deoxy-3-fluoro-D-mannose; methyl 4-azido-3-fluoro-3,4,6-trideoxy-alpha-D-mannopyranoside; fluorination with DAST; nucleophilic displacement; Vibrio cholerae O : 1 ID TRIS(DIMETHYLAMINO)SULFONIUM DIFLUOROTRIMETHYLSILICATE TASF; METHYL ALPHA-GLYCOSIDE; VIBRIO-CHOLERAE O-1; ANTIGENIC DETERMINANTS; DEOXYFLUORO SUGARS; DIMETHYL-SULFOXIDE; RAPID SYNTHESIS; BINDING; OGAWA; POLYSACCHARIDE AB Based on a literature precedent, preparation of methyl 4-azido-3,4,6-trideoxy-3-fluoro-alpha -D-mannopyranoside (18) was attempted via fluorination of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha -D-altropyranoside with diethylaminosulfur trifluoride (DAST). Contrary to expectations, the reaction took place with retention of configuration at the site of the fluorination yielding methyl 4-azido-2-O-benzyl-3,4,6-trideoxy-3-fluoro-alpha -D-altropyranoside. Treatment with DAST of methyl 4-azido-2-O-benzyl-4,6-dideoxy-alpha -D-allopyranoside (8), or its 2-(p-methoxybenzyl) analog 9 resulted in fluorination with inversion of configuration at position 3, to give the corresponding 3-deoxy-3-fluoro glucopyranosides 10 and 11, respectively. Accordingly, compound 18 was prepared from 11, by de-p-methoxybenzylation at O-2, followed by inversion of configuration at C-2 in the resulting methyl 4-azido-3,4,6-trideoxy-3-fluoro-alpha -D-glucopyranoside. The 2-O-methyl analog of 18 (19) was prepared by methylation of 18. Compounds 18 and 19 were converted, conventionally, into the 3-fluoro analogs of the terminal determinants of the O-PS of Vibrio cholerae O:1, serotype Inaba and Ogawa, respectively. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 NIDDK, NIH, LMC, Bethesda, MD 20892 USA. American Univ, Dept Chem, Washington, DC 20016 USA. RP Kovac, P (reprint author), NIDDK, NIH, LMC, Bldg 8,Room B1A24, Bethesda, MD 20892 USA. NR 26 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD AUG 30 PY 2001 VL 334 IS 3 BP 195 EP 205 DI 10.1016/S0008-6215(01)00188-4 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 470NL UT WOS:000170878000004 PM 11513826 ER PT J AU Gao, Y Voigt, J Zhao, H Pais, GCG Zhang, XC Wu, L Zhang, ZY Burke, TR AF Gao, Y Voigt, J Zhao, H Pais, GCG Zhang, XC Wu, L Zhang, ZY Burke, TR TI Utilization of a peptide lead for the discovery of a novel PTP1B-binding motif SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TYROSINE-PHOSPHATASE 1B; CONTAINING PHOSPHOTYROSYL MIMETICS; PROTEIN-TYROSINE; INHIBITORY PEPTIDES; SIGNAL-TRANSDUCTION; STRUCTURAL BASIS; DERIVATIVES; ETHERS; DESIGN AB Examination of the PTP1B inhibitory potency of an extensive series of phosphotyrosyl (pTyr) mimetics (Xxx) expressed in the EGFr-derived hexapeptide platform Ac-Asp-Ala-Asp-Xxx-Leu-amide previously led to the finding of high inhibitory potency when Xxx = 4-(phosphono-difluoromethyl)phenylalanyl (F(2)Pmp) (K-i = 0.2 muM) and when Xxx = 3-carboxy-4-carboxy-methyloxyphenylalanyl (K-i = 3.6 muM). In the first instance, further work led from the F(2)Pmp-containing peptide to monomeric inhibitor, 6-(phosphonodifluoromethyl)-2-naphthoic acid (Ki = 22 muM), and to the pseudo-dipeptide mimetic, N-[6-(phosphonodifluoromethyl)-2-naphthoyl]-glutamic acid (K-i = 12 muM). In the current study, a similar approach was applied to the 3-carboxy-4-carboxymethyloxyphenylalanyl-containing peptide, which led to the preparation of monomeric 5-carboxy-6-carboxymethyloxy-2-naphthoic acid (K-i = 900 muM). However, contrary to expectations based on the aforementioned F(2)Pmp work, incorporation of this putative pTyr mimetic into the pseudo-dipeptide, N-[5-carboxy-6-carboxymethyloxy-2-naphthoyl]-glutamic acid, resulted in a substantial loss of binding affinity. A reevaluation of binding orientation for 5-carboxy-6-carboxymethyloxy-2-naphthoic acid was therefore undertaken, which indicated a 180 degrees reversal of the binding orientation within the PTP1B catalytic site. In the new orientation, the naphthyl 2-carboxyl group, and not the o-carboxy carboxymethyloxy groups, mimics a phosphoryl group. Indeed, when 5-carboxy-2-naphthoic acid itself was examined at neutral pH for inhibitory potency, it was found to have K-i = 31 +/- 7 muM, which is lower than parent 5-carboxy-6-carboxymethyloxy-2-naphthoic acid. In this fashion, 5-carboxy-2-naphthoic acid (or more appropriately, 6-carboxy-1-naphthoic acid) has been identified as a novel PTP1B binding motif. C1 NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Canc Res Ctr, Bldg 376,Boyles St,POB B, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 FU NIGMS NIH HHS [GM 55242] NR 32 TC 17 Z9 20 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 30 PY 2001 VL 44 IS 18 BP 2869 EP 2878 DI 10.1021/jm010020r PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 467RD UT WOS:000170716800003 PM 11520195 ER PT J AU Liu, CS Riley, AM Yang, XN Shears, SB Potter, BVL AF Liu, CS Riley, AM Yang, XN Shears, SB Potter, BVL TI Synthesis and biological activity of D- and L-chiro-Inositol 2,3,4,5-tetrakisphosphate: Design of a novel and potent inhibitor of Ins(3,4,5,6)P-4 1-kinase/Ins(1,3,4)P-3 5/6-kinase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID D-MYO-INOSITOL; CELL LINE T-84; MYOINOSITOL 3,4,5,6-TETRAKISPHOSPHATE; CHLORIDE SECRETION; 1,4,5,6-TETRAKISPHOSPHATE; 1,4,5-TRISPHOSPHATE; MESSENGER; ANALOGS; 1,3,4-TRISPHOSPHATE; CONDUCTANCE AB The synthesis of a novel and potent Ins(3,4,5,6)P-4 1-kinase/Ins(1,3,4)P-3 5/6 kinase inhibitor and its enantiomer is described. D-chiro-Inositol 2,3,4,5-tetrakisphosphate [D-chiro-Ins(2,3,4,5)P-4, 3, Figure 1] and L-chiro-inositol 2,3,4,5-tetrakisphosphate [L-chiro-Ins(2,3,4,5)P-4, ent-3] were synthesized from D-1,6-di-O-benzyl-chiro-inositol and L-1,6-di-O-benzyl-chiro-inositol, respectively. We examined inhibition of the multifunctional Ins(3,4,5,6)P-4 1-kinase/Ins(1,3,4)P-3 5/6kinase from bovine aorta by 3 and ent-3. Compound 3 was a potent inhibitor with an IC50 of 1.5 muM, and ent-3 was more than 20-fold less active. The results are compared to those for other inhibitory inositol polyphosphates with structure-activity relationship discussion. Compound 3 is a useful lead for development of further inhibitors of this important enzyme, and ent-3 should find applications in the newly emerging Ins(1,4,5,6)P-4 signaling pathway. C1 Univ Bath, Dept Pharm & Pharmacol, Wolfson Lab Med Chem, Bath BA2 7AY, Avon, England. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Potter, BVL (reprint author), Univ Bath, Dept Pharm & Pharmacol, Wolfson Lab Med Chem, Claverton Down, Bath BA2 7AY, Avon, England. RI Potter, Barry/A-1845-2012 NR 29 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 AUG 30 PY 2001 VL 44 IS 18 BP 2984 EP 2989 DI 10.1021/jm000553k PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 467RD UT WOS:000170716800015 PM 11520207 ER PT J AU Kafkafi, N Mayo, C Drai, D Golani, I Elmer, G AF Kafkafi, N Mayo, C Drai, D Golani, I Elmer, G TI Natural segmentation of the locomotor behavior of drug-induced rats in a photobeam cage SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE open field; SEE; lowess; exploratory behavior; stops; amphetamine; phencyclidine ID EXPLORATORY-BEHAVIOR; RATTUS-NORVEGICUS; LOW RESPONDERS; DEXAMPHETAMINE; HYPOTHESIS AB Recently, Drai et al. (J Neurosci Methods 96 (2000) 119) have introduced an algorithm that segments rodent locomotor behavior into natural units of 'staying in place' (lingering) behavior versus going between places (progression segments). This categorization, based on the maximum speed attained within the segment, was shown to be intrinsic to the data, using the statistical method of Gaussian Mixture Model. These results were obtained in normal rats and mice using very large (650 or 320 cm) circular arenas and a video tracking system. In the present study, we reproduce these results with amphetamine, phencyclidine and saline injected rats, using data measured by a standard photobeam tracking system in square 45 cm cages. An intrinsic distinction between two or three 'gears' could be shown in all animals. The spatial distribution of these gears indicates that. as in the large arena behavior, they correspond to the difference between 'staying in place' behavior and 'going between places'. The robustness of this segmentation over arena size, different measurement system and dose of two psychostimulant drugs indicates that this is an intrinsic, natural segmentation of rodent locomotor behavior. Analysis of photobeam data that is based on this segmentation has thus a potential use in psychopharmacology research. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Inst Drug Abuse, Baltimore, MD 21224 USA. Tel Aviv Univ, IL-69978 Tel Aviv, Israel. Univ Maryland, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. RP Kafkafi, N (reprint author), Natl Inst Drug Abuse, Baltimore, MD 21224 USA. NR 25 TC 27 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD AUG 30 PY 2001 VL 109 IS 2 BP 111 EP 121 DI 10.1016/S0165-0270(01)00392-2 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 474FB UT WOS:000171094700004 PM 11513945 ER PT J AU Mitz, AR Boring, SA Wise, SP Lebedev, MA AF Mitz, AR Boring, SA Wise, SP Lebedev, MA TI A novel food-delivery device for neurophysiological and neuropsychological studies in monkeys SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE neurophysiology; neuropsychology; primate; automatic feeder; pellet dispenser ID NEURONAL-ACTIVITY; MOTOR; PREMOTOR; CORTEX AB Neurophysiological and neuropsychological studies in monkeys sometimes require an automated food-pellet dispenser. Commercially available dispensers typically sequester the pellet until delivery and, once delivered, the pellet's availability cannot be controlled. The custom-designed dispenser described here overcomes those two limitations. The device is composed of two separate units: a feeder and an electronic controller. The feeder manipulates food pellets with actuators driven by air pressure and delivers them into a serving bowl. The controller's settings determine whether the monkey can retrieve a pellet from the bowl. If the experiment requires that the pellet be visible and within reach, but unavailable for retrieval, the controller enables a trap-door mechanism at the bottom of the bowl. Any motion near the serving bowl, such as that caused by the approach of a monkey's hand, will then trigger the opening of the trap door, which causes the pellet to fall into an enclosed pellet collector. This rapid pellet-removal mechanism can also be triggered by other computer-controlled contingencies. Two of these dispensers have been in operation in an applied laboratory setting for over 2 years. Published by Elsevier Science B.V. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. Mechatron Solut, Millersville, MD USA. RP Mitz, AR (reprint author), NIMH, Lab Syst Neurosci, 49 Convent Dr,Bldg 49,Room B1EE17, Bethesda, MD 20892 USA. RI Lebedev, Mikhail/H-5066-2016 OI Lebedev, Mikhail/0000-0003-0355-8723 NR 7 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD AUG 30 PY 2001 VL 109 IS 2 BP 129 EP 135 DI 10.1016/S0165-0270(01)00406-X PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 474FB UT WOS:000171094700006 PM 11513947 ER PT J AU Deitsch, KW Calderwood, MS Wellems, TE AF Deitsch, KW Calderwood, MS Wellems, TE TI Malaria - Cooperative silencing elements in var genes SO NATURE LA English DT Article ID PLASMODIUM-FALCIPARUM; ANTIGENIC VARIATION; ERYTHROCYTES; TRANSCRIPTION; EXPRESSION; SWITCHES C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Deitsch, KW (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 158 Z9 160 U1 0 U2 9 PU MACMILLAN PUBLISHERS LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD AUG 30 PY 2001 VL 412 IS 6850 BP 875 EP 876 DI 10.1038/35091146 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 467EG UT WOS:000170689000034 PM 11528468 ER PT J AU Rasmussen, SB Kordon, E Callahan, R Smith, GH AF Rasmussen, SB Kordon, E Callahan, R Smith, GH TI Evidence for the transforming activity of a truncated Int6 gene, in vitro SO ONCOGENE LA English DT Article DE Int6; eIF3-p48; transformation; mammary gland; epithelial cells ID MAMMARY EPITHELIAL-CELLS; C-HA-RAS; HTLV-I TAX; RNA 5' CAP; TRANSLATION INITIATION; GROWTH-FACTOR; TUMOR VIRUS; MALIGNANT TRANSFORMATION; TRANSGENIC MICE; PROSTATE-CANCER AB Int6/eIF3-p48 was first identified as a common integration site for MMTV in mouse mammary tumors. In all cases, the MMTV integration event resulted in an interruption of the normal Int6 transcript from one allele leaving the second allele intact and operative. We hypothesize that insertion of MMTV into Int6 results in a mutated allele that encodes a shortened Int6 mRNA and protein (Int6sh), which either modifies normal Int6 function or possesses a new independent function. To confirm the transforming potential of the mutation and its dominant function, we transfected two mammary epithelial cell lines, MCF10A (human), and HC11 (mouse), with Int6sh under the control of the elongation factor-la (eEF1A) promoter. Expression of Int6sh in MCF10A and HC11 mammary epithelial cells leads to anchorage-independent growth in soft agar indicative of a transformed phenotype. Colonies selected from agar exhibited high levels of mutated Int6sh and wild type Int6 RNA transcripts by RT-PCR and Northern blot analysis. In addition, Int6sh transformed MCF10A and HC11 cells formed nodular growths, in vivo, in immune compromised hosts. NIH3T3 cells, mouse embryo fibroblasts, were also transformed to anchorage-independent growth in vitro by Int6sh expression. These observations provide direct evidence that the Int6 mutations observed in MMTV-induced tumors and hyperplasia contribute to the malignant transformation of the mammary epithelial cells. C1 NCI, NIH, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Acad Nacl Med Buenos Aires, Buenos Aires, DF, Argentina. RP Smith, GH (reprint author), NCI, NIH, Tumor Immunol & Biol Lab, 10 Center Dr,Room 8B07, Bethesda, MD 20892 USA. NR 41 TC 48 Z9 48 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 30 PY 2001 VL 20 IS 38 BP 5291 EP 5301 DI 10.1038/sj.onc.1204624 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 465DZ UT WOS:000170575500005 PM 11536042 ER PT J AU DiNardo, DNM Butcher, DT Robinson, DP Archer, TK Rodenhiser, DI AF DiNardo, DNM Butcher, DT Robinson, DP Archer, TK Rodenhiser, DI TI Functional analysis of CpG methylation in the BRCA1 promoter region SO ONCOGENE LA English DT Article DE BRCA1; methylation; expression; CREB ID CANCER SUSCEPTIBILITY GENE; SPORADIC BREAST-CANCER; TUMOR-SUPPRESSOR GENE; OVARIAN-CANCER; DNA METHYLATION; MESSENGER-RNA; ISLAND; ESTROGEN; BINDING; TRANSCRIPTION AB Understanding the role for DNA methylation in tumorigenesis has evolved from defining the location and extent of methylation in a variety of cancer-related genes to clarifying the functional and site-specific effects of aberrant methylation on gene expression, Our objectives were to characterize the functional effects of DNA methylation in the BRCA1 promoter and to clarify the functional status of the BRCA1 CRE (cAMP response element) motif Luciferase reporter assays confirm that an intact CRE is important for BRCA1 expression in transient transfections. Luciferase activities were decreased in constructs where the CRE recognition sequence was altered and when constructs were methylated in vitro. Gel mobility shift and competition assays identified a DNA-protein complex recognizing the CRE motif that we were able to supershift using CREB-specific antibody. Furthermore this CRE is methylation sensitive, and we localized this methylation effect to a CpG dinucleotide within the BRCA1 CRE motif. The consequences of aberrant DNA methylation at specific transcription factor motifs, along with the multiple mutational events that can occur in a variety of essential genes such as BRCA1, paint a complex picture where both genetic and epigenetic changes contribute to tumour formation. C1 Univ Western Ontario, London Reg Canc Ctr, London, ON N6A 4L6, Canada. Univ Western Ontario, Child Hlth Res Inst, London, ON, Canada. Univ Western Ontario, Dept Biochem, London, ON, Canada. Univ Western Ontario, Dept Paediat, London, ON, Canada. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Rodenhiser, DI (reprint author), Univ Western Ontario, London Reg Canc Ctr, Room 4068,790 Commissioners Rd E, London, ON N6A 4L6, Canada. NR 38 TC 39 Z9 39 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 30 PY 2001 VL 20 IS 38 BP 5331 EP 5340 DI 10.1038/sj.onc.1204697 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 465DZ UT WOS:000170575500008 PM 11536045 ER PT J AU Jain, N Yang, G Tabibi, SE Yalkowsky, SH AF Jain, N Yang, G Tabibi, SE Yalkowsky, SH TI Solubilization of NSC-639829 SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE solubilization; NSC-639829; dimethyl aniline ID FLAVOPIRIDOL; PH AB Solubilization using pH combined with cosolvents, surfactants, and complexants are investigated for NSC-639829, an investigational anti-tumor agent. The intrinsic solubility of the drug is approximately 30 ng/ml and it has an ionizable dimethyl aniline group with an approximate base pK(a) of 5. Samples buffered at pH 1.0, 2.0, and 7.0 with various concentrations of the solubilizing agents were used to study the solubilization of NSC-629829 when present as charged and uncharged species. The solubilization of NSC-639829 was found to be much more effective when the drug was present primarily in ionized form. At pH values 1.0 and 2.0 where the surfactant (SLS) and complexant (SBE beta CD) carried a negative charge enhanced solubilities of more than a million-fold were observed for the drug. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA. NCI, Pharmaceut Resources Branch, NIH, Bethesda, MD 20892 USA. RP Jain, N (reprint author), Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, 1703 E Mabel St, Tucson, AZ 85721 USA. FU NCI NIH HHS [CM-77 109] NR 8 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD AUG 28 PY 2001 VL 225 IS 1-2 BP 41 EP 47 DI 10.1016/S0378-5173(01)00773-6 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 464GU UT WOS:000170525500004 PM 11489553 ER PT J AU Huang, W Alexander, GE Chang, L Shetty, HU Krasuski, JS Rapoport, SI Schapiro, MB AF Huang, W Alexander, GE Chang, L Shetty, HU Krasuski, JS Rapoport, SI Schapiro, MB TI Brain metabolite concentration and dementia severity in Alzheimer's disease - A H-1 MRS study SO NEUROLOGY LA English DT Article; Proceedings Paper CT 6th Annual Meeting of the International-Society-for-Magnetic-Resonance-in-Medicine CY APR 17-25, 1998 CL SYDNEY, AUSTRALIA SP Int Soc Magnet Resonance Med ID MAGNETIC-RESONANCE SPECTROSCOPY; PROTON NMR-SPECTROSCOPY; IN-VIVO; SYNAPSE LOSS; INOSITOL; RELAXATION; IMPAIRMENT; DIAGNOSIS; CORTEX; VOLUME AB Objective: H-1-MRS studies have shown abnormalities in brain levels of inyo-inositol (mI) and N-acetyl aspartate (NAA) in AD, but the relation of these abnormalities with dementia severity was not examined. The authors sought to determine whether altered brain levels of mI and other metabolites occur in mild AD and whether they change as dementia severity worsens. Methods: The authors used H-1-MRS with external standards to measure absolute brain concentrations of mI, NAA, total creatine (Cr), and choline (Cho)-containing compounds in 21 subjects with AD and 17 age- and sex-matched controls in occipital and left and right parietal regions. Results: Concentrations of NAA were significantly decreased, whereas mI and Cr concentrations were significantly increased in all three brain regions in subjects with AD compared with controls. Higher concentrations of mI and Cr occurred even in mild AD. A discriminant analysis of the H-1-MRS data combined with CSF volume measurements distinguished subjects with AD, ranging from mild to severe dementia, from controls with 100% correct classification. NAA concentration, though not other metabolites, was positively correlated with Mini-Mental State Examination score. Conclusion: The measurements with H-1-MRS of absolute metabolite concentrations in the neocortex showed abnormal concentrations of brain metabolites in AD; these metabolite concentrations do not necessarily correlate with disease severity. Although changes in myo-inositol and creatine occur in the early stages of AD, abnormalities of N-acetyl aspartate do not occur in mild AD but progressively change with dementia severity. Further, subjects with mild AD can be differentiated from controls with H-1-MRS. C1 NIA, Sect Brain Physiol, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Radiol, Stony Brook, NY 11794 USA. Arizona State Univ, Arizona Alzheimers Dis Res Ctr, Tempe, AZ USA. Arizona State Univ, Dept Psychol, Tempe, AZ 85287 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Childrens Hosp, Med Ctr, Div Neurol, Cincinnati, OH 45229 USA. RP Schapiro, MB (reprint author), Childrens Hosp, Med Ctr, Div Pediat Neurol, 3333 Burnet Ave, Cincinnati, OH 45229 USA. NR 33 TC 97 Z9 105 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 28 PY 2001 VL 57 IS 4 BP 626 EP 632 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 466BF UT WOS:000170623900010 PM 11524470 ER PT J AU Mills, GB Lu, YL Kohn, EC AF Mills, GB Lu, YL Kohn, EC TI Linking molecular therapeutics to molecular diagnostics: Inhibition of the FRAP/RAFT/TOR component of the PI3K pathway preferentially blocks PTEN mutant cells in vitro and in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID HUMAN PROSTATE-CANCER; TUMOR-SUPPRESSOR; SIGNAL-TRANSDUCTION; ANTITUMOR-ACTIVITY; OVARIAN-CANCER; S6 KINASE; RAPAMYCIN; BREAST; GROWTH; EXPRESSION C1 Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77030 USA. NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. RP Mills, GB (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM gmills@mall.mdanderson.org NR 33 TC 114 Z9 118 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 28 PY 2001 VL 98 IS 18 BP 10031 EP 10033 DI 10.1073/pnas.191379498 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 468BJ UT WOS:000170738000004 PM 11526226 ER PT J AU Deprez, E Tauc, P Leh, H Mouscadet, JF Auclair, C Hawkins, ME Brochon, JC AF Deprez, E Tauc, P Leh, H Mouscadet, JF Auclair, C Hawkins, ME Brochon, JC TI DNA binding induces dissociation of the multimeric form of HIV-1 integrase: A time-resolved fluorescence anisotropy study SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VIRUS TYPE-1 INTEGRASE; PHOTO-CROSS-LINKING; N-TERMINAL DOMAIN; VIRAL-DNA; ACTIVE-SITE; IN-VITRO; PROTEIN; RESIDUES; SEQUENCE; COMPLEX AB Self-assembly of HIV-1 integrase (IN) in solution has been studied previously by time-resolved fluorescence, using tryptophan anisotropy decay. This approach provides information on the size of macromolecules via the determination of rotational correlation times (theta). We have shown that, at submicromolar concentration, IN is characterized by a long rotational correlation time (theta (20 degreesC) = 90-100 ns) corresponding to a high-order oligomeric form, likely a tetramer. In the present work, we investigated the self-assembly properties of the DNA-bound IN by using three independent fluorophores. Under enzymatic assay conditions (10(-7) M IN, 2 x 10(-8) M DNA), using either fluorescein-labeled or fluorescent guanosine analog-containing oligonucleotides that mimic a viral end long terminal repeat sequence, we found that the DNA-IN complex was characterized by shorter theta (20 degreesC) values of 15.5-19.5 and 23-27 ns, calculated from experiments performed at 25 degreesC and 37 degreesC, respectively. These results were confirmed by monitoring the Trp anisotropy decay as a function of the DNA substrate concentration: the theta of IN shifted from 90-100 ns to lower values (< 30 ns) upon increasing the DNA concentration. Again, the normalized theta (20 degreesC) values were significantly higher when monitored at 37 degreesC as compared with 25 degreesC. These results indicate that upon binding the viral DNA end, the multimeric enzyme undergoes a dissociation, most likely into a homogenous monomeric form at 25 degreesC and into a monomer-dimer equilibrium at 37 degreesC. C1 ENS Cachan, Ctr Natl Rech Sci, UMR 8532, Lab Biotechnol Pharmacogenet Appl, F-94235 Cachan, France. Inst Gustave Roussy, Ctr Natl Rech Sci, UMR 8532, Lab Physicochim & Pharmacol Macromol, F-94805 Villejuif, France. NCI, Pediat Branch, Bethesda, MD 20892 USA. RP Brochon, JC (reprint author), ENS Cachan, Ctr Natl Rech Sci, UMR 8532, Lab Biotechnol Pharmacogenet Appl, 61 Ave President Wilson, F-94235 Cachan, France. NR 36 TC 68 Z9 70 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 AUG 28 PY 2001 VL 98 IS 18 BP 10090 EP 10095 DI 10.1073/pnas.181024498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 468BJ UT WOS:000170738000016 PM 11504911 ER PT J AU Matesic, LE Yip, R Reuss, AE Swing, DA O'Sullivan, TN Fletcher, CF Copeland, NG Jenkins, NA AF Matesic, LE Yip, R Reuss, AE Swing, DA O'Sullivan, TN Fletcher, CF Copeland, NG Jenkins, NA TI Mutations in Mlph, encoding a member of the Rab effector family, cause the melanosome transport defects observed in leaden mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COAT-COLOR PHENOTYPE; MYOSIN-V; DILUTE SUPPRESSOR; EPITHELIAL-CELLS; NEUROTRANSMITTER RELEASE; MEMBRANE TRAFFICKING; RECYCLING ENDOSOMES; MOUSE MELANOCYTES; VESICLE TRANSPORT; PURKINJE-CELLS AB The d, ash, and In coat color mutations provide a unique model system for the study of vesicle transport in mammals. All three mutant loci encode genes that are required for the polarized transport of melanosomes, the specialized, pigment-containing organelles of melanocytes, to the neighboring keratinocytes and eventually into coat hairs. Genetic studies suggest that these genes function in the same or overlapping pathways and are supported by biochemical studies showing that d encodes an actin-based melanosome transport motor, MyoVa, whereas ash encodes Rab27a, a protein that localizes to the melanosome and is postulated to serve as the MyoVa receptor. Here we show that In encodes melanophilin (Mlph), a previously undescribed protein with homology to Rab effectors such as granuphilin, Slp3-a, and rabphilin-3A. Like all of these effectors, Mlph possesses two Zn2+-binding CX2CX13,14CX2C motifs and a short aromatic-rich amino acid region that is critical for Rab binding. However, Mlph does not contain the two Ca2+-binding C-2 domains found in these and other proteins involved in vesicle transport, suggesting that it represents a previously unrecognized class of Rab effectors. Collectively, our data show that Mlph is a critical component of the melanosome transport machinery and suggest that Mlph might function as part of a transport complex with Rab27a and MyoVa. C1 NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Jenkins, NA (reprint author), NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RI Yip, Richard/J-5289-2012 NR 58 TC 159 Z9 160 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 AUG 28 PY 2001 VL 98 IS 18 BP 10238 EP 10243 DI 10.1073/pnas.181336698 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 468BJ UT WOS:000170738000041 PM 11504925 ER PT J AU Orlic, D Kajstura, J Chimenti, S Limana, F Jakoniuk, I Quaini, F Nadal-Ginard, B Bodine, DM Leri, A Anversa, P AF Orlic, D Kajstura, J Chimenti, S Limana, F Jakoniuk, I Quaini, F Nadal-Ginard, B Bodine, DM Leri, A Anversa, P TI Mobilized bone marrow cells repair the infarcted heart, improving function and survival SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GROWTH-FACTOR-I; SKELETAL MYOBLAST TRANSPLANTATION; HEMATOPOIETIC STEM-CELLS; MYOCARDIAL-INFARCTION; CELLULAR BASIS; EXPRESSION; MOUSE; VIVO; BRAIN; BLOOD AB Attempts to repair myocardial infarcts by transplanting cardiomyocytes or skeletal myoblasts have failed to reconstitute healthy myocardium and coronary vessels integrated structurally and functionally with the remaining viable portion of the ventricular wall. The recently discovered growth and transdifferentiation potential of primitive bone marrow cells (BMC) prompted us, in an earlier study, to inject in the border zone of acute infarcts Lin(-) c-kit(POS) BMC from syngeneic animals. These BMC differentiated into myocytes and vascular structures, ameliorating the function of the infarcted heart. Two critical determinants seem to be required for the transdifferentiation of primitive BMC: tissue damage and a high level of pluripotent cells. On this basis, we hypothesized here that BMC, mobilized by stem cell factor and granulocyte-colony stimulating factor, would home to the infarcted region, replicate, differentiate, and ultimately promote myocardial repair. We report that, in the presence of an acute myocardial infarct, cytokine-mediated translocation of BMC resulted in a significant degree of tissue regeneration 27 days later. Cytokine-induced cardiac repair decreased mortality by 68%, infarct size by 40%, cavitary dilation by 26%, and diastolic stress by 70%. Ejection fraction progressively increased and hemodynamics significantly improved as a consequence of the formation of 15 X 10(6) new myocytes with arterioles and capillaries connected with the circulation of the unaffected ventricle. In conclusion, mobilization of primitive BMC by cytokines might offer a noninvasive therapeutic strategy for the regeneration of the myocardium lost as a result of ischemic heart disease and, perhaps, other forms of cardiac pathology. C1 New York Med Coll, Dept Med, Inst Cardiovasc Res, Valhalla, NY 10595 USA. NHGRI, Hematopoiesis Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. RP Anversa, P (reprint author), New York Med Coll, Dept Med, Inst Cardiovasc Res, Valhalla, NY 10595 USA. FU NHLBI NIH HHS [R01 HL065577, HL-38132, HL-39902, HL-43023, HL-65577, HL-66923, P01 HL043023, R01 HL038132, R01 HL039902]; NIA NIH HHS [AG-15756, AG-17042, R01 AG017042] NR 39 TC 1481 Z9 1718 U1 4 U2 96 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 AUG 28 PY 2001 VL 98 IS 18 BP 10344 EP 10349 DI 10.1073/pnas.181177898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 468BJ UT WOS:000170738000059 PM 11504914 ER PT J AU Moir, S Malaspina, A Ogwaro, KM Donoghue, ET Hallahan, CW Ehler, LA Liu, SY Adelsberger, J Lapointe, R Hwu, P Baseler, M Orenstein, JM Chun, TW Mican, JAM Fauci, AS AF Moir, S Malaspina, A Ogwaro, KM Donoghue, ET Hallahan, CW Ehler, LA Liu, SY Adelsberger, J Lapointe, R Hwu, P Baseler, M Orenstein, JM Chun, TW Mican, JAM Fauci, AS TI HIV-1 induces phenotypic and functional perturbations of B cells in chronically infected individuals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; IMMUNE-DEFICIENCY SYNDROME; SYSTEMIC-LUPUS-ERYTHEMATOSUS; T-DEPENDENT ANTIGEN; HUMAN LYMPHOCYTES-B; COMPLEMENT RECEPTORS; ANTIBODY-RESPONSE; HOMOSEXUAL MEN; EXPRESSION; VIRUS AB A number of perturbations of B cells has been described in the setting of HIV infection; however, most remain poorly understood. To directly address the effect of HIV replication on B cell function, we investigated the capacity of B cells isolated from HIV-infected patients to respond to a variety of stimuli before and after reduction of viremia by effective antiretroviral therapy. B cells taken from patients with high levels of plasma viremia were defective in their proliferative responses to various stimuli. Viremia was also associated with the appearance of a subpopulation of B cells that expressed reduced levels of CD21. After fractionation into CD21(high)- and CD21(low)-expressing B cells, the CD21(low) fraction showed dramatically reduced proliferation in response to B cell stimuli and enhanced secretion of immunoglobulins when compared with the CD21(high) fraction. Electron microscopic analysis of each fraction revealed cells with plasmacytoid features in the CD21(low) B cell population but not in the CD21(high) fraction. These results indicate that HIV viremia induces the appearance of a subset of B cells whose function is impaired and which may be responsible for the hypergammaglobulinemia associated with HIV disease. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. George Washington Univ, Dept Pathol, Washington, DC 20037 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A02, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-CO-56000] NR 36 TC 182 Z9 184 U1 1 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 AUG 28 PY 2001 VL 98 IS 18 BP 10362 EP 10367 DI 10.1073/pnas.181347898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 468BJ UT WOS:000170738000062 PM 11504927 ER PT J AU Smoot, LM Smoot, JC Graham, MR Somerville, GA Sturdevant, DE Migliaccio, CAL Sylva, GL Musser, JM AF Smoot, LM Smoot, JC Graham, MR Somerville, GA Sturdevant, DE Migliaccio, CAL Sylva, GL Musser, JM TI Global differential gene expression in response to growth temperature alteration in group A Streptococcus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE temperature regulation; microarray; real-time TaqMan reverse transcription-PCR; iron ID FERRIC-UPTAKE REGULATOR; GROUP-A STREPTOCOCCUS; PSEUDOMONAS-AERUGINOSA; SUPEROXIDE-DISMUTASE; ESCHERICHIA-COLI; VIRULENCE GENES; EXOTOXIN-A; ENVIRONMENTAL SIGNALS; STAPHYLOCOCCUS-AUREUS; PATHOGENIC BACTERIA AB Pathogens are exposed to different temperatures during an infection cycle and must regulate gene expression accordingly. However, the extent to which virulent bacteria alter gene expression in response to temperatures encountered in the host is unknown. Group A Streptococcus (GAS) is a human-specific pathogen that is responsible for illnesses ranging from superficial skin infections and pharyngitis to severe invasive infections such as necrotizing fasciitis and streptococcal toxic shock syndrome. GAS survives and multiplies at different temperatures during human infection. DNA microarray analysis was used to investigate the influence of temperature on global gene expression in a serotype M1 strain grown to exponential phase at 29 degreesC and 37 degreesC. Approximately 9% of genes were differentially expressed by at least 1.5-fold at 29 degreesC relative to 37 degreesC, including genes encoding transporter proteins, proteins involved in iron homeostasis, transcriptional regulators, phage-associated proteins, and proteins with no known homologue. Relatively few known virulence genes were differentially expressed at this threshold. However, transcription of 28 genes encoding proteins with predicted secretion signal sequences was altered, indicating that growth temperature substantially influences the extracellular proteome. TaqMan real-time reverse transcription-PCR assays confirmed the microarray data. We also discovered that transcription of genes encoding hemolysins, and proteins with inferred roles in iron regulation, transport, and homeostasis, was influenced by growth at 40 degreesC. Thus, GAS profoundly alters gene expression in response to temperature. The data delineate the spectrum of temperature-regulated gene expression in an important human pathogen and provide many unforeseen lines of pathogenesis investigation. C1 NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. RP Musser, JM (reprint author), NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, 903 S 4th St, Hamilton, MT 59840 USA. RI Somerville, Greg/B-1326-2013 OI Somerville, Greg/0000-0002-0991-8737 NR 45 TC 147 Z9 150 U1 0 U2 9 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 AUG 28 PY 2001 VL 98 IS 18 BP 10416 EP 10421 DI 10.1073/pnas.191267598 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 468BJ UT WOS:000170738000071 PM 11517341 ER PT J AU Dosemeci, A Tao-Cheng, JH Vinade, L Winters, CA Pozzo-Miller, L Reese, TS AF Dosemeci, A Tao-Cheng, JH Vinade, L Winters, CA Pozzo-Miller, L Reese, TS TI Glutamate-induced transient modification of the postsynaptic density SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID LONG-TERM POTENTIATION; DEPENDENT PROTEIN-KINASE; RAT DENTATE GYRUS; MAINTENANCE PHASE; SEQUENTIAL-CHANGES; CEREBRAL-ISCHEMIA; INTRACEREBRAL MICRODIALYSIS; AXOSPINOUS SYNAPSES; HIPPOCAMPAL-NEURONS; TRANSLOCATION AB Depolarization of rat hippocampal neurons with a high concentration of external potassium induces a thickening of postsynaptic densities (PSDs) within 1.5-3 min. After high-potassium treatment, PSDs thicken 2.1-fold in cultured neurons and 1.4-fold in hippocampal slices compared with their respective controls. Thin-section immunoelectron microscopy of hippocampal cultures indicates that at least part of the observed thickening of PSDs can be accounted for by an accumulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) on their cytoplasmic faces. Indeed, PSD-associated gold label for CaMKII increases 5-fold after depolarization with potassium. The effects of high-potassium treatment on the composition and structure of the PSDs are mimicked by direct application of glutamate. In cultures, glutamate-induced thickening of PSDs and the accumulation of CaMKII on PSDs are reversed within 5 min of removal of glutamate and Ca2+ from the extracellular medium. These results suggest that PSDs are dynamic structures whose thickness and composition are subject to rapid and transient changes during synaptic activity. C1 Marine Biol Labs, Woods Hole, MA 02543 USA. Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA. NINDS, Electron Microscopy Facil, Bethesda, MD 20892 USA. NINDS, Neurobiol Lab, Bethesda, MD 20892 USA. RP Marine Biol Labs, Woods Hole, MA 02543 USA. EM dosemeci@marinebio.mbl.edu NR 24 TC 98 Z9 103 U1 4 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 AUG 28 PY 2001 VL 98 IS 18 BP 10428 EP 10432 DI 10.1073/pnas.181336998 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 468BJ UT WOS:000170738000073 PM 11517322 ER PT J AU Paolocci, N Saavedra, WF Miranda, KM Martignani, C Isoda, T Hare, JM Espey, MG Fukuto, JM Feelisch, M Wink, DA Kass, DA AF Paolocci, N Saavedra, WF Miranda, KM Martignani, C Isoda, T Hare, JM Espey, MG Fukuto, JM Feelisch, M Wink, DA Kass, DA TI Nitroxyl anion exerts redox-sensitive positive cardiac inotropy in vivo by calcitonin gene-related peptide signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NITRIC-OXIDE SYNTHASE; SODIUM-NITROPRUSSIDE; VENTRICULAR MYOCYTES; POTENT VASODILATOR; MYOCARDIAL INJURY; L-ARGININE; RAT AORTA; MECHANISM; OXIDATION; NO AB Nitroxyl anion (NO-) is the one-electron reduction product of nitric oxide (NO.) and is enzymatically generated by NO synthase in vitro. The physiologic activity and mechanism of action of NO- in vivo remains unknown. The NO- generator Angeli's salt (AS, Na2N2O3) was administered to conscious chronically instrumented dogs, and pressure-dimension analysis was used to discriminate contractile from peripheral vascular responses. AS rapidly enhanced left ventricular contractility and concomitantly lowered cardiac preload volume and diastolic pressure (venodilation) without a change in arterial resistance. There were no associated changes in arterial or venous plasma cGMP. The inotropic response was similar despite reflex blockade with hexamethonium or volume reexpansion, indicating its independence from baroreflex stimulation. However, reflex activation did play a major role in the selective venodilation observed under basal conditions. These data contrasted with the pure NO donor diethylamine/NO, which induced a negligible inotropic response and a more balanced veno/arterial dilation. AS-induced positive inotropy, but not systemic vasodilatation, was highly redox-sensitive, being virtually inhibited by coinfusion of N-acetyl-L-cysteine. Cardiac inotropic signaling by NO- was mediated by calcitonin gene-related peptide (CGRP), as treatment with the selective CGRP-receptor antagonist CGRP-(8-37) prevented this effect but not systemic vasodilation. Thus, NO- is a redox-sensitive positive inotrope with selective venodilator action, whose cardiac effects are mediated by CGRP-receptor stimulation. This fact is evidence linking NO- to redox-sensitive cardiac contractile modulation by nonadrenergic/noncholinergic peptide signaling. Given its cardiac and vascular properties, NO- may prove useful for the treatment of cardiovascular diseases characterized by cardiac depression and elevated venous filling pressures. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. Univ Calif Los Angeles, Dept Mol Pharmacol, Los Angeles, CA 90095 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Biomed Engn, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21287 USA. RP Kass, DA (reprint author), Johns Hopkins Univ Hosp, Halsted 500,600 N Wolfe St, Baltimore, MD 21287 USA. RI Miranda, Katrina/B-7823-2009; Feelisch, Martin/C-3042-2008 OI Feelisch, Martin/0000-0003-2320-1158 FU NHLBI NIH HHS [HL-47511, P50-HL52307, R01 HL047511] NR 37 TC 180 Z9 183 U1 2 U2 17 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 AUG 28 PY 2001 VL 98 IS 18 BP 10463 EP 10468 DI 10.1073/pnas.181191198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 468BJ UT WOS:000170738000079 PM 11517312 ER PT J AU Souici, AC Fitzhugh, AL Keefer, LK Felley-Bosco, E AF Souici, AC Fitzhugh, AL Keefer, LK Felley-Bosco, E TI L-tyrosine and nitric oxide synergize to prevent cytotoxic effects of superoxide SO TOXICOLOGY LA English DT Article DE nitric oxide; reactive oxygen species; reactive nitrogen species; L-tyrosine; epithelial cells; oxidative damage ID HYDROGEN-PEROXIDE; XANTHINE-OXIDASE; PEROXYNITRITE FORMATION; LIPID-PEROXIDATION; PHYSIOLOGICAL PH; IN-VIVO; NITRATION; CELLS; MACROPHAGES; OXYGEN AB We found previously that the nitric oxide donor DEA/NO enhanced lipid peroxidation, DNA fragmentation, and cytotoxicity in human bronchial epithelial cells (BEAS-2B) when they were cultured in LHC-8 medium containing the superoxide-generating system hypoxanthine/xanthine oxidase (HX/XO). We have now discovered that DEA/NO's prooxidant action can be reversed by raising the L-tyrosine concentration from 30 to 400 muM. DEA/NO also protected the cells when they were cultured in Dulbecco's Modified Eagle's Medium (DMEM), whose standard concentration Of L-tyrosine is 400 muM. Similar trends were seen with the colon adenoma cell line CaCo-2. Since HPLC analysis of cell-free DMEM or LHC-8 containing 400 PM L-tyrosine, DEA/NO, and HX/XO revealed no evidence of L-tyrosine nitration, our data suggest the existence of an as-yet uncharacterized mechanism by which L-tyrosine can influence the biochemical and toxicological effects of reactive nitrogen species. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Inst Pharmacol & Toxicol, CH-1005 Lausanne, Switzerland. NCI, Intramural Res Support Program, SAIC, Frederick, MD 21702 USA. NCI, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Felley-Bosco, E (reprint author), Inst Pharmacol & Toxicol, Bugnon 27, CH-1005 Lausanne, Switzerland. RI Keefer, Larry/N-3247-2014; Felley-Bosco, Emanuela/E-7484-2017 OI Keefer, Larry/0000-0001-7489-9555; Felley-Bosco, Emanuela/0000-0002-3408-0294 FU NCI NIH HHS [N01-CO-56000] NR 42 TC 2 Z9 2 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD AUG 28 PY 2001 VL 165 IS 2-3 BP 163 EP 170 DI 10.1016/S0300-483X(01)00428-0 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 470HT UT WOS:000170865900009 PM 11522374 ER PT J AU Fechner, JH Dong, YC Hong, XN Brunner, KG Tsuchida, M Neville, D Scharff, J Lee, F Oberley, TD Peters, D Schultz, JM Manthei, ER Hamawy, MM Knechtle, SJ AF Fechner, JH Dong, YC Hong, XN Brunner, KG Tsuchida, M Neville, D Scharff, J Lee, F Oberley, TD Peters, D Schultz, JM Manthei, ER Hamawy, MM Knechtle, SJ TI Graft survival in a rhesus renal transplant model after immunotoxin-mediated T-cell depletion is enhanced by mycophenolate and steroids SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-Society-of-Transplantation CY MAY 15-19, 1999 CL CHICAGO, ILLINOIS SP Amer Soc Transplantat ID MONOCLONAL-ANTIBODIES; IMMUNOSUPPRESSIVE ACTIVITY; WORKING CLASSIFICATION; ALLOGRAFT REJECTION; NONHUMAN-PRIMATES; TOLERANCE; LYMPHOCYTES; ANTI-CD3-IMMUNOTOXIN; MONKEYS; PERITRANSPLANT AB Background. Anti-CD3 immunotoxin (IT), a T-cell-depleting agent, prolongs survival of renal allografts in a rhesus monkey model without the need for longterm immunosuppression. In this study we sought to further prolong allograft survival by giving short-term conventional immunosuppression. simultaneous with IT administration. Methods. MHC class II mismatched, juvenile rhesus monkeys were paired as donor and recipient for renal transplantation. Recipients received two to three daily doses of IT starting on the day of transplantation. Additional immunosuppression was given for no more than 60 days. Graft function was monitored by serum creatinine and renal biopsies. Flow cytometry was used to monitor T-cell recovery. Results. Graft survival time (GST) in animals receiving IT was prolonged compared with controls with 50% of IT-treated monkeys surviving > 100 days. Animals treated with IT plus mycophenolate mofetil (MMF) and steroids had significantly enhanced GST (mean GST, 305 days) compared with those treated with IT alone (mean GST, 94 days). In contrast, addition of cyclosporine or 40-O-[2-Hydroxyethyl]rapamycin did not significantly increase graft survival time. A comparison among animals from all treatment groups with short (< 100 days) and long (> 100 days) GST demonstrated that those with the shorter GST had a higher blood T-cell count 2 weeks after transplantation. Full recovery of CD4(+) T cells required longer than 6 months. Conclusions. A combination with MMF and steroids given for 4 days after renal allograft transplantation significantly increases GST in IT-treated monkeys. We hypothesize that MMF and steroids suppress the initial T-cell activation mediated by IT. C1 Univ Wisconsin, Dept Surg, Madison, WI 53792 USA. Univ Wisconsin, Dept Radiol, Madison, WI 53792 USA. Univ Wisconsin, Dept Pathol, Madison, WI 53792 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Knechtle, SJ (reprint author), Room H4-784 CSC,600 Highland Ave, Madison, WI 53792 USA. RI Fechner, John/C-5962-2016 OI Fechner, John/0000-0002-8220-7237 FU NIAID NIH HHS [R01 AI40597] NR 21 TC 7 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2001 VL 72 IS 4 BP 581 EP 587 DI 10.1097/00007890-200108270-00005 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 472DP UT WOS:000170968400005 PM 11544415 ER PT J AU Cho, CS Burkly, LC Fechner, JH Kirk, AD Oberley, TD Dong, YC Brunner, KG Peters, D Tenhoor, CN Nadeau, K Yagci, G Ishido, N Schultz, JM Tsuchida, M Hamawy, MM Knechtle, SJ AF Cho, CS Burkly, LC Fechner, JH Kirk, AD Oberley, TD Dong, YC Brunner, KG Peters, D Tenhoor, CN Nadeau, K Yagci, G Ishido, N Schultz, JM Tsuchida, M Hamawy, MM Knechtle, SJ TI Successful conversion from conventional immunosuppression to anti-CD154 monoclonal antibody costimulatory molecule blockade in rhesus renal allograft recipients SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Society-of-Transplantation CY MAY 13-17, 2000 CL CHICAGO, ILLINOIS SP Amer Soc Transplantat ID INTRAHEPATIC ISLET ALLOGRAFTS; LONG-TERM SURVIVAL; TRANSPLANTATION TOLERANCE; HUMANIZED ANTI-CD154; REJECTION; INDUCTION; IMMUNOTOXIN; REQUIREMENT; RAPAMYCIN; PRIMATES AB Background. Several conventional forms of nosuppression. have been shown to antagonize the efficacy of anti-CD154 monoclonal antibody- (mAb) based costimulatory molecule blockade immunotherapy. Our objective was to determine if allograft recipients treated with a conventional immunosuppressive regimen could be sequentially converted to anti-CD154 mAb monotherapy without compromising graft survival. Methods. Outbred juvenile rhesus monkeys underwent renal allotransplantation from MHC-disparate donors. After a 60-day course of triple therapy immunosuppression. with steroids, cyclosporine, and mycophenolate mofetil, monkeys were treated with: (1) cessation of all immunosuppression (control); (2) seven monthly doses of 20 mg/kg hu5C8 (maintenance), or; (3) 20 mg/kg hu5C8 on posttransplant days 60, 61, 64, 71, 79, and 88 followed by five monthly doses (induction+maintenance). Graft rejection was defined by elevation in serum creatinine >1.5 mg/dl combined with histologic evidence of rejection. Results. Graft survival for the three groups were as follows: group I (control): 70, 75, > 279 days; group 2 (maintenance): 83, 349, > 293 days, and; group 3 (induction+ maintenance): 355, > 377, > 314 days. Acute rejection developing in two of four monkeys after treatment with conventional immunosuppression was successfully reversed with intensive hu5CS monotherapy. Conclusions. Renal allograft recipients can be successfully converted to CD154 blockade monotherapy after 60 days of conventional immunosuppression. An induction phase of anti-CD154 mAb appears to be necessary for optimal conversion. Therefore, although concurrent administration of conventional immunosuppressive agents including steroids and calcineurin inhibitors has been shown to inhibit the efficacy of CD154 blockade, sequential conversion from these agents to CD154 blockade appears to be effective. C1 Univ Wisconsin Hosp & Clin, Dept Surg, Div Transplantat, Clin Sci Ctr H4 784, Madison, WI 53792 USA. Univ Wisconsin Hosp & Clin, Dept Pathol, Madison, WI 53792 USA. Biogen Inc, Cambridge, MA 02142 USA. NIDDK, USN, Med Res Ctr, Navy Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. RP Knechtle, SJ (reprint author), Univ Wisconsin Hosp & Clin, Dept Surg, Div Transplantat, Clin Sci Ctr H4 784, 600 Highland Ave, Madison, WI 53792 USA. RI Kirk, Allan/B-6905-2012; Fechner, John/C-5962-2016 OI Fechner, John/0000-0002-8220-7237 FU NIAID NIH HHS [P01 AI43900] NR 20 TC 30 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2001 VL 72 IS 4 BP 587 EP 597 DI 10.1097/00007890-200108270-00006 PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 472DP UT WOS:000170968400006 PM 11544416 ER PT J AU Cox, ED Hoffmann, SC DiMercurio, BS Wesley, RA Harlan, DM Kirk, AD Blair, PJ AF Cox, ED Hoffmann, SC DiMercurio, BS Wesley, RA Harlan, DM Kirk, AD Blair, PJ TI Cytokine polymorphic analyses indicate ethnic differences in the allelic distribution of interleukin-2 and interleukin-6 SO TRANSPLANTATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; TRANSFORMING GROWTH-FACTOR-BETA-1 GENE; DEPENDENT DIABETES-MELLITUS; RENAL-ALLOGRAFT REJECTION; CORONARY HEART-DISEASE; INTERFERON-GAMMA; MYCOPHENOLATE-MOFETIL; RACIAL-DIFFERENCES; IL-2 PRODUCTION; BLOOD-PRESSURE AB Background. Polymorphisms in the regulatory regions of cytokine genes affect protein production and are associated with allograft outcome. Ethnic origin has been identified as a significant prognostic factor for several immune-mediated diseases and for outcome after allotransplantation. A clear relationship between cytokine polymorphisms and ethnicity has not been shown. Methods. One hundred sixty subjects including 102 whites and 43 African-Americans were studied. Using polymerase chain reaction-based assays and, in some cases, restriction enzyme digestion, we determined genetic polymorphisms for the cytokines interleukin (IL)-2, IL-6, IL-10, tumor necrosis factor-alpha, transforming growth factor-beta, and interferon-gamma (IFN-gamma). Genetic polymorphism. frequencies were then compared to ethnicity using chi-square analysis and Fisher's exact two-tailed tests. Results. For both the IL-2 and IL-6 genes, we found that whites and African-Americans differed significantly (P <0.05) in their allelic distribution and genotype frequency. A trend toward ethnic distribution was noted among the alleles and genotypes for the IL-10 and IFN-gamma genes. We found no correlation between ethnicity and either allelic distribution or genotype frequency for the tumor necrosis factor-alpha or transforming growth factor-beta genes. When comparisons were made between patients with or without a history of kidney failure, the allelic or genotypic distributions for the IL-6 and IFN-gamma genes were found to significantly differ. Conclusions. Our work demonstrates a correlation between ethnicity and polymorphisms in several cytokine genes. In addition, we found that patients requiring renal transplantation differ from the general population with regard to certain cytokine gene polymorphisms. These findings may have relevance in making prognostic determinations or tailoring immunomodulatory regimens after renal transplantation. C1 NIDDKD, Natl Naval Med Ctr, Navy Transplantat & Autoimmun Branch, Bethesda, MD 20889 USA. Walter Reed Army Med Ctr, Dept Surg, Washington, DC 20307 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Blair, PJ (reprint author), NIDDK, Natl Naval Med Ctr, Navy Transplantat & Autoimmun Branch, Bldg 46,Room 2421,8901 Wisconsin Ave, Bethesda, MD 20889 USA. RI Kirk, Allan/B-6905-2012; e-, a/F-9947-2012 NR 61 TC 117 Z9 121 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD AUG 27 PY 2001 VL 72 IS 4 BP 720 EP 726 DI 10.1097/00007890-200108270-00027 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 472DP UT WOS:000170968400027 PM 11544437 ER PT J AU La Vecchia, C Brinton, LA McTiernan, A AF La Vecchia, C Brinton, LA McTiernan, A TI Menopause, hormone replacement therapy and cancer SO MATURITAS LA English DT Review DE menopause; hormone replacement therapy (HRT); cancer ID ESTROGEN-PROGESTIN-REPLACEMENT; EPITHELIAL OVARIAN-CANCER; EXOGENOUS FEMALE HORMONES; LARGE-BOWEL-CANCER; STATES CASE-CONTROL; TERM FOLLOW-UP; BREAST-CANCER; ENDOMETRIAL CANCER; COLORECTAL-CANCER; RISK-FACTORS AB Objective: To comparatively review available evidence on hormone replacement therapy (HRT) and cancer. Methods: Qualitative literature review. Results: Most potential favorable and adverse effects on cancer risk of HRT are restricted to current users. On the basis of observational epidemiological data, the RR of breast cancer is moderately elevated in current and recent HRT users, and increases by about 2.3% per year with longer duration of use, but the effect drops after cessation and largely, if not totally, disappears after about 5 years. Unopposed estrogen use is strongly related to endometrial cancer risk, but cyclic combined oestrogen-progestin treatment appears to largely or totally reduce this side effect, if progestin are used for at least 14 days per cycle. However, combined HRT may be associated with higher risk of breast cancer as compared to unopposed estrogens. HRT has been inversely related to colorectal cancer, although the issue of causal relation remains open to discussion. No consistent association was reported for ovarian, liver, other digestive or lung cancer. Conclusions: Recommendations for prolonged HRT use must be considered on an individual basis, taking into account the presence of other risk factors mainly for breast cancer, such as family history of breast cancer or a personal history of benign breast disease, as well as individual risk for other chronic diseases. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Ist Ric Farmacol Mario Negri, I-20157 Milan, Italy. Univ Milan, Ist Stat Med & Biometria, I-20133 Milan, Italy. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP La Vecchia, C (reprint author), Ist Ric Farmacol Mario Negri, Via Eritrea 62, I-20157 Milan, Italy. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 157 TC 35 Z9 37 U1 2 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-5122 J9 MATURITAS JI Maturitas PD AUG 25 PY 2001 VL 39 IS 2 BP 97 EP 115 PG 19 WC Geriatrics & Gerontology; Obstetrics & Gynecology SC Geriatrics & Gerontology; Obstetrics & Gynecology GA 469LK UT WOS:000170816800001 PM 11514109 ER PT J AU Himmelmann, B Terry, C Dey, BR Lopaczynski, W Nissley, P AF Himmelmann, B Terry, C Dey, BR Lopaczynski, W Nissley, P TI Anchorage-independent growth of fibroblasts that express a truncated IGF-I receptor SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE IGF-I receptor; anchorage-independent growth; MAP kinase; P13-kinase; EGF; PDGF ID STAT3 ACTIVATION; INSULIN-RECEPTOR; TRANSFORMING ACTIVITIES; CELL-TRANSFORMATION; TERMINAL TRUNCATION; PROTEIN-KINASE; MITOGENESIS; MUTATION; TYROSINE-1251; TUMORIGENESIS AB The purpose of this investigation was to study signaling by an insulin-like growth factor I receptor (IGF-I R) that lacks the extracellular portion of the receptor. We transfected IGF-I R-negative mouse embryo fibroblasts with a truncated IGF-I R consisting of only the transmembrane and cytoplasmic part of the beta subunit. Proliferation as assessed by counting cells was the same for vector only transfectants and the truncated receptor transfectants in defined medium containing EGF and PDGF. In contrast, anchorage-independent growth as measured by colony formation in soft agar was markedly increased for the truncated IGF-I R transfectants compared to the vector transfectants. MAP-kinase activity in the truncated IGF-I R transfectants was not higher than in the vector transfectants; however, PI 3-kinase activity was significantly higher in the IGF-I R transfectants. These results provide evidence that an IGF-I receptor consisting of only the transmembrane and cytoplasmic domain of the beta subunit can signal pathways leading to anchorage-independent growth. C1 NCI, Endocrinol Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Nissley, P (reprint author), NCI, Endocrinol Sect, Metab Branch, NIH, Bldg 10,Room 4N115, Bethesda, MD 20892 USA. NR 32 TC 3 Z9 3 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD AUG 24 PY 2001 VL 286 IS 3 BP 472 EP 477 DI 10.1006/bbrc.2001.5417 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 468FY UT WOS:000170748500006 PM 11511082 ER PT J AU Kim, T Tao-Cheng, JH Eiden, LE Loh, YP AF Kim, T Tao-Cheng, JH Eiden, LE Loh, YP TI Chromogranin A, an "on/off" switch controlling dense-core secretory granule biogenesis SO CELL LA English DT Article ID TERMINAL DOMAINS; CELLS; EXPRESSION; AGGREGATION; PROTEIN; GENE; PH; VESICLES; PEPTIDES; PATHWAY AB We present evidence that regulation of dense-core secretory granule biogenesis and hormone secretion in endocrine cells is dependent on chromogranin A (CGA). Downregulation of CGA expression in a neuroendocrine cell line, PC12, by antisense RNAs led to profound loss of dense-core secretory granules, impairment of regulated secretion of a transfected prohormone, and reduction of secretory granule proteins. Transfection of bovine CGA into a CGA-deficient PC12 clone rescued the regulated secretory phenotype. Stable transfection of CGA into a CGA-deficient pituitary cell line, 6T3, lacking a regulated secretory pathway, restored regulated secretion. Overexpression of CGA induced dense-core granules, immunoreactive for CGA, in nonendocrine fibroblast CV-1 cells. We conclude that CGA is an "on/off" switch that alone is sufficient to drive dense-core secretory granule biogenesis and hormone sequestration in endocrine cells. C1 NICHHD, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. NINDS, EM Facil, Bethesda, MD 20892 USA. NIMH, Lab Cellular & Mol Regulat, Mol Neurosci Sect, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Dev Neurobiol Lab, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. OI Eiden, Lee/0000-0001-7524-944X NR 30 TC 290 Z9 301 U1 1 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 24 PY 2001 VL 106 IS 4 BP 499 EP 509 DI 10.1016/S0092-8674(01)00459-7 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 466UU UT WOS:000170665200013 PM 11525735 ER PT J AU Horan, B Gardner, EL Dewey, SL Brodie, JD Ashby, CR AF Horan, B Gardner, EL Dewey, SL Brodie, JD Ashby, CR TI The selective sigma(1) receptor agonist, 1-(3,4-dimethoxyphenethyl)-4-(phenylpropyl) piperazine (SA4503), blocks the acquisition of the conditioned place preference response to (-)-nicotine in rats SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE conditioned place preference; nicotine; sigma receptor AB We examined the effect of the sigma (1) receptor agonist, 1-(3,4-dimethoxyphenethyl)-4-(phenylpropyl)piperazine (SA4503), on the acquisition of the conditioned place preference response to subcutaneously administered (-)-nicotine in rats. (-)-Nicotine, but not SA4503 or vehicle, produced a significant conditioned place preference response. Pretreatment of animals with either 1 or 3 mg/kg of SA4503 significantly attenuated the conditioned place preference response to)-nicotine. (C) 2001 Published by Elsevier Science B.V. C1 St Johns Univ, Coll Pharm & Allied Hlth Profess, Pharmaceut Hlth Sci Dept, Jamaica, NY 11439 USA. NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. RP Ashby, CR (reprint author), St Johns Univ, Coll Pharm & Allied Hlth Profess, Pharmaceut Hlth Sci Dept, 8000 Utopia Pkwy, Jamaica, NY 11439 USA. NR 8 TC 16 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD AUG 24 PY 2001 VL 426 IS 1-2 BP R1 EP R2 DI 10.1016/S0014-2999(01)01229-8 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 470NX UT WOS:000170879000020 PM 11525784 ER PT J AU Yuan, PX Huang, LD Jiang, YM Gutkind, JS Manji, HK Chen, G AF Yuan, PX Huang, LD Jiang, YM Gutkind, JS Manji, HK Chen, G TI The mood stabilizer valproic acid activates mitogen-activated protein kinases and promotes neurite growth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SUBGENUAL PREFRONTAL CORTEX; HUMAN NEUROBLASTOMA-CELLS; DNA-BINDING ACTIVITY; OUTGROWTH IN-VITRO; C-JUN; TRANSCRIPTION FACTOR; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; MAP KINASE; PC12 CELLS AB The mood-stabilizing agents lithium and valproic acid (VPA) increase DNA binding activity and transactivation activity of AP-1 transcription factors, as wen as the expression of genes regulated by AP-1, in cultured cells and brain regions involved in mood regulation. In the present study, we found that VPA activated extracellular signal-regulated kinase (ERK), a kinase known to regulate AP-1 function and utilized by neurotrophins to mediate their diverse effects, including neuronal differentiation, neuronal survival, long term neuroplasticity, and potentially learning and memory. VPA-induced activation of ERK was blocked by the mitogen-activated protein kinase/ERK kinase inhibitor PD098059 and dominant-negative Ras and Raf mutants but not by dominant-negative stress-activated protein kinase/ERK kinase and mitogen-activated protein kinase kinase 6 mutants. VPA also increased the expression of genes regulated by the ERK pathway, including growth cone-associated protein 43 and Bcl-2, promoted neurite growth and cell survival, and enhanced norepinephrine uptake and release. These data demonstrate that VPA is an ERK pathway activator and produces neurotrophic effects. C1 NIMH, Unit Mol Neurotherapeut, Mol Pathophysiol Lab, NIH, Bethesda, MD 20892 USA. Wayne State Univ, Sch Med, Mol Pathophysiol Lab, Dept Psychiat & Behav Neurosci, Detroit, MI 48201 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Chen, G (reprint author), NIMH, Unit Mol Neurotherapeut, Mol Pathophysiol Lab, NIH, Bldg 49,Rm B1EE16,49 Convert Dr, MSC 4405, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009; Chen, Guang/A-2570-2017 FU NIMH NIH HHS [MH57743] NR 57 TC 240 Z9 251 U1 1 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 AUG 24 PY 2001 VL 276 IS 34 BP 31674 EP 31683 DI 10.1074/jbc.M104309200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 465WT UT WOS:000170613500029 PM 11418608 ER PT J AU Wang, LH Yang, XY Mihalic, K Xiao, WH Li, DP Farrar, WL AF Wang, LH Yang, XY Mihalic, K Xiao, WH Li, DP Farrar, WL TI Activation of estrogen receptor blocks interleukin-6-inducible cell growth of human multiple myeloma involving molecular cross-talk between estrogen receptor and STAT3 mediated by co-regulator PLAS3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOKINE RECEPTORS; TRANSCRIPTIONAL ACTIVATION; SIGNAL-TRANSDUCTION; PROTEIN INHIBITOR; ER-ALPHA; APOPTOSIS; PROMOTER; PIAS3; BETA; EXPRESSION AB Estrogen receptors (ERs)(1) highly expressed by multiple myeloma (NM) cells and stimulation of estrogenic ligands leads to cell apoptosis. Interleukin (IL)-6 is a major growth factor in the pathogenesis of MM. However, little is known concerning the molecular consequences of ER activation on IL-6-regulated AM cell growth. Here we show that the ER agonist 17 beta -estradiol completely abolished IL-6-inducible AM cell proliferation. By contrast, the ER antagonist ICI 182,780 overcame the inhibitory effect of estrogen. Estrogen blocked STAT3 DNA binding and transactivation but failed to affect the mRNA expression of IL-6 receptor chains or activation of JAK2 and STAT3. Estrogen-activated ER did not associate directly with STAT3. Estrogen induced the mRNA expression of PIAS3 ((p) under bar rotein (i) under bar nhibitor of (a) under bar ctivated (S) under bar TAT (3) under bar) and increased PIAS3 physical association with STAT3, suggesting a possible mechanism of STAT3 inhibition requiring PIAS3 as a co-regulator modulating the cross-talk between ER and STAT3. These data directly demonstrate STAT3 to be a molecular participant in ER inhibition of the IL-6 signaling pathway in human AM cells and provides the molecular basis for the potential use of estrogenic ligands in the treatment of AM or other tumors where IL-6 has an autocrine or paracrine role. C1 Sci Applicat Int Corp, Intramural Res Support Program, NCI, Frederick, MD 21702 USA. NCI, Div Basic Sci, Mol Immunoregulat Lab, Cytokine Mol Mech Sect, Frederick, MD 21702 USA. RP Wang, LH (reprint author), Sci Applicat Int Corp, Intramural Res Support Program, NCI, Frederick, MD 21702 USA. RI Xiao, Weihua/N-2775-2013 OI Xiao, Weihua/0000-0001-9102-6326 FU NCI NIH HHS [N01-CO-56000] NR 54 TC 55 Z9 57 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 AUG 24 PY 2001 VL 276 IS 34 BP 31839 EP 31844 DI 10.1074/jbc.M105185200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 465WT UT WOS:000170613500051 PM 11429412 ER PT J AU Shi, CS Kehrl, JH AF Shi, CS Kehrl, JH TI PYK2 links G(q)alpha and G(13)alpha signaling to NF-kappa B activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; PHOSPHOINOSITIDE 3-KINASE; MARGINAL ZONE; TYROSINE KINASE; CELLS; AKT; REQUIREMENT; BRADYKININ; PROTEINS; ABSENCE AB Signaling via a variety of G-protein-coupled receptors (GPCRs) leads to activation of nuclear factor (NF)-kappaB. Evidence exists for a signaling pathway initiated by the B2 type bradykinin receptor via G(q) activation, which leads to the sequential stimulation of phosphoinositide 3-kinase (PI3K), the serine/threonine kinase Akt, I kappaB kinases, and finally nuclear factor NF-kappaB-dependent transcription. GPCR-mediated G(q)alpha or G(13)alpha activation also potently stimulates the tyrosine kinase PYK2. In this study we tested whether G(q)alpha- and/or G(13)alpha -induced PYK2 activation contributes to GPCR-mediated NF-kappaB activation. Among the GTPase-deficient forms of G alpha tested, G(13)alpha and G(q)alpha most potently stimulated an NF-kappaB-dependent reporter gene. PYK2 activated the same reporter gene and synergized with either G(q)alpha Q209L (QL) or G(13)alpha Q226L (QL). Placing PYK2 upstream of both PI3K and Akt activation, PYK2 activated Aht through a PI3K-dependent pathway, and either a dominant negative form of Aht or the PI3K inhibitor LY294002 blocked PYK2-stimulated NF-kappaB-dependent transcription. Placing PYK2 downstream of G-protein activation, a kinase-dead form of PYK2, PYK2 (KD), blocked NF-kappaB-dependent transcription triggered by signaling through the muscarinic receptor type 1 and either G(q)alpha QL or G(13)alpha QL. PYK2 (KD) also blocked Akt activation by the same stimuli. These results indicate that PYK2 can link G-protein activation through PI3K, Akt, and I kappaB kinase to NF-kappaB activation. C1 NIAID, Immunoregulat Lab, Cell Mol Immunol Sect B, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, Immunoregulat Lab, Cell Mol Immunol Sect B, NIH, Bldg 10 Rm 11B08,10 Ctr DR MSC 1876, Bethesda, MD 20892 USA. NR 24 TC 51 Z9 52 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 AUG 24 PY 2001 VL 276 IS 34 BP 31845 EP 31850 DI 10.1074/jbc.M101043200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 465WT UT WOS:000170613500052 PM 11435419 ER PT J AU Gibson, CW Yuan, ZA Hall, B Longenecker, G Chen, EH Thyagarajan, T Sreenath, T Wright, JT Decker, S Piddington, R Harrison, G Kulkarni, AB AF Gibson, CW Yuan, ZA Hall, B Longenecker, G Chen, EH Thyagarajan, T Sreenath, T Wright, JT Decker, S Piddington, R Harrison, G Kulkarni, AB TI Amelogenin-deficient mice display an amelogenesis imperfecta phenotype SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DYNAMIC LIGHT-SCATTERING; TARGETED DISRUPTION; NONSENSE MUTATION; MESSENGER-RNAS; ENAMEL MATRIX; GENE AMGX; PROTEINS; AIH1; TOOTH; PROTOONCOGENE AB Dental enamel is the hardest tissue in the body and cannot be replaced or repaired, because the enamel secreting cells are lost at tooth eruption. X-linked amelogenesis imperfecta (MIM 301200), a phenotypically diverse hereditary disorder affecting enamel development, is caused by deletions or point mutations in the human X-chromosomal amelogenin gene. Although the precise functions of the amelogenin proteins in enamel formation are not well defined, these proteins constitute 90% of the enamel organic matrix. We have disrupted the amelogenin locus to generate amelogenin null mice, which display distinctly abnormal teeth as early as 2 weeks of age with chalky-white discoloration. Microradiography revealed broken tips of incisors and molars and scanning electron microscopy analysis indicated disorganized hypoplastic enamel. The amelogenin null phenotype reveals that the amelogenins are apparently not required for initiation of mineral crystal formation but rather for the organization of crystal pattern and regulation of enamel thickness. These null mice will be useful for understanding the functions of amelogenin proteins during enamel formation and for developing therapeutic approaches for treating this developmental defect that affects the enamel. C1 Univ Penn, Sch Dent Med, Dept Anat & Histol, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Dept Biochem, Philadelphia, PA 19104 USA. NIDCR, Funct Genom Unit, NIH, Bethesda, MD 20892 USA. NIDCR, Gene Targeting Facil, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Dept Pediat Dent, Chapel Hill, NC 27599 USA. RP Gibson, CW (reprint author), Univ Penn, Sch Dent Med, Dept Anat & Histol, 4010 Locust St, Philadelphia, PA 19104 USA. FU NIDCR NIH HHS [Z01DE00694-010DIR, DE10149, DE11089, DE12879] NR 41 TC 279 Z9 281 U1 2 U2 16 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 AUG 24 PY 2001 VL 276 IS 34 BP 31871 EP 31875 DI 10.1074/jbc.M104624200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 465WT UT WOS:000170613500056 PM 11406633 ER PT J AU Zheng, LX Schickling, O Peter, ME Lenardo, MJ AF Zheng, LX Schickling, O Peter, ME Lenardo, MJ TI The death effector domain-associated factor plays distinct regulatory roles in the nucleus and cytoplasm SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR YY1; CELL-DEATH; CONTAINING PROTEIN; SIGNALING COMPLEX; CD95 FAS/APO-1; APOPTOSIS; FADD; FAS; INTERACTS; RECEPTOR AB Homophilic interactions of death effector domains (DEDs) are crucial for the signaling pathways of death receptor-mediated apoptosis. The machinery that regulates proper oligomerization and autoactivation of procaspase-8 and/or procaspase-10 during T lymphocyte activation determines whether the cells will undergo caspase-mediated apoptosis or proliferation. We screened a yeast two-hybrid library by using the DEDs contained in the prodomains of procaspase-8 and procaspase-10 and isolated a DED-associated factor (DEDAF) that interacts with several DED-containing proteins but does not itself contain a DED. DEDAF is highly conserved between human and mouse (98% amino acid identity) and is homologous to a nuclear regulatory protein YAF-2. DEDAF is expressed at the highest levels in lymphoid tissues and placenta. DEDAF interacts with FADD, procaspase-8, and procaspase-10 in the cytosol as well as with the DED-containing DNA-binding protein (DEDD) in the nucleus. At the cell membrane, DEDAF augmented the formation of CD95-FADD-caspase-8 complexes and enhanced death receptor- as well as DED-mediated apoptosis. In the nucleus, DEDAF caused the DEDD protein to relocalize from subnuclear structures to a diffuse distribution in the nucleoplasm. Our data therefore suggest that DEDAF may be involved in the regulation of both cytoplasmic and nuclear events of apoptosis. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 24 TC 52 Z9 58 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 AUG 24 PY 2001 VL 276 IS 34 BP 31945 EP 31952 DI 10.1074/jbc.M102799200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 465WT UT WOS:000170613500066 PM 11395500 ER PT J AU Reyes-Cruz, G Hu, JX Goldsmith, PK Steinbach, PJ Spiegel, AM AF Reyes-Cruz, G Hu, JX Goldsmith, PK Steinbach, PJ Spiegel, AM TI Human Ca2+ receptor extracellular domain - Analysis of function of lobe I loop deletion mutants SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-SENSING RECEPTOR; CELL-SURFACE EXPRESSION; N-LINKED GLYCOSYLATION; SIGNAL-TRANSDUCTION; IDENTIFICATION; DIMERIZATION; MUTATIONS AB The G protein-coupled Ca2+ receptor (CaR) possesses an similar to 600-residue extracellular domain involved in ligand binding and receptor activation. Based on an alignment of the amino acid sequence of the CaR with that of bacterial periplasmic-binding proteins, the first similar to 530 residues of the extracellular domain are believed to form a domain resembling a bilobed Venus's flytrap (VFT). Four insertions in the CaR sequence that do not align with those of bacterial periplasmic-binding proteins correspond to four loops within lobe I of the VFT. We constructed a series of deletion mutants of these four loops and tested their ability to form fully processed CaR as well as their ability to be activated by Ca2+. As many as 21 residues (365-385) of loop III could be deleted without impairing receptor expression or activation. Deletion of portions of either loops I (50-59) or IV (438-445) did not impair receptor expression but significantly reduced Ca2+ activation. Deletion of the entire loop II (117-137) abolished receptor expression and function, but the replacement of even a single residue within this deletion mutant led to expression of a monomeric form of the receptor showing increased Ca2+ sensitivity but reduced maximal activation. Our results reveal that certain residues within loops I and IV are dispensable in formation of the VFT domain but are critical for Ca2+ activation of the receptor. In contrast, the residues in loop II are critical for maintaining the inactive state of the CaR. We discuss these results in light of the recently defined crystal structure of the homologous domain of the type 1 metabotropic glutamate receptor. C1 NIH, CIT, Ctr Mol Modeling, Bethesda, MD 20892 USA. NIDCD, Mol Pathophysiol Sect, Bethesda, MD 20892 USA. RP Reyes-Cruz, G (reprint author), NIH, CIT, Ctr Mol Modeling, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. NR 19 TC 24 Z9 24 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 AUG 24 PY 2001 VL 276 IS 34 BP 32145 EP 32151 DI 10.1074/jbc.M102977200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 465WT UT WOS:000170613500092 PM 11399760 ER PT J AU Smith, SM Khoroshev, M Marx, PA Orenstein, J Jeang, KT AF Smith, SM Khoroshev, M Marx, PA Orenstein, J Jeang, KT TI Constitutively dead, conditionally live, HIV-1 genomes - Ex vivo implications for a live virus vaccine SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; NEF GENE; TYPE-1 REPLICATION; MAMMALIAN-CELLS; ATTENUATED SIV; TAT PROTEIN; IN-VIVO; TRANSCRIPTION; INFECTION AB An effective vaccine against AIDS is unlikely to be available for many years. As we approach two decades since the first identification of human immunodeficiency virus, type 1 (HIV-1), currently, only one subunit vaccine candidate has reached phase 3 of clinical trials. The subunit approach has been criticized for its inability to elicit effectively cytotoxic T-lymphocyte (CTL) response, which is felt by many to be needed for protection against HIV-1 infection. In subhuman primates, a live attenuated simian immunodeficiency virus (SIV) vaccine candidate, capable of inducing CTL, has been found to confer prophylactic immunity sufficient to prevent simian AIDS. Because replication competent (live) attenuated viruses could over time revert to virulence, such a live attenuated approach has largely been dismissed for HIV-1. Here, we describe the creation of constitutively dead conditionally live (CDCL) HIV-1 genomes. These genomes are constitutively defective for the Tat/TAR axis and are conditionally dependent on tetracycline for attenuated replication with robust expression of viral antigens. Our results suggest that CDCL genomes merit consideration as safer "live" attenuated HIV-1 vaccine candidates. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, St Michaels Med Ctr, Newark, NJ 07102 USA. Tulane Reg Primate Res Ctr, Covington, LA 70433 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. George Washington Univ, Sch Med, Dept Pathol, Washington, DC 20037 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Rm 306,900 Rockville Pike, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008 FU NIAID NIH HHS [AI46316-02] NR 42 TC 30 Z9 32 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 24 PY 2001 VL 276 IS 34 BP 32184 EP 32190 DI 10.1074/jbc.M101604200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 465WT UT WOS:000170613500097 PM 11397795 ER PT J AU Spizz, G Blackshear, PJ AF Spizz, G Blackshear, PJ TI Overexpression of the myristoylated alanine-rich C-kinase substrate inhibits cell adhesion to extracellular matrix components SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT TYROSINE PHOSPHORYLATION; CHONDROITIN SULFATE PROTEOGLYCANS; MARCKS-RELATED PROTEIN; MEMBRANE ASSOCIATION; MEDIATED PHOSPHORYLATION; CALMODULIN-BINDING; MOLECULAR-CLONING; BRAIN-DEVELOPMENT; CYTOCHALASIN-B; ACTIN AB Mice lacking the myristoylated alanine-rich C-kinase substrate, or MARCKS protein, exhibit abnormalities consistent with a defect in the ability of neurons to migrate appropriately during forebrain development. To investigate the possibility that this phenotype could be due to disruption of normal cellular adhesion to extracellular matrix, an assay was developed in which 293 cells co-expressing MARCKS and green fluorescent protein were tested for their adhesion competence on various substrates. Fluorescence-activated cell sorting of adherent and non-adherent green fluorescent protein-expressing cells demonstrated that wild-type MARCKS inhibited adhesion of cells to fibronectin, whereas a non-myristoylated mutant did not inhibit adhesion of cells to a variety of substrates. The fibronectin competitive inhibitor RGD peptide inhibited adhesion of cells expressing all MARCKS variants equally. Cytochalasin D inhibited the adhesion of cells expressing non-myristoylated MARCKS, but did not further decrease the adhesion of cells expressing adhesion-inhibitory proteins. Confocal microscopy demonstrated the presence of inhibitory, myristoylated MARCKS at the. plasma membrane, suggesting that localization at this region might be important for MARCKS to inhibit cellular adhesion. These data suggest a possible myristoylation-dependent function of MARCKS to inhibit cellular adhesion to extracellular matrix proteins, indicating a potential mechanism for the cell migration defects seen in the MARCKS-deficient. mice. C1 NIEHS, Off Clin Res, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Off Clin Res, NIH, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 64 TC 37 Z9 37 U1 1 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 AUG 24 PY 2001 VL 276 IS 34 BP 32264 EP 32273 DI 10.1074/jbc.M103960200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 465WT UT WOS:000170613500107 PM 11413143 ER PT J AU Mayer, ML Olson, R Gouaux, E AF Mayer, ML Olson, R Gouaux, E TI Mechanisms for ligand binding to GluR0 ion channels: Crystal structures of the glutamate and serine complexes and a closed Apo state SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE glutamate receptors; ion channels; ligand binding; X-ray crystallography; equilibrium centrifugation ID X-RAY STRUCTURE; SALMONELLA-TYPHIMURIUM; ESCHERICHIA-COLI; ACTIVE-TRANSPORT; SEDIMENTATION EQUILIBRIUM; ANOMALOUS DIFFRACTION; ANGSTROM RESOLUTION; PROTEIN-STRUCTURE; AMPA RECEPTORS; ACTIVATION AB High-resolution structures of the ligand binding core of GluR0, a glutamate receptor ion channel from Synechocystis PCC 6803, have been solved by X-ray diffraction. The GluR0 structures reveal homology with bacterial periplasmic binding proteins and the rat GluR2 AMPA subtype neurotransmitter receptor. The ligand binding site is formed by a cleft between two globular alpha/beta domains. L-Glutamate binds in an extended conformation, similar to that observed for glutamine binding protein (GlnBP). However, the L-glutamate gamma -carboxyl group interacts exclusively with Asn51 in domain 1, different from the interactions of ligand with domain 2 residues observed for GluR2 and GlnBP. To address how neutral amino acids activate GluR0 gating we solved the structure of the binding site complex with L-serine. This revealed solvent molecules acting as surrogate ligand atoms, such that the serine OH group makes solvent-mediated hydrogen bonds with Asn51. The structure of a ligand-free, closed-cleft conformation revealed an extensive hydrogen bond network mediated by solvent molecules. Equilibrium centrifugation analysis revealed dimerization of the GluR0 ligand binding core with a dissociation constant of 0.8 muM. In the crystal, a symmetrical dimer involving residues in domain 1 occurs along a crystallographic 2-fold axis and suggests that tetrameric glutamate receptor ion channels are assembled from dimers of dimers. We propose that ligand-induced conformational changes cause the ion channel to open as a result of an increase in domain 2 separation relative to the dimer interface. C1 NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. RP Mayer, ML (reprint author), NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49,Room 5A78,49 Convent Dr MSC 4495, Bethesda, MD 20892 USA. RI Mayer, Mark/H-5500-2013 FU NCRR NIH HHS [S10 RR12848] NR 58 TC 116 Z9 122 U1 1 U2 5 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD AUG 24 PY 2001 VL 311 IS 4 BP 815 EP 836 DI 10.1106/jmbi.2001.4884 PG 22 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 466RR UT WOS:000170659500014 PM 11518533 ER PT J AU Roca, AL Georgiadis, N Pecon-Slattery, J O'Brien, SJ AF Roca, AL Georgiadis, N Pecon-Slattery, J O'Brien, SJ TI Genetic evidence for two species of elephant in Africa SO SCIENCE LA English DT Article ID ALIGNMENT AB Elephants from the tropical forests of Africa are morphologically distinct from savannah or bush elephants. Dart-biopsy samples from 195 free-ranging African elephants in 21 populations were examined for DNA sequence variation in four nuclear genes (1732 base pairs). Phylogenetic distinctions between African forest elephant and savannah elephant populations corresponded to 58% of the difference in the same genes between elephant genera Loxodonta (African) and Elephas (Asian). Large genetic distance, multiple genetically fixed nucleotide site differences, morphological and habitat distinctions, and extremely limited hybridization of gene flow between forest and savannah elephants support the recognition and conservation management of two African species: Loxodonta africana and Loxodonta cyclotis. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. Mpala Res Ctr, Nanyuki, Kenya. RP O'Brien, SJ (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. NR 35 TC 168 Z9 176 U1 17 U2 86 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 AUG 24 PY 2001 VL 293 IS 5534 BP 1473 EP 1477 DI 10.1126/science.1059936 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 465XV UT WOS:000170616000040 PM 11520983 ER PT J AU Wu, YT Marsh, JW AF Wu, YT Marsh, JW TI Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA SO SCIENCE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; QUIESCENT CD4 LYMPHOCYTES; NEF GENE; MESSENGER-RNA; IN-VITRO; REPLICATION; ACTIVATION; INFECTION; EXPRESSION; PROTEIN AB The quiescent nature of most peripheral T cells poses an effective limitation to human immunodeficiency virus (HIV) replication and, in particular, to viral integration into the host chromatin. Two HIV proteins, Nef and Tat, increase T cell activity, but a requirement of integration for viral gene expression would preclude a rote for these proteins in resting cells. Here, we report that HIV infection leads to selective transcription of the nef and tat genes before integration. This preintegration transcription in quiescent cells leads to increased T cell activation and viral replication. C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Marsh, JW (reprint author), NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 31 TC 253 Z9 259 U1 1 U2 7 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 AUG 24 PY 2001 VL 293 IS 5534 BP 1503 EP 1506 DI 10.1126/science.1061548 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 465XV UT WOS:000170616000048 PM 11520990 ER PT J AU Peculis, BA DeGregorio, S McDowell, K AF Peculis, BA DeGregorio, S McDowell, K TI The U8 snoRNA gene family: identification and characterization of distinct, functional U8 genes in Xenopus SO GENE LA English DT Article DE ribosomal RNA; pre-ribosomal RNA processing; ribosome biogenesis; small nucleolar ribonucleoprotein particle; sequence heterogeneity; Xenopus laevis; oocyte ID SMALL NUCLEAR-RNA; SMALL NUCLEOLAR RNAS; 3' END FORMATION; RIBOSOMAL-RNA; U1 SNRNA; SEQUENCE; LAEVIS; ELEMENTS; U3; TRANSCRIPTION AB U8 snoRNA is the RNA component of a small nucleolar ribonucleoprotein (U8 snoRNP) required for accumulation of mature 5.8S and 28S rRNAs, components of the large ribosomal subunit. We have identified two putative U8 genes in Xenopus laevis. Sequence analysis of the coding regions of these two genes indicate that both differ at several positions from the previously characterized U8 RNA and that the two differ from each other. Functional analysis of these genes indicates that both are transcribed in vivo, produce stable U8 transcripts, and are capable of facilitating pre-rRNA processing in vivo. These data demonstrate that natural sequence variation exists among the U8 snoRNA genes in Xenopus. Alignment of these three Xenopus U8 sequences with the previously described mammalian U8 homologues in mouse, rat and human has provided information about evolutionarily conserved sequence and structural elements in U8 RNA. Identification and. functional characterization of these naturally occurring variants in Xenopus has helped identify regions in U8 RNA that may be critical for function. Published by Elsevier Science B.V. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06510 USA. RP Peculis, BA (reprint author), NIDDK, Genet & Biochem Branch, NIH, 10 Ctr Dr,8N322, Bethesda, MD 20892 USA. NR 39 TC 7 Z9 7 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 AUG 22 PY 2001 VL 274 IS 1-2 BP 83 EP 92 DI 10.1016/S0378-1119(01)00596-0 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 482PM UT WOS:000171584500008 PM 11675000 ER PT J AU Michaud, DS Giovannucci, E Willett, WC Colditz, GA Stampfer, MJ Fuchs, CS AF Michaud, DS Giovannucci, E Willett, WC Colditz, GA Stampfer, MJ Fuchs, CS TI Physical activity, obesity, height, and the risk of pancreatic cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BODY-FAT DISTRIBUTION; NATIONAL DEATH INDEX; GROWTH-FACTOR-I; DIABETES-MELLITUS; ACTIVITY QUESTIONNAIRE; NUTRITIONAL FACTORS; INSULIN; MORTALITY; MEN; GLUCOSE AB Context Diabetes mellitus and elevated postload plasma glucose levels have been associated with an increased risk of pancreatic cancer in previous studies. By virtue of their influence on insulin resistance, obesity and physical inactivity may increase risk of pancreatic cancer. Objective To examine obesity, height, and physical activity in relation to pancreatic cancer risk. Design and Setting Two US cohort studies conducted by mailed questionnaire, the Health Professionals Follow-Up Study (initiated in 1986) and the Nurses' Health Study (initiated in 1976), with 10 to 20 years of follow-up. Participants A total of 46648 men aged 40 to 75 years and 117041 women aged 30 to 55 years who were free of prior cancer at baseline and had complete data on height and weight. Main Outcome Measures Relative risk of pancreatic cancer, analyzed by self-reported body mass index (BMI), height, and level of physical activity. Results During follow-up, we documented 350 incident pancreatic cancer cases. Individuals with a BMI of at least 30 kg/m(2) had an elevated risk of pancreatic cancer compared with those with a BMI of less than 23 kg/m(2) (multivariable relative risk [RR], 1.72; 95% confidence interval [CI], 1.19-2.48), Height was associated with an increased pancreatic cancer risk (multivariable RR, 1.81; 95% CI, 1.31-2.52 for the highest vs lowest categories). An inverse relation was observed for moderate activity (multivariable RR, 0.45; 95% CI, 0.29-0.70 for the highest vs lowest categories; P for trend <.001). Total physical activity was not associated with risk among individuals with a BMI of less than 25 kg/m(2) but was inversely associated with risk among individuals with a BMI of at least 25 kg/m(2) (pooled multivariable RR, 0.59; 95% CI, 0.37-0.94 for the top vs bottom tertiles of total physical activity; P for trend=.04). Conclusion In 2 prospective cohort studies, obesity significantly increased the risk of pancreatic cancer. Physical activity appears to decrease the risk of pancreatic cancer, especially among those who are overweight. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Michaud, DS (reprint author), NCI, 6120 Execut Blvd,EPS Room 7026, Rockville, MD 20852 USA. RI Michaud, Dominique/I-5231-2014; Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA 86102, CA 55075, CA 87969] NR 50 TC 326 Z9 333 U1 2 U2 22 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 AUG 22 PY 2001 VL 286 IS 8 BP 921 EP 929 DI 10.1001/jama.286.8.921 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 465EU UT WOS:000170577300026 PM 11509056 ER PT J AU Scuteri, A Bos, AJG Brant, LJ Talbot, L Lakatta, EG Fleg, JL AF Scuteri, A Bos, AJG Brant, LJ Talbot, L Lakatta, EG Fleg, JL TI Hormone replacement therapy and longitudinal changes in blood pressure in postmenopausal women SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; ESTROGEN REPLACEMENT; NITRIC-OXIDE; MENOPAUSE; HYPERTENSION; ESTRADIOL; HEALTH; ARTERY; AGE; PREVENTION AB Background: The incidence of hypertension in postmenopausal women exceeds that in age-matched men. Longitudinal studies relating hormone replacement therapy (HRT) to blood pressure changes are sparse. Objective: To investigate the association between HRT and longitudinal changes In blood pressure In postmenopausal women. Design: Longitudinal observational study. Setting: Community-dwelling volunteers. Patients: 226 healthy, normotensive postmenopausal women from the Baltimore Longitudinal Study of Aging with a mean (+/- SD) age of 64 +/- 10 years were followed for 5.7 +/- 5.3 years. Seventy-seven women used both estrogen and progestin, and 149 used neither. Measurements: Lifestyle variables, blood pressure, and traditional cardiovascular risk factors were measured at baseline and approximately every 2 years thereafter. Results: Systolic blood pressure at baseline was similar in HRT users and nonusers (133.9 +/- 16.0 mm Hg vs. 132.4 +/- 14.8 mm Hg). Over time, average systolic blood pressure increased less in HRT users than nonusers, independent of other cardiovascular risk factors, physical activity, and alcohol use. For example, HRT users who were 55 years of age at their first Baltimore Longitudinal Study of Aging visit experienced a 7.6-mm Hg average increase in systolic blood pressure over 10 years; in contrast, the average increase in nonusers was 18.7 mm Hg. The lesser increase in systolic blood pressure in HRT users was more evident at older age. Diastolic blood pressure, which did not change statistically over time in either group, was not associated with HRT. Conclusion: Postmenopausal women taking HRT have a smaller increase in systolic blood pressure over time than those not taking HRT. This difference is intensified at older ages. C1 NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. RP Fleg, JL (reprint author), NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 47 TC 57 Z9 62 U1 0 U2 2 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 AUG 21 PY 2001 VL 135 IS 4 BP 229 EP 238 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 465KE UT WOS:000170587500001 PM 11511137 ER PT J AU Illei, GG Austin, HA Crane, M Collins, L Gourley, MF Yarboro, CH Vaughan, EM Kuroiwa, T Danning, CL Steinberg, AD Klippel, JH Balow, JE Boumpas, DT AF Illei, GG Austin, HA Crane, M Collins, L Gourley, MF Yarboro, CH Vaughan, EM Kuroiwa, T Danning, CL Steinberg, AD Klippel, JH Balow, JE Boumpas, DT TI Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID STEM-CELL TRANSPLANTATION; MYCOPHENOLATE-MOFETIL THERAPY; CONTROLLED TRIAL; INTRAVENOUS CYCLOPHOSPHAMIDE; AUTOIMMUNE-DISEASE; ERYTHEMATOSUS; GLOMERULONEPHRITIS; AZATHIOPRINE; PREDNISONE; PROGNOSIS AB Background: controlled trials in lupus nephritis have demonstrated that cyclophosphamide therapy is superior to corticosteroid therapy alone. The long-term effectiveness and side-effect profiles of pulse immunosuppressive regimens warrant further study. Objective: To define the long-term risk and benefit of monthly treatment with boluses of methylprednisolone, cyclophosphamide, or both. Design: Extended follow-up (median, 11 years) of a randomized, controlled trial. Setting: U.S. government research hospital. Patients: 82 patients with proliferative lupus nephritis. Measurements: Rates of treatment failure (defined as need for supplemental immunosuppressive therapy or doubling of serum creatinine concentration, or death) and adverse events. Results: In an intention-to-treat survival analysis, the likelihood of treatment failure was significantly lower in the cyclophosphamide (P = 0.04) and combination therapy (P = 0.002) groups than In the methylprednisolone group. Combination therapy and cyclophosphamide therapy alone did not differ statistically in terms of effectiveness or adverse events. Of patients who completed the protocol (n = 65), the proportion of patients who had doubling of serum creatinine concentration was significantly lower in the combination group than in the cyclophosphamide group (relative risk, 0.095 [95% Cl, 0.01 to 0.842]). Conclusion: With extended follow-up, pulse cyclophosphamide continued to show superior efficacy over pulse methylprednisolone alone for treatment of lupus nephritis. The combination of pulse cyclophosphamide and methylprednisolone appears to provide additional benefit over pulse cyclophosphamide alone and does not confer additional risk for adverse events. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Skin Dis & Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Mitretek Syst, Mclean, VA USA. RP Illei, GG (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9S-205, Bethesda, MD 20892 USA. NR 33 TC 256 Z9 280 U1 0 U2 1 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 AUG 21 PY 2001 VL 135 IS 4 BP 248 EP 257 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 465KE UT WOS:000170587500003 PM 11511139 ER PT J AU Michalik, L Desvergne, B Tan, NS Basu-Modak, S Escher, P Rieusset, J Peters, JM Kaya, G Gonzalez, FJ Zakany, J Metzger, D Chambon, P Duboule, D Wahli, W AF Michalik, L Desvergne, B Tan, NS Basu-Modak, S Escher, P Rieusset, J Peters, JM Kaya, G Gonzalez, FJ Zakany, J Metzger, D Chambon, P Duboule, D Wahli, W TI Impaired skin wound healing in peroxisome proliferator-activated receptor (PPAR)alpha and PPAR beta mutant mice SO JOURNAL OF CELL BIOLOGY LA English DT Article DE mouse keratinocytes; PPAR gene expression; PPAR gene targeted disruption; skin wound healing; nuclear hormone receptors ID EPIDERMAL PERMEABILITY BARRIER; DIFFERENTIAL EXPRESSION; TARGETED DISRUPTION; TRANSGENIC MICE; ACID RECEPTOR; ALPHA; GAMMA; RAT; KERATINOCYTES; GLUCOCORTICOIDS AB We show here that the alpha, beta, and gamma isotypes of peroxisome proliferator-activated receptor (PPAR) are expressed in the mouse epidermis during fetal development and that they disappear progressively from the interfollicular epithelium after birth. Interestingly, PPAR alpha and beta expression is reactivated in the adult epidermis after various stimuli, resulting in keratinocyte proliferation and differentiation such as tetradecanoylphorbol acetate topical application, hair plucking, or skin wound healing. Using PPAR alpha, beta, and gamma mutant mice, we demonstrate that PPAR alpha and beta are important for the rapid epithelialization of a skin wound and that each of them plays a specific role in this process. PPAR alpha is mainly involved in the early inflammation phase of the healing, whereas PPAR beta is implicated in the control of keratinocyte proliferation. In addition and very interestingly, PPAR beta mutant primary keratinocytes show impaired adhesion and migration properties. Thus, the findings presented here reveal unpredicted roles for PPAR alpha and beta in adult mouse epidermal repair. C1 Univ Lausanne, Inst Biol Anim, CH-1015 Lausanne, Switzerland. Univ Hosp Geneva, Dept Dermatol, CH-1212 Geneva, Switzerland. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Geneva, Dept Zool, CH-1211 Geneva 4, Switzerland. Coll France, Inst Genet & Biol Mol & Cellulaire, CNRS, INSERM,ULP, F-67404 Illkirch Graffenstaden, France. RP Wahli, W (reprint author), Univ Lausanne, Inst Biol Anim, Batiment Biol, CH-1015 Lausanne, Switzerland. RI Peters, Jeffrey/D-8847-2011; Wahli, Walter/B-1398-2009; Desvergne, Beatrice/C-8892-2016 OI Wahli, Walter/0000-0002-5966-9089; Desvergne, Beatrice/0000-0001-5483-288X NR 47 TC 308 Z9 317 U1 2 U2 12 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 AUG 20 PY 2001 VL 154 IS 4 BP 799 EP 814 DI 10.1083/jcb.200011148 PG 16 WC Cell Biology SC Cell Biology GA 467CX UT WOS:000170683900013 PM 11514592 ER PT J AU Chen, WJ Jin, WW Tian, HS Sicurello, P Frank, M Orenstein, JM Wahl, SM AF Chen, WJ Jin, WW Tian, HS Sicurello, P Frank, M Orenstein, JM Wahl, SM TI Requirement for transforming growth factor beta 1 in controlling T cell apoptosis SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE TCR; mitochondrial membrane potential; Fas/TNF-alpha receptor Smad3; Bcl-XL ID TUMOR-NECROSIS-FACTOR; ACTIVATION-INDUCED APOPTOSIS; TGF-BETA; FAS-LIGAND; CYTOCHROME-C; PROTEASE ACTIVATION; TARGETED DISRUPTION; IFN-GAMMA; IN-VIVO; DEATH AB Transforming growth factor (TGF)-beta1, a potent immunoregulatory molecule, was found to control the life and death decisions of T lymphocytes. Both thymic and peripheral T cell apoptosis was increased in mice lacking TGF-beta1 (TGF-beta1(-/-)) compared with wild-type littermates. Engagement of the T cell receptor enhanced this aberrant T cell apoptosis, as did signaling through either the death receptor Fas or the tumor necrosis factor alpha receptor in peripheral T cells. Strikingly, TGF-beta was localized within the mitochondria of normal T cells, and the absence of TGF-beta1 resulted in disruption of mitochondrial membrane potential (Delta Psi (m)), which marks the point of no return in a cell condemned to die. This TGF-beta -dependent regulation of viability appears dissociable from the TGF-beta1 membrane receptor-Smad3 signaling pathway, but associated with a mitochondrial antiapoptotic protein Bcl-XL. Thus, TGF-beta1 may protect T cells at multiple sites in the death pathway, particularly by maintaining the essential integrity of mitochondria. These findings may have broad implications not only for T cell selection and death in immune responses and in the generation of tolerance, but also for defining the mechanisms of programmed cell death in general. C1 NIDCR, NIH, OIIB, Cellular Immunol Sect, Bethesda, MD 20892 USA. George Washington Univ, Dept Pathol, Washington, DC 20037 USA. RP Wahl, SM (reprint author), NIDCR, NIH, OIIB, Cellular Immunol Sect, Rm 332,Bldg 30, Bethesda, MD 20892 USA. NR 58 TC 93 Z9 104 U1 0 U2 0 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 AUG 20 PY 2001 VL 194 IS 4 BP 439 EP 453 DI 10.1084/jem.194.4.439 PG 15 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 466DH UT WOS:000170628700008 PM 11514601 ER PT J AU Yannoutsos, N Wilson, P Yu, W Chen, HT Nussenzweig, A Petrie, H Nussenzweig, MC AF Yannoutsos, N Wilson, P Yu, W Chen, HT Nussenzweig, A Petrie, H Nussenzweig, MC TI The role of recombination activating gene (RAG) reinduction in thymocyte development in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE T cell receptor alpha chain; gene rearrangement; regulation of gene expression; T cell receptor editing; recombination activating gene ID T-CELL-RECEPTOR; TCR-ALPHA ENHANCER; DNA-LIGASE-IV; V(D)J RECOMBINATION; ANTIGEN RECEPTOR; V-ALPHA; ALLELIC EXCLUSION; IMMUNE-SYSTEM; IN-VIVO; PROMOTER AB Assembly of T cell receptor (TCR)alpha/beta genes by variable/diversity/joining (V[D]J) rearrangement is an ordered process beginning with recombination activating gene (RAG) expression and TCR beta recombination in CD4(-)CD8(-)CD25(+) thymocytes. In these cells, TCR beta expression leads to clonal expansion, RAG downregulation, and TCR beta allelic exclusion. At the subsequent CD4(+)CD8(+) stage, RAG expression is reinduced and V(D)J recombination is initiated at the TCR alpha locus. This second wave of RAG expression is terminated upon expression of a positively selected alpha/beta TCR. To examine the physiologic role of the second wave of RAG expression, we analyzed mice that cannot reinduce RAG expression in CD4(+)CD8(+) T cells because the transgenic locus that directs RAG1 and RAG2 expression in these mice is missing a distal regulatory element essential for reinduction. In the absence of RAG reinduction we find normal numbers of CD4(+)CD8(+) cells but a 50-70% reduction in the number of mature CD4(+)CD8(-) and CD4(-)CD8(+) thymocytes. TCR alpha rearrangement is restricted to the 5' end of the J alpha cluster and there is little apparent secondary TCR alpha recombination. Comparison of the TCR alpha genes expressed in wild-type or mutant mice shows that 65% of all alpha/beta T cells carry receptors that are normally assembled by secondary TCR alpha rearrangement. We conclude that RAG reinduction in CD4(+)CD8(+) thymocytes is not required for initial TCR alpha recombination but is essential for secondary TCR alpha recombination and that the majority of TCR alpha chains expressed in mature T cells are products of secondary recombination. C1 Rockefeller Univ, Lab Mol Immunol, New York, NY 10021 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Program Immunol, New York, NY 10021 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Yannoutsos, N (reprint author), Rockefeller Univ, Lab Mol Immunol, Box 220,1230 York Ave, New York, NY 10021 USA. NR 68 TC 52 Z9 52 U1 0 U2 1 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 AUG 20 PY 2001 VL 194 IS 4 BP 471 EP 480 DI 10.1084/jem.194.4.471 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 466DH UT WOS:000170628700010 PM 11514603 ER PT J AU van Elsas, A Sutmuller, RPM Hurwitz, AA Ziskin, J Villasenor, J Medema, JP Overwijk, W Restifo, NP Melief, CJM Offringa, R Allison, JP AF van Elsas, A Sutmuller, RPM Hurwitz, AA Ziskin, J Villasenor, J Medema, JP Overwijk, W Restifo, NP Melief, CJM Offringa, R Allison, JP TI Elucidating the autoimmune and antitumor effector mechanisms of a treatment based on cytotoxic T lymphocyte antigen-4 blockade in combination with a B16 melanoma vaccine: Comparison of prophylaxis and therapy SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE immunotherapy; prophylaxis; T lymphocyte; TRP-2; depigmentation ID TYROSINASE-RELATED PROTEIN-2; COLONY-STIMULATING FACTOR; FLICE-INHIBITORY PROTEIN; TUMOR REJECTION ANTIGEN; CTLA-4 BLOCKADE; PROSTATE-CANCER; IMMUNE-RESPONSE; CELL RESPONSES; DENDRITIC CELL; VITILIGO AB We have previously shown that small B16 melanomas can be successfully treated using a combination of anti-cytotoxic T lymphocyte antigen (CTLA)-4 monoclonal antibody with a granulocyte/macrophage colony-stimulating factor (GM-CSF) producing irradiated tumor cell vaccine. Regression of tumors results in long-lasting immunity and is frequently accompanied by autoimmune depigmentation. Here we examine the cellular and molecular mechanisms of this combined treatment. Histological examination of depigmented lesions revealed infiltration of polymorphonuclear cells and deposition of antibody. The combination therapy also induced tumor rejection and skin depigmentation in B cell-deficient and in CD4(+) T cell-depleted mice. Both effects of the treatment absolutely required CD8(+) T cells. Analysis of the response in successfully treated mice revealed elevated levels of CD8(+) T cells specific for a nonameric peptide consisting of residues 180-188 of the melanocyte differentiation antigen tyrosinase-related protein (TRP)2. There was no evidence of reactivity to the melanocyte antigens gp100, tyrosinase, Mart1/MelanA, or TRP1. Fas-FasL interactions and perforin played a role in mounting the effector response, whereas the tumor necrosis factor pathway was not required. The cellular requirements for tumor rejection in this therapeutic setting were strikingly different from those in a prophylactic setting. In particular, if mice received a prophylactic vaccine consisting of anti-CTLA-4 and B16-GM-CSF before tumor challenge, full protection was obtained even in the absence of CD8(+) T cells. Our data demonstrate that therapeutic autoreactive CD8(+) T cell responses can effectively be generated in tumor-bearing mice and stresses the value of studying tumor immunity in a therapeutic rather than a prophylactic setting. C1 Univ Calif Berkeley, Howard Hughes Med Inst, Canc Res Lab, Berkeley, CA 94720 USA. Leiden Univ, Dept Immunohematol, Med Ctr, NL-2300 RC Leiden, Netherlands. Leiden Univ, Blood Bank, Med Ctr, NL-2300 RC Leiden, Netherlands. NIH, Surg Branch, Bethesda, MD 20892 USA. RP Allison, JP (reprint author), Univ Calif Berkeley, Howard Hughes Med Inst, Canc Res Lab, 401 LSA, Berkeley, CA 94720 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [CA57986] NR 40 TC 227 Z9 230 U1 0 U2 5 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 AUG 20 PY 2001 VL 194 IS 4 BP 481 EP 489 DI 10.1084/jem.194.4.481 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 466DH UT WOS:000170628700011 PM 11514604 ER PT J AU Dasmahapatra, AK Wimpee, BAB Trewin, AL Hutz, RJ AF Dasmahapatra, AK Wimpee, BAB Trewin, AL Hutz, RJ TI 2,3,7,8-Tetrachlorodibenzo-p-dioxin increases steady-state estrogen receptor-beta mRNA levels after CYP1A1 and CYP1B1 induction in rat granulosa cells in vitro SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 82nd Annual Meeting of the Endocrine-Society CY JUN 21-24, 2000 CL TORONTO, CANADA SP Endocrine Soc DE TCDD; granulosa cells; ER-beta; CYP1A1; CYP1B1; AHR; ARNT ID BREAST-CANCER-CELLS; ARYL-HYDROCARBON RECEPTOR; DIFFERENTIAL EXPRESSION; IN-VITRO; POLYCHLORINATED-BIPHENYLS; EPITHELIAL-CELLS; GENE-EXPRESSION; MESSENGER-RNAS; AH RECEPTOR; OVARY AB Previous in-vitro investigations or rat granulosa cells (GC) have shown that 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) inhibits estrogen secretion and FSH-induced aromatase activity. Although TCDD exerted no effect on basal aromatase enzyme activity, TCDD did reduce steady-state aromatase mRNA levels in GC using competitive RT-PCR. TCDD is hypothesized to induce these changes through aromatic hydrocarbon receptor(AHR)-mediated gene transcription and the modulation of the estrogen receptor (ER)-signaling pathway. In this study we show that rat GC express mRNA for AHR and the AHR nuclear translocator (ARNT) as well as biomarkers of TCDD action, CYP1A1 and CYP1B1 mRNA. Basal CYP1A1 and ER-alpha mRNAs were present only in trace amounts. By relative RT-PCR analysis we showed that CYP1A1 and CYP1B1 mRNA were induced significantly by TCDD at 6 h and that induction or CYP1A1 was maintained throughout the experiment. Using competitive RT-PCR, we observed no significant change in the mRNA levels of ARNT between control and TCDD-treated GC. Both AHR and ER-beta mRNA levels increased significantly at 48 h with TCDD compared with controls. Since ER-beta mRNA was not increased significantly until 48 h in culture, we suggest that in rat GC, the observed ER-beta mRNA increase by TCDD might be a result of CYP1A1/CYP1B1 catalyzed estrogen metabolism and aromatase mRNA inhibition via AHR. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Wisconsin, Dept Biol Sci, Milwaukee, WI 53211 USA. Univ Wisconsin, NIEHS, Marine & Freshwater Biomed Sci Ctr, Milwaukee, WI 53211 USA. RP Hutz, RJ (reprint author), Univ Wisconsin, Dept Biol Sci, 308 Lapham Hall,3209 N Maryland Ave, Milwaukee, WI 53211 USA. FU PHS HHS [E508342, E504184] NR 31 TC 31 Z9 31 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD AUG 20 PY 2001 VL 182 IS 1 BP 39 EP 48 DI 10.1016/S0303-7207(01)00545-7 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 468DV UT WOS:000170743600005 PM 11500237 ER PT J AU Koletar, SL Heald, AE Finkelstein, D Hafner, R Currier, JS McCutchan, JA Vallee, M Torriani, FJ Powderly, WG Fass, RJ Murphy, RL AF Koletar, SL Heald, AE Finkelstein, D Hafner, R Currier, JS McCutchan, JA Vallee, M Torriani, FJ Powderly, WG Fass, RJ Murphy, RL CA ACTG 888 Study Team TI A prospective study of discontinuing primary and secondary Pneumocystis carinii pneumonia prophylaxis after CD4 cell count increase to > 200 X 10(6)/I SO AIDS LA English DT Article DE discontinuing primary and secondary prophylaxis; Pneumocystis carinii pneumonia ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS INFECTION; OPPORTUNISTIC INFECTIONS; TRIMETHOPRIM-SULFAMETHOXAZOLE; AIDS PATIENTS; HIV-1-INFECTED PATIENTS; SULFONE PROPHYLAXIS; MAINTENANCE THERAPY; RANDOMIZED TRIAL AB Objective: To assess the incidence of Pneumocystis carinii pneumonia (PCP) after discontinuation of either primary or secondary prophylaxis. Design: This was a prospective, non-randomized, non-blinded study. Setting: Twenty-five University-based AIDS Clinical Trials Group units. Participants: Participants either had a CD4 cell count less than or equal to 100 x 10(6)/l at any time in the past and no history of confirmed PCP (group I; n = 144), or had a confirmed episode of PCP greater than or equal to 6 months prior to study entry (group II; n = 129). All subjects had sustained CD4 cell counts > 200 x 10(6)/l in response to antiretroviral therapy. Interventions: Subjects discontinued PCP prophylaxis within 3 months or at the time of study entry. Evaluations for symptoms of PCP and CD4 cell counts were performed every 8 weeks. Prophylaxis was resumed if two consecutive CD4 cell counts were < 200 x 10(6)/l. Main outcome measure(s): The main outcome was development of PCP. Results: No cases of PCP occurred in 144 subjects (median follow-up, 82 weeks) in group I or in the 129 subjects (median follow-up, 63 weeks) in group II (95% upper confidence limits on the rates of 1.3 per 100 person-years and 1.96 per 100 person-years for groups I and II, respectively). Eight subjects (five in group I and three in group II) resumed PCP prophylaxis after two consecutive CD4 cell counts < 200 x 10(6)/l. Conclusions: The risk of developing initial or recurrent PCP after discontinuing prophylaxis is low in HIV-infected individuals who have sustained CD4 cell count increases in response to antiretroviral therapy. Neither lifelong primary nor secondary PCP prophylaxis is necessary. (C) 2001 Lippincott Williams & Wilkins. C1 Ohio State Univ Hosp, Columbus, OH 43210 USA. Duke Univ, Med Ctr, Durham, NC USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Washington Univ, Sch Med, St Louis, MO USA. Northwestern Univ, Sch Med, Chicago, IL USA. RP Koletar, SL (reprint author), N1135 Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. FU NIAID NIH HHS [AI25924] NR 46 TC 25 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD AUG 17 PY 2001 VL 15 IS 12 BP 1509 EP 1515 DI 10.1097/00002030-200108170-00008 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 463KA UT WOS:000170474300008 PM 11504983 ER PT J AU Al-Harthi, L Kovacs, A Coombs, RW Reichelderfer, PS Wright, DJ Cohen, MH Cohn, J Cu-Uvin, S Watts, H Lewis, S Beckner, S Landay, A AF Al-Harthi, L Kovacs, A Coombs, RW Reichelderfer, PS Wright, DJ Cohen, MH Cohn, J Cu-Uvin, S Watts, H Lewis, S Beckner, S Landay, A CA WHS 001 Study Team TI A menstrual cycle pattern for cytokine levels exists in HIV-positive women: implication for HIV vaginal and plasma shedding SO AIDS LA English DT Article DE bacterial vaginosis; chemokines; cytokines; HIV; lymphocytes; menstrual cycle; viral load; women ID HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE GENITAL-TRACT; SECRETORY COMPONENT; REPRODUCTIVE-TRACT; EPITHELIAL-CELLS; EXPRESSION; ENDOMETRIUM; SECRETIONS; ESTRADIOL; IGA AB Objectives: To evaluate the effect of the menstrual cycle in HIV-positive women on plasma and genital cytokine levels, interrelationships between vaginal and plasma cytokines, CD4 and CD8 T cell fluctuations, and genital and plasma viral loads. Methods: Plasma and cervicovaginal lavage specimens were collected from 55 HIV-positive women with CD4 cell counts < 350 cells/mul during phases of the menstrual cycle. Samples were assayed for IL-1 beta, IL-6, IL-4, IL-8, IL-10, TGF beta, TNF alpha, INF gamma, MIP1 alpha, MIP1 beta, RANTES, and TNFR-II using enzyme-linked immunosorbent assays. CD4 and CD8 T cell expression was evaluated by flow cytometry. Repeated measures regression models were used to assess the effect of the menstrual cycle on cytokines and viral load. Multivariate repeated regression models were used to assess the correlation among selected cytokines and between selected cytokines and HIV viral load. Results: Vaginal IL-1 beta, IL-4, IL-6, IL-8, IL-10, MIP1 beta, RANTES, TGF beta, and TNFR-II were significantly elevated during menses but were not altered during other phases. Plasma cytokine levels were not altered during the menstrual cycle. A positive Candida culture increased vaginal IL-8 during menses, whereas vaginal discharge was associated with a reduction in vaginal IL-4, IL-10, and RANTES. CD4 and CD8 cell numbers did not vary with the menstrual cycle. Vaginal cytokine levels correlated only with vaginal viral load, in a sampling method-dependent manner. Conclusion: We provide evidence of elevated vaginal cytokine levels during menses, which appear to regulate vaginal and not plasma HIV shedding, suggesting that a menstrual cycle pattern exists for cytokine production in HIV-positive women impacting vaginal shedding of HIV. (C) 2001 Lippincott Williams & Wilkins. C1 Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, Chicago, IL 60612 USA. Univ So Calif, Sch Med, LAC & USC Comprehens Maternal Child & Adolescent, Los Angeles, CA USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. NICHHD, NIH, Bethesda, MD USA. WESTAT Corp, Rockville, MD 20850 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Wayne State Univ, Detroit, MI USA. Brown Univ, Providence, RI 02912 USA. NIAID, Bethesda, MD 20892 USA. New York State Dept Hlth, Albany, NY USA. SUNY Stony Brook, Hlth Sci Ctr, Brooklyn, NY USA. St Lukes Roosevelt Hosp, New York, NY USA. Miriam Hosp, Providence, RI 02906 USA. RP Al-Harthi, L (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Immunol Microbiol, 1653 W Congress Pkwy,Room 1577 JSC, Chicago, IL 60612 USA. FU NICHD NIH HHS [N01-HD-3-3162] NR 25 TC 50 Z9 51 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD AUG 17 PY 2001 VL 15 IS 12 BP 1535 EP 1543 DI 10.1097/00002030-200108170-00011 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 463KA UT WOS:000170474300011 PM 11504986 ER PT J AU Goldstein, AM Liu, L Sherman, MG Hogg, D Tucker, MA Struewing, JP AF Goldstein, AM Liu, L Sherman, MG Hogg, D Tucker, MA Struewing, JP TI A common founder for the V126D CDKN2A mutation in seven North American melanoma-prone families SO BRITISH JOURNAL OF CANCER LA English DT Article DE melanoma; CDKN2A; V126D; founder ID MALIGNANT-MELANOMA; PHENOTYPE ANALYSIS; P16; INHIBITION; HAPLOTYPE; CDK4; P16(INK4); INK4A; MDM2; P53 AB One of the most common melanoma-related CDKN2A mutations reported in North America is the V126D mutation. We examined nine markers surrounding CDKN2A in three American and four Canadian families carrying the V126D mutation. All seven families had a haplotype consistent with a common ancestor/founder for this mutation. In addition, the mutation appears to have originated 34-52 generations ago (1-LOD-unit support interval 13-98 generations). (C) 2001 Cancer Research Campaign. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Toronto, Dept Med, Toronto, ON M5S 1A8, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A8, Canada. Toronto Sunnybrook Reg Canc Ctr, Div Med Oncol, Toronto, ON M4N 3M5, Canada. RP Goldstein, AM (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Struewing, Jeffery/C-3221-2008; Tucker, Margaret/B-4297-2015; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 25 TC 20 Z9 21 U1 1 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG 17 PY 2001 VL 85 IS 4 BP 527 EP 530 DI 10.1054/bjoc.2001.1944 PG 4 WC Oncology SC Oncology GA 466CN UT WOS:000170626900010 PM 11506491 ER PT J AU Thykjaer, T Christensen, M Clark, AB Hansen, LRT Kunkel, TA Orntoft, TF AF Thykjaer, T Christensen, M Clark, AB Hansen, LRT Kunkel, TA Orntoft, TF TI Functional analysis of the mismatch repair system in bladder cancer SO BRITISH JOURNAL OF CANCER LA English DT Article DE mismatch repair; bladder; microsatellite; MSH3; MSH6 ID TRANSITIONAL-CELL CARCINOMA; COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN SOLID TUMORS; MICROSATELLITE INSTABILITY; DNA MISMATCH; URINARY-BLADDER; COLORECTAL-CANCER; TISSUE-CULTURE; ALLELIC LOSSES; COLON-CANCER AB In bladder cancer the observed microsatellite instability indicates that mismatch repair deficiency could be a frequently involved factor in bladder cancer progression. To investigate this hypothesis we analysed extracts of seven bladder cancer cell lines and, as a novel approach, five clinical cancer samples for mismatch repair activity. We found that one cell line (T24) and three of the clinical samples had a reduced repair capacity, measured to similar to 20% or less. The T24 cell extract was unable to repair a G-G mismatch and showed reduced repair of a 2-base loop, consistent with diminished function of the MSH2-MSH6 heterodimer. The functional assay was combined with measurement for mutation frequency, microsatellite analysis, sequencing, MTT assay, immunohistochemical analysis and RT-PCR analysis of the mismatch repair genes MSH2, MSH3, MSH6, PMS1, PMS2 and MLH1. A > 7-fold relative increase in mutation frequency was observed for T24 compared to a bladder cancer cell line with a fully functional mismatch repair system. Neither microsatellite instability, loss of repair nor mismatch repair gene mutations were detected. However, RT-PCR analysis of mRNA levels did detect changes in the ratio of expression of the Mut S and Mut L homologues. The T24 cell line had the lowest MSH6 expression level of the cell lines tested. Identical RT-PCR analysis of seventeen clinical samples (normal urothelium, 7; pTa low stage, 5; and pT1-4 high stage, 5) indicated a significant change in the expression ratio between MSH3/MSH6 (P < 0.004), MSH2/MSH3 (P < 0.012) and PMS2/MLH1 P < 0.005, in high stage bladder tumours compared to normal urothelium and low stage tumours. Collectively, the data suggest that imbalanced expression of mismatch repair genes could lead to partial loss of mismatch repair activity that is associated with invasive bladder cancer. (C) 2001 Cancer Research Campaign http://www.bjcancer.com. C1 Aarhus Univ, Skejby Hosp, Dept Clin Biochem, DK-8200 Aarhus N, Denmark. NIEHS, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Univ Copenhagen, Inst Mol Pathol, Fac Hlth, DK-2100 Copenhagen, Denmark. RP Thykjaer, T (reprint author), Aarhus Univ, Skejby Hosp, Dept Clin Biochem, DK-8200 Aarhus N, Denmark. NR 52 TC 21 Z9 24 U1 1 U2 2 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD AUG 17 PY 2001 VL 85 IS 4 BP 568 EP 575 DI 10.1054/bjoc.2001.1949 PG 8 WC Oncology SC Oncology GA 466CN UT WOS:000170626900017 PM 11506498 ER PT J AU Vaisman, A Tissier, A Frank, EG Goodman, MF Woodgate, R AF Vaisman, A Tissier, A Frank, EG Goodman, MF Woodgate, R TI Human DNA polymerase iota promiscuous mismatch extension SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XERODERMA-PIGMENTOSUM; GENE ENCODES; THYMINE DIMER; FIDELITY; BYPASS; REPLICATION; ETA; MUTAGENESIS; PROTEIN; MISINSERTION AB Human DNA polymerase iota is a low-fidelity template copier that preferentially catalyzes the incorporation of the wobble base G, rather than the Watson-Crick base A, opposite template T (Tissier, A., McDonald, CF. P., Frank, E. G., and Woodgate, R. (2000) Genes Dev. 14, 1642-1650; Johnson, R. E., Washington, M. T., Haracska, L., Prakash, S., and Prakash, L. (2000) Nature 406, 10151019; Zhang, Y., Yuan, F., Wu, X., and Wang, Z. (2000) Mol. Cell. Biol. 20,7099-7108). Here, we report on its ability to extend all 12 possible mispairs and 4 correct pairs in different sequence contexts. Extension from both matched and mismatched primer termini is generally most efficient and accurate when A is the next template base. In contrast, extension occurs less efficiently and accurately when T is the target template base. A striking exception occurs during extension of a G:T mispair, where the enzyme switches specificity, "preferring" to make a correct A.T base pair immediately downstream from an originally favored G:T mispair. Polymerase L generates a variety of single and tandem mispairs with high frequency, implying that it may act as a strong mutator when copying undamaged DNA templates in vivo. Even so, its limited ability to catalyze extension from a relatively stable primer/template containing a "buried" mismatch suggests that polymerase iota -catalyzed errors are confined to short template regions. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. Univ So Calif, Dept Sci Biol, Hedco Mol Biol Labs, Los Angeles, CA 90089 USA. Univ So Calif, Dept Chem, Hedco Mol Biol Labs, Los Angeles, CA 90089 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bldg 6,Rm 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Vaisman, Alexandra/C-3766-2013 OI Vaisman, Alexandra/0000-0002-2521-1467 FU NIGMS NIH HHS [GM2554, GM21422] NR 47 TC 41 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 17 PY 2001 VL 276 IS 33 BP 30615 EP 30622 DI 10.1074/jbc.M102694200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 463JG UT WOS:000170472900006 PM 11402031 ER PT J AU Goossens, A Dever, TE Pascual-Ahuir, A Serrano, R AF Goossens, A Dever, TE Pascual-Ahuir, A Serrano, R TI The protein kinase Gcn2p mediates sodium toxicity in yeast SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GUANINE-NUCLEOTIDE EXCHANGE; UNCHARGED TRANSFER-RNA; MEMBRANE H+-ATPASE; SACCHAROMYCES-CEREVISIAE; TRANSLATIONAL REGULATION; SALT TOLERANCE; SIGNAL-TRANSDUCTION; GENE-EXPRESSION; ION HOMEOSTASIS; FACTOR EIF2B AB Phosphorylation of the a-subunit of eukaryotic initiation factor 2 (eIF2 alpha) is a conserved mechanism regulating protein synthesis in response to various stresses. A screening for negative factors in yeast salt stress tolerance has led to the identification of Gcn2p, the single yeast eIF2a kinase that is activated by amino acid starvation in the general amino acid control response. Mutation of other components of this regulatory circuit such as GCN1 and GCN3 also resulted in improved NaCl tolerance. The gcn2 phenotype was not accompanied by changes in sodium or potassium homeostasis. NaCl induced a Gcn2p-dependent phosphorylation of eIF2a and translational activation of Gcn4p, the transcription factor that mediates the general amino acid control response. Mutations that activate Gcn4p function, such as gcd7-201, cpc2, and deletion of the translational regulatory region of the GCN4 gene, also cause salt sensitivity. It can be postulated that sodium activation of the Gcn2p pathway has toxic effects on growth under NaCl stress and that this novel mechanism of sodium toxicity may be of general significance in eukaryotes. C1 Univ Politecn Valencia, CSIC, Inst Biol Mol & Celular Plantas, Valencia 46022, Spain. NICHHD, Lab Eukaryotic Gene Regulat, Bethesda, MD 20892 USA. RP Serrano, R (reprint author), Univ Politecn Valencia, CSIC, Inst Biol Mol & Celular Plantas, Camino Vera S-N, Valencia 46022, Spain. RI Pascual-ahuir, Amparo/K-1338-2014 NR 57 TC 42 Z9 44 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 17 PY 2001 VL 276 IS 33 BP 30753 EP 30760 DI 10.1074/jbc.M102960200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 463JG UT WOS:000170472900024 PM 11408481 ER PT J AU Basanez, G Zhang, J Chau, BN Maksaev, GI Frolov, VA Brandt, TA Burch, J Hardwick, JM Zimmerberg, J AF Basanez, G Zhang, J Chau, BN Maksaev, GI Frolov, VA Brandt, TA Burch, J Hardwick, JM Zimmerberg, J TI Pro-apoptotic cleavage products of Bcl-x(L) form cytochrome c-conducting pores in pure lipid membranes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BCL-2 PROTEIN FAMILY; CELL-DEATH; ION-CHANNEL; CASPASE ACTIVATION; BAX; RELEASE; MITOCHONDRIA; INHIBITION; PATHWAY; PERMEABILIZATION AB During apoptotic cell death, cells usually release apoptogenic proteins such as cytochrome c from the mitochondrial intermembrane space. If Bcl-2 family proteins induce such release by increasing outer mitochondrial membrane permeability, then the pro-apoptotic, but not anti-apoptotic activity of these proteins should correlate with their permeabilization of membranes to cytochrome c. Here, we tested this hypothesis using pro-survival full-length Bcl-x(L) and pro-death Bcl-x(L) cleavage products (Delta N612Bcl-x(L) and Delta N76Bcl-x(L)). Unlike Bcl-x(L), Delta N61Bcl-x(L) and Delta N76Bcl-x(L) caused the release of cytochrome c from mitochondria in vivo and in vitro. Recombinant Delta N61Bcl-x(L) and Delta N76Bcl-x(L), as well as Bcl-xL, cleaved in situ by caspase 3-possessed intrinsic pore-forming activity as demonstrated by their ability to efficiently permeabilize pure lipid vesicles. Furthermore, only Delta N61Bcl-x(L) and Delta N76Bcl-x(L), but not Bcl-x(L), formed pores large enough to release cytochrome c and to destabilize planar lipid bilayer membranes through reduction of pore line tension. Because Bcl-x(L) and its C-terminal cleavage products bound similarly to lipid membranes and formed oligomers of the same size, neither lipid affinity nor protein-protein interactions appear to be solely responsible for the increased membrane-perturbing activity elicited by Bcl-x(L) cleavage. Taken together, these data are consistent with the hypothesis that Bax-like proteins oligomerize to form lipid-containing pores in the outer mitochondrial membrane, thereby releasing intermembrane apoptogenic factors into the cytosol. C1 NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Russian Acad Sci, Frumkin Inst Electrochem, Moscow 117071, Russia. RP Basanez, G (reprint author), NICHHD, Lab Cellular & Mol Biophys, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. RI Basanez, Gorka/L-9509-2014; OI Basanez, Gorka/0000-0002-7475-7861; Frolov, Vadim/0000-0002-0653-5669 FU NINDS NIH HHS [NS34175, NS37402] NR 71 TC 106 Z9 110 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 AUG 17 PY 2001 VL 276 IS 33 BP 31083 EP 31091 DI 10.1074/jbc.M103879200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 463JG UT WOS:000170472900066 PM 11399768 ER PT J AU Olah, Z Karai, L Iadarola, MJ AF Olah, Z Karai, L Iadarola, MJ TI Anandamide activates vanilloid receptor 1 (VR1) at acidic pH in dorsal root ganglia neurons and cells ectopically expressing VR1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SENSITIVE SENSORY NERVES; GATED NA+ CHANNEL; CAPSAICIN-RECEPTOR; ENDOPLASMIC-RETICULUM; SUBSTANCE-P; INFLAMMATORY MEDIATORS; CANNABINOID RECEPTORS; ION-CHANNEL; RAT; CALCIUM AB The vanilloid receptor type 1 (VR1) is a heat-activated ionophore preferentially expressed in nociceptive neurons of trigeminal and dorsal root ganglia (DRG). VR1, which binds and is activated by capsaicin and other vanilloid compounds, was noted to interact with the endocannabinoid anandamide (ANA) and certain inflammatory metabolites of arachidonic acid in a pH-dependent manner. At pH less than or equal to 6.5 ANA induced Ca-45(2+) uptake either in primary cultures of DRG neurons or cells ectopically expressing C-terminally tagged recombinant forms of VR1 with an EC50 = similar to 10 mum at PH 5.5. Capsazepine, a potent antagonist of vanilloids, inhibited ANA-induced Ca2+ transport in both cell systems. Vanilloids displaced [H-3]ANA in VRI-expressing cells, suggesting competition for binding to VR1. Ratiometric determination of intracellular free calcium and confocal imaging of the VR1-green fluorescent fusion protein revealed that, at low PH (less than or equal to 6.5), ANA could induce an elevation of intracellular free Ca2+ and consequent intracellular membrane changes in DRG neurons or transfected cells expressing VR1. These actions of ANA were similar to the effects determined previously for vanilloids. The ligand-induced changes in Ca2+ at PH less than or equal to 6.5 are consistent with the idea that ANA and other eicosanoids act as endogenous ligands of VR1 in a conditional fashion in vivo. The PH dependence suggests that tissue acidification in inflammation, ischemia, or traumatic injury can sensitize VR1 to eicosanoids and transduce pain from the periphery. C1 NIDCR, Neuronal Gene Express Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Olah, Z (reprint author), NIDCR, Neuronal Gene Express Unit, Pain & Neurosensory Mechanisms Branch, NIH, Bldg 49,Rm 1A19,49 Convent Dr,MSC-4410, Bethesda, MD 20892 USA. NR 60 TC 99 Z9 102 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 AUG 17 PY 2001 VL 276 IS 33 BP 31163 EP 31170 DI 10.1074/jbc.M101607200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 463JG UT WOS:000170472900076 PM 11333266 ER PT J AU Verdugo, DE Cancilla, MT Ge, X Gray, NS Chang, YT Schultz, PG Negishi, M Leary, JA Bertozzi, CR AF Verdugo, DE Cancilla, MT Ge, X Gray, NS Chang, YT Schultz, PG Negishi, M Leary, JA Bertozzi, CR TI Discovery of estrogen sulfotransferase inhibitors from a purine library screen SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Letter ID MAMMARY EPITHELIAL-CELLS; L-SELECTIN; RHIZOBIUM-MELILOTI; TYROSINE SULFATION; CRYSTAL-STRUCTURE; SULFURYL TRANSFER; MECHANISM; NODULATION; EXPRESSION; PROTEIN C1 Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Ctr New Direct Organ Synth, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Novartis Res Fdn, Genomics Inst, San Diego, CA 92121 USA. NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. NYU, Dept Chem, New York, NY 10003 USA. RP Bertozzi, CR (reprint author), Univ Calif Berkeley, Dept Chem, Berkeley, CA 94720 USA. RI Chang, Young-Tae/B-2780-2010 OI Chang, Young-Tae/0000-0002-1927-3688 NR 26 TC 67 Z9 68 U1 0 U2 3 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 AUG 16 PY 2001 VL 44 IS 17 BP 2683 EP 2686 DI 10.1021/jm010171u PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 463YV UT WOS:000170505600002 PM 11495578 ER PT J AU Thomas, JB Atkinson, RN Rothman, RB Fix, SE Mascarella, SW Vinson, NA Xu, H Dersch, CM Lu, YF Cantrell, BE Zimmerman, DM Carroll, FI AF Thomas, JB Atkinson, RN Rothman, RB Fix, SE Mascarella, SW Vinson, NA Xu, H Dersch, CM Lu, YF Cantrell, BE Zimmerman, DM Carroll, FI TI Identification of the first trans-(3R,4R)-dimethyl-4-(3-hydroxyphenyl)piperidine derivative to possess highly potent and selective opioid kappa receptor antagonist activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Letter ID N-SUBSTITUENT; (+)-(3R,4R)-DIMETHYL-4-(3-HYDROXYPHENYL)PIPERIDINE; SERIES AB A structurally novel opioid kappa receptor selective ligand has been identified. This compound, (3R)-7-hydroxy-N-((1S)-1-{[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethyl-1-piperi- dinyl]methyl}-2-methylpropyl)-1,2,3,4-tetrahydro-3-isoquino-linecarboxamide (JDTic, 10) demonstrated high affinity for the kappa receptor in the binding assay (kappa K-i = 0.3 nM) and highly potent and selective kappa antagonism in the [S-35]GTP-gamma -S assay using cloned opioid receptors (kappa K-i = 0.006 nM, mu/kappa ratio = 570, delta/kappa ratio > 16600). C1 Res Triangle Inst, Res Triangle Pk, NC 27709 USA. NIDA, Addict Res Ctr, Clin Psychopharmacol Sect, NIH, Baltimore, MD 21224 USA. Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Carroll, FI (reprint author), Res Triangle Inst, POB 12194, Res Triangle Pk, NC 27709 USA. FU NIDA NIH HHS [DA09045] NR 15 TC 71 Z9 72 U1 0 U2 6 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 AUG 16 PY 2001 VL 44 IS 17 BP 2687 EP 2690 DI 10.1021/jm015521r PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 463YV UT WOS:000170505600003 PM 11495579 ER PT J AU Baraldi, PG Cacciari, B Moro, S Romagnoli, R Ji, XD Jacobson, KA Gessi, S Borea, PA Spalluto, G AF Baraldi, PG Cacciari, B Moro, S Romagnoli, R Ji, XD Jacobson, KA Gessi, S Borea, PA Spalluto, G TI Fluorosulfonyl- and bis-(beta-chloroethyl)amino-phenylamino functionalized pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine derivatives: Irreversible antagonists at the human A(3) adenosine receptor and molecular modeling studies SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; A3-ADENOSINE RECEPTOR; AFFINITY LABEL; HIGHLY POTENT; MAST-CELLS; BINDING; AGONIST; CLONING; A(1); RADIOLIGAND AB A series of pyrazolotriazolopyrimidines was previously reported to be highly potent and selective human A(3) adenosine receptor antagonists (Baraldi et al. J. Med. Chem. 2000, 43, 4768-4780). A derivative having a methyl group at the N-8 pyrazole combined with a 4-methoxyphenylcarbamoyl moiety at N-5 position, displayed a K-i value at the hA(3) receptor of 0.2 nM. We now describe chemically reactive derivatives which act as irreversible inhibitors of this receptor. Electrophilic groups, specifically sulfonyl fluoride and nitrogen mustard (bis-(beta -chloroethyl)amino) moieties, have been incorporated at the 4-position of the aryl urea group. Membranes containing the recombinant hA3 receptor were preincubated with the compounds and washed exhaustively. The loss of ability to bind radioligand following this treatment indicated irreversible binding. The most potent compound in irreversibly binding to the receptor was 14, which contained a sulfonyl fluoride moiety and a propyl group at the N-8 pyrazole nitrogen. The bis-(beta -chloroethyl)amino derivatives displayed a much smaller degree of irreversible binding than the sulfonyl fluoride derivatives. A computer-generated model of the human A(3) receptor was built and analyzed to help interpret these results. The model of the A(3) transmembrane region was derived using primary sequence comparison, secondary structure predictions, and three-dimensional homology building, using the recently published crystal structure of rhodopsin as a template. According to our model, sulfonyl fluoride derivatives could dock within the hypothetical TM binding domain, adopting two different energetically favorable conformations. We have identified two amino acids, Ser247 and Cys251, both in TM6, as potential nucleophilic partners of the irreversible binding to the receptor. C1 Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy. Univ Studi Trieste, Dipartimento Sci Farmaceut, I-34127 Trieste, Italy. Univ Padua, Dipartimento Sci Farmaceut, Mol Modeling Sect, I-35131 Padua, Italy. NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. Univ Studi Ferrara, Dipartimento Med Clin & Sperimentale, Sez Farmacol, I-44100 Ferrara, Italy. RP Baraldi, PG (reprint author), Univ Ferrara, Dipartimento Sci Farmaceut, Via Fossato Mortara 17-19, I-44100 Ferrara, Italy. RI Moro, Stefano/A-2979-2012; Jacobson, Kenneth/A-1530-2009; Romagnoli, Romeo/G-9887-2015; Baraldi, Pier Giovanni/B-7933-2017 OI Moro, Stefano/0000-0002-7514-3802; Jacobson, Kenneth/0000-0001-8104-1493; NR 56 TC 30 Z9 30 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD AUG 16 PY 2001 VL 44 IS 17 BP 2735 EP 2742 DI 10.1021/jm010818a PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 463YV UT WOS:000170505600009 PM 11495585 ER PT J AU Wilson, RI Kunos, G Nicoll, RA AF Wilson, RI Kunos, G Nicoll, RA TI Presynaptic specificity of endocannabinoid signaling in the hippocampus SO NEURON LA English DT Article ID DEPOLARIZATION-INDUCED SUPPRESSION; CALCIUM-CHANNEL INVOLVEMENT; CANNABINOID CB1 RECEPTORS; BETA-GAMMA-SUBUNITS; RAT HIPPOCAMPUS; N-TYPE; SYNAPTIC TRANSMISSION; GABA RELEASE; AREA CA1; MESENTERIC VASODILATION AB Endocannabinoids are retrograde messengers released by neurons to modulate the strength of their synaptic inputs. Endocannabinoids are thought to mediate the suppression of GABA release that follows depolarization of a hippocampal CA1 pyramidal neuron-termed "depolarization-induced suppression of inhibition" (DSI). Here, we report that DSI is absent in mice which lack cannabinoid receptor-1 (CB1). Pharmacological and kinetic evidence suggests that CB1 activation inhibits presynaptic Ca2+ channels through direct G protein inhibition. Paired recordings show that endocannabinoids selectively inhibit a subclass of synapses distinguished by their fast kinetics and large unitary conductance. Furthermore, cannabinoid-sensitive inputs are unusual among central nervous system synapses in that they use N- but not P/Q-type Ca2+ channels for neurotransmitter release. These results indicate that endocannabinoids are highly selective, rapid modulators of hippocampal inhibition. C1 Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. RI Wilson, Rachel/E-2227-2012 NR 55 TC 340 Z9 351 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD AUG 16 PY 2001 VL 31 IS 3 BP 453 EP 462 DI 10.1016/S0896-6273(01)00372-5 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 465QG UT WOS:000170601000013 PM 11516401 ER PT J AU Klebanoff, MA Carey, JC Hauth, JC Hillier, SL Nugent, RP Thom, EA Ernest, JM Heine, RP Wapner, RJ Trout, W Moawad, A Leveno, KJ AF Klebanoff, MA Carey, JC Hauth, JC Hillier, SL Nugent, RP Thom, EA Ernest, JM Heine, RP Wapner, RJ Trout, W Moawad, A Leveno, KJ CA Natl Inst Child Hlth Human Dev Net TI Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LOW-BIRTH-WEIGHT; BACTERIAL VAGINOSIS; CONTROLLED TRIAL; PREMATURITY; DISEASE; FLORA; CREAM; RISK AB Background: Infection with Trichomonas vaginalis during pregnancy has been associated with preterm delivery. It is uncertain whether treatment of asymptomatic trichomoniasis in pregnant women reduces the occurrence of preterm delivery. Methods: We screened pregnant women for trichomoniasis by culture of vaginal secretions. We randomly assigned 617 women with asymptomatic trichomoniasis who were 16 to 23 weeks pregnant to receive two 2-g doses of metronidazole (320 women) or placebo (297 women) 48 hours apart. We treated women again with the same two-dose regimen at 24 to 29 weeks of gestation. The primary outcome was delivery before 37 weeks of gestation. Results: Between randomization and follow-up, trichomoniasis resolved in 249 of 269 women for whom follow-up cultures were available in the metronidazole group (92.6 percent) and 92 of 260 women with follow-up cultures in the placebo group (35.4 percent). Data on the time and characteristics of delivery were available for 315 women in the metronidazole group and 289 women in the placebo group. Delivery occurred before 37 weeks of gestation in 60 women in the metronidazole group (19.0 percent) and 31 women in the placebo group (10.7 percent) (relative risk, 1.8; 95 percent confidence interval, 1.2 to 2.7; P=0.004). The difference was attributable primarily to an increase in preterm delivery resulting from spontaneous preterm labor (10.2 percent vs. 3.5 percent; relative risk, 3.0; 95 percent confidence interval, 1.5 to 5.9). Conclusions: Treatment of pregnant women with asymptomatic trichomoniasis does not prevent preterm delivery. Routine screening and treatment of asymptomatic pregnant women for this condition cannot be recommended. (N Engl J Med 2001;345:487-93.) Copyright (C) 2001 Massachusetts Medical Society. C1 Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA. George Washington Univ, Ctr Biostat, Rockville, MD USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Obstet & Gynecol, Winston Salem, NC 27103 USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Texas, Dept Obstet & Gynecol, San Antonio, TX 78285 USA. RP Klebanoff, MA (reprint author), NICHHD, 6100 Execut Blvd,Rm 7B05,MSC 7510, Bethesda, MD 20892 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [U10 HD27860, U10 HD21410, U10 HD21414] NR 22 TC 207 Z9 212 U1 1 U2 5 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 AUG 16 PY 2001 VL 345 IS 7 BP 487 EP 493 DI 10.1056/NEJMoa003329 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 462QM UT WOS:000170431300002 PM 11519502 ER PT J AU Lin, FYC Szu, SC Van Bay, P AF Lin, FYC Szu, SC Van Bay, P TI A Salmonella typhi Vi conjugate vaccine. Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. Dong Thap Prov Hosp, Cao Lanh, Vietnam. RP Lin, FYC (reprint author), NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 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 AUG 16 PY 2001 VL 345 IS 7 BP 546 EP 546 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 462QM UT WOS:000170431300019 ER PT J AU Heppner, C Bilimoria, KY Agarwal, SK Kester, MB Whitty, LJ Guru, SC Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ Burns, AL AF Heppner, C Bilimoria, KY Agarwal, SK Kester, MB Whitty, LJ Guru, SC Chandrasekharappa, SC Collins, FS Spiegel, AM Marx, SJ Burns, AL TI The tumor suppressor protein menin interacts with NF-kappa B proteins and inhibits NF-kappa B-mediated transactivation SO ONCOGENE LA English DT Article DE MEN1; MEN1 gene; menin; NF-kappa B; transcriptional repression; oncogene; Rel-homology domain ID JUND-ACTIVATED TRANSCRIPTION; GENE-MUTATIONS; P65; FAMILY; IDENTIFICATION; EXPRESSION; PRODUCT; SUBUNIT; CANCER; P300 AB Multiple endocrine neoplasia type I is an autosomal dominant tumor syndrome. Manifestations include neoplasms of the parathyroid glands, entero pancreatic neuroendocrine cells, and the anterior pituitary gland. The MEN1 tumor suppressor gene encodes menin, a 610 amino acid nuclear protein without sequence homology to other proteins. To elucidate menin function, we used immunoprecipitation to identify interacting proteins. The NF-kappaB proteins p50, p52 and p65 were found to interact specifically and directly with menin in vitro and in vivo. The region of NF-kappaB proteins sufficient for binding to menin is the N-terminus. Furthermore, amino acids 305-381 of menin are essential for this binding. Menin represses p65-mediated transcriptional activation on NF-kappaB sites in a dose-dependent and specific manner. Also, PMA (phorbol 12-myristate 13-acetate)-stimulated NF-kappaB activation is suppressed by menin. These observations suggest that menin's ability to interact with NF-kappaB proteins and its modulation of NF-kappaB transactivation contribute to menin's tumor suppressor function. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. RP Burns, AL (reprint author), Univ Klin Koln, Klin & Poliklin Innere Med 2, D-50924 Cologne, Germany. RI Agarwal, Sunita/D-1428-2016 OI Agarwal, Sunita/0000-0002-7557-3191 NR 38 TC 172 Z9 180 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD AUG 16 PY 2001 VL 20 IS 36 BP 4917 EP 4925 DI 10.1038/sj.onc.1204529 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 462VE UT WOS:000170439800001 PM 11526476 ER PT J AU Palmer, JR Hatch, EE Rao, RS Kaufman, RH Herbst, AL Noller, KL Titus-Ernstoff, L Hoover, RN AF Palmer, JR Hatch, EE Rao, RS Kaufman, RH Herbst, AL Noller, KL Titus-Ernstoff, L Hoover, RN TI Infertility among women exposed prenatally to diethylstilbestrol SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE diethylstilbestrol; infertility ID ADENOSIS DESAD PROJECT; GENITAL-TRACT CHANGES; INUTERO; PREGNANCY; DAUGHTERS; UTERO; EXPERIENCE; HISTORY AB Although it is well established that women exposed to diethylstilbestrol in utero have an increased risk of spontaneous abortion, ectopic pregnancy, and preterm delivery, it is not known whether they also have an increased risk of infertility. The authors assessed this question in data from a collaborative follow-up study of the offspring of women who took diethylstilbestrol during pregnancy. In 1994, 1,753 diethylstilbestrol-exposed and 1,050 unexposed women from an ongoing cohort study (National Cooperative Diethylstilbestrol Adenosis Study and Dieckmann cohorts) provided data on difficulties in conceiving and reasons for the difficulty. Age-adjusted relative risks were computed for the association of diethylstilbestrol exposure with specific types of infertility. A greater proportion of exposed than unexposed women were nulligravid (relative risk (RR) = 1.3, 95% confidence interval (CI): 1.1, 1.5), and a greater proportion had tried to become pregnant for at least 12 months without success (RR = 1.8, 95% CI: 1.6, 2.1). Diethylstilbestrol exposure was significantly associated with infertility due to uterine and tubal problems, with relative risks of 7.7 (95% CI: 2.3, 25) and 2.4 (95% CI: 1.2, 4.6), respectively. The present findings indicate that diethylstilbestrol-exposed women have a higher risk of infertility than do unexposed women and that the increased risk of infertility is primarily due to uterine or tubal problems. C1 Boston Univ, Sch Med, Slone Epidemiol Unit, Brookline, MA 02446 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Massachusetts, Med Ctr, Dept Obstet & Gynecol, Worcester, MA USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. RP Palmer, JR (reprint author), Boston Univ, Sch Med, Slone Epidemiol Unit, 1371 Beacon St, Brookline, MA 02446 USA. FU NCI NIH HHS [N01-CP-51017, N01-CP-21168] NR 20 TC 52 Z9 52 U1 1 U2 4 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 AUG 15 PY 2001 VL 154 IS 4 BP 316 EP 321 DI 10.1093/aje/154.4.316 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 464XB UT WOS:000170557700005 PM 11495854 ER PT J AU Wong, LJC Chen, TJ Dai, P Bird, L Muenke, M AF Wong, LJC Chen, TJ Dai, P Bird, L Muenke, M TI Novel SNP at the common primer site of exon IIIa of FGFR2 gene causes error in molecular diagnosis of craniosynostosis syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE FGFR2; diagnosis error; primer mismatch; craniosynostosis; Crouzon syndrome; Pfeiffer syndrome; Apert syndrome ID CROUZON-SYNDROME; JACKSON-WEISS; MUTATIONS; AMPLIFICATION; PFEIFFER; DNA AB Most mutations in Crouzon, Pfeiffer, and Apert syndromes are in the extracellular, third immunoglobulin-like domain and adjacent linker regions (exons IIIa and IIIc) of the fibroblast growth factor receptor 2 (FGFR2) gene. Using the published primers for PCR, a patient with Crouzon syndrome was found to be homozygous for a mutation that results in a Q289P amino acid substitution in FGFR2. Two additional patients; one with Apert syndrome and P253R mutation, the other with Pfeiffer syndrome and S267P mutation, also appeared to be homozygous. Using a new primer located 146 bp 5' of exon IIIa for PCR followed by sequencing revealed an A to G polymorphism at -61 position of exon IIIa. All three patients were heterozygous for both the mutation and the polymorphism. These results indicate that the polymorphism and the mutation are not on the same chromosome. The single nucleotide polymorphism is located at the second to the last base of the Tend of the published primer. This primer mismatch caused the failure of amplification of the normal chromosome and thus, the apparent homozygosity. The frequency of this novel polymorphism was determined to be 0.03 by studying 326 chromosomes from the general population. We propose that a new primer should be used for mutational analysis of exon IIIa of FGFR2 to avoid misdiagnosis caused by primer mismatch. (C) 2001 Wiley-Liss, Inc. C1 Georgetown Univ, Med Ctr, Inst Mol & Human Genet, Washington, DC 20007 USA. Childrens Hosp, San Diego, CA USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Wong, LJC (reprint author), Georgetown Univ, Med Ctr, Inst Mol & Human Genet, M4000,3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 14 TC 9 Z9 9 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 AUG 15 PY 2001 VL 102 IS 3 BP 282 EP 285 DI 10.1002/ajmg.1461 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 459WE UT WOS:000170273800012 PM 11484208 ER PT J AU Preas, HL Jubran, A Vandivier, RW Reda, D Godin, PJ Banks, SM Tobin, MJ Suffredini, AF AF Preas, HL Jubran, A Vandivier, RW Reda, D Godin, PJ Banks, SM Tobin, MJ Suffredini, AF TI Effect of endotoxin on ventilation and breath variability - Role of cyclooxygenase pathway SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE endotoxemia; respiratory center; Fourier analysis; sepsis; respiratory muscles ID VARIATIONAL ACTIVITY; NORMAL HUMANS; ANTIINFLAMMATORY THERAPY; CARDIOVASCULAR-RESPONSE; HUMAN VOLUNTEERS; BREATHLESSNESS; HYPERCAPNIA; ACTIVATION; PULMONARY; IBUPROFEN AB To evaluate the effects of endotoxemia on respiratory controller function, 12 subjects were randomized to receive endotoxin or saline; six also received ibuprofen, a cyclooxygenase inhibitor, and six received placebo. Administration of endotoxin produced fever, increased respiratory frequency, decreased inspiratory time, and widened alveolar-arterial oxygen tension gradient (all p less than or equal to 0.001); these responses were blocked by ibuprofen. Independent of ibuprofen, endotoxin produced dyspnea, and it increased fractional inspiratory time, minute ventilation, and mean inspiratory flow (all p less than or equal to 0.025). Endotoxin altered the autocorrelative behavior of respiratory frequency by increasing its autocorrelation coefficient at a lag of one breath, the number of breath lags with significant serial correlations and its correlated fraction (all p < 0.05); these responses were blocked by ibuprofen. Changes in correlated behavior of respiratory frequency were related to changes in arterial carbon dioxide tension (r = 0.86; p < 0.03). Endotoxin decreased the oscillatory fraction of inspiratory time in both the placebo (p < 0.05) and ibuprofen groups (p = 0.06). In conclusion, endotoxin produced increases in respiratory motor output and dyspnea independent of fever and symptoms, and it curtailed the freedom to vary respiratory timing-a response that appears to be mediated by the cyclooxygenase pathway. C1 NIH, Clin Care Med Dept, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Vet Affairs Edward Hines Jr Hosp, Div Pulm & Crit Care Med, Hines, IL USA. Loyola Univ, Stritch Sch Med, Hines, IL USA. RP Suffredini, AF (reprint author), NIH, Clin Care Med Dept, Warren G Magnuson Clin Ctr, Bldg 10,Room 7043,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. NR 41 TC 44 Z9 48 U1 0 U2 1 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 AUG 15 PY 2001 VL 164 IS 4 BP 620 EP 626 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 469LL UT WOS:000170816900021 PM 11520726 ER PT J AU Moss, J Avila, NA Barnes, PM Litzenberger, RA Bechtle, J Brooks, PG Hedin, CJ Hunsberger, S Kristof, AS AF Moss, J Avila, NA Barnes, PM Litzenberger, RA Bechtle, J Brooks, PG Hedin, CJ Hunsberger, S Kristof, AS TI Prevalence and clinical characteristics of lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE lymphangioleiomyomatosis; tuberous sclerosis complex; lung function ID PULMONARY LYMPHANGIOLEIOMYOMATOSIS; CT; LYMPHANGIOMYOMATOSIS AB The true prevalence of pulmonary lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex (TSC) is unknown. The prevalence of LAM, radiological features, and lung function in patients with TSC was measured. The presence of LAM, as defined by the presence of cysts by high-resolution chest computed tomography (HRCT) scan, was determined in patients with TSC without prior pulmonary disease (Group 1). To determine the significance of early detection, severity of disease in screened patients (Group 1) was compared with that in patients with TSC with a prior diagnosis of LAM (Group 2). Forty-eight patients with TSC and no prior history of LAM were screened. Of the 38 females, 13 (34%) had LAM; LAM was absent in males. Lung function was preserved in patients with TSC who were found to have LAM by screening. In patients previously known to have LAM, FEV, and DLCO correlated inversely with severity of disease as assessed by CT scan. The prevalence of LAM in women with TSC was 34%, similar to 10-fold that previously reported, consistent with a large hitherto unrecognized subclinical population of patients at risk for pulmonary complications. C1 NHLBI, Pulm Crit Care Med Branch, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr,NIH, Bethesda, MD 20892 USA. RP Moss, J (reprint author), NHLBI, Pulm Crit Care Med Branch, Dept Diagnost Radiol, Warren G Magnuson Clin Ctr,NIH, 9000 Rockville Pike,Bldg 10,Room 6D05,MSC 1590, Bethesda, MD 20892 USA. EM mossj@nhlbi.nih.gov NR 12 TC 160 Z9 168 U1 1 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD AUG 15 PY 2001 VL 164 IS 4 BP 669 EP 671 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 469LL UT WOS:000170816900030 PM 11520735 ER PT J AU Peter, JF Tomer, KB AF Peter, JF Tomer, KB TI A general strategy for epitope mapping by direct MALDI-TOF mass spectrometry using secondary antibodies and cross-linking SO ANALYTICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; 3-DIMENSIONAL STRUCTURE; DISCONTINUOUS EPITOPE; LIMITED PROTEOLYSIS; CRYSTAL-STRUCTURE; PEPTIDE ANTIGENS; PROTEIN ANTIGENS; COMPLEX; IDENTIFICATION; EXCISION AB The combination of limited proteolysis and MALDI-TOF mass spectrometry has become an important tool for the determination of epitopes but works best with highly purified antibodies. Here we report the use of capture antibodies to reduce the need for purification of the antibody in the mass spectrometric determination of the epitope. In this new method, a secondary Fc-specific antibody, covalently bound to Sepharose beads, is used to capture the primary antibody (the antibody of interest). After capture, the two antibodies are cross-linked. The antigen is then bound to the immobilized antibodies and subjected to proteolysis using several successive proteinases. In this study, this strategy is demonstrated with a crude mouse anti-ACTH IgG solution and adrenocorticotropin (ACTH). Comparing this strategy with previous methods where the antibody is bound directly to activated beads, the new method (1) results in a higher binding capacity of the bound antibody to ACM, (2) does not require purification of the antibody of interest, and (3) dramatically reduces the chemical background in the MALDI mass spectra. C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. RP Tomer, KB (reprint author), Natl Inst Environm Hlth Sci, NIH, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. RI Tomer, Kenneth/E-8018-2013 NR 32 TC 25 Z9 26 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD AUG 15 PY 2001 VL 73 IS 16 BP 4012 EP 4019 DI 10.1021/ac010258n PG 8 WC Chemistry, Analytical SC Chemistry GA 463NT UT WOS:000170482800032 PM 11534730 ER PT J AU Nath, MD Peterson, DL AF Nath, MD Peterson, DL TI In vitro assembly of feline immunodeficiency virus capsid protein: Biological role of conserved cysteines SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE FIV; HIV; capsid protein; assembly; site-directed mutagenesis; DSC ID LYMPHOTROPIC VIRUS; GAG PRECURSOR; ANIMAL-MODELS; CORE ANTIGENS; LENTIVIRUS; PARTICLES; INFECTION; AIDS; MORPHOGENESIS; MORPHOLOGY AB Core assembly, a key step in the retroviral life cycle, is poorly understood. Previous studies have shown that the entire gag region is needed to form the assembled particles. In this report, we have shown that the assembly process is driven by recombinant capsid protein (p26) of feline immunodeficiency virus itself. Proteins are expressed in a bacterial system and soluble forms of wild-type and modified proteins are purified from bacterial extracts and are examined on gel-filtration chromatography fitted to an HPLC system. It has also been shown that changing residue Cys190 (one of the two conserved cysteines of feline immunodeficiency virus which are also conserved for all the immunodeficiency viruses including HM to serine by site-directed mutagenesis disrupts the assembly process. In addition, this modification causes considerable thermal instability of the protein while substitutions at nonconserved cysteines do not significantly affect the thermal stability and assembly of the protein. These findings indicate that conserved cysteine residues play a vital role in the capsid protein assembly and, therefore, are critical for virus infectivity. (C) 2001 Academic Press. C1 NCI, Frederick Canc Res & Dev Ctr, NIH, Frederick, MD 21702 USA. Virginia Commonwealth Univ, Dept Biochem & Mol Biophys, Richmond, VA 23298 USA. RP Nath, MD (reprint author), NCI, Frederick Canc Res & Dev Ctr, NIH, Bldg 567,Room 261, Frederick, MD 21702 USA. FU NIAID NIH HHS [AI 15955] NR 39 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD AUG 15 PY 2001 VL 392 IS 2 BP 287 EP 294 DI 10.1006/abbi.2001.2449 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 463UF UT WOS:000170495100015 PM 11488604 ER PT J AU Osuch, EA Benson, B Geraci, M Podell, D Herscovitch, P McCann, UD Post, RM AF Osuch, EA Benson, B Geraci, M Podell, D Herscovitch, P McCann, UD Post, RM TI Regional cerebral blood flow correlated with flashback intensity in patients with posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE PTSD; trauma provocation; PET; cerebral perfusion; functional neuroimaging ID POSITRON-EMISSION-TOMOGRAPHY; SUBSTANCE-ABUSE HISTORIES; CHILDHOOD SEXUAL ABUSE; SCRIPT-DRIVEN IMAGERY; INTRAVENOUS (H2O)-O-15; SYMPTOM PROVOCATION; ANXIETY; PTSD; PET; STIMULI AB Back-ground: Nuclear imaging studies have examined cerebral bloodflow (rCBF) in subjects with posttraumatic stress disorder (PTSD) using symptom evocation paradigms. To date, no such studies have investigated rCBF as related to subjects' reports of flashback intensity. Methods: Subjects with varying traumatic histories and longstanding PTSD were studied Using [O-15]-H2O positron emission tomography with an auditory script of their traumatic event. Eight subjects had three resting scans followed by their script and additional scans. Heart rate responses as well as the presence of flashbacks and their intensity, were recorded. rCBF was correlated with flashback intensity in each subject's scan. Combined analysis of all subjects' data yielded common regions related to the flashback experience. Results: rCBF correlated directly with flashback intensity in the brainstem, lingula, bilateral insula, right putamen and left hippocampal and perihippocampal, somatosensory! and cerebellar regions. Inverse correlations with rCBF were found in bilateral dorsolateral prefrontal, right fusiform. and right medial temporal cortices. Conclusions: This study correlated flashback intensity and rCBF in a group of patients with chronic PTSD suggesting involvement of brainstem, and areas associated with motor control, complex visual/spatial cues and memory. (C) 2001 Society of Biological Psychiatry. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Ctr Nursing Dept, NIH, Bethesda, MD USA. NIH, PET Dept, Ctr Clin, Bethesda, MD USA. Johns Hopkins Sch Med, Dept Psychiat, Baltimore, MD USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Rm 3N-212, Bethesda, MD 20892 USA. RI Osuch, Elizabeth/B-5009-2015 OI Osuch, Elizabeth/0000-0001-5946-1862 NR 31 TC 95 Z9 97 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD AUG 15 PY 2001 VL 50 IS 4 BP 246 EP 253 DI 10.1016/S0006-3223(01)01107-6 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 466QF UT WOS:000170655700003 PM 11522258 ER PT J AU Stetler-Stevenson, M Arthur, DC Jabbour, N Xie, XY Molldrem, J Barrett, AJ Venzon, D Rick, ME AF Stetler-Stevenson, M Arthur, DC Jabbour, N Xie, XY Molldrem, J Barrett, AJ Venzon, D Rick, ME TI Diagnostic utility of flow cytometric immunophenotyping in myelodysplastic syndrome SO BLOOD LA English DT Article ID ANEMIA; EXPRESSION; CRITERIA; CELLS AB The myelodysplastic syndromes (MDSs) are characterized by bilineage or trilineage dysplasia. Although diagnostic criteria are well established for MDS, a significant number of patients have blood and bone marrow findings that make diagnosis and classification difficult. Flow cytometric immunophenotyping is an accurate and highly sensitive method for detection of quantitative and qualitative abnormalities in hematopoietic cells. Flow cytometry was used to study hematopoietic cell populations in the bone marrow of 45 patients with straightforward MDS. The results were compared with those obtained in a series of patients with aplastic anemia, healthy donors, and patients with a history of nonmyeloid neoplasia in complete remission. The immunophenotypic abnormalities associated with MDS were defined, and the diagnostic utility of flow cytometry was compared, with morphologic and cytogenetic evaluations in 20 difficult cases. Although morphology and cytogenetics were adequate for diagnosis in most cases, flow cytometry could detect immunophenotypic abnormalities in cases when combined morphology and cytogenetics were nondiagnostic. It is concluded that flow cytometric immunophenotyping may help establish the diagnosis of MDS, especially when morphology and cytogenetics are indeterminate. (C) 2001 by The American Society of Hematology. C1 NCI, DCS, Pathol Lab,Div Clin Sci, Flow Cytometry Unit,NIH, Bethesda, MD 20892 USA. NCI, Lab Pathol, Div Clin Sci, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Hematol Serv, Bethesda, MD 20892 USA. RP Stetler-Stevenson, M (reprint author), NCI, DCS, Pathol Lab,Div Clin Sci, Flow Cytometry Unit,NIH, Bldg 10,Rm 2N-108, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 17 TC 176 Z9 190 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 AUG 15 PY 2001 VL 98 IS 4 BP 979 EP 987 DI 10.1182/blood.V98.4.979 PG 9 WC Hematology SC Hematology GA 461KU UT WOS:000170364100013 PM 11493442 ER PT J AU Taylor, ML Dastych, J Sehgal, D Sundstrom, M Nilsson, G Akin, C Mage, RG Metcalfe, DD AF Taylor, ML Dastych, J Sehgal, D Sundstrom, M Nilsson, G Akin, C Mage, RG Metcalfe, DD TI The Kit-activating mutation D816V enhances stem cell factor-dependent chemotaxis SO BLOOD LA English DT Article ID RECEPTOR TYROSINE KINASE; LIGAND-INDEPENDENT ACTIVATION; BLOOD MONONUCLEAR-CELLS; PROTOONCOGENE C-KIT; HUMAN MAST-CELLS; PERIPHERAL-BLOOD; CATALYTIC DOMAIN; POINT MUTATION; MASTOCYTOSIS; LINE AB The D816V mutation of c-kit has been detected in patients with mastocytosis. This mutation leads to constitutive tyrosine kinase activation of Kit. Because stem cell factor (SCF), the ligand for Kit (CD117(+)), is a chemoattractant for CD117+ cells and one feature of mastocytosis is an abnormal collection of mast cells in tissues derived from CD34(+)CD117(+) mast cell precursors, the hypothesis was considered that the D816V mutation would enhance chemotaxis of these precursor cells. Constructs encoding wild-type Kit or Kit bearing the D816V mutation were transfected into Jurkat cells, labeled with Calcein-AM, and migration to SCF assessed in the presence or absence of tyrosine kinase inhibitors. Chemotaxis to SCF was enhanced in D816V transfectants compared to wild-type Kit transfectants (P < .002). Migration of both transfectants was inhibited by tyrosine kinase inhibitors, although D816V transfectants were more sensitive. Chemotaxis was next performed on CD34(+)CD117(+) circulating mast cell precursors obtained from patients with mastocytosis. Analysis of prechemotaxis and migrated cells showed that whereas less than 10% in the prechemotaxis sample had the D816V mutation, 40% to 80% of migrated cells had this mutation. These results demonstrate that the D816V Kit mutation enhances chemotaxis of CD117(+) cells, offering one explanation for increased mast cells observed in tissues of patients with mastocytosis. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Int Inst Mol & Cell Biol, Lab Mol Immunol, Warsaw, Poland. Uppsala Univ, Dept Genet & Pathol, S-75148 Uppsala, Sweden. RP Taylor, ML (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C207,10 Ctr Dr,MSC1881, Bethesda, MD 20892 USA. NR 26 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD AUG 15 PY 2001 VL 98 IS 4 BP 1195 EP 1199 DI 10.1182/blood.V98.4.1195 PG 5 WC Hematology SC Hematology GA 461KU UT WOS:000170364100042 PM 11493470 ER PT J AU Jaju, RJ Fidler, C Haas, OA Strickson, AJ Watkins, F Clark, K Cross, NCP Cheng, JF Aplan, PD Kearney, L Boultwood, J Wainscoat, JS AF Jaju, RJ Fidler, C Haas, OA Strickson, AJ Watkins, F Clark, K Cross, NCP Cheng, JF Aplan, PD Kearney, L Boultwood, J Wainscoat, JS TI A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; CHROMOSOME-TRANSLOCATION; NUCLEOPORIN NUP98; FUSION; T(7-11)(P15-P15); COACTIVATORS; RECURRENT; CANCER; HOXA9; SITE AB The recurrent translocation t(5;11)(q35; p15.5) associated with a 5q deletion, del(5q), has been reported in childhood acute myeloid leukemia (AML). We report the cloning of the translocation breakpoints in de novo childhood AML harboring a cryptic t(5;11)(q35;p15.5). Fluorescence in situ hybridization (FISH) analysis demonstrated that the nucleoporin gene (NUP98) at 11p15.5 was disrupted by this translocation. By using 3'-rapid amplification of complementary DNA ends (3'-RACE) polymerase chain reaction, we identified a chimeric messenger RNA that results in the in-frame fusion of NUP98 to a novel gene, NSD1. The NSD1 gene has 2596 amino acid residues and a 85% homology to the murine Nsd1 with the domain structure being conserved. The NSD1 gene was localized to 5q35 by FISH and is widely expressed. The reciprocal transcript, NSDI-NUP98, was also detected by reverse transcriptase-polymerase chain reaction. This is the first report in which the novel gene NSD1 has been implicated in human malignancy. C1 Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, LRF Mol Haematol Unit, Oxford OX3 9DU, England. Univ Oxford, John Radcliffe Hosp, Inst Mol Med, MRC,Mol Haematol Unit, Oxford OX3 9DU, England. St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria. Hammersmith Hosp, Imperial Coll Sch Med, Dept Haematol, London, England. Lawrence Berkeley Natl Lab, Div Life Sci, Berkeley, CA USA. NCI, Div Clin Sci, Gaithersburg, MD USA. RP Jaju, RJ (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Lab Sci, LRF Mol Haematol Unit, Oxford OX3 9DU, England. RI Cross, Nicholas/B-4817-2009; Aplan, Peter/K-9064-2016 OI Cross, Nicholas/0000-0001-5481-2555; NR 20 TC 154 Z9 162 U1 0 U2 5 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 AUG 15 PY 2001 VL 98 IS 4 BP 1264 EP 1267 DI 10.1182/blood.V98.4.1264 PG 4 WC Hematology SC Hematology GA 461KU UT WOS:000170364100054 PM 11493482 ER PT J AU Gerber, LH AF Gerber, LH TI Cancer rehabilitation into the future SO CANCER LA English DT Article DE cancer; rehabilitation; function; disability ID AEROBIC EXERCISE; QUALITY; LIFE; VALIDATION; SURVIVAL; THERAPY; CARE AB The 5-year survival for many cancer sites exceeds 50%, suggesting that these patients are living longer and may be considered to have a chronic illness. The incidence of cancer increases from 500 in 100,000 to 2000-4000 in 100,000 as women or men age from 50 to 80 years. Our population is aging and the prevalence of cancer is increasing. Treatments for cancer are quite complex, and they are often delivered to elders who have a variety of medical problems and are receiving additional medications that may complicate overall patient management. Hence, these patients may have extremely complex functional problems. Cancer patients need comprehensive care designed to relieve symptoms of pain, fatigue, and weakness. They need education to help support their ability to reach functional independence and maintain quality of life. Rehabilitation professionals are essential for the comprehensive care of cancer patients throughout the phases of their disease: treatment planning, treatment, remission, recurrence, and end of life. The needs of this population can better be served if several processes are put into effect. Rehabilitation professionals must be trained to manage problems associated with cancer and its treatments. Research about what are effective and efficient rehabilitation treatments must be done to determine how best to treat cancer patients throughout the various phases of their illness. Physicians and patients must be alerted to the importance of rehabilitation interventions to the overall function of these patients. (C) 2001 American Cancer Society. C1 NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Gerber, LH (reprint author), NIH, Dept Rehabil Med, Bldg 10,Room 6S235,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 22 Z9 22 U1 2 U2 2 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 AUG 15 PY 2001 VL 92 IS 4 SU S BP 975 EP 979 DI 10.1002/1097-0142(20010815)92:4+<975::AID-CNCR1409>3.0.CO;2-B PG 5 WC Oncology SC Oncology GA 466VD UT WOS:000170666100003 PM 11519023 ER PT J AU Gruvberger, S Ringner, M Chen, YD Panavally, S Saal, LH Borg, A Ferno, M Peterson, C Meltzer, PS AF Gruvberger, S Ringner, M Chen, YD Panavally, S Saal, LH Borg, A Ferno, M Peterson, C Meltzer, PS TI Estrogen receptor status in breast cancer is associated with remarkably distinct gene expression patterns SO CANCER RESEARCH LA English DT Article ID ARTIFICIAL NEURAL NETWORKS; CADHERIN EXPRESSION; CDNA MICROARRAYS; MAMMARY-GLAND; P-CADHERIN; C/EBP-BETA; CELLS; CLASSIFICATION; IDENTIFICATION; CARCINOMA AB To investigate the phenotype associated with estrogen receptor a (ER) expression in breast carcinoma, gene expression profiles of 58 node-negative breast carcinomas discordant for ER status were determined using DNA microarray technology. Using artificial neural networks as well as standard hierarchical clustering techniques, the tumors could be classified according to ER status, and a list of genes which discriminate tumors according to ER status was generated. The artificial neural networks could accurately predict ER status even when excluding top discriminator genes, including ER itself. By reference to the serial analysis of gene expression database, we found that only a small proportion of the 100 most important ER discriminator genes were also regulated by estradiol in MCF-7 cells. The results provide evidence that ER+ and ER- tumors display remarkably different gene-expression phenotypes not solely explained by differences in estrogen responsiveness. C1 NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Lund Univ, Dept Oncol, SE-22100 Lund, Sweden. Lund Univ, Dept Theoret Phys, Complex Syst Div, SE-22100 Lund, Sweden. RP Meltzer, PS (reprint author), NHGRI, Canc Genet Branch, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. RI Saal, Lao/A-2919-2011; Ringner, Markus/G-3641-2011 OI Saal, Lao/0000-0002-0815-1896; Ringner, Markus/0000-0001-5469-8940 NR 33 TC 475 Z9 491 U1 1 U2 14 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 AUG 15 PY 2001 VL 61 IS 16 BP 5979 EP 5984 PG 6 WC Oncology SC Oncology GA 464EW UT WOS:000170521100006 PM 11507038 ER PT J AU Rasko, JEJ Klenova, EM Leon, J Filippova, GN Loukinov, DI Vatolin, S Robinson, AF Hu, YJ Ulmer, J Ward, MD Pugacheva, EM Neiman, PE Morse, HC Collins, SJ Lobanenkov, VV AF Rasko, JEJ Klenova, EM Leon, J Filippova, GN Loukinov, DI Vatolin, S Robinson, AF Hu, YJ Ulmer, J Ward, MD Pugacheva, EM Neiman, PE Morse, HC Collins, SJ Lobanenkov, VV TI Cell growth inhibition by the multifunctional multivalent zinc-finger factor CTCF SO CANCER RESEARCH LA English DT Article ID C-MYC GENE; TRANSCRIPTION FACTOR; PROTEIN; SEQUENCES; REGIONS AB The 11-zinc finger protein CCTC-binding factor (CTCF) employs different sets of zinc fingers to form distinct complexes with varying CTCF-target sequences (CTSs) that mediate the repression or activation of gene expression and the creation of hormone-responsive gene silencer, and of diverse vertebrate enhancer-blocking elements (chromatin insulators). To determine how these varying effects would integrate in vivo, we engineered a variety of expression systems to study effects of CTCF on cell growth. Here we show that ectopic expression of CTCF in many cell types inhibits cell clonogenicity by causing profound growth retardation without apoptosis. In asynchronous cultures, the cell-cycle profile of CTCF-expressing cells remained unaltered, which suggested that progression through the cycle was slowed at multiple points. Although conditionally induced CTCF caused the S-phase block, CTCF can also arrest cell division. Viable CTCF-expressing cells could be maintained without dividing for several days. While MYC is the well-characterized CTCF target, the inhibitory effects of CTCF on cell growth could not be ascribed solely to repression of MYC, suggesting that additional CTS-driven genes involved in growth-regulatory circuits, such as p19ARF, are likely to contribute to CTCF-induced growth arrest. These findings indicate that CTCF may regulate cell-cycle progression at multiple steps within the cycle, and ade. to the growing evidence for the function of CTCF as a tumor suppresser gene. C1 NIAID, Mol Pathol Sect, LIP, NIH, Bethesda, MD 20892 USA. Centenary Inst Canc Med & Cell Biol, Gene Therapy Res Unit, Newtown, NSW 2042, Australia. Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. Univ Cantabria, Fac Med, Santander 39011, Spain. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Lobanenkov, VV (reprint author), NIAID, Mol Pathol Sect, LIP, NIH, 7 Ctr Dr,Room 7-303,MSC 0760, Bethesda, MD 20892 USA. RI Rasko, John/F-5754-2013; OI Morse, Herbert/0000-0002-9331-3705 FU NCI NIH HHS [R01 CA68360, CA71732, R01 CA20068] NR 20 TC 63 Z9 67 U1 0 U2 5 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 AUG 15 PY 2001 VL 61 IS 16 BP 6002 EP 6007 PG 6 WC Oncology SC Oncology GA 464EW UT WOS:000170521100010 PM 11507042 ER PT J AU Rokman, A Ikonen, T Mononen, N Autio, V Matikainen, MP Koivisto, PA Tammela, TLJ Kallioniemi, OP Schleutker, J AF Rokman, A Ikonen, T Mononen, N Autio, V Matikainen, MP Koivisto, PA Tammela, TLJ Kallioniemi, OP Schleutker, J TI ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer SO CANCER RESEARCH LA English DT Article AB The ELAC2/HPC2 gene at 17p11 is the first candidate gene identified for human prostate cancer (PRCA) based on linkage analysis and positional cloning (S. V. Tavtigian et at. Nat. Genet., 27:172-180, 2001). A truncating mutation was found in one hereditary prostate cancer (HPC) family, whereas two missense variants, Ser217Leu and Ala541Thr, were reported to be associated with increased PRCA risk in the general population. Here, we screened for mutations of the ELAC2/HPC2 gene in 66 Finnish HPC families. Several sequence variants, including a new exonic variant (Glu622Val) were found, but none of the mutations were truncating. We then analyzed the frequency of the three found missense variants in 1365 individuals, including hereditary (n = 107) and un;elected (n = 467) PRCA, benign prostatic hyperplasia (n = 223), and population controls (568 healthy male blood donors). Ser217Leu and Ala541Thr variants carried no significantly elevated risk for HPC or PRCA, although the latter variant was associated with benign prostatic hyperplasia. The previously undescribed Glu622Val variant had a 1.0% population prevalence, but a significantly higher frequency in PRCA cases (3.0% odds ratio, 2.94; 95% confidence interval, 1.05-8.23). We conclude that ELAC2/HPC2 truncating mutations are rare in HPC, but that rare variants of the ELAC2/HPC2 require additional study as risk factors for PRCA in the general population. C1 Tampere Univ, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, FIN-33101 Tampere, Finland. Univ Tampere, Tampere Sch Publ Hlth, FIN-33014 Tampere, Finland. Tampere Univ Hosp, Dept Urol, FIN-33521 Tampere, Finland. Tampere Univ, Sch Med, FIN-33521 Tampere, Finland. Tampere Univ Hosp, Dept Clin Genet, FIN-33521 Tampere, Finland. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP Rokman, A (reprint author), Tampere Univ, Inst Med Technol, Canc Genet Lab, POB 607, FIN-33101 Tampere, Finland. RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 FU NHGRI NIH HHS [1-HG-55389] NR 10 TC 63 Z9 64 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 AUG 15 PY 2001 VL 61 IS 16 BP 6038 EP 6041 PG 4 WC Oncology SC Oncology GA 464EW UT WOS:000170521100017 PM 11507049 ER PT J AU Prins, GS Birch, L Couse, JF Choi, I Katzenellenbogen, B Korach, KS AF Prins, GS Birch, L Couse, JF Choi, I Katzenellenbogen, B Korach, KS TI Estrogen imprinting of the developing prostate gland is mediated through stromal estrogen receptor alpha: Studies with alpha ERKO and beta ERKO mice SO CANCER RESEARCH LA English DT Article ID ADULT-RAT PROSTATE; MESSENGER-RIBONUCLEIC-ACID; PRENATAL EXPOSURE; EXPRESSION; ANDROGEN; MOUSE; DIETHYLSTILBESTROL; SYSTEM; LOBES; ALTERS AB Neonatal exposure of rodents to high doses of estrogen permanently imprints the growth and function of the prostate and predisposes this gland to hyperplasia and severe dysplasia analogous to prostatic intraepithelial neoplasia with aging. Because the rodent prostate gland expresses estrogen receptor (ER)-alpha within a subpopulation of stromal cells and ER beta within epithelial cells, the present study was undertaken to determine the specific ER(s) involved in mediating prostatic developmental estrogenization. Wild-type (WT) mice, homozygous mutant ER (ERKO) alpha -/- mice, and beta ERKO -/- mice were injected with 2 mug of diethylstilbestrol (DES) or oil (controls) on days 1, 3, and 5 of life. Reproductive tracts were excised on days 5 or 10 (prepubertal), day 30 (pubertal), day 90 (young adult), or with aging at 6, 12, and 18 months of age. Prostate complexes were microdissected and examined histologically for prostatic lesions and markers of estrogenization. Immunocytochemistry was used to examine expression of androgen receptor, ER alpha, ER beta, cytokeratin 14 (basal cells), cytokeratin 18 (luminal cells), and dorsolateral protein over time in the treated mice. In WT-DES mice, developmental estrogenization of the prostate was observed at all of the time points as compared with WT-oil mice. These prostatic imprints included transient up-regulation of ER alpha, down-regulation of androgen receptor, decreased ER beta levels in adult prostate epithelium, lack of DLP secretory protein, and a continuous layer of basal cells lining the ducts. With aging, epithelial dysplasia and inflammatory cell infiltrate were observed in the ventral and dorsolateral prostate lobes. In contrast, the prostates of alpha ERKO mice exhibited no response to neonatal DES either immediately after exposure or throughout life up to 18 months of age. Furthermore, neonatal DES treatment of beta ERKO mice resulted in a prostatic response similar to that observed in WT animals. The present findings indicate that ER alpha is the dominant ER form mediating the developmental estrogenization of the prostate gland. If epithelial ER beta is involved in some component of estrogen imprinting, its role would be considered minor and would require the presence of ER alpha expression in the prostatic stromal cells. C1 Univ Illinois, Dept Urol, Chicago, IL 60612 USA. NIEHS, Reprod & Dev Toxicol Lab, Receptor Biol Sect, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC USA. Univ Illinois, Dept Mol & Integrat Physiol, Urbana, IL 61801 USA. RP Prins, GS (reprint author), Univ Illinois, Dept Urol, M-C 955, Chicago, IL 60612 USA. OI Korach, Kenneth/0000-0002-7765-418X FU NCI NIH HHS [CA-18119]; NIDDK NIH HHS [DK-40890, R01 DK040890] NR 48 TC 197 Z9 203 U1 1 U2 4 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 AUG 15 PY 2001 VL 61 IS 16 BP 6089 EP 6097 PG 9 WC Oncology SC Oncology GA 464EW UT WOS:000170521100026 PM 11507058 ER PT J AU Kawakami, K Kawakami, M Joshi, BH Puri, RK AF Kawakami, K Kawakami, M Joshi, BH Puri, RK TI Interleukin-13 receptor-targeted cancer therapy in an immunodeficient animal model of human head and neck cancer SO CANCER RESEARCH LA English DT Article ID CELL CARCINOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; ALPHA CHAIN; SIGNAL-TRANSDUCTION; (IL)-13 BINDING; SARCOMA-CELLS; CLONING; IL-13; COMPONENT AB Although interleukin-13 receptors (IL-13R) are overexpressed on several head and neck cancer cell lines, a majority of cell lines express only low levels of IL-13R. We have found that the primary interletikin-13-binding protein IL-13R alpha2 chain plays an important role in ligand binding and internalization. We showed that the gene transfer of IL-13R alpha2 chain into various solid tumor cell lines that express few IL-13Rs can dramatically sensitize cells to the cytotoxic effect of a recombinant chimeric protein composed of interleukin-13 and a mutated form of Pseudomonas exotoxin A, IL13-PE38QQR. Based on the expression of IL-13R,,Ne have classified five head and neck cancer cell lines into two groups: (a) IL-13R alpha2 chain-positive cell lines (SCC-25 and KCCT873); and (b) IL-13R alpha2 chain-negative cell lines (A253, YCUT891, and KCCT871). By plasm id-mediated stable gene transfer, we demonstrate that rot only IL-13R alpha2 chain-positive head and neck cancer cell lines but also IL13R alpha2 chain-negative cell lines can dramatically increase sensitivity to IL-13 toxin by 520-1000-fold compared with mock-transfected control cells after genetic alteration to express high levels of the IL-13R alpha2 chain. In animal studies, i.p. or intratumoral administration of IL13-PE38QQR given daily or on alternate days for 3-5 days showed dramatic tumor response with complete remission in intratumorally injected tumors in both IL-13R alpha2 chain-positive and -negative but transfected with IL13R alpha2 chain head and neck tumor implanted s.c. in nude mice. These results demonstrate that by using a combination approach of gene transfer and systemic or locoregional cytotoxin therapy, the IL-13R represents a new potent target for head and neck cancer therapy. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellulare & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellulare & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 31 TC 59 Z9 61 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 AUG 15 PY 2001 VL 61 IS 16 BP 6194 EP 6200 PG 7 WC Oncology SC Oncology GA 464EW UT WOS:000170521100040 PM 11507072 ER PT J AU Gruys, ME Back, TC Subleski, J Wiltrout, TA Lee, JK Schmidt, L Watanabe, M Stanyon, R Ward, JM Wigginton, JM Wiltrout, RH AF Gruys, ME Back, TC Subleski, J Wiltrout, TA Lee, JK Schmidt, L Watanabe, M Stanyon, R Ward, JM Wigginton, JM Wiltrout, RH TI Induction of transplantable mouse renal cell cancers by streptozotocin: In vivo growth, metastases, and angiogenic phenotype SO CANCER RESEARCH LA English DT Article ID COLON-CARCINOMA CELLS; NUDE-MICE; ORTHOTOPIC IMPLANTATION; TUMOR-CELLS; MUTATIONS; THERAPY; MODEL; GENE; TUMORIGENESIS; BEHAVIOR AB Interleukin-2-based regimens of biological therapy have shown some clinical promise for the treatment of kidney cancer in humans, although the mechanisms responsible for tumor regression occurring in these patients remain unclear. Preclinical insight into these mechanisms is limited by a paucity of orthotopic animal models of kidney cancer. We have used streptozotocin, an antibiotic and diabetogenic nitrosamine compound derived from Streptomyces achromogenes to induce new kidney tumors in BALB/c mice. Single or multiple doses of streptozotocin induced kidney tumors in up to 25% of mice by 50-90 weeks of age, with up to 18% characterized as renal cell carcinomas (RCCs). Several transplantable lines were obtained from the RCCs, and one of these lines was subsequently cloned. The initial tumor isolates and sublines were histologically reconfirmed to be RCCs, and all grew progressively but slowly (mean survival times, 57 to > 100 days) in vivo after intrarenal implant. None of the primary isolates or sublines revealed mutations in either the VHL or Ras genes, although karyotype analysis and chromosome painting revealed the consistent presence of a submetacentric chromosome resulting from the fusion of chromosomes 16 and 19. Biological characterization of these tumors revealed several features analogous to the growth of human kidney cancers, including a propensity for the formation of lung metastases and high vascularity. This hypervascularity is evident by both gross and microscopic analysis and correlates with the expression of several proangiogenic genes. Overall, the features of orthotopic transplantability, slower in vivo growth (relative to the rapid growth rates of other transplantable mouse kidney tumors), propensity for lung metastases, and hypervascularity may make these tumors valuable models for the study of new therapeutic strategies based on antineovascular agents and antitumor cytokines. C1 NCI, FCRDC, LEI, Off Lab Anim Resources, Ft Detrick, MD 21702 USA. Sci Applicat Int Corp, IRSP, Canc Res Ctr, Expt Immunol Lab, Frederick, MD USA. Sci Applicat Int Corp, IRSP, Canc Res Ctr, Lab Genom Divers, Frederick, MD USA. Ctr Canc Res, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Wiltrout, RH (reprint author), NCI, FCRDC, LEI, Off Lab Anim Resources, Bldg 560,Room 31-93, Ft Detrick, MD 21702 USA. OI Stanyon, Roscoe/0000-0002-7229-1092 NR 41 TC 18 Z9 18 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 AUG 15 PY 2001 VL 61 IS 16 BP 6255 EP 6263 PG 9 WC Oncology SC Oncology GA 464EW UT WOS:000170521100048 PM 11507080 ER PT J AU Levy, CS Kogulan, P Gill, VJ Croxton, MB Kane, JG Lucey, DR AF Levy, CS Kogulan, P Gill, VJ Croxton, MB Kane, JG Lucey, DR TI Endocarditis caused by penicillin-resistant viridans streptococci: 2 cases and controversies in therapy SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID INFECTIVE ENDOCARDITIS; MITIS AB Although penicillin-resistant viridans streptococci have been isolated from samples from the mouth, blood, and wounds in increasing numbers, viridans streptococci isolated from patients with endocarditis have remained sensitive to penicillin for the past 5 decades. We report the cases of 2 patients with penicillin-resistant viridans streptococcal endocarditis, review 6 other cases from the literature, and summarize 2 studies that used an animal model of penicillin-resistant viridans streptococcal endocarditis. C1 Washington Hosp Ctr, Dept Infect Dis, Infect Dis Serv, Washington, DC 20010 USA. Washington Hosp Ctr, Microbiol Serv, Washington, DC 20010 USA. Georgetown Univ, Med Ctr, Infect Dis Serv, Washington, DC 20007 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Pathol, Microbiol Serv, Bethesda, MD 20892 USA. RP Levy, CS (reprint author), Washington Hosp Ctr, Dept Infect Dis, Infect Dis Serv, Room 2A-56,110 Irving St NW, Washington, DC 20010 USA. NR 10 TC 26 Z9 29 U1 0 U2 1 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 AUG 15 PY 2001 VL 33 IS 4 BP 577 EP 579 DI 10.1086/321910 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 456WB UT WOS:000170104800029 PM 11462199 ER PT J AU Cai, ML Huang, Y Ghirlando, R Wilson, KL Craigie, R Clore, GM AF Cai, ML Huang, Y Ghirlando, R Wilson, KL Craigie, R Clore, GM TI Solution structure of the constant region of nuclear envelope protein LAP2 reveals two LEM-domain structures: one binds BAF and the other binds DNA SO EMBO JOURNAL LA English DT Article DE LAP2; LEM motif; NMR; structure ID LAMINA-ASSOCIATED POLYPEPTIDE-2; DREIFUSS MUSCULAR-DYSTROPHY; RESIDUAL DIPOLAR COUPLINGS; TO-AUTOINTEGRATION FACTOR; NMR STRUCTURES; STRUCTURE REFINEMENT; MEMBRANE PROTEIN; RETROVIRAL DNA; CELL-CYCLE; COMPLEX AB The nuclear envelope proteins LAP2, emerin and MAN1 share a conserved similar to 40-residue 'LEM' motif. Loss of emerin causes Emery-Dreifuss muscular dystrophy. We have solved the solution NMR structure of the constant region of human LAP2 (residues 1-168). Human LAP2(1-168) has two structurally independent, non-interacting domains located at residues 1-50 ('LAP2-N') and residues 111-152 (LEM-domain), connected by an similar to 60-residue flexible linker. The two domains are structurally homologous, comprising a helical turn followed by two helices connected by an 11-12-residue loop. This motif is shared by subdomains of T4 endonuclease VII and transcription factor rho, despite negligible (less than or equal to 15%) sequence identity. NMR chemical shift mapping demonstrated that the LEM-domain binds BAF (barrier-to-autointegration factor), whereas LAP2-N binds DNA. Both binding surfaces comprise helix 1, the N-terminus of helix 2 and the inter-helical loop. Binding selectivity is determined by the nature of the surface residues in these binding sites, which are predominantly positively charged for LAP2-N and hydrophobic for the LEM-domain. Thus, LEM and LEM-like motifs form a common structure that evolution has customized for binding to BAF or DNA. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Cell Biol & Anat, Sch Med, Baltimore, MD 21205 USA. RP Clore, GM (reprint author), NIDDKD, Phys Chem Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. RI Clore, G. Marius/A-3511-2008; Ghirlando, Rodolfo/A-8880-2009 OI Clore, G. Marius/0000-0003-3809-1027; FU NIGMS NIH HHS [R0I GM48646, R01 GM048646] NR 51 TC 124 Z9 130 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 2001 VL 20 IS 16 BP 4399 EP 4407 DI 10.1093/emboj/20.16.4399 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 467LD UT WOS:000170702500010 PM 11500367 ER PT J AU Heymann, JAW Sarker, R Hirai, T Shi, D Milne, JLS Maloney, PC Subramaniam, S AF Heymann, JAW Sarker, R Hirai, T Shi, D Milne, JLS Maloney, PC Subramaniam, S TI Projection structure and molecular architecture of OxIT, a bacterial membrane transporter SO EMBO JOURNAL LA English DT Article DE electron cryo-microscopy; major facilitator superfamily; membrane transporter; two-dimensional crystallization ID THIOL CROSS-LINKING; MICROBIAL GENOME ANALYSES; ESCHERICHIA-COLI; LACTOSE PERMEASE; OXALOBACTER-FORMIGENES; PROTEIN; CAPABILITIES; PROKARYOTES; RESOLUTION; OXALATE AB The major facilitator superfamily (MFS) represents the largest collection of evolutionarily related members within the class of membrane 'carrier' proteins. OAT, a representative example of the MFS, is an oxalate-transporting membrane protein in Oxalobacter formigenes. From an electron crystallographic analysis of two-dimensional crystals of OAT, we have determined the projection structure of this membrane transporter. The projection map at 6 Angstrom resolution indicates the presence of 12 transmembrane helices in each monomer of OxlT, with one set of six helices related to the other set by an approximate internal two-fold axis. The projection map reveals the existence of a central cavity, which we propose to be part of the pathway of oxalate transport. By combining information from the projection map with related biochemical data, we present probable models for the architectural arrangement of transmembrane helices in this protein superfamily. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA. RP Subramaniam, S (reprint author), NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RI Hirai, Teruhisa/G-2105-2015 OI Hirai, Teruhisa/0000-0002-2114-8149 NR 24 TC 50 Z9 54 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD AUG 15 PY 2001 VL 20 IS 16 BP 4408 EP 4413 DI 10.1093/emboj/20.16.4408 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 467LD UT WOS:000170702500011 PM 11500368 ER PT J AU Ghidelli, S Donze, D Dhillon, N Kamakaka, RT AF Ghidelli, S Donze, D Dhillon, N Kamakaka, RT TI Sir2p exists in two nucleosome-binding complexes with distinct deacetylase activities SO EMBO JOURNAL LA English DT Article DE NET1; nucleosome; SIR2; SIR3; SIR4 ID SILENT MATING LOCI; RESOLUTION STRUCTURAL-ANALYSIS; NATURAL YEAST TELOMERE; SACCHAROMYCES-CEREVISIAE; CHROMATIN STRUCTURE; PROTEIN SIR2; HETEROCHROMATIN ORGANIZATION; HISTONE DEACETYLASE; MOLECULAR-MODEL; N-TERMINUS AB The absolute requirement for the histone deacetylase activity of Sir2p in silencing coupled with the conservation of Sir2p-like proteins in larger eukaryotes suggests that this molecule plays an important role in gene regulation in all organisms. Here we report the purification and characterization of two Sir2p-containing protein complexes; one of which contains Sir4p and the other Net1p. The Sir4p-containing complex has an NAD-dependent histone deacetylase activity, while the Net1p-containing complex possesses deacetylase activity but only weak NAD-dependent histone deacetylase activity. Finally, we demonstrate that the Sir2p-containing complexes bind nucleosomes efficiently and partially restrict accessibility of the linker DNA to enzymatic probes. C1 NICHHD, Unit Chromatin & Transcript, NIH, Bethesda, MD 20892 USA. RP Kamakaka, RT (reprint author), NICHHD, Unit Chromatin & Transcript, NIH, Bldg 18T,Room 106,18 Lib Dr, Bethesda, MD 20892 USA. NR 58 TC 67 Z9 67 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 AUG 15 PY 2001 VL 20 IS 16 BP 4522 EP 4535 DI 10.1093/emboj/20.16.4522 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 467LD UT WOS:000170702500022 PM 11500379 ER PT J AU Dalgaard, JZ Klar, AJS AF Dalgaard, JZ Klar, AJS TI A DNA replication-arrest site RTS1 regulates imprinting by determining the direction of replication at mat1 in S-pombe SO GENES & DEVELOPMENT LA English DT Article DE differentiation; imprinting; mating-type switching; Schizosaccharomyces pombe; termination of DNA replication ID RIBOSOMAL-RNA GENES; FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; SACCHAROMYCES-CEREVISIAE; CELLS; TERMINATION; INITIATION; INHERITANCE; ASYMMETRY; ELEMENTS AB Mating-type switching in Schizosaccharomyces pombe involves a strand-specific, alkali-labile imprint at the mat1 (mating-type) locus. The imprint is synthesized during replication in a swi1, swi3, and polyinerase alpha (swi7) dependent manner and is dependent on mat1 being replicated in a specific direction. Here we show that the direction of replication at mat1 is controlled by a cis-acting polar terminator of replication (RTS1). Two-dimensional gel analysis of replication intermediates reveals that RTS1 only terminates replication forks moving in the centromere-distal direction. A genetic analysis shows that RTS1 optimizes the imprinting process. Transposing the RTS1 element to the distal side of mat1 abolishes imprinting of the native mat1 allele but restores imprinting of an otherwise unimprinted inverted mat1 allele. These data provide conclusive evidence for the "direction of replication model" that explains the asymmetrical switching pattern of S. pombe, and identify a DNA replication-arrest element implicated in a developmental process. Such elements could play a more general role during development and differentiation in higher eukaryotes by regulating the direction of DNA replication at key loci. C1 Marie Curie Res Inst, Oxted RH8 0TL, Surrey, England. NCI, Frederick Canc Res & Dev Ctr, Dept Hlth & Human Serv, Div Basic Sci,Gene Regulat & Chromosome Biol Lab, Frederick, MD 21701 USA. RP Marie Curie Res Inst, The Chart, Oxted RH8 0TL, Surrey, England. EM j.dalgaard@mcri.ac.uk NR 35 TC 70 Z9 75 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 EI 1549-5477 J9 GENE DEV JI Genes Dev. PD AUG 15 PY 2001 VL 15 IS 16 BP 2060 EP 2068 DI 10.1101/gad.200801 PG 9 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 463ZM UT WOS:000170507300006 PM 11511538 ER PT J AU Panchision, DM Pickel, JM Studer, L Lee, SH Turner, PA Hazel, TG McKay, RDG AF Panchision, DM Pickel, JM Studer, L Lee, SH Turner, PA Hazel, TG McKay, RDG TI Sequential actions of BMP receptors control neural precursor cell production and fate SO GENES & DEVELOPMENT LA English DT Article DE bone morphogenetic protein; receptor; neural; development; precursor cell ID BONE MORPHOGENETIC PROTEINS; WING IMAGINAL DISC; GROWTH-FACTOR-BETA; CREST STEM-CELLS; SPINAL-CORD; TRANSCRIPTION FACTORS; SIGNALING PATHWAY; NERVOUS-SYSTEM; I RECEPTORS; CAENORHABDITIS-ELEGANS AB Bone morphogenetic proteins (BMPs) have diverse and sometimes paradoxical effects during embryonic development. To determine the mechanisms underlying BMP actions, we analyzed the expression and function of two BMP receptors, BMPR-IA and BMPR-IB, in neural precursor cells in vitro and in vivo. Neural precursor cells always express Bmpr-1a, but Bmpr-1b is not expressed until embryonic day 9 and is restricted to the dorsal neural tube surrounding the source of BMP ligands. BMPR-IA activation induces (and Sonic hedgehog prevents) expression of Rmpr-1b along with dorsal identity genes in precursor cells and promotes their proliferation. When BMPR-IB is activated, it limits precursor cell numbers by causing mitotic arrest. This results in apoptosis in early gestation embryos and terminal differentiation in mid-gestation embryos. Thus, BMP actions are first inducing (through BMPR-IA) and then terminating (through BMPR-IB), based on the accumulation of BMPR-IB relative to BMPR-IA. We describe a feed-forward mechanism to explain how the sequential actions of these receptors control the production and fate of dorsal precursor cells from neural stem cells. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Lab Stem Cell & Tumor Biol Neurosurg & Cellular B, New York, NY 10021 USA. RP McKay, RDG (reprint author), NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 88 TC 218 Z9 238 U1 0 U2 9 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 AUG 15 PY 2001 VL 15 IS 16 BP 2094 EP 2110 DI 10.1101/gad.894701 PG 17 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 463ZM UT WOS:000170507300009 PM 11511541 ER PT J AU Nansel, T Simons-Morton, B Scheidt, P Overpeck, MD AF Nansel, T Simons-Morton, B Scheidt, P Overpeck, MD TI Systemic vs individualistic approaches to bullying - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. Maternal & Child Hlth Bur, Hlth Resources & Serv Adm, Rockville, MD USA. RP Nansel, T (reprint author), Natl Inst Child Hlth & Human Dev, Bethesda, MD 20892 USA. OI Nansel, Tonja/0000-0002-8298-7595 NR 6 TC 0 Z9 0 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD AUG 15 PY 2001 VL 286 IS 7 BP 787 EP 788 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 462PU UT WOS:000170429600016 ER PT J AU Massad, LS Ahdieh, L Benning, L Minkoff, H Greenblatt, RM Watts, H Miotti, P Anastos, K Moxley, M Muderspach, LI Melnick, S AF Massad, LS Ahdieh, L Benning, L Minkoff, H Greenblatt, RM Watts, H Miotti, P Anastos, K Moxley, M Muderspach, LI Melnick, S TI Evolution of cervical abnormalities among women with HIV-1: Evidence from surveillance cytology in the women's interagency HIV study SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; papanicolaou smear; cervix ID HUMAN-IMMUNODEFICIENCY-VIRUS; SQUAMOUS INTRAEPITHELIAL LESIONS; PAPANICOLAOU SMEARS; SEROPOSITIVE WOMEN; INFECTED WOMEN; RISK-FACTORS; NEOPLASIA; PREVALENCE; IMMUNOSUPPRESSION; COLPOSCOPY AB Objective: To determine incidence, progression, and regression rates for abnormal cervical cytology and their correlates among women with HIV. Methods: In a multicenter prospective cohort study conducted October 1, 1994, through September 30, 1999 at university, public, and private medical centers and clinics, 1639 HIV-seropositive and 452 seronegative women were evaluated every 6 months for up to 5 years using history, cervical cytology, T-cell subsets, and quantitative plasma HIV RNA. Human papillomavirus (HPV) typing at baseline was determined by polymerase chain reaction. Cytology was read using the Bethesda system, with any smear showing at least atypia considered abnormal. Poisson regression identified factors associated with incident cytologic abnormalities whereas logistic regression identified those associated with progression and regression after an abnormality. Results: At least one abnormal smear was found during all of follow-up among 73.0% of HIV-seropositive patients and 42.3% of seronegatives (p < .001). Only 5.9% of seropositives ever developed high-grade lesions, and the proportion with high-grade findings did not rise over time. Incidence of atypical squamous cells of uncertain significance (ASCUS) or more severe lesions among HIV-seropositive patients and seronegative patients was 26.4 and 11.0/100 woman-years (rate ratio [RR], 2.4; 95% confidence interval [CI], 1.9-3.0), whereas that of at least low-grade squamous intraepithelial lesions (SIL) was 8.9 and 2.2/100 (RR, 4.0; Cl, 2.6-6.1). HIV status, detection of the presence of human papillomavirus (HPV), CD4 lymphocyte count, and HIV RNA level predicted incidence of abnormal cytology (p < .05); HPV detection and HIV RNA level predicted progression (p < .01); and HPV detection, CD4 lymphocyte count, and HIV RNA level predicted regression (p < 00.1). Rates of incidence, progression, and regression of abnormal cytology did not differ between HIV seronegative women and seropositive women with CD4 lymphocyte counts > 200/mm(3) and HIV RNA levels < 4000/ml of similar HPV status. Conclusions: Although HIV infected women were at high risk for abnormal cytology, high-grade changes were uncommon. HIV status, HPV detection, CD4 lymphocyte count, and HIV RNA level predicted the incidence of cervical cytologic abnormalities. Progression was significantly increased only among the most immunosuppressed women, while regression was significantly reduced in all HIV seropositive women except those with the best controlled HIV disease. C1 Cook Cty Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, Chicago, IL 60612 USA. Rush Med Coll, Chicago, IL 60612 USA. Johns Hopkins Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Natl Inst Child Hlth, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. Catholic Med Ctr Brooklyn, Jamaica, NY USA. Catholic Med Ctr Queens, Jamaica, NY USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ So Calif, Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA. NCI, Bethesda, MD 20892 USA. RP Massad, LS (reprint author), Cook Cty Hosp, Dept Obstet & Gynecol, Div Gynecol Oncol, 1835 W Harrison St, Chicago, IL 60612 USA. FU NIAID NIH HHS [U01-AI-31834, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590]; NICHD NIH HHS [U01-HD-32632] NR 30 TC 87 Z9 90 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD AUG 15 PY 2001 VL 27 IS 5 BP 432 EP 442 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 466QN UT WOS:000170656400003 PM 11511819 ER PT J AU Woo, EW Messmann, R Sausville, EA Figg, WD AF Woo, EW Messmann, R Sausville, EA Figg, WD TI Quantitative determination of perifosine, a novel alkylphosphocholine anticancer agent, in human plasma by reversed-phase liquid chromatography-electrospray mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE perifosine; alkylphosphocholine ID MITOGENIC SIGNAL-TRANSDUCTION; HEXADECYLPHOSPHOCHOLINE; ANALOGS; CANCER; MILTEFOSINE; IONIZATION; TARGET AB A sensitive and selective reversed-phase LC-ESI-MS method to quantitate perifosine in human plasma was developed and validated. Sample preparation utilized simple acetonitrile precipitation without an evaporation step. With a Develosil UG-30 column (10X4 mm I.D.), perifosine and the internal standard hexadecylphosphocholine were baseline separated at retention times of 2.2 and 1.1 min, respectively. The mobile phase consisted of eluent A, 95% 9 mM ammonium formate (pH 8) in acetonitrile-eluent B, 95% acetonitrile in 9 mM ammonium formate (pH 8) (A-B, 40:60, v/v), and the flow-rate was 0.5 ml/min. The detection utilized selected ion monitoring in the positive-mode at m/z 462.3 and 408.4 for the protonated molecular ions of perifosine and the internal standard, respectively. The lower limit of quantitation of perifosine was 4 ng/ml in human plasma, and good linearity was observed in the 4-2000 ng/ml range fitted by linear regression with 1/x weight. The total LC-MS run time was 5 min. The validated LC-MS assay was applied to measure perifosine plasma concentrations from patients enrolled on a phase I clinical trial for pharmacokinetic/pharmacodynamic analyses. Published by Elsevier Science B.V. C1 NCI, Med Branch, Clin Pharmacokinet Sect, Bethesda, MD 20852 USA. NCI, Div Canc Treatment & Diagnosis, Bethesda, MD 20852 USA. RP Figg, WD (reprint author), NCI, Med Branch, NIH, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 19 TC 20 Z9 20 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD AUG 15 PY 2001 VL 759 IS 2 BP 247 EP 257 DI 10.1016/S0378-4347(01)00231-6 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 453KP UT WOS:000169915300006 PM 11499478 ER PT J AU Merino, ME Navid, F Christensen, BL Toretsky, JA Helman, LJ Cheung, NKV Mackall, CL AF Merino, ME Navid, F Christensen, BL Toretsky, JA Helman, LJ Cheung, NKV Mackall, CL TI Immunomagnetic purging of Ewing's sarcoma from blood and bone marrow: Quantitation by real-time polymerase chain reaction SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MINIMAL RESIDUAL DISEASE; PEDIATRIC SOLID TUMORS; HIGH-DOSE THERAPY; PERIPHERAL-BLOOD; PROGENITOR CELLS; RT-PCR; NEUROECTODERMAL TUMOR; TRANSPLANTATION; CHEMOTHERAPY; EXPRESSION AB Purpose: A propensity for hematogenous spread with resulting contamination of autologous cell products complicates cellular therapies for Ewing's sarcoma. We used a new approach to purge artificially contaminated cellular specimens of Ewing's sarcoma and show the capacity for real-time polymerase chain reaction (PCR) to quantify the contamination level of Ewing's sarcoma in such specimens. Patients and Methods: Binding of monoclonal antibody (MoAb) 8H9 to Ewing's sarcoma cell lines and normal hematopoietic cells was studied using flow cytometry. Using real-time PCR-based amplification of t(11;22), levels of Ewing's contamination of experimental and clinical cellular products were monitored. Purging was accomplished using immunomagnetic-based depletion. Monitoring of the function of residual hematopoietic progenitors and T cells was performed using functional assays. Results: MoAb 8H9 shows binding to Ewing's sarcoma but spares normal hematopoietic tissues. Nested real-time PCR is capable of detecting contaminating Ewing's sarcoma cells with a sensitivity of one cell in 10(6) normal cells. After 8H9-based purging, a 2- to 3-log reduction in contaminating Ewing's sarcoma was shown by real-time PCR, with purging to PCR negativity at levels of contamination of 1:10(6). Levels of contamination in clinical samples ranged from 1:10(5) to 10(6). Therefore, 8H9-based purging of clinical samples is predicted to reduce tumor cell contamination to a level below the limit of detection of PCR. Conclusion: These results demonstrate a new approach for purging contaminated cellular products of Ewing's sarcoma and demonstrate the capacity of realtime PCR to provide accurate quantitative estimates of circulating tumor burden in this disease. J Clin Oncol 19:3649-3659. (C) 2001 by American Society of Clinical Oncology. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. RP Merino, ME (reprint author), NCI, Pediat Oncol Branch, NIH, 9000 Rockville Pk, Bethesda, MD 20892 USA. NR 44 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD AUG 15 PY 2001 VL 19 IS 16 BP 3649 EP 3659 PG 11 WC Oncology SC Oncology GA 462ZZ UT WOS:000170453500007 PM 11504746 ER PT J AU Rajagopalan, S Fu, J Long, EO AF Rajagopalan, S Fu, J Long, EO TI Cutting edge: induction of IFN-gamma production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIGNALING PATHWAY; ACTIVATION; PREGNANCY; P49 AB Activated NK cells lyse tumor cells and virus-infected cells and produce IFN-gamma upon contact with sensitive target cells. The regulation of these effector responses in resting NK cells is not well understood. We now describe a receptor, KIR2DL4, that has the unique property of inducing IFN-gamma production, but not cytotoxicity, by resting NK cells in the absence of cytokines. In contrast, the NK cell-activation receptors CD16 and 2B4 induced cytotoxicity but not IFN-gamma production. The induction by KIR2DL4 of IFN-gamma production by resting NK cells was blocked by an inhibitor of the p38 mitogen-activated protein kinase signaling pathway, in contrast to the IL-2-induced IFN-gamma secretion that was sensitive to inhibition of the extracellular signal-regulated kinase mitogen-activated protein kinase pathway. These results reveal a functional dichotomy (cytokine production vs cytotoxicity) in the response of resting NK cells, as dictated by the signals of individual receptors. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Rajagopalan, S (reprint author), NIAID, Immunol Lab, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 24 TC 170 Z9 184 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 AUG 15 PY 2001 VL 167 IS 4 BP 1877 EP 1881 PG 5 WC Immunology SC Immunology GA 471VP UT WOS:000170949600007 PM 11489965 ER PT J AU Tanchot, C Barber, DL Chiodetti, L Schwartz, RH AF Tanchot, C Barber, DL Chiodetti, L Schwartz, RH TI Adaptive tolerance of CD4(+) T cells in vivo: Multiple thresholds in response to a constant level of antigen presentation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR TRANSGENIC MICE; IN-VIVO; PERIPHERAL TOLERANCE; POSITIVE SELECTION; PRESENTING CELLS; INDUCTION; CTLA-4; CD4+; REPERTOIRE; ANERGY AB The in vivo T cell response to persistent Ag contains a hyporesponsive phase following an initial expansion and subsequent partial deletion of the responding cells. The mechanism(s) responsible for this tolerance process is poorly understood. In this study, we describe a new paired transgenic model (TCR and Ag), which within 7-14 days produces 20-40 million hyporesponsive T cells. This state is characterized by an 85-95% reduction in all cytokine production, an impairment of re-expression of CD25 and CD69, and a desensitization of the proliferative response to Ag. TCR levels were normal, and in vivo mixing experiments showed no evidence for active suppression. The hyporesponsiveness partially dissipated without proliferation when the cells were transferred into a non-Ag-bearing host. If the second host expressed Ag, the T cells initially regained responsiveness, but then slowly entered an even deeper state of tolerance characterized by an additional 7- to 10-fold lowering of cytokine production and a greater desensitization of proliferation. Surprisingly, this readaptation took place with the same level of Ag presentation, suggesting that other parameters can influence the tolerance threshold. Both the readjustment in sensitivity and the reversal without Ag convincingly demonstrate for the first time a truly adaptive tolerance process in CD4(+) T cells in vivo. The Journal of Immunology, 2001. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Room111,MSC-0420, Bethesda, MD 20892 USA. NR 44 TC 96 Z9 98 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2001 VL 167 IS 4 BP 2030 EP 2039 PG 10 WC Immunology SC Immunology GA 471VP UT WOS:000170949600027 PM 11489985 ER PT J AU Bortell, R Moss, J McKenna, RC Rigby, MR Niedzwiecki, D Stevens, LA Patton, WA Mordes, JP Greiner, DL Rossini, AA AF Bortell, R Moss, J McKenna, RC Rigby, MR Niedzwiecki, D Stevens, LA Patton, WA Mordes, JP Greiner, DL Rossini, AA TI Nicotinamide adenine dinucleotide (NAD) and its metabolites inhibit T lymphocyte proliferation: Role of cell surface NAD glycohydrolase and pyrophosphatase activities SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ARGININE ADP-RIBOSYLTRANSFERASES; MOLECULAR CHARACTERIZATION; RIBOSYLATION ACTIVITY; DIABETES PREVENTION; ECTO-ENZYME; MARKER RT6; RAT RT6.2; BB RATS; EXPRESSION; MOUSE AB The presence of NAD-metabolizing enzymes (e.g., ADP-ribosyltransferase (ART)2) on the surface of immune cells suggests a potential immunomodulatory activity for ecto-NAD or its metabolites at sites of inflammation and cell lysis where extracellular levels of NAD may be high. In vitro, NAD inhibits mitogen-stimulated rat T cell proliferation. To investigate the mechanism of inhibition, the effects of NAD and its metabolites on T cell proliferation were studied using ART2a(+) and ART2b(+) rat T cells. NAD and ADP-ribose, but not nicotinamide, inhibited proliferation of mitogen-activated T cells independent of ART2 allele-specific expression. Inhibition by P2 purinergic receptor agonists was comparable to that induced by NAD and ADP-ribose; these compounds were more potent than P1 agonists. Analysis of the NAD-metabolizing activity of intact rat T cells demonstrated that ADP-ribose was the predominant metabolite, consistent with the presence of cell surface NAD glycohydrolase (NADase) activities. Treatment of T cells with phosphatidylinositol-specific phospholipase C removed much of the NADase activity, consistent with at least one NADase having a GPI anchor; ART2(-) T cell subsets contained NADase activity that was not releasable by phosphatidylinositol-specific phospholipase C treatment. Formation of AMP from NAD and ADP-ribose also occurred, a result of cell surface pyrophosphatase activity. Because AMP and its metabolite, adenosine, were less inhibitory to rat T cell proliferation than was NAD or ADP-ribose, pyrophosphatases may serve a regulatory role in modifying the inhibitory effect of ecto-NAD on T cell activation. These data suggest that T cells express multiple NAD and adenine nucleotide-metabolizing activities that together modulate immune function. C1 Univ Massachusetts, Sch Med, Dept Med, Diabet Div, Worcester, MA 01655 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Bortell, R (reprint author), Univ Massachusetts, Sch Med, Dept Med, Diabet Div, 373 Plantat St,Suite 218, Worcester, MA 01655 USA. FU NIDDK NIH HHS [DK32520, DK36024, DK25306, DK41235] NR 60 TC 28 Z9 34 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2001 VL 167 IS 4 BP 2049 EP 2059 PG 11 WC Immunology SC Immunology GA 471VP UT WOS:000170949600029 PM 11489987 ER PT J AU Zhao, YD Gran, B Pinilla, C Markovic-Plese, S Hemmer, B Tzou, A Whitney, LW Biddison, WE Martin, R Simon, R AF Zhao, YD Gran, B Pinilla, C Markovic-Plese, S Hemmer, B Tzou, A Whitney, LW Biddison, WE Martin, R Simon, R TI Combinatorial peptide libraries and biometric score matrices permit the quantitative analysis of specific and degenerate interactions between clonotypic TCR and MHC peptide ligands SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MYELIN BASIC-PROTEIN; T-CELL EPITOPES; MULTIPLE-SCLEROSIS LESIONS; ARTIFICIAL NEURAL-NETWORK; INDIVIDUAL AMINO-ACIDS; BINDING PEPTIDES; CLASS-I; HLA-DR; ANTIGEN RECOGNITION; MOLECULAR MIMICRY AB The interaction of TCRs with MHC peptide ligands can be highly flexible, so that many different peptides are recognized by the same TCR in the context of a single restriction element. We provide a quantitative description of such interactions, which allows the identification of T cell epitopes and molecular mimics. The response of T cell clones to positional scanning synthetic combinatorial libraries is analyzed with a mathematical approach that is based on a model of independent contribution of individual amino acids to peptide Ag recognition. This biometric analysis compares the information derived from these libraries composed of trillions of decapeptides with all the millions of decapeptides contained in a protein database to rank and predict the most stimulatory peptides for a given T cell clone. We demonstrate the predictive power of the novel strategy and show that, together with gene expression profiling by cDNA microarrays, it leads to the identification of novel candidate autoantigens in the inflammatory autoimmune disease, multiple sclerosis. C1 NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Torrey Pines Inst Mol Studies & Mixture Sci, San Diego, CA 92121 USA. Univ Marburg, Dept Neurol, Clin Neuroimmunol Grp, Marburg, Germany. RP Simon, R (reprint author), NCI, Mol Stat & Bioinformat Sect, Biometr Res Branch, NIH, 6130 Execut Blvd,Room 8134,MSC 7434, Bethesda, MD 20892 USA. RI Gran, Bruno/A-2288-2013 OI Gran, Bruno/0000-0001-6384-2342 NR 59 TC 72 Z9 75 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2001 VL 167 IS 4 BP 2130 EP 2141 PG 12 WC Immunology SC Immunology GA 471VP UT WOS:000170949600039 PM 11489997 ER PT J AU Butcher, BA Kim, L Johnson, PF Denkers, EY AF Butcher, BA Kim, L Johnson, PF Denkers, EY TI Toxoplasma gondii tachyzoites inhibit proinflammatory cytokine induction in infected macrophages by preventing nuclear translocation of the transcription factor NF-kappa B SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; GERMINAL CENTER REACTIONS; CELL-MEDIATED-IMMUNITY; IFN-GAMMA; HOST-CELL; DENDRITIC CELLS; TNF-ALPHA; T-CELLS; SPLENIC MICROARCHITECTURE; ADAPTIVE IMMUNITY AB Control of microbial infection requires regulated induction of NF-kappaB-dependent proinflammatory cytokines such as IL-12 and TNF-alpha. Activation of this important transcription factor is driven by phosphorylation-dependent degradation of the inhibitory I kappaB molecule, an event which enables NF-kappaB translocation from the cytoplasm to the nucleus. In this study, we show that intracellular infection of macrophages with the protozoan parasite Toxoplasma gondii induces rapid I kappaB phosphorylation and degradation. Nevertheless, NF-kappaB failed to translocate to the nucleus, enabling the parasite to invade cells without triggering proinflammatory cytokine induction. Infected cells subsequently subjected to LPS triggering were severely crippled in IL-12 and TNF-alpha production, a result of tachyzoite-induced blockade of NF-kappaB nuclear translocation. Our results are the first to demonstrate the ability of an intracellular protozoan to actively interfere with the NF-kappaB activation pathway in macrophages. an activity that may enable parasite survival within the host. C1 Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. NCI, Frederick Canc Res & Dev Ctr, Eukaryot Transcript Regulat Sect, Regulat Cell Growth Lab, Frederick, MD 21702 USA. RP Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. EM eydl@cornell.edu RI Johnson, Peter/A-1940-2012 OI Johnson, Peter/0000-0002-4145-4725 FU NIAID NIH HHS [AI-47888] NR 61 TC 131 Z9 140 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD AUG 15 PY 2001 VL 167 IS 4 BP 2193 EP 2201 PG 9 WC Immunology SC Immunology GA 471VP UT WOS:000170949600047 PM 11490005 ER PT J AU Shibata, M Wang, RYH Yoshiba, M Shih, JWK Alter, HJ Mitamura, K AF Shibata, M Wang, RYH Yoshiba, M Shih, JWK Alter, HJ Mitamura, K TI The presence of a newly identified infectious agent (SEN virus) in patients with liver diseases and in blood donors in Japan SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; UNITED-STATES; NON-A; POSTTRANSFUSION HEPATITIS; TT VIRUS; NON-B; UNKNOWN ETIOLOGY; DNA; FULMINANT; FAILURE AB The existence of the newly discovered SEN virus (SENV) was investigated in 379 Japanese patients with liver diseases and in 277 blood donors, to determine whether SENV is associated with non-A-E hepatitis. SENV DNA was detected by seminested polymerase chain reaction, with primers directed to 2 SENV strains: SENV-H and SENV-D. SENV was detected in 7 (32%) of 22 patients with fulminant hepatitis, in 15 (17%) of 86 patients with acute hepatitis, in 38 (27%) of 139 patients with chronic hepatitis, in 29 (31%) of 93 patients with liver cirrhosis, in 5 (33%) of 15 patients with autoimmune hepatitis, in 11 (46%) of 24 patients with primary biliary cirrhosis, and in 27 blood donors (10%). Infection occurred more frequently in patients with liver diseases than in blood donors; however, there were no significant differences in SENV-positive rates between patients with non-A-C hepatitis and those with acute or chronic hepatitis due to known hepatitis virus or nonviral liver disease. This study did not suggest SENV as a possible causative agent of non-A-C hepatitis. C1 Showa Univ, Sch Med, Dept Internal Med 2, Shinagawa Ku, Tokyo 1428666, Japan. Showa Univ, Fujigaoka Hosp, Div Gastroenterol, Kanagawa, Japan. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Mitamura, K (reprint author), Showa Univ, Sch Med, Dept Internal Med 2, Shinagawa Ku, 1-5-8 Hatanodai, Tokyo 1428666, Japan. NR 31 TC 61 Z9 67 U1 0 U2 0 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 AUG 15 PY 2001 VL 184 IS 4 BP 400 EP 404 DI 10.1086/322050 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 456WA UT WOS:000170104700002 PM 11471096 ER PT J AU Cohn, MA Frankel, SS Rugpao, S Young, MA Willett, G Tovanabutra, S Khamboonruang, C VanCott, T Bhoopat, L Barrick, S Fox, C Quinn, TC Vahey, M Nelson, KE Weissman, D AF Cohn, MA Frankel, SS Rugpao, S Young, MA Willett, G Tovanabutra, S Khamboonruang, C VanCott, T Bhoopat, L Barrick, S Fox, C Quinn, TC Vahey, M Nelson, KE Weissman, D TI Chronic inflammation with increased human immunodeficiency virus (HIV) RNA expression in the vaginal epithelium of HIV-infected Thai women SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Conference on Retroviruses and Opportunistic Infections CY FEB 04-08, 2001 CL CHICAGO, ILLINOIS ID SEXUALLY-TRANSMITTED DISEASES; LANGERHANS CELL TROPISM; BACTERIAL VAGINOSIS; RISK-FACTORS; TYPE-1 RNA; MALE TRANSMISSION; RHESUS MACAQUES; FEMALE; PLASMA; COMPARTMENTALIZATION AB Thai residents have a greater risk of heterosexual transmission of human immunodeficiency virus (HIV) than do US residents. To analyze host factors associated with heterosexual transmission, vaginal epithelial biopsies from HIV-seropositive Thai and US women were evaluated for tissue virus load and histologic makeup. In all, 84% of Thai and 14% of US women exhibited a chronic inflammatory T cell infiltrate in the vaginal epithelium. In Thai tissue, the infiltrate was associated with elevated levels of HIV RNA in the epidermis. Uninfected Thai women also had vaginal epithelial inflammation. Inflammation did not correlate with sexually transmitted diseases or HIV disease stage. The higher rates and increased risk of heterosexual transmission in Thailand may be due to chronic inflammation at the site where the virus is transmitted, which leads to the accumulation of activated T cells. Such cells might act as targets for initial viral infection and subsequently as reservoirs that support efficient transmission. C1 Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. NIAID, Howard Hughes Med Inst, Res Scholars Program, NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD USA. Henry M Jackson Fdn Adv Mil Med, Rockville, MD USA. Mol Histol Lab, Gaithersburg, MD USA. Johns Hopkins Univ, Div Infect Dis, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Georgetown Univ, Dept Infect Dis, Washington, DC USA. Georgetown Univ, Dept Obstet & Gynecol, Washington, DC USA. Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Washington, DC 20306 USA. Chiang Mai Univ, Res Inst Hlth Sci, Chiang Mai 50000, Thailand. RP Weissman, D (reprint author), Univ Penn, Dept Med, Div Infect Dis, 536 Johnson Pavil, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [HL-62060]; NIAID NIH HHS [AI-45318, AI-35173] NR 35 TC 24 Z9 24 U1 0 U2 0 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 AUG 15 PY 2001 VL 184 IS 4 BP 410 EP 417 DI 10.1086/322780 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 456WA UT WOS:000170104700004 PM 11471098 ER PT J AU Van Goor, F Li, YX Stojilkovic, SS AF Van Goor, F Li, YX Stojilkovic, SS TI Paradoxical role of large-conductance calcium-activated K+ (BK) channels in controlling action potential-driven Ca2+ entry in anterior pituitary cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE somatotrophs; gonadotrophs; bursting; voltage-gated Ca2+ channels; delayed rectifier K+ channels; domain Ca2+ ID PIG THALAMIC NEURONS; RAT CHROMAFFIN CELLS; POTASSIUM CHANNELS; BETA-SUBUNIT; NEUROTRANSMITTER RELEASE; RAPID INACTIVATION; SMOOTH-MUSCLE; OSCILLATIONS; CURRENTS; INFLUX AB Activation of high-conductance Ca2+-activated K+ (BK) channels normally limits action potential duration and the associated voltage-gated Ca2+ entry by facilitating membrane repolarization. Here we report that BK channel activation in rat pituitary somatotrophs prolongs membrane depolarization, leading to the generation of plateau-bursting activity and facilitated Ca2+ entry. Such a paradoxical role of BK channels is determined by their rapid activation by domain Ca2+, which truncates the action potential amplitude and thereby limits the participation of delayed rectifying K+ channels during membrane repolarization. Conversely, pituitary gonadotrophs express relatively few BK channels and fire single spikes with a low capacity to promote Ca2+ entry, whereas an elevation in BK current expression in a gonadotroph model system leads to the generation of plateau-bursting activity and high-amplitude Ca2+ transients. C1 NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Univ British Columbia, Dept Math, Vancouver, BC V6T 1Z2, Canada. Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z2, Canada. RP Stojilkovic, SS (reprint author), NICHHD, Endocrinol & Reprod Res Branch, NIH, Bldg 49,Room 6A36, Bethesda, MD 20892 USA. NR 55 TC 70 Z9 70 U1 1 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 2001 VL 21 IS 16 BP 5902 EP 5915 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 460PR UT WOS:000170318200011 PM 11487613 ER PT J AU Bridgman, PC Dave, S Asnes, CF Tullio, AN Adelstein, RS AF Bridgman, PC Dave, S Asnes, CF Tullio, AN Adelstein, RS TI Myosin IIB is required for growth cone motility SO JOURNAL OF NEUROSCIENCE LA English DT Article DE growth cones; motility; myosin; actin; traction force; knock-out mice ID F-ACTIN FLOW; TRACTION FORCES; LOCOMOTING CELLS; FOCAL ADHESIONS; FILOPODIA; SUBSTRATE; LOCALIZATION; KERATOCYTES; FIBROBLASTS; ISOFORMS AB Growth cones are required for the forward advancement and navigation of growing axons. Modulation of growth cone shape and reorientation of the neurite are responsible for the change of outgrowth direction that underlies navigation. Change of shape involves the reordering of the cytoskeleton. Reorientation of the neurite requires the generation of tension, which is supplied by the ability of the growth cone to crawl on a substrate. The specific molecular mechanisms responsible for these activities are unknown but are thought to involve actomyosin-generated force combined with linkage to the cell surface receptors that are responsible for adhesion (Heidemann and Buxbaum, 1998). To test whether myosin IIB is responsible for the force generation, we quantified shape dynamics and filopodial-mediated traction force in growth cones from myosin IIB knock-out (KO) mice and compared them with neurons from normal littermates. Growth cones from the KO mice spread less, showed alterations in shape dynamics and actin organization, and had reduced filopodial-mediated traction force. Although peak traction forces produced by filopodia of KO cones were decreased significantly, KO filopodia occasionally developed forces equivalent to those in the wild type. This indicates that other myosins participate in filopodial-dependent traction force. Therefore, myosin IIB is necessary for normal growth cone spreading and the modulation of shape and traction force but acts in combination with other myosins for some or all of these activities. These activities are essential for growth cone forward advancement, which is necessary for outgrowth. Thus outgrowth is slowed, but not eliminated, in neurons from the myosin IIB KO mice. C1 Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Bridgman, PC (reprint author), Washington Univ, Sch Med, Dept Anat & Neurobiol, Box 8108, St Louis, MO 63110 USA. OI Adelstein, Robert/0000-0002-8683-2144 FU NINDS NIH HHS [NS26150] NR 42 TC 145 Z9 147 U1 2 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 2001 VL 21 IS 16 BP 6159 EP 6169 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 460PR UT WOS:000170318200037 PM 11487639 ER PT J AU Farinas, I Jones, KR Tessarollo, L Vigers, AJ Huang, E Kirstein, M de Caprona, DC Coppola, V Backus, C Reichardt, LF Fritzsch, B AF Farinas, I Jones, KR Tessarollo, L Vigers, AJ Huang, E Kirstein, M de Caprona, DC Coppola, V Backus, C Reichardt, LF Fritzsch, B TI Spatial shaping of cochlear innervation by temporally regulated neurotrophin expression SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neurotrophins; ear innervation; development of ear innervation; ear and neurotrophin expression; NT-3; sensory neuron survival ID DEVELOPING INNER-EAR; SENSORY NEURONS; MUTANT MICE; TARGET INNERVATION; NT-3 ACTIVATION; TRK RECEPTORS; MESSENGER-RNA; IN-VIVO; GANGLIA; BDNF AB Previous work suggested qualitatively different effects of neurotrophin 3 (NT-3) in cochlear innervation patterning in different null mutants. We now show that all NT-3 null mutants have a similar phenotype and lose all neurons in the basal turn of the cochlea. To understand these longitudinal deficits in neurotrophin mutants, we have compared the development of the deficit in the NT-3 mutant to the spatial-temporal expression patterns of brain-derived neurotrophic factor (BDNF) and NT-3, using lacZ reporters in each gene and with expression of the specific neurotrophin receptors, trkB and trkC. In the NT-3 mutant, almost normal numbers of spiral ganglion neurons form, but fiber outgrowth to the basal turn is eliminated by embryonic day (E) 13.5. Most neurons are lost between E13.5 and E15.5. During the period preceding apoptosis, NT-3 is expressed in supporting cells, whereas BDNF is expressed mainly in hair cells, which become postmitotic in an apical to basal temporal gradient. During the period of neuronal loss, BDNF is absent from the basal cochlea, accounting for the complete loss of basal turn neurons in the NT-3 mutant. The spatial gradients of neuronal loss in these two mutants appear attributable to spatial-temporal gradients of neurotrophin expression. Our immunocytochemical data show equal expression of their receptors, TrkB and TrkC, in spiral sensory neurons and thus do not relate to the basal turn loss. Mice in which NT-3 was replaced by BDNF show a qualitative normal pattern of innervation at E13.5. This suggests that the pattern of expression of neurotrophins rather than their receptors is essential for the spatial loss of spiral sensory neurons in NT-3 null mutants. C1 Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. Univ Calif San Francisco, Dept Physiol, Program Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Howard Hughes Med Inst, San Francisco, CA 94143 USA. Univ Valencia, Dept Biol Celular, E-46100 Burjassot, Spain. Univ Colorado, Dept Biol, Boulder, CO 80309 USA. Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Fritzsch, B (reprint author), Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. RI Coppola, Vincenzo/E-2917-2011; Farinas, Isabel/L-7118-2014; Kirstein, Martina/L-9247-2014; OI Coppola, Vincenzo/0000-0001-6163-1779; Farinas, Isabel/0000-0003-2903-4960; Kirstein, Martina/0000-0001-8716-2309; Fritzsch, Bernd/0000-0002-4882-8398 FU NIDCD NIH HHS [P 50 DC 00215]; NIMH NIH HHS [P50 MH048200-100005]; NINDS NIH HHS [KO1 NS01872]; PHS HHS [48200] NR 48 TC 196 Z9 198 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 AUG 15 PY 2001 VL 21 IS 16 BP 6170 EP 6180 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 460PR UT WOS:000170318200038 PM 11487640 ER PT J AU Chen, JJ Li, ZS Pan, H Murphy, DL Tamir, H Koepsell, H Gershon, MD AF Chen, JJ Li, ZS Pan, H Murphy, DL Tamir, H Koepsell, H Gershon, MD TI Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: Abnormal intestinal motility and the expression of cation transporters SO JOURNAL OF NEUROSCIENCE LA English DT Article DE serotonin reuptake transporter; enteric nervous system; gastrointestinal motility; organic cation transporters; dopamine transporter; SERT knock-out mice ID DELAYED-TYPE HYPERSENSITIVITY; ENTERIC NERVOUS-SYSTEM; GUINEA-PIG ILEUM; VASCULARLY PERFUSED ILEUM; IRRITABLE-BOWEL-SYNDROME; TRYPTOPHAN-HYDROXYLASE; MYENTERIC PLEXUS; GASTROINTESTINAL-TRACT; DOPAMINE-TRANSPORTER; 5-HYDROXYTRYPTAMINE-LIKE IMMUNOREACTIVITY AB The enteric serotonin reuptake transporter (SERT) has been proposed to play a critical role in serotonergic neurotransmission and in the initiation of peristaltic and secretory reflexes. We analyzed potential compensatory mechanisms and enteric function in the bowels of mice with a targeted deletion of SERT. The guts of these animals were found to lack mRNA encoding SERT; moreover, high-affinity uptake of 5-HT into epithelial cells, mast cells, and enteric neurons was present in the SERT +/+ bowel but absent in the SERT -/- bowel. However, both the SERT +/+ gut and the -/- gut expressed molecules capable of transporting 5-HT, but with affinities and selectivity much lower than those of SERT. These included the dopamine transporter (DAT) and polyspecific organic cation transporters OCT-1 and OCT-3. DAT and OCT immunoreactivities were present in both the submucosal and myenteric plexuses, and the OCTs were also located in the mucosal epithelium. 5-HT was found in all of its normal sites in the SERT -/- bowel, which contained mRNA encoding tryptophan hydroxylase, but no 5-HT was present in the blood of SERT -/- animals. Stool water and colon motility were increased in most SERT -/- animals; however, the increase in motility (diarrhea) occasionally alternated irregularly with decreased motility (constipation). The watery diarrhea is probably attributable to the potentiation of serotonergic signaling in SERT -/- mice, whereas the transient constipation may be caused by episodes of enhanced 5-HT release leading to 5-HT receptor desensitization. C1 Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY 10032 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Wurzburg, Inst Anat, D-97070 Wurzburg, Germany. RP Gershon, MD (reprint author), Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, 630 W 168th St, New York, NY 10032 USA. FU NINDS NIH HHS [NS12969] NR 97 TC 239 Z9 253 U1 0 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 2001 VL 21 IS 16 BP 6348 EP 6361 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 460PR UT WOS:000170318200056 PM 11487658 ER PT J AU Knutson, B Adams, CM Fong, GW Hommer, D AF Knutson, B Adams, CM Fong, GW Hommer, D TI Anticipation of increasing monetary reward selectively recruits nucleus accumbens SO JOURNAL OF NEUROSCIENCE LA English DT Article DE nucleus accumbens; caudate; reward; anticipation; FMRI; human ID BRAIN ACTIVITY; HUMAN AMYGDALA; BASAL GANGLIA; DOPAMINE; FMRI; ACTIVATION; MONKEY; VISUALIZATION; RESPONSES; STRIATUM AB Comparative studies have implicated the nucleus accumbens (NAcc) in the anticipation of incentives, but the relative responsiveness of this neural substrate during anticipation of rewards versus punishments remains unclear. Using event-related functional magnetic resonance imaging, we investigated whether the anticipation of increasing monetary rewards and punishments would increase NAcc blood oxygen level-dependent contrast (hereafter, "activation") in eight healthy volunteers. Whereas anticipation of increasing rewards elicited both increasing self-reported happiness and NAcc activation, anticipation of increasing punishment elicited neither. However, anticipation of both rewards and punishments activated a different striatal region (the medial caudate). At the highest reward level ($5.00), NAcc activation was correlated with individual differences in self-reported happiness elicited by the reward cues. These findings suggest that whereas other striatal areas may code for expected incentive magnitude, a region in the NAcc codes for expected positive incentive value. C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Knutson, B (reprint author), NIAAA, NIH, Bldg 10,Room 6S240,MS 1610, Bethesda, MD 20892 USA. NR 30 TC 264 Z9 265 U1 5 U2 46 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD AUG 15 PY 2001 VL 21 IS 16 BP art. no. EP RC159 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 460PR UT WOS:000170318200001 ER PT J AU Gerhardt, GA Hoffman, AF AF Gerhardt, GA Hoffman, AF TI Effects of recording media composition on the responses of Nafion-coated carbon fiber microelectrodes measured using high-speed chronoamperometry SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article; Proceedings Paper CT Symposium on Sensors for Brain Mapping CY JUN 06-08, 2000 CL LUND, SWEDEN SP Swedish Med Res Council, Swedish Council Engn Sci, Swedish Nat Sci Res Council, Swedish Natl Board Ind & Tech Dev, CMA Microdialysis AB, Pfizer Inc, Boehringer Ingelheim KG, Univ Lund, Wallenberg Neurosci Ctr, Karolinska Inst DE dopamine; serotonin; norepinephrine; nafion-coated microelectrodes; chronoamperometry ID APPLIED UPTAKE INHIBITORS; SCAN CYCLIC VOLTAMMETRY; VENTRAL TEGMENTAL AREA; SUBSTANTIA-NIGRA; RAT STRIATUM; ELECTROCHEMICAL MEASUREMENTS; CALIBRATION FACTORS; DOPAMINE CLEARANCE; NUCLEUS-ACCUMBENS; RELEASE AB The present study concerns methodological issues of electrochemical recordings using Nafion-coated 30 mum diameter single carbon fiber microelectrodes for high-speed chronoamperometric measurements of biogenic amines. First, the single carbon fiber microelectrodes were coated with Nafion and dried at 85 vs. 200 degreesC and their recording properties were determined. Second, the effects of shifts in solution pH, ionic strength, changes in recording solution levels of Ca2+ or Mg2+ and temperature on the recording characteristics and sensitivity of Nafion-coated high temperature dried (200 degreesC) single carbon fiber microelectrodes for measures of dopamine were studied. These studies showed that the high temperature drying of the Nafion produced a microelectrode with better recording properties: higher selectivity for cations versus anions, increased differences between the reduction and oxidation current ratios for the identification of dopamine versus serotonin, and more rapid response times. In addition, these studies demonstrated that the chronoamperometric recordings were insensitive to small changes in pH and divalent cations such as Ca2+ or Mg2+. However, increases in ionic strength decreased the sensitivity of the microelectrodes, while increases in temperature produced increases in the sensitivity of the microelectrodes for biogenic amines. These data support that Nafion-coated high temperature (200 degreesC) dried microelectrodes have enhanced recording properties as compared to microelectrodes, which are coated with Nafion and dried at 85 degreesC. In addition, high-speed chronoamperometric. recordings of biogenic. amines are not affected by solution changes in divalent cations (Ca2+ or Mg2+). (C) 2001 Elsevier Science B.V. All rights reserved. C1 Univ Kentucky, Dept Anat & Neurobiol, Chandler Med Ctr, Lexington, KY 40536 USA. Univ Kentucky, Morris K Udall Parkinsons Dis Res Ctr Excellence, Chandler Med Ctr, Lexington, KY 40536 USA. NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD USA. RP Gerhardt, GA (reprint author), Univ Kentucky, Dept Anat & Neurobiol, Chandler Med Ctr, 800 Rose St,306 Davis Mills Bldg, Lexington, KY 40536 USA. RI Hoffman, Alexander/H-3035-2012 OI Hoffman, Alexander/0000-0002-2676-0628 FU NIA NIH HHS [AG06434]; NIMH NIH HHS [MH 01245]; NINDS NIH HHS [NS39787] NR 29 TC 60 Z9 60 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD AUG 15 PY 2001 VL 109 IS 1 BP 13 EP 21 DI 10.1016/S0165-0270(01)00396-X PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 475YM UT WOS:000171197700003 PM 11489295 ER PT J AU Sanchez-Pernaute, R Studer, L Bankiewicz, KS Major, EO McKay, RDG AF Sanchez-Pernaute, R Studer, L Bankiewicz, KS Major, EO McKay, RDG TI In vitro generation and transplantation of precursor-derived human dopamine neurons SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE Parkinson disease; 6-hydroxydopamine; stem cells; neural transplantation; dopamine; human ID EXPANDED MESENCEPHALIC PRECURSORS; MICROTUBULE-ASSOCIATED PROTEIN; NEURAL PROGENITOR CELLS; CENTRAL-NERVOUS-SYSTEM; OLFACTORY-BULB; STEM-CELLS; RAT-BRAIN; DIFFERENTIATION; FETAL; CALRETININ AB The use of in vitro expanded human CNS precursors has the potential to overcome some of the ethical, logistic and technical problems of fetal tissue transplantation in Parkinson disease. Cultured rat mesencephalic precursors proliferate in response to bFGF and upon mitogen withdrawal, differentiate into functional dopamine neurons that alleviate motor symptoms in Parkinsonian rats (Studer et al. [1998] Nat. Neurosci. 1:290-295). The successful clinical application of CNS precursor technology in Parkinson disease will depend on the efficient in vitro generation of human dopaminergic neurons. We demonstrate that human dopamine neurons can be generated from both midbrain and cortical precursors. Transplantation of midbrain precursor-derived dopamine neurons into Parkinsonian rats resulted in grafts rich in tyrosine hydroxylase positive neurons 6 weeks after transplantation. No surviving tyrosine hydroxylase positive neurons could be detected when dopamine neurons derived from cortical precursors were grafted. Our data demonstrate in vitro derivation of human dopamine neurons from expanded CNS precursors and encourage further studies that systematically address in vivo function and clinical potential. (C) 2001 Wiley-Liss, Inc. C1 Lab Stem Cell & Tumor Biol Neurosurg & Cellular B, New York, NY USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD USA. NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Studer, L (reprint author), Mem Sloan Kettering Canc Ctr, Lab Stem Cell & Tumor Biol, 1275 York Ave,Box 256, New York, NY 10021 USA. EM studerl@mskcc.org NR 27 TC 100 Z9 105 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD AUG 15 PY 2001 VL 65 IS 4 BP 284 EP 288 DI 10.1002/jnr.1152 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 459EF UT WOS:000170237500002 PM 11494363 ER PT J AU Pastwa, E Neumann, RD Winters, TA AF Pastwa, E Neumann, RD Winters, TA TI In vitro repair of complex unligatable oxidatively induced DNA double-strand breaks by human cell extracts SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; IONIZING-RADIATION; MAMMALIAN-CELLS; PROTEIN-KINASE; BLEOMYCIN; DAMAGE; IDENTIFICATION; ENDS; ELECTROPHORESIS; RECOMBINATION AB We describe a new assay for in vitro repair of oxidatively induced DNA double-strand breaks (DSBs) by HeLa cell nuclear extracts. The assay employs linear plasmid DNA containing DNA DSBs produced by the radiomimetic drug bleomycin. The bleomycin-induced DSB possesses a complex structure similar to that produced by oxidative processes and ionizing radiation. Bleomycin DSBs are composed of blunt ends or ends containing a single 5'-base overhang. Regardless of the 5'-end structure, all bleomycin-induced DSBs possess 3'-ends blocked by phosphoglycolate. Cellular extraction and initial end joining conditions for our assay were optimized with restriction enzyme-cleaved DNA to maximize ligation activity. Parameters affecting ligation such as temperature, time, ionic strength, ATP utilization and extract protein concentration were examined. Similar reactions were performed with the bleomycin-linearized substrate. In all cases, end-joined molecules ranging from dimers to higher molecular weight forms were produced and observed directly in agarose gels stained with Vistra. Green and imaged with a Fluorlmager 595. This detection method is at least 50-fold more sensitive than ethidium bromide and permits detection of less than or equal to0.25 ng double-stranded DNA per band in post-electrophoretically stained agarose gels. Consequently, our end-joining reaction requires less than or equal to 100 ng substrate DNA and greater than or equal to 50% conversion of substrate to product is achieved with simple substrates such as restriction enzyme-cleaved DNA. Using our assay we have observed a 6-fold lower repair rate and a lag in reaction initiation for bleomycin-Induced DSBs as compared to blunt-ended DNA. Also, end joining reaction conditions are DSB end group dependent. In particular, bleomycin-induced DSB repair, is considerably more sensitive to inhibition by increased ionic strength than repair of blunt-ended DNA. C1 NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Med Univ Lodz, Inst Physiol & Biochem, Dept Gen Chem, Lodz, Poland. RP Winters, TA (reprint author), NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 40 TC 22 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD AUG 15 PY 2001 VL 29 IS 16 BP art. no. EP e78 DI 10.1093/nar/29.16.e78 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 466BD UT WOS:000170623700025 PM 11504886 ER PT J AU Sasahara, K Sakurai, M Nitta, K AF Sasahara, K Sakurai, M Nitta, K TI Pressure effect on denaturant-induced unfolding of hen egg white lysozyme SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE protein unfolding; intermediate state; hydrostatic pressure; cooperativity; stability ID STREPTOMYCES SUBTILISIN INHIBITOR; X-RAY-SCATTERING; MOLTEN-GLOBULE; ALPHA-LACTALBUMIN; FOLDING INTERMEDIATE; HYDROSTATIC-PRESSURE; GUANIDINIUM CHLORIDE; COLD DENATURATION; PROTEIN-STRUCTURE; RIBONUCLEASE-A AB The influence of hydrostatic pressure (less than or equal to 100 MPa) on denaturant-induced unfolding of hen egg white lysozyme was investigated by means of ultraviolet spectroscopy at various temperatures. Assuming a two-state transition model, the dependence of Gibbs free-energy change of unfolding on the denaturant concentration was calculated. Under applied hydrostatic pressure, these data were interpreted as suggesting that a two-state model is not applicable in a restricted temperature range; the dominant effect of hydrostatic pressure is to affect the cooperativity in protein unfolding due to a chemical equilibrium shift in the direction of the reduction in the system volume. The deviation from the two-state transition model appears to be rationalized by assuming that applied pressure induces an intermediate conformation between the native and unfolded states of the protein. The implication of the thermodynamic stability of protein under pressure was discussed. (C) 2001 Wiley-Liss, Inc. C1 Hokkaido Univ, Grad Sch Sci, Div Biol Sci, Sapporo, Hokkaido, Japan. Sci Univ Tokyo Oshamambe, Fac Ind Sci & Technol, Oshamambe, Hokkaido, Japan. RP Sasahara, K (reprint author), NIH, Bldg 8,Room 222, Bethesda, MD 20892 USA. NR 64 TC 17 Z9 18 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD AUG 15 PY 2001 VL 44 IS 3 BP 180 EP 187 DI 10.1002/prot.1083 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 457DH UT WOS:000170121500002 PM 11455591 ER PT J AU Tcherkasskaya, O Uversky, VN AF Tcherkasskaya, O Uversky, VN TI Denatured collapsed states in protein folding: Example of apomyoglobin SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE apomyoglobin; fluorescence energy transfer; denatured collapsed state; molten globule state; protein folding ID MOLTEN GLOBULE STATE; X-RAY-SCATTERING; SPERM WHALE APOMYOGLOBIN; PARTIALLY FOLDED STATES; HUMAN PROTHYMOSIN-ALPHA; CARBONIC-ANHYDRASE-B; CONFORMATIONAL STATES; GUANIDINIUM CHLORIDE; ESCHERICHIA-COLI; STRUCTURAL CHARACTERIZATION AB Experimental approaches, including circular dichroism, small angle X-ray scattering, steady-state fluorescence, and fluorescence energy transfer, were applied to study the 3D-structure of apomyolgobin in different conformational states. These included the native and molten globules, along with either less ordered conformations induced by the addition of anions or completely unfolded states. The results show that the partially folded forms of apomyoglobin stabilized by KCl and/or Na2SO4 under unfolding conditions (pH 2) exhibit a significant amount of secondary structure (circular dichroism), low packing density of protein molecules (SAXS), and native-like dimensions of the AGH core (fluorescence energy transfer). This finding indicates that a native-like tertiary fold of the polypeptide chain, i.e., the spatial organization of secondary structure elements, most likely emerges prior to the formation of the molten globule state. (C) 2001 Wiley-Liss, Inc.* C1 NIH, Lab Expt & Computat Biol, NCI, Bethesda, MD 20892 USA. Univ Calif Santa Cruz, Dept Chem & Biochem, Santa Cruz, CA 95064 USA. RAS, Inst Biol Instrumentat, Pushchino, Moscow Region, Russia. RP Tcherkasskaya, O (reprint author), NIH, Lab Expt & Computat Biol, NCI, Bldg 10, Bethesda, MD 20892 USA. RI Uversky, Vladimir/F-4515-2011 OI Uversky, Vladimir/0000-0002-4037-5857 NR 89 TC 67 Z9 67 U1 0 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD AUG 15 PY 2001 VL 44 IS 3 BP 244 EP 254 DI 10.1002/prot.1089 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 457DH UT WOS:000170121500008 PM 11455597 ER PT J AU Wiethoff, AJ Harkema, JR Koretsky, AP Brown, WE AF Wiethoff, AJ Harkema, JR Koretsky, AP Brown, WE TI Identification of mucosal injury in the murine nasal airways by magnetic resonance imaging: Site-specific lesions induced by 3-methylindole SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE MRI; nasal airways; 3-methylindole ID MICE; DAMAGE; TOOL AB A magnetic resonance imaging (MRI) technique was developed to identify mucosal damage to the nasal passages of mice resulting from exposure to respiratory toxicants. 3-Methylindole (3-MI) was chosen as a model nasal toxicant because systemic administration of this compound in mice results in a well-characterized necrotizing nasal lesion that is restricted to the olfactory mucosa. MRI technology allows imaging of the same mice before and at time points after injection. In addition, morphological alterations and increases in the area of sinus cavity airspace can be followed as a function of dose and time following exposure. For 3-MI, the cross-sectional area of the sinus airspaces increased by 1.7-fold in mice injected with 200 mg/kg and 2.6-fold in mice injected with 300 mg/kg at 3 days after injection. Alterations in the nasal turbinates lined by olfactory mucosa were identified 1, 3, and 6 days postadministration of 3-MI using MR1. Postmortem histological examination of the nasal tissue confirmed the intranasal location and distribution of the 3-MI-induced lesions observed by MRI. MRI can be a useful technique to identify toxicant-induced mucosal injury in the nasal passages at an in-plane resolution less than 60 mum. (C) 2001 Academic Press. C1 Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. Michigan State Univ, Coll Vet Med, Dept Pathol, E Lansing, MI 48824 USA. NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA. RP Brown, WE (reprint author), Carnegie Mellon Univ, Dept Biol Sci, 4400 5th Ave, Pittsburgh, PA 15213 USA. RI Koretsky, Alan/C-7940-2015 OI Koretsky, Alan/0000-0002-8085-4756 FU NCRR NIH HHS [P41RR-03631] NR 15 TC 11 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD AUG 15 PY 2001 VL 175 IS 1 BP 68 EP 75 DI 10.1006/taap.2001.9235 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 466EJ UT WOS:000170631300008 PM 11509028 ER PT J AU Kirk, AD Tadaki, DK Celniker, A Batty, DS Berning, JD Colonna, JO Cruzata, F Elster, EA Gray, GS Kampen, RL Patterson, NB Szklut, P Swanson, J Xu, H Harlan, DM AF Kirk, AD Tadaki, DK Celniker, A Batty, DS Berning, JD Colonna, JO Cruzata, F Elster, EA Gray, GS Kampen, RL Patterson, NB Szklut, P Swanson, J Xu, H Harlan, DM TI Induction therapy with monoclonal antibodies specific for CD80 and CD86 delays the onset of acute renal allograft rejection in non-human primates SO TRANSPLANTATION LA English DT Article ID TRANSPLANTATION TOLERANCE; GRAFT-SURVIVAL; CTLA4IG; DONOR; CD28; B7-1; COSTIMULATION; EXPRESSION; RECIPIENT; MODEL AB CD80 and CD86 (also known as B7-1 and B7-2, respectively) are both ligands for the T cell costimulatory receptors CD28 and CD152. Both CD80 and CD86 mediate T cell costimulation, and as such, have been studied for their role in promoting allograft rejection. In this study we demonstrate that administering monoclonal antibodies specific for these B7 ligands can delay the onset of acute renal allograft rejection in rhesus monkeys. The most durable effect results from simultaneous administration of both anti-B7 antibodies. The mechanism of action does not involve global depletion of T or B cells. Despite in vitro and in vivo evidence demonstrating the effectiveness of the anti-B7 antibodies in suppressing T cell responsiveness to alloantigen, their use does not result in durable tolerance. Prolonged therapy with murine anti-B7 antibodies is limited by the development of neutralizing antibodies, but that problem was avoided when humanized anti-B7 reagents are used. Most animals develop rejection and an alloantibody response although still on antibody therapy and before the development of a neutralizing antibody response. Anti-B7 antibody therapy may have use as an adjunctive agent for clinical allotransplantation, but using the dosing regimens we used, is not a tolerizing therapy in this nonhuman primate model. C1 NIDDK, Navy Transplantat & Autoimmun Branch, Bethesda, MD 20889 USA. Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. Genet Inst Wyeth Ayerst, Cambridge, MA 02140 USA. RP Kirk, AD (reprint author), Room 11S-219,Bldg 10,Center Dr, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012 FU NIAID NIH HHS [AI43900-01] NR 24 TC 96 Z9 102 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 AUG 15 PY 2001 VL 72 IS 3 BP 377 EP 384 DI 10.1097/00007890-200108150-00005 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 465JZ UT WOS:000170587000005 PM 11502964 ER PT J AU Rajagopalan, S Shah, M Luciano, A Crystal, R Nabel, EG AF Rajagopalan, S Shah, M Luciano, A Crystal, R Nabel, EG TI Adenovirus-mediated gene transfer of VEGF(121) improves lower-extremity endothelial function and flow reserve SO CIRCULATION LA English DT Article DE gene therapy; angiogenesis; growth substances; endothelium; nitric oxide ID GROWTH-FACTOR; ANGIOGENESIS; HINDLIMB; ISCHEMIA; CELLS AB Background-Vascular endothelial growth factor (VEGF) currently is being evaluated in clinical angiogenesis trials involving patients with peripheral arterial disease. We hypothesized that delivery of VEGF to the skeletal muscle of the lower extremity using an adenoviral vector (Ad(GV)VEGF(121.10)) would improve peripheral endothelial function. Accordingly, we investigated lower-extremity endothelial function in patients enrolled in a Phase I adenovirus-mediated gene delivery trial of VEGF(121.10), Methods and Results-Blood flow to the index extremity was measured by thermodilution at baseline and 30 days after administration of Ad(GV)VEGF(121.10), in response to the infusion of endothelium-dependent and -independent agonists (acetylcholine and nitroglycerin, respectively) into the ipsilateral femoral artery. There was no difference in basal flow before or after treatment with Ad(GV)VEGF(121.10). In response to acetylcholine (150 mug/min and 300 mug/min), there was a 0.9-fold (0.33 +/- 0.03 to 0.32 +/- 0.03 L/min) and 1.2-fold (0.33 +/- 0.03 to 0.490 +/- 0.02 L/inin) change in flow before Ad(GV)/TGF(121.10) treatment. After Ad(GV)VEGF(121.10) treatment, flow increased 2.4-fold (0.310 +/- 0.04 to 0.730 +/- 0.10 L/min) and 2.3-fold (0.31 +/- 0.04 to 0.7 +/- 0.08 L/min), respectively (P <0.05 before Ad(GV)VEGF(121.10) treatment versus after Ad(GV)VEGF(121.10) for both doses). Infusion of nitroglycerin resulted in a 1.8-fold increase in flow before Ad(GV)VEGF(121.10) (0.33 +/- 0.03 to 0.58 +/- 0.06 L/min) compared with a 2.4-fold increase (0.31 +/- 0.04 to 0.73 +/- 0.09 L/min) after Ad(GV)VEGF(121.10) (P=NS before Ad(GV)VEGF(121.10) versus after Ad(GV)VEGF(121.10)). Lower-extremity flow reserve increased in all patients in response to at least I dose of acetylcholine. Peak walking times increased concomitant with improvement in endothelial function. Conclusions-Adenoviral gene transfer of VEGF(121.10) appears to modulate endothelial function and lower-extremity flow reserve in patients with peripheral arterial disease. C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. Cornell Univ, Weil Med Coll, Presbyterian Hosp, New York, NY USA. RP Rajagopalan, S (reprint author), L3119 Womens Hosp, Div Cardiol, Sect Vasc Med, 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. FU NCRR NIH HHS [M01-RR00042] NR 11 TC 96 Z9 100 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 AUG 14 PY 2001 VL 104 IS 7 BP 753 EP 755 DI 10.1161/hc3201.095192 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 463YX UT WOS:000170505800013 PM 11502697 ER PT J AU Litvan, I Phipps, M Pharr, VL Hallett, M Grafman, J Salazar, A AF Litvan, I Phipps, M Pharr, VL Hallett, M Grafman, J Salazar, A TI Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy SO NEUROLOGY LA English DT Article ID CROSSOVER CLINICAL-TRIAL; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; BASAL GANGLIA; DOUBLE-BLIND; DEMENTIA; NUCLEUS; RELIABILITY; THERAPY; SCALE AB Objective: There is no effective treatment for progressive supranuclear palsy (PSP). Because results of immunochemical and pharmacologic studies suggest that the cholinergic system may play a role in the cognitive and motor features of PSP, the authors investigated the effects of donepezil (10 mg/day), an acetylcholinesterase inhibitor, in 21 patients with PSP (mean age SD; 65.7 +/- 4.7 years) by a randomized, double-blind, placebo-controlled crossover trial. Methods: Donepezil and placebo were administered for 6 weeks each with a 1-month washout period. Patients were evaluated before and at the end of each treatment phase. Outcome measures evaluated neuropsychiatric, global cognitive, frontal, memory, motor, and activities of daily living (ADL) status. Results: Two patients withdrew during the washout phase because of unrelated medical problems. Donepezil-induced systemic side effects were transient and generally mild. Because of worsening of motor function, three patients received 5 mg/day of donepezil. All patients achieved blood and CSF therapeutic levels of donepezil. While the patients were taking donepezil, their Double Memory Test scores improved, whereas their ADL/mobility scores significantly worsened. Conclusion: The findings suggest that acetylcholinesterase inhibitors such as donepezil have at best selective, modest effects on cognition in patients with PSP. In light of its deleterious effects on ADL/mobility, donepezil is not recommended for this patient population. C1 Henry M Jackson Fdn, Cognit Neuropharmacol Unit, Bethesda, MD 20817 USA. Henry M Jackson Fdn, Def & Vet Head Injury Program, Bethesda, MD 20817 USA. NINDS, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Litvan, I (reprint author), Henry M Jackson Fdn, Cognit Neuropharmacol Unit, Champlain Bldg,6410 Rockledge Dr,Suite 600, Bethesda, MD 20817 USA. OI Phipps, Michael/0000-0001-8398-5404; Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 48 TC 67 Z9 67 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD AUG 14 PY 2001 VL 57 IS 3 BP 467 EP 473 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 462FR UT WOS:000170410500021 PM 11502915 ER PT J AU Ogasawara, Y Lacourciere, G Stadtman, TC AF Ogasawara, Y Lacourciere, G Stadtman, TC TI Formation of a selenium-substituted rhodanese by reaction with selenite and glutathione: Possible role of a protein perselenide in a selenium delivery system SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ESCHERICHIA-COLI; SELENOPHOSPHATE; BIOSYNTHESIS; ENZYME; SELENOCYSTEINE; METABOLISM; REDUCTASE; ACID AB Selenophosphate is the active selenium-donor compound required by bacteria and mammals for the specific synthesis of Secys-tRNA, the precursor of selenocysteine in selenoenzymes. Although free selenide can be used in vitro for the synthesis of selenophosphate, the actual physiological selenium substrate has not been identified. Rhodanese (EC 2.3.1.1) normally occurs as a persulfide of a critical cysteine residue and is believed to function as a sulfur-delivery protein. Also, it has been demonstrated that a selenium-substituted rhodanese (E-Se form) can exist in vitro. In this study, we have prepared and characterized an E-Se rhodanese. Persulfide-free bovine-liver rhodanese (E form) did not react with SeO32- directly, but in the presence of reduced glutathione (GSH) and SeO32- E-Se rhodanese was generated. These results indicate that the intermediates produced from the reaction of GSH with SeO32- are required for the formation of a selenium-substituted rhodanese. E-Se rhodanese was stable in the presence of excess GSH at neutral pH at 37 degreesC. E-Se rhodanese could effectively replace the high concentrations of selenide normally used in the selenophosphate synthetase in vitro assay in which the selenium-dependent hydrolysis of ATP is measured. These results show that a selenium-bound rhodanese could be used as the selenium donor in the in vitro selenophosphate synthetase assay. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Meiji Pharmaceut Univ, Dept Environm Biol, Tokyo 2048588, Japan. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2120,MSC 8012,50 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 52 Z9 57 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 AUG 14 PY 2001 VL 98 IS 17 BP 9494 EP 9498 DI 10.1073/pnas.171320998 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600009 PM 11493708 ER PT J AU Oubrahim, H Stadtman, ER Chock, PB AF Oubrahim, H Stadtman, ER Chock, PB TI Mitochondria play no roles in Mn(II)-induced apoptosis in HeLa cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MANGANESE-SUPEROXIDE-DISMUTASE; TUMOR NECROSIS FACTOR; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; ACRIDINE-ORANGE; LYMPHOMA-CELLS; PC12 CELLS; CARDIOLIPIN; ACTIVATION; MEMBRANE AB Manganese(II) has been shown to exhibit catalase-like activity under physiological conditions. In the course of studies to test the antioxidant activity of Mn(II) on HeLa cells, it was observed at high concentrations; (1-2 mM) that Mn(II) also induced apoptosis, as judged by changes in cell morphology, caspase-3 activation, cleavage of poly(ADP) ribose, and DNA condensation. However, in contrast to established mechanisms,the Mn(II)-induced apoptosis is associated with an increase rather than a decrease in mitochondrial inner-membrane potential, as monitored by the fluorescent probe tetra methyl rhodamine ethyl ester. Based on immunochemical analysis, Mn(II)-induced apoptosis does not lead to the release of cytochrome c into the cytosol. These and other measurements show that treatment with Mn(II) leads to enhancement of the mitochondrial "membrane mass," has no effect on mitochondrial volume, and does not affect the permeability transition pore. Together, these results support the view that Mn(II)-induced apoptosis occurs by a heretofore unrecognized mechanism. In addition, it was demonstrated that Mn(II) treatment leads to an increase in the production of reactive oxygen species (peroxides) and to the induction of the manganese superoxide dismutase and catalase activities but has no effect on the Cu,Zn-superoxide dismutase level. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2140,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. NR 34 TC 79 Z9 84 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 AUG 14 PY 2001 VL 98 IS 17 BP 9505 EP 9510 DI 10.1073/pnas.181319898 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600011 PM 11493712 ER PT J AU Zheng, L Annab, LA Afshari, CA Lee, WH Boyer, TG AF Zheng, L Annab, LA Afshari, CA Lee, WH Boyer, TG TI BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BREAST-CANCER; ANDROGEN-RECEPTOR; CELL-LINE; DNA-DAMAGE; EXPRESSION; TRANSACTIVATION; ACTIVATION; INDUCTION; COMPLEXES; MUTATIONS AB Mutational inactivation of BRCA1 confers a cumulative lifetime risk of breast and ovarian cancers. However, the underlying basis for the tissue-restricted tumor-suppressive properties of BRCA1 remains poorly defined. Here we show that BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor a (ER alpha), a principal determinant of the growth, differentiation, and normal functional status of breasts and ovaries. In Brca1-null mouse embryo fibroblasts and BRCA1-deficient human ovarian cancer cells, ER alpha exhibited ligand-independent transcriptional activity that was not observed in Brca1-proficient cells. Ectopic expression in Brca1-deficient cells of wild-type BRCA1, but not clinically validated BRCA1 missense mutants, restored ligand-independent repression of ER alpha in a manner dependent upon apparent histone deacetylase activity. In estrogen-dependent human breast cancer cells, chromatin immunoprecipitation analysis revealed the association of BRCA1 with ER alpha at endogenous estrogen-response elements before, but not after estrogen stimulation. Collectively, these results reveal BRCA1 to be a ligand-reversible barrier to transcriptional activation by unliganded promoter-bound ER alpha and suggest a possible mechanism by which functional inactivation of BRCA1 could promote tumorigenesis through inappropriate hormonal regulation of mammary and ovarian epithelial cell proliferation. C1 Univ Texas, Hlth Sci Ctr, Dept Mol Med, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Inst Biotechnol, San Antonio, TX 78245 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Lee, WH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Mol Med, 15355 Lambda Dr, San Antonio, TX 78245 USA. FU NCI NIH HHS [P01 CA030195, P01CA30195, P01 CA081020, P01CA81020] NR 34 TC 143 Z9 152 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 AUG 14 PY 2001 VL 98 IS 17 BP 9587 EP 9592 DI 10.1073/pnas.171174298 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600025 PM 11493692 ER PT J AU Nagashima, M Shiseki, M Miura, K Hagiwara, K Linke, SP Pedeux, R Wang, XW Yokota, J Riabowol, K Harris, CC AF Nagashima, M Shiseki, M Miura, K Hagiwara, K Linke, SP Pedeux, R Wang, XW Yokota, J Riabowol, K Harris, CC TI DNA damage-inducible gene p331NG2 negatively regulates cell proliferation through acetylation of p53 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE p33ING1; PHD-finger; apoptosis; cell cycle ID CANDIDATE TUMOR-SUPPRESSOR; WILD-TYPE P53; TRANSCRIPTIONAL REPRESSION; HEPATOCELLULAR-CARCINOMA; POTENTIAL MEDIATOR; HUMAN FIBROBLASTS; TERMINAL DOMAIN; PHOSPHORYLATION; APOPTOSIS; P33(ING1) AB The p33ING1 protein is a regulator of cell cycle, senescence, and apoptosis. Three alternatively spliced transcripts of p33ING1 encode p47ING1a, p33ING1b, and p24ING1c. We cloned an additional ING family member, p33ING2/ING1L. Unlike p33ING1b, p33ING2 is induced by the DNA-damaging agents etoposide and neocarzinostatin. p33ING1b and p33ING2 negatively regulate cell growth and survival in a p53-dependent manner through induction of Gi-phase cell-cycle arrest and apoptosis. p33ING2 strongly enhances the transcriptional-transactivation activity of p53. Furthermore, p33ING2 expression increases the acetylation of p53 at Lys-382. Taken together, p33ING2 is a DNA damage-inducible gene that negatively regulates cell proliferation through activation of p53 by enhancing its acetylation. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Calgary, Hlth Sci Ctr, Dept Biochem & Mol Biol, Calgary, AB T2N 1N4, Canada. Univ Calgary, Hlth Sci Ctr, Dept Oncol, Calgary, AB T2N 1N4, Canada. Natl Canc Ctr, Res Inst, Div Biol, Tokyo 1040045, Japan. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C05, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 57 TC 150 Z9 159 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 AUG 14 PY 2001 VL 98 IS 17 BP 9671 EP 9676 DI 10.1073/pnas.161151798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600039 PM 11481424 ER PT J AU Caplen, NJ Parrish, S Imani, F Fire, A Morgan, RA AF Caplen, NJ Parrish, S Imani, F Fire, A Morgan, RA TI Specific inhibition of gene expression by small double-stranded RNAs in invertebrate and vertebrate systems SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DEPENDENT PROTEIN-KINASE; MESSENGER-RNA; C-ELEGANS; DROSOPHILA CELLS; GERM-LINE; INTERFERENCE; POLYMERASE; DEGRADATION; TRANSGENE; ZEBRAFISH AB Short interfering RNAs (siRNAs) are double-stranded RNAs of approximate to 21-25 nucleotides that have been shown to function as key intermediaries in triggering sequence-specific RNA degradation during posttranscriptional gene silencing in plants and RNA interference in invertebrates. siRNAs have a characteristic structure, with 5'-phosphate/3'-hydroxyl ends and a 2-base 3' overhang on each strand of the duplex. In this study, we present data that synthetic siRNAs can induce gene-specific inhibition of expression in Caenorhabditis elegans and in cell lines from humans and mice. In each case, the interference by siRNAs was superior to the inhibition of gene expression mediated by single-stranded antisense oligonucleotides. The siRNAs seem to avoid the well documented nonspecific effects triggered by longer double-stranded RNAs in mammalian cells. These observations may open a path toward the use of siRNAs as a reverse genetic and therapeutic tool in mammalian cells. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Carnegie Inst Washington, Dept Embryol, Baltimore, MD 21210 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Asthma & Allergy Ctr, Div Clin Immunol,Dept Med, Baltimore, MD 21224 USA. Johns Hopkins Univ, Biol Grad Program, Baltimore, MD 21218 USA. RP Caplen, NJ (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,10C103, Bethesda, MD 20892 USA. RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 FU NIAID NIH HHS [FI AI446962]; NIGMS NIH HHS [AF R01-GM37706, R01 GM037706, T32-GM07321] NR 50 TC 744 Z9 837 U1 3 U2 24 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 AUG 14 PY 2001 VL 98 IS 17 BP 9742 EP 9747 DI 10.1073/pnas.171251798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600052 PM 11481446 ER PT J AU Cho, YS Kim, MK Cheadle, C Neary, C Becker, KG Cho-Chung, YS AF Cho, YS Kim, MK Cheadle, C Neary, C Becker, KG Cho-Chung, YS TI Antisense DNAs as multisite genomic modulators identified by DNA microarray SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROTEIN-KINASE-A; RI-ALPHA SUBUNIT; CYCLIC-AMP; EXPRESSION PATTERNS; OVARIAN-CANCER; BREAST-CANCER; CAMP; OLIGODEOXYNUCLEOTIDE; DIFFERENTIATION; GROWTH AB Antisense oligodeoxynucleotides can selectively block disease-causing genes, and cancer genes have been chosen as potential targets for antisense drugs to treat cancer. However, nonspecific side effects have clouded the true antisense mechanism of action and hampered clinical development of antisense therapeutics. Using DNA microarrays, we have conducted a systematic characterization of gene expression in cells exposed to antisense, either exogenously or endogenously. Here, we show that in a sequence-specific manner, antisense targeted to protein kinase A Ria alters expression of the clusters of coordinately expressed genes at a specific stage of cell growth, differentiation, and activation. The genes that define the proliferation-transformation signature are down-regulated, whereas those that define the differentiation-reverse transformation signature are up-regulated in antisense-treated cancer cells and tumors, but not in host livers, In this differentiation signature, the genes showing the highest induction include genes for the G proteins Rap1 and Cdc42. The expression signature induced by the exogenously supplied antisense oligodeoxynucleotide overlaps strikingly with that induced by endogenous antisense gene overexpression. Defining antisense DNAs on the basis of their effects on global gene expression can lead to identification of clinically relevant antisense therapeutics and can identify which molecular and cellular events might be important in complex biological processes, such as cell growth and differentiation. C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, NIH, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. OI Becker, Kevin/0000-0002-6794-6656 FU NCI NIH HHS [N02-BC-76212] NR 32 TC 69 Z9 72 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD AUG 14 PY 2001 VL 98 IS 17 BP 9819 EP 9823 DI 10.1073/pnas.171314398 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600065 PM 11481453 ER PT J AU Levine, M Wang, YH Padayatty, SJ Morrow, J AF Levine, M Wang, YH Padayatty, SJ Morrow, J TI A new recommended dietary allowance of vitamin C for healthy young women SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ASCORBIC-ACID; DEHYDROASCORBIC ACID; TRANSPORT; DEPLETION; PLASMA; F-2-ISOPROSTANES; QUANTIFICATION; ACCUMULATION; METABOLITE; VOLUNTEERS AB The recently released Recommended Dietary Allowance of vitamin C for women, 75 mg daily, was based on data for men. We now report results of a depletion-repletion study with healthy young women hospitalized for 186 +/- 28 days, using vitamin C doses of 30-2,500 mg daily. The relationship between dose and steady-state plasma concentration was sigmoidal. Only doses above 100 mg were beyond the linear portion of the curve. Plasma and circulating cells saturated at 400 mg daily, with urinary elimination of higher doses. Biomarkers of endogenous oxidant stress, plasma and urine F-2-isoprostanes, and urine levels of a major metabolite of F-2-isoprostanes were unchanged by vitamin C at all doses, suggesting this vitamin does not alter endogenous lipid peroxidation in healthy young women. By using Food and Nutrition Board guidelines, the data indicate that the Recommended Dietary Allowance for young women should be increased to 90 mg daily. C1 NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. RP Levine, M (reprint author), NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bldg 10,Room 4D52 MSC 1372, Bethesda, MD 20892 USA. RI Padayatty, Sebastian/A-8581-2012 OI Padayatty, Sebastian/0000-0001-8758-3170 FU NCI NIH HHS [CA77839, P01 CA077839]; NIDDK NIH HHS [P30 DK026657, DK48831, R01 DK048831, Z01 DK054506, DK26657]; NIGMS NIH HHS [P50 GM015431, GM15431, P01 GM015431] NR 30 TC 211 Z9 226 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 AUG 14 PY 2001 VL 98 IS 17 BP 9842 EP 9846 DI 10.1073/pnas.171318198 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600069 PM 11504949 ER PT J AU Kappe, SHI Gardner, MJ Brown, SM Ross, J Matuschewski, K Ribeiro, JM Adams, JH Quackenbush, J Cho, J Carucci, DJ Hoffman, SL Nussenzweig, V AF Kappe, SHI Gardner, MJ Brown, SM Ross, J Matuschewski, K Ribeiro, JM Adams, JH Quackenbush, J Cho, J Carucci, DJ Hoffman, SL Nussenzweig, V TI Exploring the transcriptome of the malaria sporozoite stage SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Plasmodium yoelii yoelii; expressed sequence tag ID PARASITE PLASMODIUM-FALCIPARUM; ERYTHROCYTE BINDING-PROTEINS; EXPRESSED SEQUENCE TAGS; TOXOPLASMA-GONDII; UNCONVENTIONAL MYOSINS; APICOMPLEXAN PARASITES; SHIKIMATE PATHWAY; GAMMA-INTERFERON; GLIDING MOTILITY; GENE-EXPRESSION AB Most studies of gene expression in Plasmodium have been concerned with asexual and/or sexual erythrocytic stages. Identification and cloning of genes expressed in the preerythrocytic stages lag far behind. We have constructed a high quality cDNA library of the Plasmodium sporozoite stage by using the rodent malaria parasite A yoelii, an important model for malaria vaccine development. The technical obstacles associated with limited amounts of RNA material were overcome by PCR-amplifying the transcriptome before cloning. Contamination with mosquito RNA was negligible. Generation of 1,972 expressed sequence tags (EST) resulted in a total of 1,547 unique sequences, allowing insight into sporozoite gene expression. The circumsporozoite protein (CS) and the sporozoite surface protein 2 (SSP2) are well represented in the data set. A BLASTX search with all tags of the nonredundant protein database gave only 161 unique significant matches (P(N) less than or equal to 10(-4)), whereas 1,386 of the unique sequences represented novel sporozoite-expressed genes. We identified ESTs for three proteins that may be involved in host cell invasion and documented their expression in sporozoites. These data should facilitate our understanding of the preerythrocytic Plasmodium life cycle stages and the development of preerythrocytic vaccines. C1 NYU, Sch Med, Dept Pathol, Kaplan Canc Ctr,Michael Heidelberger Div, New York, NY 10015 USA. Inst Genom Res, Rockville, MD 20850 USA. NYU, Med Ctr, New York, NY 10016 USA. NIAID, Med Entomol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Notre Dame, Dept Biol Sci, Notre Dame, IN 46556 USA. USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. Celera Genom, Rockville, MD 20850 USA. RP Kappe, SHI (reprint author), NYU, Sch Med, Dept Pathol, Kaplan Canc Ctr,Michael Heidelberger Div, New York, NY 10015 USA. RI Adams, John/G-1800-2015; OI Adams, John/0000-0003-3707-7979; Matuschewski, Kai/0000-0001-6147-8591; Ribeiro, Jose/0000-0002-9107-0818 FU NIAID NIH HHS [R01 AI033656, R01 AI033656-07, AI-47102, R01 AI047102] NR 48 TC 98 Z9 102 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 AUG 14 PY 2001 VL 98 IS 17 BP 9895 EP 9900 DI 10.1073/pnas.171185198 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600078 PM 11493695 ER PT J AU Itoh, Y Esaki, T Kaneshige, M Suzuki, H Cook, M Sokoloff, L Cheng, SY Nunez, J AF Itoh, Y Esaki, T Kaneshige, M Suzuki, H Cook, M Sokoloff, L Cheng, SY Nunez, J TI Brain glucose utilization in mice with a targeted mutation in the thyroid hormone alpha or beta receptor gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cerebral glucose utilization; 2-[C-14]deoxyglucose; cretinism; synapse ID DEVELOPING RAT-BRAIN; NERVOUS-SYSTEM; EXPRESSION; CELLS; ACID; TRANSCRIPTION; TEMPERATURE; REPRESSION; RESISTANCE; ISOFORM AB Brain glucose utilization is markedly depressed in adult rats made cretinous after birth. To ascertain which subtype of thyroid hormone (TH) receptors, TR alpha1 or TR beta, is involved in the regulation of glucose utilization during brain development, we used the 2-[C-14]deoxyglucose method in mice with a mutation in either their TR alpha or TR beta gene. A C insertion produced a frameshift mutation in their carboxyl terminus. These mutants lacked TH binding and transactivation activities and exhibited potent dominant negative activity. Glucose utilization in the homozygous TR beta PV mutant mice and their wild-type siblings was almost identical in 19 brain regions, whereas it was markedly reduced in all brain regions of the heterozygous TR alpha PV mice. These suggest that the all receptor mediates the TH effects in brain. Inasmuch as local cerebral glucose utilization is closely related to local synaptic activity, we also examined which thyroid hormone receptor is involved in the expression of synaptotagmin-related gene 1 (Srg1), a TH-positively regulated gene involved in the formation and function of synapses [Thompson, C. C. (1996) J. Neurosci. 16, 7832-7840]. Northern analysis showed that Srg1 expression was markedly reduced in the cerebellum of TR alpha (PV/+) mice but not TR beta (PV/PV) mice. These results show that the same receptor, TR alpha1, is involved in the regulation by TH of both glucose utilization and Srg1 expression. C1 NIMH, Cerebral Metab Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP NIMH, Cerebral Metab Lab, NIH, Bldg 36, Bethesda, MD 20892 USA. EM louis@shiloh.nimh.nih.gov NR 54 TC 55 Z9 56 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 AUG 14 PY 2001 VL 98 IS 17 BP 9913 EP 9918 DI 10.1073/pnas.171319498 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600081 PM 11481455 ER PT J AU Sun, DQ Samuelson, LC Yang, TX Huang, YN Paliege, A Saunders, T Briggs, J Schnermann, J AF Sun, DQ Samuelson, LC Yang, TX Huang, YN Paliege, A Saunders, T Briggs, J Schnermann, J TI Mediation of tubuloglomerular feedback by adenosine: Evidence from mice lacking adenosine 1 receptors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLOMERULAR-FILTRATION RATE; RABBIT AFFERENT ARTERIOLES; SMOOTH-MUSCLE CELLS; ANGIOTENSIN-II; RENAL MICROCIRCULATION; HENLE FLOW; PRESSURE; KIDNEY; INHIBITION; MECHANISM AB Adenosine is a determinant of metabolic control of organ function increasing oxygen supply through the A2 class of adenosine receptors and reducing oxygen demand through A1 adenosine receptors (A1AR). In the kidney, activation of A1AR in afferent glomerular arterioles has been suggested to contribute to tubuloglomerular feedback (TGF), the vasoconstriction elicited by elevations in [NaCl] in the macula densa region of the nephron. To further elucidate the role of A1AR in TGF, we have generated mice in which the entire A1AR coding sequence was deleted by homologous recombination. Homozygous A1AR mutants that do not express A1AR mRNA transcripts and do not respond to A1AR agonists are viable and without gross anatomical abnormalities. Plasma and urinary electrolytes were not different between genotypes. Likewise, arterial blood pressure, heart rates, and glomerular filtration rates were indistinguishable between A1AR(+/+), A1AR(+/-), and A1AR(-/-) mice. TGF responses to an increase in loop of Henle flow rate from 0 to 30 nl/min, whether determined as change of stop flow pressure or early proximal flow rate, were completely abolished in A1AR(-/-) mice (stop flow pressure response, -6.8 +/- 0.55 mmHg and -0.4 +/- 0.2 in A1AR(+/+) and A1AR(-/-) mice; early proximal flow rate response, -3.4 +/- 0.4 nl/min and +0.02 +/- 0.3 nl/min in A1AR(+/+) and A1AR(-/-) mice). Absence of TGF responses in A1AR-deficient mice suggests that adenosine is a required constituent of the juxtaglomerular signaling pathway. A1AR null mutant mice are a promising tool to study the functional role of A1AR in different target tissues. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Physiol, Ann Arbor, MI 48109 USA. RP Schnermann, J (reprint author), NIDDKD, NIH, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [DK 37448] NR 39 TC 290 Z9 293 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 AUG 14 PY 2001 VL 98 IS 17 BP 9983 EP 9988 DI 10.1073/pnas.171317998 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 464NX UT WOS:000170539600093 PM 11504952 ER PT J AU Erlinger, TP Guallar, E Miller, ER Stolzenberg-Solomon, R Appel, LJ AF Erlinger, TP Guallar, E Miller, ER Stolzenberg-Solomon, R Appel, LJ TI Relationship between systemic markers of inflammation and serum beta-carotene levels SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; ACUTE-PHASE RESPONSE; C-REACTIVE PROTEIN; KILLER-CELL ACTIVITY; MIDDLE-AGED ADULTS; ALPHA-TOCOPHEROL; CARDIOVASCULAR-DISEASE; MALE SMOKERS; LUNG-CANCER; PLASMA-CONCENTRATIONS AB Background: Low serum levels of beta -carotene have been associated with increased risk of cancer and cardiovascular disease. However, in clinical trials, supplementation of the diet with beta -carotene either had no benefit or caused harm. This pattern of findings raises the possibility that confounding by other factors might explain the association between serum beta -carotene level and disease risk. Methods: We used data from 14470 current smokers, ex-smokers, and never smokers aged 18 years or older who participated in the Third National Health and Nutrition Examination Survey to assess the relationship between serum beta -carotene and markers of inflammation (C-reactive protein and white blood cell count). Results: After adjustment for beta -carotene intake and other factors, geometric mean levels of serum beta -carotene for individuals with undetectable (<0.22 mg/dL), mildly elevated (0.22-0.99 mg/dQ, and clinically elevated (greater than or equal to1.0 mg/dQ C-reactive protein levels were 18.0, 16.1, and 13.6 mug/dL, respectively, in never smokers; 18.1, 15.7, and 13.9 mug/dL in ex-smokers; and 11.3, 10.2, and 9.4 mug/dL in current smokers (P < .001 for all). In corresponding analyses, white blood cell count was also inversely related to serum beta -carotene concentration (P < .05 for all). Conclusions: The strong and inverse association of serum beta -carotene level with C-reactive protein level and white blood cell count suggests that the relationship between serum beta -carotene concentration and disease risk might be confounded by inflammation. More broadly, for beta -carotene and likely other nutrients, it seems unwise to interpret biomarker data as prima facie evidence of dietary intake without a more complete understanding of the physiologic processes that affect nutrient levels. C1 Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Erlinger, TP (reprint author), Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA. EM terlinge@jhmi.edu RI Guallar, Eliseo/D-3807-2014 OI Guallar, Eliseo/0000-0002-4471-9565 FU BHP HRSA HHS [T32PE10025] NR 42 TC 58 Z9 59 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD AUG 13 PY 2001 VL 161 IS 15 BP 1903 EP 1908 DI 10.1001/archinte.161.15.1903 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 459DZ UT WOS:000170236900015 PM 11493133 ER PT J AU Park, G Shao, J Lu, FH Rogers, RD Chasteen, ND Brechbiel, MW Planalp, RP AF Park, G Shao, J Lu, FH Rogers, RD Chasteen, ND Brechbiel, MW Planalp, RP TI Copper(II) complexes of novel N-alkylated derivatives of cis,cis-1,3,5-triaminocyclohexane. 1. Preparation and structure SO INORGANIC CHEMISTRY LA English DT Article ID PHOSPHATE DIESTER HYDROLYSIS; ELECTRONIC-PROPERTIES; MOLECULAR-STRUCTURE; CRYSTAL-STRUCTURE; LIGAND; REACTIVITY; CATALYSTS; ION AB Novel N,N',N " -trialkylated derivatives of cis, cis-1,3,5-triaminocyclohexane (tach), designated tach-R-3, were prepared through alkylation of N-protected tach with subsequent acid deprotection, to afford N-methyl, N-ethyl, and N-n-propyl derivatives as their trihydrobromide salts. The tach-neopentyl(3) and tach-furan(3) derivatives were prepared by formation of the imine from tach and pivaldehyde or furan-2-carboxaldehyde, respectively, followed by reduction of the imine, Complexes [Cu(tach-R-3)Cl-2] (R = Me, Et, n-Pr, CH2-2-thienyl, and CH2-2-furanyl) were prepared from CuCl2 in MeOH or MeOH-Et2O solvent. Crystallographic characterization of [Cu(tach-Et-3)Br0.8Cl1.2] (Pnma, a = 8.2265(1) Angstrom, b = 12.5313(1) Angstrom, c = 15.3587(3) Angstrom, Z = 4) reveals a square-based pyramidal CuN3X2 coordination sphere in which one nitrogen donor occupies the apical position at a slightly longer distance (Cu-N = 2.218(5) Angstrom) than those of the basal nitrogens (Cu-N = 2.053(2) Angstrom). The solution phase (pH 7.4 buffered and methanol) and solid-phase structures of [Cu(tach-R-3)Cl-2] have been studied extensively by EPR and visible-near-IR spectroscopies. The square-based pyramidal structure is retained in solution, according to correspondence of solution and solid-state data. In aqueous solution, halide is replaced by water, as indicated by the, high-energy UV-vis spectral shifts and bonding parameters of [Cu(tach-Et-3)](2+)(aq) derived from EPR data. The proposed aqueous-phase species, in the pH range 7.4 to 10.1, is [Cu(tach-Et-3)(H2O)(2)](2+). The complex [Cu(tach-Me-3)](2+)-(aq) does not appear to dimerize or form metal-hydroxo species at pH 7.4, in contrast to other Cu(Il)-triamine complexes, e.g., [Cu(1,4,7-triazacyclononane)](2+) (aq) and [Cu(tach-H-3)](2+)(aq) (the complex of unalkylated tach). This difference is attributed to the steric effect of the N-alkyl groups in the tach-R-3 series. C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. Univ Alabama, Tuscaloosa, AL 35487 USA. NIH, Radiat Oncol Branch, Chem Sect, Bethesda, MD 20892 USA. RP Planalp, RP (reprint author), Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 FU NIGMS NIH HHS [R37 GM20194] NR 45 TC 15 Z9 15 U1 3 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD AUG 13 PY 2001 VL 40 IS 17 BP 4167 EP 4175 DI 10.1021/ic000829e PG 9 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 461UJ UT WOS:000170381600010 PM 11487319 ER PT J AU Deal, KA Park, G Shao, J Chasteen, ND Brechbiel, MW Planalp, RP AF Deal, KA Park, G Shao, J Chasteen, ND Brechbiel, MW Planalp, RP TI Copper(II) complexes of novel N-alkylated derivatives of cis,cis-1,3,5-triaminocyclohexane. 2. Metal-promoted phosphate diester hydrolysis SO INORGANIC CHEMISTRY LA English DT Article ID DINUCLEAR COBALT(III) COMPLEX; PHOSPHODIESTER HYDROLYSIS; MOLECULAR-STRUCTURE; REACTIVITY; ION; DNA; CLEAVAGE; CRYSTAL; ENZYMES; PYROPHOSPHATE AB Aqueous copper(II) N,N',N"-trimethyl-cis,cis-1,3,5-triaminocyclohexane (Cu(tach-Me-3)(2+)(aq)) promotes the hydrolysis of activated phosphate diesters in aqueous medium at pH 7.2. This complex is selective for cleavage of the phosphate diester sodium bis(p-nitrophenyl) phosphate (BNPP), the rate of hydrolysis of the monoester disodium p-nitrophenyl phosphate being 1000 times slower. The observed rate acceleration of BNPP hydrolysis is slightly greater than that observed for other Cu(II) complexes, such as [Cu([9]aneN(3))Cl-2] ([9]aneN(3) = 1,4,7-triazacyclononane). The rate of hydrolysis is first-order in phosphate ester at low ester concentration and second-order in [Cu(tach-Me3)]2+(aq), suggesting the involvement of two metal complexes in the mechanism of substrate hydrolysis. The reaction exhibits saturation kinetics with respect to BNPP concentration according to a modified Michaelis-Menten mechanism: 2CuL + S reversible arrow LCu-S-CuL --> 2CuL + products' (K-M = 12.3 +/- 1.8 mM(2), k(cat) = (4.0 +/- 0.4) x 10(-4) s(-1), 50 degreesC) where CuL = [Cu(tach-Me3)]2+, S = BNPP, and LCu-S-CuL is a substrate-bridged dinuclear complex. EPR data indicate that the dicopper complex is formed only in the presence of BNPP; the active LCu-S-CuL intermediate species then slowly decays to products, regenerating monomeric CuL. C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. NIH, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. RP Planalp, RP (reprint author), Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. FU NIGMS NIH HHS [R37-GM20194] NR 52 TC 30 Z9 30 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD AUG 13 PY 2001 VL 40 IS 17 BP 4176 EP 4182 DI 10.1021/ic000830d PG 7 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 461UJ UT WOS:000170381600011 PM 11487320 ER PT J AU Wilk, A Chmielewski, MK Grajkowski, A Phillips, LR Beaucage, SL AF Wilk, A Chmielewski, MK Grajkowski, A Phillips, LR Beaucage, SL TI The 4-oxopentyl group as a labile phosphate/thiophosphate protecting group for synthetic oligodeoxyribonucleotides SO TETRAHEDRON LETTERS LA English DT Article ID SULFUR-TRANSFER REAGENT; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; MONOMERS AB An efficient and economical method for the solid-phase synthesis of oligodeoxyribonucleotides and their phosphorothioate analogues is described. The method entails the use of the 4-oxopentyl group for phosphate thiophosphate protection. Post-synthesis removal of the protecting group is easily and rapidly achieved under mild conditions at ambient temperature using either pressurized gaseous amines or concentrated ammonium hydroxide. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 12 TC 22 Z9 22 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD AUG 13 PY 2001 VL 42 IS 33 BP 5635 EP 5639 DI 10.1016/S0040-4039(01)01094-2 PG 5 WC Chemistry, Organic SC Chemistry GA 460LU UT WOS:000170309700012 ER PT J AU Takiguchi, M Cherrington, NJ Hartley, DP Klaassen, CD Waalkes, MP AF Takiguchi, M Cherrington, NJ Hartley, DP Klaassen, CD Waalkes, MP TI Cyproterone acetate induces a cellular tolerance to cadmium in rat liver epithelial cells involving reduced cadmium accumulation SO TOXICOLOGY LA English DT Article DE cyproterone acetate; cadmium toxicity; cadmium accumulation; zinc efflux ID BINDING PROTEIN; PROGESTERONE PRETREATMENT; HEPATIC METALLOTHIONEIN; ZINC TRANSPORTER; C3H MICE; TOXICITY; GLUTATHIONE; RESISTANCE; TESTOSTERONE; EXPRESSION AB Several reports indicate that some steroids. in particular sex steroid hormones, can modify cadmium toxicity. We recently reported that cyproterone acetate (CA), a synthetic steroidal antiandrogen that is closely related in structure to progesterone, affects cadmium toxicity in mice. In the present study, we investigated the effect of CA on cadmium toxicity in a rat liver epithelial cell line (TRL 1215) in vitro. Cells were exposed to various concentrations of CA (0. 1, 10. or 50 muM) for 24 h and subsequently exposed to cadmium (0. 50, or 100 muM: as CdCl2) for an additional 24 It. CA pretreatment resulted in a clear decrease in the sensitivity to cadmium. Additional time course study showed CA pretreatment provided protection against cadmium toxicity but only when given for 6 or more hours prior to cadmium exposure. Cellular cadmium accumulation was markedly reduced (60% decrease) in cells pretreated for 6 or more hours with CA. In the presence of protein synthesis inhibitors the protective effect of CA toward cadmium toxicity was abolished. However. in the presence of the GSH synthesis inhibitor, L-buthionine (S.R)-suifoximide (BSO), the protective effect of CA toward cadmium toxicity remained. CA alone increased metallothionein (NIT) levels 2.4-fold, while cadmium (50 muM) alone resulted in a 8.9-fold increase over control. However, cadmium-induced MT synthesis was markedly decreased by CA pretreatment probably because of reduced cadmium accumulation. Analysis of various metal transporters by bDNA signal amplification assay revealed that the ZnT-1 transporter gene, which encodes for a membrane protein associated with zinc efflux, was expressed three-fold more in CA treated cells than control. These data show that CA pretreatment provides protection against cadmium toxicity in vitro and indicate that this protection is due to a decreased accumulation of cadmium rather than through activation of NIT synthesis. This decrease of cellular cadmium accumulation appears to be related to events that require protein synthesis and may be due to activation of the genes associated with zinc efflux. Published by Elsevier Science Ireland Ltd. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. Univ Kansas, Med Ctr, Dept Pharmacol Toxicol & Therapeut, Kansas City, KS 66160 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, 111 Alexander Dr,POB 12233,MD F0-09, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [F32 ES005883] NR 44 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD AUG 13 PY 2001 VL 165 IS 1 BP 13 EP 25 DI 10.1016/S0300-483X(01)00402-4 PG 13 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 465KB UT WOS:000170587200002 PM 11551428 ER PT J AU Chiao, C Bader, T Stenger, JE Baldwin, W Brady, J Barrett, JC AF Chiao, C Bader, T Stenger, JE Baldwin, W Brady, J Barrett, JC TI HIV type 1 Tat inhibits tumor necrosis factor alpha-induced repression of tumor necrosis factor receptor p55 and amplifies tumor necrosis factor alpha activity in stably tat-transfected HeLa cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; KAPPA-B ACTIVATION; HUMAN ENDOTHELIAL-CELLS; FACTOR TNF RECEPTOR; EPITHELIAL-CELLS; MONOCLONAL-ANTIBODIES; TRANSCRIPTION FACTOR; SURFACE EXPRESSION; CELLULAR-RESPONSE; MESSENGER-RNA AB The human immunodeficiency virus type 1 (HIV-1) Tat protein is a key regulatory protein in the HIV-1 replication cycle. Tat interacts with cellular transcriptional factors and cytokines, such as tumor necrosis factor (TNF-alpha), and alters the expression of a variety of genes in HIV-1-infected and noninfected cells. To further elucidate the mechanisms by which HIV-1 Tat amplifies the activity of TNF-alpha, we transfected the HIV-1 tat gene into an epithelial (HeLa) cell line. We observed that Tat-expressing cells had increased NF-kappaB-dependent trans-activational activity due to enhanced NF-kappaB-DNA binding in response to TNF-alpha treatment. Tumor necrosis factor receptor (TNFR) p55 was the prominent receptor, as neutralizing antibodies to TNFR p55, but not to TNFR p75, blocked TNF-alpha -mediated NF-kappaB activation. Furthermore, tat-transfected cells were more sensitive to TNF-alpha -induced. cytotoxicity and only the neutralizing antibodies to TNFR p55 completely protected the cells. To determine whether TNFR p55 was involved in amplification of cellular response to TNF-alpha by HIV-1 Tat, we investigated the effect of TNF-alpha on TNFR p55 expression in the tat-transfected cells. TNF-alpha treatment resulted in a reduction in both TNFR p55 mRNA and protein levels in the control cells but not in the tat-transfected cells as determined with Northern blot and Western blot analyses, respectively. Our results indicate that HIV-1 Tat may inhibit TNF-alpha -induced repression of TNFR p55 and thereby amplify TNF-alpha activity in these stably transfected cells. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NCI, Virol Lab, Bethesda, MD 20892 USA. RP Barrett, JC (reprint author), NIEHS, Mol Carcinogenesis Lab, MD C206,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. NR 52 TC 6 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG 10 PY 2001 VL 17 IS 12 BP 1125 EP 1132 DI 10.1089/088922201316912736 PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 464XA UT WOS:000170557600004 PM 11522182 ER PT J AU Palmer, S Margot, N Gilbert, H Shaw, N Buckheit, R Miller, M AF Palmer, S Margot, N Gilbert, H Shaw, N Buckheit, R Miller, M TI Tenofovir, adefovir, and zidovudine susceptibilities of primary human immunodeficiency virus type 1 isolates with non-B subtypes or nucleoside resistance SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID LONG TERMINAL REPEAT; REVERSE-TRANSCRIPTASE; DRUG SUSCEPTIBILITY; HIV TYPE-1; PHYLOGENETIC ANALYSIS; GENETIC SUBTYPES; IN-VIVO; SEQUENCE; LAMIVUDINE; DIVERSITY AB New antiretroviral drugs with activity against strains of human immunodeficiency virus type 1 (HIV-1) with non-B subtypes and with resistance to current antiretroviral drugs are needed. The activity of two nucleotide analogs, tenofovir and adefovir (PMPA and PMEA, respectively), against non-B subtypes and nucleoside-resistant primary HIV-1 isolates was assessed. Tenofovir and adefovir were fully active against a panel of subtypes A, C, D, E, F, G, and group O primary HIV-1 isolates as compared with their respective activity against subtype B isolates. Moreover, the susceptibility of a panel of 10 primary HIV-1 isolates with >10-fold mean resistance to zidovudine, lamivudine, and abacavir was within 2.2-fold of wild-type tenofovir susceptibility for each isolate. An oral prodrug of tenofovir, tenofovir disoproxil fumarate (DF), is currently in phase III clinical trials for the treatment of HIV-1 infection. These in vitro susceptibility results suggest that tenofovir DF may be active in vivo against HIV-1 with nucleoside resistance as well as against HIV-1 with non-B subtypes. C1 So Res Inst, Infect Dis Res Dept, Frederick, MD 21701 USA. Gilead Sci Inc, Foster City, CA 94404 USA. RP Palmer, S (reprint author), NCI, HIV Drug Resistance Program, Bldg 535,Room 109,Sulton St, Frederick, MD 21702 USA. NR 51 TC 34 Z9 36 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG 10 PY 2001 VL 17 IS 12 BP 1167 EP 1173 DI 10.1089/088922201316912772 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 464XA UT WOS:000170557600008 PM 11522186 ER PT J AU Gao, F Trask, SA Hui, HX Mamaeva, O Chen, YL Theodore, TS Foley, BT Korber, BT Shaw, GM Hahn, BH AF Gao, F Trask, SA Hui, HX Mamaeva, O Chen, YL Theodore, TS Foley, BT Korber, BT Shaw, GM Hahn, BH TI Molecular characterization of a highly divergent HIV type 1 isolate obtained early in the AIDS epidemic from the Democratic Republic of Congo SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; ORIGIN AB Numerous complete human immunodeficiency virus type 1 (HIV-1) genomes have been characterized for contemporary viruses, but few isolates obtained early in the HIV-1 epidemic have been studied. In this article, we describe the molecular characterization of an HIV-1 isolate (83CD003) that was obtained from an AIDS patient in Kinshasa, Democratic Republic of Congo (DRC) in 1983. The complete 83CD003 genome was sequenced in its entirety and found to encode uninterrupted open reading frames for all viral genes. Phylogenetic analysis revealed that 83CD003 was a member of the major (M) group of HIV-1, but did not group with any of the known subtypes. Rather, it formed an independent lineage in all regions of its genome that was roughly equidistant from representatives of all other subtypes. Similarly, 83CD003 also did not cluster with any of several unclassified group M sequences that have been reported more recently to circulate in the DRC, suggesting that it may represent an early group M lineage that is either rare or has gone extinct. The molecular clone of 83CD003 yielded an infectious virus after transfection into mammalian cells and its biological properties can be further studied. C1 Univ Alabama, Dept Med, Birmingham, AL 35294 USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Univ Alabama, Howard Hughes Med Inst, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Gao, F (reprint author), Univ Alabama, Dept Med, 701 19th St S,LHRB 639, Birmingham, AL 35294 USA. OI Foley, Brian/0000-0002-1086-0296; Korber, Bette/0000-0002-2026-5757 FU NIAID NIH HHS [N01 AI 85338, P20 AI 27767, R01 AI 40951, UO1 AI 41530] NR 19 TC 11 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG 10 PY 2001 VL 17 IS 12 BP 1217 EP 1222 DI 10.1089/088922201316912826 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 464XA UT WOS:000170557600013 PM 11522191 ER PT J AU Liu, R Liu, H Chen, X Kirby, M Brown, PO Zhao, KJ AF Liu, R Liu, H Chen, X Kirby, M Brown, PO Zhao, KJ TI Regulation of CSF1 promoter by the SWI/SNF-like BAF complex SO CELL LA English DT Article ID RNA ADENOSINE-DEAMINASE; HANDED Z-DNA; FORMING SEQUENCES; NUCLEAR FACTOR-1; HUMAN GENOME; ZAB DOMAIN; CHROMATIN; TRANSCRIPTION; NUCLEOSOME; BINDING AB The mammalian BAF complex regulates gene expression by modifying chromatin structure. In this report, we identify 80 genes activated and 2 genes repressed by the BAF complex in SW-13 cells. We find that prior binding of NFI/CTF to the NFI/CTF binding site in CSF1 promoter is required for the recruitment of the BAF complex and the BAF-dependent activation of the promoter. Furthermore, the activation of the CSF1 promoter requires Z-DNA-forming sequences that are converted to Z-DNA structure upon activation by the BAF complex. The BAF complex facilitates Z-DNA formation in a nucleosomal template in vitro. We propose a model in which the BAF complex promotes Z-DNA formation which, in turn, stabilizes the open chromatin structure at the CSF1 promoter. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Zhao, KJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 45 TC 224 Z9 231 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 10 PY 2001 VL 106 IS 3 BP 309 EP 318 DI 10.1016/S0092-8674(01)00446-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 462RJ UT WOS:000170433300009 PM 11509180 ER PT J AU Nelson, G Hoon, MA Chandrashekar, J Zhang, YF Ryba, NJP Zuker, CS AF Nelson, G Hoon, MA Chandrashekar, J Zhang, YF Ryba, NJP Zuker, CS TI Mammalian sweet taste receptors SO CELL LA English DT Article ID PUTATIVE PHEROMONE RECEPTORS; PROTEIN-COUPLED RECEPTORS; GLUTAMATE RECEPTORS; MULTIGENE FAMILY; MICE; EXPRESSION; RESPONSES; G-ALPHA(16); PREFERENCE; HAMSTER AB The sense of taste provides animals with valuable information about the quality and nutritional value of food. Previously, we identified a large family of mammalian taste receptors involved in bitter taste perception (the T2Rs). We now report the characterization of mammalian sweet taste receptors. First, transgenic rescue experiments prove that the Sac locus encodes T1R3, a member of the T1R family of candidate taste receptors. Second, using a heterologous expression system, we demonstrate that T1R2 and T1R3 combine to function as a sweet receptor, recognizing sweet-tasting molecules as diverse as sucrose, saccharin, dulcin, and acesulfame-K. Finally, we present a detailed analysis of the patterns of expression of T1Rs and T2Rs, thus providing a view of the representation of sweet and bitter taste at the periphery. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. RP Zuker, CS (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NR 38 TC 900 Z9 934 U1 16 U2 141 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTES AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD AUG 10 PY 2001 VL 106 IS 3 BP 381 EP 390 DI 10.1016/S0092-8674(01)00451-2 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 462RJ UT WOS:000170433300015 PM 11509186 ER PT J AU Dbaibo, GS El-Assaad, W Krikorian, A Liu, B Diab, K Idriss, NZ El-Sabban, M Driscoll, TA Perry, DK Hannun, YA AF Dbaibo, GS El-Assaad, W Krikorian, A Liu, B Diab, K Idriss, NZ El-Sabban, M Driscoll, TA Perry, DK Hannun, YA TI Ceramide generation by two distinct pathways in tumor necrosis factor alpha-induced cell death SO FEBS LETTERS LA English DT Article DE cell deaths; apoptosis; ceramide; sphingomyelinase; ceramide synthase ID INDUCED APOPTOSIS; NEUTRAL SPHINGOMYELINASE; ACID SPHINGOMYELINASE; GLUTATHIONE; BCL-2; DAUNORUBICIN; BIOSYNTHESIS; INVOLVEMENT AB Ceramide accumulation in the cell can occur from either hydrolysis of sphingomyelin or by de novo synthesis. In this study, we found that blocking de novo ceramide synthesis significantly inhibits ceramide accumulation and subsequent cell death in response to tumor necrosis factor alpha. When cells were pre-treated with glutathione, a proposed cellular regulator of neutral sphingomyelinase, inhibition of ceramide accumulation at early time points was achieved with attenuation of cell death. Inhibition of both pathways achieved near-complete inhibition of ceramide accumulation and cell death indicating that both pathways of ceramide generation are stimulated. This illustrates the complexity of ceramide generation in cytokine action. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Amer Univ Beirut, Med Ctr, Dept Pediat, Beirut, Lebanon. Amer Univ Beirut, Dept Biochem, Beirut, Lebanon. Amer Univ Beirut, Dept Human Morphol, Beirut, Lebanon. NIEHS, Lab Pharmacol & Chem, Neuropharmacol SEct, Res Triangle Pk, NC 27709 USA. Duke Univ, Dept Pediat, Durham, NC 27710 USA. Med Univ S Carolina, Coll Med, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. RP Dbaibo, GS (reprint author), Amer Univ Beirut, Med Ctr, Dept Pediat, POB 113-6044, Beirut, Lebanon. FU NIGMS NIH HHS [GM 43825] NR 26 TC 77 Z9 79 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 10 PY 2001 VL 503 IS 1 BP 7 EP 12 DI 10.1016/S0014-5793(01)02625-4 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 464AE UT WOS:000170509300002 PM 11513845 ER PT J AU Kleuser, B Maceyka, M Milstien, S Spiegel, S AF Kleuser, B Maceyka, M Milstien, S Spiegel, S TI Stimulation of nuclear sphingosine kinase activity by platelet-derived growth factor SO FEBS LETTERS LA English DT Article DE nuclear sphingosine kinase; sphingosine; sphingosine-1-phosphate ID PROGRAMMED CELL-DEATH; SWISS 3T3 CELLS; RAT-LIVER; FUNCTIONAL-CHARACTERIZATION; NEUTRAL SPHINGOMYELINASE; MOLECULAR-CLONING; SPHINGOSINE-1-PHOSPHATE; CHROMATIN; APOPTOSIS; CERAMIDE AB Subcellular fractionation revealed that a significant fraction of total sphingosine kinase, the enzyme that phosphorylates sphingosine to form the bioactive lipid metabolite sphingosine-1-phosphate, resides in the nuclei of Swiss 3T3 cells, localized to both the nuclear envelope and the nucleoplasm. Platelet-derived growth factor, in addition to rapidly stimulating cytosolic sphingosine kinase, also induced a large increase in nucleoplasm-associated activity after 12-24 h that correlated with progression of cells to the S-phase of the cell cycle and translocation of sphingosine kinase-green fluorescent protein fusion protein to the nuclear envelope. Our results add sphingosine kinase to the growing list of lipid-metabolizing enzymes associated with the nucleus, and suggest that sphingosine-1-phosphate may also play a role in signal transduction in the nucleus. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20007 USA. Free Univ Berlin, Inst Pharm, D-1000 Berlin, Germany. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Georgetown Univ, Med Ctr, Dept Biochem & Mol Biol, W226A New Res Bldg,3970 Reservoir Rd NW, Washington, DC 20007 USA. RI Maceyka, Michael/B-9277-2008 FU NIGMS NIH HHS [GM43880] NR 34 TC 50 Z9 53 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD AUG 10 PY 2001 VL 503 IS 1 BP 85 EP 90 DI 10.1016/S0014-5793(01)02697-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 464AE UT WOS:000170509300017 PM 11513860 ER PT J AU Martin-Romero, FJ Kryukov, GV Lobanov, AV Carlson, BA Lee, BJ Gladyshev, VN Hatfield, DL AF Martin-Romero, FJ Kryukov, GV Lobanov, AV Carlson, BA Lee, BJ Gladyshev, VN Hatfield, DL TI Selenium metabolism in Drosophila - Selenoproteins, selenoprotein mRNA expression, fertility, and mortality SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SELENOPHOSPHATE SYNTHETASE; SELENOCYSTEINE INSERTION; SELD HOMOLOG; GENE; MELANOGASTER; TRANSLATION; EUKARYOTES; MECHANISM; TISSUES; GENOME AB Selenocysteine is a rare amino acid in protein that is encoded by UGA with the requirement of a downstream mRNA stem-loop structure, the selenocysteine insertion sequence element. To detect selenoproteins in Drosophila, the entire genome was analyzed with a novel program that searches for selenocysteine insertion sequence elements, followed by selenoprotein gene signature analyses. This computational screen and subsequent metabolic labeling with (75)Se and characterization of selenoprotein mRNA expression resulted in identification of three selenoproteins: selenophosphate synthetase 2 and novel G-rich and BthD selenoproteins that had no homology to known proteins. To assess a biological role for these proteins, a simple chemically defined medium that supports growth of adult Drosophila and requires selenium supplementation for optimal survival was devised. Flies survived on this medium supplemented with 10(-8) to 10(-6) m selenium or on the commonly used yeast-based complete medium at about twice the rate as those on a medium without selenium or with > 10(-6) M selenium. This effect correlated with changes in selenoprotein mRNA expression. The number of eggs laid by Drosophila was reduced approximately in half in the chemically defined medium compared with the same medium supplemented with selenium. The data provide evidence that dietary selenium deficiency shortens, while supplementation of the diet with selenium normalizes the Drosophila life span by a process that may involve the newly identified selenoproteins. C1 NCI, Basic Res Lab, Sect Mol Biol Selenium, NIH, Bethesda, MD 20892 USA. Univ Nebraska, Beadle Ctr, Dept Biochem, Lincoln, NE 68588 USA. Seoul Natl Univ, Sch Biol Sci, Mol Genet Lab, Seoul 151742, South Korea. RP Hatfield, DL (reprint author), NCI, Basic Res Lab, Sect Mol Biol Selenium, NIH, Bethesda, MD 20892 USA. EM hatfield@dc37a.nci.nih.gov RI Kryukov, Gregory/A-9592-2008; Gladyshev, Vadim/A-9894-2013; OI Martin-Romero, Francisco Javier/0000-0001-6796-7396 FU NIGMS NIH HHS [GM61603] NR 26 TC 81 Z9 92 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD AUG 10 PY 2001 VL 276 IS 32 BP 29798 EP 29804 DI 10.1074/jbc.M100422200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 464XE UT WOS:000170558000027 PM 11389138 ER EF