FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Balonov, M Kaidanovsky, G Zvonova, I Kovtun, A Bouville, A Luckyanov, N Voilleque, P AF Balonov, M Kaidanovsky, G Zvonova, I Kovtun, A Bouville, A Luckyanov, N Voilleque, P TI Contributions of short-lived radioiodines to thyroid doses received by evacuees from the Chernobyl area estimated using early in vivo activity measurements SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT Workshop on Internal Dosimetry of Radionuclides CY SEP 09-12, 2002 CL NEW COLL, OXFORD, ENGLAND SP Natl Radiol Protect Board, Inst Radioprotect & Surete Nucl, European Radiat Dosimetry Grp, European Late Effects Project Grp, European Commiss, Res Directorate Gen, Biol & Environm Res Program, USA DOE, WHO HO NEW COLL ID RECONSTRUCTION; ACCIDENT; IODINE; I-131 AB A series of in vivo gamma spectrometric measurements of 65 people evacuated from Pripyat 1.5 days after the Chernobyl Nuclear Power Plant Unit 4 explosion was performed in St Petersburg, Russia, its early as 30 April 1986. The historical spectra and interviews were recently processed and the results used for thyroid dose estimation. Activities of I-131 in thyroid and Te-132 in lungs were determined easily; for estimation of I-132 and I-133 activities in thyroid. sophisticated methods of spectral processing were developed. According to thyroid measurement data, the mean ratio of I-133/I-131 activities (at the time of the accident) inhaled by residents of Pripyat was 2.0. The mean ratio of thyroid dose from I-133 inhalation to that caused by I-131 amounts to 0.3, which confirms the accuracy of dose estimates based on the evolution of the Chernobyl accident. The mean ratio of I-132 activity in thyroid to that of Te-132 in lungs was assessed from the human measurement data to be 0.2, which is in reasonable agreement with the metabolic properties of these radionuclides. The mean ratio of thyroid dose from I-132 originating from Te-132 deposited in lungs to the dose caused by I-131 was 0.13 +/- 0.02 for Pripyat residents who did not take KI pills and 0.9 +/- 0.1 for persons who took KI pills. Thus, the contribution of short-lived radioiodines to total thyroid dose of Pripyat residents, which was on average 30% for persons who did not use stable iodine prophylaxis, and about 50% for persons who took KI pills on 26-27 April, should be accounted for in the assessment of thyroid health effects. C1 Inst Radiat Hyg, St Petersburg, Russia. Inst Ind & Marine Med, St Petersburg, Russia. NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. MJP Risk Assessment Inc, Denver, CO USA. RP Balonov, M (reprint author), IAEA, Wagramerstr 5,POB 100, A-1400 Vienna, Austria. FU PHS HHS [263-MQ-110756, 263-MQ-014380] NR 17 TC 28 Z9 30 U1 0 U2 3 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD TN23 1YW, KENT, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2003 VL 105 IS 1-4 BP 593 EP 599 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 725FM UT WOS:000185533200117 PM 14527033 ER PT J AU Likhtarev, I Minenko, V Khrouch, V Bouville, A AF Likhtarev, I Minenko, V Khrouch, V Bouville, A TI Uncertainties in thyroid dose reconstruction after Chernobyl SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT Workshop on Internal Dosimetry of Radionuclides CY SEP 09-12, 2002 CL NEW COLL, OXFORD, ENGLAND SP Natl Radiol Protect Board, Inst Radioprotect & Surete Nucl, European Radiat Dosimetry Grp, European Late Effects Project Grp, European Commiss, Res Directorate Gen, Biol & Environm Res Program, USA DOE, WHO HO NEW COLL ID CANCER; ACCIDENT; BYELARUS AB The most significant impact of the Chernobyl accident of 26 April 1986 is the increased incidence of thyroid cancer among Belarusians, Russians and Ukrainians who were exposed as children to radioiodines in fallout resulting from atmospheric releases. The US National Cancer Institute (NCI), in cooperation with the ministries of health of Belarus and Ukraine, is involved in epidemiological studies of thyroid diseases related to the accident. Individual thyroid doses, as well as uncertainties, have been estimated for the members of the cohort studies (approximately 13,000 Ukrainians and 12,000 Belarusians). The cohort subjects, who were selected from the large group of children whose thyroids were monitored for gamma radiation within it few weeks of the accident, provided personal information on their residence history and dietary habits during interviews. Thyroid dose estimates range from 1 mGy to more than 20 Gy. The uncertainties are found to be approximately log-normally distributed, with geometric standard deviations ranging from 1.6 to 5.0. The medians of the geometric standard deviations are 1.7 for the Ukrainian subjects and 2.1 for the Belarusian subjects. The major sources Of uncertainty in the thyroid dose estimates are found to be those related to the thyroid mass of the subject and to the estimation of the thyroidal content of I-131 at the time of thyroid monitoring. C1 Ukrainian Acad Technol Sci, Radiat Protect Inst, UA-04050 Kiev, Ukraine. Res Clin Inst Radiat Med & Endocrinol, Minsk, Byelarus. State Res Ctr, Inst Biophys, Moscow 123182, Russia. NCI, DHHS, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Ukrainian Acad Technol Sci, Radiat Protect Inst, Melnikova 53, UA-04050 Kiev, Ukraine. EM Likh@rpi.kiev.ua NR 14 TC 28 Z9 34 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 EI 1742-3406 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2003 VL 105 IS 1-4 BP 601 EP 608 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 725FM UT WOS:000185533200118 PM 14527034 ER PT J AU Lubin, JH AF Lubin, JH TI Studies of radon and lung cancer in North America and China SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT International Workshop on Health and Biological Effects of Low-Dose Ionising Radiation CY NOV 04-05, 2002 CL ROME, ITALY ID RESIDENTIAL RADON; INDOOR RADON; RISK; EXPOSURE; SMOKING; WOMEN AB Studies of radon-exposed underground miners indicate that residential radon is the second leading cause of lung cancer. Seven case-control studies of residential radon have been conducted in North America and two in China, and represent all studies in these areas which included 200 or more lung cancer cases and used long-term radon detectors. North American studies enrolled 4081 cases and 5281 controls, and Chinese studies enrolled 1076 cases and 2015 controls. Based on analyses of pooled data, odds ratios (ORs) and 95% confidence limits at 100 Bq m(-3) were 1.106 (1.00,1.28) for the North American studies and 1.139 (1.01,1.37) for the Chinese studies. Tests of homogeneity of ORs within populations were not significant. Among subjects with complete dosimetry for the 5-30 y exposure period prior to interview, ORs at 100 Bq m(-3) were 1.205 (1.03,1.50) for the North American studies and 1.279 (1.07,0.75) for the Chinese studies. Results are consistent with extrapolations from miners and indicate an excess lung cancer risk from residential radon. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC-7244, Bethesda, MD 20892 USA. NR 26 TC 29 Z9 29 U1 0 U2 5 PU NUCLEAR TECHNOLOGY PUBL PI ASHFORD PA PO BOX 7, ASHFORD TN23 1YW, KENT, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PY 2003 VL 104 IS 4 BP 315 EP 319 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 731KX UT WOS:000185884200003 PM 14579887 ER PT J AU Kuzmenok, O Potapnev, M Potapova, S Smolnikova, V Rzheutsky, V Yarilin, AA Savino, W Belyakov, IM AF Kuzmenok, O Potapnev, M Potapova, S Smolnikova, V Rzheutsky, V Yarilin, AA Savino, W Belyakov, IM TI Late effects of the Chernobyl radiation accident on T cell-mediated immunity in cleanup workers SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; PERIPHERAL-BLOOD LYMPHOCYTES; RESPONSES; EXPRESSION; ACTIVATION; MITOGENS; MUCOSAL; SUBSETS; SYSTEM AB The main goal of this investigation was to evaluate the abnormal T-cell immunity in cleanup workers who took part in the cleanup after the Chernobyl accident in 1986. Peripheral blood mononuclear cells (MNCs) of apparently healthy cleanup workers (n = 134) were used to analyze the phenotype and proliferative response to mitogens in vitro. Evaluation of the MNC phenotype of cleanup workers did not reveal a significant disturbance in the T-cell subpopulation content except for an increase in CD3(+)CD16(+)56(+) (NKT) cells. Immunophenotyping of phytohemagglutinin (PHA)-activated MNCs demonstrated suppression of CD4(+) T-cell propagation and augmentation of CD8(+) T-cell propagation in vitro compared to control individuals. DNA synthesis in the MNCs of cleanup workers was markedly inhibited after activation for 3 days with suboptimal concentrations of PHA, pokeweed mitogen and PMA. In contrast to control individuals, the monocytes of cleanup workers were able to stimulate the proliferation of T cells from healthy individuals but inhibited the proliferation of T cells from cleanup workers. This study affords a better understanding of the response of MNCs to stimulation with suboptimal concentrations of PHA and provides an approach to a more accurate analysis of the immunological disorders found after exposure to radiation from Chernobyl-related activities. (C) 2003 by Radiation Research Society. C1 NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA. Inst Oswaldo Cruz, Oswaldo Cruz Fdn, Dept Immunol, Lab Thymus Res, BR-21045900 Rio De Janeiro, Brazil. Belarussian Ctr Pediat Oncol & Hematol, Lesnoye 223052, Minsk District, Byelarus. Belarussian Res Inst Hematol & Blood Transfus, Minsk 223059, Byelarus. Belarussian Dispensary Radiat Med, Minsk 220000, Byelarus. Inst Immunol, Moscow, Russia. RP Belyakov, IM (reprint author), NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bldg 10,Rm 6B-12,MSC1578, Bethesda, MD 20892 USA. NR 36 TC 12 Z9 14 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2003 VL 159 IS 1 BP 109 EP 116 DI 10.1667/0033-7587(2003)159[0109:LEOTCR]2.0.CO;2 PG 8 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 633CC UT WOS:000180260800012 PM 12492374 ER PT J AU Tawn, EJ Whitehouse, CA Daniel, CP Tarone, RE Bothwell, AM Fisher, A AF Tawn, EJ Whitehouse, CA Daniel, CP Tarone, RE Bothwell, AM Fisher, A TI Somatic cell mutations at the glycophorin A locus in erythrocytes of radiation workers from the Sellafield nuclear facility SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; CHERNOBYL CLEANUP WORKERS; A GPA LOCUS; MUTANT FREQUENCIES; PROLONGED IRRADIATION; RECEPTOR LOCI; BIODOSIMETRY; EXPOSURE; ASSAY; GENE AB The glycophorin A (GPA) somatic mutation assay for NO and NN mutant erythrocytes was performed on 245 current and 48 retired workers who had been occupationally exposed to radiation at the British Nuclear Fuels plc facility at Sella-field. A positive association with increasing age was found for current workers for both NO and NN frequencies of 0.14 +/- 0.05 x 10(-6) (P = 0.012) and 0.25 +/- 0.07 x 10(-6) (P = 0.0003) per year, respectively. No association with age was found for the retired workers. In a comparison of ever-smokers with never-smokers, no difference was observed for NO frequencies for current workers, but a significantly higher frequency was found for ever-smokers in the retired group (P = 0.001). NN mutant frequencies were slightly higher in ever-smokers than in never-smokers for both current and retired workers, but in neither case was the increase significant. In age-adjusted analyses for NO mutant frequencies, a slight positive radiation dose response was found for current workers (1.6 +/- 3.8 x 10(-6) per Sv), for retired workers (2.9 +/- 2.5 x 10(-6) per Sv), and in the combined analysis (2.6 +/- 2.2 x 10(-6) per Sv), but in no case did this reach significance. Similar analyses for NN mutant frequencies revealed a positive dose response for current workers (4.7 +/- 4.6 x 10(-6) per Sv) and a negative response for retired workers (-2.4 +/- 3.6 x 10(-6) per Sv) that was maintained in the combined analysis (-1.4 +/- 2.8 x 10(-6) per Sv), but none of these slopes was significantly different from zero. The results suggest that the GPA mutation assay is insufficiently sensitive to be used as a biological marker of low-dose chronic exposure and provide further evidence that, in contrast to high acute radiation exposure, protracted exposure is much less effective at inducing somatic mutations in vivo. (C) 2003 by Radiation Research Society. C1 Westlakes Res Inst, Genet Unit, Moor Row CA24 3JY, Cumbria, England. NCI, Div Epidemiol & Genet, Bethesda, MD 20892 USA. RP Tawn, EJ (reprint author), Westlakes Res Inst, Genet Unit, Moor Row CA24 3JY, Cumbria, England. NR 35 TC 3 Z9 3 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JAN PY 2003 VL 159 IS 1 BP 117 EP 122 DI 10.1667/0033-7587(2003)159[0117:SCMATG]2.0.CO;2 PG 6 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 633CC UT WOS:000180260800013 ER PT J AU Szajek, LP Der, M Divel, J Huang, BX Plascjak, P Eckelman, WC AF Szajek, LP Der, M Divel, J Huang, BX Plascjak, P Eckelman, WC TI Production and radioassay of Tc-94m for PET studies SO RADIOCHIMICA ACTA LA English DT Article DE Tc-94m; sestamibi; radioassay; PET imaging; solvent extraction; quality control ID POSITRON-EMISSION-TOMOGRAPHY; ISONITRILE; PURITY AB The radionuclide Tc-94m with its positron branching ratio of 72%, positron end-point energy of 2.47 MeV, and relatively short half-life of 52 minutes is suitable for quantitative measurements using PET. Tc-94m can be produced by proton bombardment of isotopically enriched [Mo-94]MoO3. We prepare Tc-94m as pertechnetate in saline solution using a wet-chemical separation procedure employing a semi-automated apparatus. Tc-94m sestamibi and other radiopharmaceuticals are routinely produced from this reagent. C1 NIH, Warren G Magnuson Clin Ctr, Positron Emiss Tomog Dept, Bethesda, MD 20892 USA. RP Szajek, LP (reprint author), NIH, Warren G Magnuson Clin Ctr, Positron Emiss Tomog Dept, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 16 TC 5 Z9 5 U1 0 U2 1 PU R OLDENBOURG VERLAG PI MUNICH PA LEKTORAT M/N, K BERBER-NERLINGER, POSTFACH 80 13 60, D-81613 MUNICH, GERMANY SN 0033-8230 J9 RADIOCHIM ACTA JI Radiochim. Acta PY 2003 VL 91 IS 10 BP 613 EP 616 DI 10.1524/ract.91.10.613.22472 PG 4 WC Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 734QG UT WOS:000186067600009 ER PT J AU Choyke, PL Glenn, GM Walther, MM Zbar, B Linehan, WM AF Choyke, PL Glenn, GM Walther, MM Zbar, B Linehan, WM TI Hereditary renal cancers SO RADIOLOGY LA English DT Review DE angiomyolipoma; genes and genetics; kidney, CT; kidney neoplasms; sclerosis, tuberous; state of the art; von Hippel-Lindau disease ID HIPPEL-LINDAU-DISEASE; NONPOLYPOSIS COLORECTAL-CANCER; TUBEROUS SCLEROSIS COMPLEX; TUMOR-SUPPRESSOR GENE; PARENCHYMAL SPARING SURGERY; HOGG-DUBE-SYNDROME; SICKLE-CELL DISEASE; MEDULLARY CARCINOMA; PULMONARY LYMPHANGIOLEIOMYOMATOSIS; LAPAROSCOPIC CRYOABLATION AB Hereditary renal cancer syndromes can lead to multiple bilateral kidney tumors that occur at a younger age than do nonhereditary renal cancers. Imaging plays-an important role in the diagnosis and management of these syndromes. During the past decade, several new hereditary renal syndromes have been discovered but are not yet widely known. Whereas previously, the list of hereditary renal cancers in adults included von Hippel-Lindau disease and a rare form of chromosomal translocation, the list now includes the following syndromes: tuberous sclerosis, hereditary papillary renal cancer, Birt-Hogg-Dube syndrome, hereditary leiomyoma renal cell carcinoma, familial renal oncocytoma, hereditary nonpolyposis colon cancer, and medullary carcinoma of the kidney. In addition, a number of newly described but poorly understood syndromes are under investigation. Even at this early stage, it is clear that elucidation of the underlying genetic mutations that cause hereditary renal cancer syndromes will have profound implications for understanding the origins of nonhereditary renal tumors. These studies will likely culminate in a better understanding of the causes of renal cancer, its prevention, and, ultimately, its cure. (C) RSNA, 2002. C1 NCI, Imaging Sci Program, NIH, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Immunobiol Lab, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Imaging Sci Program, NIH, 10 Ctr Dr,Rm 1C660, Bethesda, MD 20892 USA. NR 123 TC 104 Z9 107 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2003 VL 226 IS 1 BP 33 EP 46 DI 10.1148/radiol.2261011296 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 630KR UT WOS:000180106500007 PM 12511666 ER PT J AU Yao, L Mehta, U AF Yao, L Mehta, U TI Infraspinatus muscle atrophy: Implications? SO RADIOLOGY LA English DT Article DE muscles, injuries; muscles, MR; shoulder, injuries; shoulder, MR ID SUPRASCAPULAR NERVE AB PURPOSE: To evaluate associated findings in patients who exhibited atrophy of infraspinatus muscle at magnetic resonance (MR) examination of their shoulders to clarify implications of this abnormality. MATERIALS AND-METHODS: With an electronic database search, cases of advanced infraspinatus muscle atrophy in patients who underwent MR imaging during a 1-year period for evaluation of shoulder pain or dysfunction were identified. The analysis was restricted to cases interpreted by one reader who applied a standardized method of reporting. Associated MR imaging findings in these cases were tabulated. RESULTS: Advanced infraspinatus muscle atrophy was encountered in 51 (4.3%) of 1,1191 MR examinations of the shoulder. Tears of the infraspinatus tendon were present in only 27 (53%) of 51 cases. In 46 (90%) of 51 cases, a full-thickness tear was present in the anterior portion of the rotator cuff. In 10 (20%) of 51 cases with infraspinatus muscle atrophy, cuff muscle atrophy was confined to the infraspinatus muscle. Cuff muscle atrophy was isolated to the infraspinatus muscle in four (17%) of 24 cases in which atrophy of the infraspinatus muscle was present despite an intact tendon. In none of the 51 cases was there a mass in the suprascapular or sphenoglenoid notch. CONCLUSION: Infraspinatus muscle atrophy typically occurs with tendon tears in the anterior aspect of the rotator cuff. Concomitant atrophy in the supraspinatus muscle often is present, but infraspinatus muscle atrophy can occur in isolation, and this finding does not imply that the infraspinatus tendon is ruptured. (C) RSNA, 2002. C1 NIH, Dept Radiol, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. RP Yao, L (reprint author), NIH, Dept Radiol, Bldg 10,Rm 1C640,10 Ctr Dr, Bethesda, MD 20892 USA. NR 9 TC 17 Z9 17 U1 1 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2003 VL 226 IS 1 BP 161 EP 164 DI 10.1148/radiol.2261011818 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 630KR UT WOS:000180106500024 PM 12511685 ER PT J AU Oguz, KK Browner, NM Calhoun, VD Wu, C Kraut, MA Yousem, DM AF Oguz, KK Browner, NM Calhoun, VD Wu, C Kraut, MA Yousem, DM TI Correlation of functional MR imaging activation data with simple reaction times SO RADIOLOGY LA English DT Article DE brain, cortex; brain, function; brain, MR; magnetic resonance (MR), functional imaging ID CEREBRAL GLUCOSE-METABOLISM; SEX-DIFFERENCES; BLOOD-FLOW; AGE; FMRI; STIMULATION; SIGNAL; STATE AB PURPOSE: To determine the relationship between subject reaction times (RTs) and activation volume in the brain during visuomotor functional magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-four subjects performed a simple RT task during single-event functional MR imaging, and RTs were recorded. The six subjects with the fastest RTs were designated the fast RT group, and the six subjects with the slowest RTs were designated the slow RT group. The data were processed with noncorrected height threshold (P <.001) for individual comparisons and corrected height threshold (P <.05) for group comparisons (t tests). The activation volumes in both occipital lobes, the left sensorimotor cortex, and the supplemental motor cortices were compared for the two groups. RESULTS: The mean RT +/- SD was 342 msec +/- 20.15 for the fast RT group and 475 +/- 17 for the slow RT group (P <.0001). More voxels of activation were msec 36. seen in the fast RT group than in the slow RT group in the occipital lobes, left sensorimotor cortices, and supplemental motor cortices on individual and group maps. This difference was statistically significant in the left sensorimotor (P =.03) and left visual (P =.05) cortices. In the right visual cortex, a trend toward more activation in the fast RT group was noted (P =.15). There was a negative correlation between RTs and activation volume in the left sensorimotor cortex (P =.048). CONCLUSION: There was a greater activation volume in motor and visual cortices in the fast RT group than in the slow RT group. (C) RSNA, 2002. C1 Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Div Neuroradiol, Baltimore, MD 21287 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Div Psychiat, Baltimore, MD 21287 USA. RP Yousem, DM (reprint author), Johns Hopkins Univ Hosp, Russell H Morgan Dept Radiol & Radiol Sci, Div Neuroradiol, 600 N Wolfe St,Phipps B-112, Baltimore, MD 21287 USA. RI Calhoun, Vince/H-7146-2013 OI Calhoun, Vince/0000-0001-9058-0747 NR 43 TC 13 Z9 14 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JAN PY 2003 VL 226 IS 1 BP 188 EP 194 DI 10.1148/radiol.2261020141 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 630KR UT WOS:000180106500028 PM 12511689 ER PT J AU Dams, R Murphy, CM Lambert, WE Huestis, MA AF Dams, R Murphy, CM Lambert, WE Huestis, MA TI Urine drug testing for opioids, cocaine, and metabolites by direct injection liquid chromatography/tandem mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID ABUSE-TREATMENT PATIENTS; SOLID-PHASE EXTRACTION; ECGONINE METHYL-ESTER; FORENSIC TOXICOLOGY; BODY-FLUIDS; RAPID CONFIRMATION/QUANTITATION; CLINICAL TOXICOLOGY; PERFORMANCE; METHAMPHETAMINE; BENZOYLECGONINE AB A sensitive and specific liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the simultaneous quantification of opioids, cocaine, and metabolites in urine was developed and validated. A 10-muL aliquot of urine was injected directly onto the LC/MS/MS system. The lack of sample preparation substantially reduced total analysis time. Separation was performed by reversed-phase chromatography with gradient elution for all analytes in 26 min. Atmospheric pressure chemical ionization (APCI) was a rugged and efficient ionization technique for basic drugs. Identification and quantification was based on selected reaction monitoring (SRM). Calibration, with deuterated internal standards, was performed by linear regression analysis (weighting factor 1/x). Limits of quantitation (LOQ) were established between 10-100ng/mL and linearity was obtained up to a maximum of 10 000 ng/mL with an average correlation coefficient (R-2) > 0.99. Analytical validation criteria for specificity, precision, accuracy, dilution integrity, matrix effect, and stability were fulfilled. The method proved to be simple and time efficient, and was applicable for illicit drug use monitoring and methadone treatment compliance in clinical research projects at the National Institute on Drug Abuse (NIDA). Published in 2003 by John Wiley Sons, Ltd. C1 NIDA, Chem & Drug Metab Sect, NIH, Baltimore, MD 21224 USA. State Univ Ghent, Toxicol Lab, B-9000 Ghent, Belgium. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Sect, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 40 TC 77 Z9 77 U1 5 U2 16 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2003 VL 17 IS 14 BP 1665 EP 1670 DI 10.1002/rcm.1098 PG 6 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 699CY UT WOS:000184039400020 PM 12845594 ER PT J AU Cheng, X Shin, YG Levine, BS Smith, AC Tomaszewski, JE van Breemen, RB AF Cheng, X Shin, YG Levine, BS Smith, AC Tomaszewski, JE van Breemen, RB TI Quantitative analysis of betulinic acid in mouse, rat and dog plasma using electrospray liquid chromatography/mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID TUMOR AB Betulinic acid is under development as a therapeutic agent for the treatment of metastatic malignant melanoma. In support of pharmacokinetic and toxicological evaluations, a robust assay based on liquid chromatography/mass spectrometry (LC/MS) was developed for the quantitative analysis of betulinic acid. Sample preparation consisted of deproteinization of the plasma by the addition of three volumes of acetonitrile and one volume of methanol followed by centrifugation. Aliquots of the supernatant were analyzed using an isocratic reversed-phase high-performance liquid chromatography (HPLC) system coupled to a negative ion electrospray mass spectrometer. Deprotonated molecules of betulinic acid and the isomeric internal standard oleanolic acid were detected using selected ion monitoring at m/z 455. The limit of detection of betulinic acid was 0.5 pg (1.1 fmol) injected on-column (50 pg/mL, 10 muL injection volume), and the limit of quantitation was 2 pg (4.4 fmol, 200 pg/mL, 10 muL injection volume). Betulinic acid was stable in plasma samples at -20"C for at least 3 weeks. The intra-day and inter-day coefficients of variation of the assay were less than or equal to6.4 and less than or equal to9.0%, respectively. The utility of the assay was demonstrated by analyzing betulinic acid spiked into mouse, rat and dog plasma, by determining the extent of binding of betulinic acid to plasma proteins, and by measuring betulinic acid in mouse and rat plasma following intraperitoneal or intravenous administration in vivo. At 15 and 25 muLg/mL in mouse, rat or dog plasma, betulinic acid was 99.99% bound to serum proteins, and, at 5 mug/mL, betulinic acid was greater than or equal to99.97% bound. Copyright (C) 2003 John Wiley Sons, Ltd. C1 Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA. Univ Illinois, Toxicol Res Lab, Chicago, IL USA. NCI, Bethesda, MD 20892 USA. RP van Breemen, RB (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, 833 S Wood St, Chicago, IL 60612 USA. FU NCI NIH HHS [N01-CM-87103] NR 6 TC 18 Z9 19 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 2003 VL 17 IS 18 BP 2089 EP 2092 DI 10.1002/rcm.1155 PG 4 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 719XM UT WOS:000185230400010 PM 12955738 ER PT B AU Wu, CO Yu, KF Yuan, VWS AF Wu, CO Yu, KF Yuan, VWS BE Akritas, MG Politis, DN TI Covariate centering and scaling in varying-coefficient regression with application to longitudinal growth studies SO RECENT ADVANCES AND TRENDS IN NONPARAMETRIC STATISTICS LA English DT Proceedings Paper CT International Conference on Recent Advances and Trends in NonParametric Statistics CY JUL 15-19, 2002 CL IRAKLION, GREECE ID NONPARAMETRIC REGRESSION; CONFIDENCE BANDS; MODELS AB We propose a class of time-varying coefficient models with centered or standardized (both centered and scaled) covariates, discuss the practical benefits of covariate transformation, and develop a comprehensive set of nonparametric estimation and confidence procedures based on these models. We demonstrate the practical properties of our methods through a fetal growth study and a simulation. Our results suggest that covariate centering or standardization can lead to superior statistical estimates and better biological interpretations. C1 NHLBI, Off Biostat Res, DECA, DHHS, Bethesda, MD 20892 USA. RP Wu, CO (reprint author), NHLBI, Off Biostat Res, DECA, DHHS, Bethesda, MD 20892 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-51378-7 PY 2003 BP 377 EP 391 DI 10.1016/B978-044451378-6/50025-9 PG 15 WC Statistics & Probability SC Mathematics GA BY29E UT WOS:000188793600025 ER PT J AU Dupont, J Dunn, S Barrett, JC LeRoth, D AF Dupont, J Dunn, S Barrett, JC LeRoth, D TI Microarray analysis and identification of novel molecules involved in insulin-like growth factor-1 receptor signaling and gene expression SO RECENT PROGRESS IN HORMONE RESEARCH, VOL 58 SE RECENT PROGRESS IN HORMONE RESEARCH LA English DT Review ID FACTOR-I RECEPTOR; TYROSINE KINASE-ACTIVITY; AMINO-ACID RESIDUE; IGF-1 RECEPTOR; DIFFERENTIAL PHOSPHORYLATION; TRANSDUCTION PATHWAYS; BINDING-SPECIFICITY; INTERACTING PROTEIN; CYTOPLASMIC DOMAINS; SKIN KERATINOCYTES AB The insulin receptor (IR) and the insulin-like growth factor-1 receptor (IGF-1R) are members of the same subfamily of receptor tyrosine kinases. The two receptors phosphorylate many of the same substrates and activate the same signaling modules, including the mitogen-activated protein kinase (MAPK) and phosphatidyl inositol 3' kinase (PI3K) signaling pathways. Although the IR and IGF-1R share some redundant functions in metabolism, cell growth, differentiation, and apoptosis, they also exhibit distinct physiological roles. Some of these may be due to differences in tissue distribution, receptor structure, formation of hybrid receptors, or mechanisms of ligand binding. However, the divergent effects of insulin and IGF-1 also may be explained by specificity in the intracellular signals generated by insulin and IGF-1. In particular, the IR and IGF-1R are capable of triggering their own biological responses by using specific or preferential substrates, molecular adapters, or signaling pathways. In a recent study, we used cDNA microarray analysis to identify genes differentially regulated by insulin and IGF-1. Mouse NIH-3T3 fibroblasts expressing either the wild-type human IGF-1R or IR were stimulated with either IGF-1 or insulin, respectively. We identified 39 genes differentially regulated by insulin and IGF-1. Most of these genes had not been reported previously to be responsive to insulin or IGF-1. The genes induced by IGF- I generally were involved in mitogenesis or differentiation, while the genes found to be induced by insulin did not conform to any particular category, In a separate study, immortalized breast epithelial cells were stimulated with IGF-1 and a cDNA microarray analysis was used to generate a profile of IGF-1-regulated genes. A number of genes known to be involved in angiogenesis were found to be regulated by IGF-1. These results strongly suggest that this technology may be extremely useful in identifying groups of genes that are specifically regulated by different ligands and their activated receptors. C1 Univ F Rabelais, CNRS, INRA, UMR 6073, F-37380 Nouzilly, France. British Columbia Res Inst Childrens & Womens Hlth, Vancouver, BC, Canada. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Clin Endocrinol Branch, Bethesda, MD 20892 USA. RP Dupont, J (reprint author), Univ F Rabelais, CNRS, INRA, UMR 6073, F-37380 Nouzilly, France. NR 75 TC 43 Z9 49 U1 1 U2 3 PU ENDOCRINE SOC PI BETHESDA PA 4350 EAST WEST HIGHWAY SUITE 500, BETHESDA, MD 20814-4410 USA SN 0079-9963 J9 RECENT PROG HORM RES PY 2003 VL 58 BP 325 EP 342 DI 10.1210/rp.58.1.325 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA BW63Z UT WOS:000182666800015 PM 12795426 ER PT J AU Turco, SJ Sacks, DL AF Turco, SJ Sacks, DL TI Control of Leishmania-sand fly interactions by polymorphisms in lipophosphoglycan structure SO RECOGNITION OF CARBOHYDRATES IN BIOLOGICAL SYSTEMS, PART B: SPECIFIC APPLICATIONS SE METHODS IN ENZYMOLOGY LA English DT Review ID DEVELOPMENTAL MODIFICATION; MAJOR PROMASTIGOTES; DONOVANI; STAGE; VECTOR; MIDGUT; METACYCLOGENESIS; BIOSYNTHESIS; BINDING; MUTANT C1 Univ Kentucky, Ctr Med, Dept Biochem, Lexington, KY 40536 USA. NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. RP Turco, SJ (reprint author), Univ Kentucky, Ctr Med, Dept Biochem, Lexington, KY 40536 USA. FU NIAID NIH HHS [AI20941] NR 17 TC 5 Z9 5 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 363 BP 377 EP 381 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX80D UT WOS:000186474800028 PM 14579590 ER PT J AU Szu, SSC Bystricky, S AF Szu, SSC Bystricky, S TI Physical, chemical, antigenic, and immunologic characterization of polygalacturonan, its derivatives, and Vi antigen from Salmonella typhi SO RECOGNITION OF CARBOHYDRATES IN BIOLOGICAL SYSTEMS, PART B: SPECIFIC APPLICATIONS SE METHODS IN ENZYMOLOGY LA English DT Review ID CAPSULAR POLYSACCHARIDE; CALCIUM-IONS; CONJUGATE VACCINES; ACETYL DERIVATIVES; O-ACETYLATION; BINDING; PECTIN; FEVER; IMMUNOGENICITY; DISSOCIATION C1 NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. RP Szu, SSC (reprint author), NICHHD, Dev & Mol Immun Lab, NIH, Bethesda, MD 20892 USA. NR 44 TC 10 Z9 10 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 363 BP 552 EP 567 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX80D UT WOS:000186474800041 PM 14579603 ER PT J AU Saksena, R Chernyak, A Karavanov, A Kovac, P AF Saksena, R Chernyak, A Karavanov, A Kovac, P TI Conjugating low molecular mass carbohydrates to proteins 1. Monitoring the progress of conjugation SO RECOGNITION OF CARBOHYDRATES IN BIOLOGICAL SYSTEMS PT A: GENERAL PROCEDURES SE METHODS IN ENZYMOLOGY LA English DT Review ID VIBRIO-CHOLERAE O-1; DIETHYL SQUARATE; O-POLYSACCHARIDE; SEROTYPE INABA; SERUM-ALBUMIN; OGAWA; LIPOPOLYSACCHARIDE; IDENTIFICATION; VACCINES; ANTIGEN C1 NIDDK, Med Chem Lab, Sect Carbohydrates, NIH, Bethesda, MD 20892 USA. Ciphergen Biosyst Inc, Palo Alto, CA 94306 USA. RP Saksena, R (reprint author), NIDDK, Med Chem Lab, Sect Carbohydrates, NIH, 8 Ctr Dr,Bldg 8, Bethesda, MD 20892 USA. NR 34 TC 11 Z9 12 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 362 BP 125 EP 139 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX38T UT WOS:000185102400010 PM 12968361 ER PT J AU Saksena, R Chernyak, A Poirot, E Kovac, P AF Saksena, R Chernyak, A Poirot, E Kovac, P TI Conjugating low molecular mass carbohydrates to proteins 2. Recovery of excess ligand used in the conjugation reaction SO RECOGNITION OF CARBOHYDRATES IN BIOLOGICAL SYSTEMS PT A: GENERAL PROCEDURES SE METHODS IN ENZYMOLOGY LA English DT Review ID VIBRIO-CHOLERAE O-1; METHYL ALPHA-GLYCOSIDES; SQUARIC ACID DIESTER; O-SPECIFIC ANTIGEN; SEROTYPE-INABA; DIETHYL SQUARATE; COUPLING REAGENT; BLOCK SYNTHESIS; POLYSACCHARIDE; OGAWA C1 NIDDK, Med Chem Lab, Sect Carbohydrates, NIH, Bethesda, MD 20892 USA. RP Saksena, R (reprint author), NIDDK, Med Chem Lab, Sect Carbohydrates, NIH, 8 Ctr Dr,Bldg 8, Bethesda, MD 20892 USA. NR 41 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 362 BP 140 EP 159 PG 20 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX38T UT WOS:000185102400011 PM 12968362 ER PT J AU Rifkind, JM Nagababu, E Ramasamy, S Ravi, LB AF Rifkind, JM Nagababu, E Ramasamy, S Ravi, LB TI Hemoglobin redox reactions and oxidative stress SO REDOX REPORT LA English DT Article; Proceedings Paper CT Meeting on Redox Metabolism in Malaria: From Genes to Drugs CY FEB 03-07, 2003 CL BELLAGIO, ITALY ID HEME DEGRADATION; HYDROGEN-PEROXIDE; NITRITE; BLOOD; SUPEROXIDE; OXYGEN AB The role of hemoglobin in transporting oxygen is dependent on the reversible binding of oxygen to Fe(II) hemoglobin with molecular oxygen released at reduced oxygen pressures. The partially oxygenated hemoglobin formed with the release of oxygen from hemoglobin is susceptible to redox reactions where the functional Fe(II) heme is oxidized to Fe(III) and the substrate is reduced. In this article, we review two important redox reactions of hemoglobin and discuss the ramifications of these reactions. The reduction of oxygen to superoxide starts a cascade of oxidative reactions, which are a source for red cell-induced oxidative stress. The reduction of nitrite to nitric oxide produces a labile form of nitric oxide that can be a source for oxidative stress, but can also have important physiological functions. C1 NIA, Mol Dynam Sect, Baltimore, MD 21224 USA. RP Rifkind, JM (reprint author), NIA, Mol Dynam Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 12 TC 21 Z9 22 U1 0 U2 2 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 1351-0002 J9 REDOX REP JI Redox Rep. PY 2003 VL 8 IS 5 BP 234 EP 237 DI 10.1179/135100003225002817 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 759JW UT WOS:000187735400002 PM 14962355 ER PT J AU Dive, D Gratepanche, S Yera, H Becuwe, P Daher, W Delplace, P Odberg-Ferragut, C Capron, M Khalife, J AF Dive, D Gratepanche, S Yera, H Becuwe, P Daher, W Delplace, P Odberg-Ferragut, C Capron, M Khalife, J TI Superoxide dismutase in Plasmodium: a current survey SO REDOX REPORT LA English DT Article; Proceedings Paper CT Meeting on Redox Metabolism in Malaria: From Genes to Drugs CY FEB 03-07, 2003 CL BELLAGIO, ITALY ID OXIDATIVE STRESS; FALCIPARUM; IRON; MALARIA; BERGHEI; DEFENSE; GENERATION; PARASITES; MECHANISM; CATALASE C1 Inst Pasteur, INSERM, U547, F-59019 Lille, France. NIAID, MVDU, NIH, Rockville, MD 20852 USA. Hop Cochin, Serv Parasitol Mycol, F-75674 Paris, France. Univ Henri Poincare Nancy, Cellular & Dev Biol Lab, Vandoeuvre Les Nancy, France. Univ Sci & Technol Lille, CNRS, UMR 8576, Unite Glycobiol Struct & Fonctionnelle, Villeneuve Dascq, France. RP Dive, D (reprint author), Inst Pasteur, INSERM, U547, 1,Rue Pr Calmette,BP 245, F-59019 Lille, France. NR 39 TC 11 Z9 12 U1 0 U2 0 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 1351-0002 J9 REDOX REP JI Redox Rep. PY 2003 VL 8 IS 5 BP 265 EP 267 DI 10.1179/135100003225002871 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 759JW UT WOS:000187735400008 PM 14962361 ER PT B AU Wellems, TE AF Wellems, TE BE Knobler, SL Lemon, SM Najafi, M Burroughs, T TI Malaria and the problem of chloroquine resistance SO RESISTANCE PHENOMENON IN MICROBES AND INFECTIOUS DISEASE VECTORS: IMPLICATIONS FOR HUMAN HEALTH AND STRATEGIES FOR CONTAINMENT LA English DT Proceedings Paper CT Workshop Forum on Emerging Infections CY FEB 06-07, 2002 CL WASHINGTON, D.C. SP US Dept HHS, NIH, Ctr Dis Control & Prevent, US FDA, US Dept Def, US Dept State, US Dept Vet Affairs, USDA, Amer Soc Microbiol, Burroughs Wellcome Fund, Eli Lilly & Co, Pfizer, GlaxoSmithKline, Wyeth Ayerst Labs C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08854-2 PY 2003 BP 52 EP 59 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology SC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology GA BY20U UT WOS:000188244000004 ER PT J AU Phillips, AW Zhang, PS Truckenmiller, ME Keir, SD Bouvier, M Tornatore, C Freed, WJ AF Phillips, AW Zhang, PS Truckenmiller, ME Keir, SD Bouvier, M Tornatore, C Freed, WJ TI Platelet-derived growth factor-producing cells immortalized from rat mesencephalon with SV40 large T antigen transduced by an AAV vector SO RESTORATIVE NEUROLOGY AND NEUROSCIENCE LA English DT Article DE Adeno-associated virus; AAV; SV40 large T; neurotrophic factors; PDGF ID CENTRAL-NERVOUS-SYSTEM; ADENOASSOCIATED VIRUS VECTORS; ADENO-ASSOCIATED VIRUS; LARGE TUMOR-ANTIGEN; FETAL GLIAL-CELLS; GENE-TRANSFER; DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; PROGENITOR-CELL; FACTOR PDGF AB Purpose: Adeno-associated virus (AAV) can infect a wide variety of mammalian cell types and is capable of infecting both dividing and non-dividing cell populations. Here we report the construction of a recombinant AAV vector which expresses the SV40 large T protein (AAV-T) and the use of this vector to immortalize primary cells from embryonic rat mesencephalon. Methods: The AAV-T vector was constructed by introducing the BamH1 fragment of the pCMV/SVE/Neo plasmid containing T antigen and SV40 regulatory elements into the JM48 plasmid containing the inverted terminal repeats of AAV. Neuronal cultures from E-12 rat mesencephalon were grown in defined media supplemented with basic fibroblast growth factor. These cells were infected with the AAV-T vector. Results: A cell line (designated RMAT) and six subclones were established from these cultures through multiple passages. This cell line was immunoreactive for SV40 large T antigen and the cytoskeletal proteins nestin and vimentin. Morphological differentiation and expression of neurofilament 160 kDa were induced by exposure to dibutyrl cyclic AMP. Immunoassays performed to measure endogenous production of growth factors showed that RMAT cells produced high levels of platelet-derived growth factor (PDGF). Conclusions: AAV may be a useful vector for the transduction of oncogenes to produce cell lines. C1 NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, DHHS,NIH, Baltimore, MD 21224 USA. NINDS, Lab Mol Med & Neurosci, DHHS, NIH, Bethesda, MD 20892 USA. RP Freed, WJ (reprint author), NIDA, Cellular Neurobiol Res Branch, Intramural Res Program, DHHS,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 52 TC 6 Z9 7 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0922-6028 J9 RESTOR NEUROL NEUROS JI Restor. Neurol. Neurosci. PY 2003 VL 21 IS 1-2 BP 1 EP 10 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 699MU UT WOS:000184061200001 PM 12808197 ER PT S AU Narfstrom, K Bragadottir, R Redmond, TM Rakoczy, PE van Veen, T Bruun, A AF Narfstrom, K Bragadottir, R Redmond, TM Rakoczy, PE van Veen, T Bruun, A BE LaVail, MM Hollyfield, JG Anderson, RE TI Functional and structural evaluation after AAV.RPE65 gene transfer in the canine model of leber's congenital amaurosis SO RETINAL DEGENERATIONS: MECHANISMS AND EXPERIMENTAL THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on Retinal Degenerations (RD2002) CY SEP 30-OCT 05, 2002 CL BURGENSTOCK, SWITZERLAND ID RETINAL-PIGMENT EPITHELIUM; MICROSOMAL PROTEIN; RPE65; DYSTROPHY; MUTATIONS; BLINDNESS; VISION; DOGS C1 Univ Missouri, Columbia, MO 65201 USA. Univ Hosp Oslo, Oslo, Norway. NEI, NIH, Bethesda, MD 20892 USA. Univ Western Australia, Lions Eye Inst, Perth, WA 6009, Australia. Univ Lund Hosp, Dept Ophthalmol, S-22185 Lund, Sweden. RP Narfstrom, K (reprint author), Univ Missouri, Columbia, MO 65201 USA. OI Redmond, T. Michael/0000-0002-1813-5291 NR 16 TC 22 Z9 22 U1 0 U2 1 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47781-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 533 BP 423 EP 430 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental; Ophthalmology SC Genetics & Heredity; Research & Experimental Medicine; Ophthalmology GA BX82V UT WOS:000186576800054 PM 15180294 ER PT S AU Rakoczy, PE Lai, CM Yu, MJT Daniels, DM Brankov, M Rae, BC Stoddart, CW Barnett, NL Martin-Iverson, MT Redmond, TM Narfstrom, K Zhou, XH Constable, IJ AF Rakoczy, PE Lai, CM Yu, MJT Daniels, DM Brankov, M Rae, BC Stoddart, CW Barnett, NL Martin-Iverson, MT Redmond, TM Narfstrom, K Zhou, XH Constable, IJ BE LaVail, MM Hollyfield, JG Anderson, RE TI Assessment of rAAV-mediated gene therapy in the RPE65(-/-) mouse SO RETINAL DEGENERATIONS: MECHANISMS AND EXPERIMENTAL THERAPY SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on Retinal Degenerations (RD2002) CY SEP 30-OCT 05, 2002 CL BURGENSTOCK, SWITZERLAND ID RECOMBINANT ADENOASSOCIATED VIRUS; MODEL; MUTATIONS; DISEASE; RETINA; VECTOR; VISION C1 Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia. UWA, Lions Eye Inst, Perth, WA, Australia. Univ Queensland, Vis Touch & Hearing Res Ctr, St Lucia, Qld 4067, Australia. UWA, Dept Pharmacol, Perth, WA, Australia. NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD USA. Univ Missouri, Coll Vet Med, Dept Vet Med & Surg, Columbia, MO 65211 USA. Univ N Carolina, Virus Vector Core Facil, Gene Therapy Ctr, Chapel Hill, NC USA. RP Rakoczy, PE (reprint author), Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia. RI Barnett, Nigel/F-1226-2010; OI Barnett, Nigel/0000-0002-0704-2233; Redmond, T. Michael/0000-0002-1813-5291 NR 15 TC 4 Z9 4 U1 0 U2 0 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0065-2598 BN 0-306-47781-5 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2003 VL 533 BP 431 EP 438 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental; Ophthalmology SC Genetics & Heredity; Research & Experimental Medicine; Ophthalmology GA BX82V UT WOS:000186576800055 PM 15180295 ER PT B AU Mascola, J AF Mascola, J BE Vicari, M Dodet, B Girard, M TI The protective effect of passively transferred neutralizing antibody in the setting of active cellular immunity SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 13th International Cent Gardes Symposium CY OCT 27-29, 2002 CL ANNECY, FRANCE SP Merieux Fdn, Aventis Pasteur, Participat IAVI ID HUMAN-IMMUNODEFICIENCY-VIRUS; RHESUS-MONKEYS; T-CELLS; HIV-1; TRANSMISSION; CHALLENGE; RESPONSES; INFECTION; MACAQUES C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Mascola, J (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-389-6 PY 2003 BP 39 EP 44 PG 6 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BX14W UT WOS:000184433300007 ER PT B AU Martin, MA AF Martin, MA BE Vicari, M Dodet, B Girard, M TI The passive transfer of high titered polyclonal neutralizing IgG can confer sterilizing immunity to pig-tailed challenged with SHIVDH12 SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 13th International Cent Gardes Symposium CY OCT 27-29, 2002 CL ANNECY, FRANCE SP Merieux Fdn, Aventis Pasteur, Participat IAVI ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1/SIV CHIMERIC VIRUS; ENVELOPE GLYCOPROTEIN; T-LYMPHOCYTE; ANTIBODY; INFECTION; MACAQUES; VIREMIA; GP120; PROTECTION C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, MA (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-389-6 PY 2003 BP 59 EP 63 PG 5 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BX14W UT WOS:000184433300010 ER PT B AU Berzofsky, JA AF Berzofsky, JA BE Vicari, M Dodet, B Girard, M TI Enhancing mucosal and systemic T-cell responses and efficacy of HIV/SIV vaccines SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 13th International Cent Gardes Symposium CY OCT 27-29, 2002 CL ANNECY, FRANCE SP Merieux Fdn, Aventis Pasteur, Participat IAVI ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; VIRAL-INFECTION; ALPHA SYNERGIZE; LYMPHOCYTES; CTL; IMMUNIZATION; PROTECTION; MACAQUES; IL-12 C1 NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Metab Branch, Mol Immunogenet & Vaccine Res Sect, NIH, Bethesda, MD 20892 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-389-6 PY 2003 BP 89 EP 93 PG 5 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BX14W UT WOS:000184433300015 ER PT B AU Arthur, LO Crise, B Chertova, EN Benveniste, R Desrosiers, R Hoxie, J Bess, JW Henderson, LE Lifson, J AF Arthur, LO Crise, B Chertova, EN Benveniste, R Desrosiers, R Hoxie, J Bess, JW Henderson, LE Lifson, J BE Vicari, M Dodet, B Girard, M TI Inactivated immunodeficiency viruses: Inactivation procedures and modifications to potentially enhance vaccine efficacy SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 13th International Cent Gardes Symposium CY OCT 27-29, 2002 CL ANNECY, FRANCE SP Merieux Fdn, Aventis Pasteur, Participat IAVI ID HIV-1 IMMUNOGEN; IMMUNIZATION; INFECTIVITY C1 NCI, FCRDC, AVP, SAIC Frederick, Frederick, MD 21701 USA. RP Arthur, LO (reprint author), NCI, FCRDC, AVP, SAIC Frederick, Frederick, MD 21701 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-389-6 PY 2003 BP 133 EP 137 PG 5 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BX14W UT WOS:000184433300022 ER PT B AU Flores, J AF Flores, J BE Vicari, M Dodet, B Girard, M TI Challenges and approaches to the conduct of clinical trials in developing countries SO RETROVIRUSES OF HUMAN AIDS AND RELATED ANIMAL DISEASES LA English DT Proceedings Paper CT 13th International Cent Gardes Symposium CY OCT 27-29, 2002 CL ANNECY, FRANCE SP Merieux Fdn, Aventis Pasteur, Participat IAVI ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN MONOCLONAL-ANTIBODIES; SYNERGISTIC NEUTRALIZATION; HIV-1 VACCINE; CLADE B; IMMUNITY; POTENT C1 NIAID, Vaccine & Prevent Res Program, Div AIDS, Bethesda, MD 20893 USA. RP Flores, J (reprint author), NIAID, Vaccine & Prevent Res Program, Div AIDS, 6700B Rockledge Dr, Bethesda, MD 20893 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU EDITIONS SCIENTIFIQUES ET MEDICALES ELSEVIER PI PARIS PA 23, RUE LINOIS, 75724 PARIS, FRANCE BN 2-84299-389-6 PY 2003 BP 185 EP 189 PG 5 WC Immunology; Infectious Diseases; Medicine, Research & Experimental; Virology SC Immunology; Infectious Diseases; Research & Experimental Medicine; Virology GA BX14W UT WOS:000184433300028 ER PT J AU Sander, D Grafman, J Zalla, T AF Sander, D Grafman, J Zalla, T TI The human amygdala: an evolved system for relevance detection SO REVIEWS IN THE NEUROSCIENCES LA English DT Review DE social cognition; emotion; appraisal; evolutionary; psychology; temporal lobe; human brain ID FACE PROCESSING IMPAIRMENTS; FACIAL EXPRESSIONS; NEURAL RESPONSES; PREFRONTAL CORTEX; EMOTIONAL FACES; INTACT RECOGNITION; VOCAL EXPRESSIONS; FEAR RECOGNITION; SOCIAL-BEHAVIOR; ENHANCED MEMORY AB Evidence from pioneering animal research has suggested that the amygdala is involved in the processing of aversive stimuli, particularly fear-related information. Fear is central in the evolution of the mammalian brain: it is automatically and rapidly elicited by potentially dangerous and deadly events. The view that the amygdala shares the main characteristics of modular systems, e.g. domain specificity, automaticity, and cognitive impenetrability, has become popular in neuroscience. Because of its computational properties, it has been proposed to implement a rapid-response 'fear module'. In this article, we review recent patient and neuroimaging data of the human brain and argue that the fundamental criteria for the amygdala to be a modular system are not met. We propose a different computational view and suggest the notion of a specific involvement of the human amygdala in the appraisal of relevant events that include, but are not restricted to, fear-related stimuli. Considering the amygdala as a 'relevance detector' would integrate the 'fear module' hypothesis with the concept of an evolved neural system devoted to the processing of a broader category of biologically relevant stimuli. In primates, socially relevant events appear to have become, through evolution, the dominant elements of the amygdala's domain of specificity. C1 Inst Cognit Sci, F-69675 Bron, France. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. Univ Geneva, Psychol Sect, Geneva Emot Res Grp, Geneva, Switzerland. OI Grafman, Jordan H./0000-0001-8645-4457 NR 112 TC 430 Z9 431 U1 9 U2 60 PU FREUND & PETTMAN PUBLISHERS PI EAST YORKSHIRE PA ENHOLMES HALL, PATRINGTON, EAST YORKSHIRE HU12 OPR, ENGLAND SN 0334-1763 J9 REV NEUROSCIENCE JI Rev. Neurosci. PY 2003 VL 14 IS 4 BP 303 EP 316 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 744JH UT WOS:000186625100001 PM 14640318 ER PT S AU Heinzen, RA AF Heinzen, RA BE Hechemy, KE AvsicZupanc, T Childs, JE Raoult, DA TI Rickettsial actin-based motility - Behavior and involvement of cytoskeletal regulators SO RICKETTSIOLOGY: PRESENT AND FUTURE DIRECTIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Rickettsiae and Rickettsial Diseases CY SEP 04-07, 2002 CL LJUBLJANA, SLOVENIA SP Amer Soc Rickettsiol, DADE Behring, European Soc Clin Microbiol & Infect Dis, FOCUS Technol, Inst Mikrobiol Imunol, KEMOMED d o o, KRKA D D, LEK D D, Med Fakulteta Ljubljana, MEDILINE D O O, MINIST ZA SOLSTVO ZNANOST SPORT RS, PANIBIO Inc, Prirodoslovini Muzej Slovenije DE motility; actin; N-WASP; Arp2/3 complex; rickettsia ID ALDRICH-SYNDROME PROTEIN; WASP-FAMILY PROTEINS; ARP2/3 COMPLEX; N-WASP; LISTERIA-MONOCYTOGENES; SHIGELLA-FLEXNERI; PLAQUE ASSAY; VERO CELLS; POLYMERIZATION; NUCLEATION AB Actin-based motility (ABM) is employed by spotted fever group (SFG) rickettsiae, such as Rickettsia rickettsii, to promote cell-to-cell spread. Time-lapse video microscopy revealed that ABM is not strictly confined to SFG rickettsiae as typhus group R. typhi moved at approximately the same rate as R. rickettsii (approximately 4 mum/min), but in a highly erratic fashion. A number of common behaviors were observed between ABM of R. typhi and R. rickettsii, such as entrance into plasma membrane protrusions, formation of new actin tails only on the old surface of newly formed daughter cells, and quick (within 15 sec) reassembly of the actin tail to the opposite pole upon contact with cellular structures that impede forward movement. This last behavior suggests that the rickettsial protein(s) required for ABM is uniformly localized to both poles of the bacterium and possibly throughout the rickettsial surface. Functional roles in rickettsial ABM for neuronal Wiskott-Aldrich syndrome protein (N-WASP) and the actin-related protein (Arp)2/3 complex, critical regulators of ABM of other pathogens, have not been established. Domains of N-WASP that have characterized inhibitory effects on N-WASP or Arp2/3 complex function were expressed in HeLa cells infected with R. rickettsii. Shigella flexneri-infected cells were used as a control. When ectopically expressed, the VCA domain of N-WASP (VCA) acts as a dominant/negative with respect to Arp2/3 complex function and N-WASP missing VCA (DeltaVCA) acts as a dominant/negative form of N-WASP. Expression of VCA or DeltaVCA severely inhibited S. flexneri ABM (no Shigella motility observed in the majority of expressing cells) while only moderately inhibiting ABM of R. rickettsii (approximately 35% decrease in the rate of ABM). In addition, ectopically expressed full-length GFP-N-WASP was recruited by S. flexneri but not R. rickettsii, and Arp3 was detected by indirect immunofluorescence in S. flexneri actin tails but not within R. rickettsii actin tails. Collectively, these data suggest that rickettsial ABM is independent of N-WASP and Arp2/3 complex function. C1 Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. FU NIAID NIH HHS [AI-43502] NR 38 TC 38 Z9 41 U1 2 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-444-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 990 BP 535 EP 547 PG 13 WC Genetics & Heredity; Immunology; Infectious Diseases; Multidisciplinary Sciences SC Genetics & Heredity; Immunology; Infectious Diseases; Science & Technology - Other Topics GA BX09Q UT WOS:000184284900095 PM 12860687 ER PT S AU Howe, D Melnicakova, J Barak, I Heinzen, RA AF Howe, D Melnicakova, J Barak, I Heinzen, RA BE Hechemy, KE AvsicZupanc, T Childs, JE Raoult, DA TI Fusogenicity of the Coxiella burnetii parasitophorous vacuole SO RICKETTSIOLOGY: PRESENT AND FUTURE DIRECTIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Rickettsiae and Rickettsial Diseases CY SEP 04-07, 2002 CL LJUBLJANA, SLOVENIA SP Amer Soc Rickettsiol, DADE Behring, European Soc Clin Microbiol & Infect Dis, FOCUS Technol, Inst Mikrobiol Imunol, KEMOMED d o o, KRKA D D, LEK D D, Med Fakulteta Ljubljana, MEDILINE D O O, MINIST ZA SOLSTVO ZNANOST SPORT RS, PANIBIO Inc, Prirodoslovini Muzej Slovenije DE Coxiella; parasitophorous vacuole; protein synthesis; fusion ID CHLAMYDIA-TRACHOMATIS; LEGIONELLA-PNEUMOPHILA; INCLUSION MEMBRANE; IDENTIFICATION; MACROPHAGES; TRAFFICKING; VESICLES; PATHWAYS; PROTEIN; SHELTER AB This study investigated whether C burnetii protein synthesis and replication is required for maintenance of the fusogenic character of the Coxiella parasitophorous vacuole (PV). Vero cells were infected with C. burnetii, (Nine Mile strain in phase II) at a multiplicity of infection of approximately 10 and simultaneously treated with bacteriostatic concentrations of chloramphenicol or carbenicillin. At 96 h post-infection, cells were viewed by phase contrast microscopy for PV maturation. Mature, spacious PV containing multiple nonreplicating C. burnetii were clearly visible in infected Vero cells treated with the cell wall inhibitor carbenicillin. Conversely, mature, spacious PV did not form in cells treated with the protein synthesis inhibitor chloramphenicol. Rather, immunofluorescence microscopy revealed individual C. burnetii in small, tight PV scattered throughout the cytoplasm. Like mature PV, these PV localized with the lysosomal glycoprotein LAMP-1, but not the early endosome protein EEA.1. This result suggests that de novo C. burnetii protein synthesis, but not replication, is required for homotypic fusion and maturation of nascent C. burnetii PV. We next examined whether sustained C. burnetii protein synthesis is necessary for maintenance of PV fusogenicity. J774A.1 murine macrophage-like cells with mature C. burnetii PV were incubated with latex beads and the trafficking of beads to PV was quantified. Fusion of PV with bead-laden vacuoles was severely inhibited in cells treated with chloramphenicol. These results suggest that sustained C. burnetii protein synthesis is required for PV fusion with other vacuoles of the endocytic pathway. C1 Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. Slovak Acad Sci, Inst Virol, Bratislava 84245, Slovakia. Slovak Acad Sci, Inst Mol Biol, Bratislava 84251, Slovakia. RP Heinzen, RA (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. FU NCRR NIH HHS [RR-15553] NR 17 TC 26 Z9 27 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-444-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 990 BP 556 EP 562 PG 7 WC Genetics & Heredity; Immunology; Infectious Diseases; Multidisciplinary Sciences SC Genetics & Heredity; Immunology; Infectious Diseases; Science & Technology - Other Topics GA BX09Q UT WOS:000184284900097 PM 12860689 ER PT S AU Ge, H Chuang, YE Zhao, S Temenak, JJ Ching, WM AF Ge, H Chuang, YE Zhao, S Temenak, JJ Ching, WM BE Hechemy, KE AvsicZupanc, T Childs, JE Raoult, DA TI Genomic studies of Rickettsia prowazekii virulent and avirulent strains SO RICKETTSIOLOGY: PRESENT AND FUTURE DIRECTIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Rickettsiae and Rickettsial Diseases CY SEP 04-07, 2002 CL LJUBLJANA, SLOVENIA SP Amer Soc Rickettsiol, DADE Behring, European Soc Clin Microbiol & Infect Dis, FOCUS Technol, Inst Mikrobiol Imunol, KEMOMED d o o, KRKA D D, LEK D D, Med Fakulteta Ljubljana, MEDILINE D O O, MINIST ZA SOLSTVO ZNANOST SPORT RS, PANIBIO Inc, Prirodoslovini Muzej Slovenije DE epidemic typhus; Rickettsia prowazekii; DNA microarray; virulence ID AGROBACTERIUM-TUMEFACIENS; LEGIONELLA-PNEUMOPHILA; ESCHERICHIA-COLI; CELL-DIVISION; VIRB4 ATPASE; FTSK; PROTEIN; RESOLUTION; SEGREGATION; GENE C1 USN, Med Res Ctr, Silver Spring, MD 20910 USA. NCI, NIH, Gaithersburg, MD 20877 USA. US FDA, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Ching, WM (reprint author), USN, Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. NR 17 TC 6 Z9 6 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-444-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 990 BP 671 EP 677 PG 7 WC Genetics & Heredity; Immunology; Infectious Diseases; Multidisciplinary Sciences SC Genetics & Heredity; Immunology; Infectious Diseases; Science & Technology - Other Topics GA BX09Q UT WOS:000184284900113 PM 12860705 ER PT S AU Ren, Q Robertson, SJ Howe, D Barrows, LF Heinzen, RA AF Ren, Q Robertson, SJ Howe, D Barrows, LF Heinzen, RA BE Hechemy, KE AvsicZupanc, T Childs, JE Raoult, DA TI Comparative DNA microarray analysis of host cell transcriptional responses to infection by Coxiella burnetii or Chlamydia trachomatis SO RICKETTSIOLOGY: PRESENT AND FUTURE DIRECTIONS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT International Conference on Rickettsiae and Rickettsial Diseases CY SEP 04-07, 2002 CL LJUBLJANA, SLOVENIA SP Amer Soc Rickettsiol, DADE Behring, European Soc Clin Microbiol & Infect Dis, FOCUS Technol, Inst Mikrobiol Imunol, KEMOMED d o o, KRKA D D, LEK D D, Med Fakulteta Ljubljana, MEDILINE D O O, MINIST ZA SOLSTVO ZNANOST SPORT RS, PANIBIO Inc, Prirodoslovini Muzej Slovenije DE Coxiella; Chlamydia; DNA microarray; transcription; gene expression; inflammation ID FEVER AB DNA microarray analysis was conducted to investigate the transcriptional responses of the human monocytic leukemia cell line THP-1 to infection by Chlamydia trachomatis or Coxiella burnetii. RNA was isolated from mock infected cells and cells infected for 36 hours using TRIzol reagent. Biotinylated probes synthesized from RNA samples were hybridized to an Affymetrix U133A human genome chip consisting of 18,462 human gene probe sets. A total of 335 and 548 THP-1 genes were up- or downregulated at least twofold in cells infected with C. burnetii or C. trachomatis, respectively, when compared to uninfected cells. There was a high degree of overlap in transcriptional responses to infection with shared responses observed for 39 downregulated and 189 upregulated genes. Numerous pathogen-specific transcriptional responses were also observed. Quantitative RT-PCR and immunoblotting confirmed up- or down-regulation of a subset of THP-1 genes in response to infection by C. burnetii. This study provides insight into the host transcriptional responses to infection by Chlamydia and Coxiella that may affect the infectious cycle of each organism. C1 Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. RP Heinzen, RA (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. FU NCRR NIH HHS [RR-15553] NR 6 TC 37 Z9 37 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-444-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 990 BP 701 EP 713 PG 13 WC Genetics & Heredity; Immunology; Infectious Diseases; Multidisciplinary Sciences SC Genetics & Heredity; Immunology; Infectious Diseases; Science & Technology - Other Topics GA BX09Q UT WOS:000184284900118 PM 12860710 ER PT J AU Cabrera, JE Jin, DJ AF Cabrera, JE Jin, DJ TI Construction, purification, and characterization of Escherichia coli RNA polymerases tagged with different fluorescent proteins SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID CHROMOSOME C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Cabrera, JE (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Rm 5144, Bethesda, MD 20892 USA. NR 13 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 3 EP 10 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300001 PM 14712629 ER PT S AU Kireeva, ML Lubkowska, L Komissarova, N Kashlev, M AF Kireeva, ML Lubkowska, L Komissarova, N Kashlev, M BE Adhya, S Garges, S TI Assays and affinity purification of biotinylated and nonbiotinylated forms of double-tagged core RNA polymerase II from Saccharomyces cerevisiae SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE Methods in Enzymology LA English DT Review ID ESCHERICHIA-COLI; TRANSCRIPTION TERMINATION; ELONGATION COMPLEX; IMMUNOAFFINITY PURIFICATION; ANGSTROM RESOLUTION; DNA HYBRID; YEAST; PROTEINS; ENZYME; MOLECULES C1 NCI, Frederick Canc Res & Dev Ctr, Canc Res Ctr, Frederick, MD 21702 USA. RP NCI, Frederick Canc Res & Dev Ctr, Canc Res Ctr, Bldg 539,Rm 222, Frederick, MD 21702 USA. NR 33 TC 29 Z9 29 U1 0 U2 5 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182273-7 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 138 EP 155 PG 18 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300012 PM 14712640 ER PT J AU Huang, Y Hamada, M Maraia, RJ AF Huang, Y Hamada, M Maraia, RJ TI RNA polymerase III from the fission yeast, Schizosaccharomyces pombe SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID TRANSCRIPTION TERMINATION C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Tokyo, Dept Integrated Biosci, Tokyo, Japan. RP Huang, Y (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 165 EP 173 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300014 PM 14712642 ER PT J AU Zhi, HJ Jin, DJ AF Zhi, HJ Jin, DJ TI Purification of highly-active and soluble Escherichia coli sigma(70) polypeptide overproduced at low temperature SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID RNA-POLYMERASE; TRANSCRIPTION; INITIATION; PROTEIN; SUBUNIT; BINDING C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zhi, HJ (reprint author), NCI, Mol Biol Lab, NIH, Bldg,37,Rm 5144, Bethesda, MD 20892 USA. NR 17 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 174 EP 180 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300015 PM 14712643 ER PT J AU Martin, RG Rosner, JL AF Martin, RG Rosner, JL TI Analysis of microarray data for the marA, soxS, and rob regulons of Escherichia coli SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID MULTIPLE ANTIBIOTIC-RESISTANCE; TRANSCRIPTIONAL ACTIVATION; BINDING-SITES; PROMOTERS; EXPRESSION; ORIENTATION; STRESS C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Martin, RG (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 14 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 278 EP 280 PG 3 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300024 PM 14712652 ER PT J AU Sukhodolets, MV Garges, S Jin, DJ AF Sukhodolets, MV Garges, S Jin, DJ TI Purification and activity assays of RapA, the RNA polymerase-associated homolog of the SWI/SNF protein superfamily SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID CHROMATIN; CHROMATOGRAPHY; HELICASES; FAMILY C1 NCI, Dev Genet Sect, Mol Biol Lab, CCR,NIH, Bethesda, MD 20892 USA. RP Sukhodolets, MV (reprint author), NCI, Dev Genet Sect, Mol Biol Lab, CCR,NIH, Bldg 37,Rm 5138, Bethesda, MD 20892 USA. NR 12 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 283 EP + PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300025 PM 14712653 ER PT J AU Zhi, HJ Yang, WX Jin, DJ AF Zhi, HJ Yang, WX Jin, DJ TI Escherichia coli proteins eluted from mono Q chromatography, a final step during RNA polymerase purification procedure SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID BACTERIAL HOMOLOG; SIGMA FACTORS; TRANSCRIPTION; HFQ; NUSA; SWI2/SNF2; COMPLEX; RAPA C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zhi, HJ (reprint author), NCI, Mol Biol Lab, NIH, Bldg 37,Rm 5144, Bethesda, MD 20892 USA. NR 18 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 291 EP 300 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300026 PM 14712654 ER PT J AU Weissman, JD Raval, A Singer, DS AF Weissman, JD Raval, A Singer, DS TI Assay of an intrinsic acetyltransferase activity of the transcriptional coactivator CIITA SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID CLASS-II TRANSACTIVATOR; CREB BINDING-PROTEIN; HISTONE ACETYLTRANSFERASES; TAF(II)250; GENES; EXPRESSION C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Weissman, JD (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Rm 4B36, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 378 EP 386 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300033 PM 14712661 ER PT J AU Rishi, V Vinson, C AF Rishi, V Vinson, C TI Dominant-negative mutants of helix-loop-helix proteins: Transcriptional inhibition SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID DNA-BINDING; GENE-EXPRESSION; B/HLH/Z DOMAIN; BASIC REGION; COILED-COIL; IN-VIVO; FAMILY; RECOGNITION; CHROMATIN; USF C1 NCI, Lab Metabol, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Rishi, V (reprint author), NCI, Lab Metabol, NIH, Bldg 37,Rm 2D24, Bethesda, MD 20892 USA. NR 39 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 454 EP 466 PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300039 PM 14712667 ER PT J AU Lewis, DEA AF Lewis, DEA TI Identification of promoters of Esherichia coli and phage in transcription section plasmid pSA850 SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID GAL PROMOTERS; INHIBITION; RNA C1 NCI, Lab Mol Biol, Bethesda, MD 20892 USA. RP Lewis, DEA (reprint author), NCI, Lab Mol Biol, 37 Convent Dr,Rm 5138, Bethesda, MD 20892 USA. NR 6 TC 15 Z9 15 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 370 BP 618 EP 645 PG 28 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24S UT WOS:000188419300052 PM 14712680 ER PT J AU Karamychev, VN Tatusov, A Komissarova, N Kashlev, M Neumann, RD Zhurkin, VB Panyutin, IG AF Karamychev, VN Tatusov, A Komissarova, N Kashlev, M Neumann, RD Zhurkin, VB Panyutin, IG TI Iodine-125 radioprobing of E-coli RNA polymerase transcription elongation complexes SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID STRUCTURAL BASIS; DNA HYBRID C1 NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Lab Computat & Expt Biol, NIH, Bethesda, MD 20892 USA. RP Karamychev, VN (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. NR 19 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 371 BP 106 EP 120 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24T UT WOS:000188419500007 PM 14712694 ER PT J AU Mustaev, A Zaychikov, E Grachev, M Kozlov, M Severinov, K Epshtein, V Korzheva, N Bereshchenko, O Markovtsov, V Lukhtanov, E Tsarev, I Maximova, T Kashlev, M Bass, I Nikiforov, V Goldfarb, A AF Mustaev, A Zaychikov, E Grachev, M Kozlov, M Severinov, K Epshtein, V Korzheva, N Bereshchenko, O Markovtsov, V Lukhtanov, E Tsarev, I Maximova, T Kashlev, M Bass, I Nikiforov, V Goldfarb, A TI Strategies and methods of cross-linking of RNA polymerase active center SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID TRANSCRIPTION ELONGATION COMPLEX; BETA-SUBUNIT; FUNCTIONAL TOPOGRAPHY; INITIATING SUBSTRATE; PROMOTER COMPLEX; DERIVATIVES; NUCLEOTIDE; RIFAMPICIN; MODEL; SITE C1 Publ Hlth Res Inst, New York, NY 10016 USA. Max Planck Inst Biochem, D-8000 Munich, Germany. Russian Acad Sci, Inst Mol Genet, Moscow 123182, Russia. Russian Acad Sci, Limnol Inst, Ulanbatorskaya 3664033, Russia. NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Frederick, MD 21702 USA. Publ Hlth Res Inst, Newark, NJ 07103 USA. Epoch Pharmaceut Inc, Bothell, WA 98021 USA. Rutgers State Univ, Waksman Inst Microbiol, Piscataway, NJ 08854 USA. RP Mustaev, A (reprint author), Publ Hlth Res Inst, 455 1st Ave, New York, NY 10016 USA. RI Severinov, Konstantin/C-8545-2016 FU NIGMS NIH HHS [GM30717, GM49242] NR 26 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 371 BP 191 EP 206 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24T UT WOS:000188419500014 PM 14712701 ER PT J AU King, RA Sen, RJ Weisberg, RA AF King, RA Sen, RJ Weisberg, RA TI Using a lac repressor roadblock to analyze the E-coli transcription elongation complex SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID RNA-POLYMERASE-II; DNA-BINDING PROTEIN; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; TERNARY COMPLEXES; CONTROL REGION; TERMINATION; OPERATOR; MECHANISM; SEQUENCE C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP King, RA (reprint author), NICHD, Genet Mol Lab, NIH, Bldg 6B,Room 3B-308, Bethesda, MD 20892 USA. NR 42 TC 9 Z9 9 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 371 BP 207 EP 218 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24T UT WOS:000188419500015 PM 14712702 ER PT J AU Komissarova, N Kireeva, ML Becker, J Sidorenkov, I Kashlev, M AF Komissarova, N Kireeva, ML Becker, J Sidorenkov, I Kashlev, M TI Engineering of elongation complexes of bacterial and yeast RNA polymerases SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID TRANSCRIPT CLEAVAGE FACTORS; ESCHERICHIA-COLI; DNA HYBRID; TERNARY COMPLEXES; NASCENT RNA; PROCESSIVITY; TERMINATION; INITIATION; BUBBLE; MODEL C1 NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Frederick, MD 21702 USA. RP Komissarova, N (reprint author), NCI, Frederick Canc Res & Dev Ctr, Ctr Canc Res, Frederick, MD 21702 USA. NR 25 TC 41 Z9 44 U1 0 U2 5 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 371 BP 233 EP 251 PG 19 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24T UT WOS:000188419500017 PM 14712704 ER PT J AU West, KL Postnikov, YV Birger, Y Bustin, M AF West, KL Postnikov, YV Birger, Y Bustin, M TI Chromatin decompaction method by HMGN proteins SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID NUCLEOSOMAL BINDING DOMAIN; MOBILITY GROUP PROTEIN-14; CORE HISTONE ACETYLATION; CHROMOSOMAL-PROTEINS; TRANSCRIBED GENES; NASCENT CHROMATIN; GLOBIN CHROMATIN; TAIL DOMAINS; LINKER DNA; HMG-17 C1 NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP West, KL (reprint author), NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RI Bustin, Michael/G-6155-2015 NR 61 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 371 BP 521 EP 536 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24T UT WOS:000188419500039 PM 14712726 ER PT J AU Walter, W Kireeva, ML Tchernajenko, V Kashlev, M Studitsky, VM AF Walter, W Kireeva, ML Tchernajenko, V Kashlev, M Studitsky, VM TI Assay of the fate of the nucleosome during transcription by RNA polymerase II SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID DNA HYBRID; POSITIONED NUCLEOSOMES; ELONGATION; TEMPLATES; PROCESSIVITY; INITIATION; CHROMATIN C1 Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA. NCI, Ctr Canc Res, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Walter, W (reprint author), Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA. RI Studitsky, Vasily/A-9382-2014 FU NIGMS NIH HHS [GM58650] NR 20 TC 8 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 371 BP 564 EP 577 PG 14 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24T UT WOS:000188419500042 PM 14712729 ER PT J AU Murphy, H Cashel, M AF Murphy, H Cashel, M TI Isolation of RNA polymerase suppressors of a (p)ppGpp deficiency SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID COLI RPOB GENE; ESCHERICHIA-COLI; GUANOSINE TETRAPHOSPHATE; ALARMONE (P)PPGPP; IN-VIVO; PPGPP; PROMOTERS; MUTATIONS; MUTANTS; TRANSCRIPTION C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, H (reprint author), NICHD, Genet Mol Lab, NIH, Bldg 6,Room 3B-314, Bethesda, MD 20892 USA. NR 22 TC 35 Z9 35 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 371 BP 596 EP 601 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24T UT WOS:000188419500044 PM 14712731 ER PT J AU Mortin, MA AF Mortin, MA TI Mutational analysis of drosophila RNA polymerase II SO RNA POLYMERASES AND ASSOCIATED FACTORS, PT D SE METHODS IN ENZYMOLOGY LA English DT Review ID HOMOLOGOUS RECOMBINATION; MELANOGASTER; SUBUNIT; COMPONENTS; SEQUENCE; GENOME; GENES C1 NICHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Mortin, MA (reprint author), NICHD, Genet Mol Lab, NIH, Bldg 6B,Room 3B-331, Bethesda, MD 20892 USA. RI Mortin, Mark/B-4251-2008 NR 21 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2003 VL 371 BP 615 EP 629 PG 15 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BY24T UT WOS:000188419500046 PM 14712733 ER PT S AU Lederhendler, II AF Lederhendler, II BE King, JA Ferris, CF Lederhendler, II TI Introduction - Behavioral neuroscience and childhood mental illness SO ROOTS OF MENTAL ILLNESS IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Editorial Material CT Conference on Roots of Mental Illness in Children CY MAR 15-17, 2003 CL New York, NY SP NY Acad Sci, NIMH, Janssen Pharmaceutica Inc DE childhood mental illness; behavioral neuroscience; imaging; genetics; development ID ATYPICAL DEVELOPMENT; PRIMATE AMYGDALA; SOCIAL-BEHAVIOR; MONKEYS; STRESS; BRAIN; FEAR; PSYCHOPATHOLOGY; EXPERIENCE; EXTINCTION AB Advances in the treatment of mental illness depend, in part, on the elimination of barriers to the use of new basic research findings. Some of the barriers originate in the different research perspectives adopted by clinical and basic researchers. Clinical research is driven by the need to recruit and examine classes of individuals, and so the conceptual framework focuses largely on categories of disorders. Basic researchers, including psychologists and behavioral neuroscientists, investigate fundamental features of behavior such as emotion regulation, attention, or arousal; therefore, disorders are commonly approached from a "dimensional" framework. In the broadest sense dimensions are those features that are common to multiple disorders. Categories are an effort to draw distinctions among disorders. The differences between these frameworks, and the perspectives held among clinicians and basic scientists, are not dichotomous. Many clinicians investigate fundamental aspects of pathophysiology and behavior that apply to multiple disorders, and many basic researchers are developing animal "models" of categorical disorders. It is timely and important to examine these approaches critically, and to work toward formulating perspectives that capture the strengths of each group of researchers so that their common goal of translating research findings into treatments for childhood mental health disorders is strengthened. C1 NIMH, Bethesda, MD 20892 USA. RP Lederhendler, II (reprint author), NIMH, 6001 Execut Blvd,MSC 9637, Bethesda, MD 20892 USA. EM ilu@helix.nih.gov; ilu@helix.nih.gov NR 38 TC 1 Z9 1 U1 29 U2 31 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-478-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1008 BP 1 EP 10 DI 10.1196/ammals.1301.001 PG 10 WC Psychology, Developmental; Multidisciplinary Sciences; Pediatrics; Psychology SC Psychology; Science & Technology - Other Topics; Pediatrics GA BY70S UT WOS:000189443700001 PM 14998867 ER PT S AU Suomi, SJ AF Suomi, SJ BE King, JA Ferris, CF Lederhendler, II TI Gene-environment interactions and the neurobiology of social conflict SO ROOTS OF MENTAL ILLNESS IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Roots of Mental Illness in Children CY MAR 15-17, 2003 CL New York, NY SP NY Acad Sci, NIMH, Janssen Pharmaceutica Inc DE rhesus monkeys; impulsive aggression; 5-HAA; gene-environment interactions ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID MONOAMINE; NONHUMAN PRIMATE MODEL; RHESUS-MONKEYS; SEVERE AGGRESSION; BEHAVIOR; STRESS AB Recent research has disclosed marked individual differences in biobehavioral responses to social conflicts exhibited by rhesus monkeys across the life span. For example, approximately 5-10% of rhesus monkeys growing up in the wild consistently exhibit impulsive and/or inappropriately aggressive responses to mildly stressful situations throughout development; those same individuals also show chronic deficits in their central serotonin metabolism. These characteristic patterns of biobehavioral response emerge early in life and remain remarkably stable from infancy to adulthood. Laboratory studies have demonstrated that although these characteristics are highly heritable, they are also subject to major modification by specific early experiences, particularly those involving early social attachment relationships. Moreover, genetic and early experience factors can interact, often in dramatic fashion. For example, a specific polymorphism in the serotonin transporter gene is associated with deficits in early neurobehavioral functioning and serotonin metabolism, extreme aggression, and excessive alcohol consumption among monkeys who experienced insecure early attachment relationships, but not in monkeys who developed secure attachment relationships with their mothers during infancy. Because daughters tend to develop the same type of attachment relationships with their own offspring that they experienced with their mothers early in life, such early experiences provide a possible nongenetic mechanism for transmitting these patterns to subsequent generations. C1 NICHHD, Comparat Ethol Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Suomi, SJ (reprint author), NICHD, Comparat Ethol Lab, NIH, DHHS, 6705 Rockledge Dr,Suite 8030, Bethesda, MD 20892 USA. EM ss148k@nih.gov NR 27 TC 62 Z9 63 U1 1 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-478-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1008 BP 132 EP 139 DI 10.1196/annals.1301.014 PG 8 WC Psychology, Developmental; Multidisciplinary Sciences; Pediatrics; Psychology SC Psychology; Science & Technology - Other Topics; Pediatrics GA BY70S UT WOS:000189443700013 PM 14998879 ER PT S AU Leibenluft, E Blair, RJR Charney, DS Pine, DS AF Leibenluft, E Blair, RJR Charney, DS Pine, DS BE King, JA Ferris, CF Lederhendler, II TI Irritability in pediatric mania and other childhood psychopathology SO ROOTS OF MENTAL ILLNESS IN CHILDREN SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Roots of Mental Illness in Children CY MAR 15-17, 2003 CL New York, NY SP NY Acad Sci, NIMH, Janssen Pharmaceutica Inc DE irritability; childhood psychopathology; reactive aggression; childhood mania; bipolar disorder (BPD) ID HOSPITALIZED AGGRESSIVE-CHILDREN; DEFICIT HYPERACTIVITY DISORDER; POSITRON-EMISSION-TOMOGRAPHY; BIPOLAR DISORDER; CONDUCT DISORDER; PERSONALITY-DISORDERS; FACIAL EXPRESSIONS; DOUBLE-BLIND; IMIPRAMINE BINDING; PREFRONTAL CORTEX AB Irritability is an important symptom in childhood psychopathology that has received relatively little research attention. Recent controversy concerning the diagnosis of mania in children has focused attention on how little is known about how to assess irritability in a systematic way, and about its diagnostic associations. For example, subtyping irritability according to course (chronic vs. episodic), precipitants, and family history may facilitate the identification of psychopathology and the study of pathophysiology. While normative and pathologic irritability can be differentiated reliably, the validity of the distinction is unclear. In addition, there is a need for scales designed to measure the severity of irritability in children with mood and anxiety disorders. In order to facilitate research, we propose a definition of irritability from the perspective of affective neuroscience. Because reactive aggression may be a helpful animal model for irritability, we review the neural circuitry mediating this behavior. Behavioral paradigms that evoke frustration, as well as those that assess the ability to inhibit a prepotent motor response, maintain attentional focus, execute response reversal, recognize angry faces, and regulate emotional responses, may be useful in the study of irritability. Examples of such paradigms are described, and the pharmacology of irritability is reviewed briefly. C1 NIMH, Dept Hlth & Human Serv, NIH, Mood & Anxiety Program, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), NIMH, Dept Hlth & Human Serv, NIH, Mood & Anxiety Program, Room 4N-208,10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA. EM LEIBS@MAIL.NIH.GOV NR 108 TC 78 Z9 78 U1 16 U2 28 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-478-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1008 BP 201 EP 218 DI 10.1196/annals.1301.022 PG 18 WC Psychology, Developmental; Multidisciplinary Sciences; Pediatrics; Psychology SC Psychology; Science & Technology - Other Topics; Pediatrics GA BY70S UT WOS:000189443700020 PM 14998886 ER PT S AU Wurtz, RH Sommer, MA AF Wurtz, RH Sommer, MA BE Heywood, CA Milner, AD Blakemore, C TI Identifying corollary discharges for movement in the primate brain SO ROOTS OF VISUAL AWARENESS: A FESTSCHRIFT IN HONOR OF ALAN COWEY SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Conference on the Roots of Visual Awareness CY SEP, 2002 CL OXFORD, ENGLAND ID FRONTAL EYE FIELD; MONKEY SUPERIOR COLLICULUS; ORIENTING GAZE SHIFTS; HEAD-FREE CAT; RHESUS-MONKEY; TECTORETICULOSPINAL SYSTEM; VISUAL-CORTEX; REVERSIBLE INACTIVATION; VISUOMOTOR FUNCTIONS; CENTRAL THALAMUS AB The brain keeps track of the movements it makes so as to process sensory input accurately and coordinate complex movements gracefully. In this chapter we review the brain's strategies for keeping track of fast, saccadic eye movements. One way it does this is by monitoring copies of saccadic motor commands, or corollary discharges. It has been difficult to identify corollary discharge signals in the primate brain, although in some studies the influence of corollary discharge, for example on visual processing, has been found. We propose four criteria for identifying corollary discharge signals in primate brain based on our experiences studying a pathway from superior colliculus, in the brainstem, through mediodorsal thalamus to frontal eye field, in the prefrontal cortex. First, the signals must originate from a brain structure involved in generating movements. Second, they must begin just prior to movements and represent spatial attributes of the movements. Third, eliminating the signals should not impair movements in simple tasks not requiring corollary discharge. Fourth, eliminating the signals should, however, disrupt movements in tasks that require corollary discharge, such as a double-step task in which the monkey must keep track of one saccade in order to correctly generate another. Applying these criteria to the pathway from superior colliculus to frontal eye field, we concluded that it does indeed convey corollary discharge signals. The extent to which cerebral cortex actually uses these signals, particularly in the realm of sensory perception, remains unknown pending further studies. Moreover, many other ascending pathways from brainstem to cortex remain to be explored in behaving monkeys, and some of these, too, may carry corollary discharge signals. C1 NEI, NIH, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Wurtz, RH (reprint author), NEI, NIH, Sensorimotor Res Lab, Bldg 49,Room 2A50,MSC 4435,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 63 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50978-X J9 PROG BRAIN RES PY 2003 VL 144 BP 47 EP 60 DI 10.1016/S0079-6123(03)14400-3 PG 14 WC Neurosciences SC Neurosciences & Neurology GA BY05P UT WOS:000187421400003 ER PT S AU Pessoa, L Ungerleider, LG AF Pessoa, L Ungerleider, LG BE Heywood, CA Milner, AD Blakemore, C TI Neuroimaging studies of attention and the processing of emotion-laden stimuli SO ROOTS OF VISUAL AWARENESS: A FESTSCHRIFT IN HONOR OF ALAN COWEY SE PROGRESS IN BRAIN RESEARCH LA English DT Article; Proceedings Paper CT Conference on the Roots of Visual Awareness CY SEP, 2002 CL OXFORD, ENGLAND ID HUMAN EXTRASTRIATE CORTEX; EVENT-RELATED FMRI; VISUAL-ATTENTION; SELECTIVE ATTENTION; FACIAL EXPRESSIONS; STRIATE CORTEX; HUMAN AMYGDALA; PARIETAL PATIENT; RECEPTIVE-FIELD; PERCEPTUAL LOAD AB Because the processing capacity of the visual system is limited, selective attention to one part of the visual field comes at the cost of neglecting other parts. In this paper, we review evidence from single-cell studies in monkeys and functional magnetic resonance imaging (fMRI) studies in humans for neural competition and how competition is biased by, attention. We Suggest that, at the neural level, an important consequence of attention is to enhance the influence of behaviorally relevant stimuli at the expense of irrelevant ones, providing a mechanism for the filtering of distracting information in Cluttered visual scenes. Psychophysical evidence suggests that processing outside the focus of attention is attenuated and may be even eliminated under some conditions. A major exception to the critical role of attention may be in the neural processing of emotion-laden stimuli, which are reported to be processed automatically, namely. without attention. Contrary to this prevailing view, in a recent study we found that all brain regions responding differentially to faces with emotional content, including the amygdala, did so only when sufficient resources were available to process those faces. After reviewing our findings, we discuss their implications, in particular (1) how emotional stimuli can bias competition for processing resources; (2) the source of the biasing signal for emotional stimuli: (3) how Visual information reaches the amygdala; and finally (4) the relationship between attention and awareness. C1 NIMH, Lab Brain & Cognit, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Pessoa, L (reprint author), NIMH, Lab Brain & Cognit, NIH, Dept Hlth & Human Serv, 49 Convent Dr,Bldg 49,Room 1B80, Bethesda, MD 20892 USA. NR 90 TC 5 Z9 5 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 0-444-50978-X J9 PROG BRAIN RES PY 2003 VL 144 BP 171 EP 182 DI 10.1016/S0079-6123(03)14401-2 PG 12 WC Neurosciences SC Neurosciences & Neurology GA BY05P UT WOS:000187421400012 ER PT J AU Lebowitz, BD Vitiello, B Norquist, GS AF Lebowitz, BD Vitiello, B Norquist, GS TI Approaches to multisite clinical trials. The National Institute of Mental Health Perspective SO SCHIZOPHRENIA BULLETIN LA English DT Article DE clinical effectiveness; public health; NIMH; research strategy ID EFFICACY; CHILDREN; DISORDER AB The Division of Services and Intervention Research of the National Institute of Mental Health (NIMH) utilizes a variety of methodologies and approaches in the development of its clinical trials program. In this article, we describe the need for large multisite trials; the mechanisms for addressing this need; and the various approaches that have been used. In the course of carrying out this initiative, we have created opportunities for the Institute and its trial investigators to receive advice and input from the field. We describe the role and function of the trial coordinating center and NIMH staff. We identify the first steps to be taken in the initiation of a trial and highlight the opportunity for ancillary studies. Finally, we enumerate some of the pitfalls of large clinical trials and discuss measures taken to anticipate and address them. C1 NIMH, Adult & Geriatr Treatment & Prevent Res Branch, Bethesda, MD 20892 USA. NIMH, Child & Adolescent Treatment & Prevent Intervent, Bethesda, MD 20892 USA. NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Lebowitz, BD (reprint author), NIMH, Adult & Geriatr Treatment & Prevent Res Branch, 6001 Execut Blvd,Room 7160,MSC 9635, Bethesda, MD 20892 USA. NR 10 TC 6 Z9 6 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2003 VL 29 IS 1 BP 7 EP 13 PG 7 WC Psychiatry SC Psychiatry GA 701KJ UT WOS:000184166500002 PM 12908657 ER PT J AU Coleman, RL AF Coleman, RL TI Home sweet home SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material AB The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Account series. We hope that mental health professionals-the Bulletin's primary audience-will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex-patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized, and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients with experiences they believe should be shared might encourage these patients to submit their articles to EEI Communications, Schizophrenia Bulletin, First Person Accounts, 66 Canal Center Plaza, Suite 200, Alexandria, VA 22314. C1 NIMH, Bethesda, MD 20892 USA. RP Coleman, RL (reprint author), NIMH, 6001 Execut Blvd,Rm 8184,MSC 9663, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2003 VL 29 IS 2 BP 399 EP 400 PG 2 WC Psychiatry SC Psychiatry GA 728AN UT WOS:000185693200019 PM 14552513 ER PT J AU Maier, W Cornblatt, BA Merikangas, KR AF Maier, W Cornblatt, BA Merikangas, KR TI Transition to schizophrenia and related disorders: Toward a taxonomy of risk SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; vulnerability factors; prodromal symptoms; early recognition; early prevention; treatment strategies ID EARLY INTERVENTION; INITIAL PRODROME; PSYCHOSIS; PREVENTION; CHILDHOOD; ATTENTION; RELATIVES; STEP AB The early detection and prevention of schizophrenia and other psychotic disorders are receiving rapidly growing: attention subsequent to the suggestion that poorer outcome is associated with delayed onset of treatment among patients in their first psychotic episode. Although the first generation of so-called "prodromal" research programs has produced encouraging preliminary results, more information is necessary on the conversion rates from prodromal states to schizophrenia in specific samples. Early recognition and prevention strategies require a new taxonomy that classifies subjects by their status of risk of imminent onset of psychosis. Without additional knowledge of the mechanisms through which particular constellations of vulnerability factors, precursors, and prodromal symptoms predict the onset of schizophrenia, it is difficult to judge the effects of existing programs. In this paper, we discuss three sets. of issues that will need to be resolved before these preventive programs can be implemented into routine care: (1) optimization of predicting the onset of psychotic disorders; (2) development and evaluation of alternative treatment strategies depending on the presenting risk status; and (3) evaluation of costs and benefits of identifying subjects at risk of psychosis/schizophrenia and receiving a specific preventive treatment. C1 Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany. Albert Einstein Coll Med, Bronx, NY 10467 USA. Zucker Hillside Hosp, Glen Oaks, NY USA. Zucker Hillside Hosp, Recognit & Prevent RAP Program, Lake Success, NY USA. Schneider Childrens Hosp, Lake Success, NY USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Maier, W (reprint author), Univ Bonn, Dept Psychiat, Sigmund Freud Str 25, D-53105 Bonn, Germany. EM Wolfgang.Maier@ukb.uni-bonn.de NR 29 TC 15 Z9 16 U1 2 U2 3 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2003 VL 29 IS 4 BP 693 EP 701 PG 9 WC Psychiatry SC Psychiatry GA 772ZT UT WOS:000188873800006 PM 14989407 ER PT J AU Heinssen, RK Cuthbert, BN Breiling, J Colpe, LJ Dolan-Sewell, R AF Heinssen, RK Cuthbert, BN Breiling, J Colpe, LJ Dolan-Sewell, R TI Overcoming barriers to research in early serious mental illness: Issues for future collaboration SO SCHIZOPHRENIA BULLETIN LA English DT Article DE prodrome; schizophrenia; risk factors; methodology ID EPISODE SCHIZOPHRENIA; AFFECTIVE-DISORDER; CLINICAL-TRIALS; SAMPLE-SIZE; PSYCHOSIS; 1ST-EPISODE; DEFICITS; PATHOPHYSIOLOGY; ABNORMALITIES; CONSEQUENCES AB Several methodological barriers impede discovery of early illness pathways in schizophrenia, including small samples, elongated study periods, and failure to integrate procedures and data across prodromal and first episode projects. A compounding factor is the tendency for single-site studies to focus narrowly on schizophrenia risk factors, rather than exploring vulnerability mechanisms that may cut across DSM-IV boundaries. To address these concerns, we discuss the merits of an integrated multisite approach to research that promotes large-scale investigation into the earliest phases of serious mental illness. The distinctive characteristics of this collaborative approach to early serious mental illness research could include (1) subject recruitment across several sites; (2) a broad diagnostic focus; (3) a core clinical and neuroscience assessment protocol; (4) longitudinal evaluation of subjects through a range of outcomes; and (5) an iterative approach to psychopathology research. This model represents a method for exploring prodromal phenotypes, for discovering causal risk mechanisms, and for investigating the biological and environmental interactions that define the early course of several disorders, including schizophrenia, bipolar illness, and borderline personality disorder. This strategy could speed discovery of clinical tools most relevant to the earliest stages of serious mental illness; i.e., better methods of screening, diagnosing, and treating mental disorders before symptoms and impairments solidify into chronic disabilities. C1 NIMH, DMDBA, Psychot Disorders Res Program, Bethesda, MD 20892 USA. NIMH, DMDBA, Adult Psychopathol & Prevent Res Branch, Bethesda, MD 20892 USA. NIMH, DMDBA, Impulse Control & Behav Disorders Program, Bethesda, MD 20892 USA. NIMH, DMDBA, Epidemiol & Risk Factors Program, Bethesda, MD 20892 USA. NIMH, DMDBA, Mood Anxiety & Regulatory Disorders Program, Bethesda, MD 20892 USA. RP Heinssen, RK (reprint author), NIMH, DMDBA, Psychot Disorders Res Program, 6001 Execut Blvd,Room 6181,MSC 9625, Bethesda, MD 20892 USA. EM rheinsse@mail.nih.gov NR 41 TC 11 Z9 11 U1 5 U2 10 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2003 VL 29 IS 4 BP 737 EP 745 PG 9 WC Psychiatry SC Psychiatry GA 772ZT UT WOS:000188873800010 PM 14989411 ER PT J AU Weiner, SK AF Weiner, SK TI First person account: Living with the delusions and effects of schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Article AB The article that follows is part of the Schizophrenia Bulletin's ongoing First Person Account series. We hope that mental health professionals-the Bulletin's primary audience-will take this opportunity to learn about the issues and difficulties confronted by consumers of mental health care. In addition, we hope that these accounts will give patients and families a better sense of not being alone in confronting the problems that can be anticipated by persons with serious emotional difficulties. We welcome other contributions from patients, ex-patients, or family members. Our major editorial requirement is that such contributions be clearly written and organized, and that a novel or unique aspect of schizophrenia be described, with special emphasis on points that will be important for professionals. Clinicians who see articulate patients with experiences they believe should be shared might encourage these patients to submit their articles to Schizophrenia Bulletin, First Person Accounts, EEI Communications, 66 Canal Center Plaza, Suite 200, Alexandria, VA 22314.-The Editors. C1 NIMH, Bethesda, MD 20892 USA. RP Weiner, SK (reprint author), NIMH, 6001 Execut Blvd,Rm 8184, Bethesda, MD 20892 USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PY 2003 VL 29 IS 4 BP 877 EP 879 PG 3 WC Psychiatry SC Psychiatry GA 772ZT UT WOS:000188873800021 PM 14989422 ER PT J AU Ringeisen, H Henderson, K Hoagwood, K AF Ringeisen, H Henderson, K Hoagwood, K TI Context matters: Schools and the "research to practice gap" in children's mental health SO SCHOOL PSYCHOLOGY REVIEW LA English DT Article ID ADOLESCENT PSYCHOTHERAPY; DRUG-ABUSE; CARE; SYSTEMS; PREVENTION; POPULATION; PSYCHOLOGY; DISORDERS; FRAMEWORK; OUTCOMES AB Reviews have identified mental health interventions that are relevant to schools; unfortunately, this research pays insufficient attention to the school context. Several aspects of school context likely influence the ability of schools to change current practices or adopt new ones. Relying on an organizational framework, a three-level model of school context particularly relevant to the delivery of mental health interventions: (a) individual, (b) organizational, and (c) state or national-level factors are described. This article argues that effective school-based mental health care will result from the marriage of system reform efforts, capacity building, and the delivery of empirically driven intervention strategies. C1 NIMH, Div Serv & Intervent Res, Bethesda, MD USA. US Dept Educ, Off Special Educ Programs, Mclean, VA USA. Columbia Univ, New York State Dept Mental Hlth, New York, NY 10027 USA. RP Ringeisen, H (reprint author), 6001 Execut Blvd,Rm 7146 MSE 9631, Bethesda, MD 20892 USA. NR 72 TC 102 Z9 102 U1 3 U2 9 PU NATL ASSN SCHOOL PSYCHOLOGISTS PI BETHESDA PA 4340 EAST WEST HWY, STE 402, BETHESDA, MD 20814 USA SN 0279-6015 J9 SCHOOL PSYCHOL REV JI Sch. Psychol. Rev. PY 2003 VL 32 IS 2 BP 153 EP 168 PG 16 WC Psychology, Educational SC Psychology GA 707VH UT WOS:000184530200001 ER PT J AU Kurosaka, K Kobayashi, Y AF Kurosaka, K Kobayashi, Y TI Macrophage responses during phagocytosis of apoptotic cells and their regulatory mechanism SO SEIKAGAKU LA Japanese DT Article ID PROINFLAMMATORY CYTOKINES; BETA; RECOGNITION; CLEARANCE; PROTEASES; RECEPTOR C1 NCI, Mol Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Toho Univ, Fac Sci, Dept Biomol Sci, Funabashi, Chiba 2748510, Japan. NR 15 TC 0 Z9 0 U1 0 U2 0 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0037-1017 J9 SEIKAGAKU JI Seikagaku PD JAN PY 2003 VL 75 IS 1 BP 59 EP 62 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 642ZT UT WOS:000180838000009 PM 12645136 ER PT S AU Kashyap, V Borgida, A AF Kashyap, V Borgida, A BE Fensel, D Sycara, K Mylopoulos, J TI Representing the UML (R) semantic network using OWL (Or "What's in a semantic web link?") SO SEMANTIC WEB - ISWC 2003 SE LECTURE NOTES IN COMPUTER SCIENCE LA English DT Article; Proceedings Paper CT 2nd International Semantic Web Conference CY OCT 20-23, 2003 CL SANIBEL, FLORIDA SP ist, DAML, network inference, Springer Sci Online, DERI, Tontotext, Semantic Web Enabled Serv, AKT, Knowledge Management Solut, ENIGMATEC Corp, Elsevier, SWAP, ESPERONTO, Nokia, MONDECA, France Telecom R&D ID SYSTEM; UMLS AB The Semantic Network, a component of the Unified Medical Language System (UMLS), describes core biomedical knowledge consisting of semantic types and relationships. It is a well established, semi-formal ontology in widespread use for over a decade. We expected to "publish" this ontology on the Semantic Web, using OWL, with relatively little effort. However, we ran into a number of problems concerning alternative interpretations of the SN notation and the inability to express some of the interpretations in OWL. We detail these problems, as a cautionary tale to others planning to publish pre-existing ontologies on the Semantic Web, as a list of issues to consider when describing formally concepts in any ontology, and as a collection of criteria for evaluating alternative representations, which could form part of a methodology of ontology development. C1 Natl Lib Med, LHCNBC, Bethesda, MD 20894 USA. Rutgers State Univ, Dept Comp Sci, New Brunswick, NJ 08903 USA. RP Kashyap, V (reprint author), Natl Lib Med, LHCNBC, 8600 Rockville Pike, Bethesda, MD 20894 USA. NR 21 TC 12 Z9 12 U1 0 U2 2 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-20362-1 J9 LECT NOTES COMPUT SC PY 2003 VL 2870 BP 1 EP 16 PG 16 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Software Engineering; Computer Science, Theory & Methods SC Computer Science GA BY18Y UT WOS:000188096900001 ER PT J AU Barrett, J AF Barrett, J TI Allogeneic stem cell transplantation for chronic myeloid leukemia SO SEMINARS IN HEMATOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; TOTAL-BODY IRRADIATION; CYTOTOXIC T-LYMPHOCYTES; PRETRANSPLANT INTERFERON-ALPHA; DONOR LEUKOCYTE TRANSFUSIONS; LINEAGE-SPECIFIC CHIMERISM; MINIMAL RESIDUAL DISEASE; SINGLE-CENTER EXPERIENCE C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bldg 10 Room 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 98 TC 32 Z9 40 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD JAN PY 2003 VL 40 IS 1 BP 59 EP 71 DI 10.1053/shem.2003.50003 PG 13 WC Hematology SC Hematology GA 641RQ UT WOS:000180760000007 PM 12563612 ER PT J AU Hardick, J Hsieh, YH Tulloch, S Kus, J Tawes, J Gaydos, CA AF Hardick, J Hsieh, YH Tulloch, S Kus, J Tawes, J Gaydos, CA TI Surveillance of Chlamydia trachomatis and Neisseria gonorrhoeae infections in women in detention in Baltimore, Maryland SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; LIGASE CHAIN-REACTION; REACTION ASSAY; UNITED-STATES; JAILED WOMEN; URINE; HEALTH; EPIDEMIOLOGY; PREVALENCE AB Background: In conjunction with a program to expand syphilis and HIV infection services, women were also offered screening for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) during intake at the Baltimore Women's Detention Center. Goal: The goal was to assess the effectiveness of a routine screening program for CT and GC in women in a detention setting. The association among infection, race, and area of residence was also explored. Study Design: CT and GC prevalences were determined and analyzed by demographic data, including zip code, for 1858 women enrolled over a 48-week period. Informed consent was obtained, and infections were detected with use of urine samples tested by ligase chain reaction. Results: Overall, the population had prevalence rates of 5.9% (109/ 1858) and 3.4% (63/1858) for CT and GC respectively. Among whites, CT and GC prevalences were 9.0% (29/323) and 8.7% (28/323), respectively. Among African Americans the prevalence rates were 5.1% (77/1510) and 2.3% (34/1510) for CT and GC, respectively. White women < 25 years of age were associated with the highest CT and GC prevalences, at 20.0% (13/65) and 13.9% (9/65), respectively. African American women <25 years of age also were associated with the highest CT and GC prevalences, at 13.9% (24/173) and 5.8% (10/173), respectively. Multivariate analysis of risk factors and demographic data indicated that ages <25 years and 25 to 34 years, white race, and certain zip codes of residence were risk factors for infection. Conclusion: This study illustrated that urine-based screening for CT and GC is feasible in detention settings and can be productive in high-prevalence areas. Geographic analysis demonstrated no definitive relationship among race, infection, and area of residence, although it did demonstrate clustering of infected individuals and could be useful in future interventions. These findings demonstrated the need for implementing screening programs for sexually transmitted infections in detention centers. C1 Johns Hopkins Univ, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD USA. RP Hardick, J (reprint author), Johns Hopkins Univ, Ross Bldg,Room 1147,720 Rutland Ave, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010 NR 28 TC 20 Z9 21 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JAN PY 2003 VL 30 IS 1 BP 64 EP 70 DI 10.1097/00007435-200301000-00013 PG 7 WC Infectious Diseases SC Infectious Diseases GA 633NN UT WOS:000180289500013 PM 12514445 ER PT J AU Cai, HX Chadwick, R AF Cai, HX Chadwick, R TI Radial structure of traveling waves in the inner ear SO SIAM JOURNAL ON APPLIED MATHEMATICS LA English DT Article DE cochlear mechanics; traveling wave; fluid-solid interaction; radial modes ID GUINEA-PIG COCHLEA; BASILAR-MEMBRANE; MODEL; MOTION; MICROMECHANICS; MECHANICS; ORGAN; VIBRATIONS; FLUID; CORTI AB We develop a hybrid approach for modeling the cochlea, in which we let the WKB method determine the axial propagation of waves and restrict the numerics to transverse planes, where we solve a fluid-solid interaction eigenvalue problem. The cochlear fluid is treated as viscous and incompressible. Viscous effects are confined to oscillatory boundary layers and the thin gap between the reticular lamina (RL) and the lower surface of the tectorial membrane (TM). Our model includes axial fluid coupling and also axial elastic coupling via a basilar membrane (BM) modeled as an orthotropic clamped plate. Three-dimensional (3D) flow is solved in two-dimensional (2D) domains, with interactions with 2D elastic domains representing the organ of Corti (OC) and the TM. The OC contains inhomogeneities representing discrete cellular structures. We have computed the interaction between the BM, TM, OC, and the cochlear fluid to find the complex-valued wavenumber-frequency relation and vibrational modes. The details of the cochlear fluid flow and pressure fields are calculated, along with displacements of the elastic structures. Simulation of passive radial modes in the apical region of a guinea pig cochlea for frequencies less than 1 kHz indicates monophasic vibration of the BM and a synchronous rotation of three rows of outer hair cell stereocilia induced by a shearing motion between the RL and TM. C1 NIDCD, Lab Cellular Biol, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA. RP Cai, HX (reprint author), NIDCD, Lab Cellular Biol, Sect Auditory Mech, NIH, Bethesda, MD 20892 USA. NR 40 TC 10 Z9 10 U1 0 U2 7 PU SIAM PUBLICATIONS PI PHILADELPHIA PA 3600 UNIV CITY SCIENCE CENTER, PHILADELPHIA, PA 19104-2688 USA SN 0036-1399 J9 SIAM J APPL MATH JI SIAM J. Appl. Math. PY 2003 VL 63 IS 4 BP 1105 EP 1120 AR PII S0036139901388957 DI 10.1137/S0036139901388957 PG 16 WC Mathematics, Applied SC Mathematics GA 690BT UT WOS:000183528000001 ER PT S AU Blakely, WF Miller, AC Grace, MB McLeland, CB Luo, L Muderhwa, JM Miner, VL Prasanna, PGS AF Blakely, WF Miller, AC Grace, MB McLeland, CB Luo, L Muderhwa, JM Miner, VL Prasanna, PGS BE Hei, TK Wu, HL TI Radiation biodosimetry: Applications for spaceflight SO SPACE LIFE SCIENCES: BIODOSIMETRY, BIOMARKERS AND LATE STOCHASTIC EFFECTS OF SPACE RADIATION SE ADVANCES IN SPACE RESEARCH LA English DT Article; Proceedings Paper CT World Space Congress CY OCT 10-19, 2002 CL HOUSTON, TEXAS SP Comm Space Res ID EARLY DOSE ASSESSMENT; BLOOD-LYMPHOCYTES; SPACE-FLIGHTS; BIOLOGICAL DOSIMETRY; ASTRONAUTS; EXPRESSION; EXPOSURE; BIOMARKERS; PROPOSAL; STATION AB The multiparametric dosimetry system that we are developing for medical radiological defense applications could be adapted for spaceflight environments. The system complements the internationally accepted personnel dosimeters and cytogenetic analysis of chromosome aberrations, considered the best means of documenting radiation doses for health records. Our system consists of a portable hematology analyzer, molecular biodosimetry using nucleic acid and antigen-based diagnostic equipment, and a dose assessment management software application. A dry-capillary tube reagent-based centrifuge blood cell counter (QBC Autoread Plus, Beckon Dickinson Bioscience) measures peripheral blood lymphocytes and monocytes, which could determine radiation dose based on the kinetics of blood cell depletion. Molecular biomarkers for ionizing radiation exposure (gene expression changes, blood proteins) can be measured in real time using such diagnostic detection technologies as miniaturized nucleic acid sequences and antigen-based biosensors, but they require validation of dose-dependent targets and development of optimized protocols and analysis systems. The Biodosimetry Assessment Tool, a software application, calculates radiation dose based on a patient's physical signs and symptoms and blood cell count analysis. It also annotates location of personnel dosimeters, displays a summary of a patient's dosimetric information to healthcare professionals, and archives the data for further use. These radiation assessment diagnostic technologies can have dual-use applications supporting general medical-related care. Published by Elsevier Science Ltd on behalf of COSPAR. C1 Armed Forces Radiobiol Res Inst, Biol Dosimetry Team, Bethesda, MD 20889 USA. NCI, Mol Pharmacol Branch, Div Canc Treatment, NIH, Bethesda, MD 20892 USA. RP Blakely, WF (reprint author), Armed Forces Radiobiol Res Inst, Biol Dosimetry Team, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. NR 34 TC 28 Z9 31 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI KIDLINGTON PA THE BOULEVARD, LANGFORD LANE,, KIDLINGTON OX5 1GB, OXFORD, ENGLAND SN 0273-1177 J9 ADV SPACE RES PY 2003 VL 31 IS 6 BP 1487 EP 1493 DI 10.1016/S0273-1177(03)00085-1 PG 7 WC Engineering, Aerospace; Astronomy & Astrophysics; Geosciences, Multidisciplinary; Meteorology & Atmospheric Sciences SC Engineering; Astronomy & Astrophysics; Geology; Meteorology & Atmospheric Sciences GA BX38D UT WOS:000185090300001 PM 12971403 ER PT S AU Macho, L Koska, J Ksinantova, L Pacak, K Hoff, T Noskov, VB Grigoriev, AI Vigas, M Kvetnansky, R AF Macho, L Koska, J Ksinantova, L Pacak, K Hoff, T Noskov, VB Grigoriev, AI Vigas, M Kvetnansky, R BE Hei, TK Wu, HL TI The response of endocrine system to stress loads during space flight in human subject SO SPACE LIFE SCIENCES: BIODOSIMETRY, BIOMARKERS AND LATE STOCHASTIC EFFECTS OF SPACE RADIATION SE ADVANCES IN SPACE RESEARCH LA English DT Article; Proceedings Paper CT World Space Congress CY OCT 10-19, 2002 CL HOUSTON, TEXAS SP Comm Space Res ID HORMONAL CHANGES; COSMONAUTS; INSULIN; GLUCOSE; PLASMA; BODY; SPACEFLIGHT AB The responses of endocrine system to the exposure to stress-work load and hormonal changes during oral glucose tolerance tests were studied in the Slovak astronaut before (three weeks before flight), during (on the 4th and the 6th days of space flight), and after space flight (1-3 days and 15-17 days after space flight) on board of space station MIR. Blood samples during the tests were collected via cannula inserted into cubital vein, centrifuged in the special appliance Plasma-03, frozen in Kryogem-03, and at the end of the 8-day space flight transferred to Earth in special container for hormonal analysis. Preflight workload produced an increase of plasma norepinephrine and a moderate elevation of epinephrine levels. Plasma levels of insulin, growth hormone, prolactin and cortisol were not markedly changed immediately or 10 min after the end of work load. The higher increases of plasma growth hormone, prolactin and catecholamine levels were noted after workload during space flight as compared to preflight response. The higher plasma glucose and insulin levels were noted during the oral glucose tolerance test in space flight and also in the post flight period. Plasma epinephrine levels were slightly decreasing during glucose tolerance test; however, plasma norepinephrine levels were not changed. The similar patterns of catecholamine levels during glucose tolerance test were found when compared the preflight, in-flight and post flight values. These data demonstrate the changes of the dynamic responses of endocrine system to stress-work and metabolic loads during space flight in human subject. (C) 2003 COSPAR. Published by Elsevier Science Ltd. All rights reserved. C1 Slovak Acad Sci, Inst Expt Endocrinol, Bratislava 83306, Slovakia. NICHHD, NIH, Bethesda, MD 20892 USA. Russian Acad Sci, State Res Ctr, Inst Biomed Problems, Moscow 123007, Russia. RP Macho, L (reprint author), Slovak Acad Sci, Inst Expt Endocrinol, Vlarska 3, Bratislava 83306, Slovakia. NR 21 TC 15 Z9 20 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI KIDLINGTON PA THE BOULEVARD, LANGFORD LANE,, KIDLINGTON OX5 1GB, OXFORD, ENGLAND SN 0273-1177 J9 ADV SPACE RES PY 2003 VL 31 IS 6 BP 1605 EP 1610 DI 10.1016/S0273-1177(03)00097-8 PG 6 WC Engineering, Aerospace; Astronomy & Astrophysics; Geosciences, Multidisciplinary; Meteorology & Atmospheric Sciences SC Engineering; Astronomy & Astrophysics; Geology; Meteorology & Atmospheric Sciences GA BX38D UT WOS:000185090300014 PM 12971416 ER PT J AU Gibson, AS Baden, DA Lambert, MI Lambert, EV Harley, YXR Hampson, D Russell, VA Noakes, TD AF Gibson, AS Baden, DA Lambert, MI Lambert, EV Harley, YXR Hampson, D Russell, VA Noakes, TD TI The conscious perception of the sensation of fatigue SO SPORTS MEDICINE LA English DT Article ID MAXIMAL OXYGEN-UPTAKE; PERCEIVED EXERTION; MUSCLE FATIGUE; PROLONGED EXERCISE; FACIAL EXPRESSIONS; DYNAMIC EXERCISE; HIGH-INTENSITY; HUMANS; BRAIN; CARBOHYDRATE AB In this review, fatigue is described as a conscious sensation rather than a physiological occurrence. We suggest that the sensation of fatigue is the conscious awareness of changes in subconscious homeostatic control systems, and is derived from a temporal difference between subconscious representations of these homeostatic control systems in neural-networks that are induced by changes in the level of activity. These mismatches are perceived by consciousness-producing structures in the brain as the sensation of fatigue. In this model, fatigue is a complex emotion affected by factors such as motivation and drive, other emotions such as anger and fear, and memory of prior activity. It is not clear whether the origin of the conscious sensation of fatigue is associated with particular localised brain structures, or is the result of electrophysiological synchronisation of entire brain activity. C1 NINDS, Human Motor Control Unit, NIH, Bethesda, MD 20892 USA. Univ Cape Town, Dept Human Biol, Res Unit Exercise Sci & Sports Med, ZA-7925 Cape Town, South Africa. Univ Southampton, Dept Psychol, Southampton SO9 5NH, Hants, England. RP Gibson, AS (reprint author), Univ Cape Town, SSISA, Dept Human Biol, Res Unit Exercise Sci & Sports Med, ZA-7725 Newlands, South Africa. OI Lambert, Michael/0000-0001-8979-1504 NR 73 TC 91 Z9 101 U1 6 U2 18 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0112-1642 J9 SPORTS MED JI Sports Med. PY 2003 VL 33 IS 3 BP 167 EP 176 PG 10 WC Sport Sciences SC Sport Sciences GA 668VH UT WOS:000182313500001 PM 12656638 ER PT J AU Proschan, MA AF Proschan, MA TI The geometry of two-stage tests SO STATISTICA SINICA LA English DT Article DE double sampling; type I error rate; p-value; positive quadrant tests ID ADAPTIVE INTERIM ANALYSES; SAMPLE-SIZE; CLINICAL-TRIALS; DESIGNS AB Sample size calculations require specification of the treatment effect, but what if this is not known? Two-stage tests use the first stage to estimate the treatment effect and modify the sample size accordingly. The purpose of this paper is to unify the theory of two-stage testing based on treatment effect. The conditional error function approach of Proschan and Hunsberger (1995) is shown to be a useful way to evaluate the properties of any two-stage test. The connection between two-stage tests and positive quadrant tests is exploited to motivate certain conditional error functions. C1 NHLBI, Off Biostat Res, Rockledge Ctr 2, Bethesda, MD 20892 USA. RP Proschan, MA (reprint author), NHLBI, Off Biostat Res, Rockledge Ctr 2, 6701 Rockledge Dr,MSC 7938,Room 8222, Bethesda, MD 20892 USA. NR 12 TC 9 Z9 9 U1 0 U2 0 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JAN PY 2003 VL 13 IS 1 BP 163 EP 177 PG 15 WC Statistics & Probability SC Mathematics GA 651HC UT WOS:000181313600010 ER PT J AU Chen, SS Revoltella, RP Papini, S Michelini, M Fitzgerald, W Zimmerberg, J Margolis, L AF Chen, SS Revoltella, RP Papini, S Michelini, M Fitzgerald, W Zimmerberg, J Margolis, L TI Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems SO STEM CELLS LA English DT Article DE embryonic stem cell; collagen matrix; three-dimensional structure ID COLONY-STIMULATING FACTOR; GRANULOCYTE-MACROPHAGE CSF; CENTRAL-NERVOUS-SYSTEM; IN-VITRO; NEURAL PRECURSORS; ES CELLS; DOPAMINERGIC-NEURONS; BETA-TUBULIN; TUMOR PROGRESSION; GM-CSF AB In the course of normal embryogenesis, embryonic stem (ES) cells differentiate along different lineages in the context of complex three-dimensional (3D) tissue structures. In order to study this phenomenon in vitro under controlled conditions, 3D culture systems are necessary. Here, we studied in vitro differentiation of rhesus monkey ES cells in 3D collagen matrixes (collagen gels and porous collagen sponges). Differentiation of ES cells in these 3D systems was different from that in monolayers. ES cells differentiated in collagen matrixes into neural, epithelial, and endothelial lineages. The abilities of ES cells to form various structures in two chemically similar but topologically different matrixes were different. In particular, in collagen gels ES cells formed gland-like circular structures, whereas in collagen sponges ES cells were scattered through the matrix or formed aggregates. Soluble factors produced by feeder cells or added to the culture medium facilitated ES cell differentiation into particular lineages. Coculture with fibroblasts in collagen gel facilitated ES cell differentiation into cells of a neural lineage expressing nestin, neural cell adhesion molecule, and class III beta-tubulin. In collagen sponges, keratinocytes facilitated ES cell differentiation into cells of an endothelial lineage expressing factor VIII. Exogenous granulocyte-macrophage colony-stimulating factor further enhanced endothelial differentiation. Thus, both soluble factors and the type of extracellular matrix seem to be critical in directing differentiation of ES cells and the formation of tissue-like structures. Three-dimensional culture systems are a valuable tool for studying the mechanisms of these phenomena. C1 NICHD, NASA, NIH, Ctr 3 Dimens Tissue Culture,Lab Cellular & Mol Bi, Bethesda, MD 20892 USA. CNR, Inst Biomed Technol, Unit Immunobiol & Cell Differentiat, I-56100 Pisa, Italy. RP Margolis, L (reprint author), NICHD, NASA, NIH, Ctr 3 Dimens Tissue Culture,Lab Cellular & Mol Bi, Bethesda, MD 20892 USA. NR 56 TC 58 Z9 65 U1 0 U2 6 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2003 VL 21 IS 3 BP 281 EP 295 DI 10.1634/stemcells.21-3-281 PG 15 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 683CK UT WOS:000183129600005 PM 12743323 ER PT J AU Akel, S Petrow-Sadowski, C Laughlin, MJ Ruscetti, FW AF Akel, S Petrow-Sadowski, C Laughlin, MJ Ruscetti, FW TI Neutralization of autocrine transforming growth factor-beta in human cord blood CD34(+)CD38(-)Lin(-) cells promotes stem-cell-factor-mediated erythropoietin-independent early erythroid progenitor development and reduces terminal differentiation SO STEM CELLS LA English DT Article DE transforming growthfactor-beta 1; serum free; autocrine regulation; erythropoiesis; anti-TGF-beta ID HUMAN HEMATOPOIETIC PROGENITORS; HUMAN BONE-MARROW; HUMAN MAST-CELLS; TGF-BETA; C-KIT; STEM/PROGENITOR CELLS; GROWTH-FACTOR-BETA-1; PROLIFERATION; FACTOR-BETA-1; PURIFICATION AB Transforming growth factor (TGF)-beta1 exerts autocrine and paracrine effects on hematopoiesis. Here, we have attempted to evaluate the effect of endogenous TGF-beta1 on early erythroid development from primitive human hematopoietic stem cells (HSCs) and to assess the effects of TGF-beta1 on different phases of erythropoiesis. Cord blood CD34(+)CD38(-) lineage-marker-negative (Lin(-)) cells were cultured in serum-free conditions using various combinations of stem cell factor (SCF), erythropoietin (Epo), and TGF-beta-neutralizing antibody. Generation of erythroid progenitors was assessed using colony assay and flow cytometry. Terminal erythroid differentiation was examined when SCF/Epo-stimulated cells were recultured in the presence of Epo with and without TGF-beta1. Anti-TGF-beta augmented the proliferation of CD34(+)CD38(-)Lin(-) cells (day 21) in SCF-stimulated (6.4-fold +/- 1.5-fold) and SCF/Epo-stimulated (2.9-fold +/- 1.2-fold) cultures. Cells stimulated by SCF/Epo underwent similar levels of erythroid differentiation with and without anti-TGF-beta. While SCF alone stimulated the production of tryptase-positive mast cells, cells stimulated by SCF/anti-TGF-beta were predominantly erythroid (CD36(+)CD14(-) and glycophorin A positive). A distinct expansion of erythroid progenitors (CD34(+)CD36(+)CD14(-)) with the potential to form erythroid colonies was seen, revealing early Epo-independent erythroid development. In contrast, the kinetics of erythroid progenitor generation from primitive HSCs indicate that TGF-beta1 is not inhibitory in late erythropoiesis, but it accelerated the conversion of large BFU-E into colony-forming units-erythroid. Finally, TGF-beta1 accelerated Epo-induced terminal erythroid differentiation and resulted in a greater level of enucleation (22% +/- 6% versus 7% +/- 3%) in serum-free conditions. Serum addition stimulated enucleation (54% +/- 18%), which was lower (26% +/- 14%) with anti-TGF-beta, suggesting that optimal erythroid enucleation is Epo dependent, requiring serum factors including TGF-beta1. C1 NCI, Ctr Canc Res, Basic Res Lab, Leukocyte Biol Sect, Frederick, MD 21702 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. Case Western Reserve Univ, Ireland Canc Ctr, Allogene Transplant Program, Cleveland, OH 44106 USA. RP Ruscetti, FW (reprint author), NCI, Ctr Canc Res, Basic Res Lab, Leukocyte Biol Sect, Bldg 567,Room 254, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 50 TC 25 Z9 29 U1 0 U2 1 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2003 VL 21 IS 5 BP 557 EP 567 DI 10.1634/stemcells.21-5-557 PG 11 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 719QG UT WOS:000185214500006 PM 12968110 ER PT J AU Luo, YQ Cai, JG Ginis, I Sun, YY Lee, SL Yu, SX Hoke, A Rao, M AF Luo, YQ Cai, JG Ginis, I Sun, YY Lee, SL Yu, SX Hoke, A Rao, M TI Designing, testing, and validating a focused stem cell microarray for characterization of neural stem cells and progenitor cells SO STEM CELLS LA English DT Article DE embryonic stem cells; neural stem cells; focus array; microarray; functional genomics ID SPINAL-CORD; GENE; EMBRYO; PRECURSORS; CANCER; CNS AB Fetal neural stem cells (NSCs) have received great attention not only for their roles in normal development but also for their potential use in the treatment of neurodegenerative disorders. To develop a robust method of assessing the state of stem cells, we have designed, tested, and validated a rodent NSC array. This array consists of 260 genes that include cell type-specific markers for embryonic stem (ES) cells and neural progenitor cells as well as growth factors, cell cycle-related genes, and extracellular matrix molecules known to regulate NSC biology. The 500-bp polymerase chain reaction products amplified and validated by using gene-specific primers were arrayed along with positive controls. Blanks were included for quality control, and some genes were arrayed in duplicate. No cross-hybridization was detected. The quality of the arrays and their sensitivity were also examined by using probes prepared by conventional reverse transcriptase or by using amplified probes prepared by linear polymerase replication (LPR). Both methods showed good reproducibility, and probes prepared by LPR labeling appeared to detect expression of a larger proportion of expressed genes. Expression detected by either method could be verified by RT-PCR with high reproducibility. Using these stem cell chips, we have profiled liver, ES, and neural cells. The cell types could be readily distinguished from each other. Nine markers specific to mouse ES cells and 17 markers found in neural cells were verified as robust markers of the stem cell state. Thus, this focused neural stem array provides a convenient and useful tool for detection and assessment of NSCs and progenitor cells and can reliably distinguish them from other cell populations. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21224 USA. SuperArray Biosci Corp, Frederick, MD USA. NIA, Gerontol Res Ctr, Neurosci Lab, Baltimore, MD 21224 USA. RP Rao, M (reprint author), Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21224 USA. OI Hoke, Ahmet/0000-0003-1215-3373 NR 22 TC 20 Z9 21 U1 0 U2 2 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2003 VL 21 IS 5 BP 575 EP 587 DI 10.1634/stemcells.21-5-575 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 719QG UT WOS:000185214500008 PM 12968112 ER PT J AU Zeng, XM Chen, J Sanchez, JF Coggiano, M Dillon-Carter, O Petersen, J Freed, WJ AF Zeng, XM Chen, J Sanchez, JF Coggiano, M Dillon-Carter, O Petersen, J Freed, WJ TI Stable expression of hrGFP by mouse embryonic stem cells: Promoter activity in the undifferentiated state and during dopaminergic neural differentiation SO STEM CELLS LA English DT Article DE embryonic stem cells; promoter; hrGFP; neural differentiation; nestin; TH ID ES CELLS; TYROSINE-HYDROXYLASE; TRANSGENE EXPRESSION; NERVOUS-SYSTEM; GLIAL-CELLS; IN-VITRO; NEURONS; GENES; CNS; PROGENITORS AB Three promoters, cellular polypeptide chain elongation factor 1 alpha (EF1), cytomegalovirus (CMV), and Rous sarcoma virus (RSV) were examined for stable transgene expression, in mouse embryonic stem (ES) cells and their progeny during dopaminergic neural differentiation. In undifferentiated ES cells the EF1 promoter was highly effective, while CMV had moderate activity. After 3 months in culture, expression of humanized renilla green fluorescent protein (hrGFP) was unchanged for the EF1 promoter and decreased for CMV. At the nestin-positive stage of differentiation, hrGFP and nestin were colocalized in about 20% of cells for EF1, in contrast to 80% of cells for the CMV promoter. In tyrosine hydroxylase (TH)-positive neurons neither the EF1 nor CMV promoter were effective. The RSV promoter was inactive in undifferentiated, nestin-positive, and TH-positive cells. Thus, EF1 and CMV are effective promoters for transgene expression in undifferentiated ES cells and nestin-positive neural precursors. C1 NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Zeng, XM (reprint author), NIDA, Dev & Plast Sect, Cellular Neurobiol Res Branch, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 53 Z9 53 U1 0 U2 0 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2003 VL 21 IS 6 BP 647 EP 653 DI 10.1634/stemcells.21-6-647 PG 7 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 737BB UT WOS:000186207600004 PM 14595124 ER PT J AU Tuli, R Tuli, S Nandi, S Wang, ML Alexander, PG Haleem-Smith, H Hozack, WJ Manner, PA Danielson, KG Tuan, RS AF Tuli, R Tuli, S Nandi, S Wang, ML Alexander, PG Haleem-Smith, H Hozack, WJ Manner, PA Danielson, KG Tuan, RS TI Characterization of multipotential mesenchymal progenitor cells derived from human trabecular bone SO STEM CELLS LA English DT Article DE mesenchymal progenitor cell; chondrogenesis; osteogenesis; adipogenesis; tissue engineering ID MARROW STROMAL CELLS; STEM-CELLS; IN-VITRO; CHONDROGENIC DIFFERENTIATION; TELOMERASE EXPRESSION; ALKALINE-PHOSPHATASE; MONOCLONAL-ANTIBODY; INVITRO; ADHESION; CULTURE AB The in vitro culture of human trabecular bone-derived cells has served as a useful system for the investigation of the biology of osteoblasts. The recent discovery in our laboratory of the multilineage mesenchymal differentiation potential of cells derived from collagenase-treated human trabecular bone fragments has prompted further interest in view of the potential application of mesenchymal progenitor cells (MPCs) in the repair and regeneration of tissue damaged by disease or trauma. Similar to human MPCs derived from bone marrow, a clearer understanding of the variability associated with obtaining these bone-derived cells is required in order to optimize the design and execution of applicable studies. In this study, we have identified the presence of a CD73(+), STRO-1(+), CD105(+), CD34(-), CD45(-), CD144(-) cell population resident within collagenase-treated, culture-processed bone fragments, which upon migration established a homogeneous population of MPCs. Additionally, we have introduced a system of culturing these MPCs that best supports and maintains their optimal differentiation potential during long-term culture expansion. When cultured as described, the trabecular bone-derived cells display stem cell-like capabilities, characterized by a stable undifferentiated phenotype as well as the ability to proliferate extensively while retaining the potential to differentiate along the osteoblastic, adipocytic, and chondrocytic lineages, even when maintained in long-term in vitro culture. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. George Washington Univ, Dept Orthopaed Surg, Washington, DC USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Dept Hlth & Human Serv, Bldg 50,Room 1503,50 S Dr,MSC 8022, Bethesda, MD 20892 USA. NR 40 TC 185 Z9 198 U1 0 U2 15 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PY 2003 VL 21 IS 6 BP 681 EP 693 DI 10.1634/stemcells.21-6-681 PG 13 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 737BB UT WOS:000186207600008 PM 14595128 ER PT S AU Antani, S Long, LR Thoma, GR Lee, DJ AF Antani, S Long, LR Thoma, GR Lee, DJ BE Yeung, MM Lienhart, RW Li, CS TI Evaluation of shape indexing methods for content-based retrieval of x-ray images SO STORAGE AND RETRIEVAL FOR MEDIA DATABASES 2003 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Storage and Retrieval for Media Databases 2003 CY JAN 22-23, 2003 CL SANTA CLARA, CA SP Soc Imaging Sci & Technol, SPIE DE content-based image retrieval; medical image databases; shape representation; performance evaluation ID PLANAR CURVES; DATABASES; REPRESENTATION; SCALE; RECOGNITION; MULTISCALE AB Efficient content-based image retrieval of biomedical images is a challenging problem of growing research interest. Feature representation algorithms used in indexing medical images on the pathology of interest have to address conflicting goals of reducing feature dimensionality while retaining important and often subtle biomedical features. At the Lister Hill National Center for Biomedical Communications, a R&D division of the National Library of Medicine, we are developing a content-based image retrieval system for digitized images of a collection of 17,000 cervical and lumbar x-rays taken as a part of the second National Health and Nutrition Examination Survey (NHANES II). Shape is the only feature that effectively describes various pathologies identified by medical experts as being consistently and reliably found in the image collection. In order to determine if the state of the art in shape representation methods is suitable for this application, we have evaluated representative algorithms selected from the literature. The algorithms were tested on a subset of 250 vertebral shapes. In this paper we present the requirements of an ideal algorithm, define the evaluation criteria, and present the results and our analysis of the evaluation. We observe that while the shape methods perform well on visual inspection of the overall shape boundaries, they fall short in meeting the needs of determining similarity between the vertebral shapes based on the pathology. C1 Natl Lib Med, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. RP Antani, S (reprint author), Natl Lib Med, Commun Engn Branch, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD 20894 USA. OI Antani, Sameer/0000-0002-0040-1387 NR 26 TC 8 Z9 8 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-4821-4 J9 P SOC PHOTO-OPT INS PY 2003 VL 5021 BP 405 EP 416 DI 10.1117/12.476289 PG 12 WC Computer Science, Information Systems; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BW41C UT WOS:000181923900039 ER PT J AU Wattigney, WA Croft, JB Mensah, GA Alberts, MJ Shephard, TJ Gorelick, PB Nilasena, DS Hess, DC Walker, MD Hanley, DF Shwayder, P Girgus, M Neff, LJ Williams, JE LaBarthe, DR Collins, JL AF Wattigney, WA Croft, JB Mensah, GA Alberts, MJ Shephard, TJ Gorelick, PB Nilasena, DS Hess, DC Walker, MD Hanley, DF Shwayder, P Girgus, M Neff, LJ Williams, JE LaBarthe, DR Collins, JL TI Establishing data elements for the Paul Coverdell National Acute Stroke Registry - Part 1: Proceedings of an expert panel SO STROKE LA English DT Article DE data collection; registry; stroke assessment; stroke, acute; thrombolytic therapy ID ACUTE ISCHEMIC-STROKE; RANDOMIZED TRIALS; CARE; STATE; PREVENTION; EMERGENCY; QUALITY; TPA AB Background and Purpose-Stroke is the third-leading cause of death and a leading cause of disability in adults in the United States. In recent years, leaders in the stroke care community identified a national registry as a critical tool to monitor the practice of evidence-based medicine for acute stroke patients and to target areas for continuous quality of care improvements. An expert panel was convened by the Centers for Disease Control and Prevention to recommend a standard list of data elements to be considered during development of prototypes of the Paul Coverdell National Acute Stroke Registry. Methods-A multidisciplinary panel of representatives of the Brain Attack Coalition, professional associations, nonprofit stroke organizations, and federal health agencies convened in February 2001 to recommend key data elements. Agreement was reached among all participants before an element was added to the list. Results-The recommended elements included patient-level data to track the process of delivering stroke care from symptom onset through transport to the hospital, emergency department diagnostic evaluation, use of thrombolytic therapy when indicated, other aspects of acute care, referral to rehabilitation services, and 90-day follow-up. Hospital-level measures pertaining to stroke center guidelines were also recommended to augment patient-level data. Conclusions-Routine monitoring of the suggested parameters could promote community awareness campaigns, support quality improvement interventions for stroke care and stroke prevention in each state, and guide professional education in hospital and emergency system settings. Such efforts would reduce disability and death among stroke patients. C1 Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. NW Univ, Sch Med, Chicago, IL USA. Stroke Syst Consulting, Dallas, TX USA. Rush Med Coll, Chicago, IL 60612 USA. Ctr Medicare & Medicaid Serv, Dallas, TX USA. Med Coll Georgia, Augusta, GA 30912 USA. VA Med Ctr, Augusta, GA USA. NINDS, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Natl Stroke Assoc, Denver, CO USA. Amer Stroke Assoc, Div Amer Heart Assoc, Dallas, TX USA. RP Wattigney, WA (reprint author), Ctr Dis Control & Prevent, 4770 Buford Hwy NE,Mailstop K-47, Atlanta, GA 30341 USA. OI Mensah, George/0000-0002-0387-5326 NR 22 TC 46 Z9 51 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 151 EP 156 DI 10.1161/01.STR.0000048160.41821.B5 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100040 PM 12511767 ER PT J AU Chalela, JA Latour, LL Jeffries, N Warach, S AF Chalela, JA Latour, LL Jeffries, N Warach, S TI Hemorrhage and early MRI evaluation from the emergency room (HEME-ER): A prospective, single center comparison of MRI to CT for the emergency diagnosis of intracranial hemorrhage in patients with suspected acute cerebrovascular disease SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 239 EP 240 PG 2 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100068 ER PT J AU Kidwell, CS Chalela, JA Saver, JL Davis, SM Warach, S AF Kidwell, CS Chalela, JA Saver, JL Davis, SM Warach, S CA HEME Investigators TI Hemorrhage early MRI evaluation (HEME) study: Preliminary results of a multicenter trial of neuroimaging in patients with acute stroke symptoms within 6 hours of onset SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Univ Calif Los Angeles, Stroke Ctr, Los Angeles, CA USA. Royal Melbourne Hosp, Melbourne, Vic, Australia. NINDS, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 239 EP 239 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100066 ER PT J AU Kang, DW Latour, LL Chalei, JA Dambrosia, J Warach, S AF Kang, DW Latour, LL Chalei, JA Dambrosia, J Warach, S TI Early and late recurrence of ischemic lesions on diffusion weighted MRI following acute ischemic stroke: Evidence for a prolonged stroke-prone state? SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, 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 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 240 EP 240 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100070 ER PT J AU Latour, LL Kang, DW Chalela, JA Ezzeddine, MA Warach, S AF Latour, LL Kang, DW Chalela, JA Ezzeddine, MA Warach, S TI Evidence of early blood brain barrier disruption following acute stroke humans: An imaging marker of reperfusion injury? SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 240 EP 240 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100069 ER PT J AU Janardhan, V Wolf, PA Kase, CS Massaro, J D'Agostino, RB Franzblau, C Wilson, PWF AF Janardhan, V Wolf, PA Kase, CS Massaro, J D'Agostino, RB Franzblau, C Wilson, PWF TI Anticardiolipin antibodies and the risk of ischemic stroke and transient ischemic attack: The framingham cohort and offspring study SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Boston Univ, Med Ctr, Dept Neurol, Boston, MA USA. Boston Univ, Dept Neurol, Sch Med, NHLBI,Framingham Heart Study, Boston, MA 02118 USA. Boston Univ, Dept Epidemiol & Biostat, Boston, MA USA. Boston Univ, Dept Math & Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol & Biochem, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 244 EP 244 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100090 ER PT J AU Lyden, P AF Lyden, P CA TNK Stroke Investigators TI Pilot study of tenecteplase (TNK) in acute ischemic stroke: Preliminary report SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Univ Calif San Diego, Stroke Ctr, San Diego, CA 92103 USA. NINDS, Washington, DC USA. Univ Virginia, Washington, DC USA. NR 0 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 246 EP 246 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100104 ER PT J AU Chalela, JA Kang, DW Latour, LL Warach, S AF Chalela, JA Kang, DW Latour, LL Warach, S TI String of pearls sign on diffusion MRI is associated with large artery atherosclerosis SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 258 EP 258 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100162 ER PT J AU Han, MK Kang, DW Bae, HJ Oh, GS Jeong, SW Roh, JK AF Han, MK Kang, DW Bae, HJ Oh, GS Jeong, SW Roh, JK TI Aphasia in striatocapsular infarction may be explained by concomitant small cortical Infarctions of cortical language zones SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Eulji Univ Hosp, Taejon, South Korea. NINDS, Stroke Branch, Bethesda, MA USA. Eulji Univ, Sch Med, Seoul, South Korea. Seoul Natl Univ Hosp, Seoul 110744, South Korea. RI Bae, Hee-Joon/J-5503-2012; Han, Moon-Ku/J-5703-2012 NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 259 EP 259 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100169 ER PT J AU Chalela, JA Haymore, JB Davis, LA Kang, DW Warach, S AF Chalela, JA Haymore, JB Davis, LA Kang, DW Warach, S TI Cerebral microbleeds are associated with advanced age but not with hypertensive end-organ damage SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 262 EP 262 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100186 ER PT J AU Kang, DW Chalela, JA Warach, S AF Kang, DW Chalela, JA Warach, S TI TOAST classification of stroke etiology is associated with specific ischemic lesion patterns on acute diffusion-weighted imaging SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 262 EP 262 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100185 ER PT J AU Nadareishvili, ZG Li, H Maric, D Barker, JL Dambrosia, J Chalela, JA Haymore, J Davis, LA Warach, S Hallenbeck, JM Baird, AE AF Nadareishvili, ZG Li, H Maric, D Barker, JL Dambrosia, J Chalela, JA Haymore, J Davis, LA Warach, S Hallenbeck, JM Baird, AE TI CD4+CD28-cells in acute ischemic stroke SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 268 EP 268 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100219 ER PT J AU Nadareishvili, ZG Li, H Dambrosia, J Chalela, JA Haymore, J Davis, L Warach, S Hallenbeck, J Baird, AE AF Nadareishvili, ZG Li, H Dambrosia, J Chalela, JA Haymore, J Davis, L Warach, S Hallenbeck, J Baird, AE TI Cytokine expression by peripheral blood mommuclear cells in acute stroke SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 268 EP 268 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100218 ER PT J AU Worrall, BB De Graba, TJ Nadler, JL Gerrity, RG Teichberg, D Becker, KG Lee, KS AF Worrall, BB De Graba, TJ Nadler, JL Gerrity, RG Teichberg, D Becker, KG Lee, KS TI Carotid atherosclerosis in a pig model SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 Univ Virginia, Charlottesville, VA 22903 USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. Med Coll Georgia, Augusta, GA 30912 USA. NIA, DNA Array Unit, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 273 EP 273 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100245 ER PT J AU Nadareishvili, ZG Wolcott, K McCarron, R Hamm, T Ketron, G AF Nadareishvili, ZG Wolcott, K McCarron, R Hamm, T Ketron, G TI T cell receptor VB profile in carotid atherosclerotic plaque SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 274 EP 274 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100250 ER PT J AU Lynch, JK Nyquist, P Nadareishvili, ZG Baird, AE AF Lynch, JK Nyquist, P Nadareishvili, ZG Baird, AE TI Hospital admission for TIA in the United States SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 282 EP 282 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100291 ER PT J AU Lynch, JK AF Lynch, JK TI The hospitalization of childhood stroke in the United States, 1979-2000 SO STROKE LA English DT Meeting Abstract CT 28th International Stroke Conference CY FEB 13-15, 2003 CL PHOENIX, ARIZONA C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JAN PY 2003 VL 34 IS 1 BP 287 EP 287 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 632XX UT WOS:000180251100317 ER PT J AU Krahn, JM Beard, WA Miller, H Grollman, AP Wilson, SH AF Krahn, JM Beard, WA Miller, H Grollman, AP Wilson, SH TI Structure of DNA polymerase beta with the mutagenic DNA lesion 8-oxodeoxyguanine reveals structural insights into its coding potential SO STRUCTURE LA English DT Article DE DNA polymerase; fidelity; mutagenesis; oxidative DNA damage; X-ray crystallography; 8-oxodeoxyguanine ID NUCLEOTIDE INCORPORATION; REVERSE-TRANSCRIPTASE; CRYSTAL-STRUCTURES; TERNARY COMPLEXES; LARGE FRAGMENT; B-DNA; ETA; EFFICIENT; 7,8-DIHYDRO-8-OXOGUANINE; CONFORMATION AB Oxidative damage to DNA generates 8-oxo-7,8-dihy-dro-2'-deoxyguanosine (8-oxodG). During DNA replication and repair synthesis, 8-oxodG can pair with cytosine or adenine. The ability to accurately replicate through this lesion depends on the DNA polymerase. We report the first structure of a polymerase with a promutagenic DNA lesion, 8-oxodG, in the confines of its active site. The modified guanine residue is in an anti conformation and forms Watson-Crick hydrogen bonds with an incoming dCTP. To accommodate the oxygen at C8, the 5'-phosphate backbone of the templating nucleotide flips 180degrees. Thus, the flexibility of the template sugar-phosphate backbone near the polymerase active site is one parameter that influences the anti-syn equilibrium of 8-oxodG. Our results provide insights into the mechanisms employed by polymerases to select the complementary dNTP. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. SUNY Stony Brook, Dept Pharmacol Sci, Biol Chem Lab, Stony Brook, NY 11794 USA. RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Miller, Holly/I-6942-2015 OI Miller, Holly/0000-0002-9076-5335 FU NCI NIH HHS [CA-47995] NR 42 TC 104 Z9 106 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD JAN PY 2003 VL 11 IS 1 BP 121 EP 127 AR PII S0969-2126(02)00930-9 DI 10.1016/S0969-2126(02)00930-9 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 643KP UT WOS:000180860700016 PM 12517346 ER PT J AU Aung, AT Hichman, NJ Moolchan, ET AF Aung, AT Hichman, NJ Moolchan, ET TI Health and performance related reasons for wanting to quit: Gender differences among teen smokers SO SUBSTANCE USE & MISUSE LA English DT Article DE adolescent smoking; reasons for quitting; gender; health; performance ID SMOKING CESSATION; NICOTINE DEPENDENCE; LIFE-STYLE; ADOLESCENTS; POPULATION; PREDICTORS; BEHAVIORS; EXERCISE; YOUTH; WOMEN AB Adolescents frequently state health as a broad-ranging reason for wanting to quit smoking. Much less is known regarding performance-related reasons. We hypothesized that more male than female smokers want to quit for performance-related reasons (e.g., to improve athletic performance). As part of a telephone screen to determine eligibility for participation in a cessation trial in Baltimore, Maryland, 1999-2001, 509 teenage smokers [mean age 15.78 +/- 1.65 years (range 11-21), 60.9% female, 32.6% African-American] were asked the open-ended question: "Why do you want to quit?" Responses were subsequently grouped into categories that included health, performance, cost, social influences, setting an example for others, self-efficacy, cosmetics, no perceived positive reinforcement, or unknown reasons. Health was the most commonly stated primary and overall reason for wanting to quit among both boys and girls. Sixty-five percent of teen smokers endorsing health reasons were girls, and 51% of those endorsing performance-related reasons were boys (chi(2)(2) = 7.78, p = 0.02). Recognizing the greater concern for performance-related issues among boys is important for designing and engaging young smokers into cessation interventions. C1 NIDA, NIH, IRP, Teen Tobacco Addict Treatment Res Clin, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, NIH, IRP, Teen Tobacco Addict Treatment Res Clin, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 28 Z9 28 U1 8 U2 12 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6084 J9 SUBST USE MISUSE JI Subst. Use Misuse PY 2003 VL 38 IS 8 BP 1095 EP 1107 DI 10.1081/JA-120017652 PG 13 WC Substance Abuse; Psychiatry; Psychology SC Substance Abuse; Psychiatry; Psychology GA 705EY UT WOS:000184383800004 PM 12901450 ER PT S AU Sermesant, M Faris, O Evans, F McVeigh, E Coudiere, Y Delingette, H Ayache, N AF Sermesant, M Faris, O Evans, F McVeigh, E Coudiere, Y Delingette, H Ayache, N BE Ayache, N Delingette, H TI Preliminary validation using in vivo measures of a macroscopic electrical model of the heart SO SURGERY SIMULATION AND SOFT TISSUE MODELING, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Article; Proceedings Paper CT International Symposium on Surgery Simulation and Soft Tissue Modeling CY JUN 12-13, 2003 CL JUAN LES PINS, FRANCE SP Inst Natl Rech Informat Automat, Ctr Natl Rech Sci, Conseil Reg Reg Provence Alpes Cote Azur, Conseil Gen Alpes Maritimes AB This article describes an experimental protocol to obtain in vivo macroscopic measures of the cardiac electrical activity in a canine heart coupled with simulations done using macroscopic models of the canine myocardium. Electrical propagation simulations are conducted along with preliminary qualitative comparisons. Two different models are compared, one built from dissection and highly smoothed and one measured from Diffusion Tensor Imaging (DTI). Validating a macroscopic model with in vivo measurements of the electrical activity should allow a future use of the model in a predictive way, for instance in radio-frequency ablation planning. C1 INRIA Sophia Antipolis, Epidaure Res Project, F-06902 Sophia Antipolis, France. NHLBI, NIH, Cardiac Energet Lab, Bethesda, MD 20892 USA. Univ Nantes, Math Lab, CNRS, UMR 6629, F-44035 Nantes, France. RP Sermesant, M (reprint author), INRIA Sophia Antipolis, Epidaure Res Project, 2004 Route Lucioles, F-06902 Sophia Antipolis, France. EM Maxime.Sermesant@inria.fr OI Sermesant, Maxime/0000-0002-6256-8350; Coudiere, Yves/0000-0003-2687-3232 NR 15 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 3-540-40439-2 J9 LECT NOTES COMPUT SC PY 2003 VL 2673 BP 230 EP 243 PG 14 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Education, Scientific Disciplines; Medicine, Research & Experimental SC Computer Science; Education & Educational Research; Research & Experimental Medicine GA BX29P UT WOS:000184848300022 ER PT J AU Xu, H Lu, YF Rothman, RB AF Xu, H Lu, YF Rothman, RB TI Opioid peptide receptor studies. 16. Chronic morphine alters G-protein function in cells expressing the cloned mu opioid receptor SO SYNAPSE LA English DT Article DE opioid receptors; G-proteins; opiate tolerance ID NEUROBLASTOMA SH-SY5Y CELLS; ANTI-OPIATE PEPTIDES; GAMMA-S BINDING; AGONIST EFFICACY; TOLERANCE; DEPENDENCE; SITES; RAT; DESENSITIZATION; MEMBRANES AB Chronic morphine treatment results in functional uncoupling of the mu opioid receptor and its G protein in both cell culture and animal models. In the present study, Chinese hamster ovary (CHO) cells stably expressing the cloned human mu opioid receptor (hMOR-CHO cells) were incubated with 1 muM of morphine (or no drug) for 20 h. Subsequently, we assessed DAMGO- and morphine-stimulated [S-35]-GTP-gamma-S binding and agonist-mediated inhibition of forskolin-stimulated AMP accumulation. Using a single concentration of [S-35]-GTP-gamma-S (0.05 nM), chronic morphine treatment did not significantly change basal [S-35] -GTP-gamma-S binding, shifted the morphine EC50 from 59 nM to 146 nM, and decreased the maximal stimulation (E-max) from 201% to 177%. Similar results were observed with DAMGO. Binding surface analysis resolved two [S-35] -GTP-gamma-S binding sites (high-affinity and low-affinity sites). In control cells, morphine stimulated [S-35]-GTP-gamma-S binding by increasing the B-max of the high-affinity site. In morphine-treated cells, morphine stimulated [S-35] -GTP-gamma-S binding by decreasing the high-affinity K-d without changing the B-max. Morphine treatment increased the EC50 (5-11-fold) for agonist-mediated inhibition of forskolin-stimulated cAMP accumulation. These changes were not observed in cells expressing a mutant mu opioid receptor which does not develop morphine tolerance, suggesting that the changes in [S-35] -GTP-gamma-S binding observed in hMOR-CHO cells result from the development of morphine tolerance.Published 2002 Wiley-Liss, Inc. C1 NIDA, CPS, DIR, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, CPS, DIR, Intramural Res Program,NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 28 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JAN PY 2003 VL 47 IS 1 BP 1 EP 9 DI 10.1002/syn.10144 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 622BH UT WOS:000179626100001 PM 12422367 ER PT J AU Sharan, N Chong, VZ Nair, VD Mishra, RK Hayes, RJ Gardner, EL AF Sharan, N Chong, VZ Nair, VD Mishra, RK Hayes, RJ Gardner, EL TI Cocaine treatment increases expression of a 40 kDa catecholamine-regulated protein in discrete brain regions SO SYNAPSE LA English DT Article DE dopamine; oxidative stress; free radicals; anisomycin; spin trapping agent; neuroprotection ID TERT-BUTYL NITRONE; EXTRACELLULAR DOPAMINE LEVELS; MEDIAL PREFRONTAL CORTEX; RAT NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; MOLECULAR MECHANISMS; ABSORBING PROTEINS; FREE-RADICALS; ALPHA; PHARMACOLOGY AB Previous reports from our laboratory have described brain-specific catecholamine-regulated proteins, which bind dopamine and related catecholamines. Evidence from the molecular cloning of a 40 kDa catecholamine-regulated protein (CRP40) revealed that CRP40 is dopamine-inducible and has properties similar to those of the 70 kDa heat shock protein (HSP70) family. The present study investigates the effects of acute and chronic cocaine treatment on CRP40 expression in the striatum, nucleus accumbens, prefrontal cortex, and medulla. Acute treatment with cocaine increased CRP40 expression in the nucleus accumbens and striatum, whereas chronic treatment with cocaine increased CRP40 expression in the nucleus accumbens only. Neither of these treatments affected CRP40 levels in the prefrontal cortex or medulla. In addition, pretreatment with the spin-trapping agent alpha-phenyl-tert-butylnitrone did not attenuate cocaine-induced expression of CRP40, suggesting that the observed increases in CRP40 levels were not caused by free radicals. On the other hand, pretreatment with anisomycin, a protein synthesis inhibitor, blocked the cocaine-induced expression of CRP40. Thus, protein synthesis may be involved in the observed CRP40 level increases. Furthermore, neither acute nor chronic cocaine treatment affected levels of inducible or constitutively expressed HSP70, which indicates a specificity of cocaine's effects on CRP40. Since cocaine has been shown to increase extracellular dopamine levels, these findings suggest that increased expression of CRP40 is associated with high extracellular levels of dopamine (or its metabolites). Elevated levels of CRP40 could play a protective role for dopamine neurons in response to increased oxidative stress that has been shown to be induced by cocaine and that can lead to apoptosis and neurodegeneration. (C) 2002 Wiley-Liss, Inc. C1 McMaster Univ, Dept Psychiat & Behav Neurosci, Hlth Sci Ctr, Hamilton, ON L8N 3Z5, Canada. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Mishra, RK (reprint author), McMaster Univ, Dept Psychiat & Behav Neurosci, Hlth Sci Ctr, 4N78,1200 Main St W, Hamilton, ON L8N 3Z5, Canada. RI Mishra, Ram/B-3885-2009 NR 45 TC 16 Z9 16 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JAN PY 2003 VL 47 IS 1 BP 33 EP 44 DI 10.1002/syn.10140 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 622BH UT WOS:000179626100005 PM 12422371 ER PT J AU Chong, HS Brechbiel, MW AF Chong, HS Brechbiel, MW TI A short and efficient synthesis of mono-substituted 1,4,7-triazacyclononanes SO SYNTHETIC COMMUNICATIONS LA English DT Article DE triazacyclononane; pendant substituted macrocycle; mono-substituted tacn ID COMPLEXES AB A convenient synthesis of 1,4,7-Triazacyclononane (tacn) derivatives substituted with a single pendant donor group: is described. Monosubstituted tacns with a hydroxylalkyl, an aminoalkyl, or a benzyl group are synthesized via efficient cyclization of inexpensive starting materials followed by detosylation. C1 NCI, Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NCI, Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Rm B3B69, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov NR 13 TC 8 Z9 8 U1 2 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0039-7911 J9 SYNTHETIC COMMUN JI Synth. Commun. PY 2003 VL 33 IS 7 BP 1147 EP 1154 DI 10.1081/SCC-120017190 PG 8 WC Chemistry, Organic SC Chemistry GA 677JR UT WOS:000182804200012 ER PT J AU Sharma, GVM Ilangovan, A Narayanan, VL Gurjar, MK AF Sharma, GVM Ilangovan, A Narayanan, VL Gurjar, MK TI First synthesis of aza-calanolides - a new class of anti-HIV active compounds SO TETRAHEDRON LA English DT Article DE pyranocoumarin; calanolide; aza-calanolide; anti-HIV; quinolinone synthesis ID HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; DERIVATIVES; INHIBITORS; TREE AB First synthesis of (+/-)-aza-calanolides, starting from dimethoxy aniline, is achieved. These new compounds exhibited potent in vitro anti-HIV reverse transcriptase activity. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Indian Inst Chem Technol, Discovery Lab D211, Div Organ Chem 3, Hyderabad 500007, Andhra Pradesh, India. NCI, Drug Synth & Chem Branch, Bethesda, MD 20692 USA. Natl Chem Lab, Div Organ Chem Technol, Pune 411008, Maharashtra, India. RP Sharma, GVM (reprint author), Indian Inst Chem Technol, Discovery Lab D211, Div Organ Chem 3, Hyderabad 500007, Andhra Pradesh, India. EM esmvee@iict.ap.nic.in NR 16 TC 10 Z9 11 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD JAN 1 PY 2003 VL 59 IS 1 BP 95 EP 99 AR PII S0040-4020(02)01456-4 PG 5 WC Chemistry, Organic SC Chemistry GA 633FH UT WOS:000180271500008 ER PT S AU Grajkowski, A Cieslak, J Chmielewski, MK Marchan, V Phillips, LR Wilk, A Beaucage, SL AF Grajkowski, A Cieslak, J Chmielewski, MK Marchan, V Phillips, LR Wilk, A Beaucage, SL BE ChoChung, YS Gewirtz, AM Stein, CA TI Conceptual "heat-driven" approach to the synthesis of DNA oligonucleotides on microarrays SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE deoxyribonucleoside cyclic N-acylphosphoramidites; deoxyribonucleoside phosphoramidites; solid-phase oligonucleotide synthesis; heat-sensitive phosphate protecting groups; nucleobase protection; 5 '-hydroxyl protection; 3 '-O-acetylthymidine 5 '-O-carbonates; cyclodeesterification; cyclodecarbonation; thermolytic deprotection; microarrays ID PHOSPHATE/THIOPHOSPHATE PROTECTING GROUP; PHASE OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; GENE-EXPRESSION PATTERNS; LIGHT-DIRECTED SYNTHESIS; ARRAYS; HYBRIDIZATION; DISCOVERY AB The discovery of deoxyribonucleoside cyclic N-acylphosphoramidites, a novel class of phosphoramidite monomers for solid-phase oligonucleotide synthesis, has led to the development of a number of phosphate protecting groups that can be cleaved from DNA oligonucleotides under thermolytic neutral conditions. These include the 2-(N-formyl-N-methyl) amino ethyl, 4-oxopentyl, 3-(N-tert-butyl)carboxamido-1-propyl, 3-(2-pyridyl)-1-propyl, 2-[N-methyl-N-(2-pyridyl)]aminoethyl, and 4-methythiobutyl groups. When used for 5'-hydroxyl protection of nucleosides, the analogous 1-phenyl-2-[N-methyl-N-(2-pyridyl)]aminoethyloxycarbonyI group exhibited excellent thermolytic properties, which may permit an iterative "heat-driven" synthesis of DNA oligonucleotides on microarrays. In this regard, progress has been made toward the use of deoxyribonucleoside cyclic N-acylphosphoramidites in solid-phase oligonucleotide syntheses without nucleobase protection. Given that deoxyribonucleoside cyclic N-acylphosphoramidites produce oligonucleotides with heat-sensitive phosphate protecting groups, blocking the 5'-hydroxyl of these monomers with, for example, the thermolabile 1-phenyl-2-[N-methyl-N-(2pyridyl)]aminoethyloxycarbonyl group may provide a convenient thermocontrolled method for the synthesis of oligonucleotides on microarrays. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NCI, Biol Testing Branch, Dev Therapeut Program, Frederick, MD 21701 USA. US Pharmacopeia, Rockville, MD 20852 USA. RP US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov RI Marchan, Vicente/K-9751-2014 OI Marchan, Vicente/0000-0002-1905-2156 NR 26 TC 11 Z9 11 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 1 EP 11 DI 10.1196/annals.1281.003 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400001 PM 14751818 ER PT S AU Caplen, NJ Mousses, S AF Caplen, NJ Mousses, S BE ChoChung, YS Gewirtz, AM Stein, CA TI Short interfering RNA (siRNA)-mediated RNA interference (RNAi) in human cells SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE siRNAs; short interfering RNAs; RNA interference; RNAi gene silencing ID DOUBLE-STRANDED-RNA; FUNCTIONAL GENOMIC ANALYSIS; METASTATIC BREAST-CANCER; CULTURED-MAMMALIAN-CELLS; VECTOR-BASED RNAI; GENE-EXPRESSION; C-ELEGANS; CAENORHABDITIS-ELEGANS; PROTEIN-KINASE; CHEMICAL-MODIFICATIONS AB Transient gene silencing in mammalian cells can be mediated by double stranded RNA (dsRNAs) molecules of similar to20-25 nucleotides termed short interfering (siRNAs). Naturally occurring siRNAs in lower eukaryotes have characteristic structural elements; however, little is known about what features are critical for an exogenous siRNA to mediate RNAi in mammals. We have recently determined some of the critical parameters that influence the efficiency of siRNA-mediated RNAi in mammalian cells and have been considering the use of RNAi as a functional genomics tool, particularly for high throughput analysis, and the potential use of RNAi as a therapeutic tool. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Canc Drug Dev Lab, Translat Genom Res Inst, Bethesda, MD 20892 USA. RP NHGRI, Med Genet Branch, NIH, Bldg 10,Room 10C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM ncaplen@mail.nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 NR 63 TC 56 Z9 59 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 56 EP 62 DI 10.1196/annals.1281.007 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400005 PM 14751822 ER PT S AU Cho-Chung, YS AF Cho-Chung, YS BE ChoChung, YS Gewirtz, AM Stein, CA TI CRE-enhancer DNA decoy - A tumor target-based genetic tool SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE cAMP response element (CRE); transcription factor decoy; palindrome/hairpin; oligonucleotides; cancer; growth inhibition; DNA microarrays ID TRANSCRIPTION FACTOR AP-2; BREAST-CANCER CELLS; MIXED-BACKBONE OLIGONUCLEOTIDES; AMP RESPONSE ELEMENT; NUCLEAR-PROTEIN CBP; RI-ALPHA SUBUNIT; VIRUS TYPE-I; CYCLIC-AMP; GROWTH ARREST; DIFFERENTIAL ACTIVATION AB Enhancer DNA decoy oligonucleotides (ODNs) inhibit transcription by competing for transcription factors. A decoy ODN composed of the cAMP response element (CRE) inhibits CRE-directed gene transcription and tumor growth without affecting normal cell growth. We used DNA microarrays to analyze the global gene expression in tumors exposed to the CRE-decoy ODN. The CRE decoy upregulated the AP-2beta transcription factor gene in tumors but not in the livers of host animals. The upregulated expression of AP-2beta was clustered with other upregulated genes involved in development and cell differentiation. Concomitantly, another cluster of genes involved in cell proliferation and transformation was downregulated. The observed alterations indicate that CRE-directed transcription favors tumor growth. Evidence presented here suggests that the CRE-decoy ODN may provide a target-based genetic tool for treating cancer, viral diseases, and other diseases in which CRE-directed transcription is abnormally used. C1 NCI, Cellular Biochem Sect, Basic Res Lab, NIH, Bethesda, MD 20892 USA. RP NCI, Cellular Biochem Sect, Basic Res Lab, NIH, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov NR 48 TC 5 Z9 5 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 124 EP 133 DI 10.1196/annals.1281.011 PG 10 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400013 PM 14751830 ER PT S AU Panyutin, IG Sedelnikova, OA Karamychev, VN Neumann, RD AF Panyutin, IG Sedelnikova, OA Karamychev, VN Neumann, RD BE ChoChung, YS Gewirtz, AM Stein, CA TI Antigene radiotherapy - Targeted radiodamage with I-125-labeled triplex-forming oligonucleotides SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE triple-helix; oligonucleotides; gene-targeting; radiotherapy; iodine-125 ID LOCALIZATION SIGNAL PEPTIDE; AUGER-ELECTRON EMITTERS; MAMMALIAN-CELLS; GENE; DNA; I-125; DECAY AB Antigene radiotherapy is based upon damaging selected genes by a high dose of radiation from radionuclides delivered to this gene by a sequence-specific DNA-binding molecule. Here we describe our recent trials of antigene radiotherapy using the human mdr1 gene over-expressed in KR-V1 cells as a model. As a delivery molecule, we used a triplex-forming oligonucleotide (TFO) with a binding site in intron 14 of mdr1. This TFO was labeled with an Auger-electron-emitting radionuclide I-125. Decay of I-125 releases a shower of low energy electrons that produce DNA strand breaks mostly within 10 bp from the decay site. Targeting in situ was assessed by restriction enzyme digestion of the DNA recovered from the TFO-treated cells followed by Southern hybridization with DNA probes flanking the target sequence. Double-strand breaks in the target sequence were detected in purified nuclei and digitonin-permeabilized cells, but not in the intact cells when TFO were delivered with liposomes. On the basis of these observations we hypothesized that there are cytoplasmic factors that bind such TFO and deliver them into the nucleus, but do not release them inside the nucleus, thus preventing TFO from binding their genomic targets. To test this hypothesis we (i) delivered TFO along with an excess of unlabeled oligonucleotide with an arbitrary sequence ("ballast") and (ii) conjugated TFO with a nuclear localization sequence peptide (NLS). We have found that TFO/NLS conjugates cleaved the target in a concentration-dependent manner regardless of the presence of the "ballast" oligonucleotide. In contrast,TFO without NLS cleaved the target only in the presence of an excess of the "ballast." These results may provide a new insight into the mechanism of intracellular transport of oligonucleotides. C1 NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, CC, Bethesda, MD 20892 USA. RP NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, CC, Bldg 10,Rm 1C401, Bethesda, MD 20892 USA. EM igorp@helix.nih.gov NR 20 TC 14 Z9 16 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 134 EP 140 DI 10.1196/annals.1281.012 PG 7 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400014 PM 14751831 ER PT S AU Majumdar, A Puri, N McCollum, N Richards, S Cuenoud, B Miller, P Seidman, MM AF Majumdar, A Puri, N McCollum, N Richards, S Cuenoud, B Miller, P Seidman, MM BE ChoChung, YS Gewirtz, AM Stein, CA TI Gene targeting by triple helix-forming oligonucleotides SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE DNA triple helix; gene targeting; psoralen crosslinking; cell cycle ID DNA; CHROMATIN; RNA; TRANSCRIPTION; RECOGNITION; KNOCKOUT; 3RD AB Effective gene targeting reagents would have widespread utility for genomic manipulation including transgenic cell and animal construction and for gene therapy. They would also be useful in basic research as probes of chromatin structure, and as tools for studying the repair and mutagenesis of targeted DNA damage. We are developing triple helix-forming oligonucleotides (TFOs) for gene targeting in living mammalian cells. Challenges to TFO bioactivity include the impediments to the biochemistry of triplex formation presented by the physiological environment and the charge repulsion between the duplex and the third strand. In addition, there are biological constraints to target access imposed by mammalian chromatin structure. Here we describe the oligonucleotide modification format that appears to support biological activity of TFOs. In addition we show that manipulation of the cell biology, specifically the cell cycle, has a dramatic influence on TFO bioactivity. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Novartis Pharmaceut, Horsham RH12 4AB, W Sussex, England. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD 21205 USA. RP NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM seidmanm@grc.nia.nih.gov NR 24 TC 15 Z9 15 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 141 EP 153 DI 10.1196/annals.1281.013 PG 13 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400015 PM 14751832 ER PT S AU Marquez, VE Eritja, R Kelley, JA Vanbemmel, D Christman, J AF Marquez, VE Eritja, R Kelley, JA Vanbemmel, D Christman, J BE ChoChung, YS Gewirtz, AM Stein, CA TI Potent inhibition of HhaI DNA methylase by the aglycon of 2-(1H)-pyrimidinone riboside (Zebularine) at the G(C)under-barGC recognition domain SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE DNA methyltransferase; methylation inhibitor; cytidine deaminase; inhibitor; 2-(1H)-pyrimidinone; 5-azacytosine; zebularine; 5-azacytidine; 2'-deoxy-5-azacytidine; gene reactivation ID NUCLEIC-ACID COMPONENTS; CYTIDINE DEAMINASE; 2-PYRIMIDINONE NUCLEOSIDES; ESCHERICHIA-COLI; PYRIMIDIN-2-ONE NUCLEOSIDES; MSPI DNA; ANALOGS; METHYLTRANSFERASE; MECHANISM; CYTOSINE AB A short oligodeoxynucleotide (ODN) with 2-(1H)-pyrimidinone at the HhaI DNA methyltransferase target site (GCGC) is shown to induce a level of inhibition of methyl transfer and thermal stability of the complex with the enzyme identical to that achieved with a similar ODN substituted with 5-azacytosine. The drugs responsible for these effects-zebularine and 5-azacytidine/2'-deoxy-5-azacytidine-are contrasted in terms of chemical stability and possible metabolic activation by a brief structure-activity analysis. C1 NCI, Ctr Canc Res, Med Chem Lab, Ft Detrick, MD 21702 USA. CSIC, Ctr Invest & Desarrollo, E-08034 Barcelona, Spain. Univ Nebraska, Med Ctr, Dept Biochem & Mol Biol, Omaha, NE 68198 USA. Univ Nebraska, Coll Med, Eppley Canc Ctr, Omaha, NE 68198 USA. RP NCI, Ctr Canc Res, Med Chem Lab, 376 Boyles St,Bldg 376,Rm 104, Ft Detrick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov RI eritja, ramon/B-5613-2008 OI eritja, ramon/0000-0001-5383-9334 NR 41 TC 15 Z9 15 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 154 EP 164 DI 10.1196/annals.1281.014 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400016 PM 14751833 ER PT S AU Mani, S Goel, S Nesterova, M Martin, RM Grindel, JM Rothenberg, ML Zhang, R Tortora, G Cho-Chung, YS AF Mani, S Goel, S Nesterova, M Martin, RM Grindel, JM Rothenberg, ML Zhang, R Tortora, G Cho-Chung, YS BE ChoChung, YS Gewirtz, AM Stein, CA TI Clinical studies in patients with solid tumors using a second-generation antisense oligonucleotide (GEM (R) 231) targeted against protein kinase A type I SO THERAPEUTIC OLIGONUCLEOTIDES: ANTISENSE, RNAI, TRIPLE-HELIX, GENE REPAIR, ENHANCER DECOYS, CPG AND DNA CHIPS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 6th NIH Symposium on Therapeutic Oligonucleotides CY DEC 16-17, 2002 CL Bethesda, MD SP NIH Therapeut Oligonucleotides Interest Grp, NCI, Doris Duke Charitable Fdn, Genta Inc, NIH Interest Grp Fdn DE oligonucleotide; PKA type I; solid tumors; antisense; mixed backbone ID RI-ALPHA-SUBUNIT; ANTITUMOR-ACTIVITY; CANCER XENOGRAFTS; PROSTATE-CANCER; BREAST-CANCER; THERAPY; GROWTH; EXPRESSION; ONCOLOGY; PHARMACOKINETICS AB GEM((R))231 is a second-generation antisense oligonucleotide targeted against the RIalpha regulatory subunit of cAMP-dependent protein kinase type I (PKA-I). Excessive expression of PKA-I is associated with cell proliferation and transformation, and increased levels of secreted extracellular PKA (ECP-KA) are found in the serum of cancer patients. Preclinical studies have demonstrated single-agent antitumor activity of GEM 231 in a variety of human cancer xenograft models, and additive or synergistic antitumor activity has been observed with taxane and/or camptothecin-based combinations. Based on prior safety (MTD) data demonstrating dose-dependent, reversible, and cumulative transaminitis, and high peak plasma concentration (C-max)-dependent changes in activated partial thromboplastin time (aPTT) with GEM 231 2-h twice-weekly infusions, an alternative schedule of GEM 231 given as a single agent was evaluated in patients with advanced solid tumors. Fourteen patients (median age similar to60 yrs) with advanced solid malignancies received a total of 78 weeks of therapy. GEM 231 was infused via a CADD pump at 80 mg/m(2)/day (d) for 3 d/wk (n = 1), then for 5 d/wk at 80 (n = 3), 120 (n = 8), and 180 mg/m(2)/d (n = 2). One cycle was defined as 4 weeks of therapy. Apparent dose dependency for the occurrence of transaminitis was readily reversible. At 180 mg/m(2)/d, 2 of 2 patients had cycle 1 dose-limiting toxicity (DLT) transaminitis. One patient treated at 120 mg/m(2)/d experienced grade 3 transaminase elevations after 8 weeks of therapy, but when serum transaminase values rapidly improved he resumed treatment at 80 mg/m(2)/d for 6 weeks until tumor progression was documented. Another patient at 120 mg/m(2)/d developed grade 3 esophagitis after weeks, limiting further dosing. One patient (lung cancer) demonstrated stable disease for 9 weeks. Overall, plasma aPTT was minimally prolonged and changes were transient, peaked at the end of each infusion, and were not associated with spontaneous bleeding. A constitutive symptom (e.g., low-grade fatigue) was common, cumulative, and reversible following discontinuation of therapy. Serum ECPKA was measured by enzymatic assay and Western blotting from blood drawn at the beginning and end of each infusion. Serum ECPKA levels demonstrated a trend to decline with the treatment. In addition to single agent schedules, combination trials were undertaken to assess safety and possible interaction of GEM 231 with taxanes (paclitaxel, docetaxel), given once every 3 weeks (one cycle). While trials using the 2-h twice-weekly GEM 231 infusions are ongoing, preliminary results from both studies show that it is safe to combine paclitaxel or docetaxel with GEM 231. Overall, it is also feasible to administer GEM 231 in combination with taxane or nontaxane chemotherapy (e.g., camptothecins). Phase I combination studies are currently underway to further explore the clinical, pharmacokinetic, and biologic profile of GEM 231 with chemotherapy. C1 Albert Einstein Coll Med, Bronx, NY 10461 USA. Dept Oncol, Bronx, NY 10461 USA. AECCC, Bronx, NY 10461 USA. NCI, Bethesda, MD 20892 USA. Hydribon Inc, Cambridge, MA USA. Pharma Solut, Alpharetta, GA USA. Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Univ Alabama Birmingham, Birmingham, AL USA. Univ Naples Federico II, Naples, Italy. RP Yeshiva Univ Albert Einstein Coll Med, Jack D Weiler Hosp, Rm 2S-49,1825 Eastchester Rd, Bronx, NY 10461 USA. EM smani@montefiore.org OI Tortora, Giampaolo/0000-0002-1378-4962 FU NCI NIH HHS [CA 13330-30] NR 34 TC 19 Z9 19 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-470-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 1002 BP 252 EP 262 DI 10.1196/annals.1281.028 PG 11 WC Biotechnology & Applied Microbiology; Oncology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Biotechnology & Applied Microbiology; Oncology; Research & Experimental Medicine; Science & Technology - Other Topics GA BY69H UT WOS:000189440400023 PM 14751840 ER PT J AU Horne, MK Brokaw, KJ AF Horne, MK Brokaw, KJ TI Antithrombin activity of lepirudin adsorbed to silicone (polydimethylsiloxane) tubing SO THROMBOSIS RESEARCH LA English DT Article DE lepirudin; silicone; polydimethylsiloxane; venous catheters ID RECOMBINANT HIRUDIN; ARTIFICIAL SURFACES; VENOUS CATHETERS; ALPHA-THROMBIN; ADSORPTION; HEPARIN; BLOOD C1 NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Hematol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Rm 2C306,Bldg 10, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov NR 16 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2003 VL 112 IS 1-2 BP 111 EP 115 DI 10.1016/j.thromres.2003.10.009 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 775KP UT WOS:000189039700018 PM 15013282 ER PT J AU Horne, MK Chang, R AF Horne, MK Chang, R TI Pharmacokinetics of pulse-sprayed recombinant tissue plasminogen activator for deep venous thrombosis SO THROMBOSIS RESEARCH LA English DT Article DE alteplase; thrombolysis; deep vein thrombosis ID ACUTE MYOCARDIAL-INFARCTION; PERIPHERAL ARTERIAL; THROMBOLYSIS; FIBRIN; UROKINASE C1 NIH, WG Magnuson Clin Ctr, Dept Lab Med, Bethesda, MD USA. NIH, WG Magnuson Clin Ctr, Dept Radiol, Bethesda, MD USA. RP Horne, MK (reprint author), NIH, Clin Pathol Dept, Hematol Serv, Room 2C306,Bldg 10, Bethesda, MD 20892 USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2003 VL 111 IS 1-2 BP 111 EP 114 DI 10.1016/j.thromres.2003.07.011 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 758CT UT WOS:000187615500018 PM 14644088 ER PT J AU Dogulu, CF Kansu, T Leung, MYK Baxendale, V Wu, SM Ozguc, M Chan, WY Rennert, OM AF Dogulu, CF Kansu, T Leung, MYK Baxendale, V Wu, SM Ozguc, M Chan, WY Rennert, OM TI Evidence for genetic susceptibility to thrombosis in idiopathic intracranial hypertension SO THROMBOSIS RESEARCH LA English DT Article DE idiopathic intracranial hypertension; genetic susceptibility; thrombosis ID ACTIVATED PROTEIN-C; FACTOR-V GENE; FAMILIAL PSEUDOTUMOR CEREBRI; INTRA-CRANICAL HYPERTENSION; VENOUS THROMBOSIS; CEREBROSPINAL-FLUID; RISK FACTOR; MUTATION; RESISTANCE; DISEASE C1 NICHD, Lab Clin Genom, NIH, Bethesda, MD 20892 USA. Hacettepe Univ, Dept Neurol, Ankara, Turkey. Hacettepe Univ, Dept Med Biol, Ankara, Turkey. RP Dogulu, CF (reprint author), NICHD, Lab Clin Genom, NIH, 49 Convent Dr,Room 2C09,MSC 4429, Bethesda, MD 20892 USA. EM doguluc@mail.nih.gov RI Kansu, Tulay/B-6280-2012 OI Kansu, Tulay/0000-0002-1986-4680 NR 44 TC 8 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2003 VL 111 IS 6 BP 389 EP 395 DI 10.1016/j.thromres.2003.09.030 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 763DE UT WOS:000188057700011 PM 14698658 ER PT S AU Roberts, AB Russo, A Felici, A Flanders, KC AF Roberts, AB Russo, A Felici, A Flanders, KC BE NilsenHamilton, M Werb, Z Keshet, E TI Smad3: A key player in pathogenetic mechanisms dependent on TGF-beta SO TISSUE REMODELING SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Symposium on Tissue Remodeling CY AUG 01-04, 2002 CL IOWA STATE UNIV, AMES, IOWA SP Cell Biol Program, Mayo Clin Canc Ctr, Iowa State Univ, Dept Biochem, Biophys & Mol Biol, Iowa State Unvi, Coll Agr, F Wendell Miller Trust, Iowa State Univ Biotechnol Council, Natl Anim Dis Ctr HO IOWA STATE UNIV DE TGF-beta; Smad2; Smad3; wound healing; fibrosis; signaling ID MICE LACKING SMAD3; GROWTH-FACTOR; SIGNAL-TRANSDUCTION; EARLY ENDOSOMES; TARGETED DISRUPTION; FYVE DOMAIN; RESPONSES; RAS; INTERNALIZATION; RADIATION AB Transforming growth factor-beta (TGF-beta), a key player in a large variety of physiological and disease processes, signals through transmembrane receptor serine/threonine kinases to activate novel signaling intermediates called Smad proteins, which then modulate transcription of target genes. We have utilized mice with a targeted deletion of Smad3, one of two homologous proteins involved in signaling from TGF-beta/activin, to investigate the function of this particular pathway in transducing such effects of TGF-beta. The dramatic results of the absence of Smad3 on parameters of healing of cutaneous wounds, such as reepithelialization and influx of inflammatory cells, as well as on fibrosis as modeled by radiation fibrosis of skin in mice, suggest that signaling flux through Smad3 is critical for chemotactic activity of TGF-beta, inhibitory effects of TGF-beta on keratinocyte proliferation and migration, and chemoattraction and elaboration of extracellular matrix by fibroblasts in fibrotic diseases. We recently identified a novel molecule, TLP for TRAP-1-like protein, which selectively interferes with Smad3 signaling, and are currently investigating whether levels of this protein might be altered in disease to change the relative flow of information from Smad2 and Smad3. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP Roberts, AB (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bldg 41,Room C629,41 Lib Dr,MSC 5055, Bethesda, MD 20892 USA. NR 43 TC 127 Z9 143 U1 1 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-416-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 995 BP 1 EP 10 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Cell Biology; Science & Technology - Other Topics GA BW93F UT WOS:000183697500002 PM 12814934 ER PT J AU Suttie, A Nyska, A Haseman, JK Moser, GJ Hackett, TR Goldsworthy, TL AF Suttie, A Nyska, A Haseman, JK Moser, GJ Hackett, TR Goldsworthy, TL TI A grading scheme for the assessment of proliferative lesions of the mouse prostate in the TRAMP model SO TOXICOLOGIC PATHOLOGY LA English DT Article DE grading; quantitation; histopathology; mouse prostatic cancer; TRAMP ID TRANSGENIC MOUSE; CANCER; PROGRESSION; MICE; CARCINOGENESIS; RESTRICTION; ANTIGEN; CARCINOMA AB To improve the precision and consistency of experimental results, we have developed a scoring system for proliferative epithelial lesions in the mouse prostate based on histological growth patterns observed in individual lobes. Severity of proliferative lesions was divided into 6 categories; the grade of the most advanced lesion was identified for each lobe and its distribution estimated semiquantitatively. A numerical score combining grade and distribution of the most advanced lesion in each lobe was assigned and termed the "distribution-adjusted lesion grade"; the mean of these scores was calculated for each treatment group. Using this grading scheme, we assessed lesion development in ad libitum-fed and 20%-diet-restricted groups of TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice that were started on study at 7 weeks of age and sacrificed when 11 and 20 weeks old. The anterior, dorsal, lateral, and ventral prostate lobes showed clear reductions in lesion severity in diet-restricted TRAMPs at 11 and 20 weeks. This method for scoring the epithelial pathology of the prostate in the TRAMP model with minimal to severe proliferative lesions utilizes the natural history of lesion development for assessing the effects of chemical and dietary interventions. C1 Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Suttie, A (reprint author), Integrated Lab Syst Inc, POB 13501, Res Triangle Pk, NC 27709 USA. FU NIEHS NIH HHS [N01-ES-95446] NR 18 TC 43 Z9 44 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN-FEB PY 2003 VL 31 IS 1 BP 31 EP 38 DI 10.1080/01926230390173842 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 631LL UT WOS:000180169200005 PM 12597447 ER PT J AU Nyska, A Suttie, A Bakshi, S Lomnitski, L Grossman, S Bergman, M Ben-Shaul, V Crocket, P Haseman, JK Moser, G Goldsworthy, TL Maronpot, RR AF Nyska, A Suttie, A Bakshi, S Lomnitski, L Grossman, S Bergman, M Ben-Shaul, V Crocket, P Haseman, JK Moser, G Goldsworthy, TL Maronpot, RR TI Slowing tumorigenic progression in TRAMP mice and prostatic carcinoma cell lines using natural anti-oxidant from spinach, NAO - A comparative study of three anti-oxidants SO TOXICOLOGIC PATHOLOGY LA English DT Article DE anti-oxidant; spinach; TRAMP mice; prostate; hyperplasia; cancer ID WATER-SOLUBLE ANTIOXIDANT; GREEN TEA POLYPHENOLS; N-ACETYLCYSTEINE; OXIDATIVE STRESS; TRANSGENIC MOUSE; INDUCED ENDOTOXEMIA; CANCER PROGRESSION; DNA-DAMAGE; BLACK TEA; IN-VITRO AB The TRAMP model and human prostatic cancer (PCA) cell lines DU145 and PC3 are useful for chemopreventive studies. We compared the efficacy of 3 anti-oxidants [a water-soluble natural anti-oxidant, NAO (200 mg/kg), found in spinach leaves; epigallocatechin-3 gallate, EGCG (200 mg/kg), a major green tea polyphenol; and N-acetylcysteine, NAC (125 mg/kg)] plus vehicle in slowing spontaneous tumorigenic progression in TRAMP and wild-type male mice. Sacrifices occurred on weeks 5, 9, and 13. Prostatic histopathology and oxidative-stress blood markers were evaluated. Hyperplasias were ranked by a combination of severity grade and distribution (focal, multifocal, and diffuse). The effectivity of each tested compound in reducing the severity/focalness of hyperplasia varied from lobe to lobe. NAO exerted a significant effect on the dorsal and lateral lobes; NAC, on the anterior and ventral lobes, and EGCG, on the ventral lobe. When the most severe hyperplasia in all 4 lobes of TRAMPs was evaluated, only NAO reduced hyperplasia at weeks 9 and 13. Plasma peroxide levels in TRAMPs were reduced following oral administration of NAO or NAC for 13 weeks; EGCG only slightly reduced these levels. In NAO-treated DU145 and PC3 PCA cells, inhibition of cellular proliferation occurred in a dose-dependent manner, increasing numbers of G1 cells and reducing ROS levels. The anti-oxidative and antiproliferative properties of NAO may explain its efficacy in slowing the spontaneous prostatic carcinogenic process in the TRAMP and its effects in the cell lines. C1 NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst, Res Triangle Pk, NC 27709 USA. Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. Analyt Sci Inc, Durham, NC 27713 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Nyska, A (reprint author), NIEHS, Lab Expt Pathol, MD B3-06,POB 12233, Res Triangle Pk, NC 27709 USA. EM nyska@niehs.nih.gov NR 65 TC 26 Z9 26 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 JAN-FEB PY 2003 VL 31 IS 1 BP 39 EP 51 DI 10.1080/01926230390173833 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA 631LL UT WOS:000180169200006 PM 12597448 ER PT J AU Waalkes, MP Ward, JM Liu, J Diwan, BA AF Waalkes, MP Ward, JM Liu, J Diwan, BA TI Transplacental carcinogenicity of inorganic arsenic in the drinking water: induction of hepatic, ovarian, pulmonary, and adrenal tumors in mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE arsenic; carcinogenesis; transplacental; animal models; mice ID DIMETHYLARSINIC ACID; CHRONIC STIMULATION; INTERNAL CANCERS; SKIN NEOPLASIA; GROWTH-FACTORS; F344/NCR RATS; ANIMAL-MODEL; WELL WATER; MORTALITY; TOXICITY AB Arsenic is a known human carcinogen, but development of rodent models of inorganic arsenic carcinogenesis has been problematic. Since gestation is often a period of high sensitivity to chemical carcinogenesis, we performed a transplacental carcinogenicity study in mice using inorganic arsenic, Groups (n = 10) of pregnant C3H mice were given drinking water containing sodium arsenite (NaAsO2) at 0 (control), 42.5, and 85 ppm arsenite ad libitum from day 8 to 18 of gestation. These doses were well tolerated and body weights of the dams during gestation and of the offspring subsequent to birth were not reduced. Darns were allowed to give birth, and offspring were weaned at 4 weeks and then put into separate gender-based groups (it = 25) according to maternal exposure level. The offspring received no additional arsenic treatment. The study lasted 74 weeks in males and 90 weeks in females. A complete necropsy was performed on all mice and tissues were examined by light microscopy in a blind fashion. In male offspring, there was a marked increase in hepatocellular carcinoma incidence in a dose-related fashion (control, 12%; 42.5 ppm, 38%; 85 ppm, 61%) and in liver tumor multiplicity (tumors per liver; 5.6-fold over control at 85 ppm), In males, there was also a dose-related increase in adrenal tumor incidence and multiplicity. In female offspring. dose-related increases Occurred in ovarian tumor incidence (control, 8%; 42.5 ppm, 26% 85 ppm, 38%) and lung carcinoma incidence (control, 0% 42.5 ppm, 4%; 85 ppm, 21%). Arsenic exposure also increased the incidence of proliferative lesions of the uterus and oviduct. These results demonstrate that oral inorganic arsenic exposure, as a single agent, can induce tumor formation in rodents and establishes inorganic arsenic as a complete transplacental carcinogen in mice. The development of this rodent model of inorganic arsenic carcinogenesis has important implications in defining the mechanism of action for this common environmental carcinogen. (C) 2003 Elsevier Science (USA), All rights reserved. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Sci, Frederick, MD 21702 USA. NCI, Intraumural Res Support Program, Sci Applicat Int Corp, Frederick, MD 21702 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 NCI NIH HHS [N01-CO-12400] NR 43 TC 182 Z9 191 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE 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 JAN 1 PY 2003 VL 186 IS 1 BP 7 EP 17 DI 10.1016/S0041-008X(02)00022-4 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 646PE UT WOS:000181042800002 PM 12583988 ER PT J AU Hirsch, DS Stanley, KT Chen, LX Jacques, KM Puertollano, R Randazzo, PA AF Hirsch, DS Stanley, KT Chen, LX Jacques, KM Puertollano, R Randazzo, PA TI Arf regulates interaction of GGA with mannose-6-phosphate receptor SO TRAFFIC LA English DT Article DE ADP-ribosylation factor; clathrin adaptor; GGA; mannose-6-phosphate receptor; membrane traffic ID ADP-RIBOSYLATION FACTOR; MANNOSE 6-PHOSPHATE RECEPTOR; GTPASE-ACTIVATING PROTEIN; COP-COATED VESICLES; GOLGI MEMBRANES; LYSOSOMAL-ENZYME; BINDING PROTEIN; ADAPTER COMPLEX; ENDOCYTIC PATHWAY; KDEL RECEPTOR AB The role of ADP-ribosylation factor (Arf) in Golgi associated, gamma-adaptin homologous, Arf-interacting protein (GGA)-mediated membrane traffic was examined. GGA is a clathrin adaptor protein that binds Arf through its GAT domain and the mannose-6-phosphate receptor through its VHS domain. The GAT and VHS domains interacted such that Arf and mannose-6-phosphate receptor binding to GGA were mutually exclusive. In vivo , GGA bound membranes through either Arf or mannose-6-phosphate receptor. However, mannose-6-phosphate receptor excluded Arf from GGA-containing structures outside of the Golgi. These data are inconsistent with predictions based on the model for Arf's role in COPI veside coat function. We propose that Arf recruits GGA to a membrane and then, different from the current model, 'hands-off' GGA to mannose-6-phosphate receptor. GGA and mannose-6-phosphate receptor are then incorporated into a transport intermediate that excludes Arf . C1 NCI, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Bldg 37 Room 6032, Bethesda, MD 20892 USA. NR 57 TC 21 Z9 21 U1 1 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD JAN PY 2003 VL 4 IS 1 BP 26 EP 35 DI 10.1034/j.1600-0854.2003.40105.x PG 10 WC Cell Biology SC Cell Biology GA 635WQ UT WOS:000180423300005 PM 12535273 ER PT S AU Hallett, M AF Hallett, M BE Paulus, W Tergau, F Nitsche, MA Rothwell, JG Ziemann, U Hallett, M TI Surround inhibition SO TRANSCRANIAL MAGNETIC STIMULATION AND TRANSCRANIAL DIRECT CURRENT STIMULATION SE SUPPLEMENTS TO CLINICAL NEUROPHYSIOLOGY LA English DT Proceedings Paper CT 2nd International Symposium on Transcranial Magnetic Simulation (TMS)/Transcranial Direct Current Simulation Symposium (tDCS) CY JUN 11-14, 2003 CL GOTTINGEN, GERMANY ID HUMAN MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; FOCAL HAND DYSTONIA; RECIPROCAL INHIBITION; INTRACORTICAL INHIBITION; VOLUNTARY MOVEMENT; PREMOTOR CORTEX; PRIMATE MOTOR; BASAL GANGLIA; EXCITABILITY C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Rm 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 40 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-424X BN 0-444-51438-4 J9 SUPPL CLIN NEUROPHYS PY 2003 VL 56 BP 153 EP 159 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA BY35E UT WOS:000189003100013 PM 14677389 ER PT J AU Stroncek, DF Njoroge, JM Procter, JL Childs, RW Miller, J AF Stroncek, DF Njoroge, JM Procter, JL Childs, RW Miller, J TI A preliminary comparison of flow cytometry and tube agglutination assays in detecting red blood cell-associated C3d SO TRANSFUSION MEDICINE LA English DT Article DE autoimmune haemolytic anaemia; Coombs' test; direct antiglobulin test; flow cytometry; red blood cells ID HEMOLYTIC-ANEMIA AB This study compared flow cytometric analysis with tube agglutination assays for the detection of red blood cell (RBC)-associated complement and immunoglobulins (Igs). RBCs from 20 patients with reactive tube direct antiglobulin tests (DATs) were evaluated by flow cytometry with anti-C3d, anti-IgG, anti-IgM and anti-IgA. Serial samples were also tested from a patient at risk of passenger lymphocyte haemolysis. Results of flow cytometry and tube assays for anti-IgG were as follows: 12 of 20 samples reactive in both; six of 20 nonreactive in both; two of 20 discordant with a reactive tube and a nonreactive flow cytometry assay. Anti-C3d results showed nine of 20 reactive in both and 11 of 20 discordant with a nonreactive tube and a reactive flow cytometry assay. In the IgM flow cytometry assay, three samples were reactive with anti-IgM. Samples from a group A woman who was transplanted with stem cells from a group B donor showed that on days 3 through 6 post-transplant, the flow cytometry assays for anti-IgG and/or anti-C3d were reactive, whilst the tube assays were nonreactive. In conclusion, flow cytometric analysis is more sensitive than the tube assay for the detection of RBC-associated C3d. Further studies are needed to determine the correlation of C3d levels with clinical sequelae. C1 NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bldg 10,Room 1C711,10 Ctr Dr,MSC-1184, Bethesda, MD 20892 USA. NR 13 TC 13 Z9 13 U1 2 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0958-7578 J9 TRANSFUSION MED JI Transfus. Med. PD JAN PY 2003 VL 13 IS 1 BP 35 EP 41 DI 10.1046/j.1365-3148.2003.00415.x PG 7 WC Hematology SC Hematology GA 645JD UT WOS:000180971700005 PM 12581452 ER PT J AU Stroncek, D Dale, JK Straus, SE AF Stroncek, D Dale, JK Straus, SE TI Autoimmune lymphoproliferative syndrome: An inherited disorder with a high incidence of autoimmune cytopenias SO TRANSFUSION MEDICINE AND HEMOTHERAPY LA English DT Review DE autoimmune lymphoproliferative syndrome; autoimmune hemolytic anemia; autoimmune thrombocytopenia; autoimmune neutropenia; Fas ID CANALE-SMITH-SYNDROME; IDIOPATHIC THROMBOCYTOPENIC PURPURA; FAS GENE-MUTATIONS; LYMPHOCYTE APOPTOSIS; DEFECTIVE LYMPHOCYTE; DOMINANT; DISEASE; LYMPHADENOPATHY; AUTOANTIBODIES; NEUTROPENIA AB Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder associated with abnormal lymphocyte apoptosis, lymphoproliferation, and autoimmunity. It is inherited as an autosomal dominant disorder with variable penetrance. The mutations in most ALPS patients are in the gene encoding the lymphocyte protein Fas (CD95, APO-1). Clinical manifestations of ALPS develop in infancy or early childhood. Severe lymphadenopathy and splenomegaly are common. Clinically significant autoantibodies most often are directed to red blood cells, neutrophils, and platelets. Hemolytic anemia, autoimmune neutropenia, and immune thrombocytopenia purpura occur frequently. ALPS patients have lymphocytosis and a number of lymphocyte abnormalities, including the marked expansion of T lymphocytes that express a T-cell receptors but neither CD4 nor CD8 surface markers (TCRalphabeta+ CD4- CD8-) cells. Lymphoproliferation in ALPS patients is generally benign, but they are at increased risk for the development of Hodgkin's and non-Hodgkin's lymphoma. The study of ALPS patients is providing important clues to lymphocyte homeostasis and the mechanisms responsible for the development of autoimmunity and lymphomas. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Stroncek, D (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 35 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1660-3796 J9 TRANSFUS MED HEMOTH JI Transfus. Med. Hemother. PY 2003 VL 30 IS 6 BP 270 EP 275 DI 10.1159/000075861 PG 6 WC Hematology; Immunology SC Hematology; Immunology GA 760CQ UT WOS:000187794000003 ER PT J AU Usdin, TB Dobolyi, A Ueda, H Palkovits, M AF Usdin, TB Dobolyi, A Ueda, H Palkovits, M TI Emerging functions for tuberoinfundibular peptide of 39 residues SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID SUBPARAFASCICULAR THALAMIC NUCLEUS; HORMONE-RELATED PEPTIDE; PARATHYROID-HORMONE; PTH2 RECEPTOR; RAT; PROTEIN; EXPRESSION; AGONIST; TIP39; HYPOTHALAMUS AB Tuberoinfundibular peptide of 39 residues (TIP39), a neuropeptide recently purified from the hypothalamus, appears to be an endogenous ligand for the parathyroid hormone 2 (PTH2) receptor. PTH2 receptors are present in several central nervous system and peripheral areas and are particularly concentrated in the hypothalamus, limbic areas and the outer layers of the spinal cord dorsal horn. TIP39-containing neuronal cell bodies have been identified in the subparafascicular area and the medial paralemniscal nucleus, two brainstem regions that project widely through the entire neuraxis. Treatment of hypothalamic explants with TIP39, and intraventricular injection of the peptide, suggest that it might stimulate hypothalamic-releasing factor secretion. Injection of TIP39, and sequestration of endogenous TIP39 by intrathecal injection of an antibody to TIP39, have provided evidence that it is involved in some aspects of pain sensitivity. Thus, TIP39 might be a new neuromodulator. C1 NIMH, Genet Lab, Bethesda, MD 20892 USA. Nagasaki Univ, Sch Pharmaceut Sci, Dept Mol Pharmacol & Neurosci, Nagasaki 8528521, Japan. RP Usdin, TB (reprint author), NIMH, Genet Lab, Bldg 36,Room 3D06,36 Convent Dr, Bethesda, MD 20892 USA. RI Dobolyi, Arpad/B-9089-2008; Palkovits, Miklos/F-2707-2013; OI Palkovits, Miklos/0000-0003-0578-0387 NR 27 TC 30 Z9 30 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD JAN PY 2003 VL 14 IS 1 BP 14 EP 19 AR PII S1043-2760(02)00002-4 DI 10.1016/S1043-2760(02)00002-4 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 630ER UT WOS:000180095000006 PM 12475607 ER PT J AU Mocellin, S Panelli, MC Wang, E Nagorsen, D Marincola, FM AF Mocellin, S Panelli, MC Wang, E Nagorsen, D Marincola, FM TI The dual role of IL-10 SO TRENDS IN IMMUNOLOGY LA English DT Review ID NECROSIS-FACTOR-ALPHA; HUMAN-MELANOMA CELLS; CLASS-I EXPRESSION; DENDRITIC CELLS; CYTOKINE PRODUCTION; HUMAN ENDOTOXEMIA; IMMUNE-RESPONSE; TUMOR-GROWTH; ADENOCARCINOMA CELLS; EFFECTOR FUNCTION AB Classification of cytokines as pro-versus anti-inflammatory might not apply to the pleiotropic effects of interleukin-10 (IL-10). Several reports suggest that IL-10 enhances the function of natural killer cells, which leads, through pathogen destruction, to increased antigen availability. In addition, by inhibiting the maturation of antigen-presenting cells (APCs), IL-10 preserves their ability for antigen uptake while simultaneously hampering their migration to draining lymph nodes. This review suggests that this 'antigen-loading' phase might constitute an important component of the innate immune reaction to a pathogen. Additional proinflammatory stimuli might subsequently lead to maturation of 'loaded' APCs that could migrate to draining lymph nodes or recruit and activate adaptive immune effectors locally. C1 NIH, Ctr Clin, Dept Transfus Med, Immunogenet Sect, Bethesda, MD 20892 USA. Univ Padua, Surg Branch, Dept Oncol & Surg Sci, I-35128 Padua, Italy. RP Marincola, FM (reprint author), NIH, Ctr Clin, Dept Transfus Med, Immunogenet Sect, 10 Ctr Dr,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 65 TC 268 Z9 284 U1 1 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD JAN PY 2003 VL 24 IS 1 BP 36 EP 43 AR PII S1471-4906(02)00009-1 DI 10.1016/S1471-4906(02)00009-1 PG 8 WC Immunology SC Immunology GA 632GQ UT WOS:000180215900013 PM 12495723 ER PT J AU Sandor, M Weinstock, JV Wynn, TA AF Sandor, M Weinstock, JV Wynn, TA TI Granulomas in schistosome and mycobacterial infections: a model of local immune responses SO TRENDS IN IMMUNOLOGY LA English DT Review ID NITRIC-OXIDE SYNTHASE; SUBSTANCE-P RECEPTOR; BACILLUS-CALMETTE-GUERIN; INDUCED LIVER GRANULOMAS; MURINE SCHISTOSOMIASIS; IFN-GAMMA; T-CELLS; MACROPHAGE ACTIVATION; NEUROKININ-1 RECEPTOR; INFLAMMATORY CELLS AB Granulomatous immune responses are interesting models for the effector phase of immunity, in that granulomas can be part of both immune protection and disease pathology during the course of various infectious and autoimmune diseases. Focusing mainly on granulomas induced by Schistosoma or Mycobacterium infection, this article reviews T-cell recruitment, local cytokine networks and the regulation of cytokine networks by neuropeptides in granulomas. In addition, different activation pathways for macrophages residing in granulomas are discussed. Granulomas are unique inflammatory sites that offer a challenging and rewarding model to study immunity. C1 Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Med Sci Ctr, Madison, WI 53706 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. NIAID, Parasit Dis Lab, Schistosomiasis Immunol & Pathol Unit, Immunol Sect,NIH, Bethesda, MD 20892 USA. RP Sandor, M (reprint author), Univ Wisconsin, Sch Med, Dept Pathol & Lab Med, Med Sci Ctr, Room 5468,1300 Univ Ave, Madison, WI 53706 USA. RI Wynn, Thomas/C-2797-2011 FU NIAID NIH HHS [AI 48087-02, R01 AI 46430-01]; NIDDK NIH HHS [DK 02428, DK 25295, DK 38327, DK 58755] NR 78 TC 69 Z9 69 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD JAN PY 2003 VL 24 IS 1 BP 44 EP 52 DI 10.1016/S1471-4906(02)00006-6 PG 9 WC Immunology SC Immunology GA 632GQ UT WOS:000180215900014 PM 12495724 ER PT J AU Young, MR Yang, HS Colburn, NH AF Young, MR Yang, HS Colburn, NH TI Promising molecular targets for cancer prevention: AP-1, NF-kappa B and Pdcd4 SO TRENDS IN MOLECULAR MEDICINE LA English DT Review ID C-JUN; NEOPLASTIC TRANSFORMATION; SKIN CARCINOGENESIS; HUMAN KERATINOCYTES; DELETION MUTANT; TUMOR-FORMATION; PROTO-ONCOGENE; FRA-1 GENE; JB6 CELLS; MOUSE AB There are still many unanswered questions regarding the processes by which extracellular signals are transduced from plasma-membrane receptors to the transcription machinery in the nucleus and the translation machinery in the cytoplasm. Some of these gene expression events become misregulated as a result of environmental or endogenous exposure to agents that cause multistage carcinogenesis. We are now beginning to identify and validate the crucial molecular events that drive the rate-limiting steps of carcinogenesis and to target these events for cancer prevention. Transcription factors AP-1 and nuclear factor kappaB can be specifically targeted to prevent cancer induction in mouse models. A protein known as program med-cell-death-4 is a new potential molecular target that has a surprising mode of action. C1 NCI, Gene Regulat Sect, Basic Res Lab, Frederick, MD 21702 USA. RP Young, MR (reprint author), NCI, Gene Regulat Sect, Basic Res Lab, Frederick, MD 21702 USA. RI Yang, Hsin-Sheng/A-6419-2008 NR 61 TC 121 Z9 122 U1 0 U2 7 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 JAN PY 2003 VL 9 IS 1 BP 36 EP 41 AR PII S1471-4914(02)00009-6 DI 10.1016/S1471-4914(02)00009-6 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 639EQ UT WOS:000180615000007 PM 12524209 ER PT J AU Kuner, T Seeburg, PH Guy, HR AF Kuner, T Seeburg, PH Guy, HR TI A common architecture for K+ channels and ionotropic glutamate receptors? SO TRENDS IN NEUROSCIENCES LA English DT Editorial Material ID POTASSIUM CHANNEL; SUBSTITUTED CYSTEINES; SCANNING MUTAGENESIS; SELECTIVITY FILTER; N-GLYCOSYLATION; ION CHANNELS; M2 SEGMENT; PORE; ACCESSIBILITY; TOPOLOGY AB K+ channels and ionotropic glutamate receptors are thought to share a common architecture in their transmembrane pores. This oft-cited hypothesis has been derived from sequence comparisons, topology profiling and analogies to a bacterial glutamate receptor with a K+-channel pore. Although none of these arguments provides sufficient evidence for structural kinship, existing structural data and a new pedigree of bacterial glutamate receptors offer strong support. Comparisons of the patterns of pore-lining residues and mapping of functional determinants reveal extensive structural similarities, and new homologs of bacterial glutamate receptors strengthen the evolutionary link between glutamate receptors and K+ channels. C1 Max Planck Inst Med Res, Dept Cell Physiol, D-69120 Heidelberg, Germany. Max Planck Inst Med Res, Dept Mol Neurosci, D-69120 Heidelberg, Germany. NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Kuner, T (reprint author), Max Planck Inst Med Res, Dept Cell Physiol, Jahnstr 29, D-69120 Heidelberg, Germany. EM kuner@mpimf-heidelberg.mpg.de NR 39 TC 81 Z9 88 U1 1 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD JAN PY 2003 VL 26 IS 1 BP 27 EP 32 AR PII S0166-2236(02)00010-3 DI 10.1016/S0166-2236(02)00010-3 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 632GR UT WOS:000180216000009 PM 12495860 ER PT J AU Fauci, AS AF Fauci, AS TI Introduction to the Proceedings of the 4th World Congress on Tuberculosis SO TUBERCULOSIS LA English DT Editorial Material C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PY 2003 VL 83 IS 1-3 BP 3 EP 3 DI 10.1016/S1472-9792(02)00086-0 PG 1 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 689WQ UT WOS:000183516300002 ER PT J AU Hasan, Z Shah, BH Mahmood, A Young, DB Hussain, R AF Hasan, Z Shah, BH Mahmood, A Young, DB Hussain, R TI The effect of mycobacterial virulence and viability on MAP kinase signalling and TNF alpha production by human monocytes SO TUBERCULOSIS LA English DT Article DE mycobacterium; human monocytes; TNF alpha; MAPK activation ID TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-KINASE; NITRIC-OXIDE SYNTHASE; HUMAN MACROPHAGES; BOVIS BCG; IN-VITRO; NONPATHOGENIC MYCOBACTERIA; TUBERCULOSIS INFECTION; CULTURED MACROPHAGES; CELLULAR ACTIVATION AB Setting: The success of Mycobacterium tuberculosis as a human pathogen depends on its ability to tolerate and perhaps manipulate host defense mechanisms. Objective: To determine the induction of tumour necrosis factor-alpha (TNFalpha), a central mediator of immunity, by human monocytes infected with virulent M. tuberculosis, M. leprae and attenuated M. bovis BCG. Design: Mycobacteria-induced cellular activation pathways of TNFalpha production was investigated using an inhibitor of protein tyrosine kinase (PTKs) and an inhibitor of mitogen-activated protein (MAP) kinases. Results:TNFalpha production was significantly lower during infection with virulent M. tuberculosis than with BCG and this differential response was independent of mycobacterial viability. TNFalpha production involved the PTK and MAP kinase pathways. Reduced TNFalpha induction by M. tuberculosis was associated with a reduction in the extent and duration of phosphorylation of extracellular-signal regulated kinases (ERK 1/2). Infection with M. leprae triggered low and transient ERK 1/2 activation as well as low TNFalpha production. Conclusion: Maintenance of the differential response in both live and heat-killed preparations suggests that the reduced TNFalpha response associated with virulent mycobacteria is due to differences in the presence of components capable of triggering host pattern recognition receptors, rather than events associated with phagosome trafficking or the active release of intracellular modulators. (C) 2003 Elsevier Ltd. All rights reserved. C1 Aga Khan Univ, Dept Microbiol, Karachi 74800, Pakistan. NICHD, NIH, Bethesda, MD USA. Univ London Imperial Coll Sci Technol & Med, CMMI, London, England. RP Hasan, Z (reprint author), Aga Khan Univ, Dept Microbiol, Stadium Rd,POB 3500, Karachi 74800, Pakistan. RI Hussain, Rabia/E-9982-2015; Hasan, Zahra/F-5111-2015; Hussain, Rabia/M-6649-2015 OI Hussain, Rabia/0000-0001-9995-8742 NR 61 TC 24 Z9 26 U1 0 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 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PY 2003 VL 83 IS 5 BP 299 EP 309 DI 10.1016/S1472-9792(03)00003-9 PG 11 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 728DR UT WOS:000185700400004 PM 12972343 ER PT S AU Verma, M Srivastava, S AF Verma, M Srivastava, S BE Senn, HJ Morant, R TI New cancer biomarkers deriving from NCI early detection research SO TUMOR PREVENTION AND GENETICS SE RECENT RESULTS IN CANCER RESEARCH LA English DT Proceedings Paper CT 2nd International Conference on Tumor Prevention and Genetics CY FEB 14-16, 2002 CL ST GALLEN UNIV, ST GALLEN, SWITZERLAND HO ST GALLEN UNIV ID LUNG-CANCER; PROTEOMIC APPROACH; MASS-SPECTROMETRY; MARKERS; IDENTIFICATION; GLYCOSYLATION; COMBINATION; EXPRESSION; DISCOVERY AB Cancer is not a single disease but an accumulation of several events, genetic and epigenetic, arising in a single cell over a long time interval. A high priority in the cancer field is to identify these events. This can be achieved by characterizing cancer-associated genes and their protein products. Identifying the molecular alterations that distinguish any particular cancer cell from a normal cell will ultimately help to define the nature and predict the pathologic behavior of that cancer cell. It will also indicate the responsiveness to treatment of that particular tumor. Understanding the profile of molecular changes in any particular cancer will be extremely useful as it will become possible to correlate the resulting phenotype of that cancer with molecular events. Achieving these goals and knowledge will provide an opportunity for discovering new biomarkers for early cancer detection and developing prevention approaches. This will also help us identify new targets for therapeutic development. Advancement in technology includes methods and tools that enable research including, but not limited to, instrumentation, techniques, devices, and analysis tools (e.g., computer software). Resources such as databases, reagents, and tissue repositories are different than technologies. The identification and definition of the molecular profiles of cancer will require the development and dissemination of high-throughput molecular analysis technologies, as well as elucidation of all of the molecular species embedded in the genome of cancer and normal cells. The main challenge in cancer control and prevention is to detect the cancer early. This could then enable effective interventions and therapies contributing to reduction in mortality and morbidity. At a specific time, biomarkers serve as molecular signposts of the physiologic state of a cell. These signposts are the result of genes, their products (proteins) and other organic chemicals made by the cell. Biomarkers could prove to be vital for the identification of early cancer and subjects at risk of developing cancer as a normal cell progresses through the complex process of transformation to a cancerous state. This chapter discusses ongoing research in genetic and proteomic approaches to identify molecular signatures such as protein profiles, microsatellite instability, hypermethylation, and single nucleotide polymorphisms. Other topics covered here include the use of genomics and proteomics as high-throughput technology platforms to facilitate biomarker-aided detection of early cancer. Other areas covered include issues surrounding the analysis, validation, and predictive value of biomarkers using such technologies. Recent advances in noninvasive techniques, such as buccal cell isolates serving as viable sources of biomarkers, complementary to traditional sources such as serum or plasma, are also presented. The review also brings attention to the efforts of the Early Detection Research Network (EDRN) at the National Cancer Institute (NCI), in bringing together scientific expertise from leading national and international institutions, to identify and validate biomarkers for the detection of precancerous and cancerous cells in determining risk for developing cancer. The network's serious determined efforts in linking discovery to process development, resulting in early detection tests and clinical assessment, are also discussed. C1 NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, Rockville, MD 20852 USA. RP Srivastava, S (reprint author), NCI, Canc Biomarkers Res Grp, Div Canc Prevent, NIH, 6130 Execut Blvd,EPN-3142, Rockville, MD 20852 USA. NR 20 TC 44 Z9 46 U1 0 U2 3 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-44062-3 J9 RECENT RES CANCER PY 2003 VL 163 BP 72 EP 84 PG 13 WC Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Oncology; Genetics & Heredity; Research & Experimental Medicine GA BX13P UT WOS:000184369100007 PM 12903844 ER PT S AU Szabo, E Kalebic, T AF Szabo, E Kalebic, T BE Senn, HJ Morant, R TI Chemoprevention of lung cancer: New directions SO TUMOR PREVENTION AND GENETICS SE RECENT RESULTS IN CANCER RESEARCH LA English DT Proceedings Paper CT 2nd International Conference on Tumor Prevention and Genetics CY FEB 14-16, 2002 CL ST GALLEN UNIV, ST GALLEN, SWITZERLAND HO ST GALLEN UNIV ID 2ND PRIMARY TUMORS; BETA-CAROTENE; VITAMIN-A; LIPOXYGENASE INHIBITORS; BRONCHIAL EPITHELIUM; SQUAMOUS METAPLASIA; RANDOMIZED TRIAL; TYROSINE KINASE; FORMER SMOKERS; BREAST-CANCER AB The refractoriness of advanced lung cancer to current treatment modalities requires new approaches to reduce the public health burden associated with this disease. One strategy that is currently being tested is chemoprevention, which aims to prevent the development of cancer in populations that are at high risk for cancer due to a variety of genetic or environmental factors. The key to the success of this approach, however, requires the identification of appropriately targeted efficacious, non-toxic agents as well as the methodologies to efficiently test them. Given the lack of success of previous phase III definitive lung cancer chemoprevention trials, there is a need for smaller scale phase II trials with molecular, imaging, or histologic endpoints to demonstrate preliminary safety and efficacy. The identification of molecular pathways critical to lung carcinogenesis offers the opportunity to develop targeted therapies for prevention. Means of optimizing the risk/benefit ratio associated with treatment include regional drug delivery that minimizes systemic toxicities and combination therapies. Identification of the most appropriate cohorts, such as former smokers without ongoing DNA damage due to carcinogen exposure, may uncover benefits that are hidden in a mixed population. Equally important is the identification of appropriate study endpoints that are predictive of patient outcomes such as cancer incidence. Further understanding of lung cancer biology will be critical to the success of future clinical trials. C1 NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Szabo, E (reprint author), NCI, Lung & Upper Aerodigest Canc Res Grp, Div Canc Prevent, 6130 Execut Blvd,Room 2132, Bethesda, MD 20892 USA. NR 45 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0080-0015 BN 3-540-44062-3 J9 RECENT RES CANCER PY 2003 VL 163 BP 172 EP 181 PG 10 WC Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Oncology; Genetics & Heredity; Research & Experimental Medicine GA BX13P UT WOS:000184369100016 PM 12903853 ER PT S AU Haller, K Jeang, KT AF Haller, K Jeang, KT BE Sugamura, K Uchiyama, T Matsuoka, M Kannagi, M TI Clastogenic and aneugenic DNA damage in HTLV-1 Tax-expressing cells SO TWO DECADES OF ADULT T-CELL LEUKEMIA AND HTLV-I RESEARCH SE GANN MONOGRAPH ON CANCER RESEARCH LA English DT Proceedings Paper CT Symposium on Two Decades since the Discovery of the Viral Pathogenesis of ATL CY APR, 2001 CL KYOTO, JAPAN SP Japanese Canc Assoc ID VIRUS TYPE-1 TAX; SPINDLE ASSEMBLY CHECKPOINT; POLYMERASE CHAIN-REACTION; NF-KAPPA-B; MITOTIC CHECKPOINT; SACCHAROMYCES-CEREVISIAE; CYCLE ARREST; I TAX; LEUKEMIA LYMPHOMA; HUMAN-LYMPHOCYTES AB The probability of developing cancer increases with advancing age. Presentation of cancer is the net outcome between processes which generate abnormal cells and those which eliminate them. It has been estimated that the number of sporadic genetic changes needed to convert a normal to a malignant cell are so numerous that one might not mathematically expect cancers to emerge during a human lifespan. However, the fact that cancers are commonly seen suggests that cells are not simply subject to ambient mistakes. Indeed, it is now clear that in many cases cells show an accelerated proclivity for genetic mutations after the acquisition of a "mutator" phenotype. Such mutator phenotype could either arise spontaneously or be induced after infection with an oncogenic virus such as human T cell leukemia virus type I (HTLV-I). In this chapter, we explore the evidence supporting the notion that HTLV-I Tax functions early in ATL-transformation by conferring a imitator phenotype to cells. We review how Tax affects cellular genetic stability by dysregulation of the mitotic spindle assembly checkpoint and other repair pathways to produce aneuploidy and clastogenic DNA damage. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Haller, K (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 66 TC 0 Z9 0 U1 0 U2 0 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0072-0151 BN 3-8055-7543-2 J9 GANN MONOGR CANC RES PY 2003 IS 50 BP 93 EP 102 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Virology SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Virology GA BW75V UT WOS:000183073300010 ER PT S AU Johnson, JM Fukumoto, R Franchini, G AF Johnson, JM Fukumoto, R Franchini, G BE Sugamura, K Uchiyama, T Matsuoka, M Kannagi, M TI Functional role of the HTLV-1 p12(I) protein SO TWO DECADES OF ADULT T-CELL LEUKEMIA AND HTLV-I RESEARCH SE GANN MONOGRAPH ON CANCER RESEARCH LA English DT Proceedings Paper CT Symposium on Two Decades since the Discovery of the Viral Pathogenesis of ATL CY APR, 2001 CL KYOTO, JAPAN SP Japanese Canc Assoc ID T-CELL LEUKEMIA; VIRUS TYPE-I; READING-FRAME-I; TROPICAL SPASTIC PARAPARESIS; HIV-1 NEF PROTEIN; TAX PROTEIN; CONSTITUTIVE ACTIVATION; INTERLEUKIN-2 RECEPTOR; JAK/STAT ACTIVATION; PRIMARY LYMPHOCYTES C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. RP Johnson, JM (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. NR 75 TC 0 Z9 0 U1 0 U2 0 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0072-0151 BN 3-8055-7543-2 J9 GANN MONOGR CANC RES PY 2003 IS 50 BP 103 EP 113 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Virology SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Virology GA BW75V UT WOS:000183073300011 ER PT S AU Yamano, Y Tomaru, U Jacobson, S AF Yamano, Y Tomaru, U Jacobson, S BE Sugamura, K Uchiyama, T Matsuoka, M Kannagi, M TI Role of HTLV-I specific CTL in HAM/TSP SO TWO DECADES OF ADULT T-CELL LEUKEMIA AND HTLV-I RESEARCH SE GANN MONOGRAPH ON CANCER RESEARCH LA English DT Proceedings Paper CT Symposium on Two Decades since the Discovery of the Viral Pathogenesis of ATL CY APR, 2001 CL KYOTO, JAPAN SP Japanese Canc Assoc ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; CELL LEUKEMIA-VIRUS; CD8(+) T-CELLS; BLOOD MONONUCLEAR-CELLS; CENTRAL-NERVOUS-SYSTEM; PROVIRAL DNA LOAD; POLYMERASE CHAIN-REACTION; SPINAL-CORD LESIONS; PERIPHERAL-BLOOD AB Human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic, progressive neurological disease characterized by marked degeneration of the spinal cord and the presence of infiltrating T cells and macrophages. HAM/TSP patients harbor very high frequencies of HTLV-I infected T cells and HTLV-I specific CD8+ T cells in both peripheral blood and cerebrospinal fluid. The use of novel molecular and immunological methods has improved our understanding of the underlying pathological mechanisms operative in HAM/TSP. Information presented in this review suggests that HTLV-I infected T cells and HTLV-I specific CD8+ T cells accumulate in central nervous system (CNS), in which high cellular immune response continuously driven by this virus may contribute to the inflammatory process within CNS lesions in HAM/TSP patients. C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Yamano, Y (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 72 TC 0 Z9 0 U1 0 U2 0 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0072-0151 BN 3-8055-7543-2 J9 GANN MONOGR CANC RES PY 2003 IS 50 BP 171 EP 182 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Virology SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Virology GA BW75V UT WOS:000183073300016 ER PT S AU Maloney, EM Blattner, WA AF Maloney, EM Blattner, WA BE Sugamura, K Uchiyama, T Matsuoka, M Kannagi, M TI HTLV-I worldwide patterns and disease associations SO TWO DECADES OF ADULT T-CELL LEUKEMIA AND HTLV-I RESEARCH SE GANN MONOGRAPH ON CANCER RESEARCH LA English DT Proceedings Paper CT Symposium on Two Decades since the Discovery of the Viral Pathogenesis of ATL CY APR, 2001 CL KYOTO, JAPAN SP Japanese Canc Assoc ID VIRUS TYPE-I; T-CELL LEUKEMIA; TROPICAL SPASTIC PARAPARESIS; TRINIDAD-AND-TOBAGO; SEXUALLY-TRANSMITTED DISEASES; INJECTING DRUG-USERS; DEFICIENCY SYNDROME AIDS; INFECTED BLOOD-DONORS; NON-HODGKIN-LYMPHOMA; HIGH PROVIRAL LOAD AB The 1980 publication reporting the discovery of the first human retrovirus, human T-lymphotropic virus type I (HTLV-I), culminated a decadelong search for the human homologue to cancer-causing retroviruses initially identified in the first decade of the 20th century. HTLVA-II, the second human retrovirus, was discovered in 1982. This review will focus on HTLV-I. Since the discovery of HTLV-I, extensive progress has been made in characterizing the worldwide distribution and disease associations of this virus. The geographic distribution of HTLV-I varies based on the three types, termed Cosmopolitan, Central African, and Australo-Melanesian. Of these three types, the most widespread worldwide is the Cosmopolitan strain, having four subtypes: subtype A (Transcontinental), subtype B (Japanese), subtype C (West African), and subtype D (North African). Japan and the Caribbean are major areas of HTLV-I endemicity where prevalence ranges from 3 to 15% and is characterized by an age-dependent rise commencing in adolescence, with higher rates in females compared to males. HTLV-I is transmitted from mother to child usually via breastfeeding, parenterally by transfusion of infected cellular blood products or exposure to contaminated needles, and sexually from male to female, female to male and male to male. Heightened transmission is associated with the presence of high antibody titer and elevated proviral load, while elevated tax-specific antibody is linked to decreased transmission. A history of sexually transmitted infection, particularly those causing an ulcerative genital lesion, is also associated with increased risk for HTLV-I transmission. Diseases associated with HTLV-I share an inability to down-modulate viral expression. Some conditions such as adult T-cell leukerma/lymphoma, originally detected in Japan in 1977, result from a monoclonal expansion of HTLV-I infected T-cells. The ability of HTLV-I and particularly the Tax protein to disrupt cell cycle regulatory pathways provides a model for understanding the pathogenesis of HTLV-associated disease. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Maloney, EM (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 155 TC 0 Z9 0 U1 0 U2 1 PU JAPAN SCIENTIFIC SOC PRESS PI TOKYO PA 2-10 HONGO, 6-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0072-0151 BN 3-8055-7543-2 J9 GANN MONOGR CANC RES PY 2003 IS 50 BP 339 EP 361 PG 23 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Virology SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Virology GA BW75V UT WOS:000183073300028 ER PT S AU Schotte, F Wulff, M Anfinrud, P AF Schotte, F Wulff, M Anfinrud, P BE Miller, DR Murnane, MM Scherer, NF Weiner, AM TI Watching a protein as it functions: real-time observations using picosecond crystallography SO ULTRAFAST PHENOMENA XIII SE SPRINGER SERIES IN CHEMICAL PHYSICS LA English DT Proceedings Paper CT 13th International Conference on Ultrafast Phenomena CY MAY 12-17, 2002 CL VANCOUVER, CANADA SP Opt Soc Amer ID LIGAND-BINDING; MYOGLOBIN AB The structural changes associated with ligand translocation in myoglobin have been investigated with picosecond time-resolved x-ray crystallography. These studies, conducted on the ID09 beamline at the ESRF in Grenoble, France, unveil the protein's structural evolution with < 2 Angstrom resolution. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Schotte, F (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0172-6218 BN 3-540-00089-5 J9 SPRINGER SERIES CHEM PY 2003 VL 71 BP 602 EP 604 PG 3 WC Physics, Applied; Physics, Atomic, Molecular & Chemical SC Physics GA BW56Z UT WOS:000182432900186 ER PT S AU Parsegian, VA AF Parsegian, VA BE Bezrukov, SM TI Forces and fluctuations: Nourished by noise SO UNSOLVED PROBLEMS OF NOISE AND FLUCTUATIONS SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 3rd International Conference on Unsolved Problems of Noise and Fluctuations in Physics, Biology and High Technology CY SEP 03-06, 2002 CL NIH, BETHESDA, MD SP NICHD, NINDS, NIDCD HO NIH C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Parsegian, VA (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0127-6 J9 AIP CONF PROC PY 2003 VL 665 BP 9 EP 16 PG 8 WC Biophysics; Engineering, Biomedical; Physics, Applied SC Biophysics; Engineering; Physics GA BW87Q UT WOS:000183446000001 ER PT S AU Ospeck, M Iwasa, KH AF Ospeck, M Iwasa, KH BE Bezrukov, SM TI Noise in the outer hair cell and gain control in the ear SO UNSOLVED PROBLEMS OF NOISE AND FLUCTUATIONS SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 3rd International Conference on Unsolved Problems of Noise and Fluctuations in Physics, Biology and High Technology CY SEP 03-06, 2002 CL NIH, BETHESDA, MD SP NICHD, NINDS, NIDCD HO NIH ID BASILAR-MEMBRANE; HEARING; COCHLEA AB We present a minimal model of a local resonance inside the mammalian cochlea in which a feedback loop containing an outer hair cell is poised on a dynamical instability. This model results in an amplifier essentially equivalent to a van der Pol oscillator in its weakly nonlinear limit. The feedback loop automatically seeks the instability where gain and gain compression are optimized. The outer hair cell's average membrane potential is the control parameter which sets amplifier gain. We briefly investigate noise sources inside the outer hair cell which contribute to the feedback loop oscillating in a noise-driven limit-cycle. Experimentally this limit-cycle is increased by 3 to 5 times in high external noise environments. A half millivolt shift due to efferent stimulation can account for the observed 50 percent reduction in both the size of the noisy limit-cycle oscillation and the feedback loop gain. C1 NIDCD, Biophys Sect, NIH, Bethesda, MD 20892 USA. RP Ospeck, M (reprint author), NIDCD, Biophys Sect, NIH, 50 South Dr,MSC 8027, Bethesda, MD 20892 USA. NR 23 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0127-6 J9 AIP CONF PROC PY 2003 VL 665 BP 116 EP 124 PG 9 WC Biophysics; Engineering, Biomedical; Physics, Applied SC Biophysics; Engineering; Physics GA BW87Q UT WOS:000183446000014 ER PT S AU Bezrukov, SM AF Bezrukov, SM BE Bezrukov, SM TI Sensing nature's electric fields: Ion channels as active elements of linear amplification SO UNSOLVED PROBLEMS OF NOISE AND FLUCTUATIONS SE AIP Conference Proceedings LA English DT Proceedings Paper CT 3rd International Conference on Unsolved Problems of Noise and Fluctuations in Physics, Biology and High Technology CY SEP 03-06, 2002 CL NIH, BETHESDA, MD SP NICHD, NINDS, NIDCD HO NIH ID NOISE; CONDUCTORS; SKATES; LIMITS AB Given the parameters of familiar cellular elements - voltage-sensitive ion channels, carriers, pumps, phospholipid insulators, and electrolytic conductors - is it possible to construct an amplifier whose sensitivity matches the 5 nV/cm threshold found in behavioral experiments on elasmobranch fish? Or, in addition to clever circuitry that uses commonly known elements and principles, do we need something else to understand this sensitivity? The resolution of this question is important not only for studies in sensory biophysics seeking to reveal underlying mechanisms and molecular structures. More generally, it deepens our appreciation of the stochastic nature of inter- and intra-cellular control circuits. Here I analyze a simplified circuit involving negative differential resistance of voltage-sensitive ion channels. The analysis establishes an off-equilibrium criterion for amplification, shows that ion channels are the dominant noise sources, and, by minimizing channel noise within the given constraints, demonstrates that generic voltage-sensitive ion channels are likely candidates for the active elements of the linear cellular amplifiers. Finally, I highlight a number of unsolved issues. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. NR 15 TC 1 Z9 1 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0127-6 J9 AIP CONF PROC PY 2003 VL 665 BP 142 EP 149 PG 8 WC Biophysics; Engineering, Biomedical; Physics, Applied SC Biophysics; Engineering; Physics GA BW87Q UT WOS:000183446000017 ER PT S AU Berezhkovskii, A Hummer, G AF Berezhkovskii, A Hummer, G BE Bezrukov, SM TI Random walk model for single-file transport of water molecules through carbon nanotubes SO UNSOLVED PROBLEMS OF NOISE AND FLUCTUATIONS SE AIP Conference Proceedings LA English DT Proceedings Paper CT 3rd International Conference on Unsolved Problems of Noise and Fluctuations in Physics, Biology and High Technology CY SEP 03-06, 2002 CL NIH, BETHESDA, MD SP NICHD, NINDS, NIDCD HO NIH AB A one-dimensional random walk model has been used to describe the single-file transport of water molecules through the interior channel of a carbon nanotube. Here, we derive expressions for the translocation and return probabilities of a molecule that has entered the channel; the distribution of the number of molecules traversing the tube in a unidirectional conduction pulse; the average time spent in the tube by molecules that either translocate through the tube or exit at the entry site; the average duration of unidirectional conduction bursts; and the average reversal time between oppositely directed conduction pulses. C1 NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Berezhkovskii, A (reprint author), NIH, Ctr Informat Technol, Math & Stat Comp Lab, Bldg 10, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 1 U2 4 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0127-6 J9 AIP CONF PROC PY 2003 VL 665 BP 267 EP 272 PG 6 WC Biophysics; Engineering, Biomedical; Physics, Applied SC Biophysics; Engineering; Physics GA BW87Q UT WOS:000183446000032 ER PT S AU Kuznetsov, VA AF Kuznetsov, VA BE Bezrukov, SM TI Stochastic model of evolution of conserved protein coding sequences SO UNSOLVED PROBLEMS OF NOISE AND FLUCTUATIONS SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 3rd International Conference on Unsolved Problems of Noise and Fluctuations in Physics, Biology and High Technology CY SEP 03-06, 2002 CL NIH, BETHESDA, MD SP NICHD, NINDS, NIDCD HO NIH ID NETWORKS; GENOME AB We study statistical distributions of events appearing for a variety of evolutionary conserved sequences encoded in a variety of genomes. Skewed empirical distributions of the number of non-redundant domain-to-protein links in bacterial, archaeal and eukaryotic proteomes [1,2], and the number of links between conserved order orthologous groups of genes in genomes of prokaryotes [3] are analyzed. The Kolmogorov forward differential-difference equations for a linear birth-death evolution process are used to explain these distributions. These equations provide a limiting solution in form of the terms of hypergeometric Gauss series F-2(1)(a,1;b+1;theta). We show that the limiting probability function associated with this series fits both empirical distributions well. For the case of domain-to-protein links distributions, the degenerate F-2(1)-function at theta = 1 (the Waring distribution) holds true for eukaryotic proteomes; however, for many archaeal and bacterial proteomes the distribution degenerates to the Yule distribution. These results indicate the critical changes of the conserved protein-coding sequences organization in the course of progressive evolution from prokaryotic to eukaryotic organisms and predict the number of the domains in the eukaryotic proteomes. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Kuznetsov, VA (reprint author), NICHHD, Lab Integrat & Med Biophys, NIH, 13 South Dr, Bethesda, MD 20892 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 0-7354-0127-6 J9 AIP CONF PROC PY 2003 VL 665 BP 369 EP 380 PG 12 WC Biophysics; Engineering, Biomedical; Physics, Applied SC Biophysics; Engineering; Physics GA BW87Q UT WOS:000183446000043 ER PT J AU Klein, EA Thompson, IM Lippman, SM Goodman, PJ Albanes, D Taylor, PR Coltman, C AF Klein, EA Thompson, IM Lippman, SM Goodman, PJ Albanes, D Taylor, PR Coltman, C TI SELECT: the selenium and vitamin E cancer prevention trial SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS LA English DT Article DE prostate cancer; chemoprevention; selenium; vitamin E ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; KINASE-C ACTIVITY; PROSTATE-CANCER; BETA-CAROTENE; ALPHA-TOCOPHEROL; COLORECTAL-CANCER; LUNG-CANCER; COLON-CANCER; FOLLOW-UP AB Purpose: Growing evidence suggests that both selenium and vitamin E may reduce the risk of prostate cancer. SELECT is a randomized, prospective, double-blind study designed to determine if selenium and vitamin E can reduce the risk of prostate cancer among healthy men. Materials and methods: The preclinical and epidemiologic evidence regarding chemoprevention with selenium and vitamin E were reviewed. Secondary analyses from randomized trials of both agents were included in the analysis. Data from these analyses as well as evidence from the Prostate Cancer Prevention Trial were used to develop the schema of SELECT. Results: Preclinical, epidemiologic, and Phase III data suggest that both selenium and vitamin E have potential efficacy in prostate cancer prevention. The experience of the Prostate Cancer Prevention Trial and the rapid accrual of SELECT during its first year demonstrate the interest and dedication of healthy men to long-term studies of cancer prevention. A total of 32,400 men are planned to be randomized in SELECT. Conclusions: SELECT is the second large-scale study of chemoprevention for prostate cancer. Enrollment began in 2001 with final results anticipated in 2013. (C) 2003 Elsevier Science Inc. All rights reserved. C1 Cleveland Clin Fdn, Dept Urol, Sect Urol Oncol, Cleveland, OH 44195 USA. SW Oncol Grp, San Antonio, TX USA. NCI, Div Clin Sci, Canc Prevent Studies Branch, Washington, DC USA. Fred Hutchinson Canc Res Ctr, SW Oncol Grp, Ctr Stat, Seattle, WA 98104 USA. MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Div Urol, San Antonio, TX USA. RP Cleveland Clin Fdn, Dept Urol, Sect Urol Oncol, Cleveland, OH 44195 USA. EM kleine@ccf.org RI Albanes, Demetrius/B-9749-2015 NR 56 TC 72 Z9 78 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1078-1439 EI 1873-2496 J9 UROL ONCOL-SEMIN ORI JI Urol. Oncol.-Semin. Orig. Investig. PD JAN-FEB PY 2003 VL 21 IS 1 BP 59 EP 65 AR PII S1078-1439(01)0000-0 DI 10.1016/S1078-1439(02)00301-0 PG 7 WC Oncology; Urology & Nephrology SC Oncology; Urology & Nephrology GA 694BZ UT WOS:000183755100012 PM 12684129 ER PT J AU Peebles, RS Hashimoto, K Graham, BS AF Peebles, RS Hashimoto, K Graham, BS TI The complex relationship between respiratory syncytial virus and allergy in lung disease SO VIRAL IMMUNOLOGY LA English DT Review ID EOSINOPHIL CATIONIC PROTEIN; AIRWAY HYPERRESPONSIVENESS; SUBSEQUENT DEVELOPMENT; INTERFERON-GAMMA; CHILDHOOD ASTHMA; IMMUNE-RESPONSES; VIRAL-INFECTION; SENSITIZED MICE; T-CELLS; BRONCHIOLITIS AB Epidemiologic studies suggest a strong link between severe respiratory syncytial virus (RSV)-induced bronchiolitis in infancy and allergic disease; however, the mechanisms determining this relationship are currently unknown. In this review article, we summarize data from human clinical studies that explore the association between RSV infection and allergy, some that suggest that RSV bronchiolitis requiring hospitalization leads to an increased incidence of the allergic phenotype and others that suggest that pre-existing allergy is a risk factor for severe RSV bronchiolitis. We also review the published murine models that combine RSV infection and allergic sensitization that attempt to explain the complex relationship between these two factors in regard to lung immunopathology and physiologic dysfunction. C1 Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37240 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Peebles, RS (reprint author), Vanderbilt Univ, Sch Med, Dept Med, 221 Kirkland Hall, Nashville, TN 37240 USA. FU NIAID NIH HHS [R01-AI-45512] NR 49 TC 18 Z9 18 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PY 2003 VL 16 IS 1 BP 25 EP 34 DI 10.1089/088282403763635429 PG 10 WC Immunology; Virology SC Immunology; Virology GA 666VW UT WOS:000182198000004 PM 12725686 ER PT J AU Basta, S Bennink, JR AF Basta, S Bennink, JR TI A survival game of hide and seek: Cytomegaloviruses and MHC class I antigen presentation pathways SO VIRAL IMMUNOLOGY LA English DT Review ID CD8(+) T-CELLS; NATURAL-KILLER-CELLS; NEWLY SYNTHESIZED PROTEINS; MURINE CYTOMEGALOVIRUS; DENDRITIC CELLS; HEAVY-CHAINS; CROSS-PRESENTATION; IMMUNE EVASION; ENDOPLASMIC-RETICULUM; VIRAL INTERFERENCE AB Cytomegaloviruses (CMV) are members of the ubiquitous family of herpesviruses, which escape immunological clearance and persist throughout life in the infected host. Cytomegaloviruses have developed numerous strategies that permit them to co-exist with their host even as an anti-virus immune response endangers their long-term survival. A considerable number of these strategies are aimed at MHC class I presentation of viral proteins to CD8(+) T cells (T-CD8+). Although the gamut of CMV immune evasion will be briefly examined, the primary focus of this review is on the host ability to counteract the strategies developed by CMV to inhibit antigen processing and presentation. A primary mechanism used by the immune system is the recognition of very early virus proteins including recognition of the immunomodulatory proteins themselves. We further speculate that cross-presentation of antigen is an adaptive immune response to the inhibition of direct presentation. Other mechanisms, such as the evolution of pAPC subsets, may also allow the immune system to adapt to a variety of different infectious pathogens while preventing cytopathic infection of all pAPCs. C1 NIAID, LVD, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Bennink, JR (reprint author), NIAID, LVD, Viral Immunol Sect, NIH, Bldg 4,Room 209,MSC 0440,4 Ctr Dr, Bethesda, MD 20892 USA. NR 85 TC 51 Z9 55 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PY 2003 VL 16 IS 3 BP 231 EP 242 DI 10.1089/088282403322396064 PG 12 WC Immunology; Virology SC Immunology; Virology GA 727KE UT WOS:000185656500001 PM 14583141 ER PT S AU Cerritelli, ME Conway, JF Cheng, NQ Trus, BL Steven, AC AF Cerritelli, ME Conway, JF Cheng, NQ Trus, BL Steven, AC BE Chiu, W Johnson, JE TI Molecular mechanisms in bacteriophage T7 procapsid assembly, maturation, and DNA containment SO VIRUS STRUCTURE SE ADVANCES IN PROTEIN CHEMISTRY LA English DT Review ID HERPES-SIMPLEX-VIRUS; DOUBLE-STRANDED DNA; BIOLOGICAL MACROMOLECULES; CRYOELECTRON MICROSCOPY; ELECTRON CRYOMICROSCOPY; 3-DIMENSIONAL STRUCTURE; CONFORMATIONAL-CHANGES; CAPSID MATURATION; TAIL CONNECTOR; GENOMIC DNA C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. Inst Biol Struct, F-38027 Grenoble, France. Ctr Informat Technol, Computat Biol & Engn Lab, NIH, Bethesda, MD 20892 USA. RP NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RI Conway, James/A-2296-2010 OI Conway, James/0000-0002-6581-4748 NR 83 TC 38 Z9 39 U1 1 U2 10 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-3233 BN 0-12-034264-2 J9 ADV PROTEIN CHEM JI Adv.Protein Chem. PY 2003 VL 64 BP 301 EP + PG 28 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BX58L UT WOS:000185760200009 PM 13677051 ER PT J AU Aronson, DL Krizek, DM Rick, ME AF Aronson, DL Krizek, DM Rick, ME TI von Willebrand factor-cleaving protease content of Cohn plasma fractions SO VOX SANGUINIS LA English DT Letter ID THROMBOTIC THROMBOCYTOPENIC PURPURA C1 NIH, Dept Lab Med, CC, Bethesda, MD 20892 USA. RP Aronson, DL (reprint author), NIH, Dept Lab Med, CC, Bldg 10,Room 2C390,10 Ctr Dr, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2003 VL 85 IS 2 BP 123 EP 123 DI 10.1046/j.1423-0410.2003.00339.x PG 1 WC Hematology SC Hematology GA 717FV UT WOS:000185076900013 PM 12925168 ER PT J AU Reesink, HW Engelfriet, CP Muylle, L Wendel, S Dickmeiss, E Krusius, T Maki, T Lin, CK O'Riordan, J Prati, D Rebulla, P Shirato, T Nakajima, K Dupuis, HM Flanagan, P Carasa, MAV Gallastegui, RA Turek, P Hewitt, P Bernat, JL Bianco, C Dodd, R Klein, H AF Reesink, HW Engelfriet, CP Muylle, L Wendel, S Dickmeiss, E Krusius, T Maki, T Lin, CK O'Riordan, J Prati, D Rebulla, P Shirato, T Nakajima, K Dupuis, HM Flanagan, P Carasa, MAV Gallastegui, RA Turek, P Hewitt, P Bernat, JL Bianco, C Dodd, R Klein, H TI Future counselling of donors and recipients of blood products concerning prion-related diseases SO VOX SANGUINIS LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; SPONGIFORM ENCEPHALOPATHY; TRANSMISSION; INFECTIVITY; VARIANT C1 Sanquin Blood Bank Reg NW, NL-1006 CX Amsterdam, Netherlands. Sanquin Diagnost Serv, NL-1006 CX Amsterdam, Netherlands. Red Cross Flanders, Blood Serv, B-1050 Brussels, Belgium. Hosp Sirio Libanes Blood Bank, BR-01308050 Sao Paulo, Brazil. Rigshosp, Blood Bank, Sect 2034, DK-2100 Copenhagen, Denmark. Finnish Red Cross & Blood Transfus Serv, Expert Serv, Helsinki 00310, Finland. Finnish Red Cross & Blood Transfus Serv, Lab Serv, Helsinki 00310, Finland. Hong Kong Red Cross, Blood Transfus Serv, Kowloon, Peoples R China. Irish Blood Transfus Serv, NBC, Dublin, Ireland. Osped Alessandro Manzoni, Dept Blood Transfus & Hematol, I-23900 Lecco, Italy. Osped Maggiore, IRCCS, I-20122 Milan, Italy. Japan Red Cross Soc, Blood Serv Dept, Tokyo, Japan. Japanese Red Cross, Cent Blood Ctr, Minato Ku, Tokyo 1050011, Japan. New Zealand Blood Serv, Epsom, Auckland, New Zealand. Ctr Vasco Transfus & Teijidos Humanos, Galdakao 48960, Vizcaya, Spain. Minist Sanidad & Consumo, Unidad Hemoterapia, Madrid, Spain. Inst Hematol & Blood Transfus, Prague 12820, Czech Republic. Natl Blood Serv, Colindale Ctr, London NW9 5BG, England. Dartmouth Hitchcock Med Ctr, Neurol Sect, Lebanon, NH 03756 USA. Amer Blood Ctr, Washington, DC 20005 USA. Amer Red Cross, Jerome H Holland Lab Biomed Sci, Rockville, MD USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Reesink, HW (reprint author), Sanquin Blood Bank Reg NW, Plesmanlaan 125, NL-1006 CX Amsterdam, Netherlands. RI Rebulla, Paolo/I-7684-2015 OI Rebulla, Paolo/0000-0002-3875-5754 NR 24 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2003 VL 85 IS 2 BP 126 EP 148 PG 23 WC Hematology SC Hematology GA 717FV UT WOS:000185076900016 PM 12925171 ER PT J AU Kwon, SW Procter, J Dale, JK Straus, SE Stroncek, DF AF Kwon, SW Procter, J Dale, JK Straus, SE Stroncek, DF TI Neutrophil and platelet antibodies in autoimmune lymphoproliferative syndrome SO VOX SANGUINIS LA English DT Article DE apoptosis; autoantibodies; autoimmune lymphoproliferative syndrome; neutrophil antibodies; platetet antibodies ID IDIOPATHIC THROMBOCYTOPENIC PURPURA; CANALE-SMITH-SYNDROME; FAS GENE-MUTATIONS; LYMPHOCYTE APOPTOSIS; DISORDER; FEATURES AB Background and Objectives Autoimmune lymphoproliferative syndrome (ALPS), is an inherited disorder characterized by defective lymphocyte apoptosis, lymphadenopathy, splenomegaly, accumulation of T-cell receptor (TCR)-alphabeta(+) CD4(-) CD8(-) T cells (double-negative T cells) and autoimmunity. We investigated the incidence and nature of neutrophil and platelet antibodies in patients with ALPS. Materials and Methods Sera from 26 patients with ALPS were tested for neutrophil antibodies by granulocyte immunofluorescence, granulocyte agglutination and monoclonal antibody immobilization assays of granulocyte antigens, and for platelet antibodies using a solid-phase antibody-detection system. Results Neutrophil antibodies were detected in 46% of patients with ALPS. Antibody specificity could be defined in eight of the 12 patients with neutrophil antibodies. Among these eight patients, four had antibodies directed against more than one antigen. Overall, 14 antibodies directed to specific antigens were identified: three were directed to the HNA-1a antigen of FcgammaRIIIb; two to the HNA-1b antigen of Fcgamma-RIIIb; two to epitopes common to all FcgammaRIIIb molecules; four to the HNA-2a antigen of the NB1 glycoprotein; and three to neutrophil beta(2) integrins. Platelet antibodies were detected in 35% of patients with ALPS. No antibody specificities were identified among the platelet antibodies. There was no association between the detection of neutrophil antibodies and a history of clinical neutropenia, or between the detection of platelet antibodies and a history of clinical thromobocytopenia. Conclusions Neutrophil and platelet antibodies are important markers of ALPS, but do not always cause clinical cytopenias. The specificities of neutrophil antibody were similar to those found in children with autoimmune neutropenia but without ALPS. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Stroncek, DF (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, 10 Ctr Dr,MSC-1184,Bldg 10,Room 1C711, Bethesda, MD 20892 USA. NR 20 TC 27 Z9 28 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2003 VL 85 IS 4 BP 307 EP 312 DI 10.1111/j.0042-9007.2003.00374.x PG 6 WC Hematology SC Hematology GA 747GE UT WOS:000186796200008 PM 14633257 ER PT B AU Simons-Morton, BG Haynie, DL AF Simons-Morton, BG Haynie, DL BE Borenstein, MH Davidson, L Keyes, CLM Moore, KA TI Growing up drug free: A developmental challenge SO WELL-BEING: POSITIVE DEVELOPMENT ACROSS THE LIFE COURSE SE CROSSCURRENTS IN CONTEMPORARY PSYCHOLOGY LA English DT Proceedings Paper CT Conference on Well-Being CY JUN 20-22, 2000 CL ATLANTA, GA ID SUBSTANCE-ABUSE PREVENTION; EARLY-ADOLESCENT BOYS; ALCOHOL-USE; YOUNG ADULTHOOD; CIGARETTE-SMOKING; PROBLEM BEHAVIOR; CONTINUED USE; SCHOOL; CHILDREN; DRINKING C1 NICHHD, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, Bethesda, MD 20892 USA. RP Simons-Morton, BG (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Prevent Res Branch, Bethesda, MD 20892 USA. OI Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 78 TC 3 Z9 3 U1 4 U2 4 PU LAWRENCE ERLBAUM ASSOC PUBL PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430 USA BN 0-8058-4035-4 J9 CROSS CONT PY 2003 BP 109 EP 122 PG 14 WC Psychology, Developmental; Pediatrics SC Psychology; Pediatrics GA BW36S UT WOS:000181753000009 ER PT J AU Riley, AL Keith, VM AF Riley, AL Keith, VM TI Work and housework conditions and depressive symptoms among married women: The importance of occupational status SO WOMEN & HEALTH LA English DT Article DE work conditions; occupational status and depressive symptoms; married women's mental health ID JOB-SATISFACTION; DETERMINANTS; DISTRESS AB Using the American Changing Lives Survey, a nationally representative sample of adults residing in the United States, this research examines housewives' subjective evaluations of their housework and the subjective evaluations of paid employment among three groups of married women-professionals, sales-clerical, and service-blue collar wives. A major goal was to assess the usefulness of disaggregating employed women by occupational status. Depressive symptoms were regressed on five work conditions-autonomy, physical and time demands, boredom, and feeling appreciated-along with sociodemographic characteristics. The results indicate professional wives report fewer symptoms than homemakers, sales-clerical, and service-blue collar wives. Differences between professionals and homemakers are largely accounted for by professional women's more advantaged economic position. Nonprofessional employed women are more depressed than professionals even when their disadvantaged working conditions are controlled. We discuss the findings in view of research on the stress of combining full-time employment with homemaking and argue that balancing these two roles may be more difficult for some employed women than for others.(C) 2003 by The Haworth Press,inc. All rights reserved. C1 NIH, Ctr Sci Review, Bethesda, MD 20892 USA. Arizona State Univ, Dept Sociol, Tempe, AZ 85287 USA. RP Riley, AL (reprint author), NIH, Ctr Sci Review, Bldg 10, Bethesda, MD 20892 USA. EM rileyann@csr.nih.gov; vkeith@asu.edu NR 31 TC 6 Z9 6 U1 1 U2 8 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0363-0242 J9 WOMEN HEALTH JI Women Health PY 2003 VL 38 IS 4 BP 1 EP 17 DI 10.1300/J013v38n04_01 PG 17 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 770RA UT WOS:000188743400001 PM 14750773 ER PT S AU Makrigiannakis, A Zoumakis, E Kalantaridou, S Chrousos, G Gravanis, A AF Makrigiannakis, A Zoumakis, E Kalantaridou, S Chrousos, G Gravanis, A BE Creatsas, G Mastorakos, G Chrousos, GP TI Uterine and embryonic trophoblast CRH promotes implantation and maintenance of early pregnancy SO WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC AND REPRODUCTIVE ISSUES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th Athens Congress on Womens Health and Diseases CY SEP 26-29, 2002 CL ATHENS, GREECE SP Univ Athens, Med Sch, Second Dept Obstet & Gynecol, Int Federat Obstet & Gynecol, Hellen Soc Obstet, Hellen Soc Pediat & Adolescent Gynecol DE endometrium; FasL; opioids; CRH; implantation; extravillous trophoblast; decidualization; apoptosis ID CORTICOTROPIN-RELEASING HORMONE; ENDOMETRIAL STROMAL CELLS; FACTOR (CRF)-LIKE IMMUNOREACTIVITY; BLASTOCYST IMPLANTATION; RECEPTOR; DECIDUALIZATION; EXPRESSION; DIFFERENTIATION; PROSTAGLANDINS; IDENTIFICATION AB Epithelial cells of human endometrium and differentiated endometrial stromal cells express the corticotropin-releasing hormone (CRH) gene. CRH is also produced by the human placental cytotrophoblast. Endometrial and placental CRH is under the endocrine control of gonadal steroids as well as under an autocrine/paracrine regulation by prostanoids and interleukins. Human endometrium, myometrium and placenta also express the relevant receptors. Invasive trophoblasts promote apoptosis of activated Fas-expressing human T lymphocytes, an effect potentiated by CRH and inhibited by the CRH type 1 antagonist, antalarmin. Female rats treated with antalarmin during the first 6 days of gestation had a dose-dependent decrease of implantation sites and live embryos, and significantly decreased endometrial FasL expression. Our data suggest important physiological roles of endometrial and placental CRH in the regulation of decidualization, blastocyst implantation, and early maternal tolerance. C1 Univ Crete, Sch Med, Dept Obstet & Gynecol, Iraklion, Greece. Pediat & Reprod Endocrionol Branch, NIH, Bethesda, MD 20892 USA. Univ Crete, Sch Med, Dept Pharmacol, Iraklion 71110, Greece. Univ Ioannina, Sch Med, Dept Obstet & Gynecol, GR-45110 Ioannina, Greece. RP Makrigiannakis, A (reprint author), Univ Crete, Sch Med, Dept Obstet & Gynecol, Iraklion, Greece. NR 28 TC 3 Z9 3 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-458-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 997 BP 85 EP 92 DI 10.1196/annals.1290.010 PG 8 WC Multidisciplinary Sciences; Obstetrics & Gynecology SC Science & Technology - Other Topics; Obstetrics & Gynecology GA BY06G UT WOS:000187495800010 PM 14644813 ER PT S AU Kalantaridou, SN Makrigiannakis, A Mastorakos, G Chrousos, GP AF Kalantaridou, SN Makrigiannakis, A Mastorakos, G Chrousos, GP BE Creatsas, G Mastorakos, G Chrousos, GP TI Roles of reproductive corticotropin-releasing hormone SO WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC AND REPRODUCTIVE ISSUES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th Athens Congress on Womens Health and Diseases CY SEP 26-29, 2002 CL ATHENS, GREECE SP Univ Athens, Med Sch, Second Dept Obstet & Gynecol, Int Federat Obstet & Gynecol, Hellen Soc Obstet, Hellen Soc Pediat & Adolescent Gynecol DE uterine CRH; implantation; placental CRH; parturition; ovarian CRH ID ENDOMETRIAL STROMAL CELLS; PITUITARY-ADRENAL AXIS; HUMAN-PLACENTA; HUMAN MYOMETRIUM; BINDING PROTEIN; FETAL MEMBRANES; HUMAN-PREGNANCY; FACTOR CRF; IN-VITRO; RECEPTOR AB Corticotropin-releasing hormone (CRH), the principal regulator of the hypothalamic-pituitary-adrenal axis, as well as its receptors, have been identified in most female reproductive tissues, including the uterus, placenta, and ovary. Endometrial CRH may participate in decidualization, implantation, and early maternal tolerance; placental CRH may participate in the physiology of pregnancy and the onset of parturition, and ovarian CRH may participate in follicular maturation, ovulation, and luteolysis. The hypercortisolism of the latter half of pregnancy can he explained by increased levels of placental CRH in plasma. This hypercortisolism is followed by a transient suppression of hypothalamic CRH secretion in the postpartum period, which may explain the blues or depression and autoimmune phenomena frequently observed during this period. C1 Univ Ioannina, Sch Med, Dept Obstet & Gynecol, GR-45110 Ioannina, Greece. Univ Crete, Sch Med, Dept Obstet & Gynecol, GR-71110 Iraklion, Greece. Univ Athens, Aretaie Hosp, Sch Med, Dept Obstet & Gynecol 2, Athens, Greece. Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. RP Kalantaridou, SN (reprint author), Univ Hosp Ioannina, Dept Obstet & Gynecol, Panepistimiou Ave, Ioannina 45500, Greece. NR 41 TC 25 Z9 25 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-458-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 997 BP 129 EP 135 DI 10.1196/annals.1290.015 PG 7 WC Multidisciplinary Sciences; Obstetrics & Gynecology SC Science & Technology - Other Topics; Obstetrics & Gynecology GA BY06G UT WOS:000187495800016 PM 14644819 ER PT S AU Kanaka-Gantenbein, C Mastorakos, G Chrousos, GP AF Kanaka-Gantenbein, C Mastorakos, G Chrousos, GP BE Creatsas, G Mastorakos, G Chrousos, GP TI Endocrine-related causes and consequences of intrauterine growth retardation SO WOMEN'S HEALTH AND DISEASE: GYNECOLOGIC AND REPRODUCTIVE ISSUES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 5th Athens Congress on Womens Health and Diseases CY SEP 26-29, 2002 CL ATHENS, GREECE SP Univ Athens, Med Sch, Second Dept Obstet & Gynecol, Int Federat Obstet & Gynecol, Hellen Soc Obstet, Hellen Soc Pediat & Adolescent Gynecol DE IUGR; SGA; fetal origin; adult disease; metabolic syndrome; insulin resistance; diabetes mellitus type 2; cardiovascular disease; premature adrenarche; polycystic ovary syndrome ID LOW-BIRTH-WEIGHT; FOR-GESTATIONAL-AGE; REDUCED FETAL GROWTH; IMPAIRED GLUCOSE-TOLERANCE; ISCHEMIC-HEART-DISEASE; ADULT DISEASE; INSULIN-RESISTANCE; PRECOCIOUS PUBARCHE; PRENATAL EXPOSURE; BLOOD-PRESSURE AB The term intrauterine growth retardation (IUGR) is assigned to newborns born with a birth weight and/or birth length below the tenth percentile for their gestational age. Intrauterine growth retardation is usually due to maternal, fetal factors, or placental insufficiency, while endocrine factors represent just a small minority in its etiology. Main endocrine-related causes of IUGR are disorders in insulin or insulin-like growth factor-I (IGF-I) secretion or action. Newborns with IUGR are at increased risk to develop a metabolic syndrome later in life, namely obesity, arterial hypertension, hypercholesterolemia, cardiovascular disease, impaired glucose tolerance, or diabetes mellitus type 2. This association is the result of the adaptational changes of the fetal endocrine-metabolic mechanisms to the impaired intrauterine milieu to assure survival in the short term. The persistence of these changes after birth can be detrimental in adult life. Furthermore, premature adrenarche, as well as ovarian hyperandrogenism, seem to be associated with IUGR in girls, demonstrating that IUGR may have long-lasting effects on both somatic health and reproductive function. Finally, the intrauterine exposure of the fetus to stressors may affect the individual's ability to face stress in postnatal life. Therefore, if optimization of somatic and psychosocial well-being of the individual is the golden goal of medicine, special attention should be paid to maintain an optimal intrauterine milieu devoid of any stressors With adequate nutrient supply and to reserve ideal psychosocial support to the pregnant woman. C1 Univ Athens, Agia Sofia Childrens Hosp, Sch Med, Dept Pediat Endocrinol,Dept Pediat 1, Athens, Greece. Univ Athens, Aretaie Hosp, Sch Med, Dept Obstet & Gynecol 2, Athens, Greece. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Kanaka-Gantenbein, C (reprint author), Tymfristou 52, Athens 15234, Greece. NR 55 TC 45 Z9 52 U1 0 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-458-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2003 VL 997 BP 150 EP 157 DI 10.1196/annals.1290.017 PG 8 WC Multidisciplinary Sciences; Obstetrics & Gynecology SC Science & Technology - Other Topics; Obstetrics & Gynecology GA BY06G UT WOS:000187495800018 PM 14644821 ER PT J AU Beatty, LA AF Beatty, LA TI Substance abuse, disabilities, and black women: An issue worth exploring SO WOMEN & THERAPY LA English DT Article DE drug abuse; substance abuse; disabilities; Black women; co-morbidities ID AFRICAN-AMERICAN WOMEN; CRACK USERS; WHITES; PREVALENCE; DRINKING; PATTERNS; HIV; HISPANICS; INFECTION; SAMPLES AB This paper presents information on the incidence and causes of substance abuse and disabilities in Black women, identifying common problems and risks. Drug abuse is technically a disability; however, there is little in the literature that jointly addresses issues of drug addiction and disability. Black women are the second largest group of women with disabilities and one of the largest groups to suffer the consequences of drug use such as HIV/AIDS, a rising source of disability highly correlated with drug abuse. Psychiatric co-morbidities related to disabilities and drug abuse are identified. Implications for research and treatment are discussed. (C) 2003 by The Haworth Press, Inc. All rights reserved. C1 NIDA, Special Populat Off, NIH, Bethesda, MD 20892 USA. RP Beatty, LA (reprint author), 9007 Wallace Rd, Lanham, MD 20706 USA. NR 54 TC 2 Z9 2 U1 0 U2 0 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 0270-3149 J9 WOMEN THER JI Women Ther. PY 2003 VL 26 IS 3-4 BP 223 EP 236 DI 10.1300/J015v26n03_04 PG 14 WC Psychology, Multidisciplinary; Women's Studies SC Psychology; Women's Studies GA 691XG UT WOS:000183630800004 ER PT J AU Bosworth, HB Bastian, LA Rimer, BK Siegler, IC AF Bosworth, HB Bastian, LA Rimer, BK Siegler, IC TI Coping styles and personality domains related to menopausal stress SO WOMENS HEALTH ISSUES LA English DT Article DE personality; coping style; stress; menopause; climacteric symptoms per manuscript ID HORMONE REPLACEMENT THERAPY; POSTMENOPAUSAL WOMEN; DEPRESSIVE SYMPTOMS; NEUROTICISM; EXPERIENCE; COMMUNITY; SITUATION; DISTRESS; ADULTS; SAMPLE AB Purpose. Examine the role of coping styles and personality domains in relationship to stress associated with menopause. Data/Information. Data are from 170 women ages 45 to 54 who completed a mailed questionnaire and a telephone interview that assessed women's stress associated with menopause, coping style, personality, menopausal symptoms, depressive symptoms, and use of hormone replacement therapy. Results. Rating menopause as stressful was associated with higher levels of neuroticism, seeking social support, and avoidance, and lower levels of agreeableness in unadjusted analyses. In a multivariate model, menopausal symptoms, seeking social support, and neuroticism accounted for 21% of the variance in rating menopause as stressful. Conclusions. Health care providers treating women going through menopause should be aware that the stress response to the menopause transition is multifactorial and is associated with women's individual personalities and coping styles. C1 Vet Affairs Med Ctr, Durham, NC 27705 USA. Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Duke Univ, Ctr Aging & Human Dev, Durham, NC USA. Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Durham, NC USA. NCI, Div Canc Control & Populat Studies, Bethesda, MD 20892 USA. RP Bosworth, HB (reprint author), Vet Affairs Med Ctr, 508 Fulton St,Bldg 16,Room 70, Durham, NC 27705 USA. FU NCI NIH HHS [5P01-CA72099] NR 37 TC 22 Z9 25 U1 3 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1049-3867 J9 WOMEN HEALTH ISS JI Womens Health Iss. PD JAN-FEB PY 2003 VL 13 IS 1 BP 32 EP 38 AR PII S1049-3867(02)00192-5 DI 10.1016/S1049-3867(02)00192-5 PG 7 WC Public, Environmental & Occupational Health; Women's Studies SC Public, Environmental & Occupational Health; Women's Studies GA 649KC UT WOS:000181206300005 PM 12598057 ER PT J AU Philp, D Badamchian, M Scheremeta, B Nguyen, M Goldstein, AL Kleinman, HK AF Philp, D Badamchian, M Scheremeta, B Nguyen, M Goldstein, AL Kleinman, HK TI Thymosin beta(4) and a synthetic peptide containing its actin-binding domain promote dermal wound repair in db/db diabetic mice and in aged mice SO WOUND REPAIR AND REGENERATION LA English DT Article ID ENDOTHELIAL-CELLS; PROSTATE-CANCER; LIVING CELLS; BETA-4; PROTEINS; EXPRESSION; REGULATOR; GENE AB Impaired wound healing is a problem for immobilized patients, diabetics, and the elderly. Thymosin beta(4) has previously been found to promote dermal and corneal repair in normal rats. Here we report that thymosin beta(4) was also active in accelerating wound repair in full-thickness dermal wounds in both db/db diabetic and aged mice. We found that thymosin beta(4) in either phosphate-buffered saline or a hydrogel formulation is active in promoting dermal wound repair in normal rats. In diabetic mice, where healing is delayed, we found that wound contracture and collagen deposition were significantly increased in the mice treated with thymosin beta(4) in either phosphate buffered saline solution or a hydrogel formulation. No difference was observed in keratinocyte migration, with all of the diabetic animals showing almost complete coverage of the wound at 8 days. Wound healing in 26-month-old (aged) animals was significantly delayed. Thymosin beta(4) accelerated wound healing in these aged mice, with increases in keratinocyte migration, wound contracture, and collagen deposition. The hydrogel formulation generally showed similar wound healing activity with thymosin beta(4) in PBS. The actin-binding domain of thymosin beta(4) duplicated in a seven-amino acid synthetic peptide, LKKTETQ, was able to promote repair in the aged animals comparable to that observed with the parent molecule. These studies show that thymosin beta(4) is active for wound repair in models of impaired healing and may have efficacy in chronic wounds in humans. C1 NIH, Cell Biol Sect, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Biochem & Mol Biol, Washington, DC 20037 USA. RP Kleinman, HK (reprint author), NIH, Cell Biol Sect, Natl Inst Dent & Craniofacial Res, 30-433,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. NR 31 TC 77 Z9 83 U1 1 U2 8 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1067-1927 J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JAN-FEB PY 2003 VL 11 IS 1 BP 19 EP 24 DI 10.1046/j.1524-475X.2003.11105.x PG 6 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 642JV UT WOS:000180801100004 PM 12581423 ER PT J AU Swanson, WF Johnson, WE Cambre, RC Citino, SB Ouigley, KB Brousset, DM Morals, RN Moreira, N O'Brien, SJ Wildt, DE AF Swanson, WF Johnson, WE Cambre, RC Citino, SB Ouigley, KB Brousset, DM Morals, RN Moreira, N O'Brien, SJ Wildt, DE TI Reproductive status of endemic felid species in Latin American zoos and implications for ex situ conservation SO ZOO BIOLOGY LA English DT Article DE electroejaculation; semen; cats; breeding; testosterone; cortisol; nutrition; exhibitry; cryopreservation ID LAPAROSCOPIC ARTIFICIAL-INSEMINATION; JAGUARS PANTHERA-ONCA; DOMESTIC CAT; PHYLOGEOGRAPHIC PATTERNS; MITOCHONDRIAL-DNA; ENDANGERED FELIDS; PUMA; CONCOLOR; SPERMATOZOA; EVOLUTION AB Reproductive evaluations were conducted on 185 male cats representing eight endemic Latin American species that were maintained in 44 zoos and private facilities in 12 Latin American countries. Reproductive assessments (testicular measures, ejaculate quality, and blood testosterone/cortisol concentration) were used to establish normative values for large- and small-sized cats in Latin American collections. Data also were analyzed using multiple regression to study the impact of proven breeder status, diet, and various animal housing combinations. Most felids (>95%) in the survey were of wild-born origin, and <20% had produced offspring in captivity. Larger felids had bigger testes and produced more semen, but tended to produce low-sperm-density ejaculates. The ejaculates of small felids were more sperm-concentrated, but contained fewer total spermatozoa. Sperm motility was unrelated to species size, and certain species (puma, margay, tigrina, and jaguarundi) consistently produced few (<40%) normal sperm forms. Across species, >50% of males had low sperm counts (< 1 million total sperm per ejaculate). Among large cats (jaguars and pumas), proven breeders had larger (P<0.05) testes, greater semen volume, and more normal sperm than nonbreeders. Males on adequate diets had higher (P<0.05) circulating cortisol. Among small-sized felids, proven breeders had higher (P<0.05) testosterone, and males housed alone or paired with a conspecific female had more (P<0.05) total sperm per ejaculate and greater (P<0.05) seminal and testicular volumes. Fifty-nine ejaculates (potentially representing similar to 100 artificial insemination (AI) or 26,000 in vitro fertilization (IVF) procedures) were cryopreserved for a felid genome resource bank. In conclusion, breeding success and reproductive traits for many endemic felids in Latin American zoos appear to be suboptimal, and likely would benefit from improvements in diet and exhibitry. Technology transfer and continued training of zoo staff and scientists in Latin American countries are essential if these zoos are to achieve their tremendous conservation potential for felids and other threatened endemic species. C1 Cincinnati Zoo & Bot Garden, Ctr Conservat & Res Endangered Wildlife, Cincinnati, OH 45220 USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Smithsonian Natl Zool Pk, Conservat & Res Ctr, Washington, DC USA. White Oak Conservat Ctr, Yulee, FL USA. Hornocker Wildlife Res Inst, Moscow, ID USA. Univ Nacl Autonoma Mexico, Fac Med Vet & Zootech, Coyoacan, Mexico. Univ Fed Parana, Setor Ciencias Biol, BR-80060000 Curitiba, Parana, Brazil. Univ Fed Parana, Curso Med Vet, Palotina, Brazil. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Swanson, WF (reprint author), Cincinnati Zoo & Bot Garden, Ctr Conservat & Res Endangered Wildlife, 3400 Vine St, Cincinnati, OH 45220 USA. EM william.swanson@cincinnatizoo.org RI Moreira, Nei/C-6399-2013; Johnson, Warren/D-4149-2016; Morais, Rosana/R-4928-2016 OI Moreira, Nei/0000-0002-9236-667X; Johnson, Warren/0000-0002-5954-186X; Morais, Rosana/0000-0002-0816-4371 NR 60 TC 29 Z9 32 U1 9 U2 42 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0733-3188 J9 ZOO BIOL JI Zoo Biol. PY 2003 VL 22 IS 5 BP 421 EP 441 DI 10.1002/zoo.10093 PG 21 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 738UG UT WOS:000186305800001 ER PT J AU Jin, RS Horning, M Mayer, ML Gouaux, E AF Jin, RS Horning, M Mayer, ML Gouaux, E TI Mechanism of activation and selectivity in a ligand-gated ion channel: Structural and functional studies of GluR2 and quisqualate SO BIOCHEMISTRY LA English DT Article ID GLUTAMATE-RECEPTOR CHANNELS; ELECTRON-DENSITY MAPS; AMINO-ACID RECEPTORS; CRYSTAL-STRUCTURES; KAINATE RECEPTORS; HIPPOCAMPAL-NEURONS; BINDING DOMAIN; ESCHERICHIA-COLI; NERVOUS-SYSTEM; AMPA RECEPTOR AB Glutamate is the major excitatory neurotransmitter in the mammalian brain. The (S)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazole)propionic acid (AMPA)-subtype glutamate receptor, a ligand-gated ion channel, mediates most of the fast excitatory synaptic transmission in the mammalian central nervous system. Here we present electrophysiological, biochemical, and crystallographic data on the interactions between quisqualate and the GluR2 receptor ion channel and its corresponding ligand binding core. Quisqualate is a high-affinity, full agonist which like AMPA and glutamate elicits maximum peak current responses, and stabilizes the ligand binding core in a fully closed conformation, reinforcing the concept that full agonists produce similar conformational changes [Armstrong, N., and Gouaux, E. (2000) Neuron 28, 165-181]. Nevertheless, the mechanism of quisqualate binding is different from that of AMPA but similar to that of glutamate, illustrating that quisqualate is a faithful glutamate analogue. A detailed comparison of the three agonist complexes reveals distinct binding mechanisms, particularly in the region of a hydrophobic pocket that is proximal to the anionic gamma-substituents, and demonstrates the importance of agonist-water-receptor interactions. The hydrophobic pocket, which is predicted to vary in chemical character between receptor subtypes, probably plays an important role in determining receptor subtype specificity. C1 Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. NICHHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Gouaux, E (reprint author), Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. RI Mayer, Mark/H-5500-2013; Jin, Rongsheng/M-7797-2013 OI Jin, Rongsheng/0000-0003-0348-7363 NR 53 TC 85 Z9 88 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 31 PY 2002 VL 41 IS 52 BP 15635 EP 15643 DI 10.1021/bi020583k PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631MP UT WOS:000180171800020 PM 12501192 ER PT J AU Kunos, G Batkai, S Offertaler, L Mo, F Liu, J Karcher, J Harvey-White, J AF Kunos, G Batkai, S Offertaler, L Mo, F Liu, J Karcher, J Harvey-White, J TI The quest for a vascular endothelial cannabinoid receptor SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article; Proceedings Paper CT Symposium on Cannabinoids: Chemistry and Biology CY AUG 16-17, 2001 CL BETHESDA, MARYLAND SP Natl Inst Hlth DE endocannabinoids; hypotension; vasorelaxation; G proteins; endothelium; mesenterium ID MESENTERIC ARTERIAL BED; SENSORY NERVES MEDIATE; CB1 RECEPTOR; HYPERPOLARIZING FACTOR; NORADRENALINE RELEASE; CORONARY-ARTERIES; 2-ARACHIDONOYL GLYCEROL; ENDOGENOUS CANNABINOIDS; VANILLOID RECEPTORS; INDUCED HYPOTENSION AB This review examines pharmacological and biochemical evidence that suggests the existence of an as yet undefined endothelial receptor that mediates endocannabinoid-induced vasodilation. The signaling mechanisms triggered through this receptor and its potential physiological role are also discussed. Since vasodilation is often associated with hypotension, mechanisms involved in the hypotensive actions of cannabinoids, including the endocannabinoids anandamide and 2-arachidonoylglycerol, are also briefly reviewed. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, NIH, 12420 Parklawn Dr MSC-8115, Bethesda, MD 20892 USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 NR 76 TC 33 Z9 37 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD DEC 31 PY 2002 VL 121 IS 1-2 BP 45 EP 56 AR PII S0009-3084(02)00145-7 DI 10.1016/S0009-3084(02)00145-7 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 642VU UT WOS:000180826800005 PM 12505689 ER PT J AU Pollock, JD AF Pollock, JD TI Gene expression profiling: methodological challenges, results, and prospects for addiction research SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article; Proceedings Paper CT Symposium on Cannabinoids: Chemistry and Biology CY AUG 16-17, 2001 CL BETHESDA, MD SP Natl Inst Hlth DE gene expression profiling; serial analysis of gene expression (SAGE); massive parallel signature sequencing; microarrays; experimental design and statistical analysis; drug abuse; substance abuse; addiction ID NF-KAPPA-B; PROTEIN-PROTEIN INTERACTIONS; COMPLETE GENOME SEQUENCE; NUCLEUS-ACCUMBENS; MICROARRAY DATA; MOUSE-BRAIN; OLIGONUCLEOTIDE ARRAYS; DENDRITIC SPINES; CHRONIC EXPOSURE; CLUSTER-ANALYSIS AB This review describes the current methods used to profile gene expression. These methods include microarrays, spotted arrays, serial analysis of gene expression (SAGE), and massive parallel signature sequencing (MPSS). Methodological and statistical problems in interpreting microarray and spotted array experiments are also discussed. Methods and formats such as minimum information about microarray experiments (MIAME) needed to share gene expression data are described. The last part of the review provides an overview of the application of gene-expression profiling technology to substance abuse research and discusses future directions. Published by Elsevier Science Ireland Ltd. C1 Natl Inst Drug Abuse, Genet & Mol Neurobiol Res Branch, Rockville, MD 20850 USA. RP Natl Inst Drug Abuse, Genet & Mol Neurobiol Res Branch, 6001 Execut Blvd, Rockville, MD 20850 USA. EM jp183r@nih.gov RI Pollock, Jonathan/B-1554-2009 NR 102 TC 36 Z9 36 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0009-3084 EI 1873-2941 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD DEC 31 PY 2002 VL 121 IS 1-2 BP 241 EP 256 AR PII S0009-3084(02)00160-3 DI 10.1016/S0009-3084(02)00160-3 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 642VU UT WOS:000180826800020 PM 12505704 ER PT J AU Gardner, EL AF Gardner, EL TI Addictive potential of cannabinoids: the underlying neurobiology SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article; Proceedings Paper CT Symposium on Cannabinoids: Chemistry and Biology CY AUG 16-17, 2001 CL BETHESDA, MARYLAND SP Natl Inst Hlth DE addiction; brain stimulation reward; cannabis; cannabinoids; conditioned place preference; dopamine; limbic; marijuana; medial forebrain bundle; meso-accumbens; mesolimbic; microdialysis; nucleus accumbens; reinforcement; reinstatement; relapse; reward; self-administration; self-stimulation; ventral tegmental area ID CONDITIONED PLACE PREFERENCE; SELF-ADMINISTRATION BEHAVIOR; FREELY-MOVING RATS; MESOLIMBIC DOPAMINE TRANSMISSION; STIMULUS REWARD ASSOCIATIONS; MOUSE-BRAIN SYNAPTOSOMES; VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; RECEPTOR ANTAGONIST; INTRAVENOUS COCAINE AB Drugs that are addictive in humans have a number of commonalities in animal model systems-(1) they enhance electrical brain-stimulation reward in the core meso-accumbens reward circuitry of the brain, a circuit encompassing that portion of the medial forebrain bundle (MFB) which links the ventral tegmental area (VTA) of the mesencephalic midbrain with the nucleus accumbens (Acb) of the ventral limbic forebrain; (2) they enhance neural firing of a core dopamine (DA) component of this meso-accumbens reward circuit; (3) they enhance DA tone in this reward-relevant meso-accumbens DA circuit, with resultant enhancement of extracellular Acb DA; (4) they produce conditioned place preference (CPP), a behavioral model of incentive motivation; (5) they are self-administered; and (6) they trigger reinstatement of drug-seeking behavior in animals behaviorally extinguished from intravenous drug self-administration behavior and, perforce, pharmacologically detoxified from their self-administered drug. Cannabinoids were long considered `anomalous', in that they were believed to not interact with these brain reward processes or support drug-seeking and drug-taking behavior in these animal model systems. However, it is now clear-from the published data of several research groups over the last 15 years-that this view of cannabinoid action on brain reward processes and reward-related behaviors is untenable. This paper reviews those data, and concludes that cannabinoids act on brain reward processes and reward-related behaviors in strikingly similar fashion to other addictive drugs. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Inst Drug Abuse, Intramural Res Program, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. RP Gardner, EL (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Dept Hlth & Human Serv, NIH, Bldg C,Room 272,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NCRR NIH HHS [RR05397]; NIAAA NIH HHS [AA09547]; NIDA NIH HHS [DA02089, DA03622] NR 214 TC 50 Z9 54 U1 7 U2 12 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD DEC 31 PY 2002 VL 121 IS 1-2 BP 267 EP 290 AR PII S0009-3084(02)00162-7 DI 10.1016/S0009-3084(02)00162-7 PG 24 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 642VU UT WOS:000180826800022 PM 12505706 ER PT J AU Yoon, M Jeong, S Nicol, CJ Lee, H Han, MY Kim, JJ Seo, YJ Ryu, C Oh, GT AF Yoon, M Jeong, S Nicol, CJ Lee, H Han, MY Kim, JJ Seo, YJ Ryu, C Oh, GT TI Fenofibrate regulates obesity and lipid metabolism with sexual dimorphism SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE fenofibrate; lipid; obesity; PPAR alpha; sex ID PPAR-GAMMA ACTIVATORS; FATTY-ACID OXIDATION; BODY-WEIGHT; FEMALE RATS; FOOD-INTAKE; RECEPTOR; ALPHA; GENE; HOMEOSTASIS; EXPRESSION AB To determine whether the PPARalpha agonist fenofibrate regulates obesity and lipid metabolism with sexual dimorphism, we examined the effects of fenofibrate on body weight, white adipose tissue (WAT) mass, circulating lipids, and the expression of PPARa target genes in both sexes of high fat diet-fed C57BL/6J mice. Both sexes of mice fed a high-fat diet for 14 weeks exhibited increases in body weight, visceral WAT mass, as well as serum triglycerides and cholesterol, although these effects were more pronounced among males. Feeding a high fat diet supplemented with fenofibrate (0.05% w/w) reduced all of these effects significantly in males except serum cholesterol level. Females on a fenofibrate-enriched high fat diet had reduced serum triglyceride levels, albeit to a smaller extent compared to males, but did not exhibit decreases in body weight, WAT mass, and serum cholesterol. Fenofibrate treatment resulted in hepatic induction of PPARalpha target genes encoding enzymes for fatty acid beta-oxidation, the magnitudes of which were much higher in males compared to females, as evidenced by results for acyl-CoA oxidase, a first enzyme of the beta-oxidation system. These results suggest that observed sexually dimorphic effects on body weight, WAT mass and serum lipids by fenofibrate may involve sexually related elements in the differential activation of PPARalpha. C1 Mokwon Univ, Dept Life Sci, Taejon 302729, South Korea. Korea Res Inst Biosci & Biotechnol, Genet Resources Ctr, Taejon 305600, South Korea. NIH, Div Basic Sci, Lab Metab, Bethesda, MD 20892 USA. RP Yoon, M (reprint author), Mokwon Univ, Dept Life Sci, Taejon 302729, South Korea. NR 32 TC 38 Z9 38 U1 0 U2 3 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD DEC 31 PY 2002 VL 34 IS 6 BP 481 EP 488 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 637HA UT WOS:000180504600012 PM 12526091 ER PT J AU Kang, KR Kim, JS Chung, S Park, MH Kim, YW Lim, DK Lee, SY AF Kang, KR Kim, JS Chung, S Park, MH Kim, YW Lim, DK Lee, SY TI Deoxyhypusine synthase is phosphorylated by protein kinase C in vivo as well as in vitro SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE amino acids; calcium/diglycerides; eukaryotic initiation factors; phosphorylation; protein kinase C; protein kinases ID YEAST SACCHAROMYCES-CEREVISIAE; EUKARYOTIC CELL-PROLIFERATION; HYPUSINE-CONTAINING PROTEIN; RAT TESTIS; IDENTIFICATION; PURIFICATION; ACTIVATION; EXPRESSION; VIABILITY; GENE AB Deoxyhypusine synthase catalyzes the first step in the posttranslational synthesis of an unusual amino acid, hypusine, in the eukaryotic translation initiation factor 5A (eIF-5A) precursor protein. We earlier observed that yeast recombinant deoxyhypusine synthase was phosphorylated by protein kinase C (PKC) in vitro (Kang and Chung 1999) and the phosphorylation rate was synergistically increased to a 3.5-fold following treatment with phosphatidylserine (P.Ser)/diacylglycerol (DAG)/ Ca2+ , suggesting a possible involvement of PKC. We have extended study on the phosphorylation of deoxyhypusine synthase in vivo in different cell lines in order to define its role on the regulation of eIF5A in the cell. Deoxyhypusine synthase was found to be phosphorylated by endogenous kinases in CHO, NIH3T3, and chicken embryonic cells. The highest degree of phosphorylation was found in CHO cells. Moreover, phosphorylation of deoxyhypusine synthase in intact CHO cells was revealed and the expression of phosphorylated deoxyhypusine synthase was significantly diminished by diacyl ethylene glycol (DAEG), a PKC inhibitor, and enhanced by phorbol 12-myristate 13-acetate (PMA) or Ca2+/DAG. Endogenous PKC in CHO cell and cell lysate was able to phosphorylate deoxyhypusine synthase and this modification is enhanced by PMA or Ca2+ plus DAG. Close association of PKC with deoxyhypusine synthase in the CHO cells was evident in the immune coprecipitation and was PMA-, and Ca2+/phospholipid-dependent. These results suggest that phosphorylation of deoxyhypusine synthase was PKC-dependent cellular event and open a path for possible regulation in the interaction with eIF5A precursor for hypusine synthesis. C1 Gyeongsang Natl Univ, Coll Med, Dept Biochem, Chinju, South Korea. Gyeongsang Natl Univ, Coll Med, Res Inst Life Sci, Chinju, South Korea. Ajou Univ, Sch Med, Dept Hematooncol, Suwon 442721, South Korea. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Gyeongsang Natl Univ, Coll Med, Dept Ophthalmol, Chinju 660751, South Korea. Seoul Paik Hosp, Eye Hosp 21C, Seoul 100032, South Korea. RP Kang, KR (reprint author), Gyeongsang Natl Univ, Coll Med, Dept Biochem, Chinju, South Korea. NR 22 TC 2 Z9 2 U1 0 U2 2 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD DEC 31 PY 2002 VL 34 IS 6 BP 489 EP 495 PG 7 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 637HA UT WOS:000180504600013 PM 12526092 ER PT J AU Cheng, Y Prud'homme, RK Chik, J Rau, DC AF Cheng, Y Prud'homme, RK Chik, J Rau, DC TI Measurement of forces between galactomannan polymer chains: Effect of hydrogen bonding SO MACROMOLECULES LA English DT Article ID DNA DOUBLE HELICES; COLLAGEN TRIPLE HELICES; X-RAY-DIFFRACTION; HYDRATION FORCES; INTERMOLECULAR FORCES; GUAR GALACTOMANNANS; VISCOSITY; PROTEINS; BILAYERS; XANTHAN AB Packing free energies and structural transitions of concentrated arrays of guar galacto-mannan macromolecules and of guars modified by hydroxypropyl substitution (HPG) have been studied using the osmotic stress method combined with X-ray scattering. All show a liquid crystalline structure with packing free energies that are very similar for guar and HPG and well described by the model of Selinger and Bruinsma for entropic steric repulsion between chains. In addition, a transition from the liquid crystalline form to a crystalline structure is observed as native guar becomes more densely packed. This transition is related to the propensity of guar to form intermolecular hydrogen bonds in solutions. Hydroxypropyl substitution of galactomannan hydroxyl groups causes steric interference that decreases the stability of this hydrogen-bonded crystalline structure. Even for moderately hydroxypropyl-substituted guar (similar to0.3 HP/sugar residue), the transition occurs at a much higher osmotic pressure than for native guar. The extra work needed to crystallize this HPG compared with guar is calculated to be 3 kT/mannose unit or 6-7 kT per hydroxypropyl group. No transition was found for more highly substituted guars. Urea increased the osmotic pressure necessary for the transition of guar but also resulted in new crystalline packing structure. C1 Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. Natl Inst Child Hlth & Human Dev, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Princeton Univ, Dept Chem Engn, Princeton, NJ 08544 USA. EM yu_cheng@merck.com; prudhomm@princeton.edu NR 36 TC 26 Z9 26 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 EI 1520-5835 J9 MACROMOLECULES JI Macromolecules PD DEC 31 PY 2002 VL 35 IS 27 BP 10155 EP 10161 DI 10.1021/ma020887e PG 7 WC Polymer Science SC Polymer Science GA 630CC UT WOS:000180089100038 ER PT J AU Maceyka, M Payne, SG Milstien, S Spiegel, S AF Maceyka, M Payne, SG Milstien, S Spiegel, S TI Sphingosine kinase, sphingosine-1-phosphate, and apoptosis SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Review DE sphingosine; sphingosine-1-phosphate; sphingosine kinase; ceramide; apoptosis ID PROTEIN-COUPLED RECEPTOR; SIGNAL-TRANSDUCTION PATHWAYS; PROGRAMMED CELL-DEATH; GROWTH-FACTOR; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; HL-60 CELLS; SACCHAROMYCES-CEREVISIAE; CERAMIDE SYNTHASE; HUMAN-PLATELETS AB The sphingolipid metabolites ceramide (Cer), sphingosine (Sph), and sphingosine-1-phosphate (S1P) play an important role in the regulation of cell proliferation, survival, and cell death. Cer and Sph usually inhibit proliferation and promote apoptosis, while the further metabolite S1P stimulates growth and suppresses apoptosis. Because these metabolites are interconvertible, it has been proposed that it is not the absolute amounts of these metabolites but rather their relative levels that determines cell fate. The relevance of this "sphingolipid rheostat" and its role id regulating cell fate has been home out by work in many labs using many different cell types and experimental manipulations. A central finding of these studies is that Sph kinase (SphK), the enzyme that phosphorylates Sph to form S1P, is a critical regulator of the sphingolipid rheostat, as it not only produces the pro-growth, anti-apoptotic messenger S1P, but also decreases levels of pro-apoptotic Cer and Sph. Given the role of the sphingolipid rheostat in regulating growth and apoptosis, it is not surprising that sphingolipid metabolism is often found to be disregulaied in cancer, a disease characterized by enhanced cell growth, diminished cell death, or both. Anticancer therapeutics targeting SphK are potentially clinically relevant. Indeed, inhibition of SphK has been shown to suppress gastric tumor growth [Cancer Res. 54 (1991) 1613] and conversely, overexpression of SphK increases tumorigenicity [Curr. Biol. 10 (2000) 1527]. Moreover, S1P has also been shown to regulate angiogenesis, or new blood vessel fort-nation [Cell 99 (1999) 301], which is critical for tumor progression. Furthermore, there is intriguing new evidence that S1P can act in an autocrine and/or paracrine fashion [Science 291 (2001) 1800] to regulate blood vessel formation [J. Clin. Invest. 106 (2000) 951]. Thus, SphK may not only protect tumors from apoptosis, it may also increase their vascularization, further enhancing growth. The cytoprotective effects of SphK/S1P may also be important for clinical benefit, as S1P has been shown to protect oocytes from radiation-induced cell death in vivo [Nat. Med. 6 (2000) 1109]. Here we review the growing literature on the regulation of SphK and the role of SphK and its product, S1P, in apoptosis. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Biochem, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Biochem, 1101 E Marshall St, Richmond, VA 23298 USA. RI Maceyka, Michael/B-9277-2008 FU NCI NIH HHS [CA61774]; NIGMS NIH HHS [GM43880] NR 107 TC 368 Z9 386 U1 0 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD DEC 30 PY 2002 VL 1585 IS 2-3 BP 193 EP 201 AR PII S1388-1981(02)00341-4 DI 10.1016/S1388-1981(02)00341-4 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 640NL UT WOS:000180694800019 PM 12531554 ER PT J AU Nomura, M McKenna, E Korach, KS Pfaff, DW Ogawa, S AF Nomura, M McKenna, E Korach, KS Pfaff, DW Ogawa, S TI Estrogen receptor-beta regulates transcript levels for oxytocin and arginine vasopressin in the hypothalamic paraventricular nucleus of male mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE estrogen receptor beta; estrogen receptor alpha oxytocin; arginine vasopressin; corticotropin-releasing hormone; hypothalamus; paraventricular nucleus; supraoptic nucleus; medial preoptic area; aggression; anxiety ID MESSENGER-RIBONUCLEIC-ACID; GENE-EXPRESSION; FEMALE RAT; RNA EXPRESSION; ER-ALPHA; PROGESTIN RECEPTORS; SUPRAOPTIC NUCLEI; OVARIAN-STEROIDS; STRIA TERMINALIS; SEX-DIFFERENCES AB Estrogen receptor (ER)-beta. unlike ER-alpha, is localized in the hypothalamic paraventricular nucleus (PVN) which also contains neuropeptide synthesizing neurons, such as oxytocin (OT), arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH). Although it is known that some ER-beta containing neurons co-express OT and AVF, but not CRH, in the PVN, it is not yet determined whether ER-beta activation may indeed play a role in estrogenic regulation on syntheses of these neuropeptides. In the present study, we tested this hypothesis by comparing the effects of estrogen on the levels of OT, AVP and CRH messenger RNA (mRNA) between ER-beta knockout (PERKO) and wild type (WT) control male mice. Mice were gonadectomized and implanted with either a pellet containing estradiol benzoate (2.5-5.0 mug/day) or a placebo pellet for 21 days. In situ hybridization histochemistry revealed that estrogen treatment resulted in a significant increase in OT transcripts (151.6+/-6.0%) and a decrease in AVP transcripts (77.8+/-5.2%) in the PVN of WT mice, compared to the placebo control group. This estrogenic regulation of OT and AVP mRNA levels in the PVN was completely abolished in betaERKO mice. Similar genotype differences in the effects of estrogen on the numbers of OT- and AVP-containing cells were found in immunocytochemical studies performed in a separate set of mice. On the other hand, the expression of CRH mRNA in the PVN was not affected by estrogen treatment in either WT or betaERKO mice. Furthermore, estrogen did not cause any changes in the levels of OT or AVP mRNA, regardless of genotype, in the supraoptic nucleus where, unlike in rats, ER-beta containing neurons are rarely found in mice. Finally, estrogen significantly increased OT mRNA levels in both betaERKO and WT in the medial preoptic area, which contains both ER-alpha and ER-beta. These results suggest that ER-beta activation may play a critical role in estrogenic regulation of OT and AVP gene expression in the PVN. (C) 2002 Published by Elsevier Science B.V. C1 Rockefeller Univ, Neurobiol & Behav Lab, New York, NY 10021 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Ogawa, S (reprint author), Rockefeller Univ, Neurobiol & Behav Lab, Box 275,1230 York Ave, New York, NY 10021 USA. RI chen, xuanlan/H-4158-2011; OI Korach, Kenneth/0000-0002-7765-418X NR 60 TC 69 Z9 71 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD DEC 30 PY 2002 VL 109 IS 1-2 BP 84 EP 94 AR PII S0169-328X(02)00525-9 DI 10.1016/S0169-328X(02)00525-9 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 641PA UT WOS:000180752600011 ER PT J AU Vaisman, A Frank, EG McDonald, JP Tissier, A Woodgate, R AF Vaisman, A Frank, EG McDonald, JP Tissier, A Woodgate, R TI pol iota-dependent lesion bypass in vitro SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE DNA replication; fidelity; hypermutation; Rad30; Rad30B; Y-family DNA polymerases ID HUMAN DNA-POLYMERASE; DEOXYCYTIDYL TRANSFERASE-ACTIVITY; ESCHERICHIA-COLI DINB; THYMINE-THYMINE DIMER; SACCHAROMYCES-CEREVISIAE; ERROR-PRONE; TRANSLESION SYNTHESIS; XERODERMA-PIGMENTOSUM; CRYSTAL-STRUCTURE; UV-MUTAGENESIS AB Based upon phylogenetic relationships, the broad Y-family of DNA polymerases can be divided into various subfamilies consisting of UmuC (polV)-like; DinB (polIV/polkappa)-like; Rev1-like, Rad30A (poleta)-like and Rad30B (poliota)-like polymerases. The polIV/polkappa-like polymerases are most ubiquitous, having been identified in bacteria, archaea and eukaryotes. In contrast, the polV-like polymerases appear restricted to bacteria (both Gram positive and Gram negative). Rev1 and poleta-like polymerases are found exclusively in eukaryotes, and to date, poliota-like polymerases have only been identified in higher eukaryotes. In general, the in vitro properties of polymerases characterized within each sub-family are quite similar. An exception to this rule occurs with the poliota-like polymerases, where the enzymatic properties of Drosophila melanogaster poliota are more similar to that of Saccharomyces cerevisiae and human poleta than to the related human poliota. For example, like poleta, Drosophila poliota can bypass a cis-syn thymine-thymine dimer both accurately and efficiently, while human poliota bypasses the same lesion inefficiently and with low-fidelity. Even in cases where human poliota can efficiently insert a base opposite a lesion (such as a synthetic abasic site, the 3'T of a 6-4-thymine-thymine pyrimidine-pyrimidone photoproduct or opposite benzo[a]pyrene diol epoxide deoxyadenosine adducts), further extension is often limited. Thus, although poliota most likely arose from a genetic duplication of poleta millions of years ago as eukaryotes evolved, it would appear that poliota from humans (and possibly all mammals) has been further subjected to evolutionary pressures that have "tailored" its enzymatic properties away from lesion bypass and towards other function(s) specific for higher eukaryotes. The identification of such functions and the role that mammalian poliota plays in lesion bypass in vivo, should hopefully be forthcoming with the construction of human cell lines deleted for poliota and the identification of mice deficient in poliota. C1 NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bethesda, MD 20892 USA. RP Woodgate, R (reprint author), NICHHD, Sect DNA Replicat Repair & Mutagenesis, NIH, Bldg 6,Room 1A13,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Vaisman, Alexandra/C-3766-2013 OI Vaisman, Alexandra/0000-0002-2521-1467 NR 105 TC 31 Z9 36 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 DEC 29 PY 2002 VL 510 IS 1-2 SI SI BP 9 EP 22 AR PII S0027-5107(02)00248-8 DI 10.1016/S0027-5107(02)00248-8 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 631QW UT WOS:000180179300002 PM 12459439 ER PT J AU Shin, BS Maag, D Roll-Mecak, A Arefin, MS Burley, SK Lorsch, JR Dever, TE AF Shin, BS Maag, D Roll-Mecak, A Arefin, MS Burley, SK Lorsch, JR Dever, TE TI Uncoupling of initiation factor eIF5B/IF2 GTPase and translational activities by mutations that lower ribosome affinity SO CELL LA English DT Article ID ELONGATION-FACTOR-G; SACCHAROMYCES-CEREVISIAE; TRANSFER-RNA; LATE EVENTS; FACTOR IF2; BINDING; YEAST; HYDROLYSIS; VISUALIZATION; TRANSLOCATION AB Translation initiation factor eIF5B/IF2 is a GTPase that promotes ribosomal subunit joining. We show that eIF5B mutations in Switch I, an element conserved in all GTP binding domains, impair GTP hydrolysis and general translation but not eIF5B subunit joining function. Intragenic suppressors of the Switch I mutation restore general translation, but not eIF5B GTPase activity. These suppressor mutations reduce the ribosome affinity of eIF5B and increase AUG skipping/leaky scanning. The uncoupling of translation and eIF5B GTPase activity suggests a regulatory rather than mechanical function for eIF5B GTP hydrolysis in translation initiation. The translational defect suggests eIF5B stabilizes Met-tRNAi(Met) binding and that GTP hydrolysis by eIF5B is a checkpoint monitoring 80S ribosome assembly in the final step of translation initiation. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Rockefeller Univ, Lab Mol Biophys, New York, NY 10021 USA. RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. OI Lorsch, Jon/0000-0002-4521-4999 FU NIGMS NIH HHS [GM62128, GM61262] NR 33 TC 73 Z9 75 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 27 PY 2002 VL 111 IS 7 BP 1015 EP 1025 DI 10.1016/S0092-8674(02)01171-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 630AU UT WOS:000180086000011 PM 12507428 ER PT J AU Ribas, C Takesono, A Sato, M Hildebrandt, JD Lanier, SM AF Ribas, C Takesono, A Sato, M Hildebrandt, JD Lanier, SM TI Pertussis toxin-insensitive activation of the heterotrimeric G-proteins G(i)/G(o) by the NG108-15 G-protein activator SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ASYMMETRIC CELL-DIVISION; ALPHA-SUBUNITS; DROSOPHILA; INTEGRATION; G(ALPHA-I2); G-ALPHA(O); EXCHANGE; PARTNER; SYSTEM; YEAST AB A ligand-independent activator of heterotrimeric brain G-protein was partially purified from detergent-solubilized extracts of the neuroblastoma-glioma cell hybrid NG108-15. The G-protein activator (NG108-15 G-protein activator (NG-GPA)) increased [S-35]guanosine 5'-O-(thiotriphosphate) ([S-35]GTPgammaS) to purified brain G-protein in a magnesium-dependent manner and promoted GDP dissociation from Galpha(o). The NG-GPA also increased GTPgammaS binding to purified, recombinant Galpha(i2), Galpha(i3), and Galpha(o), but minimally altered nucleotide binding to purified transducin. The NG-GPA increased GTPgammaS binding to membrane-bound G-proteins and inhibited basal, forskolin- and hormone-stimulated adenylyl cyclase activity in DDT1-MF-2 cell membranes. In contrast to G-protein coupled receptor-mediated activation of heterotrimeric G-proteins in DDT1-MF-2 cell membrane preparations, the action of the NG-GPA was not altered by treatment of the cells with pertussis toxin. ADP-ribosylation of purified brain G-protein also failed to alter the increase in GTPgammaS binding elicited by the NG-GPA. Thus, the NG-GPA acts in a manner distinct from that of a G-protein coupled receptor and other recently described receptor-independent activators of G-protein signaling. These data indicate the presence of unexpected regulatory domains on G(i)/G(o) proteins and suggest the existence of pertussis toxin-insensitive modes of signal input to G(i)/G(o) signaling systems. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol & Expt Therapeut, New Orleans, LA 70112 USA. NHGRI, Bethesda, MD 20892 USA. Univ Autonoma Madrid, Ctr Biol Mol, Severo Ochoa CSIC, E-28049 Madrid, Spain. Med Univ S Carolina, Dept Pharmacol, Charleston, SC 29425 USA. RP Lanier, SM (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Pharmacol & Expt Therapeut, 1901 Perdido St, New Orleans, LA 70112 USA. FU NIDDK NIH HHS [DK37219]; NIMH NIH HHS [MH59931]; NINDS NIH HHS [R01-NS24821] NR 27 TC 11 Z9 11 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50223 EP 50225 DI 10.1074/jbc.C200567200 PG 3 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700003 PM 12426323 ER PT J AU Yu, CL Chen, Y Cline, GW Zhang, DY Zong, HH Wang, YL Bergeron, R Kim, JK Cushman, SW Cooney, GJ Atcheson, B White, MF Kraegen, EW Shulman, GI AF Yu, CL Chen, Y Cline, GW Zhang, DY Zong, HH Wang, YL Bergeron, R Kim, JK Cushman, SW Cooney, GJ Atcheson, B White, MF Kraegen, EW Shulman, GI TI Mechanism by which fatty acids inhibit insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase activity in muscle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SOLID-PHASE EXTRACTION; SKELETAL-MUSCLE; RESISTANCE; HUMANS; TRIGLYCERIDE; TISSUE; SPECTROSCOPY; ASSOCIATION; THETA; RAT AB Recent studies have demonstrated that fatty acids induce insulin resistance in skeletal muscle by blocking insulin activation of insulin receptor substrate-1 (IRS-1)-associated phosphatidylinositol 3-kinase (PI3-kinase). To examine the mechanism by which fatty acids mediate this effect, rats were infused with either a lipid emulsion (consisting mostly of 18:2 fatty acids) or glycerol. Intracellular C18:2 CoA increased in a time-dependent fashion, reaching an similar to6-fold elevation by 5 h, whereas there was no change in the concentration of any other fatty acyl-CoAs. Diacylglycerol (DAG) also increased transiently after 3-4 h of lipid infusion. In contrast there was no increase in intracellular ceramide or triglyceride concentrations during the lipid infusion. Increases in intracellular C18:2 CoA and DAG concentration were associated with protein kinase C (PKC)-theta activation and a reduction in both insulin-stimulated IRS-1 tyrosine phosphorylation and IRS-1 associated PI3-kinase activity, which were associated with an increase in IRS-1 Ser(307) phosphorylation. These data support the hypothesis that an increase in plasma fatty acid concentration results in an increase in intracellular fatty acyl-CoA and DAG concentrations, which results in activation of PKC-theta leading to increased IRS-1 Ser(307) phosphorylation. This in turn leads to decreased IRS-1 tyrosine phosphorylation and decreased activation of IRS-1-associated PI3-kinase activity resulting in decreased insulin-stimulated glucose transport activity. C1 Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06510 USA. NIDDK, NIH, Bethesda, MD 20814 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Garvan Inst Med Res, Sydney, NSW, Australia. RP Shulman, GI (reprint author), Yale Univ, Sch Med, Boyer Ctr Mol Med, Howard Hughes Med Inst, 295 Congress Ave,BCMM 254,Box 9812, New Haven, CT 06536 USA. FU NIDDK NIH HHS [P30 DK-45735, R01 DK-40936, R01 DK040936] NR 21 TC 861 Z9 894 U1 1 U2 49 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50230 EP 50236 DI 10.1074/jbc.M200958200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700005 PM 12006582 ER PT J AU Kajava, AV Zolov, SN Pyatkov, KI Kalinin, AE Nesmeyanova, MA AF Kajava, AV Zolov, SN Pyatkov, KI Kalinin, AE Nesmeyanova, MA TI Processing of Escherichia coli alkaline phosphatase - Sequence requirements and possible conformations of the-6 to-4 region of the signal peptide SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BACTERIAL CYTOPLASMIC MEMBRANE; SITE-DIRECTED MUTAGENESIS; GRAM-NEGATIVE BACTERIA; PROTEIN TRANSLOCATION; BETA-LACTAMASE; CRYSTAL-STRUCTURE; LIPID BILAYER; IN-VIVO; CLEAVAGE; PHOSPHOLIPIDS AB Analysis of the precursors of bacterial exported proteins revealed that those having bulky hydrophobic residues at position -5 have a high incidence of Pro residues at positions -6 and -4, Val at position -3, and Ser at positions -4 and -2. This led to a hypothesis that the previously observed inhibition of processing by bulky residues at position -5 can be suppressed by introduction of Pro, Ser, or Val in the corresponding nearby positions. Subsequent mutational analysis of Escherichia coli alkaline phosphatase showed that, as it was predicted, Pro on either side of bulky hydrophobic -5 Leu, Ile, or Tyr completely restores efficiency of the maturation. Introduction of Val at position -3 also partially suppresses the inhibition imposed by -5 Leu, while a Ser residue at position -4 or -2 does not restore processing. In addition, effective maturation of a mutant with Pro residues at positions from -6 throughout -4 proved that polyproline conformation of this region is permissive for processing. To understand the effects of the mutations, we modeled a peptide substrate into the active site of the signal peptidase using the known position of the beta-lactam inhibitor. The inhibitory effect of the -5 residue and its suppression by either Pro -6 or Pro -4 can be explained if we assume that Pro-containing -6 to -4 regions adopt a polyproline conformation whereas the region without Pro residues has a beta-conformation. These results permit us to specify sequence requirements at -6, -5, and -4 positions for efficient processing and to improve the prediction of yet unknown cleavage sites. C1 NIH, CIT, Ctr Mol Modeling, Bethesda, MD 20892 USA. Russian Acad Sci, Skryabin Inst Biochem & Physiol Microorganisms, Lab Prot Secret Bacteria, Pushchino 142290, Moscow Region, Russia. Inst Cellular Biophys, Pushchino 142290, Russia. RP Kajava, AV (reprint author), CNRS, UPR 1086, CRBM, 1919 Route de Mende, F-34293 Montpellier 5, France. RI Zolov, Sergey/C-4017-2008; Zolov, Sergey/D-9761-2011; Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 54 TC 8 Z9 8 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50396 EP 50402 DI 10.1074/jbc.M205781200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700025 PM 12393890 ER PT J AU Touz, MC Gottig, N Nash, TE Lujan, HD AF Touz, MC Gottig, N Nash, TE Lujan, HD TI Identification and characterization of a novel secretory granule calcium-binding protein from the early branching eukaryote Giardia lamblia SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYST WALL PROTEIN; ENDOPLASMIC-RETICULUM; PRIMITIVE EUKARYOTE; INTRACELLULAR CALCIUM; MOLECULAR CHAPERONES; ANTIGENIC VARIATION; VESICLE FORMATION; CELLS; TRANSPORT; GOLGI AB Giardia lamblia is a flagellate protozoan that infects humans and other mammals and the most frequently isolated intestinal parasite worldwide. Giardia trophozoites undergo essential biological changes to survive outside the intestine of their host by differentiating into infective cysts. Cyst formation, or encystation, is considered one of the most primitive adaptive responses developed by eukaryotes early in evolution and crucial for the transmission of the parasite among susceptible hosts. During this process, proteins that will assemble into the extracellular cyst wall (CWP1 and CWP2) are transported to the cell surface within encystation-specific secretory vesicles (ESVs) by a developmentally regulated secretory pathway. Cyst wall proteins (CWPs) are maintained as a dense material inside the ESVs, but after exocytosis, they form the fibrillar matrix of the cyst wall. Little is known about the molecular mechanisms involved in granule biogenesis and discharge in Giardia, as well as the assembly of the extracellular wall. In this work, we provide evidences that a novel 54-kDa protein that exclusively localizes to the ESVs is induced during encystation similar to CWPs, proteolytically processed during granule maturation, and able to bind calcium in vitro. The gene encoding this molecule predicts a novel protein (called gGSP for (G) under bar. lamblia (G) under bar ranule-(s) under bar pecific (P) under bar rotein) without homology to any other protein reported in public databases. Nevertheless, it possesses characteristics of calcium-sequestering molecules of higher eukaryotes. Inhibition of gGSP expression abolishes cyst wall formation, suggesting that this secretory granule protein regulates Ca2+-dependent degranulation of ESVs during cyst wall formation. C1 Univ Nacl Cordoba, Catedra Bioquim & Biol Mol, Fac Ciencias Med, RA-5000 Cordoba, Argentina. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Lujan, HD (reprint author), Univ Nacl Cordoba, Catedra Bioquim & Biol Mol, Fac Ciencias Med, Pabellon Argentina 2 Piso, RA-5000 Cordoba, Argentina. NR 61 TC 31 Z9 31 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50557 EP 50563 DI 10.1074/jbc.M202558200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700049 PM 12354777 ER PT J AU Phan, J Zdanov, A Evdokimov, AG Tropea, JE Peters, HK Kapust, RB Li, M Wlodawer, A Waugh, DS AF Phan, J Zdanov, A Evdokimov, AG Tropea, JE Peters, HK Kapust, RB Li, M Wlodawer, A Waugh, DS TI Structural basis for the substrate specificity of tobacco etch virus protease SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RHINOVIRUS 3C PROTEASE; HEPATITIS-A VIRUS; CRYSTAL-STRUCTURE; X-RAY; SERINE-PROTEASE; GENE-PRODUCT; PROTEINASES; POLYPROTEIN; DESIGN; FOLD AB Because of its stringent sequence specificity, the 3C-type protease from tobacco etch virus (TEV) is frequently used to remove affinity tags from recombinant proteins. It is unclear, however, exactly how TEV protease recognizes its substrates with such high selectivity. The crystal structures of two TEV protease mutants, inactive C151A and autolysis-resistant S219D, have now been solved at 2.2- and 1.8-Angstrom resolution as complexes with a substrate and product peptide, respectively. The enzyme does not appear to have been perturbed by the mutations in either structure, and the modes of binding of the product and substrate are virtually identical. Analysis of the protein-ligand interactions helps to delineate the structural determinants of substrate specificity and provides guidance for reengineering the enzyme to further improve its utility for biotechnological applications. C1 NCI, Macromol Crystallog Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, NIH, POB B, Frederick, MD 21702 USA. RI ID, IMCACAT/D-5867-2014 FU NCI NIH HHS [N01-CO-56000] NR 39 TC 119 Z9 122 U1 2 U2 26 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50564 EP 50572 DI 10.1074/jbc.M207224200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700050 PM 12377789 ER PT J AU Sukumaran, SK Quon, MJ Prasadarao, NV AF Sukumaran, SK Quon, MJ Prasadarao, NV TI Escherichia coli K1 internalization via caveolae requires caveolin-1 and protein kinase C alpha interaction in human brain microvascular endothelial cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; CELLULAR CAVEOLAE; MEMBRANE DOMAINS; INVASION; INVOLVEMENT; RECEPTOR; PHOSPHORYLATION; ENDOCYTOSIS; ACTIVATION; REVEALS AB The morbidity and mortality associated with Escherichia coli K1 meningitis during the neonatal period have remained significant over the last decade and are once again on the rise. Transcytosis of brain microvascular endothelial cells (BMEC) by E. coli within an endosome to avoid lysosomal fusion is crucial for dissemination into the central nervous system. Central to E. coli internalization of BMEC is the expression of OmpA (outer membrane protein A), which interacts with its receptor for the actin reorganization that leads to invasion. However, nothing is known about the nature of the signaling events for the formation of endosomes containing E. coli K1. We show here that E. coli K1 infection of human BMEC (HBMEC) results in activation of caveolin-1 for bacterial uptake via caveolae. The interaction of caveolin-1 with phosphorylated protein kinase Calpha (PKCalpha) at the E. coli attachment site is critical for the invasion of HBMEC. Optical sectioning of confocal images of infected HBMEC indicates continuing association of caveolin-1 with E. coli during transcytosis. Overexpression of a dominant-negative form of caveolin-1 containing mutations in the scaffolding domain blocked the interaction of phospho-PKCalpha with caveolin-1 and the E. coli invasion of HBMEC, but not actin cytoskeleton rearrangement or the phosphorylation of PKCalpha. The interaction of caveolin-1 with phospho-PKCalpha was completely abrogated in HBMEC overexpressing dominant-negative forms of either focal adhesion kinase or PKCalpha. Treatment of HBMEC with a cell-permeable peptide that represents the scaffolding domain, which was coupled to an antennapedia motif of a Drosophila transcription factor significantly blocked the interaction of caveolin-1 with phospho-PKCalpha and E. coli invasion. These results show that E. coli K1 internalizes HBAMC via caveolae and that the scaffolding domain of caveolin-1 plays a significant role in the formation of endosomes. C1 Childrens Hosp, Div Infect Dis, Los Angeles, CA 90027 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90027 USA. NIH, Diabet Unit, Clin Invest Lab, NCCAM, Bethesda, MD 20892 USA. RP Prasadarao, NV (reprint author), Childrens Hosp, Div Infect Dis, MS 51,4650 Sunset Blvd, Los Angeles, CA 90027 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915 FU NIAID NIH HHS [AI40567] NR 38 TC 43 Z9 47 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50716 EP 50724 DI 10.1074/jbc.M208830200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700069 PM 12386163 ER PT J AU Martin, AG Fearnhead, HO AF Martin, AG Fearnhead, HO TI Apocytochrome c blocks caspase-9 activation and Bax-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ONCOGENE-DEPENDENT APOPTOSIS; WD-40 REPEAT REGION; CYTOCHROME-C; NEGATIVE REGULATION; APAF-1 APOPTOSOME; CELL-DEATH; FACTOR-I; RELEASE; PROCASPASE-9; MITOCHONDRIA AB Complex networks of signaling pathways control the apoptotic response and, therefore, cell survival. However, these networks converge on a common machinery, of which the caspase cysteine proteases are key components. Diverse apoptotic stimuli release holocytochrome c from mitochondria, allowing holocytochrome c to bind apoptotic protease activating factor-1 (Apaf-1), which in turn binds caspase-9 both activating this caspase and forming an Apaf-1/caspase-9 holoenzyme. Cytochrome c lacking heme (the apo form) cannot support caspase activation, although the reason for this has not been studied. Here we show that apocytochrome c still binds Apaf-1 and that it can block holo-dependent caspase activation in a cell-free system. In addition we show that overexpression of apocytochrome c blocks Bax-induced apoptosis in cells. Thus it is possible to modulate cell survival by interfering with the Apaf-1/cytochrome c interaction. Given the key role played by Apaf-1/cytochrome c in the apoptotic process, and the role of apoptosis in degenerative disease, this interaction may serve as a novel therapeutic target. C1 NCI, Apoptosis Sect, Regulat Cell Growth Lab, NIH, Frederick, MD 21702 USA. RP Fearnhead, HO (reprint author), NCI, Apoptosis Sect, Regulat Cell Growth Lab, NIH, Frederick, MD 21702 USA. RI Fearnhead, Howard/D-4826-2012; OI Garcia Martin, Angel/0000-0002-3831-2769; Fearnhead, Howard/0000-0002-8054-9794 NR 51 TC 40 Z9 40 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50834 EP 50841 DI 10.1074/jbc.M209369200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700084 PM 12393884 ER PT J AU Ichida, M Nemoto, S Finkel, T AF Ichida, M Nemoto, S Finkel, T TI Identification of a specific molecular repressor of the peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MITOCHONDRIAL BIOGENESIS; HEPATIC GLUCONEOGENESIS; NUCLEAR RECEPTORS; PGC-1; TRANSCRIPTION; OXIDATION AB The nuclear co-activator PGC-1alpha is a pivotal regulator of numerous pathways controlling both metabolism and overall energy homeostasis. Inappropriate increases in PGC-1alpha activity have been linked to a number of pathological conditions including heart failure and diabetes mellitus. Previous studies (Puigserver, P., Adelmant, G., Wu, Z., Fan, M., Xu, J., O'Malley, B., and Spiegelman, B. M. (1999) Science 286, 1368-1371) have demonstrated an inhibitory domain within PGC-1a that limits transcriptional activity. Using this inhibitory domain in a yeast two-hybrid screen, we demonstrate that PGC-1alpha directly associates with the orphan nuclear receptor estrogen-related receptor-alpha (ERR-alpha). The binding of ERR-alpha to PGC-1alpha requires the C-terminal AF2 domain of ERR-alpha. PGC-1alpha and ERR-alpha have a similar pattern of expression in human tissues, with both being present predominantly in organs with high metabolic needs such as skeletal muscle and kidney. Similarly, we show that in mice physiological stimuli such as fasting coordinately induces PGC-1alpha and ERR-alpha transcription. We also demonstrate that under normal conditions PGC-1alpha is located within discrete nuclear speckles, whereas the expression of ERR-alpha results in PGC-1alpha redistributing uniformly throughout the nucleoplasm. Finally, we show that the expression of ERR-alpha can dramatically and specifically repress PGC-1alpha transcriptional activity. These results suggest a novel mechanism of transcriptional control wherein ERR-alpha can function as a specific molecular repressor of PGC-1alpha activity. In addition, our results suggest that other co-activators might also have specific repressors, thereby identifying another layer of combinatorial complexity in transcriptional regulation. C1 NHLBI, Mol Biol Lab, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NHLBI, Mol Biol Lab, Cardiovasc Branch, NIH, Bldg 10-6N-240,10 Ctr Dr, Bethesda, MD 20892 USA. NR 26 TC 97 Z9 99 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 50991 EP 50995 DI 10.1074/jbc.M210262200 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700104 PM 12397057 ER PT J AU Qi, HY Hyndman, JB Bernstein, HD AF Qi, HY Hyndman, JB Bernstein, HD TI DnaK promotes the selective export of outer membrane protein precursors in SecA-deficient Escherichia coli SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL RECOGNITION PARTICLE; MALTOSE-BINDING PROTEIN; HEAT-SHOCK PROTEINS; CHAPERONE SECB; TRIGGER FACTOR; PREPROTEIN TRANSLOCASE; SUBSTRATE-SPECIFICITY; TARGETING PATHWAY; IN-VITRO; INSERTION AB Consistent with many other results indicating that SecA plays an essential role in the translocation of presecretory proteins across the Escherichia coli inner membrane, we previously found that a similar to95% depletion of SecA completely blocks the export of periplasmic proteins in vivo. Surprisingly, we found that about 25% of the outer membrane protein (OMP) OmpA synthesized after SecA depletion was gradually translocated across the inner membrane. In this study we analyzed the export of several other OMPs after SecA depletion. We found that 25-50% of each OMP as well as an OmpA-alkaline phosphatase fusion protein was exported from SecA-deficient cells. This partial export was completely abolished by the SecA inhibitor sodium azide and therefore still required the participation of SecA. Examination of a variety of OmpA derivatives, however, ruled out the possibility that OMPs are selectively translocated in SecA-deficient cells because SecA binds to their N termini with unusually high affinity. Export after SecA depletion was observed in cells that lack SecB, the primary targeting factor for OMPs, but was abolished by partial inactivation of DnaK. Furthermore, OmpA could be isolated in a stable complex with DnaK. The data strongly suggest that OMPs require only a relatively low level of translocase activity to cross the inner membrane because they can be preserved in a prolonged export-competent state by DnaK. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bldg 5,Rm 201, Bethesda, MD 20892 USA. NR 47 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 27 PY 2002 VL 277 IS 52 BP 51077 EP 51083 DI 10.1074/jbc.M209238200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 631QD UT WOS:000180177700115 PM 12403776 ER PT J AU Lebetkin, EH Chen, LJ Burka, LT AF Lebetkin, EH Chen, LJ Burka, LT TI Disposition of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in B6C3F1 mice and F344 rats SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID STRONG MUTAGEN 3-CHLORO-4-(DICHLOROMETHYL)-5-HYDROXY-2(5H)-FURANONE; DRINKING-WATER; E-2-CHLORO-3-(DICHLOROMETHYL)-4-OXO-BUTENOIC ACID; CHLORINATED DRINKING; IN-VIVO; EXCRETION; CARCINOGENICITY; GENOTOXICITY; INDUCTION; STABILITY AB 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) is a mutagenic by-product of chlorination of drinking water, particularly where the water contains humic matter. MX has been estimated to account for 50% of the mutagenic activity in some drinking water. A bioassay in rats demonstrated an increased tumor incidence, primarily in liver and thyroid glands. This study was designed to provide disposition/metabolism information in mice to evaluate the necessity of a National Toxicology Program chronic bioassay and to provide data for female rats. Radioactivity was rapidly absorbed and excreted near equally in urine (42-54%) and feces (46-51%) 72 h following oral administration of C-14-labeled MX at single doses from 0.2 to 20 mg/kg to male and female mice and female rats. A larger percentage (71-73%) of MX-derived radioactivity was excreted in urine after an iv dose (0.2 mg/kg) in both female rats and male mice. Most MX-derived radioactivity was excreted within the first 24 h postdosing. MX was transformed to urinary and biliary metabolites. A major extremely polar urinary metabolite was tentatively identified as 1-hydroxy-1,2,2-ethanetricarboxylic acid. This metabolite is likely transformed from the MX degradation product 2-hydroxy-3-formyl-4-oxo-2-butenoic acid. Oral administration produced highest tissue/blood ratios in the following order: forestomach (>100), glandular stomach, intestine, and kidney. Intravenous administration resulted in high, prolonged levels of radioactivity in blood compared to oral dosing. Therefore, MX disposition appears to be dominated by its chemical reactivity with highest concentrations of radioactivity being found at the site of administration. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Burka, LT (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. NR 23 TC 3 Z9 3 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD DEC 27 PY 2002 VL 65 IS 24 BP 2101 EP 2118 DI 10.1080/00984100290071522 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 623NY UT WOS:000179710800004 PM 12515589 ER PT J AU Wang, XW Hussain, SP Huo, TI Wu, CG Forgues, M Hofseth, LJ Brechot, C Harris, CC AF Wang, XW Hussain, SP Huo, TI Wu, CG Forgues, M Hofseth, LJ Brechot, C Harris, CC TI Molecular pathogenesis of human hepatocellular carcinoma SO TOXICOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress of Toxicology (ICT IX) CY JUL 08-12, 2001 CL QUEENSLAND, AUSTRALIA DE hepatocellular carcinoma; hepatitis B virus; HBx; oxyradical overload diseases; p53; cDNA microarray ID HEPATITIS-B-VIRUS; X-PROTEIN; P53-INDUCED APOPTOSIS; GENE-EXPRESSION; P53; DISEASE; HEMOCHROMATOSIS; TRANSCRIPTION; CIRRHOSIS; MUTATION AB Primary hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. However, the viral-chemical etiology as well as molecular mechanisms of HCC pathogenesis remains largely unknown. Recent studies in our laboratory have identified several potential factors that may contribute to the pathogenesis of HCC. Oxidative stress and chronic inflammation have been linked to an increased risk of liver cancer. For example, oxyradical overload diseases such as Wilson disease and hemochromatosis result in the generation of oxygen/nitrogen species that can cause mutations in the p53 tumor suppressor gene. The Hepatitis B virus X gene (HBx), a viral transactivator with oncogenic potentials, has been shown to bind to and inactivate p53-mediated apoptosis. HBx mutants derived from HCC have a diminished ability to act as a transactivator. However, they still retain the ability to bind to and abrogate p53-mediated apoptosis. The comparison of gene expression profiles between HBx-expressing primary human hepatocytes and HBV-infected liver samples by cDNA microarrays indicate a unique alteration of a subset of oncogenes and tumor suppressor genes including p53. Our studies implicate both viral and endogenous chemical processes in the etiology of HCC, and p53 may be a common target for the inactivation during liver carcinogenesis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. Necker Inst, Paris, France. RP Wang, XW (reprint author), NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RI Wang, Xin/B-6162-2009 NR 27 TC 112 Z9 120 U1 3 U2 17 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 DEC 27 PY 2002 VL 181 BP 43 EP 47 DI 10.1016/S0300-483X(02)00253-6 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 639TX UT WOS:000180646400008 PM 12505283 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Transgenic models in xenobiotic metabolism and toxicology SO TOXICOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress of Toxicology (ICT IX) CY JUL 08-12, 2001 CL QUEENSLAND, AUSTRALIA DE P450s; chemical carcinogens; gene knockout mice; cancer susceptibility; xenobiotic-metabolizing enzymes ID TARGETED DISRUPTION; EPOXIDE HYDROLASE; MICE; GENE; SUSCEPTIBILITY; ACETAMINOPHEN; TOXICITY; CYP2E1 AB There exist in animals a large number of enzymes that primarily metabolize xenobiotics including drugs, toxins and carcinogens. While these enzymes are known to activate or inactivate toxins and carcinogens in vitro, it had not been demonstrated until recently whether they are responsible for the biological effects of these chemicals in intact animal models. In order to determine the biological affects of xenobiotic-metabolizing enzymes, gene knockout mice were made that lack expression of certain P450s (CYT1A1, CYP1A2, CYP1B1 and CYP2E1), microsomal and cytosolic epoxide hydrolases, and NADPH:quinone oxidoreductase. These mice have no deleterious phenotypes indicating that xenobiotic-metabolizing enzymes have no direct role in mammalian development and physiological homeostasis even though all the genes and enzymes examined are conserved in mammals. However, in many cases, mice lacking certain xenobiotic-metabolizing enzymes confer resistance to acute toxicities and chemical carcinogenesis thus demonstrating that these enzymes mediate the deleterious effects of chemicals. The use of xenobiotic metabolism null animal models to study the mechanisms of actions of toxins and carcinogens will be reviewed. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, NIH, Bldg 37,Rm 3E-24, Bethesda, MD 20892 USA. NR 11 TC 13 Z9 13 U1 2 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 DEC 27 PY 2002 VL 181 BP 237 EP 239 AR PII S0300-483X(02)00288-3 DI 10.1016/S0300-483X(02)00288-3 PG 3 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 639TX UT WOS:000180646400042 PM 12505317 ER PT J AU Weed, DL AF Weed, DL TI Environmental epidemiology - Basics and proof of cause-effect SO TOXICOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress of Toxicology (ICT IX) CY JUL 08-12, 2001 CL QUEENSLAND, AUSTRALIA DE causal inference; cause; epidemiology; toxicology ID INFERENCE; TOXICOLOGY AB Bringing epidemiology and toxicology together to better understand cause and effect relationships requires attention to several interconnected problems: problems of commitment, complexity, and of communication. The most fundamental of these is commitment as it is reflected in the basic purpose of environmental epidemiology. The purpose of epidemiology is not to prove cause-effect relationships, and not only because scientific proof is elusive. The purpose of epidemiology is to acquire knowledge about the determinants and distributions of disease and to apply that knowledge to improve public health. A key problem, therefore, is how much and what kinds of evidence are sufficient to warrant public health (typically preventive) actions? The assessment of available evidence lays the foundation for the problem of complexity: relevant evidence arrives from toxicologic and epidemiological investigations, and reflects the acquisition of knowledge from many levels of scientific understanding: molecular, cellular, tissue, organ systems, complete organisms (man and mouse), relationships between individuals, and on to social and political processes that may impact human health. How to combine evidence from several levels of understanding will require the effective communication of current methodological practices. The practice of causal inference in contemporary environmental epidemiology, for example, relies upon three largely qualitative methods: systematic narrative reviews, criteria-based inference methods, and (increasingly) meta-analysis. These methods are described as they are currently used in practice and several key problems in that practice are highlighted including the relevance to public health practice of toxicological evidence. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Div Canc Prevent, Off Prevent Oncol, EPS T41, Bethesda, MD 20892 USA. RP Weed, DL (reprint author), NCI, Div Canc Prevent, Off Prevent Oncol, EPS T41, 6130 Execut Blvd,Suite 3109, Bethesda, MD 20892 USA. NR 11 TC 21 Z9 22 U1 1 U2 3 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 DEC 27 PY 2002 VL 181 BP 399 EP 403 AR PII S0300-483X(02)00476-6 DI 10.1016/S0300-483X(02)00476-6 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 639TX UT WOS:000180646400067 PM 12505342 ER PT J AU Amin, RP Hamadeh, HK Bushel, PR Bennett, L Afshari, CA Paules, RS AF Amin, RP Hamadeh, HK Bushel, PR Bennett, L Afshari, CA Paules, RS TI Genomic interrogation of mechanism(s) underlying cellular responses to toxicants SO TOXICOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress of Toxicology (ICT IX) CY JUL 08-12, 2001 CL QUEENSLAND, AUSTRALIA DE toxicogenomics; microarray; toxicity ID COMPLEMENTARY-DNA MICROARRAY; GENE-EXPRESSION PATTERNS; SAMPLE CLASSIFICATION; CDNA MICROARRAY; TOXICOLOGY; TOXICOGENOMICS; PROFILES; TECHNOLOGY; TOXICITY; REVEALS AB Assessment of the impact of xenobiotic exposure on human health and disease progression is complex. Knowledge of mode(s) of action, including mechanism(s) contributing to toxicity and disease progression, is valuable for evaluating compounds. Toxicogenomics, the subdiscipline which merges genomics with toxicology, holds the promise to contributing significantly toward the goal of elucidating mechanism(s) by studying genome-wide effects of xenobiotics. Global gene expression profiling, revolutionized by microarray technology and a crucial aspect of a toxicogenomic study, allows measuring transcriptional modulation of thousands of genes following exposure to a xenobiotic. We use our results from previous studies on compounds representing two different classes of xenobiotics (barbiturate and peroxisome proliferator) to discuss the application of computational approaches for analyzing microarray data to elucidate mechanism(s) underlying cellular responses to toxicants. In particular, our laboratory demonstrated that chemical-specific patterns of gene expression can be revealed using cDNA microarrays. Transcript profiling provides discrimination between classes of toxicants, as well as, genome-wide insight into mechanism(s) of toxicity and disease progression. Ultimately, the expectation is that novel approaches for predicting xenobiotic toxicity in humans will emerge from such information. Published by Elsevier Science Ireland Ltd. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Paules, RS (reprint author), NIEHS, POB 12233,Mail Drop F1-05, Res Triangle Pk, NC 27709 USA. EM paules@niehs.nih.gov NR 35 TC 54 Z9 56 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD DEC 27 PY 2002 VL 181 BP 555 EP 563 AR PII S0300-483X(02)00481-X DI 10.1016/S0300-483X(02)00481-X PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 639TX UT WOS:000180646400091 PM 12505366 ER PT J AU Cherstvy, AG Kornyshev, AA Leikin, S AF Cherstvy, AG Kornyshev, AA Leikin, S TI Temperature-dependent DNA condensation triggered by rearrangement of adsorbed cations SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID PROTON-RELAXATION ENHANCEMENT; X-RAY-DIFFRACTION; DOUBLE HELICES; RODLIKE POLYELECTROLYTES; HYDRATION FORCES; DEOXYRIBONUCLEIC-ACID; THERMAL-DENATURATION; MULTIVALENT CATIONS; RAMAN-SPECTROSCOPY; METAL COMPLEXES AB A model is suggested explaining observed temperature-favored aggregation of DNA in the presence of Mn(2+) salts. The interaction between DNA helices is described in terms of screened Coulomb forces and the entropy gain upon DNA aggregation is ascribed to Mn(2+) repartitioning between binding sites in minor and major grooves. The model rationalizes both the observed force vs separation and entropy vs separation curves provided that the energy and entropy associated with transition of one Mn(2+) ion from minor to major groove are DeltaE(ads)=3-5 k(B)T and DeltaS(ads)=2-5 k(B) correspondingly. Although these values appear to be reasonable, no experimental information that would allow their validation is presently available and other interpretations of the observed force curves cannot be excluded. C1 Res Ctr Julich, Inst Mat & Proc Energy Syst, D-52425 Julich, Germany. Natl Acad Sci Belarus, Inst Phys, Minsk 220072, Byelarus. Univ Dusseldorf, Inst Theoret Phys 2, D-40225 Dusseldorf, Germany. Univ London Imperial Coll Sci Technol & Med, Fac Phys Sci, Dept Chem, London SW7 2AY, England. NICHHD, NIH, DHHS, Bethesda, MD 20892 USA. RP Cherstvy, AG (reprint author), Res Ctr Julich, Inst Mat & Proc Energy Syst, D-52425 Julich, Germany. EM a.cherstvy@fz-juelich.de RI Leikin, Sergey/A-5518-2008; Kornyshev, Alexei/C-3404-2008 OI Leikin, Sergey/0000-0001-7095-0739; NR 70 TC 55 Z9 55 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 26 PY 2002 VL 106 IS 51 BP 13362 EP 13369 DI 10.1021/jp026343w PG 8 WC Chemistry, Physical SC Chemistry GA 628GQ UT WOS:000179985100037 ER PT J AU Phornphutkul, C Introne, WJ Perry, MB Bernardini, I Murphey, MD Fitzpatrick, DL Anderson, PD Huizing, M Anikster, Y Gerber, LH Gahl, WA AF Phornphutkul, C Introne, WJ Perry, MB Bernardini, I Murphey, MD Fitzpatrick, DL Anderson, PD Huizing, M Anikster, Y Gerber, LH Gahl, WA TI Natural history of alkaptonuria SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HOMOGENTISATE 1,2-DIOXYGENASE GENE; 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE; MUTATIONS; INHIBITION; NTBC; ACID; HGO AB Background: Alkaptonuria, caused by mutations in the HGO gene and a deficiency of homogentisate 1,2-dioxygenase, results in an accumulation of homogentisic acid (HGA), ochronosis, and destruction of connective tissue. There is no effective therapy for this disorder, although nitisinone inhibits the enzyme that produces HGA. We performed a study to delineate the natural history of alkaptonuria. Methods: We evaluated 58 patients with alkaptonuria (age range, 4 to 80 years), using clinical, radiographic, biochemical, and molecular methods. A radiographic scoring system was devised to assess the severity of spinal and joint damage. Two patients were treated with nitisinone for 10 and 9 days, respectively. Results: Life-table analyses showed that joint replacement was performed at a mean age of 55 years and that renal stones developed at 64 years, cardiac-valve involvement at 54 years, and coronary-artery calcification at 59 years. Linear regression analysis indicated that the radiographic score for the severity of disease began increasing after the age of 30 years, with a more rapid increase in men than in women. Twenty-three new HGO mutations were identified. In a 51-year-old woman, urinary HGA excretion fell from 2.9 to 0.13 g per day after a 10-day course of nitisinone (7 days at a dose of 0.7 mg per day and 3 days at 2.8 mg per day). In a 59-year-old woman, urinary HGA fell from 6.4 g to 1.7 g per day after nine days of treatment with nitisinone (0.7 mg per day). Plasma tyrosine levels in these patients rose from approximately 1.1 mg per deciliter (60 micromol per liter) in both to approximately 12.8 mg per deciliter (700 micromol per liter) and 23.6 mg per deciliter (1300 micromol per liter), respectively, with no clinical signs or symptoms. Conclusions: The reported data on the natural history of alkaptonuria provide a basis for the evaluation of long-term therapies. Although nitisinone can reduce HGA production in humans with homogentisate 1,2-dioxygenase deficiency, the long-term safety and efficacy of this treatment require further evaluation. C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, Bethesda, MD 20892 USA. Natl Inst Hlth Clin Ctr, Dept Rehabil Med, Bethesda, MD USA. Armed Forces Inst Pathol, Dept Radiol Pathol, Washington, DC 20306 USA. Univ Maryland, Med Ctr, Dept Radiol, Baltimore, MD 21201 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Gahl, WA (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Rm 10C-103, Bethesda, MD 20892 USA. NR 39 TC 177 Z9 187 U1 1 U2 15 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 26 PY 2002 VL 347 IS 26 BP 2111 EP 2121 DI 10.1056/NEJMoa021736 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 629FZ UT WOS:000180040900004 PM 12501223 ER PT J AU Horng, S Emanuel, EJ Wilfond, B Rackoff, J Martz, K Grady, C AF Horng, S Emanuel, EJ Wilfond, B Rackoff, J Martz, K Grady, C TI Descriptions of benefits and risks in consent forms for phase 1 oncology trials SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID I CLINICAL-TRIALS; INFORMED CONSENT; THERAPEUTIC RESPONSE; CANCER; QUALITY; IMPACT; ETHICS; AGENTS AB Background: Ethicists have suggested that written consent forms encourage participants in phase 1 cancer trials to expect benefit from the experimental agent and to overlook serious risks. Methods: To evaluate the written description of direct benefit as well as risk, all consent forms for 1999 phase 1 cancer trials were compiled from 80 percent of the National Cancer Institute-designated cancer centers and from six of eight large pharmaceutical developers of anticancer drugs. In each case, we evaluated the characteristics of the trial, the descriptions of the purpose and procedures of the research, the promise of benefit, the description of risks, and the description of alternatives. Results: Of 272 forms, 268 explicitly mentioned that the trial was research, and 249 stated that the purpose of the trial was testing for safety. Nearly all forms (269) mentioned the right to withdraw from the trial. Almost all forms (260) referred to the experimental agent as ``treatment'' or ``therapy.'' Only one consent form promised direct benefit to subjects. Most forms (181) mentioned death as a risk, and very few (14) mentioned cure as even a possible benefit. Most (229) stated that there was unknown risk involved and indicated that severe or permanent harms were possible (224). Conclusions: Consent forms for phase 1 oncology studies almost never promise direct benefit to subjects, rarely mention cure, and usually communicate the seriousness and unpredictability of risk. Although there is room for improvement, the substance of these forms is unlikely to be the primary source of misunderstanding by subjects in phase 1 oncology trials. C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. RP Grady, C (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bldg 10,Rm 1C118, Bethesda, MD 20892 USA. NR 31 TC 66 Z9 68 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 26 PY 2002 VL 347 IS 26 BP 2134 EP 2140 DI 10.1056/NEJMsa021182 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 629FZ UT WOS:000180040900007 PM 12501226 ER PT J AU Fisher, B Anderson, S Bryant, J AF Fisher, B Anderson, S Bryant, J TI Radical and simple mastectomy - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA 15212 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 26 PY 2002 VL 347 IS 26 BP 2171 EP 2171 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 629FZ UT WOS:000180040900027 ER PT J AU Sarlis, NJ Gourgiotis, L Filie, AC AF Sarlis, NJ Gourgiotis, L Filie, AC TI Misclassification of cytologic diagnoses in patients with follicular lesions or follicular neoplasms of the thyroid gland - Implications for patient care and clinical research SO CANCER CYTOPATHOLOGY LA English DT Editorial Material ID FINE-NEEDLE ASPIRATION; EXPERIENCE; NODULES; BIOPSY C1 NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NCI, Cytopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Sarlis, NJ (reprint author), NIDDK, DIR, NIH, Bldg 10,Rm 8D12C,10 Ctr Dr,MSC 1758, Bethesda, MD 20892 USA. NR 12 TC 11 Z9 13 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD DEC 25 PY 2002 VL 96 IS 6 BP 323 EP 324 DI 10.1002/cncr.10884 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 625GC UT WOS:000179807900002 PM 12478678 ER PT J AU Antzutkin, ON Leapman, RD Balbach, JJ Tycko, R AF Antzutkin, ON Leapman, RD Balbach, JJ Tycko, R TI Supramolecular structural constraints on Alzheimer's beta-amyloid fibrils from electron microscopy and solid-state nuclear magnetic resonance SO BIOCHEMISTRY LA English DT Article ID QUANTUM NMR EXCITATION; C-13 CHEMICAL-SHIFTS; SYNCHROTRON X-RAY; SECONDARY-STRUCTURE; PLAQUE COMPETENCE; VIRULENCE FACTOR; ROTATIONAL-ECHO; SHEET STRUCTURE; AMINO-ACIDS; C-ALPHA AB We describe electron microscopy (EM), scanning transmission electron microscopy (STEM), and solid-state nuclear magnetic resonance (NMR) measurements on amyloid fibrils formed by the 42-residue beta-anlyloid peptide associated with Alzheimer's disease (Abeta(1-42)) and by residues 10-35 of the full-length peptide (Abeta(10-35)). These measurements place constraints on the supramolecular structure of the amyloid fibrils, especially the type of beta-sheets present in the characteristic amyloid cross-beta structural motif and the assembly of these beta-sheets into a fibril. EM images of negatively stained Abeta(10-35) fibrils and measurements of fibril mass per length (WPL) by STEM show a strong dependence of fibril morphology and MPL on pH. Abeta(10-35) fibrils formed at pH 3.7 are single "protofilaments" with MPL equal to twice the value expected for a single cross-beta layer. Abeta(10-35) fibrils formed at pH 7.4 are apparently pairs of protofilaments or higher order bundles. EM and STEM data for Abeta(1-42) fibrils indicate that protofilaments with MPL equal to twice the value expected for a single cross-beta layer are also formed by Abeta(1-42) and that these protofilaments exist singly and in pairs at pH 7.4. Solid-state NMR measurements of intermolecular distances in Abeta(10-35) fibrils, using multiple-quantum C-13 NMR, C-13-C-13 dipolar recoupling, and N-15-C-13 dipolar recoupling techniques, support the in-register parallel beta-sheet organization previously established by Lynn, Meredith, Botto, and co-wotkers [Benzinger et al. (1998) Proc. Nad. Acad. Sci. U.S.A. 95, 13407-13412; Benzingger et al. (2000) Biochemistry 39, 3491-3499] and show that this beta-sheet organization is present at pH 3.7 as well as pH 7.4 despite the differences in fibril morphology and MPL. Solid-state NMR measurements of intermolecular distances in Abeta(1-42) fibrils, which represent the first NMR data on Abeta(1-42) fibrils, also indicate an in-register parallel beta-sheet organization. These results, along with previously reported data on Abeta(1-40) fibrils, suggest that the supramolecular structures of Abeta(10-35), Abeta(1-40), and Abeta(1-42) fibrils are quite similar. A schematic structural model of these fibrils, consistent with known experimental EM, STEM, and solid-state, NMR data, is presented. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Lulea Univ Technol, Div Chem, S-97187 Lulea, Sweden. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA. NR 75 TC 209 Z9 210 U1 10 U2 45 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 24 PY 2002 VL 41 IS 51 BP 15436 EP 15450 DI 10.1021/bi0204185 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 628UN UT WOS:000180015100040 PM 12484785 ER PT J AU Curra, A Modugno, N Inghilleri, M Manfredi, M Hallett, M Berardelli, A AF Curra, A Modugno, N Inghilleri, M Manfredi, M Hallett, M Berardelli, A TI Transcranial magnetic stimulation techniques in clinical investigation SO NEUROLOGY LA English DT Article ID MOTOR-EVOKED-POTENTIALS; CORTICAL SILENT PERIOD; AMYOTROPHIC-LATERAL-SCLEROSIS; MULTIPLE-SCLEROSIS; PARKINSONS-DISEASE; BRAIN-STIMULATION; CORTEX EXCITABILITY; CONDUCTION TIME; CORPUS-CALLOSUM; NEURON DISEASE AB Transcranial magnetic stimulation (TMS) is a technique that can activate cortical motor areas and the corticospinal tract without causing the subject discomfort. Since TMS was introduced, numerous applications of the technique have been developed for the evaluation of neurologic diseases. Standard TMS applications (central motor conduction time, threshold and amplitude of motor evoked potentials) allow the evaluation of motor conduction in the CNS. Conduction studies provide specific information in neurologic conditions characterized by clinical and subclinical upper motor neuron involvement. In addition, they have proved useful in monitoring motor abnormalities and the recovery of motor function. TMS also gives information on the pathophysiology of the processes underlying the various clinical conditions. More complex TMS applications (paired-pulse stimulation, silent period, ipsilateral silent period, input-output curve, and evaluation of central fatigue) allow investigation into the mechanisms of diseases causing changes in the excitability of cortical motor areas. These techniques are also useful in monitoring the effects of neurotrophic drugs on cortical activity. TMS applications have an important place among the investigative tools to study patients with motor disorders. C1 Univ Roma La Sapienza, Dipartimento Sci Neurol, I-00185 Rome, Italy. IRCCS, Ist Neurol Mediterraneo Neuromed, Pozzilli, IS, Italy. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Berardelli, A (reprint author), Univ Roma La Sapienza, Dipartimento Sci Neurol, Viale Univ 30, I-00185 Rome, Italy. OI modugno, nicola/0000-0001-5243-1775; Inghilleri, Maurizio/0000-0001-5365-3417 NR 61 TC 114 Z9 116 U1 1 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 24 PY 2002 VL 59 IS 12 BP 1851 EP 1859 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 627JY UT WOS:000179931100006 PM 12503582 ER PT J AU Linker, G Mirza, N Manetti, G Meyer, M Putnam, KT Sunderland, T AF Linker, G Mirza, N Manetti, G Meyer, M Putnam, KT Sunderland, T TI Fine-needle, negative-pressure lumbar puncture: A safe technique for collecting CSF SO NEUROLOGY LA English DT Editorial Material ID HEADACHES C1 NIMH, Geriatr Psychiat Branch, Ctr Clin, Bethesda, MD 20892 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, Ctr Clin, Bldg 10,Room 3N218,10 Ctr Dr,MSC 1275, Bethesda, MD 20892 USA. NR 7 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 24 PY 2002 VL 59 IS 12 BP 2008 EP 2009 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 627JY UT WOS:000179931100041 PM 12499507 ER PT J AU Dalakas, MC AF Dalakas, MC TI Mechanisms of action of IVIg and therapeutic considerations in the treatment of acute and chronic demyelinating neuropathies SO NEUROLOGY LA English DT Article ID INTRAVENOUS IMMUNE GLOBULIN; GUILLAIN-BARRE-SYNDROME; GAMMA-GLOBULIN; IMMUNOGLOBULIN THERAPY; FC RECEPTOR; MYASTHENIA-GRAVIS; KAWASAKI SYNDROME; CONTROLLED TRIAL; IGG-ANTIBODIES; CROSS-LINKING AB Intravenous immunoglobulin (IVIg) is an immunomodulating agent that has multiple activities, including modulation of complement activation products, suppressing idiotypic antibody, saturating Fe receptors on macrophages, and suppressing various inflammatory mediators including cytokines, chemokines, and metalloproteinases. Because all these factors are implicated to various degrees in the pathogenesis of immune-mediated demyelination of the PNS, administration of IVIg could be beneficial in treating neuropathies by suppressing the immune-mediated processes that are directed against myelin or axonal antigenic targets. This article outlines the actions of IVIg in CIDP and other autoimmune neuropathies based on data derived from in vivo and in vitro studies. The predominant mechanisms by which IVIg exerts its action on these neuropathies appear to be a combined effect on complement inactivation, neutralization of idiotypic antibodies, cytokine inhibition, and saturation of Fc receptors on endoneurial macrophages. C1 NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 79 TC 90 Z9 93 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 24 PY 2002 VL 59 IS 12 SU S BP S13 EP S21 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 629TN UT WOS:000180065100004 PM 12499466 ER PT J AU Kieseier, BC Dalakas, MC Hartung, HP AF Kieseier, BC Dalakas, MC Hartung, HP TI Immune mechanisms in chronic inflammatory demyelinating neuropathy SO NEUROLOGY LA English DT Article ID GUILLAIN-BARRE-SYNDROME; PERIPHERAL NERVOUS-SYSTEM; EXPERIMENTAL ALLERGIC NEURITIS; VASCULITIC NEUROPATHY; HUMAN-MELANOMA; POLYNEUROPATHY; EXPRESSION; SERUM; POLYRADICULONEUROPATHY; POLYNEURITIS AB Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired, immune-mediated peripheral neuropathy. In recent years, the application of basic principles of general immunology has widened our understanding of the etiology and immunopathogenesis of this neuropathy. Although both cellular and humoral factors have been implicated, the data are still fragmentary and insufficient for a unified hypothesis. This review summarizes the present knowledge of the fundamental immune mechanisms related to the immunopathogenesis of CIDP and discusses the role of T cells, activated macrophages, cytokines, co-stimulatory molecules, and anti-myelin antibodies. An important factor in current approaches to the therapy of CIDP is the increasingly recognized concomitant axonal loss that occurs secondary to primary demyelination. C1 Univ Dusseldorf, Dept Neurol, D-40225 Dusseldorf, Germany. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Hartung, HP (reprint author), Univ Dusseldorf, Dept Neurol, Moorenstr 5, D-40225 Dusseldorf, Germany. NR 49 TC 44 Z9 49 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 24 PY 2002 VL 59 IS 12 SU S BP S7 EP S12 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 629TN UT WOS:000180065100003 PM 12499465 ER PT J AU Lee, JH Pestova, TV Shin, BS Cao, C Choi, SK Dever, TE AF Lee, JH Pestova, TV Shin, BS Cao, C Choi, SK Dever, TE TI Initiation factor eIF5B catalyzes second GTP-dependent step in eukaryotic translation initiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SACCHAROMYCES-CEREVISIAE; NUCLEOTIDE SPECIFICITY; FACTOR IF2; IN-VITRO; GCN4; REINITIATION; HYDROLYSIS; RIBOSOMES; MUTANTS; PROTEIN AB Initiation factors IF2 in bacteria and elF2 in eukaryotes are GTPases that bind Met-tRNA(Met) to the small ribosomal subunit. eIF5B, the eukaryotic ortholog of IF2, is a GTPase that promotes ribosomal subunit joining. Here we show that elF5B GTPase activity is required for protein synthesis. Mutation of the conserved Asp-759 in human elF5B GTP-binding domain to Asn converts elF5B to an XTPase and introduces an XTP requirement for subunit joining and translation initiation. Thus, in contrast to bacteria where the single GTPase IF2 is sufficient to catalyze translation initiation, eukaryotic cells require hydrolysis of GTP by both elF2 and elF5B to complete translation initiation. C1 Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. SUNY Hlth Sci Ctr, Dept Microbiol & Immunol, Brooklyn, NY 11203 USA. Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow, Russia. RP Dever, TE (reprint author), Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. OI Dever, Thomas/0000-0001-7120-9678 FU NIGMS NIH HHS [R01 GM063940, R01GM63940] NR 23 TC 63 Z9 65 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 2002 VL 99 IS 26 BP 16689 EP 16694 DI 10.1073/pnas.262569399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600035 PM 12471154 ER PT J AU Petkova, AT Ishii, Y Balbach, JJ Antzutkin, ON Leapman, RD Delaglio, F Tycko, R AF Petkova, AT Ishii, Y Balbach, JJ Antzutkin, ON Leapman, RD Delaglio, F Tycko, R TI A structural model for Alzheimer's beta-amyloid fibrils based on experimental constraints from solid state NMR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-13 CHEMICAL-SHIFTS; X-RAY-DIFFRACTION; MAGIC-ANGLE; DISTANCE MEASUREMENTS; SECONDARY-STRUCTURE; AMINO-ACIDS; DISEASE; PROTEIN; PEPTIDE; BACKBONE AB We present a structural model for amyloid fibrils formed by the 40-residue beta-amyloid peptide associated with Alzheimer's disease (Abeta(1-40)), based on a set of experimental constraints from solid state NMR spectroscopy. The model additionally incorporates the cross-beta structural motif established by x-ray fiber diffraction and satisfies constraints on Abeta(1-40) fibril dimensions and mass-per-length determined from electron microscopy. Approximately the first 10 residues of Abeta(1-40) are structurally disordered in the fibrils. Residues 12-24 and 30-40 adopt beta-strand conformations and form parallel p-sheets through intermolecular hydrogen bonding. Residues 25-29 contain a bend of the peptide backbone that brings the two beta-sheets in contact through sidechain-sidechain interactions. A single cross-beta unit is then a double-layered beta-sheet structure with a hydrophobic core and one hydrophobic face. The only charged sidechains in the core are those of D23 and K28, which form salt bridges. Fibrils with minimum mass-per-length and diameter consist of two cross-beta units with their hydrophobic faces juxtaposed. C1 Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Lulea Univ Technol, Dept Chem, S-97187 Lulea, Sweden. Off Res Serv, Div Bioengn & Phys Sci, NIH, Bethesda, MD 20892 USA. RP Tycko, R (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Chem Phys Lab, NIH, Bldg 5,Rm 112, Bethesda, MD 20892 USA. RI Ishii, Yoshitaka/F-4558-2014 OI Ishii, Yoshitaka/0000-0002-7724-6469 NR 51 TC 1248 Z9 1267 U1 29 U2 240 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 2002 VL 99 IS 26 BP 16742 EP 16747 DI 10.1073/pnas.262663499 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600044 PM 12481027 ER PT J AU Ferraris, JD Persaud, P Williams, CK Chen, Y Burg, MB AF Ferraris, JD Persaud, P Williams, CK Chen, Y Burg, MB TI CAMP-independent role of PKA in tonicity-induced transactivation of tonicity-responsive enhancer/osmotic response element-binding protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NF-KAPPA-B; OSMOTIC RESPONSE; TRANSCRIPTIONAL ACTIVATION; MAMMALIAN-CELLS; PHOSPHORYLATION; HYPERTONICITY; GENE; KINASE AB Hypertonicity-induced increase in activity of the transcription factor tonicity-responsive enhancer/osmotic response element-binding protein (TonEBP/OREBP) protects renal cells by increasing transcription of genes, including those involved in increased accumulation of organic osmolytes. We previously showed that hypertonicity increases transactivating activity of TonEBP/OREBP. Assay with a binary GAL4 transactivation system showed that the 984 C-terminal amino acids of TonEBP/OREBP (amino acids 548-1531) contain a tonicity-dependent transactivation domain (TAD). Also, amino acids 548-1531 undergo tonicity-dependent phosphorylation, and some inhibitors of protein kinases reduce the tonicity-dependent transactivation. In the present studies we examined the role of protein kinase A (PKA). Results: (i) An inhibitor of PKA (H89) reduces tonicity-dependent increases in transactivation, ORE/TonE reporter activity, and induction of aldose reductase and betaine transporter mRNAs. (ii) overexpression of the catalytic subunit of PKA (PKAc) increases transactivation activity of amino acids 548-1531 and activity of an ORE/TonE reporter. The increases are much greater under isotonic than under hypertonic conditions. (iii) A dominant-negative PKAc reduces activity of an ORE/TonE reporter. (iv) PKAc activity increases with tonicity but cAMP does not. (v) TonEBP/OREBP and PKAc coimmunoprecipitate. (vi) amino acids 872-1271, including N- and C-terminal polyglutamine stretches, demonstrate tonicity-dependent transactivation, albeit less than amino acids 548-1531, and a similar role for PKA. Conclusions: (i) PKA plays an important role in TonEBP/OREBP activation of tonicity-dependent gene expression; (h) PKA activation of TonEBP/OREBP appears to be cAMP-independent; and (iii) amino acids 872-1271 are sufficient for tonicity-dependent transactivation of TonEBP/OREBP. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ferraris, JD (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. NR 26 TC 69 Z9 70 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 2002 VL 99 IS 26 BP 16800 EP 16805 DI 10.1073/pnas.2226597 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600054 PM 12482947 ER PT J AU Liu, H Abecasis, GR Heath, SC Knowles, A Demars, S Chen, YJ Roos, JL Rapoport, JL Gogos, JA Karayiorgou, M AF Liu, H Abecasis, GR Heath, SC Knowles, A Demars, S Chen, YJ Roos, JL Rapoport, JL Gogos, JA Karayiorgou, M TI Genetic variation in the 22q11 locus and susceptibility to schizophrenia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CARDIO-FACIAL SYNDROME; LINKAGE DISEQUILIBRIUM; DELETION SYNDROME; ASSOCIATION; ADULTS; GENOME AB An increased prevalence of microdeletions at the 22q11 locus has been reported in samples of patients with schizophrenia. 22q11 microdeletions represent the highest known genetic risk factor for the development of schizophrenia, second only to that of the monozygotic cotwin of an affected individual or the offspring of two schizophrenic parents. It is therefore clear that a schizophrenia susceptibility locus maps to chromosome 22q11. In light of evidence for suggestive linkage for schizophrenia in this region, we hypothesized that, whereas deletions of chromosome 22c11 1 may account for only a small proportion of schizophrenia cases in the general population (up to approximate to2%), nondeletion variants of individual genes within the 22q11 region may make a larger contribution to susceptibility to schizophrenia in the wider population. By studying a dense collection of markers (average one single nucleotide polymorphism/20 kb over 1.5 Mb) in the vicinity of the 22q11 locus, in both family- and population-based samples, we present here results consistent with this assumption. Moreover, our results are consistent with contribution from more than one gene to the strikingly increased disease risk associated with this locus. Finer-scale haplotype mapping has identified two subregions within the 1.5-Mb locus that are likely to harbor candidate schizophrenia susceptibility genes. C1 Rockefeller Univ, Human Neurogenet Lab, New York, NY 10021 USA. NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Univ Pretoria, Dept Psychiat, ZA-0083 Pretoria, South Africa. Weskoppies Hosp, ZA-0083 Pretoria, South Africa. Columbia Univ Coll Phys & Surg, Dept Physiol & Cellular Biophys, Ctr Neurobiol & Behav, New York, NY 10032 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. RP Karayiorgou, M (reprint author), Rockefeller Univ, Human Neurogenet Lab, 1230 York Ave, New York, NY 10021 USA. RI Abecasis, Goncalo/B-7840-2010; Heath, Simon/J-4138-2012; OI Abecasis, Goncalo/0000-0003-1509-1825; Roos, Johannes/0000-0002-0572-1072 FU NCRR NIH HHS [M01 RR00102, M01 RR000102]; NIMH NIH HHS [R01 MH061399, R01 MH61399-01] NR 34 TC 123 Z9 128 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 2002 VL 99 IS 26 BP 16859 EP 16864 DI 10.1073/pnas.232186099 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600064 PM 12477929 ER PT J AU Strausberg, RL Feingold, EA Grouse, LH Derge, JG Klausner, RD Collins, FS Wagner, L Shenmen, CM Schuler, GD Altschul, SF Zeeberg, B Buetow, KH Schaefer, CF Bhat, NK Hopkins, RF Jordan, H Moore, T Max, SI Wang, J Hsieh, F Diatchenko, L Marusina, K Farmer, AA Rubin, GM Hong, L Stapleton, M Soares, MB Bonaldo, MF Casavant, TL Scheetz, TE Brownstein, MJ Usdin, TB Toshiyuki, S Carninci, P Prange, C Raha, SS Loquellano, NA Peters, GJ Abramson, RD Mullahy, SJ Bosak, SA McEwan, PJ McKernan, KJ Malek, JA Gunaratne, PH Richards, S Worley, KC Hale, S Garcia, AM Gay, LJ Hulyk, SW Villalon, DK Muzny, DM Sodergren, EJ Lu, XH Gibbs, RA Fahey, J Helton, E Ketteman, M Madan, A Rodrigues, S Sanchez, A Whiting, M Madan, A Young, AC Shevchenko, Y Bouffard, GG Blakesley, RW Touchman, JW Green, ED Dickson, MC Rodriguez, AC Grimwood, J Schmutz, J Myers, RM Butterfield, YSN Kryzywinski, MI Skalska, U Smailus, DE Schnerch, A Schein, JE Jones, SJM Marra, MA AF Strausberg, RL Feingold, EA Grouse, LH Derge, JG Klausner, RD Collins, FS Wagner, L Shenmen, CM Schuler, GD Altschul, SF Zeeberg, B Buetow, KH Schaefer, CF Bhat, NK Hopkins, RF Jordan, H Moore, T Max, SI Wang, J Hsieh, F Diatchenko, L Marusina, K Farmer, AA Rubin, GM Hong, L Stapleton, M Soares, MB Bonaldo, MF Casavant, TL Scheetz, TE Brownstein, MJ Usdin, TB Toshiyuki, S Carninci, P Prange, C Raha, SS Loquellano, NA Peters, GJ Abramson, RD Mullahy, SJ Bosak, SA McEwan, PJ McKernan, KJ Malek, JA Gunaratne, PH Richards, S Worley, KC Hale, S Garcia, AM Gay, LJ Hulyk, SW Villalon, DK Muzny, DM Sodergren, EJ Lu, XH Gibbs, RA Fahey, J Helton, E Ketteman, M Madan, A Rodrigues, S Sanchez, A Whiting, M Madan, A Young, AC Shevchenko, Y Bouffard, GG Blakesley, RW Touchman, JW Green, ED Dickson, MC Rodriguez, AC Grimwood, J Schmutz, J Myers, RM Butterfield, YSN Kryzywinski, MI Skalska, U Smailus, DE Schnerch, A Schein, JE Jones, SJM Marra, MA CA Mammalian Gene Collection MGC Pro TI Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN GENOME; CLONES; RESOURCES; PROGRAMS AB The National Institutes of Health Mammalian Gene Collection (MGC) Program is a multiinstitutional effort to identify and sequence a cDNA clone containing a complete ORF for each human and mouse gene. ESTs were generated from libraries enriched for full-length cDNAs and analyzed to identify candidate full-ORF clones, which then were sequenced to high accuracy. The MGC has currently sequenced and verified the full ORF for a nonredundant set of >9,000 human and >6,000 mouse genes. Candidate full-ORF clones for an additional 7,800 human and 3,500 mouse genes also have been identified. All MGC sequences and clones are available without restriction through public databases and clone distribution networks (see http://mgc.nci.nih.gov). C1 NCI, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Natl Ctr Biotechnol Informat, Natl Lib Med, NIH, Bethesda, MD 20894 USA. NCI, Ctr Bioinformat, Rockville, MD 20892 USA. Frederick Inc, SAIC, NCI, Frederick, MD 21702 USA. Invitrogen Corp, Carlsbad, CA 92008 USA. BD Biosci CLONTECH, Palo Alto, CA 94303 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. Univ Iowa, Iowa City, IA 52242 USA. NIMH, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RIKEN, Genome Sci Lab, Genom Sci Lab, Wako, Saitama 3510198, Japan. Lawrence Livermore Natl Lab, IMAGE Consortium, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. Incyte Genom Inc, Palo Alto, CA 94304 USA. Agencourt Biosci Corp, Beverly, MA 01915 USA. Baylor Coll Med, Baylor Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. Inst Syst Biol, Seattle, WA 98103 USA. NIH, Intramural Sequencing Ctr, Gaithersburg, MD 20877 USA. Stanford Univ, Stanford Human Genome Ctr, Dept Genet, Sch Med, Palo Alto, CA 94304 USA. Univ British Columbia, Genome Sci Ctr, British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. RP Strausberg, RL (reprint author), NCI, NIH, 31 Ctr Dr,Room 10A07, Bethesda, MD 20892 USA. RI Tang, Macy/B-9798-2014; Carninci, Piero/K-1568-2014; Schein, Jacquie/G-3674-2015; Jones, Steven/C-3621-2009; Marra, Marco/B-5987-2008; OI Carninci, Piero/0000-0001-7202-7243; McKernan, Kevin/0000-0002-3908-1122; Rubin, Gerald/0000-0001-8762-8703 FU NHGRI NIH HHS [U54 HG003273] NR 18 TC 1220 Z9 1335 U1 4 U2 62 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 2002 VL 99 IS 26 BP 16899 EP 16903 DI 10.1073/pnas.242603899 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600071 PM 12477932 ER PT J AU Mohlke, KL Erdos, MR Scott, LJ Fingerlin, TE Jackson, AU Silander, K Hollstein, P Boehnke, M Collins, FS AF Mohlke, KL Erdos, MR Scott, LJ Fingerlin, TE Jackson, AU Silander, K Hollstein, P Boehnke, M Collins, FS TI High-throughput screening for evidence of association by using mass spectrometry genotyping on DNA pools SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SINGLE-NUCLEOTIDE POLYMORPHISMS; SNP ALLELE FREQUENCIES; PRIMER EXTENSION; DHPLC; SAMPLES; DISEASE AB To facilitate positional cloning of complex trait susceptibility loci, we are investigating methods to reduce the effort required to identify trait-associated alleles. We examined primer extension analysis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry to screen single-nucleotide polymorphisms (SNPs) for association by using DNA pools. We tested whether this method can accurately estimate allele frequency differences between pools while maintaining the high-throughput nature of assay design, sample handling, and scoring. We follow up interesting allele frequency differences in pools by genotyping individuals. We tested DNA pools of 182, 228, and 499 individuals using 16 SNPs with minor allele frequencies 0.026-0.486 and allele frequency differences 0.001-0.108 that we had genotyped previously on individuals and 381 SNPs that we had not. Precision, as measured by the average standard deviation among 16 semi-dependent replicates, was 0.021 +/- 0.011 for the 16 SNPs and 0.018 +/- 0.008 for the 291/381 SNPs used in further analysis. For the 16 SNPs, the average absolute error in predicting allele frequency differences between pools was 0.009; the largest errors were 0.031, 0.028, and 0.027. We determined that compensating for unequal peak heights in heterozygotes improved precision of allele frequency estimates but had only a very minor effect on accuracy of allele frequency differences between pools. Based on these data and assuming pools of 500 individuals, we conclude that at significance level 0.05 we would have 95% (82%) power to detect population allele frequency differences of 0.07 for control allele frequencies of 0.10 (0.50). C1 Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. RP Collins, FS (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. FU NHGRI NIH HHS [R01 HG000376, T32 HG000040, Z01 HG000040, HG00376] NR 26 TC 82 Z9 86 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 2002 VL 99 IS 26 BP 16928 EP 16933 DI 10.1073/pnas.262661399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600076 PM 12482934 ER PT J AU Bera, TK Zimonjic, DB Popescu, NC Sathyanarayana, BK Kumar, V Lee, B Pastan, I AF Bera, TK Zimonjic, DB Popescu, NC Sathyanarayana, BK Kumar, V Lee, B Pastan, I TI POTE, a highly homologous gene family located on numerous chromosomes and expressed in prostate, ovary, testis, placenta, and prostate cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IN-SITU HYBRIDIZATION; HUMAN GENOME; SEGMENTAL DUPLICATIONS; NEOPLASTIC PROSTATE; ALPHA-SATELLITES; GREAT APES; DATABASE; EVOLUTION; SEQUENCES; PROTEINS AB We have identified a gene located on chromosomes 21 that is expressed in normal and neoplastic prostate, and in normal testis, ovary, and placenta. We name this gene POTE (expressed in prostate, ovary, testis, and placenta). The POTE gene has 11 exons and 10 introns and spans approximate to32 kb of chromosome 21q11.2 region. The 1.83-kb mRNA of POTE encodes a protein of 66 kDa. Ten paralogs of the gene have been found dispersed among eight different chromosomes (2, 8, 13, 14, 15, 18, 21, and 22) with preservation of ORFs and splice junctions. The synonymous-nonsynonymous ratio indicates that the genes were duplicated rather recently but are diverging at a rate faster than the average for other paralogous genes. In prostate and in testis, at least five different paralogs are expressed. In situ hybridization shows that POTE is expressed in basal and terminal cells of normal prostate epithelium. It is also expressed in some prostate cancers and in the LnCAP prostate cancer cell line. The POTE protein contains seven ankyrin repeats between amino acids 140 and 380. Expression of POTE in prostate cancer and its undetectable expression in normal essential tissues make POTE a candidate for the immunotherapy of prostate cancer. The existence of a large number of closely related but rapidly diverging members, their location on multiple chromosomes and their limited expression pattern suggest an important role for the POTE gene family in reproductive processes. C1 NCI, NIH, Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, NIH, Expt Carcinogenesis Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, NIH, Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. EM pasta@helix.nih.gov NR 40 TC 45 Z9 50 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 24 PY 2002 VL 99 IS 26 BP 16975 EP 16980 DI 10.1073/pnas.262655399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600084 PM 12475935 ER PT J AU Bukreyev, A Skiadopoulos, MH McAuliffe, J Murphy, BR Collins, PL Schmidt, AC AF Bukreyev, A Skiadopoulos, MH McAuliffe, J Murphy, BR Collins, PL Schmidt, AC TI More antibody with less antigen: Can immunogenicity of attenuated live virus vaccines be improved? SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; COLONY-STIMULATING FACTOR; HEMAGGLUTININ-NEURAMINIDASE; SURFACE GLYCOPROTEINS; CANDIDATE VACCINE; DENDRITIC CELLS; PROTEIN; RECOMBINANTS; REPLICATION; CHIMPANZEES AB New or improved vaccines against viruses such as influenza, parainfluenza types 1-3, measles, dengue, and respiratory syncytial virus would prevent an enormous burden of morbidity and mortality. Vaccines or vaccine candidates exist against these viral diseases, but all could potentially be improved if the immunogenicity of the vaccine could be enhanced. We found that the immunogenicity in primates of a live-attenuated vaccine candidate for parainfluenza virus type 3, an enveloped RNA virus that is an important etiologic agent of pediatric respiratory tract disease, could be enhanced by expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) from an extra gene inserted into the genome of a cDNA-derived virus, Expression of GM-CSF by the live attenuated recombinant virus did notperse affect the level of pulmonary viral replication in rhesus monkeys after topical administration, which was 40-fold lower than that of WT parainfluenza virus type 3. Despite that, the expressed extra gene augmented the virus-specific serum antibody response to a level that was (i) 3- to 6-fold higher than that induced by the same virus with an unrelated RNA insert of equal length and (ii) equal to the response induced by nonattenuated WT virus. In addition, topical immunization with the attenuated virus expressing GM-CSF induced a greater number of virus-specific IFN-gamma-secreting T lymphocytes in the peripheral blood of monkeys than did immunization with the control virus bearing an unrelated RNA insert. These findings show that the immunogenicity of a live-attenuated vaccine virus in primates can be enhanced without increasing the level of virus replication. Thus, it might be possible to develop live-attenuated vaccines that are as immunogenic as parental WT virus or, possibly, even more so. C1 NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bukreyev, A (reprint author), NIAID, Resp Viruses Sect, Infect Dis Lab, NIH, 50 S Dr,Room 6517, Bethesda, MD 20892 USA. NR 25 TC 12 Z9 12 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 DEC 24 PY 2002 VL 99 IS 26 BP 16987 EP 16991 DI 10.1073/pnas.252649299 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 630HN UT WOS:000180101600086 PM 12482928 ER PT J AU Nash, HA Scott, RL Lear, BC Allada, R AF Nash, HA Scott, RL Lear, BC Allada, R TI An unusual cation channel mediates photic control of locomotion in Drosophila SO CURRENT BIOLOGY LA English DT Article ID CENTRAL COMPLEX; ION CHANNELS; MELANOGASTER; PROTEIN; MUTANTS; BRAIN; ORGANIZATION; ANESTHETICS; SENSITIVITY; MUTATIONS AB A unique family of putative ion channels that are related to voltage-gated sodium and calcium channels has been identified in genomic and cDNA studies of metazoans [1, 2]. Aside from evidence for expression of family members in the nervous system [2, 3], little is known about the operation of the channel or its functional significance. In the present study, this conserved family's sole Drosophila member, a gene known both as CG1517 [4, 5] and as Dmalpha1U [1], is shown to correspond to the narrow abdomen (na) gene and is the locus of a set of mutations that affect sensitivity to anesthetics [6-8]. Immunohistochemistry of adult heads reveals that the channel is expressed in the neuropil of the central complex and optic lobe; expression is severely depressed in the mutants. In addition to previously described defects, the mutant phenotype is demonstrated here to include dysfunction in the coupling between light and locomotor behavior. Most dramatically, mutant flies have an inversion of relative locomotor activity in light versus dark. The involvement of the channel in daily rhythms of the fruit fly is especially provocative because the human ortholog lies in a candidate region linked to bipolar disorder [9], a disease frequently associated with altered diurnal behavior [10]. C1 NIH, Mol Biol Lab, Bethesda, MD 20892 USA. Northwestern Univ, Dept Physiol & Neurobiol, Evanston, IL 60208 USA. RP Nash, HA (reprint author), NIH, Mol Biol Lab, Bldg 10, Bethesda, MD 20892 USA. RI Lear, Bridget/A-1350-2013 NR 42 TC 51 Z9 51 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD DEC 23 PY 2002 VL 12 IS 24 BP 2152 EP 2158 AR PII S0960-9822(02)01358-1 DI 10.1016/S0960-9822(02)01358-1 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 633RH UT WOS:000180295900026 PM 12498692 ER PT J AU Arnoult, D Parone, P Martinou, JC Antonsson, B Estaquier, J Ameisen, JC AF Arnoult, D Parone, P Martinou, JC Antonsson, B Estaquier, J Ameisen, JC TI Mitochondrial release of apoptosis-inducing factor occurs downstream of cytochrome c release in response to several proapoptotic stimuli SO JOURNAL OF CELL BIOLOGY LA English DT Article DE mitochondria; AIF; caspases; Bax; Bid ID CELL-DEATH; BAX; ACTIVATION; MEMBRANES AB Mitochondrial outer membrane permeabilization by proapoptotic Bcl-2 family proteins, such as Bax, plays a crucial role in apoptosis induction. However, whether this only causes the intracytosolic release of inducers of caspase-dependent death, such as cytochrome c, or also of caspase-independent death, such as apoptosis-inducing factor (AIF) remains unknown. Here, we show that on isolated mitochondria, Bax causes the release of cytochrome c, but not of AIF, and the association of AIF with the mitochondrial inner membrane provides a simple explanation for its lack of release upon Bax-mediated outer membrane permeabilization. In cells overexpressing Bax or treated either with the Bax- or Bak-dependent proapoptotic drugs staurosporine or actinomycin D, or with hydrogen peroxide, caspase inhibitors did not affect the intracytosolic translocation of cytochrome c, but prevented that of AIF. These results provide a paradigm for mitochondria-dependent death pathways in which AIF cannot substitute for caspase executioners because its intracytosolic release occurs downstream of that of cytochrome c. C1 Univ Paris 07, INSERM, Inst Natl Sante & Rech Med, EMI U 9922,CHU Bichat,IFR02,AP HP, F-75018 Paris, France. Univ Geneva, Dept Cell Biol, CH-1211 Geneva, Switzerland. Serono Int SA, Serono Pharmaceut Res Inst, CH-1228 Geneva, Switzerland. RP Arnoult, D (reprint author), Natl Inst Neurol Disorders & Stroke, Biochem Sect, NIH, Bldg 10,Rm 4N258, Bethesda, MD 20892 USA. OI Estaquier, Jerome/0000-0002-9432-8044 NR 20 TC 204 Z9 217 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 23 PY 2002 VL 159 IS 6 BP 923 EP 929 DI 10.1083/jcb.200207071 PG 7 WC Cell Biology SC Cell Biology GA 631CT UT WOS:000180150200002 PM 12486111 ER PT J AU Karbowski, M Lee, YJ Gaume, B Jeong, SY Frank, S Nechushtan, A Santel, A Fuller, M Smith, CL Youle, RJ AF Karbowski, M Lee, YJ Gaume, B Jeong, SY Frank, S Nechushtan, A Santel, A Fuller, M Smith, CL Youle, RJ TI Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis SO JOURNAL OF CELL BIOLOGY LA English DT Article ID ENDOPLASMIC-RETICULUM; PROAPOPTOTIC BAX; OUTER-MEMBRANE; CELL-DEATH; BCL-X; PROTEIN; MORPHOLOGY; GTPASE; DNM1P AB We find that Bax, a proapoptotic member of the Bcl-2 family, translocates to discrete foci on mitochondria during the initial stages of apoptosis, which subsequently become mitochondrial scission sites. A dominant negative mutant of Drp1, Drp1(K38A), inhibits apoptotic scission of mitochondria, but does not inhibit Bax translocation or coalescence into foci. However, Drp1(K38A) causes the accumulation of mitochondrial fission intermediates that are associated with clusters of Bax. Surprisingly, Drp1 and Mfn2, but not other proteins implicated in the regulation of mitochondrial morphology, colocalize with Bax in these foci. We suggest that Bax participates in apoptotic fragmentation of mitochondria. C1 NINDS, NIH, Bethesda, MD 20892 USA. SNB, Biochem Sect, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Dev Biol, Palo Alto, CA 94305 USA. RP Youle, RJ (reprint author), BSSNB, NIH, 10 Ctr Dr,MSC 1414,Bldg 10,Rm 5D-37, Bethesda, MD 20892 USA. OI Fuller, Margaret T/0000-0002-3804-4987 NR 25 TC 476 Z9 501 U1 3 U2 21 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 23 PY 2002 VL 159 IS 6 BP 931 EP 938 DI 10.1083/jcb.200209124 PG 8 WC Cell Biology SC Cell Biology GA 631CT UT WOS:000180150200003 PM 12499352 ER PT J AU Burgess, S Walker, M Wang, F Seller, JR White, HD Knight, PJ Trinick, J AF Burgess, S Walker, M Wang, F Seller, JR White, HD Knight, PJ Trinick, J TI The prepower stroke conformation of myosin V SO JOURNAL OF CELL BIOLOGY LA English DT Article DE titling lever; force; thermal ratchet; mechanism; walking ID SMOOTH-MUSCLE MYOSIN; X-RAY STRUCTURES; MOTOR DOMAIN; MOLECULAR MOTOR; SCALLOP MYOSIN; ADP RELEASE; ELECTRON-MICROSCOPY; KINETIC MECHANISM; LIGHT-CHAIN; F-ACTIN AB We have used electron microscopy and single-particle image processing to study head conformation in myosin V molecules. We find that in the presence of ATP, many heads have a sharply angled conformation that is rare in its absence. The sharply angled conformation is similar to a myosin 11 atomic structure proposed to mimic the prepower stroke state. The leading head in molecules attached to actin by both heads has a similar conformation, but is also sharply angled in a second plane by tethering through the trail head. The lead head lever joins the motor domain similar to5 nm axially from where it joins the trail motor. These positions locate the converter subdomain and show the lead motor is in the prepower stroke conformation. Tethering by the trail head places the lead head motor domain at the correct axial position along the actin for binding, but at the wrong orientation. Attachment is achieved either by bending the lead head lever throughout its length or at the pliant point. The microscopy shows that most of the walking stride is produced by changes in lever angle brought about by converter movement, but is augmented by distortion produced by thermal energy. C1 Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England. Natl Heart Lung & Blood Inst, Lab Mol Cardiol, NIH, Bethesda, MD 20892 USA. Eastern Virginia Med Sch, Dept Physiol Sci, Norfolk, VA 23507 USA. RP Trinick, J (reprint author), Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. FU NIAMS NIH HHS [R01 AR040964, AR40964] NR 51 TC 92 Z9 92 U1 2 U2 9 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 23 PY 2002 VL 159 IS 6 BP 983 EP 991 DI 10.1083/jcb.200208172 PG 9 WC Cell Biology SC Cell Biology GA 631CT UT WOS:000180150200008 PM 12499355 ER PT J AU Liu, DG Wang, XZ Gao, Y Li, BH Yang, D Burke, TR AF Liu, DG Wang, XZ Gao, Y Li, BH Yang, D Burke, TR TI Synthesis of N-Fmoc 3-(4-(di-(tert-butyl)phosphonomethyl)phenyl)pipecolic acid as a conformationally constrained phosphotyrosyl mimetic suitably protected for peptide synthesis SO TETRAHEDRON LA English DT Article DE tripeptide; inhibitor; mimetic ID SIGNAL-TRANSDUCTION INHIBITORS; PHOSPHATE-CONTAINING LIGANDS; STRUCTURE-BASED DESIGN; SH2 DOMAIN BINDING; ASYMMETRIC-SYNTHESIS; PIPECOLIC ACID; GRB2; ANTAGONISTS; DERIVATIVES; AZIDATION AB Phosphonomethylphenylalanine (Pmp, 2) has shown wide utility as a hydrolytically stable phosphtyrosyl (pTyr, 1) mimetic, particularly in Src homology 2 (SH2) domain-binding peptides. (2S,3R)-3-(4-(phosphonomethyl)phenyl)pipecolic acid (3) represents a variant of Pmp having phi and chi(1) torsion angles constrained through incorporation into the piperidinyl ring structure contained within pipecolic acid. Reported herein is the enantioselective preparation of 3, in an orthogonally protected form (4) suitable for use in peptide synthesis. Stereochemistries at both the 2- and 3-positions are derived inductively from a single chiral center provided by the commercially available Evans chiral auxiliary, (4S)-4-benzyl-1,3-oxazolidin-2-one. Incorporation of 4 into a Grb2 SH2 domain-directed tripeptide (18) showed that Grb2 SH2 domain-binding affinity was reduced relative to the parent Pmp-containing tripeptide (19). Although conformational constraint did not enhance affinity in this case, novel amino acid analogue 4 may serve as a useful tool for the induction of defined phosphotyrosyl geometry in peptides directed at other signal transduction targets. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. RP Burke, TR (reprint author), NCI, Ctr Canc Res, Med Chem Lab, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014 NR 28 TC 12 Z9 12 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD DEC 23 PY 2002 VL 58 IS 52 BP 10423 EP 10428 AR PII S0040-4020(02)01421-7 DI 10.1016/S0040-4020(02)01421-7 PG 6 WC Chemistry, Organic SC Chemistry GA 625QN UT WOS:000179827300018 ER PT J AU Rossouw, JE AF Rossouw, JE TI Hormones for coronary disease - full circle SO LANCET LA English DT Editorial Material ID ESTROGEN-REPLACEMENT; TRIAL; ATHEROSCLEROSIS; PREVENTION C1 US Dept HHS, NHLBI, Bethesda, MD 20014 USA. RP Rossouw, JE (reprint author), US Dept HHS, NHLBI, Bethesda, MD 20014 USA. NR 9 TC 8 Z9 8 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 21 PY 2002 VL 360 IS 9350 BP 1996 EP 1997 DI 10.1016/S0140-6736(02)12030-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 628CH UT WOS:000179974200002 PM 12504389 ER PT J AU Agrawal, M Emanuel, EJ AF Agrawal, M Emanuel, EJ TI Death and dignity: dogma disputed SO LANCET LA English DT Editorial Material ID RANDOMIZED CONTROLLED TRIAL; OF-LIFE; ILL PATIENTS; CARE; QUALITY; END C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Agrawal, M (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 18 TC 5 Z9 5 U1 0 U2 3 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 21 PY 2002 VL 360 IS 9350 BP 1997 EP 1998 DI 10.1016/S0140-6736(02)12031-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 628CH UT WOS:000179974200003 PM 12504390 ER PT J AU Stadtman, TC AF Stadtman, TC TI A gold mine of fascinating enzymes: Those remarkable, strictly anaerobic bacteria, Methanococcus vannielii and Clostridium sticklandii SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FORMATE DEHYDROGENASE-H; AMINO-ACID-SEQUENCE; HUMAN THIOREDOXIN REDUCTASE; LUNG ADENOCARCINOMA CELLS; ESCHERICHIA-COLI; GLYCINE REDUCTASE; SELENOPHOSPHATE SYNTHETASE; GLUTATHIONE-PEROXIDASE; SELENOPROTEIN-A; TRANSFER-RNAS C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, TC (reprint author), NHLBI, Biochem Lab, NIH, Bldg 3, Bethesda, MD 20892 USA. NR 65 TC 4 Z9 4 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49091 EP 49100 DI 10.1074/jbc.X200005200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900001 PM 12403767 ER PT J AU He, YZ Szapary, D Simons, SS AF He, YZ Szapary, D Simons, SS TI Modulation of induction properties of glucocorticoid receptor-agonist and -antagonist complexes by coactivators involves binding to receptors but is independent of ability of coactivators to augment transactivation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NUCLEAR RECEPTORS; TRANSCRIPTIONAL COACTIVATOR; ESTROGEN-RECEPTOR; HORMONE-BINDING; HISTONE ACETYLTRANSFERASE; INTERACTING PROTEIN-1; VITAMIN-D-3 RECEPTOR; GENE-TRANSCRIPTION; STEROID-RECEPTORS; CO-REPRESSOR AB Coactivators such as TIF2 and SRC-1 modulate the positioning of the dose-response curve for agonist-bound glucocorticoid receptors (GRs) and the partial agonist activity of antiglucocorticoid complexes. These properties of coactivators differ from their initially defined activities of binding to, and increasing the total levels of transactivation by, agonist-bound steroid receptors. We now report that constructs of TIF2 and SRC-1 lacking the two activation domains (AD1 and AD2) have significantly less ability to increase transactivation but retain most of the activity for modulating the dose-response curve and partial agonist activity. Mammalian two-hybrid experiments show that the minimum TIF2 segment with modulatory activity (TIF2.4) does not interact with p300, CREB-binding protein, or PCAF, which also modulates GR activities. DRIP150 and DRIP205 have been implicated in coactivator actions but are unable to modulate GR activities. The absence of synergism by PCAF or DRIP150 with SRC-1 or TIF2, respectively, further suggests that these other factors are not involved. The ability of a TIF2.4 fragment (i.e. TIF2.37), which is not known to interact with proteins, to block the actions of TIF2.4 suggests that an unidentified binder mediates the modulatory activity of TIF2. Pull-down experiments with GST/TIF2.4 demonstrate a direct interaction of TIF2 with GR in a hormone-dependent fashion that requires the receptor interaction domains of TIF2 and is equally robust with agonists and most antiglucocorticoids. These observations, which are confirmed in mammalian two-hybrid assays, suggest that the capacity of coactivators such as TIF2 to modulate the partial agonist activity of antisteroids is mediated by the binding of coactivators to GR-antagonist complexes. In conclusion, the modulatory activity of coactivators with GR-agonist and -antagonist complexes is mechanistically distinct from the ability of coactivators to augment the total levels of transactivation and appears to involve the binding to both GR-steroid complexes and an unidentified TIF2-associated factor(s). C1 NIDDK, LMCB, Steroid Hormones Sect, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, LMCB, Steroid Hormones Sect, NIH, Bldg 8,Rm B2A-07, Bethesda, MD 20892 USA. NR 73 TC 34 Z9 34 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49256 EP 49266 DI 10.1074/jbc.M205536200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900020 PM 12376547 ER PT J AU Ma, YC Greener, T Pacold, ME Kaushal, S Greene, LE Eisenberg, E AF Ma, YC Greener, T Pacold, ME Kaushal, S Greene, LE Eisenberg, E TI Identification of domain required for catalytic activity of auxilin in supporting clathrin uncoating by Hsc70 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COATED VESICLES; MOLECULAR CHAPERONE; MEDIATED ENDOCYTOSIS; ASSEMBLY PROTEIN; DNAJ HOMOLOGS; IN-VIVO; HSP70; DISSOCIATION; ATPASE; BINDING AB During clathrin-mediated endocytosis Hsc70, supported by the J-domain protein auxilin, uncoats clathrin-coated vesicles. Auxilin contains both a clathrin-binding domain and a J-domain that binds Hsc70, and it has been suggested that these two domains are both necessary and sufficient for auxilin activity. To test this hypothesis, we created a chimeric protein consisting of the J-domain of auxilin linked to the clathrin-binding domain of the assembly protein AP180. This chimera supported uncoating, but unlike auxilin it acted stoichiometrically rather than catalytically because, like Hsc70, it remained associated with the uncoated clathrin. This observation supports our proposal that Hsc70 chaperones uncoated clathrin by inducing formation of a stable Hsc70-clathrin-AP complex. It also shows that Hsc70 acts by dissociating individual clathrin triskelions rather than cooperatively destabilizing clathrin-coated vesicles. Because the chimera lacks the C-terminal subdomain of the auxilin clathrin-binding domain, it seemed possible that this subdomain is required for auxilin to act catalytically, and indeed its deletion caused auxilin to act stoichiometrically. In contrast, deletion of the N-terminal subdomain weakened auxilinclathrin binding and prevented auxilin from polymerizing clathrin. Therefore the C-terminal subdomain of the clathrin-binding domain of auxilin is required for auxilin to act catalytically, whereas the N-terminal subdomain strengthens auxilin-clathrin binding. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Eisenberg, E (reprint author), NHLBI, Cell Biol Lab, NIH, 50 South Dr,Rm 2537,MSC 8017, Bethesda, MD 20892 USA. NR 30 TC 26 Z9 26 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49267 EP 49274 DI 10.1074/jbc.M203695200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900021 PM 12377777 ER PT J AU Basanez, G Sharpe, JC Galanis, J Brandt, TB Hardwick, JM Zimmerberg, J AF Basanez, G Sharpe, JC Galanis, J Brandt, TB Hardwick, JM Zimmerberg, J TI Bax-type apoptotic proteins porate pure lipid bilayers through a mechanism sensitive to intrinsic monolayer curvature SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NONBILAYER LIPIDS; PHOSPHOCHOLINE CYTIDYLYLTRANSFERASE; PHOSPHOLIPID-MEMBRANES; LYSOPHOSPHATIDIC ACID; CATALYTIC DOMAIN; LEADER PEPTIDASE; PORE FORMATION; BCL-X(L); PHOSPHATIDYLETHANOLAMINE; MITOCHONDRION AB During apoptosis, Bax-type proteins permeabilize the outer mitochondrial membrane to release intermembrane apoptogenic factors into the cytosol via a poorly understood mechanism. We have proposed that Bax and DeltaN76Bcl-X-L (the Bax-like cleavage fragment of Bcl-X-L) function by forming pores that are at least partially composed of lipids (lipidic pore formation). Since the membrane monolayer must bend during lipidic pore formation, we here explore the effect of intrinsic membrane monolayer curvature on pore formation. Nonlamellar lipids with positive intrinsic curvature such as lysophospholipids promoted membrane permeabilization, whereas nonlamellar lipids with negative intrinsic curvature such as diacylglycerol and phosphatidylethanolamine inhibited membrane permeabilization. The differential effects of nonlamellar lipids on membrane permeabilization were not correlated with lipid-induced changes in membrane binding or insertion of Bax or DeltaN76Bcl-X-L. Altogether, these results are consistent with a model whereby Bax-type proteins change the bending propensity of the membrane to form pores comprised at least in part of lipids in a structure of net positive monolayer curvature. C1 NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NIH, Gen Inst Med Sci, Bethesda, MD 20892 USA. Johns Hopkins Sch Publ Hlth & Med, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Sch Publ Hlth & Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. Johns Hopkins Sch Publ Hlth & Med, Dept Neurol, Baltimore, MD 21205 USA. RP Zimmerberg, J (reprint author), NICHD, Lab Cellular & Mol Biophys, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov RI Basanez, Gorka/L-9509-2014 OI Basanez, Gorka/0000-0002-7475-7861 NR 40 TC 170 Z9 175 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49360 EP 49365 DI 10.1074/jbc.M206069200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900033 PM 12381734 ER PT J AU Li, J Chen, PL Sinogeeva, N Gorospe, M Wersto, RP Chrest, FJ Barnes, J Liu, YS AF Li, J Chen, PL Sinogeeva, N Gorospe, M Wersto, RP Chrest, FJ Barnes, J Liu, YS TI Arsenic trioxide promotes histone H3 phosphoacetylation at the chromatin of CASPASE-10 in acute promyelocytic leukemia cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANS-RETINOIC ACID; INDUCED APOPTOSIS; DOWN-REGULATION; PMLRAR-ALPHA; IN-VITRO; PHOSPHORYLATION; TRANSCRIPTION; DEACETYLASE; REMISSION; APL AB Arsenic trioxide (As2O3) is highly effective for the treatment of acute promyelocytic leukemia, even in patients who are unresponsive to all-trans-retinoic acid therapy. As2O3 is believed to function primarily by promoting apoptosis, but the underlying molecular mechanisms remain largely unknown. In this report, using cDNA arrays, we have examined the changes in gene expression profiles triggered by clinically achievable doses of As2O3 in acute promyelocytic leukemia NB4 cells. CASPASE-10 expression was found to be potently induced by As2O3. Accordingly, caspase-10 activity also substantially increased in response to AS(2)O(3) treatment. A selective inhibitor of caspase-10, Z-AEVD-FMK, effectively blocked caspase-3 activation and significantly attenuated AS(2)O(3)-triggered apoptosis. Interestingly, the treatment of NB4 cells with AS(2)O(3) markedly increased histone H3 phosphorylation at serine 10, an event that is associated with acetylation of the lysine 14 residue. Chromatin immunoprecipitation assays revealed that AS(2)O(3) potently enhances histone H3 phosphoacetylation at the CASPASE-10 locus. These results suggest that the effect of As2O3 on histone H3 phosphoacetylation at the CASPASE-10 gene may play an important role in the induction of apoptosis and thus contribute to its therapeutic effects on acute promyelocytic leukemia. C1 NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIA, Res Resources Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Liu, YS (reprint author), NIA, Cellular & Mol Biol Lab, Intramural Res Program, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Liu, Yusen/E-3527-2011 NR 38 TC 50 Z9 50 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49504 EP 49510 DI 10.1074/jbc.M207836200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900053 PM 12388546 ER PT J AU Wolkow, CA Munoz, MJ Riddle, DL Ruvkun, G AF Wolkow, CA Munoz, MJ Riddle, DL Ruvkun, G TI Insulin receptor substrate and p55 orthologous adaptor proteins function in the Caenorhabditis elegans daf-2/insulin-like signaling pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DAUER LARVA DEVELOPMENT; AGE-1 PI3 KINASE; LIFE-SPAN; PHOSPHOINOSITIDE 3-KINASE; TRANSCRIPTION FACTOR; INTERACTING GENES; FAMILY MEMBER; MICE LACKING; LONGEVITY; DAF-2 AB An insulin-like signaling pathway regulates development and lifespan in Caenorhabditis elegdns. Genetic screens that identified many components of the C. elegans insulin pathway did not identify homologs of insulin receptor substrates or the phosphoinositide 3-kinase (PI3K) adaptor/regulatory subunit, which are both required for signaling by mammalian insulin/insulin-like growth factor I pathways. The C. elegans genome contains one homolog of each protein. The C. elegans versions of insulin receptor substrate (IST-1) and PI3K p50/p55 (AAP-1) share moderate sequence similarity with their vertebrate and Drosophila counterparts. Genetic experiments show that ist-1 and aap-1 potentiate C. elegans insulin-like signaling, although they are not required for signaling in the pathway under most conditions. Worms lacking AAP-1 activity because of the mutation aap-1(m889) constitutively arrest development at the dauer larval stage when raised at high temperatures. aap-1 mutants also live longer than wild-type animals, a phenotype observed in other C. elegans mutants with defects in DAF-2 signaling. Interestingly, IST-1 appears to be required for signaling through a pathway that may act in parallel to AGE-1/PI3K. C1 Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA. NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Wolkow, CA (reprint author), Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. RI Munoz, Manuel/F-7841-2016 FU Intramural NIH HHS [NIH0011061953, Z01 AG000320-06]; NIA NIH HHS [AG 12689, AG 14161, R01 AG014161]; NIGMS NIH HHS [GM 60151] NR 43 TC 62 Z9 68 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 DEC 20 PY 2002 VL 277 IS 51 BP 49591 EP 49597 DI 10.1074/jbc.M207866200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900065 PM 12393910 ER PT J AU Caterina, JJ Skobe, Z Shi, J Ding, YL Simmer, JP Birkedal-Hansen, H Bartlett, JD AF Caterina, JJ Skobe, Z Shi, J Ding, YL Simmer, JP Birkedal-Hansen, H Bartlett, JD TI Enamelysin (matrix metalloproteinase 20)-deficient mice display an amelogenesis imperfecta phenotype SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MATRIX PROTEINS; MOUSE ENAMELYSIN; MESSENGER-RNAS; BOVINE ENAMEL; CLONING; TOOTH; GENE; EXPRESSION; LOCALIZATION; CELLS AB Enamelysin is a tooth-specific matrix metalloproteinase that is expressed during the early through middle stages of enamel development. The enamel matrix proteins amelogenin, ameloblastin, and enamelin are also expressed during this same approximate developmental time period, suggesting that enamelysin may play a role in their hydrolysis. In support of this interpretation, recombinant enamelysin was previously demonstrated to cleave recombinant amelogenin at virtually all of the precise sites known to occur in vivo. Thus, enamelysin is likely an important amelogenin-processing enzyme. To characterize the in vivo biological role of enamelysin during tooth development, we generated an enamelysin-deficient mouse by gene targeting. Although mice heterozygous for the mutation have no apparent phenotype, the enamelysin null mouse has a severe and profound tooth phenotype. Specifically, the null mouse does not process amelogenin properly, possesses an altered enamel matrix and rod pattern, has hypoplastic enamel that delaminates from the dentin, and has a deteriorating enamel organ morphology as development progresses. Our findings demonstrate that enamelysin activity is essential for proper enamel development. C1 Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. NIDCR, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA. Forsyth Inst, Biostruct Core Facil, Boston, MA 02115 USA. Univ Michigan, Sch Dent, Dept Biol & Mat Sci, Ann Arbor, MI 48108 USA. Harvard Univ, Sch Med, Dept Oral & Dev Biol, Boston, MA 02115 USA. RP Bartlett, JD (reprint author), Forsyth Inst, Dept Cytokine Biol, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE 14084, R01 DE014084] NR 54 TC 154 Z9 156 U1 1 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49598 EP 49604 DI 10.1074/jbc.M209100200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900066 PM 12393861 ER PT J AU Swamynathan, SK Piatigorsky, J AF Swamynathan, SK Piatigorsky, J TI Orientation-dependent influence of an intergenic enhancer on the promoter activity of the divergently transcribed mouse Shsp/alpha B-crystallin and Mkbp/HspB2 genes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAT-SHOCK-PROTEIN; NON-LENTICULAR TISSUES; ALPHA-A-CRYSTALLIN; BETA-GLOBIN; TRANSGENIC MICE; CORE PROMOTERS; SHARED ENHANCER; SKELETAL-MUSCLE; 3RD INTRON; LENS AB The mouse Shsp/alphaB-crystallin and Mkbp/HspB2 genes are closely linked and divergently transcribed. In this study, we have analyzed the contribution of the intergenic enhancer to Sitsp/alphaB-crystallin and Mkbp/HspB2 promoter activity using dual-reporter vectors in transient transfection and transgenic mouse experiments. Deletion of the enhancer reduced Shsp/alphaB-crystallin promoter activity by 30- and 93-fold and Mkbp/HspB2 promoter activity by 6- and 10-fold in transiently transfected mouse lens alpha-TN4 and myoblast C2C12 cells, respectively. Surprisingly, inversion of the enhancer reduced Shsp/alphaB-crystallin promoter activity by 17-fold, but did not affect Mkbp/HspB2 promoter activity in the transfected cells. In contrast, enhancer activity was orientation-independent in combination with a heterologous promoter in transfected cells. Transgenic mouse experiments established the orientation dependence and Shsp/alphaB-crystallin promoter preference of the intergenic enhancer in its native context. The orientation dependence and preferential effect of the Shsp/alphaB-crystallin enhancer on the Shsp/alphaB-crystallin promoter provide an example of adaptive changes in gene regulation accompanying the functional diversification of duplicated genes during evolution. C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bldg 6,Rm 201,6 Ctr Dr, Bethesda, MD 20892 USA. OI Swamynathan, Shivalingappa/0000-0002-9158-1511 NR 63 TC 30 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49700 EP 49706 DI 10.1074/jbc.M209700200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900080 PM 12403771 ER PT J AU Kajava, AV AF Kajava, AV TI What curves alpha-solenoids? Evidence for an alpha-helical toroid structure of Rpn1 and Rpn2 proteins of the 26 S proteasome SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANAPHASE-PROMOTING COMPLEX; LEUCINE-RICH REPEAT; SECONDARY STRUCTURE PREDICTION; F1F0 ATP SYNTHASE; CRYSTAL-STRUCTURE; ANKYRIN REPEAT; CROSS-LINKING; SUBUNIT-C; DOMAIN; MOTIF AB The alpha-helical solenoid proteins adopt a variety of elongated curved structures. They have been examined to identify the interactions that determine their curvature. A sequence pattern characteristic for strongly curved alpha-helical solenoids has been constructed and was found to match protein sequences containing the proteasome/cyclosome repeats. Based on this, a structural model of the repeat-containing domains of the Rpn1/S2 and Rpn2/S1 proteins, which represent the largest subunits of the 26 S proteasome, has been proposed. The model has a novel architecture resembling an a-helical toroid. Molecular modeling shows that these toroids have a central pore that would allow passage of an unfolded protein substrate through it. This implies that the Rpn1 and Rpn2 toroids are aligned along the common axial pores of the ATPase hexamer and form an "antechamber'' of the 26 S proteasome. The proposed quaternary structure agrees with the available experimental data. It is suggested that the function of this antechamber is assistance to the ATPases in the unfolding of protein substrates prior to proteolysis. An evolutionary link between the PC repeat-containing proteins and tetratricopeptide repeat proteins is proposed. C1 NIH, Ctr Mol Modeling, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Kajava, AV (reprint author), CNRS, Ctr Rech Biochim Macromol, UPR 1086, 1919 Route Mende, F-34293 Montpellier 5, France. RI Kajava, Andrey/E-1107-2014 OI Kajava, Andrey/0000-0002-2342-6886 NR 66 TC 53 Z9 53 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49791 EP 49798 DI 10.1074/jbc.M204982200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900092 PM 12270919 ER PT J AU Willcocks, JP Mulquiney, PJ Ellory, JC Veech, RL Radda, GK Clarke, K AF Willcocks, JP Mulquiney, PJ Ellory, JC Veech, RL Radda, GK Clarke, K TI Simultaneous determination of low free Mg2+ and pH in human sickle cells using P-31 NMR spectroscopy SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INTRACELLULAR FREE MAGNESIUM; NUCLEAR-MAGNETIC-RESONANCE; ANEMIA RED-CELLS; ADENOSINE 5'-TRIPHOSPHATE; DISSOCIATION-CONSTANT; POTASSIUM-TRANSPORT; HUMAN-ERYTHROCYTES; IONIZED MAGNESIUM; HUMAN HEMOGLOBIN; CHEMICAL-SHIFTS AB The concentrations of free magnesium, [Mg2+](free), [H+], and [ATP] are important in the dehydration of red blood cells from patients with sickle cell anemia, but they are not easily measured. Consequently, we have developed a rapid, noninvasive NMR spectroscopic method using the phosphorus chemical shifts of ATP and 2,3-diphosphoglycerate (DPG) to determine [Mg2+](free) and pH(i) simultaneously in fully oxygenated whole blood. The method employs theoretical equations expressing the observed chemical shift as a function of pH, K+, and [Mg2+](free), over a pH range of 5.75-8.5 and [Mg2+](free) range 0-5 mm. The equations were adjusted to allow for the binding of hemoglobin to ATP and DPG, which required knowledge of the intracellular concentrations of ATP, DPG, K+, and hemoglobin. Normal oxygenated whole blood (n = 33) had a pH(i) of 7.20. +/- 0.02, a [Mg2+](free) of 0.41 +/- 0.03 mM and [DPG] of 7.69 +/- 0.47 mm. Under the same conditions, whole sickle blood (n = 9) had normal [ATP] but significantly lower pH(i) (7.10 +/- 0.03) and [Mg2+](free) (0.32 +/- 0.05 mM) than normal red cells, whereas [DPG] (10.8 +/- 1.2 mm) was significantly higher. Because total magnesium was normal in sickle cells, the lower [Mg2+](free) could be attributed to increased [DPG] and therefore greater magnesium binding capacity of sickle cells. C1 Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. Univ Oxford, Dept Physiol, Oxford OX1 3QU, England. NIAAA, Rockville, MD 20852 USA. RP Clarke, K (reprint author), Univ Oxford, Dept Biochem, S Parks Rd, Oxford OX1 3QU, England. FU British Heart Foundation [PS/02/002/14893] NR 54 TC 15 Z9 17 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 20 PY 2002 VL 277 IS 51 BP 49911 EP 49920 DI 10.1074/jbc.M207551200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 629AU UT WOS:000180028900106 PM 12297506 ER PT J AU Chen, P Wang, HG Du, QZ Ito, Y AF Chen, P Wang, HG Du, QZ Ito, Y TI Purification of long-chain fatty acid ester of epigallocatechin-3-O-gallate by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE counter-current chromatography; epigallocatechin-3-O-gallate; epigallocatechin-3-O-gallate-4 '-hexadecanate; fatty acids; catechins ID TEA AB Epigallocatechin-3-O-gallate (EGCG) was modified by catalytic esterification with hexadecanoyl chloride. A long-chain fatty acid ester derivative was obtained from the purification of this reaction product by high-speed counter-current chromatography using a solvent system composed of n-hexane-ethyl acetate-methanol-water v/v). The structure of the derivative, epigallocatechin-3-O-gallate-4'-hexadecanate, was elucidated by IR, MS and H-1 NMR. Published by Elsevier Science B.V. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. Zhejiang Univ, Dept Chem, Hangzhou 310027, Peoples R China. Hangzhou Univ Commerce, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. RP Ito, Y (reprint author), NHLBI, Biophys Chem Lab, NIH, Bldg 50,Rm 3334, Bethesda, MD 20892 USA. RI wang, huigang/C-9265-2009 NR 7 TC 5 Z9 7 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD DEC 20 PY 2002 VL 982 IS 1 BP 163 EP 165 AR PII S0021-9673(02)01604-7 DI 10.1016/S0021-9673(02)01604-7 PG 3 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 618VH UT WOS:000179437600013 PM 12489865 ER PT J AU Loeffler, J Bauer, R Hebart, H Douek, DC Rauser, G Bader, P Einsele, H AF Loeffler, J Bauer, R Hebart, H Douek, DC Rauser, G Bader, P Einsele, H TI Quantification of T-cell receptor excision circle DNA using fluorescence resonance energy transfer and the LightCycler system SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article DE thymic output; LightCycler; PCR-ELISA; TREC ID BONE-MARROW TRANSPLANTATION; RECENT THYMIC EMIGRANTS; IMMUNE RECONSTITUTION; REPERTOIRE; INFECTION; INFUSIONS; ADULTS; GRAFTS; BLOOD; AGE AB T-cell receptor excision circles (TRECs) are circular, stable extrachromosomal DNA fragments and are generated during V(D)J gene recombination, a process responsible for diversity of the T-cell receptor repertoire. Here we describe a sensitive, rapid and easy to perform real-time PCR assay based on the LightCycler technique for the quantification of TRECs among peripheral blood cells and a comparison of this assay with conventional PCR-ELISA. By LightCycler, a sensitivity of 20 copies of plasmid deltaRec-psiJa Signal Joint TREC DNA was achieved whereas by PCR-ELISA, a detection limit of 2 copies was demonstrated. In blood samples from healthy individuals (n = 52) a median TREC count of 1.6 x 10(4) copies [range 2 x 10(1) to 2 x 10(5)]/2 x 10(5) peripheral blood mononuclear cells (PBMNCs) and in cord blood, a median TREC count of 1.45 x 10(5) copies [range 1.2 x 10(5) to 1.6 x 10(5)]/2 x 10(5) PBMNCs) could be detected. No significant difference was found in 15 individuals when unfractionated PBMNCs (median count of 1.1 x 10(5) copies/2 x 10(5) PBMNCs) or magnetic associated cell sorter (MACS)-sorted CD45RA+ T-cells (median count of 2.5 x 10(5) copies/2 x 10(5) cells) were analyzed for TREC counts. In addition, we examined the number of deltaRec-psiJa Signal Joint TREC in paediatric (n = 6) and adult patients (n = 7) after allogeneic stem cell transplantation. In children, we observed a median TREC count of 5.7 x 10(4) copies/2 x 10(5) PBMNCs after 1 x 10(4) and 5.6 x 10(4) copies/2 x 10(5) PBMNCs after 2 years, and in adults, a median count of 3.6 x 10(4) copies/2 x 10(5) PBMNCs after 1 x 10(4) and 1.1 x 10(4) copies/2 x 10(5) PBMNCs after 2 years. In conclusion, the LightCycler-based real-time PCR assay described offers a very sensitive and rapid tool for the quantification of TREC DNA. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Tubingen, Med Klin, Abt 2, D-72076 Tubingen, Germany. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. Univ Tubingen, Kinder Klin, Abt Hamatol & Onkol, D-72076 Tubingen, Germany. RP Loeffler, J (reprint author), Univ Tubingen, Med Klin, Abt 2, Otfried Mueller Str 10, D-72076 Tubingen, Germany. NR 27 TC 16 Z9 18 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD DEC 20 PY 2002 VL 271 IS 1-2 BP 167 EP 175 AR PII S0022-1759(02)00337-X DI 10.1016/S0022-1759(02)00337-X PG 9 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 621YX UT WOS:000179619900016 PM 12445739 ER PT J AU Zangen, A Hyodo, K AF Zangen, A Hyodo, K TI Transcranial magnetic stimulation induces increases in extracellular levels of dopamine and glutamate in the nucleus accumbens SO NEUROREPORT LA English DT Article DE acetylcholine; dopamine; glutamate; microdialysis; nucleus accumbens; transcranial magnetic stimulation ID VENTRAL TEGMENTAL AREA; MOLECULAR MECHANISMS; RAT STRIATUM; IN-VIVO; RELEASE; SEROTONIN; NEURONS; SYSTEM; REWARD; BRAIN AB Transcranial magnetic stimulation (TMS) is a non-invasive approach used for stimulating the human brain. Repetitive stimulation over the prefrontal cortex has proven effective in the treatment of major depression, however the mechanism of the antidepressant action is unknown. Since the nucleus accumbens is a major region implicated in reward circuitry and depressive disorders, we used the microdialysis technique to study some of the neurochemical changes induced in that region during and after acute TMS. Magnetic stimulation was applied over the frontal or the caudal cortex of the rat brain using a special coil design and microdialysis samples were collected before, during and after the stimulation session. The extracellular levels of both dopamine and glutamate in the nucleus accumbens were increased during the stimulation while the extracellular levels of acetylcholine were not affected. Stimulation over the caudal cortex caused a greater increase in dopamine levels than the stimulation over the frontal cortex, while such difference was not observed for glutamate levels. The changes in dopamine and glutamate extracellular levels in the nucleus accumbens may play a role in the antidepressant effect of TMS and it is therefore suggested that the effect of stimulation over caudal cortical sites on depressive patients will be examined. C1 Natl Inst Drug Abuse, NIH, Baltimore, MD 21224 USA. AIST, Inst Human Sci & Biomed Engn, Tsukuba, Ibaraki 3058564, Japan. RP Zangen, A (reprint author), Natl Inst Drug Abuse, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 25 TC 74 Z9 80 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD DEC 20 PY 2002 VL 13 IS 18 BP 2401 EP 2405 DI 10.1097/01.wnr.0000048021.74602.f2 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 640DV UT WOS:000180673200005 PM 12499837 ER PT J AU Chang, KO Kim, Y Green, KY Saif, LJ AF Chang, KO Kim, Y Green, KY Saif, LJ TI Cell-culture propagation of porcine enteric calicivirus mediated by intestinal contents is dependent on the cyclic AMP signaling pathway SO VIROLOGY LA English DT Article DE porcine enteric calicivirus; intestinal content; virus growth; signaling pathway ID VIRUS-LIKE PARTICLES; SERIAL PROPAGATION; INHIBITION; SURAMIN; CYCLASE; KINASE; DEGRADATION; CAPSIDS; PIGS; RNA AB Enteric caliciviruses are emerging pathogens in humans and animals, but they do not replicate in cell culture except for the porcine enteric calicivirus (PEC) Cowden strain. The PEC Cowden strain grows in pig kidney (LLC-PK) cells, but only in the presence of intestinal contents (IC) from uninfected gnotobiotic pigs in the medium. In this study, we investigated the relationship between IC and growth of Cowden PEC. Pretreatment of cells or the virus with IC or transfection of viral RNA into cells did not induce virus growth unless the medium was supplemented with IC. Among modulators of cell signal transduction, the G protein uncoupler suramin, adenylate cyclase (AC) inhibitor, MDL-12,330A, and the cAMP-dependent protein kinase (PKA) inhibitor, N-(2-[bromocinnamulamino]ethyl)-5-isoquinolinesulfonamide (NBEI) inhibited the effect of IC on virus growth for up to 72 h. These data indicate that PEC virus replication may be dependent on an initial cAMP signaling pathway induced by IC. (C) 2002 Elsevier Science (USA). C1 Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Dept Vet Prevent Med, Wooster, OH 44691 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Saif, LJ (reprint author), Ohio State Univ, Ohio Agr Res & Dev Ctr, Food Anim Hlth Res Program, Dept Vet Prevent Med, 1680 Madison Ave, Wooster, OH 44691 USA. FU NIAID NIH HHS [R01AI49716] NR 30 TC 23 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 20 PY 2002 VL 304 IS 2 BP 302 EP 310 DI 10.1006/viro.2002.1665 PG 9 WC Virology SC Virology GA 629QM UT WOS:000180060400016 PM 12504571 ER PT J AU Yamashita, T Wada, R Proia, RL AF Yamashita, T Wada, R Proia, RL TI Early developmental expression of the gene encoding glucosylceramide synthase, the enzyme controlling the first committed step of glycosphingolipid synthesis SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE glucosylceramide synthase; glycosphingolipid; UDP-glucose ID STORAGE DISORDERS; MICE; THERAPY; DIFFERENTIATION; TYPE-2; RAFTS AB Glycosphingolipids (GSLs) are ubiquitous plasma membrane components composed of a ceramide lipid anchor attached to one of a diverse complement of oligosaccharide structures. Fundamentally important activities have been attributed to GSLs including formation of plasma membrane structures involved in membrane trafficking, signal transduction and cell-cell interactions. Glucosylceramide synthase converts ceramide to glucosylceramide, a core structure of the vast majority of GSLs. Disruption of the gene encoding glucosylceramide synthase (Ugcg) caused embryonic lethality in mice during gastrulation. To further investigate the role of GSL synthesis during embryogenesis, we produced mice with a Lacz reporter gene inserted into the glucosylceramide synthase locus. These mice allowed the visualization of glucosylceramide synthase expression during early embryonic development. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Proia, RL (reprint author), NIDDKD, Genet Dev & Dis Branch, NIH, Bldg 10,Room 9N-314,10 Ctr DR MSC 1821, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 23 TC 16 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD DEC 19 PY 2002 VL 1573 IS 3 BP 236 EP 240 AR PII S0304-4165(02)00389-6 DI 10.1016/S0304-4165(02)00389-6 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 615AJ UT WOS:000179223400007 PM 12417405 ER PT J AU Neamati, N Lin, ZW Karki, RG Orr, A Cowansage, M Strumberg, D Pais, GCG Voigt, JH Nicklaus, MC Winslow, HE Zhao, H Turpin, JA Yi, JZ Skalka, AM Burke, TR Pommier, Y AF Neamati, N Lin, ZW Karki, RG Orr, A Cowansage, M Strumberg, D Pais, GCG Voigt, JH Nicklaus, MC Winslow, HE Zhao, H Turpin, JA Yi, JZ Skalka, AM Burke, TR Pommier, Y TI Metal-dependent inhibition of HIV-1 integrase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID VIRUS TYPE-1 INTEGRASE; CATALYTIC DOMAIN; ZINC FINGERS; IN-VITRO; STRAND-TRANSFER; ACTIVE-SITE; REPLICATION; DISCOVERY; DESIGN; AIDS AB Human immunodeficiency virus type 1 integrase (HIV-1 IN) is an essential enzyme for effective viral, replication. Therefore, IN inhibitors are being sought for chemotherapy against AIDS. We had previously identified a series of salicylhydrazides as potent inhibitors of IN in vitro (Neamati, N.; et al. J. Med. Chem. 1998, 41, 3202-3209.). Herein, we report the design, synthesis, and antiviral activity of three novel mercaptosalicylhydrazide (MSH) derivatives. MSHs were effective against the IN catalytic core domain and inhibited IN binding to HIV LTR DNA. They also inhibited catalytic activities of IN in IN-DNA preassembled complexes. Site-directed mutagenesis and molecular modeling studies suggest that MSHs bind to cysteine 65 and chelate Mg2+ at the active site of HIV-1 IN. Contrary to salicylhydrazides, the MSHs are 300-fold less cytotoxic and exhibit antiviral activity. They are also active in Mg2+-based assays, while IN inhibition by salicylhydrazides is strictly Mn2+-dependent. Additionally, in target and cell-based assays, the MSHs have no detectable effect on other retroviral targets, including reverse transcriptase, protease, and virus attachment, and exhibit no detectable activity against human topoisomerases I and II at concentrations that effectively inhibit IN. These data suggest that MSHs are selective inhibitors of HIV-1 IN and may serve as leads for antiviral therapeutics. C1 Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. So Res Inst, Frederick, MD 21701 USA. NCI, Div Basic Sci, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Neamati, N (reprint author), Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, 1985 Zonal Ave, Los Angeles, CA 90089 USA. EM neamati@usc.edu RI Nicklaus, Marc/N-4183-2014; Burke, Terrence/N-2601-2014; OI Nicklaus, Marc/0000-0002-4775-7030 NR 52 TC 63 Z9 65 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 19 PY 2002 VL 45 IS 26 BP 5661 EP 5670 DI 10.1021/jm0201417 PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 625KC UT WOS:000179814800009 PM 12477350 ER PT J AU Xu, B Stephens, A Kirschenheuter, G Greslin, AF Cheng, XQ Sennelo, J Cattaneo, M Zighetti, ML Chen, AS Kim, SA Kim, HS Bischofberger, N Cook, G Jacobson, KA AF Xu, B Stephens, A Kirschenheuter, G Greslin, AF Cheng, XQ Sennelo, J Cattaneo, M Zighetti, ML Chen, AS Kim, SA Kim, HS Bischofberger, N Cook, G Jacobson, KA TI Acyclic analogues of adenosine bisphosphates as P2Y receptor antagonists: Phosphate substitution leads to multiple pathways of inhibition of platelet aggregation SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID NUCLEOTIDE RECEPTORS; BIOLOGICAL-ACTIVITY; ALCOHOLS; ADP; IDENTIFICATION; DERIVATIVES; ACTIVATION; BLOOD; ATP AB Activation by ADP of both P2Y(1) and P2Y(12) receptors in platelets contributes to platelet aggregation, and antagonists at these receptor subtypes have antithrombotic properties. In an earlier publication, we have characterized the SAR as P2Y(1) receptor antagonists of acyclic analogues of adenine nudeotides, containing two phosphate groups on a symmetrically branched aliphatic chain, attached at the 9-position of adenine. In this study, we have focused on antiaggregatory effects of P2Y antagonists related to a 2-chloro-N-6-methyladenine-9-(2-methylpropyl) scaffold, containing uncharged substitutions of the phosphate groups. For the known nucleotide (cyclic and acyclic) bisphosphate antagonists of P2Y(1) receptors, there was a significant correlation between inhibition of aggregation induced by 3.3 muM ADP in rat platelets and inhibition of P2Y(1) receptor-induced phospholipase C (PLC) activity previously determined in turkey erythrocytes. Substitution of the phosphate groups with nonhydrolyzable phosphonate groups preserved platelet antiaggregatory activity. Substitution of one of the phosphate groups with O-acyl greatly reduced the inhibitory potency, which tended to increase upon replacement of both phosphate moieties of the acyclic derivatives with uncharged (e.g., ester) groups. In the series of nonsymmetrically substituted monophosphates, the optimal antagonist potency occurred with the phenylcarbamate group. Among symmetrical diester derivatives, the optimal antagonist potency occurred with the di(phenylacetyl) group. A dipivaloyl derivative, a representative uncharged diester, inhibited ADP-induced aggregation in both rat (K-i 3.6 muM) and human platelets. It antagonized the ADP-induced inhibition of the cyclic AMP pathway in rat platelets (IC50 7 muM) but did not affect hP2Y(1) receptor-induced PLC activity measured in transfected astrocytoma cells. We propose that the uncharged derivatives are acting as antagonists of a parallel pro-aggregatory receptor present an platelets, that is, the P2Y(12) receptor. Thus, different substitution of the same nucleoside scaffold can target either of two P2Y receptors in platelets. C1 NIDDK, Mol Recognit Sect, NIH, LBC, Bethesda, MD 20892 USA. Univ Milan, Osped Maggiore, IRCCS, Hemophilia & Thrombosis Ctr, Milan, Italy. Univ Milan, DMCO, Osped Sao Paolo, Hematol & Thrombosis Unit, Milan, Italy. Gilead Sci Inc, Foster City, CA 94404 USA. Gilead Sci Inc, Boulder, CO 80301 USA. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, NIH, LBC, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; OI Jacobson, Kenneth/0000-0001-8104-1493; Cattaneo, Marco/0000-0002-7343-4534 NR 36 TC 61 Z9 62 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 DEC 19 PY 2002 VL 45 IS 26 BP 5694 EP 5709 DI 10.1021/jm020173u PG 16 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 625KC UT WOS:000179814800012 PM 12477353 ER PT J AU Owens, DF Kriegstein, AR AF Owens, DF Kriegstein, AR TI Developmental neurotransmitters? SO NEURON LA English DT Editorial Material ID BRAIN; GABA C1 NINDS, Mol Biol Lab, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Dept Pathol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Ctr Neurobiol & Behav, New York, NY 10032 USA. RP Owens, DF (reprint author), NINDS, Mol Biol Lab, Bethesda, MD 20892 USA. NR 12 TC 58 Z9 61 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 19 PY 2002 VL 36 IS 6 BP 989 EP 991 DI 10.1016/S0896-6273(02)01136-4 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 628TA UT WOS:000180011600001 PM 12495613 ER PT J AU Petrucelli, L O'Farrell, C Lockhart, PJ Baptista, M Kehoe, K Vink, L Choi, P Wolozin, B Farrer, M Hardy, J Cookson, MR AF Petrucelli, L O'Farrell, C Lockhart, PJ Baptista, M Kehoe, K Vink, L Choi, P Wolozin, B Farrer, M Hardy, J Cookson, MR TI Parkin protects against the toxicity associated with mutant alpha-synuclein: Proteasome dysfunction selectively affects catecholaminergic neurons SO NEURON LA English DT Article ID INDUCED CELL-DEATH; SUBSTANTIA-NIGRA; WILD-TYPE; UBIQUITIN SYSTEM; TRANSGENIC MICE; PRIMARY CULTURE; BODY FORMATION; DISEASE; DEGRADATION; GENE AB One hypothesis for the etiology of Parkinson's disease (PD) is that subsets of neurons are vulnerable to a failure in proteasome-mediated protein turnover. Here we show that overexpression of mutant alpha-synuclein increases sensitivity to proteasome inhibitors by decreasing proteasome function. Overexpression of parkin decreases sensitivity to proteasome inhibitors in a manner dependent on parkin's ubiquitin-protein E3 ligase activity, and antisense knockdown of parkin increases sensitivity to proteasome inhibitors. Mutant alpha-synuclein also causes selective toxicity to catecholaminergic neurons in primary midbrain cultures, an effect that can be mimicked by the application of proteasome inhibitors. Parkin is capable of rescuing the toxic effects of mutant alpha-synuclein or proteasome inhibition in these cells. Therefore, parkin and alpha-synuclein are linked by common effects on a pathway associated with selective cell death in catecholaminergic neurons. C1 NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Mayo Clin Jacksonville, Neurogenet Lab, Jacksonville, FL 32224 USA. Loyola Univ, Med Ctr, Dept Pharmacol, Maywood, IL 60153 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, Bethesda, MD 20892 USA. RI Hardy, John/C-2451-2009; Lockhart, Paul/E-7753-2011 OI Lockhart, Paul/0000-0003-2531-8413 FU NINDS NIH HHS [P01-NS40256, R01-NS41816-01] NR 53 TC 391 Z9 404 U1 1 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 19 PY 2002 VL 36 IS 6 BP 1007 EP 1019 DI 10.1016/S0896-6273(02)01125-X PG 13 WC Neurosciences SC Neurosciences & Neurology GA 628TA UT WOS:000180011600006 PM 12495618 ER PT J AU Straus, SE AF Straus, SE TI Perspective - Herbal medicines - What's in the bottle?. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NR 0 TC 41 Z9 42 U1 1 U2 2 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2002 VL 347 IS 25 BP 1997 EP 1998 DI 10.1056/NEJMp020148 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 626LT UT WOS:000179874500002 PM 12490680 ER PT J AU Eknoyan, G Beck, GJ Cheung, AK Daugirdas, JT Greene, T Kusek, JW Allon, M Bailey, J Delmez, JA Depner, TA Dwyer, JT Levey, AS Levin, NW Milford, E Ornt, DB Rocco, MV Schulman, G Schwab, SJ Teehan, BP Toto, R AF Eknoyan, G Beck, GJ Cheung, AK Daugirdas, JT Greene, T Kusek, JW Allon, M Bailey, J Delmez, JA Depner, TA Dwyer, JT Levey, AS Levin, NW Milford, E Ornt, DB Rocco, MV Schulman, G Schwab, SJ Teehan, BP Toto, R CA HEMO Study Grp TI Effect of dialysis dose and membrane flux in maintenance hemodialysis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NATIONAL COOPERATIVE DIALYSIS; UREA REDUCTION RATIO; MORTALITY; BETA(2)-MICROGLOBULIN; CLEARANCE; MORBIDITY; PRODUCT; MODELS; REUSE; LIFE AB Background: The effects of the dose of dialysis and the level of flux of the dialyzer membrane on mortality and morbidity among patients undergoing maintenance hemodialysis are uncertain. Methods: We undertook a randomized clinical trial in 1846 patients undergoing thrice-weekly dialysis, using a two-by-two factorial design to assign patients randomly to a standard or high dose of dialysis and to a low-flux or high-flux dialyzer. Results: In the standard-dose group, the mean (+/-SD) urea-reduction ratio was 66.3+/-2.5 percent, the single-pool Kt/V was 1.32+/-0.09, and the equilibrated Kt/V was 1.16+/-0.08; in the high-dose group, the values were 75.2+/-2.5 percent, 1.71+/-0.11, and 1.53+/-0.09, respectively. Flux, estimated on the basis of beta(sub 2)-microglobulin clearance, was 3+/-7 ml per minute in the low-flux group and 34+/-11 ml per minute in the high-flux group. The primary outcome, death from any cause, was not significantly influenced by the dose or flux assignment: the relative risk of death in the high-dose group as compared with the standard-dose group was 0.96 (95 percent confidence interval, 0.84 to 1.10; P=0.53), and the relative risk of death in the high-flux group as compared with the low-flux group was 0.92 (95 percent confidence interval, 0.81 to 1.05; P=0.23). The main secondary outcomes (first hospitalization for cardiac causes or death from any cause, first hospitalization for infection or death from any cause, first 15 percent decrease in the serum albumin level or death from any cause, and all hospitalizations not related to vascular access) also did not differ significantly between either the dose groups or the flux groups. Possible benefits of the dose or flux interventions were suggested in two of seven prespecified subgroups of patients. Conclusions: Patients undergoing hemodialysis thrice weekly appear to have no major benefit from a higher dialysis dose than that recommended by current U.S. guidelines or from the use of a high-flux membrane. C1 Cleveland Clin Fdn, Dept Biostat & Epidemiol, HEMO Data Coordinating Ctr, Cleveland, OH 44195 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Utah, Salt Lake City, UT USA. Vet Affairs Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. Univ Illinois, Chicago, IL USA. Vet Affairs Chicago Hlth Care Syst, Chicago, IL USA. NIDDKD, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Washington Univ, St Louis, MO USA. Univ Calif Davis, Sacramento, CA 95817 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Beth Israel Med Ctr, New York, NY 10003 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Rochester, Rochester, NY USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Vanderbilt Univ, Nashville, TN USA. Duke Univ, Durham, NC USA. Lankenau Hosp & Med Res Ctr, Wynnewood, PA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. RP Beck, GJ (reprint author), Cleveland Clin Fdn, Dept Biostat & Epidemiol, HEMO Data Coordinating Ctr, Wb4,9500 Euclid Ave, Cleveland, OH 44195 USA. OI Dwyer, Johanna/0000-0002-0783-1769 NR 38 TC 991 Z9 1026 U1 9 U2 39 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2002 VL 347 IS 25 BP 2010 EP 2019 DI 10.1056/NEJMoa021583 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 626LT UT WOS:000179874500004 PM 12490682 ER PT J AU Walsh, TJ AF Walsh, TJ TI Echinocandins - An advance in the primary treatment of invasive candidiasis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID SURVEILLANCE; CANDIDEMIA C1 NCI, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Bethesda, MD 20892 USA. NR 10 TC 55 Z9 56 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2002 VL 347 IS 25 BP 2070 EP 2072 DI 10.1056/NEJMe020142 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 626LT UT WOS:000179874500013 PM 12490691 ER PT J AU Herbrecht, R Patterson, TF Bennett, JE AF Herbrecht, R Patterson, TF Bennett, JE TI Voriconazole versus amphotericin B for invasive aspergillosis. Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Hop Hautepierre, F-67098 Strasbourg, France. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. NIAID, Bethesda, MD 20892 USA. RP Herbrecht, R (reprint author), Hop Hautepierre, F-67098 Strasbourg, France. RI Herbrecht, Raoul/D-3471-2013; OI Herbrecht, Raoul/0000-0002-9381-4876 NR 1 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 19 PY 2002 VL 347 IS 25 BP 2080 EP 2081 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 626LT UT WOS:000179874500024 ER PT J AU Franchini, G Nacsa, J Hel, Z Tryniszewska, E AF Franchini, G Nacsa, J Hel, Z Tryniszewska, E TI Immune intervention strategies for HIV-1 infection of humans in the SIV macaque model SO VACCINE LA English DT Article; Proceedings Paper CT Meeting on Therapeutic Vaccines Against HIV and Cancers CY JUN 23-26, 2002 CL ANNECY, FRANCE DE macaque model; HIV immune therapy; cytokines; vaccines ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CYTOTOXIC T-LYMPHOCYTES; STRUCTURED TREATMENT INTERRUPTIONS; RANDOMIZED CONTROLLED TRIAL; PROTEASE INHIBITOR THERAPY; PHASE-II TRIAL; SUBCUTANEOUS INTERLEUKIN-2; RHESUS-MONKEYS; CD8(+) LYMPHOCYTES AB Studies in the SlVmac macaque model have demonstrated that the extent of virus-specific CD4+ and CD8+ T-cell responses induced by vaccination prior to virus-challenge exposure correlate with viremia containment following establishment of infection. These findings led to the hypothesis that active immunization with vaccines able to induce virus-specific T-cell responses following the establishment of infection could also ameliorate the virological outcome. Here, we will review the relative effect of ART and vaccination during primary SIVmac infection of macaques. Published by Elsevier Science Ltd. C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Med Acad Bialystok, Dept Pediat 3, PL-15274 Bialystok, Poland. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. NR 117 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD DEC 19 PY 2002 VL 20 SU 4 BP A52 EP A60 AR PII S0264-410X(02)00388-2 DI 10.1016/S0264-410X(02)00388-2 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 631GR UT WOS:000180160200009 PM 12477429 ER PT J AU Ma, K Wang, K AF Ma, K Wang, K TI Interaction of nebulin SH3 domain with titin PEVK and myopalladin: implications for the signaling and assembly role of titin and nebulin SO FEBS LETTERS LA English DT Article DE circular dichroism; nuclear magnetic resonance; fluorescence; SH3 domain of nebulin; myopalladin; PEVK ID SKELETAL-MUSCLE; Z-LINE; THIN-FILAMENTS; TERMINAL SH3; PROTEIN; BINDING; SARCOMERE; SPECTROSCOPY; ARCHITECTURE; NEBULETTE AB Skeletal muscle nebulin is thought to determine thin filament length and regulate actomyosin interaction in a calcium/calmodulin or S100 sensitive manner. We have investigated the binding of nebulin SH3 with proline-rich peptides derived from the 28-mer PEVK modules of titin and the Z-line protein myopalladin, using fluorescence, circular dichroism and nuclear magnetic resonance techniques. Of the six peptides studied, PR2 of titin (VPEKKAPVAPPK) and myopalladin MyoP2 ((646)VKEPPPVLAKPK(657)) bind to nebulin SH3 with micromolar affinity (similar to31 and 3.4 muM, respectively), whereas the other four peptides bind weakly (> 100 muM). Sequence analysis of titins reveals numerous SH3 binding motifs that are highly enriched in the PEVK segments of titin isoforms. Our findings suggest that titin PEVK and myopalladin may play signaling roles in targeting and orientating nebulin to the Z-line during sarcomere assembly. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 NIAMSD, Muscle Proteom & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, K (reprint author), NIAMSD, Muscle Proteom & Nanotechnol Sect, Muscle Biol Lab, NIH, B50,Rm 1140, Bethesda, MD 20892 USA. NR 29 TC 46 Z9 51 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 18 PY 2002 VL 532 IS 3 BP 273 EP 278 AR PII S00145793(02)03655-4 DI 10.1016/S0014-5793(02)03655-4 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 626QP UT WOS:000179884800003 PM 12482578 ER PT J AU Jung, ID Lee, J Yun, SY Park, CG Choi, WS Lee, HW Choi, OH Han, JW Lee, HY AF Jung, ID Lee, J Yun, SY Park, CG Choi, WS Lee, HW Choi, OH Han, JW Lee, HY TI Cdc42 and Rac1 are necessary for autotaxin-induced tumor cell motility in A2058 melanoma cells SO FEBS LETTERS LA English DT Article DE autotaxin; Rac1; Cdc42; focal adhesion kinase ID FOCAL ADHESION KINASE; GTP-BINDING PROTEIN; ACTIN STRESS FIBERS; TYROSINE PHOSPHORYLATION; LYSOPHOSPHATIDIC ACID; STIMULATING PROTEIN; GROWTH-FACTORS; RHO; ACTIVATION; GTPASES AB Autotaxin (ATX) is a strong motogen that can increase invasiveness and angiogenesis. In the present study, we investigated the signal transduction mechanism of ATX-induced tumor cell motility. Unlike N19RhoA expressing cells, the cells expressing N17Cdc42 or N17Rac1 showed reduced motility against ATX. ATX activated Cdc42 and Rac1 and increased complex formation between these small G proteins and p21-activated kinase (PAK). Furthermore, ATX phosphorylated focal adhesion kinase (FAK) that was not shown in cells expressing dominant negative mutants of Cdc42 or Rac1. Collectively, these data strongly indicate that Cdc42 and Rac1 are essential for ATX-induced tumor cell motility in A2058 melanoma cells, and that PAK and FAK might be also involved in the process. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Konyang Univ, Coll Med, Nonsan 320711, South Korea. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. Meharry Med Coll, Dept Biochem, Nashville, TN 37208 USA. RP Lee, HY (reprint author), Konyang Univ, Coll Med, Nonsan 320711, South Korea. EM hoi@konyang.ac.kr NR 40 TC 27 Z9 28 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 18 PY 2002 VL 532 IS 3 BP 351 EP 356 AR PII S0014-5793(02)03698-0 DI 10.1016/S0014-5793(02)03698-0 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 626QP UT WOS:000179884800016 PM 12482591 ER PT J AU Le Gouill, C Innamorati, G Birnbaumer, M AF Le Gouill, C Innamorati, G Birnbaumer, M TI An expanded V2 receptor retention signal SO FEBS LETTERS LA English DT Article DE V2 receptor; phosphorylation; recycling; dephosphorylation; retention motif; arrestin ID PROTEIN-COUPLED RECEPTOR; VASOPRESSIN RECEPTOR; BETA-ARRESTIN; PHOSPHORYLATION; RESENSITIZATION; TRAFFICKING; DEPHOSPHORYLATION; SEQUESTRATION; ENDOCYTOSIS; MECHANISM AB Following ligand-promoted internalization the human type 2 vasopressin receptor (hV2R) is not recycled to the cell surface after removal of the agonist. A retention motif consisting of a serine triplet present in the cytoplasmic tail was previously found to require for retention, but serine 357, and threo-nines 359, 360 located upstream were not examined. Evidence is now presented that substitution of these amino acids did not change V2 internalization although it reduced the levels of arginine vasopressin (AVP)-induced phosphorylation as compared to the wild type (WT). Contrary to the WT hV2R, these mutant receptors were recycled to the cell surface after a 2 h incubation in the absence of AVP identifying these changed residues as additional members of the retention motif of the hV2R. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 Univ Calif Los Angeles, Sch Med, Dept Anesthesiol, Los Angeles, CA 90095 USA. RP Birnbaumer, M (reprint author), NIEHS, Bldg 101,Room F187A,MD F2-10,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. OI Innamorati, Giulio/0000-0003-0123-8777 FU NIDDK NIH HHS [R01 DK 41-244] NR 19 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 18 PY 2002 VL 532 IS 3 BP 363 EP 366 AR PII S0014-5793(02)03709-2 DI 10.1016/S0014-5793(02)03709-2 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 626QP UT WOS:000179884800018 PM 12482593 ER PT J AU Miller, FG AF Miller, FG TI Ethical significance of ethics-related empirical research SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CLINICAL RESEARCH C1 NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10 Rm 1C118, Bethesda, MD 20892 USA. NR 6 TC 13 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 18 PY 2002 VL 94 IS 24 BP 1821 EP 1822 PG 2 WC Oncology SC Oncology GA 625PQ UT WOS:000179825200001 PM 12488467 ER PT J AU Wong, M Pagano, JS Schiller, JT Tevethia, SS Raab-Traub, N Gruber, J AF Wong, M Pagano, JS Schiller, JT Tevethia, SS Raab-Traub, N Gruber, J TI New associations of human papillomavirus, simian virus 40, and Epstein-Barr virus with human cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID SQUAMOUS-CELL CARCINOMA; INVASIVE BREAST CANCERS; NONMELANOMA SKIN-CANCER; EPITHELIAL-CELLS; LATENT MEMBRANE-PROTEIN-1; GASTRIC-CARCINOMA; NECK CANCERS; TYPE-16 E6; IN-SITU; INFECTION C1 NCI, Biol Carcinogenesis Branch, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Penn State Univ, Dept Microbiol & Immunol, Hershey, PA USA. RP Wong, M (reprint author), NCI, Biol Carcinogenesis Branch, 6130 Execut Blvd,Suite 5000,Rm 5010, Bethesda, MD 20892 USA. NR 56 TC 45 Z9 45 U1 2 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 18 PY 2002 VL 94 IS 24 BP 1832 EP 1836 PG 5 WC Oncology SC Oncology GA 625PQ UT WOS:000179825200008 PM 12488476 ER PT J AU Hiatt, RA Klabunde, C Breen, N Swan, J Ballard-Barbash, R AF Hiatt, RA Klabunde, C Breen, N Swan, J Ballard-Barbash, R TI Cancer screening practices from National Health Interview Surveys: Past, present, and future SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID BREAST-CANCER; UNITED-STATES; COLORECTAL-CANCER; OLDER WOMEN; PREVENTIVE CARE; MAMMOGRAPHY USE; WHITE WOMEN; KNOWLEDGE; BEHAVIOR; BLACK AB The National Health Interview Survey (NHIS) has provided data about health behaviors at the national level since 1957. The 1987 and 1992 Cancer Control Supplements to the NHIS, along with other supplemental surveys administered intermittently on self-reported cancer-related behaviors, have contributed to important research and public health purposes. In this article, we reviewed 73 papers published between 1980 and 2001 that used NHIS data, including the first report from the 1998 NHIS, to examine what has been learned from past surveys. Our goal was to facilitate future analyses of recently released data on cancer screening practices from the Cancer Control Supplement to the 2000 NHIS, which is now known as the Cancer Control Module. We categorized the papers according to which of the following three study approaches they used: trends in screening rates, correlates of these rates with factors that may influence screening, and linkages or comparisons of NHIS data with other surveys or sources of information. We summarize knowledge gained in cancer screening for each of these three categories and identify areas that could benefit from more research. We highlight some of the new information available for the first time on the Cancer Control Module of the 2000 NHIS as fresh opportunities for cancer control research. Finally, we describe how the Cancer Control Supplements to the NHIS are integrated with the objectives of and developments in national cancer surveillance research that have emerged from federal planning efforts and collaborations with national partners in cancer surveillance in recent years. C1 NCI, NIH, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Hiatt, RA (reprint author), NCI, NIH, Div Canc Control & Populat Sci, EPN 6142,6130 Execut Blvd, Bethesda, MD 20892 USA. NR 77 TC 98 Z9 98 U1 4 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 18 PY 2002 VL 94 IS 24 BP 1837 EP 1846 PG 10 WC Oncology SC Oncology GA 625PQ UT WOS:000179825200009 PM 12488477 ER PT J AU Djousse, L Dorgan, JF Zhang, YQ Schatzkin, A Hood, M D'Agostino, RB Copenhafer, DL Kreger, BE Ellison, RC AF Djousse, L Dorgan, JF Zhang, YQ Schatzkin, A Hood, M D'Agostino, RB Copenhafer, DL Kreger, BE Ellison, RC TI Alcohol consumption and risk of lung cancer: The Framingham study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CIGARETTE-SMOKING; MORTALITY; COHORT; DRINKING; EXPERIENCE; BEVERAGE; TOBACCO; SMOKERS; MEN AB Background: Reports on the association between alcohol consumption and the risk of lung cancer have been inconsistent. The purpose of this study was to assess this association in a cohort study. Methods: This study included 4265 participants in the original population-based Framingham Study cohort and 4973 subjects in the offspring cohort. Alcohol consumption data were collected periodically for both cohorts. We used the risk sets method to match control subjects to each case patient based on age, sex, smoking variables, and year of birth. We used a conditional logistic regression model to estimate the relative risk of lung cancer according to alcohol consumption. Results: Alcohol consumption was generally light to moderate (i.e., <12 g/day) in both cohorts. During mean follow-ups of 32.8 years in the original and 16.2 years in the offspring cohorts, 269 cases of lung cancer occurred. In categories of total alcohol consumption of 0, 0.1-12, 12.1-24, and greater than 24 g/day, the crude incidence rates of lung cancer were 7.4, 13.6, 16.4, and 25.2 cases per 10 000 person-years, respectively, in the original cohort and 6.6, 4.3, 7.9, and 12.3 cases per 10 000 person-years, respectively, in the offspring cohort. However, after adjustment for age, sex, pack-years of smoking, smoking status, and year of birth in a multivariable conditional logistic regression model, relative risks for lung cancer from the lowest to the highest category of alcohol consumption were 1.0 (referent), 1.0 (95% confidence interval [CI] = 0.5 to 2.1), 1.0 (95% CI = 0.5 to 2.3), and 1.1 (95% CI = 0.5 to 2.3), respectively, in the original cohort and 1.0, 1.4 (95% CI = 0.5 to 3.6), 1.1 (95% CI = 0.3 to 3.6), and 2.0 (95% CI = 0.7 to 5.7), respectively, in the offspring cohort. Conclusion: Alcohol consumption among subjects in the Framingham Study, most of whom were light to moderate drinkers, was not statistically significantly associated with the risk of lung cancer. C1 Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Evans Dept Med, Boston, MA 02118 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. RP Djousse, L (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Rm B-612,715 Albany St, Boston, MA 02118 USA. RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 FU NHLBI NIH HHS [N01-HC-38038] NR 26 TC 25 Z9 26 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 18 PY 2002 VL 94 IS 24 BP 1877 EP 1882 PG 6 WC Oncology SC Oncology GA 625PQ UT WOS:000179825200013 PM 12488481 ER PT J AU Achanzar, WE Brambila, EM Diwan, BA Webber, MM Waalkes, MP AF Achanzar, WE Brambila, EM Diwan, BA Webber, MM Waalkes, MP TI Inorganic arsenite-induced malignant transformation of human prostate epithelial cells SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ANIMAL-MODEL; WELL WATER; MORTALITY; OVEREXPRESSION; CARCINOGENESIS; ASSOCIATION; EXPRESSION AB Although several epidemiologic studies show an association between arsenic exposure and prostate cancer, it is still unknown whether human prostate epithelial cells are directly susceptible to arsenic-induced transformation. This study was designed to determine whether the nontumorigenic human prostate epithelial cell line RWPE-1 could be malignantly transformed in vitro by arsenite. RWPE-1 cells were continuously exposed to 5 muM arsenite and monitored for signs of transformation, assessed as changes in matrix metalloproteinase-9 levels. After 29 weeks of exposure, the arsenite-exposed RWPE-1 cells (referred to as CAsE-PE) showed a marked increase in matrix metalloproteinase-9 secretion, a common finding in prostate malignancies. Malignant transformation was confirmed when CAsE-PE cells produced aggressive undifferentiated malignant epithelial tumors in nude mice. The tumors stained positive for human prostate-specific antigen, confirming their origin. These results are the firs; report of arsenite-induced malignant transformation of a human epithelial cell line and provide an important in vitro model for studying the mechanisms underlying arsenic-induced carcinogenesis in humans. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. NCI, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21701 USA. Michigan State Univ, Dept Med, E Lansing, MI 48824 USA. Michigan State Univ, Dept Zool, E Lansing, MI 48824 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, MD F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. FU NCI NIH HHS [N0-1-CO-12400] NR 24 TC 85 Z9 87 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 18 PY 2002 VL 94 IS 24 BP 1888 EP 1891 PG 4 WC Oncology SC Oncology GA 625PQ UT WOS:000179825200015 PM 12488483 ER PT J AU Albert, MR Ostheimer, KG Liewehr, DJ Steinberg, SM Breman, JG AF Albert, MR Ostheimer, KG Liewehr, DJ Steinberg, SM Breman, JG TI Smallpox manifestations and survival during the Boston epidemic of 1901 to 1903 SO ANNALS OF INTERNAL MEDICINE LA English DT Article AB Clinical records of 243 patients with smallpox consecutively admitted to the Southampton Street smallpox hospital in Boston, Massachusetts, during the 1901-1903 epidemic were reviewed. Smallpox was divided into five categories of varying severity; 47% of patients had varioloid, a relatively mild form of the disease usually occurring in previously vaccinated individuals with incomplete immunity. Survival information is available for 206 patients, of whom 36 (17.5%) died. Vaccination status, disease severity, and age were associated with survival, whereas sex, birthplace, and race were not. While full recovery often took weeks, most deaths occurred 7 to 14 days after the onset of symptoms, and all deaths occurred within 18 days of symptom onset. Smallpox was eradicated worldwide in 1977, but knowledge of the disease is essential because its cause, variola. virus, is considered a potential biological weapon. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Yale New Haven Med Ctr, New Haven, CT 06504 USA. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr,MSC 6705,Bldg 16,Room 214, Bethesda, MD 20892 USA. NR 21 TC 7 Z9 7 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 DEC 17 PY 2002 VL 137 IS 12 BP 993 EP 1000 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 626DR UT WOS:000179857500008 PM 12484715 ER PT J AU Grundy, SM Becker, D Clark, LT Cooper, RS Denke, MA Howard, WJ Hunninghake, DB Illingworth, R Luepker, RV McBride, P McKenney, JM Pasternak, RC Stone, NJ Van Horn, L Brewer, HB Cleeman, JI Ernst, ND Gordon, D Levy, D Rifkind, B Rossouw, JE Savage, P Haffner, SM Orloff, DG Proschan, MA Schwartz, JS Sempos, CT Shero, ST Murray, EZ Keller, SA Jehle, AJ AF Grundy, SM Becker, D Clark, LT Cooper, RS Denke, MA Howard, WJ Hunninghake, DB Illingworth, R Luepker, RV McBride, P McKenney, JM Pasternak, RC Stone, NJ Van Horn, L Brewer, HB Cleeman, JI Ernst, ND Gordon, D Levy, D Rifkind, B Rossouw, JE Savage, P Haffner, SM Orloff, DG Proschan, MA Schwartz, JS Sempos, CT Shero, ST Murray, EZ Keller, SA Jehle, AJ CA Natl Cholesterol Educ Program Expert TI Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Final Report SO CIRCULATION LA English DT Article ID CORONARY-HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; ACUTE MYOCARDIAL-INFARCTION; C-REACTIVE PROTEIN; COST-EFFECTIVENESS ANALYSIS; TRANS-FATTY-ACIDS; SCANDINAVIAN-SIMVASTATIN-SURVIVAL; FAMILIAL COMBINED HYPERLIPIDEMIA; HORMONE REPLACEMENT THERAPY C1 Amer Heart Assoc, Dallas, TX USA. Amer Pharmacists Assoc, Washington, DC USA. Natl Med Assoc, Silver Spring, MD USA. Amer Coll Cardio, Washington, DC USA. Amer Dietet Assoc, Chicago, IL USA. Natl Heart Lung & Blood Inst, Bethesda, MD USA. RP Grundy, SM (reprint author), Amer Heart Assoc, Dallas, TX USA. NR 1119 TC 451 Z9 551 U1 11 U2 39 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD DEC 17 PY 2002 VL 106 IS 25 BP 3143 EP 3421 PG 279 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 629JD UT WOS:000180045800014 PM 12485966 ER PT J AU Tapia, JA Bragado, MJ Garcia-Marin, LJ Jensen, RT AF Tapia, JA Bragado, MJ Garcia-Marin, LJ Jensen, RT TI Cholecystokinin-stimulated tyrosine phosphorylation of PKC-delta in pancreatic acinar cells is regulated bidirectionally by PKC activation SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE protein kinase C; pancreatic acinus; PKC inhibitor; phospholipase C; diacylglycerol ID PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; ACTIN CYTOSKELETON; RAT PANCREAS; IN-VITRO; CCK; ASSOCIATION; RECEPTORS; SRC; TRANSLOCATION AB PKC-delta is important in cell growth, apoptosis, and secretion. Recent studies show its stability is regulated by tyrosine phosphorylation (TYR-P), which can be stimulated by a number of agents. Many of these stimuli also activate phospholipase C (PLC) cascades and little is known about the relationship between these cascades and PKC-delta TYR-P. Cholecystokinin (CCK) stimulates PKCs but it is unknown if it causes PKC-delta TYR-P and if so, the relationship between these cascades is unknown. In rat pancreatic acini, CCK-8 stimulated rapid PKC-delta TYR-P by activation of the low affinity CCKA receptor state. TPA had a similar effect. BAPTA did not decrease CCK-stimulated PKC-delta TYR-P but instead, increased it. A23187 did not stimulate PKC-delta TYR-R Wortmannin and LY 294002 did not alter CCK-stimulated PKC-delta TYR-P. GF 109203X, at low concentrations, increased PKC-delta TYR-P stimulated by CCK or TPA and at higher concentrations, inhibited it. The cPKC inhibitors, Go 6976 and safingol, caused a similar increase in TPA- and CCK-stimulated PKC-delta TYR-P. These results demonstrate that CCKA receptor activation causes PKC-delta TYR-P through activation of only one of its two receptor affinity states. This PKC-delta TYR-P is not directly influenced by changes in [Ca2+](i); however, the resultant activation of PKC-alpha has an inhibitory effect. Therefore, CCK activates both stimulatory and inhibitory PKC cascades regulating PKC-delta TYR-P and, hence, likely plays an important role in regulating PKC-delta degradation and cellular abundance. Published by Elsevier Science B.V. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Extremadura, Dept Fisiol, Caceres 10071, Spain. Univ Extremadura, Dept Bioquim Biol Mol & Genet, Caceres 10071, Spain. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. RI Garcia-Marin, Luis /L-4680-2014; Tapia, Jose/C-5181-2008; Bragado, Maria/L-6988-2014 OI Garcia-Marin, Luis /0000-0002-1795-7381; Tapia, Jose/0000-0002-3614-6867; Bragado, Maria/0000-0001-7770-0775 NR 54 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD DEC 16 PY 2002 VL 1593 IS 1 BP 99 EP 113 AR PII S0167-4889(02)00346-4 DI 10.1016/S0167-4889(02)00346-4 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 630BL UT WOS:000180087600012 PM 12431789 ER PT J AU Zambito, AM Knipling, L Wolff, J AF Zambito, AM Knipling, L Wolff, J TI Charge variants of tubulin, tubulin S, membrane-bound and palmitoylated tubulin from brain and pheochromocytoma cells SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE alpha and beta tubulin; tubulin S; high resolution isoelectric focusing; isoelectric point ID IMMOBILIZED PH GRADIENTS; BETA-TUBULIN; ALPHA-TUBULIN; POSTTRANSLATIONAL MODIFICATION; BINDING-SITE; ISOFORMS; PURIFICATION; LOCALIZATION; ISOTYPES; KINESIN AB Isoelectric focusing (IEF) of only similar to 1 mug of rat brain tubulin yields 27-30 distinct charge variants in the pH range of 4.5-5.4 with band separations of 0.01-0.02 pH units as detected by silver staining. Variants can be efficiently transferred from the immobilized gradient strip to polyvinylidene difluoride (PVDF) membranes for reaction with monoclonal antibodies. C-terminal-directed antibodies to alpha- and beta-tubulin yield patterns similar to N-terminal-directed antibodies. Removal of the acidic C-termini with subtilisin to form tubulin S increases the pI values by similar to I pH unit, leads to a loss in the isoelectric distinction between the alpha- and beta-tubulin variants seen by N-terminal-directed antibodies, and abolishes reactions with all beta-variants and all but three alpha variants by C-terminal-directed antibodies (TU-04 and TU-14). Many, but not all, of the variants are substrates for autopalmitoylation of rat brain tubulin. The distribution of isoelectric variants differs between cytoplasm and membrane fractions from PC12 pheochromocytoma cells. A potential role for different variants is suggested. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wolff, J (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 2A23,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD DEC 16 PY 2002 VL 1601 IS 2 BP 200 EP 207 AR PII S1570-9639(02)00472-7 DI 10.1016/S1570-9639(02)00472-7 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 619MG UT WOS:000179479300011 PM 12445483 ER PT J AU Bres, V Tagami, H Peloponese, JM Loret, E Jeang, KT Nakatani, Y Emiliani, S Benkirane, M Kiernan, RE AF Bres, V Tagami, H Peloponese, JM Loret, E Jeang, KT Nakatani, Y Emiliani, S Benkirane, M Kiernan, RE TI Differential acetylation of Tat coordinates its interaction with the co-activators cyclin T1 and PCAF SO EMBO JOURNAL LA English DT Article DE cyclin T1; differential acetylation; HIV-1; PCAF; Tat ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA-POLYMERASE-II; HISTONE ACETYLTRANSFERASE ACTIVITY; TRANSCRIPTIONAL COACTIVATORS P300; PROTEINS SPECIFICALLY ASSOCIATE; CARBOXYL-TERMINAL DOMAIN; CREB-BINDING-PROTEIN; HIV-1 TAT; P-TEFB; IN-VITRO AB The HIV-1 transactivator protein, Tat, is an atypical transcriptional activator that functions through binding, not to DNA, but to a short leader RNA, TAR. Although details of its functional mechanism are still unknown, emerging findings suggest that Tat serves primarily to adapt co-activator complexes such as p300, PCAF and P-TEFb to the HIV-1 long terminal repeat. Hence, an understanding of how Tat interacts with these cofactors is crucial. It has recently been shown that acetylation at a single lysine, residue 50, regulated the association of Tat with PCAF. Here, we report that in the absence of Tat acetylation, PCAF binds to amino acids 20-40 within Tat. Interestingly, acetylation of Tat at Lys28 abrogates Tat-PCAF interaction. Acetylation at Lys50 creates a new site for binding to PCAF and dictates the formation of a ternary complex of Tat-PCAF-P-TEFb. Thus, differential lysine acetylation of Tat coordinates the interactions with its co-activators, cyclin T1 and PCAF. Our results may help in understanding the ordered recruitment of Tat co-activators to the HIV-1 promoter. C1 CNRS, UPR 1142, Inst Genet Humaine, Lab Virol Mol & Transfert Gene, Montpellier, France. CNRS, UPR 9027, Inst Biol Struct & Microbiol, Lab Ingn Syst Macromol, Marseille, France. Inst Cochin, Dept Malad Infect, Paris, France. NIAID, Mol Virol Lab, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Res Ctr, Boston, MA USA. RP Kiernan, RE (reprint author), CNRS, UPR 1142, Inst Genet Humaine, Lab Virol Mol & Transfert Gene, Montpellier, France. RI Jeang, Kuan-Teh/A-2424-2008 NR 54 TC 69 Z9 72 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 16 PY 2002 VL 21 IS 24 BP 6811 EP 6819 DI 10.1093/emboj/cdf669 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 627TJ UT WOS:000179952000019 PM 12486002 ER PT J AU Greenwell, TN Zangen, A Martin-Schild, S Wise, RA Zadina, JE AF Greenwell, TN Zangen, A Martin-Schild, S Wise, RA Zadina, JE TI Endomorphin-1 and-2 immunoreactive cells in the hypothalamus are labeled by fluoro-gold injections to the ventral tegmental area SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE opioid; reward; reinforcement; immunocytochemistry ID ENDOGENOUS OPIOID SYSTEMS; BRAIN-STIMULATION REWARD; MEDIAL FOREBRAIN-BUNDLE; MU-OPIATE RECEPTOR; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA; SPINAL-CORD; RAT-BRAIN; IMMUNOHISTOCHEMICAL LOCALIZATION; AUTORADIOGRAPHIC LOCALIZATION AB Endomorphin-1 and -2 (EM1, EM2) are endogenous opioids with high affinity and selectivity for the mu-opioid receptor. Cells expressing EM-like immunoreactivity (EM-LI) are present in the hypothalamus, and fibers containing EM-LI project to many brain regions, including the ventral tegmental area (VTA). The VTA is one of the most sensitive brain regions for the rewarding and locomotor effects of opioids. It contains mu-opioid receptors, which are thought to mediate gamma-aminobutyric acid-dependent disinhibition of dopamine transmission to the nucleus accumbens. We investigated whether hypothalamic EM-LI cells project to the VTA, where they could play a natural role in this circuitry. The retrograde tracer Fluoro-Gold (FG) was microinjected into the anterior or posterior VTA in rats. Nine days later, colchicine was injected, and 24 hours later, the animals were perfused and processed for fluorescence immunocytochemistry. Numerous FG-labeled cells were detected in the hypothalamus. Both EM1-LI and EM2-LI cells were present in the periventricular nucleus, between the dorsomedial and ventromedial hypothalamus and between the ventromedial and arcuate nuclei. Subpopulations of EM1-LI and EM2-LI cells were labeled by FG. Injections of FG to the anterior and posterior VTA were both effective in producing double-labeled cells, and an anterior-posterior topographical organization between the VTA and hypothalamus was observed. The results support the idea that some endomorphin-containing neurons in the hypothalamus project to the VTA, where they may modulate reward and locomotor circuitry. C1 Vet Affairs Med Ctr, New Orleans, LA 70112 USA. Tulane Univ, Sch Med, Program Neurosci, New Orleans, LA 70112 USA. NIDA, NIH, Baltimore, MD 21224 USA. Tulane Univ, Sch Med, Dept Med, New Orleans, LA 70112 USA. RP Zadina, JE (reprint author), Vet Affairs Med Ctr, 1601 Perdido St, New Orleans, LA 70112 USA. RI Wise, Roy/A-6465-2012; OI Greenwell, Thomas/0000-0001-6069-0064 FU NIDA NIH HHS [DA06040, DA011655] NR 72 TC 14 Z9 14 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD DEC 16 PY 2002 VL 454 IS 3 BP 320 EP 328 DI 10.1002/cne.10464 PG 9 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 620XL UT WOS:000179558800010 PM 12442322 ER PT J AU Parker, MW Chen, Y Hallenbeck, JM Ford, BD AF Parker, MW Chen, Y Hallenbeck, JM Ford, BD TI Neuregulin expression after focal stroke in the rat SO NEUROSCIENCE LETTERS LA English DT Article DE stroke; glial growth factor; heregulin; acetylcholine receptor inducing activity; focal cerebral ischemia ID NERVOUS-SYSTEM; BRAIN; CELLS; RECEPTOR; ISOFORMS; ISCHEMIA; INJURY; DEATH; ARIA AB Upregulation of neuregulin has been demonstrated in traumatic brain injury, but a role for neuregulin in ischemic brain injury has not been investigated. Therefore, we used a rat permanent middle cerebral artery occlusion model to examine the distribution of neuregulin after the onset of ischemic stroke. We found an increase in immunohistochemical staining for neuregulin in the penumbral regions of the cortex. The increase in neuregulin appeared to be neuronal. There was no neuregulin co-localization with astrocytes or macrophages. These results demonstrate that neuregulin is induced in neurons following ischemic stroke and may be involved in neuroprotection and repair. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 Morehouse Sch Med, Inst Neurosci, Dept Anat & Neurobiol, Atlanta, GA 30310 USA. Johns Hopkins Sch Med, Baltimore, MD USA. NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA. RP Ford, BD (reprint author), Morehouse Sch Med, Inst Neurosci, Dept Anat & Neurobiol, 720 Westview Dr,Sw,MRC 223, Atlanta, GA 30310 USA. FU NINDS NIH HHS [NS34194] NR 18 TC 21 Z9 23 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 DEC 16 PY 2002 VL 334 IS 3 BP 169 EP 172 AR PII S0304-3940(02)01126-6 DI 10.1016/S0304-3940(02)01126-6 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 624MK UT WOS:000179763300007 PM 12453622 ER PT J AU Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Corey, D Levy, D AF Singh, JP Larson, MG O'Donnell, CJ Tsuji, H Corey, D Levy, D TI Genome scan linkage results for heart rate variability (The Framingham Heart Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article AB There is a substantial heritable component to the beat-to-beat variation in heart rate. However, the molecular mechanisms underlying the control of heart rate variability (HRV) remain unknown. The present study sought to identify chromosomal regions linked to HRV phenotypes. The first 2 hours of ambulatory electrocardiographic recordings obtained from Framingham Heart Study subjects attending a routine examination were processed for HRV. HRV variables analyzed included very-low-frequency power, low-frequency power, and high-frequency power. Gender-specific residuals were used for log-transformed HRV data after adjustment for age, HR, systolic and diastolic blood pressures, and coffee and alcohol consumption. In conjunction with a 16-cM genome-wide scan, HRV data were available for 725 subjects in 230 extended families, including 390 sibling pairs. Variance component log-of-the-odds (LOD) scores were obtained. The highest multipoint LOD score's were obtained for log very-low frequency on chromosome 15 at 62 cM (LOD 1.84) and for log low frequency on chromosome 2 at 153 cM (LOD 1.81). These data suggest there may be influential genetic regions contributing to HRV. Further studies are warranted to identify genes in these regions that may influence autonomic tone. Recognition of the genetic determinants of HRV may provide additional insights into the pathophysiology of the autonomic nervous system and offer clues to its modulation. (C) 2002 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Div Epidemiol & Prevent Med, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Clin Epidemiol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayne Ave,Suite 2, Framingham, MA 01702 USA. FU NHLBI NIH HHS [N01-HC-38038] NR 23 TC 27 Z9 27 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 15 PY 2002 VL 90 IS 12 BP 1290 EP 1293 AR PII S0002-9149(02)02865-5 DI 10.1016/S0002-9149(02)02865-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 628PD UT WOS:000180004000003 PM 12480036 ER PT J AU Merz, CNB Olson, MB Johnson, BD Bittner, V Hodgson, TK Berga, SL Braunstein, GD Pepine, CJ Reis, SE Sopko, G Kelsey, SF AF Merz, CNB Olson, MB Johnson, BD Bittner, V Hodgson, TK Berga, SL Braunstein, GD Pepine, CJ Reis, SE Sopko, G Kelsey, SF TI Cholesterol-lowering medication, cholesterol level, and reproductive hormones in women: The Women's Ischemia Syndrome Evaluation (WISE) SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID FUNCTIONAL-CAPACITY; CLINICAL-TRIALS; SIMVASTATIN; PLASMA AB PURPOSE: Reproductive hormones such as estrogen, progesterone, and testosterone are synthesized from a common cholesterol precursor pathway. We hypothesized that use of statins and the resultant lower blood lipoprotein levels would be associated with lower reproductive hormone levels in women. We also sought to evaluate this association, independent of statin use, particularly among premenopausal women of childbearing age. METHODS: We enrolled 453 (114 pre-, 30 peri-, and 309 postmenopausal) women with coronary risk factors.(mean [+/- SD age, 58 +/- 13 years) who were undergoing coronary angiography for suspected ischemia at four academic medical centers. Blood lipoprotein levels (total cholesterol, triglycerides, low-density lipoprotein [LDL] cholesterol, high-density lipoprotein cholesterol) and serum reproductive hormone levels (estradiol, bioavailable estradiol, estrone, progesterone) were measured. RESULTS: Use of statins was associated with lower lipoprotein levels, but not lower reproductive hormone levels, in all women. Mean estradiol levels were not significantly lower among premenopausal women with very low LDL cholesterol levels compared with women with higher LDL cholesterol levels (estradiol: 71 +/- 52 pg/mL vs. 88 +/- 67 pg/mL, P = 0.32). CONCLUSION: Among women undergoing coronary angiography for suspected myocardial ischemia, the use of statins, or lower cholesterol levels, are not associated with significantly lower levels of reproductive hormones. C1 Univ Pittsburgh, WISE Coordinating Ctr, Dept Epidemiol, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Med Ctr, Dept Cardiol, Pittsburgh, PA USA. Univ Florida, Div Cardiovasc Med, Gainesville, FL USA. Univ Pittsburgh, Sch Med, Div Reprod Endocrinol, Pittsburgh, PA USA. Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. Cedars Sinai Med Ctr, Cedars Sinai Res Inst, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. RP Merz, CNB (reprint author), Univ Pittsburgh, WISE Coordinating Ctr, Dept Epidemiol, Grad Sch Publ Hlth, 127 Parran Hall,130 DeSoto St, Pittsburgh, PA 15261 USA. RI Reis, Steven/J-3957-2014 NR 19 TC 12 Z9 12 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2002 VL 113 IS 9 BP 723 EP 727 AR PII S0002-9343(02)01366-9 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 632MU UT WOS:000180227700003 ER PT J AU Zhang, YQ Kiel, DP Ellison, RC Schatzkin, A Dorgan, JF Kreger, BE Cupples, LA Felson, DT AF Zhang, YQ Kiel, DP Ellison, RC Schatzkin, A Dorgan, JF Kreger, BE Cupples, LA Felson, DT TI Bone mass and the risk of prostate cancer: The Framingham Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article ID GROWTH-FACTOR-I; VITAMIN-D; IGF-I; UNITED-STATES; ELDERLY MEN; DENSITY; OSTEOPOROSIS; CALCIUM; WOMEN; TESTOSTERONE AB PURPOSE: To examine the relation of bone mass-a potential biologic marker for cumulative exposure to androgens, insulin-like growth factors, and calcium intake-to subsequent development of prostate cancer. METHODS: We used radiogrammetry to measure the second metacarpal cortical area of 1012 white men with no history of prostate cancer who had undergone posteroanterior hand radiography between 1967 and 1970. Participants were followed until the end of 1999. All incident cases of prostate cancer were confirmed histologically. We examined bone mass in relation to the risk of prostate cancer using a Cox proportional hazards model. RESULTS: During follow-up, 106 men developed prostate cancer. Incidence rates per 1000 person-years were 3.8 among men in the lowest quartile of bone mass, 4.8 in the second quartile, 7.4 in the third quartile, and 6.5 in the highest quartile. Compared with men in the lowest quartile of bone mass, the multivariate-adjusted rate ratio was 1.3 (95% confidence interval [Cl]: 0.7 to 2.5) for those in the second quartile, 1.9 (95% CI: 1.0 to 3.4) in the third quartile, and 1.6 (95% Cl: 0.9 to 3.0) in the highest quartile (P for trend = 0.06). CONCLUSION: Men with high bone mass may be at an increased risk of prostate cancer. Although the biological mechanisms underlying this relation are not understood; cumulative exposure to high levels of androgen, insulin-like growth factor 1, or calcium intake may be involved. C1 Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA USA. NCI, Div Canc Prevent & Control, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Zhang, YQ (reprint author), Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, 715 Albany St,Room B-612, Boston, MA 02118 USA. OI Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01-HC-38-38]; NIAMS NIH HHS [AR 47785, AR/AG 41398] NR 40 TC 18 Z9 19 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD DEC 15 PY 2002 VL 113 IS 9 BP 734 EP 739 AR PII S0002-9343(02)01382-7 DI 10.1016/S0002-9343(02)01382-7 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 632MU UT WOS:000180227700005 PM 12517363 ER PT J AU Geraci, M Anderson, TS Slate-Cothren, S Post, RM McCann, UD AF Geraci, M Anderson, TS Slate-Cothren, S Post, RM McCann, UD TI Pentagastrin-induced sleep panic attacks: Panic in the absence of elevated baseline arousal SO BIOLOGICAL PSYCHIATRY LA English DT Article DE sleep panic; expectancy bias; pharmacological challenge; pentagastrin; social phobia; arousal ID DISORDER PATIENTS; HEALTHY-SUBJECTS; CHOLECYSTOKININ-TETRAPEPTIDE; ENHANCED SENSITIVITY; LACTATE INFUSIONS; CLINICAL FINDINGS; ANXIETY; DEPRIVATION; YOHIMBINE; CAFFEINE AB Background: It has been suggested that pharmacological challenges that induce panic attacks are confounded by effects of environmental stress, elevated baseline arousal, and expectancy bias. Methods: To control for effects of arousal and cognition on the panicogenic effects of pentagastrin, pharmacological challenges were conducted during sleep in seven patients with panic disorder or social phobia. All patients had previously experienced pentagastrin-induced panic while awake. Infusions of normal saline and pentagastrin (0.6 mug/kg) were administered in fixed order and timed so that pentagastrin infusions took place during the transition from Stage 2 to Stage 3 sleep. Long intravenous lines were placed for remote blood sampling and subsequent analysis of plasma adrenocorticotropic hormone and cortisol. Measures of anxiety and panic were obtained at baseline and upon awakening after pharmacological challenge. Results: All seven subjects awoke within seconds following pentagastrin infusion. Four patients reported symptoms that met criteria for panic. Neither baseline anxiety nor neuroendocrine measures were predictive of panic. Conclusions: These data demonstrate the ability to induce panic during a period of diminishing arousal and indicate that panic attacks can occur in the absence of elevated arousal and environmental stress. (C) 2002 Society of Biological Psychiatry. C1 NIH, Ctr Clin, Dept Nursing, Bethesda, MD 20892 USA. Temple Univ, Dept Criminal Justice, Philadelphia, PA 19122 USA. Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21224 USA. RP McCann, UD (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 5510 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 38 TC 11 Z9 11 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD DEC 15 PY 2002 VL 52 IS 12 BP 1183 EP 1189 AR PII S0006-3223(02)01402-6 DI 10.1016/S0006-3223(02)01402-6 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 634QW UT WOS:000180352800008 PM 12488064 ER PT J AU Oliveira, SHP Taub, DD Nagel, J Smith, R Hogaboam, CM Berlin, A Lukacs, NW AF Oliveira, SHP Taub, DD Nagel, J Smith, R Hogaboam, CM Berlin, A Lukacs, NW TI Stem cell, factor induces eosinophil activation and degranulation: mediator release and gene array analysis SO BLOOD LA English DT Article ID MACROPHAGE-DERIVED CHEMOKINE; INDUCED AIRWAY HYPERREACTIVITY; C-KIT RECEPTOR; MAST-CELLS; IN-VIVO; DNA-SYNTHESIS; MURINE MODEL; INFLAMMATION; FIBROBLASTS; LIGAND AB Eosinophils are effector cells that play an important role in the damage induced by the allergic process by releasing inflammatory mediators and proteolytic factors after activation. Stem cell factor (SCF) is a primary cytokine involved in hematopoiesis and mast cell differentiation, proliferation, and activation. Studies have also indicated that SCF is directly involved in pathogenesis of allergic airway inflammation. In the present study, we examined the ability of SCF to activate murine eosinophils for increased mediator release and up-regulation of chemokines. Initial data demonstrated that eosinophils have significant levels of surface c-kit protein, SCF receptor. SCF-activated eosinophils degranulate and release eosinophil peroxidase and leukotriene C-4 in a dose-dependent manner. In addition, SCF was further shown to induce the release of CC chemokines, RANTES, macrophage-derived chemokine (MDC), macrophage inflammatory protein-1beta (MIP-1beta), and C10 from eosinophils. To identify the extent of SCF-induced activation of eosinophils, we also performed gene array analysis using an array containing 1153 genes related to inflammation, including cytokines and their receptors, growth factors, structural and cytoskeletal genes, signal transduction genes as well as several other classes related to immune/inflammatory responses. The gene analysis indicated that more than 150 genes were significantly up-regulated in eosinophils after SCF stimulation. The gene array results were verified using a quantitative real-time polymerase chain reaction analysis to identify the expression of several chemokine and chemokine receptor genes. Altogether, these studies indicate that SCF is a potent eosinophil degranulator tor and activator that may play a number of roles during an inflammatory/immune response. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. NIA, Dept Immunol, Baltimore, MD 21224 USA. RP Lukacs, NW (reprint author), Univ Michigan, Sch Med, Dept Pathol, 1301 Catherine St, Ann Arbor, MI 48109 USA. RI Oliveira, Sandra/F-6908-2014; hogaboam, cory /M-3578-2014 FU NHLBI NIH HHS [HL31963, HL59178]; NIAID NIH HHS [AI36302] NR 53 TC 50 Z9 51 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4291 EP 4297 DI 10.1182/blood.V100.13.4291 PG 7 WC Hematology SC Hematology GA 624KX UT WOS:000179759800010 PM 12453875 ER PT J AU Taylor, JG Tang, DC Savage, SA Leitman, SF Heller, SI Serjeant, GR Rodgers, GP Chanock, SJ AF Taylor, JG Tang, DC Savage, SA Leitman, SF Heller, SI Serjeant, GR Rodgers, GP Chanock, SJ TI Variants in the VCAM1 gene and risk for symptomatic stroke in sickle cell disease SO BLOOD LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; COLONY-STIMULATING FACTOR; ADHESION MOLECULE-1; LINKAGE DISEQUILIBRIUM; ENDOTHELIAL-CELLS; DNA POLYMORPHISM; ISCHEMIC STROKE; SUSCEPTIBILITY; CHILDREN; CRISIS AB Stroke is a major cause of morbidity and mortality in sickle cell (SS) disease. Genetic risk factors have been postulated to contribute to this clinical outcome. The human genome project hats substantially increased the catalog of variations in genes, many of which could modify the risk for manifestations of disease outcome in a monogenic disease, namely SS. VCAM1 is a cell adhesion molecule postulated to play a critical role in the pathogenesis of SS disease. We identified a total of 33 single nucleotide polymorphisms (SNPs) by sequencing the entire coding region, 2134 bp upstream of the 5' end of the published cDNA, 217 bp downstream of the 3' end of the cDNA, and selected intronic regions of the VCAM1 locus. Allelic frequencies for selected SNPs were determined in a healthy population. We subsequently analyzed 4 nonsynonymous coding, 2 synonymous coding, and 4 common promoter SNPs in a genetic association study of clinically apparent stroke in SS disease conducted in a cohort derived from a single institution in Jamaica (51 symptomatic cases and 51 matched controls). Of the 10 candidate SNPs analyzed in this pilot study, the variant allele of the nonsynonymous SNP, VCAM1 G1238C, may be associated with protection from stroke (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15-0.83, P=.04). Further study is required to confirm the importance of this variant in VCAM1 as a clinically useful modifier of outcome in SS disease. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, Gaithersburg, MD 20877 USA. NIDDK, Mol & Clin Hematol Branch, Bethesda, MD USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ W Indies, MRC Labs, Kingston 7, Jamaica. RP Chanock, SJ (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, 8717 Grovemont Cir, Gaithersburg, MD 20877 USA. RI Savage, Sharon/B-9747-2015; OI Savage, Sharon/0000-0001-6006-0740; Taylor, James/0000-0002-4421-1809 NR 55 TC 59 Z9 61 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4303 EP 4309 DI 10.1182/blood-2001-12-0306 PG 7 WC Hematology SC Hematology GA 624KX UT WOS:000179759800012 PM 12393616 ER PT J AU Byrd, JC Mrozek, K Dodge, RK Carroll, AJ Edwards, CG Arthur, DC Pettenati, MJ Patil, SR Rao, KW Watson, MS Koduru, PRK Moore, JO Stone, RM Mayer, RJ Feldman, EJ Davey, FR Schiffer, CA Larson, RA Bloomfield, CD AF Byrd, JC Mrozek, K Dodge, RK Carroll, AJ Edwards, CG Arthur, DC Pettenati, MJ Patil, SR Rao, KW Watson, MS Koduru, PRK Moore, JO Stone, RM Mayer, RJ Feldman, EJ Davey, FR Schiffer, CA Larson, RA Bloomfield, CD TI Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461) SO BLOOD LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the American-Society-of-Hematology CY DEC 07-11, 2001 CL ORLANDO, FLORIDA SP Amer Soc Hematol ID ACUTE PROMYELOCYTIC LEUKEMIA; INTENSIVE POSTREMISSION CHEMOTHERAPY; ACUTE NONLYMPHOCYTIC LEUKEMIA; INTERNAL TANDEM DUPLICATION; ACUTE MYELOGENOUS LEUKEMIA; COLONY-STIMULATING FACTOR; HIGH-DOSE CYTARABINE; TRANS-RETINOIC ACID; POOR-PROGNOSIS; CLINICAL-SIGNIFICANCE AB We analyzed prospectively 1213 adults with de novo acute myeloid leukemia (AML) to ascertain the prognostic impact of cytogenetic abnormalities on complete remission (CR) rate, 5-year cumulative incidence of relapse (CIR), and 5-year overall survival (OS). All patients received similar induction therapy. Median follow-up for surviving patients was 8.3 years. Nonprioritized cytogenetics distinguished t(8;21) and inv(16)/t(16;16) as conferring a significantly better prognosis than normal karyotype. Prognostic impact of many abnormalities could not be determined independently because of their association with complex karyotype. Neither complex karyotype nor secondary aberrations affected outcome of patients with t(8;21), inv(16)/t(16;16), or t(9;11). Among other patients, those with complex karyotypes had significantly worse outcomes than cytogenetically normal patients. Based on outcome for specific cytogenetic abnormalities and karyotype complexity, patients were divided into 3 risk groups: favorable (CR 88%, CIR 54%, OS 55%), intermediate (CR 67%, CIR 67%, OS 24%), and adverse (CR 32%, CIR 92%, OS 5%). Multivariate analyses confirmed the major contribution of cytogenetics to the probability of attaining CR, CIR, and OS. For the adverse-risk group, the probability of achieving CR was 4.0 and 11.9 times lower, the probability of relapse 3.0 and 4.4 times higher, and the risk of death 2711 and 4.3 times higher than those for the intermediate and favorable groups, respectively. We conclude that although the prognostic impact of many recurring abnormalities has not been ascertained independently of complex karyotype, cytogenetics is among the most useful factors predicting attainment of CR, CIR, and long-term survival in adult AML. C1 Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. CALGB Stat Ctr, Durham, NC USA. Univ Alabama, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. Wake Forest Univ, Med Ctr, Winston Salem, NC USA. Univ Iowa, Iowa City, IA USA. Univ N Carolina, Chapel Hill, NC USA. Washington Univ, St Louis, MO USA. N Shore Univ Hosp, Manhasset, NY USA. Duke Univ, Med Ctr, Durham, NC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cornell Univ, Weill Med Coll, New York, NY USA. SUNY Upstate Med Univ, Syracuse, NY USA. Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA. Univ Chicago, Chicago, IL 60637 USA. RP Byrd, JC (reprint author), Ohio State Univ, Div Hematol & Oncol, B302A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA31946, CA 77658, CA16058] NR 59 TC 939 Z9 1007 U1 1 U2 11 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4325 EP 4336 DI 10.1182/blood-2002-03-0772 PG 12 WC Hematology SC Hematology GA 624KX UT WOS:000179759800015 PM 12393746 ER PT J AU Roesler, J Brenner, S Bukovsky, AA Whiting-Theobald, N Dull, T Kelly, M Civin, CI Malech, HL AF Roesler, J Brenner, S Bukovsky, AA Whiting-Theobald, N Dull, T Kelly, M Civin, CI Malech, HL TI Third-generation, self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34(+) cells from patients with X-linked chronic granulomatous disease SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; HUMAN-IMMUNODEFICIENCY-VIRUS; MEDIATED GENE-TRANSFER; LONG-TERM ENGRAFTMENT; MURINE LEUKEMIA-VIRUS; BONE-MARROW CELLS; CORD-BLOOD; LENTIVIRAL VECTORS; IN-VIVO; TRANSGENE EXPRESSION AB HIV-1-derived lentivectors are promising for gene transfer into hematopoietic stem cells but require preclinical in vivo evaluation relevant to specific human diseases. Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice accept human hematopoietic stem cell graft, providing a unique opportunity for in vivo evaluation of therapies targeting human hematopoietic diseases. We demonstrate for the first time that hematopoietic stem cells from patients with X-linked chronic granulomatous disease (X-CGD) give rise to X-CGD-phenotype neutrophils in the NOD/SCID model that can be corrected using VSV-G-pseudotyped, 3rd-generation, self-inactivating (SIN) lentivector encoding gp91(phox). We transduced X-CGD patient-mobilized CD34(+) peripheral blood stem cells (CD34(+)PBSCs) with lentivector-gp91(phox) or amphotropic oncoretrovirus MFGS-gp91(phox) and evaluated correction ex vivo and in vivo in NOD/SCID mice. Only lentivector transduced CD34(+)PBSCs under ex vivo conditions nonpermissive for cell division, but both vectors performed best under conditions permissive for proliferation (multiple growth factors). Under the latter conditions, lentivector and MFGS achieved significant ex vivo correction of X-CGD CD34(+)PBSCs (18% and 54% of cells expressing gp91(phox), associated with 53% and 163% of normal superoxide production, respectively). However, lentivector, but not MFGS, achieved significant correction of human X-CGD neutrophils arising in vivo in NOD/SCID mice that underwent transplantation (20% and 2.4%, respectively). Thus, 3rd-generation SIN lentivector-gp91(phox) performs well as assessed in human X-CGD neutrophils differentiating in vivo, and our studies suggest that the NOD/SCID model is generally applicable for in vivo study of therapies evaluated in human blood cells expressing a specific disease phenotype. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Cell Genesys, Foster City, CA USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Malech, HL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Rm 11N113,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013; OI Malech, Harry/0000-0001-5874-5775 FU NCI NIH HHS [P01 CA70970] NR 56 TC 42 Z9 44 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 15 PY 2002 VL 100 IS 13 BP 4381 EP 4390 DI 10.1182/blood-2001-12-0165 PG 10 WC Hematology SC Hematology GA 624KX UT WOS:000179759800022 PM 12393624 ER PT J AU Sloand, EM Kim, S Fuhrer, M Risitano, AM Nakamura, R Maciejewski, JP Barrett, AJ Young, NS AF Sloand, EM Kim, S Fuhrer, M Risitano, AM Nakamura, R Maciejewski, JP Barrett, AJ Young, NS TI Fas-mediated apoptosis is important in regulating cell replication and death in trisomy 8 hematopoietic cells but not in cells with other cytogenetic abnormalities SO BLOOD LA English DT Article ID SEVERE APLASTIC-ANEMIA; MYELODYSPLASTIC SYNDROMES; LEUKEMIA AB Increased apoptosis of hematopoietic progenitor cells has been implicated in the pathophysiology of cytopenias associated with myelodysplastic syndromes (MDSs), and inhibition by immunosuppression may account for the success of this treatment in some patients. We examined bone marrow and peripheral blood of 25 patients with chromosomal abnormalities associated with MDS (monosomy 7, trisomy 8, and 5q-) for evidence of apoptosis. When fresh bone marrow was examined, the number of apoptotic and Fas-expressing CD34 cells was increased in patients with trisomy 8, but decreased in monosomy 7, as compared with healthy control donor marrow. Fas expression was increased in the trisomy 8 cells and decreased in the monosomy 7 cells when compared with normal cells from the same patient. Trisomy 8 cells were more likely to express activated caspase-3 than were normal cells. For bone marrow cells cultured with Fas agonist or Fas antagonist, the percentage of cells with trisomy 8 was significantly decreased in most cases after Fas receptor triggering and increased by Fas ligand (Fas-L) antagonist (P < 0.01), suggesting increased Fas susceptibility of cells with trisomy 8. No such changes were seen in cultures of cells with 5q- or monosomy 7. Fas antagonist facilitated the expansion of cells with trisomy 8 only. Cells with trisomy 8 appear to be more susceptible to Fas-mediated apoptosis. Clinical data demonstrating the responsiveness of some patients with trisomy 8 to anti-thymocyte globulin (ATG) and cyclosporine (CsA) would favor an active role of the immune system in this syndrome. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Sloand, EM (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103, Bethesda, MD 20892 USA. NR 21 TC 55 Z9 60 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 DEC 15 PY 2002 VL 100 IS 13 BP 4427 EP 4432 DI 10.1182/blood-2002-01-0096 PG 6 WC Hematology SC Hematology GA 624KX UT WOS:000179759800027 PM 12393649 ER PT J AU Chute, JP Saini, AA Chute, DJ Wells, MR Clark, WB Harlan, DM Park, J Stull, MK Civin, C Davis, TA AF Chute, JP Saini, AA Chute, DJ Wells, MR Clark, WB Harlan, DM Park, J Stull, MK Civin, C Davis, TA TI Ex vivo culture with human brain endothelial cells increases the SCID-repopulating capacity of adult human bone marrow SO BLOOD LA English DT Article ID HUMAN HEMATOPOIETIC-CELLS; CORD BLOOD-CELLS; MOBILIZED PERIPHERAL-BLOOD; IMMUNE-DEFICIENT MICE; STEM-CELLS; PROGENITOR CELLS; IN-VITRO; CD34(+) CELLS; IMMUNODEFICIENT MICE; NOD/SCID MICE AB Adult human bone marrow (ABM) is an important source of hematopoietic stem cells for transplantation in the treatment of malignant and nonmalignant diseases. However, in contrast to the recent progress that has been achieved with umbilical cord blood, methods to expand ABM stem cells for therapeutic applications have been disappointing. In this study, we describe a novel culture method that uses human brain endothelial cells (HUBECs) and that supports the quantitative expansion of the most primitive measurable cell within the adult bone marrow compartment, the nonobese diabetic/severe combined immunodeficient. (NOD/SCID) repopulating cell (SRC). Coculture of human ABM CD34(+) cells with brain endothelial cells for 7 days supported a 5.4-fold increase in CD34(+) cells, induced more than 95% of the CD34(+)/CD38(-) subset to enter cell division, and produced progeny that engrafted NOD/SCID mice at significantly higher rates than fresh ABM CD34(+) cells. Using a limiting dilution analysis, we found the frequency of SRCs within fresh ABM CD34(+) cells to be 1 in 9.9 x 10(5) cells. Following HUBEC culture, the estimated frequency of SRCs increased to 1 in 2.4 x 10(5) cells. All mice that received transplants of HUBEC-cultured cells showed B-lymphoid and myeloid differentiation, indicating that a primitive hematopoietic cell was preserved during culture. Noncontact HUBEC cultures also maintained SRCs at a level comparable to contact HUBEC cultures, suggesting that cell-to-cell contact was not required. These data demonstrate that human brain endothelial cells possess a unique hematopoietic activity that increases the repopulating capacity of adult human bone marrow. C1 Large Scale Biol Corp, Vacaville, CA 95688 USA. NIDDKD, Stem Cell Biol Lab, NIH, Navy Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Off Chief Med Examiner, Baltimore, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. RP Chute, JP (reprint author), Large Scale Biol Corp, 3333 Vaca Valley Pkwy, Vacaville, CA 95688 USA. FU NCI NIH HHS [P01 CA70970] NR 55 TC 60 Z9 63 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 DEC 15 PY 2002 VL 100 IS 13 BP 4433 EP 4439 DI 10.1182/blood-2002-04-1238 PG 7 WC Hematology SC Hematology GA 624KX UT WOS:000179759800028 PM 12393435 ER PT J AU Tisdale, JF Maciejewski, JP Nunez, O Rosenfeld, SJ Young, NS AF Tisdale, JF Maciejewski, JP Nunez, O Rosenfeld, SJ Young, NS TI Late complications following treatment for severe aplastic anemia (SAA) with high-dose cyclophosphamide (Cy): follow-up of a randomized trial SO BLOOD LA English DT Article ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; BONE-MARROW TRANSPLANTATION; REMISSION; THERAPY; CELLS AB High-dose cyclophosphamide (Cy) has been promoted as curative therapy for severe aplastic anemia (SAA). However, our randomized trial comparing antithymocyte globulin (ATG) and Cy was terminated early because of excess morbidity/early mortality in the Cy arm. We now report ana lysis of secondary endpoints at a median of 38 months. Relapse occurred in 6 (46%) of 13 responders in the ATG arm versus 2 (25%) of 8 in the Cy arm (P = .38). Five (310/6) of 16 patients in the ATG arm and 4 (27%) of 15 patients in the Cy arm had evidence of paroxysmal nocturnal hemoglobinuria (PNH) at diagnosis, with no substantial change in the overall percentage of glycophosphatidyl inositol (GPI)-anchored protein-deficient neutrophils over. extended follow-up in individual patients in either arm. Bone marrow cytogenetic abnormalities have been observed among surviving patients in both arms (2 of 14 ATG versus 1 of 12 Cy, P = .70). High-dose Cy does not prevent relapse or clonal evolution in SAA. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, Bldg 10,Room 9N116, Bethesda, MD 20892 USA. NR 14 TC 30 Z9 32 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 DEC 15 PY 2002 VL 100 IS 13 BP 4668 EP 4670 DI 10.1182/blood-2002-02-0494 PG 3 WC Hematology SC Hematology GA 624KX UT WOS:000179759800059 PM 12393567 ER PT J AU Daling, JR Malone, KE Doody, DR Voigt, LF Bernstein, L Coates, RJ Marchbanks, PA Norman, SA Weiss, LK Ursin, G Berlin, JA Burkman, RT Deapen, D Folger, SG McDonald, JA Simon, MS Strom, BL Wingo, PA Spirtas, R AF Daling, JR Malone, KE Doody, DR Voigt, LF Bernstein, L Coates, RJ Marchbanks, PA Norman, SA Weiss, LK Ursin, G Berlin, JA Burkman, RT Deapen, D Folger, SG McDonald, JA Simon, MS Strom, BL Wingo, PA Spirtas, R TI Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma SO CANCER LA English DT Article DE histologic types of breast carcinoma; combined hormone replacement therapy; regimens of hormone replacement therapy; ductal; lobular ID ESTROGEN PLUS PROGESTIN; CANCER RISK; POSTMENOPAUSAL WOMEN; CELLS; TERM AB BACKGROUND. The incidence of invasive lobular carcinoma, has been increasing among postmenopausal women in some parts of the United States. Part of this may be due to changes in classification over time. However, the use of combined (estrogen and progestin) hormone replacement therapy (CHRT) also has increased during the last decade and may account in part for the increase in invasive lobular breast carcinoma. METHODS. A large, multicenter case-control study of Caucasian and African-American women who were diagnosed at age < 65 years with their first invasive breast tumor from July 1, 1994 through April 30, 1998 was conducted. In-person interviews were conducted with 1749 postmenopausal patients, and their responses were compared with the responses of 1953 postmenopausal control women identified through random-digit dialing who met the study criteria of being postmenopausal at the time of diagnosis. Polytomous logistic regression was used to calculate the odds ratio (OR) as an estimate of the relative risk and to compute the 95% confidence interval (95%CI) associated with the use of various regimens of hormone replacement therapy (HRT) among women diagnosed with ductal breast carcinoma, lobular (or mixed lobular and ductal) breast carcinoma, and a grouping of other histologic types of breast carcinoma. RESULTS. Ever use of unopposed estrogen therapy (ERT) was not associated with an increase in the risk of any histologic type of breast carcinoma. The risk of invasive lobular breast carcinoma and the risk of breast carcinoma of the grouping of other histologies increased among women currently using CHRT (OR, 2.2; 95%CI, 1.4-3.3; and OR, 1.9; 95%CI, 1.0-3.4, respectively). The risk increase was greater for the mixed lobular-ductal type than for the pure lobular type of breast carcinoma, although the difference was not statistically significant. There was some indication that 5 years of continuous CHRT (greater than or equal to 25 days per month of progestin) was associated with a higher risk of lobular breast carcinoma (OR, 2.5; 95%CI, 1.4-4.3) compared with sequential CHRT (<25 days per month of progestin; OR, 1.5; 95%CI, 0.8-2.6). Current use of continuous CHRT was only moderately associated with risk of ductal breast carcinoma. CONCLUSIONS. Postmenopausal women who take CHRT appear to be at an increased risk of lobular breast carcinoma. Data from this study suggest that neither ERT use nor CHRT substantially increase the risk of ductal breast carcinoma among women age < 65 years. Cancer 2002;95:2455-64. Published 2002 by the American Cancer Society.* C1 Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA. Ctr Dis Control & Prevent, Canc Div, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Wayne State Univ, Karmanos Canc Inst, Div Epidemiol, Detroit, MI 48202 USA. Bay State Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. Wayne State Univ, Div Hematol & Oncol, Karmanos Canc Inst, Detroit, MI USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, Bethesda, MD 20892 USA. RP Daling, JR (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N MP 381,POB 19024, Seattle, WA 98109 USA. FU NCI NIH HHS [N01 CN 0532, N01 PC 67010, N01 PC 67006, N01 CN 65064]; NICHD NIH HHS [Y01 HD 7022, N01 HD 3-3174, N01 HD 3-3175, N01 HD-3-3176, N01 HD 2-3166] NR 28 TC 109 Z9 109 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 15 PY 2002 VL 95 IS 12 BP 2455 EP 2464 DI 10.1002/cncr.10984 PG 10 WC Oncology SC Oncology GA 622GM UT WOS:000179638700002 PM 12467057 ER PT J AU Doong, H Vrailas, A Kohn, EC AF Doong, H Vrailas, A Kohn, EC TI What's in the 'BAG'? - a functional domain analysis of the BAG-family proteins SO CANCER LETTERS LA English DT Review DE apoptosis; stress response; migration; Hsp70; silencer of death domains; BcL-2; survival; proliferation; chaperone ID E3 UBIQUITIN LIGASE; VITAMIN-D-RECEPTOR; DEATH DOMAINS; CELL-DEATH; BCL-2-BINDING PROTEIN; MOLECULAR CHAPERONES; PANCREATIC-CANCER; INDUCED APOPTOSIS; EXPRESSION; SCYTHE AB Bcl-2-associated athanogene (BAG)-family proteins are BAG domain-containing proteins that interact with the heat shock proteins 70, both constitutive Hsc70 and inducible Hsp70. BAG-family proteins bind through the BAG domain to the ATPase domain of Hsc70/Hsp70. The BAG domain, approximately 110 amino acids in length, is a conserved region at the carboxyl terminus and consists of three anti-parallel alpha helices based on X-ray crystallography and NMR studies. The second and third alpha-helices of the BAG domain interact with the ATP-binding pocket of Hsc70/Hsp70. Currently, six human BAG proteins have been reported, four of which have been shown to functionally bind Hsc70/Hsp70. BAG-family proteins regulate chaperone protein activities through their interaction with Hsc70/Hsp70. Over-expression of BAG-family proteins is found in several cancers and has been demonstrated in the laboratory to enhance cell survival and proliferation. The anti-apoptotic activities of BAG-family proteins may be dependent on their interactions with Hsc70/Hsp70 and/or binding to Bcl-2. Both BAGA and BAG-3/CAIR-1 interact with Bcl-2 and have been shown to have a supra-additive anti-apoptotic effect with Bcl-2. Several N-terminal domains or motifs have been identified in BAG-family proteins as well. These domains enable BAG-family proteins to partner with other proteins and potentially alter the activity of those target proteins by recruiting Hsc70/Hsp70. BAG-family proteins participate in a wide variety of cellular processes including cell survival (stress response), proliferation, migration and apoptosis. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Canc Res Ctr, Pathol Lab, Molec Signaling Sect,NIH, Bethesda, MD 20892 USA. RP Doong, H (reprint author), NCI, Canc Res Ctr, Pathol Lab, Molec Signaling Sect,NIH, Bethesda, MD 20892 USA. NR 53 TC 137 Z9 139 U1 2 U2 10 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 15 PY 2002 VL 188 IS 1-2 BP 25 EP 32 AR PII S0304-3835(02)00456-1 DI 10.1016/S0304-3835(02)00456-1 PG 8 WC Oncology SC Oncology GA 621ND UT WOS:000179595300004 PM 12406544 ER PT J AU Shah, AH Tabayoyong, WB Kundu, SD Kim, SJ Van Parijs, L Liu, VC Kwon, E Greenberg, NM Lee, C AF Shah, AH Tabayoyong, WB Kundu, SD Kim, SJ Van Parijs, L Liu, VC Kwon, E Greenberg, NM Lee, C TI Suppression of tumor metastasis by blockade of transforming growth factor beta signaling in bone marrow cells through a retroviral-mediated gene therapy in mice SO CANCER RESEARCH LA English DT Article ID PROSTATE-CANCER CELLS; TGF-BETA; DOWN-REGULATION; II RECEPTOR; FACTOR-BETA-1; TGF-BETA-1; INHIBITION; RESISTANCE; DISRUPTION; INDUCTION AB Transforming growth factor B (TGF-beta) is a potent immunosuppressive cytokine that is frequently associated with mechanisms of tumor escape from inummosurveillance. We report that transplantation of murine bone marrow (BM) expressing a dominant-negative TGF-beta type 11 receptor (TbetaRIIDN) leads to the generation of mature leukocytes capable of a potent antitumor response in vivo. Hematopoietic precursors in murine BM from donor mice were rendered insensitive to TGF-beta via retroviral expression of the TbetaRIIDN construct and were transplanted in C57BL/6 mice before tumor challenge. After i.v. administration of 5 x 10(5) B16-F10 murine melanoma cells into TbetaRIIDN-BM transplanted recipients, survival of challenged mice at 45 days was 70% (7 of 10) versus 0% (0 of 10) for vector-control treated mice, and surviving TbetaRIIDN-BM mice showed a virtual absence of metastatic lesions in the lung. We also investigated the utility of the TGF-beta-targeted approach in a mouse metastatic model of prostate cancer, TRAMP-C2. Treatment of male C57BL/6 mice with TbetaRIlDN-BM resulted in the survival of 80% (4 of 5) of recipients versus 0% (0 of 5) in green fluorescent protein-BM recipients or wild-type controls. Cytolytic T-cell assays indicate that a specific T-cell response against B16-F10 cells was generated in the TbetaRIIDN-BM-treated mice, suggesting that a gene therapy approach to inducing TGF-beta insensitivity in transplanted BM cells may be a potent anticancer therapy. C1 Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Mayo Clin & Mayo Fdn, Dept Urol, Rochester, MN 55905 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. RP Lee, C (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, 303 E Chicago Ave,Tarry 16-733, Chicago, IL 60611 USA. NR 21 TC 47 Z9 56 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2002 VL 62 IS 24 BP 7135 EP 7138 PG 4 WC Oncology SC Oncology GA 627JF UT WOS:000179929500001 PM 12499244 ER PT J AU Ahmed, F Wyckoff, J Lin, EY Wang, WG Wang, YR Hennighausen, L Miyazaki, J Jones, J Pollard, JW Condeelis, JS Segall, JE AF Ahmed, F Wyckoff, J Lin, EY Wang, WG Wang, YR Hennighausen, L Miyazaki, J Jones, J Pollard, JW Condeelis, JS Segall, JE TI GFP expression in the mammary gland for imaging of mammary tumor cells in transgenic mice SO CANCER RESEARCH LA English DT Article ID GREEN FLUORESCENT PROTEIN; HUMAN BREAST-CANCER; GENE; METASTASIS; INVASION AB To examine the behavior of tumor cells in tumors developing directly from mammary tissue in transgenic models, we have evaluated transgenic mice expressing green fluorescent protein (GFP). Using the mouse mammary virus promoter (MMTV) to directly drive expression of GFP, we find low levels of fluorescence in the mammary and salivary glands of transgenic animals. Using MMTV-Cre or WAP-Cre in combination with the Cre-activatable CAG-CAT-EGFP construct, we find stronger expression of GFP that is still tissue specific. These animals provide a range of expression of GFP that is suitable for analysis of transgenic mammary tumors and metastases in vivo at the single cell level of resolution. C1 Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol, Bronx, NY 10461 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Osaka Univ, Sch Med, Div Stem Cell Regulat Res, Osaka 5650871, Japan. RP Segall, JE (reprint author), Yeshiva Univ Albert Einstein Coll Med, Dept Anat & Struct Biol, 1300 Morris Pk Ave, Bronx, NY 10461 USA. NR 21 TC 79 Z9 81 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2002 VL 62 IS 24 BP 7166 EP 7169 PG 4 WC Oncology SC Oncology GA 627JF UT WOS:000179929500008 PM 12499251 ER PT J AU Beatty, J Terry, A MacDonald, J Gault, E Cevario, S O'Brien, SJ Cameron, E Neil, JC AF Beatty, J Terry, A MacDonald, J Gault, E Cevario, S O'Brien, SJ Cameron, E Neil, JC TI Feline immunodeficiency virus integration in B-cell lymphoma identifies a candidate tumor suppressor gene on human chromosome 15q15 SO CANCER RESEARCH LA English DT Article ID (FIV)-ASSOCIATED LYMPHOMA; GENOME ORGANIZATION; TRANSFORMATION; PROTEIN; CANCER; FORM; HIV AB Infection with immunosuppressive lentiviruses is associated with increased cancer risk, but most studies have implicated indirect mechanisms as the tumor cells generally lack integrated viral sequences. An exception was found in a B-cell lymphoma (Q254) where the tumor cells contained a single integrated feline immunodeficiency virus genome. Additional analysis now indicates that feline immunodeficiency virus integration in lymphoma Q254 resulted in promoter insertion and truncation of a conserved gene on feline chromosome B3, whereas the unaffected allele of the gene appeared to be transcriptionally down-regulated. The orthologous human gene (FLJ12973), is expressed ubiquitously and encodes a WD-repeat protein with structural similarity to DDB2, the small subunit of the xeroderma pigmentosum XP-E complex. Moreover, the gene is located within a region of frequent tumor-specific deletions on chromosome 15q15. These observations demonstrate the direct mutagenic potential of the lentiviruses and identify a new candidate tumor suppressor gene. C1 Univ Glasgow, Sch Vet, Inst Comparat Med, Mol Oncol Lab, Glasgow G61 1QH, Lanark, Scotland. NCI, Lab Genom Divers, Frederick, MD 21702 USA. RP Neil, JC (reprint author), Univ Glasgow, Sch Vet, Inst Comparat Med, Mol Oncol Lab, Glasgow G61 1QH, Lanark, Scotland. NR 24 TC 16 Z9 16 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2002 VL 62 IS 24 BP 7175 EP 7180 PG 6 WC Oncology SC Oncology GA 627JF UT WOS:000179929500010 PM 12499253 ER PT J AU Hildesheim, J Bulavin, DV Anver, MR Alvord, WG Hollander, MC Vardanian, L Fornace, AJ AF Hildesheim, J Bulavin, DV Anver, MR Alvord, WG Hollander, MC Vardanian, L Fornace, AJ TI Gadd45a protects against UV irradiation-induced skin tumors, and promotes apoptosis and stress signaling via MAPK and p53 SO CANCER RESEARCH LA English DT Article ID N-TERMINAL KINASE; ULTRAVIOLET-RADIATION; CELL-GROWTH; P38 MAPK; C-JUN; DAMAGING AGENTS; GENE FAMILY; MOUSE SKIN; ACTIVATION; DNA AB Skin cancer is the most frequent form of malignancy in the world, and UV radiation is the primary environmental carcinogen responsible for its development. Herein we demonstrate that Gadd45a is a critical factor protecting the epidermis against UV radiation-induced tumorigenesis by promoting damaged keratinocytes to undergo apoptosis and/or cell cycle arrest, two crucial events that prevent the expansion of mutant or deregulated cells. Whereas Gadd45a has been implicated in cell cycle arrest, apoptosis, and DNA repair, to determine the physiological function of endogenous Gadd45a after genotoxic stress, the skin of Gadd45a-null mice was targeted with UV radiation. We report that Gadd45a induces apoptosis and cell cycle arrest by maintaining p38 and c-JNK MAPK activation in keratinocytes. The absence of Gadd45a results in loss of sustained p38/JNK MAPK activity beyond 15-30 min after UV radiation that leads to inadequate p53 activation and loss of normal activation of G(1) and G(2) checkpoints. Moreover, loss of Gadd45a dramatically reduces UV-induced apoptotic keratinocytes, "sunburn cells." Consequently, Gadd45a-null mice are more prone to tumors relative to wild-type mice. Therefore, we conclude that Gadd45a, like p53, is a key component protecting skin against UV-induced tumors. C1 NCI, Gene Response Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Pathol Histotechnol Lab, Frederick, MD 21702 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. RP Fornace, AJ (reprint author), NCI, Gene Response Sect, Ctr Canc Res, NIH, Bldg 37,Room 6144,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU PHS HHS [N01-C0-12400, N01-C0-12401] NR 76 TC 174 Z9 183 U1 2 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2002 VL 62 IS 24 BP 7305 EP 7315 PG 11 WC Oncology SC Oncology GA 627JF UT WOS:000179929500031 PM 12499274 ER PT J AU Murakami, T Maki, W Cardones, AR Fang, H Kyi, AT Nestle, FO Hwang, ST AF Murakami, T Maki, W Cardones, AR Fang, H Kyi, AT Nestle, FO Hwang, ST TI Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER METASTASIS; NOD/SCID MICE; CUTTING EDGE; LYMPH-NODES; FACTOR-I; INHIBITOR; PROLIFERATION; ENGRAFTMENT; MIGRATION; INTEGRINS AB The chemokine receptors CC chemokine receptor (CCR) 7 and CXC cbemokine receptor (CXCR) 4 have been implicated in cancer metastasis. To evaluate whether CXCR4 is sufficient to increase tumor metastasis in an organ-specific manner, we transduced murine B16 melanoma cells with CXCR4 (CXCR4-B16) and followed the metastatic fate of the transduced cells in both i.v. and s.c. inoculation models of metastasis. CXCR4-B16 cells demonstrated marked increases (>10-fold) in pulmonary metastasis compared with vector (pLNCX2)-B16 after i.v. and s.c. inoculation of tumor cells. The increase in metastasis could be completely inhibited by T22, a small peptide antagonist of CXCR4. As early as 24 and 48 h after i.v. injection, CXCR4-B16 cells were significantly increased in the lung compared with control B16 cells by 5- and 10-fold (P < 0.05), respectively. CXCR4-B16 cells adhered better to both dermal and pulmonary microvascular endothelial cells relative to control B16 cells. Moreover, CXCL12 promoted the growth of CXCR4-B16 cells in vitro. Whereas expression of CXCR4 in B16 cells dramatically enhanced pulmonary metastasis, metastasis to the lymph nodes, liver, and kidney was rare. Immunohistochemical staining of both primary human cutaneous melanoma and pulmonary metastases revealed CXCR4 expression. Thus, CXCR4 plays a potentially important role in promoting organ-selective metastasis, possibly by stimulating tumor adhesion to microvascular endothelial cells and by enhancing the growth of tumor cells under stress. C1 NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Zurich, Sch Med, Dept Dermatol, CH-8091 Zurich, Switzerland. RP Hwang, ST (reprint author), Bldg 10 Room 12N246,10 Ctr Dr, Bethesda, MD 20892 USA. NR 34 TC 271 Z9 282 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 15 PY 2002 VL 62 IS 24 BP 7328 EP 7334 PG 7 WC Oncology SC Oncology GA 627JF UT WOS:000179929500033 PM 12499276 ER PT J AU Feld, R Paesmans, M Freifeld, AG Klastersky, J Pizzo, PA Rolston, KVI Rubenstein, E Talcott, JA Walsh, TJ AF Feld, R Paesmans, M Freifeld, AG Klastersky, J Pizzo, PA Rolston, KVI Rubenstein, E Talcott, JA Walsh, TJ TI Methodology for clinical trials involving patients with cancer who have febrile neutropenia: Updated guidelines of the Immunocompromised Host Society/Multinational Association for Supportive Care in Cancer, with emphasis on outpatient studies SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PREDICTION RULE; FEVER; CHEMOTHERAPY; THERAPY AB Two multinational organizations, the Immunocompromised Host Society and the Multinational Association for Supportive Care in Cancer, have produced for investigators and regulatory bodies a set of guidelines on methodology for clinical trials involving patients with febrile neutropenia. The guidelines suggest that response (i. e., success of initial empirical antibiotic therapy without any modification) be determined at 72 h and again on day 5, and the reasons for modification should be stated. Blinding and stratification are to be encouraged, as should statistical consideration of trials specifically designed for showing equivalence. Patients enrolled in outpatient studies should be selected by use of a validated risk model, and patients should be carefully monitored after discharge from the hospital. Response and safety parameters should be recorded along with readmission rates. If studies use these guidelines, comparisons between studies will be simpler and will lead to further improvements in patient therapy. C1 Princess Margaret Hosp, Dept Hematol & Oncol, Toronto, ON M4G 2M9, Canada. Inst Jules Bordet, B-1000 Brussels, Belgium. Nebraska Med Ctr, Omaha, NE USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. MD Anderson Hoscp & Canc Ctr, Houston, TX USA. NCI, Bethesda, MD 20892 USA. RP Feld, R (reprint author), Princess Margaret Hosp, Dept Hematol & Oncol, 610 Univ Ave, Toronto, ON M4G 2M9, Canada. NR 18 TC 37 Z9 39 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2002 VL 35 IS 12 BP 1463 EP 1468 DI 10.1086/344650 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 623MM UT WOS:000179707200006 PM 12471564 ER PT J AU Webster, MJ Weickert, CS Herman, MM Kleinman, JE AF Webster, MJ Weickert, CS Herman, MM Kleinman, JE TI BDNF mRNA expression during postnatal development, maturation and aging of the human prefrontal cortex SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE dorsolateral prefrontal cortex; occipital cortex; adolescent; neurotrophic factor ID FACTOR MESSENGER-RNA; NERVE GROWTH-FACTOR; NEUROTROPHIC FACTOR INCREASES; SEPTAL CHOLINERGIC NEURONS; HUMAN CEREBRAL-CORTEX; ADULT-RAT FOREBRAIN; VISUAL-CORTEX; IN-VIVO; CORTICAL-NEURONS; HUMAN-BRAIN AB Brain derived neurotrophic factor (BDNF) is widely distributed in the central nervous system (CNS) and has survival-promoting actions on a variety of CNS neurons. We have examined changes in the level of BDNF mRNA expression in the dorsolateral prefrontal cortex (DLPFC) of the postnatal human brain using both RNAse protection assay and in situ hybridization. Expression of BDNF mRNA in the DLPFC was compared to that in the occipital cortex. BDNF mRNA levels vary between layers, with layer VI consistently higher than other layers in both the DLPFC and occipital regions. BDNF mRNA levels increase approximately one-third from infancy to adulthood, i.e. they are relatively low during infancy and adolescence, peak during young adulthood, and are maintained at a constant level throughout adulthood and aging. The significant increase in BDNF mRNA levels in the DLPFC during the young adult period coincides with the time when the frontal cortex matures both structurally and functionally. The increase in BDNF at this critical time in human development may have important implications for the etiology and treatment of the severe mental disorders that tend to present during this time. Published by Elsevier Science B.V. C1 Uniformed Serv Univ Hlth Sci, Stanley Lab Brain Res, Dept Psychiat, Bethesda, MD 20814 USA. NIMH, Clin Brain Disorders Branch, IRP, NIH, Bethesda, MD 20892 USA. RP Webster, MJ (reprint author), Uniformed Serv Univ Hlth Sci, Stanley Lab Brain Res, Dept Psychiat, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. RI Shannon Weickert, Cynthia/G-3171-2011 NR 90 TC 45 Z9 49 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD DEC 15 PY 2002 VL 139 IS 2 BP 139 EP 150 AR PII S0165-3806(02)00540-0 DI 10.1016/S0165-3806(02)00540-0 PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 629XG UT WOS:000180077200005 ER PT J AU Badenhorst, P Voas, M Rebay, I Wu, C AF Badenhorst, P Voas, M Rebay, I Wu, C TI Biological functions of the ISWI chromatin remodeling complex NURF SO GENES & DEVELOPMENT LA English DT Article DE NURF; chromatin remodeling; ISWI; Drosophila; JAK/STAT pathway ID GAGA TRANSCRIPTION FACTOR; DOSAGE COMPENSATION; IN-VIVO; DROSOPHILA-MELANOGASTER; HISTONE OCTAMER; HOMEOTIC GENES; PROTEIN; ENCODES; FAMILY; EXPRESSION AB The nucleosome remodeling factor (NURF) is one of several ISWI-containing protein complexes that catalyze ATP-dependent nucleosome sliding and facilitate transcription of chromatin in vitro. To establish the physiological requirements of NURF, and to distinguish NURF genetically from other ISWI-containing complexes, we isolated mutations in the gene encoding the large NURF subunit, nurf301. We confirm that NURF is required for transcription activation in vivo. In animals lacking NURF301, heat-shock transcription factor binding to and transcription of the hsp70 and hsp26 genes are impaired. Additionally, we show that NURF is required for homeotic gene expression. Consistent with this, nurf301 mutants recapitulate the phenotypes of Enhancer of bithorax, a positive regulator of the Bithorax-Complex previously localized to the same genetic interval. Finally, mutants in NURF subunits exhibit neoplastic transformation of larval blood cells that causes melanotic tumors to form. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. MIT, Dept Biol, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Wu, C (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. OI Badenhorst, Paul/0000-0002-2542-0250 NR 57 TC 142 Z9 150 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD DEC 15 PY 2002 VL 16 IS 24 BP 3186 EP 3198 DI 10.1101/gad.1032202 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 632BJ UT WOS:000180203000007 PM 12502740 ER PT J AU Xu, XM Carlson, BA Grimm, TA Kutza, J Berry, MJ Arreola, R Fields, KH Shanmugam, I Jeang, KT Oroszlan, S Combs, GF Marx, PA Gladyshev, VN Clouse, KA Hatfield, DL AF Xu, XM Carlson, BA Grimm, TA Kutza, J Berry, MJ Arreola, R Fields, KH Shanmugam, I Jeang, KT Oroszlan, S Combs, GF Marx, PA Gladyshev, VN Clouse, KA Hatfield, DL TI Rhesus monkey simian immunodeficiency virus infection as a model for assessing the role of selenium in AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE immunodeficiency diseases; AIDS; molecular biology; selenium; HIV ID SELENOCYSTEINE TRANSFER RNASEC; HIV-1 TAT PROTEIN; GLUTATHIONE-PEROXIDASE; TRANSFER-RNA; T-CELLS; SERUM SELENIUM; DEFICIENCY; REPLICATION; BLOOD; SUPPLEMENTATION AB The objective of this study was to determine whether simian immunodeficiency virus (SIV) infection of rhesus macaques could be used as a model system to assess the role of selenium in AIDS. Plasma and serum selenium levels were determined by standard assays in monkeys before and after inoculation of SIV. SIV-infected cells or cells expressing the HIV Tat protein were labeled with Se-75, and protein extracts were prepared and electrophoresed to analyze selenoprotein expression. Total tRNA was isolated from CEMx174 cells infected with SIV or from KK1 cells infected with HIV, and selenocysteine tRNA isoforms were characterized by reverse phase chromatography. SIV-infected monkeys show a decrease in blood selenium levels similar to that observed in AIDS with development of SAIDS. Cells infected with SIV in vitro exhibit reduced selenoprotein levels and an accumulation of small molecular weight selenium compounds relative to uninfected cells. Examination of the selenocysteine tRNA isoforms in HIV-infected KK1 cells or SIV-infected CEMx174 cells reveals an isoform distribution characteristic of selenium-deficient cells. Furthermore, transfection of Jurkat E6 cells with the Tat gene selectively altered selenoprotein synthesis, with GPX4 and Sep 15 being the most inhibited and TR1 the most enhanced. Taken together, the data show that monkeys infected with SIV in vivo and cells infected with SIV in vitro will provide appropriate models for investigating the mechanism(s) responsible for reduced selenium levels that accompany the progression of AIDS in HIV disease. C1 NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20857 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Thyroid, Boston, MA 02115 USA. NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA. Cornell Univ, Div Nutr Sci, Dept Nutr, Ithaca, NY 14853 USA. Tulane Univ, Hlth Sci Ctr, Sch Publ Hlth & Trop Med, Covington, LA USA. Tulane Natl Primate Res Ctr, Covington, LA USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68583 USA. RP Hatfield, DL (reprint author), NCI, Sect Mol Biol Selenium, Basic Res Lab, NIH, Bldg 37,Room 2D09, Bethesda, MD 20892 USA. RI Jeang, Kuan-Teh/A-2424-2008; Gladyshev, Vadim/A-9894-2013 FU NCRR NIH HHS [P51 RR 000164]; NIAID NIH HHS [R01 AI 41952] NR 39 TC 10 Z9 11 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS JI JAIDS PD DEC 15 PY 2002 VL 31 IS 5 BP 453 EP 463 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 624TA UT WOS:000179776100001 PM 12473832 ER PT J AU Engels, EA Frisch, M Lubin, JH Gail, MH Biggar, RJ Goedert, JJ AF Engels, EA Frisch, M Lubin, JH Gail, MH Biggar, RJ Goedert, JJ TI Prevalence of hepatitis C virus infection and riskfor hepatocellular carcinoma and non-Hodgkin lymphoma in AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE cancer; hepatocellular carcinoma; non-Hodgkin lymphoma; hepatitis C virus; epidemiology; HIV; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIRAL-INFECTIONS; HIV-INFECTION; ASSOCIATION; POPULATION; MORTALITY; CIRRHOSIS; COINFECTION; HEMOPHILIA; ANTIBODIES AB Hepatitis C virus (HCV) infection is highly prevalent in some subpopulations with AIDS. HCV is linked to hepatocellular carcinoma (HCC) and possibly non-Hodgkin lymphoma (NHL), but the impact of AIDS on these associations is uncertain. We used U.S. registry data to study HCC and NHL risk in 304,411 adults with AIDS, comparing cohort subgroups with high prevalence (hemophiliacs and injection drug users) or low prevalence (homosexual men, heterosexuals, and others) of HCV infection. The ratio of observed to expected cancer cases (standardized incidence ratio [SIR]) measured risk relative to the general population. Sixty-one HCC cases were observed (SIR, 7.5; 95% confidence interval, 5.7-9.6). Risk for HCC was higher in subgroups with high prevalence of HCV infection than in subgroups with low prevalence of HCV infection (SIR: 11.4 versus 5.5, respectively; p = .004). Subjects developed the following NHL grades: low, 35 cases; intermediate, 1035 cases; high, 784 cases; and unspecified, 1395 cases. For each NHL grade, SIRs were highest in subgroups with low prevalence of HCV infection. These data suggest an effect of HCV infection on HCC risk among adults with AIDS. On the other hand, NHL risk was not higher for groups in whom HCV infection was prevalent. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Statens Serum Inst, Danish Epidemiol Res, Danish Epidemiol Sci Ctr, DK-2300 Copenhagen, Denmark. RP Engels, EA (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8010, Bethesda, MD 20892 USA. RI Frisch, Morten/E-9206-2016 OI Frisch, Morten/0000-0002-3864-8860 NR 38 TC 31 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS JI JAIDS PD DEC 15 PY 2002 VL 31 IS 5 BP 536 EP 541 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 624TA UT WOS:000179776100012 PM 12473843 ER PT J AU Das, D Eurenius, KP Billings, EM Sherwood, P Chatfield, DC Hodoscek, M Brooks, BR AF Das, D Eurenius, KP Billings, EM Sherwood, P Chatfield, DC Hodoscek, M Brooks, BR TI Optimization of quantum mechanical molecular mechanical partitioning schemes: Gaussian delocalization of molecular mechanical charges and the double link atom method SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID GEOMETRY OPTIMIZATION; ENZYME PHOSPHOLIPASE-A2; ELECTRONIC-STRUCTURE; QM/MM CALCULATIONS; GAS-PHASE; SYSTEMS; ENERGY; FIELD; MODEL; DYNAMICS AB Two new techniques for modeling chemical processes in condensed phases with combined quantum mechanical and molecular mechanical (QM/MM) potentials are introduced and tested on small, model compounds. The first technique, the double link atom (DLA) method, is an extension of the traditional, single link atom (SLA) method to avoid some of the problems with the latter method. These problems are primarily electrostatic, as the SLA method can produce an unphysical overall charge or dipole. The second technique, the delocalized Gaussian MM charge (DGMM) method, is an empirical way to include the delocalized character of the electron density of atoms in the MM region. This can be important for the electrostatic interaction of the QM region with nearby atoms in the MM region, and it can simplify the rules governing which classical interactions are included in the energies and forces. Even for very short distances, the DGMM method does not require the neglect of the MM host in the QM calculation. The DGMM method can be used for modeling reactions in solution, and it can be combined with methods such as the link atom, frozen orbital, or pseudopotential methods for terminating the QM region at a covalent bond. The DLA and the DGMM methods have been combined effectively. Presented here are tests on small, model systems that mimic properties important for reactions in proteins, in particular rotational barriers, proton affinities, and deprotonation energies. The new methods yield improved energetics for model compounds, vis-a-vis a point-MM-charge and SLA treatment. (C) 2002 American Institute of Physics. C1 NHLBI, Biophys Chem Lab, Computat Biophys Sect, NIH, Bethesda, MD 20892 USA. CLRC Daresbury Lab, Warrington WA4 4AD, Cheshire, England. RP NHLBI, Biophys Chem Lab, Computat Biophys Sect, NIH, Bldg 10, Bethesda, MD 20892 USA. EM brb@nih.gov RI Sherwood, Paul/B-9033-2012 OI Sherwood, Paul/0000-0002-4611-5052 NR 46 TC 131 Z9 131 U1 2 U2 21 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 15 PY 2002 VL 117 IS 23 BP 10534 EP 10547 DI 10.1063/1.1520134 PG 14 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 619UC UT WOS:000179495000014 ER PT J AU Waghe, A Rasaiah, JC Hummer, G AF Waghe, A Rasaiah, JC Hummer, G TI Filling and emptying kinetics of carbon nanotubes in water SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID FLUID EXPERIMENTS; SIMULATION; DYNAMICS AB The kinetics of water filling and emptying the interior channel of carbon nanotubes is studied by molecular dynamics simulations. Filling and emptying occur predominantly by sequential addition of water to or removal from a single-file chain inside the nanotube. Advancing and receding water chains are orientationally ordered. This precludes simultaneous filling from both tube ends, and forces chain rupturing to occur at the tube end where a water molecule donates a hydrogen bond to the bulk fluid. We use transition path concepts and a Bayesian approach to identify a transition state ensemble that we characterize by its commitment probability distribution. At the transition state, the tube is filled with all but one water molecule. Filling thermodynamics and kinetics depend sensitively on the strength of the attractive nanotube-water interactions. This sensitivity increases with the length of the tubes. (C) 2002 American Institute of Physics. C1 Univ Maine, Dept Chem, Orono, ME 04469 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Univ Maine, Dept Chem, Orono, ME 04469 USA. EM rasaiah@maine.edu; gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 24 TC 178 Z9 179 U1 4 U2 32 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD DEC 15 PY 2002 VL 117 IS 23 BP 10789 EP 10795 DI 10.1063/1.1519861 PG 7 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 619UC UT WOS:000179495000038 ER PT J AU Fine, HA AF Fine, HA TI Primary central nervous system lymphoma: Time to ask the question SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material C1 NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Fine, HA (reprint author), NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. NR 6 TC 8 Z9 9 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 DEC 15 PY 2002 VL 20 IS 24 BP 4615 EP 4617 PG 3 WC Oncology SC Oncology GA 634QK UT WOS:000180351700002 PM 12488403 ER PT J AU Chaudhry, S Freebern, WJ Smith, JL Butscher, WG Haggerty, CM Gardner, K AF Chaudhry, S Freebern, WJ Smith, JL Butscher, WG Haggerty, CM Gardner, K TI Cross-regulation of T cell growth factor expression by p53 and the tax oncogene SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CREB-BINDING-PROTEIN; VIRUS TYPE-I; NF-KAPPA-B; TUMOR-SUPPRESSOR PROTEIN; WILD-TYPE P53; LEUKEMIA-VIRUS; GENE-EXPRESSION; COACTIVATOR CBP; TRANSCRIPTIONAL ACTIVATION; TRANSFORMED-CELLS AB In this study, we demonstrate that p53 directly inhibits expression of the T cell growth factor (IL-2) in activated T cells. This repression is independent of the intrinsic transcriptional activity of p53 and is mediated by the Tax-responsive CD28RE-3'-12-O-tetradecanoylphorbol-13-acetate response element (AP1) element of the IL-2 promoter. Coexpression of the Tax oncogene causes full reversal of this repression through coordinate targeting of p300, CREB, and the NF-kappaB pathways. Paradoxically, IL-2 repression by p53 is not reversed by mdm2. Instead, mdm2 represses the IL-2 promoter by a mechanism that is synergistic with p53 and resistant to Tax reversal. The p300 structure-function studies show that these effects are linked to competitive associations among p53, Tax, and mdm2 with multiple domains of p300. The functional outcome of these antagonistic associations is revealed further by the observation that Tax and p53 induce apoptosis in activated T cells through separate and mutually exclusive pathways. Interestingly, both pathways are abrogated by mdm2. These results provide evidence that a dynamic interplay, between Tax and specific elements of the p53 network, mediates growth factor expression and programmed cell death in activated T cells. C1 NCI, Pathol Lab, Ctr Adv Technol, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, Ctr Adv Technol, NIH, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Microbiol, Washington, DC 20059 USA. RP Gardner, K (reprint author), NCI, Pathol Lab, Ctr Adv Technol, NIH, Room 134C,8717 Grovemont Circle, Bethesda, MD 20892 USA. NR 64 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD DEC 15 PY 2002 VL 169 IS 12 BP 6767 EP 6778 PG 12 WC Immunology SC Immunology GA 624MN UT WOS:000179763600017 PM 12471108 ER PT J AU Kawakami, K Kawakami, M Puri, RK AF Kawakami, K Kawakami, M Puri, RK TI IL-13 receptor-targeted cytotoxin cancer therapy leads to complete eradication of tumors with the aid of phagocytic cells in nude mice model of human cancer SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; CARCINOMA-CELLS; ALPHA CHAIN; SIGNAL-TRANSDUCTION; SYSTEMIC DELIVERY; IN-VIVO; PROTEIN; BINDING; GENE AB Tumor-directed therapeutic approaches require unique or overexpressed specific Ag or receptor as a target to achieve selective tumor killing. However, heterogeneous expression of these targets on tumor cells limits the efficacy of this form of therapy. In this study, we forced abundant expression of IL-13Ralpha2 chain by plasmid-mediated gene transfer in head and neck, as well as prostate tumors to provide a potential target. This was followed by successfully treating xenograft tumor-bearing nude mice with IL-13R-directed cytotoxin (IL13-PE38QQR). Although we did not observe an indirect cytotoxic bystander effect conveyed to nontransduced tumor cells in vitro, our approach in vivo led to a complete regression of established tumors transfected with IL-13Ralpha12 chain in most animals. We found that the tumor eradication was achieved in part by infiltration of macrophages and NK cells, assessed by immunohistochemistry. Moreover, head and neck tumors xenografted in macrophage-depleted nude mice were less sensitive to the antitumor effect of IL-13 cytotoxin. Because we did not observe vector-related toxicity in any vital organs, our novel combination strategy of gene transfer of IL-13Ralpha2 chain and receptor-directed cytotoxin therapy may be a useful approach for the treatment of localized cancer. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 35 TC 19 Z9 19 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 DEC 15 PY 2002 VL 169 IS 12 BP 7119 EP 7126 PG 8 WC Immunology SC Immunology GA 624MN UT WOS:000179763600058 PM 12471149 ER PT J AU Pivovarova, NB Pozzo-Miller, LD Hongpaisan, J Andrews, SB AF Pivovarova, NB Pozzo-Miller, LD Hongpaisan, J Andrews, SB TI Correlated calcium uptake and release by mitochondria and endoplasmic reticulum of CA3 hippocampal dendrites after afferent synaptic stimulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE calcium; endoplasmic reticulum; mitochondria; hippocampus; synaptic activity; electron probe x-ray microanalysis ID BACKPROPAGATING ACTION-POTENTIALS; ELECTRON-PROBE ANALYSIS; MOTOR-NERVE TERMINALS; SYMPATHETIC NEURONS; PYRAMIDAL NEURONS; CA2+ RELEASE; INOSITOL 1,4,5-TRISPHOSPHATE; POSTTETANIC POTENTIATION; INTERNAL STORES; MULTIPLE-MODES AB Mitochondria and endoplasmic reticulum (ER) are important modulators of intracellular calcium signaling pathways, but the role of these organelles in shaping synaptic calcium transients in dendrites of pyramidal neurons remains speculative. We have measured directly the concentrations of total Ca (bound plus free) within intracellular compartments of proximal dendrites of CA3 hippocampal neurons at times after synaptic stimulation corresponding to the peak of the cytoplasmic free Ca2+ transient (1 sec), to just after its decay (30 sec), and to well after its return to prestimulus levels (180 sec). Electron probe microanalysis of cryosections from rapidly frozen slice cultures has revealed that afferent mossy fiber stimulation evokes large, rapid elevations in the concentration of total mitochondrial Ca ([Ca](mito)) in depolarized dendrites. A single tetanus (50 Hz/1 sec) elevated [Ca](mito) more than fivefold above characteristically low basal levels within 1 sec of stimulation and >10-fold by 30 sec after stimulation. This strong Ca accumulation was reversible, because [Ca](mito) had recovered by 180 sec after the tetanus. Ca sequestered within mitochondria was localized to small inclusions that were distributed heterogeneously within, and probably among, individual mitochondria. By 30 sec after stimulation an active subpopulation of ER cisterns had accumulated more Ca than had mitochondria despite a similar to1 sec delay before the onset of accumulation. Active ER cisterns retained their Ca load much longer (>3 min) than mitochondria. The complementary time courses of mitochondrial versus ER Ca2+ uptake and release suggest that these organelles participate in a choreographed interplay, each shaping dendritic Ca2+ signals within characteristic regimes of cytosolic Ca2+ concentration and time. C1 Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. Univ Alabama Birmingham, Dept Neurobiol, Birmingham, AL 35294 USA. Univ Alabama Birmingham, Civitan Int Res Ctr, Birmingham, AL 35294 USA. Marine Biol Lab, Woods Hole, MA 02543 USA. RP Natl Inst Neurol Disorders & Stroke, Neurobiol Lab, NIH, Bldg 36,Room 2A-21,36 Convent Dr, Bethesda, MD 20892 USA. EM sba@helix.nih.gov NR 72 TC 49 Z9 49 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2002 VL 22 IS 24 BP 10653 EP 10661 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 626FG UT WOS:000179861100020 PM 12486158 ER PT J AU Fu, WM Lu, CB Mattson, MP AF Fu, WM Lu, CB Mattson, MP TI Telomerase mediates the cell survival-promoting actions of brain-derived neurotrophic factor and secreted amyloid precursor protein in developing hippocampal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Akt; apoptosis; insulin-like growth factor; MAP kinase; neurogenesis; TERT ID CEREBELLAR GRANULE NEURONS; HUMAN NEUROBLASTOMA-CELLS; NERVE GROWTH-FACTOR; NF-KAPPA-B; REVERSE-TRANSCRIPTASE; PHOSPHATIDYLINOSITOL 3-KINASE; MOUSE TELOMERASE; RAT HIPPOCAMPAL; MESSENGER-RNA; HYPOGLYCEMIC DAMAGE AB Telomerase, a reverse transcriptase that maintains chromosome ends (telomeres) during successive cell divisions in mitotic cells is present in neuroblasts and early postmitotic embryonic neurons but is absent from adult neurons. The signals that control telomerase levels during development are unknown, as are the functions of telomerase in developing neurons. We now report that telomerase activity and levels of its catalytic subunit telomerase reverse transcriptase (TERT) are increased in embryonic hippocampal neurons by brain-derived neurotrophic factor (BDNF) and a secreted form of beta-amyloid precursor protein (sAPP). BDNF and sAPP promote the survival of the embryonic neurons, and these trophic effects are blocked when TERT production is suppressed using antisense technology. Telomerase is required for the long-term survival of early postmitotic neurons during a time window of similar to1 week in culture; telomerase is then downregulated and is not required for BDNF and sAPP survival signaling in mature neurons. The increase in telomerase activity and trophic effects of BDNF and sAPP are mediated by phosphatidylinositol-3 kinase and p42/p44 MAP kinases. Our findings demonstrate a requirement for telomerase in the cell survival-promoting actions of BDNF and sAPP in early postmitotic hippocampal neurons, suggesting a previously unknown role for telomerase in mediating the biological actions of neurotrophic factors during brain development. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr-4F 02, Baltimore, MD 21224 USA. RI Mattson, Mark/F-6038-2012 NR 80 TC 61 Z9 68 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 DEC 15 PY 2002 VL 22 IS 24 BP 10710 EP 10719 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 626FG UT WOS:000179861100026 PM 12486164 ER PT J AU Hollon, TR Bek, MJ Lachowicz, JE Ariano, MA Mezey, E Ramachandran, R Wersinger, SR Soares-da-Silva, P Liu, ZF Grinberg, A Drago, J Young, WS Westphal, H Jose, PA Sibley, DR AF Hollon, TR Bek, MJ Lachowicz, JE Ariano, MA Mezey, E Ramachandran, R Wersinger, SR Soares-da-Silva, P Liu, ZF Grinberg, A Drago, J Young, WS Westphal, H Jose, PA Sibley, DR TI Mice lacking D-5 dopamine receptors have increased sympathetic tone and are hypertensive SO JOURNAL OF NEUROSCIENCE LA English DT Article DE D-5 receptor; gene knock-out; hypertension; sympathetic tone; oxytocin; vasopressin ID NERVOUS-SYSTEM; PROGESTERONE RECEPTORS; BLOOD-PRESSURE; VASOPRESSIN; RAT; D5; GENE; OXYTOCIN; BRAIN; ANTAGONISTS AB Dopamine is an important transmitter in the CNS and PNS, critically regulating numerous neuropsychiatric and physiological functions. These actions of dopamine are mediated by five distinct receptor subtypes. Of these receptors, probably the least understood in terms of physiological functions is the D-5 receptor subtype. To better understand the role of the D-5 dopamine receptor (DAR) in normal physiology and behavior, we have now used gene-targeting technology to create mice that lack this receptor subtype. We find that the D-5 receptor-deficient mice are viable and fertile and appear to develop normally. No compensatory alterations in other dopamine receptor subtypes were observed. We find, however, that the mutant mice develop hypertension and exhibit significantly elevated blood pressure (BP) by 3 months of age. This hypertension appears to be caused by increased sympathetic tone, primarily attributable to a CNS defect. Our data further suggest that this defect involves an oxytocin-dependent sensitization of V-1 vasopressin and non-NMDA glutamatergic receptor-mediated pathways, potentially within the medulla, leading to increased sympathetic outflow. These results indicate that D-5 dopamine receptors modulate neuronal pathways regulating blood pressure responses and may provide new insights into mechanisms for some forms of essential hypertension in humans, a disease that afflicts up to 25% of the aged adult population in industrialized societies. C1 NINDS, Mol Neuropharmacol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Pediat, Washington, DC 20007 USA. Schering Plough Res Inst, CNS Cardiovasc Res, Kenilworth, NJ 07033 USA. Chicago Med Sch, Dept Neurosci, N Chicago, IL 60064 USA. NIMH, Sect Neural Gene Express, Bethesda, MD 20892 USA. Fac Med Porto, Inst Pharmacol & Therapeut, Oporto, Portugal. NICHHD, Lab Mammalian Gene & Dev, NIH, Bethesda, MD 20892 USA. RP Sibley, DR (reprint author), NINDS, Mol Neuropharmacol Sect, NIH, Bldg 10,Room 5C108,10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009; Soares-da-Silva, Patricio/A-6704-2015 OI Young, W Scott/0000-0001-6614-5112; Soares-da-Silva, Patricio/0000-0002-2446-5078 NR 49 TC 97 Z9 105 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2002 VL 22 IS 24 BP 10801 EP 10810 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 626FG UT WOS:000179861100035 PM 12486173 ER PT J AU Neumaier, JF Vincow, ES Arvanitogiannis, A Wise, RA Carlezon, WA AF Neumaier, JF Vincow, ES Arvanitogiannis, A Wise, RA Carlezon, WA TI Elevated expression of 5-HT1B receptors in nucleus accumbens efferents sensitizes animals to cocaine SO JOURNAL OF NEUROSCIENCE LA English DT Article DE herpes simplex virus; gene transfer; ventral tegmental area; conditioned place preference; locomotor hyperactivity ID VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; IN-SITU HYBRIDIZATION; FREELY MOVING RATS; MESSENGER-RNA; EXTRACELLULAR DOPAMINE; SEROTONIN(1B) RECEPTOR; BEHAVIORAL SENSITIZATION; INVIVO MICRODIALYSIS; INTRAVENOUS COCAINE AB Although the effects of psychostimulants on brain dopamine systems are well recognized, the direct actions of cocaine on serotonin systems also appear to be important to its addictive properties. For example, serotonin actions at 5-HT1B receptors in the ventral tegmental area (VTA) modulate cocaine-induced dopamine release in the nucleus accumbens (NAcc) and alter the rewarding and stimulant properties of cocaine. However, the mechanisms of these effects have been unclear, because several neuron types in VTA express 5-HT1B receptors. One possibility is that 5-HT1B receptors on the terminals of GABAergic projections from NAcc to VTA inhibit local GABA release, thereby disinhibiting VTA neurons. We tested this hypothesis directly by using viral-mediated gene transfer to overexpress 5-HT1B receptors in NAcc projections to VTA. A viral vector containing either epitope hemagglutinin-tagged 5-HT1B and green fluorescent protein (HA1B-GFP) cassettes or green fluorescent protein cassette alone (GFP-only) was injected into the NAcc shell, which sends projections to the VTA. HA1B-GFP injection induced elevated expression of 5-HT1B, receptors in neuronal fibers in VTA and increased cocaine-induced locomotor hyperactivity without affecting baseline locomotion. Overexpression of 5-HT1B receptors also shifted the dose-response curve for cocaine-conditioned place preference to the left, indicating alterations in the rewarding effects of cocaine. Thus, increased expression of 5-HT1B receptors in NAcc efferents, probably in the terminals of medium spiny neurons projecting to the VTA, may contribute to psychomotor sensitization and offer an important target for regulating the addictive effects of cocaine. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Harborview Med Ctr, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Psychiat, Belmont, MA 02478 USA. McLean Hosp, Belmont, MA 02478 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Neumaier, JF (reprint author), Univ Washington, Harborview Med Ctr, Box 359911,325 9th Ave, Seattle, WA 98104 USA. RI Wise, Roy/A-6465-2012 NR 63 TC 82 Z9 84 U1 1 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2002 VL 22 IS 24 BP 10856 EP 10863 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 626FG UT WOS:000179861100041 PM 12486179 ER PT J AU Markowska, AL Savonenko, AV AF Markowska, AL Savonenko, AV TI Effectiveness of estrogen replacement in restoration of cognitive function after long-term estrogen withdrawal in aging rats SO JOURNAL OF NEUROSCIENCE LA English DT Article DE ovariectomy; cholinergic system; scopolamine; working memory; attention; body weight ID FOREBRAIN CHOLINERGIC NEURONS; NUCLEUS BASALIS MAGNOCELLULARIS; SPATIAL MEMORY TASK; T-MAZE ALTERNATION; MEDIAL SEPTAL AREA; RADIAL-ARM MAZE; AGED RATS; WORKING-MEMORY; POSTMENOPAUSAL WOMEN; ALZHEIMERS-DISEASE AB Recent studies suggest that some aspects of learning and memory may be altered by a midlife loss of estrogen, indicating a potential causal relationship between the deficiency of ovarian hormones and cognitive aging. In this study, the effects of estrogen withdrawal and replacement were tested in middle-aged Fischer-344 rats using different memory tasks. Estrogen withdrawal accelerated the rate of cognitive aging. A deficit first occurred 4 months after ovariectomy in working memory, which was tested in a delayed-nonmatching-to-position task, and progressed from long-delay to short-delay trials. Reference memory, which was tested in a place discrimination task and a split-stem T-maze, was not affected by aging or ovariectomy. The efficacy of estrogen in ameliorating the cognitive deficit in old rats depended on the type of treatment (acute vs chronic) and whether the aging-related decline in a particular cognitive process was aggravated by estrogen withdrawal. Chronic estrogen treatment (implants) was effective in improving working memory only when primed with repeated injections of estrogen, indicating that simulating the estrogen fluctuations of the estrous cycle may be more effective than the widely used mode of chronic pharmacological treatment. A challenge with scopolamine revealed that ovariectomy-induced cognitive deterioration coincided with a compromised cholinergic system. Importantly, the estrogen treatment that had restored effectively the cognitive abilities of old ovariectomized rats did not reduce their sensitivity to scopolamine. Taking into consideration that estrogen was highly effective against the amnestic action of scopolamine when tested in young-adult rats, these data emphasize that mechanisms of the protective effect of estrogen differ in young and old rats. C1 Johns Hopkins Univ, Dept Psychol, Neuromnemon Lab, Baltimore, MD 21218 USA. RP Markowska, AL (reprint author), NIA, Gateway Bldg,Suite 2C-212, Bethesda, MD 20892 USA. FU NIA NIH HHS [AG15947] NR 60 TC 148 Z9 150 U1 2 U2 8 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 15 PY 2002 VL 22 IS 24 BP 10985 EP 10995 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 626FG UT WOS:000179861100056 PM 12486194 ER PT J AU Tomasiewicz, HG Flaherty, DB Soria, JP Wood, JG AF Tomasiewicz, HG Flaherty, DB Soria, JP Wood, JG TI Transgenic zebrafish model of neurodegeneration SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE FTDP-17 mutant human tau; transgenic model system; cytoskeletal disruption; Alzheimer's disease ID PRIMARY HIPPOCAMPAL-NEURONS; PAIRED HELICAL FILAMENTS; CENTRAL-NERVOUS-SYSTEM; HUMAN TAU-PROTEIN; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; FTDP-17 MUTATIONS; NEUROFIBRILLARY PATHOLOGY; GROWING AXONS; MUTANT-TAU AB In Alzheimer's disease (AD), the microtubule-associated protein, tau, is compromised in its normal association with microtubules and forms into paired helical filaments (PHF) that are the hallmark cytoskeletal pathology of the disease. Several posttranslational modifications of tau including phosphorylation have been implicated in AD pathogenesis. In addition, and importantly, mutations in the genes encoding human tau have recently been implicated in a variety of hereditary dementias, collectively termed frontotemporal dementia with parkinsonism linked to chromosome 17 (FTDP-17). This has rekindled interest in the importance of tau in neurodegenerative diseases (cf. Vogel [1998] Science 280:1524-1525; Goedert et al. [1998] Neuron 21:955-958; D'Souza et al. [1999] PNAS 96:5598-5603). Despite significant progress in the field of tau biology and neurodegenerative diseases, several important issues remain unresolved. The early functional consequences of tau alterations in living neurons is incompletely understood, and it is not clear how tau in neurodegenerative diseases becomes redistributed from its normal concentration in neuronal axons to pathological inclusions in neuronal soma known as neurofibrillary tangles (NFT). One of the reasons for these gaps in knowledge is the relative paucity of model systems to study these processes. We have developed a transgenic model system to study the functional consequences and trafficking patterns in zebrafish neurons of human tau either mutated on sites associated with hereditary dementias or altered at select posttranslational modification sites. The overall guiding hypothesis is that the model allows dissection of a hierarchy of events relevant to potential mechanisms of neurodegenerative diseases related to critical early stages in development of disease. We showed that a FTDP-17 mutant form of human tau expressed in zebrafish neurons produced a cytoskeletal disruption that closely resembled the NFT in human disease. This model system will prove useful in the study of other mutant taus in vertebrate neurons in vivo, and the approaches developed here will have broad usefulness in the study of functional consequences and potential genetic analyses of introducing into living vertebrate neurons other molecules involved in the pathogenesis of neurodegenerative diseases. (C) 2002 Wiley-Liss, Inc. C1 Emory Univ, Dept Cell Biol, Atlanta, GA 30322 USA. Univ Wisconsin, NIEHS, Marine & Freshwater Biomed Sci Ctr, Great Lakes WATER Inst, Milwaukee, WI 53201 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. RP Wood, JG (reprint author), Emory Univ, Dept Cell Biol, Atlanta, GA 30322 USA. FU NIA NIH HHS [AG11123] NR 68 TC 52 Z9 55 U1 1 U2 12 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD DEC 15 PY 2002 VL 70 IS 6 BP 734 EP 745 DI 10.1002/jnr.10451 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 620PN UT WOS:000179541900003 PM 12444595 ER PT J AU Dalakas, MC AF Dalakas, MC TI Pro-inflammatory cytokines and motor neuron dysfunction: Is there a connection in post-polio syndrome? SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Editorial Material ID POSTPOLIOMYELITIS MUSCULAR-ATROPHY; CHRONIC-FATIGUE-SYNDROME; CENTRAL-NERVOUS-SYSTEM; PARALYTIC POLIOMYELITIS; NEUROMUSCULAR SYMPTOMS; INFECTION; TRIAL; DENERVATION; MECHANISMS; ANTIBODIES C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. NR 37 TC 10 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD DEC 15 PY 2002 VL 205 IS 1 BP 5 EP 8 AR PII S0022-510X(02)00314-3 DI 10.1016/S0022-510X(02)00314-3 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 618VE UT WOS:000179437300003 PM 12409176 ER PT J AU Gardner, EL Schiffer, WK Horan, BA Highfield, D Dewey, SL Brodie, JD Ashby, CR AF Gardner, EL Schiffer, WK Horan, BA Highfield, D Dewey, SL Brodie, JD Ashby, CR TI Gamma-vinyl GABA, an irreversible inhibitor of GABA transaminase, alters the acquisition and expression of cocaine-induced sensitization in male rats SO SYNAPSE LA English DT Article DE gamma-vinyl GABA; cocaine; sensitization; locomotion; stereotypy ID VENTRAL TEGMENTAL AREA; EXCITATORY AMINO-ACIDS; 5-HT3 RECEPTOR ANTAGONIST; MEDIAL PREFRONTAL CORTEX; BEHAVIORAL SENSITIZATION; BRAIN GABA; NUCLEUS-ACCUMBENS; 4-AMINO-HEX-5-ENOIC ACID; B RECEPTORS; DOPAMINE AB We examined the effect of (+/-)-gamma-vinyl GABA (GVG, Vigabatrin), an irreversible inhibitor of the enzyme GABA transaminase, on the acquisition and expression of cocaine-induced sensitization in albino male Sprague-Dawley rats. Animals received a single injection of 1 ml/kg i.p. of 0.9% saline or 15 mg/kg i.p. of (-)-cocaine and locomotor activity was assessed using automated locomotor cages and stereotyped behaviors were scored using a 4-point rating scale (Day 1). Subsequently, animals were given 15 mg/kg i.p. of cocaine every 48 h in their home cage for 1 week (Days 3, 5, and 7) and then given no treatment for 1 week. A challenge injection of 15 mg/kg i.p. of cocaine, but not vehicle, produced a significant increase in locomotor activity and stereotyped behaviors on Day 15 compared to animals that received cocaine on Day 1. Administration of 75 mg/kg i.p. of GVG 2.5 h before the cocaine injections did not significantly alter the acquisition of cocaine-induced locomotor sensitization. However, 150 mg/kg i.p. of GVG significantly attenuated the acquisition of cocaine-induced locomotor sensitization. Administration of 150 mg/kg i.p. of GVG 2.5 h before the cocaine challenge injection on Day 15 significantly attenuated the expression of cocaine-induced locomotor sensitization. Acquisition and expression of cocaine-induced sensitization of stereotypy was also significantly attenuated by 150 mg/kg i.p. of GVG. Since sensitization may be one of the factors involved in relapse to drug use, the present results, in combination with previous findings that GVG blocks the rewarding and incentive motivating effects of cocaine, suggest that GVG might prove useful in the treatment of cocaine addiction. (C) 2002 Wiley-Liss, Inc. C1 St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Hlth Sci, Jamaica, NY 11439 USA. NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. NYU, Sch Med, Dept Psychiat, New York, NY 10016 USA. RP Ashby, CR (reprint author), St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Hlth Sci, 8000 Utopia Pkwy, Jamaica, NY 11439 USA. OI Brodie, Jonathan/0000-0002-2254-8654 NR 77 TC 27 Z9 28 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 0887-4476 J9 SYNAPSE JI Synapse PD DEC 15 PY 2002 VL 46 IS 4 BP 240 EP 250 DI 10.1002/syn.10138 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 608GQ UT WOS:000178838200004 PM 12373739 ER PT J AU Li, RM Mannon, RB Kleiner, D Tsokos, M Bynum, M Kirk, AD Kopp, JB AF Li, RM Mannon, RB Kleiner, D Tsokos, M Bynum, M Kirk, AD Kopp, JB TI BK virus and SV40 co-infection in polyomavirus nephropathy SO TRANSPLANTATION LA English DT Article ID RENAL-ALLOGRAFT RECIPIENTS; LARGE-T-ANTIGEN; INTERSTITIAL NEPHRITIS; SIMIAN VIRUS-40; CHOROID-PLEXUS; DNA-SEQUENCES; SIMIAN-VIRUS-40; DISEASE; URINE; DIAGNOSIS AB Background.. Polyomavirus (PV) nephropathy has been attributed to reactivation of BK virus (BKV) or more rarely JC virus (JCV). The simian virus (SV) 40 is PV that was likely introduced into the human population through contaminated vaccines. The purpose of this study was to identify and characterize the PV that is associated with PV nephropathy. Methods. The clinical diagnosis of PV nephropathy (PVN) was made in patients with acute deterioration in renal function whose renal biopsies showed typical viral cytopathic changes in tubular epithelial cells and staining for PV T antigen. Polymerase chain reaction (PCR) amplification of DNA from peripheral blood mononuclear cells (PBMC), urinary cells, and renal biopsy tissue was performed using specific primers for the transcription control regions of BKV, JCV, and SV40, respectively. Results. Six cases of PV nephropathy were identified in 91 renal transplant recipients (7%). Immunosuppressive therapy was modified in all patients. Renal function stabilized or improved in four patients and deteriorated in two patients, and one patient has lost his allograft, after follow-up from 2 to 25 months. PCR detection demonstrated BKV genome in three of five PBMC samples, six of six urinary cell samples, and two of four renal biopsies. SV40 genome was detected in two of five PBMC samples, one of six urinary cell samples, and two of four renal biopsies. Infectious SV40 and BKV was demonstrated in CV-1 co-cultures using urine from one patient. JCV was not detected in any PVN sample. Co-infection with BKV and SV40 was found in two PVN patients. Urine samples obtained 12 months after transplant from 26 transplant recipients without PVN on simultaneous protocol renal biopsy were analyzed by PCR; BKV genome was demonstrated in 5 of 25 samples, JCV genome was demonstrated in 3 of 25 samples, and SV40 genome was demonstrated in 0 of 25 samples. Conclusion. The authors report molecular evidence that co-infection with BKV and SV40 occurs in renal transplant patients with PVN, suggesting that SV40 may contribute to PVN after renal transplant. C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NIDDKD, Transplantat & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NIH, Pathol Lab, Ctr Clin, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, 10-3N116, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012; OI Kleiner, David/0000-0003-3442-4453; Kopp, Jeffrey/0000-0001-9052-186X NR 27 TC 88 Z9 96 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2002 VL 74 IS 11 BP 1497 EP 1504 DI 10.1097/01.TP.0000042485.92082.5B PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 627FB UT WOS:000179921700004 PM 12490781 ER PT J AU Gleit, ZL Fuchimoto, Y Yamada, K Melendy, E Scheier-Dolberg, R Monajati, L Coburn, RC Neville, DM Sachs, DH Huang, CA AF Gleit, ZL Fuchimoto, Y Yamada, K Melendy, E Scheier-Dolberg, R Monajati, L Coburn, RC Neville, DM Sachs, DH Huang, CA TI Variable relationship between chimerism and tolerance after hematopoietic cell transplantation without myelosuppressive conditioning SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; WHOLE-BODY IRRADIATION; LARGE-ANIMAL-MODEL; MIXED CHIMERISM; ALLOGRAFT TOLERANCE; MINIATURE SWINE; MONOCLONAL-ANTIBODIES; PREPARATIVE REGIMEN; T-CELLS; INDUCTION AB Background. We have previously described a mixed chimerism protocol that avoids myelosuppressive conditioning and permits hematopoietic cell transplantation across MHC barriers without the need for whole body irradiation in miniature swine. Here, we report our current experience including animals conditioned without thymic irradiation, and we, attempt to define the relationship between long-term chimerism and stable tolerance in these animals. Methods. Recipient swine received in vivo T-cell depletion, with or without thymic irradiation on day -2. Cyclosporine was administered for 30 to 60 days beginning on day -1. A total of 1 to 2 x 10(10)/kg cytokine-mobilized donor hematopoietic cells were infused during 3 days. Chimerism was determined by flow cytometry. In vitro tolerance assays and donor-matched kidney transplantation were performed after cessation of cyclosporine. Results. Most recipients maintained stable chimerism (26 of 35) and were specifically tolerant to donor-matched cells in vitro regardless of whether they received thymic irradiation. Donor-matched kidney transplantations performed in chimeric animals without in vitro antidonor immune responses were accepted without immunosuppression. Some animals developed in vitro evidence of antidonor MHC responsiveness despite the persistence of donor cells in the peripheral blood. Donor-matched kidney transplantations performed in the face of these responses were rejected. Conclusions. These data indicate that this nonmyelosuppressive protocol can induce stable chimerism. and robust tolerance even in animals conditioned without thymic irradiation. However, the data also demonstrate that macrochimerism does not always correlate with tolerance. Lack of in vitro antidonor immune responses in chimeric animals is an important predictor of renal allograft acceptance in this model. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA 02129 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Huang, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, MGH E,Bldg 149-9019,13th St, Boston, MA 02129 USA. FU NCI NIH HHS [1R01 CA79989-01A1]; NHLBI NIH HHS [1R01 HL63430-01]; NIAID NIH HHS [1F32AI-10306] NR 24 TC 23 Z9 23 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD DEC 15 PY 2002 VL 74 IS 11 BP 1535 EP 1544 DI 10.1097/01.TP.0000041571.28969.FA PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 627FB UT WOS:000179921700010 PM 12490786 ER PT J AU Mulshine, JL Smith, RA Field, JK Hirsch, FR AF Mulshine, JL Smith, RA Field, JK Hirsch, FR TI Tobacco money: up in smoke? SO LANCET LA English DT Letter C1 NCI, Intervent Sect, Cell & Canc Biol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Univ Liverpool, Roy Castle Int Ctr, Liverpool L69 3BX, Merseyside, England. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. RP Mulshine, JL (reprint author), NCI, Intervent Sect, Cell & Canc Biol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD DEC 14 PY 2002 VL 360 IS 9349 BP 1979 EP 1980 DI 10.1016/S0140-6736(02)11880-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 626KC UT WOS:000179870200051 PM 12493299 ER PT J AU Zhu, J Nathan, C Jin, WW Sim, D Ashcroft, GS Wahl, SM Lacomis, L Erdjument-Bromage, H Tempst, P Wright, CD Ding, AH AF Zhu, J Nathan, C Jin, WW Sim, D Ashcroft, GS Wahl, SM Lacomis, L Erdjument-Bromage, H Tempst, P Wright, CD Ding, AH TI Conversion of proepithelin to epithelins: Roles of SLPI and elastase in host defense and wound repair SO CELL LA English DT Article ID LEUKOCYTE PROTEASE INHIBITOR; SECRETORY LEUKOPROTEASE INHIBITOR; PROTEINASE-INHIBITOR; HUMAN-NEUTROPHILS; EPITHELIN/GRANULIN PRECURSOR; BACTERIAL LIPOPOLYSACCHARIDE; GRANULIN/EPITHELIN PRECURSOR; 2-HYBRID SYSTEM; GENE-EXPRESSION; GROWTH-FACTORS AB Increased leukocyte elastase activity in mice lacking secretory leukocyte protease inhibitor (SLPI) leads to impaired wound healing due to enhanced activity of TGFbeta and perhaps additional mechanisms. Proepithelin (PEPI), an epithelial growth factor, can be converted to epithelins (EPIs) in vivo by unknown mechanisms with unknown consequences. We found that PEPI and EPIs exert opposing activities. EPIs inhibit the growth of epithelial cells but induce them to secrete the neutrophil attractant IL-8, while PEPI blocks neutrophil activation by tumor necrosis factor, preventing release of oxidants and proteases. SLPI and PEPI form complexes, preventing elastase from converting PEPI to EPIs. Supplying PEPI corrects the wound-healing defect in SLPI null mice. Thus, SLPI/elastase act via PEPI/EPIs to operate a switch at the interface between innate immunity and wound healing. C1 Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY 10021 USA. Cornell Univ, Program Pharmacol, Weill Grad Sch Med Sci, New York, NY 10021 USA. Cornell Univ, Program Immunol, Weill Grad Sch Med Sci, New York, NY 10021 USA. Cornell Univ, Program Mol Biol, Weill Grad Sch Med Sci, New York, NY 10021 USA. NIDCR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Program Mol Biol, New York, NY 10021 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Ding, AH (reprint author), Cornell Univ, Dept Microbiol & Immunol, Weill Med Coll, New York, NY 10021 USA. RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [P30 CA08748]; NIAID NIH HHS [AI46382]; NIGMS NIH HHS [GM61710] NR 70 TC 342 Z9 355 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 13 PY 2002 VL 111 IS 6 BP 867 EP 878 DI 10.1016/S0092-8674(02)01141-8 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 626GC UT WOS:000179862600012 PM 12526812 ER PT J AU Shumyatsky, GP Tsvetkov, E Malleret, G Vronskaya, S Hatton, M Hampton, L Battey, JF Dulac, C Kandel, ER Bolshakov, VY AF Shumyatsky, GP Tsvetkov, E Malleret, G Vronskaya, S Hatton, M Hampton, L Battey, JF Dulac, C Kandel, ER Bolshakov, VY TI Identification of a signaling network in lateral nucleus of amygdala important for inhibiting memory specifically related to learned fear SO CELL LA English DT Article ID LONG-TERM POTENTIATION; BOMBESIN-LIKE PEPTIDES; BASOLATERAL AMYGDALA; SYNAPTIC PLASTICITY; CA3-CA1 SYNAPSES; KINASE PATHWAYS; DEFICIENT MICE; MESSENGER-RNA; RECEPTOR; PROTEIN AB We identified the Grp gene, encoding gastrin-releasing peptide, as being highly expressed both in the lateral nucleus of the amygdala, the nucleus where associations for Pavlovian learned fear are formed, and in the regions that convey fearful auditory information to the lateral nucleus. Moreover, we found that GRP receptor (GRPR) is expressed in GABAergic interneurons of the lateral nucleus. GRP excites these interneurons and increases their inhibition of principal neurons. GRPR-deficient mice showed decreased inhibition of principal neurons by the interneurons, enhanced long-term potentiation (LTP), and greater and more persistent long-term fear memory. By contrast, these mice performed normally in hippocampus-dependent Morris maze. These experiments provide genetic evidence that GRP and its neural circuitry operate as a negative feedback regulating fear and establish a causal relationship between Grpr gene expression, LTP, and amygdala-dependent memory for fear. C1 Columbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, New York, NY 10032 USA. NINDS, NIH, Bethesda, MD 20892 USA. Harvard Univ, Howard Hughes Med Inst, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02478 USA. RP Kandel, ER (reprint author), Columbia Univ, Howard Hughes Med Inst, Ctr Neurobiol & Behav, 1051 Riverside Dr, New York, NY 10032 USA. RI Tsvetkov, Evgeny/B-6573-2016; Tsvetkov, Evgeny/C-1085-2016 OI Tsvetkov, Evgeny/0000-0002-6784-0907; Tsvetkov, Evgeny/0000-0001-9339-1677 FU NIDA NIH HHS [DA15098]; NINDS NIH HHS [NS44185] NR 49 TC 202 Z9 210 U1 0 U2 16 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD DEC 13 PY 2002 VL 111 IS 6 BP 905 EP 918 DI 10.1016/S0092-8674(02)01116-9 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 626GC UT WOS:000179862600015 PM 12526815 ER PT J AU Orlic, D Hill, JM Arai, AE AF Orlic, D Hill, JM Arai, AE TI Stem cells for myocardial regeneration SO CIRCULATION RESEARCH LA English DT Review DE stem cells; plasticity; ischemia; infarction; myocardial regeneration ID CARDIOVASCULAR MAGNETIC-RESONANCE; COLONY-STIMULATING FACTOR; CORONARY-ARTERY DISEASE; BONE-MARROW; IN-VIVO; CONTRACTILE FUNCTION; MAST-CELL; C-KIT; STRESS ECHOCARDIOGRAPHY; NONINVASIVE DETECTION AB Stem cells are being investigated for their potential use in regenerative medicine. A series of remarkable studies suggested that adult stem cells undergo novel patterns of development by a process referred to as transdifferentiation or plasticity. These observations fueled an exciting period of discovery and high expectations followed by controversy that emerged from data suggesting cell-cell fusion as an alternate interpretation for transdifferentiation. However, data supporting stem cell plasticity are extensive and cannot be easily dismissed. Myocardial regeneration is perhaps the most widely studied and debated example of stem cell plasticity. Early reports from animal and clinical investigations disagree on the extent of myocardial renewal in adults, but evidence indicates that cardiomyocytes are generated in what was previously considered a postmitotic organ. On the basis of postmortem microscopic analysis, it is proposed that renewal is achieved by stem cells that infiltrate normal and infarcted myocardium. To further understand the role of stem cells in regeneration, it is incumbent on us to develop instrumentation and technologies to monitor myocardial repair over time in large animal models. This may be achieved by tracking labeled stem cells as they migrate into myocardial infarctions. In addition, we must begin to identify the environmental cues that are needed for stem cell trafficking and we must define the genetic and cellular mechanisms that initiate transdifferentiation. Only then will we be able to regulate this process and begin to realize the full potential of stem cells in regenerative medicine. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Mol Biol Lab, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Orlic, D (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr 4442, Bethesda, MD 20892 USA. EM dorlic@nhgri.nih.gov NR 117 TC 212 Z9 264 U1 1 U2 24 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 DEC 13 PY 2002 VL 91 IS 12 BP 1092 EP 1102 DI 10.1161/01.RES.0000046045.00846.B0 PG 11 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 629JE UT WOS:000180045900004 PM 12480809 ER PT J AU Strutz, N Villmann, C Breitinger, HG Werner, M Wenthold, RJ Kizelsztein, P Teichberg, VI Hollmann, M AF Strutz, N Villmann, C Breitinger, HG Werner, M Wenthold, RJ Kizelsztein, P Teichberg, VI Hollmann, M TI Kainate-binding proteins are rendered functional ion channels upon transplantation of two short pore-flanking domains from a kainate receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLUTAMATE-RECEPTOR; LIGAND-BINDING; N-GLYCOSYLATION; NERVOUS-SYSTEM; ACID RECEPTORS; SUBUNIT; EXPRESSION; IDENTIFICATION; AGONIST; GENE AB Kainate-binding proteins belong to an elusive class of putative ionotropic glutamate receptors that to date have not been shown to form functional ion channels in heterologous expression systems, despite binding glutamatergic agonists with high affinity. To test the hypothesis that inefficient or interrupted signal transduction from the ligand-binding site via linker domains to the ion pore (gating) might be responsible for this apparent lack of function, we transplanted the short homologous linker sequences from the fully functional rat kainate receptor GluR6 into frog kainate-binding protein. We were able to generate chimeric receptors that are functional in the Xenopus oocyte expression system and in human embryonic kidney 293 cells. The linker domains A and B in particular appear to be crucial for gating, because a functional kainate-binding protein was observed when at least parts of both linkers were derived from GluR6. We speculate that to enable signal transduction from the ligand-binding site to the ion pore of the frog kainate-binding protein, the linker structure of the protein has to undergo an essential conformational alteration, possibly mediated by an as yet unknown subunit or modulatory protein. C1 Ruhr Univ Bochum, Dept Biochem Receptor Biochem 1, D-44780 Bochum, Germany. Univ Erlangen Nurnberg, Inst Biochem, D-91054 Erlangen, Germany. NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Strutz, N (reprint author), Ruhr Univ Bochum, Dept Biochem Receptor Biochem 1, D-44780 Bochum, Germany. NR 40 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 48035 EP 48042 DI 10.1074/jbc.M209647200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600010 PM 12370171 ER PT J AU Gao, ZG Hwang, D Bataille, F Lefevre, M York, D Quon, M Ye, JP AF Gao, ZG Hwang, D Bataille, F Lefevre, M York, D Quon, M Ye, JP TI Serine phosphorylation of insulin receptor substrate 1 by inhibitor kappa B kinase complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; TNF-ALPHA; OKADAIC ACID; PHOSPHATIDYLINOSITOL 3-KINASE; SKELETAL-MUSCLE; IKK-BETA; RESISTANCE; PATHWAY; IRS-1 AB Insulin resistance contributes importantly to the pathophysiology of type 2 diabetes mellitus. One mechanism mediating insulin resistance may involve the phosphorylation of serine residues in insulin receptor substrate-1 (IRS-1), leading to impairment in the ability of IRS-1 to activate downstream phosphatidylinositol 3-kinase-dependent pathways. Insulin-resistant states and serine phosphorylation of IRS-1 are associated with the activation of the inhibitor kappaB kinase (IKK) complex. However, the precise molecular mechanisms by which IKK may contribute to the development of insulin resistance are not well understood. In this study, using phosphospecific antibodies against rat IRS-1 phosphorylated at Ser(307) (equivalent to Ser(312) in human IRS-1), we observed serine phosphorylation of IRS-1 in response to TNF-alpha or calyculin A treatment that paralleled surrogate markers for IKK activation. The phosphorylation of human IRS-1 at Ser(312) in response to tumor necrosis factor-alpha was significantly reduced in cells pretreated with the IKK inhibitor 15 deoxy-prostaglandin J(2) as well as in cells derived from IKK knock-out mice. We observed interactions between endogenous IRS-1 and IKK in intact cells using a co-immunoprecipitation approach. Moreover, this interaction between IRS-1 and IKK in the basal state was reduced upon IKK activation and increased serine phosphorylation of IRS-1. Data from in vitro kinase assays using recombinant IRS-1 as a substrate were consistent with the ability of IRS-1 to function as a direct substrate for IKK with multiple serine phosphorylation sites in addition to Ser(312). Taken together, our data suggest that IRS-1 is a novel direct substrate for IKK and that phosphorylation of IRS-1 at Ser(312) (and other sites) by IKK may contribute to the insulin resistance mediated by activation of inflammatory pathways. C1 Louisiana State Univ, Pennington Biomed Res Ctr, Gene Regulat Lab, Baton Rouge, LA 70808 USA. NIH, Diabet Unit, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Ye, JP (reprint author), Louisiana State Univ, Pennington Biomed Res Ctr, Gene Regulat Lab, 6400 Perkins Rd, Baton Rouge, LA 70808 USA. RI Quon, Michael/B-1970-2008; Lefevre, Michael/B-5030-2014; OI Lefevre, Michael/0000-0002-2046-3593; Quon, Michael/0000-0002-9601-9915 NR 62 TC 419 Z9 436 U1 4 U2 27 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 48115 EP 48121 DI 10.1074/jbc.M209459200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600020 PM 12351658 ER PT J AU Mandrich, L Caputo, E Martin, BM Rossi, M Manco, G AF Mandrich, L Caputo, E Martin, BM Rossi, M Manco, G TI The Aes protein and the monomeric alpha-galactosidase from Escherichia coli form a non-covalent complex - Implications for the regulation of carbohydrate metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HORMONE-SENSITIVE LIPASE; ARCHAEON ARCHAEOGLOBUS-FULGIDUS; SEQUENCE SIMILARITY; TRANSCRIPTIONAL ACTIVATOR; THERMOPHILIC ESTERASE; THERMOSTABLE ESTERASE; HIGH-TEMPERATURE; MALTOSE SYSTEM; SUBFAMILY; EXPRESSION AB Aes, a 36-kDa acetylesterase from Escherichia coli, belongs to the hormone-sensitive lipase family, and it is involved in the regulation of MaIT, the transcriptional activator of the maltose regulon. The activity of MaIT is depressed through a direct protein-protein interaction with Aes. Although the effect is clear-cut, the meaning of this interaction and the conditions that trigger it still remain elusive. To perform a comparative thermodynamic study between the mesophilic Aes protein and two homologous thermostable enzymes, Aes was overexpressed in E. coli and purified. At the last step of the purification procedure the enzyme was eluted from a Mono Q HR 5/5 column as a major form migrating, anomalously, at 56 kDa on a calibrated Superdex 75 column. A minor peak that contains the Aes protein and a polypeptide of 50 kDa was also detected. By a combined analysis of size-exclusion chromatography and surface-enhanced laser desorption ionization-time of flight mass spectrometry, it was possible to demonstrate the presence in this peak of a stable 87-kDa complex containing the Aes protein itself and the 50-kDa polypeptide in a 1:1 ratio. The homodimeric molecular species of Aes and of the 50-kDa polypeptide were also detected. The esterase activity associated with the 87-kDa complex, when assayed with p-nitrophenyl butanoate as substrate, proved 6-fold higher than the activity of the major Aes form of 56 kDa. Amino-terminal sequencing highlighted that the 50-kDa partner of Aes in the complex was the alpha-galactosidase from E. coli. The E. coli cells harboring plasmid pT7-SCII-aes and, therefore, expressing Aes were hampered in their growth on a minimal medium containing raffinose as a sole carbon source. Because alpha-galactosidase is involved in the metabolism of raffinose, the above findings suggest a potential role of Aes in the regulation of carbohydrate metabolism in E. coli. C1 CNR, Ist Biochim Prot, I-80131 Naples, Italy. NIMH, Unit Mol Struct, Bethesda, MD 20892 USA. RP Manco, G (reprint author), CNR, Ist Biochim Prot, Via P Castellino 111, I-80131 Naples, Italy. EM manco@dafne.ibpe.na.cnr.it OI CAPUTO, EMILIA/0000-0002-6485-8802; Manco, Giuseppe/0000-0001-6191-3952 NR 32 TC 15 Z9 16 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 48241 EP 48247 DI 10.1074/jbc.M207398200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600037 PM 12374803 ER PT J AU Cai, H Li, ZM Dikalov, S Holland, SM Hwang, JN Jo, H Dudley, SC Harrison, DG AF Cai, H Li, ZM Dikalov, S Holland, SM Hwang, JN Jo, H Dudley, SC Harrison, DG TI NAD(P)H oxidase-derived hydrogen peroxide mediates endothelial nitric oxide production in response to angiotensin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE CELLS; PROTEIN-KINASE; TYROSINE PHOSPHORYLATION; SUPEROXIDE PRODUCTION; RECEPTOR STIMULATION; NADPH OXIDASE; ACTIVATION; INCREASES; GENERATION; EXPRESSION AB Recently, it has been shown that the exogenous addition of hydrogen peroxide (H2O2) increases endothelial nitric oxide (NO.) production. The current study is designed to determine whether endogenous levels of H2O2 are ever sufficient to stimulate NO. production in intact endothelial cells. NO. production was detected by a NO.- specific microelectrode or by an electron spin resonance spectroscopy using Fe2+-(DETC)(2) as a NO.-specific spin trap. The addition of H2O2 to bovine aortic endothelial cells caused a potent and dose-dependent increase in NO. release. Incubation with angiotensin II (10(-7) mol) elevated intracellular H2O2 levels, which were attenuated with PEG-catalase. Angiotensin II increased NO' production by 2-fold, and this was prevented by Losartan and by PEG-catalase, suggesting a critical role of AT1 receptor and H2O2 in this response. In contrast, NO. production evoked by either bradykinin or calcium ionophore A23187 was unaffected by PEG-catalase. As in bovine aortic endothelial cells, angiotensin II doubled NO. production in aortic endothelial cells from C57BL/6 mice but had no effect on NO. production in endothelial cells from p47(phox-/-) mice. In contrast, A23187 stimulated NO. production to a similar extent in endothelial cells from wild-type and p47(phox-/-) mice. In summary, the present study provides direct evidence that endogenous H2O2, derived from the NAD(P)H oxidase, mediates endothelial NO. production in response to angiotensin II. Under disease conditions associated with elevated levels of angiotensin II, this response may represent a compensatory mechanism. Because angiotensin II also stimulates O-2((&BULL;) over bar) production from the NAD(P)H oxidase, the H2O2 stimulation of NO. may facilitate peroxynitrite formation in response to this octapeptide. C1 Emory Univ, Sch Med, Div Cardiol, Dept Med, Atlanta, GA 30322 USA. Georgia Tech, Dept Biomed Engn, Atlanta, GA 30322 USA. Vet Affairs Med Ctr, Atlanta, GA 30033 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Cai, H (reprint author), Emory Univ, Sch Med, Div Cardiol, Dept Med, Suite 319,Woodruff Mem Res Bldg,1639 Pierce Dr, Atlanta, GA 30322 USA. FU NHLBI NIH HHS [HL64828, HL39006, HL59248] NR 44 TC 128 Z9 136 U1 1 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 DEC 13 PY 2002 VL 277 IS 50 BP 48311 EP 48317 DI 10.1074/jbc.M208884200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600046 PM 12377764 ER PT J AU Guo, YS Cheng, JZ Jin, GF Gutkind, JS Hellmich, MR Townsend, CM AF Guo, YS Cheng, JZ Jin, GF Gutkind, JS Hellmich, MR Townsend, CM TI Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways - Evidence for involvement of Erk5 kinase and transactivation of the epidermal growth factor receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; JUN NH2-TERMINAL KINASE; COLON-CANCER-CELLS; TRANSCRIPTION FACTOR; EGF RECEPTOR; CCKB/GASTRIN RECEPTOR; INDEPENDENT PATHWAY; GENE-EXPRESSION; FACTOR-ALPHA; FACTOR-I AB Gastrin is a hormone produced by G-cells in the normal gastric antrum. However, colorectal carcinoma cells may aberrantly produce gastrin and exhibit increased expression of cholecystokinin B (CCK-B)/gastrin receptors. Gastrin is trophic for the normal gastric oxyntic mucosa and exerts a growth-promoting action on gastrointestinal malignancy. Thus, gastrin may act as an autocrine/paracrine or endocrine factor in the initiation and progression of colorectal carcinoma. The molecular mechanisms involved have not been elucidated. Hypergastrinemia induced by Helicobacter pylori infection is associated with increased cyclooxygenase-2 (COX-2) expression in gastric and colorectal tissues, suggesting the possibility that gastrin up-regulates COX-2 expression in these tissues; this has not been confirmed. We report here that gastrin significantly increases the expression of COX-2 mRNA and protein, the activity of the COX-2 promoter, and the release of prostaglandin E-2 from a rat intestinal epithelial cell line transfected with the CCK-B receptor. These actions were dependent upon the activation of multiple MAPK signal pathways, including ERK5 kinase; transactivation of the epidermal growth factor receptor; and the increased expression and activities of transcription factors ELK-1, activating transcription factor-2, c-Fos, c-Jun, activator protein-1, and myocyte enhancer factor-2. Thus, our findings identify the signaling pathways coupling the CCK-B receptor with up-regulation of COX-2 expression. This effect may contribute to this hormone-dependent gastrointestinal carcinogenesis, especially in the colon. C1 Univ Texas, Med Branch, Dept Surg, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Ophthalmol, Galveston, TX 77555 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Guo, YS (reprint author), Univ Texas, Med Branch, Dept Surg, 301 Univ Blvd, Galveston, TX 77555 USA. RI Gutkind, J. Silvio/A-1053-2009 FU NIDDK NIH HHS [P01 DK35608, R01 DK48345] NR 50 TC 70 Z9 70 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 48755 EP 48763 DI 10.1074/jbc.M209016200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600102 PM 12239223 ER PT J AU Nie, ZZ Stanley, KT Stauffer, S Jacques, KM Hirsch, DS Takei, J Randazzo, PA AF Nie, ZZ Stanley, KT Stauffer, S Jacques, KM Hirsch, DS Takei, J Randazzo, PA TI AGAP1, an endosome-associated, phosphoinositide-dependent ADP-ribosylation factor GTPase-activating protein that affects actin cytoskeleton SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLECKSTRIN HOMOLOGY DOMAINS; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; EXCHANGE FACTORS; CHOLERA-TOXIN; ARF6 GTPASE; FAMILY; RAS; BINDING; ASAP1 AB We have identified three members of the AGAP subfamily of ASAP family ADP-ribosylation factor GTPase-activating proteins (Arf GAPs). In addition to the Arf GAP domain, these proteins contain GTP-binding protein-like, ankyrin repeat and pleckstrin homology domains. Here, we have characterized the ubiquitously expressed AGAP1/KIAA1099. AGAP1 had Arf GAP activity toward Arf1>Arf5>Arf6. Phosphatidylinositol 4,5-bisphosphate and phosphatidic acid synergistically stimulated GAP activity. As found for other ASAP family Arf GAPs, the pleckstrin homology domain was necessary for activity. Deletion of the GTP-binding protein-like domain affected lipid dependence of Arf GAP activity. In vivo effects of AGAP1 were distinct from other ASAP family Arf GAPs. Overexpressed AGAP1 induced the formation of and was associated with punctate structures containing the endocytic markers transferrin and Rab4. AP1 was redistributed from the trans-Golgi to the punctate structures. Like other ASAP family members, AGAP1 overexpression inhibited the formation of PDGF-induced ruffles. However, distinct from other ASAP family members, AGAP1 also induced the loss of actin stress fibers. Thus, AGAP1 is a phosphoinositide-dependent Arf GAP that impacts both the endocytic compartment and actin. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 4118, Bethesda, MD 20892 USA. NR 45 TC 64 Z9 66 U1 2 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 48965 EP 48975 DI 10.1074/jbc.M202969200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600129 PM 12388557 ER PT J AU Mulligan-Kehoe, MJ Kleinman, HK Drinane, M Wagner, RJ Wieland, C Powell, RJ AF Mulligan-Kehoe, MJ Kleinman, HK Drinane, M Wagner, RJ Wieland, C Powell, RJ TI A truncated plasminogen activator inhibitor-1 protein blocks the availability of heparin-binding vascular endothelial growth factor A isoforms SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID REACTIVE-CENTER LOOP; TISSUE-TYPE; STRUCTURAL REQUIREMENTS; TUMOR ANGIOGENESIS; FACTOR-RECEPTOR; CELL APOPTOSIS; UROKINASE-TYPE; SITE LOOP; VITRONECTIN; ANGIOSTATIN AB We have made deletions of the porcine plasminogen activator inhibitor-1 (PAI-1) gene to obtain recombinant truncated PAI-1 proteins to examine functions of the PAI-1 isoforms. We previously reported that one recombinant truncated protein, rPAI-1(23), induces the formation of angiostatin by cleaving plasmin. The rPAI-1(23) protein is also able to bind urokinase plasminogen activator and plasminogen and then reduce the amount of plasmin that is formed. We have now prepared three different truncated rPAI-1 proteins and demonstrate that PAI-1 conformations control the release of heparin-binding vascular endothelial growth factor (VEGF) isoforms. The rPAI-1(23) isoform can regulate the functional activity of heparan sulfate-binding VEGF-A isoforms by blocking the activation of VEGF from heparan sulfate. The rPAI-1(23) conformation induced extensive apoptosis in cultured endothelial cells and thus reduced the number of proliferating cells. The rPAI-1(23) isoform inhibited migration of VEGF-stimulated sprouting from chick aortic rings by 65%, thus displaying a role in anti-angiogenic mechanisms. This insight into anti-angiogenic functions related to PAI-1 conformational changes could provide potential intervention points in angiogenesis associated with atherosclerotic plaques and cancer. C1 Dartmouth Coll, Dartmouth Med Sch, Vasc Surg Sect, Dept Surg, Hanover, NH 03756 USA. NIDCR, Craniofacial Dev Biol & Res Branch, NIH, Bethesda, MD 20892 USA. RP Mulligan-Kehoe, MJ (reprint author), Dartmouth Coll Sch Med, Borwell 530 E,1 Med Ctr Dr, Lebanon, NH 03756 USA. FU NHLBI NIH HHS [R01-HL59590] NR 77 TC 9 Z9 11 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 13 PY 2002 VL 277 IS 50 BP 49077 EP 49089 DI 10.1074/jbc.M208757200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624YK UT WOS:000179789600142 PM 12381729 ER PT J AU El Setouhy, M Agbenyega, T Anto, F Clerk, CA Koram, KA English, M Molyneux, C Peshu, N English, M Molyneux, C Juma, R Kumwend, N Mfutso-Bengu, J Molyneux, M Taylor, T Taylor, T Diarra, DA Maiga, S Sylla, M Youssouf, D Falade, CO Gbadegesin, S Lie, R Mugusi, F Ngassapa, D Ecuru, J Talisuna, A Emanuel, E Grady, C Wendler, D Higgs, E Plowe, C Sugarman, J AF El Setouhy, M Agbenyega, T Anto, F Clerk, CA Koram, KA English, M Molyneux, C Peshu, N English, M Molyneux, C Juma, R Kumwend, N Mfutso-Bengu, J Molyneux, M Taylor, T Taylor, T Diarra, DA Maiga, S Sylla, M Youssouf, D Falade, CO Gbadegesin, S Lie, R Mugusi, F Ngassapa, D Ecuru, J Talisuna, A Emanuel, E Grady, C Wendler, D Higgs, E Plowe, C Sugarman, J CA 2001 Conf Ethical Aspects Res Dev TI Fair benefits for research in developing countries SO SCIENCE LA English DT Editorial Material ID CLINICAL RESEARCH; TRIALS; WORLD C1 Ain Shams Univ, Cairo, Egypt. Sch Med Sci, Kumasi, Ghana. Minist Hlth, Navrongo, Ghana. Univ Ghana, Legon, Ghana. Kenya Govt Med Res Ctr, Kilifi, Kenya. Wellcome Trust Res Labs, Kilifi, Kenya. KEMRI, Nairobi, Kenya. Univ Malawi, Coll Med, Blantyre, Malawi. Michigan State Univ, Coll Osteopath Med, E Lansing, MI 48824 USA. Univ Mali, Barnako, Mali. Eglise Protestante Barnako Coura, Barnako, Mali. Univ Ibadan, Coll Med, Ibadan, Nigeria. Howard Univ, Washington, DC 20059 USA. Univ Bergen, N-5020 Bergen, Norway. Muhimbili Univ, Coll Hlth Sci, Dar Es Salaam, Tanzania. Uganda Natl Council Sci & Technol, Kampala, Uganda. Minist Hlth, Kampala, Uganda. NIAID, Dept Clin Bioeth & Res, NIH, Bethesda, MD 20892 USA. NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Duke Univ, Raleigh, NC USA. RP Emanuel, E (reprint author), Ain Shams Univ, Cairo, Egypt. NR 11 TC 52 Z9 54 U1 0 U2 5 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD DEC 13 PY 2002 VL 298 IS 5601 BP 2133 EP 2134 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624RA UT WOS:000179773700026 ER PT J AU Kwong, PD Doyle, ML Casper, DJ Cicala, C Leavitt, SA Majeed, S Steenbeke, TD Venturi, M Chaiken, I Fung, M Katinger, H Parren, PWLH Robinson, J Van Ryk, D Wang, LP Burton, DR Freire, E Wyatt, R Sodroski, J Hendrickson, WA Arthos, J AF Kwong, PD Doyle, ML Casper, DJ Cicala, C Leavitt, SA Majeed, S Steenbeke, TD Venturi, M Chaiken, I Fung, M Katinger, H Parren, PWLH Robinson, J Van Ryk, D Wang, LP Burton, DR Freire, E Wyatt, R Sodroski, J Hendrickson, WA Arthos, J TI HIV-1 evades antibody-mediated neutralization through conformational masking of receptor-binding sites SO NATURE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODY; TYPE-1 GP120; EFFICIENT NEUTRALIZATION; CELLS; RETROVIRUS; EPITOPES; COMPLEX; FUSION AB The ability of human immunodeficiency virus (HIV-1) to persist and cause AIDS is dependent on its avoidance of antibody-mediated neutralization. The virus elicits abundant, envelope-directed antibodies that have little neutralization capacity(1). This lack of neutralization is paradoxical, given the functional conservation and exposure of receptor-binding sites on the gp120 envelope glycoprotein, which are larger than the typical antibody footprint(2) and should therefore be accessible for antibody binding. Because gp120-receptor interactions involve conformational reorganization(3), we measured the entropies of binding for 20 gp120-reactive antibodies. Here we show that recognition by receptor-binding-site antibodies induces conformational change. Correlation with neutralization potency and analysis of receptor-antibody thermodynamic cycles suggested a receptor-binding-site 'conformational masking' mechanism of neutralization escape. To understand how such an escape mechanism would be compatible with virus-receptor interactions, we tested a soluble dodecameric receptor molecule and found that it neutralized primary HIV-1 isolates with great potency, showing that simultaneous binding of viral envelope glycoproteins by multiple receptors creates sufficient avidity to compensate for such masking. Because this solution is available for cell-surface receptors but not for most antibodies, conformational masking enables HIV-1 to maintain receptor binding and simultaneously to resist neutralization. C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NIAID, 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. GlaxosmithKline Pharmaceut, Dept Biol Struct, King Of Prussia, PA 19406 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Tanox Biosyst Inc, Cell Biol, Houston, TX 77025 USA. Univ Agr & Forestry, Inst Appl Microbiol, A-1190 Vienna, Austria. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Kwong, PD (reprint author), NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. OI Parren, Paul/0000-0002-4365-3859 NR 30 TC 562 Z9 584 U1 1 U2 27 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 12 PY 2002 VL 420 IS 6916 BP 678 EP 682 DI 10.1038/nature01188 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624GK UT WOS:000179751800048 PM 12478295 ER PT J AU Gilman, AG Simon, MI Bourne, HR Harris, BA Long, R Ross, EM Stull, JT Taussig, R Bourne, HR Arkin, AP Cobb, MH Cyster, JG Devreotes, PN Ferrell, JE Fruman, D Gold, M Weiss, A Stull, JT Berridge, MJ Cantley, LC Catterall, WA Coughlin, SR Olson, EN Smith, TF Brugge, JS Botstein, D Dixon, JE Hunter, T Lefkowitz, RJ Pawson, AJ Sternberg, PW Varmus, H Subramaniam, S Sinkovits, RS Li, J Mock, D Ning, YH Saunders, B Sternweis, PC Hilgemann, D Scheuermann, RH DeCamp, D Hsueh, R Lin, KM Ni, Y Seaman, WE Simpson, PC O'Connell, TD Roach, T Simon, MI Choi, S Eversole-Cire, P Fraser, I Mumby, MC Zhao, YM Brekken, D Shu, HJ Meyer, T Chandy, G Do Heo, W Liou, J O'Rourke, N Verghese, M Mumby, SM Han, HP Brown, HA Forrester, JS Ivanova, P Milne, SB Casey, PJ Harden, TK Arkin, AP Doyle, J Gray, ML Meyer, T Michnick, S Schmidt, MA Toner, M Tsien, RY Natarajan, M Ranganathan, R Sambrano, GR AF Gilman, AG Simon, MI Bourne, HR Harris, BA Long, R Ross, EM Stull, JT Taussig, R Bourne, HR Arkin, AP Cobb, MH Cyster, JG Devreotes, PN Ferrell, JE Fruman, D Gold, M Weiss, A Stull, JT Berridge, MJ Cantley, LC Catterall, WA Coughlin, SR Olson, EN Smith, TF Brugge, JS Botstein, D Dixon, JE Hunter, T Lefkowitz, RJ Pawson, AJ Sternberg, PW Varmus, H Subramaniam, S Sinkovits, RS Li, J Mock, D Ning, YH Saunders, B Sternweis, PC Hilgemann, D Scheuermann, RH DeCamp, D Hsueh, R Lin, KM Ni, Y Seaman, WE Simpson, PC O'Connell, TD Roach, T Simon, MI Choi, S Eversole-Cire, P Fraser, I Mumby, MC Zhao, YM Brekken, D Shu, HJ Meyer, T Chandy, G Do Heo, W Liou, J O'Rourke, N Verghese, M Mumby, SM Han, HP Brown, HA Forrester, JS Ivanova, P Milne, SB Casey, PJ Harden, TK Arkin, AP Doyle, J Gray, ML Meyer, T Michnick, S Schmidt, MA Toner, M Tsien, RY Natarajan, M Ranganathan, R Sambrano, GR CA Alliance Cellular Signaling TI Overview of the Alliance for Cellular Signaling SO NATURE LA English DT Editorial Material AB The Alliance for Cellular Signaling is a large-scale collaboration designed to answer global questions about signalling networks. Pathways will be studied intensively in two cells-B lymphocytes (the cells of the immune system) and cardiac myocytes-to facilitate quantitative modelling. One goal is to catalyse complementary research in individual laboratories; to facilitate this, all alliance data are freely available for use by the entire research community. C1 Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Physiol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Mol Biol & Oncol, Dallas, TX 75390 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. CALTECH, Howard Hughes Med Inst, Dept Biol, Pasadena, CA 91125 USA. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Cardiovasc Res, San Francisco, CA 94143 USA. Aventis Pharmaceut, Bridgewater, NJ 08807 USA. NIGMS, Pharmacol Physiol & Biol Chem Div, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, EO Lawrence Berkeley Natl Lab, Dept Bioengn, Berkeley, CA 94720 USA. Univ Calif Berkeley, EO Lawrence Berkeley Natl Lab, Dept Chem, Berkeley, CA 94720 USA. Johns Hopkins Univ, Dept Cell Biol & Anat, Baltimore, MD 21205 USA. Stanford Univ, Sch Med, Ctr Clin Sci Res, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada. Babraham Inst, Cambridge CB2 4AT, England. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Univ Washington, Sch Med, Dept Pharmacol, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Boston Univ, BMERC, Boston, MA 02215 USA. Univ Michigan, Sch Med, Dept Biol Chem, Ann Arbor, MI 48109 USA. Salk Inst Biol Studies, San Diego, CA 92186 USA. Duke Univ, Med Ctr, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Diego, San Diego Supercomp Ctr, La Jolla, CA 92037 USA. Vet Affairs Med Ctr, Dept Rheumatol, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, Dept Cardiol, San Francisco, CA 94121 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA. MIT, Harvard MIT Div Hlth Sci & Technol, Dept Elect & Med Engn, Cambridge, MA 02139 USA. MIT, Dept Elect Engn & Comp Sci, Dept Elect & Med Engn, Cambridge, MA 02139 USA. Univ Montreal, Dept Biochem, Montreal, PQ H3C 3J7, Canada. Shriners Burn Hosp, Boston, MA 02114 USA. Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. RP Gilman, AG (reprint author), Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. RI Arkin, Adam/A-6751-2008; Brekken, Deirdre/I-7999-2012; Ivanova, Pavlina/K-8307-2012; Cantley, Lewis/D-1800-2014; O'Connell, Timothy/D-5048-2013; OI Arkin, Adam/0000-0002-4999-2931; Cantley, Lewis/0000-0002-1298-7653; Brekken, Deirdre/0000-0003-2790-0108; Natarajan, Madhusudan/0000-0003-1607-2917; Cobb, Melanie/0000-0003-0833-5473 FU NCI NIH HHS [T32 CA121938] NR 0 TC 343 Z9 346 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 12 PY 2002 VL 420 IS 6916 BP 703 EP 706 DI 10.1038/nature01304 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624GK UT WOS:000179751800054 PM 12478301 ER PT J AU Becerra, SP Amaral, J AF Becerra, SP Amaral, J TI Erythropoietin - An endogenous retinal survival factor SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 NEI, Bethesda, MD 20892 USA. RP Becerra, SP (reprint author), NEI, Bethesda, MD 20892 USA. NR 5 TC 58 Z9 66 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 12 PY 2002 VL 347 IS 24 BP 1968 EP 1970 DI 10.1056/NEJMcibr022629 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 623ZX UT WOS:000179735800012 PM 12477950 ER PT J AU Stevnsner, T Nyaga, S de Souza-Pinto, NC van der Horst, GTJ Gorgels, TGMF Hogue, BA Thorslund, T Bohr, VA AF Stevnsner, T Nyaga, S de Souza-Pinto, NC van der Horst, GTJ Gorgels, TGMF Hogue, BA Thorslund, T Bohr, VA TI Mitochondrial repair of 8-oxoguanine is deficient in Cockayne syndrome group B SO ONCOGENE LA English DT Article DE base excision repair; oxidative damage; mitochondria; Cockayne syndrome ID RNA-POLYMERASE-II; TRANSCRIPTION-COUPLED REPAIR; OXIDATIVE BASE DAMAGE; HAMSTER OVARY CELLS; INDUCED DNA-DAMAGE; ACTIVE GENES; PREFERENTIAL REPAIR; INDUCED APOPTOSIS; FACTOR CSB/ERCC6; EXCISION-REPAIR AB Reactive oxygen species, which are prevalent in mitochondria, cause oxidative DNA damage including the mutagenic DNA lesion 7,8-dihydroxyguanine (8-oxoG). Oxidative damage to mitochondrial DNA has been implicated as a causative factor in a wide variety of degenerative diseases, and in cancer and aging. 8-oxoG is repaired efficiently in mammalian mitochondrial DNA by enzymes in the base excision repair pathway, including the 8-oxoguanine glycosylase (OGG1), which incizes the lesion in the first step of repair. Cockayne syndrome (CS) is a segmental premature aging syndrome in humans that has two complementation groups, CSA and CSB. Previous studies showed that CSB-deficient cells have reduced capacity to repair 8-oxoG. This study examines the role of the CSB gene in regulating repair of 8-oxoG in mitochondrial DNA in human and mouse cells. 8-oxoG repair was measured in liver cells from CSB deficient mice and in human CS-B cells carrying expression vectors for wild type or mutant forms of the human CSB gene. For the first time we report that CSB stimulates repair of 8-oxoG in mammalian mitochondrial DNA. Furthermore, evidence is presented to support the hypothesis that wild type CSB regulates expression of OGG1. C1 NIA, Lab Mol Gerontol, IRP, NIH, Baltimore, MD 21224 USA. Aarhus Univ, Dept Mol Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus C, Denmark. Erasmus Univ, Ctr Biomed Genet, Ctr Genet Med, Dept Cell Biol & Genet, NL-3000 DR Rotterdam, Netherlands. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, IRP, NIH, Box 1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Souza-Pinto, Nadja/C-3462-2013; van der Horst, Gijsbertus/E-3661-2015; OI Souza-Pinto, Nadja/0000-0003-4206-964X; Thorslund, Tina/0000-0001-9207-0070 NR 48 TC 69 Z9 71 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 12 PY 2002 VL 21 IS 57 BP 8675 EP 8682 DI 10.1038/sj.onc.1205994 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 623ZG UT WOS:000179734400001 PM 12483520 ER PT J AU Kalaitzidis, D Davis, RE Rosenwald, A Staudt, LM Gilmore, TD AF Kalaitzidis, D Davis, RE Rosenwald, A Staudt, LM Gilmore, TD TI The human B-cell lymphoma cell line RC-K8 has multiple genetic alterations that dysregulate the Rel/NF-kappa B signal transduction pathway SO ONCOGENE LA English DT Article DE RC-K8; c-Rel; Rel; Rel-nrg; NF-kappa B; I kappa B ID C-REL; GASTROINTESTINAL-TRACT; TRANSCRIPTION FACTORS; HODGKINS-DISEASE; ALPHA-GENE; V-REL; MUTATIONS; EXPRESSION; PHOSPHORYLATION; TRANSFORMATION AB The human large B-cell lymphoma cell line RC-K8 has a rearranged REL locus that directs the production of a chimeric protein, termed REL-NRG (Non-Rel Gene). In this study, we show that RC-K8 cells have constitutively nuclear heterodimeric and homodimeric DNA-binding complexes that consist of p50, REL, and REL-NRG. In vitro, IkappaBalpha can block the DNA-binding activity of wildtype REL homodimers but not REL-NRG homodimers. In vivo, REL-NRG cannot activate transcription of a kappaB site reporter plasmid, suggesting that it is a transcription repressing or blocking REL protein. By Western blotting, no IkappaBalpha protein can be detected in extracts of RC-K8 cells. The absence of IkappaBalpha protein in RC-K8 cells appears to be due to mutations that cause premature termination of translation in three of the four copies of the IKBA gene in RC-K8 cells. Re-expression of wild-type IkappaBalpha or a super-repressor form of IkappaBalpha in RC-K8 cells is cytotoxic; in contrast, expression of a dominant-negative form of IkappaB kinase does not affect the growth of RC-K8 cells. By cDNA microarray analysis, a number of previously identified Rel/NF-kappaB target genes are overexpressed in RC-K8 cells, consistent with there being transcriptionally active REL complexes. Taken together, our results suggest that the growth of RC-K8 cells is dependent on the activity of nuclear wild-type REL dimers, while the contribution of REL-NRG to the transformed state of RC-K8 cells is less clear. Nevertheless, the RC-K8 cell line is the first tumor cell line identified with mutations in genes encoding multiple proteins in the Rel/NF-kappaB signal transduction pathway. C1 Boston Univ, Dept Biol, Boston, MA 02215 USA. NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gilmore, TD (reprint author), Boston Univ, Dept Biol, 5 Cummington St, Boston, MA 02215 USA. FU NCI NIH HHS [CA47763]; NICHD NIH HHS [T32-HD07387] NR 45 TC 38 Z9 38 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 12 PY 2002 VL 21 IS 57 BP 8759 EP 8768 DI 10.1038/sj.onc.1206033 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 623ZG UT WOS:000179734400010 PM 12483529 ER PT J AU Curino, A Mitola, DJ Aaronson, H McMahon, GA Raja, K Keegan, AD Lawrence, DA Bugge, TH AF Curino, A Mitola, DJ Aaronson, H McMahon, GA Raja, K Keegan, AD Lawrence, DA Bugge, TH TI Plasminogen promotes sarcoma growth and suppresses the accumulation of tumor-infiltrating macrophages SO ONCOGENE LA English DT Review DE fibrosarcoma; tumor-infiltrating macrophages; plasminogen activator; stroma ID RECEPTOR-BOUND UROKINASE; LEWIS LUNG-CARCINOMA; SPONTANEOUS METASTASIS MODEL; SQUAMOUS-CELL CARCINOMA; GENE-INACTIVATED MICE; HUMAN COLON-CANCER; LATENT TGF-BETA; ACTIVATOR INHIBITOR-1; DEFICIENT MICE; BREAST-CANCER AB The specific functions of plasminogen, stromal plasminogen activator, stromal plasminogen activator receptor, and stromal plasminogen activator inhibitor in the progression of the murine soft tissue sarcoma, T241 were investigated. Negation of plasminogen to the tumor blunted the orthotopic growth of the sarcoma in syngeneic mice. The reduced tumor growth was associated with a dramatic increase in tumor-infiltrating F4/80-positive macrophages and a diminution of vessel density, but not with obvious differences in fibrin and collagen deposition, or invasiveness of the tumor. Ablation of plasminogen activation by the tumor stroma only modestly impaired the prolonged growth of the sarcoma, suggesting that tumor cell-produced plasminogen activator is sufficient to mediate productive plasminogen activation. Plasminogen facilitated sarcoma progression, angiogenesis, and suppression of macrophage infiltration in the absence of either stromal urokinase plasminogen activator receptor or stromal plasminogen activator inhibitor. These data demonstrate that tumor cell-produced plasminogen activator and host plasminogen cooperate to facilitate soft tissue sarcoma growth and suppress the accumulation of tumor-infiltrating macrophages. C1 Natl Inst Dent Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Amer Red Cross, Dept Immunol, Rockville, MD 20855 USA. Amer Red Cross, Dept Vasc Biol, Rockville, MD 20855 USA. RP Bugge, TH (reprint author), Natl Inst Dent Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. FU NHLBI NIH HHS [P01 HL54710, R01 HL55747] NR 113 TC 20 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD DEC 12 PY 2002 VL 21 IS 57 BP 8830 EP 8842 DI 10.1038/sj.onc.1205951 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 623ZG UT WOS:000179734400016 PM 12483535 ER PT J AU Cooper, GS AF Cooper, GS TI Hormone replacement following early menopause SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID AGE C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Cooper, GS (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 11 PY 2002 VL 288 IS 22 BP 2824 EP 2825 DI 10.1001/jama.288.22.2824 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 623YM UT WOS:000179732600024 PM 12472322 ER PT J AU Graziano, G Lee, B AF Graziano, G Lee, B TI Hydration entropy change from the hard sphere model SO BIOPHYSICAL CHEMISTRY LA English DT Article DE entropy; hydration; hard sphere mixture; hydrophobicity ID SCALED-PARTICLE THEORY; HYDROPHOBIC HYDRATION; NONPOLAR SOLUTES; CAVITY FORMATION; SIZE DEPENDENCE; FREE-ENERGIES; THERMODYNAMIC PROPERTIES; SOLVENT REORGANIZATION; MOLECULAR LIQUIDS; HYDROGEN-BONDS AB The gas to liquid transfer entropy change for a pure non-polar liquid can be calculated quite accurately using a hard sphere model that obeys the Camahan-Starling equation of state. The same procedure fails to produce a reasonable value for hydrogen bonding liquids such as water, methanol and ethanol. However, the size of the molecules increases when the hydrogen bonds are turned off to produce the hard sphere system and the volume packing density rises. We show here that the hard sphere system that has this increased packing density reproduces the experimental transfer entropy values rather well. The gas to water transfer entropy values for small non-polar hydrocarbons is also not reproduced by a hard sphere model, whether one uses the normal (2.8 Angstrom diameter) or the increased (3.2 Angstrom) size for water. At least part of the reason that the hard sphere model with 2.8 Angstrom size water produces too small entropy change is that the size of water is too small for a system without hydrogen bonds. The reason that the 3.2 Angstrom model also produces too small entropy values is that this is an overly crowded system and that the free volume introduced in the system by the addition of a solute molecule produces too much of a relief to this crowding. A hard sphere model, in which the free volume increase is limited by requiring that the average surface-to-surface distance between the solute and water molecules is the same as that between the increased-size water molecules, does approximately reproduce the experimental hydration entropy values. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Sannio, Fac Sci, I-82100 Benevento, Italy. RP Lee, B (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 5120,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. OI Graziano, Giuseppe/0000-0001-6935-8172 NR 53 TC 12 Z9 12 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC 10 PY 2002 VL 101 BP 173 EP 185 AR PII S0301-4622(02)00199-0 DI 10.1016/S0301-4622(02)00199-0 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 631JU UT WOS:000180165100019 PM 12487999 ER PT J AU Murphy, LD Zimmerman, SB AF Murphy, LD Zimmerman, SB TI Hypothesis: the RNase-sensitive restraint to unfolding of spermidine nucleoids from Escherichia coli is composed of cotranslational insertion linkages SO BIOPHYSICAL CHEMISTRY LA English DT Article DE DNA; nucleoid; Escherichia coli; ribonuclease; urea; spermidine ID DEOXYRIBONUCLEIC-ACID; DNA CONDENSATION; COMPACT FORM; PROTEINS; POLYAMINES; CHROMOSOME; CYTOPLASM; MEMBRANE; RELEASE AB The genomic DNA of bacteria is highly localized in one or a few bodies known as nucleoids. A number of restraints to the unfolding of the DNA of spermidine nucleoids from Escherichia coli were previously associated with characteristic urea concentrations (U-m values). The dominant restraint to unfolding was sensitive to pancreatic RNase and underwent a cooperative transition at U-m=3.2 M urea. The losses of the RNase-sensitive restraint caused by urea or pancreatic RNase appear to result from breakage of cotranslational insertion linkages which joined the nucleoid to the cell envelope in growing cells. This conclusion is based upon effects from exposures of cells to antibiotics (chloramphenicol, rifampicin, streptomycin), treatment of nucleoid preparations with formaldehyde or concentrated NaCl solutions, and effects of urea on purified ribosomes. The specific RNase-sensitive and urea-sensitive components of the spermidine nucleoids are suggested to be the mRNA and ribosomes, respectively, of cotranslational insertion linkages. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Zimmerman, SB (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Mol Biol Lab, NIH, Bldg 5,Rm 328W, Bethesda, MD 20892 USA. NR 55 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC 10 PY 2002 VL 101 BP 321 EP 331 AR PII S0301-4622(02)00163-1 DI 10.1016/S0301-4622(02)00163-1 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 631JU UT WOS:000180165100031 PM 12488011 ER PT J AU Shiao, YH Kamata, SI Li, LM Hooth, MJ DeAngelo, AB Anderson, LM Wolf, DC AF Shiao, YH Kamata, SI Li, LM Hooth, MJ DeAngelo, AB Anderson, LM Wolf, DC TI Mutations in the VHL gene from potassium bromate-induced rat clear cell renal tumors SO CANCER LETTERS LA English DT Article DE drinking water; von Hippel-Lindau; kidney ID SUPPRESSOR GENE; LIPID-PEROXIDATION; SOMATIC MUTATIONS; LINDAU-DISEASE; CARCINOMA; IDENTIFICATION; KIDNEY; CANCER; CARCINOGENICITY; GLUTATHIONE AB Potassium bromate (KBrO3) is a rat renal carcinogen and a major drinking water disinfection by-product in water disinfected with ozone. Clear cell renal tumors, the most common form of human renal epithelial neoplasm, are rare in animals but are inducible by KBrO3 in F344 rats. Detection of cytoplasmic periodic acid-Schiff-positive granules in clear cell tumors, indicative of glycogen accumulation, provides evidence of their biochemical similarity to human counterparts. Mutation in the coding region of the von Hippel-Lindau (VHL) gene is frequently detected in human clear cell renal carcinomas. Detection of VHL mutations in KBrO3-induced rat renal tumors could enhance the relevancy of these rat renal tumors for human health risk assessment. Formalin-fixed paraffin-embedded control tissues and renal tumors from male F344 rats exposed to KBrO3 in the drinking water for 2 years were examined microscopically and were microdissected for DNA extraction. The coding sequence and a promoter region of the VHL gene were examined by polymerase chain reaction-single strand conformation polymorphism and/or DNA sequencing. Two of nine clear cell renal tumors carried the same C to T mutation at the core region of the Sp1 transcription factor binding motif in the VHL promoter and one of four untreated animals had C to T mutation outside the highly conserved core region. Mutation in the VHL coding sequence was only detected in one tumor. No VHL mutations were observed in three chromophilic tumors. KBrO3-induced rat renal tumors are morphologically similar to their human counterpart but the genetic basis of tumorigenesis is different. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 NCI, Lab Comparat Carcinogenesis, NIH, Frederick, MD USA. US EPA, Enviornm Carcinogenesis Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. RP Wolf, DC (reprint author), NCI, Lab Comparat Carcinogenesis, NIH, Frederick, MD USA. NR 39 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 10 PY 2002 VL 187 IS 1-2 BP 207 EP 214 AR PII S0304-3835(02)00407-X DI 10.1016/S0304-3835(02)00407-X PG 8 WC Oncology SC Oncology GA 618NP UT WOS:000179424400027 PM 12359370 ER PT J AU Lloyd-Jones, DM Larson, MG Leip, EP Beiser, A D'Agostino, RB Kannel, WB Murabito, JM Vasan, RS Benjamin, EJ Levy, D AF Lloyd-Jones, DM Larson, MG Leip, EP Beiser, A D'Agostino, RB Kannel, WB Murabito, JM Vasan, RS Benjamin, EJ Levy, D TI Lifetime risk for developing congestive heart failure - The Framingham Heart Study SO CIRCULATION LA English DT Article DE heart failure; risk factors; hypertension; myocardial infarction ID DISEASE; HYPERTENSION; PROGRESSION; PREVENTION; COMMUNITY AB Background-Congestive heart failure (CHF) is an increasing public health problem. Methods and Results-Among Framingham Heart Study subjects who were free of CHF at baseline, we determined the lifetime risk for developing overt CHF at selected index ages. We followed 3757 men and 4472 women from 1971 to 1996 for 124 262 person-years; 583. subjects developed CHF and 2002 died without prior CHF. At age 40 years, the lifetime risk for CHF was 21.0% (95% CI 18.7% to 23.2%) for men and 20.3% (95% CI 18.2% to 22.5%) for women. Remaining lifetime risk did not change with advancing index age because of rapidly increasing CHF incidence rates. At age 80 years, the lifetime risk was 20.2% (95% CI 16.1% to 24.2%) for men and 19.3% (95% CI 16.5% to 22.2%) for women. Lifetime risk for CHF doubled for subjects with blood pressure greater than or equal to160/100 versus <140/90 mm Hg. In a secondary analysis, we only considered those who developed CHF without an antecedent myocardial infarction; at age 40 years, the lifetime risk for CHF was 11.4% (95% CI 9.6% to 13.2%) for men and 15.4% (95% CI 13.5% to 17.3%) for women. Conclusions-When established clinical criteria are used to define overt CHF, the lifetime risk for CHF is 1 in 5 for both men and women. For CHF occurring in the absence of myocardial infarction, the lifetime risk is 1 in 9 for men and 1 in 6 for women, which highlights the risk of CHF that is largely attributable to hypertension. These results should assist in predicting the population burden of CHF and placing greater emphasis on prevention of CHF through hypertension control and prevention of myocardial infarction. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02215 USA. RP Lloyd-Jones, DM (reprint author), NHLBI, Framingham Heart Study, NIH, 73 Mt Wayte Ave, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, K23 HL04253] NR 19 TC 661 Z9 693 U1 1 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 10 PY 2002 VL 106 IS 24 BP 3068 EP 3072 DI 10.1161/01.CIR.00000.39105.49749.6F PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 624WQ UT WOS:000179785000027 PM 12473553 ER PT J AU Koh, KK Schenke, WH Cannon, RO Waclawiw, MA Csako, G AF Koh, KK Schenke, WH Cannon, RO Waclawiw, MA Csako, G TI Statin attenuates increase in C-reactive protein during estrogen replacement therapy in postmenopausal women - Response SO CIRCULATION LA English DT Letter ID ADHESION MOLECULES; INFLAMMATION C1 Gachon Med Coll, Inchon, South Korea. NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Koh, KK (reprint author), Gachon Med Coll, Inchon, South Korea. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 10 PY 2002 VL 106 IS 24 BP E198 EP E199 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 624WQ UT WOS:000179785000008 ER PT J AU Vasconcelos, OM Raju, R Dalakas, MC AF Vasconcelos, OM Raju, R Dalakas, MC TI GNE mutations in an American family with quadriceps-sparing IBM and lack of mutations in s-IBM SO NEUROLOGY LA English DT Article ID ACETYLGLUCOSAMINE 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; ENZYME AB Analysis for GNE mutations was performed in an American, non-Iranian Jewish, family with quadriceps-sparing inclusion body myopathy (QS-IBM) and in 11 patients with sporadic IBM (s-IBM). Two novel nonallosteric site missense mutations were found in the QS-IBM kinship. No mutations were identified in s-IBM patients. After 8 years of follow-up and severe disease progression, the quadriceps muscle in the QS-IBM patient remains strong despite subclinical involvement documented with repeat MRI and muscle biopsy. C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. RI Raju, Raghavan/E-9219-2011 NR 10 TC 32 Z9 33 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 10 PY 2002 VL 59 IS 11 BP 1776 EP 1779 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 622VZ UT WOS:000179669000021 PM 12473769 ER PT J AU Calabresi, PA Austin, H Racke, MK Goodman, A Choyke, P Maloni, H McFarland, HF AF Calabresi, PA Austin, H Racke, MK Goodman, A Choyke, P Maloni, H McFarland, HF TI Impaired renal function in progressive multiple sclerosis SO NEUROLOGY LA English DT Article ID GLOMERULAR-FILTRATION RATE AB The authors analyzed renal function in 25 patients with progressive MS. The mean glomerular filtration rate (GFR) was 92 mL/min/1.73 m(2), compared to the predicted GFR of 110 (p < 0.001). Nine of the 25 (36%) patients had abnormally low GFR (<90). The mean serum creatinine for patients with MS was lower than predicted normal values and poorly estimated GFR using standard equations. These data document impaired renal function in patients with progressive MS and have implications for treatment of these patients with potentially nephrotoxic drugs. C1 Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA. NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Sch, Dept Neurol, Dallas, TX 75230 USA. Univ Rochester, Sch Med, Dept Neurol, Rochester, NY USA. RP Calabresi, PA (reprint author), Univ Maryland, Sch Med, Dept Neurol, 655 W Baltimore St,Room 12-027, Baltimore, MD 21201 USA. NR 10 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD DEC 10 PY 2002 VL 59 IS 11 BP 1799 EP 1801 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 622VZ UT WOS:000179669000029 PM 12473777 ER PT J AU Kvaratskhelia, M Miller, JT Budihas, SR Pannell, LK Le Grice, SFJ AF Kvaratskhelia, M Miller, JT Budihas, SR Pannell, LK Le Grice, SFJ TI Identification of specific HIV-1 reverse transcriptase contacts to the viral RNA : tRNA complex by mass spectrometry and a primary amine selective reagent SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; PRIMER-BINDING-SITE; STRAND DNA-SYNTHESIS; SURFACE-TOPOLOGY; GENETIC-ANALYSIS; INITIATION; TRNA(3)(LYS); COMPLEMENTARY; TRNA(LYS,3); ELONGATION AB We have devised a high-resolution protein footprinting methodology to dissect HIV-1 reverse transcriptase (RT) contacts to the viral RNA:tRNA complex. The experimental strategy included modification of surface-exposed lysines in RT and RT-viral RNA:tRNA complexes by the primary amine selective reagent NHS-biotin, SDS/PAGE separation of p66 and p51 polypepticles, in gel proteolysis, and comparative mass spectrometric analysis of peptide fragments. The lysines modified in free RT but protected from biotinylation in the nucleoprotein complex were readily revealed by this approach. Results of a control experiment examining the RT-DNA:DNA complex were in excellent agreement with the crystal structure data on the identical complex. Probing the RT-viral RNA:tRNA complex revealed that a majority of protein contacts are located in the primer-template binding cleft in common with the RT-DNA:DNA and RT-RNA:DNA species. However, our footprinting data indicate that the p66 fingers subdomain makes additional contacts to the viral RNA:tRNA specific for this complex and not detected with DNA:DNA. The protein footprinting method described herein has a generic application for high-resolution solution structural studies of multiprotein-nucleic acid contacts. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Le Grice, SFJ (reprint author), NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NR 34 TC 44 Z9 46 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 10 PY 2002 VL 99 IS 25 BP 15988 EP 15993 DI 10.1073/pnas.252550199 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624VY UT WOS:000179783400032 PM 12461175 ER PT J AU Reeves, JD Gallo, SA Ahmad, N Miamidian, JL Harvey, PE Sharron, M Pohlmann, S Sfakianos, JN Derdeyn, CA Blumenthal, R Hunter, E Doms, RW AF Reeves, JD Gallo, SA Ahmad, N Miamidian, JL Harvey, PE Sharron, M Pohlmann, S Sfakianos, JN Derdeyn, CA Blumenthal, R Hunter, E Doms, RW TI Sensitivity of HIV-1 to entry inhibitors correlates with envelope/coreceptor affinity, receptor density, and fusion kinetics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTORS; DISEASE PROGRESSION; MEMBRANE-FUSION; MEDIATED FUSION; 6-HELIX BUNDLE; V3 LOOP; GP120; CCR5; GP41 AB HIV entry inhibitors include coreceptor antagonists and the fusion inhibitor T-20. T-20 binds the first helical region (HR1) in the gp41 subunit of the viral envelope (Env) protein and prevents conformational changes required for membrane fusion. HR1 appears to become accessible to T-20 after Env binds CD4, whereas coreceptor binding is thought to induce the final conformational changes that lead to membrane fusion. Thus, T-20 binds to a structural intermediate of the fusion process. Primary viruses exhibit considerable variability in T-20 sensitivity, and determinants outside of HR1 can affect sensitivity by unknown mechanisms. We studied chimeric Env proteins containing different V3 loop sequences and found that gp120/coreceptor affinity correlated with T-20 and coreceptor antagonist sensitivity, with greater affinity resulting in increased resistance to both classes of entry inhibitors. Enhanced affinity resulted in more rapid fusion kinetics, reducing the time during which Env is sensitive to T-20. Reduced coreceptor expression levels also delayed fusion kinetics and enhanced virus sensitivity to T-20, whereas increased coreceptor levels had the opposite effect. A single amino acid change (K421D) in the bridging sheet region of the primary virus strain YU2 reduced affinity for CCR5 and increased T-20 sensitivity by about 30-fold. Thus, mutations in Env that affect receptor engagement and membrane fusion rates can alter entry inhibitor sensitivity. Because coreceptor expression levels are typically limiting in vivo, individuals who express lower coreceptor levels may respond more favorably to entry inhibitors such as T-20, whose effectiveness we show depends in part on fusion kinetics. C1 Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA. NCI, Lab Expt & Computat Biol, Canc Res Ctr, Frederick, MD 21702 USA. Univ Alabama, Ctr AIDS Res, Birmingham, AL 35294 USA. RP Reeves, JD (reprint author), Univ Penn, Dept Microbiol, 225 Johnson Pavilion,3610 Hamilton Walk, Philadelphia, PA 19104 USA. RI Reeves, Jacqueline/I-5379-2012; OI Gallo, Stephen/0000-0001-6043-2153; Pohlmann, Stefan/0000-0001-6086-9136 FU NIAID NIH HHS [R01 AI040880, AI40880]; NIMHD NIH HHS [L60 MD003100] NR 35 TC 317 Z9 323 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 10 PY 2002 VL 99 IS 25 BP 16249 EP 16254 DI 10.1073/pnas.252469399 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 624VY UT WOS:000179783400077 PM 12444251 ER PT J AU Edskes, HK Wickner, RB AF Edskes, HK Wickner, RB TI Conservation of a portion of the S-cerevisiae Ure2p prion domain that interacts with the full-length protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Arthur M Sackler Colloquium on Self-Perpetuating Structural States in Biology, Disease and Genetics CY MAR 22-24, 2002 CL WASHINGTON, D.C. SP Natl Acad Sci, Authur M Sackler ID SACCHAROMYCES-CEREVISIAE; SUP35 PROTEIN; GUANIDINE-HYDROCHLORIDE; NUCLEAR-LOCALIZATION; SCRAPIE PRION; YEAST PRIONS; IN-VITRO; GENE; HSP104; TRANSCRIPTION AB The [URE3] prion of Saccharomyces cerevisiae is a self-propagating inactive amyloid form of the Ure2 protein. Ure2p residues 1-65 constitute the prion domain, and the remaining C-terminal portion regulates nitrogen catabolism. We have examined the URE2 genes of wild-type isolates of S. cerevisiae and those of several pathogenic yeasts and a filamentous fungus. We find that the normal function of the S. cerevisiae Ure2p in nitrogen regulation is fully complemented by the Ure2p of Candida albicans, Candida glabrata, Candida kefyr, Candida maltosa, Saccharomyces bayanus, and Saccharomyces para-doxus, all of which have high homology in the C-terminal nitrogen regulation domain. However, there is considerable divergence of their N-terminal domains from that of Ure2p of S. cerevisiae. [URE3(Sc)] showed efficient transmission into S. cerevisiae ure2Delta cells if expressing a Ure2p of species within Saccharomyces. However, [URE3(Sc)) did not seed self-propagating inactivation of the Ure2p's from the other yeasts. When overexpressed as a fusion with green fluorescent protein, residues 5-47 of the S. cerevisiae prion domain are necessary for curing the [URE3] prion. Residues 11-39 are necessary for an inactivating interaction with the full-length Ure2p. A nearly identical region is highly conserved among many of the yeasts examined in this study, despite the wide divergence of sequences found in other parts of the N-terminal domains. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov NR 63 TC 63 Z9 74 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 10 PY 2002 VL 99 SU 4 BP 16384 EP 16391 DI 10.1073/pnas.162349599 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 626VP UT WOS:000179894800003 PM 12177423 ER PT J AU Bradley, ME Edskes, HK Hong, JY Wickner, RB Liebman, SW AF Bradley, ME Edskes, HK Hong, JY Wickner, RB Liebman, SW TI Interactions among prions and prion "strains" in yeast SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Arthur M Sackler Colloquium on Self-Perpetuating Structural States in Biology, Disease and Genetics CY MAR 22-24, 2002 CL WASHINGTON, D.C. SP Natl Acad Sci, Authur M Sackler ID NON-MENDELIAN FACTOR; DE-NOVO APPEARANCE; SACCHAROMYCES-CEREVISIAE; PSI+ PRION; PROTEIN HSP104; SUP35 PROTEIN; URE3 PRION; PROPAGATION; INDUCTION; MUTATION AB Prions are "infectious" proteins. When Sup35, a yeast translation termination factor, is aggregated in its [PSI+] prion form its function is compromised. When Rnq1 is aggregated in its [PIN+] prion form, it promotes the de novo appearance of [PSI+]. Heritable variants (strains) of [PSI+] with distinct phenotypes have been isolated and are analogous to mammalian prion strains with different pathologies. Here, we describe heritable variants of the [PIN+] prion that are distinguished by the efficiency with which they enhance the de novo appearance of [PSI+]. Unlike [PSI+] variants, where the strength of translation termination corresponds to the level of soluble Sup35, the phenotypes of these [PIN+] variants do not correspond to levels of soluble Rnq1. However, diploids and meiotic progeny from crosses between either different [PSI+], or different [PIN+] variants, always have the phenotype of the parental variant with the least soluble Sup35 or Rnq1, respectively. Apparently faster growing prion variants cure cells of slower growing or less stable variants of the same prion. We also find that YDJ1 overexpression eliminates some but not other [PIN+] variants and that prions are destabilized by meiosis. Finally, we show that, like its affect on [PSI+] appearance, [PIN+] enhances the de novo appearance of [URE3]. Surprisingly, [PSI+] inhibited [URE3] appearance. These results reinforce earlier reports that heterologous prions interact, but suggest that such interactions can not only positively, but also negatively, influence the de novo generation of prions. C1 Univ Illinois, Dept Biol Sci, Mol Biol Lab, Chicago, IL 60607 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Univ Illinois, Dept Biol Sci, Mol Biol Lab, 900 S Ashland Ave, Chicago, IL 60607 USA. EM SUEL@uic.edu FU NIGMS NIH HHS [R01 GM056350, GM56350] NR 60 TC 139 Z9 139 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 10 PY 2002 VL 99 SU 4 BP 16392 EP 16399 DI 10.1073/pnas.152330699 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 626VP UT WOS:000179894800004 PM 12149514 ER PT J AU Burgess-Beusse, B Farrell, C Gaszner, M Litt, M Mutskov, V Recillas-Targa, F Simpson, M West, A Felsenfeld, G AF Burgess-Beusse, B Farrell, C Gaszner, M Litt, M Mutskov, V Recillas-Targa, F Simpson, M West, A Felsenfeld, G TI The insulation of genes from external enhancers and silencing chromatin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT Arthur M Sackler Colloquium on Self-Perpetuating Structural States in Biology, Disease and Genetics CY MAR 22-24, 2002 CL WASHINGTON, D.C. SP Natl Acad Sci, Author M Sackler ID BETA-GLOBIN LOCUS; HISTONE H3; BLOCKING ACTIVITY; LYSINE 9; METHYLATION; DOMAIN; CTCF; BOUNDARIES; CONSERVATION; TRANSITIONS AB Insulators are DNA sequence elements that can serve in some cases as barriers to protect a gene against the encroachment of adjacent inactive condensed chromatin. Some insulators also can act as blocking elements to protect against the activating influence of distal enhancers associated with other genes. Although most of the insulators identified so far derive from Drosophila, they also are found in vertebrates. An insulator at the 5' end of the chicken beta-globin locus marks a boundary between an open chromatin domain and a region of constitutively condensed chromatin. Detailed analysis of this element shows that it possesses both enhancer blocking activity and the ability to screen reporter genes against position effects. Enhancer blocking is associated with binding of the protein CTCF; sites that bind CTCF are found at other critical points in the genome. Protection against position effects involves other properties that appear to be associated with control of histone acetylation and methylation. Insulators thus are complex elements that can help to preserve the independent function of genes embedded in a genome in which they are surrounded by regulatory signals they must ignore. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. OI West, Adam/0000-0003-3502-7804 NR 23 TC 183 Z9 187 U1 1 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD DEC 10 PY 2002 VL 99 SU 4 BP 16433 EP 16437 DI 10.1073/pnas.162342499 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 626VP UT WOS:000179894800010 PM 12154228 ER PT J AU Jones, DW Chambless, LE Folsom, AR Heiss, G Hutchinson, RG Sharrett, AR Szklo, M Taylor, HA AF Jones, DW Chambless, LE Folsom, AR Heiss, G Hutchinson, RG Sharrett, AR Szklo, M Taylor, HA TI Risk factors for coronary heart disease in African Americans - The Atherosclerosis Risk in Communities Study, 1987-1997 SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID UNITED-STATES; RACIAL-DIFFERENCES; WHITE MEN; CARDIOVASCULAR-DISEASE; SOCIOECONOMIC-STATUS; STROKE MORTALITY; BLOOD-PRESSURE; EVANS COUNTY; SHORT-TERM; BLACK AB Background: As part of the Atherosclerosis Risk in Communities Study, the race-specific incidence rates and risk factor prediction for coronary heart disease (CHD) were determined for black and white persons over 7 to 10 years of follow-up, from 1987 to 1997. Methods: The sample included 14 062 men and women (2298 black women, 5686 white women, 1396 black men, and 4682 white men) aged 45 to 64 years who were free of clinical CHD at baseline. Results: Average age-adjusted incidence rates (95% confidence intervals) for CHD per 1000 person-years were as follows: black women, 5.1 (4.2-6.2); white women, 4.0 (3.5-4.6); black men, 10.6 (8.9-12.7); and white men, 12.5 (11.5-13.7). Incidence rates (95% confidence intervals) using a definition for CHD that excluded revascularization procedures were as follows: black women, 4.9 (4.6-6.0); white women, 2.9 (2.5-3.4); black men, 9.2 (7.6-11.1); and white men, 7.9 (7.0-8.8). In a multivariable analysis, hypertension was a particularly strong risk factor in black women, with hazard rate ratios (95% confidence intervals) as follows: black women, 4.8 (2.5-9.0); white women, 2.1 (1.6-2.9); black men, 2.0 (1.3-3.0); and white men, 1.6 (1.3-1.9). Diabetes mellitus was somewhat more predictive in white women than in other groups. Hazard rate ratios (95% confidence intervals) were as follows: black women, 1.8 (1.2-2.8); white women, 3.3 (2.4-4.6); black men, 1.6 (1.1-2.5); and white men, 2.0 (1.6-2.6). Low-density lipoprotein cholesterol level was similarly predictive in all race-sex groups (hazard rate ratio, 1.2-1.4 per SD increment of low-density lipoprotein cholesterol level). High-density lipoprotein cholesterol level seemed somewhat more protective in white than in black persons. Conclusions: Findings from this study, along with clinical trial evidence showing efficacy, support aggressive management of traditional risk factors in black persons, as in white persons. Understanding the intriguing racial differences in risk factor prediction may be an important part of further elucidating the causes of CHD and may lead to better methods of preventing and treating CHD. C1 Univ Mississippi, Med Ctr, Dept Med, Div Hypertens, Jackson, MS 39216 USA. Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39216 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Jones, DW (reprint author), Univ Mississippi, Med Ctr, Dept Med, Div Hypertens, 2500 N State St, Jackson, MS 39216 USA. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55019, N01-HC-55020, N01-HC-55022, N01-HC-55021, N01-HC-55018, N01-HC-55016] NR 57 TC 83 Z9 85 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD DEC 9 PY 2002 VL 162 IS 22 BP 2565 EP 2571 DI 10.1001/archinte.162.22.2565 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 625EY UT WOS:000179805000007 PM 12456228 ER PT J AU Iouk, T Kerscher, O Scott, RJ Basrai, MA Wozniak, RW AF Iouk, T Kerscher, O Scott, RJ Basrai, MA Wozniak, RW TI The yeast nuclear pore complex functionally interacts with components of the spindle assembly checkpoint SO JOURNAL OF CELL BIOLOGY LA English DT Article DE nucleoporins; cell cycle; kinetochore; mads; nuclear transport ID MEMBRANE-PROTEIN POM152P; SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; MITOTIC SPINDLE; TRANSPORT; KINETOCHORES; MAD2; NUCLEOPORINS; ENVELOPE; NUP170P AB A physical and functional link between the nuclear pore complex (NPC) and the spindle checkpoint machinery has been established in the yeast Saccharomyces cerevisiae. We show that two proteins required for the execution of the spindle checkpoint, Mad1p and Mad2p, reside predominantly at the NPC throughout the cell cycle. There they are associated with a subcomplex of nucleoporins containing Nup53p, Nup170p, and Nup157p. The association of the Mad1p-Mad2p complex with the NPC requires Mad1p and is mediated in part by Nup53p. On activation of the spindle checkpoint, we detect changes in the interactions between these proteins, including the release of Mad2p (but not Mad1p) from the NPC and the accumulation of Mad2p at kinetochores. Accompanying these events is the Nup53p-dependent hyperphosphorylation of Mad1p. On the basis of these results and genetic analysis of double mutants, we propose a model in which Mad1p bound to a Nup53p-containing complex sequesters Mad2p at the NPC until its release by activation of the spindle checkpoint. Furthermore, we show that the association of Mad1p with the NPC is not passive and that it plays a role in nuclear transport. C1 Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2H7, Canada. NCI, Ctr Canc Res, Genet Branch, NIH, Bethesda, MD 20889 USA. RP Wozniak, RW (reprint author), Univ Alberta, Dept Cell Biol, 5-14 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada. NR 55 TC 101 Z9 106 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD DEC 9 PY 2002 VL 159 IS 5 BP 807 EP 819 DI 10.1083/jcb.200205068 PG 13 WC Cell Biology SC Cell Biology GA 625KB UT WOS:000179814700009 PM 12473689 ER PT J AU Maher, BA Russo, E Straus, SE AF Maher, BA Russo, E Straus, SE TI A conversation with Stephen E. Straus SO SCIENTIST LA English DT Editorial Material C1 The Scientist, Philadelphia, PA 19104 USA. Nat Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. RP Maher, BA (reprint author), The Scientist, 3535 Market St,Suite 200, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCIENTIST INC PI PHILADELPHIA PA 3535 MARKET ST, SUITE 200, PHILADELPHIA, PA 19104-3385 USA SN 0890-3670 J9 SCIENTIST JI Scientist PD DEC 9 PY 2002 VL 16 IS 24 BP 34 EP 34 PG 1 WC Information Science & Library Science; Multidisciplinary Sciences SC Information Science & Library Science; Science & Technology - Other Topics GA 624LK UT WOS:000179761000016 ER PT J AU Eltom, MA Mbulaiteye, SM Dada, AJ Whitby, D Biggar, RJ AF Eltom, MA Mbulaiteye, SM Dada, AJ Whitby, D Biggar, RJ TI Transmission of human herpesvirus 8 by sexual activity among adults in Lagos, Nigeria SO AIDS LA English DT Article DE Africa; chancroid; commercial sex workers; Hemophilus ducreyi; Herpesvirus simplex; KSHV; sexually transmitted diseases; syphilis ID SARCOMA-ASSOCIATED HERPESVIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; KAPOSIS-SARCOMA; HUMAN-HERPESVIRUS-8 INFECTION; HTLV-I; AFRICA; SEROPREVALENCE; PERFORMANCE; POPULATION; ANTIBODIES AB Background: Human herpesvirus 8 (HHV-8) infection is common in Africa, but prevalence varies geographically. Studies in Europe and America suggest spread through homosexual contact, but evidence of heterosexual spread is inconsistent. We examined the association between HHV-8 and markers of risky sexual activity in Nigeria. Methods: The study subjects included an adult referent population at relatively low risk of HIV infection, patients attending a sexually transmitted disease (STD) clinic, and female commercial sex workers (CSW). Sera were collected between 1991 and 1994 to study the epidemiology of retroviruses and STD in Lagos, Nigeria. Residual samples were tested for HHV-8 antibodies using a K8.1 enzyme immunoassay and for antibodies to syphilis, chancroid, herpes simplex virus 2, HIV-1/2, and HTLV-1. Associations were sought using chi square tests and logistic regression. Results: Overall, HHV-8 prevalence was 26.5% in 2002 study subjects, being higher among CSW and STD patients (31% in each) than in the referent population (19%). HHV-8 prevalence in women was approximately half that in men in both the referent and the STD populations. Increasing age and STD were each associated with HHV-8-seropositivity in men and women, and among women being a CSW was also a risk factor. HHV-8 antibodies were more frequently detected in those with laboratory evidence of STD in each group. Having at least one STD was associated with having HHV-8 antibodies. Conclusion: The higher prevalence of HHV-8 antibody in groups with multiple sexual partners and the association with STD among individuals both support the sexual transmission of HHV-8 in African adults. (C) 2002 Lippincott Williams Wilkins. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Hlth Promot Consultancy, Lagos, Nigeria. NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Frederick, MD 21701 USA. RP Eltom, MA (reprint author), 6120 Execut Blvd,EPS Room 8014, Rockville, MD 20852 USA. NR 18 TC 50 Z9 52 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD DEC 6 PY 2002 VL 16 IS 18 BP 2473 EP 2478 DI 10.1097/00002030-200212060-00014 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 631BC UT WOS:000180146000014 PM 12461423 ER PT J AU Koshimizu, T Ueno, S Tanoue, A Yanagihara, N Stojilkovic, SS Tsujimoto, G AF Koshimizu, T Ueno, S Tanoue, A Yanagihara, N Stojilkovic, SS Tsujimoto, G TI Heteromultimerization modulates P2X receptor functions through participating extracellular and C-terminal subdomains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANTERIOR-PITUITARY-CELLS; ION CHANNELS; ATP RECEPTOR; SENSORY NEURONS; DESENSITIZATION; SUBUNITS; IDENTIFICATION; PHARMACOLOGY; EXPRESSION; SITE AB P2X purinergic receptors (P2XRs) differ among themselves with respect to their ligand preferences and channel kinetics during activation, desensitization, and recovery. However, the contributions of distinct receptor subdomains to the subtype-specific behavior have been incompletely characterized. Here we show that homomeric receptors having the extracellular domain of the P2X(3) subunit in the P2X(2a)-based backbone (P2X(2a)/X(3)ex) mimicked two intrinsic functions of P2X(3)R, sensitivity to alphabeta-methylene ATP and ecto-ATPase-dependent recovery from endogenous desensitization; these two functions were localized to the N- and C-terminal halves of the P2X(3) extracellular loop, respectively. The chimeric P2X(2a)R/X(3)ex receptors also desensitized with accelerated rates compared with native P2X(2a)R, and the introduction of P2X(2) C-terminal splicing into the chimeric subunit (P2X(2b)/X(3)ex) further increased the rate of desensitization. Physical and functional heteromerization of native P2X(2a) and P2X(2b) subunits was also demonstrated. In heteromeric receptors, the ectodomain of P2X(3) was a structural determinant for ligand selectivity and recovery from desensitization, and the C terminus of P2X(2) was an important factor for the desensitization rate. Furthermore, [gamma-P-32]8-azido ATP, a photoreactive agonist, was effectively cross-linked to P2X(3) subunit in homomeric receptors but not in heteromeric P2X(2) + P2X(3)Rs. These results indicate that heteromeric receptors formed by distinct P2XR subunits develop new functions resulting from integrative effects of the participating extracellular and C-terminal subdomains. C1 NICHD, Dept Mol & Cell Pharmacol, NIH, Bethesda, MD 20892 USA. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Univ Occupat & Environm Hlth, Dept Pharmacol, Japan Sch Med, Tokyo 1548567, Japan. RP Tsujimoto, G (reprint author), Natl Res Inst Child Hlth & Dev, Dept Mol Cell Pharmacol, Setagaya Ku, 3-35-31 Taishido, Tokyo 154, Japan. OI Koshimizu, Taka-aki/0000-0001-5292-7535 NR 36 TC 25 Z9 25 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 6 PY 2002 VL 277 IS 49 BP 46891 EP 46899 DI 10.1074/jbc.M205274200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622TT UT WOS:000179663700010 PM 12361958 ER PT J AU Jacques, KM Nie, ZZ Stauffer, S Hirsch, DS Chen, LX Stanley, KT Randazzo, PA AF Jacques, KM Nie, ZZ Stauffer, S Hirsch, DS Chen, LX Stanley, KT Randazzo, PA TI Arf1 dissociates from the clathrin adaptor GGA prior to being inactivated by arf GTPase-activating proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ADP-RIBOSYLATION FACTOR; BINDING PROTEINS; AMINO-TERMINUS; IMPORTIN-BETA; CHOLERA-TOXIN; NONCATALYTIC DOMAIN; KDEL RECEPTOR; GOLGI-COMPLEX; RAN-GTP; TRANSPORT AB The effectors of monomeric GTP-binding proteins can influence interactions with GTPase-activating proteins (GAPs) in two ways. In one case, effector and GAP binding to the GTP-binding protein is mutually exclusive. In another case, the GTP-binding protein bound to an effector is the substrate for the GTPase-activating protein. Here predictions for these two mechanisms were tested for the Arf1 effector GGA and ASAP family Arf GAPs. GGA inhibited Arf GAP activity of ASAP1, AGAP1, ARAP1, and Arf GAP1 and inhibited binding of Arf1.GTPgammaS to AGAP1 with K-i values correlating with the K-d for the GGA.Arf1 complex. ASAP1 blocked Arf1.GTPgammaS binding to GGA with a K-i similar to the (K)d for the ASAP-Arf1-GTPgammaS complex. No interaction of GGA with ASAP1 was detected. Consistent with GGA sequestering Arf from GAPs, overexpression of GGA slowed the rate of Arf dissociation from the Golgi apparatus following treatment with brefeldin A. Mutational analysis revealed the amino-terminal a-helix and switch I of Arf1 contributed to interaction with both GGA and GAPs. These data exclude the mechanism previously documented for Arf GAP1/coatomer in which Arf1 is inactivated in a tripartite complex. Instead, termination of Arf1 signals mediated through GGA require that Arf1-GTP dissociates from GGA prior to interaction with GAP and consequent hydrolysis of GTP. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 6032, Bethesda, MD 20892 USA. NR 49 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 6 PY 2002 VL 277 IS 49 BP 47235 EP 47241 DI 10.1074/jbc.M208875200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622TT UT WOS:000179663700051 PM 12376537 ER PT J AU Beard, WA Shock, DD Vande Berg, BJ Wilson, SH AF Beard, WA Shock, DD Vande Berg, BJ Wilson, SH TI Efficiency of correct nucleotide insertion governs DNA polymerase fidelity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VIRUS REVERSE-TRANSCRIPTASE; REPLICATION FIDELITY; ESCHERICHIA-COLI; BASE-PAIRS; BETA; IOTA; DISCRIMINATION; HYPERMUTATION; PROCESSIVITY; SPECIFICITY AB DNA polymerase fidelity or specificity expresses the ability of a polymerase to select a correct nucleoside triphosphate (dNTP) from a pool of structurally similar molecules. Fidelity is quantified from the ratio of specificity constants (catalytic efficiencies) for alternate substrates (i.e. correct and incorrect dNTPs). An analysis of the efficiency of dNTP (correct and incorrect) insertion for a low fidelity mutant of DNA polymerase beta (R283A) and exonuclease-deficient DNA polymerases from five families derived from a variety of biological sources reveals that a strong correlation exists between the ability to synthesize DNA and the probability that the polymerase will make a mistake (i.e. base substitution error). Unexpectedly, this analysis indicates that the difference between low and high fidelity DNA polymerases is related to the efficiency of correct, but not incorrect, nucleotide insertion. In contrast to the loss of fidelity observed with the catalytically inefficient R283A mutant, the fidelity of another inefficient mutant of DNA polymerase beta (G274P) is not altered. Thus, although all natural low fidelity DNA polymerases are inefficient, not every inefficient DNA polymerase has low fidelity. Low fidelity polymerases appear to be an evolutionary solution to how to replicate damaged DNA or DNA repair intermediates without burdening the genome with excessive polymerase-initiated errors. 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. EM wiIson5@niehs.nih.gov NR 39 TC 82 Z9 83 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 6 PY 2002 VL 277 IS 49 BP 47393 EP 47398 DI 10.1074/jbc.M210036200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622TT UT WOS:000179663700073 PM 12370169 ER PT J AU Junn, E Lee, SS Suhr, UT Mouradian, MM AF Junn, E Lee, SS Suhr, UT Mouradian, MM TI Parkin accumulation in aggresomes due to proteasome impairment SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID UBIQUITIN-PROTEIN LIGASE; LEWY BODY DISEASE; RECESSIVE JUVENILE PARKINSONISM; ALPHA-SYNUCLEIN; INCLUSION-BODIES; NEURODEGENERATIVE DISEASES; ALZHEIMERS-DISEASE; IN-VITRO; SYNPHILIN-1; SYSTEM AB Parkinson's disease (PD) is characterized by loss of dopaminergic neurons in the substantia nigra and by the presence of ubiquitinated cytoplasmic inclusions known as Lewy bodies. alpha-Synuclein and Parkin are two of the proteins associated with inherited forms of PD and are found in Lewy bodies. Whereas numerous reports indicate the tendency of alpha-synuclein to aggregate both in vitro and in vivo, no information is available about similar physical properties for Parkin. Here we show that overexpression of Parkin in the presence of proteasome inhibitors leads to the formation of aggresome-like perinuclear inclusions. These eosinophilic inclusions share many characteristics with Lewy bodies, including a core and halo organization, immunoreactivity to ubiquitin, alpha-synuclein, synphilin-1, Parkin, molecular chaperones, and proteasome subunit as well as staining of some with thioflavin S. We propose that the process of Lewy body formation may be akin to that of aggresome-like structures. The tendency of wild-type Parkin to aggregate and form inclusions may have implications for the pathogenesis of sporadic PD. C1 NINDS, Expt Therapeut Branch, Genet Pharmacol Unit, NIH, Bethesda, MD 20892 USA. RP Mouradian, MM (reprint author), NINDS, Expt Therapeut Branch, Genet Pharmacol Unit, NIH, 10 Ctr Dr,MSC 1406, Bethesda, MD 20892 USA. OI Mouradian, M. Maral/0000-0002-9937-412X NR 52 TC 111 Z9 113 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 6 PY 2002 VL 277 IS 49 BP 47870 EP 47877 DI 10.1074/jbc.M203159200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 622TT UT WOS:000179663700133 PM 12364339 ER PT J AU He, Y Yeung, ES Chan, KC Issaq, HJ AF He, Y Yeung, ES Chan, KC Issaq, HJ TI Two dimensional mapping of cancer cell extracts by liquid chromatography-capillary electrophoresis with ultraviolet absorbance detection SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 15th international Symposium on Microscale Separations and Analysis (HPCE 2002) CY APR, 2002 CL STOCKHOLM, SWEDEN DE two-dimensional mapping; cancer cell extracts ID VOLUME SAMPLE STACKING; ZONE-ELECTROPHORESIS; PROTEINS; SEPARATION; PROTEOMICS; DRUGS AB A two-dimensional liquid chromatography/capillary electrophoresis technique was developed for rapid and comprehensive mapping of cell extracts. The cell extracts were first separated by reversed-phase HPLC based on hydrophobicity. Fractions of the effluent from the HPLC system were collected into 96-well microtiter plates and dried under vacuum. The fractions were reconstituted with deionized water, separated by capillary array electrophoresis based on charge-to-size ratio, and detected by UV absorption at 214 nm. Prior to analysis by multiplexed capillary electrophoresis, the reconstituted fractions were concentrated on-column using large volume sample stacking with polarity switching. In this way, high-resolution analysis of even the minor components in the complicated mixture was possible. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Iowa State Univ Sci & Technol, Ames Lab, USDOE, Ames, IA 50011 USA. Iowa State Univ Sci & Technol, Dept Chem, Ames, IA 50011 USA. NCI Frederick, SAIC Frederick, Frederick, MD 21702 USA. RP Yeung, ES (reprint author), Iowa State Univ Sci & Technol, Ames Lab, USDOE, Ames, IA 50011 USA. FU NCI NIH HHS [N01-CO-12400] NR 21 TC 13 Z9 14 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD DEC 6 PY 2002 VL 979 IS 1-2 BP 81 EP 89 AR PII S0021-9673(02)01503-0 DI 10.1016/S0021-9673(02)01503-0 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 618EX UT WOS:000179406700009 PM 12498235 ER PT J AU Bryant, SD George, C Flippen-Anderson, JL Deschamps, JR Salvadori, S Balboni, G Guerrini, R Lazarus, LH AF Bryant, SD George, C Flippen-Anderson, JL Deschamps, JR Salvadori, S Balboni, G Guerrini, R Lazarus, LH TI Crystal structures of dipeptides containing the Dmt-Tic pharmacophore SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DELTA-OPIOID ANTAGONISTS; X-RAY STRUCTURE; ENKEPHALIN ANALOG; RECEPTOR SELECTIVITY; HIGHLY POTENT; H-1-NMR DATA; IN-VITRO; PEPTIDE; AGONIST; DESIGN AB The crystal structures of three analogues of the potent delta-opioid receptor antagonist H-Dmt-Tic-OH (2',6'-dimethyl-L-tyrosine-L-1,2,3,4-tetrahydroisoquinoline-3-carboxylate), N,N (CH3)(2)-Dmt-Tic-OH (1), H-Dmt-Tic-NH-1-adamantane (2), and NN(CH3)2-Dmt-Tic-NH-1-adamantane (3) were determined by X-ray single-crystal analysis. Crystals of I were grown by slow evaporation, while those of 2 and 3 were grown by vapor diffusion. Compounds 1 and 3 crystallized in the monoclinic space group P2(1), and 2 crystallized in the tetragonal space group P4(3). Common backbone atom superimpositions of structures derived from X-ray diffraction studies resulted in root-mean-square (rms) deviations of 0.2-0.5 Angstrom, while all-atom superimpositions gave higher rms deviations from 0.8 to 1.2 Angstrom. Intramolecular distances between the aromatic ring centers of Dmt and Tic were 5.1 Angstrom in 1, 6.3 Angstrom in 2, and 6.5 Angstrom in 3. The orientation of the C-terminal substituent 1-adamantane in 2 and 3 was affected by differences in the psi torsion angles and strong hydrogen bonds with adjacent molecules. Despite the high delta-opioid receptor affinity exhibited by each analogue (K-i < 0.3 nM), highy-receptor affinity (K-i < 1 nM) was manifested only with the bulky C-terminal 1-adamantane analogues 2 and 3. Furthermore, the bioactivity of both 2 and 3 exhibited mu-agonism, while 3 also had potent delta-antagonist activity. Those data demonstrated that a C-terminal hydrophobic group was an important determinant for eliciting mu-agonism, whereas N-methylation maintained delta-antagonism. Furthermore, the structural results support the hypothesis that expanded dimensions between aromatic nuclei is important for acquiring mu-agonism. C1 NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. Univ Ferrara, Fac Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Ctr Biotechnol, I-44100 Ferrara, Italy. USN, Res Lab, Washington, DC 20375 USA. Univ Cagliari, Dept Toxicol, I-09126 Cagliari, Italy. RP Bryant, SD (reprint author), NIEHS, LCBRA, POB 12233,Mail Drop C3-04, Res Triangle Pk, NC 27709 USA. OI Deschamps, Jeffrey/0000-0001-5845-0010; Guerrini, Remo/0000-0002-7619-0918; SALVADORI, Severo/0000-0002-8224-2358 NR 53 TC 13 Z9 13 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 5 PY 2002 VL 45 IS 25 BP 5506 EP 5513 DI 10.1021/jm020330p PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 622EA UT WOS:000179632500012 PM 12459018 ER PT J AU Balboni, G Salvadori, S Guerrini, R Negri, L Giannini, E Jinsmaa, Y Bryant, SD Lazarus, LH AF Balboni, G Salvadori, S Guerrini, R Negri, L Giannini, E Jinsmaa, Y Bryant, SD Lazarus, LH TI Potent delta-opioid receptor agonists containing the Dmt-Tic pharmacophore SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID TETRAPEPTIDE TYR-COH JOM-13; SUPRASPINAL ANTINOCICEPTION; DIPEPTIDE ANALOGS; PEPTIDE FAMILY; G-PROTEINS; ANTAGONISTS; SELECTIVITY; DESIGN; MODEL; REPLACEMENTS AB Conversion of delta-opioid receptor antagonists containing the 2',6'-dimethyl-L-tyrosine (Dmt)-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid (Tic) pharmacophore into potent delta-agonists required a third heteroaromatic nucleus, such as 1H-benzimidazole-2-yl (Bid) and a linker of specified length both located C-terminally to Tic in the general formula H-Dmt-Tic-NH-CH(R)-R'. The distance between Tic and Bid is a determining factor responsible for the acquisition of delta agonism (2, 2', 3, 4, 6) or delta antagonism (8). Compounds containing a C-terminal Ala (1, 1'), Asp (5), or Asn (7) with an amide (1, 1', 5) or free acid group (7) served as delta-antagonist controls lacking the third heteroaromatic ring. A change in chirality of the spacer (2, 2') or inclusion of a negative charge via derivatives of Asp (4, 6) resulted in potent delta agonism and moderatey agonism, although delta-receptor affinity decreased about 10-fold for 4 while mu affinity fell by over 2 orders of magnitude. Repositioning of the negative charge in the linker altered activity: H-Dmt-Tic-NH-CH(CH2-Bid)COOH (6) maintained high delta affinity (K-i = 0.042 nM) and delta agonism (IC50 = 0.015 nM), but attachment of the free acid group to Bid [H-Dmt-Tic-NH-CH2-Bid(CH2-COOH) (9)] reconstituted delta antagonism (K-e = 0.27 nM). The data demonstrate that a linker separating the Dmt-Tic pharmacophore and Bid, regardless of the presence of a negative charge, is important in the acquisition of opioids exhibiting potent delta agonism and weaky agonism from a parent delta antagonist. C1 NIEHS, LCBRA, Res Triangle Pk, NC 27709 USA. Univ Cagliari, Dept Toxicol, I-09126 Cagliari, Italy. Univ Ferrara, Dept Pharmaceut Sci, I-44100 Ferrara, Italy. Univ Ferrara, Dept Biotechnol, I-44100 Ferrara, Italy. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol Vitorio Erspamer, I-00185 Rome, Italy. RP Lazarus, LH (reprint author), NIEHS, LCBRA, MD C3-04,POB 12233, Res Triangle Pk, NC 27709 USA. EM lazarus@niehs.nih.gov OI Guerrini, Remo/0000-0002-7619-0918 NR 46 TC 62 Z9 64 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD DEC 5 PY 2002 VL 45 IS 25 BP 5556 EP 5563 DI 10.1021/jm020336e PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 622EA UT WOS:000179632500017 PM 12459023 ER PT J AU Sostaric, JZ Riesz, P AF Sostaric, JZ Riesz, P TI Adsorption of surfactants at the gas/solution interface of cavitation bubbles: An ultrasound intensity-independent frequency effect in sonochemistry SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID AIR-WATER-INTERFACE; AQUEOUS-SOLUTION; BIMETALLIC NANOPARTICLES; EMULSION POLYMERIZATION; PALLADIUM NANOPARTICLES; PLATINUM NANOPARTICLES; ACOUSTIC CAVITATION; RECTIFIED DIFFUSION; IONIC SURFACTANTS; 20 KHZ AB A major limitation in determining the effects of ultrasound frequency in sonochemistry in relation to cavitation is that no reliable relationship exists between the energy supplied to the system and the energy converted by the cavitation process in producing a sonochemical effect. However, the current study presents a frequency effect that is independent of the energy supplied to the system. Spin-trapping of secondary carbon radicals with 3,5-dibromo-4-nitrosobenzenesulfonic acid-d(2) (DBNBS-d(2)) and electron paramagnetic resonance (EPR) have been used to determine the relative ability of two nonvolatile surfactants [sodium 1-pentanesulfonic acid (SPSo) and sodium dodecyl sulfate (SDS)] to scavenge .H atoms and .OH radicals at the gas/solution interface of cavitation bubbles. The results obtained at 354 and 1057 kHz are compared to those observed previously at 47 kHz (Sostaric, J. Z.; Riesz, P. J. Am. Chem. Soc. 2001, 123, 11010-11019). At particular bulk surfactant concentrations, both surfactants reached a limiting plateau value in radical scavenging ability. At 354 kHz (and 47 kHz), the magnitude of this plateau was greater for SPSo compared to that for SDS. However, at 1057 kHz, no difference in the plateau value was observed between SPSo and SDS. Decreasing the ultrasound intensity at constant frequency during the sonolysis of SPSo and SDS resulted in a decrease in the -(CH)-C-.- radical yield. However, there was no change in the relative plateau yield of -(CH)-C-.- radicals between SPSo and SDS. Thus, at plateau concentrations, the relative ability of these n-alkyl chain surfactants to scavenge radicals at the gas/solution interface of cavitation bubbles depends on the frequency of sonolysis but is independent of ultrasound intensity. The results were interpreted in terms of a decrease in the rate of change of the surface area of "high-energy-stable cavitation bubbles" at higher frequencies. This would affect the relative adsorption and hence radical scavenging efficiencies of SPSo and SDS at the gas/solution interface of these types of cavitation bubbles. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RP Sostaric, JZ (reprint author), NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. RI Sostaric, Joe/A-6033-2008 NR 83 TC 48 Z9 48 U1 2 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD DEC 5 PY 2002 VL 106 IS 48 BP 12537 EP 12548 DI 10.1021/jp022106h PG 12 WC Chemistry, Physical SC Chemistry GA 621YH UT WOS:000179618200025 ER PT J AU Belkaid, Y Piccirillo, CA Mendez, S Shevach, EM Sacks, DL AF Belkaid, Y Piccirillo, CA Mendez, S Shevach, EM Sacks, DL TI CD4(+)CD25(+) regulatory T cells control Leishmania major persistence and immunity SO NATURE LA English DT Article ID AZAR DERMAL LEISHMANIASIS; INTERFERON-GAMMA; KALA-AZAR; DENDRITIC CELLS; ACTIVATION; INTERLEUKIN-10; IL-10; SKIN; EXPRESSION; DISEASE AB The long-term persistence of pathogens in a host that is also able to maintain strong resistance to reinfection, referred to as concomitant immunity, is a hallmark of certain infectious diseases, including tuberculosis and leishmaniasis. The ability of pathogens to establish latency in immune individuals often has severe consequences for disease reactivation(1-3). Here we show that the persistence of Leishmania major in the skin after healing in resistant C57BL/6 mice is controlled by an endogenous population of CD4(+)CD25(+) regulatory T cells. These cells constitute 5-10% of peripheral CD4(+) T cells in naive mice and humans, and suppress several potentially pathogenic responses in vivo, particularly T-cell responses directed against self-antigens(4). During infection by L. major, CD4(+)CD25(+) T cells accumulate in the dermis, where they suppress-by both interleukin-10-dependent and interleukin-10-independent mechanisms-the ability of CD4(+)CD25(-) effector T cells to eliminate the parasite from the site. The sterilizing immunity achieved in mice with impaired IL-10 activity is followed by the loss of immunity to reinfection, indicating that the equilibrium established between effector and regulatory T cells in sites of chronic infection might reflect both parasite and host survival strategies. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Belkaid, Y (reprint author), Childrens Hosp, Div Mol Immunol, Res Fdn, 3333 Burnet Ave,MLC 7021, Cincinnati, OH 45229 USA. NR 26 TC 1148 Z9 1209 U1 5 U2 41 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 5 PY 2002 VL 420 IS 6915 BP 502 EP 507 DI 10.1038/nature01152 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 621VK UT WOS:000179611600045 PM 12466842 ER PT J AU Waterston, RH Lindblad-Toh, K Birney, E Rogers, J Abril, JF Agarwal, P Agarwala, R Ainscough, R Alexandersson, M An, P Antonarakis, SE Attwood, J Baertsch, R Bailey, J Barlow, K Beck, S Berry, E Birren, B Bloom, T Bork, P Botcherby, M Bray, N Brent, MR Brown, DG Brown, SD Bult, C Burton, J Butler, J Campbell, RD Carninci, P Cawley, S Chiaromonte, F Chinwalla, AT Church, DM Clamp, M Clee, C Collins, FS Cook, LL Copley, RR Coulson, A Couronne, O Cuff, J Curwen, V Cutts, T Daly, M David, R Davies, J Delehaunty, KD Deri, J Dermitzakis, ET Dewey, C Dickens, NJ Diekhans, M Dodge, S Dubchak, I Dunn, DM Eddy, SR Elnitski, L Emes, RD Eswara, P Eyras, E Felsenfeld, A Fewell, GA Flicek, P Foley, K Frankel, WN Fulton, LA Fulton, RS Furey, TS Gage, D Gibbs, RA Glusman, G Gnerre, S Goldman, N Goodstadt, L Grafham, D Graves, TA Green, ED Gregory, S Guigo, R Guyer, M Hardison, RC Haussler, D Hayashizaki, Y Hillier, LW Hinrichs, A Hlavina, W Holzer, T Hsu, F Hua, A Hubbard, T Hunt, A Jackson, I Jaffe, DB Johnson, LS Jones, M Jones, TA Joy, A Kamal, M Karlsson, EK Karolchik, D Kasprzyk, A Kawai, J Keibler, E Kells, C Kent, WJ Kirby, A Kolbe, DL Korf, I Kucherlapati, RS Kulbokas, EJ Kulp, D Landers, T Leger, JP Leonard, S Letunic, I Levine, R Li, J Li, M Lloyd, C Lucas, S Ma, B Maglott, DR Mardis, ER Matthews, L Mauceli, E Mayer, JH McCarthy, M McCombie, WR McLaren, S McLay, K McPherson, JD Meldrim, J Meredith, B Mesirov, JP Miller, W Miner, TL Mongin, E Montgomery, KT Morgan, M Mott, R Mullikin, JC Muzny, DM Nash, WE Nelson, JO Nhan, MN Nicol, R Ning, Z Nusbaum, C O'Connor, MJ Okazaki, Y Oliver, K Larty, EO Pachter, L Parra, G Pepin, KH Peterson, J Pevzner, P Plumb, R Pohl, CS Poliakov, A Ponce, TC Ponting, CP Potter, S Quail, M Reymond, A Roe, BA Roskin, KM Rubin, EM Rust, AG Santos, R Sapojnikov, V Schultz, B Schultz, J Schwartz, MS Schwartz, S Scott, C Seaman, S Searle, S Sharpe, T Sheridan, A Shownkeen, R Sims, S Singer, JB Slater, G Smit, A Smith, DR Spencer, B Stabenau, A Strange-Thomann, NS Sugnet, C Suyama, M Tesler, G Thompson, J Torrents, D Trevaskis, E Tromp, J Ucla, C Vidal, AU Vinson, JP von Niederhausern, AC Wade, CM Wall, M Weber, RJ Weiss, RB Wendl, MC West, AP Wetterstrand, K Wheeler, R Whelan, S Wierzbowski, J Willey, D Williams, S Wilson, RK Winter, E Worley, KC Wyman, D Yang, S Yang, SP Zdobnov, EM Zody, MC Lander, ES AF Waterston, RH Lindblad-Toh, K Birney, E Rogers, J Abril, JF Agarwal, P Agarwala, R Ainscough, R Alexandersson, M An, P Antonarakis, SE Attwood, J Baertsch, R Bailey, J Barlow, K Beck, S Berry, E Birren, B Bloom, T Bork, P Botcherby, M Bray, N Brent, MR Brown, DG Brown, SD Bult, C Burton, J Butler, J Campbell, RD Carninci, P Cawley, S Chiaromonte, F Chinwalla, AT Church, DM Clamp, M Clee, C Collins, FS Cook, LL Copley, RR Coulson, A Couronne, O Cuff, J Curwen, V Cutts, T Daly, M David, R Davies, J Delehaunty, KD Deri, J Dermitzakis, ET Dewey, C Dickens, NJ Diekhans, M Dodge, S Dubchak, I Dunn, DM Eddy, SR Elnitski, L Emes, RD Eswara, P Eyras, E Felsenfeld, A Fewell, GA Flicek, P Foley, K Frankel, WN Fulton, LA Fulton, RS Furey, TS Gage, D Gibbs, RA Glusman, G Gnerre, S Goldman, N Goodstadt, L Grafham, D Graves, TA Green, ED Gregory, S Guigo, R Guyer, M Hardison, RC Haussler, D Hayashizaki, Y Hillier, LW Hinrichs, A Hlavina, W Holzer, T Hsu, F Hua, A Hubbard, T Hunt, A Jackson, I Jaffe, DB Johnson, LS Jones, M Jones, TA Joy, A Kamal, M Karlsson, EK Karolchik, D Kasprzyk, A Kawai, J Keibler, E Kells, C Kent, WJ Kirby, A Kolbe, DL Korf, I Kucherlapati, RS Kulbokas, EJ Kulp, D Landers, T Leger, JP Leonard, S Letunic, I Levine, R Li, J Li, M Lloyd, C Lucas, S Ma, B Maglott, DR Mardis, ER Matthews, L Mauceli, E Mayer, JH McCarthy, M McCombie, WR McLaren, S McLay, K McPherson, JD Meldrim, J Meredith, B Mesirov, JP Miller, W Miner, TL Mongin, E Montgomery, KT Morgan, M Mott, R Mullikin, JC Muzny, DM Nash, WE Nelson, JO Nhan, MN Nicol, R Ning, Z Nusbaum, C O'Connor, MJ Okazaki, Y Oliver, K Larty, EO Pachter, L Parra, G Pepin, KH Peterson, J Pevzner, P Plumb, R Pohl, CS Poliakov, A Ponce, TC Ponting, CP Potter, S Quail, M Reymond, A Roe, BA Roskin, KM Rubin, EM Rust, AG Santos, R Sapojnikov, V Schultz, B Schultz, J Schwartz, MS Schwartz, S Scott, C Seaman, S Searle, S Sharpe, T Sheridan, A Shownkeen, R Sims, S Singer, JB Slater, G Smit, A Smith, DR Spencer, B Stabenau, A Strange-Thomann, NS Sugnet, C Suyama, M Tesler, G Thompson, J Torrents, D Trevaskis, E Tromp, J Ucla, C Vidal, AU Vinson, JP von Niederhausern, AC Wade, CM Wall, M Weber, RJ Weiss, RB Wendl, MC West, AP Wetterstrand, K Wheeler, R Whelan, S Wierzbowski, J Willey, D Williams, S Wilson, RK Winter, E Worley, KC Wyman, D Yang, S Yang, SP Zdobnov, EM Zody, MC Lander, ES CA Mouse Genome Sequencing Consor TI Initial sequencing and comparative analysis of the mouse genome SO NATURE LA English DT Review ID SEMINAL-VESICLE AUTOANTIGEN; SINGLE-NUCLEOTIDE POLYMORPHISMS; CONSERVED NONCODING SEQUENCES; HOMOGENEOUSLY STAINING REGION; PROLACTIN-INDUCIBLE PROTEIN; X-CHROMOSOME INACTIVATION; KILLER-CELL RECEPTORS; RADIATION HYBRID MAP; FACTOR-BINDING SITES; TRANSFER-RNA GENES AB The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism. C1 Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. MIT, Ctr Genome Res, Whitehead Inst, Cambridge, MA 02141 USA. European Bioinformat Inst, Cambridge CB10 1SD, England. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Univ Pompeu Fabra, Inst Municipal Invest Med, Res Grp Biomed Informat, Barcelona, Catalonia, Spain. GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Univ Geneva, Sch Med, Div Med Genet, CH-1211 Geneva 10, Switzerland. Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. European Mol Biol Lab, D-69117 Heidelberg, Germany. MRC, Mammalian Genet Unit, UK MRC Mouse Sequencing Consortium, Harwell OX11 0RD, Berks, England. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. Washington Univ, Dept Comp Sci, St Louis, MO 63130 USA. Univ Waterloo, Sch Comp Sci, Waterloo, ON N2L 3G1, Canada. Jackson Lab, Bar Harbor, ME 04609 USA. Yokohama Inst, RIKEN Genom Sci Ctr, Lab Genome Explorat, Kanagawa 2300045, Japan. Affymetrix Inc, Oakland, CA 94608 USA. Penn State Univ, Dept Stat, University Pk, PA 16802 USA. Penn State Univ, Dept Hlth Evaluat Sci, University Pk, PA 16802 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Univ Calif Berkeley, Dept Elect Engn, Berkeley, CA 94720 USA. Univ Oxford, Dept Human Anat & Genet, MRC, Funct Genet Unit, Oxford OX1 3QX, England. Univ Utah, Dept Human Genet, Salt Lake City, UT 84112 USA. Washington Univ, Sch Med, Howard Hughes Med Inst, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA. Inst Syst Biol, Seattle, WA 98103 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Calif Santa Cruz, Howard Hughes Med Inst, Santa Cruz, CA 95064 USA. Univ Oklahoma, Dept Chem & Biochem, Adv Ctr Genome Technol, Norman, OK 73019 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Partners Ctr Genet & Genom, Boston, MA 02115 USA. Penn State Univ, Dept Stat, University Pk, PA 16802 USA. Univ Calif Santa Barbara, Dept Comp Sci, Santa Barbara, CA 93106 USA. US DOE, Joint Genome Inst, Walnut Creek, CA 94598 USA. Univ Western Ontario, Dept Comp Sci, London, ON N6A 5B7, Canada. Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Wellcome Trust Res Labs, London NW1 2BE, England. Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA. Max Planck Inst Mol Genet, D-14195 Berlin, Germany. Genome Therapeut Corp, Waltham, MA 02453 USA. Bioinformat Solut Inc, Waterloo, ON N2L 3L2, Canada. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. MIT, Dept Biol, Cambridge, MA 02138 USA. RP Waterston, RH (reprint author), Washington Univ, Sch Med, Genome Sequencing Ctr, Campus Box 8501,4444 Forest Pk Ave, St Louis, MO 63108 USA. EM waterston@gs.washington.edu; kersli@genome.wi.mit.edu RI Torrents, David/G-5785-2015; Abril Ferrando, Josep/B-3877-2014; Carninci, Piero/K-1568-2014; Eyras, Eduardo/L-1053-2014; Antonarakis, Stylianos/N-8866-2014; Ning, Zemin/D-2411-2013; Guigo, Roderic/D-1303-2010; Kawai, Jun/A-6451-2016; Gasull, Martina/A-6630-2013; Wendl, Michael/A-2741-2008; Schultz, Joerg/B-9346-2008; Hubbard, Tim/C-2567-2008; Letunic, Ivica/A-6032-2009; Hardison, Ross/G-1142-2010; Whelan, Simon/A-6638-2011; Eyras, Eduardo/A-1560-2010; Emes, Richard/C-5341-2008; Couronne, Olivier Couronne/G-1244-2012; Zdobnov, Evgeny/K-1133-2012; Seaman, Steven/A-2755-2013; Dermitzakis, Emmanouil/B-7687-2013; Ma, Bin/C-7550-2013; Bork, Peer/F-1813-2013 OI Hinrichs, Angie/0000-0002-1697-1130; Letunic, Ivica/0000-0003-3560-4288; Ponting, Chris/0000-0003-0202-7816; Glusman, Gustavo/0000-0001-8060-5955; Dickens, Nicholas/0000-0003-0492-5855; Eddy, Sean/0000-0001-6676-4706; Rust, Alistair/0000-0001-7287-192X; Furey, Terry/0000-0001-5546-9672; Torrents, David/0000-0002-6086-9037; McCombie, W. Richard/0000-0003-1899-0682; Schultz, Brian/0000-0003-4964-976X; Goldman, Nick/0000-0001-8486-2211; Flicek, Paul/0000-0002-3897-7955; Wade, Claire/0000-0003-3413-4771; Birney, Ewan/0000-0001-8314-8497; Abril Ferrando, Josep/0000-0001-7793-589X; Carninci, Piero/0000-0001-7202-7243; Eyras, Eduardo/0000-0003-0793-6218; Antonarakis, Stylianos/0000-0001-8907-5823; Guigo, Roderic/0000-0002-5738-4477; Agarwal, Pankaj/0000-0002-4165-9990; Karlsson, Elinor/0000-0002-4343-3776; Hunt, Adrienne/0000-0002-1227-0310; Ning, Zemin/0000-0003-4359-776X; Hubbard, Tim/0000-0002-1767-9318; Hardison, Ross/0000-0003-4084-7516; Emes, Richard/0000-0001-6855-5481; Seaman, Steven/0000-0003-3349-3334; Bork, Peer/0000-0002-2627-833X NR 330 TC 3898 Z9 4058 U1 42 U2 294 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 5 PY 2002 VL 420 IS 6915 BP 520 EP 562 DI 10.1038/nature01262 PG 43 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 621VK UT WOS:000179611600053 ER PT J AU Okazaki, Y Furuno, M Kasukawa, T Adachi, J Bono, H Kondo, S Nikaido, I Osato, N Saito, R Suzuki, H Yamanaka, I Kiyosawa, H Yagi, K Tomaru, Y Hasegawa, Y Nogami, A Schonbach, C Gojobori, T Baldarelli, R Hill, DP Bult, C Hume, DA Quackenbush, J Schriml, LM Kanapin, A Matsuda, H Batalov, S Beisel, KW Blake, JA Bradt, D Brusic, V Chothia, C Corbani, LE Cousins, S Dalla, E Dragani, TA Fletcher, CF Forrest, A Frazer, KS Gaasterland, T Gariboldi, M Gissi, C Godzik, A Gough, J Grimmond, S Gustincich, S Hirokawa, N Jackson, IJ Jarvis, ED Kanai, A Kawaji, H Kawasawa, Y Kedzierski, RM King, BL Konagaya, A Kurochkin, IV Lee, Y Lenhard, B Lyons, PA Maglott, DR Maltais, L Marchionni, L McKenzie, L Miki, H Nagashima, T Numata, K Okido, T Pavan, WJ Pertea, G Pesole, G Petrovsky, N Pillai, R Pontius, JU Qi, D Ramachandran, S Ravasi, T Reed, JC Reed, DJ Reid, J Ring, BZ Ringwald, M Sandelin, A Schneider, C Semple, CAM Setou, M Shimada, K Sultana, R Takenaka, Y Taylor, MS Teasdale, RD Tomita, M Verardo, R Wagner, L Wahlestedt, C Wang, Y Watanabe, Y Wells, C Wilming, LG Wynshaw-Boris, A Yanagisawa, M Yang, I Yang, L Yuan, Z Zavolan, M Zhu, Y Zimmer, A Carninci, P Hayatsu, N Hirozane-Kishikawa, T Konno, H Nakamura, M Sakazume, N Sato, K Shiraki, T Waki, K Kawai, J Aizawa, K Arakawa, T Fukuda, S Hara, A Hashizume, W Imotani, K Ishii, Y Itoh, M Kagawa, I Miyazaki, A Sakai, K Sasaki, D Shibata, K Shinagawa, A Yasunishi, A Yoshino, M Waterston, R Lander, ES Rogers, J Birney, E Hayashizaki, Y AF Okazaki, Y Furuno, M Kasukawa, T Adachi, J Bono, H Kondo, S Nikaido, I Osato, N Saito, R Suzuki, H Yamanaka, I Kiyosawa, H Yagi, K Tomaru, Y Hasegawa, Y Nogami, A Schonbach, C Gojobori, T Baldarelli, R Hill, DP Bult, C Hume, DA Quackenbush, J Schriml, LM Kanapin, A Matsuda, H Batalov, S Beisel, KW Blake, JA Bradt, D Brusic, V Chothia, C Corbani, LE Cousins, S Dalla, E Dragani, TA Fletcher, CF Forrest, A Frazer, KS Gaasterland, T Gariboldi, M Gissi, C Godzik, A Gough, J Grimmond, S Gustincich, S Hirokawa, N Jackson, IJ Jarvis, ED Kanai, A Kawaji, H Kawasawa, Y Kedzierski, RM King, BL Konagaya, A Kurochkin, IV Lee, Y Lenhard, B Lyons, PA Maglott, DR Maltais, L Marchionni, L McKenzie, L Miki, H Nagashima, T Numata, K Okido, T Pavan, WJ Pertea, G Pesole, G Petrovsky, N Pillai, R Pontius, JU Qi, D Ramachandran, S Ravasi, T Reed, JC Reed, DJ Reid, J Ring, BZ Ringwald, M Sandelin, A Schneider, C Semple, CAM Setou, M Shimada, K Sultana, R Takenaka, Y Taylor, MS Teasdale, RD Tomita, M Verardo, R Wagner, L Wahlestedt, C Wang, Y Watanabe, Y Wells, C Wilming, LG Wynshaw-Boris, A Yanagisawa, M Yang, I Yang, L Yuan, Z Zavolan, M Zhu, Y Zimmer, A Carninci, P Hayatsu, N Hirozane-Kishikawa, T Konno, H Nakamura, M Sakazume, N Sato, K Shiraki, T Waki, K Kawai, J Aizawa, K Arakawa, T Fukuda, S Hara, A Hashizume, W Imotani, K Ishii, Y Itoh, M Kagawa, I Miyazaki, A Sakai, K Sasaki, D Shibata, K Shinagawa, A Yasunishi, A Yoshino, M Waterston, R Lander, ES Rogers, J Birney, E Hayashizaki, Y CA FANTOM Consurtium RIKEN Genome Exploration Res Grp TI Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs SO NATURE LA English DT Article ID HUMAN GENOME; GENE ONTOLOGY; SEQUENCE; PROTEIN; ELEMENTS; RNA; CLASSIFICATION; IDENTIFICATION; CHROMOSOME-22; COLLECTION AB Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics. C1 RIKEN Yokohama Inst, RIKEN Genom Sci Ctr, Lab Genome Explorat Res Grp, Tsurumi KU, Yokohama, Kanagawa 2300045, Japan. Discovery & Res Inst, Genome Sci Lab, Wako, Saitama 3510198, Japan. NTT Software Corp, Naka Ku, Kanagawa 2318554, Japan. Yokohama City Univ, Grad Sch Integrated Sci, Div Genom Informat Resources Sci Biol Supramol Sy, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. Keio Univ, Inst Adv Biosci, Yamagata 9970017, Japan. Univ Tsukuba, Inst Basic Med Sci, Tsukuba, Ibaraki 3058577, Japan. RIKEN Yokohama Inst, RIKEN Genom Sci Ctr, Bioinformat Grp, Biomed Knowledge Discovery Team, Kanagawa 2300045, Japan. Natl Inst Genet, DNA Data Bank Japan, Shizuoka 4118540, Japan. Natl Inst Genet, Ctr Informat Biol, Shizuoka 4118540, Japan. Jackson Lab, Mouse Genome Informat Grp, Bar Harbor, ME 04609 USA. Univ Queensland, Inst Mol Biosci, Brisbane, Qld 4072, Australia. Univ Queensland, ARC Special Res Ctr Funct & Appl Genom, Brisbane, Qld 4072, Australia. Inst Genom Res TIGR, Rockville, MD 20850 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. European Bioinformat Inst, Cambridge CB10 1SD, England. Osaka Univ, Grad Sch Informat Sci & Technol, Osaka 5608531, Japan. Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. Boys Town Natl Res Hosp, Omaha, NE 68131 USA. Labs Informat Technol, Singapore 119613, Singapore. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. LNCIB, Funct Genom, I-34012 Trieste, Italy. Ist Tumori Milano, I-20133 Milan, Italy. The Scripps Res Inst, Res Inst, La Jolla, CA 92037 USA. Univ Oregon, Zebrafish Int Resource Ctr, Eugene, OR 97403 USA. Rockefeller Univ, Lab Computat Genom, New York, NY 10021 USA. Univ Milan, I-20133 Milan, Italy. Burnham Inst, La Jolla, CA 92037 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Tokyo, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan. MRC, Human Genet Unit, Edinburgh, Midlothian, Scotland. Duke Univ, Med Ctr, Dept Neurobiol, Durham, NC 27710 USA. Univ Texas, SW Med Ctr, Dept Mol Genet, Howard Hughes Med Inst, Dallas, TX 75390 USA. Karolinska Inst, Ctr Genom & Bioinformat, S-17177 Stockholm, Sweden. Addenbrookes Hosp, Cambridge Inst Med Res, JDRF WT Diabet & Inflammat Lab, Cambridge CB2 2XY, England. NHGRI, NIH, Bethesda, MD 20892 USA. Canberra Hosp, Autoimmun Res Unit, Woden, ACT 2606, Australia. Appl Genom Inc, Sunnyvale, CA 94085 USA. Hirakata Ryoikuen, Osaka 5650874, Japan. Hyogo Med Univ, Inst Adv Med Sci, Nishinomiya, Hyogo 6638501, Japan. Wellcome Trust Sanger Inst, Hinxton CB10 1SA, Cambs, England. Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. Univ Bonn, Dept Psychiat, D-53105 Bonn, Germany. Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. Whitehead Inst MIT Ctr Genome Res, Cambridge, MA 02141 USA. RP Hayashizaki, Y (reprint author), RIKEN Yokohama Inst, RIKEN Genom Sci Ctr, Lab Genome Explorat Res Grp, Tsurumi KU, 1-7-22 Suehiro Cho, Yokohama, Kanagawa 2300045, Japan. EM yosihide@gsc.riken.go.jp RI Dragani, Tommaso/K-4493-2016; Kanapin, Alexander/Q-7590-2016; Schonbach, Christian/B-1998-2009; Kawaji, Hideya/N-5116-2015; gariboldi, manuela/K-4744-2016; Hume, David/C-7695-2013; Kanapin, Alexander/E-7632-2013; Pesole, Graziano/E-9051-2014; Konagaya, Akihiko/F-9302-2014; Carninci, Piero/K-1568-2014; NIKAIDO, Itoshi/K-2058-2014; Sandelin, Albin/G-2881-2011; Konno, Hideaki/N-4366-2014; Kasukawa, Takeya/N-5070-2015; Itoh, Masayoshi/N-5363-2015; Suzuki, Harukazu/N-9553-2015; Kawai, Jun/A-6451-2016; Grimmond, Sean/J-5304-2016; Yuan, Zheng/A-1344-2008; Wells, Christine/A-5071-2010; Reid, James/G-2496-2010; Zimmer, Andreas/B-8357-2009; Pesole, Graziano/C-1408-2009; Jarvis, Erich/A-2319-2008; Forrest, Alistair/A-6597-2008; Ravasi, Timothy/B-8777-2008; Wahlestedt, Claes/A-7039-2009; Teasdale, Rohan/B-2538-2009; Semple, Colin/A-5613-2009; Taylor, Martin/C-3825-2009; Konno, Hideaki/A-9191-2012; Godzik, Adam/A-7279-2009 OI King, Benjamin/0000-0001-6463-1336; Zavolan, Mihaela/0000-0002-8832-2041; Bono, Hidemasa/0000-0003-4413-0651; Dragani, Tommaso/0000-0001-5915-4598; Kanapin, Alexander/0000-0001-9802-5297; Schonbach, Christian/0000-0002-0693-7617; Kawaji, Hideya/0000-0002-0575-0308; gariboldi, manuela/0000-0001-8406-165X; Wilming, Laurens/0000-0002-4154-7358; Kanai, Akio/0000-0002-6362-2419; Reid, James/0000-0001-6997-2850; Gissi, Carmela/0000-0002-2269-079X; Schriml, Lynn/0000-0001-8910-9851; Birney, Ewan/0000-0001-8314-8497; Lenhard, Boris/0000-0002-1114-1509; Petrovsky, Nikolai/0000-0002-1580-5245; Blake, Judith/0000-0001-8522-334X; Pesole, Graziano/0000-0003-3663-0859; Carninci, Piero/0000-0001-7202-7243; NIKAIDO, Itoshi/0000-0002-7261-2570; Sandelin, Albin/0000-0002-7109-7378; Konno, Hideaki/0000-0002-8470-4835; Kasukawa, Takeya/0000-0001-5085-0802; Itoh, Masayoshi/0000-0002-1772-318X; Suzuki, Harukazu/0000-0002-8087-0836; Grimmond, Sean/0000-0002-8102-7998; Wells, Christine/0000-0003-3133-3628; Pesole, Graziano/0000-0003-3663-0859; Jarvis, Erich/0000-0001-8931-5049; Forrest, Alistair/0000-0003-4543-1675; Teasdale, Rohan/0000-0001-7455-5269; Semple, Colin/0000-0003-1765-4118; Taylor, Martin/0000-0001-7656-330X; Godzik, Adam/0000-0002-2425-852X NR 52 TC 959 Z9 1043 U1 12 U2 106 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD DEC 5 PY 2002 VL 420 IS 6915 BP 563 EP 573 DI 10.1038/nature01266 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 621VK UT WOS:000179611600054 PM 12466851 ER PT J AU Stevens, B Porta, S Haak, LL Gallo, V Fields, RD AF Stevens, B Porta, S Haak, LL Gallo, V Fields, RD TI Adenosine: A neuron-glial transmitter promoting myelination in the CNS in response to action potentials SO NEURON LA English DT Article ID OLIGODENDROCYTE PRECURSOR CELLS; CENTRAL-NERVOUS-SYSTEM; L1 ADHESION MOLECULE; ELECTRICAL-ACTIVITY; THYROID-HORMONE; RETINOIC ACID; LINEAGE CELLS; SCHWANN-CELLS; DIFFERENTIATION; PROLIFERATION AB Neuronal activity influences myelination of the brain, but the molecular mechanisms involved are largely unknown. Here, we report that oligodendrocyte progenitor cells (OPCs) express functional adenosine receptors, which are activated in response to action potential firing. Adenosine acts as a potent neuronglial transmitter to inhibit OPC proliferation, stimulate differentiation, and promote the formation of myelin. This neuron-glial signal provides a molecular mechanism for promoting oligodendrocyte development and myelination in response to impulse activity and may help resolve controversy on the opposite effects of impulse activity on myelination in the central and peripheral nervous systems. C1 NICHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RI Haak, Laurel/C-4986-2008 OI Haak, Laurel/0000-0001-5109-3700 FU NICHD NIH HHS [Z01 HD000713-11] NR 54 TC 277 Z9 285 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE,, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD DEC 5 PY 2002 VL 36 IS 5 BP 855 EP 868 DI 10.1016/S0896-6273(02)01067-X PG 14 WC Neurosciences SC Neurosciences & Neurology GA 622VL UT WOS:000179667800010 PM 12467589 ER PT J AU Scahill, L Vitiello, B AF Scahill, L Vitiello, B CA Res Units Pediat Psychopharmacolog TI Risperidone in children with autism and serious behavioral problems - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Yale Univ, New Haven, CT 06520 USA. NIMH, Bethesda, MD 20892 USA. RP Scahill, L (reprint author), Yale Univ, New Haven, CT 06520 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 5 PY 2002 VL 347 IS 23 BP 1891 EP 1891 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 621NW UT WOS:000179596900025 ER PT J AU Hel, Z Nacsa, J Tsai, WP Thornton, A Giuliani, L Tartaglia, J Franchini, G AF Hel, Z Nacsa, J Tsai, WP Thornton, A Giuliani, L Tartaglia, J Franchini, G TI Equivalent immunogenicity of the highly attenuated poxvirus-based ALVAC-SIV and NYVAC-SIV vaccine candidates in SlVmac251-infected macaques SO VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; CYTOTOXIC T-LYMPHOCYTES; IMMUNODEFICIENCY VIRUS-INFECTION; CELLULAR IMMUNE-RESPONSES; CD8(+) LYMPHOCYTES; VIRAL SUPPRESSION; ESCAPE VARIANTS; HIV-1 INFECTION; DECAY KINETICS; PLASMA VIREMIA AB Therapeutic immunization of HIV-1-infected individuals may induce and/or enhance HIV-1-specific immune responses and decrease the dependency on antiretroviral drug treatment. However, repeated immunizations with live-recombinant vectors may induce vector-specific immune responses that interfere with the elicitation of vigorous immune responses to the desired antigen. Therefore, the use of mixed-modality vaccinations may be necessary to induce sustained virus-specific immune responses in HIV-1-infected individuals treated with antiretroviral therapy (ART). Thus, the relative immunogenicity of various vaccine modalities needs to be assessed. Here we compared the immunogenicity of two vaccine candidates, the canarypox-based ALVAC-SIV-gag-pol-env (ALVAC-SIV-gpe) and the vaccinia-based NYVAC-SIV-gag-pol-env (NYVAC-SIV-gpe), in rhesus macaques infected with SIVmac251 and treated with ART by 2 weeks postinfection. Both ALVAC-SIV-gpe and NYVAC-SIV-gpe vaccine candidates induced and/or enhanced a virus-specific CD8(+) T cell response to a similar extent, as demonstrated by tetramer staining of Gag-specific CD8(+) T cells. Similarly, both vaccines elicited comparable lymphoproliferative responses (LPRs) to the SIV p27 Gag and gp120 Env proteins. Thus, both these vaccine modalities alone or in combination may be suitable candidate vaccines for immune therapy of HIV-1-infected individuals. (C) 2002 Elsevier Science (USA). C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Aventis Pasteur Ltd, Toronto, ON M2R 3T4, Canada. RP Franchini, G (reprint author), NCI, Basic Res Lab, 41-D804, Bethesda, MD 20892 USA. OI Hel, Zdenek/0000-0002-4923-4794 NR 49 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD DEC 5 PY 2002 VL 304 IS 1 BP 125 EP 134 DI 10.1006/viro.2002.1722 PG 10 WC Virology SC Virology GA 628GM UT WOS:000179984800013 PM 12490410 ER PT J AU Rao, MR Naficy, AB Darwish, MA Darwish, NM Schisterman, E Clemens, JD Edelman, R AF Rao, MR Naficy, AB Darwish, MA Darwish, NM Schisterman, E Clemens, JD Edelman, R TI Further evidence for association of hepatitis C infection with parenteral schistosomiasis treatment in Egypt SO BMC INFECTIOUS DISEASES LA English DT Article ID HIGH SEROPREVALENCE; NILE DELTA; HEPATOCELLULAR-CARCINOMA; BLOOD-DONORS; VIRUS; MODELS; EPIDEMIOLOGY; PREVALENCE; COMMUNITY; ANTIBODY AB Background: Hepatitis C virus (HCV) infection and schistosomiasis are major public health problems in the Nile Delta of Egypt. To control schistosomiasis, mass treatment campaigns using tartar emetic injections were conducted in the 1960s through 1980s. Evidence suggests that inadequately sterilized needles used in these campaigns contributed to the transmission of HCV in the region. To corroborate this evidence, this study evaluates whether HCV infections clustered within houses in which household members had received parenteral treatment for schistosomiasis. Methods: A serosurvey was conducted in a village in the Nile Delta and residents were questioned about prior treatment for schistosomiasis. Sera were evaluated for the presence of antibodies to HCV. The GEE2 approach was used to test for clustering of HCV infections, where correlation of HCV infections within household members who had been treated for schistosomiasis was the parameter of interest. Results: A history of parenteral treatment for schistosomiasis was observed to cluster within households, OR for clustering: 2.44 (95% CI: 1.47-4.06). Overall, HCV seropositivity was 40% (321/796) and was observed to cluster within households that had members who had received parenteral treatment for schistosomiasis, OR for clustering: 1.76 (95% CI: 1.05-2.95). No such evidence for clustering was found in the remaining households. Conclusion: Clustering of HCV infections and receipt of parenteral treatment for schistosomiasis within the same households provides further evidence of an association between the schistosomiasis treatment campaigns and the high HCV seroprevalence rates currently observed in the Nile delta of Egypt. C1 NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. Ain Shams Univ, Sch Med, Cairo, Egypt. Univ Maryland, Ctr Vaccine Dev, Baltimore, MD 21201 USA. RP Rao, MR (reprint author), NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. NR 24 TC 45 Z9 46 U1 1 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD DEC 4 PY 2002 VL 2 AR 29 DI 10.1186/1471-2334-2-29 PG 7 WC Infectious Diseases SC Infectious Diseases GA 636NE UT WOS:000180461600001 PM 12464161 ER PT J AU Hepp, R Cabaniols, JP Roche, PA AF Hepp, R Cabaniols, JP Roche, PA TI Differential phosphorylation of SNAP-25 in vivo by protein kinase C and protein kinase A SO FEBS LETTERS LA English DT Article DE SNAP receptor; synaptosome-associated protein of 25 kDa; exocytosis; phosphorylation ID SYNAPTOSOME-ASSOCIATED PROTEIN; NEUROTRANSMITTER RELEASE; POSSIBLE INVOLVEMENT; PC12 CELLS; MECHANISMS; EXOCYTOSIS AB SNAP-25 is a key protein required for the fusion of synaptic vesicles with the plasma membrane during exocytosis. This study establishes that SNAP-25 is differentially phosphorylated by protein kinase C and protein kinase A in neuroendocrine PC12 cells. Using phosphopeptide mapping and site-directed mutagenesis we identified both Thr138 and Ser187 as the targets of SNAP-25 phosphorylation by protein kinase C and Thr138 as the exclusive site of SNAP-25 phosphorylation by protein kinase A in vivo. Finally, despite published data to the contrary, we demonstrate that stimulation of regulated exocytosis under physiological conditions is independent of a measurable increase in SNAP-25 phosphorylation in PC12 cells. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Roche, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B36, Bethesda, MD 20892 USA. NR 17 TC 26 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 4 PY 2002 VL 532 IS 1-2 BP 52 EP 56 AR PII S0014-5793(02)03629-3 DI 10.1016/S0014-5793(02)03629-3 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 625CK UT WOS:000179799200010 PM 12459461 ER PT J AU Basanez, G Shinnar, AE Zimmerberg, J AF Basanez, G Shinnar, AE Zimmerberg, J TI Interaction of hagfish cathelicidin antimicrobial peptides with model lipid membranes SO FEBS LETTERS LA English DT Article DE antimicrobial peptides; innate immunity; cathelicidin; hagfish; lipidic pore; membrane curvature ID FUSION; DESTABILIZATION; CURVATURE; BCL-X(L); PORES AB Hagfish intestinal antimicrobial peptides (HFIAPs) are a family of polycationic peptides exhibiting potent, broad-spectrum bactericidal activity. In an attempt to unravel the mechanism of action of HFIAPs, we have studied their interaction with model membranes. Synthetic HFIAPs selectively bound to liposomes mimicking bacterial membranes, and caused the release of vesicle-encapsulated fluorescent markers in a size-dependent manner. In planar lipid bilayer membranes, HFIAPs induced erratic current fluctuations and reduced membrane line tension according to a general theory for lipidic pores, suggesting that HFIAP pores contain lipid molecules. Consistent with this notion, lipid transbilayer redistribution accompanied HFIAP pore formation, and membrane monolayer curvature regulated HFIAP pore formation. Based on these studies, we propose that HFIAPs kill target cells, at least in part, by interacting with their plasma membrane to induce formation of lipid-containing pores. Such a membrane-permeabilizing function appears to be an evolutionarily conserved host-defense mechanism of antimicrobial peptides. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 Univ Basque Country, Unidad Biofis, Ctr Mixto, UPV,CSIC,EHU, E-48080 Bilbao, Spain. Univ Basque Country, Dept Bioquim & Biol Mol, UPV, EHU, E-48080 Bilbao, Spain. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Columbia Univ Barnard Coll, Dept Chem, New York, NY 10027 USA. RP Basanez, G (reprint author), Univ Basque Country, Unidad Biofis, Ctr Mixto, UPV,CSIC,EHU, POB 644, E-48080 Bilbao, Spain. EM gbzbaasg@lg.ehu.es RI Basanez, Gorka/L-9509-2014 OI Basanez, Gorka/0000-0002-7475-7861 NR 24 TC 33 Z9 36 U1 1 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD DEC 4 PY 2002 VL 532 IS 1-2 BP 115 EP 120 AR PII S0014-5793(02)03651-7 DI 10.1016/S0014-5793(02)03651-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 625CK UT WOS:000179799200023 PM 12459474 ER PT J AU Bodenreider, O Burgun, A Rindflesch, TC AF Bodenreider, O Burgun, A Rindflesch, TC TI Assessing the consistency of a biomedical terminology through lexical knowledge SO INTERNATIONAL JOURNAL OF MEDICAL INFORMATICS LA English DT Article; Proceedings Paper CT Symposium on Natural Language Processing for Biomedical Applications CY MAR, 2002 CL NICOSIA, CYPRUS DE Unified Medical Language System; SNOMED; lexical knowledge; terminology ID LANGUAGE; UMLS AB Objective: We investigate the use of adjectival modification as a way of assessing the systematic use of linguistic phenomena to represent similar lexical or semantic features in the constituent terms of a vocabulary. Methods: Terms consisting of one or more adjectival modifiers followed by a head noun are selected from disease and procedure terms in SNOMED. Frequently co-occurring adjectival modifiers are systematically combined with the contexts (i.e., terms minus modifier) of each modifier. The existence of these combinations is checked in both SNOMED and the entire UMLS Metathesaurus; the term corresponding to the context alone is similarly checked. Relationships among terms sharing a context and between each of these terms and their context are studied. Results: Four pairs of modifiers were studied: (acute, chronic), (unilateral, bilateral), (primary, secondary), and (acquired, congenital). The numbers of contexts studied for each pair ranged from 73 to 974. The percentage of contexts associated with both modifiers ranged from 5 to 50% in SNOMED and from 10 to 60% in UMLS. The presence of the context term varied from 31 to 64% in SNOMED and from 43 to 79% in UMLS. Finally, 172 occurrences (9%) of synonymy between a modified term and the context term were found in SNOMED. One hundred and forty-five such occurrences (8%) were found in the entire Metathesaurus. Published by Elsevier Science Ireland Ltd. C1 US Natl Lib Med, Bethesda, MD 20894 USA. Univ Rennes, Lab Informat Med, Rennes, France. RP US Natl Lib Med, 8600 Rockville Pike,MS 43, Bethesda, MD 20894 USA. EM olivier@nlm.nih.gov; anita.burgun@univ-rennes1.fr; tcr@nlm.nih.gov FU Intramural NIH HHS [Z99 LM999999] NR 19 TC 15 Z9 15 U1 0 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-5056 EI 1872-8243 J9 INT J MED INFORM JI Int. J. Med. Inform. PD DEC 4 PY 2002 VL 67 IS 1-3 BP 85 EP 95 AR PII S1386(02)00051-5 DI 10.1016/S1386-5056(02)00051-5 PG 11 WC Computer Science, Information Systems; Health Care Sciences & Services; Medical Informatics SC Computer Science; Health Care Sciences & Services; Medical Informatics GA 630JU UT WOS:000180104400008 PM 12460634 ER PT J AU Iyasu, S Randall, LL Welty, TK Hsia, J Kinney, HC Mandell, F McClain, M Randall, B Habbe, D Wilson, H Willinger, M AF Iyasu, S Randall, LL Welty, TK Hsia, J Kinney, HC Mandell, F McClain, M Randall, B Habbe, D Wilson, H Willinger, M TI Risk factors for sudden infant death syndrome among Northern Plains Indians SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NURSE HOME VISITATION; CONFIDENTIAL INQUIRY; RANDOMIZED TRIAL; ALCOHOL; STILLBIRTHS; ENVIRONMENT; PREGNANCY; OUTCOMES; SMOKING; GROWTH AB Context Sudden infant death syndrome (SIDS) is a leading cause of postneonatal mortality among American Indians, a group whose infant death rate is consistently above the US national average. Objective To determine Prenatal and postnatal risk factors for SIDS among American Indians. Design, Setting, and Participants Population-based case-control study of 33 SIDS infants and 66 matched living controls among American Indians in South Dakota, North Dakota, Nebraska, and Iowa enrolled from December 1992 to November 1996 and investigated using standardized parental interview, medical record abstraction', autopsy protocol, and infant death review. Main Outcome Measures Association of SIDS with maternal socioeconomic and behavioral factors, health care utilization, and infant care practices. Results The proportions of case and control infants who were usually placed prone to sleep (15.2% and 13.6%, respectively), who shared a bed with parents (59.4% and 55.4%), or whose mothers smoked during pregnancy (69.7% and 54.6%) were similar. However, mothers of 72.7% of case infants and 45.5% of control infants engaged in binge drinking during pregnancy. Conditional logistic regression revealed significant associations between SIDS and 2 or more layers of clothing on the infant (adjusted odds ratio [aOR], 6.2; 95% confidence interval [CI], 1.4-26.5), any visits by a public health nurse (aOR, 0.2; 95% Cl, 0.1-0.8), periconceptional maternal alcohol use (aOR, 6.2; 95% Cl, 1.6-23.3), and maternal first-trimester binge drinking (aOR, 8.2; 95% Cl, 1.9-35.3). Conclusions Public health nurse visits, maternal alcohol use during the periconceptional period and first trimester, and layers of clothing are important risk factors for SIDS among Northern Plains Indians. Strengthening public health nurse visiting programs and programs to reduce alcohol consumption among women of childbearing age could potentially reduce the high rate of SIDS. C1 Ctr Dis Control & Prevent, Div Reprod Hlth, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. Aberdeen Area Indian Hlth Serv, Rapid City, SD USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts SIDS Ctr, Boston, MA USA. LCM Pathologists PC, Sioux Falls, SD USA. Clin Lab Black Hills, Rapid City, SD USA. Providence Mem Hosp, Dept Pathol, El Paso, TX USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Iyasu, S (reprint author), US FDA, Div Pediat, Off Counter Terrorism & Pediat Drug Dev, Ctr Drug Evaluat & Res, 5A-33,HFD-960,5600 Fishers Ln, Rockville, MD 20857 USA. NR 30 TC 99 Z9 102 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD DEC 4 PY 2002 VL 288 IS 21 BP 2717 EP 2723 DI 10.1001/jama.288.21.2717 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 620UA UT WOS:000179549800031 PM 12460095 ER PT J AU Doan, LX Yagi, H Jerina, DM Whalen, DL AF Doan, LX Yagi, H Jerina, DM Whalen, DL TI Chloride ion catalyzed conformational inversion of carbocation intermediates in the hydrolysis of a benzo[a]pyrene 7,8-diol 9,10-epoxide SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ANTI-BENZOPYRENE DIOL EPOXIDE; CIS ADDUCT FORMATION; CARCINOGEN BENZOPYRENE; STEREOCHEMISTRY; MECHANISMS; PH AB A highly efficient procedure for converting 7beta, 8alpha-dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahy-drobenzo[a]pyrene (1) to its trans-9, 10-chlorohydrin (5) with excellent yield and purity by the reaction of anhydrous HCI in THF has been developed. The rate of reaction of 5 has been determined as a function of sodium chloride concentration in 1:1 dioxane-water solutions. A large common ion rate depression for the reaction of the chlorohydrin was observed, and the rate data are fit to a mechanism in which all of the tetrol products are formed by the reaction of water with the C-10 carbocation intermediate. Yet, the cis/trans ratio of tetrols from the reaction of the carbocation intermediate from the hydrolysis of chlorohydrin 5 is different than the cis/trans tetrol ratio from the acid-catalyzed hydrolysis of diol epoxide 1, which hydrolyzes via a carbocation with the same connectivity as that formed in the hydrolysis of 5. To rationalize these results, it is proposed that the S(N)1 reaction of chlorohydrin 5 yields a different distribution of carbocation conformations than that formed from the reaction of 1 with H+. The energy barrier for the inversion of these carbocation conformations must be large relative to the energy barriers for the reaction of each carbocation conformation with water. In solutions containing sufficient concentrations of chloride ion, however, a lower energy pathway via a halohydrin exists for the interconversion of the carbocation conformations. Thus, chloride ion catalyzes the interconversion of these two carbocation conformations. C1 Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Whalen, DL (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21250 USA. EM whalen@umbc.edu NR 22 TC 9 Z9 9 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD DEC 4 PY 2002 VL 124 IS 48 BP 14382 EP 14387 DI 10.1021/ja020436+ PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 620AP UT WOS:000179510800030 PM 12452712 ER PT J AU Zhu, JX Song, XQ Lin, HP Young, DC Yan, SQ Marquez, VE Chen, CS AF Zhu, JX Song, XQ Lin, HP Young, DC Yan, SQ Marquez, VE Chen, CS TI Using cyclooxygenase-2 inhibitors as molecular platforms to develop a new class of apoptosis-inducing agents SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PROSTATE-CANCER CELLS; BIOLOGICAL EVALUATION; ENDOTHELIAL-CELLS; COX-2 INHIBITION; GROWTH-FACTOR; CELECOXIB; NSAIDS; ANGIOGENESIS; PREVENTION AB Background. The cyclooxygenase-2 (COX-2) inhibitor celecoxib is thought to act as a chemopreventive agent by sensitizing cancer cells to apoptotic signals. Other COX-2 inhibitors, such as rofecoxib, are two orders of magnitude less potent than celecoxib at inducing apoptosis. The molecular structures of celecoxib and rofecoxib were used as starting points to examine the structural features that contribute to this discrepancy. Methods: We used a systematic chemical approach to modify the structures of celecoxib and rofecoxib to produce a series of compounds that were tested for their effects on the viability of human prostate cancer PC-3 cells and their ability to induce apoptosis in these cells. Cell viability was measured by the trypan blue dye exclusion assay, and apoptosis was measured by an enzyme-linked immunosorbent assay that quantifies DNA cleavage and by western blot detection of poly(ADP-ribose) polymerase (PARP) cleavage. Western blotting was used to monitor the effects of the compounds on phosphorylation of the serine/threonine kinase Akt and extracellular signal-regulated kinase 2 (ERK2), two components of celecoxib-induced apoptosis signaling. Monte Carlo simulations were used to molecularly model the surface electrostatic potential and electron density of selected compounds. All statistical tests were two-sided. Results: The structural requirements for the induction of apoptosis in PC-3 cells were different from those for COX-2 inhibition. Structure-function analysis indicated that the induction of apoptosis by compounds derived from COX-2 inhibitors required a bulky terminal phenyl ring, a heterocyclic system with negative electrostatic potential, and a benzenesulfonamide or benzenecarboxamide moiety. These derivatives mediated apoptosis by facilitating the dephosphorylation of Akt and ERK2, irrespective of their COX-2 inhibitory activities. Conclusion: A new class of compounds that induce apoptosis by targeting Akt and ERK2 signaling pathways in human prostate cancer cells can be synthesized by modifying existing COX-2 inhibitors. C1 Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. Univ Kentucky, Coll Pharm, Div Pharmaceut Sci, Lexington, KY USA. NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21701 USA. Univ Kentucky, Coll Pharm, Div Pharmaceut Sci, Lexington, KY USA. Ohio State Univ, Ctr Comprehens Canc, Biostat Core, Columbus, OH 43210 USA. Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, Columbus, OH 43210 USA. RP Chen, CS (reprint author), Ohio State Univ, Coll Pharm, Div Med Chem & Pharmacognosy, 336 Pk Hall,500 W 12th Ave, Columbus, OH 43210 USA. FU NCI NIH HHS [CA 92307, CA 94829, P30 CA 16058] NR 42 TC 125 Z9 130 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 4 PY 2002 VL 94 IS 23 BP 1745 EP 1757 PG 13 WC Oncology SC Oncology GA 619ZF UT WOS:000179507300007 PM 12464646 ER PT J AU Gutierrez, MI Ibrahim, MM Dale, JK Greiner, TC Straus, SE Bhatia, K AF Gutierrez, MI Ibrahim, MM Dale, JK Greiner, TC Straus, SE Bhatia, K TI Discrete alterations in the BZLF1 promoter in tumor and non-tumor-associated Epstein-Barr virus SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SWITCH GENE BZLF1; TISSUE DISTRIBUTION; BURKITTS-LYMPHOMA; EBV; INFECTION; LATENCY; CELLS; IDENTIFICATION; MUTATIONS; GENOTYPES AB Background: Although the Epstein-Barr virus (EBV) is associated with malignant and nonmalignant diseases, its lytic replication is predominately associated with nonmalignant diseases such as acute infectious mononucleosis (IM) or chronic active EBV infection. Lytic replication is also associated with type B EBV more than with type A EBV. Sustained lytic replication, however, is not compatible with tumor growth. We investigated whether control of an EBV lytic regulatory gene, BZLF1, differed in these diseases. Methods: Polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and direct DNA sequence analyses were used to characterize the promoter sequence of BZLF1 (Zp) in 52 tumors (34 non-Hodgkin's lymphomas, 13 post-transplant lymphoproliferative disease samples, and five nasopharyngeal carcinomas), and in peripheral blood lymphocytes from seven patients with chronic active EBV, six with IM, and 40 healthy, EBV-seropositive individuals. All sequences were compared with the prototype EBV strain B95.8 sequence. All statistical tests were two-sided. Results: Three polymorphic Zp sequences were detected. Among the malignant samples, sequence Zp-P, associated with 84% of type A EBV, was identical to that of EBV strain B95.8, whereas a second sequence (Zp-V3), associated exclusively with type B EBV (P<001), contained three base substitutions. Among the nonmalignant samples, a distinct polymorphism, Zp-V4, containing the substitutions detected in Zp-V3 and an additional base change, was identified in all samples from chronic active EBV, IM, and healthy individuals, but in none of the malignant samples (P<001). Zp-V4 was independent of the EBV type. Conclusions: Polymorphisms in the regulatory sequences of BZLF1 are differentially distributed among malignant and nonmalignant cells and may identify EBV subtypes with various lytic activities, including those not associated with malignancies. C1 Univ Nebraska, Dept Pathol, Lincoln, NE USA. King Faisal Specialist Hosp & Res Ctr, KFNCCC&R, Riyadh 11211, Saudi Arabia. Univ Nebraska, Dept Pathol, Omaha, NE 68182 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Bhatia, K (reprint author), POB 3354,MBC 98-16, Riyadh 11211, Saudi Arabia. NR 31 TC 16 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 4 PY 2002 VL 94 IS 23 BP 1757 EP 1763 PG 7 WC Oncology SC Oncology GA 619ZF UT WOS:000179507300008 PM 12464647 ER PT J AU Hildesheim, A Apple, RJ Chen, CJ Wang, SS Cheng, YJ Klitz, W Mack, SJ Chen, IH Hsu, MM Yang, CS Brinton, LA Levine, PH Erlich, HA AF Hildesheim, A Apple, RJ Chen, CJ Wang, SS Cheng, YJ Klitz, W Mack, SJ Chen, IH Hsu, MM Yang, CS Brinton, LA Levine, PH Erlich, HA TI Association of HLA class I and II alleles and extended haplotypes with nasopharyngeal carcinoma in Taiwan SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID EPSTEIN-BARR-VIRUS; NONRADIOACTIVE OLIGONUCLEOTIDE PROBES; LINKAGE DISEQUILIBRIUM; OCCUPATIONAL EXPOSURE; CERVICAL NEOPLASIA; CIGARETTE-SMOKING; UNITED-STATES; CHINESE; RISK; POLYMORPHISM AB Background: Nasopharyngeal carcinoma (NPC), which occurs at a disproportionately high rate among Chinese individuals, is associated with Epstein-Barr virus (EBV). Human leukocyte antigen (HLA) polymorphisms appear to play a role in NPC, because they are essential in the immune response to viruses. We used high-resolution HLA genotyping in a case-control study in Taiwan to systematically evaluate the association between various HLA alleles and NPC. Methods: We matched 366 NPC case patients to 318 control subjects by age, sex, and geographic residence. Participants were interviewed and provided blood samples for genotyping. High-resolution (polymerase chain reaction-based) genotyping of HLA class I (A and B) and II (DRB1, DQA1, DQB1, and DPB1) genes was performed in two phases. In phase 1, 210 case patients and 183 control subjects were completely genotyped. In phase II, alleles associated with NPC in the phase I analysis were evaluated in another 156 case patients and 135 control subjects. Extended haplotypes were inferred. Results: We found a consistent association between HLA-A*0207 (common among Chinese but not among Caucasians) and NPC (odds ratio [OR] = 2.3, 95% confidence interval [CI] = 1.5 to 3.5) but not between HLA-A*0201 (most common HLA-A2 allele in Caucasians) and NPC (OR = 0.79, 95% CI = 0.55 to 1.2). Individuals with HLA-B*4601, which is in linkage disequilibrium with HLA-A*0207, had an increased risk for NPC (OR = 1.8, 95% CI = 1.2 to 2.5) as did individuals with HLA-A*0207 and HLAB*4601 (OR = 2.8, 95 % CI = 1.7 to 4.4). Individuals homozygous for HLA-A*1101 had decreased risks for NPC (OR = 0.24, 95 % CI = 0. 13 to 0.46). The extended haplotype HLA-A*3303-B*5801/2-DRB1*0301-DQB1*0201/2-DPB1*0401, specific to this ethnic group, was associated with a statistically significantly increased risk for NPC (OR = 2.6, 95% CI = 1.1 to 6.4). Conclusions: The restriction of the association of HLA-A2 with NPC to HLA-A*0207 probably explains previously observed associations of HLA-A2 with NPC among Chinese but not Caucasians. The extended haplotypes associated with NPC might, in part, explain the higher rates of NPC in this ethnic group. C1 NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. Natl Taiwan Univ Hosp, Dept Otolaryngol, Taipei, Taiwan. Mackay Mem Hosp, Dept Otolaryngol, Taipei, Taiwan. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Natl Taiwan Univ, Coll Med, Grad Inst Microbiol, Taipei, Taiwan. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei, Taiwan. Roche Mol Syst, Atlanta, GA USA. RP Hildesheim, A (reprint author), NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Rm 7062, Rockville, MD 20852 USA. RI Chen, Chien-Jen/C-6976-2008; apple, raymond/I-4506-2012; Brinton, Louise/G-7486-2015; OI apple, raymond/0000-0002-8007-0345; Brinton, Louise/0000-0003-3853-8562; Mack, Steven/0000-0001-9820-9547 NR 58 TC 110 Z9 129 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD DEC 4 PY 2002 VL 94 IS 23 BP 1780 EP 1789 PG 10 WC Oncology SC Oncology GA 619ZF UT WOS:000179507300011 PM 12464650 ER PT J AU Weiger, WA Smith, M Boon, H Richardson, MA Kaptchuk, TJ Eisenberg, DM AF Weiger, WA Smith, M Boon, H Richardson, MA Kaptchuk, TJ Eisenberg, DM TI Advising patients who seek complementary and alternative medical therapies for cancer SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; METASTATIC BREAST-CANCER; CONTROLLED CLINICAL-TRIAL; STRUCTURED PSYCHIATRIC INTERVENTION; POSTOPERATIVE ARM LYMPHEDEMA; CHINESE HERBAL PREPARATION; VITAMIN-E SUPPLEMENTATION; PINEAL HORMONE MELATONIN; DEEP TISSUE MASSAGE; DIETARY-FAT INTAKE AB Many patients with cancer use complementary and alternative medical (CAM) therapies. Physicians need authoritative information on CAM therapies to responsibly advise patients who seek these interventions. This article summarizes current evidence on the efficacy and safety of selected CAM therapies that are commonly used by patients with cancer. The following major categories of interventions are covered: dietary modification and supplementation, herbal products and other biological agents, acupuncture, massage, exercise, and psychological and mind-body therapies. Two categories of evidence on efficacy are considered: possible effects on disease progression and survival and possible palliative effects. In evaluating evidence on safety, two types of risk are considered: the risk for direct adverse effects and the risk for interactions with conventional treatments. For each therapy, the current balance of evidence on efficacy and safety points to whether the therapy may be reasonably recommended, accepted (for example, dietary fat reduction in well-nourished patients with breast or prostate cancer), or discouraged (for example, high-dose vitamin A supplementation). This strategy allows the development of an approach for providing responsible, evidence-based, patient-centered advice to persons with cancer who seek CAM therapies. C1 Harvard Univ, Sch Med, Landmark Ctr,Osher Inst, Div Res & Educ Complementary & Integrat Med Thera, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Canadian Col Naturopath Med, Toronto, ON, Canada. Univ Toronto, Toronto, ON, Canada. NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Weiger, WA (reprint author), Harvard Univ, Sch Med, Landmark Ctr,Osher Inst, Div Res & Educ Complementary & Integrat Med Thera, 2nd Floor W,Suite 22A,401 Pk Dr, Boston, MA 02215 USA. FU NIAMS NIH HHS [U24 AR 43441] NR 206 TC 125 Z9 129 U1 3 U2 15 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD DEC 3 PY 2002 VL 137 IS 11 BP 889 EP 903 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 622GY UT WOS:000179639700005 PM 12458989 ER PT J AU Acharya, A Ruvinov, SB Gal, J Moll, JR Vinson, C AF Acharya, A Ruvinov, SB Gal, J Moll, JR Vinson, C TI A heterodimerizing leucine zipper coiled coil system for examining the specificity of a position interactions: Amino acids I, V, L, N, A, and K SO BIOCHEMISTRY LA English DT Article ID OLIGOMERIZATION STATE; TRANSCRIPTION FACTOR; CRYSTAL-STRUCTURE; DNA-BINDING; ELECTROSTATIC INTERACTIONS; HYDROPHOBIC CORE; BASIC REGION; PROTEIN; STABILITY; GCN4 AB We use a heterodimerizing leucine zipper system to examine the contribution of the interhelical a-a' interaction to dimer stability for six amino acids (A, V, L, 1, K. and N). Circular dichroism (CD) spectroscopy monitored the thermal denaturation of 36 heterodimers that generate six homotypic and 30 heterotypic a-a' interactions. Isoleucine (I-I) is the most stable homotypic a-a' interaction, being 9.2 kcal/mol per dimer more stable than the A-A interaction and 4.0 kcal/mol per dimer more stable than either the L-L or V-V interaction, and 7.0 kcal/mol per dimer more stable than the N-N interaction, Only lysine was less stable than alanine. An alanine-based double-mutant thermodynamic cycle calculated coupling energies between the a and a' positions in the heterodimer. The aliphatic amino acids L, V, and I prefer to form homotypic interactions with coupling energies of -0.6 to -0.9 kcal/mol per dimer. but the heterotypic aliphatic interactions have positive coupling energies of < 1.0 kcal/mol per dimer. The asparagine homotypic interaction has a coupling energy of -0.5 kcal/mol pet, dimer. while heterotypic interactions with the aliphatic amino acids produce coupling energies ranging from 2.6 to 4.9 kcal/mol per dimer. The homotypic K-K interaction is 2.9 kcal/mol per dimer less stable than the A-A interaction, but the coupling energy is only 0.3 kcal/mol per dimer. Heterotypic interactions with lysine and either asparagine or aliphatic amino acids produce similar coupling energies ranging from -0.2 to -0.7 kcal/mol per dimer. Thus, of the amino acids that were examined, asparagine contribute, the most to dimerization specificity because of the large positive coupling energies in heterotypic interactions with the aliphatic amino acids which results in the N-N homotypic interaction. C1 NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Vinson, C (reprint author), NCI, Metab Lab, NIH, Bethesda, MD 20892 USA. NR 49 TC 75 Z9 76 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD DEC 3 PY 2002 VL 41 IS 48 BP 14122 EP 14131 DI 10.1021/bi020486r PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 620CZ UT WOS:000179517000005 PM 12450375 ER PT J AU Djousse, L Rothman, KJ Cupples, LA Levy, D Ellison, RC AF Djousse, L Rothman, KJ Cupples, LA Levy, D Ellison, RC TI Serum albumin and risk of myocardial infarction and all-cause mortality in the Framingham Offspring Study SO CIRCULATION LA English DT Article DE myocardial infarction; risk factors; mortality ID CORONARY HEART-DISEASE; C-REACTIVE PROTEIN; OLDER PERSONS; DEATH; ANTIOXIDANT; PREDICTORS; PLASMA AB Background-Coronary disease remains the leading cause of death in the United States. The association between serum albumin and cardiovascular disease remains controversial. We used data collected prospectively from participants of the Framingham Offspring Study to assess whether a lower concentration of serum albumin was associated with an increased risk of myocardial infarction (MI) and all-cause mortality. Methods and Results-During 21.9 years of mean follow-up, 280 cases of MI occurred. From the highest to the lowest tertile of serum albumin, crude incidence rates of MI were 26.7, 46.7, and 67.8 cases per 10 000 person-years, respectively, for men and 5.9, 15.0, and 16.8 cases per 10 000 person-years, respectively, for women. In a Mantel-Haenszel method adjusting for age, total cholesterol, and hypertension, lower serum albumin was associated with an increased risk of MI in both sexes. From the highest to the lowest tertile of albumin, the adjusted hazard ratios (95% CI) of MI were 1.0 (reference), 1.25 (0.84 to 1.84), and 1.49 (1.01 to 2.21), respectively, for men and 1.0, 1.79 (0.88 to 3.65), and 2.12 (1.06 to 4.27), respectively, for women. The albumin-MI association was stronger among hypertensive subjects in both sexes. In addition, low albumin was associated with an increased rate of all-cause mortality in women. Conclusions-Lower serum albumin concentrations appear to be associated with an increased risk of coronary disease in both sexes and with all-cause mortality in women and could help along with traditional risk factors in identifying people at risk of MI. C1 Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP Djousse, L (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Dept Med, Room B-612,715 Albany St,B-612, Boston, MA 02118 USA. RI Djousse, Luc/F-5033-2017; OI Djousse, Luc/0000-0002-9902-3047; Ellison, Robert Curtis/0000-0002-0582-7467; Cupples, L. Adrienne/0000-0003-0273-7965; Rothman, Kenneth/0000-0003-2398-1705 FU NHLBI NIH HHS [N01-HC-38038] NR 29 TC 82 Z9 87 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD DEC 3 PY 2002 VL 106 IS 23 BP 2919 EP 2924 DI 10.1161/01.CIR.0000042673.07632.76 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 623HY UT WOS:000179698600013 PM 12460872 ER PT J AU Kim, TH Skelding, KA Nabel, EG Simari, RD AF Kim, TH Skelding, KA Nabel, EG Simari, RD TI What can cardiovascular gene transfer learn from genomics: and vice versa? SO PHYSIOLOGICAL GENOMICS LA English DT Article DE gene therapy; vectors ID NITRIC-OXIDE SYNTHASE; SEVERE COMBINED IMMUNODEFICIENCY; ENDOTHELIAL GROWTH-FACTOR; SALT-SENSITIVE RATS; CYSTIC-FIBROSIS; THERAPEUTIC ANGIOGENESIS; HINDLIMB ISCHEMIA; RABBIT MODEL; ADENOVIRUS; EXPRESSION AB The field of gene transfer has developed in an era of expanding biomedical knowledge. The potential for gene transfer to treat cardiovascular disease is great, yet identified and unidentified barriers remain. Gene transfer and its ultimate application, gene therapy, require extensive details of not only the mechanism of disease but the biological implications of the vectors used to deliver the therapeutic genes as well. Many of these details are becoming available via the study of genomics. Genomics, the study of complete genetic sequences, holds the potential for enabling and amplifying the therapeutic hopes for gene transfer. Identification of new therapeutic genes, new regulatory sequences, and establishing the patterns of gene expression from tissues exposed to vectors and transgenes will rapidly advance the application of gene transfer. Finally, there are historical and ongoing lessons learned from the development of gene transfer that may be applicable to the challenging field of genomics and may enable its future success. C1 Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Program Mol Med, Div Cardiovasc Dis, Rochester, MN 55905 USA. Chung Ang Univ Hosp, Dept Internal Med, Div Cardiovasc Dis, Seoul 140757, South Korea. NHLBI, Bethesda, MD 20892 USA. RP Simari, RD (reprint author), Mayo Clin & Mayo Fdn, Dept Biochem & Mol Biol, Program Mol Med, Div Cardiovasc Dis, 200 1st St SW, Rochester, MN 55905 USA. NR 34 TC 1 Z9 1 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD DEC 3 PY 2002 VL 11 IS 3 BP 179 EP 182 DI 10.1152/physiolgenomics.00063.2002 PG 4 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 621MG UT WOS:000179592800006 PM 12464691 ER PT J AU Kiyatkin, EA AF Kiyatkin, EA TI Dopamine in the nucleus accumbens: cellular actions, drug- and behavior-associated fluctuations, and a possible role in an organism's adaptive activity SO BEHAVIOURAL BRAIN RESEARCH LA English DT Review DE an organism's activity; adaptation; striatum; ventral tegmental area (VTA); tonic DA release; phasic fluctuations in DA release; glutamate; GABA; DA cell recording; electrochemistry; drug-taking behavior; heroin self-administration ID VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; STRIATAL NEURONAL-ACTIVITY; MEDIAL PREFRONTAL CORTEX; CENTRAL NERVOUS-SYSTEM; EXTRACELLULAR DOPAMINE; UNRESTRAINED RATS; SINGLE-UNIT; MESOLIMBIC DOPAMINE; SYNAPTIC PLASTICITY AB This review expounds the idea that the analysis of dopamine (DA) action on target cells under behaviorally relevant conditions and behavior-related changes in DA activity can offer new information to clarify the functional significance of mesocorticolimbic DA. In contrast to the traditional association of DA with certain behavioral processes and mechanisms (activation, arousal, conditioning, motivation, reinforcement, sensorimotor integration, etc.), evaluation of DA activity during well-controlled behaviors established by different reinforcers can provide important clues for determining the role of DA in the development and regulation of goal-directed behavior. This review summarizes the results of our microiontophoretic studies of striatal neurons in awake, unrestrained rats, particularly the action of DA on spontaneously active and glutamate (GLU)-stimulated cells, the pattern of DAGLU interaction, and the role of tonic DA release in regulating the activity and afferent responsiveness of these units. We present the results of our iontophoretic studies of ventral tegmental area (VTA) neurons in freely moving animals suggesting the complexity and limitations in their identification as DA- and non-DA cells under behaviorally relevant conditions. We also consider technical and methodological problems related to electrophysiological and electrochemical evaluation of DA transmission in behaving animals. Finally, we discuss parallels and differences in the activity of presumed DA VTA neurons and changes of nucleus accumbens DA-dependent electrochemical signal during heroin self-administration (SA) behavior. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov FU NIDA NIH HHS [DA00335, DA02451] NR 109 TC 36 Z9 40 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD DEC 2 PY 2002 VL 137 IS 1-2 BP 27 EP 46 AR PII S0166-4328(02)00283-8 DI 10.1016/S0166-4328(02)00283-8 PG 20 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 623FF UT WOS:000179692100003 PM 12445714 ER PT J AU Lee, K Zhang, MC Yang, DJ Burke, TR AF Lee, K Zhang, MC Yang, DJ Burke, TR TI Design and synthesis of a beta-amino phosphotyrosyl mimetic suitably protected for peptide synthesis SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID SIGNAL-TRANSDUCTION INHIBITORS; SOLID-PHASE SYNTHESIS; HIGH-AFFINITY; SH2 DOMAIN; TERT-BUTANESULFINIMINES; ASYMMETRIC-SYNTHESIS; O-PHOSPHOTYROSINE; GRB2-SH2 DOMAIN; PTB DOMAIN; ACIDS AB Mimetics of phosphotyrosine (pTyr) such as phosphonomethylphertylalanine (Pmp) have traditionally retained a-amino functionality. However, beta-amino acids represent isomeric variants, which may exhibit properties that are distinct from the parent. Reported herein is the first beta-amino pTyr mimetic (Pmp(beta)) bearing protection suitable for peptide synthesis. Preparation of Pmp(beta) was accomplished enantioselectively in 43% overall yield from commercially available 4-vinylbenzyl chloride. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. Univ Michigan, Dept Hematol Oncol, Ann Arbor, MI 48109 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RI Burke, Terrence/N-2601-2014 NR 33 TC 12 Z9 12 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD DEC 2 PY 2002 VL 12 IS 23 BP 3399 EP 3401 AR PII S0960-894X(02)00783-7 DI 10.1016/S0960-894X(02)00783-7 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 616JL UT WOS:000179300600010 PM 12419370 ER PT J AU Sarafianos, SG Clark, AD Das, K Tuske, S Birktoft, JJ Ilankumaran, P Ramesha, AR Sayer, JM Jerina, DM Boyer, PL Hughes, SH Arnold, E AF Sarafianos, SG Clark, AD Das, K Tuske, S Birktoft, JJ Ilankumaran, P Ramesha, AR Sayer, JM Jerina, DM Boyer, PL Hughes, SH Arnold, E TI Structures of HIV-1 reverse transcriptase with pre- and post-translocation AZTMP-terminated DNA SO EMBO JOURNAL LA English DT Article DE drug resistance; HIV; nucleotide excision; reverse transcriptase; translocation ID IMMUNODEFICIENCY-VIRUS TYPE-1; POLYMERASE ACTIVE-SITE; DOUBLE-STRANDED DNA; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; STERIC HINDRANCE; TEMPLATE-PRIMER; DRUG-RESISTANCE; 3TC RESISTANCE; MECHANISM AB AZT (3'-azido-3'-deoxythymidine) resistance involves the enhanced excision of AZTMP from the end of the primer strand by HIV-1 reverse transcriptase. This reaction can occur when an AZTMP-terminated primer is bound at the (n) under bar ucleotide-binding site (pretranslocation complex N) but not at the '(p) under bar riming' site (post-translocation complex P). We determined the crystal structures of N and P complexes at 3.0 and 3.1 Angstrom resolution. These structures provide insight into the structural basis of AZTMP excision and the mechanism of translocation. Docking of a dNTP in the P complex structure suggests steric crowding in forming a stable ternary complex that should increase the relative amount of the N complex, which is the substrate for excision. Structural differences between complexes N and P suggest that the conserved YMDD loop is involved in translocation, acting as a springboard that helps to propel the primer terminus from the N to the P site after dNMP incorporation. C1 Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NCI, HIV Drug Reistance Program, Frederick, MD 21702 USA. RP Arnold, E (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, 679 Hoes Lane, Piscataway, NJ 08854 USA. OI Sarafianos, Stefan G/0000-0002-5840-154X FU NIAID NIH HHS [AI 27690, R37 AI027690]; NIGMS NIH HHS [GM56690, R01 GM056690] NR 31 TC 156 Z9 162 U1 0 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 DEC 2 PY 2002 VL 21 IS 23 BP 6614 EP 6624 DI 10.1093/emboj/cdf637 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 625NL UT WOS:000179822500032 PM 12456667 ER PT J AU Shih, IH Melek, M Jayaratne, ND Gellert, M AF Shih, IH Melek, M Jayaratne, ND Gellert, M TI Inverse transposition by the RAG1 and RAG2 proteins: role reversal of donor and target DNA SO EMBO JOURNAL LA English DT Article DE chromosomal translocation; RAG1; 2 recombinase; transposition; V(D)J recombination ID V(D)J RECOMBINATION; MU TRANSPOSASE; 2 STEPS; CLEAVAGE; GENE; TRANSLOCATIONS; INITIATION; 12/23-RULE; LEUKEMIA; LYMPHOMA AB The lymphoid-specific proteins RAG1 and RAG2 initiate V(D)J recombination by introducing DNA double-strand breaks at the recombination signal sequences (RSSs). In addition to DNA cleavage, the versatile RAG1/2 complex is capable of catalyzing several other reactions, including hybrid joint formation and the transposition of signal ends into a second DNA. Here we show that the RAG1/2 complex also mediates an unusual strand transfer reaction, inverse transposition, in which non-RSS DNA is cleaved and subsequently transferred to an RSS sequence by direct transesterification. Characterization of the reaction products and requirements suggests that inverse transposition is related to both hybrid joint formation and signal-end transposition. This aberrant activity provides another possible mechanism for some chromosomal translocations present in lymphoid tumors. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gellert, M (reprint author), NIDDKD, Mol Biol Lab, NIH, Bldg 5,Room 241, Bethesda, MD 20892 USA. NR 40 TC 11 Z9 11 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD DEC 2 PY 2002 VL 21 IS 23 BP 6625 EP 6633 DI 10.1093/emboj/cdf630 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 625NL UT WOS:000179822500033 PM 12456668 ER PT J AU Long, EO Rajagopalan, S AF Long, EO Rajagopalan, S TI Stress signals activate natural killer cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID MHC CLASS-I; PEPTIDE BINDING-SPECIFICITY; HLA-E; CRYSTAL-STRUCTURE; T-CELLS; INHIBITORY RECEPTOR; NKG2D RECEPTOR; NK CELLS; RECOGNITION; MOLECULES C1 NIAID, Immunogenet Lab, NIA, Rockville, MD 20852 USA. RP Long, EO (reprint author), NIAID, Immunogenet Lab, NIA, 12441 Parklawn Dr, Rockville, MD 20852 USA. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 29 TC 24 Z9 30 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 DEC 2 PY 2002 VL 196 IS 11 BP 1399 EP 1402 DI 10.1084/jem.20021747 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 623AZ UT WOS:000179682000001 PM 12461075 ER PT J AU Schiavoni, G Mattei, F Sestili, P Borghi, P Venditti, M Morse, HC Belardelli, F Gabriele, L AF Schiavoni, G Mattei, F Sestili, P Borghi, P Venditti, M Morse, HC Belardelli, F Gabriele, L TI ICSBP is essential for the development of mouse type I interferon-producing cells and for the generation and activation of CD8 alpha(+) dendritic cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE transcription factor; dendritic cell subsets; interferon; differentiation; maturation ID SEQUENCE-BINDING-PROTEIN; LYMPH-NODES; TRANSCRIPTION FACTOR; MYELOID PROGENITOR; ADAPTIVE IMMUNITY; IFN-GAMMA; SPLEEN; VIVO; RESPONSES; SUBSETS AB Interferon (IFN) consensus sequence-binding protein (ICSBP) is a transcription factor playing a critical role in the regulation of lineage commitment, especially in myeloid cell differentiation. In this study, we have characterized the phenotype and activation pattern of subsets of dendritic cells (DCs) in ICSBP-/- mice. Remarkably, the recently identified mouse IFN-producing cells (mIPCs) were absent in all lymphoid organs from ICSBP-/- mice, as revealed by lack of CD11c(low)B220(+)Ly6C(+)CD11b(-) cells. In parallel, CD11c(+) cells isolated from ICSBP-/- spleens were unable to produce type I IFNs in response to viral stimulation. ICSBP-/- mice also displayed a marked reduction of the DC subset expressing the CD8alpha marker (CD80alpha(+) DCs) in spleen, lymph nodes, and thymus. Moreover, ICSBP-/- CD8alpha(+) IDCs exhibited a markedly impaired phenotype when compared with WT DCs. They expressed very low levels of costimulatory molecules (intercellular adhesion molecule [ICAM]-1, CD40, CD80, CD86) and of the T cell area-homing chemokine receptor CCR7, whereas they showed higher levels of CCR2 and CCR6, as revealed by reverse transcription PCR. In addition, these cells were unable to undergo full phenotypic activation upon in vitro culture in presence of maturation stimuli such as lipopolysaccharide or poly (I:C), which paralleled with lack of Toll-like receptor (TLR)3 mRNA expression. Finally, cytokine expression pattern was also altered in ICSBP-/- DCs, as they did not express interleukin (IL)-12p40 or IL-15, but they displayed detectable IL-4 mRNA levels. On the whole, these results indicate that ICSBP is a crucial factor in the regulation of two possibly linked processes: (a) the development and activity of mIPCs, whose lack in ICSBP-/- mice may explain their high susceptibility to virus infections; (b) the generation and activation of CD8alpha(+) DCs, whose impairment in ICSBP-/- mice can be responsible for the defective generation of a Th1 type of immune response. C1 Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Gabriele, L (reprint author), Ist Super Sanita, Virol Lab, Viale Regina Elena 299, I-00161 Rome, Italy. RI Mattei, Fabrizio/J-6585-2016; OI Mattei, Fabrizio/0000-0002-5357-7773; Schiavoni, Giovanna/0000-0001-9135-0556; Morse, Herbert/0000-0002-9331-3705; Gabriele, Lucia/0000-0002-1483-866X NR 58 TC 237 Z9 240 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 2 PY 2002 VL 196 IS 11 BP 1415 EP 1425 DI 10.1084/jem.20021263 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 623AZ UT WOS:000179682000003 PM 12461077 ER PT J AU Mayer, DCG Mu, JB Feng, XR Su, XZ Miller, LH AF Mayer, DCG Mu, JB Feng, XR Su, XZ Miller, LH TI Polymorphism in a Plasmodium falciparum erythrocyte-binding ligand changes its receptor specificity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Plasmodium falciparum malaria; erythrocyte; parasite polymorphism; Gerbich negative; BAEBL ID PROTEIN; INVASION; FAMILY; VIVAX; MEROZOITES; ADHESION; DOMAINS; COMPLEX AB Recognition of human erythrocytes by Plasmodium species depends in part on Region II of the Duffy binding-like family of parasite ligands, which includes BA erythrocyte binding ligand (BAEBL) of P. falciparum. In previous studies of BAEBL from two clones, Dd2/Nm from Vietnam and E12 from Papua New Guinea (PNG), it was found that BAEBL bound different erythrocyte receptors. Because of variation in binding specificity, we studied the sequence and erythrocyte binding specificity of Region II of BAEBL in P. falciparum clones from different parts of the world. We observed five nucleotide substitutions leading to five amino acid changes and five polymorphisms in Region II of BAEBL in parasites from both PNG and other parts of the world. We expressed four of the polymorphisms on COS cells and determined their binding to enzyme-treated erythrocytes and to Gerbich-negative erythrocytes. We also performed erythrocyte-binding assay using the native protein from radiolabeled culture supernatant. Both assays demonstrated that each of the four polymorphisms in the parasite ligand, BAEBL, bound to a different receptor on erythrocytes. These results suggest that P. falciparum has evolved multiple invasion pathways dependent on polymorphisms in the BAEBL ligand. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Miller, LH (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 4 Ctr Dr,Bldg 4,Rm B1-41, Bethesda, MD 20892 USA. RI feng, xiaorong/G-4811-2010; OI feng, xiaorong/0000-0001-8410-3020; Su, Xinzhuan/0000-0003-3246-3248 NR 30 TC 77 Z9 78 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD DEC 2 PY 2002 VL 196 IS 11 BP 1523 EP 1528 DI 10.1084/jem.20020750 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 623AZ UT WOS:000179682000013 PM 12461087 ER PT J AU Mateja, A Devedjiev, Y Krowarsch, D Longenecker, K Dauter, Z Otlewski, J Derewenda, ZS AF Mateja, A Devedjiev, Y Krowarsch, D Longenecker, K Dauter, Z Otlewski, J Derewenda, ZS TI The impact of Glu -> Ala and Glu -> Asp mutations on the crystallization properties of RhoGDI: the structure of RhoGDI at 1.3 angstrom resolution SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID RGS-LIKE DOMAIN; CRYSTAL-STRUCTURE; SURFACE RESIDUES; PDZ-RHOGEF; FAMILY; PURIFICATION; EXPRESSION; REFINEMENT; PROTEINS; COMPLEX AB It is hypothesized that surface residues with high conformational entropy, specifically lysines and glutamates, impede protein crystallization. In a previous study using a model system of Rho-specific guanine nucleotide dissociation inhibitor (RhoGDI), it was shown that mutating Lys residues to Ala results in enhanced crystallizability, particularly when clusters of lysines are targeted. It was also shown that one of these mutants formed crystals that yielded diffraction to 2.0 Angstrom, a significant improvement on the wild-type protein crystals. In the current paper, an analysis of the impact of surface mutations replacing Glu residues with Ala or Asp on the stability and crystallization properties of RhoGDI is presented. The Glu --> Ala (Asp) mutants are generally more likely to produce crystals of the protein than the wild-type and in one case the resulting crystals yielded a diffraction pattern to 1.2 Angstrom resolution. This occurs in spite of the fact that mutating surface Glu residues almost invariably affects the protein's stability, as illustrated by the reduced DeltaG between folded and unfolded forms measured by isothermal equilibrium denaturation. The present study strongly supports the notion that rational surface mutagenesis can be an effective tool in overcoming problems stemming from the protein's recalcitrance to crystallization and may also yield dramatic improvements in crystal quality. C1 Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. Univ Wroclaw, Inst Biochem & Mol Biol, PL-50137 Wroclaw, Poland. Brookhaven Natl Lab, NCI, Macromol Crystallog Lab, Synchrotron Radiat Res Sect, Upton, NY 11973 USA. RP Derewenda, ZS (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. RI Otlewski, Jacek/B-6340-2008 FU NIGMS NIH HHS [GM62615] NR 22 TC 64 Z9 66 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD DEC PY 2002 VL 58 BP 1983 EP 1991 DI 10.1107/S090744490201394X PN 12 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 619GV UT WOS:000179468800003 PM 12454455 ER PT J AU Asojo, OA Afonina, E Gulnik, SV Yu, B Erickson, JW Randad, R Medjahed, D Silva, AM AF Asojo, OA Afonina, E Gulnik, SV Yu, B Erickson, JW Randad, R Medjahed, D Silva, AM TI Structures of Ser205 mutant plasmepsin II from Plasmodium falciparum at 1.8 angstrom in complex with the inhibitors rs367 and rs370 SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID HEMOGLOBIN DEGRADATION; COMBINATORIAL LIBRARY; ASPARTIC PROTEINASE; PROTEASE; PATHWAY; SPECIFICITY; REFINEMENT; MOLSCRIPT; CYSTEINE; POTENT AB Plasmepsin II is one of the four catalytically active plasmepsins found in the food vacuole of Plasmodium falciparum. These enzymes initiate hemoglobin degradation by cleavage at the alpha-chain between Phe33 and Leu34. The crystal structures of Ser205 mutant plasmepsin II from P. falciparum in complex with two inhibitors have been refined at a resolution of 1.8 Angstrom in the space group I222 and to R factors of 19.9 and 19.5%. Each crystal contains one monomer in the asymmetric unit. Both inhibitors have a Phe-Leu core and incorporate tetrahedral transition-state mimetic hydroxypropylamine. The inhibitor rs367 possesses a 2,6-dimethylphenyloxyacetyl group at the P2 position and 3-aminobenzamide at the P2' position, while rs370 has the same P2 group but 4-aminobenzamide in the P2' position. These complexes reveal key conserved hydrogen bonds between the inhibitor and the binding-cavity residues, notably with the flap residues Val78 and Ser79, the catalytic dyad Asp34 and Asp214 and the residues Ser218 and Gly36 that are in proximity to the catalytic dyad. The structures also show unexpected conformational variability of the binding cavity of plasmepsin II and may reflect the mode of binding of the hemoglobin alpha-chain for cleavage. C1 NCI, Struct Biochem Program, SAIC, Frederick, MD 21702 USA. RP Asojo, OA (reprint author), NCI, Struct Biochem Program, SAIC, Frederick, MD 21702 USA. RI Asojo, Oluwatoyin/C-2005-2012 OI Asojo, Oluwatoyin/0000-0002-4043-2700 FU NCI NIH HHS [N01 CO-74102] NR 36 TC 67 Z9 67 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD DEC PY 2002 VL 58 BP 2001 EP 2008 DI 10.1107/S0907444902014695 PN 12 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 619GV UT WOS:000179468800005 PM 12454457 ER PT J AU Andrykovitch, M Guo, W Routzahn, KM Gu, YJ Anderson, DE Reshetnikova, LS Knowlton, JR Waugh, DS Ji, XH AF Andrykovitch, M Guo, W Routzahn, KM Gu, YJ Anderson, DE Reshetnikova, LS Knowlton, JR Waugh, DS Ji, XH TI Crystallization and preliminary X-ray diffraction studies of NusG, a protein shared by the transcription and translation machines SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID RHO-DEPENDENT TERMINATION; RNA-POLYMERASE-II; ESCHERICHIA-COLI; ELONGATION-FACTOR; ANTITERMINATION; LAMBDA; RATES; SPT4 AB N-utilization factor G (NusG) from Aquifex aeolicus (Aa) was overexpressed in Escherichia coli, purified and crystallized using the hanging-drop vapor-diffusion technique. The drops consisted of 2.5 mul protein solution (similar to30 mg ml(-1) in 20 mM Tris-HCl pH 8.0, 200 mM NaCl, 2 mM EDTA and 10 mM DTT) and 2.5 mul reservoir solution (0.085 M Na HEPES pH 7.5, 15% glycerol, 11% 2-propanol and 20% PEG 4000) derived from condition number 41 of the Hampton Cryo Screen. The crystals grew at 291 +/- 1 K and reached dimensions of 0.2 x 0.1 x 0.05 mm in 5-7 d. The crystals, which diffracted to 2.45 Angstrom resolution, belonged to space group C222(1), with unit-cell parameters a = 65.95, b = 124.58, c = 83.60 Angstrom. One AaNusG molecule is present in the asymmetric unit, corresponding to a solvent content of 59.80% (Matthews coefrcient = 3.06 Angstrom(3) Da(-1)). Crystal structure determination is in progress. C1 NCI, Biomol Struct Sect, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. NCI, Prot Engn Sect, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. RP Ji, XH (reprint author), NCI, Biomol Struct Sect, Macromol Crystallog Lab, NIH, Frederick, MD 21702 USA. RI Gu, Yijun/B-6017-2012; Ji, Xinhua/C-9664-2012 OI Ji, Xinhua/0000-0001-6942-1514 NR 21 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD DEC PY 2002 VL 58 BP 2157 EP 2158 DI 10.1107/S0907444902015810 PN 12 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 619GV UT WOS:000179468800033 PM 12454485 ER PT J AU Olsen, BE Hinderaker, SG Bergsjo, P Lie, RT Olsen, OHE Gasheka, P Kvale, G AF Olsen, BE Hinderaker, SG Bergsjo, P Lie, RT Olsen, OHE Gasheka, P Kvale, G TI Causes and characteristics of maternal deaths in rural northern Tanzania SO ACTA OBSTETRICIA ET GYNECOLOGICA SCANDINAVICA LA English DT Article DE maternal mortality; malaria in pregnancy; essential obstetric services; avoidable death; Tanzania ID DAR-ES-SALAAM; MALARIA TRANSMISSION; POSTPARTUM PERIOD; MORTALITY; PREGNANCY; DISTRICT; AFRICA AB Background. To assess causes and characteristics of maternal deaths in a poorly characterized area. Methods. A health facility- and population-based study, with an audit of case series on maternal deaths, was done in two divisions with 42 villages (population 143 000), in Mbulu and Hanang districts, Arusha region, Tanzania. In 1995, all known deaths of women between 15 and 50 years, who were residents of the study area, were recorded from all the health facilities and villages in the study area. Supplementary data from the health facilities were collected in 1996. Verbal autopsies, health facility and antenatal records, and additional oral information were used to assess each maternal death. Results. Forty-five maternal deaths were identified, 26 in 1995 and 19 in 1996. Thirteen of the deaths were direct, while 32 were indirect. Hemorrhage was the main cause of direct obstetric deaths and cerebral malaria of indirect death, accounting for 20 cases, with most of them occurring during an epidemic season. Twenty-four of the women, including 10 of those dying of malaria, died postpartum. Most of the deceased women sought help at a health facility as the first place of seeking help, and used the hospital ambulance. Fourteen of the deaths (31%) were considered possibly avoidable under the prevailing circumstances, with delay in seeking help being most common. Conclusions. Addressing malaria as a major cause of maternal death, both in pregnancy and postpartum, in epidemic-prone areas, and increased community and family awareness of when to seek help could be important factors in reducing maternal deaths. C1 Univ Bergen, Ctr Int Hlth, N-5021 Bergen, Norway. Haydom Lutheran Hosp, Mbulu, Tanzania. Univ Bergen, Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway. Univ Bergen, Sect Med Stat, Dept Publ Hlth & Primary Hlth Care, Bergen, Norway. Natl Inst Environm Hlth Sci, Dept Hlth & Human Serv, Publ Hlth Serv, NIH, Chapel Hill, NC USA. RP Olsen, BE (reprint author), Univ Bergen, Ctr Int Hlth, Armauer Hansen House, N-5021 Bergen, Norway. NR 41 TC 24 Z9 24 U1 0 U2 3 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-6349 J9 ACTA OBSTET GYN SCAN JI Acta Obstet. Gynecol. Scand. PD DEC PY 2002 VL 81 IS 12 BP 1101 EP 1109 DI 10.1034/j.1600-0412.2002.811202.x PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 624FR UT WOS:000179750100002 PM 12519105 ER PT J AU Stopka, TJ Singer, M Teng, W Horton, J Compton, W AF Stopka, TJ Singer, M Teng, W Horton, J Compton, W TI Pharmacy access to over-the-counter syringes in Connecticut: Implications for HIV and hepatitis prevention among injection-drug users SO AIDS & PUBLIC POLICY JOURNAL LA English DT Article ID INCREASED LEGAL ACCESS; NEEDLE EXCHANGE; UNITED-STATES; PARTICIPANTS; IMPACT AB Injection-drug use is implicated as one of the primary causes of HIV and hepatitis transmission. Sharing of previously used and potentially contaminated syringes by injection-drug users (IDUs) has a cascade effect on communities, and places IDUs, their sexual partners, and related infants at increased risk for acquiring such blood-borne illnesses. Improved access to sterile syringes can decrease transmission risk among these overlapping populations. While exemplary syringe-exchange programs (SEPs) exist internationally and pharmacies have been found to be effective, legal, and accessible sources of sterile syringes for IDUs, moralistic and judgmental viewpoints continue to abound, to the detriment of effective HIV- and hepatitis-prevention efforts. During the early 1990s, decriminalization of syringe possession and legalization of SEPs, as well as over-the-counter sales of syringes in pharmacies, fostered improved access to sterile syringes among IDUs in Connecticut. Documented reductions in HIV prevalence followed, and effective harm-reduction programs began to gain momentum throughout the state. In more recent years, however, access to sterile syringes has been deterred in some areas of the state. Recent results from a Connecticut study that examined the willingness of pharmacists to sell over-the-counter (OTC) syringes indicate that urban pharmacists are willing to sell OTC syringes at significantly lower rates than suburban pharmacists are (56 percent versus 78 percent, respectively; p < .05). Further, ethnic bias may influence some pharmacists' willingness to sell OTC syringes in parts of Connecticut. Addressing the barriers to effective and widespread OTC syringe sales should be a high priority in HIV- and hepatitis-prevention efforts. C1 Hispan Hlth Council, Ctr Community Hlth Res, Hartford, CT USA. Yale Univ, Ctr Outcomes Res & Evaluat, Hlth Syst, New Haven, CT USA. Washington Univ, St Louis, MO USA. Entrenar Inc, Kirkwood, MO USA. NIDA, Div Epidemiol, Serv Prevent & Res, Bethesda, MD USA. RP Stopka, TJ (reprint author), Calif State Off AIDS, Sacramento, CA USA. EM lstopka@dhs.ca.gov; anthro8566@aol.com NR 33 TC 1 Z9 1 U1 1 U2 2 PU UNIV PUBLISHING GROUP PI HAGERSTOWN PA 138 W WASHINGTON ST, STE 403-405, HAGERSTOWN, MD 21740 USA SN 0887-3852 J9 AIDS PUBLIC POLICY J JI Aids Public Policy J. PD WIN PY 2002 VL 17 IS 4 BP 115 EP 126 PG 12 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 852HA UT WOS:000223745200001 ER PT J AU Thakar, MR Patke, D Lakhashe, SK Bhonge, L Kulkarni, SV Tripathy, SP Gupte, N Brookmeyer, R Quinn, TC Paranjape, RS Bollinger, RC AF Thakar, MR Patke, D Lakhashe, SK Bhonge, L Kulkarni, SV Tripathy, SP Gupte, N Brookmeyer, R Quinn, TC Paranjape, RS Bollinger, RC TI Consistent subtype-specific anti-HIV type 1 T lymphocyte responses in Indian subjects recently infected with HIV type 1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID VIRAL LOAD; VIREMIA; PROGRESSION; PROTEINS; DISEASE; PUNE; AIDS AB Anti-HIV-1-specific T cell responses in early HIV-1 infection have been found to be important in deciding the course of disease progression. But there are few data concerning nonsubtype B HIV infection. HIV-1 subtype C is the most prevalent subtype in India. HIV-1 Gag-specific T cell responses in 12 Indian subjects with recent HIV-1 infection were characterized by an ELISpot assay at two consecutive visits and their correlation with plasma viral load and CD4(+) T lymphocyte counts was studied. Ten of the 12 subjects demonstrated T cell responses to either one or both Gag B and C peptides, on at least one visit. Five of 10 responders showed a consistent response (response at both visits): 4 exhibited a Gag C-specific consistent response and 1 showed a consistent response to Gag B. The remaining five patients, showing response at only one of the two visits, were considered inconsistent responders. None of the individuals showed a consistent response to both B and C Gag peptides. Marginally significant correlation was observed between consistency of the response and lower plasma viral load (p = 0.062). The subtype-specific Gag C response was also found to be correlated with lower viral load as compared with the response to Gag B (r = -0.336,p = 0.054 for subtype C and r = -0.234, p = 0.13 for subtype B). The data suggest that the patients exhibiting consistent subtype-specific responses to HIV-1 Gag might have better control of viral replication in early HIV infection. C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Thakar, MR (reprint author), Natl AIDS Res Inst, G-73,MIDC Bhosari, Pune 411026, Maharashtra, India. RI Lakhashe, Samir/F-1150-2014 FU NIAID NIH HHS [1 R01 AI41369-01A1, N01-AI-35173-113] NR 19 TC 12 Z9 12 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 DEC PY 2002 VL 18 IS 18 BP 1389 EP 1393 DI 10.1089/088922202320935465 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 625JM UT WOS:000179813400007 PM 12487810 ER PT J AU Osier, MV Pakstis, AJ Goldman, D Edenberg, HJ Kidd, JR Kidd, KK AF Osier, MV Pakstis, AJ Goldman, D Edenberg, HJ Kidd, JR Kidd, KK TI A proline-threonine substitution in codon 351 of ADH1C is common in Native Americans SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol dehydrogenase; coding variation; allele frequency; linkage disequilibrium ID ALCOHOL-METABOLIZING GENES; LINKAGE DISEQUILIBRIUM; DEHYDROGENASE GENOTYPES; POLYMORPHISM; RISK; MEN; POPULATION; EXPRESSION; DEPENDENCE AB Background: The alcohol dehydrogenase (ADH) genes have been repeatedly associated with protection against alcoholism. Until now, only four protein coding variants have been identified (ADH1C Arg271Gln, Ile349Val, ADH1B Arg47His, and Arg369Cys), and only two of these (ADH1C Ile349Val and ADH1B Arg47His) have been routinely tested in association studies with alcoholism. Methods: The new ADH1C*351Thr allele was identified by direct sequencing of DNA samples that gave different typing results for the ADH1C Ile349Val polymorphism with different typing protocols. Results: A new coding variant has been identified at codon 351 of ADH1C. This allele is found in most Native American populations that we have studied with allele frequencies of the new ADH1C*351Thr allele as high as 26%. Only two instances of this allele have been seen in a large survey of African and Eurasian populations. Conclusions: The changes in charge, size, and rotational mobility caused by this amino acid substitution should be significant. Because this new variant codes for a new enzyme form in Native Americans, the kinetics of this enzyme should be studied and considered in studies of the role of ADH1C in the protection against alcoholism in Native Americans. C1 Yale Univ, Dept Genet, New Haven, CT 06520 USA. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN USA. RP Kidd, KK (reprint author), Yale Univ, Dept Genet, 333 Cedar St, New Haven, CT 06520 USA. RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Edenberg, Howard/0000-0003-0344-9690 FU NIAAA NIH HHS [AA09379]; NIGMS NIH HHS [GM57672] NR 25 TC 24 Z9 25 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2002 VL 26 IS 12 BP 1759 EP 1763 DI 10.1097/01.ALC.0000042013.13899.75 PG 5 WC Substance Abuse SC Substance Abuse GA 631LP UT WOS:000180169500001 PM 12500098 ER PT J AU Thiele, GM Szabo, G Kovacs, EJ Bautista, AP Sosa, L Jerrells, TR AF Thiele, GM Szabo, G Kovacs, EJ Bautista, AP Sosa, L Jerrells, TR TI Modulation of immunity and viral-host interactions by alcohol SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; immune modulation; infection; hepatitis C virus; simian immunodeficiency virus; scavenger receptors; murine cytomegalovirus; burn injury; cytokines/chemokines ID TUMOR-NECROSIS-FACTOR; HEPATITIS-C VIRUS; MURINE CYTOMEGALOVIRUS-INFECTION; ACUTE ETHANOL TREATMENT; MALONDIALDEHYDE-ACETALDEHYDE ADDUCTS; MACROPHAGE INFLAMMATORY PROTEIN-2; ADHESION MOLECULE-1 EXPRESSION; MYELOID DENDRITIC CELLS; INDUCED LIVER-DISEASE; GROWTH-FACTOR-BETA AB This manuscript represents the proceedings of a symposium at the 2001 RSA Meeting in Montreal, Canada. The organizers/chairs were Gyongyi Szabo and Geoffrey M. Thiele. The presentations were (1) Introduction, by Gyongyi Szabo; (2) Chemokine dysregulation after acute ethanol exposure, by Elizabeth J. Kovacs; (3) Chemokine production and innate immunity in the livers of simian immunodeficiency virus-infected Macaca mulatta following chronic alcohol administration, by Abraham P. Bautista; (4) Influence of ethanol consumption on the severity and progression of hepatitis associated with cytomegalovirus infection, by Laura Sosa and Thomas R. Jerrells; (5) Scavenger receptor involvement in the immune response to the metabolites of chronic ethanol ingestion, by Geoffrey M. Thiele; and (6) Mechanisms of impaired accessory cell functions due to alcohol exposure and hepatitis C infection, by Gyongyi Szabo. C1 Univ Nebraska, Med Ctr, Omaha VA Med Ctr, Dept Internal Med,Res Serv 151, Omaha, NE 68105 USA. Univ Nebraska, Med Ctr, Dept Pathol Microbiol, Omaha VA Med Ctr, Omaha, NE USA. Univ Massachusetts, Sch Med, Dept Med, Div Gastroenterol, Worcester, MA USA. Loyola Univ Chicago, Stritch Sch Med, Dept Cell Biol Neurobiol & Anat, Maywood, IL USA. Loyola Univ Chicago, Stritch Sch Med, Dept Surg, Maywood, IL USA. Louisiana State Univ, Hlth Sci Ctr, NIAAA, Sponsored Alcohol Res Ctr,Dept Physiol, New Orleans, LA USA. Louisiana State Univ, Hlth Sci Ctr, NIAAA, Sponsored Alcohol Res Ctr,Dept Med, New Orleans, LA USA. Tulane Reg Primate Ctr, Covington, LA USA. RP Thiele, GM (reprint author), Univ Nebraska, Med Ctr, Omaha VA Med Ctr, Dept Internal Med,Res Serv 151, 4101 Woolworth Ave, Omaha, NE 68105 USA. OI Thiele, Geoffrey/0000-0001-5688-8596 FU NIAAA NIH HHS [AA12034, AA012450, AA07582, AA07731, AA11134, AA12034-S1, F30AA05487, P50 AA 09803, R01AA07818, R29/R01AA10435]; NIGMS NIH HHS [GM55344] NR 120 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2002 VL 26 IS 12 BP 1897 EP 1908 DI 10.1111/j.1530-0277.2002.tb02498.x PG 12 WC Substance Abuse SC Substance Abuse GA 631LP UT WOS:000180169500018 PM 12500115 ER PT J AU Fertig, JB AF Fertig, JB TI Overview - Alcohol and tobacco: Mechanisms and treatment SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material C1 NIAAA, Treatment Res Branch, Div Clin & Prevent Res, Bethesda, MD 20892 USA. RP Fertig, JB (reprint author), NIAAA, Treatment Res Branch, Div Clin & Prevent Res, 6000 Execut Blvd, Bethesda, MD 20892 USA. NR 1 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD DEC PY 2002 VL 26 IS 12 BP 1909 EP 1910 DI 10.1097/01.ALC.0000040845.55554.69 PG 2 WC Substance Abuse SC Substance Abuse GA 631LP UT WOS:000180169500019 ER PT J AU Walsh, CR O'Donnell, CJ Camargo, CA Giugliano, RP Lloyd-Jones, DM AF Walsh, CR O'Donnell, CJ Camargo, CA Giugliano, RP Lloyd-Jones, DM TI Elevated serum creatinine is associated with 1-year mortality after acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID STAGE RENAL-DISEASE; COOPERATIVE CARDIOVASCULAR PROJECT; CORONARY-ARTERY DISEASE; LONG-TERM SURVIVAL; RANDOMIZED TRIAL; ELDERLY PATIENTS; HEART-DISEASE; RISK-FACTORS; DYSFUNCTION; REVASCULARIZATION AB Background Cardiovascular mortality is high in individuals with end-stage renal disease. However, less is known about the prognostic importance of moderate, renal insufficiency in patients with acute myocardial infarction. Methods We studied all patients with acute myocardial infarction admitted through the emergency department to an urban, academic hospital over 1 year. Patients were classified as having elevated (> 133 mumol/L [1.5 mg/dL]) or normal 133 mumol/L) serum creatinine at presentation. Results Of 483 patients, 22% had elevated creatinine and 786/. had normal creatinine. By 1 year, 46% of patients with elevated creatinine and 15% of patients with normal creatinine had died (P < .001). The unadjusted hazard ratio for 1-year mortality was increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 3.85, 95% CI 2.61-5.67). After adjustment for baseline characteristics and treatment, the multivariable-adjusted hazard ratio for 1-year mortality remained increased in patients with elevated creatinine compared with those with normal creatinine (hazard ratio 2.40, 95% CI 1.55-3.72). There was an important modification of the prognostic value of creatinine by the presence of congestive heart failure at presentation (P value for interaction =.04). The adjusted hazard ratio for 1-year death associated with elevated creatinine compared with normal creatinine was 3.89 (95% CI 1.87-8.07) in patients without congestive heart failure and 1.92 (95% CI 1.10-3.36) in patients with congestive heart failure. Conclusions Elevated serum creatinine at presentation is associated with 1-year mortality, after acute myocardial infarction. Further study is needed to optimize treatment after myocardial infarction in this high-risk group. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiol Div, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA USA. RP O'Donnell, CJ (reprint author), Premium Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [HL-03533, HL-07575] NR 38 TC 68 Z9 73 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD DEC PY 2002 VL 144 IS 6 BP 1003 EP 1011 DI 10.1067/mhj.2002.125504 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 631UY UT WOS:000180186200009 PM 12486424 ER PT J AU Hees, PS Fleg, JL Lakatta, EG Shapiro, EP AF Hees, PS Fleg, JL Lakatta, EG Shapiro, EP TI Left ventricular remodeling with age in normal men versus women: Novel insights using three-dimensional magnetic resonance imaging SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID IDIOPATHIC DILATED CARDIOMYOPATHY; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; HEART-FAILURE; AORTIC REGURGITATION; MITRAL REGURGITATION; EXERCISE CAPACITY; SHAPE; MASS; POPULATION AB Echocardiogrophic left ventricular (IV) wall thickness increases with age, suggesting IV hypertrophy. However, autopsy studies have shown no change, or even a decrease, in IV mass with age. With many pathologies, IV remodeling results in changes in ventricular shape. Age-associated IV shape change might explain this discrepancy, although this has not been studied. Magnetic resonance imaging (MRI) was used in 336 healthy, normotensive adults (mean age 56 +/- 18 years; 200 women, 136 men) to measure IV mass, end-diastolic IV wall thickness, length, diameter, and shape. Echocardiographic IV mass was measured in a subset of 86 subjects by a standard algorithm. In women, IV wall thickness increased by 14% (r = 0.19, p <0.02), whereas IV length decreased by 9% (r = -0.26, p = 0.0006); IV diameter was unchanged. Thus, IV mass did not vary with age (r -0.04, p = 0.06) and the sphericity index decreased (r = -0.165, p <0.05). In men, IV wall thickness and diameter were unrelated to age, but there was an 11% decrease in IV length (r = -0.29, p 0.003); therefore, there was an 11% decrease in IV mass (r = -0.20, p = 0.019) and a decrease in the sphericity index (r = -0.218, p <0.04). No change occurred in echocardiographic IV mass with age in either gender, although echocardiographic IV wall thickness increased in both. The left ventricle becomes more spherical with age in normal adults due to reduced IV lengths In women, increased IV wall thickness offsets the decreasing IV length, whereas in men, IV wall thickness' fails to compensate, resulting in decreased IV mass with age. (C) 2002 by Excerpta Medica, Inc. C1 Johns Hopkins Med Inst, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sch Med, Div Cardiol, Baltimore, MD 21205 USA. NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. RP Hees, PS (reprint author), Johns Hopkins Bayview Med Ctr, Div Cardiol, 4940 Eastern Ave, Baltimore, MD 21224 USA. FU NHLBI NIH HHS [1R01 HL46223] NR 23 TC 53 Z9 56 U1 0 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2002 VL 90 IS 11 BP 1231 EP 1236 AR PII S0002-9149(02)02840-0 DI 10.1016/S0002-9149(02)02840-0 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 621YN UT WOS:000179618800010 PM 12450604 ER PT J AU Fetsch, PA Simone, NL Bryant-Greenwood, PK Marincola, FM Filie, AC Petricoin, EF Liotta, LA Abati, A AF Fetsch, PA Simone, NL Bryant-Greenwood, PK Marincola, FM Filie, AC Petricoin, EF Liotta, LA Abati, A TI Proteomic evaluation of archival cytologic material using SELDI affinity mass spectrometry - Potential for diagnostic applications SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 90th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 03-09, 2001 CL ATLANTA, GEORGIA SP US & Canadian Acad Pathol DE proteomics; SELDI; protein fingerprint; protein biochip; archival cytologic samples; melanoma; clear cell sarcoma; renal cell carcinoma; reactive mesothelial cells ID LASER CAPTURE MICRODISSECTION; CANCER-RESEARCH; CELL CARCINOMA; BREAST-CANCER; TISSUE; MELANOMA; IDENTIFICATION; TECHNOLOGIES; PROGRESSION; BIOMARKERS AB Proteomic studies of cells via surface-enhanced laser desorption/ionization spectrometry (SELDI) analysis have enabled rapid, reproducible protein profiling directly from crude samples. We applied this technique to archival cytology material to determine whether distinct, reproducible protein fingerprints could be identified for potential diagnostic purposes in blinded specimens. Rapid Romanowsky-stained cytocentrifuged specimens from fine-needle aspirates of metastatic malignant melanoma (with both known cutaneous primary and unknown primary sites), clear cell sarcoma, and renal cell card. noma and reactive effusions were examined using the SELDI technology. A unique characteristic fingerprint was identified for each disease entity. Fifteen "blinded" unknown samples then were analyzed. When the protein profile fingerprints were plotted against the known fingerprints for the aforementioned diagnoses, the appropriate match or diagnosis was obtained in 13 (87%) of 15 cases. These preliminary findings suggest a substantial potential for SELDI applications to specific pathologic diagnoses. C1 NCI, Cytophathol Sect, NIH, Pathol Lab, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. US FDA, Clin Prote Program, Bethesda, MD 20014 USA. RP Abati, A (reprint author), NCI, Cytophathol Sect, NIH, Pathol Lab, Bldg 10,Room 2A19, Bethesda, MD 20892 USA. NR 32 TC 55 Z9 59 U1 0 U2 1 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD DEC PY 2002 VL 118 IS 6 BP 870 EP 876 DI 10.1092/HCRY7A2X09D9GYYA PG 7 WC Pathology SC Pathology GA 619JA UT WOS:000179471800008 PM 12472280 ER PT J AU Lugassy, C Haroun, RI Brem, H Tyler, BM Jones, RV Fernandez, PM Patierno, SR Kleinman, HK Barnhill, RL AF Lugassy, C Haroun, RI Brem, H Tyler, BM Jones, RV Fernandez, PM Patierno, SR Kleinman, HK Barnhill, RL TI Pericytic-like angiotropism of glioma and melanoma cells SO AMERICAN JOURNAL OF DERMATOPATHOLOGY LA English DT Article DE melanoma; glioma; angiotumoral complex; pericytic-like angiotropism; extravascular migratory metastasis; laminin ID EXTRACELLULAR-MATRIX; IMMUNOHISTOCHEMICAL OBSERVATIONS; BASEMENT-MEMBRANE; LAMININ; MIGRATION; TUMOR; METASTASIS; ANGIOGENESIS; COMPONENTS; MODELS AB We have identified in malignant melanoma an angiotumoral complex in which tumor cells occupy a pericytic location along the endothelium of microvessels without evidence of intravasation. We have suggested that this pericytic-like angiotropism could be a marker of an extravascular migration of tumor cells along the abluminal surface of vessels. The extravascular migratory metastasis proposed for melanoma has close analogies with glioma migration. To compare our hypothesis of extravascular migration by melanoma with the migration of glioma cells, we have used the B16 murine melanoma cell line and the GL26 murine glioma cell line in an in vivo murine brain tumor model and in vitro using endothelial cells that have formed capillary-like structures and have been cocultivated with tumor cells. In the brain tumors, a clear progression of glioma and melanoma cells was observed along the abluminal surface of vessels, where they occupied a pericytic location along the periendothelial laminin. In vitro, time-lapse videomicroscopy recorded the migration of tumor cells toward endothelial tubules. After 24 hours, both the melanoma cells and the glioma cells were localized along the external surfaces of the vascular tubules, occupying a pericytic-like location. These similarities between glioma and melanoma support the hypothesis of an extravascular migration of melanoma cells, particularly along the abluminal surface of vessels. C1 George Washington Univ, Med Ctr, Dept Dermatol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Pathol, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Pharmacol, Washington, DC 20037 USA. George Washington Univ, Program Mol & Cellular Oncol, Washington, DC 20037 USA. Johns Hopkins Univ, Sch Med, Dept Neurosurg & Oncol, Baltimore, MD USA. NIH, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. RP Barnhill, RL (reprint author), George Washington Univ, Med Ctr, Dept Dermatol, 6A-404,2150 Penn Ave NW, Washington, DC 20037 USA. FU NCI NIH HHS [U01-CA52857] NR 28 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0193-1091 J9 AM J DERMATOPATH JI Am. J. Dermatopathol. PD DEC PY 2002 VL 24 IS 6 BP 473 EP 478 DI 10.1097/00000372-200212000-00003 PG 6 WC Dermatology SC Dermatology GA 619ZE UT WOS:000179507200003 PM 12454598 ER PT J AU Froenicke, L Anderson, LK Wienberg, J Ashley, T AF Froenicke, L Anderson, LK Wienberg, J Ashley, T TI Male mouse recombination maps for each autosome identified by chromosome painting SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID MEIOTIC RECOMBINATION; SYNAPTONEMAL COMPLEXES; CROSSING-OVER; SACCHAROMYCES-CEREVISIAE; LYCOPERSICON-ESCULENTUM; CROSSOVER INTERFERENCE; CHIASMA DISTRIBUTION; PACHYTENE BIVALENTS; HUMAN SPERMATOCYTES; SOLANACEOUS PLANTS AB Linkage maps constructed from genetic analysis of gene order and crossover frequency provide few clues to the basis of genomewide distribution of meiotic recombination, such as chromosome structure, that influences meiotic recombination. To bridge this gap, we have generated the first cytological recombination map that identifies individual autosomes in the male mouse. We prepared meiotic chromosome (synaptonemal complex [SC]) spreads from 110 mouse spermatocytes, identified each autosome by multicolor fluorescence in situ hybridization of chromosome-specific DNA libraries, and mapped 1 2,000 sites of recombination along individual autosomes, using immunolocalization of MLH1, a mismatch repair protein that marks crossover sites. We show that SC length is strongly correlated with crossover frequency and distribution. Although the length of most SCs corresponds to that predicted from their mitotic chromosome length rank, several SCs are longer or shorter than expected, with corresponding increases and decreases in MLH1 frequency. Although all bivalents share certain general recombination features, such as few crossovers near the centromeres and a high rate of distal recombination, individual bivalents have unique patterns of crossover distribution along their length. In addition to SC length, other, as-yet-unidentified, factors influence crossover distribution leading to hot regions on individual chromosomes, with recombination frequencies as much as six times higher than average, as well as cold spots with no recombination. By reprobing the SC spreads with genetically mapped BACs, we demonstrate a robust strategy for integrating genetic linkage and physical contig maps with mitotic and meiotic chromosome structure. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA. Tech Univ, Inst Human Genet, Munich, Germany. GSF Forschungszentrum, Munich, Germany. Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. Natl Canc Inst, Comparat Mol Cytogenet Sect, Genet Branch, Frederick, MD USA. RP Ashley, T (reprint author), Yale Univ, Sch Med, Dept Genet, 333 Cedar St, New Haven, CT 06510 USA. FU NIGMS NIH HHS [R01-GM55300] NR 59 TC 116 Z9 121 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2002 VL 71 IS 6 BP 1353 EP 1368 DI 10.1086/344714 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 621KD UT WOS:000179586800010 PM 12432495 ER PT J AU Suchy, SF Nussbaum, RL AF Suchy, SF Nussbaum, RL TI The deficiency of PIP2 5-phosphatase in Lowe syndrome affects actin polymerization SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GREEN FLUORESCENT PROTEIN; CELL-CELL ADHESION; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; OCULOCEREBRORENAL SYNDROME; EPITHELIAL-CELLS; OCRL1 GENE; GELSOLIN; DIFFERENTIATION; FIBROBLASTS; MUTATIONS AB Lowe syndrome is a rare X-linked disorder characterized by bilateral congenital cataracts, renal Fanconi syndrome, and mental retardation. Lowe syndrome results from mutations in the OCRL1 gene, which encodes a phosphatidylinositol 4,5 bisphosphate 5-phosphatase located in the trans-Golgi network. As a first step in identifying the link between ocrl1 deficiency and the clinical disorder, we have identified a reproducible cellular abnormality of the actin cytoskeleton in fibroblasts from patients with Lowe syndrome. The cellular abnormality is characterized by a decrease in long actin stress fibers, enhanced sensitivity to actin depolymerizing agents, and an increase in punctate F-actin staining in a distinctly anomalous distribution in the center of the cell. We also demonstrate an abnormal distribution of two actin-binding proteins, gelsolin and alpha-actinin, proteins regulated by both PIP2 and Ca+2 that would be expected to be altered in Lowe cells. Actin polymerization plays a key role in the formation, maintenance, and proper function of tight junctions and adherens junctions, which have been demonstrated to be critical in renal proximal tubule function, and in the differentiation of the lens. These findings point to a general mechanism to explain how this PIP2 5-phosphatase deficiency might produce the Lowe syndrome phenotype. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Suchy, SF (reprint author), NHGRI, NIH, Bldg 49,Room 4A 66, Bethesda, MD 20892 USA. NR 27 TC 78 Z9 81 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2002 VL 71 IS 6 BP 1420 EP 1427 DI 10.1086/344517 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 621KD UT WOS:000179586800015 PM 12428211 ER PT J AU Groussin, L Kirschner, LS Vincent-Dejean, C Perlemoine, K Jullian, E Delemer, B Zacharieva, S Pignatelli, D Carney, JA Luton, JP Bertagna, X Stratakis, CA Bertherat, J AF Groussin, L Kirschner, LS Vincent-Dejean, C Perlemoine, K Jullian, E Delemer, B Zacharieva, S Pignatelli, D Carney, JA Luton, JP Bertagna, X Stratakis, CA Bertherat, J TI Molecular analysis of the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene in patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology: Augmented PKA signaling is associated with adrenal tumorigenesis in PPNAD SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SPOTTY SKIN PIGMENTATION; PSAMMOMATOUS MELANOTIC SCHWANNOMA; FAMILIAL CARDIAC MYXOMAS; ENDOCRINE OVERACTIVITY; DUCTAL ADENOMA; ALPHA SUBUNIT; CAMP; CREB; TRANSCRIPTION; ABNORMALITIES AB We studied 11 new kindreds with primary pigmented nodular adrenocortical disease (PPNAD) or Carney complex (CNC) and found that 82% of the kindreds had PRKAR1A gene defects (including seven novel inactivating mutations), most of which led to nonsense mRNA and, thus, were not expressed in patients' cells. However, a previously undescribed base substitution in intron 6 (exon 6 IVS +1G-->T) led to exon 6 skipping and an expressed shorter PRKAR1A protein. The mutant protein was present in patients' leukocytes and tumors, and in vitro studies indicated that the mutant PRKAR1A activated cAMP-dependent protein kinase A (PKA) signaling at the nuclear level. This is the first demonstration of an inactivating PRKAR1A mutation being expressed at the protein level and leading to stimulation of the PKA pathway in CNC patients. Along with the lack of allelic loss at the PRKAR1A locus in most of the tumors from this kindred, these data suggest that alteration of PRKAR1A function (not only its complete loss) is sufficient for augmenting PKA activity leading to tumorigenesis in tissues affected by CNC. C1 Hop Cochin, Serv Malad Endocriniennes & Metab, Dept Endocrinol, F-75014 Paris, France. Univ Paris 05, Inst Cochin,Dept Endocrinol, CNRS,UMR 8104, INSERM,U576, Paris, France. NICHHD, Unit Genet & Endocrinol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. CHU Reims, Dept Endocrinol, Reims, France. Clin Ctr endocrinol & Gerontol, Dept Endocrinol, Sofia, Bulgaria. Fac Med Porto, Inst Histol & Embryol, Oporto, Portugal. Mayo Clin, Rochester, MN USA. COMETE Network, Paris, France. RP Hop Cochin, Serv Malad Endocriniennes & Metab, Dept Endocrinol, 27 Rue Fg St Jacques, F-75014 Paris, France. EM jerome.bertherat@cch.ap-hop-paris.fr NR 32 TC 122 Z9 125 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD DEC PY 2002 VL 71 IS 6 BP 1433 EP 1442 DI 10.1086/344579 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 621KD UT WOS:000179586800017 PM 12424709 ER PT J AU Thurston, GD Chen, LC AF Thurston, GD Chen, LC TI Risk communication in the aftermath of the World Trade Center disaster SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article; Proceedings Paper CT 23rd Annual Meeting of the New York/New Jersey Occupational Safety and Health Educational Research Center (UOSHERC) CY APR 05, 2002 CL NEW YORK, NEW YORK SP New York/New Jersey Occupati Safety Hlth Educat Res Ctr DE air pollution; dust; particulate matter; soot; risk assessment C1 NYU, NIEHS, Ctr Excellence, Dept Environm Med,Sch Med, Tuxedo Pk, NY 10987 USA. RP Thurston, GD (reprint author), NYU, NIEHS, Ctr Excellence, Dept Environm Med,Sch Med, 57 Old Forge Rd, Tuxedo Pk, NY 10987 USA. RI Cjem, Lung-Chi/H-5030-2012; OI Chen, Lung Chi/0000-0003-1154-2107 FU NIEHS NIH HHS [ES00260] NR 0 TC 8 Z9 8 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 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD DEC PY 2002 VL 42 IS 6 BP 543 EP 544 DI 10.1002/ajim.10163 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 619YW UT WOS:000179506400012 PM 12439880 ER PT J AU O'Grady, NP Alexander, M Dellinger, EP Gerberding, JL Heard, SO Maki, DG Masur, H McCormick, RD Mermel, LA Pearson, ML Raad, II Randolph, A Weinstein, RA AF O'Grady, NP Alexander, M Dellinger, EP Gerberding, JL Heard, SO Maki, DG Masur, H McCormick, RD Mermel, LA Pearson, ML Raad, II Randolph, A Weinstein, RA TI Guidelines for the prevention of intravascular catheter-related infections SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Review ID CENTRAL VENOUS CATHETER; BLOOD-STREAM INFECTION; INTENSIVE-CARE-UNIT; TOTAL PARENTERAL-NUTRITION; PERIPHERAL INTRAVENOUS CATHETERS; RESISTANT STAPHYLOCOCCUS-AUREUS; RANDOMIZED CONTROLLED TRIAL; DOUBLE-BLIND TRIAL; ANTISEPTIC-IMPREGNATED CATHETER; SERRATIA-MARCESCENS BACTEREMIA AB Background: Although many catheter-related bloodstream infections (CR-BSIs) are preventable, measures to reduce these infections are not uniformly implemented. Objective: To update an existing evidenced-based guideline that promotes strategies to prevent CR-BSIs. Data sources: The MEDLINE database, conference proceedings, and bibliographies of review articles and book chapters were searched for relevant articles. Studies included: Laboratory-based studies, controlled clinical trials, prospective interventional trials, and epidemiological investigations. Outcome measures: Reduction in CR-BSI, catheter colonization, or catheter-related infection. Synthesis: The recommended preventive strategies with the strongest supportive evidence are education and training of healthcare providers who insert and maintain catheters; maximal sterile barrier precautions during central venous catheter insertion; use of a 2 % chlorhexidine preparation for skin antisepsis; no routine replacement of central venous catheters for prevention of infection; and use of antiseptic/antibiotic impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (i.e. education and training, maximal sterile barrier precautions and 2 % chlorhexidine for skin antisepsis). Conclusion: Successful implementation of these evidence-based interventions can reduce the risk for serious catheter-related infection. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. SCCM, Des Plaines, IL 60016 USA. IDSA, Alexandria, VA 22314 USA. INS, Cambridge, MA USA. Univ Washington, Dept Surg, Seattle, WA 98195 USA. CDC, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Univ Massachusetts, Sch Med, Dept Anesthesiol, Worcester, MA USA. ACCP, Northbrook, IL 60062 USA. ASCCA, Chicago, IL USA. Univ Wisconsin, Sch Med, Infect Dis Sect, Madison, WI USA. Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. APIC, Washington, DC 20005 USA. Rhode Isl Hosp, Div Infect Dis, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med Specialties, Houston, TX 77030 USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Cook Cty Hosp, Div Infect Dis, Chicago, IL 60612 USA. Rush Med Coll, Chicago, IL 60612 USA. SHEA, Mt Royal, NJ 08061 USA. RP O'Grady, NP (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. OI Randolph, Adrienne/0000-0002-3084-3071 NR 183 TC 130 Z9 137 U1 3 U2 21 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD DEC PY 2002 VL 30 IS 8 BP 476 EP 489 DI 10.1067/mic.2002.129427 PG 14 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 627JQ UT WOS:000179930400004 PM 12461511 ER PT J AU Sigmon, HD Larson, EL AF Sigmon, HD Larson, EL TI Research opportunities in biodefense for the National Institute of Nursing Research SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article AB The threat of bioterrorism and the need for biodefense are new challenges for the scientific community Bioterrorism already has had significant effects on the nation's health. Researchers involved in nursing research are addressing these effects and the many issues relevant to biodefense. To explore the role and potential contributions of nursing research in these arenas, the National Institute of Nursing Research recently convened a science work group. The work group highlighted current knowledge in biodefense, suggested opportunities for nursing research, and proposed specific research topics and research training needs. The topics are integral to the strategic plan on biodefense developed by the National institutes of Health and include biologic, behavioral, applied/translational, and health systems research. C1 NINR, Off Extramural Programs, Bethesda, MD 20892 USA. Columbia Univ, Sch Nursing, New York, NY USA. RP Sigmon, HD (reprint author), NINR, Off Extramural Programs, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD DEC PY 2002 VL 30 IS 8 BP 490 EP 494 DI 10.1067/mic.2002.128876 PG 5 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 627JQ UT WOS:000179930400005 PM 12461512 ER PT J AU Agodoa, L AF Agodoa, L TI Racial disparities in kidney health: The puzzle to solve SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material C1 NIDDKD, Off Minor Hlth Res Coordinat, NIH, Bethesda, MD 20892 USA. RP Agodoa, L (reprint author), NIDDKD, Off Minor Hlth Res Coordinat, NIH, Bethesda, MD 20892 USA. NR 5 TC 8 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD DEC PY 2002 VL 40 IS 6 BP 1337 EP 1339 DI 10.1053/ajkd.2002.37395 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 621HA UT WOS:000179581900030 PM 12460057 ER PT J AU Wendler, D Prasad, K Wilfond, B AF Wendler, D Prasad, K Wilfond, B TI Does the current consent process minimize the risks of genetics research? SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE future disclosure; recall AB Completion of the human genome project is expected to lead to an increase in the number of individuals who participate in genetics research. The current informed consent process-developed prior to widespread genetics research-may not be sufficient to minimize the research risks that these individuals face. The current consent process focuses on informing individuals of the risks of research participation prior to their research enrollment. However, the risks of genetics research often are influenced by what subjects disclose to others after their research participation has ended. To assess whether the current consent process helps subjects remember the risks of future disclosures and, thereby, minimize the risks of genetics research, we interviewed 130 individuals who had previously participated in genetics research. Nineteen percent recalled that their samples would undergo genetic testing; 16% recalled that samples might be used for future research; 15% recalled that release of research records could affect their insurance status. These data suggest that current consent practices may not minimize the risks of genetics research. To address this concern, Institutional Review Boards and investigators should consider implementing supplemental mechanisms to help subjects remember when forgetting aspects of their research participation could place them at increased risk. Published 2002 Wiley-Liss, Inc. C1 NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. Natl Human Genome Res Inst Hlth, Med Genet Branch, Bethesda, MD USA. RP Wendler, D (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 8 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD DEC 1 PY 2002 VL 113 IS 3 BP 258 EP 262 DI 10.1002/ajmg.10818 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 614CV UT WOS:000179171500006 PM 12439893 ER PT J AU Letterie, GS Catherino, WH AF Letterie, GS Catherino, WH TI A 7.5-MHz finger-grip ultrasound probe for real-time intraoperative guidance during complex reproductive surgical procedures SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE image-guided surgery; intraoperative ultrasound; mullerian abnormalities; leiomyoma AB OBJECTIVE: A 7.5-MHz finger-grip probe was used to monitor intra-abdominal reproductive surgery in two groups of patients. STUDY DESIGN: The first group of patients underwent transabdominal myomectomy for multiple uterine leiomyomas (n = 3) and the second group underwent uterine reconstruction and excision of obstructive uterine horn (n = 3). Intraoperative real-time imaging was accomplished by direct application of the finger-grip probe to the uterine serosa by using saline solution as a transmission media. Ultrasound imaging and surgical dissection were carried out both sequentially and simultaneously. RESULTS: In the first group of patients, the finger-grip probe provided precise location of the leiomyomas and intraoperative guidance for dissection during the myomectomy. In the second group of patients, the finger probe provided images of intrauterine anatomy in one patient who had a normal-sized and normal-shaped uterus with an obstructed intracavitary horn and hematometrium. In two other patients, the obstructed uterine horn extended deep into the pelvis lateral to the vagina. Real-time imaging provided intraoperative monitoring of depth of dissection into the paravaginal space. CONCLUSION: The finger-grip probe demonstrated intrauterine anatomy and enabled a more directed surgical approach, both in placement of uterine incisions for surgical reconstruction and excision of obstructed horns for mullerian abnormalities and in identification and dissection for leiomyomas. C1 Virginia Mason Med Ctr, Ctr Fertil & Reprod Endocrinol, Seattle, WA 98110 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Letterie, GS (reprint author), Virginia Mason Med Ctr, Ctr Fertil & Reprod Endocrinol, 1100 9th Ave,X11-FC, Seattle, WA 98110 USA. NR 3 TC 7 Z9 8 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD DEC PY 2002 VL 187 IS 6 BP 1588 EP 1590 DI 10.1067/mob.2002.128400 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 630VQ UT WOS:000180131200057 PM 12501068 ER PT J AU Wong, TY Klein, R Nieto, FJ Moraes, SAD Mosley, TH Couper, DJ Klein, BEK Boland, LL Hubbard, LD Sharrett, AR AF Wong, TY Klein, R Nieto, FJ Moraes, SAD Mosley, TH Couper, DJ Klein, BEK Boland, LL Hubbard, LD Sharrett, AR TI Is early age-related maculopathy related to cognitive function? The atherosclerosis risk in communities study SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; ALZHEIMERS-DISEASE; MACULAR DEGENERATION; APOLIPOPROTEIN-E; CARDIOVASCULAR-DISEASE; RETINAL PATHOLOGY; POPULATION; DEMENTIA; PREVALENCE; IMPAIRMENT AB PURPOSE: Age-related maculopathy (ARM) and cognitive impairment are both neurodegenerative disorders associated with aging and have been hypothesized to share common pathogenic pathways. We describe the association between cognitive function and ARM in middle,aged persons. DESIGN: Population based, cross-sectional study involving participants of the Atherosclerosis Risk in communities Study, an ongoing cardiovascular investigation of persons 5 1 to 70 years of age, examined every 3 years between 1987 to 1998. METHODS: At visit three (1993-1995), retinal photographs were obtained and evaluated for ARM using a modification of the Wisconsin ARM Grading System. Cognitive function was assessed using standardized tests (Delayed Word Recall, Digit Symbol, and Word Fluency) at visits two (1990-1992) and four (1996-1998) and averaged for analysis. Severe cognitive impairment was defined as scores falling in the lowest 10th percentile of the population. RESULTS: Data were available in 9286 persons after exclusion of persons with stroke or using antipsychotic medication. After adjusting for age, gender, race, education, diabetes, hypertension, cigarette smoking, and alcohol consumption, persons with severe cognitive impairment based on Word Fluency Test scores were more likely to have early ARM (odds ratio [OR]: 1.6, 95% confidence interval [Cl]: 1.1-2.2) and its components, soft drusen (OR: 1.6; 95% Cl: 1.1-2.3) and pigmentary abnormality (OR: 1.5; 95% Cl: 0.9-2.5) than those without severe impairment. However, severe cognitive impairment in scores of the other two cognitive function tests was not associated with ARM. CONCLUSION: These population-based data suggest a weak association between cognitive function and early ARM in middle-aged persons. C1 Natl Univ Singapore, Dept Ophthalmol, Singapore 119074, Singapore. Natl Univ Singapore, Singapore Eye Res Inst, Singapore 119074, Singapore. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Wong, TY (reprint author), Natl Univ Singapore, Dept Ophthalmol, 10 Lower Kent Ridge Rd, Singapore 119074, Singapore. FU NHLBI NIH HHS [N01-HC-55015, N01-HC-35125, N01-HC-35126, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022] NR 43 TC 31 Z9 32 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2002 VL 134 IS 6 BP 828 EP 835 AR PII S0002-9394(02)01672-0 PG 8 WC Ophthalmology SC Ophthalmology GA 624BA UT WOS:000179738600005 PM 12470750 ER PT J AU Latkany, PA Jabs, DA Smith, JR Rosenbaum, JT Tessler, H Schwab, IR Walton, RC Thorne, JE Maguire, AM AF Latkany, PA Jabs, DA Smith, JR Rosenbaum, JT Tessler, H Schwab, IR Walton, RC Thorne, JE Maguire, AM TI Multifocal choroiditis in patients with familial juvenile systemic granulomatosis SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID ARTHRITIS BLAU-SYNDROME; SKIN RASH; RHEUMATOID-ARTHRITIS; UVEITIS; SARCOIDOSIS; CHROMOSOME-16; INVOLVEMENT; ARTERITIS; DISEASE; LINKAGE AB PURPOSE: To document clinical features of uveitis in patients with familial juvenile systemic granulomatosis. DESIGN: Retrospective chart review. METHODS: Ophthalmologic examination, medical history, and clinical course in 16 patients from eight families examined at six academic medical centers. RESULTS: Of the 16 patients, 15 had evidence of panuveitis with multifocal choroiditis. One patient had only an anterior uveitis. Ischemic optic neuropathy, presumably due to a small vessel vasculopathy, and retinal vasculopathy each occurred in one patient. Ocular complications were common, including cataracts in 11, glaucoma in six, band keratopathy in six, cystoid macular edema in six, and optic disk edema in six. All 16 patients had polyarthritis, and at least nine had skin rash. Often patients were misdiagnosed initially as having either juvenile rheumatoid arthritis or sarcoidosis. CONCLUSIONS: Familial juvenile systemic granulomatosis is an uncommon genetic disease characterized by polyarthritis and uveitis. Panuveitis and multifocal choroiditis often may be present. Patients with a diagnosis of juvenile rheumatoid arthritis but having a family history of the disease and multifocal choroiditis should be suspected of having familial juvenile systemic granulomatosis. C1 Johns Hopkins Univ, Sch Med, Dept Ophthalmol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Oregon Hlth Sci Univ, Dept Ophthalmol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Univ Illinois, Dept Ophthalmol, Chicago, IL 60680 USA. Univ Calif Davis, Dept Ophthalmol, Sacramento, CA 95817 USA. NEI, Bethesda, MD 20892 USA. Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. RP Jabs, DA (reprint author), Wilmer Eye Inst, 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. FU NEI NIH HHS [EY00405]; NIAID NIH HHS [T32 AI07451] NR 22 TC 30 Z9 30 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD DEC PY 2002 VL 134 IS 6 BP 897 EP 904 AR PII S0002-9394(02)01709-9 DI 10.1016/S0002-9394(02)01709-9 PG 8 WC Ophthalmology SC Ophthalmology GA 624BA UT WOS:000179738600015 PM 12470760 ER PT J AU van de Rijn, M Perou, CM Tibshirani, R Haas, P Kallioniemi, C Kononen, J Torhorst, J Sauter, G Zuber, M Kochli, OR Mross, F Dieterich, H Seitz, R Ross, D Botstein, D Brown, P AF van de Rijn, M Perou, CM Tibshirani, R Haas, P Kallioniemi, C Kononen, J Torhorst, J Sauter, G Zuber, M Kochli, OR Mross, F Dieterich, H Seitz, R Ross, D Botstein, D Brown, P TI Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TISSUE MICROARRAYS; CANCER; ARRAYS; TUMORS AB While several prognostic factors have been identified in breast carcinoma, the clinical outcome remains hard to predict for individual patients. Better predictive markers are needed to help guide difficult treatment decisions. in a previous study of 78 breast carcinoma specimens, we noted an association between poor clinical outcome and the expression of cytokeratin 17 and/or cytokeratin 5 mRNAs. Here we describe the results of immunohistochemistry studies using monoclonal antibodies against these markers to analyze more than 600 paraffin-embedded breast tumors in tissue microarrays. We found that expression of cytokeratin 17 and/or cytokeratin 5/6 in tumor cells was associated with a poor clinical outcome. Moreover, multivariate analysis showed that in node-negative breast carcinoma, expression of these cytokeratins was a prognostic factor independent of tumor size and tumor grade. C1 Stanford Univ, Ctr Med, Dept Pathol L235, Stanford, CA 94305 USA. Stanford Univ, Ctr Med, Dept Hlth Res & Policy Stat, Stanford, CA 94305 USA. Stanford Univ, Ctr Med, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Ctr Med, Dept Biochem, Stanford, CA 94305 USA. Stanford Univ, Ctr Med, Howard Hughes Med Inst, Stanford, CA 94305 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC USA. Univ Basel, Inst Pathol, Basel, Switzerland. Natl Inst Hlth, Canc Genet Branch, Bethesda, MD USA. Diomeda Life Sci Inc, Rockville, MD USA. Univ Basel, Dept Surg, Univ Frauenklin, Basel, Switzerland. Kreiskrankenhaus, Lorrach, Germany. Frauenklin, Rheinfelden, Germany. Appl Genon Inc, Huntsville, AL USA. Appl Genon Inc, Sunnyvale, CA USA. RP van de Rijn, M (reprint author), Stanford Univ, Ctr Med, Dept Pathol L235, 300 Pasteur Dr, Stanford, CA 94305 USA. OI Perou, Charles/0000-0001-9827-2247 FU NCI NIH HHS [U01 CA085129] NR 17 TC 361 Z9 370 U1 0 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD DEC PY 2002 VL 161 IS 6 BP 1991 EP 1996 DI 10.1016/S0002-9440(10)64476-8 PG 6 WC Pathology SC Pathology GA 622TP UT WOS:000179663400005 PM 12466114 ER PT J AU Campbell, WH Anderson, WK Burckart, GJ Clark, AM DiGate, RJ Lee, VHL Rogers, ME Miller, KW AF Campbell, WH Anderson, WK Burckart, GJ Clark, AM DiGate, RJ Lee, VHL Rogers, ME Miller, KW TI Institutional and faculty roles and responsibilities in the emerging environment of university-wide interdisciplinary research structures: Report of the 2001-2002 Research and Graduate Affairs Committee SO AMERICAN JOURNAL OF PHARMACEUTICAL EDUCATION LA English DT Article C1 Univ N Carolina, Sch Pharm, Chapel Hill, NC 27514 USA. SUNY Buffalo, Sch Pharm, Buffalo, NY 14260 USA. Univ Pittsburgh, Sch Pharm, Pittsburgh, PA USA. Univ Mississippi, Sch Pharm, University, MS 38677 USA. Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. Univ So Calif, Sch Pharm, Los Angeles, CA USA. NIGMS, Bethesda, MD USA. Amer Assoc Coll Pharm, Alexandria, VA USA. RP Campbell, WH (reprint author), Univ N Carolina, Sch Pharm, Chapel Hill, NC 27514 USA. RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 NR 12 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC COLL PHARMACY PI ALEXANDRIA PA 1426 PRINCE STREET, ALEXANDRIA, VA 22314-2815 USA SN 0002-9459 J9 AM J PHARM EDUC JI Am. J. Pharm. Educ. PD WIN PY 2002 VL 66 SU S BP 28S EP 33S PG 6 WC Education, Scientific Disciplines; Pharmacology & Pharmacy SC Education & Educational Research; Pharmacology & Pharmacy GA 693HA UT WOS:000183710000007 ER PT J AU Liu, MT Rayport, S Jiang, Y Murphy, DL Gershon, MD AF Liu, MT Rayport, S Jiang, Y Murphy, DL Gershon, MD TI Expression and function of 5-HT3 receptors in the enteric neurons of mice lacking the serotonin transporter SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE serotonin receptors; small intestine; enteric nervous system; electrophysiology ID GUINEA-PIG INTESTINE; SPLICE VARIANTS; GASTROINTESTINAL-TRACT; MYENTERIC GANGLIA; AFFERENT-FIBERS; DEFICIENT MICE; RAT-BRAIN; CELL-LINE; IN-VITRO; 5-HYDROXYTRYPTAMINE AB The actions of enteric 5-HT are terminated by 5-HT transporter (SERT)-mediated uptake, and gastrointestinal motility is abnormal in SERT -/- mice. We tested the hypothesis that adaptive changes in enteric 5-HT3 receptors help SERT -/- mice survive despite inefficient 5-HT inactivation. Expression of mRNA encoding enteric 5-HT3A subunits was similar in SERT +/+ and -/- mice, but that of 5-HT3B subunits was fourfold less in SERT -/- mice. 5-HT3B mRNA was found, by in situ hybridization, in epithelial cells and enteric neurons. 5-HT evoked a fast inward current in myenteric neurons that was pharmacologically identified as 5-HT3 mediated. The EC50 of the 5-HT response was lower in SERT +/+ (18 muM) than in SERT -/- (36 muM) mice and desensitized rapidly in a greater proportion of SERT -/- neurons; however, peak amplitudes, steady-state current, and decay time constants were not different. Adaptive changes thus occur in the subunit composition of enteric 5-HT3 receptors of SERT -/- mice that are reflected in 5-HT3 receptor affinity and desensitization. C1 Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Liu, MT (reprint author), Columbia Univ Coll Phys & Surg, Dept Anat & Cell Biol, 630 W 168th St, New York, NY 10032 USA. FU NCRR NIH HHS [RR-10506, RR-13701]; NIDA NIH HHS [DA-00356]; NINDS NIH HHS [NS-12969] NR 71 TC 54 Z9 56 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 2002 VL 283 IS 6 BP G1398 EP G1411 DI 10.1152/ajpgi.00203.2002 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 615KM UT WOS:000179244400022 PM 12388212 ER PT J AU Qu, W Ikejima, K Zhong, Z Waalkes, MP Thurman, RG AF Qu, W Ikejima, K Zhong, Z Waalkes, MP Thurman, RG TI Glycine blocks the increase in intracellular free Ca2+ due to vasoactive mediators in hepatic parenchymal cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE intracellular calcium; prostaglandin E-2; strychnine ID GATED CHLORIDE CHANNEL; CYTOSOLIC-FREE CALCIUM; REPERFUSION INJURY; KUPFFER CELLS; AMINO-ACIDS; RAT-LIVER; STIMULATION; HEPATOCYTES; PROTECTION; RECEPTORS AB Recently, glycine has been shown to prevent liver injury after endotoxin treatment in vivo. We demonstrated that ethanol and endotoxin stimulated Kupffer cells to release PGE(2), which elevated oxygen consumption in parenchymal cells. Because glycine has been reported to protect renal tubular cells, isolated hepatocytes, and perfused livers against hypoxic injury, the purpose of this study was to determine whether glycine prevents increases in intracellular free Ca2+ concentration ([Ca2+](i)) in hepatic parenchymal cells by agonists released during stress, such as with PGE(2) and adrenergic hormones. Liver parenchymal cells isolated from female Sprague-Dawley rats were cultured for 4 h in DMEM/F12 medium, and [Ca2+](i) in individual cells was assessed fluorometrically using the fluorescent calcium indicator fura 2. PGE(2) caused a dose-dependent increase in [Ca2+](i) from basal values of 130 +/- 10 to maximal levels of 434 +/- 55 nM. EGTA partially prevented this increase, indicating that either extracellular calcium or agonist binding is Ca2+ dependent. 8-(Diethylamino)octyl 3,4,5-trimethoxybenzoate (TMB-8), an agent that prevents the release of Ca2+ from intracellular stores, also partially blocked the increase in [Ca2+](i) caused by PGE(2), suggesting that intracellular Ca2+ pools are involved. Together, these results are consistent with the hypothesis that both the intracellular and extracellular Ca2+ pools are involved in the increase in [Ca2+](i) caused by PGE(2). Interestingly, glycine, which activates anion (i.e., chloride) channels, blocked the increase in [Ca2+](i) due to PGE(2) in a dose-dependent manner. Low-dose strychnine, an antagonist of glycine-gated chloride channel in the central nervous system, partially reversed the inhibition by glycine. When extracellular Cl- was omitted, glycine was much less effective in preventing the increase in [Ca2+](i) due to PGE(2). Phenylephrine, an alpha(1)-type adrenergic receptor agonist, also increased [Ca2+](i), as expected, from 159 +/- 20 to 432 +/- 43 nM. Glycine also blocked the increase in [Ca2+](i) due to phenylephrine, and the effect was also reversed by low-dose strychnine. Together, these data indicate that glycine rapidly blocks the increase in [Ca2+](i) in hepatic parenchymal cells due to agonists released during stress, most likely by actions on a glycine-sensitive anion channel and that this may be a major aspect of glycine-induced hepatoprotection. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pharmacol, Hepatobiol & Toxicol Lab, Chapel Hill, NC 27599 USA. RP Qu, W (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, POB 12233,Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM qu@niehs.nih.gov FU NIAAA NIH HHS [AA-09156, AA-03624] NR 30 TC 23 Z9 28 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD DEC PY 2002 VL 283 IS 6 BP G1249 EP G1256 DI 10.1152/ajpgi.00197.2002 PG 8 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 615KM UT WOS:000179244400005 PM 12388211 ER PT J AU Elkjaer, ML Kwon, TH Wang, WD Nielsen, J Knepper, MA Frokiaer, J Nielsen, S AF Elkjaer, ML Kwon, TH Wang, WD Nielsen, J Knepper, MA Frokiaer, J Nielsen, S TI Altered expression of renal NHE3, TSC, BSC-1, and ENaC subunits in potassium-depleted rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE hypokalemia; sodium transport; kidney; urine concentration ID THICK ASCENDING LIMB; IMMUNOELECTRON MICROSCOPIC LOCALIZATION; NA-CL COTRANSPORTER; PROXIMAL TUBULE; BICARBONATE REABSORPTION; METABOLIC-ACIDOSIS; MOLECULAR-CLONING; INTRACELLULAR PH; NA+/H+ EXCHANGER; RABBIT KIDNEY AB The purpose of this study was to examine whether hypokalemia is associated with altered abundance of major renal Na(+) transporters that may contribute to the development of urinary concentrating defects. We examined the changes in the abundance of the type 3 Na(+)/H(+) exchanger (NHE3), Na(+)-K(+)-ATPase, the bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter (BSC-1), the thiazide-sensitive Na(+)-Cl(-) cotransporter (TSC), and epithelial sodium channel (ENaC) subunits in kidneys of hypokalemic rats. Semiquantitative immunoblotting revealed that the abundance of BSC-1 (57%) and TSC (46%) were profoundly decreased in the inner stripe of the outer medulla (ISOM) and cortex/outer stripe of the outer medulla (OSOM), respectively. These findings were confirmed by immunohistochemistry. Moreover, total kidney abundance of all ENaC subunits was significantly reduced in response to the hypokalemia: alpha-subunit (61%), beta-subunit (41%), and gamma-subunit (60%), and this was confirmed by immunohistochemistry. In contrast, the renal abundance of NHE3 in hypokalemic rats was dramatically increased in cortex/OSOM (736%) and ISOM (210%). Downregulation of BSC-1, TSC, and ENaC may contribute to the urinary concentrating defect, whereas upregulation of NHE3 may be compensatory to prevent urinary Na(+) loss and/or to maintain intracellular pH levels. C1 Aarhus Univ, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Dongguk Univ, Sch Med, Dept Physiol, Kyungju 780714, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Water & Salt Res Ctr, Bldg 233, DK-8000 Aarhus, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 50 TC 29 Z9 29 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2002 VL 283 IS 6 BP F1376 EP F1388 DI 10.1152/ajprenal.00186.2002 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 613AA UT WOS:000179106600020 PM 12388387 ER PT J AU Hu, P Meyers, S Liang, FX Deng, FM Kachar, B Zeidel, ML Sun, TT AF Hu, P Meyers, S Liang, FX Deng, FM Kachar, B Zeidel, ML Sun, TT TI Role of membrane proteins in permeability barrier function: uroplakin ablation elevates urothelial permeability SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE urothelium; uroplakin; permeability; vesicoureteral reflux; knockout ID MAMMALIAN URINARY-BLADDER; ASYMMETRIC UNIT MEMBRANE; PLASMA-MEMBRANE; APICAL MEMBRANE; EPITHELIUM; DIFFERENTIATION; VESICLES; PROTONS; SOLUTES; MARKERS AB Although water, small nonelectrolytes, and gases are freely permeable through most biological membranes, apical membranes of certain barrier epithelia exhibit extremely low permeabilities to these substances. The role of integral membrane proteins in this barrier function has been unclear. To study this problem, we have ablated the mouse gene encoding uroplakin III (UPIII), one of the major protein subunits in urothelial apical membranes, and measured the permeabilities of these membranes. Ablation of the UPIII gene greatly diminishes the amounts of uroplakins on the apical urothelial membrane (Hu P, Deng FM, Liang FX, Hu CM, Auerbach AB, Shapiro E, Wu XR, Kachar B, and Sun TT. J Cell Biol 151: 961-972, 2000). Our results indicate that normal mouse urothelium exhibits high transepithelial resistance and low urea and water permeabilities. The UPIII-deficient urothelium exhibits a normal transepithelial resistance (normal 2,024 +/- 122, knockout 2,322 +/- 114 Omega.cm(2); P > 0.5). However, the UPIII-deficient apical membrane has a significantly elevated water permeability (normal 0.91 +/- 0.06, knockout 1.83 +/- 0.14 cm/s x 10(-5); P < 0.05). The urea permeability of the UPIII-deficient membrane also increased, although to a lesser extent (normal 2.22 +/- 0.24, knockout 2.93 +/- 0.31 cm/s x 10(-6); P = 0.12). These results indicate that reduced targeting of uroplakins to the apical membrane does not significantly alter the tight junctional barrier but does double the water permeability. We provide the first demonstration that integral membrane proteins contribute to the apical membrane permeability barrier function of urothelium. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Physiol, Pittsburgh, PA 15213 USA. NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Pharmacol, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, Dept Urol, New York, NY 10016 USA. Natl Inst Deafness & Other Commun Disorders, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. RP Zeidel, ML (reprint author), Univ Pittsburgh, Sch Med, Dept Med, Rm 1218 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15213 USA. EM Zeidel@msx.dept-med.pitt.edu FU NIDDK NIH HHS [DK 3975, DK 43955, DK 48217, DK 52206, DK 57269] NR 37 TC 138 Z9 140 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2002 VL 283 IS 6 BP F1200 EP F1207 DI 10.1152/ajprenal.00043.2002 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 613AA UT WOS:000179106600004 PM 12388410 ER PT J AU Kwon, TH Nielsen, J Masilamani, S Hager, H Knepper, MA Frokiaer, J Nielsen, S AF Kwon, TH Nielsen, J Masilamani, S Hager, H Knepper, MA Frokiaer, J Nielsen, S TI Regulation of collecting duct AQP3 expression: response to mineralocorticoid SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE adrenalectomy; aquaporin; glucocorticoid; mineralocorticoid; vasopressin ID GLOMERULAR-FILTRATION RATE; NA-CL COTRANSPORTER; ADRENAL INSUFFICIENCY; WATER CHANNELS; ARGININE VASOPRESSIN; CONCENTRATING DEFECT; ALTERED EXPRESSION; MOLECULAR-CLONING; DEFICIENT RATS; DISTAL TUBULE AB Adrenocortical steroid hormones are importantly involved in the regulation of extracellular fluid volume. The present study was aimed at examining whether aldosterone and/or glucocorticoid regulates the abundance of aquaporin-3 (AQP3), -2, and -1 in rat kidney. In protocol 1, rats were adrenalectomized, followed by aldosterone replacement, dexamethasone replacement, or combined aldosterone and dexamethasone replacement (rats had free access to water but received a fixed amount of food). Protocol 2 was identical to protocol 1, except that all groups received fixed daily food and water intake. In both protocols 1 and 2, aldosterone deficiency was associated with increased fractional Na excretion and severe hyperkalemia. Semiquantitative immunoblotting revealed that aldosterone deficiency was associated with a dramatic downregulation of AQP3 abundance. Consistent with this, immunocytochemistry and immunoelectron microscopy revealed a marked decrease in AQP3 labeling in the basolateral plasma membranes of collecting duct principal cells. In contrast, AQP1 and AQP2 abundance and distribution were unchanged. Glucocorticoid deficiency revealed no changes in AQP3, -2, or -1 abundance. In protocol 3, Na restriction (to increase endogenous aldosterone levels) or exogenous aldosterone infusion in either normal rats or vasopressin-deficient Brattleboro rats was associated with a major increase in AQP3 abundance. In protocol 4, aldosterone levels were clamped by infusion of aldosterone, while Na intake was altered from a low to a high level. Under these circumstances, there were no changes in AQP3 or AQP2 abundance, although the level of the thiazide-sensitive Na-Cl cotransporter was decreased. In conclusion, the results uniformly demonstrate that aldosterone regulates AQP3 abundance independently of Na intake. In contrast, changes in glucocorticoid levels in these models do not influence AQP3 or AQP2 abundance. Therefore, in the collecting duct aldosterone may regulate, at least in part, AQP3 expression in addition to regulating Na and K transport. C1 Aarhus Univ, Water & Salt Res Ctr, Inst Anat, DK-8000 Aarhus C, Denmark. Dongguk Univ, Sch Med, Dept Physiol, Kyungju 780714, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Water & Salt Res Ctr, Inst Anat, Bldg 233, DK-8000 Aarhus C, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 51 TC 39 Z9 40 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2002 VL 283 IS 6 BP F1403 EP F1421 DI 10.1152/ajprenal.00059.2002 PG 19 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 613AA UT WOS:000179106600022 PM 12388415 ER PT J AU Wang, WD Li, CL Kwon, TH Knepper, MA Frokiaer, J Nielsen, S AF Wang, WD Li, CL Kwon, TH Knepper, MA Frokiaer, J Nielsen, S TI AQP3, p-AQP2, and AQP2 expression is reduced in polyuric rats with hypercalcemia: prevention by cAMP-PDE inhibitors SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE nephrogenic diabetes insipidus; urinary concentration mechanism; vasopressin ID NEPHROGENIC DIABETES-INSIPIDUS; URINARY CONCENTRATING ABILITY; WATER CHANNELS; COLLECTING DUCT; RENAL AQUAPORINS; PLASMA-MEMBRANE; REABSORPTION; MICE; COTRANSPORTER; PERMEABILITY AB The purpose of this study was to evaluate whether hypercalcemia is associated with downregulation of renal aquaporins (AQPs), including AQP1, AQP2, phosphorylated AQP2 (p-AQP2), AQP3, and AQP4, and if this is the case, to test whether cAMP-phosphodiesterase (PDE) inhibitor treatment can prevent AQP downregulation and prevent the development of polyuria. Vitamin D-induced hypercalcemia in rats was associated with increased urine output and reduced urine osmolality, consistent with previous findings (Levi M, Peterson L, and Berl T. Kidney Int 23: 489-497, 1983). Semiquantitative immunoblotting revealed a significant reduction in the abundance of inner medullary AQP2 (52 +/- 6% of control levels), consistent with previous studies, and of AQP2, which is phosphorylated at the PKA phosphorylation consensus site serine 256 (p-AQP2; 36 +/- 8%). Moreover, AQP3 abundance was also significantly decreased (45 +/- 7 and 61 +/- 6% of control levels in inner medulla and whole kidney, respectively). Consistent with this, immunohistochemistry demonstrated reduced AQP3 immunolabeling along the entire collecting duct. AQP4 expression was not reduced. Surprisingly, total kidney AQP1 abundance was also reduced (60 +/- 6%). AQP1 expression was reduced in the cortex and outer stripe of the outer medulla (48 +/- 7%; i.e., in proximal tubules). In contrast, AQP1 levels were not changed in the inner stripe of the outer medulla or in the inner medulla (i.e., descending thin limbs and vasa recta). Treatment with the cAMP-PDE inhibitors rolipram and milrinone in combination (inhibiting PDE IV and PDE III isoenzymes) at day 2 and onward completely prevented the hypercalcemia-induced downregulation of AQP2 and AQP3 (but not AQP1) and completely prevented the development of polyuria. In conclusion, AQP3, AQP2, and p-AQP2 are downregulated and are likely to play critical roles in the development of polyuria associated with vitamin D-induced hypercalcemia. Moreover, PDE inhibitor treatment significantly pre-vented the reduced expression of collecting duct AQPs and prevented the development of polyuria. C1 Aarhus Univ, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Dongguk Univ, Sch Med, Dept Physiol, Kyungji 780714, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Aarhus Univ, Water & Salt Res Ctr, Bldg 233, DK-8000 Aarhus C, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 38 TC 30 Z9 30 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD DEC PY 2002 VL 283 IS 6 BP F1313 EP F1325 DI 10.1152/ajprenal.00040.2002 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 613AA UT WOS:000179106600015 PM 12388409 ER PT J AU Selemon, LD Kleinman, JE Herman, MM Goldman-Rakic, PS AF Selemon, LD Kleinman, JE Herman, MM Goldman-Rakic, PS TI Smaller frontal gray matter volume in postmortem schizophrenic brains SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 7th International Congress on Schizophrenia Research CY APR 17-21, 1999 CL SANTA FE, NM ID FIRST-EPISODE SCHIZOPHRENIA; PREFRONTAL CORTEX; TEMPORAL-LOBE; REDUCTION; ABNORMALITIES; PATHOLOGY; DENSITY; REGIONS; NUMBER; HIPPOCAMPUS AB Objective: The prefrontal cortex exhibits prominent functional, biochemical, and anatomic abnormalities in schizophrenic patients. However, smaller than normal volume of the frontal lobe has not been found in previous postmortem studies of schizophrenic subjects, and magnetic resonance imaging (MRI) scans of schizophrenic subjects have not consistently revealed frontal volumetric deficits. The variability in MRI findings may be related partly to difficulty in defining the posterior border of the frontal lobe. in this study, precise measurements of frontal lobe volume from postmortem brains were derived by defining the posterior border according to the brain atlas of Talairach and Tournoux and by applying stereologic methods to estimate gray and white matter volumes. Method: Whole, or nearly whole, formalin-fixed left hemispheres from 14 schizophrenic and 19 normal comparison subjects were analyzed. Total cortical gray and white matter volumes, as well as frontal cortical gray and white matter volumes, were measured by using the Cavalieri method. Results: only frontal gray matter volume was significantly smaller in the schizophrenic subjects than in the comparison subjects (12% difference). The differences between groups in total gray and white matter volumes and frontal white matter volume (6%-8% smaller in the schizophrenic subjects than in the comparison subjects) did not reach statistical significance. Conclusions: The smaller frontal gray matter volume observed in schizophrenic brains suggests that pathology of the frontal lobe may be more severe than that of the three posterior lobes and may account for the prominence of prefrontal dysfunction associated with schizophrenia. C1 Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Selemon, LD (reprint author), Yale Univ, Sch Med, Dept Neurobiol, 333 Cedar St, New Haven, CT 06520 USA. EM ldselemon@aol.com FU NIMH NIH HHS [MH 44866, MH 59329] NR 48 TC 58 Z9 59 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2002 VL 159 IS 12 BP 1983 EP 1991 DI 10.1176/appi.ajp.159.12.1983 PG 9 WC Psychiatry SC Psychiatry GA 622YF UT WOS:000179675000007 PM 12450946 ER PT J AU Vythilingam, M Heim, C Newport, J Miller, AH Anderson, E Bronen, R Brummer, M Staib, L Vermetten, E Charney, DS Nemeroff, CB Bremner, JD AF Vythilingam, M Heim, C Newport, J Miller, AH Anderson, E Bronen, R Brummer, M Staib, L Vermetten, E Charney, DS Nemeroff, CB Bremner, JD TI Childhood trauma associated with smaller hippocampal volume in women with major depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CORTICOTROPIN-RELEASING HORMONE; GERIATRIC DEPRESSION; NONHUMAN-PRIMATES; COGNITIVE FUNCTION; ANXIETY DISORDERS; PLASMA-CORTISOL; TEMPORAL-LOBE; DENTATE GYRUS; SEXUAL ABUSE AB Objective: Smaller hippocampal volume has been reported only in some but not all studies of unipolar major depressive disorder. Severe stress early in life has also been associated with smaller hippocampal volume and with persistent changes in the hypothalamic-pituitary-adrenal axis. However, prior hippocampal morphometric studies in depressed patients have neither reported nor controlled for a history of early childhood trauma. In this study, the volumes of the hippocampus and of control brain regions were measured in depressed women with and without childhood abuse and in healthy nonabused comparison subjects. Method: Study participants were 32 women with current unipolar major depressive disorder-21 with a history of prepubertal physical and/or sexual abuse and 11 without a history of prepubertal abuse-and 14 healthy nonabused female volunteers. The volumes of the whole hippocampus, temporal lobe, and whole brain were measured on coronal MRI scans by a single rater who was blind to the subjects' diagnoses. Results: The depressed subjects with childhood abuse had an 18% smaller mean left hippocampal volume than the nonabused depressed subjects and a 15% smaller mean left hippocampal volume than the healthy subjects. Right hippocampal volume was similar across the three groups. The right and left hippocampal volumes in the depressed women without abuse were similar to those in the healthy subjects. Conclusions: A smaller hippocampal volume in adult women with major depressive disorder was observed exclusively in those who had a history of severe and prolonged physical and/or sexual abuse in childhood. An unreported history of childhood abuse in depressed subjects could in part explain the inconsistencies in hippocampal volume findings in prior studies in major depressive disorder. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Yale Univ, Sch Med, Dept Radiol, New Haven, CT 06520 USA. Univ Utrecht, Med Ctr, Dept Psychiat, Utrecht, Netherlands. RP Vythilingam, M (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K North Dr,Room 111,MSC 2670, Bethesda, MD 20892 USA. RI Heim, Christine/A-1183-2009; Bremner, James/B-1632-2013; OI Vermetten, Eric/0000-0003-0579-4404; Staib, Lawrence/0000-0002-9516-5136 FU NIMH NIH HHS [P50 MH058922, MH 42088, MH 51761, MH 56120, MH 58922, R01 MH042088, R01 MH056120, R01 MH056120-12] NR 70 TC 399 Z9 410 U1 13 U2 37 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2002 VL 159 IS 12 BP 2072 EP 2080 DI 10.1176/appi.ajp.159.12.2072 PG 9 WC Psychiatry SC Psychiatry GA 622YF UT WOS:000179675000020 PM 12450959 ER PT J AU Fahlke, C Garpenstrand, H Oreland, L Suomi, SJ Higley, JD AF Fahlke, C Garpenstrand, H Oreland, L Suomi, SJ Higley, JD TI Platelet monoamine oxidase activity in a nonhuman primate model of type 2 excessive alcohol consumption SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID PERSONALITY; SEROTONIN; BEHAVIOR AB Objective: Low platelet monoamine oxidase (MAO) activity is associated with "type 2 alcoholism." MAO activity is also affected by cigarette smoking. Since most alcoholics are smokers, it is difficult to evaluate the possible effect of platelet MAO activity on alcoholism independently of the effects of smoking. The authors investigated the relationship between platelet MAO activity and excessive alcohol consumption in rhesus macaques. Method: Platelet MAO activity and CSF metabolite concentrations were measured. The authors also investigated level of voluntary alcohol intake and social dominance rank. Results: Subjects with low platelet MAO activity consumed alcohol to excess, had low CSF 5-hydroxyindoleacetic acid concentrations, and were less competent socially. Conclusions: These findings show that nonhuman primates that exhibit type 2-like alcohol features display low platelet MAO activity and support the notion that platelet MAO activity is a biologic marker for central serotonergic activity. The results also challenge the hypothesis that low platelet MAO activity in type 2 alcoholism is simply an artifact of smoking. C1 Univ Gothenburg, Dept Psychol, SE-40530 Gothenburg, Sweden. NIH, Labs Comparat Ethol, Poolesville, MD USA. NIH, Clin Studies Primate Unit, Poolesville, MD USA. Uppsala Univ, Dept Neurosci, Pharmacol Unit, Uppsala, Sweden. RP Fahlke, C (reprint author), Univ Gothenburg, Dept Psychol, POB 500, SE-40530 Gothenburg, Sweden. NR 10 TC 36 Z9 36 U1 0 U2 0 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD DEC PY 2002 VL 159 IS 12 BP 2107 EP 2109 DI 10.1176/appi.ajp.159.12.2107 PG 3 WC Psychiatry SC Psychiatry GA 622YF UT WOS:000179675000028 PM 12450967 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI 100 years of the Pan American Health Organization SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 9 TC 8 Z9 8 U1 1 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2002 VL 92 IS 12 BP 1888 EP 1889 DI 10.2105/AJPH.92.12.1888 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 619BL UT WOS:000179453400008 PM 12453801 ER PT J AU Fee, E Brown, TM Lazarus, J Theerman, P AF Fee, E Brown, TM Lazarus, J Theerman, P TI Domestic violence - Medieval and modern SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article C1 NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20892 USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. NR 7 TC 0 Z9 1 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD DEC PY 2002 VL 92 IS 12 BP 1908 EP 1908 DI 10.2105/AJPH.92.12.1908 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 619BL UT WOS:000179453400013 PM 12453806 ER PT J AU Eichacker, PQ Gerstenberger, EP Banks, SM Cui, XZ Natanson, C AF Eichacker, PQ Gerstenberger, EP Banks, SM Cui, XZ Natanson, C TI Meta-analysis of acute lung injury and acute respiratory distress syndrome trials testing low tidal volumes SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID MECHANICAL VENTILATION; PERMISSIVE HYPERCAPNIA; AIRWAY PRESSURES; MORTALITY; STRATEGY; ARDS C1 NCI, Ctr Clin, Crit Care Med Dept, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NCI, Ctr Clin, Crit Care Med Dept, 10 Ctr Dr,Bldg 10,Room 7D43, Bethesda, MD 20892 USA. NR 25 TC 237 Z9 254 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD DEC 1 PY 2002 VL 166 IS 11 BP 1510 EP 1514 DI 10.1164/rrcm.200208-956OC PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 621LT UT WOS:000179590900017 PM 12406836 ER PT J AU Pawliczak, R Huang, XL Nanavaty, UB Lawrence, M Madara, P Shelhamer, JH AF Pawliczak, R Huang, XL Nanavaty, UB Lawrence, M Madara, P Shelhamer, JH TI Oxidative stress induces arachidonate release from human lung cells through the epithelial growth factor receptor pathway SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID CYTOSOLIC PHOSPHOLIPASE A(2); ACTIVATED PROTEIN-KINASE; TUMOR-NECROSIS-FACTOR; RHEUMATOID SYNOVIAL FIBROBLASTS; HYDROGEN-PEROXIDE; ACID RELEASE; ENDOTHELIAL-CELLS; GENE-EXPRESSION; PHOSPHORYLATION; INJURY AB Oxidative stress is thought to be a factor influencing many inflammatory responses, including arachidonic acid (AA) release. We have studied the effect of hydrogen peroxide on AA and prostaglandin E-2 release, cytosolic phospholipase (cPLA(2)) steady-state mRNA, cPLA(2) protein levels, cPLA(2) enzyme activity, and cPLA(2) phosphorylation in a human lung epithelial cell line: A549 cells. Hydrogen peroxide caused a dose-dependent increase of A23187-stimulated AA and prostaglandin E-2 release, with a maximum effect at 1 h. This effect is associated with a maximum specific cPLA(2) activity at 1 h, and with a significant increase in cPLA(2) Serine 505 phosphorylation. All these effects were abolished, in a dose-related manner, by the epithelial growth factor receptor kinase inhibitor, AG 1478. To further investigate the pathway leading to the increase cPLA(2) phosphorylation, we used cells transfected with a Ras dominant negative vector and mitogen-activated protein kinase/extracellular signal-regulated kinase (MEK) and p38 kinase inhibitors. Cells transfected with the Ras dominant negative vector exhibited diminished hydrogen peroxide-induced AA release and cPLA(2) phosphorylation as compared with cells transfected with the Ras expression vector. Both MEK and p38 kinase inhibitors inhibited the hydrogen peroxide effect on AA release and specific cPLA(2) activity. Finally, cells stably transfected with an antisense cPLA(2) vector exhibited diminished A23187-stimulated AA release in response to hydrogen peroxide as compared with cells stably transfected with empty expression vector. Collectively, these data show that hydrogen peroxide increases cPLA(2) activity through its phosphorylation utilizing an epithelial growth factor/Ras/extracellular signal-regulated kinase and p38 pathway. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. Med Univ Lodz, Dept Allergy & Clin Immunol, Lodz, Poland. RP Shelhamer, JH (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bldg 10,Rm D43,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Pawliczak, Rafal/S-9649-2016; OI Pawliczak, Rafal/0000-0001-6784-453X NR 35 TC 37 Z9 37 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2002 VL 27 IS 6 BP 722 EP 731 DI 10.1165/rcmb.2002-0033OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 625AU UT WOS:000179795200011 PM 12444032 ER PT J AU Rice, AB Ingram, JL Bonner, JC AF Rice, AB Ingram, JL Bonner, JC TI p38 Mitogen-activated protein kinase regulates growth factor-induced mitogenesis of rat pulmonary myofibroblasts SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID CYCLIN D1 EXPRESSION; MAP KINASE; RECEPTOR EXPRESSION; VANADIUM PENTOXIDE; LUNG FIBROBLASTS; FIBROSIS; INHIBITION; PATHWAY; CELLS; PROLIFERATION AB Myofibroblast proliferation is a central feature of pulmonary fibrogenesis. Several growth factors, including platelet-derived growth factor (PDGF) and epidermal growth factor (EGF), stimulate myofibroblast growth by activating extracellular signal regulated kinases 1 and 2 (ERK1/2). In this report, we demonstrate that PDGF-BB and EGF also activate the p38 mitogen-activated protein (MAP) kinase. Inhibition of p38 activity with the pyridinylimidazole compound SB203580 enhanced both PDGF-BB and EGF-stimulated DNA synthesis in rat lung myofibroblasts. ERK1/2 phosphorylation in response to either PDGF-BB or EGF treatment was significantly increased by pretreatment of cells with SB203580. We also demonstrated that ERK1/2-induced phosphorylation of PHAS-1 substrate was enhanced by inhibition of p38 MAP kinase with SB203580. However, SB203580 did not significantly increase growth factor-induced activation of MEK, the upstream kinase that phosphorylates ERK1/2. p38 MAP kinase was co-immunoprecipitated with ERK1/2 following growth factor stimulation. Collectively, these data demonstrate that p38 MAP kinase activation negatively regulates PDGF- and EGF-mediated growth responses by directly interacting with ERK1/2 and suppressing its phosphorylation. C1 NIEHS, Airway Inflammat Grp, Pulm Pathobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Bonner, JC (reprint author), NIEHS, Airway Inflammat Grp, Pulm Pathobiol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 31 TC 23 Z9 24 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD DEC PY 2002 VL 27 IS 6 BP 759 EP 765 DI 10.1165/rcmb.2002-0070OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 625AU UT WOS:000179795200016 PM 12444037 ER PT J AU Klabunde, CN Jones, E Brown, ML Davis, WW AF Klabunde, CN Jones, E Brown, ML Davis, WW TI Colorectal cancer screening with double-contrast barium enema: A national survey of diagnostic radiologists SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID COST-EFFECTIVENESS; HOSPITAL VOLUME; SURGEON VOLUME; COLONOSCOPY; RECOMMENDATIONS; SURVEILLANCE; GUIDELINES; POLYPS; ISSUES; RISK AB OBJECTIVE. This article describes diagnostic radiologists' colorectal cancer screening activities and beliefs about screening effectiveness and future capacity for screening with double-contrast barium enema, and compares radiologists' opinions about colorectal cancer screening with those of primary care physicians. MATERIALS AND METHODS. We surveyed a nationally representative sample of diagnostic radiologists. Of 381 eligible radiologists, 312 (82%) responded. Descriptive statistics and chi-square tests were used to assess radiologists' opinions about double-contrast barium enema volume and capacity and to compare radiologists' beliefs about colorectal cancer screening with those of primary care physicians. Logistic regression was used to identify characteristics of radiologists who receive referrals for or perform a higher volume of screening double-contrast barium enema and of those who expect the volume of double-contrast barium enemas to increase. RESULTS. Seventy-five percent of radiologists said that double-contrast barium enema is a "very effective" colorectal cancer screening procedure compared with 33% of primary care physicians. Although 86% of radiologists reported performing one or more screening double-contrast barium enema procedures during a typical month, only 27% indicated that they did so I I or more times. Fifteen percent of radiologists said that their double-contrast barium enema volume had increased over the past 3 years, and 50% expect an increase over the next 3 years. Only 8% said that the capacity of facilities and personnel to meet the demand for double-contrast barium enemas in their geographic area of practice is inadequate. Geographic region and belief in double-contrast barium enema efficacy were predictors of double-contrast barium enema volume and referrals. CONCLUSION. Most diagnostic radiologists perform colorectal cancer. screening with double-contrast barium enema, but procedure volumes are modest. Because primary care physicians view double-contrast barium enema less positively than do radiologists, radiologists' expectations for an increased volume of double-contrast barium enemas over the next few years may not be realized. C1 NCI, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NCI, Stat Res & Applicat Branch, Surveillance Res Program, Bethesda, MD 20892 USA. RP Klabunde, CN (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Execut Plaza N,Rm 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. FU NCI NIH HHS [N01-PC-85169] NR 37 TC 15 Z9 16 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD DEC PY 2002 VL 179 IS 6 BP 1419 EP 1427 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 618FK UT WOS:000179407900009 PM 12438029 ER PT J AU Pavlovich, CP Walther, MA Eyler, RA Hewitt, SM Zbar, B Linehan, WM Merino, MJ AF Pavlovich, CP Walther, MA Eyler, RA Hewitt, SM Zbar, B Linehan, WM Merino, MJ TI Renal tumors in the Birt-Hogg-Dube syndrome SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Birt-Hogg-Dube syndrome; kidney cancer; chromophobe renal cell carcinoma; clear cell (conventional) renal cell carcinoma oncocytosis ID HIPPEL-LINDAU-DISEASE; CELL-CARCINOMA; SUPPRESSOR GENE; TUBEROUS SCLEROSIS; SOMATIC MUTATIONS; INTERCALATED CELLS; KIDNEY NEOPLASIA; ALLELE LOSS; CLASSIFICATION; IDENTIFICATION AB Birt-Hogg-Dube (BHD) syndrome is an autosomal dominant, genodermatosis characterized by the development of small dome-shaped papules on the face, neck, and upper trunk (fibrofolliculomas). In addition to these benign hair follicle tumors, BHD confers an increased risk of renal neoplasia and spontaneous pneumothorax. To date, there has been no systematic pathologic analysis of the renal tumors associated with this syndrome. We reviewed 130 solid renal tumors resected from 30 patients with BHD in 19 different families. Preoperative computed tomography scans demonstrated a mean of 5.3 tumors per patient (range 1-28 tumors), the largest tumors avera -ing 5.7 cm in diameter ( +/-3.4 cm, range 1.2-15 cm). Multiple and bilateral tumors were noted at an early age (mean 50.7 years). The resected tumors consisted predominantly of chromophobe renal cell carcinomas (44 of 130, 34%) or of hybrid oncocytic neoplasms that had areas reminiscent of chromophobe renal cell carcinoma and oncocytoma (65 of 130, 50%). Twelve clear cell (conventional) renal carcinomas (12 of 130, 9%) were diagnosed in nine patients. These tumors were on average larger (4.7 +/- 4.2 cm) than the chromophobe (3.0 +/- 2.5 cm) and hybrid tumors (2.2 +/- 2.4 cm). Microscopic oncocytosis was found in the renal parenchyma of most patients, including the parenchyma of five patients with evidence of clear cell renal cell carcinoma. Our findings suggest that microscopic oncocytic lesions may be precursors of hybrid oncocytic tumors, chromophobe renal cell carcinomas, and perhaps clear cell renal cell carcinomas in patients with BHD syndrome. Recognition by the pathologist of the unusual renal tumors associated with BHD may assist in the clinical diagnosis of the syndrome. C1 NCI, Ctr Canc Res, Pathol Lab, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Surg Pathol Sect, Urol Oncol Branch,Lab Immunnibiol, Bethesda, MD 20892 USA. RP Merino, MJ (reprint author), NCI, Ctr Canc Res, Pathol Lab, Bldg 10,Rm 2N212, Bethesda, MD 20892 USA. OI Hewitt, Stephen/0000-0001-8283-1788 NR 39 TC 264 Z9 272 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD DEC PY 2002 VL 26 IS 12 BP 1542 EP 1552 DI 10.1097/00000478-200212000-00002 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 621LP UT WOS:000179590600002 PM 12459621 ER PT J AU McKenzie, FE Baird, JK Beier, JC Lal, AA Bossert, WH AF McKenzie, FE Baird, JK Beier, JC Lal, AA Bossert, WH TI A biologic basis for integrated malaria control SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; PARASITES; MODELS AB In a series of models of Plasmodium falciparum dynamics, spontaneous local extinctions of the parasite sometimes occurred under steady, perennial-transmission conditions. These extinctions occurred only with extremely low mosquito densities or when the parameter describing the duration of human infection-blocking immunity was at its maximum value, and, simultaneously, those describing vector survivorship and the duration of human infectivity were at their minimum values. The range and frequency of extinctions increased with seasonal transmission, and decreased with the emergence of recombinant genotypes. Here we extend the immunity parameter up to levels that would describe a successful vaccine, and examine the combined influences of seasonality, genotype cross-reactivity, meiotic recombination, and human population turnover on parasite persistence. As Ross did 90 years ago, we conclude that malaria control programs that encompass several methods and targets of intervention are the most likely to succeed. Success is more likely if programs are cognizant of local circumstances of transmission, and, within that context, aim to reduce vector survivorship and human infectivity as well as augment human immunity. C1 Fogarty Int Ctr, NIH, Bethesda, MD 20892 USA. Tulane Univ, Dept Trop Med, New Orleans, LA 70112 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Parasit Dis, Atlanta, GA USA. Harvard Univ, Cambridge, MA 02138 USA. RP McKenzie, FE (reprint author), Fogarty Int Ctr, NIH, Room 306,Bldg 16, Bethesda, MD 20892 USA. FU FIC NIH HHS [D43 TW001142, D43 TW-01142]; Intramural NIH HHS [Z99 TW999999]; NIAID NIH HHS [U19 AI-45511, U19 AI045511] NR 19 TC 24 Z9 24 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2002 VL 67 IS 6 BP 571 EP 577 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 628QJ UT WOS:000180007500004 PM 12518846 ER PT J AU Bryan, JP Iqbal, M Tsarev, S Malik, IA Duncan, JF Ahmed, A Khan, A Khan, A Rafiqui, AR Purcell, RH Legters, LJ AF Bryan, JP Iqbal, M Tsarev, S Malik, IA Duncan, JF Ahmed, A Khan, A Khan, A Rafiqui, AR Purcell, RH Legters, LJ TI Epidemic of hepatitis E in a military unit in Abbottabad, Pakistan SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID E VIRUS-INFECTION; ENTERICALLY-TRANSMITTED HEPATITIS; WATER-BORNE HEPATITIS; NON-B HEPATITIS; NON-A; ANTIBODY; OUTBREAK; TRANSMISSION; INDIA; ASSOCIATION AB An outbreak of hepatitis caused by hepatitis E virus (HEV) in Abbottabad, Pakistan was traced to fecal contamination of a water system. Of 109 men hospitalized with hepatitis, 104 (95%) had serologic evidence of acute hepatitis E (IgM antibody to HEV [anti-HEV]), three (3%) probably had acute hepatitis E (high titers of IgG anti-HEV without IgM), and two had acute hepatitis A. Among a subset of 44 men with acute hepatitis E from whom three serum specimens were obtained over a four-month period, the anti-HEV IgG geometric mean titers (GMTs) decreased from 1 519 during the outbreak to 657 at four months. The IgM anti-HEV was detected in 40 (91%) of 44 sera obtained at admission (GMT = 533 during acute disease). but in only six (14%) four months later. The prevalence of anti-HEV in this population before the outbreak was estimated to e 30%. The presence of IgG anti-HEV appeared to protect against clinical hepatitis or development of serologic evidence of new infection with HEV. This is the second major epidemic of hepatitis E in the Pakistani military confirmed by an anti-HEV enzyme-linked immunosorbent assay (ELISA). Evidence that pre-existing antibody as measured by this ELISA protects against disease is important for assessment of vaccine development. C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. Pakistan US Lab Seroepidemiol, Rawalpindi, Pakistan. NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Bryan, JP (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 39 TC 34 Z9 37 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2002 VL 67 IS 6 BP 662 EP 668 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 628QJ UT WOS:000180007500017 PM 12518859 ER PT J AU Siqueland, L Crits-Christoph, P Gallop, B Gastfriend, D Lis, J Frank, A Griffin, M Blaine, J Luborsky, L AF Siqueland, L Crits-Christoph, P Gallop, B Gastfriend, D Lis, J Frank, A Griffin, M Blaine, J Luborsky, L TI Who starts treatment: Engagement in the NIDA Collaborative Cocaine Treatment Study SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT Conference on College of Problems in Drug Dependence CY JUN 14, 1998 CL SCOTTSDALE, ARIZONA ID PSYCHOSOCIAL TREATMENTS; NATIONAL-INSTITUTE; DEPENDENCE; RECRUITMENT; PERFORMANCE; ATTRITION; RETENTION; ABUSERS; DROPOUT; TRIALS AB This study addressed the role of demographic variables, severity of drug dependence, and drug-related problems in facilitating or impeding engagement into a research treatment. Patients were tracked through various stages of entry for the research treatment: phone screening, intake, and randomization to treatment. Results suggested that certain demographic factors put patients more at risk for dropping out at intake and randomization. African-American and unemployed patients were less likely to stay in treatment at both stages, with largest differences at intake. Younger patients were less likely to complete both phases, with bigger differences noted at randomization. Patients with more days of cocaine use and patients referred from advertisements were less likely to keep their intake appointments. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. McLean Hosp, Belmont, MA 02178 USA. NIDA, Treatment Res Branch, Bethesda, MD 20892 USA. RP Siqueland, L (reprint author), Univ Penn, Sch Med, 3535 Market St,6th Fl, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [U01-DA07673, U01-DA07085, U01-DA07090, R01 DA012249, U01-DA07663, U01-DA07693, U18 DA007090, K05-DA00168, K02-DA 00326]; NIMH NIH HHS [K02-MH00756, P30-MH-45178] NR 32 TC 13 Z9 13 U1 3 U2 3 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 2002 VL 11 IS 1 BP 10 EP 23 DI 10.1080/10550490252801602 PG 14 WC Substance Abuse SC Substance Abuse GA 524LQ UT WOS:000174015200002 PM 11876580 ER PT J AU Siqueland, L Crits-Christoph, P Gallop, R Barber, JP Griffin, ML Thase, ME Daley, D Frank, A Gastfriend, DR Blaine, J Connolly, MB Gladis, M AF Siqueland, L Crits-Christoph, P Gallop, R Barber, JP Griffin, ML Thase, ME Daley, D Frank, A Gastfriend, DR Blaine, J Connolly, MB Gladis, M TI Retention in psychosocial treatment of cocaine dependence: Predictors and impact on outcome SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SUBSTANCE-ABUSE TREATMENT; CLINICAL-TRIALS; EARLY ATTRITION; PSYCHOTHERAPY; ABSTINENCE; PARTICIPATION; SEVERITY AB This report describes retention in treatment in the National Institute on Drug Abuse Collaborative Cocaine Treatment Study (CCTS), a multi-site trial of four psychosocial treatments for 487 cocaine dependent patients. Younger, African-American, and unemployed patients were retained in treatment for fewer days than their counterparts. African-American patients who lived with a partner were retained in treatment for less time than if they lived alone. Higher psychiatric severity kept men in treatment longer but put women at risk for dropping out sooner. Patients who completed the full treatment used drugs less often than patients who dropped out, but outcome did not differ at each month. Patients in the drug counseling condition stayed in treatment for fewer days than patients in psychotherapy, but they were more likely to be abstinent after dropout. Patients with higher psychiatric severity were more at risk continuing to use drugs after dropout. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. McLean Hosp, Belmont, MA 02178 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NIDA, Bethesda, MD 20892 USA. RP Siqueland, L (reprint author), Univ Penn, Sch Med, 3535 Market St,6th Fl, Philadelphia, PA 19104 USA. FU NIDA NIH HHS [U01-DA07663, K05-DA00168, R01 DA012249, U01-DA07085, U01-DA07090, U01-DA07673, U01-DA07693, U18 DA007090, K02-DA 00326]; NIMH NIH HHS [K02-MH00756, P30-MH-45178] NR 43 TC 47 Z9 47 U1 4 U2 6 PU BRUNNER-ROUTLEDGE PI PHILADELPHIA PA 325 CHESTNUT ST, 8TH FL, PHILADELPHIA, PA 19106 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD WIN PY 2002 VL 11 IS 1 BP 24 EP 40 DI 10.1080/10550490252801611 PG 17 WC Substance Abuse SC Substance Abuse GA 524LQ UT WOS:000174015200003 PM 11876581 ER PT J AU Kumon, Y Hosokawa, T Suehiro, T Ikeda, Y Sipe, JD Hashimoto, K AF Kumon, Y Hosokawa, T Suehiro, T Ikeda, Y Sipe, JD Hashimoto, K TI Acute-phase, but not constitutive serum amyloid A (SAA) is chemotactic for cultured human aortic smooth muscle cells SO AMYLOID-JOURNAL OF PROTEIN FOLDING DISORDERS LA English DT Article DE atherosclerosis; inflammation; cytokine; migration; chemotaxis; chemoattractant ID GENE-EXPRESSION; CHOLESTEROL; INDUCTION; MIGRATION; ADHESION AB The human serum amyloid A (SAA) protein family is subclassfied as acute phase SAA (A-SAA), which comprises the SAA I and SAA2 allelic variants, and constitutive SAA (C-SAA), which is the SAA 4 isoform. Extrahepatic production of A-SAA occurs in many organs and tissues of the body, including smooth muscle cells (SMC) of the aorta. A-SAA has been shown to act locally as a chemoattractant for neutrophils, monocytes and lymphocytes via the N-formyl peptide receptor-like (fPRL1). In order to gain further understanding of the physiological significance of local production of A-SAA by SMC, the effect of exogenous ASAA on the in vitro migration of human aortic SMC was investigated. Increased SMC migration in the presence of A-SAA was detectable after six hours and continued to increase up to 24 hours after incubation. The increased migration was dose-dependent over the concentration range 10 to 100 mug/ml The mode of A-SAA stimulated SMC migration was by chemotaxis not chemokinesis. Exogenous constitutive SAA (C-SAA) did not affect SMC migration. Stimulation of SMC migration by A-SAA was inhibited by both polyclonal and monoclonal antibodies to human SAA1 and also by the inhibitors of fPRL1 signaling, wortmannin, bisindolylmaleimide and pertussis toxin. The results herein indicate that A-SAA, but not C-SAA, may serve as an autocrine factor to influence SMC migration in situations of aortic tissue injury and inflammation. C1 Kochi Med Sch, Dept Internal Med 2, Kochi 7838505, Japan. NIH, Musculoskeletal & Dent Sci IRG, Ctr Sci Review, Bethesda, MD 20892 USA. RP Kumon, Y (reprint author), Kochi Med Sch, Dept Internal Med 2, Kohasu Okoh Cho, Kochi 7838505, Japan. NR 17 TC 21 Z9 21 U1 1 U2 1 PU PARTHENON PUBLISHING GROUP PI LANCASTER PA RICHMOND HOUSE, WHITE CROSS, SOUTH ROAD, LANCASTER LA1 4XQ, ENGLAND SN 1350-6129 J9 AMYLOID JI Amyloid-J. Protein Fold. Disord. PD DEC PY 2002 VL 9 IS 4 BP 237 EP 241 DI 10.3109/13506120209114099 PG 5 WC Biochemistry & Molecular Biology; Medicine, General & Internal; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; General & Internal Medicine; Research & Experimental Medicine GA 635QC UT WOS:000180409500003 PM 12557751 ER PT J AU Hess, S van Beek, J Pannell, LK AF Hess, S van Beek, J Pannell, LK TI Acid hydrolysis of silk fibroins and determination of the enrichment of isotopically labeled amino acids using precolumn derivatization and high-performance liquid chromatography-electrospray ionization-mass spectrometry SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE Marfey's reagent; hydrolysis; amino acid; isotope natural products; liquid chromatography; electrospray-mass spectrometry ID SAMIA-CYNTHIA-RICINI; BOMBYX-MORI; SPIDER SILK; MECHANICAL-PROPERTIES; PROTEIN; NMR; SEQUENCE; DESIGN; MODEL; GENE AB Silk fibroins from moth larvae and spiders are composed of highly repetitive Ala- and Gly-rich blocks that determine their structure, properties, and function. To investigate the metabolic integration of isotopically labeled amino acids in the excreted silk, the enrichment of ingested tracers was determined after acid hydrolysis of the fibroins. Thus, spiders and moth larvae were fed with stable isotope tracers such as [1-C-13]Ala or [1-C-13]Gly and silked. After hydrolysis of the silk proteins, the corresponding amino acids were derivatized with Nalpha-(2,4-dinitro-5-fluorophenyl)-L-alaninamide (Marfey's reagent) and separated by liquid chromatography. The isotopical enrichment of the amino acids was determined by online electrospray mass spectrometry and calculated by newly developed software. Depending on the feeding protocol, enrichments of up to 58% in Gly and 31% in Ala were found in the investigated silks. The highly enriched silk fibroins are suitable for further structural investigation such as solid-state nuclear magnetic resonance. Published by Elsevier Science (USA). C1 NIDDKD, Struct Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA. Swiss Fed Inst Technol, CH-8093 Zurich, Switzerland. RP Hess, S (reprint author), NIDDKD, Struct Mass Spectrometry Facil, NIH, Bldg 8,Rm B2A27, Bethesda, MD 20892 USA. RI Hess, Sonja/K-4842-2013 OI Hess, Sonja/0000-0002-5904-9816 NR 33 TC 23 Z9 24 U1 3 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD DEC 1 PY 2002 VL 311 IS 1 BP 19 EP 26 AR PII S0003-2697(02)00402-5 DI 10.1016/S0003-2697(02)00402-5 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 625PH UT WOS:000179824500003 PM 12441148 ER PT J AU Shahabi, L Powell, LH Musick, MA Pargament, KI Thoresen, CE Williams, D Underwood, L Ory, MA AF Shahabi, L Powell, LH Musick, MA Pargament, KI Thoresen, CE Williams, D Underwood, L Ory, MA TI Correlates of self-perceptions of spirituality in American adults SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID RATED HEALTH; DISEASE; MORTALITY; RELIGION; RISK AB To advance knowledge in the study, of spirituality and physical health, we examined sociodemographic, behavioral, and attitudinal correlates of self-perceptions of spirituality. Participants were a nationally representative sample of 7,422 adult respondents to the 1998 General Social Survey. The), were asked, among other things, to rate themselves on the depth of their spirituality and the depth of their religiousness. Results indicated that, after adjustment for religiousness, self-perceptions of spirituality were positively correlated with beingfemale (r = .07, p < .01), having a higher education (r =. 12, p < .001), and having no religion (r =. 10, p < .001) and inversely correlated with age (r = -.06, p < .05) and being Catholic (r = -.08, p < .01). After adjustment for these sociodeinographic factors, self-perceptions of spirituality were associated with high levels of religious or spiritual activities (range in cot-relations = .12-38, all p < .001), low cynical mistrust, and low political conservatism (both r = -.08, p < .01). The population was divided into 4 groups based on their self-perceptions of degree of spirituality and degree of religiousness. The spiritual and religious group had a higher frequency of attending services, praying, meditating, reading the Bible, and daily spiritual experience than any of the other 3 groups (all differences p < .05) and had less distress and less mistrust than the religious-only group (p < .05 for both). However, they were also more intolerant than either of the nonreligious groups (p < .05 for both) and similar on intolerance to the religious-only group. We conclude that sociodemographic factors could confound any observed association between spirituality and health and should be controlled. Moreover, individuals who perceive themselves to be both spiritual and religious may be at particularly low risk for morbidity and mortality based on their good psychological status and ongoing restorative activities. C1 Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. Univ Texas, Austin, TX 78712 USA. Bowling Green State Univ, Bowling Green, OH 43403 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Michigan, Ann Arbor, MI 48109 USA. NIA, Bethesda, MD 20892 USA. RP Powell, LH (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Suite 470,1700 W Van buren, Chicago, IL 60612 USA. FU NICHD NIH HHS [R24 HD050959-07, R24 HD050959-06] NR 25 TC 54 Z9 55 U1 2 U2 9 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD WIN PY 2002 VL 24 IS 1 BP 59 EP 68 DI 10.1207/S15324796ABM2401_07 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 543NM UT WOS:000175108100007 PM 12008795 ER PT J AU Forbes, MS Ghribi, O Herman, MM Savory, J AF Forbes, MS Ghribi, O Herman, MM Savory, J TI Aluminum-induced dendritic pathology revisited: Cytochemical and electron microscopic studies of rabbit cortical pyramidal neurons SO ANNALS OF CLINICAL AND LABORATORY SCIENCE LA English DT Article DE Alzheimer's disease; aluminum neurotoxicity; neurofilamentous arrays, aluminum maltolate ID EXPERIMENTAL NEUROFIBRILLARY DEGENERATION; ALZHEIMERS-DISEASE; NEUROFILAMENT-PROTEIN; PHOSPHORYLATION; APOPTOSIS; TANGLES; BRAIN; PERIKARYA; LESIONS; MALTOL AB Intracisternal administration of aluminum maltolate induces biochemical and histological changes ill the rabbit brain. The primary histological response to this aluminum intoxication is the appearance within many neuronal somata and dendrites of intensely argyrophilic masses of fibrillar material. Ultrastructural examination Of these bodies in both conventionally-prepared and silver-stained sections shows them to be composed of neurofilaments. For this reason, we have elected to call these argyrophilic masses "neurofilamentous arrays (NFAs)." At their zenith, NFAs in cortical pyramidal neurons comprise thousands of filaments interconnected by periodic crossbridges. NFAs begin to be formed within both somata and dendrites as isolated groups of neurofilaments, which apparently go on to assemble en masse within the cytoplasm. In symptomatic animals, many cortical neurons are rich in NFAs, yet lack classic cytological signs of degeneration, such as nuclear pyknosis. Though silver staining reveals extensive NFAs only in aluminum-exposed brains, there is a strong degree of immunostaining for phosphorylated neurofilamentous epitopes in both untreated and Al-injected animals. This suggests that protein subunits that are already present in the neurons under normal circumstances are recruited, in the presence of aluminum, to form NFAs through the directed assembly of masses of oriented filaments. C1 Univ Virginia, Sch Med, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22908 USA. Univ Virginia, Hlth Sci Ctr, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. NIMH, NIH, Bethesda, MD 20892 USA. RP Savory, J (reprint author), Univ Virginia, Sch Med, Hlth Sci Ctr, Dept Pathol, POB 800214, Charlottesville, VA 22908 USA. NR 35 TC 12 Z9 13 U1 0 U2 0 PU INST CLINICAL SCIENCE INC PI PHILADELPHIA PA 1833 DELANCEY PLACE, PHILADELPHIA, PA 19103 USA SN 0091-7370 J9 ANN CLIN LAB SCI JI Ann. Clin. Lab. Sci. PD WIN PY 2002 VL 32 IS 1 BP 75 EP 86 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 519YN UT WOS:000173753200011 PM 11848622 ER PT J AU Escribano, L Akin, C Castells, M Orfao, A Metcalfe, DD AF Escribano, L Akin, C Castells, M Orfao, A Metcalfe, DD TI Mastocytosis: current concepts in diagnosis and treatment SO ANNALS OF HEMATOLOGY LA English DT Review DE mastocytosis; mast cells; mast cell mediators; diagnosis; therapy ID MAST-CELL DISEASE; BULLOUS URTICARIA PIGMENTOSA; MACULARIS ERUPTIVA PERSTANS; BONE-MARROW TRANSPLANTATION; H-3 RECEPTOR ANTAGONISTS; C-KIT MUTATION; FC-EPSILON-RI; SYSTEMIC MASTOCYTOSIS; CUTANEOUS MASTOCYTOSIS; INTERFERON-ALPHA AB Mastocytosis consists of a group of disorders characterized by a pathologic increase in mast cells in tissues including skin, bone marrow, liver, spleen, and lymph nodes. Mastocytosis is a rare disease. Because of this, general practitioners have limited exposure to its clinical manifestations, diagnosis, classification, and management. Diagnosis of mastocytosis is suspected on clinical grounds and is established by histopathologic examination of involved tissues such as skin and bone marrow. The most common clinical sign of mastocytosis is the presence of typical skin lesions of urticaria pigmentosa. Most patients experience symptoms related to mast cell mediator release, and prevention of the effects of these mediators on tissues constitutes the major therapeutic goal in the management of mastocytosis. Despite recent advances in knowledge about the pathophysiology, diagnosis, and classification of mastocytosis, a curative treatment for mastocytosis does not now exist. Management of patients within all categories of mastocytosis includes: (1) a careful counseling of patients (parents in pediatric cases) and care providers, (2) avoidance of factors triggering acute mediator release, (3) treatment of acute mast cell mediator release, (4) treatment of chronic mast cell mediator release, and if indicated (5) an attempt to treat organ infiltration by mast cells. The goal of this manuscript is to provide an overview of the mediators produced and released by mast cells, the diagnostic criteria for the different variants of mastocytosis, and the treatment options currently available. C1 Hosp Ramon y Cajal, Unidad Mastocitosis, E-28034 Madrid, Spain. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Salamanca, Ctr Invest Canc, Serv Cent Citometria, Salamanca 37007, Spain. RP Escribano, L (reprint author), Hosp Ramon y Cajal, Unidad Mastocitosis, Carretera Colmenar Km 9-1, E-28034 Madrid, Spain. OI Akin, Cem/0000-0001-6301-4520 NR 176 TC 105 Z9 110 U1 2 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0939-5555 J9 ANN HEMATOL JI Ann. Hematol. PD DEC PY 2002 VL 81 IS 12 BP 677 EP 690 DI 10.1007/s00277-002-0575-z PG 14 WC Hematology SC Hematology GA 629HZ UT WOS:000180045400001 PM 12483363 ER PT J AU Levy, LM Ziemann, U Chen, R Cohen, LG AF Levy, LM Ziemann, U Chen, R Cohen, LG TI Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation SO ANNALS OF NEUROLOGY LA English DT Article ID HUMAN MOTOR CORTEX; ACTIVITY-DEPENDENT REGULATION; GAMMA-AMINOBUTYRIC-ACID; ISCHEMIC NERVE BLOCK; H-1 MR SPECTROSCOPY; SOMATOSENSORY CORTEX; NMR-SPECTROSCOPY; VISUAL-CORTEX; CORTICAL PLASTICITY; GABAERGIC NEURONS AB Recovery of function after acute injury to the central nervous system may be controlled by the availability of gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the cerebral cortex. Acute lesions as well as manipulation of sensory inputs can lead to rapid reorganization of the cerebral cortex, occurring within minutes to hours. Reduction of cortical inhibitory tone through a decrease in the availability of GABA has been suggested as a possible mechanism; however, the degree and temporal course of the changes in brain GABA are not known. A novel method using two-dimensional J-resolved magnetic resonance spectroscopy showed that GABA levels in the human sensorimotor cortex are quickly reduced within minutes of deafferentation. This finding strongly supports the view that the release of latent corticocortical projections from tonic inhibition through decreased GABA availability is a mechanism of rapid cortical plasticity. Reduction of brain GABA can play a pivotal role in regulating the extent of rapid cortical reorganization after lesions or changes in sensory input. C1 Natl Inst Neurol Disorders & Stroke, Neuroimaging Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Neuroradiol Sect, Washington, DC 20037 USA. Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Univ Frankfurt, Neurol Clin, D-60590 Frankfurt, Germany. Toronto Western Hosp, Div Neurol, Toronto, ON M5T 2S8, Canada. RP Levy, LM (reprint author), Natl Inst Neurol Disorders & Stroke, Neuroimaging Branch, NIH, Bldg 10,5D20, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 56 TC 91 Z9 95 U1 0 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD DEC PY 2002 VL 52 IS 6 BP 755 EP 761 DI 10.1002/ana.10372 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 619WM UT WOS:000179500500010 PM 12447929 ER PT J AU Brewer, CA Pickle, L AF Brewer, CA Pickle, L TI Evaluation of methods for classifying epidemiological data on choropleth maps in series SO ANNALS OF THE ASSOCIATION OF AMERICAN GEOGRAPHERS LA English DT Article DE choropleth; classification; epidemiology; maps ID MAPPING MORTALITY; CLASS INTERVALS; CLASSIFICATION; VISUALIZATION; EXPLORATION; SCHEMES AB Our research goal was to determine which choropleth classification methods are most suitable for epidemiological rate maps. We compared seven methods using responses by fifty-six subjects in a two-part experiment involving nine series of U.S. mortality maps. Subjects answered a wide range of general map-reading questions that involved individual maps and comparisons among maps in a series. The questions addressed varied scales of map-reading, from individual enumeration units, to regions, to whole-map distributions. Quantiles and minimum boundary error classification methods were best suited for these general choropleth map-reading tasks. Natural breaks (Jenks) and a hybrid version of equal-intervals classing formed a second grouping in the results, both producing responses less than 70 percent as accurate as for quantiles. Using matched legends across a series of maps (when possible) increased map-comparison accuracy by approximately 28 percent. The advantages of careful optimization procedures in choropleth classification seem to offer no benefit over the simpler quantile method for the general map-reading tasks tested in the reported experiment. C1 Penn State Univ, Dept Geog, University Pk, PA 16802 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Brewer, CA (reprint author), Penn State Univ, Dept Geog, University Pk, PA 16802 USA. NR 86 TC 65 Z9 67 U1 3 U2 21 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0004-5608 J9 ANN ASSOC AM GEOGR JI Ann. Assoc. Am. Geogr. PD DEC PY 2002 VL 92 IS 4 BP 662 EP 681 DI 10.1111/1467-8306.00310 PG 20 WC Geography SC Geography GA 629LM UT WOS:000180051200004 ER PT J AU King, JR Nachman, S Yogev, R Hodge, J Aldrovandi, G Damle, B Smith, E Wiznia, A Acosta, EP AF King, JR Nachman, S Yogev, R Hodge, J Aldrovandi, G Damle, B Smith, E Wiznia, A Acosta, EP TI Single-dose pharmacokinetics of enteric-coated didanosine in HIV-infected children SO ANTIVIRAL THERAPY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BIOAVAILABILITY; FOOD AB Didanosine remains a cornerstone nucleoside analogue for the treatment of HIV infection. A potential problem with the buffered formulations of didanosine is the likelihood of interactions with other drugs that require an acidic pH for absorption or can be chelated by cations in the buffer. An encapsulated enteric-coated (EC) bead formulation of didanosine has been approved and is routinely used as an alternative to the chewable/dispersible buffered tablet formulation. The objective of this study was to evaluate the single-dose pharmacokinetics of didanosine EC at 240 mg/m(2) in 10 HIV-infected children. Didanosine Ill was administered at time 0 on an empty stomach with no other concomitant medications. Blood samples were collected at pre-dose, 0.5, 1, 2, 4, 8 and 12 h post-dose. Didanosine was measured in plasma using radioimmunoassay. Ten subjects completed the intensive pharmacokinetic evaluation; data are available for eight participants. Plasma concentrations of didanosine following EC administration were analysed using non-compartmental methods. Median (range) AUC(infinity), C-max,T-max and CL/F for didanosine following EC administration were 2385 (1291, 3966) ngxh/ml, 854 (300, 1799) ng/ml, 3.0 (1.0, 8.1) h and 3.3 (2.7-6.4) I/h/kg, respectively. Results from this study indicate that the didanosine Cmax is decreased and Tmax is prolonged, but total exposure of didanosine in plasma following didanosine EC administration appears similar to previous data collected in HIV-infected children following buffered didanosine administration. C1 Univ Alabama, Birmingham, AL 35294 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Frontier Sci & Technol, Amherst, NY USA. Bristol Myers Squibb Co, Princeton, NJ USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Jacobi Med Ctr, Brooklyn, NY USA. RP Acosta, EP (reprint author), Univ Alabama, Birmingham, AL 35294 USA. FU NIAID NIH HHS [UO1-AI41089] NR 11 TC 9 Z9 9 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PD DEC PY 2002 VL 7 IS 4 BP 267 EP 270 PG 4 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 662VP UT WOS:000181969800006 PM 12553481 ER PT J AU Lundeberg, L El-Nour, H Mohabbati, S Morales, M Azmitia, E Nordlind, K AF Lundeberg, L El-Nour, H Mohabbati, S Morales, M Azmitia, E Nordlind, K TI Expression of serotonin receptors in allergic contact eczematous human skin SO ARCHIVES OF DERMATOLOGICAL RESEARCH LA English DT Article DE contact eczema; serotonin; receptors ID T-LYMPHOCYTE FUNCTION; 5-HT1A RECEPTOR; IN-SITU; CELLS; RAT; HYPERSENSITIVITY; DERMATITIS; NEURONS; MOUSE; PROLIFERATION AB The expression of the serotonin (5-HT) receptors 5-HT1AR, 5-HT2AR and 5-HT3R was investigated in allergic contact eczematous human skin by an indirect fluorescence method. 5-HT1AR expression was found in basal epidermal NK1-beteb-positive cells, which were more elongated and showed longer dendritic processes in contact eczematous skin than in control skin. Immunoreactivity for 5-HT1AR was also found in the upper part of the epidermis, with no difference between eczematous and control skin. 5-HT1AR expression was also found in 33.3+/-6.5% and 63.7+/-11.3% of papillary dermal mononuclear cells in inflamed skin and control skin, respectively (P<0.001), as well as in vessel walls. Some of these mononuclear cells were tryptase-positive, and found in both eczematous and control skin. 5-HT2AR-positive cells were found in the upper part of the epidermis in eczematous skin, but were more evenly distributed in the epidermis of control skin. In addition, inflammatory dermal mononuclear cells and vessel walls showed immunoreactivity for this receptor. 5-HT3R expression was found in the basal epidermal layer of eczematous and control skin. These findings indicate a plasticity in the effects of serotonin, especially regarding 5-HT1AR, in allergic contact eczematous skin. C1 Karolinska Hosp, Dept Dermatol & Venerol, S-17176 Stockholm, Sweden. Acad Hosp, Dept Med Sci, Uppsala, Sweden. Natl Inst Drug Abuse, Baltimore, MD USA. NYU, Dept Biol & Psychiat, New York, NY USA. RP Nordlind, K (reprint author), Karolinska Hosp, Dept Dermatol & Venerol, S-17176 Stockholm, Sweden. OI Elnour, Husameldin/0000-0003-0745-9335; azmitia, efrain/0000-0002-8806-1064 NR 29 TC 20 Z9 20 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-3696 J9 ARCH DERMATOL RES JI Arch. Dermatol. Res. PD DEC PY 2002 VL 294 IS 9 BP 393 EP 398 DI 10.1007/s00403-002-0350-y PG 6 WC Dermatology SC Dermatology GA 628XM UT WOS:000180021400002 PM 12522576 ER PT J AU Postolache, TT Wehr, TA Doty, RL Sher, L Turner, EH Bartko, JJ Rosenthal, NE AF Postolache, TT Wehr, TA Doty, RL Sher, L Turner, EH Bartko, JJ Rosenthal, NE TI Patients with seasonal affective disorder have lower odor detection thresholds than control subjects SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT International Congress on Chronobiology CY AUG 28-SEP 01, 1999 CL WASHINGTON, D.C. ID WINTER DEPRESSION; SUPRACHIASMATIC NUCLEUS; OLFACTORY FUNCTION; NASAL RESISTANCE; CONTROLLED TRIAL; LIGHT TREATMENT; BRIGHT LIGHT; STIMULATION; SENSITIVITY; RESPONSES AB Background: Behavioral changes in patients with seasonal affective disorder resemble seasonal changes in photoperiodic animals. Because the olfactory system has a modulatory role in seasonal photoperiodic responses in certain species, we hypothesized that olfactory function may differ between patients with seasonal affective disorder and healthy control subjects. Methods: Fourteen patients who had winter seasonal affective disorder and 16 healthy volunteers were studied once in winter and once in the subsequent summer. We administered a phenyl ethyl alcohol detection threshold test to each side of the nose in a counterbalanced order, with the nostril contralateral to the tested site occluded. Patient and control data were compared using a 4-way repeated measure analysis of covariance (with group and gender as between-subjects factors, season and side-of-the-nose as within-subjects factors, and age as a covariate). Results: The patients exhibited lower thresholds than did the controls (F-1,F-25 = 9.2; P = .006). There was no main effect of season. Conclusion: In humans, marked seasonal behavioral rhythms with recurrent winter depression may be associated with a more acute sense of smell. C1 NIMH, Sect Biol Rhythms, NIH, Bethesda, MD 20892 USA. NIMH, St Elizabeths Hosp, Psychopharmacol Consultat Serv, Washington, DC 20032 USA. Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20007 USA. Univ Penn, Med Ctr, Ctr Smell & Taste, Philadelphia, PA 19104 USA. RP Postolache, TT (reprint author), NIMH, Sect Biol Rhythms, NIH, 10 Ctr Dr,Room 3S-231, Bethesda, MD 20892 USA. RI Doty, Richard/B-7623-2012; Doty, Richard/G-1602-2013; OI Turner, Erick/0000-0002-3522-3357 FU NIDCD NIH HHS [NIDCD P01 00161] NR 40 TC 25 Z9 26 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD DEC PY 2002 VL 59 IS 12 BP 1119 EP 1122 DI 10.1001/archpsyc.59.12.1119 PG 4 WC Psychiatry SC Psychiatry GA 623NW UT WOS:000179710600006 PM 12470128 ER PT J AU Sohn, YH Jung, HY Kaelin-Lang, A Hallett, M AF Sohn, YH Jung, HY Kaelin-Lang, A Hallett, M TI Effect of levetiracetam on rapid motor learning in humans SO ARCHIVES OF NEUROLOGY LA English DT Article ID LONG-TERM POTENTIATION; TRANSCRANIAL MAGNETIC STIMULATION; ANTIEPILEPTIC DRUGS; CORTEX; PLASTICITY; EXCITABILITY; CONNECTIONS; MECHANISMS; MODULATION; SYSTEM AB Background: The human motor cortex (M1) has a role in motor learning. Antiepileptic drugs that suppress M1 excitability may affect learning, presumably by inhibiting long-term potentiation. Levetiracetam, a new anti-epileptic drug with a unique preclinical profile, also suppresses M1 excitability, but in a way that is different from other antiepileptic drugs. The effect of levetiracetam on motor learning has yet to be addressed. Objective: To investigate whether levetiracetam alters rapid motor learning in humans. Methods: We measured pinch force and acceleration and motor excitability before and after 30 minutes of pinch practice at 0.5 Hz in 10 healthy volunteers. Either 3000 mg of levetiracetam or placebo was administered I hour before the experiment. Results: After practice, pinch acceleration was significantly increased with placebo, but not with levetiracetam. All other measures showed no significant change. Conclusion: Levetiracetam interferes with rapid motor learning; this is consistent with a negative influence on long-term potentiation. C1 NINDS, NIH, Bethesda, MD 20892 USA. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Yonsei Univ, Ctr Med, Dept Neurol, Seoul, South Korea. Yonsei Univ, Ctr Med, Brain Res Inst, Seoul, South Korea. RP Hallett, M (reprint author), NINDS, NIH, Bldg 10,Rm 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. NR 22 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2002 VL 59 IS 12 BP 1909 EP 1912 DI 10.1001/archneur.59.12.1909 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 624AJ UT WOS:000179736900009 PM 12470179 ER PT J AU Cereghino, JJ Cloyd, JC Kuzniecky, RI AF Cereghino, JJ Cloyd, JC Kuzniecky, RI CA N Am Diastat Study Grp TI Rectal diazepam gel for treatment of acute repetitive seizures in adults SO ARCHIVES OF NEUROLOGY LA English DT Article ID STATUS EPILEPTICUS; PLASMA-CONCENTRATIONS; HOME USE; CHILDREN; MIDAZOLAM; INFANTS; DRUGS AB Objective: To evaluate the efficacy and tolerability of diazepam (DZP) rectal gel (Diastat; Elan Pharmaceuticals, Dublin, Ireland) for the treatment of acute repetitive seizures in adult patients in 2 multicenter, double-blind, placebo-controlled parallel studies. Methods: Ninety-six adults 18 years or older with acute repetitive seizures, 70 of whom received treatment, were randomized into the 2 studies. Active and placebo medications were supplied in prefilled, identical-appearing delivery systems. In study 001, patients received a second dose 4 hours after the initial treatment. Patients in study 003 received only I treatment. Patients were observed for 12 hours after the first dose. Results: There was a significant reduction in seizure frequency in patients who received DZP compared with the placebo group. The median number of seizures per hour in the group treated with DZP rectal gel was 0.00, vs 0.13 in the placebo group (P=.002). In addition, significantly more DZP rectal gel-treated patients remained seizure-free during the 12-hour observation period (71% [22/31] vs 28% [11/39]). Using Kaplan-Meier life-table analysis, time to the next seizure was found to be significantly longer in DZP rectal gel-treated than placebo-treated patients (P<.001). Global assessment as provided by the caregivers was in favor of DZP rectal gel for both study 001 (P=.17) and study 003 (P=.02). Dizziness and somnolence were the only central nervous system adverse events that occurred more frequently in patients receiving DZP rectal gel than in those receiving placebo. Conclusion: In adults, rectal DZP formulated as Diastat significantly reduced the likelihood of seizure recurrence during an episode of acute repetitive seizures, with minimal safety concerns. C1 Oregon Hlth Sci Univ, Epilepsy Ctr, Portland, OR 97239 USA. Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. Univ Alabama, Epilepsy Ctr, Dept Neurol, Birmingham, AL USA. Xcel Pharmaceut, San Diego, CA USA. Elan Pharmaceut, Dublin, Ireland. NINDS, Bethesda, MD USA. RP Cereghino, JJ (reprint author), Oregon Hlth Sci Univ, Epilepsy Ctr, CDW 3,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. NR 28 TC 28 Z9 28 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD DEC PY 2002 VL 59 IS 12 BP 1915 EP 1920 DI 10.1001/archneur.59.12.1915 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 624AJ UT WOS:000179736900010 PM 12470180 ER PT J AU Drebot, MA Henchal, E Hjelle, B LeDuc, JW Repik, PM Roehrig, JT Schmaljohn, CS Shope, RE Tesh, RB Weaver, SC Calisher, CH AF Drebot, MA Henchal, E Hjelle, B LeDuc, JW Repik, PM Roehrig, JT Schmaljohn, CS Shope, RE Tesh, RB Weaver, SC Calisher, CH TI Improved clarity of meaning from the use of both formal species names and common (vernacular) virus names in virological literature SO ARCHIVES OF VIROLOGY LA English DT Editorial Material C1 Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Arthropod Borne & Infect Dis Lab, Ft Collins, CO 80523 USA. Canadian Sci Ctr Human & Anim Hlth, Populat & Publ Hlth Branch, Natl Microbiol Lab, Winnipeg, MB, Canada. USA, Med Res Inst Infect Dis, Div Virol, Dept Mol Virol, Frederick, MD 21701 USA. Univ New Mexico, Sch Med, Dept Pathol, Infect Dis & Inflammat Program, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Biol, Infect Dis & Inflammat Program, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Mol Genet & Microbiol, Infect Dis & Inflammat Program, Albuquerque, NM 87131 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Atlanta, GA 30341 USA. NIAID, Div Microbiol & Infect Dis, Virol Branch, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Vector Borne Infect Dis, Ft Collins, CO 80522 USA. Univ Texas, Med Branch, Dept Pathol, Ctr Trop Dis, Galveston, TX 77550 USA. RP Calisher, CH (reprint author), Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Arthropod Borne & Infect Dis Lab, Ft Collins, CO 80523 USA. RI Weaver, Scott/D-6490-2011; OI Roehrig, John/0000-0001-7581-0479 NR 3 TC 18 Z9 18 U1 0 U2 1 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD DEC PY 2002 VL 147 IS 12 BP 2465 EP 2471 DI 10.1007/s00705-002-0938-8 PG 7 WC Virology SC Virology GA 625FF UT WOS:000179805800017 PM 12491112 ER PT J AU Jenny, NS Tracy, RP Ogg, MS Luong, LA Kuller, LH Arnold, AM Sharrett, AR Humphries, SE AF Jenny, NS Tracy, RP Ogg, MS Luong, LA Kuller, LH Arnold, AM Sharrett, AR Humphries, SE TI In the elderly, interleukin-6 plasma levels and the-174G > C polymorphism are associated with the development of cardiovascular disease SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE inflammation; interleukin-6; atherosclerosis; elderly; cardiovascular disease ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; APPARENTLY HEALTHY-MEN; MYOCARDIAL-INFARCTION; INSULIN SENSITIVITY; SUBCLINICAL DISEASE; DIABETES-MELLITUS; GENE POLYMORPHISM; BLOOD-PRESSURE; RISK-FACTORS AB Objective-Interleukin (IL)-6-mediated inflammation is levels and the -174G>C genotype in a case-control Cardiovascular Health Study. Methods and Results-Cases included incident angina involved in cardiovascular disease (CVD). We assessed IL-6 study of men and women (average age 73 years) within the I myocardial infarction (MI) and stroke (5-year follow-up) prevalent MI, and MRI-detectable infarcts. A control group and a group free of subclinical CVD were used for comparison. The -174C allele was associated with higher C-reactive protein (11% higher, P = 0.02), fibrinogen 3% higher, P=0.02),and IL-6 (5% higher; P=0.16). IL-6 was associated with increased atherosclerosis when the control Group was compared with the Group free of subclinical CVD. No further association with CVD events was found when case groups were compared with the control group. Compared with its absence, presence of the -174C allele was associated with risk of MRI infarcts (odds ratio 1.5). Conclusions-IL-6 levels differentiated those with subclinical CVD from those without. Although the -174C allele was not associated with incident events, associations of the genotype with inflammation and MRI infarcts, combined with the plasma IL-6 results, suggest that IL-6 may chronically predispose an individual to develop atherosclerosis. (Arterioscler Thromb Vasc Biol. 2002;22:2066-2071.). C1 Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ Vermont, Coll Med, Dept Biochem, Burlington, VT 05405 USA. UCL Royal Free & Univ Coll Med Sch, Rayne Inst, Dept Med, London, England. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. NHLBI, Bethesda, MD USA. RP Tracy, RP (reprint author), Univ Vermont, Colchester Res Facil, Dept Pathol, 208 S Pk Dr,Suite 2, Colchester, VT 05446 USA. EM Russell.Tracy@uvm.edu RI Humphries, Stephen/C-5075-2008 FU NHLBI NIH HHS [N01-HC-15103, N01-HC-35129, N01-HC-85079, N01-HC-85086, R01 HL-46696] NR 38 TC 194 Z9 204 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD DEC PY 2002 VL 22 IS 12 BP 2066 EP 2071 DI 10.1161/01.ATV.0000040224.49362.60 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 629JF UT WOS:000180046000022 PM 12482836 ER PT J AU Brown, SL Greene, MH Gershon, SK Edwards, ET Braun, MM AF Brown, SL Greene, MH Gershon, SK Edwards, ET Braun, MM TI Tumor necrosis factor antagonist therapy and lymphoma development - Twenty-six cases reported to the Food and Drug Administration SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; EPSTEIN-BARR-VIRUS; RHEUMATOID-ARTHRITIS; LYMPHOPROLIFERATIVE DISORDERS; CROHNS-DISEASE; FACTOR-ALPHA; MONOCLONAL-ANTIBODY; HODGKINS-DISEASE; METHOTREXATE; RISK AB Objective. Etanercept and infliximab are tumor necrosis factor (TNF) antagonists that have been recently approved for the treatment of rheumatoid arthritis (RA) and Crohn's disease (CD). This study was undertaken to investigate the occurrence of lymphoproliferative disorders in patients treated with these agents. Methods. Relevant data in the MedWatch post-market adverse event surveillance system run by the US Food and Drug Administration were reviewed. Results. We identified 26 cases of lymphoproliferative disorders following treatment with etanercept (18 cases) or infliximab (8 cases). The majority of cases (81%) were non-Hodgkin's lymphomas. The interval between initiation of therapy with etanercept or infliximab and the development of lymphoma was very short (median 8 weeks). In 2 instances (I infliximab, 1 etanercept), lymphoma regression was observed following discontinuation of anti-TNF treatment, in the absence of specific cytotoxic therapy directed toward the lymphoma. Conclusion. Although data from a case series such as this cannot establish a clear causal relationship between exposure to these medications and the risk of lymphoproliferative disease, the known predisposition of patients with RA and CD to lymphoma, the known excess of lymphoma in other immunosuppressed populations, and the known immunosuppressive effects of the anti-TNF drugs provide a biologic basis for concern and justification for the initiation of additional epidemiologic studies to formally evaluate this possible association. C1 US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, Rockville, MD USA. RP Braun, MM (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 45 TC 397 Z9 414 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2002 VL 46 IS 12 BP 3151 EP 3158 DI 10.1002/art.10679 PG 8 WC Rheumatology SC Rheumatology GA 624HJ UT WOS:000179754000005 PM 12483718 ER PT J AU Aksentijevich, I Nowak, M Mallah, M Chae, JJ Watford, WT Hofmann, SR Stein, L Russo, R Goldsmith, D Dent, P Rosenberg, HF Austin, F Remmers, EF Balow, JE Rosenzweig, S Komarow, H Shoham, NG Wood, G Jones, J Mangra, N Carrero, H Adams, BS Moore, TL Schikler, K Hoffman, H Lovell, DJ Lipnick, R Barron, K O'Shea, JJ Kastner, DL Goldbach-Mansky, R AF Aksentijevich, I Nowak, M Mallah, M Chae, JJ Watford, WT Hofmann, SR Stein, L Russo, R Goldsmith, D Dent, P Rosenberg, HF Austin, F Remmers, EF Balow, JE Rosenzweig, S Komarow, H Shoham, NG Wood, G Jones, J Mangra, N Carrero, H Adams, BS Moore, TL Schikler, K Hoffman, H Lovell, DJ Lipnick, R Barron, K O'Shea, JJ Kastner, DL Goldbach-Mansky, R TI De novo CIAS1 mutations, cytokine activation, and evidence for genetic heterogeneity in patients with neonatal-onset multisystem inflammatory disease (NOMID) - A new member of the expanding family of pyrin-associated autoinflammatory diseases SO ARTHRITIS AND RHEUMATISM LA English DT Article ID ENCODING MEVALONATE KINASE; PERIODIC FEVER SYNDROME; MUCKLE-WELLS-SYNDROME; MENTAL-RETARDATION; DOMAIN; APOPTOSIS; ARTHROPATHY; RASH; COLD; PROTEINS AB Objective. Neonatal-onset multisystem inflammatory disease (NOMID; also known as chronic infantile neurologic, cutaneous, articular [CINCA] syndrome) is characterized by fever, chronic meningitis, uveitis, sensorineural hearing loss, urticarial skin rash, and a characteristic deforming arthropathy. We investigated whether patients with this disorder have mutations in CIAS1, the gene which causes Muckle-Wells syndrome and familial cold autoinflammatory syndrome, two dominantly inherited disorders with some similarities to NOMID/CINCA syndrome. Methods. Genomic DNA from 13 patients with classic manifestations of NOMID/CINCA syndrome and their available parents was screened for CIAS1 mutations by automated DNA sequencing. Cytokine messenger RNA (mRNA) levels were assessed by real-time polymerase chain reaction on peripheral blood leukocyte mRNA, and serum cytokine levels were assayed by enzyme-linked immunosorbent assay. Protein expression was assessed by Western blotting of lysates from plastic-adherent peripheral blood mononuclear cells. Results. In 6 of the 13 patients, we found 6 heterozygous missense substitutions in CIAS1 Five of the 6 mutations are novel. None of these sequence changes was observed in a panel of >900 chromosomes from healthy controls. Two distinct nucleotide changes in a single codon in unrelated patients resulted in the same amino acid change. In 4 mutation-positive children whose parental DNA was available, no mutation was found in the parental DNA, supporting the conclusion that the mutations arose de novo. Consistent with the recently discovered role of CIAS1 in the regulation of interleukin-1 (IL-1), we found evidence of increased IL-1beta, as well as tumor necrosis factor, IL-3, IL-5, and IL-6, but not transforming growth factor beta in a mutation-positive patient compared with normal controls. Conclusion. Our data increase the total number of known germline mutations in CIAS1 to 20, causing a spectrum of diseases ranging from familial cold autoinflammatory syndrome to Muckle-Wells syndrome to NOMID/CINCA syndrome. Mutations in CIAS1 were only found in similar to50% of the cases identified clinically as NOMID/CINCA syndrome, which raises the possibility of genetic heterogeneity. IL-1 regulation by CIAS1 suggests that IL-1 receptor blockade may constitute a rational approach to the treatment of NOMID/CINCA syndrome. C1 NIAMSD, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC USA. Hosp Pediatr Prof Dr Juan P Garrahan, Buenos Aires, DF, Argentina. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. St Christophers Hosp Children, Philadelphia, PA 19133 USA. McMaster Univ, Hamilton, ON, Canada. NIAID, NIH, Bethesda, MD 20892 USA. Univ Michigan, Ann Arbor, MI 48109 USA. St Louis Univ, St Louis, MO 63103 USA. Univ Louisville, Louisville, KY 40292 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. RP Goldbach-Mansky, R (reprint author), NIAMS, NIH, Bldg 10,Room 9S-205,10 Ctr Dr, Bethesda, MD 20892 USA. FU Intramural NIH HHS [ZIA AR041138-11] NR 45 TC 380 Z9 396 U1 1 U2 8 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2002 VL 46 IS 12 BP 3340 EP 3348 DI 10.1002/art.10688 PG 9 WC Rheumatology SC Rheumatology GA 624HJ UT WOS:000179754000028 PM 12483741 ER PT J AU Valencia, X He, LS Illei, G Lipsky, P AF Valencia, X He, LS Illei, G Lipsky, P TI CD4+CD25+T regulatory cells in systemic lupus erythematosus SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Meeting of the American College of Rheumatology CY OCT 25-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol C1 NIAMS, NIH, OCD, Bethesda, MD USA. NIAMS, NIH, AB, Bethesda, MD USA. NR 0 TC 3 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2002 VL 46 IS 12 MA SY09 BP 3404 EP 3404 PG 1 WC Rheumatology SC Rheumatology GA 624HJ UT WOS:000179754000051 ER PT J AU Nowak, M Carrasquillo, J Yarboro, C Bacharach, S Whatley, M Takada, K Illei, G AF Nowak, M Carrasquillo, J Yarboro, C Bacharach, S Whatley, M Takada, K Illei, G TI A pilot study of F-18FDG positron emission tomography(FDG-PET) to assess the distribution of activated lymphocytes in systemic lupus erythematosus (SLE) SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract CT Annual Meeting of the American College of Rheumatology CY OCT 25-29, 2002 CL NEW ORLEANS, LOUISIANA SP Amer Coll Rheumatol C1 NIH, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 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 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD DEC PY 2002 VL 46 IS 12 MA SY25 BP 3414 EP 3414 PG 1 WC Rheumatology SC Rheumatology GA 624HJ UT WOS:000179754000067 ER PT J AU Hannuksela, ML Brousseau, ME Meyn, SM Nazih, H Bader, G Shamburek, RD Alaupovic, P Brewer, HB AF Hannuksela, ML Brousseau, ME Meyn, SM Nazih, H Bader, G Shamburek, RD Alaupovic, P Brewer, HB TI In vivo metabolism of apolipoprotein E within the HDL subpopulations LpE, LpE : A-I, LpE : A-II and LpE : A-I : A-II SO ATHEROSCLEROSIS LA English DT Article DE apolipoprotein E; high-density lipoproteins; abetalipoproteinemia; apolipoprotein A-I apolipoprotein A-II; kinetics ID HIGH-DENSITY-LIPOPROTEINS; CHOLESTEROL EFFLUX; INVIVO METABOLISM; TRANSGENIC MICE; PLASMA; ABETALIPOPROTEINEMIA; PARTICLES; CHROMATOGRAPHY; DISEASE; HUMANS AB High-density lipoproteins can be separated into distinct particles based on their apolipoprotein content. In the present study, the in vivo metabolism of apoE within the apoE-containing HDL particles LpE, LpE:A-I, LpE:A-II and LpE:A-I:A-II was assessed in control subjects and in patients with abetalipoproteinemia (ABL), in whom HDL are the sole plasma lipoproteins. The metabolism of apoE within these HDL subspecies was investigated in three separate studies which differed by donor or recipient status: (1) particles purified from normolipidemic plasma and reassociated with I-125 or I-131-labeled apoE injected into normolipidemic subjects (study 1); (2) particles purified from ABL plasma injected into normolipidemic subjects (study 2); and (3) particles purified from ABL plasma injected into ABL subjects (study 3). The plasma residence times (RT, hours) in study 1 were 14.3+/-2.9, 11.3+/-3.4, and 9.1+/-1.2 for apoE within LpE:A-I:A-II, LpE:A-II and LpE:A-I, respectively, while those in study 2 were 10.1+/-2.2, 9.7+/-2.4, 7.9+/-1.0 and 7.3+/-0.8 for apoE within LpE:A-I:A-II, LpE:A-II, LpE:A-I and LpE, respectively. In study 3, RTs for apoE within LpE:ALA-II and LpE were 8.7+/-0.9 and 6.8+/-0.9, respectively. In comparison, RT for apoA-I on LpA-I:A-II has been reported to be 124.1+/-5.5 h and that for apoA-I on LpA-I 105.8+/-6.2 h. Thus, apoE within the different apoE-containing HDL particles was metabolized rapidly and at a similar rate in control and ABL subjects. The plasma RT of apoE was longest when injected on LpE:AI:A-II particles and shortest when injected on LpE. In summary, our data show that: (1) the plasma RT of apoE within HDL is approximately ten times shorter than that of apoA-I within HDL, and (2) apoE within HDL is metabolized at a slower rate when apoproteins A-I and A-II are present (LpE:A-I:A-II RT > LpE:A-II > LpE:A-I > LpE). These differences were related to the lipid and apolipoprotein composition of the HDL subspecies, and, in control subjects, to the transfer of apoE from HDL subspecies to apoB-containing lipoproteins as well. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Oulu, Dept Internal Med, SF-90220 Oulu, Finland. Univ Oulu, Bioctr, SF-90220 Oulu, Finland. Lipid & Lipoprot Lab, Oklahoma City, OK USA. RP Hannuksela, ML (reprint author), NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. NR 24 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD DEC PY 2002 VL 165 IS 2 BP 205 EP 220 AR PII S0021-9150(02)00200-9 DI 10.1016/S0021-9150(02)00200-9 PG 16 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 617FR UT WOS:000179351700004 PM 12417271 ER PT J AU Stokes, WS Schechtman, LM Hill, RN AF Stokes, WS Schechtman, LM Hill, RN TI The Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM): A review of the ICCVAM test method evaluation process and current international collaborations with the European Centre for the Validation of Alternative Methods (ECVAM) SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article; Proceedings Paper CT ECVAM Status Seminar CY JUN 04-06, 2002 CL EUROPEAN COMMISS JOINT RES CTR AMPHITHEATRE, ISPRA, ITALY HO EUROPEAN COMMISS JOINT RES CTR AMPHITHEATRE DE alternative method; animal welfare; ECVAM; ICCVAM; NICEATM; regulatory acceptance; validation ID TOXICITY; WORKSHOP AB Over the last decade, national authorities in the USA and Europe have launched initiatives to validate new and improved toxicological test methods. In the USA, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM), and its supporting National Toxicology Program Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM), were established by the Federal Government to work with test developers and Federal agencies to facilitate the validation, review, and adoption of new scientifically sound test methods, including alternatives that can reduce, refine, and replace animal use. In Europe, the European Centre for the Validation of Alternative Methods (ECVAM) was established to conduct validation studies on alternative test methods. Despite differences in organisational structure and processes, both organisations seek to achieve the adoption and use of alternative test methods. Accordingly, both have adopted similar validation and regulatory acceptance criteria, Collaborations and processes have also evolved to facilitate the international adoption of new test methods recommended by ECVAM and ICCVAM. These collaborations involve the sharing of expertise and data for test-method workshops and independent scientific peer reviews, and the adoption of processes to expedite the consideration of test methods already reviewed by the other organisation. More recently, NICEATM and ECVAM initiated a joint international validation study on in vitro methods for assessing acute systemic toxicity. These collaborations are expected to contribute to accelerated international adoption of harmonised new test methods that will support improved public health and provide for reduced and more-humane use of laboratory animals. C1 NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. US EPA, Off Prevent Pesticides & Tox Subst, Washington, DC 20460 USA. RP Stokes, WS (reprint author), NIEHS, Natl Toxicol Program, Interagcy Ctr Evaluat Alternat Toxicol Methods, Environm Toxicol Program, Mail Code EC-17,POB 12233, Res Triangle Pk, NC 27709 USA. NR 33 TC 16 Z9 16 U1 0 U2 0 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD DEC PY 2002 VL 30 SU 2 BP 23 EP 32 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 640BY UT WOS:000180667700005 PM 12513648 ER PT J AU Schechtman, LM Stokes, WS AF Schechtman, LM Stokes, WS TI ECVAM-ICCVAM: Prospects for future collaboration SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article; Proceedings Paper CT ECVAM Status Seminar CY JUN 04-06, 2002 CL EUROPEAN COMMISS JOINT RES CTR AMPHITHEATRE, ISPRA, ITALY HO EUROPEAN COMMISS JOINT RES CTR AMPHITHEATRE DE alternative method; animal welfare; collaboration; ECVAM; ESAC; ICCVAM; NICEATM; regulatory acceptance; SACATM; validation ID ALTERNATIVE METHODS AB The level and complexity of testing for hazard and risk assessment of marketed products and environmental agents has increased substantially over time, resulting in the use of greater numbers of both animals and humans for testing. Today, industry and regulatory bodies worldwide face increasing pressures to demonstrate responsible utilisation of laboratory animals, to limit their use, and to employ alternative non-animal tests. Institutions have also been established to identify, encourage the development of, conduct research on, and validate new, improved, and surrogate test methods that will reduce and replace animal use. Two such organisations are ECVAM and the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). As the evolutionary changes occurring in the field of toxicology result in an unprecedented increase in the introduction of alternative methodologies, these will strain the capacities of such alternative-methods institutions, That realisation is causing a shift in thinking and is creating an impetus to seek approaches by which to collaborate and develop more-efficient operational procedures for the validation and regulatory acceptance of alternative methods. Similarities in objectives, functions, scientific standards, and commitment to the principles of validation and animal welfare support the value of a cooperative arrangement between ECVAM and ICCVAM, to minimise duplication of effort, maximise productivity, and influence the international adoption of alternative tests. Opportunities for ECVAM-ICCVAM collaboration are discussed, which illustrate the feasibility and potential benefits of such a partnership. C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. RP Schechtman, LM (reprint author), US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD DEC PY 2002 VL 30 SU 2 BP 227 EP 236 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 640BY UT WOS:000180667700040 PM 12513682 ER PT J AU Zitikis, R Gastwirth, JL AF Zitikis, R Gastwirth, JL TI The asymptotic distribution of the S-Gini index SO AUSTRALIAN & NEW ZEALAND JOURNAL OF STATISTICS LA English DT Article; Proceedings Paper CT Symposium in honor of David Vere Jones CY APR 19-21, 2001 CL VICTORIA UNIV, WELLINGTON, NEW ZEALAND HO VICTORIA UNIV DE asymptotic normality; consistency; economic inequality; exponential distribution; Gini index; income distribution; L-statistic; Pareto distribution; S-Gini index ID INEQUALITY; CURVE AB Several generalizations of the classical Gini index, placing smaller or greater weights on various portions of income distribution, have been proposed by a number of authors. For purposes of statistical inference, the large sample distribution theory of the estimators of those measures of economic inequality is required. The present paper was stimulated by the use of bootstrap by Xu (2000) to estimate the variance of the estimator of the S-Gini index. It shows that the theory of L-statistics (Chernoff, Gastwirth Johns, 1967; Shorack & Wellner, 1986) makes possible the construction of a consistent estimator for the S-Gini index and proof of its asymptotic normality. The paper also presents an explicit formula for the asymptotic variance. The formula should be helpful in planning the size of samples from which the S-Gini index can be estimated with a prescribed margin of error. C1 Univ Western Ontario, Dept Stat & Actuarial Sci, London, ON N6A 5B7, Canada. George Washington Univ, Lab Res Stat & Probabil, Washington, DC 20052 USA. NCI, Bethesda, MD 20892 USA. RP Zitikis, R (reprint author), Univ Western Ontario, Dept Stat & Actuarial Sci, London, ON N6A 5B7, Canada. NR 22 TC 19 Z9 20 U1 2 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 1369-1473 J9 AUST NZ J STAT JI Aust. N. Z. J. Stat. PD DEC PY 2002 VL 44 IS 4 BP 439 EP 446 DI 10.1111/1467-842X.00245 PG 8 WC Statistics & Probability SC Mathematics GA 615CM UT WOS:000179228300005 ER PT J AU Catalan, J Moriguchi, T Slotnick, B Murthy, M Greiner, RS Salem, N AF Catalan, J Moriguchi, T Slotnick, B Murthy, M Greiner, RS Salem, N TI Cognitive deficits in docosahexaenoic acid-deficient rats SO BEHAVIORAL NEUROSCIENCE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; VISUAL-ACUITY DEVELOPMENT; OLFACTORY LEARNING-SET; TERM INFANTS; ARACHIDONIC-ACID; PRETERM INFANTS; ODOR DETECTION; BRAIN; DIET; OMEGA-3-FATTY-ACIDS AB This study investigated the influence of brain docosahexaenoic acid (DHA) deficiency on simple and complex olfactory-based learning and memory in 2nd generation (172) adult male rats. Rats raised and maintained on either an n-3-adequate or an n-3-deficient diet were tested for acquisition of an olfactory learning set and an olfactory memory task, and for motivation to obtain a water reward. Despite a 76% decrease in brain DHA, n-3-deficient rats were able to acquire most simple 2-odor discrimination tasks but were deficient in the acquisition of a 20-problem olfactory learning set. This deficit could not be attributed to changes in sensory capacity but, instead, appeared to represent a deficit in higher order,learning. C1 NIAAA, Lab Membrane Biochem & Biophys, Uniformed Serv Univ Hlth Sci, Sect Nutr Neurosci, Rockville, MD 20852 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. American Univ, Dept Psychol, Washington, DC 20016 USA. RP Salem, N (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Uniformed Serv Univ Hlth Sci, Sect Nutr Neurosci, 12420 Parklawn Dr, Rockville, MD 20852 USA. RI Wilkinson, Stuart/C-2802-2013 NR 48 TC 109 Z9 122 U1 0 U2 8 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD DEC PY 2002 VL 116 IS 6 BP 1022 EP 1031 DI 10.1037//0735-7044.116.6.1022 PG 10 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 623EX UT WOS:000179691300009 PM 12492301 ER PT J AU Brand, MD Pamplona, R Portero-Otin, M Requena, JR Roebuck, SJ Buckingham, JA Clapham, JC Cadenas, S AF Brand, MD Pamplona, R Portero-Otin, M Requena, JR Roebuck, SJ Buckingham, JA Clapham, JC Cadenas, S TI Oxidative damage and phospholipid fatty acyl composition in skeletal muscle mitochondria from mice underexpressing or overexpressing uncoupling protein 3 SO BIOCHEMICAL JOURNAL LA English DT Article DE peroxidation; protein oxidation; proton leak; reactive oxygen species; superoxide ID THYROID-HORMONE STATUS; PROTON PERMEABILITY; LIVER-MITOCHONDRIA; INNER MEMBRANE; HEART-MITOCHONDRIA; HYDROGEN-PEROXIDE; ENERGY-METABOLISM; ACID UNSATURATION; OXYGEN; CARDIOLIPINS AB Five markers of different kinds of oxidative damage to proteins [glutamic semialdehyde, aminoadipic semialdehyde, N-6-(carboxymethyl)lysine, N-6-(carboxyethyl)lysine and N-6-(malondialdehyde)lysine] and phospholipid fatty acyl composition were identified and measured in skeletal muscle mitochondria isolated from mice genetically engineered to underexpress or overexpress uncoupling protein 3 (UCP3). Mitochondria from UCP3-underexpressing mice had significantly higher levels of oxidative damage than wild-type controls, suggesting that UCP3 functions in vivo as part of the antioxidant defences of the cell, but mitochondria from UCP3-overexpressing mice had unaltered oxidative damage, suggesting that mild uncoupling in vivo beyond the normal basal uncoupling provides little protection against oxidative stress. Mitochondria from UCP3-underexpressing mice showed little change, but mitochondria from UCP3-overexpressing mice showed marked changes in mitochondrial phospholipid fatty acyl composition. These changes were very similar to those previously found to correlate with basal proton conductance in mitochondria from a range of species and treatments, suggesting that high protein expression, or some secondary result of uncoupling, may cause the observed correlation between basal proton conductance and phospholipid fatty acyl composition. C1 MRC, Dunn Human Nutr Unit, Cambridge CB2 2XY, England. Lleida Univ, Fac Med, Dept Basic Med Sci, Metab Physiopathol Res Grp, Lleida 25198, Spain. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. SmithKline Beecham Pharmaceut, Dept Vasc Biol, Harlow CM19 5AW, Essex, England. RP Brand, MD (reprint author), MRC, Dunn Human Nutr Unit, Hills Rd, Cambridge CB2 2XY, England. RI Portero-Otin, Manuel/B-7122-2009; Brand, Martin/A-9423-2012; Pamplona, Reinald/A-7359-2010; Cadenas, Susana/D-1523-2016; OI Portero-Otin, Manuel/0000-0002-1823-0299; Brand, Martin/0000-0003-4418-6153; Pamplona, Reinald/0000-0003-4337-6107; Cadenas, Susana/0000-0003-0726-0369 NR 42 TC 137 Z9 145 U1 0 U2 9 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD DEC 1 PY 2002 VL 368 BP 597 EP 603 DI 10.1042/BJ20021077 PN 2 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 624RX UT WOS:000179775700022 PM 12193161 ER PT J AU Roytberg, MA Ogurtsov, AY Shabalina, SA Kondrashov, AS AF Roytberg, MA Ogurtsov, AY Shabalina, SA Kondrashov, AS TI A hierarchical approach to aligning collinear regions of genomes SO BIOINFORMATICS LA English DT Article ID DNA-SEQUENCES; SELECTIVE CONSTRAINT; INTERGENIC REGIONS; C-ELEGANS; ALIGNMENT; CONSERVATION; EVOLUTION; FUGU AB Motivation: As a first approximation, similarity between two long orthologous regions of genomes can be represented by a chain of local similarities. Within such a chain, pairs of successive similarities are collinear (non-conflicting), i.e. segments involved in the nth similarity precede in both sequences segments involved in the (n+1)th similarity. However, when all similarities between two long sequences are considered, usually there are many conflicts between them. Although some conflicts can be avoided by masking transposons or low-complexity sequences, selecting only those similarities that reflect orthology and, thus, belong to the evolutionarily true chain is not trivial. Results: We propose a simple, hierarchical algorithm of finding the true chain of local similarities. Starting from similarities with low P-values, we resolve each pairwise conflict by deleting a similarity with a higher P-value. This greedy approach constructs a chain of similarities faster than when a chain optimal with respect to some global criterion is sought, and makes more sense biologically. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Inst Math Problems Biol, Pushchino 142290, Moscow Region, Russia. RP Kondrashov, AS (reprint author), NIH, Natl Ctr Biotechnol Informat, 45 Ctr Dr, Bethesda, MD 20892 USA. RI Shabalina, Svetlana/N-8939-2013; Roytberg, Mikhail/O-1299-2013 OI Shabalina, Svetlana/0000-0003-2272-7473; Roytberg, Mikhail/0000-0002-5848-367X NR 29 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD DEC PY 2002 VL 18 IS 12 BP 1673 EP 1680 DI 10.1093/bioinformatics/18.12.1673 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 627TG UT WOS:000179951800017 PM 12490453 ER PT J AU Ogurtsov, AY Roytberg, MA Shabalina, SA Kondrashov, AS AF Ogurtsov, AY Roytberg, MA Shabalina, SA Kondrashov, AS TI OWEN: aligning long collinear regions of genomes SO BIOINFORMATICS LA English DT Article AB OWEN is an interactive tool for aligning two long DNA sequences that represents similarity between them by a chain of collinear local similarities. OWEN employs several methods for constructing and editing local similarities and for resolving conflicts between them. Alignments of sequences of lengths over 10(6) can often be produced in minutes. OWEN requires memory below 20 L, where L is the sum of lengths of the compared sequences. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. Inst Math Problems Biol, Pushchino 142290, Moscow Region, Russia. RP Ogurtsov, AY (reprint author), NIH, Natl Ctr Biotechnol Informat, 45 Ctr Dr, Bethesda, MD 20892 USA. RI Shabalina, Svetlana/N-8939-2013; Roytberg, Mikhail/O-1299-2013 OI Shabalina, Svetlana/0000-0003-2272-7473; Roytberg, Mikhail/0000-0002-5848-367X NR 3 TC 34 Z9 36 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD DEC PY 2002 VL 18 IS 12 BP 1703 EP 1704 DI 10.1093/bioinformatics/18.12.1703 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 627TG UT WOS:000179951800027 PM 12490463 ER PT J AU Gilbert, PB Wei, LJ Kosorok, MR Clemens, JD AF Gilbert, PB Wei, LJ Kosorok, MR Clemens, JD TI Simultaneous inferences on the contrast of two hazard functions with censored observations SO BIOMETRICS LA English DT Article DE confidence bands; kernel estimation; martingale; survival analysis ID CONFIDENCE BANDS; NONPARAMETRIC REGRESSION; RATES AB In survival analysis, often times the pattern of instantaneous risk over time is more interesting than that of the cumulative risk. For this case, a nonparametric hazard function estimate is more appropriate for summarizing the risk experience of a group of patients than the corresponding Kaplan-Meier estimate. In comparing a new treatment with a standard therapy, it is important to know if the treatment loses it potency during the follow-up period, and if it does, one would like to know when it becomes ineffective. Unfortunately, with a plot of the differences of two Kaplan-Meier curves, it is rather difficult to capture such temporal trends. In this article, we propose simple procedures for constructing confidence bands for the contrast of two hazard functions with censored data. The simultaneous interval estimates are quite useful for identifying possible values of the contrast over time with a certain degree of confidence. The new proposals are illustrated with an example and a small simulation study. C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Dept Biostat, Seattle, WA 98109 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Wisconsin, Dept Stat & Biostat, Madison, WI 53792 USA. Univ Wisconsin, Dept Med Informat, Madison, WI 53792 USA. NICHHD, Bethesda, MD 20892 USA. RP Gilbert, PB (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. FU NCI NIH HHS [CA-75142, CA-56844]; NIAID NIH HHS [AI46703-01] NR 24 TC 26 Z9 26 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2002 VL 58 IS 4 BP 773 EP 780 DI 10.1111/j.0006-341X.2002.00773.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 620NL UT WOS:000179539400008 PM 12495131 ER PT J AU Dunson, DB Baird, DD AF Dunson, DB Baird, DD TI Bayesian modeling of incidence and progression of disease from cross-sectional data SO BIOMETRICS LA English DT Article DE current status; disease markers; factor analysis; latency; multiple outcomes; multistate model; sojourn time; tumor size ID NONPARAMETRIC-ESTIMATION; POSTERIOR DISTRIBUTIONS; MARKOV-CHAINS; SURVIVAL-DATA; SOJOURN TIME; DIAGNOSIS; ONSET; AIDS; AGE AB In the absence of longitudinal data, the current presence and severity of disease can be measured for a sample of individuals to investigate factors related to disease incidence and progression. In this article, Bayesian discrete-time stochastic models are developed for inference from cross-sectional data consisting of the age at first diagnosis, the current presence of disease, and one or more surrogates of disease severity. Semiparametric models are used for the age-specific hazards of onset and diagnosis, and a normal underlying variable approach is proposed for modeling of changes with latency time in disease severity. The model accommodates multiple surrogates of disease severity having different measurement scales and heterogeneity among individuals in disease progression. A Markov chain Monte Carlo algorithm is described for posterior computation, and the methods are applied to data from a study of uterine leiomyoma. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 NR 29 TC 9 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD DEC PY 2002 VL 58 IS 4 BP 813 EP 822 DI 10.1111/j.0006-341X.2002.00813.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 620NL UT WOS:000179539400012 ER PT J AU Skillman, AG Maurer, KW Roe, DC Stauber, MJ Eargle, D Ewing, TJA Muscate, A Davioud-Charvet, E Medaglia, MV Fisher, RJ Arnold, E Gao, HQ Buckheit, R Boyer, PL Hughes, SH Kuntz, ID Kenyon, GL AF Skillman, AG Maurer, KW Roe, DC Stauber, MJ Eargle, D Ewing, TJA Muscate, A Davioud-Charvet, E Medaglia, MV Fisher, RJ Arnold, E Gao, HQ Buckheit, R Boyer, PL Hughes, SH Kuntz, ID Kenyon, GL TI A novel mechanism for inhibition of HIV-1 reverse transcriptase SO BIOORGANIC CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA-POLYMERASES; RNASE-H; MOLECULAR DOCKING; GENERAL INHIBITOR; RIBONUCLEASE-H; NUCLEIC-ACIDS; AIDS; SENSITIVITY; MUTAGENESIS AB The human immunodeficiency virus (HIV) epidemic is an important medical problem. Although combination drug regimens have produced dramatic decreases in viral load, current therapies do not provide a cure for HIV infection. We have used structure-based design and combinatorial medicinal chemistry to identify potent and selective HIV-1 reverse transcriptase (RT) inhibitors that may work by a mechanism distinct from that of current HIV drugs. The most potent of these compounds (compound 4, 2-naphthalenesulfonic acid, 4-hydroxy-7-[[[[5-hydroxy-6-[(4-cinnamylphenyl)-azo]-7-sulfo-2-naphthalenyl]amino]carbonyl]amino]-3-[(4-cinnamylphenyl)- azo], disodium salt) has an IC50 of 90 nM for inhibition of polymerase chain extension, a K-d of 40 nM for inhibition of DNA-RT binding, and an IC50 of 25-100 nM for inhibition of RNaseH cleavage. The parent compound (1) was as effective against 10 nucleoside and non-nucleoside resistant HIV-1 RT mutants as it was against the wild-type enzyme. Compound 4 inhibited HIV-1 RT and murine leukemia virus (MLV) RT, but it did not inhibit T-4 DNA polymerase, T-7 DNA polymerase, or the Klenow fragment at concentrations up to 200 nM. Finally, compound 4 protected cells from HIV-1 infection at a concentration more than 40 times lower than the concentration at which it caused cellular toxicity. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick, MD 21702 USA. Rutgers State Univ, Dept Chem, Piscataway, NJ 08854 USA. So Res Inst, Dept Infect Dis Res, Frederick, MD 21701 USA. RP Kenyon, GL (reprint author), Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. RI Fisher, Robert/B-1431-2009; Davioud-Charvet, Elisabeth/I-3805-2013 OI Davioud-Charvet, Elisabeth/0000-0001-7026-4034 NR 42 TC 31 Z9 35 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0045-2068 J9 BIOORG CHEM JI Bioorganic Chem. PD DEC PY 2002 VL 30 IS 6 BP 443 EP 458 DI 10.1016/S0045-2068(02)00502-3 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 662WB UT WOS:000181971000005 PM 12642128 ER PT J AU Sinha, N Mohan, S Lipschultz, CA Smith-Gill, SJ AF Sinha, N Mohan, S Lipschultz, CA Smith-Gill, SJ TI Differences in electrostatic properties at antibody-antigen binding sites: Implications for specificity and cross-reactivity SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; EGG-WHITE LYSOZYME; SALT BRIDGES; CONFORMATIONAL-CHANGES; BROWNIAN DYNAMICS; CRYSTAL-STRUCTURE; POINT MUTATIONS; COMBINING SITE; ASSOCIATION; COMPLEX AB Antibodies HyHEL8, HyHEL10, and HyHEL26 (HH8, HH10, and HH26, respectively) recognize highly overlapping epitopes on hen egg-white lysozyme (HEL) with similar affinities, but with different specificities. HH8 binding to HEL is least sensitive toward mutations in the epitope and thus is most cross-reactive, HH26 is most sensitive, whereas the sensitivity of HH10 lies in between HH8 and HH26. Here we have investigated intra- and intermolecular interactions in three antibody-protein complexes: theoretical models of HH8-HEL and HH26-HEL complexes, and the x-ray crystal structure of HH10-HEL complex. Our results show that HH8-HEL has the lowest number and HH26-HEL has the highest number of intra-and intermolecular hydrogen bonds. The number of salt bridges is lowest in HH8-HEL and highest in HH26-HEL. The binding site salt bridges in HH8-HEL are not networked, and are weak, whereas, in HH26-HEL, an intramolecular salt-bridge triad at the binding site is networked to an intermolecular triad to form a pentad. The pentad and each salt bridge of this pentad are exceptionally stabilizing. The number of binding-site salt bridges and their strengths are intermediate in HH10-HEL, with an intramolecular triad. Our further calculations show that the electrostatic component contributes the most to binding energy of HH26-HEL, whereas the hydrophobic component contributes the most in the case of HH8-HEL. A "hot-spot" epitope residue Lys-97 forms an intermolecular salt bridge in HH8-HEL, and participates in the intermolecular pentad in the HH26-HEL complex. Mutant modeling and surface plasmon resonance (SPR) studies show that this hot-spot epitope residue contributes significantly more to the binding than an adjacent epitope residue, Lys-96, which does not form a salt bridge in any of the three HH-HEL complexes. Furthermore, the effect of mutating Lys-97 is most severe in HH26-HEL. Lys-96, being a charged residue, also contributes the most in HH26-HEL among the three complexes. The SPR results on these mutants also highlight that the apparent "electrostatic steering" on net on rates actually act at post-collision level stabilization of the complex. The significance of this work is the observed variations in electrostatic interactions among the three complexes. Our work demonstrates that higher electrostatics, both as a number of short-range electrostatic interactions and their contributions, leads to higher binding specificity. Strong salt bridges, their networking, and electrostatically driven binding, limit flexibilities through geometric constrains. In contrast, hydrophobic driven binding and low levels of electrostatic interactions are associated with conformational flexibility and cross-reactivity. C1 NCI, Basic Res Labs, NIH, Frederick, MD 21702 USA. RP Smith-Gill, SJ (reprint author), NCI, Basic Res Labs, NIH, Bldg 469,Rm 206, Frederick, MD 21702 USA. NR 88 TC 68 Z9 69 U1 0 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2002 VL 83 IS 6 BP 2946 EP 2968 PG 23 WC Biophysics SC Biophysics GA 633AD UT WOS:000180256300005 PM 12496069 ER PT J AU Niu, SL Litman, BJ AF Niu, SL Litman, BJ TI Determination of membrane cholesterol partition coefficient using a lipid vesicle-cyclodextrin binary system: Effect of phospholipid acyl chain unsaturation and headgroup composition SO BIOPHYSICAL JOURNAL LA English DT Article ID TRANSBILAYER MOVEMENT; SUBCELLULAR MEMBRANES; BILAYER MEMBRANES; G-PROTEIN; PHOSPHATIDYLCHOLINE; RECEPTOR; RAFTS; ACID; PHOSPHATIDYLETHANOLAMINE; SPHINGOMYELIN AB Lateral domain or raft formation in biological membranes is often discussed in terms of cholesterol-lipid interactions. Preferential interactions of cholesterol with lipids, varying in headgroup and acyl chain unsaturation, were studied by measuring the partition coefficient for cholesterol in unilamellar vesicles. A novel vesicle-cycloclextrin system was used, which precludes the possibility of cross-contamination between donor-acceptor vesicles or the need to modify one of the vesicle populations. Variation in phospholipid headgroup resulted in cholesterol partitioning in the order of sphingomyelin (SM) > phosphaticlylserine > phosphatidylcholine (PC) > phosphaticlylenthanolamine (PE), spanning a range of partition DeltaG of - 1181 cal/mol to +683 cal/mol for SM and PE, respectively. Among the acyl chains examined, the order of cholesterol partitioning was 18:0(stearic acid), 18:1n-9(oleic acid) PC > di18:1n-9PC > di18:1n-12(petroselenic acid) PC > di18:2n6(linoleic acid) PC > 16:0(palmitic acid),22:6n-3(DHA) PC > di18:3n-3(alpha-linolenic acid) PC > di22:6n-3PC with a range in partition DeltaG of 913 cal/mol. Our results suggest that the large differences observed in cholesterol-lipid interactions contribute to the forces responsible for lateral domain formation in plasma membranes. These differences may also be responsible for the heterogeneous cholesterol distribution in cellular membranes, where cholesterol is highly enriched in plasma membranes and relatively depleted in intracellular membranes. C1 NIAAA, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Litman, BJ (reprint author), 12420 Parklawm Dr Rm 158, Rockville, MD 20852 USA. NR 40 TC 137 Z9 137 U1 6 U2 26 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2002 VL 83 IS 6 BP 3408 EP 3415 PG 8 WC Biophysics SC Biophysics GA 633AD UT WOS:000180256300043 PM 12496107 ER PT J AU Wang, HD Bash, R Yodh, JG Hager, GL Lohr, D Lindsay, SM AF Wang, HD Bash, R Yodh, JG Hager, GL Lohr, D Lindsay, SM TI Glutaraldehyde modified mica: A new surface for atomic force microscopy of chromatin SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEOSOMAL ARRAY; DNA AB We have found that mica surfaces functionalized with aminopropyltriethoxysilane and aldehydes bind chromatin strongly enough to permit stable and reliable solution imaging by atomic force microscopy. The method is highly reproducible, uses very small amounts of material, and is successful even with very light degrees of surface modification. This surface is far superior to the widely used aminopropyltriethoxysilane-derivatized mica surface and permits resolution of structure on the nanometer-scale in an aqueous environment, conditions that are particularly important for chromatin studies. For example, bound nucleosomal arrays demonstrate major structural changes in response to changes in solution conditions, despite their prior fixation (to maintain nucleosome loading) and tethering to the surface with glutaraldehyde. By following individual molecules through a salt titration in a flow-through cell, one can observe significant changes in apparent nucleosome size at lower [salt] and complete loss of DNA from the polynucleosomal array at high salt. The latter result demonstrates that the DNA component in these arrays is not constrained by the tethering. The former result is consistent with the salt-induced loss of histones observed in bulk solution studies of chromatin and demonstrates that even histone components of the nucleosome are somewhat labile in these fixed and tethered arrays. We foresee many important applications for this surface in future atomic force microscopy studies of chromatin. C1 Arizona State Univ, Dept Phys & Astron, Tempe, AZ 85287 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. Midwestern Univ, Coll Osteopath Med, Div Basic Sci, Glendale, AZ 85308 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Lindsay, SM (reprint author), Arizona State Univ, Dept Phys & Astron, Tempe, AZ 85287 USA. FU NCI NIH HHS [CA 859900-02] NR 30 TC 88 Z9 92 U1 2 U2 25 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD DEC PY 2002 VL 83 IS 6 BP 3619 EP 3625 PG 7 WC Biophysics SC Biophysics GA 633AD UT WOS:000180256300065 PM 12496129 ER PT J AU Diehn, FE Costouros, NG Miller, MS Feldman, AL Alexander, HR Li, KCP Libutti, SK AF Diehn, FE Costouros, NG Miller, MS Feldman, AL Alexander, HR Li, KCP Libutti, SK TI Noninvasive fluorescent imaging reliably estimates biomass in vivo SO BIOTECHNIQUES LA English DT Article ID IN-VIVO; EXPRESSING TUMORS; GENE; METASTASIS; ANIMALS; GROWTH AB Whole-body optical imaging of small animals has emerged as a powerful, user-friendly, and high-throughput tool for assaying molecular and cellular processes as they occur in vivo. As with any imaging method, the utility of such technology relies on its ability to provide quantitative, biologically meaningful information about the physiologic or pathologic process of interest. Here we used an animal tumor model to evaluate the extent of correlation between noninvasively measured fluorescence and more traditional measurements of biomass (tumor volume and tumor weight). C57/BL6 mice were injected subcutaneously with murine colon adenocarcinoma cells that were engineered to express GFP Serial measurements of fluorescence intensities were performed with a macroscopic in vivo fluorescence system. The progressive increases in intensity correlated strongly with growth in tumor volume, as determined by caliper measurements (R-2 = 0.99). A more stringent correlation was found between fluorescence intensity and tumor weight (R-2 = 0.97) than between volume and weight (R-2 = 0.89). In a treatment experiment using tumor necrosis factor-a, fluorescence intensity (but not tumor volume) was able to differentiate between treated and control groups on day I post-treatment. These results validate the ability of noninvasive fluorescent imaging to quantify the number of viable, fluorescent cells in vivo. C1 NIH, Bethesda, MD 20892 USA. RP Libutti, SK (reprint author), Ctr Canc Res, Surg Branch, NCI, 10 Ctr Dr,Rm 3C428, Bethesda, MD 20892 USA. RI Feldman, Andrew/D-5028-2012 NR 17 TC 14 Z9 14 U1 0 U2 2 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 2002 VL 33 IS 6 BP 1250 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 628LL UT WOS:000179996500014 PM 12503309 ER PT J AU Howard, EI Cachau, RE AF Howard, EI Cachau, RE TI Ink-jet printer heads for ultra-small-drop protein crystallography SO BIOTECHNIQUES LA English DT Article ID CRYSTALLIZATION AB Mass-produced automated piezoelectric driven picoliter delivery systems (printer heads) are fast, inexpensive, and reliable devices that are capable of delivering a very large range of volumes and are ideally suited for high-throughput protein crystallography studies. We used this technology to set up under-oil crystallization experiments with drop sizes from the 200-nL to 3-muL volume range, commonly used in protein crystallography, and show its application in setting ultra-small (2 nL) drops, the smallest drop volume reported to date for this type of assay. C1 NCI, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. IFLYSIB, RA-1900 La Plata, Argentina. Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. RP Howard, EI (reprint author), NCI, SAIC, Adv Biomed Comp Ctr, 430 Miller Dr, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-12400] NR 16 TC 8 Z9 9 U1 0 U2 3 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD DEC PY 2002 VL 33 IS 6 BP 1302 EP + PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 628LL UT WOS:000179996500021 PM 12503316 ER PT J AU Arnulf, B Villemain, A Nicot, C Mordelet, E Charneau, P Kersual, J Zermati, Y Mauviel, A Bazarbachi, A Hermine, O AF Arnulf, B Villemain, A Nicot, C Mordelet, E Charneau, P Kersual, J Zermati, Y Mauviel, A Bazarbachi, A Hermine, O TI Human T-cell lymphotropic virus oncoprotein Tax represses TGF-beta 1 signaling in human T cells via c-Jun activation: a potential mechanism of HTLV-I leukemogenesis SO BLOOD LA English DT Article ID GROWTH-FACTOR-BETA; TRANSCRIPTION FACTOR AP-1; NECROSIS-FACTOR-ALPHA; TGF-BETA; TYPE-1 TAX; GENE-EXPRESSION; LEUKEMIA-LYMPHOMA; INTERFERON-ALFA; PROTEIN; BINDING AB Human T-cell leukemia virus I is the etiologic agent of adult T-cell leukemia (ATL), an aggressive T-cell malignancy. The viral oncoprotein Tax, through the activation of nuclear factorKB (NF-kappaB), CCAAT-enhancer binding protein (CREB), and activated protein-1 (AP-1) pathways, is a transcriptional regulator of critical genes for T-cell homeostasis. In ATL cells, activated AP-1 complexes induce the production of transforming growth factor [31 (TGF-beta1). TGF-beta1 is an inhibitor of T-cell proliferation and cytotoxicity. Here we show that, in contrast to normal peripheral T cells, ATL cells are resistant to TGF-beta1-induced growth inhibition. The retroviral transduction of the Tax protein in peripheral T cells resulted in the loss of TGF-beta1 sensitivity. Transient transfection of Tax in HepG2 cells specifically inhibited Smad/TGF-beta1 signaling in a dose-dependent manner. In the presence of Tax transfection, increasing amounts of Smad3 restored TGF-beta1 signaling. Tax mutants unable to activate NF-KB or CREB pathways were also able to repress Smad3 transcriptional activity. Next we have demonstrated that Tax inhibits TGF-beta1 signaling by reducing the Smad3 DNA binding activity. However, Tax did not decrease the expression and the nuclear translocation of Smad3 nor did it interact physically with Smad3. Rather, Tax induced c-Jun N-terminal kinase (JNK) activity and c-Jun phosphorylation, leading to the formation of Smad3/c-Jun complexes. Whereas c-Jun alone abrogates Smad3 DNA binding, cotransfection of Tax and of a dominant-negative form of JNK or a c-Jun antisense-restored Smad3 DNA binding activity and TGF-[31 responsiveness. In ATL and in normal T cells transduced by Tax, c-Jun was constitutively phosphorylated. Thus, we describe a new function of Tax, as a repressor of TGF-[31 signaling through JNK/c-Jun constitutive activation, which may play a critical role in ATL leukemogenesis. (Blood. 2002; 100:4129-4138) (C) 2002 by The American Society of Hematology. C1 Univ Paris 05, Hop Necker Enfants Malad, CNRS UMR 8603, F-75743 Paris 15, France. Inst Pasteur, Unite Oncol Virale, F-75724 Paris, France. Hop St Louis, INSERM U532, Inst Rech Peau, Paris, France. NCI, Basic Res Lab, Div Basic Sci, Bethesda, MD 20892 USA. Amer Univ Beirut, Dept Internal Med, Beirut, Lebanon. RP Hermine, O (reprint author), Univ Paris 05, Hop Necker Enfants Malad, CNRS UMR 8603, Batiment Sevres Porte 584,149-161 Rue Sevres, F-75743 Paris 15, France. RI MAUVIEL, Alain/F-6251-2013 NR 56 TC 61 Z9 64 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD DEC 1 PY 2002 VL 100 IS 12 BP 4129 EP 4138 DI 10.1182/blood-2001-12-0372 PG 10 WC Hematology SC Hematology GA 619BP UT WOS:000179453700036 PM 12393612 ER PT J AU Atti, E Gomez, S Wahl, SM Mendelsohn, R Paschalis, E Boskey, AL AF Atti, E Gomez, S Wahl, SM Mendelsohn, R Paschalis, E Boskey, AL TI Effects of transforming growth factor-beta deficiency on bone development: A Fourier transform-infrared imaging analysis SO BONE LA English DT Article DE transforming growth factor-beta (TGF-beta); knockout mouse; infrared imaging (IR); mineralization ID FTIR MICROSPECTROSCOPIC ANALYSIS; DEVELOPING RAT MOLARS; COLLAGEN CROSS-LINKS; TGF-BETA; GROWTH-FACTOR-BETA-1 GENE; ALKALINE-PHOSPHATASE; MINERALIZING TISSUES; INCREASED EXPRESSION; CALCIUM-PHOSPHATE; FACTOR-BETA-1 AB Transforming growth factor-beta 1 (TGF-beta1) is a cytokine member of the TGF-beta superfamily involved in the control of proliferation and differentiation of various cell types. TGF-beta1 plays an important role in bone formation and resorption. To determine the effect of TGF-beta1 deficiency on bone mineral and matrix, tibias from mice in which TGF-beta1 expression had been ablated (TGF-beta1 null) were analyzed and compared with background- and age-matched wild-type (WT) control animals by Fourier transform-infrared imaging (FTIRI) and histochemistry. FTIRI allows the characterization of nondemineralized thin tissue sections at the ultrastructural level with a spatial resolution of similar to7 pm. The spectroscopic parameters calculated were: mineral-to-matrix ratio (previously shown to correspond to ash weight); mineral crystallinity (related to the crystallographically determined crystallite size and perfection in the apatite c-axis direction); and collagen maturity (related to the ratio of pyridinoline:delf-DHLNL collagen cross-links). Several fields were selected to represent different stages of bone development within the same specimen from the secondary ossification center to the distal diaphysis. Anatomically equivalent areas were compared as a function of age and genotype. The spectroscopic results were expressed both as color-coded images and as pixel population distributions for each of the thread parameters monitored. Based on comparisons of histochemistry and FTIRI, there were distinctive age and genotype variations. At all ages examined, in the TGF-beta1 null mice growth plates, alkaline phosphatase (ALP) activity and collagen maturity were reduced, but no effect on mineral content or crystallinity was noted. In the TGF-beta1 null mice metaphyses, there was a persistence of trabeculae, but no significant alterations in mineral content or crystallinity. In contrast, mineral content, mineral crystallinity, and collagen maturity were reduced in the secondary ossification center and cortical bone of the TGF-beta1 null mice. These results, consistent with a, mechanism of impaired bone maturation in the TGF-beta1 null mice, may be directly related to TGF-beta1 deficiency and indirectly to increased expression of inflammatory cytokines in the TGFbeta1 null mice. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 Hosp Special Surg, Mineralized Tissues Lab, New York, NY 10021 USA. Rutgers State Univ, Dept Chem, Newark, NJ 07102 USA. Univ Cadiz, Dept Anat Patol, Cadiz, Spain. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Boskey, AL (reprint author), Hosp Special Surg, Mineralized Tissues Lab, 535 E 70th St, New York, NY 10021 USA. FU NIAMS NIH HHS [AR03125, AR46121]; NIDCR NIH HHS [DE04141] NR 58 TC 40 Z9 43 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD DEC PY 2002 VL 31 IS 6 BP 675 EP 684 AR PII S8756-3282(02)00905-5 DI 10.1016/S8756-3282(02)00905-5 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 630MG UT WOS:000180111300006 PM 12531561 ER PT J AU Mattei, D Mordini, N Lo Nigro, C Ghirardo, D Ferrua, MT Osenda, M Gallamini, A Bacigalupo, A Viscoli, C AF Mattei, D Mordini, N Lo Nigro, C Ghirardo, D Ferrua, MT Osenda, M Gallamini, A Bacigalupo, A Viscoli, C TI Voriconazole in the management of invasive aspergillosis in two patients with acute myeloid leukemia undergoing stem cell transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE acute myeloid leukemia; invasive aspergillosis; voriconazole; stem cell transplantation ID INTENSIVE CHEMOTHERAPY COMPLETION; BONE-MARROW TRANSPLANTATION; PULMONARY ASPERGILLOSIS; HEMATOLOGICAL MALIGNANCIES; NEUTROPENIC PATIENTS; FUNGAL INFECTION; THERAPY; IMPACT AB The management of invasive aspergillosis in patients with hematological malignancies remains controversial. A major problem is how to manage patients who had invasive aspergillosis during remission induction and consolidation therapy and then undergo SCT. Indeed in these patients the mortality rate related to invasive aspergillosis recurrence remains unacceptably high. We report two cases of patients who underwent remission induction for AML, developed invasive aspergillosis during antifungal prophylaxis with itraconazole, failed amphotericin B deoxycholate and liposomal amphotericin B treatment, were successfully treated with voriconazole and eventually underwent SCT with voriconazole prophylaxis without reactivation of invasive aspergillosis. C1 Osped S Croce, Div Ematol, Dept Hematol, I-12100 Cuneo, Italy. Osped S Croce, Dept Radiol, I-12100 Cuneo, Italy. Osped S Croce, Dept Lab, I-12100 Cuneo, Italy. San Martino Hosp, Dept Hematol, Genoa, Italy. Natl Canc Inst, Genoa, Italy. RP Mattei, D (reprint author), Osped S Croce, Div Ematol, Dept Hematol, Via Michele Coppino 26, I-12100 Cuneo, Italy. OI Mattei, Daniele /0000-0003-3152-4416 NR 23 TC 15 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD DEC PY 2002 VL 30 IS 12 BP 967 EP 970 DI 10.1038/sj.bmt.1703763 PG 4 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 630DZ UT WOS:000180093400022 PM 12476292 ER PT J AU Quong, J Eppenberger-Castori, S Moore, D Scott, GK Birrer, MJ Kueng, W Eppenberger, U Benz, CC AF Quong, J Eppenberger-Castori, S Moore, D Scott, GK Birrer, MJ Kueng, W Eppenberger, U Benz, CC TI Age-dependent changes in breast cancer hormone receptors and oxidant stress markers SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE aging; breast cancer; hormone receptors; oxidant stress markers ID SOUTHWEST-ONCOLOGY-GROUP; LIGAND-BINDING ASSAY; PROGESTERONE-RECEPTOR; ESTROGEN-RECEPTOR; GENE-EXPRESSION; TRANSCRIPTION FACTORS; PREDICTING RESPONSE; DNA-BINDING; TAMOXIFEN; METHYLATION AB Breast cancer incidence increases with age but this relationship has not been fully explored with regard to expression of estrogen receptor (ER) and ER-inducible genes (PR, pS2, Bcl2, cathepsin D), or the age-dependence of oxidant stress markers that also affect ER-inducible gene expression. In this three-part study, we first correlated age at diagnosis with expression of breast cancer markers ER, PR, pS2, Bcl2, and cathepsin D, quantitated by enzyme immunoassays from a European collective of 3000 cryobanked primary breast cancers and 300 adjacent non-malignant breast tissues. Results were then compared with ER and PR data reported to the SEER registry for 83,541 US cancers diagnosed during 1992-1997. Lastly, a homogeneous subset of 70 ER-positive tumors preselected from the European collective was blindly analyzed for age-specific changes in the DNA-binding content of redox-sensitive transcriprtion factors, AP1 and Sp1, and the oxidant stress-activated protein kinase, phosphorylated( P)-Erk5. Increases in breast tumor ER from patients aged < 30 to > 80 years mirrored 10-fold lower increases in non-malignant breast tissue ER content up to age 60, rising faster thereafter and reaching a near 25-fold differential between malignant and non-malignant breast tissue by age 80. ER-inducible markers PR, pS2, Bcl2, and cathepsin D were overexpressed in tumors relative to non-malignant breast tissue but, unlike ER, did not increase with patient age. While SEER data demonstrated that the increase in US breast cancer incidence rates after age 50 is confined to ER-positive tumors in patients of all ethnic subsets, these patients also showed a striking increase in the proportion of higher-risk ER-positive/PR-negative breast cancers arising after age 50. Mechanistically essential for ER-inducible PR expression, Sp1 DNA-binding function (but not Sp1 content) was lost with age in ER-positive tumors; and this functional defect correlated with increased tumor content of the oxidant stress marker, P-Erk5. Altogether these findings support two hypotheses: (i) dysregulated ER expression underlies the age-specific increase in breast cancer incidence after age 50; and (ii) oxidative stress and loss of Sp1 DNA-binding may contribute to an increasing incidence in higher-risk ER-positive/PR-negative breast cancers with aging. C1 Buck Inst Age Res, Canc & Dev Therapeut Program, Novato, CA USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Clin, Dept Res, Basel, Switzerland. Stiftung Tumorbank Basel, Basel, Switzerland. Calif Pacific Med Ctr, Geraldine Brush Canc Res Inst, San Francisco, CA 94115 USA. NCI, Bethesda, MD 20892 USA. RP Benz, CC (reprint author), Buck Inst Age Res, Canc & Dev Therapeut Program, 8001 Redwood Blvd, Novato, CA USA. FU NCI NIH HHS [R01-CA71468] NR 55 TC 44 Z9 48 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 IS 3 BP 221 EP 236 DI 10.1023/A:1020886801674 PG 16 WC Oncology SC Oncology GA 609WR UT WOS:000178929800005 PM 12462383 ER PT J AU Allred, DC Bryant, J Land, S Paik, S Fisher, E Julian, T Margolese, R Smith, R Mamounas, T Osborne, CK Fisher, B Wolmark, N AF Allred, DC Bryant, J Land, S Paik, S Fisher, E Julian, T Margolese, R Smith, R Mamounas, T Osborne, CK Fisher, B Wolmark, N TI Estrogen receptor expression as a predictive marker of the effectiveness of tamoxifen in the treatment of DCIS: Findings from NSABP Protocol B-24. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Pittsburgh, PA USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. NR 0 TC 53 Z9 57 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 30 BP S36 EP S36 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100032 ER PT J AU Anderson, WF Chu, KC Chang, S AF Anderson, WF Chu, KC Chang, S TI Inflammatory breast carcinoma and non-inflammatory locally advanced carcinoma of the breast, distinct clinicopathologic entities? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 303 BP S82 EP S82 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100214 ER PT J AU Bader, JL Trefzger, W Glassman, B Nichols, C AF Bader, JL Trefzger, W Glassman, B Nichols, C TI Breast cancer on the internet. What people really want to know. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Natl Canc Inst, Rockville, MD USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 320 BP S86 EP S86 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100232 ER PT J AU Elkahloun, AG AF Elkahloun, AG TI Breast cancer functional genomics. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 182 BP S58 EP S58 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100119 ER PT J AU Fisher, B Jeong, JH Bryant, J Mamounas, EP Dignam, JJ Wolmark, N AF Fisher, B Jeong, JH Bryant, J Mamounas, EP Dignam, JJ Wolmark, N TI Findings from two decades of National Surgical Adjuvant Breast and Bowel Project clinical trials involving breast cancer patients with negative axillary nodes. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 NSABP, Pittsburgh, PA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 16 BP S32 EP S32 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100017 ER PT J AU Grubbs, CJ You, M Kopelovich, L Lubet, RA AF Grubbs, CJ You, M Kopelovich, L Lubet, RA TI Chemopreventive effects of rosiglitazone, 9-cis-retinoic acid and targretin in the methylnitrosourea (MNU) induced model of mammary cancer in rats. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Univ Alabama, Birmingham, AL USA. Ohio State Univ, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 420 BP S108 EP S108 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100317 ER PT J AU Hoelz, DJ Kowalak, J Maynard, D Markey, S Hickey, RJ Schnaper, L Malkas, LH AF Hoelz, DJ Kowalak, J Maynard, D Markey, S Hickey, RJ Schnaper, L Malkas, LH TI Signaling in breast cancer: stopping DNA replication and facilitating DNA repair. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Indiana Canc Res Inst, Indianapolis, IN USA. Greater Baltimore Med Ctr, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 559 BP S140 EP S140 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100439 ER PT J AU Hoover, F Svendsen, A Thorsen, F Huszthy, P Kotin, R Afione, S Halbert, C Miller, AD Wilson, J Bjerkvig, R Lonning, PE AF Hoover, F Svendsen, A Thorsen, F Huszthy, P Kotin, R Afione, S Halbert, C Miller, AD Wilson, J Bjerkvig, R Lonning, PE TI Adeno-associated viral (AAV) vector serotypes transduce a broad host range of human breast cancer cell lines. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Haukeland Hosp, N-5021 Bergen, Norway. NIH, Bethesda, MD USA. Univ Washington, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 378 BP S101 EP S101 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100291 ER PT J AU Kim, HT Kong, G DeNardo, D Pal, S Duong, S Hilsenbeck, S Bissonnette, R Lamph, W Johnson, K Brown, P AF Kim, HT Kong, G DeNardo, D Pal, S Duong, S Hilsenbeck, S Bissonnette, R Lamph, W Johnson, K Brown, P TI Identification of genes regulated by the RXR-selective retinoid, LGD1069, in human breast cells using oligonucleotide arrays. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Baylor Coll Med, Houston, TX 77030 USA. Ligand Pharmaceut Inc, San Diego, CA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 184 BP S58 EP S58 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100120 ER PT J AU Levine, PH Coronel, SM Pogo, BGT Klouj, A Holland, JF Mourali, N Woodson, K AF Levine, PH Coronel, SM Pogo, BGT Klouj, A Holland, JF Mourali, N Woodson, K TI Increasing evidence for a human breast cancer virus. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 George Washington Univ, Sch Publ Hlth, Washington, DC 20052 USA. Mt Sinai Sch Med, New York, NY USA. Inst Salah Azaiz, Tunis, Tunisia. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 684 BP S168 EP S168 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100548 ER PT J AU Levine, PH Sherman, M Veneroso, CC AF Levine, PH Sherman, M Veneroso, CC TI The inflammatory breast cancer registry: an approach to standardization. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 George Washington Univ, Sch Publ Hlth, Washington, DC USA. Hlth Serv, Washington, DC USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 305 BP S83 EP S83 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100217 ER PT J AU Lubet, RA Grubbs, CJ You, M AF Lubet, RA Grubbs, CJ You, M TI Effects of various doses of tamoxifen and the aromatase inhibitor vorozole on RNA expression in MNU induced mammary tumors. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 NCI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 422 BP S109 EP S109 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100320 ER PT J AU Poggi, MM Danforth, DN Sciuto, LC Smith, SL Steinberg, SM Liewehr, DJ Menard, C Lippman, ME Lichter, AS Altemus, RM AF Poggi, MM Danforth, DN Sciuto, LC Smith, SL Steinberg, SM Liewehr, DJ Menard, C Lippman, ME Lichter, AS Altemus, RM TI Cancer events after 18 years of follow-up in the treatment of early-stage breast cancer with mastectomy versus breast conservation therapy. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 NCI, Bethesda, MD 20892 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 28 BP S35 EP S35 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100029 ER PT J AU Wang, J Costantino, JP Tan-Chiu, E Wickerham, DL Wolmark, N AF Wang, J Costantino, JP Tan-Chiu, E Wickerham, DL Wolmark, N TI Benign breast disease and the risk of subsequent invasive breast cancer: findings from the National Surgical Adjuvant Breast and Bowel Project's breast cancer prevention trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 32 BP S36 EP S36 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100033 ER PT J AU Zujewski, J Eng-Wong, J Reynolds, J Venzon, D Schmidt, E Chow, C Premkumar, A Merino, MJ Goldspeil, B Forman, M Stratton, P Klein, P Mershon, J Liu, ET AF Zujewski, J Eng-Wong, J Reynolds, J Venzon, D Schmidt, E Chow, C Premkumar, A Merino, MJ Goldspeil, B Forman, M Stratton, P Klein, P Mershon, J Liu, ET TI A phase 2 trial of raloxifene in premenopausal women at high risk for developing invasive breast cancer. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 25th San Antonio Breast Cancer Symposium CY DEC 11-14, 2002 CL SAN ANTONIO, TEXAS C1 Natl Canc Inst, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RI Venzon, David/B-3078-2008; Liu, Edison/C-4141-2008 NR 0 TC 2 Z9 2 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD DEC PY 2002 VL 76 SU 1 MA 417 BP S108 EP S108 PG 1 WC Oncology SC Oncology GA 624QA UT WOS:000179770100314 ER PT J AU Zeng, WH Maciejewski, JP Chen, GB Risitano, AM Kirby, M Kajigaya, S Young, NS AF Zeng, WH Maciejewski, JP Chen, GB Risitano, AM Kirby, M Kajigaya, S Young, NS TI Selective reduction of natural killer T cells in the bone marrow of aplastic anaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE NKT cells; V alpha 24J alpha Q; aplastic anaemia; autoimmune disease; CDR3 size ID NKT CELLS; ALPHA-GALACTOSYLCERAMIDE; MYELODYSPLASTIC SYNDROMES; ANTIGEN RECEPTOR; ANEMIA; TCR; RECOGNITION; PREVENTS; EXPRESSION; REPERTOIRE AB T cell- mediated suppression of haematopoiesis is believed to play an important role in the pathophysiology of aplastic anaemia ( AA) and in the pancytopenia of some myelodysplastic syndromes ( MDS). Natural- killer T ( NKT) cells belong to a unique lymphocyte subset that expresses an invariant T- cell receptor ( TCR), consisting of Valpha24JalphaQ, and common NK cell surface markers. NKT cells have been hypothesized to play a role in immune regulation, and many human autoimmune conditions are associated with NKT cell deficiency. Here we investigate the role of NKT cells in AA and MDS patients. Flow cytometry demonstrated that NKT cells, unlike other T- lymphocyte subpopulations, were disproportionally decreased in AA and MDS marrow. When we compared variability within the CDR3 region of Valpha24 in CD4(-) CD8(-) T cells derived from AA and healthy individuals, the CDR3 size of Va24 cells showed a polyclonal distribution in AA patients, while in control subjects a typical oligoclonal or monoclonal pattern was found. Southern blot and sequence analysis of Valpha24 polymerase chain reaction products revealed that the NKT cell- specific JalphaQ region was predominant in control subjects, whereas it was not, or only very weakly, detected in AA and MDS patients. These results show that NKT cells are profoundly decreased in AA and MDS, and their deficiency may, as in other human autoimmune diseases, play a role in the local immune dysregulation in AA and MDS. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Zeng, WH (reprint author), Bldg 10,Room 7c103,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 35 TC 30 Z9 36 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2002 VL 119 IS 3 BP 803 EP 809 DI 10.1046/j.1365-2141.2002.03875.x PG 7 WC Hematology SC Hematology GA 616CF UT WOS:000179283600035 PM 12437663 ER PT J AU Wang, M Tang, DC Liu, WL Chin, K Zhu, JQG Fibach, E Rodgers, GP AF Wang, M Tang, DC Liu, WL Chin, K Zhu, JQG Fibach, E Rodgers, GP TI Hydroxyurea exerts bi-modal dose-dependent effects on erythropoiesis in human cultured erythroid cells via distinct pathways SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE hydroxyurea; human erythroid cells; GATA; death receptor; egr-1 ID TRANSCRIPTION FACTOR GATA-1; GROWTH RESPONSE-1 GENE; FETAL HEMOGLOBIN; BETA-THALASSEMIA; LIQUID CULTURE; MYELODYSPLASTIC SYNDROMES; HEMATOPOIETIC STEM; COLONY GROWTH; EXPRESSION; PROGENITORS AB Hydroxyurea (HU) has been shown to increase the proportion of fetal haemoglobin (HbF) in most sickle cell patients. A low-dosage regimen increased total haemoglobin (Hb) levels in some thalassaemia intermedia patients by preferentially increasing beta-globin biosynthesis. To further characterize these apparent dose-dependent effects of HU, we examined erythroid cells exposed to HU (5-100 mumol/l) in two-phase liquid culture. Low doses (from 5 to 25 mumol/l) increased Hb levels by up to 2.7-fold, and a high dose (100 mumol/l) increased Hb levels when added at d 3-6 of phase II, with no significant changes in response to HU during the late stage of phase II culture ( 9 d). HU exposure during d 0-3 of phase II culture increased the number of erythroid colonies to a maximum of fivefold at 5 mumol/l HU. GATA-1 mRNA was downregulated at a high dose and GATA-2 was dose dependently upregulated over a lower dosage range. Treatment with 100 mumol/l HU dramatically upregulated the death receptor DR-5, caspase 3, as determined by cDNA microarray analysis. In contrast, 10 mumol/l HU modestly upregulated mRNA levels of the early growth response gene. Our results suggest that HU exerts concentration-dependent effects on HbF production and erythropoiesis and that these two effects are mediated by distinct molecular mechanisms. C1 NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NIDDKD, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N119,10 Ctr Dr, Bethesda, MD 20892 USA. NR 33 TC 22 Z9 22 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD DEC PY 2002 VL 119 IS 4 BP 1098 EP 1105 DI 10.1046/j.1365-2141.2002.03958.x PG 8 WC Hematology SC Hematology GA 623FR UT WOS:000179693100033 PM 12472594 ER PT J AU Kutlu, T Gelboin, HV Gozukara, EM AF Kutlu, T Gelboin, HV Gozukara, EM TI Cigarette smoking and secondary smoke in Turkey: Effect on placental aryl hydrocarbon hydroxylase (AHH), infant birth weight, and size SO BULLETIN OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID METABOLISM; PREGNANCY C1 Inonu Univ, Fac Med, Dept Biochem, TR-44069 Malatya, Turkey. Inonu Univ, Fac Arts & Sci, Dept Biochem, TR-44069 Malatya, Turkey. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Gozukara, EM (reprint author), Inonu Univ, Fac Med, Dept Biochem, TR-44069 Malatya, Turkey. NR 17 TC 2 Z9 2 U1 0 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0007-4861 J9 B ENVIRON CONTAM TOX JI Bull. Environ. Contam. Toxicol. PD DEC PY 2002 VL 69 IS 6 BP 855 EP 862 DI 10.1007/s00128-002-0138-y PG 8 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 617CN UT WOS:000179342800012 PM 12428163 ER PT J AU Hellemans, KGC Shaham, Y Olmstead, MC AF Hellemans, KGC Shaham, Y Olmstead, MC TI Effects of acute and prolonged opiate abstinence on extinction behaviour in rats SO CANADIAN JOURNAL OF EXPERIMENTAL PSYCHOLOGY-REVUE CANADIENNE DE PSYCHOLOGIE EXPERIMENTALE LA English DT Article ID OPPONENT-PROCESS THEORY; PHYSICAL-DEPENDENCE; HEROIN-SEEKING; NUCLEUS-ACCUMBENS; COCAINE-SEEKING; RHESUS-MONKEYS; ANIMAL-MODEL; WITHDRAWAL; MORPHINE; RELAPSE AB We examined the role of withdrawal in relapse to drug-seeking and drug-taking by testing the effects of opiate abstinence on extinction behaviour in rats trained to self-administer heroin. Male Long-Evans rats responded for IV heroin under a heterogeneous chain (Vi 120 s; Flt 1) schedule in which "seeking" responses preceded a "taking" response which produced a drug infusion. Responding was then measured in extinction during acute (6, 12, and 24 hr) and prolonged (3, 6, 12, and 25 day) abstinence. Sucrose consumption and somatic withdrawal were assessed at each testing period. During acute abstinence, responses on the "drug-seeking" manipulandum increased at 24 hr, whereas responses on the "drug-taking" manipulandum increased at 6 hr. Both responses were elevated during the 12-day abstinence test. Sucrose consumption was reduced and somatic withdrawal scores were increased in opiate-experienced rats at each test period. Results suggest that heroin abstinence has different effects on drug-seeking and drug-taking and that these effects do not temporally coincide with somatic measures of opioid withdrawal. C1 Queens Univ, Dept Psychol, Kingston, ON K7L 3N6, Canada. Natl Inst Drug Abuse, Lexington, KY 40583 USA. RP Olmstead, MC (reprint author), Queens Univ, Dept Psychol, Kingston, ON K7L 3N6, Canada. EM olmstead@psyc.queensu.ca RI shaham, yavin/G-1306-2014 NR 51 TC 8 Z9 8 U1 2 U2 5 PU CANADIAN PSYCHOLOGICAL ASSOC PI OTTAWA PA 141 LAURIER AVE WEST, STE 702, OTTAWA, ONTARIO K1P 5J3, CANADA SN 1196-1961 J9 CAN J EXP PSYCHOL JI Can. J. Exp. Psychol.-Rev. Can. Psychol. Exp. PD DEC PY 2002 VL 56 IS 4 BP 241 EP 252 DI 10.1037/h0087400 PG 12 WC Psychology, Experimental SC Psychology GA 621NU UT WOS:000179596700001 PM 12491648 ER PT J AU Mink, PJ Sherman, ME Devesa, SS AF Mink, PJ Sherman, ME Devesa, SS TI Incidence patterns of invasive and borderline ovarian tumors among white women and black women in the United States - Results from the SEER program, 1978-1998 SO CANCER LA English DT Article DE ovary; carcinoma; pathology; incidence; epidemiology; SEER; borderline; neoplasms; histology ID REPRODUCTIVE RISK-FACTORS; ORAL-CONTRACEPTIVE USE; CANCER RISK; COLLABORATIVE ANALYSIS; HISTOLOGIC TYPE; CIGARETTE-SMOKING; MORTALITY; TRENDS; AGE; CLASSIFICATION AB BACKGROUND. Malignant tumors of the ovary are the leading cause of death from gynecologic malignancies in the United States. Population-based incidence data for these neoplasms by histopathologic type and race are limited. Variation in rates may provide clues for future etiologic studies. METHODS. The authors performed a detailed, population-based analysis of U.S. incidence rates by histologic type, race, and age for invasive ovarian tumors that were diagnosed during 1978-1998 and for borderline ovarian tumors that were diagnosed during 1992-1998 using data from the U.S. Surveillance, Epidemiology, and End Results (SEER) Program. RESULTS. white women had significantly higher rates compared with black women of all types of epithelial tumors, with the white:black rate ratios ranging from 1.23 to 2.56. Black women had higher rates of gonadal stromal tumors. Among both white women and black women, total carcinoma rates did not change greatly from 1978-1982 to 1995-1998. Among white women, the reported incidence rates for invasive serous, endometrioid, and clear cell tumors increased during 1978-1998, whereas the rates of mucinous; papillary, not otherwise specified (NOS); and other epithelial tumors declined. Among black women, the reported rates of papillary, NOS tumors decreased significantly, whereas the rates of other tumor types fluctuated. Incidence rates of borderline ovarian tumors were higher among white women compared with black women and did not change significantly during 1992-1998. Serous and mucinous tumors were the predominant tumors reported for women age < 45 years, whereas serous; papillary, NOS; and other epithelial tumors predominated among older women. CONCLUSIONS. Incidence rates for malignant ovarian tumors have remained relatively stable, with higher rates for white women compared with black women. The reported rates for some specific histopathologic tumor types have changed over time, in part reflecting more specific pathologic classification. The possible effect of shifting exposure prevalence on incidence patterns warrants further study. Published 2002 by the American Cancer Society.* C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Div Canc Prevent, Rockville, MD USA. RP Mink, PJ (reprint author), Exponent Hlth Grp, 1730 Rhode Isl Ave,NW,Suite 1100, Washington, DC 20036 USA. NR 48 TC 52 Z9 54 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD DEC 1 PY 2002 VL 95 IS 11 BP 2380 EP 2389 DI 10.1002/cncr.10935 PG 10 WC Oncology SC Oncology GA 617QB UT WOS:000179371400018 PM 12436446 ER PT J AU Greenwald, P Milner, JA Anderson, DE McDonald, SS AF Greenwald, P Milner, JA Anderson, DE McDonald, SS TI Micronutrients in cancer chemoprevention SO CANCER AND METASTASIS REVIEWS LA English DT Review DE chemoprevention; micronutrients; clinical trials; prostate cancer; breast cancer; colon cancer ID VITAMIN-D-RECEPTOR; CELL-CYCLE PROGRESSION; DIETARY-FOLATE INTAKE; HUMAN PROSTATE-CANCER; ABERRANT CRYPT FOCI; BREAST-CANCER; COLON-CANCER; UNITED-STATES; GREEN TEA; ALPHA-TOCOPHEROL AB The selection of micronutrients, defined as essential and nonessential dietary components consumed in minute quantities, for testing in clinical chemoprevention trials is based on the totality of evidence arising from epidemiologic, in vitro, animal, and clinical studies. Those micronutrients that surface with chemopreventive potential, in terms of high efficacy and low toxicity, in early-phase clinical studies are then candidates for large-scale, randomized clinical chemoprevention trials with cancer endpoints. Micronutrients currently being examined in National Cancer Institute (NCI)-sponsored phase I, II, or III chemoprevention trials for prostate, breast, and colon cancers include isoflavones, lycopene, selenized yeast, selenomethionine, selenium, vitamin E, perillyl alcohol, folic acid, vitamin D, calcium, and curcumin. The response to micronutrients may vary not only in magnitude but also in direction. This variation and response likely depend on individual genetic polymorphisms and/or interactions among dietary components that influence absorption, metabolism, or site of action. Research priorities include investigation of possible molecular targets for micronutrients and whether genetic and epigenetic events dictate direction and magnitude of the response. C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Greenwald, P (reprint author), NCI, Div Canc Prevent, NIH, 6130 Execut Blvd,Suite 2040, Bethesda, MD 20892 USA. NR 128 TC 45 Z9 47 U1 0 U2 7 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 2002 VL 21 IS 3-4 BP 217 EP 230 DI 10.1023/A:1021202709003 PG 14 WC Oncology SC Oncology GA 620EM UT WOS:000179521100004 PM 12549762 ER PT J AU Lieberman, R AF Lieberman, R TI Chemoprevention of prostate cancer: Current status and future directions SO CANCER AND METASTASIS REVIEWS LA English DT Review DE chemoprevention; prostate cancer; HGPIN; GSTPI agents; biomarkers; cohorts; designs; clinical trials; PSA; antiandrogens; antiestrogens; receptor tyrosine kinase; COX-2 inhibitor ID LASER CAPTURE MICRODISSECTION; INTRAEPITHELIAL NEOPLASIA; CLINICAL-TRIALS; END-POINTS; ORNITHINE DECARBOXYLASE; ANTIINFLAMMATORY DRUGS; RADICAL PROSTATECTOMY; ANDROGEN REGULATION; PREVENTION TRIAL; AGENTS AB Prostate cancer chemoprevention can be described as the administration of natural products and pharmaceutical agents that inhibit one or more steps in the natural history of prostatic carcinogenesis. The principle components of the chemoprevention strategy are closely connected to this natural history and include: (a) agents and their molecular targets; (b) strategic intermediate endpoint biomarkers (IEBs) and their critical pathways; (c) cohorts identified by genetic and acquired risk factors and (d) efficient designs that combine these elements into a cohesive clinical trial. The primary goal is to find effective noncytotoxic agents that modulate the promotion and progression from normal epithelium to dysplasia to high-grade prostatic intraepithelial neoplasia (HGPIN) to locally invasive cancer and metastatic disease. Another important target for chemoprevention is to modulate progression to clinically aggressive disease and to maintain an androgen-sensitive clinical state and delay the emergence of androgen resistance. There is a rationale for use of antiandrogens as the lead class, e. g., 5 alpha receptor inhibitors (5ARI), for chemoprevention of prostate cancer. Nevertheless, the desire to improve the therapeutic index, achieve synergy ( 5ARI may have only modest anticancer effects) and prevent the emergence of drug ( androgen) resistance provide incentives for developing other effective agents and combinations. The availability of more than a dozen classes of noncytotoxic pharmaceutical and natural products already in clinical development create many opportunities for rational combination therapy. Several agent classes have a pharmacodynamic basis for combination with antiandrogens including antiproliferatives, selective estrogen receptor modulators ( SERMs), proapoptotic antioxidant micronutrients and selective cyclo-oxygenase (COX)-2 inhibitors. Many other rational pharmacodynamic combinations without antiandrogens are feasible. It is anticipated that in the future, a selective COX-2 inhibitor may be combined with other agent classes such as proapoptotic antioxidant micronutrients, receptor tyrosine kinase modulators, antiangiogenic modulators, antiproliferative/differentiating agents, NFkappaB modulators, IGF-1 modulators and other novel proapototic nonsteroidal drugs. A novel target for rational combinations is the hypermethylation of GST-PI leading to functional silencing of this key anticarcinogen defense enzyme in precursors ( HGPIN) and prostate cancer. Factorial designs are well suited for evaluating the individual and combined effects of each agent in a single trial design. There are a number of moderate to high-risk cohorts and clinical models of primary and secondary prevention that can be employed in both short-term developmental ( translational) trials for proof of biologic activity and in intermediate sized longer-term chemoprevention trials for proof of efficacy against prostate cancer. Strategic IEBs are needed to more efficiently monitor short-term biologic activity and validate efficacy. The emergence of new powerful tools such as gene chip cDNA microarrays for multiplex gene expression profiling and proteomic analysis of tissue based and secreted proteins will accelerate the identification of new molecular targets, strategic endpoints, cohorts at risk and the design of rational combination trials. C1 NCI, Prostate & Urol Canc Res Grp, Div Canc Prevent, Rockville, MD 20852 USA. RP Lieberman, R (reprint author), NCI, Prostate & Urol Canc Res Grp, Div Canc Prevent, 6130 Execut Blvd,Suite EPN 2102, Rockville, MD 20852 USA. NR 69 TC 35 Z9 37 U1 0 U2 4 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-7659 J9 CANCER METAST REV JI Cancer Metastasis Rev. PD DEC PY 2002 VL 21 IS 3-4 BP 297 EP 309 DI 10.1023/A:1021267128567 PG 13 WC Oncology SC Oncology GA 620EM UT WOS:000179521100010 PM 12549768 ER PT J AU Hartman, TJ Taylor, PR Alfthan, G Fagerstrom, R Virtamo, J Mark, SD Virtanen, M Barrett, MJ Albanes, D AF Hartman, TJ Taylor, PR Alfthan, G Fagerstrom, R Virtamo, J Mark, SD Virtanen, M Barrett, MJ Albanes, D TI Toenail selenium concentration and lung cancer in male smokers (Finland) SO CANCER CAUSES & CONTROL LA English DT Article DE lung cancer; selenium ID PREDIAGNOSTIC SERUM SELENIUM; SUBSEQUENT RISK; VITAMIN-A; INDICATOR; WOMEN; MEN AB Background: The objective of this investigation was to evaluate the association between toenail selenium concentration and lung cancer risk in male smokers. Methods: We conducted a nested case-control study within the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study cohort. This substudy included 250 randomly selected incident lung cancer cases and 250 controls matched on age (up to 5 years), intervention group assignment, and date of randomization (+/-15 days). Odds ratios (ORs) and 95% confidence intervals (CIs) were determined using conditional logistic regression methods. Finland began fortification of agricultural fertilizers in the fall of 1984, increasing the dietary intake, plasma, and toenail selenium concentrations for the population. The present analyses were based on the calculated residual of toenail selenium after regressing it on date of randomization. The selenium residual and the interaction of the residual with date of randomization were included in models with smoking status and body mass index as covariates. Results: We observed a suggestion of a protective association for higher selenium status among men who entered the trial early (when the range of selenium values included very low levels). The OR for men with adjusted toenail selenium concentrations at the 75th percentile compared to those with the lowest selenium concentrations ranged between 0.20 (0.09-0.44) for men randomized earliest in the trial and 0.61 (0.27-1.41) for men randomized in the fifth year. Conclusions: These results suggest that low selenium status may be associated with increased risk for lung cancer. C1 Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Helsinki, Finland. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Dept Management Serv, Silver Spring, MD USA. RP Hartman, TJ (reprint author), Penn State Univ, Dept Nutr, 5A Henderson Bldg, University Pk, PA 16802 USA. RI Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01 CN 45165] NR 31 TC 23 Z9 23 U1 1 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2002 VL 13 IS 10 BP 923 EP 928 DI 10.1023/A:1021912117067 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 634EZ UT WOS:000180328200005 PM 12588088 ER PT J AU Potischman, N Coates, RJ Swanson, CA Carroll, RJ Daling, JR Brogan, DR Gammon, MD Midthune, D Curtin, J Brinton, LA AF Potischman, N Coates, RJ Swanson, CA Carroll, RJ Daling, JR Brogan, DR Gammon, MD Midthune, D Curtin, J Brinton, LA TI Increased risk of early-stage breast cancer related to consumption of sweet foods among women less than age 45 in the United States SO CANCER CAUSES & CONTROL LA English DT Article DE breast cancer; diet; sweet foods; United States; women ID GROWTH-FACTOR-I; INSULIN-RESISTANCE; POOLED ANALYSIS; BINDING PROTEIN-3; DIETARY FACTORS; FAT; COHORT; HYPERANDROGENISM; QUESTIONNAIRE; METAANALYSIS AB Objectives: To evaluate the associations of dietary macronutrients, food groups, and eating patterns with risk of breast cancer in a population-based case-control study. Methods: In this study among women 20-44 years of age, 568 cases with breast cancer and 1451 population-based controls were included. They completed a detailed in-person interview, a self-administered food-frequency questionnaire and were measured for anthropometric indices. Logistic regression was used to estimate odds ratios (OR) and their 95% confidence intervals (CI) of breast cancer, adjusted for age, study site, race, education, alcohol consumption, oral contraceptive usage, smoking status, and body mass index. Results: There was no association between breast cancer risk and intake of calories, macronutrients, or types of fat. Risk of breast cancer was unrelated to intakes of a variety of food groups, including red meats, dairy, high-fat snacks and desserts, or foods high in animal fat. Increased risk was observed for high intake of a food group composed of sweet items, particularly sodas and desserts. Risk increased linearly with percent of calories from sweets and frequency of sweets intake. Consumption of sweets 9.8 or more times per week compared with <2.8 times per week was associated with an adjusted OR of 1.32 (95% CI = 1.0-1.8). This association did not appear to be due to the high-fat foods or carbonated beverages that comprised the food group. Compared with women reporting one or two meals and snacks per day, reduced risks were noted for women reporting six or more (OR = 0.69, 95% CI = 0.4-1.1). Conclusions: These data suggest a modest relationship between intakes of sweet items with risk of in-situ and localized breast cancer in young women. This relation is consistent with the hypothesized link of high insulin exposure and risk of breast cancer. There was some suggestion that women who ate many times during the day were at reduced risk of disease, which is also consistent with an insulin-related mechanism. C1 Ctr Dis Control & Prevent, DIv Canc Control & Populat Studies, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Div Canc Prevent, Silver Spring, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Potischman, N (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N01-CP-95604, CA57030, N01-CP-95605, N01-CP-95671, N01-CP-95672] NR 48 TC 30 Z9 30 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2002 VL 13 IS 10 BP 937 EP 946 DI 10.1023/A:1021919416101 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 634EZ UT WOS:000180328200007 PM 12588090 ER PT J AU Brown, LM Baris, D Hatcher, JL Inskip, PD Olshan, AF AF Brown, LM Baris, D Hatcher, JL Inskip, PD Olshan, AF TI Diagnostic radiation and the risk of multiple myeloma (United States) - Response SO CANCER CAUSES & CONTROL LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. RP Brown, LM (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD DEC PY 2002 VL 13 IS 10 BP 977 EP 977 DI 10.1023/A:1021922427786 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 634EZ UT WOS:000180328200012 ER PT J AU Avramis, IA Christodoulopoulos, G Suzuki, A Lang, WE Gonzalez-Gomez, I McNamara, G Sausville, EA Avramis, VI AF Avramis, IA Christodoulopoulos, G Suzuki, A Lang, WE Gonzalez-Gomez, I McNamara, G Sausville, EA Avramis, VI TI In vitro and in vivo evaluations of the tyrosine kinase inhibitor NSC 680410 against human leukemia and glioblastoma cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE tyrosine kinase; leukemia; brain tumors; apoptosis; VEGF ID ENDOTHELIAL GROWTH-FACTOR; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; ARABINOSIDE ARA-C; CYTOSINE-ARABINOSIDE; CROSS-RESISTANCE; RETINOIC ACID; CANCER CELLS AB Purpose: NSC 680410, the novel adamantyl ester of AG957, an inhibitor of the p210bcr/abl tyrosine kinase (CML, Ph+) and possibly other kinases, was tested for antitumor activity in ten human leukemia and human glioblastoma cell lines. Methods: CEM/0, seven ara-C- and/or ASNase-resistant clones, Jurkat/0, the myelomonocytic line U937 and U87 MG glioblastoma cell lines were used for these studies. The drug-resistant leukemic clones lack p53, express bcl-2 and VEGF-RI, and thus are refractory to apoptosis. Since tyrosine kinases drive many proliferative pathways and these activities are increased in many leukemic cells, we hypothesized that NSC 680410 may induce cytotoxicity in drug-resistant leukemia clones, independently of p210bcr/abl expression. Results: NSC 680410 exhibited significant anti-leukemic activity in CEM/0, Jurkat E6-1, and in the drug-resistant leukemic cell lines. The IC50 values in nine leukemia lines ranged from 17 to 216 nM. Western blot analyses after NSC 680410 treatment demonstrated caspase-3 cleavage and ELISAs showed a fivefold upregulation of its activity in cellular extracts. In addition, U87 MG human glioblastoma cells, which express VEGF-RI, were treated with the Flt-1/Fc chimera, a specific inhibitor of VEGF, and showed 30-43% cell kill in the MTT assay. Furthermore, the combination of NSC 680410 plus Flt-1/Fc chimera demonstrated an eightfold synergism against U87 MG cells in vitro. To verify this observation in vivo, a-thymic mice were inoculated orthotopically into the caudate putamen with 10(6) U87 MG cells. On day 3, five mice per group were treated i.p. with either 8.3 mg/kg NSC 680410 daily for three doses per week for 4 weeks alone or in combination with one dose of Flt-1/Fc chimera 100 mg/kg subcutaneously. Treatment with NSC 680410 alone produced no weight changes and increased the median survival to 133%, whereas treatment with NSC680410 plus Flt-1/Fc chimera increased survival to 142% over control. Control animals had large intra- and extracranial tumors while the NSC 680410-treated mice had small, only intracranial tumors with necrotic centers. The combination treatment resulted in small residual tumors around the needle track, indicating significant inhibition of tumor growth. Conclusions: These studies demonstrate that the tyrosine kinase inhibitor NSC 680410 has significant antileukemic activity in p53-null, drug-resistant human leukemia cell lines, as well as significant antitumor activity in combination with Flt-1/Fc chimera against U87 MG glioblastoma brain tumors implanted in situ in athymic mice. C1 Univ So Calif, Div Hematol Oncol, Dept Pediat,Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. USC, Dept Pathol, Keck Sch Med, Childrens Hosp Los Angeles, Los Angeles, CA USA. NCI, Rockville, MD USA. RP Avramis, VI (reprint author), Univ So Calif, Div Hematol Oncol, Dept Pediat,Keck Sch Med, Childrens Hosp Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027 USA. NR 35 TC 33 Z9 35 U1 1 U2 3 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 2002 VL 50 IS 6 BP 479 EP 489 DI 10.1007/s00280-002-0507-6 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 629HT UT WOS:000180044800007 PM 12451475 ER PT J AU Papadopoulou, MV Ji, M Ji, XH Bloomer, WD Hollingshead, MG AF Papadopoulou, MV Ji, M Ji, XH Bloomer, WD Hollingshead, MG TI Therapeutic advantage from combining paclitaxel with the hypoxia-selective cytotoxin NLCQ-1 in murine tumor- or human xenograft-bearing mice SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE NLCQ-1; paclitaxel; combined therapy; hypoxic cytotoxins; human xenografts; murine tumors ID CELL LUNG-CANCER; 9-<3-(2-NITRO-1-IMIDAZOLYL)PROPYLAMINO>-CYCLOPENTENOQUINOLINE HYDROCHLORIDE N; AFFINIC BIOREDUCTIVE AGENT; O2 TENSION MEASUREMENTS; IN-VIVO; CHEMOTHERAPEUTIC DRUGS; TIRAPAZAMINE SR-4233; PHASE-II; CISPLATIN; OXYGENATION AB Purpose: The antitumor effect of paclitaxel was investigated against murine tumors and human xenografts in combination with the hypoxia-selective cytotoxin NLCQ-1. Methods: The tumor regrowth assay was used as the endpoint and an optimal administration schedule was followed, based on previous studies. In certain cases the hypoxia-selective cytotoxin tirapazamine (TPZ) was included for comparison. NLCQ-1 was given i.p. in saline, whereas paclitaxel was given i.p. (C3H) or i.v. (athymic mice) in an appropriately formulated vehicle. Results: In the SCCVII/C3H model, when NLCQ-1 (10 mg/kg) was given 90 min after paclitaxel (8 mg/kg) twice a day 4 h apart on days 0 and 9, tumor regrowth delay was increased by 10.3 days compared to paclitaxel alone, at fivefold the original tumor size. This corresponds to 1.51 log cell kill. In the same study, TPZ resulted in 4.6 days of extra delay compared to paclitaxel alone, which corresponds to 0.91 log cell kill. Paclitaxel alone resulted in 3.9 days of tumor growth delay compared to control, or 0.42 log cell kill, but this delay was not statistically significant (P < 0.2). In the FSaIIC/C3H model, when NLCQ-1 (10 mg/kg) was given 90 min after paclitaxel (12 mg/kg) on day 0, tumor regrowth delay was increased by 5.8 days compared to paclitaxel alone, at 20-fold the original tumor size. In athymic nude mice bearing PC-3 prostate xenografts, NLCQ-1 (10 mg/kg) given 90 min before paclitaxel (8 mg/kg) for five consecutive days, increased tumor regrowth delay by 5.6 days compared to paclitaxel alone, at threefold the original tumor size. This corresponds to 0.95 log cell kill whereas the log cell kill for paclitaxel alone was 0.52. No improvement was observed in the tumor regrowth delay at any lower paclitaxel doses given in combination with NLCQ-1. No concurrent enhancement in paclitaxel-induced toxicity was observed in any of the combination treatments or in any of the models tested. NLCQ-1 alone was ineffective at the doses given. Conclusions: These results suggest that an enhancement in tumor growth delay can be achieved both in murine tumors and in human xenografts due to a synergistic interaction between NLCQ-1 and paclitaxel. C1 Evanston NW Healthcare, Radiat Med Inst, Evanston, IL 60201 USA. NCI, Biol Testing Branch, DTP, DCTD,Fairview Ctr, Frederick, MD 21702 USA. RP Papadopoulou, MV (reprint author), Evanston NW Healthcare, Radiat Med Inst, 2650 Ridge Ave, Evanston, IL 60201 USA. NR 56 TC 13 Z9 13 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD DEC PY 2002 VL 50 IS 6 BP 501 EP 508 DI 10.1007/s00280-002-0521-8 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 629HT UT WOS:000180044800010 PM 12451478 ER PT J AU Caporaso, NE AF Caporaso, NE TI Why have we failed to find the low penetrance genetic constituents of common cancers? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID COMPLEX HUMAN-DISEASES; SINGLE-NUCLEOTIDE POLYMORPHISMS; LUNG-CANCER; LINKAGE DISEQUILIBRIUM; MYELOPEROXIDASE GENE; BLADDER-CANCER; RISK; ASSOCIATION; SUSCEPTIBILITY; EPIDEMIOLOGY C1 NCI, Genet Epidemiol Branch, Rockville, MD 20892 USA. RP Caporaso, NE (reprint author), NCI, Genet Epidemiol Branch, EPS 7116,6120 Executive Blvd, Rockville, MD 20892 USA. NR 73 TC 53 Z9 54 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2002 VL 11 IS 12 BP 1544 EP 1549 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 628UE UT WOS:000180014300003 PM 12496041 ER PT J AU Laden, F Ishibe, N Hankinson, SE Wolff, MS Gertig, DM Hunter, DJ Kelsey, KT AF Laden, F Ishibe, N Hankinson, SE Wolff, MS Gertig, DM Hunter, DJ Kelsey, KT TI Polychlorinated biphenyls, cytochrome P450 1A1, and breast cancer risk in the nurses' health study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PLASMA ORGANOCHLORINE LEVELS; LUNG-CANCER; BLOOD-LEVELS; DNA-ADDUCTS; CYP1A1; POLYMORPHISMS; METABOLISM; HYDROCARBONS; ASSOCIATION; INDUCTION AB There is concern that exposures to the environmental chemicals polychlorinated biphenyls (PCBs) may contribute to breast cancer risk. An individual's susceptibility to the effects of PCBs may be partially determined by polymorphisms in the gene encoding the biotransformation enzyme cytochrome P450 1A1 (CYP1A1). PCB exposure induces CYP1A1 activity, and PCBs themselves or other xenobiotics can be metabolized to carcinogenic intermediates in the presence of the variant genotype. A previous case-control study provided evidence of an interaction between high exposures to PCBs and the CYP1A1-exon 7 polymorphism (the A to G transition at nucleotide 4889), leading to a significant increase in postmenopausal breast cancer risk. We examined the interaction of PCBs with the CYP1A1-MspI (the T to C transition at nucleotide 6235) and exon 7 polymorphisms among 367 breast cancer case-control pairs (293 postmenopausal pairs) in the Nurses' Health Study. Although there was no independent association of either the CYP1A1 variants or PCBs with breast cancer risk, the relative risk among the postmenopausal women with plasma PCB levels in the highest third of the distribution in the control group and at least one exon 7 variant allele compared with women who were homozygous for the wild-type allele and who had PCB levels in the lowest third was 2.78 (95% confidence interval, 0.99-7.82). The majority of studies have concluded that exposure to PCBs is unlikely to be a major cause of breast cancer, but these findings indicate that further studies of genetically susceptible populations are warranted. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Canc Cell Biol, Boston, MA 02115 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. Mt Sinai Sch Med, New York, NY USA. Univ Melbourne, Sch Populat Hlth, Ctr Genet Epidemiol, Carlton, Vic 3053, Australia. Harvard Univ, Sch Publ Hlth, Ctr Canc Prevent, Boston, MA 02115 USA. RP Laden, F (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. RI Kelsey, Karl/I-1252-2014 FU NCI NIH HHS [CA40356, CA/ES62984, CA49449, UO1 CA87969]; NHLBI NIH HHS [T32HL07427]; NIEHS NIH HHS [ES00002] NR 41 TC 79 Z9 85 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2002 VL 11 IS 12 BP 1560 EP 1565 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 628UE UT WOS:000180014300006 PM 12496044 ER PT J AU Simon, MS Tang, MTC Bernstein, L Norman, SA Weiss, L Burkman, RT Daling, JR Deapen, D Folger, SG Malone, K Marchbanks, PA McDonald, JA Strom, BL Wilson, HG Spirtas, R AF Simon, MS Tang, MTC Bernstein, L Norman, SA Weiss, L Burkman, RT Daling, JR Deapen, D Folger, SG Malone, K Marchbanks, PA McDonald, JA Strom, BL Wilson, HG Spirtas, R TI Do thyroid disorders increase the risk of breast cancer? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MOUSE MAMMARY-GLANDS; MEDICAL CONDITIONS; HORMONES; SUPPLEMENTS; DISEASES; HISTORY; WOMEN AB The objective of this study was to determine whether thyroid disorders or treatment of such disorders affects the risk of breast cancer. Subjects aged 35-64 years were participants in the National Institute of Child Health and Human Development Women's Contraceptive and Reproductive Experiences Study, a population-based, case-control study of invasive breast cancer that was carried out at five sites in the United States. In-person interviews were completed for 4575 women (cases) with breast cancer (2953 white and 1622 black) and 4682 control women (3021 white and 1661 black). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multiple logistic regression methods. Models included adjustment for age (5-year age groups), race (white or black), and site. A history of any thyroid disorder (OR = 1.1, 95% CI = 0.9-1.2) was not associated with breast cancer risk. Only women with a history of thyroid cancer had an increased risk, but this was restricted to parous women (parous OR = 3.4, 95% CI = 1.5-8.1; nulliparous OR = 0.5, 95 % CI = 0.04-5.1). Breast cancer risk was not associated with treatment for thyroid disorders. There was no statistical interaction between thyroid disorders, thyroid treatments, and race, menopausal status, or parity. We found no association between thyroid disorders or their associated treatments and the risk of breast cancer. C1 Wayne State Univ, Karmanos Canc Inst, Div Hematol & Oncol, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Div Epidemiol, Detroit, MI USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ Penn, Ctr Clin Epidemiol Biostat, Philadelphia, PA USA. Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA USA. Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. NICHHD, Contracept & Reprod Hlth Branch, Populat Res Ctr, Bethesda, MD USA. RP Simon, MS (reprint author), Harper Grace Hosp, 514 Hudson,3990 John R St, Detroit, MI 48201 USA. FU NICHD NIH HHS [N01-HD-2-3166, N01-HD-3-3168, Y01-HD-7022, N01-HD-3-3175, N01-HD-3-3174, N01-HD-3-3176] NR 20 TC 36 Z9 37 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2002 VL 11 IS 12 BP 1574 EP 1578 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 628UE UT WOS:000180014300008 PM 12496046 ER PT J AU van Gijssel, HE Divi, RL Olivero, OA Roth, MJ Wang, GQ Dawsey, SM Albert, PS Qiao, YL Taylor, PR Dong, ZW Schrager, JA Kleiner, DE Poirier, MC AF van Gijssel, HE Divi, RL Olivero, OA Roth, MJ Wang, GQ Dawsey, SM Albert, PS Qiao, YL Taylor, PR Dong, ZW Schrager, JA Kleiner, DE Poirier, MC TI Semiquantitation of polycyclic aromatic hydrocarbon-DNA adducts in human esophagus by immunohistochemistry and the automated cellular imaging system SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CANCER; CELLS; CHINA; RISK; QUANTITATION; NONSMOKERS; TAMOXIFEN; LINXIAN; SMOKERS AB It has been suggested that ingestion of polycyclic aromatic hydrocarbons (PAHs) may contribute to the high incidence and mortality of esophageal cancer in Linxian, China. To explore this relationship a semiquantitative immunohistochemical staining method was developed for localization of PAH-DNA adducts. Nuclear color intensity (bright field average pink intensity per nucleus for > 1000 cells) was measured using the ChromaVision Automated Cellular Imaging System (ACIS). Paraffin-embedded sections of cultured human keratinocytes exposed to increasing concentrations of 7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE) were incubated with BPDE-DNA antiserum and served as an internal positive control (standard curve). Values for nuclear staining intensity correlated directly with BPDE exposure concentration (r(2) = 0.99) and were reproducible. DNA adduct levels determined by BPDE-DNA chemiluminescence inummoassay in DNA from BPDE-exposed keratinocytes, correlated with BPDE exposure concentrations (r(2) = 0.99), showing that nuclear staining intensity determined by ACIS correlated directly with BPDE-DNA adduct levels determined by chemiluminescence immunoassay. The ACIS methodology was applied to 5 human samples from Linxian, and significantly positive nuclear PAH-DNA adduct staining was observed in this group when compared with esophageal tissue from 4 laboratory-housed monkey controls and 6 samples obtained at autopsy from smokers and nonsmokers in the United States. Nuclear PAH-DNA staining was absent from Linxian samples when serial sections were incubated with normal rabbit serum (negative control) and was significantly reduced on incubation with BPDE-DNA antiserum absorbed previously with the immunogen BPDE-DNA. These results appear to support the hypothesis that high PAH exposure levels may be etiologically associated with the development of esophageal cancer in Linxian. C1 NCI, Carcinogen DNA Interact Sect, Cellular Carcinogenesis & Tumor Promot Lab, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Canc Prevent Studies Branch, Div Canc Treatment & Diag,NIH, Bethesda, MD 20892 USA. NCI, Biometrie Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, Cellular Carcinogenesis & Tumor Promot Lab, Div Canc Treatment & Diag,NIH, Bldg 37,Rm 2A05,NIH,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. RI Qiao, You-Lin/B-4139-2012; OI Qiao, You-Lin/0000-0001-6380-0871; Kleiner, David/0000-0003-3442-4453 NR 16 TC 28 Z9 29 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD DEC PY 2002 VL 11 IS 12 BP 1622 EP 1629 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 628UE UT WOS:000180014300015 PM 12496053 ER PT J AU Mocellin, S Rossi, CR Lise, M Marincola, FM AF Mocellin, S Rossi, CR Lise, M Marincola, FM TI Adjuvant immunotherapy for solid tumors: from promise to clinical application SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Review DE adjuvant immunotherapy; solid tumor; tumor immunology ID ACTIVE-SPECIFIC-IMMUNOTHERAPY; RENAL-CELL CARCINOMA; BACILLUS-CALMETTE-GUERIN; COLONY-STIMULATING FACTOR; PHASE-I TRIAL; SUPERFICIAL BLADDER-CANCER; COOPERATIVE-ONCOLOGY-GROUP; RECOMBINANT INTERLEUKIN-2 THERAPY; BISPECIFIC MONOCLONAL-ANTIBODY; HIGH-DOSE INTERFERON-ALPHA-2B AB Although surgery remains the mainstay for the treatment of most solid tumors, investigators are seeking complementary therapies to eradicate microscopic disease, which causes tumor relapse even after an apparently complete surgical excision. Although adjuvant chemotherapy has achieved some significant results, the control of minimal residual disease is still a challenge for clinicians. Among novel therapeutic approaches, immunotherapy holds promise. This anticancer strategy aims at triggering a highly specific endogenous killing machine against tumor cells. Recent progress in tumor immunology has improved our understanding of host-immune system interactions. In particular, new technologies have fostered the identification of potentially immunogenic tumor antigens that can be used as suitable targets for immune effector cells. After observing immunotherapy-mediated clinical responses in patients with metastatic disease, investigators have started evaluating this anticancer modality in the adjuvant setting. Here, we review the immunological strategies so far explored in humans and report worldwide results following the clinical application of adjuvant immunotherapy for solid tumors. C1 Univ Padua, Dept Oncol & Surg Sci, Inst Clin Surg 2, Piano Policlin Uviversitario 6, Padua, Italy. NIH, Ctr Clin, Immunogenet Sect, Bethesda, MD 20892 USA. RP Mocellin, S (reprint author), Univ Padua, Dept Oncol & Surg Sci, Inst Clin Surg 2, Piano Policlin Uviversitario 6, Via Giustiniani 2, Padua, Italy. RI Rossi, Carlo Riccardo/A-7685-2010 OI Rossi, Carlo Riccardo/0000-0001-7875-5655 NR 165 TC 34 Z9 34 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD DEC PY 2002 VL 51 IS 11-12 BP 583 EP 595 DI 10.1007/s00262-002-0308-0 PG 13 WC Oncology; Immunology SC Oncology; Immunology GA 628XP UT WOS:000180021600001 PM 12439603 ER PT J AU Guo, HB Lee, I Kamar, M Akiyama, SK Pierce, M AF Guo, HB Lee, I Kamar, M Akiyama, SK Pierce, M TI Aberrant N-glycosylation of beta(1) integrin causes reduced alpha(5)beta(1) integrin clustering and stimulates cell migration SO CANCER RESEARCH LA English DT Article ID HUMAN HEPATOCARCINOMA CELLS; BETA-1-6 BRANCHED OLIGOSACCHARIDES; FOCAL ADHESION KINASE; ACETYLGLUCOSAMINYLTRANSFERASE-V; FIBRONECTIN RECEPTOR; LIGAND-BINDING; SIGNALING PATHWAY; FUNCTIONAL-ROLE; METASTASIS; ACTIVATION AB Altered expression of cell surface N-linked oligosaccharides is associated with the oncogenic transformation of many types of animal cells. One of the most common forms of glycosylation in transformed cells and human tumors is the highly elevated beta1,6 branching of N-linked oligosaccharides caused by increased transcription of N-acetylglucosaminyltransferase V (GnT-V). To characterize the effects of increased beta1,6 branching on cell-matrix adhesion-mediated phenotypes, human fibrosarcoma HT1080 cells were transfected with retroviral systems encoding GnT-V that used both noninducible and tetracycline-inducible promoters. Increased GnT-V expression resulted in a >25% inhibition of cell attachment to and a >50% inhibition of cell spreading on fibronectin. Both cell adhesion and spreading were suppressed by function-blocking antibodies specific for the alpha(5) and beta(1) integrin subunits of the fibronectin receptor. Cell migration toward fibronectin and invasion through Matrigel were both substantially stimulated in cells with induced expression of GnT-V. Induction of GnT-V had no effect on the level of cell surface expression of alpha(5) and beta(1), integrin subunits but did result in a more diffuse staining of the alpha(5) and beta(1), integrin subunits on the cell surface, suggesting that inhibition of integrin clustering may be causing these cells to be less adhesive and more motile. Surprisingly, there was no detectable expression of N-linked beta1,6 branching on the as subunit purified from HT1080 cells before and after induction of GnT-V; by contrast, however, the beta(1) subunit showed a basal level of beta1,6 branching that was greatly increased after induction of GnT-V. These results suggest that changes in N-linked beta1,6 branching that occur during oncogenesis alter cell-matrix adhesion and migration by modulating integrin clustering and subsequent signal transduction pathways. These effects most likely result from altered N-linked carbohydrate expression on the beta(1) integrin subunit. C1 Univ Georgia, Dept Biochem & Mol Biol, Athens, GA 30602 USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Pierce, M (reprint author), Univ Georgia, Dept Biochem & Mol Biol, Life Sci Bldg,B-314, Athens, GA 30602 USA. FU NCI NIH HHS [5R01CA64462] NR 53 TC 206 Z9 207 U1 2 U2 12 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2002 VL 62 IS 23 BP 6837 EP 6845 PG 9 WC Oncology SC Oncology GA 622HJ UT WOS:000179641000011 PM 12460896 ER PT J AU Kisley, LR Barrett, BS Bauer, AK Dwyer-Nield, LD Barthel, B Meyer, AM Thompson, DC Malkinson, AM AF Kisley, LR Barrett, BS Bauer, AK Dwyer-Nield, LD Barthel, B Meyer, AM Thompson, DC Malkinson, AM TI Genetic ablation of inducible nitric oxide synthase decreases mouse lung tumorigenesis SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BUTYLATED HYDROXYTOLUENE BHT; FACTOR-INDUCED ANGIOGENESIS; TUMOR-GROWTH; UP-REGULATION; CANCER; MICE; EXPRESSION; CYCLOOXYGENASE-2; CHEMOPREVENTION AB Inducible nitric oxide synthase (iNOS) content is elevated in human lung adenocarcinomas, and lung cancer patients exhale more nitric oxide (NO) than healthy individuals. The mechanism of this association of chronically elevated NO with tumorigenesis has not been defined. We investigated the role of iNOS in murine lung tumorigenesis, a model of human lung adenocarcinoma, using wild-type (+/+) and iNOS (-/-) mice. Genetic disruption of iNOS decreased urethane-induced lung tumor multiplicity by 80% (P < 0.0001). iNOS protein was expressed in lung tumors growing in wild-type mice and bronchiolar Clara cells isolated from normal mouse lungs, but was undetectable in whole lung extracts by inummoblotting. Because NO regulates vascular endothelial growth factor (VEGF) expression in other systems, we examined the effect of MOS deficiency on VEGF protein concentration in mouse lung tumors. VEGF concentration was 54% lower in lung tumors isolated from iNOS (-/-) mice versus controls, implying that NO modulates angiogenesis in these tumors. Lung tumors also have elevated levels of cyclooxygenase (COX) -1 and COX-2 contents relative to normal lungs, but iNOS deficiency did not change COX expression in the tumors. Chronic inflammation predisposes mice to lung tumorigenesis; accordingly, we examined whether butylated hydroxytoluene-induced chronic lung inflammation was influenced by MOS deficiency. Butylated hydroxytoluene-induced alveolar macrophage infiltration was unaffected by iNOS (-/-) status, suggesting that although NO is a critical mediator of mouse lung tumorigenesis, it is not essential in this model of lung inflammation. The substantial (80%) reduction in lung tumor multiplicity in MOS (-/-) mice strongly supports examining iNOS-specific inhibitors as potential lung cancer chemopreventive agents. C1 Univ Colorado, Hlth Sci Ctr, Ctr Canc, Dept Pharmaceut Sci, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Ctr Canc, Dept Pharmacol, Denver, CO 80262 USA. NIEHS, Lab Pulm Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Malkinson, AM (reprint author), Univ Colorado, Hlth Sci Ctr, Ctr Canc, Dept Pharmaceut Sci, Box C-238,4200 E 9th Ave, Denver, CO 80262 USA. FU NCI NIH HHS [CA58187, CA33497, R25-CA49981] NR 60 TC 92 Z9 94 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2002 VL 62 IS 23 BP 6850 EP 6856 PG 7 WC Oncology SC Oncology GA 622HJ UT WOS:000179641000013 PM 12460898 ER PT J AU Greiner, JW Zeytin, H Anver, MR Schlom, J AF Greiner, JW Zeytin, H Anver, MR Schlom, J TI Vaccine-based therapy directed against carcinoembryonic antigen demonstrates antitumor activity on spontaneous intestinal tumors in the absence of autoimmunity SO CANCER RESEARCH LA English DT Article ID CEA TRANSGENIC MICE; PHASE-I TRIAL; STIMULATING FACTOR; DENDRITIC CELLS; SELF-ANTIGEN; DIVERSIFIED PRIME; COLORECTAL-CANCER; IMMUNE-RESPONSES; DNA VACCINE; APC GENE AB By virtue of its tissue-specific expression, carcinoembryonic antigen (CEA) is an important self, tumor-associated antigen, which is expressed by different human adenocarcinomas and also serves as a target for active-specific immunotherapy. Similar to humans, CEA expression in mice transgenic for the human CEA gene (CEA.Tg) occurs predominantly along the gastrointestinal tract. CEA.Tg mice were crossed with mice bearing a mutation in the Apc gene (MIN mice), and the CEA.Tg/MIN progeny developed multiple intestinal neoplasms, which overexpress CEA to levels that are reminiscent of those reported for tubulovillous intestinal adenomas from patients. CEA.Tg/MIN mice were vaccinated with an aggressive diversified prime/boost vaccine regimen: (a) a primary vaccine consisting of recombinant vaccinia virus-expressing CEA and a triad of costimulatory molecules (TRICOM): B7.1, ICAM-1, and LFA-3 (rVCEA-TRICOM); and (b) a booster vaccine using CEA-TRICOM in a recombinant avipox (fowlpox) virus (rF-CEA-TRICOM). Granulocyte/ macrophage colony-stimulating factor was administered as a biological adjuvant with all vaccinations, either as a recombinant protein (with rV-CEA-TRICOM) or as a recombinant avipox virus (with rF-CEA-TRICOM). That vaccine regimen generated strong CEA-specific host immune responses in CEA.Tg/MIN mice, which resulted in (a) a delayed onset of adult anemia and weight loss, (b) a significant reduction in the number of intestinal tumors, and (c) improved overall survival. No evidence of autoimmunity directed against normal tissues expressing CEA was observed in mice in which the CEA-based vaccine significantly reduced intestinal tumor load. The CEA.Tg/MIN mice present a clinically relevant model in which different CEA-based vaccine strategies can be tested on the spontaneous onset of intestinal tumorigenesis. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Pathol Histotechnol Lab, Frederick, MD 21702 USA. RP Greiner, JW (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. FU PHS HHS [N01-C0-12400] NR 45 TC 80 Z9 84 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD DEC 1 PY 2002 VL 62 IS 23 BP 6944 EP 6951 PG 8 WC Oncology SC Oncology GA 622HJ UT WOS:000179641000026 PM 12460911 ER PT J AU Divi, RL Beland, FA Fu, PP Von Tungeln, LS Schoket, B Camara, JE Ghei, M Rothman, N Sinha, R Poirier, MC AF Divi, RL Beland, FA Fu, PP Von Tungeln, LS Schoket, B Camara, JE Ghei, M Rothman, N Sinha, R Poirier, MC TI Highly sensitive chemiluminescence immunoassay for benzo[a]pyrene-DNA adducts: validation by comparison with other methods, and use in human biomonitoring SO CARCINOGENESIS LA English DT Article ID HYDROCARBON-DNA ADDUCTS; POLYCYCLIC AROMATIC-HYDROCARBONS; WHITE BLOOD-CELLS; FED COAL-TAR; LUNG-CANCER; MOUSE EPIDERMIS; BREAST-TISSUE; BENZO(A)PYRENE; ASSOCIATION; MCL-5 AB A chemiluminescence immunoassay (CIA) utilizing antiserum elicited against DNA modified with (+/-)-7beta, 8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]- pyrene (BPDE) has been developed and validated to study the formation of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human tissues. Advantages include a low limit of detection for 10b-(deoxyguanosin-N-2-yl)-7beta,8alpha,9alpha-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPdG, similar to1.5 adducts/10(9) nucleotides using 20 mug DNA) and a high signal-to-noise ratio (greater than or equal to100). The CIA BPDE-DNA standard curve gave 50% inhibition at 0.60 +/- 0.08 fmol BPdG (mean +/- SE, n = 30), which was a 10-fold increase in sensitivity compared with the dissociation-enhanced lanthanide fluoroimmunoassay (DELFIA). Calf thymus DNA modified with [1,3-H-3]BPDE was assayed by radiolabeling, P-32-postlabeling, DELFIA and CIA, and all assays gave similar values. Liver DNAs from mice exposed to 0.5 and 1.0 mg [7,8-H-3]benzo[a]pyrene (BP) were assayed by the same four assays and a dose-response was obtained with all assays. The BPDE-DNA CIA was further validated in MCL-5 cells exposed to 4 muM BP for 24 h, where nuclear and mitochondrial DNA adduct levels were associated with an increase in DNA tail length measured by the Comet assay. Human peripheral blood cell (buffy coat) DNA samples (n = 43) obtained from 25 individuals who were either colorectal adenocarcinoma patients or controls were assayed by BPDE-DNA CIA. Three samples (7%) were non-detectable, and the remaining 40 samples had values between 0.71 and 2.21 PAH-DNA adducts/10(8) nucleotides. The intra-assay coefficient of variation (CV), for four wells on the same microtiter plate, was 1.85%. Sufficient DNA for two assays, on separate plates, was available for 38 of the 43 samples, and the PAH-DNA adduct values obtained were highly correlated (r(2) = 0.95). Coded duplicate DNA samples from 15 individuals were assayed four times gave an inter-assay CV of 13.8%. C1 NCI, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Jozef Fordor Natl Ctr Publ Hlth, H-1097 Budapest, Hungary. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Bldg 37,Room 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. NR 40 TC 53 Z9 56 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2002 VL 23 IS 12 BP 2043 EP 2049 DI 10.1093/carcin/23.12.2043 PG 7 WC Oncology SC Oncology GA 632YM UT WOS:000180252500008 PM 12507927 ER PT J AU Chen, XX Li, N Wang, S Hong, JG Fang, MZ Yousselfsson, J Yang, PY Newman, RA Lubet, RA Yang, CS AF Chen, XX Li, N Wang, S Hong, JG Fang, MZ Yousselfsson, J Yang, PY Newman, RA Lubet, RA Yang, CS TI Aberrant arachidonic acid metabolism in esophageal adenocarcinogenesis, and the effects of sulindac, nordihydroguaiaretic acid, and alpha-difluoromethylornithine on tumorigenesis in a rat surgical model SO CARCINOGENESIS LA English DT Article ID CELL LUNG-CANCER; BARRETTS-ESOPHAGUS; CYCLOOXYGENASE-2 EXPRESSION; LIPOXYGENASE INHIBITORS; PROSTAGLANDIN E-2; COLON CARCINOGENESIS; TUMOR PROMOTION; ASPIRIN; GROWTH; APOPTOSIS AB Human esophageal adenocarcinoma (EAC) develops in a sequence from gastroesophageal reflux disease (GERD), columnar-lined esophagus (CLE), dysplasia, and eventually to EAC. We established a rat surgical EAC model with esophagogastroduodenal anastomosis (EGDA) to mimic the staged process of esophageal adenocarcinogenesis. Profiling of the AA metabolites with mass spectrometry showed that prostaglandin E2 (PGE2), leukotriene B4 (LTB4), 15-hydroeicosatetraenoic acid (HETE), 12-HETE, 8-HETE and 5-HETE all increased at the esophagoduodenal junction after EGDA as compared with the proximal esophagus, with PGE2 as the major metabolite. Consistent with this profile, cyclooxygenase 2 (Cox2) was overexpressed in the basal cell layer of esophageal squamous epithelium, CLE cells and EAC tumor cells of the EGDA rats, as compared with the normal esophageal epithelium. Sulindac (a Cox inhibitor), nordihydroguaiaretic acid (NDGA, a lipoxygenase inhibitor) and alpha-difluoromethylornithine (DFMO, an ornithine decarboxylase inhibitor) were tested for their possible inhibitory actions against the formation of EAC in the rat EGDA model. In a short-term study (for 4 weeks after surgery), dietary administration of both sulindac (300 and 600 p.p.m.) and NDGA (100 p.p.m.) effectively reduced the EGDA-induced inflammation. In a long-term chemoprevention study (for 40 weeks after surgery), 300 p.p.m. sulindac, alone or in combination with 100 p.p.m. NDGA or 0.5% DFMO, decreased the tumor incidence from 57.7 to 26.9%, or 16.7 or 20%, respectively (P < 0.05). NDGA alone (100 and 200 p.p.m.) slightly decreased the tumor incidence to 52.4 and 37%, respectively, although the difference was not statistically significant. DFMO alone did not show significant effects on tumor incidence. Inhibition of tumor formation by sulindac was correlated with lowered levels of PGE2. In conclusion, sulindac exerted its chemopreventive effect against the formation of EAC in the rat EGDA model possibly through its inhibition of Cox. C1 Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, Susan Lehman Cullman Lab Canc Res, Piscataway, NJ 08854 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. NCI, Chemprevent Branch, Div Canc Prevent, Rockville, MD 20852 USA. RP Yang, CS (reprint author), Rutgers State Univ, Ernest Mario Sch Pharm, Dept Biol Chem, Susan Lehman Cullman Lab Canc Res, 164 Frelinghuysen Rd, Piscataway, NJ 08854 USA. FU NCI NIH HHS [CA75683, N01-CN-95108] NR 68 TC 41 Z9 46 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2002 VL 23 IS 12 BP 2095 EP 2102 DI 10.1093/carcin/23.12.2095 PG 8 WC Oncology SC Oncology GA 632YM UT WOS:000180252500014 PM 12507933 ER PT J AU Tsutsui, T Kumakura, S Yamamoto, A Kanai, H Tamura, Y Kato, T Anpo, M Tahara, H Barrett, JC AF Tsutsui, T Kumakura, S Yamamoto, A Kanai, H Tamura, Y Kato, T Anpo, M Tahara, H Barrett, JC TI Association of p16(INK4a) and pRb inactivation with immortalization of human cells SO CARCINOGENESIS LA English DT Article ID NORMAL HUMAN FIBROBLASTS; LI-FRAUMENI SYNDROME; CO-60 GAMMA-RAYS; 4-NITROQUINOLINE 1-OXIDE; EPITHELIAL-CELLS; TELOMERE LENGTH; SENESCENCE; EXPRESSION; CANCER; RB AB To examine the association of cell cycle regulatory gene inactivation with human cell immortalization, we determined the expression status of INK4a, Rb, and WAF1/CIP1, in eleven in vitro immortalized human cell lines, including fibroblasts and keratinocytes. Two human papillomavirus type 16 E6 expressing cell lines with telomerase activity, including a fibroblast cell line and a keratinocyte cell line, expressed no detectable p16(INK4a). These cell lines had a hyperphosphorylated pRb and reduced expression of p21(WAF1/CIP1). All of seven fibroblast cell lines immortalized either spontaneously or by Co-60, X-rays, 4-nitroquinoline 1-oxide or aflatoxin 131, maintaining their telomeres by the ALT (alternative lengthening of telomeres) pathway, displayed loss of expression of p16(INK4a) and hyperphosphorylation of pRb. Levels of p21(WAF1/CIP1) expression varied among the cell lines. Two fibroblast cell lines that became immortalized following infection with a retrovirus vector encoding human telomerase catalytic subunit (hTERT) cDNA were also accompanied by inactivation of p16I(NK4a) and pRb pathways. Acquisition of telomerase activity alone was not sufficient for immortalization of these cell lines. Taken together, all the cell lines including fibroblasts and keratinocytes, with either telomerase activity or the ALT pathway for telomere maintenance showed loss of expression of p16I(N14a) and hyperphosphorylation of pRb. These demonstrate the association of inactivation of both p16I(NK4a) and pRb with immortalization of human cells including fibroblasts and epithelial cells and telomerase-positive cells and ALT-positive cells. C1 NIEHS, Res Triangle Pk, NC 27709 USA. Nippon Dent Univ Tokyo, Sch Dent Tokyo, Dept Pharmacol, Tokyo 1028159, Japan. Hiroshima Univ, Grad Sch Biomed Sci, Dept Cellular & Mol Biol, Hiroshima 7348551, Japan. NCI, Bethesda, MD 20892 USA. RP Barrett, JC (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 38 TC 42 Z9 52 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2002 VL 23 IS 12 BP 2111 EP 2117 DI 10.1093/carcin/23.12.2111 PG 7 WC Oncology SC Oncology GA 632YM UT WOS:000180252500016 PM 12507935 ER PT J AU Mei, JM Borchert, GL Donald, SP Phang, JM AF Mei, JM Borchert, GL Donald, SP Phang, JM TI Matrix metalloproteinase(s) mediate(s) NO-induced dissociation of beta-catenin from membrane bound E-cadherin and formation of nuclear beta-catenin/LEF-1 complex SO CARCINOGENESIS LA English DT Article ID COLONIC EPITHELIAL-CELLS; NITRIC-OXIDE; COLORECTAL-CANCER; EXPRESSION; MATRILYSIN; APC; TRANSCRIPTION; PROGRESSION; POLYPOSIS; INVASION AB Modulation of the adenomatous polyposis coli (APC)-beta-catenin pathway by inflammatory mediators and extracellular matrix may be important in colon carcinogenesis. We have recently shown that nitric oxide (NO) induces the accumulation of cytosolic beta-catenin and subsequent formation of the nuclear beta-catenin/lymphocyte enhancing factor (LEF)-1 complex in conditionally immortalized young mouse colonic epithelial (YAMC) cells. In the present study, we explored the mechanism(s) through which NO exerts its effect on cytosolic beta-catenin accumulation and nuclear beta-catenin/LEF-1 complex formation. We found that NO-induced degradation of the membrane bound E-cadherin at tight junctions. Using an anti-E-cadherin antibody specific for its extracellular domain, we detected a 50 kDa degradation fragment of E-cadherin (120 kDa) from the culture medium conditioned by YAMC cells exposed to the NO-releasing drug, NOR-1, for 4 and 24 h. As beta-catenin is normally bound to transmembrane E-cadherin and thus anchored to the cytoskeleton structure, the degradation of E-cadherin induced by NO may cause dissociation of beta-catenin from membrane bound E-cadherin. This was demonstrated by the detection of beta-catenin accumulation in the soluble cytosolic fractions in YAMC after exposure to NO-releasing drugs. Furthermore, the degradation of E-cadherin and the release of beta-catenin to cytosol were accompanied by the formation of nuclear beta-catenin/LEF-1 complex, demonstrating the dissociation of beta-catenin from E-cadherin may be responsible for the activation of beta-catenin/LEF-1 transcription complex. Co-treatment with NO donors and broad-spectrum matrix metalloproteinase (MMP) inhibitors TIMP-1 (100 ng/ml), GM6001 (10 muM) and GM1489 (10 muM) abolished the degradation of E-cadherin induced by NO as demonstrated by western blot analysis. These MMP inhibitors also blocked the cytosolic accumulation of beta-catenin and nuclear formation of beta-catenin/LEF-1 complex. The sum effect of MMP inhibitors demonstrated that NO-induced activation of MMP may cause the degradation of E-cadherin and the subsequent dissociation of beta-catenin, thereby contributing to the cytosolic accumulation of beta-catenin and nuclear formation of beta-catenin/LEF-1 complex. C1 NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, Frederick, MD 21701 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Phang, JM (reprint author), NCI, Metab & Canc Susceptibil Sect, Basic Res Lab, Ctr Canc Res, Frederick, MD 21701 USA. FU NCI NIH HHS [N01-CO-12400] NR 24 TC 43 Z9 47 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2002 VL 23 IS 12 BP 2119 EP 2122 DI 10.1093/carcin/23.12.2119 PG 4 WC Oncology SC Oncology GA 632YM UT WOS:000180252500017 PM 12507936 ER PT J AU Yu, MS Snyderwine, EG AF Yu, MS Snyderwine, EG TI H-ras oncogene mutations during development of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced rat mammary gland cancer SO CARCINOGENESIS LA English DT Article ID NITROSO-N-METHYLUREA; SPRAGUE-DAWLEY RATS; GENE-MUTATIONS; CHEMICAL CARCINOGENESIS; PRENEOPLASTIC LESIONS; TREATED RATS; DIETARY-FAT; DNA ADDUCT; CARCINOMAS; ACTIVATION AB Laser capture microdissection, polymerase chain reaction-restriction fragment length polymorphism analysis, and DNA sequencing was used to detect H-ras codon 12 and 13 mutations during the stages of mammary gland cancer development in rats exposed to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a carcinogen found in cooked meat. Ten oral doses of PhIP (75 mg/kg, p.o., once per day) were administered to adolescent female Sprague-Dawley rats and mammary glands examined histologically for intraductal proliferations (IDPs), carcinoma in situ and carcinomas 7-14 weeks later. Mammary gland epithelial cells from normal tissue and distinct lesions were collected from glass slides and analyzed for mutations. H-ras codon 12/13 mutations were detected in 73%, 75%, 100%, and 100% of normal mammary glands, IDPs, carcinoma in situ, and carcinoma, respectively, after PhIP treatment. The spectrum of activating mutations included G(35) to A or C base substitution mutations in codon 12, and G(37) to T or A base substitution mutations in codon 13. The spectrum of H-ras mutations was similar among normal mammary gland from PhIP treated rats, preneoplastic lesions, and carcinomas. Furthermore, the spectrum of mutations was consistent with the involvement of PhIP-guanine adduct formation. The results support the notion that mutations in H-ras codons 12 and 13 are largely PhIP-DNA adduct-induced and involved in the initiation and development of mammary gland cancer in rats exposed to PhIP. C1 NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Snyderwine, EG (reprint author), NCI, Chem Carcinogenesis Sect, Expt Carcinogenesis Lab, NIH, Bldg 37,Room 4146,37 Convent Dr,MSC 4262, Bethesda, MD 20892 USA. NR 38 TC 17 Z9 17 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD DEC PY 2002 VL 23 IS 12 BP 2123 EP 2128 DI 10.1093/carcin/23.12.2123 PG 6 WC Oncology SC Oncology GA 632YM UT WOS:000180252500018 PM 12507937 ER PT J AU Smith, GH Strickland, P Daniel, CW AF Smith, GH Strickland, P Daniel, CW TI Putative epithelial stem cell loss corresponds with mammary growth senescence SO CELL AND TISSUE RESEARCH LA English DT Article DE mammary stem cells; transplantation; immortality and growth senescence; mouse (BALB/c) ID ADULT HUMAN BREAST; MYOEPITHELIAL CELLS; DIFFERENTIATION; GLAND; EXPRESSION; TISSUES; GENES AB Since the advent of transmission electron microscopy of tissues capable of growth and regeneration, cell and developmental biologists have postulated that the undifferentiated cells observed within these tissues represent tissue-specific stern or progenitor cells. However, no studies have addressed the issue of whether these undifferentiated, putative stem cells persist in growth senescent tissues. Serially transplanted mammary epithelium consistently displays growth senescence beginning at the third transplant generation. This process is not uniform throughout the transplanted population and complete growth quiescence for all portions of a given outgrowth is reached subsequent to the 6th transplant generation. Mammary epithelial cells bearing the morphological characteristics of undifferentiated stem cells likewise disappear from senescent populations simultaneous with growth cessation. In premalignant mammary epithelial populations, which exhibit indefinitely prolonged growth potential. both of these cell types are maintained. This observation provides further support for the conclusion that these ultrastructurally distinct mammary cells represent the mammary stem/progenitor cell population. C1 NCI, Sect Mammary Stem Cell Biol, Basic Res Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Calif Santa Cruz, Sinsheimer Labs, Santa Cruz, CA 95064 USA. RP Smith, GH (reprint author), NCI, Sect Mammary Stem Cell Biol, Basic Res Lab, Ctr Canc Res,NIH, Bldg 10, Room 5B56,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 25 TC 21 Z9 23 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-766X J9 CELL TISSUE RES JI Cell Tissue Res. PD DEC PY 2002 VL 310 IS 3 BP 313 EP 320 DI 10.1007/s00441-002-0641-9 PG 8 WC Cell Biology SC Cell Biology GA 628XQ UT WOS:000180021700007 PM 12457230 ER PT J AU Kim, MS Jo, H Um, JY Yi, JM Kim, DK Choi, SC Kim, TH Nah, YH Kim, HM Lee, YM AF Kim, MS Jo, H Um, JY Yi, JM Kim, DK Choi, SC Kim, TH Nah, YH Kim, HM Lee, YM TI Agonists of proteinase-activated receptor 2 induce TNF-alpha secretion from astrocytoma cells SO CELL BIOCHEMISTRY AND FUNCTION LA English DT Article DE PAR2; CCF-STTGI; TNF-alpha; MAPK; trypsin; tryptase ID SIGNAL-REGULATED KINASE; VEIN ENDOTHELIAL-CELLS; NECROSIS-FACTOR-ALPHA; RECEPTOR-2-ACTIVATING PEPTIDES; MOLECULAR-CLONING; HUMAN BRAIN; EXPRESSION; TRYPTASE; TRYPSIN; THROMBIN AB Proteinase-activated receptor 2 (PAR2) is cleaved and activated by trypsin or mast cell tryptase, and may play an important role in inflammation. We have investigated the potential of PAR2 agonists to modulate TNF-alpha secretion from human astrocytoma cell line CCF-STTG1. We found that CCF-STTG1 expresses PAR2 by RT-PCR and Western blot analysis. Agonists such as trypsin, the peptide SLIGKV-NH2 (corresponding to the PAR2 tethered ligand), or mast cell tryptase directly signal to CCF-STTG1 to stimulate secretion of TNF-a but do not stimulate in the presence of soybean trypsin inhibitor (SBTI) or VKGILS-NH2 (reverse peptide). The secretion of TNF-a by trypsin was significantly blocked by pretreatment with either 50 mum PD98059 or 1 muM SB203580. Furthermore, trypsin stimulated the activation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase homologue in CCF-STTG1 without any detectable activation of c-Jun N-terminal kinase (JNK). These results show that trypsin may induce TNF-alpha secretion following activation of ERK and p38 via PAR2 in CCF-STTG1. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Wonkwang Univ, Coll Pharm, Dept Oriental Pharm, Iksan 570749, Cheonbuk, South Korea. NIAID, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. Wonkwang Univ, Sch Med, Dept Internal Med, Iksan 570749, Cheonbuk, South Korea. RP Lee, YM (reprint author), Wonkwang Univ, Coll Pharm, Dept Oriental Pharm, Iksan 570749, Cheonbuk, South Korea. RI Um, Jae-Young/G-8787-2013 NR 37 TC 24 Z9 27 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0263-6484 J9 CELL BIOCHEM FUNCT JI Cell Biochem. Funct. PD DEC PY 2002 VL 20 IS 4 BP 339 EP 345 DI 10.1002/cbf.982 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 615KT UT WOS:000179244900011 PM 12415569 ER PT J AU Krieg, RC Uihlein, D Murthum, T Endlicher, E Hausmann, F Messmann, H Knuechel, R AF Krieg, RC Uihlein, D Murthum, T Endlicher, E Hausmann, F Messmann, H Knuechel, R TI Improving the use of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) for the gastrointestinal tract by esterification - An in vitro study SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE photodynamic diagnosis; PDD; photodynamic therapy; PDT; ALA; PPIX; in vitro; gastrointestinal neoplasia ID PHOTODYNAMIC THERAPY; ADENOCARCINOMA CELLS; AMINOLEVULINIC-ACID; BETA TRANSPORTERS; ESTERS; COLON; SENSITIZATION; ACCUMULATION; DERIVATIVES; CARCINOMA AB Possible approaches to improve the diagnostic and therapeutic effects of 5-aminolevulinic acid (ALA)-induced protoporphyrin IX (PPIX) are the esterification of ALA for enhanced uptake and the choice of wavelength for irradiation. The human colonic cell lines HT29 [G2] and CCD 18 (fibroblasts) were incubated with 0.6 mM ALA, ALA-hexylester or -benzylester respectively, and for further assays with hypotaurine, in addition. PPIX-accumulation was analyzed by flow cytometry and fluorescence spectroscopy. PPIX formation kinetics were continuously recorded. Incubated cells were irradiated with an incoherent light source lambda=400-700 nm or lambda=590-700 nm, respectively. After PDT treatment, clonogenicity assays were performed to determine cell viability. Esterification leads to increased PPIX-accumulation, decreased time for production of detectable amounts of PPIX as well as increased response to PDT. Tumor specificity is always maintained or exceeds values for ALA alone. ALA enters the cells via beta transporter whereas esters by passive diffusion. Altering irradiation wavelengths showed the independence of wavelength rather than light dose. Results emphasize the role of heme metabolism for generating tumor specificity rather than the process of ALA-uptake, an important detail for future clinical application. C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Regensburg, Inst Pathol, D-93053 Regensburg, Germany. Univ Regensburg, Dept Internal Med 1, D-93053 Regensburg, Germany. Univ Regensburg, Inst Inorgan Chem, D-93053 Regensburg, Germany. Zentraklinikum Augsburg, Med Klin 3, D-86156 Augsburg, Germany. RP Krieg, RC (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM krieg@cber.fda.gov NR 28 TC 3 Z9 3 U1 0 U2 2 PU CELLULAR & MOLECULAR BIOLOGY PI NOISY-LE-GRAND PA PROF R WEGMANN RESIDENCE HAUSSMANN 1 AVENUE DU PAVE NEUF, 93160 NOISY-LE-GRAND, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD DEC PY 2002 VL 48 IS 8 BP 917 EP 923 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 658BA UT WOS:000181700700013 PM 12699251 ER PT J AU Ju, C Reilly, TP Bourdi, M Radonovich, MF Brady, JN George, JW Pohl, LR AF Ju, C Reilly, TP Bourdi, M Radonovich, MF Brady, JN George, JW Pohl, LR TI Protective role of Kupffer cells in acetaminophen-induced hepatic injury in mice SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID INDUCED LIVER-INJURY; ENCAPSULATED DICHLOROMETHYLENE DIPHOSPHONATE; GADOLINIUM CHLORIDE ALTERS; ANTIGEN-PRESENTING CELLS; NECROSIS-FACTOR-ALPHA; RAT-LIVER; NONPARENCHYMAL CELLS; PARTIAL-HEPATECTOMY; OXIDATIVE STRESS; PROTEIN ADDUCTS AB Hepatic injury induced by various toxic agents, including acetaminophen (APAP), has been attributed, in part, to the production of proinflammatory cytokines and other mediators by resident Kupffer cells within the liver. However, recent evidence from our laboratory has demonstrated that hepato-protective factors, such as interleukin (IL)-10 and cyclooxygenase-derived mediators, are also upregulated in response to hepatic damage to help protect against exacerbated injury, and Kupffer cells have been suggested to be a source of these modulatory factors. In other models, Kupffer cells also serve important regulatory functions in pathophysiological states of the liver. Therefore, we reevaluated the role of Kupffer cells in a murine model of APAP-induced liver injury using liposome-entrapped clodronate (liposome/clodronate) as an effective Kupffer cell-depleting agent. We show that in contrast to pretreatment of mice with a widely used macrophage inhibitor, gadolinium chloride, which did not deplete Kupffer cells but moderately protected against APAP-induced hepatotoxicity as reported previously, the intravenous injection of liposome/clodronate caused nearly complete elimination of Kupffer cells and significantly increased susceptibility to A-PAP-induced liver injury as compared with mice pretreated with empty liposomes. This increased susceptibility was apparently unrelated to the metabolism of APAP since liposome/clodronate pretreatment did not alter APAP-protein adduct levels. Instead, Kupffer cell depletion by liposome/clodronate led to significant decreases in the levels of hepatic mRNA expression of several hepato-regulatory cytokines and mediators, including IL-6, IL-10, IL-18 binding protein and complement 1q, suggesting that Kupffer cells are a significant source for production of these mediators in this model. Our findings indicate that, in addition to their protoxicant activities, Kupffer cells can also have an important protective function in the liver through the production of a variety of modulatory factors which may counteract inflammatory responses and/or stimulate liver regeneration. C1 NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Basic Res Lab, Virus Tumor Biol Sect, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ju, C (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. NR 72 TC 167 Z9 177 U1 1 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 BP 1504 EP 1513 DI 10.1021/tx0255976 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500003 PM 12482232 ER PT J AU Ramos, LA Ponten, I Dipple, A Kumar, S Yagi, H Sayer, JM Kroth, H Kalena, G Jerina, DM AF Ramos, LA Ponten, I Dipple, A Kumar, S Yagi, H Sayer, JM Kroth, H Kalena, G Jerina, DM TI Site-specific mutagenesis in Escherichia coli by N-2-deoxyguanosine adducts derived from the highly carcinogenic fjord-region benzo[c]phenanthrene 3,4-diol 1,2-epoxides SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID (+)-ANTI-BENZOPYRENE DIOL EPOXIDE; POLYCYCLIC AROMATIC-HYDROCARBONS; TEMPLATE-PRIMER JUNCTION; SINGLE-STRANDED VECTOR; DNA-ADDUCTS; DEOXYGUANOSINE ADDUCTS; DEOXYADENOSINE ADDUCTS; SOLUTION CONFORMATION; SEQUENCE CONTEXT; MUTATIONAL CONSEQUENCES AB Although there have been numerous studies of site-specific mutagenesis by dGuo adducts of benzo[a]pyrene diol epoxides (B[a]P DEs), the present study represents the first example of site-specific mutagenesis by dGuo adducts of the highly carcinogenic benzo[c]phenanthrene 3,4-diol 1,2-epoxides (B[c]Ph DEs). The eight adducts that would result from cis- and trans-opening at C-1 of four optically active isomers of B[c]Ph DEs by the N-2-amino group of dGuo were incorporated into 5'-TTCGAATCCTTCCCCC (context III) and 5'-GGGGTTCCCGAGCGGC (context IV) at the underlined site. These modified oligonucleotides along with unmodified controls were ligated into single-stranded M13mp7L2, which were then used to transfect SOS-induced Escherichia coli. Upon replication of the lesions in each of the two sequence contexts, mutational analysis of the progeny was performed by differential hybridization. For the 16 adducts, the mutation frequencies varied over 2 orders of magnitude with a reasonably even distribution (0.4-1% for three adducts, 1-2% for six adducts, 3-7.4% for five adducts, and one adduct each at 11 and 39%). For all but this last adduct, the mutation frequency for a given B[c]Ph DE adduct was less than for its B[a]P analogue with the same stereochemistry in the same sequence. For the vectors containing adducts with S configuration at the site of attachment of the hydrocarbon to the dGuo base, the main base substitution was G --> T followed by G --> A. In contrast, for the vectors containing adducts with R configuration, the main base substitution was G --> A. The most notable observation in the present study is the low frequency of mutations induced by the B[c]Ph DE-dGuo adducts relative to their B[a]P counterparts. A possible structural basis for this difference is proposed. C1 NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. SUNY Coll Buffalo, Environm Toxicol & Chem Lab, Great Lakes Ctr, Buffalo, NY 14222 USA. RP Jerina, DM (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. NR 48 TC 11 Z9 11 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 BP 1619 EP 1626 DI 10.1021/tx020073r PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500016 PM 12482245 ER PT J AU Nesnow, S Roop, BC Lambert, G Kadiiska, M Mason, RP Cullen, WR Mass, MJ AF Nesnow, S Roop, BC Lambert, G Kadiiska, M Mason, RP Cullen, WR Mass, MJ TI DNA damage induced by methylated trivalent arsenicals is mediated by reactive oxygen species SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID MONOMETHYLARSONOUS ACID MMA(III); RAT-LIVER CYTOSOL; MALE F344 RATS; DIMETHYLARSINIC ACID; HUMAN URINE; ENZYMATIC METHYLATION; HUMAN HEPATOCYTES; DRINKING-WATER; ORAL-EXPOSURE; FREE-RADICALS AB Arsenic is a human carcinogen; however, the mechanisms of arsenic's induction of carcinogenic effects have not been identified clearly. We have shown previously that monomethylarsonous acid (MMA(III)) and dimethylarsinous acid (DMA(III)) are genotoxic and can damage supercoiled phiX174 DNA and the DNA in peripheral human lymphocytes in culture. These trivalent arsenicals are biomethylated forms of inorganic arsenic and have been detected in the urine of subjects exposed to arsenite and arsenate. We show here by molecular, chemical, and physical methods that reactive oxygen species (ROS) are intermediates in the DNA-damaging activities of MMA(III) and DMA(III). Using the phiX174 DNA nicking assay we found that the ROS inhibitors Tiron, melatonin, and the vitamin E analogue Trolox inhibited the DNA-nicking activities of both MMA(III) and DMA(III) at low micromolar concentrations. The spin trap agent 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) also was effective at preventing the DNA nicking induced by MMA(III) and DMA(III.) ESR spectroscopy studies using DMPO identified a radical as a ROS intermediate in the DNA incubations with DMA(III). This radical adduct was assigned to the DMPO-hydroxyl free radical adduct on the basis of comparison of the observed hyperfine splitting constants and line widths with those reported in the literature. The formation of the DMPO-hydroxyl free radical adduct was dependent on time and the presence of DMA(III) and was completely inhibited by Tiron and Trolox and partially inhibited by DMSO. Using electrospray mass spectrometry, micromolar concentrations of DMA(v) were detected in the DNA incubation mixtures with DMA(III). These data are consistent with the conclusions that the DNA-damaging activity of DMA(III) is an indirect genotoxic effect mediated by ROS-formed concomitantly with the oxidation of DMA(III) to DMA(v). C1 US EPA, Div Environm Carcinogenesis, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ British Columbia, Dept Chem, Vancouver, BC, Canada. RP Nesnow, S (reprint author), US EPA, Div Environm Carcinogenesis, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. NR 48 TC 155 Z9 162 U1 5 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 BP 1627 EP 1634 DI 10.1021/tx025598y PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500017 PM 12482246 ER PT J AU Walker, CL Hodges, L Cook, J Lobenhofer, E Li, LP Bennett, L Bushel, P Afshari, C AF Walker, CL Hodges, L Cook, J Lobenhofer, E Li, LP Bennett, L Bushel, P Afshari, C TI Identification of critical determinants of agonism and antagonism in the breast by transcriptional profiling. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the American-Chemical-Society Division of Chemical Toxicology of the 224th ACS National Meeting CY AUG 18-22, 2002 CL BOSTON, MASSACHUSETTS SP Amer Chem Soc, Div Chem Toxicol C1 UT, MD Anderson Canc Ctr, Dept Carcinogenesis, Div Sci Pk Res, Smithville, TX USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 MA 5 BP 1653 EP 1653 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500025 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Transgenic animal models in toxicology studies. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the American-Chemical-Society Division of Chemical Toxicology of the 224th ACS National Meeting CY AUG 18-22, 2002 CL BOSTON, MASSACHUSETTS SP Amer Chem Soc, Div Chem Toxicol C1 NCI, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 MA 23 BP 1657 EP 1657 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500043 ER PT J AU Greenwald, P AF Greenwald, P TI Importance of cancer chemoprevention and the relationship to nutrition. SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the American-Chemical-Society Division of Chemical Toxicology of the 224th ACS National Meeting CY AUG 18-22, 2002 CL BOSTON, MASSACHUSETTS SP Amer Chem Soc, Div Chem Toxicol C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 MA 30 BP 1658 EP 1659 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500050 ER PT J AU Ruan, Q Skorvaga, M Zou, Y Van Houten, B Amin, S Geacintov, NE AF Ruan, Q Skorvaga, M Zou, Y Van Houten, B Amin, S Geacintov, NE TI Prokaryotic nucleotide excision repair of BPDE-modified DNA duplexes flanked by A : T or G : C base pairs depends on local structural disturbances caused by the lesions SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT Meeting of the American-Chemical-Society Division of Chemical Toxicology of the 224th ACS National Meeting CY AUG 18-22, 2002 CL BOSTON, MASSACHUSETTS SP Amer Chem Soc, Div Chem Toxicol C1 NYU, Dept Chem, New York, NY 10003 USA. NIEHS, NIH, Res Triangle Pk, NC USA. E Tennessee State Univ, Johnson City, TN 37614 USA. Amer Hlth Fdn, New York, NY 10017 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2002 VL 15 IS 12 MA 84 BP 1671 EP 1672 PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 627VU UT WOS:000179957500104 ER PT J AU Gilotty, L Kenworthy, L Sirian, L Black, DO Wagner, AE AF Gilotty, L Kenworthy, L Sirian, L Black, DO Wagner, AE TI Adaptive skills and executive function in autism spectrum disorders SO CHILD NEUROPSYCHOLOGY LA English DT Article ID BEHAVIOR SCALES; CHILDREN; PERFORMANCE; DEFICITS; MEMORY AB There is active debate regarding the nature of executive dysfunction in autism. Additionally, investigations have yet to show a relationship between deficits in executive function and the everyday behavioral difficulties that may originate from them. The present study examined the relationship between executive abilities and adaptive behavior in 35 children with Autism Spectrum Disorders, using two parent reports of everyday functioning, the Vineland Adaptive Behavior Scales (VABS) and the Behavior Rating Inventory of Executive Function (BRIEF). Results found several relationships: The Initiate and Working Memory domains were negatively correlated with most domains of adaptive behavior. Also, the Communication and Socialization domains of the VABS were negatively correlated with several areas of executive functioning, suggesting that impairments in executive abilities are strongly associated with the deficits in communication, play and social relationships found in children with autism. C1 Childrens Natl Med Ctr, Spring Valley Reg Outpatient Ctr, Dept Pediat, Div Psychol, Washington, DC 20009 USA. NIMH, Child & Adolescent Treatment Res Branch, Bethesda, MD 20892 USA. RP Gilotty, L (reprint author), Childrens Natl Med Ctr, Spring Valley Reg Outpatient Ctr, Dept Pediat, Div Psychol, 4900 Massachusetts Ave,Suite 320, Washington, DC 20009 USA. NR 28 TC 105 Z9 108 U1 4 U2 22 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 0929-7049 J9 CHILD NEUROPSYCHOL JI Child Neuropsychol. PD DEC PY 2002 VL 8 IS 4 BP 241 EP 248 DI 10.1076/chin.8.4.241.13504 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 680QW UT WOS:000182989700003 PM 12759821 ER PT J AU Battles, HB Wiener, LS AF Battles, HB Wiener, LS TI STARBRIGHT World: Effects of an electronic network on the social environment of children with life-threatening illnesses SO CHILDRENS HEALTH CARE LA English DT Article ID PEDIATRIC PHYSICAL DISORDERS; PAINFUL MEDICAL PROCEDURES; REALITY GRADED EXPOSURE; PSYCHOLOGICAL ADJUSTMENT; RECEIVING CHEMOTHERAPY; LEUKEMIA; CANCER; DISTRACTION; ACROPHOBIA; DISTRESS AB STARBRIGHT World (SBW) is a virtual environment designed to link seriously ill children into an interactive online community in which they can play games, learn about their medical condition, or talk with other chronically ill children. This study evaluated the impact of SBW on pain, mood, anger, loneliness, problem behavior, and willingness to return for treatment of children receiving outpatient treatment at the National Institutes of Health (NIH). To test the hypothesis that SBW provides benefit through distraction, a restricted alternating treatments design was utilized to measure anger, pain, and mood. To test the more long-term benefits of SBW, loneliness and problem behavior were measured at baseline and at the end of the study. Willingness to return was measured at each hospital visit made during the study. Process information was also collected during each SBW session (e.g., ease of use, frustration, and general enjoyment of the system). Thirty-two children participating in pediatric clinical trials at the NIH and their caregivers; participated in the study. Seventy-eight percent of participants, ages 8 to 19 years, were HIV infected and the remaining 22% had varied, but potentially life-threatening, illnesses. Children reported significantly less loneliness and were significantly more willing to return to the hospital for treatment from baseline to follow-up. They were marginally less worried after using SBW than after using the regular playroom. Parents reported that their children experienced significantly less withdrawn behavior and needed significantly less help with both anxiety and resistance in returning to the hospital for treatment after using SBW. They also reported that SBW helped their children to feel decreases inloneliness and depressed mood, and increases in energetic mood. SBW is a potentially useful tool to improve the hospital experience for seriously ill children, reduce their feelings of loneliness and isolation, and help them to be less socially withdrawn. C1 NCI, Pediat HIV Working Grp, HIV AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Battles, HB (reprint author), NCI, Pediat HIV Working Grp, HIV AIDS Malignancy Branch, 10-13N240,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 53 TC 27 Z9 28 U1 0 U2 6 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0273-9615 J9 CHILD HEALTH CARE JI Child. Health Care PD WIN PY 2002 VL 31 IS 1 BP 47 EP 68 DI 10.1207/S15326888CHC3101_4 PG 22 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 528UR UT WOS:000174262800004 ER PT J AU Brenchley, JM Douek, DC Ambrozak, DR Chatterji, M Betts, MR Davis, LS Koup, RA AF Brenchley, JM Douek, DC Ambrozak, DR Chatterji, M Betts, MR Davis, LS Koup, RA TI Expansion of activated human naive T-cells precedes effector function SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE naive T-cells; antigen-experienced T-cells; cellular proliferation; T-cell stimulation; IFN-gamma; CTLA-4; IL-7 ID IN-VIVO; HOMEOSTATIC PROLIFERATION; IMMUNOLOGICAL MEMORY; OX-40 LIGAND; INTERLEUKIN-7; SURVIVAL; REPERTOIRE; SUBSETS; MICE; DIFFERENTIATION AB Naive T-cells divide and mature, both functionally and phenotypically, upon stimulation through the T-cell receptor. Although much is known about the overall changes that occur in naive cells upon TCR stimulation, and the different memory/effector populations that arise following stimulation, the relationship between cell division and functional and phenotypical changes that occur after activation is poorly understood. Here, we examine the early stages of human naive and antigen-experienced T-cell activation, and the relationship between cell division and acquisition of effector function during the transition from resting antigen-experienced or naive T-cells into effector cells. Stimulated naive T-cells proliferate prior to acquisition of effector function, as measured by cytokine production and expression of effector-associated cell surface molecules. Additionally, we show that interlukin-7 (IL-7) can drive proliferation of naive T-cells without TCR:MHC peptide interactions. IL-7 alone does not, however, drive the proliferation of antigen-experienced T-cells. Memory T-cells will divide in response to exogenous IL-7 but only in the presence of naive T-cells and IL-2. This study contributes to the current understanding of the mechanistic differences between naive and memory T-cell responses by defining the functional and phenotypic changes that occur to T-cells after stimulation. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Dept Expt Transplantat & Immunol, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Infect Dis, Div Rheumatol, Dallas, TX USA. RP Koup, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 41 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD DEC PY 2002 VL 130 IS 3 BP 431 EP 440 PG 10 WC Immunology SC Immunology GA 618GG UT WOS:000179409900011 ER PT J AU Akel, S Kolialexi, A Mavrou, A Metaxotou, C Loukopoulos, D Yataganas, X AF Akel, S Kolialexi, A Mavrou, A Metaxotou, C Loukopoulos, D Yataganas, X TI Efficiency of interphase fluorescence in situ hybridization for BCR/ABL on peripheral blood smears for monitoring of CML patients: a comparison with bone marrow findings SO CLINICAL AND LABORATORY HAEMATOLOGY LA English DT Article DE chronic myeloid leukemia; fluorescence in situ hybridization; immunophenotyping; T lymphocytes; BCR/ABL ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; SINGLE-CELL LEVEL; PHILADELPHIA-CHROMOSOME; CHRONIC PHASE; RESIDUAL LEUKEMIA; STEM-CELLS; LYMPHOCYTES; REMISSION AB Conventional cytogenetic analysis (CCA) is the standard method for monitoring of the Philadelphia (Ph) chromosome in chronic myeloid leukemia (CML). Evaluation of breakpoint cluster region/abelson murine leukemia (BCR/ABL) fusion using interphase fluorescence in situ hybridization on peripheral blood smears (PB-FISH) might be another approach allowing more frequent and less invasive follow-up investigations. Herein, BCR/ABL fusion gene was assessed on 21 PB smears from 16 CML patients in chronic phase. Results of PB-FISH were compared with those of CCA and interphase FISH on bone marrow aspirates (BM-FISH). PB-FISH analysis was combined with CD3 immunophenotyping that allowed simultaneous investigation of the leukemic status of CD3(+) T lymphocytes and scoring CD3(-) cells for BCR/ABL fusion gene. Moreover, the frequency of BCR/ABL fusion in nonlymphoid PB cells was estimated according to the differential leukocyte counts. The incidence of BCR/ABL(+) fusion signals in CD3(+) T cells of CML patients was 5.3% (SD+/-1.9) and did not exceed the normal cut-off value of 8%. A significant correlation (P<0.001) was found between results of PB-FISH and methods of BM analysis (CCA or BM-FISH). Correction of PB-FISH results to include only nonlymphoid or CD3(-) cells reduced the mean of differences and improved agreement between PB-FISH and CCA or BM-FISH methods. The best agreement was noted between CCA and PB-FISH on nonlymphoid cells. On the other hand, results of BM-FISH agreed well with those of PB-FISH on CD3(-) cells. These findings imply that PB-FISH on nonlymphoid or CD3(-) cells is reliable and may replace BM analysis for monitoring of response to treatment in CML patients. C1 Univ Athens, Sch Med, Dept Med 1, GR-11527 Athens, Greece. Univ Athens, Sch Med, Dept Med Genet, GR-11527 Athens, Greece. RP Akel, S (reprint author), NCI, Basic Res Lab, CCR, Bldg 567,Rm 261, Frederick, MD 21702 USA. NR 21 TC 7 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0141-9854 J9 CLIN LAB HAEMATOL JI Clin. Lab. Haematol. PD DEC PY 2002 VL 24 IS 6 BP 361 EP 367 DI 10.1046/j.1365-2257.2002.00470.x PG 7 WC Hematology SC Hematology GA 619RX UT WOS:000179491800007 PM 12452817 ER PT J AU Houghton, PJ Adamson, PC Blaney, S Fine, HA Gorlick, R Haber, M Helman, L Hirschfeld, D Hollingshead, MG Israel, MA Lock, RB Maris, JM Merlino, G Patterson, W Reynolds, CP Shannon, K Yu, A Yu, J Smith, MA AF Houghton, PJ Adamson, PC Blaney, S Fine, HA Gorlick, R Haber, M Helman, L Hirschfeld, D Hollingshead, MG Israel, MA Lock, RB Maris, JM Merlino, G Patterson, W Reynolds, CP Shannon, K Yu, A Yu, J Smith, MA TI Testing of new agents in childhood cancer preclinical models: Meeting summary SO CLINICAL CANCER RESEARCH LA English DT Review ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ANTIVIRAL PROTEIN IMMUNOTOXIN; NEUROBLASTOMA-CELL-LINES; TOPOISOMERASE-I INHIBITOR; CHRONIC MYELOID-LEUKEMIA; SYSTEM TUMOR XENOGRAFTS; TRANSGENIC MOUSE MODEL; MEDULLOBLASTOMA XENOGRAFTS; ANTITUMOR-ACTIVITY; NEUROFIBROMATOSIS TYPE-1 AB A workshop on pediatric preclinical testing, sponsored by the National Cancer Institute and the Children's Oncology Group Phase 1 Consortium, was held on June 26-27, 2001 in Bethesda, Maryland. Drs. Peter Adamson, Peter Houghton, and Malcolm Smith organized and hosted the meeting. There were 20 participants from 12 institutions. The primary objectives of the workshop included: (a) development of a working inventory of available preclinical models (including human tumor xenografts in immunodeficient mice, transgenic and syngeneic tumors, and selected in vitro models), with a basic understanding of the strengths and weaknesses of each as possible components of a preclinical testing program; (b) identification of the key scientific issues related to establishment of a program for preclinical testing of new agents for their applicability to childhood cancers; and (c) identification of the key infrastructure requirements for a program for preclinical testing of new agents for their applicability to childhood cancers. This report is a synthesis of the workshop's presentations and discussions. C1 St Jude Childrens Res Hosp, Memphis, TN 38101 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Texas Childrens Canc Ctr, Houston, TX 77024 USA. Neurol Oncol Branch, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ New S Wales, Childrens Canc Inst Australia Med Res, Kensington, NSW 2033, Australia. Sydney Childrens Hosp, Childrens Canc Inst Australia Med Res, Randwick, NSW, Australia. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20852 USA. NCI, Biol Testing Branch, Frederick, MD 21702 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Lebanon, NH 03756 USA. NCI, Mol Genet Sect, Bethesda, MD 20892 USA. NCI, Technol Transfer Branch, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Scripps Res Inst, La Jolla, CA 92037 USA. NCI, Canc Therapy Evaluat Program, Pediat Sect, Bethesda, MD 20892 USA. RP Smith, MA (reprint author), NCI, Canc Therapy Evaluat Program, Pediat Sect, 6130 Execut Blvd,Room 7025, Bethesda, MD 20892 USA. EM smithm@ctep.nci.nih.gov RI Houghton, Peter/E-3265-2011; YU, JOHN/G-8954-2012; Lock, Richard/G-4253-2013; Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 109 TC 42 Z9 42 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 2002 VL 8 IS 12 BP 3646 EP 3657 PG 12 WC Oncology SC Oncology GA 622XR UT WOS:000179673400002 PM 12473573 ER PT J AU McCarthy, NJ Yang, XW Linnoila, IR Merino, MJ Hewitt, SM Parr, AL Paik, S Steinberg, SM Hartmann, DP Mourali, N Levine, PH Swain, SM AF McCarthy, NJ Yang, XW Linnoila, IR Merino, MJ Hewitt, SM Parr, AL Paik, S Steinberg, SM Hartmann, DP Mourali, N Levine, PH Swain, SM TI Microvessel density, expression of estrogen receptor alpha, MIB-1, p53, and c-erbB-2 in inflammatory breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID INDEPENDENT PROGNOSTIC INDICATOR; TUMOR ANGIOGENESIS; POOR-PROGNOSIS; CARCINOMA; CHEMOTHERAPY; GROWTH; OVEREXPRESSION; ASSOCIATION; EXPERIENCE; MUTATION AB Purpose and Experimental Design: The purpose is to define intratumoral microvessel density (MVD) and potential biological markers that correlate with inflammatory breast cancer (IBC), we examined MVD, estrogen receptor a (ER) status, MIB-1 proliferation index, p53, and c-erbB-2 by immunohistochemistry in archival specimens from 67 women diagnosed with breast cancer with or without the inflammatory phenotype at the Institut Salah Azaiz (Tunis, Tunisia). Results: The moderate (25-50/X400 field) to high microvessel count (>50/X400 field) was observed in 23 (51%) of 45 IBC tumors compared with 3 (14%) of 22 non-IBC tumors (P = 0.0031; chi(2) test). The presence of ER was found in 6 (14%) of 44 cases versus 7 (32%) of 22 cases in IBC and non-IBC, respectively (P = 0.10). In this series of 67 patient tumors, the median MVD count in ER-negative breast tumors was 21, whereas the median count was 4 in ER-positive breast tumors (P = 0.08; Wilcoxon rank-sum test). However, MIB-1, p53, and c-erbB-2 were not significantly different between IBC and non-IBC tumors. The intratumoral MVD between IBC and non-IBC was still statistically significant after adjustment for multiple comparisons (P 0.02; Bonferroni test). Conclusions: These data suggest that there is an increased MVD in breast cancer with the inflammatory phenotype as compared with breast cancer without the inflammatory phenotype. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20889 USA. NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20889 USA. NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20889 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20889 USA. Natl Surg Adjuvant Breast & Bowel Project Operat, Pittsburgh, PA USA. Georgetown Univ, Washington, DC USA. Ctr Ibn Zohr, Tunis, Tunisia. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. RP Swain, SM (reprint author), NCI, Canc Therapeut Branch, Ctr Canc Res, Navy Bldg 8,Room 5101, Bethesda, MD 20889 USA. RI McCarthy, Nicole/A-3468-2013; OI Hewitt, Stephen/0000-0001-8283-1788 NR 41 TC 52 Z9 54 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 2002 VL 8 IS 12 BP 3857 EP 3862 PG 6 WC Oncology SC Oncology GA 622XR UT WOS:000179673400029 PM 12473600 ER PT J AU Schneider, GP Salcedo, R Dong, HF Kleinman, HK Oppenheim, JJ Howard, OMZ AF Schneider, GP Salcedo, R Dong, HF Kleinman, HK Oppenheim, JJ Howard, OMZ TI Suradista NSC 651016 inhibits the angiogenic activity of CXCL12-stromal cell-derived factor 1 alpha SO CLINICAL CANCER RESEARCH LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; DISTAMYCIN-A DERIVATIVES; FIBROBLAST-GROWTH-FACTOR; HUMAN ENDOTHELIAL-CELLS; IN-VIVO; SULFONATED DISTAMYCIN; MOLECULAR-CLONING; EXPRESSION; CANCER; SURAMIN AB CXCL12 (stromal cell-derived factor let), a ligand for CXCR4, has been shown to induce endothelial cell chemotaxis and to stimulate angiogenesis, suggesting that it may be a significant target for antiangiogenic therapy. Here we have tested suradista NSC 651016, a compound known to inhibit CXCL12-induced monocyte chemotaxis, for its ability to inhibit CXCL12-induced angiogenic activity. NSC 651016 inhibited CXCL12-mediated endothelial cell chemotaxis in a dose-dependent manner. In addition, new vessel sprouting, by both rat and chick aorta in an angiogenesis model, was inhibited. Additionally, in vitro capillary-like structure formation induced by CXCL12 was inhibited by NSC 651016. Furthermore, NSC 651016 inhibited CXCL12-mediated angiogenesis in an in vivo s.c. assay. These data indicate that suradista NSC 651016 possesses in vitro and in vivo antiangiogenic activity and has the potential to interfere with neovacularization of tumors and their metastases. C1 NCI, Frederick, MD 21702 USA. Sci Applicat Int Corp, Mol Immunoregulat Lab, Frederick, MD USA. Sci Applicat Int Corp, Canc Res Ctr, Intramural Res Support Program, Frederick, MD USA. Natl Inst Dent & Craniofacial Res, Cell Biol Sect, Bethesda, MD 20892 USA. RP Howard, OMZ (reprint author), NCI, POB B, Frederick, MD 21702 USA. RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 FU PHS HHS [N01-C0-12400] NR 28 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC PY 2002 VL 8 IS 12 BP 3955 EP 3960 PG 6 WC Oncology SC Oncology GA 622XR UT WOS:000179673400041 PM 12473612 ER PT J AU Holubkov, R Pepine, CJ Rickens, CR Reichek, N Rogers, WJ Sharaf, BL Sopko, G Merz, CNB Kelsey, SF Olson, M Smith, KM Reis, SE AF Holubkov, R Pepine, CJ Rickens, CR Reichek, N Rogers, WJ Sharaf, BL Sopko, G Merz, CNB Kelsey, SF Olson, M Smith, KM Reis, SE CA Womens Ischemia Syndrome Evaluatio TI Electrocardiogram abnormalities predict angiographic coronary artery disease in women with chest pain: Results from the NHLBI WISE study SO CLINICAL CARDIOLOGY LA English DT Article DE coronary artery disease; chest pain; women; electrocardiogram ID ECHOCARDIOGRAPHY; ACCURACY; GENDER; HEART AB Background and hypothesis: Noninvasive risk stratification for coronary artery disease (CAD) is less accurate in women than in men. Based on recent reports that gender-specific exercise electrocardiogram (ECG) parameters predict CAD, we evaluated the independent predictive value of the resting ECG for angiographic CAD in women with chest pain. Methods: Women (n = 850, mean age 58 years) with chest pain in the NHLBI Women's Ischemia Syndrome Evaluation (WISE) underwent 12-lead ECG testing and quantitative coronary angiography. Results: Significant angiographic CAD (greater than or equal to50% stenosis in greater than or equal to 1 coronary) was present in 39% of women. Q waves in greater than or equal to2 contiguous ECG leads were present in 107 women (13%), including 49 of 657 (7%) without history of infarction. Among 585 women without prior infarction or revascularization, 48% of those with Q waves in contiguous leads versus 26% of others, had significant CAD (p = 0.003; odds ratio [OR] = 2.5, 95% confidence interval [CI] = 1.3-4.8). Women with Q waves in greater than or equal to2 inferior ECG leads were particularly likely to have CAD (63 vs. 26% of others, p < 0.001; OR = 4.6,95% CI = 2.0-10.8). Other ECG findings predictive of CAD were any ST-T abnormality (OR =1.9, 95% CI =1.3-2.8) and T-wave inversion (OR = 2.4,95% CI =1.3-4.2). In risk-adjusted analysis, inferior Q waves and T-wave inversion independently predicted significant CAD. When considered together with radionuclide perfusion test results, T-wave inversion on resting ECG added significant independent predictive value (OR = 2.8, 95% CI =1.1-7.2, p = 0.03). Conclusions: Selected resting ECG parameters independently predict angiographic CAD in women with chest pain, including women who have also undergone radionuclide stress testing. Prospective studies should consider resting ECG parameters in diagnostic algorithms for CAD in women. C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Florida, Dept Med, Div Cardiovasc Med, Gainesville, FL USA. Allegheny Gen Hlth Syst, Dept Med, Div Cardiol, Pittsburgh, PA USA. Univ Alabama, Dept Med, Div Cardiol, Birmingham, AL 35294 USA. Rhode Isl Hosp, Dept Med, Div Cardiol, Providence, RI 02903 USA. NHLBI, NIH, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. RP Reis, SE (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, 200 Lothrop St, Pittsburgh, PA 15213 USA. RI Reis, Steven/J-3957-2014 FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV-68162, N01-HV-68163, N01-HV-68164, N01-HV-68161] NR 18 TC 3 Z9 3 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD DEC PY 2002 VL 25 IS 12 BP 553 EP 558 DI 10.1002/clc.4950251204 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 621WL UT WOS:000179614000003 PM 12492124 ER PT J AU Unden, AL Elofsson, S Knox, S Lewitt, MS Brismar, K AF Unden, AL Elofsson, S Knox, S Lewitt, MS Brismar, K TI IGF-I in a normal population: relation to psychosocial factors SO CLINICAL ENDOCRINOLOGY LA English DT Article ID GROWTH-FACTOR-I; FACTOR-BINDING PROTEIN-1; SERUM-INSULIN; CIRCULATING LIPOPROTEIN(A); HORMONE DEFICIENCY; DIABETIC-PATIENTS; HEALTHY-SUBJECTS; WOMEN; MEN; DENSITY AB OBJECTIVE IGF-I has important actions on cell division, apoptosis, differentiation and metabolism, as well as on cell proliferation in vascular smooth muscle. Deficiency of GH, an important regulator of IGF-I, is associated with reduced well-being. IGF-I levels have been related to cognitive function in older individuals. The aim of the present study was to investigate the IGF-I concentrations in a normal population of men and women aged 20-74 years and to determine the influence of a variety of behavioural and psychosocial factors as well as metabolic factors on these concentrations. DESIGN Cross-sectional study. PATIENTS The study group consisted of 408 randomly selected people who had answered a questionnaire concerning health care utilization and quality of life that was administered to a random sample of 4200 people over age 17 from the northwestern region of greater Stockholm in 1995. Thirty-four men and 34 women were randomly selected from the age group 20-24 and from each 10-year age group between the ages of 25-75 years. Seventy-one per cent of the 408 people invited to come in for an examination agreed to attend, making a total sample size of 288 people. MEASUREMENTS A medical examination was performed and blood drawn in the morning after subjects had been fasting overnight. Before the examination, they were asked to fill out a questionnaire concerning lifestyle and psychosocial factors. RESULTS The distribution of IGF-I was positively skewed, but using logarithmically transformed IGF-I, a more symmetrical distribution was obtained. A linear inverse correlation was found between logarithmically transformed IGF-I levels and age which explained more than 40% of the variation in men and women. Linear correlation analysis between IGF-I and different parameters of health and disease, lifestyle and psychosocial factors, resulted in several significant correlations most of which disappeared after controlling for age. In the younger age group (20-44) there were positive correlations between IGF-I and psychosocial factors representing quality of life and psychological well-being. In the middle age group (45-59) higher IGF-I levels were related to better physical health, higher education and higher concentrations of lipoprotein Lp(a). In the older age group (over 59 years) higher levels of low-density lipoprotein-cholesterol (LDL-C) and lower levels of SHBG were associated with higher IGF-I levels. CONCLUSION In a randomly selected (nondisease) population, IGF-I concentrations show a consistent decrease with age in both men and women, accompanied by different association patterns relevant to disease risk. Levels are related to psychosocial parameters in the younger age group and metabolic impairment associated with increased cardiovascular risk in the older age groups. We speculate on the relative roles of age and cohort differences in rearing conditions in determining these differences. C1 Karolinska Hosp, Res Ctr Gen Med, S-17176 Stockholm, Sweden. Univ Stockholm, Inst Social Work, S-10691 Stockholm, Sweden. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Karolinska Inst, Dept Mol Med, Endocrine & Diabet Unit, Stockholm, Sweden. RP Unden, AL (reprint author), Karolinska Hosp, Res Ctr Gen Med, Borgmastarvillan, S-17176 Stockholm, Sweden. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 44 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD DEC PY 2002 VL 57 IS 6 BP 793 EP 803 DI 10.1046/j.1365-2265.2002.01671.x PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 620KH UT WOS:000179532200013 PM 12460330 ER PT J AU O'Grady, NP Alexander, M Dellinger, EP Gerberding, JL Heard, SO Maki, DG Masur, H McCormick, RD Mermel, LA Pearson, ML Raad, II Randolph, A Weinstein, RA AF O'Grady, NP Alexander, M Dellinger, EP Gerberding, JL Heard, SO Maki, DG Masur, H McCormick, RD Mermel, LA Pearson, ML Raad, II Randolph, A Weinstein, RA TI Guidelines for the prevention of intravascular catheter-related infections SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID CENTRAL VENOUS CATHETER; BLOOD-STREAM INFECTION; INTENSIVE-CARE-UNIT; TOTAL PARENTERAL-NUTRITION; RANDOMIZED CONTROLLED TRIAL; CRITICALLY ILL PATIENTS; PERIPHERAL INTRAVENOUS CATHETERS; RESISTANT STAPHYLOCOCCUS-AUREUS; PULMONARY-ARTERY CATHETERS; IN-LINE FILTRATION AB These guidelines have been developed for practitioners who insert catheters and for persons responsible for surveillance and control of infections in hospital, outpatient, and home health-care settings. This report was prepared by a working group comprising members from professional organizations representing the disciplines of critical care medicine, infectious diseases, health-care infection control, surgery, anesthesiology, interventional radiology, pulmonary medicine, pediatric medicine, and nursing. The working group was led by the Society of Critical Care Medicine (SCCM), in collaboration with the Infectious Disease Society of America (IDSA), Society for Healthcare Epidemiology of America (SHEA), Surgical Infection Society (SIS), American College of Chest Physicians (ACCP), American Thoracic Society (ATS), American Society of Critical Care Anesthesiologists (ASCCA), Association for Professionals in Infection Control and Epidemiology (APIC), Infusion Nurses Society (INS), Oncology Nursing Society (ONS), Society of Cardiovascular and Interventional Radiology (SCVIR), American Academy of Pediatrics (AAP), and the Healthcare Infection Control Practices Advisory Committee (HICPAC) of the Centers for Disease Control and Prevention (CDC) and is intended to replace the Guideline for Prevention of Intravascular Device-Related Infections published in 1996. These guidelines are intended to provide evidence-based recommendations for preventing catheter-related infections. Major areas of emphasis include 1) educating and training health-care providers who insert and maintain catheters; 2) using maximal sterile barrier precautions during central venous catheter insertion; 3) using a 2% chlorhexidine preparation for skin antisepsis; 4) avoiding routine replacement of central venous catheters as a strategy to prevent infection; and 5) using antiseptic/antibiotic impregnated short-term central venous catheters if the rate of infection is high despite adherence to other strategies (i.e., education and training, maximal sterile barrier precautions, and 2% chlorhexidine for skin antisepsis). These guidelines also identify performance indicators that can be used locally by health-care institutions or organizations to monitor their success in implementing these evidence-based recommendations. C1 NIH, Bethesda, MD 20892 USA. Infus Nurses Soc, Cambridge, MA USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Childrens Hosp, Boston, MA 02115 USA. Univ Washington, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Off Director, CDC, Atlanta, GA USA. CDC, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Univ Wisconsin, Sch Med, Madison, WI USA. Univ Wisconsin, Hosp & Clin, Madison, WI 53792 USA. Rhode Isl Hosp, Providence, RI USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Cook Cty Hosp, Chicago, IL 60612 USA. Rush Med Coll, Chicago, IL 60612 USA. RP O'Grady, NP (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 294 TC 105 Z9 114 U1 3 U2 21 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2002 VL 35 IS 11 BP 1281 EP 1307 DI 10.1086/344188 PG 27 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 617AK UT WOS:000179336800001 ER PT J AU Falusi, O French, AL Seaberg, EC Tien, PC Watts, DH Minkoff, H Piessens, E Kovacs, A Anastos, K Cohen, MH AF Falusi, O French, AL Seaberg, EC Tien, PC Watts, DH Minkoff, H Piessens, E Kovacs, A Anastos, K Cohen, MH TI Prevalence and predictors of Toxoplasma seropositivity in women with and at risk for human immunodeficiency virus infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; HIV; SEROPREVALENCE AB We assessed the prevalence and predictors of latent Toxoplasma infection in a large group of human immunodeficiency virus (HIV)-infected and HIV-uninfected at-risk US women. The prevalence of latent Toxoplasma infection was 15% (380 of 2525 persons) and did not differ by HIV infection status. HIV-infected women aged greater than or equal to50 years and those born outside of the United States were more likely to have latent Toxoplasma infection, with prevalences of 32% and 41%, respectively. C1 Cook Cty Hosp, Div Infect Dis, Chicago, IL 60612 USA. Rush Med Coll, Chicago, IL 60612 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NICHHD, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Maimonides Hosp, Brooklyn, NY 11219 USA. Montefiore Med Ctr, Lincoln Med & Mental Hlth Ctr, Bronx, NY 10467 USA. Georgetown Univ Hosp, Washington, DC 20007 USA. RP Falusi, O (reprint author), Cook Cty Hosp, Div Infect Dis, Durand 115,1835 W Harrison St, Chicago, IL 60612 USA. FU NCRR NIH HHS [M01 RR000071, M01 RR000083, M01-RR00071, M01-RR00083]; NIAID NIH HHS [R01 AI052065, R01 AI052065-01, U01 AI031834, U01 AI034989, U01 AI034993, U01 AI034994, U01 AI035004, U01 AI042590, U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590]; NICHD NIH HHS [U01 HD032632, U01-HD-32632] NR 13 TC 27 Z9 29 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2002 VL 35 IS 11 BP 1414 EP 1417 DI 10.1086/344462 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 617AK UT WOS:000179336800017 PM 12439806 ER PT J AU Miyazawa, N Aoki, S Toyama, K Arbab, AS Hori, M Umeda, T Araki, T Nukui, H AF Miyazawa, N Aoki, S Toyama, K Arbab, AS Hori, M Umeda, T Araki, T Nukui, H TI Velocity-coded colour magnetic resonance angiography and perfusion-weighted magnetic resonance imaging for the evaluation of extracranial-to-intracranial arterial bypass surgery SO CLINICAL NEUROLOGY AND NEUROSURGERY LA English DT Article DE major artery occlusion; extracranial-to-intracranial arterial bypass; phase contrast magnetic resonance imaging; perfusion-weighted magnetic resonance imaging; single photon emission computed tomography ID CEREBRAL BLOOD-FLOW; POSITRON EMISSION TOMOGRAPHY; MR-ANGIOGRAPHY; TC-99M-HMPAO SPECT; OXYGEN-METABOLISM; BRAIN PERFUSION; PHASE-CONTRAST; DISEASE; QUANTIFICATION; COMPLICATIONS AB Background and purpose: Velocity-coded colour magnetic resonance angiography (VCCMRA) and perfusion magnetic resonance imaging (pMRI) were evaluated as methods for investigating the efficacy of extracranial-to-intracranial arterial bypass (EC-IC bypass) by comparing the findings of VCCMRA and those of cerebral angiography and by measuring the improvement ratio after EC-IC bypass by pMRI compared to that by single photon emission computed tomography (SPECT) using the autoradiographic technique. Methods: Thirteen patients who underwent VCCMRA, angiography, SPECT, and pMRI before and after surgery were analyzed. Findings of VCCMRA were compared to those of angiography. Improvement ratio was calculated compared to the cerebellum for cerebral blood volume, mean transit time (MTT), and regional cerebral blood flow (rCBF) as measured by pMRI and quantitative SPECT. Results: Findings of VCCMRA were in good agreement with those of angiography and clearly showed the direction of bypass flow. No statistically significant correlation was observed between the improvement ratios in CBF in the hemisphere and middle cerebral artery territory on the surgical and non-surgical sides and in rCBF in the same regions of interest (ROIs) (r = -0.574, 0.09). However, a statistically significant correlation was observed between the cerebrovascular reserve capacity (CVRC) in the hemisphere on the surgical side and in MTT in the same ROIs (r = 0.955, P < 0.001). Conclusion: VCCMRA may clearly show the direction of flow in the EC-IC bypass. MIT measured by pMRI may indicate the postoperative state of CVRC. These techniques could replace angiography and positron emission tomography or SPECT in patients undergoing EC-IC bypass. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Yamanashi Med Univ, Dept Neurosurg, Tamaho, Yamanashi 4093898, Japan. Univ Tokyo, Sch Med, Dept Radiol, Bunkyo Ku, Tokyo 1138655, Japan. Yamanashi Med Univ, Dept Radiol, Tamaho, Yamanashi 4093898, Japan. NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res Clin Ctr, Bethesda, MD 20892 USA. RP Miyazawa, N (reprint author), Yamanashi Med Univ, Dept Neurosurg, 1110 Shimokato, Tamaho, Yamanashi 4093898, Japan. RI Hori, Masaaki/G-1235-2010 NR 35 TC 0 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0303-8467 J9 CLIN NEUROL NEUROSUR JI Clin. Neurol. Neurosurg. PD DEC PY 2002 VL 105 IS 1 BP 48 EP 59 AR PII S0303-8467(02)00102-6 DI 10.1016/S0303-8467(02)00102-6 PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 625GG UT WOS:000179808300012 PM 12445925 ER PT J AU Post, RA AF Post, RA TI Depression in bipolar illness: the stepchild - Preface and overview SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Editorial Material ID SUICIDE ATTEMPTS; II DISORDER; EXPRESSION; POSTMORTEM; BRAIN C1 NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Post, RA (reprint author), NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Room 3S 239,Bldg 10,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. NR 18 TC 5 Z9 5 U1 2 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2002 VL 2 IS 3-4 BP 122 EP 126 AR PII S1566-2727(02)00037-3 DI 10.1016/S1566-2772(02)00037-3 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633GE UT WOS:000180273600002 ER PT J AU Merikangas, K Yu, K AF Merikangas, K Yu, K TI Genetic epidemiology of bipolar disorder SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE genetics; epidemiology; mood disorders; linkage; association; family ID MANIC-DEPRESSIVE ILLNESS; COMPLEX HUMAN-DISEASES; POSSIBLE SUSCEPTIBILITY LOCUS; NATIONAL-COMORBIDITY-SURVEY; AFFECTIVELY ILL PARENTS; GENOME-WIDE SEARCH; PAST 10 YEARS; MAJOR DEPRESSION; PSYCHIATRIC-DISORDERS; FOLLOW-UP AB Objective: To present a summary of recent studies of the familial aggregation and the role of genetic factors in the etiology of mood disorders. Methods: Review of empirical evidence from studies of familial aggregation and association and linkage for mood disorder. Results: The weighted average risk ratio for bipolar disorder among relatives of bipolar probands is 9.2, whereas major depressive disorder (MDD) among relatives of bipolar probands compared to those of controls is 1.9. In contrast, the average risk ratio for MDD among relatives of probands with MDD compared to those of controls was 2.0, indicating only a moderate influence of familial aggregation on non-bipolar mood disorders. Despite some promising leads, there are still no confirmed linkage findings for bipolar disorder. Unresolved issues that contribute to the lack of consistency in findings from association and linkage studies including; 1) the lack of validity of classification of mood disorder phenotypes; 2) inconsistent sampling and methods of existing genetic studies of mood disorders; 3) comorbidity between mood disorders with anxiety disorders and substance use disorder are discussed. Conclusion: Collaborative studies to enhance power and to resolve inconsistencies which currently result from ascertainment and methodological differences across studies are clearly needed. Studies that focus on mood disorder endophenotypes that are closer to the actual activity of underlying genes will enhance the power to identify the genetic factors underlying mood disorders. The application of tools of genetic epidemiology to identify joint role contribution of genetic and environmental risk factors for mood disorder in general population will be critical in future research. Published by Elsevier Science B.V. C1 NIMH, Mood & Anxiety Disorder Program, NIH, Bethesda, MD 20892 USA. RP Merikangas, K (reprint author), 15K North Dr,MSC 2670, Bethesda, MD 20892 USA. NR 148 TC 7 Z9 9 U1 4 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2002 VL 2 IS 3-4 BP 127 EP 141 AR PII S1566-2772(02)00038-5 DI 10.1016/S1566-2772(02)00038-5 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633GE UT WOS:000180273600003 ER PT J AU Post, RA Denicoff, KD Leverich, GS Altshuler, LL Frye, MA Suppes, TM Keck, PE McElroy, SL Kupka, R Nolen, WA Grunze, H Walden, J AF Post, RA Denicoff, KD Leverich, GS Altshuler, LL Frye, MA Suppes, TM Keck, PE McElroy, SL Kupka, R Nolen, WA Grunze, H Walden, J TI Presentations of depression in bipolar illness SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Review DE bipolar; depression; tolerance; refractoriness; early onset; anticipation ID SUBGENUAL PREFRONTAL CORTEX; BIRTH-COHORT CHANGES; AFFECTIVE-DISORDER; LITHIUM PROPHYLAXIS; MOOD DISORDERS; NEUROANATOMICAL STRUCTURES; MAINTENANCE TREATMENT; CONTINGENT TOLERANCE; NATIONAL-INSTITUTE; SYMPTOMATOLOGY IDS AB In this paper, a variety of components and treatment characteristics of bipolar depression are addressed. In a large sample of intensively and naturalistically treated outpatients with bipolar illness, daily prospective ratings for I year showed that the total time spent depressed exceeded time spent manic by a factor of three, indicating that the depressive phases of bipolar illness in this sample were more problematic and treatment-resistant than the manic phases. Two-thirds of these patients remained substantially impaired by their illness and only one-third had minimal symptoms for the entire year. New data on discontinuation of effective adjunctive antidepressant treatment, in a small subgroup of patients initially responsive for 2 months, suggests that discontinuation may increase the risk of relapse into depression. Different patterns of treatment-resistance to mood stabilizers are discussed, including the possibilities of tolerance development and discontinuation-induced refractoriness. The characteristic phenomenological presentation and neurocognitive deficits of bipolar depression are briefly outlined. The occurrence of an earlier age of onset of depression and bipolar illness are discussed in relation to cohort and anticipation mechanisms and their possible association with the development of treatment-resistance. (C) 2002 Elsevier Science B.V. All rights reserved. C1 NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Mood Disorders Res Program, Los Angeles, CA USA. VA Med Ctr, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Univ Cincinnati, Coll Med, Biol Psychiat Program, Cincinnati, OH USA. Univ Utrecht, Ctr Med, Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. LMU, Psychiat Klin, Munich, Germany. Univ Freiburg, Dept Psychiat, Freiburg, Germany. RP NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Room 3S239,Bldg 10,MSC 1272,10 Ctr Dr, Bethesda, MD 20892 USA. EM postr@intra.nimh.nih.gov RI Nolen, Willem/E-9006-2014 NR 101 TC 14 Z9 14 U1 8 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2002 VL 2 IS 3-4 BP 142 EP 157 AR PII S1566-2772(02)00039-7 DI 10.1016/S1566-2772(02)00039-7 PG 16 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633GE UT WOS:000180273600004 ER PT J AU Leverich, GS Perez, S Luckenbaugh, DA Post, RM AF Leverich, GS Perez, S Luckenbaugh, DA Post, RM TI Early psychosocial stressors: relationship to suicidality and course of bipolar illness SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE early stress; bipolar; suicidality; abuse history; course of illness; early intervention ID MESSENGER-RNA EXPRESSION; AFFECTIVE-DISORDER; SEXUAL ABUSE; NEUROTROPHIC FACTOR; SUBSTANCE-ABUSE; MOOD DISORDERS; LIFE EVENTS; DELTA-FOSB; LITHIUM; RISK AB Substantial preclinical data support the view that early environmental stress may be associated with long-term changes in brain development and brain chemistry in association with long-lasting alterations in neuroendocrinology, behavior, and vulnerability to acquiring psychoactive drug self-administration. Similarly, a considerable clinical literature has evaluated the possible impact of early and ongoing psychosocial stress in the onset and recurrence of the unipolar and bipolar affective disorders and their comorbidities. In this article we review data on the association of the occurrence of severe environmental stressors in childhood and adolescence and subsequent course of illness in a cohort of more than 600 outpatients with bipolar I or bipolar 11 disorder studied in the Stanley Foundation Bipolar Network. Self-report of early physical or sexual abuse was used as the primary index of early stressors and a variety of other events were noted, both at illness onset and prior to the most recent affective episode. The early adversities in childhood and adolescence were associated with an earlier onset of bipolar disorder, a more adverse course of illness reported retrospectively and confirmed prospectively, more Axis 1, 11, and III comorbidities, lack or loss of ongoing social and medical supports, and an increased incidence of serious suicide attempts prior to network entry. These early extreme stressors interacted with a positive family history of affective disorders in relation to an earlier age of onset of bipolar disorder, and there also appeared to be a stressor 'dose' relationship to the incidence of prior suicide attempts. The impact and interaction of these stressors on course of illness, comorbidity, and suicide attempts are discussed in relation to the clinical and preclinical literature and opportunities for early intervention and prevention. (C) 2002 Published by Elsevier Science B.V. C1 NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP NIMH, Dept Hlth & Human Serv, NIH, Biol Psychiat Branch, Bldg 10,Room 3S 239,10 Ctr Dr,MSC 1272, Bethesda, MD 20892 USA. EM levericg@nimh.nih.gov NR 62 TC 13 Z9 13 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD DEC PY 2002 VL 2 IS 3-4 BP 161 EP 170 AR PII S1566-2772(02)00041-5 DI 10.1016/S1566-2772(02)00041-5 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 633GE UT WOS:000180273600006 ER EF