FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Seeff, LB Miller, RN Rabkin, CS Bales, ZB Smoak, BL Johnson, LD Kaplan, EL AF Seeff, LB Miller, RN Rabkin, CS Bales, ZB Smoak, BL Johnson, LD Kaplan, EL TI 45-50 year follow-up of hepatitis C virus (HCV) infection among young military recruits. SO HEPATOLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Washington, DC USA. Inst Med, Med Follow Up Agcy, Washington, DC USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. Natl Canc Inst, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NR 0 TC 2 Z9 2 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 791 BP 360A EP 360A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100789 ER PT J AU Monga, SPS Kruse, D Redman, R Mishra, B Mishra, L AF Monga, SPS Kruse, D Redman, R Mishra, B Mishra, L TI A novel ring finger protein, PRAJA1 is required for maintenance of developing liver architecture. SO HEPATOLOGY LA English DT Meeting Abstract C1 Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19122 USA. DVAMC, Washington, DC USA. VAMC, Washington, DC USA. NHGRI, CGTB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 910 BP 390A EP 390A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100910 ER PT J AU Ghany, MG Kim, BI Kleiner, DE Hoofnagle, JH Liang, TJ AF Ghany, MG Kim, BI Kleiner, DE Hoofnagle, JH Liang, TJ TI Mutant pre-S1 protein as a cause of ground glass hepatocytes during chronic HBV infection SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 934 BP 396A EP 396A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100934 ER PT J AU Farci, P Strazzera, R DeGjonnis, D Peddis, G Chessa, L Setzu, R Ghiani, A Coiana, A Wong, D Balestrieri, A Purcell, RH AF Farci, P Strazzera, R DeGjonnis, D Peddis, G Chessa, L Setzu, R Ghiani, A Coiana, A Wong, D Balestrieri, A Purcell, RH TI Evolution of the viral quasispecies tracked by sequence analysis during interferon treatment of chronic hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Cagliari, Dept Internal Med, Cagliari, Italy. RI Chessa, Luchino/H-7561-2012 OI Chessa, Luchino/0000-0002-9474-0995 NR 0 TC 1 Z9 1 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 938 BP 397A EP 397A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100938 ER PT J AU Lau, DTY Park, Y Doo, E Kleiner, DE Schmid, P Kuhns, M Hoofnagle, JH AF Lau, DTY Park, Y Doo, E Kleiner, DE Schmid, P Kuhns, M Hoofnagle, JH TI Lamivudine treatment of chronic delta hepatitis. SO HEPATOLOGY LA English DT Meeting Abstract C1 Natl Inst Genet, Los Angeles, CA USA. NIH, Liver Dis Sect, Bethesda, MD 20892 USA. NIH, Pathol Lab, Bethesda, MD 20892 USA. Abbott Diagnost, N Chicago, IL USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 978 BP 407A EP 407A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100978 ER PT J AU Seeff, LB Hollinger, FB Alter, HJ Wright, EC Bales, ZB AF Seeff, LB Hollinger, FB Alter, HJ Wright, EC Bales, ZB CA NHLBI Study Grp TI Long-term morbidity of transfusion-associated hepatitis (TAH) C. SO HEPATOLOGY LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. NIH, Blood Bank, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Washington, DC USA. NR 0 TC 12 Z9 13 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 979 BP 407A EP 407A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258100977 ER PT J AU Rose, ML Rusyn, I Germolec, DR Graves, LM Peters, JM Gonzalez, FJ Thurman, RG AF Rose, ML Rusyn, I Germolec, DR Graves, LM Peters, JM Gonzalez, FJ Thurman, RG TI Role of Kupffer cells and NF kappa B in peroxisome proliferator-induced cell proliferation. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC USA. Univ N Carolina, Curr Toxicol, Chapel Hill, NC USA. RI Rusyn, Ivan/S-2426-2016 NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1016 BP 416A EP 416A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101015 ER PT J AU Mittur, A Kaplowitz, N Kempner, ES Ookhtens, M AF Mittur, A Kaplowitz, N Kempner, ES Ookhtens, M TI Radiation inactivation of hepatic sinusoidal GSH transport system. SO HEPATOLOGY LA English DT Meeting Abstract C1 USC, Dept Med, Los Angeles, CA USA. USC, Dept Biomed Engn, Los Angeles, CA USA. USC, Res Ctr Liver Dis, Los Angeles, CA USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1064 BP 428A EP 428A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101063 ER PT J AU Baumert, TF Satoi, J Herion, D Ito, S Blum, HE Liang, TJ AF Baumert, TF Satoi, J Herion, D Ito, S Blum, HE Liang, TJ TI Detection of anti-hepatitis C virus (HCV) antibodies in HCV-infected human serum using insect-cell derived HCV-like particles. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA USA. Univ Freiburg, Dept Med 2, Freiburg, Germany. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1212 BP 465A EP 465A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101211 ER PT J AU Forns, X Farci, P Mushahwar, IK Emerson, SU Purcell, RH Bukh, J AF Forns, X Farci, P Mushahwar, IK Emerson, SU Purcell, RH Bukh, J TI Characterization of anti-E2 in chimpanzees infected with hepatitis C virus (HCV). SO HEPATOLOGY LA English DT Meeting Abstract C1 Abbott Labs, N Chicago, IL 60064 USA. NIAID, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1217 BP 467A EP 467A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101216 ER PT J AU Tan, D Conry-Cantilena, C Melpolder, J Matsumoto, A Shih, JWK Alter, HJ AF Tan, D Conry-Cantilena, C Melpolder, J Matsumoto, A Shih, JWK Alter, HJ TI Detection of HCV-RNA in serial samples of blood donors with consistent indeterminate RIBA2. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1234 BP 471A EP 471A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101234 ER PT J AU Hsia, CC Minemura, M Kashanchi, F Kim, SJ Tabor, E AF Hsia, CC Minemura, M Kashanchi, F Kim, SJ Tabor, E TI Dual effects of hepatitis B virus X gene on the transforming growth factor-beta 1 promoter: Transactivation and suppression. SO HEPATOLOGY LA English DT Meeting Abstract C1 US FDA, Div Transfus Transmitted Dis, Bethesda, MD 20014 USA. NCI, Div Basic Sci, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1285 BP 484A EP 484A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101284 ER PT J AU Reddy, R Hoofnagle, JH Tong, MJ Lee, WM Pockros, P Heathcote, EJ Albert, D AF Reddy, R Hoofnagle, JH Tong, MJ Lee, WM Pockros, P Heathcote, EJ Albert, D CA CIFN Study Grp TI Low rates of response to interferon in African-Americans with chronic hepatitis C. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Miami, Miami, FL 33152 USA. NIDDK, NIH, Bethesda, MD USA. Huntington Mem Hosp, Pasadena, CA USA. Scripps Clin, La Jolla, CA USA. Univ Toronto, Toronto, ON, Canada. Amgen Inc, Boulder, CO USA. NR 0 TC 2 Z9 2 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1339 BP 497A EP 497A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101337 ER PT J AU Philpott, CC Rashford, J Ferea, T AF Philpott, CC Rashford, J Ferea, T TI A new approach to identifying genes of iron metabolism. SO HEPATOLOGY LA English DT Meeting Abstract C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1457 BP 527A EP 527A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101456 ER PT J AU Baumert, TF Lianq, TJ Yang, C Tang, ZY Kock, J Weizsacker, FV Blum, HE AF Baumert, TF Lianq, TJ Yang, C Tang, ZY Kock, J Weizsacker, FV Blum, HE TI Functional analysis of hepatitis B virus core promotor mutations in primary Tupaia hepatocytes. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ Freiburg, Dept Med 2, Freiburg, Germany. NIDDK, Liver Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1674 BP 581A EP 581A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101674 ER PT J AU Thio, CL Carrington, M Marti, D O'Brien, SJ Vlahov, D Nelson, K Astemborski, JA Thomas, DL AF Thio, CL Carrington, M Marti, D O'Brien, SJ Vlahov, D Nelson, K Astemborski, JA Thomas, DL TI Class II HLA alleles and hepatitis B virus persistence in African-Americans SO HEPATOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. NCI, Frederick, MD 21701 USA. Johns Hopkins Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1687 BP 584A EP 584A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101685 ER PT J AU Monga, SPS Rashid, A Wildner, O Condotti, F Mishra, L AF Monga, SPS Rashid, A Wildner, O Condotti, F Mishra, L TI Ex vivo embryonic liver explant cultures: A model for studying liver development. SO HEPATOLOGY LA English DT Meeting Abstract C1 DVAMC, Washington, DC USA. Temple Univ, Fels Inst Canc Res & Mol Bio, Philadelphia, PA 19122 USA. JHU, GI Pathol, Baltimore, MD USA. NHGRI, CGTB, NIH, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1763 BP 603A EP 603A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101761 ER PT J AU Kleiner, DE Lau, DTY Hoofnagle, JH AF Kleiner, DE Lau, DTY Hoofnagle, JH TI Clinical features correlating with bile duct loss in primary biliary cirrhosis. SO HEPATOLOGY LA English DT Meeting Abstract C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 1953 BP 651A EP 651A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258101951 ER PT J AU Zhong, Z Connor, HD Mason, RP Lemasters, JJ Thurman, RG AF Zhong, Z Connor, HD Mason, RP Lemasters, JJ Thurman, RG TI Ethanol, not fat accumulation per se, increases free radical production in a low-flow, reflow liver perfusion model. SO HEPATOLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 SU S MA 2344 BP 748A EP 748A PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 125VQ UT WOS:000076258102342 ER PT J AU Sorensen, HT Friis, S Olsen, JH Thulstrup, M Mellemkjaer, L Linet, M Trichopoulos, D Vilstrup, H Olsen, J AF Sorensen, HT Friis, S Olsen, JH Thulstrup, M Mellemkjaer, L Linet, M Trichopoulos, D Vilstrup, H Olsen, J TI Risk of liver and other types of cancer in patients with cirrhosis: A nationwide cohort study in Denmark SO HEPATOLOGY LA English DT Article ID PRIMARY BILIARY-CIRRHOSIS; HEPATOCELLULAR-CARCINOMA; ALCOHOLIC CIRRHOSIS; BREAST-CANCER; SEX-HORMONES; WOMEN; CONSUMPTION; MALIGNANCIES; DISEASES; REGISTRY AB Cancer risk in patients with cirrhosis could be modified by factors such as changes in hormonal levels, impaired metabolism of carcinogens, or alteration of immunological status. We investigated the risk of liver and various forms of cancer in patients with cirrhosis in a follow-up study. We identified 11,605 1-year survivors of cirrhosis from the files of the Danish National Registry of Patients (NRP) from 1977 to 1989, Occurrence of cancer through 1993 was determined by linkage to the Danish Cancer Registry For comparison, the expected number of cancer cases was estimated from national age-, sex-, and site-specific incidence rates. Overall, 1,447 cancers were diagnosed among the study subjects, as compared with 708.1 expected, to yield a standardized incidence ratio (SIR) of 2.0 (95% CI: 1.9 to 2.2), In all diagnostic subgroups of cirrhosis, the risk of primary liver cancer, mainly hepatocellular carcinoma, was markedly elevated, with 245 observed cases and an overall 36-fold elevated risk (59.9-fold elevated for hepatocellular carcinoma and 10-fold for cholangiocarcinoma). Substantial and persistent excesses during follow-up were seen for all types of cancer associated with tobacco and alcohol habits (cancer of the lung, larynx, buccal cavity, pharynx, pancreas, urinary bladder, and kidney), while moderate excesses were seen for cancers of the colon and breast. The latter, however, were not complemented by any decrease in the risk of prostate cancer (SIR: 1.0; 95% CI: 0.7 to 1.3). A slightly increased risk was seen for testis cancer, but disappeared after 10 years. We found evidence of an increased risk for liver and several extrahepatic cancers in patients with cirrhosis, Although part of this increase is likely attributable to alcohol and tobacco consumption, our study opens up the possibility that cirrhosis plays a role in the carcinogenesis of types of cancer other than liver cancer. C1 Aarhus Univ, Dept Epidemiol & Social Med, Danish Epidemiol Sci Ctr, DK-8000 Aarhus C, Denmark. Aarhus Univ Hosp, Dept Med 5, DK-8000 Aarhus, Denmark. Danish Canc Soc, Div Canc Epidemiol, Copenhagen, Denmark. NCI, Radiat Epidemiol Branch, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Boston, MA 02115 USA. RP Sorensen, HT (reprint author), Aarhus Univ, Dept Epidemiol & Social Med, Danish Epidemiol Sci Ctr, DK-8000 Aarhus C, Denmark. FU NCI NIH HHS [MAO N01-CP-85639-04] NR 39 TC 166 Z9 169 U1 2 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 BP 921 EP 925 DI 10.1002/hep.510280404 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 124JW UT WOS:000076180000004 PM 9755226 ER PT J AU Lau, DTY Kleiner, DE Ghany, MG Park, Y Schmid, P Hoofnagle, JH AF Lau, DTY Kleiner, DE Ghany, MG Park, Y Schmid, P Hoofnagle, JH TI 10-year follow-up after interferon-alpha therapy for chronic hepatitis C SO HEPATOLOGY LA English DT Article ID TRANSFUSION-ASSOCIATED HEPATITIS; NON-B-HEPATITIS; CONTROLLED TRIAL; NON-A; VIRUS-RNA; MULTICENTER; LIVER; ASSAY; ALFA; HCV AB Sustained responses to interferon-alpha occur in 10% to 25% of patients with chronic hepatitis C, but the long-term outcome is not well defined. We evaluated the long-term clinical, histological, and virological outcomes of 10 patients with chronic hepatitis C who were treated between 1984 and 1987 with interferon-alpha-2b for 52 +/- 6 weeks (total doses of 492 +/- 116 MU), Before therapy, all 10 had hepatitis C virus (HCV) RNA, elevations of serum aminotransferases, and chronic hepatitis with fibrosis on liver biopsy. Clinical follow up was 6 to 13 years, and liver biopsies were done 5 to 11 years after initiation of therapy, HCV RNA was assayed by qualitative and quantitative reverse transcriptase-polymerase chain reaction assays, Among 5 patients who had a 6-month sustained response after therapy, all remained HCV RNA negative, and at last follow-up, 4 had normal. and 1 minimally elevated serum aminotransferase levels, Liver biopsy specimens were nonreactive for HCV RNA, and all the patients showed improvements in both inflammation and fibrosis and were either normal or had mild, nonspecific inflammatory changes. Among 5 patients without a sustained response, all continued to have HCV RNA in serum and persistent or intermittent aminotransferase elevations. Liver biopsy specimens showed little or no change in necrosis and inflammation; all except 1 patient had progression of fibrosis scores or cirrhosis, All 5 patients had symptoms of chronic hepatitis, 1 underwent liver transplantation, and another had progressive hepatic decompensation. In conclusion, patients with a 6-month posttreatment virological response have a favorable long-term clinical and histological outcome. C1 NIDDK, Liver Dis Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Natl Inst Genet, Los Angeles, CA USA. RP Lau, DTY (reprint author), NIDDK, Liver Dis Sect, Digest Dis Branch, NIH, Bldg 10,Room 9B16, Bethesda, MD 20892 USA. NR 32 TC 192 Z9 199 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 1998 VL 28 IS 4 BP 1121 EP 1127 DI 10.1002/hep.510280430 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 124JW UT WOS:000076180000030 PM 9755252 ER PT J AU Resnick, SM Maki, PM Golski, S Kraut, MA Zonderman, AB AF Resnick, SM Maki, PM Golski, S Kraut, MA Zonderman, AB TI Effects of estrogen replacement therapy on PET cerebral blood flow and neuropsychological performance SO HORMONES AND BEHAVIOR LA English DT Article DE estrogen; regional cerebral blood flow; memory; positron emission tomography; cognition ID POSITRON-EMISSION TOMOGRAPHY; SURGICALLY MENOPAUSAL WOMEN; OLDER WOMEN; POSTMENOPAUSAL WOMEN; GLUCOSE-UTILIZATION; MEMORY; BRAIN; DETERMINANTS; CYCLE; BIAS AB Reports that estrogen may protect against age-associated memory decline and Alzheimer's Disease have kindled interest in the effects of estrogen replacement therapy (ERT) on cognition and brain function. As part of a 9-year study in the Baltimore Longitudinal Study of Aging, we are performing annual magnetic resonance imaging, positron emission tomography (PET), and neuropsychological assessments to examine brain structure and function in individuals aged 55 and older. PET measurements of regional cerebral blood flow (rCBF) are obtained under 3 conditions: rest and verbal and figural delayed recognition memory tasks. Fifteen women receiving ERT (with or without the addition of progesterone) were compared with a matched sample of 17 untreated women. There were no significant differences between groups in regional brain volumes or ventricular size. However, ERT users and nonusers showed significant differences in PET-rCBF relative activation patterns during the memory tasks. During verbal memory processing, there were significant interactions in rCBF activations for the right parahippocampal gyrus, right precuneus, right frontal regions, and left hypothalamus. During figural memory processing, significant interactions were observed for right parahippocampal and inferior parietal regions and for left visual association and anterior thalamic regions. ERT users also showed better performance on neuropsychological tests of figural and verbal memory and on some aspects of the PET activation tests, although the two groups did not differ in education, overall verbal ability, or performance on other neuropsychological tests. These findings confirm our previous observation of the beneficial effects of ERT on figural memory. Moreover, differences in rCBF activation patterns between ERT users and nonusers suggest an area for future research to examine mechanisms through which ERT may influence memory and other cognitive abilities, (C) 1998 Academic Press. C1 NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Resnick, SM (reprint author), NIA, Gerontol Res Ctr, Lab Personal & Cognit, NIH, Box 3,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. OI Zonderman, Alan B/0000-0002-6523-4778 NR 51 TC 183 Z9 188 U1 0 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD OCT PY 1998 VL 34 IS 2 BP 171 EP 182 DI 10.1006/hbeh.1998.1476 PG 12 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 145AX UT WOS:000077349700010 PM 9799627 ER PT J AU Richard, G White, TW Smith, LE Bailey, RA Compton, JG Paul, DL Bale, SJ AF Richard, G White, TW Smith, LE Bailey, RA Compton, JG Paul, DL Bale, SJ TI Functional defects of Cx26 resulting from a heterozygous missense mutation in a family with dominant deaf-mutism and palmoplantar keratoderma SO HUMAN GENETICS LA English DT Article ID GAP-JUNCTION PROTEINS; MARIE-TOOTH-DISEASE; SENSORINEURAL DEAFNESS; RECESSIVE DEAFNESS; CONNEXIN FAMILY; MOUSE SKIN; EXPRESSION; GENE; COMMUNICATION; EPIDERMIS AB Mutations in GJB2 encoding the gap junction protein connexin-26 (Cx26) have been established as the basis of autosomal recessive non-syndromic hearing loss. The involvement of GJB2 in autosomal dominant deafness has also been proposed, although the putative mutation identified in one family with both deafness and palmoplantar keratoderma has recently been suggested to be merely a non-disease associated polymorphism. We have observed a similar phenotype in an Egyptian family that segregated with a heterozygous missense mutation off GJB2, leading to a non-conservative amino acid substitution (R75W). The deleterious dominant-negative effect of R75W on gap channel function was subsequently demonstrated in the paired oocyte expression system. Not only was R75W alone incapable of inducing electrical conductance between adjacent cells, but it almost completely suppressed the activity of co-expressed wildtype protein. The Cx26 mutant W77R, which has been implicated in autosomal recessive deafness, also failed to form functional gap channels by itself but did not significantly interfere with the function of wildtype Cx26. These data provide compelling evidence for the serious functional consequences of Cx26 mutations in dominant and recessive deafness. C1 Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. NIAMSD, Genet Studies Sect, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bale, SJ (reprint author), Bldg 6,Room 429,6 Ctr Dr MSC 2757, Bethesda, MD 20892 USA. OI White, Thomas/0000-0002-3285-7434 FU NIGMS NIH HHS [GM37551] NR 43 TC 194 Z9 205 U1 0 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 1998 VL 103 IS 4 BP 393 EP 399 DI 10.1007/s004390050839 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 144DA UT WOS:000077297400004 PM 9856479 ER PT J AU Leroy, E Anastasopoulos, D Konitsiotis, S Lavedan, C Polymeropoulos, MH AF Leroy, E Anastasopoulos, D Konitsiotis, S Lavedan, C Polymeropoulos, MH TI Deletions in the Parkin gene and genetic heterogeneity in a Greek family with early onset Parkinson's disease SO HUMAN GENETICS LA English DT Article AB Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease and is manifested as a movement disorder. A positive family history is the second most important risk factor for developing the illness, after age. Both autosomal dominant and recessive forms of the illness have been described. Recently deletions in a novel gene, parkin, have been associated with the autosomal recessive form of the illness in Japanese families. In this study, we demonstrate that deletions of exons 5, 6 and 7 of the parkin gene are present in two affected individuals of a Greek pedigree with early onset Parkinson's disease. However, no deletions were identified in a different branch of the same pedigree with three affected individuals. These results suggest that deletions in the parkin gene will be found in other families besides those of Japanese origin and that there must be at least one additional locus responsible for early onset autosomal recessive Parkinson's disease. C1 NIH, Gene Mapping Sect, Genet Dis Res Branch, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. Univ Ioannina, Sch Med, Dept Neurol, GR-45110 Ioannina, Greece. NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Polymeropoulos, MH (reprint author), NIH, Gene Mapping Sect, Genet Dis Res Branch, Natl Human Genome Res Inst, Bldg 49Rm4A66, Bethesda, MD 20892 USA. NR 9 TC 103 Z9 103 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 1998 VL 103 IS 4 BP 424 EP 427 DI 10.1007/s004390050845 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 144DA UT WOS:000077297400010 PM 9856485 ER PT J AU Lin, JP Cash, JM Doyle, SZ Peden, S Kanik, K Amos, CI Bale, SJ Wilder, RL AF Lin, JP Cash, JM Doyle, SZ Peden, S Kanik, K Amos, CI Bale, SJ Wilder, RL TI Familial clustering of rheumatoid arthritis with other autoimmune diseases SO HUMAN GENETICS LA English DT Article ID SHARED-EPITOPE HYPOTHESIS; MODELS; ASSOCIATION; RISK; SUSCEPTIBILITY; EPIDEMIOLOGY; SEVERITY AB Previous studies have shown that rheumatoid arthritis aggregates within families. However, no formal genetic analysis of rheumatoid arthritis in pedigrees together with other autoimmune diseases has been reported. We hypothesized that there are genetic factors in common in rheumatoid arthritis and other autoimmune diseases. Results of odds-ratio regression and complex segregation analysis in a sample of 43 Caucasian pedigrees ascertained through a rheumatoid arthritis proband or matched control proband, revealed a very strong genetic influence on the occurrence of both rheumatoid arthritis and other autoimmune diseases. In an analysis of rheumatoid arthritis alone, only one inter-class measure, parent-sibling, resulted in positive evidence of aggregation. However, three inter-class measures (parent-sibling, sibling-offspring, and parent-offspring pairs) showed significant evidence of familial aggregation with odds-ratio regression analysis of rheumatoid arthritis together with all other autoimmune diseases. Segregation analysis of rheumatoid arthritis alone revealed that the mixed model, including both polygenic and major gene components, was the most parsimonious. Similarly, segregation analysis of rheumatoid arthritis together with other autoimmune diseases revealed that a mixed model fitted the data significantly better than either major gene or polygenic models. These results were consistent with a previous study which concluded that several genes, including one with a major effect, is responsible for rheumatoid arthritis in families. Our data showed that this conclusion also held when the phenotype was defined as rheumatoid arthritis and/or other autoimmune diseases, suggesting that several major autoimmune diseases result from pleiotropic effects of a single major gene on a polygenic background. C1 Skin Biol Lab, Genet Studies Sect, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Rheumat & Immunol Dis, Cleveland, OH 44195 USA. NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Md Anderson Canc Ctr, Houston, TX 77030 USA. RP Bale, SJ (reprint author), Skin Biol Lab, Genet Studies Sect, Bldg 6,Rm 429,6 Ctr Dr MSC 2757, Bethesda, MD 20892 USA. FU NIAMS NIH HHS [AR44422] NR 39 TC 97 Z9 101 U1 1 U2 4 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 1998 VL 103 IS 4 BP 475 EP 482 DI 10.1007/s004390050853 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 144DA UT WOS:000077297400018 PM 9856493 ER PT J AU Eyaid, WM Clough, MV Root, H Scott, KM McCormick, MK Zhang, X Lisitsyn, NA Kearns, WG Francomano, CA Richards, JE McIntosh, I AF Eyaid, WM Clough, MV Root, H Scott, KM McCormick, MK Zhang, X Lisitsyn, NA Kearns, WG Francomano, CA Richards, JE McIntosh, I TI Physical mapping of the nail patella syndrome interval at 9q34: ordering of STSs and ESTs SO HUMAN GENETICS LA English DT Article ID YAC LIBRARY; CONSTRUCTION; GENOME; CLONES C1 Johns Hopkins Univ, Ctr Med Genet, Baltimore, MD 21287 USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Ophthalmol, Ann Arbor, MI 48105 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA 23510 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48105 USA. RP McIntosh, I (reprint author), Johns Hopkins Univ, Ctr Med Genet, 600 N Wolfe St,Blalock 1012G, Baltimore, MD 21287 USA. FU NCI NIH HHS [CA64534]; NEI NIH HHS [EY09580]; NIAMS NIH HHS [AR44702] NR 9 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 1998 VL 103 IS 4 BP 525 EP 526 DI 10.1007/s004390050862 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 144DA UT WOS:000077297400027 PM 9856502 ER PT J AU Sherman, ME Kurman, RJ AF Sherman, ME Kurman, RJ CA Natl Canc Inst TI Evolving concepts in endometrial carcinogenesis: Importance of DNA repair and deregulated growth SO HUMAN PATHOLOGY LA English DT Editorial Material ID UTERINE SEROUS CARCINOMA; MICROSATELLITE INSTABILITY; RISK-FACTORS; CANCER; MUTATIONS; P53; TUMORIGENESIS; COMMON C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Sherman, ME (reprint author), Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NR 28 TC 11 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 1998 VL 29 IS 10 BP 1035 EP 1038 DI 10.1016/S0046-8177(98)90409-9 PG 4 WC Pathology SC Pathology GA 128RX UT WOS:000076421100001 PM 9781637 ER PT J AU Lininger, RA Park, WS Man, YG Pham, T MacGrogan, G Zhuang, GP Tavassoli, FA AF Lininger, RA Park, WS Man, YG Pham, T MacGrogan, G Zhuang, GP Tavassoli, FA TI LOH at 16p13 is a novel chromosomal alteration detected in benign and malignant microdissected papillary neoplasms of the breast SO HUMAN PATHOLOGY LA English DT Article DE breast; neoplasms; genetics; LOH; papillary ID POLYCYSTIC KIDNEY-DISEASE; GENETIC-LINKAGE MAP; CARCINOMA; MODEL AB Papillary carcinoma of the breast is a variant of predominantly intraductal carcinoma characterized by a papillary growth pattern with fibrovascular support. Loss of heterozygosity (LOH) was evaluated at multiple chromosomal loci (including loci reported to show frequent genetic alterations in breast cancer) to determine the frequency of genetic mutations in these tumors and their precursors. Thirty-three papillary lesions of the breast (6 papillary carcinomas, 12 carcinomas arising in a papilloma, and 15 intraductal papillomas with florid epithelial hyperplasia) were retrieved from the files of the Armed Forces Institute of Pathology (AFIP). Tumor cells and normal tissue were microdissected in each case and screened for LOH at INT-2 and p53 as well as several loci on chromosome 16p13 in the TSC2/PKD1 gene region (D16S423, D16S663, D16S665). LOH on chromosome 16p13 was present in 10 of 16 (63%) informative cases of either papillary carcinoma or carcinoma arising in a papilloma as well as in 6 of 10 (60%) informative cases of intraductal papilloma with florid epithelial hyperplasia (IDH). One case showed simultaneous LOH in both the florid IDH and carcinoma components of a papilloma. LOH was not observed at either INT-2 or p53 in any of the papillary carcinomas or papillomas with florid IDH. In conclusion, a high frequency of LOH at chromosome 16p13 (the TSC2/PKD1 gene region) is in both papillary carcinomas of the breast as well as in papillomas with florid IDH, including a case with LOH present simultaneously in both components, These findings suggest that chromosome 16p contains a tumor suppressor gene that frequently is mutated early in papillary neoplasia. This is a US government work. C1 Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Inst Bergonie, Anat Pathol Lab, Bordeaux, France. RP Lininger, RA (reprint author), Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, 14th St & Alaska Ave NW,Bldg 54, Washington, DC 20306 USA. NR 25 TC 38 Z9 39 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 1998 VL 29 IS 10 BP 1113 EP 1118 DI 10.1016/S0046-8177(98)90422-1 PG 6 WC Pathology SC Pathology GA 128RX UT WOS:000076421100014 PM 9781650 ER PT J AU Semino-Mora, C Dalakas, MC AF Semino-Mora, C Dalakas, MC TI Rimmed vacuoles with beta-amyloid and ubiquitinated filamentous deposits in the muscles of patients with long-standing denervation (Postpoliomyelitis muscular atrophy): Similarities with inclusion body myositis SO HUMAN PATHOLOGY LA English DT Article DE beta-amyloid; denervation; inclusion body myositis; tubulofilaments ID INFLAMMATORY MYOPATHIES; NEUROMUSCULAR SYMPTOMS; NUCLEAR INCLUSIONS; DYSTROPHY; POLYMYOSITIS; PROTEIN; BONE AB In the chronically denervated muscles of patients with prior paralytic poliomyelitis, there are secondary myopathic features, including endomysial inflammation and rare vacuolated fibers. To assess the frequency and characteristics of the vacuoles and their similarities with those seen in inclusion body myositis (IBM), we examined 58 muscle biopsy specimens from patients with prior paralytic poliomyelitis for (1) the presence of rimmed vacuoles; (2) acid-phosphatase reactivity; (3) Congo-red-positive amyloid deposits; (4) electron microscopy, searching for tubulofilaments; and (5) immunoelectron microscopy, using antibodies against beta-amyloid and ubiquitin. We found vacuolated muscle fibers in 18 of 58 (31%) biopsies, with a mean frequency of 2.06 +/- 0.42 fibers per specimen. The vacuoles contained acid phosphatase-positive material in 6 of the 18 (33.30%) specimens and stained positive for Congo red in five (27.80%). By immunoelectron microscopy, the vacuoles contained 5.17 +/- 0.13 nm fibrils and 14.9 +/- 0.31 nm filaments that immunoreacted with antibodies to beta-amyloid and ubiquitin in a pattern identical to the one seen in IBM. We conclude that vacuolated muscle fibers containing filamentous inclusions positive for amyloid and ubiquitin are not unique to IBM and the other vacuolar myopathies but can also occur in a chronic neurogenic condition, such as postpoliomyelitis. The chronicity of the underlying disease, rather than the cause, may lead to vacuolar formation, amyloid deposition, and accumulation of ubiquitinated filaments. Copyright (C) 1998 by W.B. Saunders Company. C1 NINDS, Neuromuscular Dis Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, Med Neurol Branch, NIH, Bldg 10,Room 4N248, Bethesda, MD 20892 USA. NR 34 TC 36 Z9 37 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 1998 VL 29 IS 10 BP 1128 EP 1133 DI 10.1016/S0046-8177(98)90425-7 PG 6 WC Pathology SC Pathology GA 128RX UT WOS:000076421100017 PM 9781653 ER PT J AU Cardillo, C Kilcoyne, CM Nambi, SS Cannon, RO Quon, MJ Panza, JA AF Cardillo, C Kilcoyne, CM Nambi, SS Cannon, RO Quon, MJ Panza, JA TI Vasodilator response to systemic but not to local hyperinsulinemia in the human forearm SO HYPERTENSION LA English DT Article DE insulin; vasodilation; glucose; nitric oxide; L-NMMA ID SYMPATHETIC NEURAL ACTIVATION; SKELETAL-MUSCLE VASODILATION; NITRIC-OXIDE RELEASE; INSULIN-RESISTANCE; BLOOD-FLOW; PROTEIN-SYNTHESIS; RESPONSIVENESS; SENSITIVITY; PRESSURE AB Insulin-mediated vasodilation has been proposed as an important determinant of whole-body insulin-stimulated glucose disposal. However, it is not clear whether the vasodilator effect of insulin results from a direct action of the hormone or whether alternative mechanisms are involved. To better characterize the mechanism of insulin-mediated vasorelaxation, we compared forearm blood flow (FBF) responses to local (intra-arterial) and systemic (intravenous, euglycemic clamp) hyperinsulinemia in 10 healthy lean subjects using venous occlusion plethysmography. In addition, we assessed the effect of nitric oxide (NO) synthase inhibition by N-G-monomethyl-L-arginine (L-NMMA) on the vasodilator and metabolic responses to hyperinsulinemia. Similar forearm concentrations of insulin were achieved during local and systemic infusion (231+/-39 versus 265+/-22 mu U/mL; P=0.54). Of note, FBF did not change significantly in response to local hyperinsulinemia (from 2.6+/-0.3 to 2.4+/-0.3 mt . min(-1) . dL(-1); P=0.50). In contrast, systemic hyperinsulinemia caused a 52% increase in FBF (from 2.5+/-0.2 to 3.8+/-0.5 mL . min(-1) . dL(-1); P<0.004), which was reversed by L-NMMA (FBF decreased from 3.8+/-0.5 to 2.3+/-0.2 mL . min(-1) . dL(-1); P=0.004). We conclude that systemic, but not local, hyperinsulinemia induces vasodilation in the forearm. Our findings suggest that insulin-mediated vasodilation is not due solely to a direct stimulatory effect of insulin but involves additional mechanisms activated only during systemic hyperinsulinemia. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hypertens Endocrine Branch, NIH, Bethesda, MD 20892 USA. RP Panza, JA (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B-15, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 24 TC 37 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 1998 VL 32 IS 4 BP 740 EP 745 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131TZ UT WOS:000076592500020 PM 9774373 ER PT J AU Fedorova, OV AF Fedorova, OV TI Isolation stress and high NaCl intake in Fischer 344 x BN rats: Effects on endogenous inhibitors of the sodium pump SO HYPERTENSION LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. IM Sechenov Evolutionary Physiol & Biochem Inst, St Petersburg 194223, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 1998 VL 32 IS 4 MA PL02 BP 809 EP 809 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131TZ UT WOS:000076592500153 ER PT J AU Bagrov, AY Fedorova, OV Alvarez-Guerra, M Lakatta, EG Garay, RP AF Bagrov, AY Fedorova, OV Alvarez-Guerra, M Lakatta, EG Garay, RP TI Endogenous ligands of the sodium pump during acute and chronic salt loading of Dahl JrHsd (Rapp) rats SO HYPERTENSION LA English DT Meeting Abstract C1 NIA, Baltimore, MD 21224 USA. Hop Henri Mondor, INSERM, U400, F-94010 Creteil, France. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 1998 VL 32 IS 4 MA PL03 BP 810 EP 810 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 131TZ UT WOS:000076592500154 ER PT J AU Wen, H Balaban, RS AF Wen, H Balaban, RS TI Comments on "Hall effect imaging" - Reply SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Editorial Material C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Wen, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RI Wen, Han/G-3081-2010 OI Wen, Han/0000-0001-6844-2997 NR 8 TC 0 Z9 0 U1 1 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD OCT PY 1998 VL 45 IS 10 BP 1295 EP 1296 DI 10.1109/TBME.1998.720208 PG 2 WC Engineering, Biomedical SC Engineering GA 121EA UT WOS:000075998800013 ER PT J AU Kawahito, Y Remmers, EF Wilder, RL Longman, RE Gulko, PS Wang, JP Chen, S Chang, L Reese, VR Dracheva, S Ge, L Hoffman, JH Shepard, J Cannon, GW Griffiths, MM AF Kawahito, Y Remmers, EF Wilder, RL Longman, RE Gulko, PS Wang, JP Chen, S Chang, L Reese, VR Dracheva, S Ge, L Hoffman, JH Shepard, J Cannon, GW Griffiths, MM TI A genetic linkage map of rat chromosome 20 derived from five F-2 crosses SO IMMUNOGENETICS LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; LOCI; SUSCEPTIBILITY; MARKERS C1 NIAMSD, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Res Serv, Salt Lake City, UT 84132 USA. Univ Utah, Dept Med Rheumatol, Salt Lake City, UT 84132 USA. RP Wilder, RL (reprint author), NIH, Bldg 10,Room 9N240,10 Ctr Dr MSC 1820, Bethesda, MD 20892 USA. NR 24 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD OCT PY 1998 VL 48 IS 5 BP 335 EP 338 DI 10.1007/s002510050440 PG 4 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 124UY UT WOS:000076202000004 PM 9745010 ER PT J AU Powell, JD Ragheb, JA Kitagawa-Sakakida, S Schwartz, RH AF Powell, JD Ragheb, JA Kitagawa-Sakakida, S Schwartz, RH TI Molecular regulation of interleukin-2 expression by CD28 co-stimulation and anergy SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-CELL CLONES; UBIQUITIN-PROTEASOME PATHWAY; MESSENGER-RNA DEGRADATION; TUMOR-SUPPRESSOR PROTEIN; ANTIGEN-PRESENTING CELLS; IL-2 GENE-EXPRESSION; AP-1 SITES; NONSENSE CODONS; RICH SEQUENCES; REPRESSOR ICER AB The consequences of T-cell receptor engagement (signal 1) are profoundly affected by the presence or absence of co-stimulation (signal 2). T-cell receptor (TCR) stimulation in the absence of CD28-mediated costimulation not only results in little interleukin (IL)-2 production, but induces a long lasting hyporesponsive state known as T-cell clonal anergy. The addition of CD28 ligation to signal 1, on the other hand, results in the production of copious amounts of IL-2. Our laboratory has utilized CD4(+) Th1 clones in an effort to understand the molecular events resulting in enhanced IL-2 production by co-stimulation and the inhibition of IL-2 production in energy. Our current studies have focused on defining the post-transcriptional effects of CD28-enhanced IL-2 production. The data suggest that a major component of CD28's ability to regulate IL-2 production occurs at the level of message stability and involves the 3'-untranslated region of the message. In terms of anergy, our recent studies support the notion that it is not the result of TCR engagement in the absence of costimulation, but rather signal 1 in the absence of IL-2 receptor signaling and proliferation. Furthermore, T-cell anergy appears to be an active negative state in which IL-2 production is inhibited both at the level of signal transduction and by cis-dominant repression at the level of the IL-2 promoter. C1 NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, Bldg 4,Rm 111, Bethesda, MD 20892 USA. NR 86 TC 139 Z9 142 U1 0 U2 5 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD OCT PY 1998 VL 165 BP 287 EP 300 DI 10.1111/j.1600-065X.1998.tb01246.x PG 14 WC Immunology SC Immunology GA 142FC UT WOS:000077188400022 PM 9850868 ER PT J AU Zaks-Zilberman, M Salkowski, CA Elsasser, T Cuttitta, F Vogel, SN AF Zaks-Zilberman, M Salkowski, CA Elsasser, T Cuttitta, F Vogel, SN TI Induction of adrenomedullin mRNA and protein by lipopolysaccharide and paclitaxel (taxol) in murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; POTENTIAL ANTITUMOR AGENTS; NF-KAPPA-B; HYPOTENSIVE PEPTIDE; NITRIC-OXIDE; INDUCIBLE GENES; SEPTIC SHOCK; TYROSINE PHOSPHORYLATION; MONOCLONAL-ANTIBODY; FACTOR-ALPHA AB Lipopolysaccharide (LPS), a potent inflammatory stimulus derived from the outer membrane of gramnegative bacteria, has been implicated in septic shock. Plasma levels of adrenomedullin (Ah/I), a potent vasorelaxant, are increased in septic shock and possibly contribute to the characteristic hypotension. As macrophages play a central role in the host response to LPS, we studied AM production by LPS-stimulated macrophages. When peritoneal exudate macrophages from C3H/OuJ mice were treated with protein-free LPS (100 ng/ml) or the LPS mimetic paclitaxel (Taxol; 35 mu M), an similar to 10-fold increase in steady-state AM mRNA levels was observed, which peaked between 2 and 4 h. A three- to fourfold maximum increase in the levels of immunoreactive AM protein was detected after 6 to 8 h of stimulation. While LPS-hyporesponsive C3H/HeJ macrophages failed to respond to protein-free LPS with an increase in steady-state AM mRNA levels, increased levels were observed after stimulation of these cells with a protein-rich (butanol-extracted) LPS preparation. In addition, increased AM mRNA was observed following treatment of either C3H/OuJ or C3H/HeJ macrophages with soluble Toxoplasma gondii tachyzoite antigen or the synthetic flavone analog 5,6-dimethylxanthenone-4-acetic acid. Gamma interferon also stimulated C3H/OuJ macrophages to express increased AM mRNA levels yet was inhibitory in the presence of LPS or paclitaxel. In vivo, mice challenged intraperitoneally with 25 mu g of LPS exhibited increased AM mRNA levels in the lungs, liver, and spleen; the greatest increase (>50-fold) was observed in the liver and lungs. Thus, AM is produced, by murine macrophages, and furthermore, LPS induces AM mRNA in vivo in a number of tissues. These data support a possible role for AM in the pathophysiology of sepsis and septic shock. C1 Uniformed Serv Univ Hlth Sci, Dept Immunol & Microbiol, Bethesda, MD 20814 USA. USDA ARS, Beltsville, MD 20705 USA. NCI, Biomarkers & Prevent Res Branch, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Vogel, SN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Immunol & Microbiol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM vogel@usuhsb.usuhs.mil FU NIAID NIH HHS [AI-18797, R01 AI018797, R37 AI018797, R56 AI018797] NR 51 TC 43 Z9 44 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1998 VL 66 IS 10 BP 4669 EP 4675 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 122WU UT WOS:000076095100011 PM 9746563 ER PT J AU Hu, WG Zhu, XH Wu, YZ Jia, ZC AF Hu, WG Zhu, XH Wu, YZ Jia, ZC TI Localization of a T-cell epitope of superantigen toxic shock syndrome toxin 1 to residues 125 to 158 SO INFECTION AND IMMUNITY LA English DT Article ID CLASS-II MOLECULES; MHC CLASS-II; STAPHYLOCOCCAL-ENTEROTOXIN-B; BLOOD MONONUCLEAR-CELLS; COMPLEX CLASS-II; BINDING-SITES; IMMUNE-RESPONSES; PEPTIDE; IDENTIFICATION; STIMULATION AB Toxic shock syndrome toxin 1 (TSST-1) is a member of the staphylococcal enterotoxin superantigen family. So far, little is known about T-cell epitopes on superantigens. In this study, we developed an improved method for localizing T-cell epitopes on superantigens that involved synthetic peptides plus costimulation by CD28 or phorbol myristate acetate. Using this method, we localized a T-cell epitope to a 34-residue region, TSST-1 (residues 125 to 158), which possessed only two of four TSST-1-targeted beta-chain variable element (V beta) specificities of T-cell receptors in humans and mice, human V beta 2 and murine V beta 15. C1 Third Mil Med Univ, Dept Immunol, Chongqing 400038, Peoples R China. RP Hu, WG (reprint author), NIDCD, Sect Expt Immunol, Immunol Lab, 5 RC,2A31, Rockville, MD 20850 USA. NR 39 TC 3 Z9 4 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 1998 VL 66 IS 10 BP 4971 EP 4975 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 122WU UT WOS:000076095100053 PM 9746605 ER PT J AU Tinnell, SB Jacobs-Helber, SM Sterneck, E Sawyer, ST Conrad, DH AF Tinnell, SB Jacobs-Helber, SM Sterneck, E Sawyer, ST Conrad, DH TI STAT6, NF-kappa B and C/EBP in CD23 expression and IgE production SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD23; C/EBP; cytokine; FcR; NF-kappa B; STAT6; transcription factors ID FC-EPSILON-RII; MURINE LYMPHOCYTES-B; RECEPTOR GAMMA-CHAIN; CROSS-LINKING CD40; TARGETED DISRUPTION; CELL ACTIVATION; GENE-EXPRESSION; IL-4 RECEPTOR; IMMUNOGLOBULIN; BETA AB STAT6, NF-kappa B (p50) and C/EBP beta transcription factors (TF) were examined with respect to CD23 regulation. Electrophoretic mobility shift assay (EMSA), competition and supershift analysis demonstrated that STAT6 binds the CD23a promoter but with a lower affinity than the consensus site. STAT6(-/-) mice were analyzed for CD23 levels and showed reduced expression after CD40 ligand trimer (CD40LT) stimulation. However, normal CD23 expression and even some IgE production was induced in STAT6(-/-) mice with CD40LT/IL-4. EMSA analysis indicated that the CD23a STAT site was bound by a protein in nuclear extracts from CD40 +/- IL-4-stimulated STAT6(-/-) B cells. Western blot analysis of these nuclear extracts demonstrated the presence of STAT3 and STAT5, suggesting that these STATs can induce CD23 in this situation. Further supporting evidence was obtained by showing that IL-2 and IL-4 both synergize with CD40 in an identical manner for CD23 induction on STAT6(-/-) B cells. EMSA analysis of the two putative NF-kappa B sites confirmed binding to both, although one site bound with a higher affinity than the second. Analysis of p50(-/-) mice indicated that this subunit was not necessary for CD23 induction or CD40/IL-4-induced IgE production. Finally, no role for C/EBP was observed in CD23 induction by EMSA or by CD23 induction analysis in C/EBP beta(-/-) mice, whereas the absence of C/EBP beta did have an effect on IgE production and lipopolysaccharide-induced B cell proliferation. Based on these data, a model is presented which suggests that CD23 superinduction results from STAT and NF-kappa B interaction. C1 Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NCI, Eukaryot Transcript Regulat Grp, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Conrad, DH (reprint author), POB 980678,MCV Stn, Richmond, VA 23298 USA. FU NIAID NIH HHS [AI18697]; NIDDK NIH HHS [DK39781] NR 69 TC 48 Z9 48 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1998 VL 10 IS 10 BP 1529 EP 1538 DI 10.1093/intimm/10.10.1529 PG 10 WC Immunology SC Immunology GA 129JL UT WOS:000076460000015 PM 9796920 ER PT J AU Bernard, M Delabesse, E Smit, L Millien, C Kirsch, IR Strominger, JL Mcintyre, EA AF Bernard, M Delabesse, E Smit, L Millien, C Kirsch, IR Strominger, JL Mcintyre, EA TI Helix-loop-helix (E2-5, HEB, TAL1 and Id1) protein interaction with the TCR alpha delta enhancers SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE E2-5; E-box; HEB; helix-loop-helix; Id1; T cell acute lymphoblastic leukemia; TAL-1; transcriptional regulation ID ACUTE LYMPHOBLASTIC-LEUKEMIA; DNA-BINDING PROTEINS; B-CELL DEVELOPMENT; IN-VIVO; GENE; E2A; DIFFERENTIATION; LINEAGE; LOCUS; SCL AB In order to dissect the correlation between aberrant TAL1 basic-helix-loop-helix (b-HLH) expression and the exclusive development of T cell acute lymphoblastic leukemias (T-ALL) of the TCR alpha beta lineage, we have assessed the ability of class A b-HLH proteins to regulate the TCR alpha and delta enhancers. We demonstrate that E47S binds to TCR alpha but not to TCR delta E-boxes in vitro. Despite this, neither E2-5 nor HEB transactivate the TCRa enhancer in NIH 3T3, nor did Id1 modify endogenously driven TCR alpha [alpha E1-4] activity in a TCR alpha beta cell line. We also demonstrate that TAL1 inhibits both binding of E47S to alpha E3 and alpha E4 and endogenous transactivation of the TCR alpha enhancer. Comparison of the activity of the minimal [alpha E1-2] fragment, which contains no E-boxes, with the accessory [alpha E3-4] fragment, which contains two, suggested some contribution from the latter to TCR alpha enhancer activity in HPB-ALL, TCR [alpha E1-2] activity was partially (40%) inhibited by TAL1 but not at all by Id1, In contrast, [aE3-4] activity was almost completely inhibited by TAL1 (80%) and slightly reduced by Id1 (15%). These data demonstrate that class A b-HLH regulation of the TCR alpha enhancer E-boxes differs from their B lymphoid Ig mu counterparts and suggest a novel mechanism of transcriptional inhibition by TAL1, which may be, at least partly, independent of E-box-mediated activation, as we currently recognize it. They also clearly demonstrate that the restriction of TAL1 deregulation to T-ALL of the TCR alpha beta lineage is not due to induction of TCR alpha enhancer activity by the TAL1 protein. C1 CHU Necker Enfants Malad, CNRS, URA 1461, Paris, France. CHU Necker Enfants Malad, Dept Hematol, Paris, France. Netherlands Canc Inst, NL-1066 CX Amsterdam, Netherlands. NCI, Naval Med Ctr, Bethesda, MD 20892 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Mcintyre, EA (reprint author), Hop Necker Enfants Malad, Hematol Lab, Tour Pasteur,149 Rue Sevres, F-75743 Paris 15, France. OI DELABESSE, Eric/0000-0002-0928-0753 NR 41 TC 17 Z9 17 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1998 VL 10 IS 10 BP 1539 EP 1549 DI 10.1093/intimm/10.10.1539 PG 11 WC Immunology SC Immunology GA 129JL UT WOS:000076460000016 PM 9796921 ER PT J AU Zaitseva, MB Mojcik, CF Salomon, DR Shevach, EM Golding, H AF Zaitseva, MB Mojcik, CF Salomon, DR Shevach, EM Golding, H TI Co-ligation of alpha(4)beta(1) integrin and TCR rescues human thymocytes from steroid-induced apoptosis SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE adhesion molecules; thymus; programmed cell death ID FOCAL ADHESION KINASE; T-CELL DEVELOPMENT; THYMIC STROMAL CELLS; POSITIVE SELECTION; NEGATIVE SELECTION; CD4(+)CD8(+) THYMOCYTES; EXTRACELLULAR-MATRIX; IN-VITRO; RECEPTOR; FIBRONECTIN AB Maturation of thymocytes represents a sequence of events during which thymocytes expressing TCR with moderate avidity for self antigen/MHC are positively selected, whereas those with high or insufficient TCR avidity die.Glucocorticoids are produced intrathymically and can contribute to apoptosis of unselected thymocytes. Thymocytes differentiate in a close contact with epithelial cells, expressing vascular adhesion molecule-1 (VCAM-1) and secreting glucocorticoids, with bone marrow-derived macrophages, and with extracellular matrix containing fibronectin (FN) and collagen, Their contact with FN is mediated by alpha(4)beta(1) and alpha(5)beta(1) integrins, We examined the contribution of TCR and integrin signaling to the survival of thymocytes from dexamethasone (Dex)-induced apoptosis, We demonstrate that FN and VCAM-1 (both of which bind alpha(4)beta(1) integrin), but not collagen, considerably augment TCR-mediated protection of thymocytes from Dex-induced apoptosis, This 'survival' signal is transduced through the alpha(4)beta(1), but not through the alpha(5)beta(1) integrin, The observed protection from Dex-induced apoptosis correlated with an increase in bcl-2 protein levels. FN-alpha(4)beta(1) and VCAM-1-alpha(4)beta(1) engagement induced up-regulation bcl-2 protein, while alpha(5)beta(1) binding to FN induced a negative signal that was blocked by anti-alpha(5)beta(1) antibody, These data suggest that alpha(4)beta(1) integrin may contribute to protection of thymocytes with moderate avidity TCR from glucocorticoid-induced death during intrathymic maturation. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20857 USA. NIAID, Immunol Lab, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. RP Zaitseva, MB (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20857 USA. RI Salomon, Daniel/E-9380-2012 NR 45 TC 21 Z9 21 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD OCT PY 1998 VL 10 IS 10 BP 1551 EP 1561 DI 10.1093/intimm/10.10.1551 PG 11 WC Immunology SC Immunology GA 129JL UT WOS:000076460000017 PM 9796922 ER PT J AU Shapiro, S Coleman, EA Broeders, M Codd, M de Koning, H Fracheboud, J Moss, S Paci, E Stachenko, S Ballard-Barbash, R AF Shapiro, S Coleman, EA Broeders, M Codd, M de Koning, H Fracheboud, J Moss, S Paci, E Stachenko, S Ballard-Barbash, R CA IBSN Eur Network Pilot Proj Breast Canc S TI Breast cancer screening programmes in 22 countries: current policies, administration and guidelines SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Review DE breast cancer; screening; population-based; database; guidelines; policies ID INTERNATIONAL WORKSHOP; MAMMOGRAPHY; MORTALITY; PROJECT; REDUCTION AB Background Currently there are at least 22 countries worldwide where national, regional or pilot population-based breast cancer screening programmes have been established. A collaborative effort has been undertaken by the International Breast Cancer Screening Network (IBSN), an international voluntary collaborative effort administered from the National Cancer Institute in the US for the purposes of producing international data on the policies, funding and administration, and results of population-based breast cancer screening. Methods Two surveys conducted by the IBSN in 1990 and 1995 describe the status of population-based breast cancer screening in countries which had or planned to establish breast cancer screening programmes in their countries. The 1990 survey was sent to ten countries in the IBSN and was completed by nine countries. The 1995 survey was sent to and completed by the 13 countries in the organization at that time and an additional nine countries in the European Network. Results The programmes vary in how they have been organized and have changed from 1990 to 1995. The most notable change is the increase in the number of countries that have established or plan to establish organized breast cancel screening programmes. A second major change is in guidelines for the lower age limit for mammography screening and the use of the clinical breast examination and breast self-examination as additional detection methods. Conclusion As high quality population-based breast cancer screening programmes are implemented in more countries, they will offer an unprecedented opportunity to assess the level of coverage of the population for initial and repeat screening, evaluation of performance, and, in the longer term, outcome of screening in terms of reduction in the incidence of late-stage disease and in mortality. C1 NCI, DCCPS, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Univ Nijmegen Hosp, EUREF, Nijmegen, Netherlands. Natl Evaluat Team Breast Canc Screening, Nijmegen, Netherlands. Mater Misericordiae Hosp, Dublin 7, Ireland. Erasmus Univ, Rotterdam, Netherlands. Inst Canc Res, Surrey, England. Ctr Studio & Prevenz Oncol, I-50131 Florence, Italy. Hlth Canada, Ottawa, ON K1A 0L2, Canada. RP Ballard-Barbash, R (reprint author), NCI, DCCPS, NIH, Execut Plaza N,Room 313,6130 Execut Blvd MSC 7344, Bethesda, MD 20892 USA. RI Broeders, Mireille/C-8820-2015 NR 32 TC 163 Z9 163 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 1998 VL 27 IS 5 BP 735 EP 742 DI 10.1093/ije/27.5.735 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 139UU UT WOS:000077048700001 PM 9839727 ER PT J AU Silva, EG Tornos, C Gershenson, DM Zhuang, ZP Merino, MJ AF Silva, EG Tornos, C Gershenson, DM Zhuang, ZP Merino, MJ TI Recurrent serous borderline tumors of the ovary - Reply SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Letter C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NIH, Bethesda, MD 20892 USA. RP Silva, EG (reprint author), Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 1998 VL 17 IS 4 BP 388 EP 389 DI 10.1097/00004347-199810000-00017 PG 2 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 124AR UT WOS:000076158600017 ER PT J AU Lin, L Gillies, SD Schlom, J Pestka, S AF Lin, L Gillies, SD Schlom, J Pestka, S TI Construction of phosphorylatable chimeric monoclonal antibody CC49 with a tyrosine Src kinase recognition site SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE monoclonal antibody; chimeric antibody; tyrosine protein kinase recognition site; tyrosine protein kinase; protein kinase; tumor associated antigens; cancer therapy; cancer diagnosis ID TUMOR-ASSOCIATED ANTIGENS; COLORECTAL-CANCER; INTERFERON-ALPHA; COLON CANCER; PHASE-I; B72.3; EXPRESSION; CELLS; CARCINOMA; RADIOIMMUNOTHERAPY AB A phosphorylation site for a tyrosine kinase was introduced into chimeric monoclonal antibody CC49 (MAb-chCC49) by inserting a synthetic fragment (Tyr) encoding one tyrosine kinase phosphorylation sire into an expression vector. The phosphorylation site was created by incorporating the predicted consensus sequences for phosphorylation by the tyrosine kinase at the carboxyl terminus of the heavy chain constant region of the MAb-chCC49). The resultant modified MAb-chCC49 (MAb-chCC49Tyr) was expressed and purified. The MAb-chCC49Tyr protein can be phosphorylated by the tyrosine Src kinase with [gamma-P-32]ATP to high radiospecific activity. The P-32-labeled MAb-chCC49Tyr protein binds to cells expressing TAG-72 antigens. The introduction of phosphorylation sites into monoclonal antibodies (MAb) provides a new reagent for the diagnosis and treatment of cancer. This demonstrates that, as was described for the cAMP-dependent protein kinase site, a tyrosine phosphorylation site can also be used to introduce phosphorylation sites into proteins. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. NCI, Bethesda, MD 20892 USA. Lexigen Pharmaceut Corp, Lexington, MA 02173 USA. RP Pestka, S (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, 675 Hoes Lane, Piscataway, NJ 08854 USA. FU NCI NIH HHS [R01 CA52363, R01 CA46465] NR 38 TC 6 Z9 6 U1 0 U2 1 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 1998 VL 13 IS 4 BP 725 EP 732 PG 8 WC Oncology SC Oncology GA 121TJ UT WOS:000076029800014 PM 9735402 ER PT J AU Tully, JG Whitcomb, RF Hackett, KJ Williamson, DL Laigret, F Carle, P Bove, JM Henegar, RB Ellis, NM Dodge, DE Adams, J AF Tully, JG Whitcomb, RF Hackett, KJ Williamson, DL Laigret, F Carle, P Bove, JM Henegar, RB Ellis, NM Dodge, DE Adams, J TI Entomoplasma freundtii sp. nov., a new species from a green tiger beetle (Coleoptera : Cicindelidae) SO INTERNATIONAL JOURNAL OF SYSTEMATIC BACTERIOLOGY LA English DT Article DE Entomoplasma fueundtii sp. nov.; mollicute; green tiger beetle ID STEROL-REQUIRING MOLLICUTES; RIBOSOMAL-RNA GENE; NUCLEOTIDE-SEQUENCE; PHYLOGENETIC ANALYSIS; ACHOLEPLASMA-FLORUM; DNA; CLASSIFICATION; CLUSTER; PLANTS; RRNB AB A mollicute (strain BARC 318(T)) isolated from gut tissue of a green tiger beetle (Coleoptera: Cicindelidae) was found by dark-field microscopy to consist of non-helical, non-motile, pleomorphic coccoid forms of various sizes. In ultrastructural studies, individual cells varied in diameter from 300 to 1200 nm, were surrounded by a cytoplasmic membrane and showed no evidence of cell wall. The organisms were readily filterable through membrane filters with mean pore diameters of 450 and 300 nm, with unusually large numbers of organisms filterable through 200 nm pore membrane filters. Growth occurred over a temperature range of 15-32 degrees C with optimum growth at 30 degrees C. The organism fermented glucose and hydrolysed arginine but did not hydrolyse urea. Strain BARC 318(T) was insensitive to 500 U penicillin ml(-1) and required serum or cholesterol for growth. It was serologically distinct from all currently described sterol-requiring, fermentative Mycoplasma species and from 12 non-sterol-requiring Mesoplasma species, 13 non-sterol-requiring Acholeplasma species and 5 previously described sterol-requiring Entomoplasma species. Strain BARC 318(T) was shown to have a G+C content of 34 mol% and a genome size of 870 kbp. The 16S rDNA sequence of strain BARC 318(T) was compared to 16S rDNA sequences of several other Entomoplasma species and to other representative species of the genera Spiroplasma and Mycoplasma, and to other members of the class Mollicutes. These comparisons indicated that strain BARC 318(T) had close phylogenetic relationships to other Entomoplasma species. On the basis of these findings and other similarities in morphology, growth and temperature requirements and genomic features, the organism was assigned to the genus Entomoplasma. Strain BARC 318(T) (ATCC 51999(T)) is designated the type strain of Entomoplasma freundtii sp. nov. C1 NIAID, Mycoplasma Sect, Mol Microbiol Lab, Frederick Canc Res Facil, Frederick, MD 21702 USA. USDA, Vegetable Lab, Beltsville, MD 20705 USA. USDA, Insect Biocontrol Lab, Beltsville, MD 20705 USA. SUNY Stony Brook, Dept Anat Sci, Stony Brook, NY 11794 USA. INRA, Biol Cellulaire & Mol Lab, F-33833 Villenave Dornon, France. Univ Bordeaux 2, F-33833 Villenave Dornon, France. Perkin Elmer Appl Biosyst, Foster City, CA 94404 USA. RP Tully, JG (reprint author), NIAID, Mycoplasma Sect, Mol Microbiol Lab, Frederick Canc Res Facil, Bldg 550, Frederick, MD 21702 USA. EM jvt@cu.nih.gov NR 46 TC 6 Z9 6 U1 3 U2 7 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0020-7713 J9 INT J SYST BACTERIOL JI Int. J. Syst. Bacteriol. PD OCT PY 1998 VL 48 BP 1197 EP 1204 PN 4 PG 8 WC Microbiology SC Microbiology GA 138LU UT WOS:000076974000012 PM 9828421 ER PT J AU Lai, JC Fukushima, A Wawrousek, EF Lobanoff, MC Charukamnoetkanok, P Smith-Gill, SJ Vistica, BP Lee, RS Egwuagu, CE Whitcup, SM Gery, I AF Lai, JC Fukushima, A Wawrousek, EF Lobanoff, MC Charukamnoetkanok, P Smith-Gill, SJ Vistica, BP Lee, RS Egwuagu, CE Whitcup, SM Gery, I TI Immunotolerance against a foreign antigen transgenically expressed in the lens SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID I HISTOCOMPATIBILITY MOLECULES; PANCREATIC BETA-CELLS; T-CELLS; B-CELLS; PERIPHERAL TOLERANCE; IMMUNE-RESPONSES; SELF-TOLERANCE; MICE; MECHANISMS; CRYSTALLIN AB PURPOSE. TO extend our knowledge concerning immunotolerance against autologous lens crystallins, transgenic (Tg) mice that express a foreign antigen in their lens were generated, and the immune response against the antigen in these mice was analyzed. METHODS. Conventional techniques were used to generate lines of Tg mice that express soluble (S-) or membrane-bound (M-) hen egg lysozyme (HEL) under the control of the alpha A-crystallin promoter. The presence of HEL in various organs was determined by the particle concentration fluorescence immunoassay (PCFIA), and reverse transcription-polymerase chain reaction technique was used to detect mRNA transcripts of the molecule. To examine the development of immunity (or tolerance), Tg mice and their wild-type controls were immunized with HEL (25 mu g) in Freund's complete adjuvant and 14 days later were tested for immune response against the antigen. Cellular immunity was measured by the lymphocyte proliferation assay and cytokine production, and humoral immunity was determined by enzyme-linked immunosorbent assay. RESULTS. Eyes of the high copy number M-HEL Tg mice were dystrophic, with disrupted lens, whereas no morphologic changes were detected in the eyes of the other Tg mouse lines, All Tg mice exhibited tolerance to HEL by their cellular and humoral immune compartments. The state of immunotolerance to HEL was retained in the Tg mice for as long as 10 months after removal of the main depot of this protein, by enucleation. Measurable amounts of HEL were found in the eyes of all Tg mice, but the protein could not be detected in the serum or in other organs by the sensitive PCFIA (with a threshold of 1 ng/ml). Yet, HEL mRNA was found in the thymus of the Tg mice, suggesting that minute amounts of the protein are expressed in this organ. CONCLUSIONS. The unresponsiveness to HEL in the Tg mice seems to be due to a "central" mechanism of tolerance, mediated by a minuscule amount of HEL in the thymus. Conversely, the much larger amounts of HEL in the peripheral depot, the eyes, play a minor role if any in the tolerogenic process. It is further proposed that a similar mechanism of central tolerance is responsible for the immunotolerance against autologous lens crystallins. C1 NEI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Gery, I (reprint author), NEI, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. RI Wawrousek, Eric/A-4547-2008 NR 37 TC 29 Z9 29 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 1998 VL 39 IS 11 BP 2049 EP 2057 PG 9 WC Ophthalmology SC Ophthalmology GA 124JA UT WOS:000076177600009 PM 9761283 ER PT J AU Corleto, VD Romano, G Severi, C Annibale, B Nasoni, S Strom, R Jensen, RT Delle Fave, G AF Corleto, VD Romano, G Severi, C Annibale, B Nasoni, S Strom, R Jensen, RT Delle Fave, G TI Human circular colonic smooth muscle cells possess active somatostatin receptors SO ITALIAN JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE smooth muscle cell; somatostatin; somatostatin receptor ID GUINEA-PIG; CHOLECYSTOKININ-OCTAPEPTIDE; DISTAL COLON; NEUROPEPTIDES; CONTRACTION; RELAXATION; OCTREOTIDE; INHIBITION; BOMBESIN; MOTILITY AB Background & Aims. Somatostatin alters in vivo colonic motility in different species including humans. Few data are available on a cellular basis that could explain the effects of somatostatin on human colon motility. To address these issues we studied the effects of somatostatin on isolated human circular colonic smooth muscle cells to establish whether its actions are directly or neurally mediated Methods, Circular smooth muscle cells were prepared by enzymatic digestion from surgical specimens of human colon (Sigma) and resuspended in HEPES buffer containing protease inhibitors. Results, Cholecystokinin (1 nM), carbachol (30 nM) and KCI (20 mM) each caused a contraction of 17%, 16.5% and 15%, respectively 1 mu M of either somatostarin-14 somatostatin-28 or SMS 201-995 alone were able to produce a contraction of 5.1 %, 5.7%, and 6.8%, respectively. When smooth muscle cells were preincubated with each of the above-mentioned somatostatin analogs, cholecystokinin-mediated contraction was dose-dependently inhibited only in the presence of antiproteases. The half-maximal effective concentration (EC50) for somatostatin-14, somatostatin-28 and SMS 201-995 were similar (3.5, 5.6 3.2 nM, respectively). Conclusions, Somatostatin acts directly on human circular colonic smooth muscle cells through specific somatostatin receptors. SMS 201-995, a somatostatin receptor subtype-2 preferring analogue, shows a high affinity in inhibiting cholecysrokinin-mediated contraction, suggesting the presence of somatostatin receptor subtype-2 on human circular colonic smooth muscle cells. C1 Univ La Sapienza, Med Clin 2, Cattedra Gastroenterol 1, I-00161 Rome, Italy. Univ La Sapienza, Dept Human Biotechnol, Gastroenterol Unit 1, I-00161 Rome, Italy. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. RP Delle Fave, G (reprint author), Univ La Sapienza, Med Clin 2, Cattedra Gastroenterol 1, I-00161 Rome, Italy. NR 28 TC 7 Z9 7 U1 0 U2 0 PU PACINI EDITORE PI OSPEDALETTO PISA PA VIA DELLA GHERARDESCA-ZONA INDUSTRIALE, 56014 OSPEDALETTO PISA, ITALY SN 1125-8055 J9 ITAL J GASTROENTEROL JI Ital. J. Gastroenterol. Hepatol. PD OCT PY 1998 VL 30 IS 5 BP 505 EP 509 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 143NH UT WOS:000077261500014 PM 9836107 ER PT J AU Demeter, LM Meehan, PM Morse, G Fischl, MA Para, M Powderly, W Leedom, J Holden-Wiltse, J Greisberger, C Wood, K Timpone, J Wathen, LK Nevin, T Resnick, L Batts, DH Reichman, RC AF Demeter, LM Meehan, PM Morse, G Fischl, MA Para, M Powderly, W Leedom, J Holden-Wiltse, J Greisberger, C Wood, K Timpone, J Wathen, LK Nevin, T Resnick, L Batts, DH Reichman, RC TI Phase I study of atevirdine mesylate (U-87201E) monotherapy in HIV-1-infected patients SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1 infection; drug resistance; nonnucleoside reverse transcriptase inhibitors; atevirdine; phase I/II clinical trial ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIV-1 REVERSE-TRANSCRIPTASE; NONNUCLEOSIDE INHIBITORS; RESISTANCE MUTATIONS; PYRIDINONE DERIVATIVES; REPLICATION; ZIDOVUDINE; COMBINATION; BI-RG-587; L-697,661 AB The safety, tolerability, and antiviral activity of atevirdine (ATV), a nonnucleoside reverse transcriptase inhibitor, were studied in a phase I/II clinical trial (ACTG 187) of patients with CD4 counts less than or equal to 500/mm(3). In all, 34 HIV-1-infected patients were randomized to receive ATV for 12 weeks in doses chosen to achieve one of three serum trough levels: 5 to 13 mu M, 14 to 22 mu M, or 23 to 31 mu M Rash was the most common adverse event, with a grade 3 or 4 rash occurring in 4 patients. No significant change from baseline in HIV-1 plasma RNA mean copy number was detected at week 4 (+0.09 log(10) copies/ml, p = .30). However, some evidence indicated moderate antiviral activity at week 4, based on median changes in CD4 count (+23/mm(3);p = .05), and viral peripheral blood mononuclear cell (PBMC) titer (-0.68 log(10) copies/ml; p = .03). In addition, 2 of 4 patients with detectable baseline serum p24 antigen showed declines of >50%. HIV-1 resistance to ATV was detected in 41% of patients and was most commonly associated with RT mutations K103N and Y181C. In contrast, the Y181C mutation was not detected in ATV-resistant isolates obtained from patients enrolled in ACTG 199, a study of ATV given in combination with zidovudine. Under the conditions of this study, ATV failed to demonstrate significant antiretroviral activity. However, transient in vivo activity might have been obscured by rapid development of resistance coupled with inadequate sampling at early time points following initiation of ATV therapy. C1 Univ Rochester, Sch Med & Dent, Infect Dis Unit, Rochester, NY USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. SUNY Buffalo, Dept Pharm, Buffalo, NY 14260 USA. Univ Miami, Dept Med, Miami, FL USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. Washington Univ, Dept Med, St Louis, MO USA. Univ So Calif, Dept Med, Los Angeles, CA USA. Frontier Sci & Res Fdn, Buffalo, NY USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. Operat Ctr Social & Sci Syst, AIDS Clin Trials Grp, Bethesda, MD USA. Univ Rochester, Sch Med & Dent, Dept Microbiol & Immunol, Rochester, NY 14642 USA. RP Reichman, RC (reprint author), 601 Elmwood Ave,Box 689, Rochester, NY 14642 USA. EM Richard_Reichman@urmc.rochester.edu FU NIAID NIH HHS [AI-25903, AI-38855, AI-27658] NR 28 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1998 VL 19 IS 2 BP 135 EP 144 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 126EJ UT WOS:000076279700006 PM 9768622 ER PT J AU Tess, BH Rodrigues, LC Newell, ML Dunn, DT Lago, TDG AF Tess, BH Rodrigues, LC Newell, ML Dunn, DT Lago, TDG CA Sao Paulo Collaborative Study Vertical Transmis TI Infant feeding and risk of mother-to-child transmission of HIV-1 in Sao Paulo State, Brazil SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV-1; vertical transmission; risk factors; breastfeeding; pediatrics; Latin America; epidemiology ID HUMAN-IMMUNODEFICIENCY-VIRUS; VITAMIN-A-DEFICIENCY; BREAST-MILK; PERINATAL TRANSMISSION; POSTNATAL TRANSMISSION; TYPE-1 INFECTION; ZAMBIA; COHORT; KIGALI; RWANDA AB Although vertical transmission of HIV-1 can occur through breast-feeding, little is known about the effect of colostrum, duration of breast-feeding, mixing feeding, and nipple pathology. We used retrospective cohort data to examine the association between breast-feeding-related factors and transmission of HIV-1 from mother to child in Sao Paulo State, Brazil. Information on maternal and postnatal factors was collected by medical record review and interview. Infection status was determined for 434 children by anti-HIV-l tests performed beyond 18 months of age or diagnosis of AIDS at any age. Among 168 breast-fed children, the risk of transmission of HIV-1 was 21%, compared with 13% (p = .01) among 264 children artificially fed. Breastfeeding was independently and significantly associated with mother-to-child transmission of HIV-1 after controlling for stage of maternal HIV-1 disease (odds ratio [OR] = 2.2; 95% confidence interval [CI], 1.3-3.8). A trend was shown toward an increased risk of transmission with longer duration of breast-feeding, a history of bleeding nipples, and introduction of other liquid food before weaning, but these associations were not statistically significant. History of colostrum intake or cracked nipples without bleeding were not associated with transmission. Most of the women who breast-fed were unaware of their HIV-1 infection status at the time of delivery. Avoidance of mixed feeding and withholding of breast-feeding in the presence of bleeding nipples should be considered in further research as strategies to reduce postnatal transmission of HIV-1 in settings in which safe and sustainable alternatives for breast-feeding are not yet available. C1 Univ London, London Sch Hyg & Trop Med, London, England. Sao Paulo State Dept Hlth, Inst Hlth, Sao Paulo, Brazil. Univ London, Inst Child Hlth, London WC1N 1EH, England. RP Tess, BH (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6130 Execut Blvd,EPN-434, Rockville, MD 20852 USA. OI Newell, Marie-Louise/0000-0002-1074-7699 NR 39 TC 51 Z9 51 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD OCT 1 PY 1998 VL 19 IS 2 BP 189 EP 194 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 126EJ UT WOS:000076279700014 PM 9768630 ER PT J AU Eggleston, PA Rosenstreich, D Lynn, M Gergen, P Baker, D Kattan, M Mortimer, KM Mitchell, H Ownby, D Slavin, R Malveaux, F AF Eggleston, PA Rosenstreich, D Lynn, M Gergen, P Baker, D Kattan, M Mortimer, KM Mitchell, H Ownby, D Slavin, R Malveaux, F TI Relationship of indoor allergen exposure to skin test sensitivity in inner-city children with asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE allergens; cockroach; car; dust mite; skin test ID DUST MITE ALLERGENS; DER-P-I; FEL-D-I; COCKROACH ALLERGEN; TEST REACTIVITY; SCHOOL DUST; F-I; SENSITIZATION; RISK; POPULATION AB Background: It is important to understand the relationship between environmental allergen exposure dose and the risk of atopic individuals becoming sensitized to that allergen if we are to change the risk of sensitization and morbidity from allergic disease. Objective: The objective of these studies was to determine whether there was a dose response between current exposure to mite, cockroach, and cat allergen in inner-city children and to determine the prevalence of sensitization to these allergens. Methods: A sample of 500 children was selected from the 1528 children enrolled in the National Cooperative Inner City Asthma Study. Children were selected who had a sample of home dust and valid skin test responses performed with a MultiTest skin test device. The samples of home dust were collected from the floor and furniture in the kitchen, bedroom, and television/living room and were assayed for Der p 1, Der f 1, Bla g 1, and Eel dl allergens. Results: Each allergen level correlated significantly between rooms in individual homes. Mite (Der p 1 and Der f 1) and cat (Fel d 1) allergen levels were frequently below the detection limit of the assay. Cockroach allergen (BLa g 1) concentrations in the child's bedroom were related to the prevalence of positive skin test responses to cockroach allergen extract among the children, with an odds ratio for sensitization of 1.45 (1.11-1.92). Positive skin test responses to cockroach allergen were seen in 15% of children exposed to bedroom dust with a Bla g 1 concentration below the level of detection compared with a rate of 32% in bedrooms with Bla g 1 levels of 1 to 2 U/g and 40% to 44% among those in rooms with 4 U/g or greater. The relationship between exposure and positive skin test responses was clearly stronger among atopic children with a greater number of positive skin test responses. Conclusions: Despite widespread exposure to household allergens, the strongest relationship between exposure and sensitization was seen in the bedroom. The dose response between exposure to cockroach allergen and sensitization suggested that exposure to low doses of allergen, 2 U/g or less, was a risk factor and that the risk plateaus above 4 U/g. Atopy modified the relationship of exposure to sensitization. C1 Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. Albert Einstein Coll Med, Dept Med, Div Allergy & Immunol, New York, NY USA. New England Res Inst, Watertown, MA 02172 USA. Univ Calif Irvine, Ctr Environm & Occupat Hlth, Irvine, CA 92717 USA. Mt Sinai Sch Med, Dept Pediat, New York, NY USA. NIAID, Bethesda, MD 20892 USA. Med Coll Georgia, Sect Allergy & Immunol, Augusta, GA 30912 USA. St Louis Univ, Sch Med, Dept Med, Div Allergy & Immunol, St Louis, MO 63104 USA. Howard Univ, Coll Med, Washington, DC 20059 USA. RP Eggleston, PA (reprint author), Johns Hopkins Hosp, Dept Pediat, Div Allergy & Immunol, CMSC 11-117,600 N Wolfe St, Baltimore, MD 21287 USA. FU NIAID NIH HHS [AI30773] NR 27 TC 223 Z9 226 U1 0 U2 12 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 1998 VL 102 IS 4 BP 563 EP 570 DI 10.1016/S0091-6749(98)70272-6 PN 1 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 131XK UT WOS:000076600400005 PM 9802363 ER PT J AU Jufer, RA Walsh, SL Cone, EJ AF Jufer, RA Walsh, SL Cone, EJ TI Cocaine and metabolite concentrations in plasma during repeated oral administration: Development of a human laboratory model of chronic cocaine use SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID BUTYRYLCHOLINESTERASE; CARBOXYLESTERASE; PHARMACOKINETICS; PURIFICATION; COCAETHYLENE; MICROSOMES; CATALYZES C1 NIDA, Addict Res Ctr, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Behav Pharmacol Res Unit, Baltimore, MD 21224 USA. RP Jufer, RA (reprint author), NIDA, Addict Res Ctr, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. FU NIDA NIH HHS [DA10029] NR 25 TC 40 Z9 41 U1 0 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 1998 VL 22 IS 6 BP 435 EP 444 PG 10 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 126DQ UT WOS:000076278000007 PM 9788518 ER PT J AU Huestis, MA Cone, EJ AF Huestis, MA Cone, EJ TI Differentiating new marijuana use from residual drug excretion in occasional marijuana users SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-of-Forensic-Toxicologists CY OCT 14-19, 1996 CL DENVER, COLORADO SP Soc Forens Toxicologists ID CREATININE CLEARANCE; BIOLOGICAL VARIATION; URINARY CREATININE; ABUSED DRUGS; LONG-TERM; METABOLITES; ACID; IMMUNOASSAY; SMOKING C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 32 TC 86 Z9 91 U1 1 U2 5 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 1998 VL 22 IS 6 BP 445 EP 454 PG 10 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 126DQ UT WOS:000076278000008 PM 9788519 ER PT J AU Cone, EJ Lange, R Darwin, WD AF Cone, EJ Lange, R Darwin, WD TI In vivo adulteration: Excess fluid ingestion causes false-negative marijuana and cocaine urine test results SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Academy-of-Forensic-Sciences CY FEB 14-19, 1994 CL SAN ANTONIO, TEXAS SP AMER ACAD FORENS SCI ID ABUSED DRUGS; SPECIMENS; IMMUNOASSAY C1 NIDA, Addict Res Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Cone, EJ (reprint author), NIDA, Addict Res Ctr, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 16 TC 36 Z9 40 U1 0 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 1998 VL 22 IS 6 BP 460 EP 473 PG 14 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 126DQ UT WOS:000076278000010 PM 9788521 ER PT J AU Heishman, SJ Singleton, EG Crouch, DJ AF Heishman, SJ Singleton, EG Crouch, DJ TI Laboratory validation study of drug evaluation and classification program: Alprazolam, d-amphetamine, codeine, and marijuana SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID IONIZATION MASS-SPECTROMETRY; MAJOR METABOLITES; EYE-MOVEMENTS; DRIVERS; ALCOHOL; COCAINE; PERFORMANCE; HUMANS; URINE C1 NIDA, Div Intramural Res, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Utah, Ctr Human Toxicol, Salt Lake City, UT USA. RP Heishman, SJ (reprint author), NIDA, Addict Res Ctr, Clin Pharmacol Branch, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Sheish@intra.nida.nih.gov OI Singleton, Edward G./0000-0003-3442-877X NR 40 TC 9 Z9 9 U1 0 U2 3 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 1998 VL 22 IS 6 BP 503 EP 514 PG 12 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 126DQ UT WOS:000076278000015 PM 9788526 ER PT J AU Goldberger, BA Darraj, AG Caplan, YH Cone, EJ AF Goldberger, BA Darraj, AG Caplan, YH Cone, EJ TI Detection of methadone, methadone metabolites, and other illicit drugs of abuse in hair of methadone-treatment subjects SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article; Proceedings Paper CT 2nd International Meeting on Clinical and Forensic Aspects of Hair Analysis CY 1994 CL GENOA, ITALY ID MASS-SPECTROMETRY C1 Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. Univ Maryland, Sch Med, Dept Med & Res Technol, Baltimore, MD 21208 USA. Natl Sci Serv, Baltimore, MD 21208 USA. NIDA, Addict Res Ctr, Baltimore, MD 21224 USA. RP Goldberger, BA (reprint author), Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, POB 100275, Gainesville, FL 32610 USA. NR 8 TC 18 Z9 21 U1 0 U2 2 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 1998 VL 22 IS 6 BP 526 EP 530 PG 5 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 126DQ UT WOS:000076278000018 PM 9788529 ER PT J AU Chaussee, MS Hill, SA AF Chaussee, MS Hill, SA TI Formation of single-stranded DNA during DNA transformation of Neisseria gonorrhoeae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID NATURAL TRANSFORMATION; HEMOPHILUS TRANSFORMATION; PLASMID TRANSFORMATION; GENETIC-TRANSFORMATION; BACILLUS-SUBTILIS; COMPETENCE; SEQUENCE; RECOMBINATION; GONOCOCCI; VARIANTS AB Neisseria gonorrhoeae is naturally competent for DNA transformation. In contrast to other natural prokaryotic DNA transformation systems, single stranded donor DNA (ssDNA) has not previously been detected during transformation of N. gonorrhoeae, We have reassessed the physical nature of gonococcal transforming DNA by using a sensitive nondenaturing native blotting technique that detects ssDNA. Consistent with previous analyses, we found that the majority of donor DNA remained in the double-stranded form, and only plasmid DNAs that carried the genus specific DNA uptake sequence were sequestered in a DNase I-resistant state. However, when the DNA was examined under native conditions, S1 nuclease-sensitive ssDNA was identified in all strains tested except for those bacteria that carried the dud-1 mutation, Surprisingly, ssDNA was also found during transformation of N. gonorrhoeae comA mutants, which suggested that ssDNA was initially formed within the periplasm. C1 NIAID, Microbial Struct & Funct Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Chaussee, MS (reprint author), 903 S 4th St, Hamilton, MT 59840 USA. NR 33 TC 30 Z9 32 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 1998 VL 180 IS 19 BP 5117 EP 5122 PG 6 WC Microbiology SC Microbiology GA 122YX UT WOS:000076100000016 PM 9748444 ER PT J AU Watanabe, H Yamada, Y Kimata, K AF Watanabe, H Yamada, Y Kimata, K TI Roles of aggrecan, a large chondroitin sulfate proteoglycan, in cartilage structure and function SO JOURNAL OF BIOCHEMISTRY LA English DT Review DE cartilage matrix deficiency; G1 domain; G3 domain; link protein; nanomeria ID DEDUCED PRIMARY STRUCTURE; COMPLETE CODING SEQUENCE; MATRIX DEFICIENCY MOUSE; IN-SITU HYBRIDIZATION; CORE PROTEIN; LINK PROTEIN; BINDING-PROTEINS; GENE-EXPRESSION; TENASCIN-R; PG-M AB Aggrecan, a large aggregating proteoglycan, is one of the major structural components of cartilage. Its core protein contains three glubular domains and two glycosaminoglycan-attachment domains. These domains play various roles to maintain cartilage structure and function. An N-terminal globular domain binds hyaluronan and link protein to form huge aggregates, The chondroitin sulfate (CS) chains attach to the CS domain and provide a hydrated, viscous gel that absorbs compressive load. Two autosomal recessive chondrodysplasias, cartilage matrix deficiency (cmd) in mice and nanomelia in chicken are both caused by aggrecan gene mutations, Cmd homozygotes die shortly after birth, while the heterozygotes are born normal. However, cmd heterozygotes develop late onset of spinal disorder, which suggests aggrecan as a candidate gene predisposing individuals to spinal problems. Nanomelia is a useful model to elucidate intracellular trafficking of proteoglycans. Further studies on aggrecan will lead to prophylaxis and treatment of joint destructive diseases such as osteoarthrosis and to elucidation of cartilage development, which is essential for skeletal formation. C1 NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Aichi Med Univ, Inst Mol Sci Med, Aichi 4801195, Japan. RP Watanabe, H (reprint author), NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. EM watanabe@yoda.nidr.nih.gov NR 63 TC 156 Z9 161 U1 2 U2 18 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-924X J9 J BIOCHEM-TOKYO JI J. Biochem. (Tokyo) PD OCT PY 1998 VL 124 IS 4 BP 687 EP 693 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 129ED UT WOS:000076449600001 PM 9756610 ER PT J AU Park, G Lu, FH Ye, N Brechbiel, MW Torti, SV Torti, FM Planalp, RP AF Park, G Lu, FH Ye, N Brechbiel, MW Torti, SV Torti, FM Planalp, RP TI Novel iron complexes and chelators based on cis,cis-1,3,5-triaminocyclohexane: iron-mediated ligand oxidation and biochemical properties SO JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY LA English DT Article DE iron complexes; chelating agents; iron metabolism; oxidative dehydrogenation; cytotoxicity ID DEHYDROGENATION; DERIVATIVES; AMINES; GROWTH; CYCLE AB The interaction of Fe(II) and Fe(III) with the novel Fe(II) chelator N,N'N"-tris(2-pyridylmethyl)-cis, cis-1,3,5-triaminocyclohexane (referred to as tachpyr) gives rise to six-coordinate, low-spin, cationic complexes of Fe(II). Tachpyr also displays a cytotoxicity toward cultured bladder cancer cells that is believed to involve coordination of intracellular iron. The anaerobic reaction of tachpyr with Fe(II) salts affords the Fe(II)-tachpyr(2+) complex, but in presence of oxygen, oxidative dehydrogenation of one or two of the aminomethylene group(s) of the ligand occurs, with formal loss of H-2: R-N(H)-C(H)(2)-(2-py) --> R-N = C(H) - (2-py) + H-2. The resulting mono- and diimino Fe(II) complexes (denoted as [Fe(tachpyr-H-2)](2+) and [Fe(tachpyr-2H(2))](2+)) are an inseparable mixture, but they may be fully oxidized by H2O2 to the known tris (imino) complex Fe(II) [cis,cis-1,3,5-tris (pyridine-2-carboxaldimino)cyclohexane](2+) (or [Fe(tachpyr-3H(2))](2+)). Cyclic voltammetry of the imino complex mixture reveals an irreversible anodic wave at +0.78 V vs. NHE. Tachpyr acts as a reducing agent toward Fe(IIII) salts, affording the same two Fe(II) imino complexes as products. Tachpyr also reductively removes Fe(III) from an Fe(III)(ATP)(3) complex (which is a putative form of intracellular iron), producing the two Fe(II) imino complexes. Novel N-alkylated derivatives of tachpyr have been synthesized. N-Alkylation has two effects on tachpyr: lowering metal affinity through in creased steric hindrance, and preventing Fe(III) reduction because oxidative dehydrogenation of nitrogen is blocked. The N-methyl tachpyr derivative binds Fe(II) only weakly as a high-spin complex, and no complexation or reduction of Fe(III) is observed. Corresponding to their inability to bind iron, the N-alkylated chelators are nontoxic to cultured bladder cancer cells. A tach-based chelator with three N-propyleneamino arms is also synthesized. Studies of the chemical and biochemical properties of this chelator further support a relationship between intracellular iron chelation, iron reduction, and cytotoxicity. C1 Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Canc Biol & Internal Med, Winston Salem, NC 27157 USA. Wake Forest Univ, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. RP Planalp, RP (reprint author), Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. NR 28 TC 33 Z9 34 U1 2 U2 9 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-8257 J9 J BIOL INORG CHEM JI J. Biol. Inorg. Chem. PD OCT PY 1998 VL 3 IS 5 BP 449 EP 457 DI 10.1007/s007750050254 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Inorganic & Nuclear SC Biochemistry & Molecular Biology; Chemistry GA 132ET UT WOS:000076617900002 ER PT J AU Lee, CH Vyavahare, N Zand, R Kruth, H Schoen, FJ Bianco, R Levy, RJ AF Lee, CH Vyavahare, N Zand, R Kruth, H Schoen, FJ Bianco, R Levy, RJ TI Inhibition of aortic wall calcification in bioprosthetic heart valves by ethanol pretreatment: Biochemical and biophysical mechanisms SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article ID LATTICE RELAXATION-TIME; RAT SUBDERMAL MODEL; COLLAGEN; WATER; PREINCUBATION; PREVENTION; EFFICACY; SYSTEMS; ELASTIN; INVITRO AB The effectiveness of ethanol pretreatment on preventing calcification of glutaraldehyde-fixed porcine aortic bioprosthetic heart valve (BPHV) cusps was previously demonstrated, and the mechanism of action of ethanol was attributed in part to both lipid removal and a specific collagen conformational change. In the present work, the effect of ethanol pretreatment on BPHV aortic wall calcification was investigated using both rat subdermal and sheep circulatory implants. Ethanol pretreatment significantly inhibited calcification of BPHV aortic wall, but with less than complete inhibition. The maximum inhibition of calcification of BPHV aortic wall was achieved using an 80% ethanol pretreatment; calcium levels were 71.80 +/- 8.45 mu g/mg with 80% ethanol pretreatment compared to the control calcium level of 129.90 +/- 7.24 mu g/mg (p = 0.001). Increasing the duration of ethanol exposure did not significantly improve the inhibitory effect of ethanol on aortic wall calcification. In the sheep circulatory implants, ethanol pretreatment partly prevented BPHV aortic wall calcification with a calcium level of 28.02 +/- 4.42 mu g/mg compared to the control calcium level of 56.35 +/- 6.14 mu g/mg (p = 0.004). Infrared spectroscopy (ATR-FTIR) studies of ethanol-pretreated BPHV aortic wall (vs. control) demonstrated a significant change in protein structure due to ethanol pretreatment. The water content of the aortic wall tissue and the spin-lattice relaxation times (T-1) as assessed by proton nuclear magnetic resonance spectroscopy did not change significantly owing to ethanol pretreatment. The optimum condition of 80% ethanol pretreatment almost completely extracted both phospholipids and cholesterol from the aortic wall; despite this, significant calcification occurred. In conclusion, these results clearly demonstrate that ethanol pretreatment is significantly but only partially effective for inhibition of calcification of BPHV aortic wall and this effect may be due in part to lipid extraction and protein structure changes caused by ethanol. It is hypothesized that ethanol pretreatment may be of benefit for preventing bioprosthetic aortic wall calcification only in synergistic combination with another agent. (C) 1998 John Wiley & Sons, Inc. C1 Childrens Hosp Philadelphia, Abramson Pediat Res Ctr, Joseph Stokes Jr Res Inst, Philadelphia, PA 19104 USA. Univ Michigan, Dept Pediat & Communicable Dis, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Biochem & Biophys, Ann Arbor, MI 48109 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. RP Levy, RJ (reprint author), Childrens Hosp Philadelphia, Abramson Pediat Res Ctr, Joseph Stokes Jr Res Inst, 1107B,34th & St & Civ Ctr Blvd, Philadelphia, PA 19104 USA. FU NHLBI NIH HHS [HL 38118] NR 34 TC 37 Z9 41 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD OCT PY 1998 VL 42 IS 1 BP 30 EP 37 DI 10.1002/(SICI)1097-4636(199810)42:1<30::AID-JBM5>3.0.CO;2-P PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 114ZD UT WOS:000075638300005 PM 9740004 ER PT J AU Ottiger, M Bax, A AF Ottiger, M Bax, A TI Characterization of magnetically oriented phospholipid micelles for measurement of dipolar couplings in macromolecules SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE alignment; bicelle; dipolar coupling; liquid crystal; protein NMR; phospholipid ID LIQUID-CRYSTALLINE MEDIUM; HUMAN UBIQUITIN; NMR; DIHEXANOYLPHOSPHATIDYLCHOLINE; RESOLUTION; RELAXATION; ASSIGNMENT; BILAYERS; PROTEINS AB Weak alignment of solute molecules with the magnetic field can be achieved in a dilute liquid crystalline medium, consisting of an aqueous mixture of dimyristoyl-phosphatidylcholine (DMPC) and dihexanoyl-phosphatidylcholine (DHPC). For a certain range of molar ratios, DMPC and DHPC can form large, disc-shaped particles, commonly referred to as bicelles (Sanders and Schwonek, 1992), which cooperatively align in the magnetic field and induce a small degree of alignment on asymmetrically shaped solute molecules. As a result, dipolar couplings between pairs of H-1, C-13 or N-15 nuclei are no longer averaged to zero by rotational diffusion and they can be readily measured, providing valuable structural information. The stability of these liquid crystals and the degree of alignment of the solute molecules depend strongly on experimental variables such as the DMPC:DHPC ratio and concentration, the preparation protocol of the DMPC/DHPC mixtures, as well as salt, temperature, and pH. The lower temperature limit for which the liquid crystalline phase is stable can be reduced to 20 degrees C by using a ternary mixture of DHPC, DMPC, and 1-myristoyl-2-myristoleoyl-sn-glycero-3-phosphocholine, or a binary mixture of DHPC and ditridecanoyl-phosphatidylcholine. These issues are discussed, with an emphasis on the use of the medium for obtaining weak alignment of biological macromolecules. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Ottiger, M (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NR 35 TC 208 Z9 213 U1 0 U2 18 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD OCT PY 1998 VL 12 IS 3 BP 361 EP 372 DI 10.1023/A:1008366116644 PG 12 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 138CR UT WOS:000076954300001 PM 9835045 ER PT J AU Cheatham, TE Srinivasan, J Case, DA Kollman, PA AF Cheatham, TE Srinivasan, J Case, DA Kollman, PA TI Molecular dynamics and continuum solvent studies of the stability of polyG-polyC and polyA-polyT DNA duplexes in solution SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID MESH EWALD METHOD; SECONDARY STRUCTURE FORMATION; FREE-ENERGY DETERMINANTS; A-DNA; B-DNA; MINOR-GROOVE; HELICAL PERIODICITY; CRYSTAL-STRUCTURES; AQUEOUS-SOLUTION; NUCLEIC-ACIDS AB Molecular dynamics simulation in explicit solvent and continuum solvent models are applied to investigate the relative stability of A- and B-form helices for two DNA sequences, dA(10)-dT(10) and dG(10)-dC(10) in three structural forms. One structural form is based on an unrestrained molecular dynamics (MD) trajectory starting from a canonical B-DNA structure, the second is based on a MD trajectory starting in a canonical B-DNA structure with the sugars constrained to be C2'-endo and the third simulation started from a canonical A-DNA structure with the sugars constrained to C3'-endo puckers. For the energetic analysis, structures were taken as snapshots from nanosecond length molecular dynamics simulations computed in a consistent fashion in explicit solvent, applying the particle mesh Ewald method and the Cornell et al. force field. The electrostatic contributions to solvation free energies are computed using both a finite-difference Poisson-Boltzmann model and a pairwise Generalized Born model. The non-electrostatic contributions to the solvation free energies are estimated with a solvent accessible surface area dependent term. To estimate the gas phase component of the relative free energy between the various structures, the mean solute internal energies (determined with the Cornell et al. molecular mechanics potential including all pairwise interactions within the solute) and estimates of the solute entropy (using a harmonic approximation) were used. Consistent with experiment, the polyG-polyC (GC) structures are found to be much more A-phillic than the polyA-polyT (AT) structures, the latter being quite A-phobic. The dominant energy components responsible for this difference comes from the internal and van der Waal energies. A perhaps less appreciated difference between the GC and AT rich sequences is suggested by the calculated salt dependence which demonstrates a significantly enhanced ability to drive GC rich sequences towards an A-form structure compared to AT rich sequences. In addition to being A-phobic, the AT structure also has a noticably larger helical repeat than GC and other mixed sequence duplexes, consistent with experiment. Analysis of the average solvent density from the trajectories shows hydration patterns in qualitative agreement with experiment and previous theoretical treatments. C1 NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. RP Cheatham, TE (reprint author), NHLBI, Biophys Chem Lab, 12A-2041,9000 Rockville Pike, Bethesda, MD 20892 USA. EM cheatham@helix.nih.gov; pak@cgl.ucsf.edu FU NCI NIH HHS [CA-25644]; NCRR NIH HHS [RR-12255] NR 74 TC 145 Z9 148 U1 0 U2 7 PU ADENINE PRESS PI SCHENECTADY PA 2066 CENTRAL AVE, SCHENECTADY, NY 12304 USA SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD OCT PY 1998 VL 16 IS 2 BP 265 EP 280 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 136HJ UT WOS:000076853100007 PM 9833666 ER PT J AU Grzesik, WJ Kuzentsov, SA Uzawa, K Mankani, M Robey, PG Yamauchi, M AF Grzesik, WJ Kuzentsov, SA Uzawa, K Mankani, M Robey, PG Yamauchi, M TI Normal human cementum-derived cells: Isolation, clonal expansion, and in vitro and in vivo characterization SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article; Proceedings Paper CT 19th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 10-14, 1997 CL CINCINNATI, OHIO SP Amer Soc Bone & Mineral Res ID PERIODONTAL-LIGAMENT CELLS; MARROW STROMAL FIBROBLASTS; BONE SIALOPROTEIN; TOOTH ROOT; IN-VITRO; INVITRO; CEMENTOGENESIS; EXPRESSION; RAT; PROTEINS AB Cultures of primary human cementum-derived cells (HCDCs) were established from healthy premolar teeth extracted for orthodontic reasons. Cementum was manually dissected, fragmented, and digested twice with collagenase. Following a thorough wash to remove liberated cells, the remaining cementum fragments were plated in Dulbecco's modified Eagle's medium/F12 medium containing 10% fetal bovine serum. Discrete colonies that contained cells exhibiting fibroblast-like morphology were visible after 14-21 days of culture. When the colonies became sufficiently large, cells from individual colonies were isolated and subcultured. Cementum-derived cells exhibited low levels or no alkaline phosphatase activity and mineralized in vitro to a lesser degree than human periodontal ligament (PDL) cells and human bone marrow stromal cell (BMSC) cultures. To study differentiation capacities of HCDCs, cells were attached to hydroxyapatite/tricalcium phosphate ceramic and transplanted subcutaneously into immunodeficient mice. The transplants were harvested 3, 6, and 8 weeks after transplantation and evaluated histologically, In human BMSC transplants, new bone tissue was formed with a prominent osteoblastic layer and osteocytes embedded in mineralized bone matrix. No osseous tissue was formed by PDL cells. Of six single colony-derived strains of HCDCs tested, three formed a bone-like tissue that featured osteocyte/cementocyte-like cells embedded within a mineralized matrix and which was lined with a layer of cells, although they were somewhat more elongated than osteoblasts, These results show that cells from normal human cementum can be isolated and expanded in vitro. Furthermore, these cells are capable of differentiating and forming mineralized tissue when transplanted into immunodeficient mice. C1 Univ N Carolina, Sch Dent, Dept Periodont, Dent Res Ctr, Chapel Hill, NC 27599 USA. NIDR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. RP Grzesik, WJ (reprint author), Univ N Carolina, Sch Dent, Dept Periodont, Dent Res Ctr, CB 7455,212B Dent Res Bldg, Chapel Hill, NC 27599 USA. RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 FU NIDCR NIH HHS [DE-10489] NR 25 TC 47 Z9 52 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD OCT PY 1998 VL 13 IS 10 BP 1547 EP 1554 DI 10.1359/jbmr.1998.13.10.1547 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 125BD UT WOS:000076216800005 PM 9783543 ER PT J AU Chariot, A Senterre-Lesenfants, S Sobel, ME Castronovo, V AF Chariot, A Senterre-Lesenfants, S Sobel, ME Castronovo, V TI Molecular cloning of a mutated HOXB7 cDNA encoding a truncated transactivating homeodomain-containing protein SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE homeobox; breast; ligase chain reaction; transcription ID HOMEOBOX GENE; DNA-BINDING; TRANSCRIPTION FACTORS; HOMEOTIC GENES; TERMINAL TAIL; EXPRESSION; DROSOPHILA; SPECIFICITY; SEQUENCE; DOMAIN AB Homeodomain-containing proteins regulate, as transcription factors, the coordinated expression of genes involved in development, differentiation, and malignant transformation. We report here the molecular cloning of a mutated HOXB7 transcript encoding a truncated homeodomain-containing protein in MCF7 cells. This is a new example of mutation affecting the coding region of a HOX gene. In addition, we detected two HOXB7 transcripts in several breast cell lines and demonstrated that both normal and mutated alleles were expressed at the RNA level in MCF7 cells as well as in a variety of breast tissues and lymphocytes, suggesting that a truncated HOXB7 protein might be expressed in vivo. Using transient co-transfection experiments, we demonstrated that both HOXB7 proteins can activate transcription from a consensus HOX binding sequence in breast cancer cells. Our results provide evidence that HOXB7 protein has transcription factor activity in vivo and that the two last amino acids do not contribute to this property. (C) 1998 Wiley-Liss, Inc. C1 NCI, Mol Pathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Liege, Metastasis Res Lab, Liege, Belgium. Univ Liege, Lab Med Chem & Med Oncol, Liege, Belgium. RP Chariot, A (reprint author), CHU, Sart Tilman, B-4000 Liege, Belgium. NR 45 TC 7 Z9 7 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 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT 1 PY 1998 VL 71 IS 1 BP 46 EP 54 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 114RD UT WOS:000075621900005 PM 9736453 ER PT J AU Carson, RE Kiesewetter, DO Jagoda, E Der, MG Herscovitch, P Eckelman, WC AF Carson, RE Kiesewetter, DO Jagoda, E Der, MG Herscovitch, P Eckelman, WC TI Muscarinic cholinergic receptor measurements with [F-18]FP-TZTP: Control and competition studies SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE FP-TZTP; muscarinic receptors; modeling; physostigmine; volume of distribution ID POSITRON EMISSION TOMOGRAPHY; C-11 RACLOPRIDE BINDING; CEREBRAL BLOOD-FLOW; IN-VIVO; PET SCANNER; HUMAN BRAIN; RAT CORTEX; M2; PHYSOSTIGMINE; ACETYLCHOLINE AB [[F-18]Fluoropropyl-TZTP (FP-TZTP) is a subtype-selective muscarinic cholinergic Ligand with potential suitability for studying Alzheimer's disease. Positron emission tomography studies in isofluorane-anesthetized rhesus monkeys were performed to assess the in vivo behavior of this radiotracer. First, control studies (n = 11) were performed to characterize the tracer kinetics and to choose an appropriate model using a metabolite-corrected arterial input function. Second, preblocking studies (n = 4) with unlabeled FP-TZTP were used to measure nonspecific binding. Third, the sensitivity of [F-18]FP-TZTP binding to changes in brain acetylcholine (ACh) was assessed by administering physostigmine, an acetylcholinesterase (AChE) inhibitor, by intravenous infusion (100 to 200 mu g.kg(-1).h(-1)) beginning 30 minutes before tracer injection (n = 7). Tracer uptake in the brain was rapid with K-1 values of 0.4 to 0.6 mL.min(-1).mL(-1) in gray matter. A model with one tissue compartment was chosen because reliable parameter estimates could not be obtained with a more complex model. Volume of distribution (V) values, determined from functional images created by pixel-by-pixel fitting, were very similar ia cortical regions, basal ganglia, and thalamus, but significantly lower (P < 0.01) in the cerebellum consistent with the distribution of M-2 cholinergic receptors. Preblocking studies with unlabeled FP-TZTP reduced V by 60% to 70% in cortical and subcortical regions. Physostigmine produced a 35% reduction in cortical specific binding (P < 0.05), consistent with increased ACh competition. The reduction in basal ganglia (12%) was significantly smaller (P < 0.05), consistent with its markedly higher AChE activity. These studies indicate that [F-18]FP-TZTP should be useful for the in vivo measurement of muscarinic receptors with position emission tomography. C1 NIH, PET Dept, Bethesda, MD 20892 USA. RP Carson, RE (reprint author), NIH, PET Dept, Bldg 10,Room 1C-401,10 Ctr Dr MSC 1180, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 39 TC 75 Z9 75 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD OCT PY 1998 VL 18 IS 10 BP 1130 EP 1142 DI 10.1097/00004647-199810000-00010 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 126WD UT WOS:000076316900011 PM 9778190 ER PT J AU Dement, JM Brown, DP AF Dement, JM Brown, DP TI Cohort mortality and case-control studies of white male chrysotile asbestos textile workers SO JOURNAL OF CLEAN TECHNOLOGY ENVIRONMENTAL TOXICOLOGY AND OCCUPATIONAL MEDICINE LA English DT Article DE asbestos; cancer; chrysotile; lung cancer; textile workers ID OCCUPATIONAL EPIDEMIOLOGY; EXPOSURE; MESOTHELIOMA; CONDUCT; DESIGN C1 Duke Univ, Med Ctr, Div Environm & Occupat Med, Durham, NC 27710 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Dement, JM (reprint author), Duke Univ, Med Ctr, Div Environm & Occupat Med, Box 2194, Durham, NC 27710 USA. EM dement00@mc.duke.edu NR 23 TC 2 Z9 2 U1 2 U2 3 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 USA SN 1052-1062 J9 J CLEAN TECHNOL E T JI J. Clean Technol. Environ. Toxicol. Occup. Med. PD OCT-DEC PY 1998 VL 7 IS 4 BP 413 EP 419 PG 7 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA ZX732 UT WOS:000074549100004 ER PT J AU Levav, M Mirsky, AF French, LM Bartko, JJ AF Levav, M Mirsky, AF French, LM Bartko, JJ TI Multinational neuropsychological testing: Performance of children and adults SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article; Proceedings Paper CT Meeting of the International-Neuropsychological-Society CY JUL, 1998 CL BUDAPEST, HUNGARY SP Int Neuropsychol Soc ID URBAN CHILDREN; CROSS; INFECTION; HIV-1; PHASE AB We obtained neuropsychological assessment data on persons from five countries whose ages range from 8 to 90 years. Participants were assessed in four languages. The results from the multivariate analyses indicate that reaction-time measures obtained in tests of sustained attention are minimally affected by country of origin and level of education. In contrast, tests assessing the ability to focus attention and solve a problem, to shift strategies, and to inhibit an automatic response tendency differ significantly by country and level of education. Most of these differences tend to disappear at about the age of 54. The data provide partial support for the hypothesis of commonality of some neuropsychological functions across cultures. C1 NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, Bethesda, MD 20892 USA. Biostat Consulting, Bethesda, MD USA. RP Levav, M (reprint author), NIMH, Sect Clin & Expt Neuropsychol, Lab Brain & Cognit, Bldg 15K,Room 108,15 North Dr,MSC 2668, Bethesda, MD 20892 USA. NR 29 TC 11 Z9 14 U1 0 U2 2 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD OCT PY 1998 VL 20 IS 5 BP 658 EP 672 PG 15 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 170ZB UT WOS:000078836300007 PM 10079042 ER PT J AU Winer, KK Yanovski, JA Sarani, B Cutler, GB AF Winer, KK Yanovski, JA Sarani, B Cutler, GB TI A randomized, cross-over trial of once-daily versus twice-daily parathyroid hormone 1-34 in treatment of hypoparathyroidism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CA2+-SENSING RECEPTOR; PHOSPHATE-METABOLISM; VITAMIN-D; BONE; CALCIUM; 1,25-DIHYDROXYVITAMIN-D3; CHILDREN; HYPERCALCIURIA; INTERMITTENT; CALCITRIOL AB Once-daily sc injection of PTH 1-34 can normalize mean serum and urine calcium levels in patients with hypoparathyroidism; however, once-daily PTH has diminishing effects on serum calcium after 12 h, such that serum calcium levels fall below the normal range in some patients. Once-daily PTR also causes a marked increase in bone turnover, with persistent increases in markers of bone formation and resorption. To test the hypothesis that a twice-daily PTH regimen can produce more physiological control than a once-daily regimen, are performed a randomized cross-over trial, lasting 28 weeks, in 17 adult subjects with hypoparathyroidism. Each 14-week study arm was divided into a 2-week inpatient dose-adjustment phase and a 12-week outpatient phase. The PTH dose (given sc once daily at 0900 h or twice daily with one dose at 0900 h and the other at 2100 h) was adjusted to maintain both serum and urine calcium within, or close to, the normal range. During the second half of the day (12-24 h), twice-daily PTH increased serum calcium and magnesium levels more effectively than once-daily PTH. In patients with calcium receptor mutations (CaR), once-daily PTH normalized urine calcium, provided that serum calcium was maintained at levels below normal range. However, twice-daily PTH treatment produced higher mean serum calcium in patients with CaR with no significant rise in urine calcium excretion, and with no significant differences in either serum or urine calcium levels between CaR and patients with acquired or idiopathic hypoparathyroidism. Thus, treatment with twice-daily PTH is the better regimen for patients with CaR to overcome their tendency to hypercalcuria while producing near-normal levels of serum calcium. The total daily PTH dose was markedly reduced with the twice-daily regimen (twice daily 46 +/- 52 vs. once daily 97 +/- 60 mu g/day, P < 0.001). We conclude that a twice-daily PTH regimen provides effective treatment of hypoparathyroidism and reduces the variation in serum calcium levels at a lower total daily PTH dose. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Winer, KK (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. OI Sarani, Babak/0000-0001-6247-3004 NR 26 TC 78 Z9 84 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD OCT PY 1998 VL 83 IS 10 BP 3480 EP 3486 DI 10.1210/jc.83.10.3480 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 126CN UT WOS:000076275500016 PM 9768650 ER PT J AU Argyropoulos, G Brown, AM Willi, SM Zhu, JG He, YF Reitman, M Gevao, SM Spruill, I Garvey, WT AF Argyropoulos, G Brown, AM Willi, SM Zhu, JG He, YF Reitman, M Gevao, SM Spruill, I Garvey, WT TI Effects of mutations in the human uncoupling protein 3 gene on the respiratory quotient and fat oxidation in severe obesity and type 2 diabetes SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE UCP3; mutation; obesity; fat oxidation; respiratory quotient; African American ID BROWN ADIPOSE-TISSUE; GLYCOSYLATED HEMOGLOBIN; NUCLEOTIDE-BINDING; THYROID-HORMONE; EXPRESSION; LEPTIN; IDENTIFICATION; SENSITIVITY; TRANSPORT; CLONING AB Human uncoupling protein 3 (UCP3) is a mitochondrial transmembrane carrier that uncouples oxidative ATP phosphorylation. With the capacity to participate in thermogenesis and energy balance, UCP3 is an important obesity candidate gene. A missense polymorphism in exon 3 (V102I) was identified in an obese and diabetic proband. A mutation introducing a stop codon in exon 4 (R143X) and a terminal polymorphism in the splice donor junction of exon 6 were also identified in a compound heterozygote that was morbidly obese and diabetic. Allele frequencies of the exon 3 and exon 6 splice junction polymorphisms were determined and found to be similar in Gullah-speaking African Americans and the Mende tribe of Sierra Leone, but absent in Caucasians. Moreover, in exon 6-splice donor heterozygotes, basal fat oxidation rates were reduced by 50%, and the respiratory quotient was markedly increased compared with wild-type individuals, implicating a role for UCP3 in metabolic fuel partitioning. C1 Med Univ S Carolina, Dept Med, Div Endocrinol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. Univ Sierra Leone, Coll Med & Allied Hlth Sci, Freetown, Sierra Leone. RP Argyropoulos, G (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol, 171 Ashley Ave, Charleston, SC 29425 USA. EM argyrog@musc.edu RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 FU NCRR NIH HHS [3MO1RR01070-20S2]; NIDDK NIH HHS [DK-38765, DK-47461] NR 35 TC 163 Z9 172 U1 2 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD OCT 1 PY 1998 VL 102 IS 7 BP 1345 EP 1351 DI 10.1172/JCI4115 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 127ZE UT WOS:000076380100008 PM 9769326 ER PT J AU Pazzaglia, PJ Post, RM Ketter, TA Callahan, AM Marangell, LB Frye, MA George, MS Kimbrell, TA Leverich, GS Cora-Locatelli, G Luckenbaugh, D AF Pazzaglia, PJ Post, RM Ketter, TA Callahan, AM Marangell, LB Frye, MA George, MS Kimbrell, TA Leverich, GS Cora-Locatelli, G Luckenbaugh, D TI Nimodipine monotherapy and carbamazepine augmentation in patients with refractory recurrent affective illness SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID CALCIUM-CHANNEL ANTAGONISTS; BEHAVIORAL DESPAIR TEST; BIPOLAR DISORDER; CSF SOMATOSTATIN; LIMBIC SEIZURES; ACUTE MANIA; VERAPAMIL; DEPRESSION; NIFEDIPINE; LITHIUM AB Of 30 patients with treatment-refractory affective illness, 10 showed a moderate to marked response to blind nimodipine monotherapy compared with placebo on the Clinical Global Impressions Scale, Fourteens inadequately responsive patients (3 unipolar [UP], 11 bipolar [BP]) were treated with the blind addition of carbamazepine. Carbamazepine augmentation of nimodipine converted four (29%) of the partial responders to more robust responders. Patients who showed an excellent response to the nimodipine-carbamazepine combination included individual patients with patterns of rapid cycling, ultradian cycling, UP recurrent brief depression, and one with BP type II depression. When verapamil was blindly substituted for nimodipine, two BP patients failed to maintain improvement but responded again to nimodipine and remained well with a blind transition to another dihydropyridine L-type calcium channel blocker (CCB), isradipine. Mechanistic implications of the response to the dihydropyridine L-type CCB nimodipine alone and in combination with carbamazepine are discussed. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Univ Mississippi, Sch Med, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Brown Univ, Sch Med, Providence, RI USA. Baylor Coll Med, Dallas, TX USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Vet Adm Med Ctr, N Little Rock, AR USA. RP Post, RM (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,10 Ctr Dr MSC 1272, Bethesda, MD 20892 USA. NR 76 TC 60 Z9 60 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD OCT PY 1998 VL 18 IS 5 BP 404 EP 413 DI 10.1097/00004714-199810000-00009 PG 10 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 126NW UT WOS:000076301000009 PM 9790159 ER PT J AU Silverman, K Wong, CJ Umbricht-Schneiter, A Montoya, ID Schuster, CR Preston, KL AF Silverman, K Wong, CJ Umbricht-Schneiter, A Montoya, ID Schuster, CR Preston, KL TI Broad beneficial effects of cocaine abstinence reinforcement among methadone patients SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID CARBON-MONOXIDE REDUCTION; MAINTENANCE PATIENTS; PAY AMOUNT; DRUG-USE; ABUSE; DEPENDENCE; PHARMACOTHERAPY; INTERVENTIONS; INCENTIVES; PROGRAMS AB Escalating reinforcement for sustained abstinence has been effective in treating cocaine abuse. Under this schedule, patients receive vouchers for cocaine-free urine samples; vouchers have monetary values that increase with the number of consecutive cocaine-free urine samples. Cocaine-abusing methadone patients were randomly assigned to receive vouchers for 12 weeks under (a) an escalating schedule (n = 20), (b) an escalating schedule with start-up bonuses (n = 20), or (c) a noncontingent schedule (n = 19). Start-up bonuses were designed to provide added reinforcement for initiating abstinence; however, they did not improve outcomes. Both contingent interventions significantly increased cocaine abstinence. In addition, the contingent interventions increased abstinence from opiates and decreased reports of cocaine craving. These results replicate the efficacy of cocaine abstinence reinforcement and show that it can have broad beneficial effects. C1 NIDA, Intramural Res Program, Clin Trials Sect, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21218 USA. NIDA, Off Director, Baltimore, MD 21224 USA. RP Preston, KL (reprint author), NIDA, Intramural Res Program, Clin Trials Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM kpreston@irp.nida.nih.gov RI Preston, Kenzie/J-5830-2013; OI Preston, Kenzie/0000-0003-0603-2479; Silverman, Kenneth/0000-0003-2724-1413 FU NIDA NIH HHS [P50 DA09258] NR 43 TC 134 Z9 135 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD OCT PY 1998 VL 66 IS 5 BP 811 EP 824 DI 10.1037//0022-006X.66.5.811 PG 14 WC Psychology, Clinical SC Psychology GA 130ZJ UT WOS:000076550300011 PM 9803700 ER PT J AU Ratliff-Schaub, K Hunt, CE Schafer, S Baird, T Crowell, D Palmer, P Smok-Pearsall, S Bak, S Cantey-Kiser, J AF Ratliff-Schaub, K Hunt, CE Schafer, S Baird, T Crowell, D Palmer, P Smok-Pearsall, S Bak, S Cantey-Kiser, J CA CHIME TI Interaction between infant sleep position and development at 56 weeks postconceptional age (PCA) SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Meeting Abstract C1 Med Coll Ohio, Dept Pediat, Toledo, OH 43699 USA. NICHD, Washington, DC USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Hawaii, Honolulu, HI 96822 USA. Univ So Calif, Los Angeles, CA USA. Rush Med Coll, Chicago, IL 60612 USA. Boston Univ, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD OCT PY 1998 VL 19 IS 5 BP 384 EP 385 PG 2 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 128NT UT WOS:000076413400030 ER PT J AU Wolffe, AP AF Wolffe, AP TI Packaging principle: How DNA methylation and histone acetylation control the transcriptional activity of chromatin SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress on Isozymes, Genes, and Gene Families CY APR 14-19, 1997 CL SAN ANTONIO, TEXAS ID NEWLY REPLICATED CHROMATIN; MAMMALIAN NUCLEI; GENE-EXPRESSION; NUCLEOSOMAL DNA; XENOPUS-LAEVIS; DE-NOVO; BINDING; REPRESSION; YEAST; METHYLTRANSFERASE AB Chromatin contains DNA, the transcriptional machinery, and structural proteins such as histones. All these components together are necessary for the physiologic control of transcription. A consideration of recent advances leads to a packaging principle for gene regulation. This packaging principle states that the transcriptional activity of a gene is largely controlled by the packaging of the template within chromatin. This assumption follows from experiments that establish the covalent modification of chromatin as a major causal influence on gene activity. DNA methylation and histone acetylation alter the nucleosomal infrastructure to repress or activate transcription. These covalent modifications can have roles in both promoter-specific events and the global control of chromosomal activity. These regulatory functions are essential for vertebrate development. J. Exp. Zool. 282..239-244, 1998. (C) 1998 Wiley-Liss, Inc.dagger. C1 NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Wolffe, AP (reprint author), NICHHD, Mol Embryol Lab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA. NR 42 TC 31 Z9 32 U1 1 U2 7 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD OCT 1 PY 1998 VL 282 IS 1-2 BP 239 EP 244 DI 10.1002/(SICI)1097-010X(199809/10)282:1/2<239::AID-JEZ25>3.3.CO;2-J PG 6 WC Zoology SC Zoology GA 112CQ UT WOS:000075476900025 PM 9723180 ER PT J AU Eddy, EM AF Eddy, EM TI HSP70-2 heat-shock protein of mouse spermatogenic cells SO JOURNAL OF EXPERIMENTAL ZOOLOGY LA English DT Article; Proceedings Paper CT 9th International Congress on Isozymes, Genes, and Gene Families CY APR 14-19, 1997 CL SAN ANTONIO, TEXAS ID RAD51 RECOMBINATION PROTEIN; CHAPERONIN-CONTAINING TCP-1; MAMMALIAN STRESS PROTEINS; MALE GERM-CELLS; GENE FAMILY; SYNAPTONEMAL COMPLEX; HSP70-RELATED GENE; BINDING-PROTEIN; MALE-MICE; DEVELOPMENTAL REGULATION AB The HSP70 heat-shock proteins are molecular chaperones that assist other proteins in folding, transport, and assembly into complexes. The genes for these proteins are either constitutively expressed (Hsc70, Grp78), or their expression is induced by heat shock and other stresses (Hsp 70-1, Hsp 70-3). Two additional genes encode proteins that are developmentally regulated and expressed specifically in spermatogenic cells (Hsp 70-2, Hsc70t). The HSP70-2 protein is synthesized during the meiotic phase of spermatogenesis and is abundant in pachytene spermatocytes. Studies in transgenic mice indicated that the region between nucleotides -640 and +1 contains promoter sequences necessary for expression of Hsp70-2 in spermatocytes. Because of the pattern of gene expression, it was hypothesized that HSP70-2 is a chaperone necessary for completion of meiosis in spermatogenic cells. The gene knockout approach was used to test this hypothesis, and it was found that male mice homozygous for the mutation were infertile, whereas homozygous females were fertile. Spermatogenesis was disrupted, with the nuclei of late pachytene spermatocytes often appearing fragmented and spermatids being absent. Disruption of spermatogenesis occurred at the G(2)-M phase transition in prophase of meiosis I, and all pachytene spermatocytes underwent apoptosis. It was demonstrated that HSP70-2 is a chaperone for Cdc2, with their association allowing Cdc2 to acquire the necessary conformation to form a heterodimer with cyclin B-1, leading to changes in Cdc2 phosphorylation and the development of kinase activity necessary for the G2-M phase transition. This appears to be the first demonstration that interaction between an HSP70 protein and a cyclin-dependent kinase is necessary for progression of the cell cycle. J. Exp. Zool. 282:261-271, 1998. (C) 1998 Wiley-Liss, Inc.dagger. C1 NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Eddy, EM (reprint author), NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, C4-01, Res Triangle Pk, NC 27709 USA. NR 94 TC 34 Z9 37 U1 1 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-104X J9 J EXP ZOOL JI J. Exp. Zool. PD OCT 1 PY 1998 VL 282 IS 1-2 BP 261 EP 271 DI 10.1002/(SICI)1097-010X(199809/10)282:1/2<261::AID-JEZ28>3.3.CO;2-9 PG 11 WC Zoology SC Zoology GA 112CQ UT WOS:000075476900028 PM 9723183 ER PT J AU Jobes, DV Chima, SC Ryschkewitsch, CF Stoner, GL AF Jobes, DV Chima, SC Ryschkewitsch, CF Stoner, GL TI Phylogenetic analysis of 22 complete genomes of the human polyomavirus JC virus SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; DNA; EVOLUTION; BRAIN; REARRANGEMENTS; SEQUENCES; DISEASE AB The polyomavirus JC (JCV) establishes a persistent infection in the kidneys, and is the virus agent that causes the demyelinating disease progressive multifocal leukoencephalopathy. PCR and DNA sequence analyses of partial JCV genomes have shown that there are at least four main JCV types, each associated with a specific geographical region. Type 1 is of European origin, Type 2 is Asian, Type 3 is found in individuals of African decent and Type 4 is a potential recombinant of Types 1 and 3, and is widely distributed throughout the population of the United States. A comprehensive phylogenetic analysis of 22 complete JCV genomes excluding part of the regulatory region was accomplished using neighbour-joining, UPGMA and maximum parsimony methods. The resulting UPGMA and parsimony phylogenies suggest that the European Type 1 strains diverged from the other types during the evolution of JCV and that each of the other genotypes (and subtypes) falls into well-supported clades. This is the first whole genome approach to phylogeny reconstruction for JCV and represents a significant improvement over earlier studies that were limited to partial JCV sequences and the neighbour-joining method. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, Bldg 36,Room 4A-27, Bethesda, MD 20892 USA. RI Chima, Sylvester Chidi/N-5564-2013 NR 32 TC 65 Z9 66 U1 0 U2 5 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING, BERKS, ENGLAND RG7 1AE SN 0022-1317 J9 J GEN VIROL JI J. Gen. Virol. PD OCT PY 1998 VL 79 BP 2491 EP 2498 PN 10 PG 8 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 124MQ UT WOS:000076186500024 PM 9780056 ER PT J AU Zoeteweij, JP Golding, H Mostowski, H Blauvelt, A AF Zoeteweij, JP Golding, H Mostowski, H Blauvelt, A TI Cutting edge: Cytokines regulate expression and function of the HIV coreceptor CXCR4 on human mature dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LANGERHANS CELLS; T-LYMPHOCYTES; INFECTION; RECEPTOR; AIDS; PROGRESSION; ENTRY; MONOCYTES; DISEASE; VIRUS AB HIV-infected dendritic cells (DC) efficiently transmit infection to CD4(+) T cells during the process of T cell activation. To further understand interactions between DC and HIV, cytokine regulation of HIV coreceptors on cultured Langerhans cells (cLC, as prototypes of mature DC) was studied. Expression of cell surface CXCR4 on cLC was up-regulated by IL-4 and TGF-beta 1 and inhibited by IFN-alpha, IFN-beta, and IFN-gamma, whereas cytokines did not appreciably regulate CCR5. Changes in cell surface CXCR4 expression on cLC correlated with T cell-tropic (X4)-HIV envelope-mediated syncytium formation and XI-HIV infection levels. A relative increase in the ratio of type 2/type 1 cytokine production, which can occur in HIV disease, may up-regulate CXCR4 expression on mature DC and promote infection by X4 viruses. Importantly, these findings suggest that cytokine dysregulation may be linked to the emergence of X4-HIV strains as HIV-infected individuals progress to AIDS. C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Blauvelt, A (reprint author), Bldg 10,Room 12N238,10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA. EM Andrew_Blauvelt@nih.gov NR 32 TC 52 Z9 53 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 OCT 1 PY 1998 VL 161 IS 7 BP 3219 EP 3223 PG 5 WC Immunology SC Immunology GA 122GY UT WOS:000076064700003 PM 9759835 ER PT J AU Durum, SK Lee, CK Geiman, TM Murphy, WJ Muegge, K AF Durum, SK Lee, CK Geiman, TM Murphy, WJ Muegge, K TI CD16 cross-linking blocks rearrangement of the TCR beta locus and development of alpha beta T cells and induces development of NK cells from thymic progenitors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; FC-GAMMA-RII/III; RECEPTOR-BETA; MICE; GENE; THYMOCYTES; LYMPHOCYTE; INTERLEUKIN-7; EXPRESSION; CHAIN AB Mouse thymocytes normally develop into T lymphocytes, but the embryonic thymus also contains precursor cells capable of developing into NK cells. Here, we describe conditions that induce pro-T cells to develop into NK cells, CD16 is expressed on thymic pro-T cells. We observed that CD16 cross-linking during culture of embryonic thymic organs suppressed rearrangement of the TCR beta locus (but did not inhibit TCR gamma locus rearrangement). Rearrangement of the TCR beta locus is normally required for development to the CD4(+)CD8(+), and this development was also suppressed by CD16 cross-linking. The ability of CD16 crosslinking to block alpha beta T cell development was not attributable to toxic effects, but rather was accompanied by promotion of development into NK cells, identified based on molecular and functional criteria. These results suggest that common lymphoid precursors can respond to environmental signals to commit to the alpha beta T vs NK developmental pathways. C1 NCI, Sci Applicat Int Corp, Frederick, MD 21702 USA. NCI, Lab Immunoregulat, Div Basic Sci, Frederick, MD 21702 USA. RP Durum, SK (reprint author), NCI, Lab Immunoregulat, Div Basic Sci, Bldg 560,Room 31-71, Frederick, MD 21702 USA. NR 20 TC 9 Z9 9 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 OCT 1 PY 1998 VL 161 IS 7 BP 3325 EP 3329 PG 5 WC Immunology SC Immunology GA 122GY UT WOS:000076064700016 PM 9759848 ER PT J AU Lindroos, PM Rice, AB Wang, YZ Bonner, JC AF Lindroos, PM Rice, AB Wang, YZ Bonner, JC TI Role of nuclear factor-kappa B and mitogen-activated protein kinase signaling pathways in IL-1 beta-mediated induction of alpha-PDGF receptor expression in rat pulmonary myofibroblasts SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR; GENE-EXPRESSION; INTERLEUKIN-1 INDUCTION; CHRYSOTILE ASBESTOS; LUNG FIBROBLASTS; INTACT-CELLS; TRANSCRIPTION; FIBROSIS; IL-1; TRANSDUCTION AB Induction of the a-platelet-derived growth factor receptor (PDGF-R alpha) by IL-1 beta in lung myofibroblasts enhances mitogenic and chemotactic responses to PDGF, and this could be a mechanism of myofibroblast hyperplasia during lung fibrogenesis. Since the regulation of many genes by IL-1 beta involves activation of NF-kappa B and mitogen-activated protein (MAP) kinases, we examined these signaling pathways in the control of PDGF-R alpha expression by IL-1 beta in cultured rat lung myofibroblasts, Treatment of cells with pyrrolidine dithiocarbamate (PDTC), an antioxidant that inhibits NF-kappa B activation, completely blocked PDGF-R alpha up-regulation by IL-1 beta as assayed by [I-125]PDGF-AA binding and PDGF-R alpha mRNA expression, suggesting a role for NF-kappa B. However, while IL-1 beta and TNF-alpha both induced nuclear binding of the Rel proteins p50 and p65 to an NF-kappa B consensus oligonucleotide in gel shift assays and caused transient degradation of inhibitor of NF-kappa B-alpha (I kappa B-alpha) in the cytoplasm of myofibroblasts, only IL-1 beta upregulated PDGF-R alpha. These results suggest that NF-kappa B activation alone is not sufficient for up-regulation of PDGF-R alpha. An investigation of MAP kinase signaling pathways revealed that IL-1 beta or PDTC activated extracellular signal-regulated kinase-2 (ERK-2) and c-jun NH2 terminal kinase-1 (JNK-1) phosphorylation of PHAS-1 and c-Jun substrates, respectively. Pretreatment of cells with the MAP kinase kinase-1 (MEK1) inhibitor PD 98059 blocked IL-1 beta-induced activation of ERK-2 by more than 90% but enhanced IL-1 beta-stimulated induction of PDGF-R alpha expression fourfold. Taken together, these data suggest that IL-1 beta activates both positive and negative signaling pathways that control the expression of PDGF-R alpha. IL-1 beta appears to mediate its negative effects on PDGF-R alpha expression via MAP kinase activation, while the factor(s) that mediate induction of PDGF-R alpha remain to be elucidated. C1 Natl Inst Environm Hlth Sci, Airway Inflammat Sect, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. RP Bonner, JC (reprint author), Natl Inst Environm Hlth Sci, Airway Inflammat Sect, Pulm Pathobiol Lab, POB 12233, Res Triangle Pk, NC 27709 USA. EM bonnerj@niehs.nih.gov NR 40 TC 28 Z9 29 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 1998 VL 161 IS 7 BP 3464 EP 3468 PG 5 WC Immunology SC Immunology GA 122GY UT WOS:000076064700033 PM 9759865 ER PT J AU Wang, RF Johnston, SL Zeng, G Topalian, SL Schwartzentruber, DJ Rosenberg, SA AF Wang, RF Johnston, SL Zeng, G Topalian, SL Schwartzentruber, DJ Rosenberg, SA TI A breast and melanoma-shared tumor antigen: T cell responses to antigenic peptides translated from different open reading frames SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFILTRATING LYMPHOCYTES; HLA-A2 MELANOMAS; METASTATIC MELANOMA; INTRON SEQUENCE; IN-VITRO; GENE; IDENTIFICATION; CANCER; IMMUNOTHERAPY; INTERLEUKIN-2 AB Infusion of TIL586 along with IL-2 into the autologous patient with metastatic melanoma resulted in the objective regression of tumor. Here, we report that screening a cDNA library from the 586mel cell line using CTL clones derived from TIL586 resulted in the isolation of a gene, CAG-3 (cancer Ag gene 3), Sequence analysis revealed that CAG-3 encodes an open reading frame identical to NY-ESO-1, which was recently reported to be recognized by autologous serum from a patient with esophageal cancer. Thus, NY-ESO-1 appears to be an immune target for both Ab- and T cell-mediated responses. Significantly, NY-ESO-l-specific CTL clones were capable of recognizing two HLA-A31-positive fresh and cultured breast tumors. To our knowledge, this represents the first direct demonstration that tumor-specific CTL clones can recognize both breast and melanoma tumor cells. A 10-mer antigenic peptide ESO10-53 (ASGPGGGAPR) was identified from the normal open reading frame of NY-ESO-1 based on its ability to sensitize HLA-A31-positive target cells for cytokine release and specific lysis, Interestingly, two additional CTL clones that were sensitized with NY-ESO-1 recognized two overlapping antigenic peptides derived from an alternative open reading frame of the same gene. These findings indicate that CTLs simultaneously responded to two different gene products translated from the normal and alternative reading frames of the same gene. Understanding of this mechanism by which the alternative reading frame is translated may have important implications in tumor immunology. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Wang, RF (reprint author), NCI, Surg Branch, NIH, Bldg 10,2B42, Bethesda, MD 20892 USA. NR 50 TC 54 Z9 55 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 OCT 1 PY 1998 VL 161 IS 7 BP 3596 EP 3606 PG 11 WC Immunology SC Immunology GA 122GY UT WOS:000076064700050 ER PT J AU Race, R Jenny, A Sutton, D AF Race, R Jenny, A Sutton, D TI Scrapie infectivity and proteinase K-resistant prion protein in sheep placenta, brain, spleen, and lymph node: Implications for transmission and antemortem diagnosis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; IMMUNOHISTOCHEMICAL DETECTION; NATURAL SCRAPIE; SUFFOLK SHEEP; VARIANT CJD; BSE; AGENT; TISSUES; DECADE; MICE AB Probable transmission of bovine spongiform encephalopathy to humans has focused intense interest on all of the transmissible spongiform encephalopathies (TSEs) and how they spread. In all TSEs, an abnormal disease-associated, proteinase K-resistant protein referred to as PrP-res or PrPSc accumulates in brain. In some species, PrP-res accumulates in other tissues as well. Sheep placenta, brain, spleen, and lymph node were analyzed in detail for PrP-res and infectivity. Both were detected in all brain and spleen samples and in placenta and lymph nodes of 80% of the scrapie-infected sheep. A perfect correlation was observed between infectivity and PrP-res detection. These results substantiate the probability that placenta plays an important role in natural transmission of scrapie, suggest that analysis of placenta for PrP-res could be the basis for an antemortem test for sheep scrapie, and show that PrP-res, scrapie infectivity, and scrapie disease are closely associated. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. Anim & Plant Hlth Inspect Serv, USDA, Natl Vet Serv Labs, Vet Serv, Ames, IA USA. Anim & Plant Hlth Inspect Serv, USDA, Vet Serv, Riverdale, MD USA. RP Race, R (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. NR 29 TC 143 Z9 145 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1998 VL 178 IS 4 BP 949 EP 953 DI 10.1086/515669 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 125QF UT WOS:000076248000004 PM 9806020 ER PT J AU Holland, SM Dorman, SE Kwon, A Pitha-Rowe, IF Frucht, DM Gerstberger, SM Noel, GJ Vesterhus, P Brown, MR Fleisher, TA AF Holland, SM Dorman, SE Kwon, A Pitha-Rowe, IF Frucht, DM Gerstberger, SM Noel, GJ Vesterhus, P Brown, MR Fleisher, TA TI Abnormal regulation of interferon-gamma, interleukin-12, and tumor necrosis factor-alpha in human interferon-gamma receptor 1 deficiency SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID MYCOBACTERIAL INFECTION; IFN-GAMMA; VISCERAL LEISHMANIASIS; CALMETTE-GUERIN; MICE; RESPONSES; GENE; TUBERCULOSIS; RESISTANT; SUSCEPTIBILITY AB Mycobacterial infections are critically controlled by interferon-gamma (IFN-gamma) and the cellular responses it elaborates, as shown by patients with mutations in the IFN-gamma receptor ligand-binding chain (IFN-gamma R1) who have disseminated nontuberculous mycobacterial infections. The immunologic sequelae of IFN-gamma R1 deficiency were characterized in 2 unrelated patients from the Indian subcontinent with novel homozygous recessive IFN-gamma R1 mutations. In vitro, these patients' peripheral blood mononuclear cells produced 10% of normal IFN-gamma and interleukin-12 (IL-12) in response to phytohemagglutinin (PHA) but normal amounts of IFN-gamma in response to PHA plus IL-12. Tumor necrosis factor-alpha (TNF-alpha) production was normal in response to endotoxin and to PHA but was not augmented by the addition of IFN-gamma, An abnormal phenotype was not found in heterozygous patient relatives. These patients demonstrate the critical role that the IFN-gamma receptor plays in the regulation of IFN-gamma, IL-12, and TNF-alpha. C1 NIAID, Host Def Lab, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Clin Immunol Lab, Bethesda, MD 20892 USA. New York Hosp, Div Pediat Infect Dis, New York, NY USA. Vest Agder Hosp, Kristiansand, Norway. RP Holland, SM (reprint author), NIAID, Host Def Lab, Bldg 10-11N103,10 Ctr Dr MSC 1886, Bethesda, MD 20892 USA. EM smh@nih.gov NR 40 TC 111 Z9 113 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1998 VL 178 IS 4 BP 1095 EP 1104 DI 10.1086/515670 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 125QF UT WOS:000076248000024 PM 9806040 ER PT J AU Cooper, PJ Espinel, I Paredes, W Guderian, RH Nutman, TB AF Cooper, PJ Espinel, I Paredes, W Guderian, RH Nutman, TB TI Impaired tetanus-specific cellular and humoral responses following tetanus vaccination in human onchocerciasis: A possible role for interleukin-10 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-RESPONSES; T-CELL; LYMPHATIC FILARIASIS; SCHISTOSOMA-MANSONI; CYTOKINE PRODUCTION; VOLVULUS INFECTION; ANTIGEN; IL-10; RESPONSIVENESS; SUPPRESSION AB Onchocerca volvulus infection has been associated with impaired cellular responses to parasite antigens, an impairment that may also extend to nonparasite antigens, To investigate the mechanism of this impaired immune response, the effect of concurrent O. volvulus infection on the immune response to tetanus toroid (TT) following tetanus vaccination was studied. The proliferative, cytokine, and antibody response to TT of O. volvulus-infected subjects (n = 19) and comparable noninfected controls (n = 20) were studied before and 6 months after vaccination with TT. Following vaccination, antibody levels, proliferative responses, and levels of interferon-gamma were significantly greater in noninfected subjects (P < .05, .001, and .05, respectively); however, infected subjects produced interleukin-10, but noninfected controls did not (P = .001). These studies indicate that concurrent infection with O. volvulus can diminish the immune response to an unrelated antigen (TT) by a mechanism that is likely to involve interleukin-10. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Hosp Vozandes, Dept Clin Invest, Quito, Ecuador. RP Cooper, PJ (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 42 TC 121 Z9 122 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1998 VL 178 IS 4 BP 1133 EP 1138 DI 10.1086/515661 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 125QF UT WOS:000076248000029 PM 9806045 ER PT J AU Bartlett, JA Berend, C Petroni, GR Ottinger, J Tyler, DL Pettinelli, C Weinhold, KJ AF Bartlett, JA Berend, C Petroni, GR Ottinger, J Tyler, DL Pettinelli, C Weinhold, KJ TI Coadministration of zidovudine and interleukin-2 increases absolute CD4 cells in subjects with waiter reed stage 2 human immunodeficiency virus infection: Results of ACTG protocol 042 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID GLYCOL-MODIFIED INTERLEUKIN-2; TYPE-1 INFECTION; RECOMBINANT INTERLEUKIN-2; PHASE-I; LYMPHOCYTES; EFFICACY; THERAPY AB Interleukin-2 (IL-2) can increase numbers of absolute CD4 cells in persons infected with the human immunodeficiency virus who are receiving antiretroviral therapy. Twenty-five subjects with >400/mm(3) absolute CD4 cells received zidovudine and low-dose intravenous or subcutaneous IL-2 (less than or equal to 10(6) U/m(2)). Absolute CD4 cells increased significantly during IL-2 treatment, and 56% of the subjects achieved a maximal increase of greater than or equal to 500 cells/mm(3). A dose-response relationship favored increasing IL-2 doses, and subcutaneous delivery offered greater increases than intravenous administration. Fifteen subjects had persistent increases of greater than or equal to 100 cells/mm(3) 6 weeks after IL-2 was discontinued. No changes occurred in delayed-type hypersensitivity or helper T cell responses to recall antigens, Cell-mediated cytotoxicities increased against Daudi cells. IL-2 was well tolerated and only 1 subject required dose reduction. Relatively low-dose IL-2 delivered by subcutaneous or intravenous routes may provide an important complement to antiretroviral therapy to Increase absolute CD4 cells with the potential for less toxicity than with higher IL-2 doses. C1 Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Canc Ctr Biostat, Durham, NC 27710 USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. RP Bartlett, JA (reprint author), Duke Univ, Med Ctr, Dept Med, Box 3238, Durham, NC 27710 USA. FU NCRR NIH HHS [RR-30-GCRC]; NIAID NIH HHS [AI-28662, AI-94028] NR 17 TC 11 Z9 11 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1998 VL 178 IS 4 BP 1170 EP 1173 DI 10.1086/515677 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 125QF UT WOS:000076248000037 PM 9806053 ER PT J AU Bukh, J Apgar, CL Engle, R Govindarajan, S Hegerich, PA Tellier, R Wong, DC Elkins, R Kew, MC AF Bukh, J Apgar, CL Engle, R Govindarajan, S Hegerich, PA Tellier, R Wong, DC Elkins, R Kew, MC TI Experimental infection of chimpanzees with hepatitis C virus of genotype 5a: Genetic analysis of the virus and generation of a standardized challenge pool SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th International Meeting on Hepatitis C Virus and Related Viruses CY MAR, 1997 CL KYOTO, JAPAN ID 5' NONCODING REGION; SEQUENCE-ANALYSIS; RNA; 3'-TERMINUS; GENOMES AB Six major genotypes (genotypes 1-6) of hepatitis C virus (HCV) have been identified. These genetic variants are being transmitted to chimpanzees, the only recognized animal model for the study of HCV. Genotype 5a (strain SA13), a variant found primarily in South Africa, has been transmitted to chimpanzees for the first time. Experimental infection of 2 chimpanzees was characterized by early appearance of viremia and peak virus titers of 10(5)-40(6) genome equivalents/mL, The HCV infection was resolved by week 15 after inoculation in 1 chimpanzee and persisted in the other. Both chimpanzees became anti-HCV-positive by week 14 after inoculation. Both chimpanzees developed viral hepatitis. The infectivity titer of a genotype 5a challenge pool prepared from the first passage of HCV in a chimpanzee was similar to 10(4) infectious doses/mL, Finally, sequence analysis of strain SA13 confirmed that genotype 5a is genetically distinct from other genotypes of HCV. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Expt Primate Virol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ So Calif, Rancho Los Amigos Med Ctr, Liver Res Lab, Downey, CA 90242 USA. Univ Witwatersrand, Dept Med, ZA-2001 Johannesburg, South Africa. RP Bukh, J (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 7,Room 201,7 Ctr Dr MSC 0740, Bethesda, MD 20892 USA. FU NCI NIH HHS [CO-56000]; NIAID NIH HHS [AI-45180, AI-52705] NR 17 TC 39 Z9 40 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT PY 1998 VL 178 IS 4 BP 1193 EP 1197 DI 10.1086/515683 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 125QF UT WOS:000076248000043 PM 9806059 ER PT J AU Hodapp, RM Fidler, DJ Smith, ACM AF Hodapp, RM Fidler, DJ Smith, ACM TI Stress and coping in families of children with Smith-Magenis syndrome SO JOURNAL OF INTELLECTUAL DISABILITY RESEARCH LA English DT Article DE Smith-Magenis syndrome; families; stress; coping; mental retardation ID PRADER-WILLI-SYNDROME; MENTAL-RETARDATION; DOWN-SYNDROME; MALADAPTIVE BEHAVIOR; PARENTAL STRESS; YOUNG-CHILDREN; SHORT-FORM; DISABILITIES; QUESTIONNAIRE; PERCEPTIONS AB To describe stress and coping in families of children with Smith-Magenis syndrome, the present authors interviewed and received questionnaires from families of 36 children with this disorder. For measures of total stress, and of parent and family problems, the best predictors were the family's number of friends and the child's degree of impairment on the Vineland socialization domain; the single best predictor of parental pessimism was the child's degree of maladaptive behaviour. Although the stress levels of the families of children with Smith-Magenis syndrome are comparable to the levels shown by the families of children with Prader-Willi and 5p- syndromes, these levels are much higher than the stress levels reported by families of children with mixed or non-specific developmental disabilities, Stress levels may be similar across aetiologies involving high levels of maladaptive behaviour, but the correlates of family stress-particularly the moderating role of family friends-seem specific to Smith-Magenis syndrome. C1 Univ Calif Los Angeles, Grad Sch Educ & Informat Studies, Los Angeles, CA 90095 USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. RP Hodapp, RM (reprint author), Univ Calif Los Angeles, Grad Sch Educ & Informat Studies, 405 Hilgard Ave, Los Angeles, CA 90095 USA. NR 42 TC 59 Z9 59 U1 0 U2 5 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0964-2633 J9 J INTELL DISABIL RES JI J. Intell. Disabil. Res. PD OCT PY 1998 VL 42 BP 331 EP 340 DI 10.1046/j.1365-2788.1998.00148.x PN 5 PG 10 WC Education, Special; Genetics & Heredity; Clinical Neurology; Psychiatry; Rehabilitation SC Education & Educational Research; Genetics & Heredity; Neurosciences & Neurology; Psychiatry; Rehabilitation GA 155KB UT WOS:000077944800001 PM 9828063 ER PT J AU Nanney, LB Skeel, A Luan, J Polis, S Richmond, A Wang, MH Leonard, EJ AF Nanney, LB Skeel, A Luan, J Polis, S Richmond, A Wang, MH Leonard, EJ TI Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Society-for-Investigative-Dermatology CY APR 23-27, 1997 CL WASHINGTON, D.C. SP Soc Invest Dermatol DE enzyme activation; keratinocytes; receptor tyrosine kinase; wound ID EPIDERMAL GROWTH-FACTOR; SKIN EPITHELIAL-CELLS; TYROSINE KINASE; MESSENGER-RNAS; WOUND REPAIR; HUMAN-SERUM; EXPRESSION; FAMILY; MSP; DIFFERENTIATION AB Macrophage stimulating protein (MSP) exists in blood as inactive pro-MSP. Cleavage yields active MSP, the ligand for a membrane receptor (RON) that is expressed on keratinocytes as well as macrophages, Because both cells have roles in tissue injury, we looked for active MSP and expressed RON in wounds. Concentration of pro-MSP + MSP in wound exudates was in the range for optimal activity. Western blot showed that MSP comprised about half the total, in contrast to less than 10% of the total in blood plasma. The presence of MSP was attributed to an exudate pro-MSP convertase that had an inhibitor profile consistent with a trypsin-like serine protease. Exudate evoked morphologic changes in macrophages in vitro like that of MSP. Removal of this activity by an anti-MSP column shows that exudate stimulation of macrophages is due to MSP. RON was infrequently detected in normal skin. RON protein was markedly upregulated in burn wound epidermis and accessory structures, in proliferating cells or differentiated cells, or both. RON was also detected on macrophages and capillaries. Tissue injury leads to cleavage of pro-MSP to MSP, which has potential to act on keratinocytes, macrophages, and capillaries, all components of the wound healing response. C1 Vanderbilt Univ, Sch Med, Dept Plast Surg, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Cell Biol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Med Dermatol, Nashville, TN 37232 USA. Dept Vet Affairs, Nashville, TN USA. NCI, Immunobiol Lab, Immunopathol Sect, Frederick, MD 21701 USA. RP Nanney, LB (reprint author), Vanderbilt Univ, Sch Med, Dept Plast Surg, S-2221,Med Ctr N, Nashville, TN 37232 USA. RI Richmond, Ann/A-3048-2014 FU NCI NIH HHS [CA56704]; NIAMS NIH HHS [P30 AR 41943]; NIGMS NIH HHS [GM 40437] NR 32 TC 47 Z9 49 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1998 VL 111 IS 4 BP 573 EP 581 DI 10.1046/j.1523-1747.1998.00332.x PG 9 WC Dermatology SC Dermatology GA 123XE UT WOS:000076150300005 PM 9764835 ER PT J AU Hengge, UR Pfutzner, W Williams, M Goos, M Vogel, JC AF Hengge, UR Pfutzner, W Williams, M Goos, M Vogel, JC TI Efficient expression of naked plasmid DNA in mucosal epithelium: Prospective for the treatment of skin lesions SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE gene therapy; mucosa; wart ID INJECTION; THERAPY; CELLS AB Mucocutaneous gene therapy offers exciting new treatment modalities for skin lesions. Transient expression of naked plasmid DNA could be used as a local treatment of various skin lesions where the corresponding gene product (protein) has therapeutic or immunization potential. We analyzed the time course, magnitude, and histologic expression of the indicator plasmid DNA (pCMV:beta-Gal) in mucosal epithelium and papilloma lesions. Upon direct injection of naked plasmid DNA (20 mu g) into oral mucosa, expression occurred at high local concentrations, up to 35-fold higher than in comparable injections into the epidermis, Due to the accelerated turnover of mucosal epithelium beta-galactosidase positive epithelial cells were detected in the basal and suprabasal layers as early as 3 h after injection, whereas only the most superficial mucosal layers demonstrated beta-galactosidase staining at 24 h post-injection. These biologic characteristics need to be taken into consideration when clinical applications of expressing naked plasmid DNA in epithelial tissues are considered. C1 Univ Essen Gesamthsch, Dept Dermatol & Venerol, D-45122 Essen, Germany. NIH, Vet Resources Program, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. RP Hengge, UR (reprint author), Univ Essen Gesamthsch, Dept Dermatol & Venerol, Hufelandstr 55, D-45122 Essen, Germany. NR 15 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD OCT PY 1998 VL 111 IS 4 BP 605 EP 608 DI 10.1046/j.1523-1747.1998.00353.x PG 4 WC Dermatology SC Dermatology GA 123XE UT WOS:000076150300010 PM 9764840 ER PT J AU Williams, SB Sano, M Smith, N Horne, M Yarchoan, R Wyvill, K Zeichner, S Taylor, P Knudson, T Gralnick, HR AF Williams, SB Sano, M Smith, N Horne, M Yarchoan, R Wyvill, K Zeichner, S Taylor, P Knudson, T Gralnick, HR TI Glycocalicin levels in the plasma of HIV+ patients: An indicator of platelet turnover SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; THROMBOCYTOPENIA AB Glycocalicin (GC) is the carbohydrate-rich portion of platelet membrane glycoprotein Ib alpha that can be cleaved from circulating platelets by proteases. The plasma GC level is an indicator of platelet turnover, Using an ELISA for GC, we assayed the plasma of 20 normal children (age 6 to 13 years), 50 HIV+ children (ages 4 to 18 years), 32 normal adults (ages 21 to 53 years), and 50 HIV+ adults (ages 24 to 66 years). The results were adjusted for individual platelet counts to give GC indexes (GCI). The normal children and the normal adults had significantly different GCI distributions (P = .002). In both normal and HIV+ individuals the GCI decreased with increasing platelet count (-.73 < r < -.34). Twenty-eight percent of the HIV+ children and 28% of the HIV+ adults had elevated GCI values, The majority of these elevated values occurred in patients with platelet counts >100,000/mu L. Neither the GCI nor the platelet count was correlated with viral load, The platelet count, however, was weakly correlated with the CD4 count in both children (r = .31) and adults (r = .30) infected with HIV. Also, the CD4 count was weakly and inversely correlated with GCI in HIV+ adults (r = -.34) and in children (r = -.24). We conclude that increased GCI and, by implication, increased platelet turnover is a relatively common feature of advanced HIV disease. Furthermore, GCI may be elevated in HIV+ patients even with a platelet count >100,000/mu L, suggesting increased platelet turnover before thrombocytopenia develops. C1 NCI, Dept Clin Pathol, Warren G Magnuson Clin Ctr, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Gralnick, HR (reprint author), NCI, Dept Clin Pathol, Warren G Magnuson Clin Ctr, NIH, Room 2C390,Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD OCT PY 1998 VL 132 IS 4 BP 303 EP 307 DI 10.1016/S0022-2143(98)90043-9 PG 5 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 130TN UT WOS:000076536600010 PM 9794701 ER PT J AU McKinney, LC Aquilla, EM Coffin, D Wink, DA Vodovotz, Y AF McKinney, LC Aquilla, EM Coffin, D Wink, DA Vodovotz, Y TI Ionizing radiation potentiates the induction of nitric oxide synthase by IFN-gamma and/or LPS in murine macrophage cell lines: role of TNF-alpha SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE monocytes/macrophages; cytokines; cellular activation ID IN-VITRO; PERITONEAL-MACROPHAGES; NO PRODUCTION; TUMOR; IRRADIATION; EXPOSURE; PROTEIN; RELEASE; MICE; CYTOTOXICITY AB Macrophages are activated to become cytotoxic by a highly coordinated set of cytokine signals. Ionizing radiation can mimic cytokine signals and lead to enhanced states of activation. We tested the ability of gamma-radiation, alone and,crith interferon-gamma (IFN-gamma) and/or lipopolysaccharide (LPS), to induce nitric oxide (NO) production in J774.1 and RAW264.7 murine macrophages, NO Tvas induced weakly, moderately, or strongly by IFN-gamma alone, LPS alone, or IFN-gamma + LPS, respectively. Radiation alone (0.5-50 Gy) did not induce NO, but enhanced NO production in a dose-dependent manner (0.5-5 Gy) when cells were exposed to IFN-gamma or LPS 24 h post-irradiation, Immunoblots showed parallel induction of nitric oxide synthase (NOS2), Application of anti-turner necrosis factor alpha (TNF-alpha) antibody before irradiation blocked induction of NO by IFN-gamma. We conclude (1) that irradiated cells produce more NO in response to either IFN-gamma or LPS and (2) that the increase is mediated by induction of TNF-alpha. C1 Armed Forces Radiobiol Res Inst, Dept Radiat Pathophysiol & Toxicol, Bethesda, MD 20814 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. RP McKinney, LC (reprint author), Armed Forces Radiobiol Res Inst, Dept Radiat Pathophysiol & Toxicol, Bethesda, MD 20814 USA. EM mckinney@mx.afrri.usuh.mil NR 39 TC 33 Z9 39 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 1998 VL 64 IS 4 BP 459 EP 466 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 126DU UT WOS:000076278300006 PM 9766626 ER PT J AU Van Dervort, AL Lam, C Culpepper, S Tuschil, AF Wesley, RA Danner, RL AF Van Dervort, AL Lam, C Culpepper, S Tuschil, AF Wesley, RA Danner, RL TI Interleukin-8 priming of human neutrophils is not associated with persistently altered calcium fluxes but is additive with lipopolysaccharide SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE cytokines; tumor necrosis factor; hydrogen peroxide; respiratory burst; superoxide ID TUMOR-NECROSIS-FACTOR; METHIONYL-LEUCYL-PHENYLALANINE; FACTOR-ALPHA; RESPIRATORY BURST; SUPEROXIDE ANION; ACTIVATING-FACTOR; ENHANCED RELEASE; OXIDATIVE BURST; G-PROTEINS; LEUKOTRIENE-B4 AB Interleukin-8 (IL-8) priming was studied in neutrophils to examine its dependency on altered calcium fluxes and for similarity to Lipopolysaccharide (LPS), IL-8 caused a rapid rise in [Ca2+](i) that returned to baseline values by 20 min, Peak [Ca2+](i) transients in response to N-formyl-methionyl-leucyl-phenylalanine (fMLP) were unaltered in IL-8-primed compared with unprimed cells, In comparison to LPS and tumor necrosis factor (TNF), IL-8 was a much weaker priming agent as measured by either O-2(-) or H2O2 production, Despite their large disparity in potency, IL-8 and LPS priming were additive using fMLP, a receptor-dependent stimulator,; and synergistic using the post-receptor, protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) to trigger the respiratory burst, In contrast, IL-8 and TNF priming were synergistic for fMLP (P = 0.05), but completely nonadditive when PMA was used as the neutrophil stimulant (P = 0.05 for subadditivity). Thus, lasting alterations in [Ca2+](i) are not a necessary characteristic of IL-8-primed cells. IL-8 and LPS appear to prime by non-overlapping pathways, whereas IL-8 and TNF appear to share mechanisms distal to protein kinase C activation. IL-8 and LPS may independently contribute to neutrophil-mediated host defense or injury by priming through distinct pathways. C1 NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Sandoz Forsch Inst, Vienna, Austria. RP Danner, RL (reprint author), NIH, Dept Crit Care Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Room 7D43, Bethesda, MD 20892 USA. NR 35 TC 12 Z9 12 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD OCT PY 1998 VL 64 IS 4 BP 511 EP 518 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 126DU UT WOS:000076278300012 PM 9766632 ER PT J AU Ottiger, M Delaglio, F Marquardt, JL Tjandra, N Bax, A AF Ottiger, M Delaglio, F Marquardt, JL Tjandra, N Bax, A TI Measurement of dipolar couplings for methylene and methyl sites in weakly oriented macromolecules and their use in structure determination SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article; Proceedings Paper CT Wallace Brey Symposium CY NOV 02, 1997 CL GAINESVILLE, FLORIDA DE dipolar couplings; molecular alignment; liquid crystal; protein; structure determination; sidechain dynamics; ubiquitin ID MAGNETIC-FIELD DEPENDENCE; LIQUID-CRYSTALLINE MEDIUM; HUMAN UBIQUITIN; NMR-SPECTRA; RESOLUTION; ANISOTROPY; PROTEINS AB A simple and effective method is described for simultaneously measuring dipolar couplings for methine, methylene, and methyl groups in weakly oriented macromolecules. The method is a J-modulated 3D version of the well-known [H-1-C-13] CT-HSQC experiment, from which the J and dipolar information are most accurately extracted by using time-domain fitting in the third, constant-time dimension. For CH2-sites, the method generally yields only the sum of the two individual C-13-H-1 couplings. Structure calculations are carried out by minimizing the deviation between the measured sum, and the sum predicted for each methylene on the basis of the structure. For rapidly spinning methyl groups the dipolar contribution to the splitting of the outer C-13 quartet components can be used directly to constrain the orientation of the C-CH3 bond. Measured sidechain dipolar couplings are in good agreement with an ensemble of NMR structures calculated without use of these couplings. (C) 1998 Academic Press. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NCI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Ottiger, M (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. NR 22 TC 104 Z9 106 U1 0 U2 13 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD OCT PY 1998 VL 134 IS 2 BP 365 EP 369 DI 10.1006/jmre.1998.1546 PG 5 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 132NE UT WOS:000076635800019 PM 9761712 ER PT J AU Sharan, SK Bradley, A AF Sharan, SK Bradley, A TI Functional characterization of BRCA1 and BRCA2: Clues from their interacting proteins SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE BRCA1; BRCA2; Rad51; BARD1; importin-alpha; interacting proteins ID CANCER SUSCEPTIBILITY GENE; EMBRYONIC CELLULAR PROLIFERATION; OVARIAN-CANCER; BREAST-CANCER; RAD51 PROTEIN; TRANSCRIPTIONAL ACTIVATION; STRAND EXCHANGE; DNA-DAMAGE; NUCLEAR PHOSPHOPROTEIN; EXPRESSION PATTERN AB The familial breast and ovarian cancer susceptibility genes, BRCA1 and BRCA2 have been the subject of extensive functional analysis studies since their cloning. Clues to their biological role in maintaining the genomic integrity were provided by studies that revealed their interaction with the recombination repair protein HsRad51. The first clue of an interaction between HsRad51 and BRCA1 came from the colocalization of the characteristic nuclear foci formed by these two proteins during S phase of the cell cycle. An interaction between murine Brca2 and MmRad51 was detected by the yeast two hybrid system. Utilizing the yeast two hybrid system and other techniques several other Brca1 and Brca2 interacting proteins have been identified like, BARD1, importin-alpha, BIPs, RNA polymerase II holoenzyme, BRAP2 etc. Recently, mutations suggesting a role as a tumor suppressor have been identified in the BARD1 gene in primary human tumors. The identification of molecules that interact with Brca1 and Brca2 has greatly enhanced our knowledge of how BRCA1 and BRCA2 may function as tumor suppressors. C1 Baylor Coll Med, Howard Hughes Med Inst, Dept Mol & Human Genet, Houston, TX 77030 USA. NCI, Mammalian Genet Lab, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Bradley, A (reprint author), Baylor Coll Med, Howard Hughes Med Inst, Dept Mol & Human Genet, 1 Baylor Plaza, Houston, TX 77030 USA. EM abradley@bcm.tmc.edu NR 75 TC 7 Z9 7 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD OCT PY 1998 VL 3 IS 4 BP 413 EP 421 DI 10.1023/A:1018788132560 PG 9 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 141MW UT WOS:000077148600006 PM 10819535 ER PT J AU Feng, YR Norwood, D Shibata, R Gee, D Xiao, X Martin, M Zeichner, SL Dimitrov, DS AF Feng, YR Norwood, D Shibata, R Gee, D Xiao, X Martin, M Zeichner, SL Dimitrov, DS TI Telomere dynamics in HIV-1 infected and uninfected chimpanzees measured by an improved method based on high-resolution two-dimensional calibration of DNA sizes SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Article DE telomeres; chimpanzees; HIV ID IMMUNODEFICIENCY-VIRUS TYPE-1; HUMAN FIBROBLASTS; LENGTH; CD4(+); LYMPHOCYTES; TURNOVER; CD8(+); CELLS AB We developed an improved method for accurately measuring telomere lengths based on two-dimensional calibration of DNA sizes combined with pulsed field electrophoresis and quantitative analysis of high-resolution gel images. This method was used to quantify the length of telomeres in longitudinal samples of peripheral blood mononuclear cells (PBMCs) from five chimpanzees infected with human immunodeficiency virus type 1 (HIV-1) and three uninfected animals, 14 to 27 years of age. The average length of the telomere restriction fragments (TRF) of infected and uninfected chimpanzees were 11.7 +/- 0.25 kbp, and 11.6 +/- 0.61 kbp, respectively, and were about 1 kbp and 3 kbp longer than those of human infants and 30 year old adults, respectively. There was a trend of a slight decrease (30-60 bp per year) in the TRF of two HIV infected chimpanzees over 30-35 months, while the TRF of,ne naive chimpanzee slightly increased over 20 months. Although the number of chimpanzees in this study is small and no statistically significant Linear dependencies on time were observed, it appears that in chimpanzees, rates of shortening of the TRF are comparable or smaller than in adult humans and are not significantly affected by HIV-I infection, which may be related to the inability of HIV-1 to cause disease in these animals. C1 NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. Maxygen, Santa Clara, CA USA. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancies Branch, NIH, Bethesda, MD 20892 USA. RP Norwood, D (reprint author), NCI, Frederick Canc Res & Dev Ctr, Lab Expt & Computat Biol, NIH, Bldg 469,Room 216,Miller Dr, Frederick, MD 21702 USA. NR 18 TC 7 Z9 7 U1 1 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD OCT PY 1998 VL 27 IS 5 BP 258 EP 265 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 158KZ UT WOS:000078115800006 PM 9926982 ER PT J AU Rosen, VM Engle, RW AF Rosen, VM Engle, RW TI Working memory capacity and suppression SO JOURNAL OF MEMORY AND LANGUAGE LA English DT Article ID FRONTAL-LOBE DAMAGE; INDIVIDUAL-DIFFERENCES; PROACTIVE-INTERFERENCE; SELECTIVE ATTENTION; INHIBITION; RETRIEVAL; SUSCEPTIBILITY; COMPREHENSION; INTELLIGENCE; MECHANISM AB Two experiments examined whether a relationship exists between an individual's working memory capacity and their ability to suppress intrusive thoughts and behaviors. In both experiments, participants learned three lists in a modified paired-associates task where the interference condition followed an AB-AC-AB design and the noninterference condition an EF-DC-AB design. Experiment 1 stressed speed, and individuals who scored high on a measure of working memory capacity (high spans) produced fewer first-list intrusions during second-list learning than did low spans. Experiment 2 stressed accuracy, and high spans in the interference condition were slower than their control to retrieve first-list responses on List 3, suggesting that they had suppressed them during second-list learning. In contrast, the low spans in the interference condition were faster than their control. The findings suggested that a relationship exists between an individual's working memory capacity and their ability to suppress intrusive thoughts and behaviors. (C) 1998 Academic Press. C1 NIMH, Bethesda, MD 20892 USA. Georgia Inst Technol, Sch Psychol, Atlanta, GA 30332 USA. RP Rosen, VM (reprint author), NIMH, Fed Bldg,Rm B1A-14,7550 Wisconsin Ave, Bethesda, MD 20892 USA. RI Engle, Randall/B-5031-2008 OI Engle, Randall/0000-0003-0816-7406 NR 50 TC 171 Z9 177 U1 6 U2 24 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0749-596X J9 J MEM LANG JI J. Mem. Lang. PD OCT PY 1998 VL 39 IS 3 BP 418 EP 436 DI 10.1006/jmla.1998.2590 PG 19 WC Linguistics; Psychology; Psychology, Experimental SC Linguistics; Psychology GA 121JM UT WOS:000076010300006 ER PT J AU McKee, TC Covington, CD Fuller, RW Bokesch, HR Young, S Cardellina, JH Kadushin, MR Soejarto, DD Stevens, PF Cragg, GM Boyd, MR AF McKee, TC Covington, CD Fuller, RW Bokesch, HR Young, S Cardellina, JH Kadushin, MR Soejarto, DD Stevens, PF Cragg, GM Boyd, MR TI Pyranocoumarins from tropical species of the genus Calophyllum: A chemotaxonomic study of extracts in the National Cancer Institute collection SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; INHIBITORY NATURAL-PRODUCTS; ANTI-HIV EVALUATION; RAIN-FOREST TREE; REVERSE-TRANSCRIPTASE; TEYSMANNII; COUMARINS; LANIGERUM; CALABA AB (+)-Calanolide A, a novel dipyranocoumarin from the Malesian tree Calophyllum lanigerum var. austrocoriaceum, and a closely related compound, (-)-calanolide B, isolated from Calophyllum teysmannii var. inophylloide, are representatives of a distinct class of nonnucleoside HIV-1 specific reverse-transcriptase inhibitor under development as an AIDS chemotherapeutic. NCI repository specimens totalling 315 organic extracts from 31 taxa of Calophyllum were analyzed for related pyranocoumarins using a simple TLC system. A total of 127 extracts was initially classified as "positive"; eight out of the 31 taxa examined, representing perhaps 28 species already described (1/7-1/8 of all the species in this genus), contained prenylated coumarins, suggesting that these compounds, while sometimes abundantly present, are not widespread in the genus. Representative members of the TLC-positive extracts were partitioned between CH2Cl2 and 25% aqueous MeOH; the CH2Cl2-soluble materials were then analyzed by TLC and H-1 NMR to confirm the presence of pyranocoumarins. The anti-HIV activity of the partitioned extracts are also presented. This study suggested that there are several distinctive coumarin chemotaxonomic markers distinguishing species of this genus. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment Diagnosis, Frederick, MD 21702 USA. RP Boyd, MR (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program, Div Canc Treatment Diagnosis, Bldg 1052,Room 121, Frederick, MD 21702 USA. NR 32 TC 72 Z9 81 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD OCT PY 1998 VL 61 IS 10 BP 1252 EP 1256 DI 10.1021/np980140a PG 5 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 133HU UT WOS:000076681800015 PM 9784162 ER PT J AU Brebion, G Smith, MJ Amador, X Malaspina, D Gorman, JM AF Brebion, G Smith, MJ Amador, X Malaspina, D Gorman, JM TI Word recognition, discrimination accuracy, and decision bias in schizophrenia: Association with positive symptomatology and depressive symptomatology SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID SIGNAL-DETECTION ANALYSIS; AUDITORY HALLUCINATIONS; RESPONSE BIAS; MEMORY; REALITY; DYSFUNCTION; PERFORMANCE; DISORDERS; SEVERITY; SYMPTOMS AB The purpose of this experiment was to replicate and Extend to a memory task Bentall and Slade's (1985) finding that hallucinations in schizophrenic patients were linked to a liberal decision bias. A word recognition task was administered to 40 schizophrenic patients and 40 normal controls that yielded two indices of performance: an index of discrimination accuracy (Pr) and one of decision bias (Br). Patients obtained a lower Pr than controls, whereas Pr was similar in both groups. In patients, Pr was selectively correlated with positive symptomatology: the more the positive symptoms, the more liberal the bias. In particular, there was a specific correlation between decision bias and hallucinations. Conversely, Pr was inversely correlated with severity of depression, but not with either positive or negative symptoms. Thus, positive symptomatology may be linked more to difficulties in distinguishing between representations of internal versus external events than to deficits in encoding external events. C1 Inst Psychiat, Dept Psychol Med, London SE5 8AF, England. New York State Psychiat Inst, Schizophrenia Res Unit, Dept Clin Psychobiol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. RP Brebion, G (reprint author), Inst Psychiat, Dept Psychol Med, 103 Denmark Hill, London SE5 8AF, England. FU NIMH NIH HHS [5P20 MH50727] NR 40 TC 37 Z9 37 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 1998 VL 186 IS 10 BP 604 EP 609 DI 10.1097/00005053-199810000-00003 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 127JQ UT WOS:000076347800003 PM 9788636 ER PT J AU Rall, JE AF Rall, JE TI The truth of science: Physical theories and reality. SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Book Review C1 NIH, Bethesda, MD 20892 USA. RP Rall, JE (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD OCT PY 1998 VL 186 IS 10 BP 653 EP 654 DI 10.1097/00005053-199810000-00012 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 127JQ UT WOS:000076347800012 ER PT J AU O'Donovan, MJ Wenner, P AF O'Donovan, MJ Wenner, P TI Mechanisms of spontaneous activity in developing spinal networks SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE spinal networks; self-organization; population behavior; synaptic depression ID ACTIVITY-DEPENDENT DEVELOPMENT; CHICK-EMBRYO; NEURAL ACTIVITY; MOTOR-ACTIVITY; CELL-DEATH; NEURONAL DIFFERENTIATION; LUMBOSACRAL MOTONEURONS; ACTIVATION PATTERNS; SYNAPTIC DEPRESSION; ELECTRICAL-ACTIVITY AB Developing networks of the chick spinal cord become spontaneously active early in development and remain so until hatching. Experiments using an isolated preparation of the spinal cord have begun to reveal the mechanisms responsible for this activity. Whole-cell and optical recordings have shown that spinal neurons receive a rhythmic, depolarizing synaptic drive and experience rhythmic elevations of intracellular calcium during spontaneous episodes. Activity is expressed throughout the neuraxis and can be produced by different parts of the cord and by the isolated brain stem, suggesting that it does not depend upon the details of network architecture. Two factors appear to be particularly important for the production of endogenous activity. The first is the predominantly excitatory nature of developing synaptic connections, and the second is the presence of prolonged activity-dependent depression of network excitability. The interaction between high excitability and depression results in an equilibrium in which episodes are expressed periodically by the network. The mechanism of the rhythmic bursting within an episode is not understood, but it may be due to a "fast" form of network depression. Spontaneous embryonic activity has been shown to play a role in neuron and muscle development, but is probably not involved in the initial formation of connections between spinal neurons. It may be important in refining the initial connections, but this possibility remains to be explored. (C) 1998 John Wiley & Sons, Inc.*. C1 Natl Inst Neurol Disorders & Stroke, Sect Dev Neurobiol, Neural Control Lab, NIH, Bethesda, MD 20892 USA. RP O'Donovan, MJ (reprint author), Natl Inst Neurol Disorders & Stroke, Sect Dev Neurobiol, Neural Control Lab, NIH, Bldg 49,Rm 3A50, Bethesda, MD 20892 USA. OI Wenner, Peter/0000-0002-7072-2194 NR 73 TC 75 Z9 76 U1 0 U2 5 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD OCT PY 1998 VL 37 IS 1 BP 131 EP 145 DI 10.1002/(SICI)1097-4695(199810)37:1<131::AID-NEU10>3.0.CO;2-H PG 15 WC Neurosciences SC Neurosciences & Neurology GA 124ET UT WOS:000076169100010 PM 9777737 ER PT J AU Fields, RD AF Fields, RD TI Effects of ion channel activity on development of dorsal root ganglion neurons SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE activity dependent development; calcium channel; growth cone; fasciculation; c-fos; myelination; synaptic plasticity; L1; NCAM; N-cadherin ID CELL-ADHESION MOLECULES; GROWTH CONE MOTILITY; ELECTRICAL-ACTIVITY; SYNAPTIC PLASTICITY; N-CADHERIN; GENE-EXPRESSION; NEURAL IMPULSES; INTRACELLULAR CALCIUM; FUNCTIONAL COMPONENTS; DEPENDENT REGULATION AB Studies of mouse dorsal root ganglion neurons in vitro demonstrate that ion channel function and regulation can influence a wide range of developmental processes. The work suggests that much as exposure to different trophic factors, the pattern of impulse activity a neuron experiences can have significant structural and functional effects during development, Studies concerning effects of ion channel activity on growth cone motility, axon fasciculation, synaptic plasticity, myelination, and intracellular signaling pathways regulating gene expression are presented in the context of changes in endogenous firing patterns during development. (C) 1998 John Wiley & Sons. Inc. C1 NICHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Fields, RD (reprint author), NICHD, Dev Neurobiol Lab, NIH, Bldg 49,Rm 5A38, Bethesda, MD 20892 USA. NR 88 TC 33 Z9 33 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD OCT PY 1998 VL 37 IS 1 BP 158 EP 170 DI 10.1002/(SICI)1097-4695(199810)37:1<158::AID-NEU12>3.0.CO;2-A PG 13 WC Neurosciences SC Neurosciences & Neurology GA 124ET UT WOS:000076169100012 PM 9777739 ER PT J AU Bruccoleri, A Brown, H Harry, GJ AF Bruccoleri, A Brown, H Harry, GJ TI Cellular localization and temporal elevation of tumor necrosis factor-alpha, interleukin-1 alpha, and transforming growth factor-beta 1 mRNA in hippocampal injury response induced by trimethyltin SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE tumor necrosis factor-alpha; interleukin-1 alpha; transforming growth factor-beta; microglia; trimethyltin; hippocampus ID CENTRAL-NERVOUS-SYSTEM; MESSENGER-RNA; RAT-BRAIN; KAINIC ACID; FACTOR-BETA; INDUCED NEURODEGENERATION; ANTIGEN EXPRESSION; MICROGLIAL CELLS; NITRIC-OXIDE; TGF-BETA AB In certain pathologic states, cytokine production may become spatially and temporally dysregulated, leading to their inappropriate production and potentially detrimental consequences. Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-beta) mediate a range of host responses affecting multiple cell types. To study the role of cytokines in the early stages of brain injury, we examined alterations in the 17-day-old mouse hippocampus during trimethyltin-induced neurodegeneration characterized by neuronal necrosis, microglia activation in the dentate, and astrocyte reactivity throughout the hippocampus. By 24 h after dosing, elevations in mRNA levels for TNF-alpha, IL-1 alpha, IL-1 beta, and IL-6 mRNA were seen. TGF-1 beta mRNA was elevated at 72 h. In situ hybridization showed that TNF-alpha and IL-1 alpha were localized to the microglia, whereas TGF-PI was expressed predominantly in hippocampal pyramidal cells. Intercellular adhesion molecule-1, EB-22, Mac-1, and glial fibrillary acidic protein mRNA levels were elevated within the first 3 days of exposure in the absence of increased inducible nitric oxide synthetase and interferon-gamma mRNA. These data suggest that pro-inflammatory cytokines contribute to the progression and pattern of neuronal degeneration in the hippocampus. C1 NIEHS, Lab Neurotoxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Harry, GJ (reprint author), NIEHS, Lab Neurotoxicol, NIH, MD C1-04,POB 12233, Res Triangle Pk, NC 27709 USA. NR 54 TC 68 Z9 68 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1998 VL 71 IS 4 BP 1577 EP 1587 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 120MJ UT WOS:000075959900028 PM 9751191 ER PT J AU Wang, GA Coon, SL Kaufman, S AF Wang, GA Coon, SL Kaufman, S TI Alternative splicing at the 3 '-cDNA of human tryptophan hydroxylase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Tryptophan hydroxylase; serotonin; human brain; alternative splicing; regulation ID AMINO-ACID HYDROXYLASES; CDNA; IDENTIFICATION; LOCALIZATION; EXPRESSION; SEQUENCE; CLONING; NEURONS; RABBIT; SITE AB Two alternatively spliced transcripts of human tryptophan hydroxylase (TPH) were identified that differed at the 3' end of the open reading frame. Comparison of the human TPH cDNA and genomic sequences revealed that an intron containing an in-frame stop codon could be alternatively spliced out of intron 11. This splicing would give rise to two human TPH isoforms with different C termini; the one that derives fl om the nonspliced intron contains a putative cyclic AMP-dependent protein kinase site, whereas the other one, which is 22 amino acids longer, does not. Analysis of various human tissues by RT-PCR revealed that the spliced TPH mRNA species was detected in all the postmortem tissues we tested, but the nonspliced species was expressed in only some tissues. C1 NIMH, Neurochem Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. RP Kaufman, S (reprint author), NIMH, Neurochem Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 22 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 1998 VL 71 IS 4 BP 1769 EP 1772 PG 4 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 120MJ UT WOS:000075959900051 PM 9751214 ER PT J AU Lane, NJ Balbo, A Fukuyama, R Rapoport, SI Galdzicki, Z AF Lane, NJ Balbo, A Fukuyama, R Rapoport, SI Galdzicki, Z TI The ultrastructural effects of beta-amyloid peptide on cultured PC12 cells: changes in cytoplasmic and intramembranous features. SO JOURNAL OF NEUROCYTOLOGY LA English DT Article ID ALZHEIMERS-DISEASE; CHOLINERGIC NEURONS; POSSIBLE MECHANISM; CALCIUM; MEMBRANES; APOPTOSIS; ACETYLCHOLINE; NEUROTOXICITY; CONDUCTANCE; RECEPTORS AB The fine structural features of cultured PC12 cells were investigated after treatment for 1, 3, or 5 days with different concentrations of the vascular form of beta-amyloid 1-40 (beta-AP). PC12 cells treated with beta-AP showed time- and concentration-dependent lysosomal system activation and cell toxicity. We observed increases in the number and size of cytoplasmic lysosomes as indicated by increased acid phosphatase reactivity. Some lysosomes were in the form of multivesicular bodies or large residual bodies that appeared to arise by autophagia or by endocytotic uptake. Double-sided plasma membrane invaginations were observed to give rise to increasingly extensive intracytoplasmic vacuolization that was correlated with duration of beta-AP treatment. Freeze-fracture studies of the intramembranous particle (IMP) population in the plasma membrane P-face showed that both control and beta-AP treated cells had two major P-face IMP populations, small-diameter (4-8 nm) IMPs, and large-diameter (greater than or equal to 9nm) IMPs. The larger category of IMPs was found to possess a greater average diameter in the beta-AP treated cells than in the control cells. These IMPs could represent modifications to existing transmembranous receptors, channels, or transducing molecules by the beta-AP. These results demonstrate that beta-AP can induce time- and concentration-dependent ultrastructural changes in PC12 cell membranes. C1 Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England. NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Lane, NJ (reprint author), Univ Cambridge, Dept Zool, Downing St, Cambridge CB2 3EJ, England. FU Wellcome Trust NR 32 TC 12 Z9 13 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-4864 J9 J NEUROCYTOL JI J. Neurocytol. PD OCT PY 1998 VL 27 IS 10 BP 707 EP 718 DI 10.1023/A:1006976400227 PG 12 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 204DN UT WOS:000080747800001 PM 10640186 ER PT J AU Kaur, D Cruess, DF Potter, WZ AF Kaur, D Cruess, DF Potter, WZ TI Effect of IL-1 alpha on the release of norepinephrine in rat hypothalamus SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE hypothalamus; HPLC; norepinephrine; rat ID PLASMA-CORTICOSTERONE; INTERLEUKIN-1; BRAIN; MECHANISMS; ACTIVATION; PROSTAGLANDINS; CATECHOLAMINE; METABOLISM; CYTOKINES; ENDOTOXIN AB The increased release of norepinephrine (NE) in the brain as part of the 'acute phase response' has been postulated to result from a direct action of IL-I on the hypothalamus. To test whether the effects of IL-1 alpha were direct, we carried out in vivo experiments using microdialysis and measured NE release in the hypothalamus using high pressure Liquid chromatography (HPLC). Two groups of male Sprague Dawley rats were either injected intraperitoneally with 1 ml of IL-1 alpha (2 mu g/ml) or had IL-l alpha 2 mu l (100 ng/ml) infused directly into the medial hypothalamus. A significant increase in extracellular hypothalamic NE was observed in the animal group treated with IL-la intraperitoneally and not in the controls or the group treated with IL-la intracerebrally. One-way ANOVA showed a significant effect of drug and route of administration with the ip IL-la treated group, differing from all other groups (vehicle ip, IL-la ic, and vehicle ic). Therefore these findings suggest that some aspects of IL-1 alpha actions on the HPA may be indirect requiring other intermediate steps or mediators outside the central nervous system. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NIMH, Clin Pharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Div Publ Hlth & Biometr, Bethesda, MD 20892 USA. Div Elly Lilly, Indianapolis, IN 46285 USA. Lilly Corp Ctr, Indianapolis, IN 46285 USA. RP Kaur, D (reprint author), NIMH, Clin Pharmacol Sect, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. NR 39 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD OCT 1 PY 1998 VL 90 IS 2 BP 122 EP 127 DI 10.1016/S0165-5728(98)00062-9 PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 136JY UT WOS:000076856700002 PM 9817439 ER PT J AU Piccardo, P Dlouhy, SR Lievens, PMJ Young, K Thomas, DP Nochlin, D Dickson, DW Vinters, HV Zimmerman, TR Mackenzie, IRA Kish, SJ Ang, LC De Carli, C Pocchiari, M Brown, P Gibbs, CJ Gajdusek, DC Bugiani, O Ironside, J Tagliavini, F Ghetti, B AF Piccardo, P Dlouhy, SR Lievens, PMJ Young, K Thomas, DP Nochlin, D Dickson, DW Vinters, HV Zimmerman, TR Mackenzie, IRA Kish, SJ Ang, LC De Carli, C Pocchiari, M Brown, P Gibbs, CJ Gajdusek, DC Bugiani, O Ironside, J Tagliavini, F Ghetti, B TI Phenotypic variability of Gerstmann-Straussler-Scheinker disease is associated with prion protein heterogeneity SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Gerstmann-Strussler-Scheinker disease (GSS); immunoblot; prion protein (PrP); PrP gene (PRNP) ID CREUTZFELDT-JAKOB-DISEASE; TRANSMISSIBLE MINK ENCEPHALOPATHY; SPONGIFORM ENCEPHALOPATHY; NEUROFIBRILLARY TANGLES; AMYLOID PROTEIN; MOLECULAR-BASIS; PRP; MUTATION; INDIANA; FAMILY AB Gerstmann-Straussler-Scheinker disease (GSS), a cerebello-pyramidal syndrome associated with dementia and caused by mutations in the prion protein gene (PRNP), is phenotypically heterogeneous. The molecular mechanisms responsible for such heterogeneity are unknown. Since we hypothesize that prion protein (PrP) heterogeneity may be associated with clinico-pathologic heterogeneity, the aim of this study was to analyze PrP in several GSS variants. Among the pathologic phenotypes of GSS, we recognize those without and with marked spongiform degeneration. In the latter (i.e. a subset of GSS P102L patients) we observed 3 major proteinase-K resistant PrP (PrPres) isoforms of ca. 21-30 kDa, similar to those seen in Creutzfeldt-Jakob disease. In contrast, the 21-30 kDa isoforms were not prominent in GSS variants without spongiform changes, including GSS A117V, GSS D202N, GSS Q212P, GSS Q217R, and 2 cases of GSS P102L. This suggests that spongiform changes in GSS are related to the presence of high levels of these distinct 21-30 kDa isoforms. Variable amounts of smaller, distinct PrPres isoforms of ca. 7-15 kDa were seen in all GSS variants. This suggests that GSS is characterized by the presence PrP isoforms that can be partially cleaved to low molecular weight PrPres peptides. C1 Indiana Univ, Sch Med, Dept Pathol & Lab Med, Indianapolis, IN 46202 USA. Ist Neurol Carlo Besta, Milan, Italy. Vet Adm Med Ctr, Seattle, WA 98108 USA. Univ Washington, Sch Med, Seattle, WA USA. Mayo Clin, Jacksonville, FL 32224 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Los Angeles, CA USA. Vancouver Gen Hosp, Vancouver, BC, Canada. Clarke Inst Psychiat, Toronto, ON M5T 1R8, Canada. Univ Toronto, Toronto, ON, Canada. Univ Kansas, Kansas City, KS USA. Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. NINDS, CNS Studies Lab, NIH, Bethesda, MD 20892 USA. Western Gen Hosp, Natl Creutzfeldt Jakob Dis Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland. RP Ghetti, B (reprint author), Indiana Univ, Sch Med, Dept Pathol & Lab Med, 635 Barnhill Dr,MS A142, Indianapolis, IN 46202 USA. OI Dickson, Dennis W/0000-0001-7189-7917 FU NIA NIH HHS [AG 10133]; NINDS NIH HHS [NS 29822] NR 47 TC 135 Z9 138 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD OCT PY 1998 VL 57 IS 10 BP 979 EP 988 DI 10.1097/00005072-199810000-00010 PG 10 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 129WN UT WOS:000076487200010 PM 9786248 ER PT J AU Krauzlis, RJ Miles, FA AF Krauzlis, RJ Miles, FA TI Role of the oculomotor vermis in generating pursuit and saccades: Effects of microstimulation SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID CAUDAL FASTIGIAL NUCLEUS; RETICULARIS TEGMENTI PONTIS; MOVEMENT-RELATED ACTIVITY; PURKINJE-CELL ACTIVITY; BRAIN-STEM NEURONS; CORTICAL AREAS MT; EYE-MOVEMENTS; SMOOTH-PURSUIT; CEREBELLAR VERMIS; MACAQUE MONKEY AB We studied the eye movements evoked by applying small amounts of current (2-50 mu A) within the oculomotor vermis of two monkeys. We first compared the eye movements evoked by microstimulation applied either during maintained pursuit or during fixation. Smooth, pursuitlike changes in eye velocity caused by the microstimulation were directed toward the ipsilateral side and occurred at short latencies (10-20 ms). The amplitudes of these pursuitlike changes were larger during visually guided pursuit toward the contralateral side than during either fixation or visually guided pursuit toward the ipsilateral side. At these same sites, microstimulation also often produced abrupt, saccadelike changes in eye velocity. In contrast to the smooth changes in eye velocity, these saccadelike effects were more prevalent during fixation and during pursuit toward the ipsilateral side. The amplitude and type of evoked eye movements could also be manipulated at single sites by changing the frequency of microstimulation. Increasing the frequency of microstimulation produced increases in the amplitude of pursuitlike changes, but only up to a certain point. Beyond this point, the value of which depended on the site and whether the monkey was fixating or pursuing, further increases in stimulation frequency produced saccadelike changes of increasing amplitude. To quantify these effects, we introduced a novel method for classifying eye movements as pursuitlike or saccadelike. The results of this analysis showed that the eye movements evoked by microstimulation exhibit a distinct transition point between pursuit and saccadelike effects and that the amplitude of eye movement that corresponds to this transition point depends on the eye movement behavior of the monkey. These results are consistent with accumulating evidence that the oculomotor vermis and its associated deep cerebellar nucleus, the caudal fastigial, are involved in the control of both pursuit and saccadic eye movements. We suggest that the oculomotor vermis might accomplish this role by altering the amplitude of a motor error signal that is common to both saccades and pursuit. C1 Salk Inst Biol Studies, La Jolla, CA 92037 USA. NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Krauzlis, RJ (reprint author), Salk Inst Biol Studies, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA. NR 78 TC 58 Z9 59 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD OCT PY 1998 VL 80 IS 4 BP 2046 EP 2062 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 129WQ UT WOS:000076487400036 PM 9772260 ER PT J AU Long, JM Kalehua, AN Muth, NJ Hengemihle, JM Jucker, M Calhoun, ME Ingram, DK Mouton, PR AF Long, JM Kalehua, AN Muth, NJ Hengemihle, JM Jucker, M Calhoun, ME Ingram, DK Mouton, PR TI Stereological estimation of total microglia number in mouse hippocampus SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE dentate gyrus; CA1; Mac-1; stereology; optical fractionator ID TRANSGENIC MICE; OPTICAL FRACTIONATOR; ARBITRARY PARTICLES; UNBIASED ESTIMATION; ALZHEIMERS-DISEASE; NEURONS; CELLS; BRAIN; ASTROCYTOSIS; EXPRESSION AB Microglia are brain cells of considerable interest because of their role in CNS inflammatory responses and strong association with neuritic plaques in Alzheimer's disease (AD). In the present study, immunocytochemistry was combined with unbiased stereology to estimate the mean total number of microglia in dentate gyrus and CA1 regions of the mouse hippocampus. Systematic-uniform-random (SUR) sections were cut through the hippocampal formation of male C57BL/6J mice (n = 7, 4-5 months) and immunostained with Mac-1, an antibody to the complement subunit 3 receptor (CR3). The total number of Mac-1 immunopositive cells was determined using the optical fractionator method. The mean total number of microglia in the mouse dentate gyrus was estimated to be 20300 (CV = 0.21) with a mean coefficient of error (CE)= 0.09. The mean total number of microglia in the mouse CA1 was estimated to be 43200 (CV = 0.24) with a CE = 0.11. Comparison of total number estimates, derived from fraction- or volume-based methods, supported stereological theory regarding the equivalence of the two techniques. The time required to determine total microglia number in both hippocampal sub-regions was approximate to 6 h per mouse from stained sections. The combination of immunocytochemistry and stereology provides a reliable means to assess microglia number that can easily be adopted for studies of transgenic and lesion-based models of aging and neurodegenerative diseases. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Essex Community Coll, Dept Psychol, Baltimore, MD 21237 USA. Univ Basel, Inst Pathol, Dept Neuropathol, CH-4003 Basel, Switzerland. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Neuropathol Lab, Baltimore, MD 21205 USA. RP Long, JM (reprint author), NIA, Gerontol Res Ctr, NIH, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM LongJ@vax.grc.nia.nih.gov NR 33 TC 56 Z9 56 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 1 PY 1998 VL 84 IS 1-2 BP 101 EP 108 DI 10.1016/S0165-0270(98)00100-9 PG 8 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 157MW UT WOS:000078067100014 PM 9821640 ER PT J AU Walcourt, A Ide, D AF Walcourt, A Ide, D TI A system for the delivery of general anesthetics and other volatile agents to the fruit-fly Drosophila melanogaster SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE microelectrode; halothane; Drosophila; electrophysiology; microfilm; giant fiber system ID GIANT FIBER ACTIVATION; DIRECT FLIGHT MUSCLES; INITIATIONS; ANATOMY; PATHWAY AB The system described here provides a simple method of delivering anesthetic vapor to the fruit-fly Drosophila melanogaster. This system delivers known concentrations of volatile anesthetic vapor obtained from liquid anesthetics in a continuous gas stream of pure humidified air. It controls for evaporation, and absorption of volatile agents, whilst allowing for extracellular electrophysiological recordings. Recordings were made from the fly's escape muscles, the jump tergotrochanter muscle (TTM) and the flight dorsal longitudinal muscle (DLM). The system minimizes the quantity of anesthetic used, making the use of more expensive and more conventional anesthetics cost effective and practicable. It also permits monitoring the fly's movements during anesthesia. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Res Serv Branch, Bethesda, MD USA. RP Walcourt, A (reprint author), NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. NR 14 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 1 PY 1998 VL 84 IS 1-2 BP 115 EP 119 DI 10.1016/S0165-0270(98)00105-8 PG 5 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 157MW UT WOS:000078067100016 PM 9821642 ER PT J AU Thomas, A Kim, DS Fields, RL Chin, H Gainer, H AF Thomas, A Kim, DS Fields, RL Chin, H Gainer, H TI Quantitative analysis of gene expression in organotypic slice-explant cultures by particle-mediated gene transfer SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the Endocrine-Society CY JUN 10-14, 1997 CL MINNEAPOLIS, MINNESOTA SP Endocrine Soc DE biolistics; GFAP; hippocampus; hypothalamus; rat; alpha-tubulin ID DENDRITIC GROWTH; CALCIUM-CHANNEL; SUBUNIT; CELLS AB Biolistics, also known as particle-mediated gene transfer, has been used as an effective method to transfect primary neurons in cultured slices when all other methods have proven unsuccessful. Most of these uses have provided qualitative or semi-quantitative data based on visual assays such as immunohistochemistry. In this paper, we describe a quantitative method of biolistics to analyze gene expression in organotypic cultures of hippocampus and hypothalamus. The method involves co-transfection of the experimental promoters and standard (cytomegalovirus or Rous sarcoma virus) promoters coupled to different reporters (luciferase or beta-galactosidase), with the standard promoter-reporter construct used to 'normalize' the experimental data. Examples and validations of this technique with various cell specific promoters are given: for example, astrocyte-specific and neuron-specific (alpha-tubulin and N-type calcium channel alpha-1B gene) promoters and various tissues (Neuro 2A cells and hippocampal rind hypothalamic organotypic slice-explants). An analysis of deletion constructs of the alpha 1B calcium channel subunit gene is described. This method should provide a new opportunity for the analysis of gene expression in diverse neuronal phenotypes. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bld 36,Rm 4D-20, Bethesda, MD 20892 USA. NR 13 TC 24 Z9 24 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 1 PY 1998 VL 84 IS 1-2 BP 181 EP 191 DI 10.1016/S0165-0270(98)00117-4 PG 11 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 157MW UT WOS:000078067100024 PM 9821650 ER PT J AU Lonser, RR Weil, RJ Morrison, PF Governale, LS Oldfield, EH AF Lonser, RR Weil, RJ Morrison, PF Governale, LS Oldfield, EH TI Direct convective delivery of macromolecules to peripheral nerves SO JOURNAL OF NEUROSURGERY LA English DT Article DE bulk flow; convection; drug delivery; macromolecule; peripheral nerve; Macaca mulatta ID BRAIN; DIFFUSION; INFUSION; TISSUE AB Object. Although many macromolecules have treatment potential for peripheral nerve disease, clinical use of these agents has been restricted because of limitations of delivery including systemic toxicity, heterogeneous dispersion, and inadequate distribution. In an effort to overcome these obstacles, the authors examined the use of convection to deliver and distribute macromolecules into peripheral nerves. Methods. For convective delivery, the authors used a gas-tight, noncompliant system that provided continuous flow through a small silica cannula (inner diameter 100 mu m, outer diameter 170 mu m) inserted into a peripheral nerve. Increases in the volume of infusion (Vi) (10, 20, 30, 40, and 80 mu L)) of C-14-labeled (nine nerves) or gadolinium-labeled (two nerves) albumin were infused unilaterally or bilaterally into the tibial nerves of six primates (Macaca mulatta at 0.5 mu l/minute. The volume of distribution (Vd), percentage recovery, and delivery homogeneity were determined using quantitative autoradiography, an imaging program developed by the National Institutes of Health, magnetic resonance (MR) imaging, scintillation counting, and kurtosis (K) analysis. One animal that was infused bilaterally with gadolinium-bound albumin (40 mu l to each nerve) underwent MR imaging and was observed for 16 weeks after infusion. The Vd increased with the Vi in a logarithmic fashion. The mean Vd/Vi ratio over all Vi was 3.7 +/- 0.8 (mean +/- standard deviation). The concentration across the perfused region was homogeneous (K = -1.07). The infusate, which was limited circumferentially by the epineurium, followed the parallel arrangement of axonal fibers and filled long segments of nerve (up to 6.8 cm). Recovery of radioactivity was 75.8 +/- 9%. No neurological deficits arose from infusion. Conclusions. Convective delivery of macromolecules to peripheral nerves is safe and reliable. It overcomes obstacles associated with current delivery methods and allows selective regional delivery of putative therapeutic agents to long sections of nerve. This technique should permit the development of new treatments for numerous types of peripheral nerve lesions. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Biomed Engn & Instrumentat Program, Div Intramural Res Resources, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37,MSC-1414, Bethesda, MD 20892 USA. NR 12 TC 37 Z9 37 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1998 VL 89 IS 4 BP 610 EP 615 DI 10.3171/jns.1998.89.4.0610 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 122LL UT WOS:000076073000014 PM 9761055 ER PT J AU Lonser, RR Gogate, N Morrison, PF Wood, JD Oldfield, EH AF Lonser, RR Gogate, N Morrison, PF Wood, JD Oldfield, EH TI Direct convective delivery of macromolecules to the spinal cord SO JOURNAL OF NEUROSURGERY LA English DT Article DE bulk flow; convection; drug delivery; macromolecule; spinal cord; pig; Macaca mulatta ID BRAIN-TISSUE; PHARMACOKINETICS; DIFFUSION; INFUSION; FLOW AB Object. Because of the limited penetration of macromolecules across the blood-spinal cord barrier, numerous therapeutic compounds with potential for treating spinal cord disorders cannot be used effectively. The authors have developed a technique to deliver and distribute macromolecules regionally in the spinal cord by using convection in the interstitial space. Methods. The authors designed a delivery system connected to a "floating" silica cannula (inner diameter 100 mu m, outer diameter 170 mu m) that provides for constant volumetric inflow to the spinal cord. A solution containing albumin that was either unlabeled or labeled with carbon-14 or gadolinium was infused at various volumes (3, 6, 10, 20, 40, or 50 mu l) at a rate of 0.1 mu l/minute into the spinal cord dorsal columns of nine swine and into the lateral columns of three primates (Macaca mulatta). Volume of distribution (Vd), concentration homogeneity, and percentage of recovery were determined using scintillation analysis, kurtosis calculation (K), and quantitative autoradiography (six swine), magnetic resonance imaging (one swine and three primates), and histological analysis (all animals). Neurological function was observed for up to 3 days in four of the swine and up to 16 weeks in the three primates. The Vd of C-14-albumin was linearly proportional (R-2 = 0.97) to the volume of infusion (Vi) (Vd/Vi = 4.4 +/- 0.5; [mean +/- standard deviation]). The increases in Vd resulting from increases in Vi were primarily in the longitudinal dimension (R-2 = 0.83 in swine; R-2 = 0.98 in primates), allowing large segments of spinal cord (up to 4.3 cm; Vi 50 mu l) to be perfused with the macromolecule. The concentration across the area of distribution was homogeneous (K = -1.1). The mean recovery of infused albumin from the spinal cord was 85.5 +/- 5.6%. Magnetic resonance imaging and histological analysis combined with quantitative autoradiography revealed the albumin infusate to be preferentially distributed along the white matter tracts. No animal exhibited a neurological deficit as a result of the infusion. Conclusions. Regional convective delivery provides reproducible, safe, region-specific, and homogeneous distribution of macromolecules over large longitudinal segments of the spinal cord. This delivery method overcomes many of the obstacles associated with current delivery techniques and provides for research into new treatments of various conditions of the spinal cord. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIH, Biomed Engn & Instrumentat Program, Div Intramural Res Resources, Bethesda, MD 20892 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D37,MSC-1414, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 15 TC 63 Z9 64 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD OCT PY 1998 VL 89 IS 4 BP 616 EP 622 DI 10.3171/jns.1998.89.4.0616 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 122LL UT WOS:000076073000015 PM 9761056 ER PT J AU Jacobson, S AF Jacobson, S TI Association of human herpesvirus-6 and multiple sclerosis: here we go again? SO JOURNAL OF NEUROVIROLOGY LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; NERVOUS-SYSTEM; DISEASE; VIRUS C1 NINDS, Viral Immunol Sect, NIH, Rockville, MD 20852 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, NIH, Bldg 10,Room 5B-16, Rockville, MD 20852 USA. NR 18 TC 21 Z9 21 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD OCT PY 1998 VL 4 IS 5 BP 471 EP 473 PG 3 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 134HD UT WOS:000076736700001 PM 9839644 ER PT J AU Cocco, P Ward, MH Dosemeci, M AF Cocco, P Ward, MH Dosemeci, M TI Occupational risk factors for cancer of the gastric cardia - Analysis of death certificates from 24 US states SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SOCIOECONOMIC-STATUS; ESOPHAGUS; ADENOCARCINOMA; TOBACCO; ALCOHOL; MORTALITY AB We evaluated the risk of gastric cardia cancer by occupation and industry in a case-control study using information from death certificates for 24 US states in 1984-1992. One thousand fifty-six cases of gastric cardia cancer were identified among men aged 20 years or more, including 1,023 whites and 33 blacks. Controls were 5,280 subjects who died of nonmalignant diseases, 5:1 matched to cases by geographic region, race, gender, and 5-year age group. Among white men, occupations with elevated risk included financial managers (odds ratio [OR] = 6.1; 95% confidence interval [CI], 1.3-28.8), janitors and cleaners (OR = 1.7; 95% CI, 1.0-2.9), production inspectors (OR = 3.2; 95% CI, 1.5-6.9), and truck drivers (OR= 1.5; 95% CI, 1.0-2.2). Industries with elevated risk included pulp and paper mills (OR = 2.0; 95% CI, 1.0-37), newspaper publishing and printing (OR = 2.6; 95% CI, 1.0-6.3), industrial and miscellaneous chemicals (OR = 2.0; 95% CI, 1.0-3.9), water supply and irrigation (OR = 5.6; 95% CI, 1.6-19.9). Among black men, risks were nonsignificantly increased for subjects employed in railroads (3 cases, 2 controls) and for carpenters (3 cases, 0 controls). We created job-exposure matrices for asbestos, inorganic dust, metal dust, lead, polycyclic aromatic hydrocarbons, nitrogen oxides, nitrosamines, sulfuric acid fertilizers, herbicides, other pesticides, and wood dust. Among white men, a consistent pattern of risk increase by level and probability of exposure was observed only for sulfuric acid mists, with a twofold excess (95% CI, 0.6-7.3) associated with high probability of high intensity exposure. A significant 30 % increase in risk was observed for those subjects with a high probability of exposure (all levels combined) to lead and a 60% increase was observed for subjects with high-level exposure to lead tall probabilities combined). However, crosstabulation of gastric cardia cancer risk by probability and level of exposure to lead did not show consistent trends. Asbestos exposure also showed an overall 50% increase but no consistent trends among white men. None of the 12 occupational hazards showed an association with risk for black men. C1 NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Cagliari, Inst Occupat Med, Cagliari, Italy. RP Ward, MH (reprint author), NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, 6130 Execut Blvd,EPN Room 418, Bethesda, MD 20892 USA. NR 18 TC 18 Z9 18 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD OCT PY 1998 VL 40 IS 10 BP 855 EP 861 DI 10.1097/00043764-199810000-00004 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 129EE UT WOS:000076449700004 PM 9800169 ER PT J AU Jacot, JL O'Neill, JT Scandling, DM West, SD McKenzie, JE AF Jacot, JL O'Neill, JT Scandling, DM West, SD McKenzie, JE TI Nitric oxide modulation of retinal, choroidal, and anterior uveal blood flow in newborn piglets SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID ENDOTHELIUM-DEPENDENT REGULATION; HIGH INTRAOCULAR-PRESSURE; L-ARGININE; MICROSPHERE METHOD; OPHTHALMIC ARTERY; VASCULAR TONE; SYNTHASE; AUTOREGULATION; DERIVATIVES; RELAXATION AB The purpose of the present study was to investigate the role of nitric oxide (NO) in modulating the resting vascular tone of the choroidal and anterior uveal circulations and the autoregulatory gain of the retina. Blood flow (ml/min/100gm dry weight) to tissues was determined in 23 anesthetized piglets (3-4 kg) using radiolabelled microspheres. Ocular Perfusion Pressure (OPP) was defined as mean arterial pressure minus intraocular pressure (IOP) which was manipulated hydrostatically by cannulation of the anterior eye chamber. The OPP was decreased during intravenous infusion (30mg/kg/hr) of either the NO-synthase inhibitor L-NAME or the inactive enantiomer D-NAME. Blood flows were determined at OPP of 60, 50, 40, 30, and 20 mmHg following initial ocular blood now measurements. Mean initial choroidal and anterior uveal blood flows with L-NAME showed a 47 +/- 12% and a 43 +/- 6% reduction (p <.001), respectively. Mean choroidal blood flows were significantly reduced (p<.01) in the L-NAME treated animals at an OPP of 60 and 50 when compared to D-NAME. Uveal blood flows were linearly correlated with OPP in the L-NAME and D-NAME treated groups. Uveal blood flow was greater following exogenous administration of L-arginine (180 mg/kg). Mean initial retinal blood flow did not differ significantly in either group. Retinal blood flow with L-NAME was reduced at OPP of 60 mmHg and below compared to D-NAME (p<.05). The degree of compensation in the autoregulatory gain of the retinal vasculature was reduced in the presence oft-NAME at an OPP of 50 mmHg and below compared to D-NAME. These data support the hypothesis that NO may be a primary mediator in maintaining resting vascular tone to the choroid and anterior uvea in vivo and that NO blockade reduces the degree of compensation in the autoregulatory gain of the retinal vasculature within a specific range of ocular perfusion pressures. C1 Uniformed Serv Univ Hlth Sci, Dept Physiol, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. RP Jacot, JL (reprint author), NEI, NIH, 9000 Rockville Pike,Bldg 6,Room 320, Bethesda, MD 20892 USA. NR 40 TC 20 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD OCT PY 1998 VL 14 IS 5 BP 473 EP 489 DI 10.1089/jop.1998.14.473 PG 17 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA 149BT UT WOS:000077585800009 PM 9811236 ER PT J AU McKinney, RE Johnson, GM Stanley, K Yong, FH Keller, A O'Donnell, KJ Brouwers, P Mitchell, WG Yogev, R Wara, DW Wiznia, A Mofenson, L McNamara, J Spector, SA AF McKinney, RE Johnson, GM Stanley, K Yong, FH Keller, A O'Donnell, KJ Brouwers, P Mitchell, WG Yogev, R Wara, DW Wiznia, A Mofenson, L McNamara, J Spector, SA CA Pediat AIDS Clinical Trials Grp Protocol 300 St TI A randomized study of combined zidovudine-lamivudine versus didanosine monotherapy in children with symptomatic therapy-naive HIV-1 infection SO JOURNAL OF PEDIATRICS LA English DT Article ID CUBIC MILLIMETER; CLINICAL-TRIALS; GROWTH AB Objective: The Pediatric AIDS Clinical Trials Group (PACTG) Protocol 300 assessed the clinical efficacy and safety of combination zidovudine/lamivudine (ZDV/3TC) compared with either didanosine (ddI) alone or combination ZDV/ddI. Study design: Children with symptomatic human immunodeficiency virus (HIV) infection, 6 weeks through 15 years of age, were stratified according to age and randomly assigned to receive ddI, ZDV/3TC, or ZDV/ddI. The primary endpoint was time to first progression of HIV disease or death. Enrollment in the ZDV/ddI arm stopped after 11 months on the basis of results of PACTG Protocol 152, but blinded follow-up continued. Results: For the 471 children who could be evaluated, the median age was 2.7 years, median CD4 cell count was 699 cells/mm(3), and median log(10) HIV RNA was 5.1/mL. Median follow-up was 9.4 months. Patients receiving ZDV/3TC had a lower risk of HIV disease progression or death than those receiving ddI alone (15 vs 38 failures, P = .0006) and a lower risk of death (3 vs 15 deaths, P = .0039). Weight and height growth rates, CD4(+) cell counts, and RNA concentrations showed results favoring ZDV/3TC. For patients concurrently randomized to all 3 treatment arms, both ZDV/3TC and ZDV/ddI recipients had lower risk of HIV disease progression than those who received ddI alone (P = .0026 and P = .0045). Conclusions: Combination therapy with either ZDV/3TC or ZDV/ddI was superior, as determined LS clinical and laboratory measures, to monotherapy with ddI. C1 Duke Univ, Med Ctr, Dept Pediat & Psychiat, Durham, NC 27710 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. NCI, Intramural Res Program, Bethesda, MD 20892 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Bronx Lebanon Hosp Ctr, Dept Pediat, Bronx, NY 10456 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Bethesda, MD 20892 USA. NIAID, Pediat Med Branch, Div Aids, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. RP McKinney, RE (reprint author), Duke Univ, Med Ctr, Dept Pediat & Psychiat, Box 3461, Durham, NC 27710 USA. OI Mofenson, Lynne/0000-0002-2818-9808 NR 26 TC 76 Z9 81 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD OCT PY 1998 VL 133 IS 4 BP 500 EP 508 DI 10.1016/S0022-3476(98)70057-5 PG 9 WC Pediatrics SC Pediatrics GA 127XL UT WOS:000076375800008 PM 9787687 ER PT J AU Tsao, LI Ladenheim, B Andrews, AM Chiueh, CC Cadet, JL Su, TP AF Tsao, LI Ladenheim, B Andrews, AM Chiueh, CC Cadet, JL Su, TP TI Delta opioid peptide [D-Ala(2),D-leu(5)]enkephalin blocks the long-term loss of dopamine transporters induced by multiple administrations of methamphetamine: Involvement of opioid receptors and reactive oxygen species SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DISMUTASE TRANSGENIC MICE; STRIATAL DOPAMINE; INDUCED NEUROTOXICITY; TYROSINE-HYDROXYLASE; RADICAL FORMATION; CAUDATE-NUCLEUS; MESSENGER-RNA; RAT; HYPERTHERMIA; PRESERVATION AB Delta opioid peptide [D-Ala(2),D-leu(5)]enkephalin (DADLE) can prolong organ preservation and increases myocardial tolerance to ischemia. Our study examined the protective property of DADLE against methamphetamine- (METH) induced dopaminergic terminal damage in the central nervous system. Because the neurotoxicity of METH involves reactive oxygen species, we also examined if DADLE might be an antioxidative agent in vitro. DADLE at 2 and 4 mg/kg (i.p.), given 30 min before each METH administration (5 or 10 mg/kg, i.p., four injections in a day at 2-hr intervals), dose-dependently blocked the METH-induced long-term dopamine transporter loss. The opioid antagonist naltrexone blocked this action of DADLE in both aspects of striata but tends not to affect the effects of DADLE in the nucleus accumbens. DADLE did not alter changes in body temperature induced by METH. The reduction of striatal dopaminergic content and tyrosine hydroxylase activity caused by METH, however, were not blocked by DADLE. In vitro, DADLE was approximately equipotent to glutathione in inhibiting both superoxide anion formation induced by xanthine oxidase and hydroxyl radical formation evoked by ferrous/citrate complex. DADLE was only slightly less potent than glutathione in inhibiting the iron/ascorbate-induced brain lipid peroxidation. These results suggest that DADLE can protect the terminal membranes of dopaminergic neurons against METH-induced insult but not the loss of dopaminergic content and tyrosine hydroxylase activity and that this action of DADLE might involve opioid receptors as well as the sequestration of free radical. C1 NIDA, Mol Neuropsychiat Sect, Intramural Res Program, Cellular Neurobiol Branch,NIH, Baltimore, MD 21224 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Su, TP (reprint author), NIDA, Mol Neuropsychiat Sect, Intramural Res Program, Cellular Neurobiol Branch,NIH, POB 5180, Baltimore, MD 21224 USA. RI Andrews, Anne/B-4442-2011 OI Andrews, Anne/0000-0002-1961-4833 NR 48 TC 52 Z9 55 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1998 VL 287 IS 1 BP 322 EP 331 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 128NV UT WOS:000076413600040 PM 9765353 ER PT J AU Ryan, RR Weber, HC Mantey, SA Hou, W Hilburger, ME Pradhan, TK Coy, DH Jensen, RT AF Ryan, RR Weber, HC Mantey, SA Hou, W Hilburger, ME Pradhan, TK Coy, DH Jensen, RT TI Pharmacology and intracellular signaling mechanisms of the native human orphan receptor BRS-3 in lung cancer cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SWISS 3T3 CELLS; NEUROMEDIN-B RECEPTORS; MAMMALIAN BOMBESIN RECEPTORS; TYROSINE PHOSPHORYLATION; CA2+ MOBILIZATION; CHO CELLS; ANALOGS; AFFINITY; FIBROBLASTS; ANTAGONISTS AB Neither the native ligand nor the cell biology of the bombesin (Bn)-related orphan receptor subtype 3 (BRS-3) is known. In this study, we used RT-PCR to identify two human lung cancer lines that contain sufficient numbers of native hBRS-3 to allow study: NCI-N417 and NCI-H720. In both cell lines, [DPhe(6),beta Ala(11),Phe(13),Nle(14)]Bn(6-14) stimulates [H-3]inositol phosphate. In NCI-N417 cells, binding of I-125-[DTyr(6),beta Ala(11),Phe(13),Nle(14)]Bn(6-14) was saturable and high-affinity. [DPhe(6),beta Ala(11),Phe(13),Nle(14)]Bn(6-14) stimulated phospholipase D activity and a concentration-dependent release of [H-3]inositol phosphate (EC50 = 25 nM) and intracellular calcium (EC50 = 14 nM); the increases in intracellular calcium were primarily from intracellular stores, hBRS-3 activation was not coupled to changes in adenylate cyclase activity, [H-3]-thymidine incorporation or cell proliferation. No naturally occurring Bn-related peptides bound or activated the hBRS-3 with high affinity. Four different bombesin receptor antagonists inhibited increases in [H-3]inositol phosphate. Using cytosensor microphysiometry, we found that [DPhe(6),beta Ala(11),Phe(13), Nle(14)]Bn(6-14) caused concentration-dependent acidification. The results show that native hBRS-3 receptors couple to phospholipases C and D but not to adenylate cyclase and that they stimulate mobilization of intracellular calcium and increase metabolism but not growth. The discovery of human cell lines with native, functional BRS-3 receptors, of new leads for a more hBRS-3-specific antagonist and of the validity of microphysiometry as an assay has yielded important tools that can be used for the identification of a native ligand for hBRS-3 and for the characterization of BRS-3-mediated biological responses. C1 NIDDK, DDB, NIH, Bethesda, MD 20892 USA. NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD 20892 USA. Tulane Univ, Peptide Res Labs, New Orleans, LA 70118 USA. RP Jensen, RT (reprint author), NIDDK, DDB, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. NR 42 TC 36 Z9 37 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD OCT PY 1998 VL 287 IS 1 BP 366 EP 380 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 128NV UT WOS:000076413600045 PM 9765358 ER PT J AU Classen, J Knorr, U Werhahn, KJ Schlaug, G Kunesch, E Cohen, LG Seitz, RJ Benecke, R AF Classen, J Knorr, U Werhahn, KJ Schlaug, G Kunesch, E Cohen, LG Seitz, RJ Benecke, R TI Multimodal output mapping of human central motor representation on different spatial scales SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON EMISSION TOMOGRAPHY; ADULT SQUIRREL-MONKEYS; CORTEX; HAND; MRI; PET; HANDEDNESS; PLASTICITY; MUSCLE AB 1. Non-invasive mapping by focal transcranial magnetic stimulation (TMS) is frequently used to investigate cortical motor function in the intact and injured human brain. We examined how TMS-derived maps relate to the underlying cortical anatomy and to cortical maps generated by functional imaging studies. 2. The centres of gravity (COGs) of TMS maps of the first dorsal intersosseus muscle (FDI) were integrated into 3-D magnetic resonance imaging (MRI) data sets in eleven subjects. In seven of these subjects the TMS-derived COGs were compared with the COG of regional cerebral blood flow increases using positron emission tomography (PET) in an index finger flexion protocol. 3. Mean TMS-derived COG projections were located on the posterior lip of the precentral gyrus and TMS-derived COG projections were in close proximity to the mean PET-derived COG, suggesting that the two methods reflect activity of similar cortical elements. 4. Criteria for a reliable assessment of the COG; and the number of positions with a minimum amplitude of two-thirds of the maximum motor-evoked potential (T3Ps) were determined as a function of the number of stimuli and extension of the stimulation field. COGs and T3Ps were compared with an estimate of the size of the human motor cortex targeting a-motoneurons of forearm muscles. This comparison suggests that TMS can retrieve spatial information on cortical organization below the macroanatomic scale of cortical regions. 5. Finally, we studied the cortical representation of hand muscles in relation to facial and foot muscle representations and investigated hemispherical asymmetries. We did not find any evidence for a different ipsi- or contralateral representation of the mentalis muscle. Also, no difference was found between FDI representations on the dominant versus the non-dominant hemisphere. C1 Univ Rostock, Neurol Klin, Zentrum Nervenheilkunde, Rostock, Germany. Univ Dusseldorf, Neurol Klin, D-4000 Dusseldorf, Germany. Univ Munich, Klinikum Grosshadern, Neurol Klin, D-8000 Munich, Germany. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. NINDS, Human Cort Physiol Unit, Med Neurol Branch, Bethesda, MD 20892 USA. RP Classen, J (reprint author), Univ Rostock, Neurol Klin & Poliklin, Zentrum Nervenheilkunde, Gehlsheimer Str 20, D-18055 Rostock, Germany. EM joseph.classen@med.uni-rostock.de NR 50 TC 72 Z9 72 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 1 PY 1998 VL 512 IS 1 BP 163 EP 179 DI 10.1111/j.1469-7793.1998.163bf.x PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 134UY UT WOS:000076763100014 PM 9729626 ER PT J AU Weihe, E Schafer, MKH Schutz, B Anlauf, M Depboylu, C Brett, C Chen, LB Eiden, LE AF Weihe, E Schafer, MKH Schutz, B Anlauf, M Depboylu, C Brett, C Chen, LB Eiden, LE TI From the cholinergic gene locus to the cholinergic neuron SO JOURNAL OF PHYSIOLOGY-PARIS LA English DT Article DE synaptic vesicle; acetylcholine; VAChT; ChAT; peripheral and central nervous system; ontogeny; cholinergic differentiation ID VESICULAR ACETYLCHOLINE TRANSPORTER; SYNAPTIC VESICLES; POTENTIAL SITES; RAT-BRAIN; EXPRESSION; ACETYLTRANSFERASE; LOCALIZATION AB The cholinergic gene locus (CGL) was first identified in 1994 as the site (human chromosome 10q11.2) at which choline acetyltransferase and a functional vesicular acetylcholine transporter are co-localized. Here, we present recent neuroanatomical, developmental, and evolutionary insights into the chemical coding of cholinergic neurotransmission that have been gleaned from the study of the CGL, and its protein products VAChT and ChAT, which comprise a synthesis-sequestration pathway that functionally defines the cholinergic phenotype. ((C) Elsevier, Paris). C1 Univ Marburg, Dept Anat & Cell Biol, D-35033 Marburg, Germany. NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Weihe, E (reprint author), Univ Marburg, Dept Anat & Cell Biol, Robert Koch Str 6, D-35033 Marburg, Germany. OI Eiden, Lee/0000-0001-7524-944X NR 20 TC 15 Z9 17 U1 2 U2 2 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 0928-4257 J9 J PHYSIOLOGY-PARIS JI J. Physiol.-Paris PD OCT-DEC PY 1998 VL 92 IS 5-6 BP 385 EP 388 DI 10.1016/S0928-4257(99)80010-2 PG 4 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 121EW UT WOS:000076001200010 PM 9789842 ER PT J AU Dai, RK Zhai, SP Wei, XX Pincus, MR Vestal, RE Friedman, FK AF Dai, RK Zhai, SP Wei, XX Pincus, MR Vestal, RE Friedman, FK TI Inhibition of human cytochrome P450 1A2 by flavones: A molecular modeling study SO JOURNAL OF PROTEIN CHEMISTRY LA English DT Article DE cytochrome P450; flavones; molecular modeling; protein folding; computational chemistry ID SITE-DIRECTED MUTAGENESIS; AMINO-ACID-SEQUENCE; PROTEIN SECONDARY STRUCTURE; CODING NUCLEOTIDE-SEQUENCE; ACTIVE-SITE; SUBSTRATE-SPECIFICITY; CRYSTAL-STRUCTURE; MICROSOMAL P450S; RAT-LIVER; 3D MODEL AB Cytochrome P450 1A2 metabolizes a number of important drugs, procarcinogens, and endogenous compounds. Several flavones, a class of phytochemicals consumed in the human diet, have been shown to differentially inhibit human P450 1A2-mediated methoxyresorufin demethylase. A molecular model of this P450 was constructed in order to elucidate the molecular basis of the P450-flavone interaction. Flavone and its 3,5,7-trihydroxy and 3,5,7-trimethoxy derivatives were docked into the active site to assess their mode of binding. The site is hydrophobic and includes several residues that hydrogen bond with substituents on the flavone nucleus. The binding interactions of these flavones in the modeled active side are consistent with their relative inhibitory potentials, namely 3,5,7-trihydroxylflavone > flavone > 3,5,7-trimethoxylAavone, toward P450 1A2-mediated methoxyresorufin demethylation. C1 NCI, Mol Carcinogenesis Lab, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Clin Pharmacol & Gerontol Res Unit, Boise, ID USA. Mt State Med Res Inst, Boise, ID USA. Idaho State Univ, Coll Pharm, Dept Pharmaceut Sci, Pocatello, ID 83209 USA. Vet Adm Med Ctr, Dept Pathol & Lab Med, Brooklyn, NY USA. SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. Univ Washington, Sch Med, Dept Med & Pharmacol, Seattle, WA 98195 USA. RP Friedman, FK (reprint author), NCI, Mol Carcinogenesis Lab, Bldg 37, Bethesda, MD 20892 USA. RI Friedman, Fred/D-4208-2016 NR 41 TC 29 Z9 30 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0277-8033 J9 J PROTEIN CHEM JI J. Protein Chem. PD OCT PY 1998 VL 17 IS 7 BP 643 EP 650 DI 10.1007/BF02780965 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 141MV UT WOS:000077148500007 PM 9853678 ER PT J AU Quyyumi, AA AF Quyyumi, AA TI Does acute improvement of endothelial dysfunction in coronary artery disease improve myocardial ischemia? A double-blind comparison of parenteral D- and L-arginine SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID NITRIC-OXIDE ACTIVITY; INHIBITS PLATELET-AGGREGATION; CHOLESTEROL-FED RABBITS; DIETARY L-ARGININE; HYPERCHOLESTEROLEMIC RABBITS; DEPENDENT VASODILATION; VASOMOTOR RESPONSE; NO PRODUCTION; RISK-FACTORS; ATHEROSCLEROSIS AB Objectives. Parenteral L-arginine will improve myocardial ischemia in patients with obstructive coronary artery disease. Background. Endothelial dysfunction causes coronary arterial constriction during stress, and L-arginine improves endothelial dysfunction, Methods. Twenty-two patients with stable coronary artery disease and exercise-induced ST-segment depression underwent assessment of forearm endothelial function with acetylcholine and symptom-limited treadmill exercise testing during dextrose 5% infusion and after double blind intravenous administration of L- and D-arginine (5 mg/kg/min) for 20 min. Results, Forearm blood flow increased with both L- and D-arginine (33% +/- 6% and 38% +/- 7%, respectively, p < 0.001). Acetylcholine-mediated forearm vasodilation also improved with both L- and D-arginine (p < 0.0001). The magnitude of improvement was similar with both enantiomers and was observed in patients throughout the range of acetylcholine responses and cholesterol levels. Heart rate and blood pressure at rest and during each stage of exercise and exercise duration remained unchanged with L- and D-arginine compared to control. Ischemic threshold, measured either as the rate-pressure product or the duration of exercise at the onset of 1-mm ST-segment depression during exercise, also remained unchanged. Serum arginine, insulin and prolactin levels (p < 0.01) increased dth both enantiomers, Conclusions. Parenteral arginine produces non-stereo specific peripheral vasodilation and improves endothelium dependent vasodilation in patients with stable coronary artery disease by stimulation of insulin dependent nitric oxide release or by non-enzymatic nitric oxide generation. Despite enhanced endothelial function, there was no improvement in myocardial ischemia during stress dth either enantiomer, Whether parenteral arginine will be of therapeutic benefit in acute coronary syndromes and oral arginine in myocardial ischemia needs to be studied further. (C) 1998 by the American College of Cardiology. C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. RP Quyyumi, AA (reprint author), NHLBI, Cardiol Branch, Bldg 10,Room 7B15,10 Ctr Dr,MSC-1650, Bethesda, MD 20892 USA. EM QUYYUMIA@GWGATE.NHLBI.NIH.GOV NR 47 TC 49 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1998 VL 32 IS 4 BP 904 EP 911 DI 10.1016/S0735-1097(98)00323-4 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 124ZZ UT WOS:000076214000007 PM 9768710 ER PT J AU Afridi, I Grayburn, PA Panza, JA Oh, JK Zoghbi, WA Marwick, TH AF Afridi, I Grayburn, PA Panza, JA Oh, JK Zoghbi, WA Marwick, TH TI Myocardial viability during dobutamine echocardiography predicts survival in patients with coronary artery disease and severe left ventricular systolic dysfunction SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 70th Scientific Session of the American-Heart-Association Meeting CY NOV 09-13, 1997 CL ORLANDO, FLORIDA SP Amer Heart Assoc ID POSITRON EMISSION TOMOGRAPHY; REDISTRIBUTION TL-201 TOMOGRAPHY; WALL-MOTION ABNORMALITIES; HIBERNATING MYOCARDIUM; EJECTION FRACTION; BYPASS-SURGERY; VIABLE MYOCARDIUM; F-18 FLUORODEOXYGLUCOSE; STRESS ECHOCARDIOGRAPHY; ISCHEMIC CARDIOMYOPATHY AB Objectives. The purpose of this study was to assess whether the presence or absence of myocardial viability during dobutamine echocardiography (DE) predicts survival in patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction. Background. In patients with CAD, the presence of myocardial viability during DE identifies viable myocardium and predicts recovery of LV systolic function after revascularization. However, there is little data on the relation between myocardial viability and clinical outcome in patients with CAD and severe LV dysfunction, Methods. We studied 318 patients with CAD and a LV ejection fraction (EF) less than or equal to 35% who underwent DE and mere followed for 18 +/- 10 months, Patients were classified into four groups. Group I (n = 85) consisted of patients who had evidence of myocardial viability and subsequently underwent revascularization, Group II (n = 119) consisted of patients with myocardial viability who did neat undergo revascularization. Group III (n = 30) consisted of patients who did not have myocardial viability and underwent revascularization, Finally, group IV (n = 84) patients lacked myocardial viability and did not undergo revascularization. Results. The four groups had similar baseline characteristics and rest LVEF. During follow-up there were 51 deaths (16%). The mortality rate was 6% in group I, 20% in group II, 17% in group III and 20% in group TV (p = 0.01, group I vs. other groups). Conclusions. In patients with CAD and severe LV dysfunction who demonstrated myocardial viability during DE, revascularization improved survival compared with medical therapy. (C) 1998 by the American College of Cardiology. C1 Univ Texas, SW Med Ctr, Div Cardiol, Dallas, TX USA. NIH, Div Cardiol, Bethesda, MD 20892 USA. Mayo Clin, Div Cardiol, Rochester, MN USA. Baylor Coll Med, Div Cardiol, Houston, TX 77030 USA. Cleveland Clin, Div Cardiol, Cleveland, OH 44106 USA. RP Afridi, I (reprint author), Vet Affairs Hosp, Sect Cardiol 111A, 4500 S Lancaster Rd, Dallas, TX 75216 USA. EM Afridi@ryburn.swmed.edu RI Marwick, Thomas/C-7261-2013 OI Marwick, Thomas/0000-0001-9065-0899 NR 41 TC 167 Z9 174 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT PY 1998 VL 32 IS 4 BP 921 EP 926 DI 10.1016/S0735-1097(98)00321-0 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 124ZZ UT WOS:000076214000009 PM 9768712 ER PT J AU Gould, KA Eickhoff-Shemek, JM Stacy, RD Mecklenburg, RE AF Gould, KA Eickhoff-Shemek, JM Stacy, RD Mecklenburg, RE TI The impact of National Cancer Institute training on clinical tobacco use cessation services by oral health teams SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID DENTISTS; QUIT AB The authors surveyed participants in a National Cancer institute, or NCI, training program that provides brief tobacco cessation services. They found significant improvements in the frequency with which practitioners ask patients about tobacco use and assist patients in stopping tobacco use. Improvements also were found in the participants' level of confidence and preparedness to help patients quit. Despite some limitations, the NCI training was shown to be an effective program for the oral health care team. C1 Univ Nebraska, Sch Hlth Phys Educ & Recreat, Omaha, NE 68182 USA. NCI, Smoking & Tobacco Control Program, Bethesda, MD 20892 USA. RP Gould, KA (reprint author), Univ Nebraska, Sch Hlth Phys Educ & Recreat, 6001 Dodge St, Omaha, NE 68182 USA. NR 19 TC 12 Z9 12 U1 0 U2 1 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1998 VL 129 IS 10 BP 1442 EP 1449 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 127HW UT WOS:000076345800033 PM 9787541 ER PT J AU Slavkin, HC AF Slavkin, HC TI Cell biology, disease susceptibility and innovative therapeutics SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article ID OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; CBFA1 C1 NIDR, Bethesda, MD 20892 USA. RP Slavkin, HC (reprint author), NIDR, 31 Ctr Dr,MSC 2290,Bldg 31,Room 2C39, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD OCT PY 1998 VL 129 IS 10 BP 1462 EP 1466 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 127HW UT WOS:000076345800036 PM 9787544 ER PT J AU Van Horn, L Donato, K Kumanyika, S Winston, M Prewitt, TE Snetselaar, L AF Van Horn, L Donato, K Kumanyika, S Winston, M Prewitt, TE Snetselaar, L TI The dietitian's role in developing and implementing the first federal obesity guidelines SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Editorial Material ID FAT DISTRIBUTION; CALORIC RESTRICTION; HEART-DISEASE; WEIGHT-LOSS; BODY-FAT; WOMEN; RISK; EXERCISE; MEN; ASSOCIATION C1 Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. NHLBI, Obes Educ Initiat, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Amer Heart Assoc, Dallas, TX 75231 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ Iowa, Iowa City, IA USA. RP Van Horn, L (reprint author), Northwestern Univ, Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 112 D335, Chicago, IL 60611 USA. NR 31 TC 2 Z9 2 U1 1 U2 1 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD OCT PY 1998 VL 98 IS 10 BP 1115 EP 1117 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 126WG UT WOS:000076317200013 PM 9787716 ER PT J AU Leveille, SG Wagner, EH Davis, C Grothaus, L Wallace, J LoGerfo, M Kent, D AF Leveille, SG Wagner, EH Davis, C Grothaus, L Wallace, J LoGerfo, M Kent, D TI Preventing disability and managing chronic illness in frail older adults: A randomized trial of a community-based partnership with primary care SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Geriatrics-Society/American-Federation-for-Aging-Research CY MAY 09, 1997 CL ATLANTA, GEORGIA SP Amer Geriatr Soc ID HEALTH-STATUS MEASURES; PHYSICAL-ACTIVITY; ELDERLY PEOPLE; MAINTAINING MOBILITY; 6-MINUTE WALK; HIP FRACTURE; LATE-LIFE; RISK; EXERCISE; INTERVENTION AB BACKGROUND: Effective new strategies that complement primary care are needed to reduce disability risks and improve self-management of chronic illness in frail older people living in the community. OBJECTIVE: To evaluate the impact of a 1-year, senior center-based chronic illness self-management and disability prevention program on health, functioning, and healthcare utilization in frail older adults. DESIGN: A randomized controlled trial. SETTING: A large senior center located in a northeast Seattle suburb. The trial was conducted in collaboration with primary care providers of two large managed care organizations. PARTICIPANTS: A total of 201 chronically ill older adults seniors aged 70 and older recruited through medical practices. INTERVENTION: A targeted, multi-component disability prevention and disease self-management program led by a geriatric nurse practitioner (GNP). MEASUREMENTS: Self-reported Physical function, physical performance tests, health care utilization, and health behaviors. RESULTS: Each of 101 intervention participants met with the GNP from 1 to 8 times (median = 3) during the study year. The intervention group showed less decline in function, as measured by disability days and lower scores on the Health Assessment Questionnaire. Other measures of function, including the SF-36 and a battery of physical performance tests, did not change with the intervention. The number of hospitalized participants increased by 69% among the controls and decreased by 38% in the intervention group(P=.083). The total number of inpatient hospital days during the study year was significantly less in the intervention group compared with controls (total days = 33 vs 116, P =.049). The intervention led to significantly higher levels of physical activity and senior center participation and significant reductions in the use of psychoactive medications. CONCLUSIONS: This project provides evidence that a community-based collaboration with primary care providers can improve function and reduce inpatient utilization in chronically ill older adults. Linking organized medical care with complementary community-based interventions may be a promising direction for research and practice. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA USA. Northshore Senior Ctr & Senior Serv Seattle King, Seattle, WA USA. PacifiCare Washington, Seattle, WA USA. RP Leveille, SG (reprint author), NIA, Epidemiol Demog & Biometry Program, 7201 Wisconsin Ave,Suite 3C-309, Bethesda, MD 20892 USA. NR 58 TC 145 Z9 145 U1 5 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1998 VL 46 IS 10 BP 1191 EP 1198 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 127HT UT WOS:000076345400001 PM 9777899 ER PT J AU Bradley, EH Peiris, V Wetle, T AF Bradley, EH Peiris, V Wetle, T TI Discussions about end-of-life care in nursing homes SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID PHYSICIAN-PATIENT COMMUNICATION; ADVANCE DIRECTIVES; MEDICAL-CARE; SUSTAINING TREATMENTS; PREFERENCES; ATTITUDES; DECISIONS; INPATIENTS; CLINICIAN; BARRIERS AB OBJECTIVE: To measure the frequency with which nursing home residents and their surrogates discuss with clinicians the resident's wishes concerning future treatment and to assess the influence of the Patient Self Determination Act (PSDA) on the frequency and nature of such discussions. DESIGN: Retrospective cohort study of residents admitted to nursing homes before and after the PSDA. SETTING: Six large (at least 120 licensed chronic care beds), randomly selected nursing homes in Connecticut. PARTICIPANTS: Six hundred randomly selected nursing home residents admitted during 1990 and 1994 to one of the six study nursing homes. MEASUREMENTS: Documented discussions concerning future treatment wishes were abstracted from residents' nursing home medical records. Participants in the discussion, as well as the timing (i.e., date) and content of the documented discussions were recorded. Sociodemographic and health status factors were also obtained from the medical record. RESULTS: A large majority of residents (71.5%) had no discussion of future treatment wishes documented in their medical record. However, the percentage of residents with documented discussions had increased since the implementation of the PSDA (36.7% post-PSDA vs 20.3% pre-PSDA). Of those in the post-PSDA cohort who had had discussions, 90% had only one discussion within the first year of admission, and more than half (58.1%) of those who had discussions discussed only life-support systems (cardiopulmonary resuscitation, artificial nutrition and hydration, and ventilation) rather than broader preferences for future treatment, including proxy decision-making. CONCLUSIONS: Despite the increased prevalence of discussions about future treatment wishes since the enactment of the PSDA, no discussions were documented for most residents. For those with documented discussions, such conversations occurred rarely and were narrow in scope, suggesting that residents' and families' roles in medical decision-making in nursing homes may be limited. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Bradley, EH (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. FU AHRQ HHS [1T32HS00052] NR 42 TC 34 Z9 34 U1 3 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1998 VL 46 IS 10 BP 1235 EP 1241 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 127HT UT WOS:000076345400007 PM 9777905 ER PT J AU Parshad, R Price, FM Schapiro, MB Sanford, KK AF Parshad, R Price, FM Schapiro, MB Sanford, KK TI Effect of DNA repair inhibitors on the in vitro test for Alzheimer's disease SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Letter ID DAMAGE C1 Howard Univ, Coll Med, Washington, DC 20059 USA. NCI, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. RP Parshad, R (reprint author), Howard Univ, Coll Med, Washington, DC 20059 USA. NR 6 TC 1 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD OCT PY 1998 VL 46 IS 10 BP 1331 EP 1333 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 127HT UT WOS:000076345400034 PM 9777930 ER PT J AU Carlson, SG Eng, E Kim, EC Perlman, EJ Copeland, TD Ballermann, BJ AF Carlson, SG Eng, E Kim, EC Perlman, EJ Copeland, TD Ballermann, BJ TI Expression of SET, an inhibitor of protein phosphatase 2A, in renal development and Wilms' tumor SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID ACUTE UNDIFFERENTIATED LEUKEMIA; HUMAN-FETAL KIDNEY; OKADAIC ACID; MESSENGER-RNA; CELL-GROWTH; GENE; KINASE; WT1; PHOSPHORYLATION; IDENTIFICATION AB The human gene set was originally identified as a component of the set-can fusion gene produced by a somatic translocation event in a case of acute undifferentiated leukemia. In the developing kidney, set was highly expressed in the zone of nephron morphogenesis. Recently, SET was shown to be a potent and specific inhibitor of protein phosphatase 2A, a family of major serine/threonine phosphatases involved in regulating cell proliferation and differentiation. The current study sought to define further the role of SET in the regulation of renal cell proliferation and tumorigenesis. The mRNA encoding SET was expressed at much higher levels in transformed human and rodent cell lines than in cultured renal epithelial and primary endothelial cells. Consistent with a role for SET in cell proliferation, set mRNA expression was markedly reduced in cells rendered quiescent by serum starvation, contact inhibition, or differentiation. Previous findings during renal development were extended by demonstrating that SET protein expression is also much greater in developing rat and human kidney than in fully differentiated, mature kidney. Finally, high levels of set mRNA and SET protein expression were found in Wilms' tumor, but not in renal cell carcinoma, adult polycystic kidney disease or in transitional cell carcinoma. C1 Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Baltimore, MD 21205 USA. Chungbuk Natl Univ, Sch Med, Cheongju, South Korea. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD USA. RP Ballermann, BJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Nephrol, Room 954 Ross Res Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Ballermann, Barbara/G-5349-2016 OI Ballermann, Barbara/0000-0002-8220-6381 FU NIDDK NIH HHS [5T32DK07712, DK09388, DK50764] NR 38 TC 54 Z9 56 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD OCT PY 1998 VL 9 IS 10 BP 1873 EP 1880 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 122YY UT WOS:000076100100013 PM 9773788 ER PT J AU Khanna, C Lund, EM Redic, KA Hayden, DW Bell, FW Goulland, EL Klausner, JS AF Khanna, C Lund, EM Redic, KA Hayden, DW Bell, FW Goulland, EL Klausner, JS TI Randomized controlled trial of doxorubicin versus dactinomycin in a multiagent protocol for treatment of dogs with malignant lymphoma SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID PROGNOSTIC FACTORS; CANINE LYMPHOMA; ACTINOMYCIN-D; RESISTANCE; REMISSION AB Objective-To compare efficacy and toxicity of 2 multiagent chemotherapeutic protocols similar in all respects except that 1 incorporated dactinomycin and the other incorporated doxorubicin for treatment of dogs with malignant lymphoma. Design-Randomized controlled trial. Animals-45 dogs with malignant lymphoma. Procedure-Dogs were randomly assigned to a doxorubicin or dactinomycin treatment group. Time to first remission, duration of first remission, survival time, and prevalence of toxicoses, particularly number of episodes of dose-limiting neutropenia and gastrointestinal toxicoses, were compared between groups. Results-37 dogs received at least 1 dose of doxorubicin (21 dogs) or dactinomycin (16). Median time to first remission was not significantly different between groups, but median duration of first remission and median survival time were significantly longer for dogs in the doxorubicin treatment group than for dogs in the dactinomycin treatment group. Number of dogs that died, number of episodes of dose-limiting neutropenia, and number of episodes of gastrointestinal toxicoses were not significantly different between groups. Clinical Implications-A multiagent chemotherapeutic protocol incorporating doxorubicin was significantly more effective in dogs with malignant lymphoma than a similar protocol incorporating dactinomycin. Despite the lower cost and lack of cardiotoxicity, dactinomycin is not an equivalent substitute for doxorubicin in the initial treatment of dogs with malignant lymphoma. C1 Univ Minnesota, Coll Vet Med, Dept Small Anim Clin Sci, St Paul, MN 55108 USA. Univ Minnesota, Coll Vet Med, Dept Vet Diagnost Med, St Paul, MN 55108 USA. Univ Minnesota, Coll Vet Med, Vet Med Teaching Hosp, St Paul, MN 55108 USA. Metropolitan Vet Referral Serv, Eden Prairie, MN 55344 USA. RP Khanna, C (reprint author), NCI, Pediat Oncol Branch, NIH, 13N240 Bldg 10, Bethesda, MD 20892 USA. NR 18 TC 32 Z9 32 U1 1 U2 1 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD OCT 1 PY 1998 VL 213 IS 7 BP 985 EP + PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 126DP UT WOS:000076277900033 PM 9776993 ER PT J AU Ostrowski, MA Krakauer, DC Li, YX Justement, SJ Learn, G Ehler, LA Stanley, SK Nowak, M Fauci, AS AF Ostrowski, MA Krakauer, DC Li, YX Justement, SJ Learn, G Ehler, LA Stanley, SK Nowak, M Fauci, AS TI Effect of immune activation on the dynamics of human immunodeficiency virus replication and on the distribution of viral quasispecies SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; CHEMOKINE RECEPTORS; HIV-1-INFECTED INDIVIDUALS; FUSION COFACTOR; T-LYMPHOCYTES; TROPIC HIV-1; IN-VIVO; PLASMA; TYPE-1 AB Virus replication in a human immunodeficiency virus (HIV)-infected individual, as determined by the steady-state level of plasma viremia, reflects a complex balance of viral and host factors. We have previously demonstrated that immunization of HIV-infected individuals with the common recall antigen, tetanus toroid, disrupts this steady state, resulting in transient bursts of plasma viremia after immunization. The present study defines the viral genetic basis for the transient bursts in viremia after immune activation. Tetanus immunization was associated with dramatic and generally reversible shifts in the composition of plasma viral quasispecies. The viral bursts in most cases reflected a nonspecific increase in viral replication secondary to an expanded pool of susceptible CD4(+) T cells. An exception to this was in a patient who harbored viruses of differing tropisms (syncytium inducing and non-syncytium inducing [NSI]). In this situation, immunization appeared to select for the replication of NSI viruses. In one of three patients, the data suggested that immune activation resulted in the appearance in plasma of virus induced from latently infected cells. These findings illustrate certain mechanisms whereby antigenic stimulation may influence the dynamics of HIV replication, including the relative expression of different viral variants. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, Dept Zool, Oxford OX1 2JD, England. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. RP Ostrowski, MA (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A11, Bethesda, MD 20892 USA. RI Nowak, Martin/A-6977-2008; Learn, Gerald/B-6934-2011 FU PHS HHS [A127757, A132885] NR 54 TC 72 Z9 72 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1998 VL 72 IS 10 BP 7772 EP 7784 PG 13 WC Virology SC Virology GA 118WN UT WOS:000075864100008 PM 9733813 ER PT J AU Jia, XY van Eden, M Busch, MG Ehrenfeld, E Summers, DF AF Jia, XY van Eden, M Busch, MG Ehrenfeld, E Summers, DF TI trans-Encapsidation of a poliovirus replicon by different picornavirus capsid proteins SO JOURNAL OF VIROLOGY LA English DT Article ID RIBOSOMAL ENTRY SITE; 5'-NONCODING REGION; IN-VITRO; RNA; VIRUS; PARTICLES; COMPLEMENTATION; IDENTIFICATION; REPLICATION; INFECTIVITY AB A trans-encapsidation assay was established to study the specificity of picornavirus RNA encapsidation. A poliovirus replicon with the luciferase gene replacing the capsid protein-coding region was coexpressed in transfected HeLa cells with capsid proteins from homologous or heterologous virus. Successful tuans-encapsidation resulted in assembly and production of virions whose replication, upon subsequent infection of HeLa cells, was accompanied by expression of luciferase activity. The amount of luciferase activity was proportional to the amount of trans-encapsidated virus produced from the cotransfection. When poliovirus capsid proteins were supplied in trans, >2 x 10(6) infectious particles/ml were produced. When coxsackievirus B3, human rhinovirus 14, mengovirus, or hepatitis A virus (HAV) capsid proteins were supplied in trans, all but HAV showed some encapsidation of the replicon. The overall encapsidation efficiency of the replicon RNA by heterologous capsid proteins was significantly lower than when poliovirus capsid was used, trans-encapsidated particles could be completely neutralized with specific antisera against each of the donor virus capsids. The results indicate that encapsidation is regulated by specific viral nucleic acid and protein sequences. C1 Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Mol Biol & Biochem, Irvine, CA 92697 USA. RP Summers, DF (reprint author), NCI, Frederick Canc Res & Dev Ctr, NIH, POB B,Bldg 427,Room 10, Frederick, MD 21702 USA. FU NIAID NIH HHS [AI 17386, AI 26350] NR 37 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1998 VL 72 IS 10 BP 7972 EP 7977 PG 6 WC Virology SC Virology GA 118WN UT WOS:000075864100030 PM 9733835 ER PT J AU Rossio, JL Esser, MT Suryanarayana, K Schneider, DK Bess, JW Vasquez, GM Wiltrout, TA Chertova, E Grimes, MK Sattentau, Q Arthur, LO Henderson, LE Lifson, JD AF Rossio, JL Esser, MT Suryanarayana, K Schneider, DK Bess, JW Vasquez, GM Wiltrout, TA Chertova, E Grimes, MK Sattentau, Q Arthur, LO Henderson, LE Lifson, JD TI Inactivation of human immunodeficiency virus type 1 infectivity with preservation of conformational and functional integrity of virion surface proteins SO JOURNAL OF VIROLOGY LA English DT Article ID HIV NUCLEOCAPSID PROTEIN; MURINE LEUKEMIA VIRUSES; T-CELLS; MONOCLONAL-ANTIBODIES; CELLULAR PROTEINS; ZINC EJECTION; ANTI-HIV; PORPHOBILINOGEN DEAMINASE; ENVELOPE GLYCOPROTEIN; DISULFIDE BENZAMIDES AB Whole inactivated viral particles have been successfully used as vaccines for some viruses, but procedures historically used for inactivation can denature virion proteins. Results have been inconsistent, with enhancement of disease rather than protection seen in some notable instances following vaccination. We used the compound 2,2'-dithiodipyridine (aldrithiol-2; AT-2) to covalently modify the essential zinc fingers in the nucleocapsid (NC) protein of human immunodeficiency virus type 1 (HIV-1) or simian immunodeficiency virus (SIV) virions, thereby inactivating infectivity. The inactivated virus was not detectably infectious in vitro (up to 5 log units of inactivation). However, in contrast to virions inactivated by conventional methods such as heat or formalin treatment, viral and host cell-derived proteins on virion surfaces retained conformational and functional integrity. Thus, immunoprecipitation of AT-2-treated virions was comparable to precipitation of matched untreated virus, even when using antibodies to conformational determinants on gp120. AT-2 inactivated virions bound to CD4(+) target cells and mediated virus-induced, CD4-dependent "fusion from without" comparably to native virions. However, viral entry assays demonstrated that the viral life cycle of AT-2-treated virions was arrested before initiation of reverse transcription. The major histocompatibility complex (MHC) class II molecules on the surface of AT-2-treated virions produced from MHC class II-expressing cells retained the ability to support class II-dependent, superantigen-triggered proliferative responses by resting T lymphocytes. These findings indicate that inactivation via this method results in elimination of infectivity with preservation of conformational and functional integrity of virion surface proteins, including both virally encoded determinants and proteins derived from the host cells in which the virus was produced. Such inactivated virions should provide a promising candidate vaccine antigen and a useful reagent for experimentally probing the postulated involvement of virion surface proteins in indirect mechanisms of HIV-1 pathogenesis. C1 NCI, Frederick Canc Res & Dev Ctr, Retroviral Pathogenesis Lab, AIDS Vaccine Program,SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Biol Prod Lab, AIDS Vaccine Program,SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Prot Chem Lab, AIDS Vaccine Program,SAIC Frederick, Frederick, MD 21702 USA. Ctr Immunol Marseille Luminy, Marseille, France. RP Lifson, JD (reprint author), NCI, Frederick Canc Res & Dev Ctr, Retroviral Pathogenesis Lab, AIDS Vaccine Program,SAIC Frederick, Bldg 535,Room 510, Frederick, MD 21702 USA. RI Bess, Jr., Julian/B-5343-2012 FU NCI NIH HHS [N01-CO-56000] NR 74 TC 301 Z9 310 U1 1 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1998 VL 72 IS 10 BP 7992 EP 8001 PG 10 WC Virology SC Virology GA 118WN UT WOS:000075864100033 PM 9733838 ER PT J AU Reddy, SM Cox, E Iofin, I Soong, W Cohen, JI AF Reddy, SM Cox, E Iofin, I Soong, W Cohen, JI TI Varicella-Zoster virus (VZV) ORF32 encodes a phosphoprotein that is posttranslationally modified by the VZV ORF47 protein kinase SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEOTIDE-SEQUENCE; REGULATORY PROTEIN; VIRAL REPLICATION; DNA-SEQUENCE; IN-VITRO; PHOSPHORYLATION; CELLS AB Varicella-zoster virus (VZV) encodes five gene products that do not have homologs in herpes simplex virus. One of these genes, VZV open reading frame 32 (ORF32), is predicted to encode a protein of 16 kDa, VZV ORF32 protein was shown to be phosphorylated and located in the cytosol of virus-infected cells. Antibody to ORF32 protein immunoprecipitated 16- and 18-kDa phosphoproteins from VZV-infected cells. Since VZV encodes two protein kinases that might phosphorylate ORF32 protein, immunoprecipitations were performed with cells infected with VZV mutants unable to express either of the viral protein kinases, Cells infected with VZV unable to express the ORF66 protein kinase contained both the 16- and 18-kDa ORF32 phosphoproteins; however, cells infected with the VZV ORF47 protein kinase mutant showed only the 16-kDa ORF32 phosphoprotein. Treatment of [S-35] methionine-labeled proteins with calf intestine alkaline phosphatase resulted in a decrease in size of the ORF32 proteins from 16 and 18 kDa to 15 and 17 kDa, respectively. VZV unable to express ORF32 protein replicated in human melanoma cells to titers similar to those seen with parental virus; however, VZV unable to express ORF32 was impaired for replication in U20S osteosarcoma cells. Thus, VZV ORF32 protein is posttranslationally modified by the ORF47 protein kinase, Since the VZV ORF47 protein kinase has recently been shown to be critical for replication in human fetal skin and lymphocytes, its ability to modify the ORF32 protein suggests that the latter protein may have a role for VZV replication in human tissues. C1 NIAID, Clin Invest Lab, Med Virol Sect, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Bldg 10,Rm 11N214, Bethesda, MD 20892 USA. NR 25 TC 28 Z9 29 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1998 VL 72 IS 10 BP 8083 EP 8088 PG 6 WC Virology SC Virology GA 118WN UT WOS:000075864100043 PM 9733848 ER PT J AU Balmelli, C Roden, R Potts, A Schiller, J De Grandi, P Nardelli-Haefliger, D AF Balmelli, C Roden, R Potts, A Schiller, J De Grandi, P Nardelli-Haefliger, D TI Nasal immunization of mice with human papillomavirus type 16 virus-like particles elicits neutralizing antibodies in mucosal secretions SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX VIRUS; FEMALE GENITAL-TRACT; SECRETORY IMMUNOGLOBULIN-A; INTRANASAL IMMUNIZATION; CHOLERA-TOXIN; IMMUNE-RESPONSES; LYMPHOID-TISSUE; IMMUNOLOGICAL SYSTEM; VASCULAR ADDRESSIN; VAGINAL SECRETIONS AB To specifically induce a mucosal antibody response to purified human papillomavirus type 16 (HPV16) virus-like particles (VLP), we immunized female BALB/c mice orally, intranasally, and/or parenterally and evaluated cholera toxin (CT) as a mucosal adjuvant. Anti-HPV16 VLP immunoglobulin G (IgG) and IgA titers in serum, saliva, and genital secretions were measured by enzyme-linked immunosorbent assay (ELISA). Systemic immunizations alone induced HPV16 VLP-specific IgG in serum and, to a lesser extent, in genital secretions but no secretory IgA. Oral immunization, even in the presence of CT, was inefficient. However, three nasal immunizations with 5 mu g of VLP given at weekly intervals to anesthetized mice induced high (>10(4)) and long-lasting (>15 weeks) titers of anti-HPV16 VLP antibodies in all samples, including IgA and IgG in saliva and genital secretions. CT enhanced the VLP-specific antibody response 10-fold in serum and to a lesser extent in saliva and genital secretions. Nasal immunization of conscious mice compared to anesthetized mice was inefficient and correlated with the absence of uptake of a marker into the lung. However, a l-mu g VLP systemic priming followed by two 5-mu g VLP intranasal boosts in conscious mice induced both HPV16 VLP-specific IgG and IgA in secretions, although the titers were lower than in anesthetized mice given three intranasal immunizations. Antibodies in serum, saliva, and genital secretions of immunized mice were strongly neutralizing in vitro (50% neutralization with ELISA titers of 65 to 125). The mucosal and systemic/mucosal HPV16 VLP immunization protocols that induced significant titers of neutralizing IgG and secretory IgA in mucosal secretions in mice may be relevant to genital HPV VLP-based human vaccine trials. C1 CHU Vaudois, Dept Gynecol, CH-1011 Lausanne, Switzerland. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Nardelli-Haefliger, D (reprint author), Inst Microbiol, Dept Gynecol, Bugnon 44, CH-1011 Lausanne, Switzerland. NR 65 TC 118 Z9 125 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1998 VL 72 IS 10 BP 8220 EP 8229 PG 10 WC Virology SC Virology GA 118WN UT WOS:000075864100060 PM 9733865 ER PT J AU Belyakov, IM Wyatt, LS Ahlers, JD Earl, P Pendleton, CD Kelsall, BL Strober, W Moss, B Berzofsky, JA AF Belyakov, IM Wyatt, LS Ahlers, JD Earl, P Pendleton, CD Kelsall, BL Strober, W Moss, B Berzofsky, JA TI Induction of a mucosal cytotoxic T-lymphocyte response by intrarectal immunization with a replication-deficient recombinant vaccinia virus expressing human immunodeficiency virus 89.6 envelope protein SO JOURNAL OF VIROLOGY LA English DT Article ID CLASS-I; MHC MOLECULE; HIV-1; INFECTION; IMMUNITY; MACAQUES; PEPTIDE; GP160; RECOGNITION; DETERMINANT AB To improve the safety of recombinant vaccinia virus vaccines, modified vaccinia virus Ankara (MVA) has been employed, because it has a replication defect in most mammalian cells. Here we apply MVA to human immunodeficiency virus type 1 (HIV-1) vaccine development by incorporating the envelope protein gp160 of HIV-1 primary isolate strain 89.6 (MVA 89.6) and use it to induce mucosal cytotoxic-T-lymphocyte (CTL) immunity. In initial studies to define a dominant CTL epitope for HIV-1 89.6 gp160, we mapped the epitope to a sequence, IGPGRAFYAR (from the V3 loop), homologous to that recognized by HIV MN loop-specific CTL and showed that HIV-1 MN-specific CTLs cross-reactively recognize the corresponding epitope from strain 89.6 presented by H-2D(d). Having defined the CTL specificity, we immunized BALB/c mice intrarectally with recombinant MVA 89.6. A single mucosal immunization with MVA 89.6 was able to elicit long-lasting antigen-specific mucosal (Peyer's patch and lamina propria) and systemic (spleen) CTL responses as effective as or more effective than those of a replication-competent vaccinia virus expressing 89.6 gp160. Immunization with MVA 89.6 led to (i) the loading of antigen-presenting cells in vivo, as measured by the ex vivo active presentation of the P18-89.6 peptide to an antigen-specific CTL line, and (ii) the significant production of the proinflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) in the mucosal sites. These results indicate that nonreplicating recombinant MVA may be at least as effective for mucosal immunization as replicating recombinant vaccinia virus. C1 NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mucosal Immun Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, Mol Immunogenet & Vaccine Res Sect, Metab Branch, NIH, Bldg 10,Room 6B-12,MSC 1578, Bethesda, MD 20892 USA. NR 39 TC 108 Z9 109 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1998 VL 72 IS 10 BP 8264 EP 8272 PG 9 WC Virology SC Virology GA 118WN UT WOS:000075864100065 PM 9733870 ER PT J AU Nihrane, A Fujita, K Willey, R Lyu, MS Silver, J AF Nihrane, A Fujita, K Willey, R Lyu, MS Silver, J TI Murine leukemia virus envelope protein in transgenic-mouse serum blocks infection in vitro (Retraction of vol 70, pg 1882, 1996) SO JOURNAL OF VIROLOGY LA English DT Correction C1 NIAID, Mol Microbiol Lab, Bethesda, MD 20892 USA. RP Nihrane, A (reprint author), NIAID, Mol Microbiol Lab, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD OCT PY 1998 VL 72 IS 10 BP 8462 EP 8462 PG 1 WC Virology SC Virology GA 118WN UT WOS:000075864100102 PM 9766975 ER PT J AU DeRenzo, EG AF DeRenzo, EG TI Power differentials, context, relationship, and emotions: Feminist ethics considerations and human subjects research SO JOURNAL OF WOMENS HEALTH LA English DT Article AB As increasing attention is paid to the ethical concerns raised by human subject research, more needs to be focused on issues usually not discussed in the research ethics literature. No longer is it sufficient to talk only about the conflicting goals of clinical care and clinical research. We need to delve more deeply into how human subjects studies are performed and examine the feminist ethics issues of power differentials, context, relationships, and emotions. The source of much of our moral discomfort with clinical trials frequently is in these components of the clinical research settings that are discussed less often. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP DeRenzo, EG (reprint author), NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 23 TC 3 Z9 3 U1 1 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1059-7115 J9 J WOMENS HEALTH JI J. Womens Health PD OCT PY 1998 VL 7 IS 8 BP 971 EP 977 DI 10.1089/jwh.1998.7.971 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 137UU UT WOS:000076935400013 PM 9812292 ER PT J AU Kopp, JB AF Kopp, JB TI Hepatocyte growth factor: Mesenchymal signal for epithelial homeostasis SO KIDNEY INTERNATIONAL LA English DT Editorial Material DE embryonic morphogenesis; tumor progression; tissue regeneration; preproHGF; scatter factor ID ACUTE-RENAL-FAILURE; REGENERATION; CELLS; RECEPTOR; INJURY; RATS; MICE; MET C1 NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDK, Kidney Dis Sect, NIH, 10-3N116, Bethesda, MD 20892 USA. OI Kopp, Jeffrey/0000-0001-9052-186X NR 17 TC 24 Z9 25 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD OCT PY 1998 VL 54 IS 4 BP 1392 EP 1393 DI 10.1046/j.1523-1755.1998.00126.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 122XN UT WOS:000076096900044 PM 9773682 ER PT J AU Burris, JA Flynn, BM Dexter, SL AF Burris, JA Flynn, BM Dexter, SL TI A novel parasite in macaques - Pseudoparasite SO LAB ANIMAL LA English DT Article C1 US FDA, Rockville, MD 20852 USA. NCI, Lab Anim Med Sect, Bethesda, MD 20892 USA. AAALAC Int, Rockville, MD USA. RP Burris, JA (reprint author), US FDA, 1451 Rockville Pike, Rockville, MD 20852 USA. NR 3 TC 1 Z9 1 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD OCT PY 1998 VL 27 IS 9 BP 21 EP 22 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 129LK UT WOS:000076464700003 ER PT J AU Coe, JE Ishak, KG Ross, MJ AF Coe, JE Ishak, KG Ross, MJ TI Estrogen-induced hepatic toxicity and hepatic cancer: differences between two closely related hamster species SO LIVER LA English DT Article DE estrogen-induced hepatic toxicity/tumors ID PERIPORTAL SINUSOIDAL DILATATION; ORAL-CONTRACEPTIVES; PROGESTERONE; RECEPTOR; LIVER; ATHEROSCLEROSIS; INDUCTION; STEROIDS; CHINESE; DISEASE AB Aims/Background: Estrogen is known to affect hepatobiliary function; however, it is unusual for high serum levels of estrogen to actually result in clinically detectable hyperbilirubinemia. Women affected by cholestatic jaundice during pregnancy share this genetic susceptibility with two Cricetulus hamsters, the Armenian hamster (Cricetulus migratorius) and the Chinese hamster (Cricetulus griseus). Nevertheless, the pathophysiologic process responsible for this estrogen induced icterus may be different in women and hamsters. The present study compares various facets of estrogen-induced icterus in these two closely related hamsters. Methods: Hamsters were injected with various estrogens and the acute and chronic effects on liver were monitored by measuring changes in serum constituents and by observing changes in hepatic structure as seen grossly and by light and electron microscopy. Results: In previous studies, hepatic tumors developed in most Armenian hamsters after chronic estrogen treatment, but in the present study, the livers of Chinese hamsters were remarkably free of neoplastic change under similar conditions. Also, when compared with the responses in the Armenian hamsters, signs of hepatic destruction and regeneration were less prevalent in estrogen-treated Chinese hamsters, and they were less susceptible to the effects of estrogen (because larger doses of estrogen were required to produce icterus and the bilirubin levels were-lower and of shorter duration). In contrast to the findings in Armenian hamsters, bile canaliculi were severely affected in livers of estrogen-treated Chinese hamsters, and hepatic microvesicular steatosis, indicative of an unusual lipodystrophy caused by estrogen, was prominent. An additional lesion peculiar to the Chinese hamster was striking sinusoidal dilatation, which may be analogous to the oral contraceptive-induced sinusoidal dilatation in humans. Conclusions: Although these two hamster species are genetically similar, the genes activated by the estrogen receptor show remarkable heterogeneity when their respective livers are examined. Comparisons within these species may provide information about the specific gene activation responsible for particular pathologic events. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Armed Forces Inst Pathol, Dept Hepat & Gastrointestinal Pathol, Washington, DC 20306 USA. RP Coe, JE (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. NR 31 TC 4 Z9 4 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0106-9543 J9 LIVER JI Liver PD OCT PY 1998 VL 18 IS 5 BP 343 EP 351 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 133WH UT WOS:000076710200008 PM 9831364 ER PT J AU Kim, YD AF Kim, YD TI Mechanisms of symptom in Bartoszynski's virus model SO MATHEMATICAL BIOSCIENCES LA English DT Article AB This paper is concerned with Bartoszynski's process for rabies viruses introduced by Bartoszynski [R. Bartoszynski, A model for risk rabies, ISI invited paper No. 9, ISI 1-9, IX Warsaw, 1975, pp. 545-552; Math. Biosci. 24 (1975) 355; W. Klonecki (Ed.) Proceedings of the IASPS Symposium to honour Jerzy Neyman, Warsaw, 1976, pp. 19-28]. Our main interests are in developing mechanisms of a symptom - how the probability of the occurrence of the symptom is related to the process. Four mechanisms are suggested based on various biological backgrounds, The main variable of interests is the survival time - the time elapsing between initial infection and the occurrence of the symptom. Analytical results about the survival functions induced from the four suggested mechanisms are studied. (C) 1998 Published by Elsevier Science Inc. All rights reserved. C1 NIH, Rockville, MD 20852 USA. RP Kim, YD (reprint author), NIH, 6100 Execut Blvd 7B13, Rockville, MD 20852 USA. NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD OCT PY 1998 VL 153 IS 1 BP 63 EP 78 DI 10.1016/S0025-5564(98)10031-7 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 133RZ UT WOS:000076700700004 PM 9810161 ER PT J AU Brooks, MM Jenkins, LS Schron, EB Steinberg, JS Cross, JA Paeth, DS AF Brooks, MM Jenkins, LS Schron, EB Steinberg, JS Cross, JA Paeth, DS CA AVID Investigators TI Quality of life at baseline - Is assessment after randomization valid? SO MEDICAL CARE LA English DT Article DE quality of life; baseline data; postrandomization data ID HEALTH AB OBJECTIVES. The purpose of this report is to examine whether differences existed between patients who completed a baseline quality of life (QoL) form before being informed about their randomized assignments versus those who completed it after knowing their randomization assignments. METHODS. in the pilot phase of the Antiarrhythmics Versus Implantable Defibrillators (AVID) study (n = 200), 113 patients completed a baseline QoL battery prior to randomization (drug versus defibrillator), 19 additional patients completed this battery after randomization, and 38 patients did not complete this battery. Baseline demographic, clinical and QoL data were compared for these groups. RESULTS. Although the two groups with QoL data were not significantly different regarding various clinical and demographic characteristics, they did have significantly different QoL profiles. Patients with QoL collected before randomization had better overall QoL scores and mental health scores. CONCLUSIONS. These data suggest that patients with worse QoL may be less willing to complete a baseline QoL form in a timely manner or that knowledge of the randomization assignment may have an effect on QoL. C1 AVID Clin Trial Ctr, Seattle, WA 98105 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Maryland, Baltimore, MD 21201 USA. NHLBI, Clin Trials Branch, Bethesda, MD 20892 USA. St Lukes Roosevelt Hosp Ctr, New York, NY USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP Brooks, MM (reprint author), AVID Clin Trial Ctr, 1107 NE 45th St,Room 505, Seattle, WA 98105 USA. OI Brooks, Maria/0000-0002-2030-7873 NR 13 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD OCT PY 1998 VL 36 IS 10 BP 1515 EP 1519 DI 10.1097/00005650-199810000-00009 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 131AR UT WOS:000076554000009 PM 9794344 ER PT J AU De Lucca, AJ Bland, JM Jacks, TJ Grimm, C Walsh, TJ AF De Lucca, AJ Bland, JM Jacks, TJ Grimm, C Walsh, TJ TI Fungicidal and binding properties of the natural peptides cecropin B and dermaseptin SO MEDICAL MYCOLOGY LA English DT Article DE cecropin B; conidia; dermaseptin; fungicidal; peptides ID CELL-WALL; ANTIBACTERIAL ACTIVITY; AMPHOTERICIN-B; ANTIFUNGAL SUSCEPTIBILITY; PHOSPHOLIPID-MEMBRANES; ANTIMICROBIAL ACTIVITY; INSECT IMMUNITY; PROTEINS; ANALOGS; YEAST AB In vitro fungicidal properties of cecropin B and dermaseptin were explored using nongerminating and germinating conidia from Aspergillus flavus, A. fumigatus, A. niger, Fusarium moniliforme and F. oxysporum. Cecropin B produced LD50 values for germinating A. flavus, A. fumigatus and A. niger conidia of 3.0, 0.5 and 2.0 mu M, respectively, while dermaseptin gave LD50 values of 4.0, 0.05 and 2.0 mu M, respectively. Cecropin B produced an LD50 value of 0.2 mu M for non-germinating F. morzilifoi me and F. oxysporum conidia, while dermaseptin did not reduce either as much as 50% at any level tested. LD50 levels for CB were 0.2 and 0.1 mu M, respectively, for germinating F. moniliforme and F. oxysporum conidia. Dermaseptin was less effective, giving LD50 values for germinating F. moniliforme and F. oxysporum conidia of 0.3 and 0.8 mu M, respectively. Neither peptide reduced conidial viabilities of non-germinating Aspergillus spp. Physicochemical studies indicated cecropin B and dermaseptin bound to ergosterol and cholesterol, conidial wall constituents, but not to chitin or beta-1,3-glucan. C1 ARS, So Reg Res Ctr, USDA, New Orleans, LA 70124 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP De Lucca, AJ (reprint author), ARS, So Reg Res Ctr, USDA, 1100 Robert E Lee Blvd, New Orleans, LA 70124 USA. EM adelucca@nola.srrc.usda.gov NR 42 TC 51 Z9 52 U1 1 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD OCT PY 1998 VL 36 IS 5 BP 291 EP 298 DI 10.1080/02681219880000461 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 130UB UT WOS:000076537800007 PM 10075498 ER PT J AU Striffler, JS Bhathena, SJ Michaelis, OE Campbell, JD Hansen, CT Scalbert, E Thibault, N Velasquez, MT AF Striffler, JS Bhathena, SJ Michaelis, OE Campbell, JD Hansen, CT Scalbert, E Thibault, N Velasquez, MT TI Long-term effects of perindopril on metabolic parameters and the heart in the spontaneously hypertensive/NIH-corpulent rat with non-insulin-dependent diabetes mellitus and hypertension SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID CONVERTING ENZYME-INHIBITION; LEFT-VENTRICULAR HYPERTROPHY; IMPAIRED GLUCOSE-TOLERANCE; MUSCLE BLOOD-FLOW; SKELETAL-MUSCLE; LIPID-METABOLISM; NIDDM PATIENTS; RESISTANCE; ENALAPRIL; CAPTOPRIL AB The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic model that exhibits both non-insulin-dependent diabetes mellitus (NIDDM) and hypertension. To determine the impact of long-term treatment with the long-acting angiotensin-coverting enzyme (ACE) inhibitor perindopril (PE) on the glucose metabolism, lipid levels, and heart in this model, studies were performed in three groups of SHR/N-cp rats maintained on a diet containing 54% carbohydrate with 18% sucrose and 36% starch. One group of obese rats received PE (0.5 to 1.0 mg/kg body weight/d) for 3 to 4 months, a second group of obese rats received no treatment, and a third group of lean rats were used as controls. The mean systolic blood pressure (SBP) increased gradually in both untreated obese and lean rats, with lean animals showing slightly higher levels compared with untreated obese rats. By contrast, SEP was reduced to normal levels in PE-treated obese rats throughout the treatment period. Compared with lean rats, obese rats showed significantly higher body weight and fasting serum levels of glucose, insulin, total cholesterol (TC), and triglyceride (TG). However, no significant differences were observed in these metabolic parameters between PE-treated and untreated obese rats. Plasma renin activity measured at the end of the treatment period was significantly higher in PE-treated rats compared with untreated obese and untreated lean rats. The mean heart weight and left ventricular weight, expressed in absolute terms or indexed to body weight, were significantly lower in PE-treated versus untreated obese and untreated lean rats. To further determine whether glucose metabolism is directly affected by PE treatment, in vitro glycogen synthesis was evaluated in isolated soleus muscles obtained from three additional groups of animals. The basal rate of muscle glycogen synthesis was significantly lower in obese compared with lean rats (P < .05), but did not differ between PE-treated and untreated obese rats. Maximal insulin-stimulated glycogen synthesis increased threefold in PE-treated obese rats, but this increase did not differ from the increases observed in untreated obese and lean rats. In conclusion, the present study shows that long-term PE treatment in obese SHR/N-cp rats with NIDDM and hypertension effectively controlled systemic arterial pressure and resulted in a significant reduction in left ventricular weight. However, these favorable effects of PE were not associated with significant improvement in glucose tolerance, hyperinsulinemia, and hyperlipidemia in this model. PE also had no direct stimulatory effects on either basal or insulin-mediated glycogen synthesis in the isolated soleus muscle of obese rats, perhaps because of the severe insulin-resistant state of the animals. Our results support the clinical observations that antihypertensive therapy with ACE inhibitors has neutral effects on glucose metabolism and insulin sensitivity in patients with combined hypertension and NIDDM. Copyright (C) 1998 by W.B. Saunders Company. C1 George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. ARS, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA. NIH, Vet Res Program, Bethesda, MD 20892 USA. Inst Rech Int Serv & Compagnie Dev, Paris, France. RP Velasquez, MT (reprint author), George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, 2150 Penn Ave NW, Washington, DC 20037 USA. NR 55 TC 11 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 1998 VL 47 IS 10 BP 1199 EP 1204 DI 10.1016/S0026-0495(98)90323-7 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 128FP UT WOS:000076395300006 PM 9781621 ER PT J AU Torpy, DJ Tsigos, C Lotsikas, AJ Defensor, R Chrousos, GP Papanicolaou, DA AF Torpy, DJ Tsigos, C Lotsikas, AJ Defensor, R Chrousos, GP Papanicolaou, DA TI Acute and delayed effects of a single-dose injection of interleukin-6 on thyroid function in healthy humans SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID NECROSIS-FACTOR-ALPHA; SERUM INTERLEUKIN-6; NONTHYROIDAL ILLNESS; HORMONE; SECRETION; ENDOCRINE; CORTISOL AB Interleukin-6 (IL-6) is produced in response to inflammatory and noninflammatory stress and acts as the principal regulator of the acute-phase protein response. IL-6 stimulates the hypothalamic-pituitary-adrenal axis and may be involved in the thyroid function abnormalities observed in nonthyroidal illness (NTI). This study examined the effects of single-dose IL-6 (3 mu g/kg subcutaneously [SC]) in healthy human subjects: 19 received IL-6 and 13 received control saline injection. The dose of IL-6 was chosen on the basis of previous studies indicating that the peak IL-6 level after injection reaches concentrations observed with major stress such as abdominal surgery. Plasma levels of thyrotropin (TSH), free thyroxine (FT4), total T-4, 3,5-3'-L-triiodothyronine (T-3), 3,3'-5'-L-triiodothyronine or reverse T-3 (rT(3)), and thyroxine-binding globulin (TBG) were measured over a 4-hour period and 24 hours after IL-6 injection. Plasma TSH levels were 27% lower 240 minutes after IL-6 relative to control levels (0.93 +/- 0.10 v 1.28 +/- 0.18 mlU/mL, P = .001), but recovered by 24 hours. Plasma FT4 was elevated at 240 minutes compared with the controls (1.16 +/- 0.04 v 1.03 +/- 0.03 ng/dL, P = .0002). T-4 levels were also elevated at 240 minutes (7.8 +/- 0.36 v 7.05 +/- 0.37 mu g/dL, P = .0003). TBG levels were not significantly changed at this time point. At 24 hours, T-3 levels were 19% lower than the control values (87.6 +/- 5.1 v 108.5 +/- 5.4 ng/dL, P = .0002); plasma rT(3) levels were elevated by 21% compared with control levels (30.6 +/- 1.7 v 24.3 +/- 1.3 ng/dL, P = .002), while FT4 levels returned to normal. The changes in T-3/rT(3) levels were reminiscent of the pattern observed in NTI that may be due to inhibition of type-1 5'-deiodinase. Cortisol levels were greatly elevated after IL-6 compared with control values; peak levels were observed 120 minutes after IL-6 injection (28.7 +/- 1.6 v 9.5 +/- 1.0 ng/dL, P < .0001). This elevation in cortisol may have contributed to the suppression of TSH levels and inhibition of type-1 5'-deiodinase activity. Alternatively, IL-6 may have suppressed TSH secretion via a direct suprapituitary action. The elevation of T-4 and FT4 levels may have been due to inhibition of T-4 degradation at the liver and/or by direct action of IL-6 on the thyroid gland. These findings demonstrate the potent effects of IL-6 on thyroid hormone metabolism in healthy individuals, and suggest that IL-6 may act directly or indirectly at two or more sites on thyroid hormone secretion and metabolism. Copyright (C) 1998 by W.B. Saunders Company. C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NIH, Dept Nursing, Ctr Clin, Bethesda, MD 20892 USA. RP Papanicolaou, DA (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg 10,Room 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. NR 27 TC 49 Z9 51 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD OCT PY 1998 VL 47 IS 10 BP 1289 EP 1293 DI 10.1016/S0026-0495(98)90338-9 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 128FP UT WOS:000076395300021 PM 9781636 ER PT J AU Quezado, MM Abati, AD Albuquerque, AV Wilson, J Merino, MJ Filie, AC AF Quezado, MM Abati, AD Albuquerque, AV Wilson, J Merino, MJ Filie, AC TI Morphologic diversity in malignant melanoma: The potential use of microdissection and the polymerase chain reaction for diagnosis SO MODERN PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE cytology; melanoma; microdissection; p16 gene; polymerase chain reaction ID FINE-NEEDLE ASPIRATION; HOMOZYGOUS DELETIONS; MONOCLONAL-ANTIBODY; FAMILIAL MELANOMA; CANCER STATISTICS; S-100 PROTEIN; CHROMOSOME 9P; HMB-45; BIOPSY; GENE AB Malignant melanoma (MM) can mimic soft tissue (ST) and epithelial neoplasms. An immunoperoxidase (IP) panel and a morphologic comparison of the primary are used in diagnosis, which can be difficult when the morphologic and IP profiles of a metastatic lesion simulate those of an ST neoplasm. Through the comparison of known genetic abnormalities in primary and metastatic neoplasms, a definitive diagnosis can be suggested on the basis of the finding of identical allelic losses through the use of microdissection (MD) and the polymerase chain reaction (PCR). Genetic alterations involving the p16 gene on chromosome 9p21 have been observed in MM. We present the case of a 56-year-old man with known MM in whom multiple metastatic lesions to the skin and an adrenal gland developed during a 5-year period. A fine-needle aspiration (FNA) of a new ST buttock lesion was performed; the specimen had cytologic features different from those of the primary neoplasm and simulated a possible primary ST neoplasm, We attempted to make a definitive diagnosis of MM in the FNA of the ST buttock lesion through a genetic comparison with the primary neoplasm as well as with the other metastatic sites. Direct-visualization MD was performed on histologic glass slides of the primary and adjacent tissue (normal control), and the metastatic lesions, along with malignant cell clusters from the buttock lesion FNA. DNA was extracted and PCR amplified with primers D9S171 and IFNA for the p16 locus at the 9p21-22 region. Loss of heterozygosity for the D9S171 marker at the p16 gene locus was identified in all of the neoplastic tissue tested. Normal skin elements did not show deletion. The combination of MD and PCR are powerful tools that can be used for the comparison of genetic abnormalities in primary and metastatic neoplasms with unusual morphologic features to help support a diagnosis with a noncontributory IF. C1 NCI, Cytopathol Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Filie, AC (reprint author), NCI, Cytopathol Sect, Pathol Lab, NIH, Bldg 10,Room 2A19, Bethesda, MD 20892 USA. NR 41 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD OCT PY 1998 VL 11 IS 10 BP 1010 EP 1015 PG 6 WC Pathology SC Pathology GA 130DX UT WOS:000076505600017 PM 9796732 ER PT J AU Honkakoski, P Zelko, I Sueyoshi, T Negishi, M AF Honkakoski, P Zelko, I Sueyoshi, T Negishi, M TI The nuclear orphan receptor CAR-retinoid X receptor heterodimer activates the phenobarbital-responsive enhancer module of the CYP2B gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HORMONE-RECEPTOR; P450; RAT; TRANSCRIPTION; SUPERFAMILY; CYTOCHROME-P-450; EXPRESSION; INDUCTION; ELEMENTS; ISOFORMS AB PBREM, the phenobarbital-responsive enhancer module of the cytochrome P-450 Cyp2b10 gene, contains two potential nuclear receptor binding sites, NR1 and NR2. Consistent with the finding that anti-retinoid X receptor (RXR) could supershift the NR1-nuclear protein complex, DNA affinity chromatography with NR1 oligonucleotides enriched the nuclear orphan receptor RXR from the hepatic nuclear extracts of phenobarbital-treated mice. In addition to RXR, the nuclear orphan receptor CAR was present in the same enriched fraction. Ln the phenobarbital-treated mice, the binding of both CAR and RXR was rapidly increased before the induction of CYP2B10 mRNA. In vitro-translated CAR bound to NR1, but only in the presence of similarly prepared RXR, PBREM was synergistically activated by transfection of CAR and RXR in HepG2 and HEK293 cells when the NR1 site was functional. A CAR-RXR heterodimer has thus been characterized as a tans-acting factor for the phenobarbital-inducible Cyp2b10 gene. C1 NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RI Zelko, Igor/L-2673-2013; OI Zelko, Igor/0000-0003-3976-3884; Honkakoski, Paavo/0000-0002-4332-3577 NR 26 TC 535 Z9 552 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 5652 EP 5658 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900004 PM 9742082 ER PT J AU Baer, M Dillner, A Schwartz, RC Sedon, C Nedospasov, S Johnson, PF AF Baer, M Dillner, A Schwartz, RC Sedon, C Nedospasov, S Johnson, PF TI Tumor necrosis factor alpha transcription in macrophages is attenuated by an autocrine factor that preferentially induces NF-kappa B p50 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID FACTOR GENE-EXPRESSION; HUMAN MONOCYTIC CELLS; GROWTH-FACTOR-BETA; LIPOPOLYSACCHARIDE INDUCTION; GEL-ELECTROPHORESIS; CYTOKINE PRODUCTION; INTERFERON-GAMMA; NUCLEAR FACTOR; MESSENGER-RNA; ACTIVATION AB Macrophages are a major source of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), which are expressed during conditions of inflammation, infection, or injury. We identified an activity secreted by a macrophage tumor cell line that negatively regulates bacterial lipopolysaccharide (LPS)-induced expression of TNF-alpha. This activity, termed TNF-alpha-inhibiting factor (TIF), suppressed the induction of TNF-alpha expression in macrophages, whereas induction of three other proinflammatory cytokines (interleukin-lp [IL-1 beta], IL-6, and monocyte chemoattractant protein 1),vas accelerated or enhanced. A similar or identical inhibitory activity was secreted by IC-21 macrophages following LPS stimulation. Inhibition of TNF-alpha expression by macrophage conditioned medium was associated with selective induction of the NF-kappa B p50 subunit. Hyperinduction of p50 occurred with delayed kinetics in LPS-stimulated macrophages but not in fibroblasts, Overexpression of p50 blocked LPS-induced transcription from a TNF-alpha promoter reporter construct, showing that this transcription factor is an inhibitor of the TNF-alpha gene. Repression of the TNF-alpha promoter by TIF required a distal region that includes three NF-kappa B binding sites with preferential affinity for p50 homodimers. Thus, the selective repression of the TNF-alpha promoter by TIF may be explained by the specific binding of inhibitory p50 homodimers. We propose that TIF serves as a negative autocrine signal to attenuate TNF-alpha expression in activated macrophages. TIF is distinct from the known TNF-alpha-inhibiting factors IL-4, IL-10, and transforming growth factor beta and may represent a novel cytokine. C1 NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Intranural Res Support Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Mol Immunoregulat Lab, Div Basic Sci, Frederick, MD 21702 USA. Michigan State Univ, Dept Microbiol, E Lansing, MI 48824 USA. Moscow MV Lomonosov State Univ, Belozersky Inst Physicochem Biol, Moscow 119899, Russia. Russian Acad Sci, VA Engelhardt Mol Biol Inst, Moscow 119899, Russia. RP Johnson, PF (reprint author), NCI, Frederick Canc Res & Dev Ctr, Adv Biosci Labs, Basic Res Program, Frederick, MD 21702 USA. EM johnsopf@ncifcrf.gov RI Johnson, Peter/A-1940-2012; Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 OI Johnson, Peter/0000-0002-4145-4725; FU NCI NIH HHS [N01-CO-56000] NR 58 TC 126 Z9 126 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 5678 EP 5689 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900007 PM 9742085 ER PT J AU Kubbutat, MHG Ludwig, RL Ashcroft, M Vousden, KH AF Kubbutat, MHG Ludwig, RL Ashcroft, M Vousden, KH TI Regulation of Mdm2-directed degradation by the C terminus of p53 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DNA-BINDING FUNCTION; TUMOR-SUPPRESSOR PROTEIN; HUMAN PAPILLOMAVIRUS E6; CELL-CYCLE ARREST; TRANSCRIPTIONAL ACTIVATION; P53-DEPENDENT APOPTOSIS; EMBRYONIC LETHALITY; MDM2-DEFICIENT MICE; MDM2 BINDING; G(1) ARREST AB The stability of the p53 tumor suppressor protein is regulated by interaction with Mdm2, the product of a p53-inducible gene. Mdm2-targeted degradation of p53 depends on the interaction between the two proteins and is mediated hv the proteasome. We show here that in addition to the N-terminal Mdm2 binding domain, the C terminus of p53 participates in the ability of p53 to be degraded by Mdm2. In contrast, alterations in the central DNA binding domain of p53, which change the conformation of the p53 protein, do not abrogate the sensitivity of the protein to Mdm2-mediated degradation. The importance of the C-terminal oligomerization domain to Mdm2-targeted degradation of p53 is likely to reflect the importance of oligomerization of the full-length p53 protein for interaction with Mdm2, as previously shown in vitro. Interestingly, the extreme C-terminal region of p53, outside the oligomerization domain, was also shown to be necessary for efficient degradation, and deletion of this region stabilized the protein without abrogating its ability to bind to Mdm2. Mdm2-resistant p53 mutants were not further stabilized following DNA damage, supporting a role for Mdm2 as the principal regulator of p53 stability in cells. The extreme C terminus of the p53 protein has previously been shown to contain several regulatory elements, raising the possibility that either allosteric regulation of p53 by this domain or interaction between this region and a third protein plays a role in determining the sensitivity of p53 to Mdm2-directed degradation. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Vousden, KH (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Bldg 560,Room 22-96,POB B, Frederick, MD 21702 USA. EM vousden@ncifcrf.gov NR 64 TC 145 Z9 146 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 5690 EP 5698 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900008 PM 9742086 ER PT J AU Li, WQ Jiang, YX Zhang, JC Soon, L Flechner, L Kapoor, V Pierce, JH Wang, LH AF Li, WQ Jiang, YX Zhang, JC Soon, L Flechner, L Kapoor, V Pierce, JH Wang, LH TI Protein kinase C-delta is an important signaling molecule in insulin-like growth factor I receptor-mediated cell transformation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID MOUSE EMBRYO FIBROBLASTS; ATP BINDING MUTANT; TYROSINE PHOSPHORYLATION; PKC-DELTA; PHOSPHATIDYLCHOLINE HYDROLYSIS; EXPRESSION; ACTIVATION; INHIBITION; MUTATIONS; TUMORIGENESIS AB To investigate the potential role of protein kinase C-delta (PKC-delta) in insulin-like growth factor I receptor (IGF-IR)-mediated cell transformation, an oncogenic gag-IGF-IR beta-fusion receptor lacking the entire extracellular domain, which was designated NM1, and a full-length IGF-IR mere coexpressed with either wild-type PKC-delta (PKC-delta WT) or an ATP-binding mutant of PKC-delta (PKC-delta K376R) in NIH 3T3 fibroblasts. While overexpression of PKC-delta WT did not affect NM1- and IGF-IR-induced focus and colony formation of NIH 3T3 cells, expression of PKC-delta K376R severely impaired these events. In contrast, NM1-mtrdiated cell growth in monolayer was not affected by coexpressing PKC-delta K376R. PKC-delta WT and PKC-delta K376R were constitutively phosphorylated on a tyrosine residue(s) in the NM1- and IGF-IR-expressing cells and were associated with them in an IGF-I-independent manner. Activated IGF-IR was able to phosphorylate purified PKC-delta in vitro and stimulated its kinase activity. Furthermore, the level of endogenous PKC-delta protein was up-regulated through transcriptional activation in response to long-term IGF-IR activation. Taken together, our results demonstrate that PKC-delta plays an important role in IGF-IR-mediated cell transformation, probably via association of the receptor with PKC-delta and its activation through protein up-regulation and tyrosine phosphorylation. Competition with endogenous PKC-delta for NM1 and IGF-IR association by PKC-delta K376R is probably an important mechanism underlying: the PKC-delta K376R-mediated inhibition of cell transformation by NM1 and IGF-IR. C1 NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. Mt Sinai Med Ctr, Dept Microbiol, New York, NY 10029 USA. RP Li, WQ (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37,Room 1E24,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Liwe@dc37a.nci.nih.gov FU NCI NIH HHS [R01 CA055054, CA55054] NR 54 TC 66 Z9 70 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 5888 EP 5898 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900028 PM 9742106 ER PT J AU Chiorini, JA Zimmermann, B Yang, L Smith, RH Ahearn, A Herberg, F Kotin, RM AF Chiorini, JA Zimmermann, B Yang, L Smith, RH Ahearn, A Herberg, F Kotin, RM TI Inhibition of PrKX, a novel protein kinase, and the cyclic AMP-dependent protein kinase PKA by the regulatory proteins of adeno-associated virus type 2 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ELEMENT-BINDING-PROTEIN; ADENOASSOCIATED VIRUS; CATALYTIC SUBUNIT; REP PROTEIN; CELLULAR-TRANSFORMATION; BOVINE PAPILLOMAVIRUS; TRANSCRIPTION FACTORS; INTEGRATION SITE; MAMMALIAN-CELLS; GENE-EXPRESSION AB Adeno-associated virus encodes four nonstructural proteins, which are known as Rep78, Rep68, Rep52, and Rep40, Expression of these nonstructural proteins affects cell growth and gene expression through processes that have not yet been characterized. Using a yeast two-hybrid screen, we have demonstrated that a stable interaction occurs between the viral proteins Rep78 and Rep52 and the putative protein kinase PrKX, which is encoded on the X chromosome. The stability and specificity of the Rep-PrKX interaction were confirmed by coimmunoprecipitation of complexes assembled in vitro and in vivo. Overexpressed PrKX, which was purified from cos cells, was shown to phosphorylate a synthetic protein kinase A (PKA) substrate. However, this activity was dramatically inhibited by stoichiometric amounts of Rep52 and weakly inhibited with Rep68, which lacks the carboxy-terminal sequence contained in Rep52, Similarly, a stable interaction was observed with Rep78, which also contains the carboxy-terminal sequence of Rep52. A stable interaction and inhibition were also observed between Rep52 and the catalytic subunit of PKA, By using surface plasmon resonance and kinetic studies, K(i)s of approximately 300 and 167 nM were calculated for Rep52 with PKA and with PrKX, respectively. Thus, Rep52 but not Rep68 can significantly inhibit the trans- and autophosphorylation activities of these kinases, The biological effects of Rep78 specific inhibition of PKA-responsive genes are illustrated by the reduction of steady-state levels of cyclic AMP-responsive-element-binding protein and cyclin A protein. C1 NHLBI, Mol Hematol Branch, NIH, Bethesda, MD 20892 USA. Ruhr Univ Bochum, Inst Physiol Chem, D-44780 Bochum, Germany. RP Kotin, RM (reprint author), NHLBI, Mol Hematol Branch, NIH, Bldg 10-7D18,10 Ctr Dr,MSC 1654, Bethesda, MD 20892 USA. RI kotin, robert/B-8954-2008; Herberg, Friedrich/B-5572-2015 OI Herberg, Friedrich/0000-0001-7117-7653 NR 55 TC 45 Z9 47 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 5921 EP 5929 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900031 PM 9742109 ER PT J AU Pinkas-Kramarski, R Shelly, M Guarino, BC Wang, LM Lyass, L Alroy, I Alamandi, M Kuo, A Moyer, JD Lavi, S Eisenstein, M Ratzkin, BJ Segar, R Bacus, SS Pierce, JH Andrews, GC Yarden, Y AF Pinkas-Kramarski, R Shelly, M Guarino, BC Wang, LM Lyass, L Alroy, I Alamandi, M Kuo, A Moyer, JD Lavi, S Eisenstein, M Ratzkin, BJ Segar, R Bacus, SS Pierce, JH Andrews, GC Yarden, Y TI ErbB tyrosine kinases and the two neuregulin families constitute a ligand-receptor network SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NEU DIFFERENTIATION FACTOR; EPIDERMAL GROWTH-FACTOR; EGF RECEPTOR; SIGNAL-TRANSDUCTION; CARDIAC DEVELOPMENT; CELLULAR-RESPONSE; BREAST-CANCER; MICE LACKING; MAP KINASE; HEREGULIN AB The recently isolated second family of neuregulins, NRG2, shares its primary receptors, ErbB-3 and ErbB-4, and induction of mammary cell differentiation with NRG1 isoforms, suggesting functional redundancy of the two growth factor families. To address this possibility, we analyzed receptor specificity of NRGs by using an engineered cellular system. The activity of isoform-specific but partly overlapping patterns of specificities that collectively activate all eight ligand-stimulatable ErbB dimers was revealed. Specifically, NRG2-beta, like NRG1-alpha, emerges as a narrow-specificity ligand, whereas NRG2-alpha is a pan-ErbB ligand that binds with different affinities to all receptor combinations, including those containing ErbB-1, but excluding homodimers of ErbB-2. The latter protein, however, displayed cooperativity with the direct NRG receptors. Apparently, signaling by all NRGs is funneled through the mitogen-activated protein kinase (MAPK). However, the duration and potency of MAPK activation depend on the identity of the stimulatory ligand-receptor ternary complex. We conclude that the NRG-ErbB network represents a complex and nonredundant machinery developed for fine-tuning of signal transduction. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Dept Biol Struct, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Dept Membrane Res & Recognit, IL-76100 Rehovot, Israel. Pfizer Inc, Cent Res, Groton, CT 06340 USA. NCI, Bethesda, MD 20892 USA. Adv Cellular Diagnost Inc, Elmhurst, IL 60126 USA. Amgen Inc, Amgen Ctr, Thousand Oaks, CA 91320 USA. RP Yarden, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. EM liyarden@wiccmail.weizmann.ac.il RI YARDEN, YOSEF/K-1467-2012 NR 68 TC 111 Z9 113 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD OCT PY 1998 VL 18 IS 10 BP 6090 EP 6101 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 120WT UT WOS:000075980900048 PM 9742126 ER PT J AU Kim, JG Armstrong, RC Berndt, JA Kim, NW Hudson, LD AF Kim, JG Armstrong, RC Berndt, JA Kim, NW Hudson, LD TI A secreted DNA-binding protein that is translated through an internal ribosome entry site (IRES) and distributed in a discrete pattern in the central nervous system SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID HEPATITIS-C VIRUS; MESSENGER-RNA; SUBVENTRICULAR ZONE; MONOCLONAL-ANTIBODY; 5'-NONCODING REGION; PICORNAVIRUS RNA; GENE-EXPRESSION; GLIAL-CELLS; INITIATION; OLIGODENDROCYTES AB Internal initiation of translation, a mechanism infrequently used by cellular messages, avoids the requirement of a methyl cap structure for translation of messenger RNAs. The mRNA transcript encoding the DNA-binding protein MYT2 represents one of the exceptional cellular messages that contains an internal ribosome entry site (IRES), The RNA pseudoknot structure located in the 5 ' untranslated region of MYT2 functions to promote translation in vivo. MYT2 was cloned by its specific binding to a TTCCA motif in the promoter region of a glial-specific gene, myelin proteolipid protein. MYT2 also recognizes single-stranded nucleic acids. In the central nervous system, MYT2 protein is found in oligodendrocyte progenitor cells, subsets of neurons, and cells of the choroid plexus together with ciliated ependymal cells. MYT2 protein can also be secreted from cells, an atypical event for a DNA-binding protein. The presence of an internal ribosome entry site in MYT2, together with the unusual localization of MYT2, suggests that this nucleic acid-binding protein may be in the class of proteins involved in cellular growth control and survival in the nervous system. C1 NINDS, LDN, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Anat & Cell Biol, Bethesda, MD 20814 USA. Kyungsan Univ, Dept Biol, Kyungsan 712240, Kyungbuk, South Korea. RP Hudson, LD (reprint author), NINDS, LDN, NIH, Bldg 36,Room 5D06,36 Convent Dr,MSC 4160, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01-HD-1-3138] NR 58 TC 27 Z9 27 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD OCT PY 1998 VL 12 IS 3 BP 119 EP 140 DI 10.1006/mcne.1998.0701 PG 22 WC Neurosciences SC Neurosciences & Neurology GA 134VT UT WOS:000076765000003 PM 9790734 ER PT J AU Paranavitana, CM AF Paranavitana, CM TI Non-radioactive detection of K-ras mutations by nested allele specific PCR and oligonucleotide hybridization SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE K-ras mutations; colon tumours; colon cancer cell lines; rapid detection ID POLYMERASE CHAIN-REACTION; POINT MUTATIONS; HUMAN-COLON; CELL-LINES; GENES; ONCOGENES; CARCINOMAS AB The development of methods to detect point mutations has been rapid over the recent years. In human colon tumours, a significant percentage of mutations are found in the K-ras gene. Faster and more sensitive methods for detection of these mutations are important for patient management and treatment. The author has extended the specificity of allele amplification of point mutations by using mismatch oligonucleotide primers in a polymerase chain reaction (PCR). It is shown that in colon tumours, the sensitivity of detecting a mutation is significantly higher when K-ras exon 1 is amplified prior to PCR with allele specific primers (mismatch PCR). It is shown that allele specific oligonucleotide probes which are non-radioactively labelled could be used to detect these point mutations. By utilizing this two-step PCR, K-ras codon 12 mutations were studied in 10 colon carcinoma cell lines and 25 colon tumours. By combining the two-step PCR together with non-radioactively labelled oligonucleotide probes, the detection of point mutations is both accurate and rapid. (C) 1998 Academic Press. C1 NCI, Tumor Immunol & Biol Lab, NIH, Bethesda, MD USA. Walter Reed Army Inst Res, Dept Bacterial Dis, Washington, DC 20307 USA. RP Paranavitana, CM (reprint author), Walter Reed Army Inst Res, Dept Bacterial Dis, Washington, DC 20307 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD OCT PY 1998 VL 12 IS 5 BP 309 EP 315 DI 10.1006/mcpr.1998.0185 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 135JY UT WOS:000076799600007 PM 9778456 ER PT J AU Geil, L Semenova, E Lerman, MI Kuzmin, I AF Geil, L Semenova, E Lerman, MI Kuzmin, I TI A PCR generated BsaJ I RFLP in the promoter of the von Hippel-Lindau disease (VHL) tumour suppressor gene SO MOLECULAR AND CELLULAR PROBES LA English DT Article ID RENAL-CARCINOMA; IDENTIFICATION; MUTATIONS C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. First Diagnost Ctr, St Petersburg 194356, Russia. NCI, Immunobiol Lab, FCRDC, Frederick, MD 21702 USA. RP Kuzmin, I (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Bldg 560 Rm 12-71, Frederick, MD 21702 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD OCT PY 1998 VL 12 IS 5 BP 343 EP 344 DI 10.1006/mcpr.1998.0190 PG 2 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 135JY UT WOS:000076799600013 PM 9778462 ER PT J AU Moriuchi, R Shibata, S Himeno, A Johren, O Hoe, KL Saavedra, JM AF Moriuchi, R Shibata, S Himeno, A Johren, O Hoe, KL Saavedra, JM TI Molecular cloning and pharmacological characterization of an atypical gerbil angiotensin II type-1 receptor and its mRNA expression in brain and peripheral tissues SO MOLECULAR BRAIN RESEARCH LA English DT Article DE renin-angiotensin system; angiotensin receptor; AT(1) receptor antagonist; gerbil; receptor sequence; in situ hybridization ID ANTAGONIST BINDING-SITE; AMINO-ACID-RESIDUES; RAT-BRAIN; GENE-EXPRESSION; NONPEPTIDE; IDENTIFICATION; SUBTYPES; MOUSE; MUTAGENESIS; AT(1A) AB In the gerbil brain, most of the [I-125]Sarcosine(1)-Angiotensin II binding sites are atypical, not sensitive to displacement with selective Angiotensin II AT(1) and AT(2) receptor ligands. A similar atypical binding profile exists in the gerbil kidney, where binding is highly expressed. We isolated a 2197 base pair clone from a gerbil kidney cDNA library which encodes a 359 amino acid protein with higher than 90% homology to other mammalian angiotensin II AT(1) receptors. When expressed in COS-7 cells, stimulation by Angiotensin Il of both the cloned gerbil receptor or the human AT(1) receptor enhanced TP, production to a similar degree. In COS-7 cells, the gerbil receptor also had a ligand affinity profile similar to that of the human AT(1) receptor, but showed greatly reduced affinity for losartan (IC50 = 3480 +/- 174 nM). In the gerbil brain, in situ hybridization revealed receptor mRNA in circumventricular organs, selective hypothalamic, midbrain and brain stem areas, and in the hippocampus, where high mRNA expression was detected in the stratum pyramidale of the CA1 and CA2 subfields, and in the stratum granulosum of the dentate gyrus. The expression pattern of receptor mRNA corresponded well with that of atypical [I-125]Sar(1)-Ang II binding. In situ hybridization and Southern blot experiments using riboprobes against the open reading frame and the 3'-untranslated region of the cloned gerbil Ang II receptor cDNA suggest that gerbils have, like other rodents, two AT(1) receptor subtypes. The receptor mRNA distribution of the cloned gerbil Ang II receptor corresponds to the distribution of AT(1A) receptors described in other rodent species. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIMH, Pharmacol Sect, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, Bldg 10,Room 2D-57,10 Ctr Dr,MSC 1514, Bethesda, MD 20892 USA. EM saavedj@irp.nimh.nih.gov RI Johren, Olaf/G-6967-2011 NR 26 TC 14 Z9 15 U1 0 U2 1 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 OCT 1 PY 1998 VL 60 IS 2 BP 234 EP 246 DI 10.1016/S0169-328X(98)00187-9 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 128XL UT WOS:000076433600010 ER PT J AU Asanuma, M Cadet, JL AF Asanuma, M Cadet, JL TI Methamphetamine-induced increase in striatal NF-kappa B DNA-binding activity is attenuated in superoxide dismutase transgenic mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE transcription factor; NF-kappa B; methamphetamine; superoxide dismutase; transgenic mice; reactive oxygen species ID TRANSCRIPTION FACTOR; RAT-BRAIN; INDUCED NEUROTOXICITY; ACTIVATION; CELLS; AP-1; EXPRESSION AB Methamphetamine injection (X4 with 2-h interval) caused dose-dependent activation of striatal NF-kappa B activity. Striatal NF-kappa B binding increased significantly at 1-3 h after the last injection of methamphetamine (10 mg/kg, i.p. X4). This induction of striatal NF-kappa B activity was significantly attenuated in Cu,Zn-superoxide dismutase transgenic mice in a gene dosage-dependent fashion. The present results suggest that reactive oxygen species generated by methamphetamine injections can activate striatal NF-kappa B DNA-binding during this drug-induced toxic process. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIDA, Intramural Res Program, Mol Neuropsychiat Sect, NIH, Baltimore, MD USA. RP Cadet, JL (reprint author), NIDA, Intramural Res Program, Mol Neuropsychiat Sect, NIH, POB 5180, Baltimore, MD USA. NR 19 TC 40 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 1 PY 1998 VL 60 IS 2 BP 305 EP 309 DI 10.1016/S0169-328X(98)00188-0 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 128XL UT WOS:000076433600018 ER PT J AU Higinbotham, KG Karavanova, ID Diwan, BA Perantoni, AO AF Higinbotham, KG Karavanova, ID Diwan, BA Perantoni, AO TI Deficient expression of mRNA for the putative inductive factor bone morphogenetic protein-7 in chemically initiated rat nephroblastomas SO MOLECULAR CARCINOGENESIS LA English DT Article DE kidney; hepatocyte growth factor; c-met; Wilms' tumor-1 gene; Wilms' tumor ID HEPATOCYTE GROWTH-FACTOR; PROSTATE-CANCER CELLS; FACTOR SCATTER FACTOR; WILMS-TUMOR; FACTOR/SCATTER FACTOR; KIDNEY DEVELOPMENT; MET PROTOONCOGENE; MESSENGER-RNA; RODENT MODEL; C-MET AB Wilms' tumor, or nephroblastoma, arises from metanephric blastema and caricatures renal organogenesis. An alteration in at least one of the genes involved in control of renal differentiation is therefore a likely event in tumorigenesis, and indeed some of the genes involved in renal development, for example, hepatocyte growth factor (HGF) and its receptor c-met, the transcription factor Wilms' tumor gene (WT1), and transforming growth factor-p family member bone morphogenetic protein (BMP)-7, have also been implicated in various models of tumorigenesis. In a comparison of mRNA expression patterns for these genes in normal rat embryonic or fetal kidney and nephroblastoma, we found that the patterns for HGF met, and VT1 detected by in situ hybridization or ribonuclease protection assay (RPA) in the nephroblastomas were similar to those of normal developing kidney. BMP-7 expression, on the other hand, was lower in most tumors examined both by in situ hybridization and RPA than in normal tissues. This deficiency in a defined inductive factor that has been shown to function in renal tubulogenesis may play a role in tumorigenesis by allowing the accumulation of blastemal populations typical of nephroblastomas. (C) 1998 Wiley-Liss, Inc. C1 NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD USA. RP Higinbotham, KG (reprint author), NCI, Frederick Canc Res & Dev Ctr, Comparat Carcinogenesis Lab, Bldg 538,Rm 205E, Frederick, MD 21702 USA. FU NCI NIH HHS [N01-CO-56000] NR 43 TC 6 Z9 6 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 1998 VL 23 IS 2 BP 53 EP 61 DI 10.1002/(SICI)1098-2744(199810)23:2<53::AID-MC1>3.0.CO;2-T PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 134VL UT WOS:000076764300001 PM 9808158 ER PT J AU Khan, QA Agarwal, R Seidel, A Frank, H Vousden, KH Dipple, A AF Khan, QA Agarwal, R Seidel, A Frank, H Vousden, KH Dipple, A TI DNA adduct levels associated with p53 induction and delay of MCF-7 cells in S phase after exposure to benzo[g]chrysene dihydrodiol epoxide enantiomers SO MOLECULAR CARCINOGENESIS LA English DT Article DE mammary carcinogenesis; polycyclic aromatic hydrocarbon; G(1) arrest ID REGION DIOL-EPOXIDES; FJORD-REGION; POLY(ADP-RIBOSE) POLYMERASE; LINE MCF-7; MOUSE SKIN; PROTEIN; BENZOPHENANTHRENE; ACCUMULATION; 3,4-DIOL-1,2-EPOXIDES; DIBENZOPYRENE AB Optically active isomers of a mammary carcinogen, anti-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide, react to different extents with DNA and generate DNA adducts that differ in their stereochemistry. In the study reported here, the effect of these two enantiomers on the progress of human breast carcinoma MCF-7 cells through the cell cycle was investigated. Each enantiomer caused the cells to accumulate in the S phase, but a higher dose of the benzo[g]chrysene 11S,12R-dihydrodiol 13R,14S-epoxide than of its enantiomer was required to induce this effect. Similarly, induction of p53 also required a higher dose of benzo[g]chrysene 11R,12R-dihydrodiol 13R,14S-epoxide. Postlabeling studies indicated that the latter enantiomer also caused less modification of MCF-7 cell DNA for a given level of exposure than did benzo[g]chrysene 11R,12S-dihydrodiol 13S,14R-epoxide. These results suggest that p53 induction and delay in the S phase are similarly related to DNA binding and that a level of binding of the order of 1 adduct per 10(5) nucleotides is associated with these effects. (C) 1998 Wiley-Liss, Inc. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. Univ Mainz, Inst Toxicol, D-6500 Mainz, Germany. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Mol Virol & Carcinogenesis Lab, Frederick, MD USA. RP Dipple, A (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Chem Carcinogenesis Lab, Frederick, MD 21702 USA. NR 31 TC 21 Z9 22 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD OCT PY 1998 VL 23 IS 2 BP 115 EP 120 DI 10.1002/(SICI)1098-2744(199810)23:2<115::AID-MC8>3.0.CO;2-R PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 134VL UT WOS:000076764300008 PM 9808165 ER PT J AU Wenink, PW Groen, AF Roelke-Parker, ME Prins, HHT AF Wenink, PW Groen, AF Roelke-Parker, ME Prins, HHT TI African buffalo maintain high genetic diversity in the major histocompatibility complex in spite of historically known population bottlenecks SO MOLECULAR ECOLOGY LA English DT Article DE African buffalo; bottleneck; MHC-DRB; PCR-RFLP; rinderpest; social organization ID BOLA-DRB3 GENE; EAST-AFRICA; DRB GENES; POLYMORPHISM; STABILITY; SELECTION; SEQUENCES; CHEETAH; MOOSE; LOCI AB Historical population collapses caused by rinderpest epidemics are hypothesized to have resulted in notable genetic losses in populations of the African buffalo. Polymorphism in the major histocompatibity complex (MHC) DRB3 gene was probed by means of restriction analysis of the sequence encoding the peptide-binding region. Nucleotide substitution patterns agreed with a positive selection acting on this fitness-relevant locus. Buffalo populations from four National Parks, situated in eastern and southern Africa, each revealed a surprisingly high allelic diversity. Current high levels of heterozygosity may be reconciled with historical bottlenecks by assuming that local extinctions were followed by fast recolonization, in accordance with the high dispersive capabilities of buffalo. The specific amplification of DRB3 alleles also enabled the assignment of individual genotypes. For each population sample a deficiency in the expected number of heterozygous animals was found. As overdominant selection on the MHC is predicted to yield an excess of heterozygous individuals, this may not be a locus-specific effect. Several other explanations are discussed, of which increased homozygosity caused by nonrandom mating of buffalo in populations seems the most probable. C1 Wageningen Univ Agr, Dept Anim Sci, Anim Breeding & Genet Grp, Wageningen, Netherlands. Wageningen Univ Agr, Dept Environm Sci, Trop & Vertebrate Ecol Grp, Wageningen, Netherlands. NCI, Lab Genom Divers, Frederick, MD 21701 USA. RP Groen, AF (reprint author), Wageningen Univ Agr, Dept Anim Sci, Anim Breeding & Genet Grp, Wageningen, Netherlands. EM Ab.Groen@alg.vf.wau.nl NR 44 TC 47 Z9 47 U1 1 U2 13 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0962-1083 J9 MOL ECOL JI Mol. Ecol. PD OCT PY 1998 VL 7 IS 10 BP 1315 EP 1322 DI 10.1046/j.1365-294x.1998.00463.x PG 8 WC Biochemistry & Molecular Biology; Ecology; Evolutionary Biology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology; Evolutionary Biology GA 127JF UT WOS:000076346800006 PM 9787443 ER PT J AU Shotelersuk, V Gahl, WA AF Shotelersuk, V Gahl, WA TI Hermansky-Pudlak syndrome: Models for intracellular vesicle formation SO MOLECULAR GENETICS AND METABOLISM LA English DT Review DE albinism; platelet storage pool deficiency; vesicle trafficking; membrane fusion; ceroid lipofuscin ID PALE EAR EP; PULMONARY FIBROSIS; PROTEIN COMPLEX; OCULOCUTANEOUS ALBINISM; GRANULOMATOUS COLITIS; SORTING SIGNALS; GENE; MOUSE; AP-3; ENDOCYTOSIS AB Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by pigment dilution, nystagmus, decreased visual acuity, a bleeding diathesis, and lysosomal accumulation of ceroid lipofuscin. Electron microscopic evidence demonstrating lack of platelet-dense bodies provides the sine qua non for diagnosing HPS. Ceroid lipofuscinosis is considered to cause several serious complications, including progressive pulmonary fibrosis leading to death in the fourth or fifth decades. currently, only symptomatic treatment can be offered. Although rare in the general population, HPS occurs in northwest Puerto Rico with a prevalence of 1 in 1800. HPS1, the first gene found to be responsible for HPS, was mapped to chromosome 10q23 and subsequently isolated and sequenced. It consists of 20 exons encoding a 700-amino acid, 79.3-kDa peptide with no homology to any known protein. All 10 HPS1 mutations reported to date, including the 16-bp duplication found in all northwest Puerto Rican patients, result in truncated proteins. The two mutations in the mouse pale ear gene (ep), which is the murine homology of HPS1, cause similarly truncated proteins. The pathologic nature of these truncation mutations may result from unstable mRNA. However, in combination with the absence of any disease-causing missense mutations, it may indicate that the C-terminus of the HPS1 peptide is functionally important. The disorder HPS displays locus heterogeneity, consistent with the existence of 14 mouse strains manifesting both hypopigmentation and a platelet storage pool deficiency. Two mouse models, pearl and mocha, have mutations in the beta 3A and delta subunits of the adaptor-3 complex, respectively. This suggests that defective vesicular trafficking, specifically cargo packaging vesicle formation, vesicle docking, or membrane fusion, may comprise the basic defect in HPS. Studies of the proteins involved in intercompartmental transport for melanosomes, platelet-dense bodies, and lysosomes should lead to a better understanding of the mechanisms of organellogenesis and to more effective therapies for HPS. (C) 1998 Academic Press. C1 NICHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NICHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 62 TC 63 Z9 63 U1 1 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD OCT PY 1998 VL 65 IS 2 BP 85 EP 96 DI 10.1006/mgme.1998.2729 PG 12 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 134LG UT WOS:000076744000003 PM 9787100 ER PT J AU Lee, J Jiao, XD Hejtmancik, JF Kaiser-Kupfer, M Chader, GJ AF Lee, J Jiao, XD Hejtmancik, JF Kaiser-Kupfer, M Chader, GJ TI Identification, isolation, and characterization of a 32-kDa fatty acid binding protein missing from lymphocytes in humans with Bietti crystalline dystrophy (BCD) SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE human lymphocytes; long-chain polyunsaturated fatty acids; n-3 polyunsaturated fatty acids; n-6 polyunsaturated fatty acids; Bietti crystalline dystrophy; retina ID DISSOCIATION-CONSTANTS; DISPLACEMENT CURVES; RECEPTOR LIGAND; EXPRESSION; RETINA; GROWTH; ASSAY; GENE AB Bietti crystalline dystrophy (BCD) is an autosomal recessive retinal degeneration characterized by intraretinal lipid inclusions with degeneration of the retina and sclerosis of the choroidal vessels, resulting clinically in progressive night blindness and constriction of the visual fields. Characterization of fatty acid metabolism in Bietti crystalline dystrophy suggested that BCD might result from abnormalities in lipid-binding proteins or one or more enzymes active in fatty acid elongation and desaturation. To further investigate the first possibility, the docosahexaenoic acid-binding proteins (DHABPs) of human lymphocytes from patients with Bietti crystalline dystrophy were studied and compared with those of normal controls. For fatty acid-binding protein (FABP) identification, lymphocyte cytosol was first subjected to Lipidex 1000 chromatography. FABPs were then cross-linked with [C-14]22:6n-3 and identified by HPLC and SDS-PAGE. Ten major peaks corresponding to calculated molecular weights of 13, 14, 32, 43, 45, 50, 64, 96, 105, and 186 kDa exhibit high-affinity binding of fatty acids. Significantly, peaks corresponding to two fatty acid-binding proteins of 32 and 45 kDa present in age-matched controls are absent from lymphocytes of patients with BCD. The 32-kDa fatty acid-binding protein present in normal individuals but absent from patients with BCD was isolated from cultured control human lymphocytes, its fatty acid-binding properties were characterized, and its amino acid composition was analyzed. It shows specific binding of 3n-3 fatty acids, consistent with the pattern of abnormalities of lipid metabolism demonstrated in patients with BCD. These results suggest that the 32- and 43-kDa FABPs are reasonable candidates for causing BCD. (C) 1998 Academic Press. C1 NIH, Retinal Cell & Mol Biol Lab, Bethesda, MD 20892 USA. NIH, Ophtalm Genet & Clin Serv Branch, Bethesda, MD 20892 USA. Natl Retinitis Pigmentosa Fdn Fighting Blindness, Hunt Valley, MD 21031 USA. RP Lee, J (reprint author), NEI, Bldg 6,Room 307, Bethesda, MD 20892 USA. NR 19 TC 45 Z9 49 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD OCT PY 1998 VL 65 IS 2 BP 143 EP 154 DI 10.1006/mgme.1998.2723 PG 12 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 134LG UT WOS:000076744000009 PM 9787106 ER PT J AU Majer, M Popov, KM Harris, RA Bogardus, C Prochazka, M AF Majer, M Popov, KM Harris, RA Bogardus, C Prochazka, M TI Insulin downregulates pyruvate dehydrogenase kinase (PDK) mRNA: Potential mechanism contributing to increased lipid oxidation in insulin-resistant subjects SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE PDK; mRNA; insulin regulation; insulin resistance; Pima Indians ID DEPENDENT DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; PIMA-INDIANS; GLUCOSE-METABOLISM; FATTY-ACIDS; OBESITY; NIDDM; PATHOGENESIS; CARBOHYDRATE; ASSOCIATION AB Oxidative metabolism of glucose is regulated by pyruvate dehydrogenase (PDH) that can be inhibited by isoforms of PDH kinase (PDK). Recently, increased PDK activity has been implicated in the pathogenesis of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) in obese subjects. Using quantitative RT-PCR, we measured mRNA of PDK2 and PDK4 isoforms in skeletal muscle biopsies from nondiabetic Pima Indians, a population with a high prevalence of NIDDM associated with obesity. PDK2 and PDK4 mRNAs were positively correlated with fasting plasma insulin concentration, 2-h plasma insulin concentration in response to oral glucose, and percentage body fat, whereas both isoforms were negatively correlated with insulin-mediated glucose uptake rates. Measurements of PDK2 and PDK4 mRNA during the hyperinsulinemic-euglycemic clamp and of PDK2 in cell culture indicated that both transcripts decrease in response to insulin. Increased fatty acid (FA) oxidation has been traditionally viewed as the cause for increased PDK activity contributing to insulin resistance in obese subjects. In contrast, our data indicate that insufficient downregulation of PDK mRNA in insulin-resistant individuals could be a cause of increased PDK expression leading to impaired glucose oxidation followed by increased FA oxidation. (C) 1998 Academic Press. C1 NIDDK, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. RP Prochazka, M (reprint author), NIDDK, Clin Diabet & Nutr Sect, Phoenix Epidemiol & Clin Res Branch, NIH, 4212 N 16th St, Phoenix, AZ 85016 USA. EM mprochazka@phx.niddk.nih.gov FU NIDDK NIH HHS [DK 47844]; NIGMS NIH HHS [GM 51262] NR 27 TC 80 Z9 82 U1 0 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD OCT PY 1998 VL 65 IS 2 BP 181 EP 186 DI 10.1006/mgme.1998.2748 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 134LG UT WOS:000076744000013 PM 9787110 ER PT J AU Shields, MJ Moffat, LE Ribaudo, RK AF Shields, MJ Moffat, LE Ribaudo, RK TI Functional comparison of bovine, murine, and human beta(2)-microglobulin: interactions with murine MHC I molecules SO MOLECULAR IMMUNOLOGY LA English DT Article DE beta(2)-microglobulin; MHC; bovine; peptide ID MAJOR HISTOCOMPATIBILITY COMPLEX; HEAVY-CHAINS; MONOCLONAL-ANTIBODIES; BETA-2 MICROGLOBULIN; ESCHERICHIA-COLI; HLA-A; BETA-2-MICROGLOBULIN; MOUSE; ANTIGENS; CELLS AB Fetal calf serum is a well known source of bovine beta(2)-microglobulin (beta(2)m) which can exchange with endogenous beta(2)m from, as well as promote peptide binding to, class I major histocompatibility (MHC I) molecules on cells cultured in vitro. Recombinant bovine beta(2)m was expressed and purified for direct functional comparison to human and murine beta(2)m for interactions with murine MHC I molecules H-2K(b), D-b, K-d, L-d, and D-d. Bovine and human beta(2)m were equivalent in stabilizing MHC I heavy chains and facilitating peptide loading, suggesting similar affinities for murine MHC I heavy chains. The activity of murine beta(2)m was significantly weaker, consistent with previous work that demonstrated the lower affinity of murine human beta(2)m for murine heavy chains compared to human beta(2)m Analysis of bovine beta(2)m in fetal calf serum revealed ten-fold higher concentrations than in adult bovine serum, levels shown to significantly affect MHC I stability and peptide loading. The ramifications for the study of MHC I molecules from cells in culture and the evolutionary implications of the higher affinity interactions of human and bovine beta(2)m are discussed. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NCI, Immune Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. RP Ribaudo, RK (reprint author), NCI, Immune Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 45 TC 28 Z9 29 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD OCT PY 1998 VL 35 IS 14-15 BP 919 EP 928 DI 10.1016/S0161-5890(98)00083-2 PG 10 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 151QC UT WOS:000077731100003 PM 9881687 ER PT J AU Cooke, BM Nicoll, CL Baruch, DI Coppel, RL AF Cooke, BM Nicoll, CL Baruch, DI Coppel, RL TI A recombinant peptide based on PfEMP-1 blocks and reverses adhesion of malaria-infected red blood cells to CD36 under flow SO MOLECULAR MICROBIOLOGY LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; HUMAN CEREBRAL MALARIA; CHONDROITIN SULFATE; ENDOTHELIAL-CELLS; IN-VITRO; ERYTHROCYTES; CYTOADHERENCE; RECEPTOR; SEQUESTRATION; ADHERENCE AB During falciparum malaria infection, severe complications ensue because parasitized red blood cells (PRBCs) adhere to endothelial cells and accumulate in the microvasculature. At the molecular level, adhesion is mediated by interaction of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP-1) on the PRBC surface with receptors on the surface of endothelial cells, including CD36. We have shown that a recombinant 179-residue subfragment of PfEMP-1 (rC1-2[1-179]), which encompasses the CD36-binding region, inhibits and reverses adhesion of PRBCs to CD36 under physiologically relevant flow conditions. rC1-2[1-179] inhibited adhesion in a concentration-dependent manner over the range 100 pM to 2 mu M, with up to 99% of adhesion blocked at the highest concentration tested. The antiadhesive activity of rC1-2[1-179] was not strain specific and almost totally ablated adhesion of four different parasite lines. Furthermore, rC1-2[1-179] showed remarkable ability to progressively reverse adhesion when flowed over adherent PRBCs for 2 h. The effect of rC1-2[1-179] was, however, specific for CD36-mediated adhesion and had no effect on adhesion mediated by CSA. Interference with binding of PRBCs to the vascular endothelium using rC1-2[1-179] or smaller organic mimetics may be a useful therapeutic approach to ameliorate severe complications of falciparum malaria. C1 Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Cooke, BM (reprint author), Monash Univ, Dept Microbiol, Clayton, Vic 3168, Australia. RI Coppel, Ross/A-6626-2008 OI Coppel, Ross/0000-0002-4476-9124 FU NIDDK NIH HHS [DK32094-10] NR 45 TC 39 Z9 40 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1998 VL 30 IS 1 BP 83 EP 90 DI 10.1046/j.1365-2958.1998.01040.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 130UJ UT WOS:000076538500008 PM 9786187 ER PT J AU Ryan, JR Levine, JF Apperson, CS Lubke, L Wirtz, RA Spears, PA Orndorff, PE AF Ryan, JR Levine, JF Apperson, CS Lubke, L Wirtz, RA Spears, PA Orndorff, PE TI An experimental chain of infection reveals that distinct Borrelia burgdorferi populations are selected in arthropod and mammalian hosts SO MOLECULAR MICROBIOLOGY LA English DT Article ID LYME-DISEASE SPIROCHETE; OUTER SURFACE PROTEIN; IXODES-RICINUS TICKS; ANTIGENIC VARIATION; CIRCULAR PLASMID; OSPC GENE; ETIOLOGIC AGENT; PHASE-VARIATION; NORTH-CAROLINA; STRAIN B31 AB The prokaryotic, spirochaetal microorganism Borrelia burgdorferi is the causative agent of Lyme disease, an arthropod-borne disease of a variety of vertebrates and the most prevalent arthropod-borne disease of humans in the United States. In order to understand better the normal life cycle of B. burgdorferi, an experimental chain of infection was devised that involved multiple sequential arthropod and mammalian passages. By examining populations of B. burgdorferi emerging from different points in this infectious chain, we demonstrate that selection of a, burgdorferi populations peculiar to arthropod or vertebrate hosts is a property of at least one of the two ecologically distinct strains we examined. Distinct B. burgdorferi populations were identified using an antigenic profile, defined by a set of monoclonal antibodies to eight B. burgdorferi antigens, and a plasmid profile, defined by the naturally occurring plasmids in the starting clonal populations. These two profiles constituted the phenotypical signature of the population. In the strain exhibiting selection in the different hosts, transition from one host to another produced a striking series of alternating phenotypical signatures down the chain of infection. At the molecular level, the alternating signatures were manifested as a reciprocal relationship between the expression of certain antigenic forms of outer surface protein (Osp) B and OspC, In the case of OspC, the antigenic changes could be correlated to the presence of one of two distinctly different alleles of the ospC gene in a full-length and presumably transcriptionally active state. In the case of OspB, two alleles were again identified. However, their differences were minor and their relationship to OspB antigenic variation more complicated. In addition to the reciprocating changes in the antigenic profile, a reciprocating change in the size (probably the multimeric state) of a 9.0 kbp supercoiled plasmid was also noted. Selection of distinct populations in the tick may be responsible for the microorganism's ability to infect a wide range of vertebrate hosts efficiently, in that the tick might provide selective pressure for the elimination of the population selected in the previous host. C1 N Carolina State Univ, Coll Vet Med, Dept Microbiol Pathol & Parasitol, Raleigh, NC 27606 USA. N Carolina State Univ, Coll Agr & Life Sci, Dept Entomol, Raleigh, NC 27606 USA. NIAID, Bacterial Pathogenesis Sect, Microscopy Branch, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Dept Entomol, Div Communicable Dis & Immunol, Washington, DC 20307 USA. RP Orndorff, PE (reprint author), N Carolina State Univ, Coll Vet Med, Dept Microbiol Pathol & Parasitol, 4700 Hillsborough St, Raleigh, NC 27606 USA. EM paul_orndorff@ncsu.edu NR 69 TC 19 Z9 19 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD OCT PY 1998 VL 30 IS 2 BP 365 EP 379 DI 10.1046/j.1365-2958.1998.01071.x PG 15 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 131BE UT WOS:000076555200014 PM 9791181 ER PT J AU Shoshani, T Zhang, SD Dey, S Pastan, I Gottesman, MM AF Shoshani, T Zhang, SD Dey, S Pastan, I Gottesman, MM TI Analysis of random recombination between human MDR1 and mouse mdr1a cDNA in a pHaMDR-dihydrofolate reductase bicistronic expression system SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; MONOCLONAL-ANTIBODIES; TRANSMEMBRANE DOMAIN; MOLECULAR EVOLUTION; MULTIPLE-MYELOMA; DRUG-RESISTANCE; LABELING SITES; IN-VITRO; MUTATIONS AB Human P-glycoprotein (Pgp) confers multidrug resistance (MDR) to otherwise sensitive cells. The homologous mouse Pgps, which are encoded by mouse mdr1a (also known as mdr3) and mdr1b (also known as mdr1), confer different degrees of resistance to the same MDR drugs and inhibitors. To create recombinants for the study of sequences responsible for these differences in drug-resistance, chimeric cDNA libraries can be constructed by homologous recombination of pools of related sequences. This mutagenesis approach is called DNA shuffling. To select for chimeric Pgp with an altered resistance profile, DNA shuffling between the homologous but not identical drug interacting transmembrane domains 5 and 6 of human MDR1 and mouse mdr1a was used. The chimeric proteins were expressed in human KB-3-1 cells. One recombinant Pgp (clone 3-4) with a novel phenotype was analyzed in detail. Inhibitors of Pgp, including verapamil and cyclosporin A, were less effective in reversing resistance of the chimeric Pgp compared with wild-type Pgp, for certain drugs. However, [I-125]iodoarylazido-prazosin photoaffinity labeling of the chimeric Pgp and its binding competition with cyclosporin A, showed that cyclosporin A competed for the photoaffinity labeling. The chimeric Pgp cells stained less well with human-specific anti-Pgp mAb MRK16 than wild-type Pgp, despite having the described epitopes for MRK16. Staining with human-specific mAb UIC2 was increased when the chimeric protein was compared with wildtype Pgp. These results suggest an alteration in exposure of human Pgp specific epitopes in this chimeric Pgp, as well as a change in the interaction of reversing agents with the chimeric protein. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1AO9,37 Convent Dr MSC4255, Bethesda, MD 20892 USA. NR 34 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 1998 VL 54 IS 4 BP 623 EP 630 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 129VV UT WOS:000076485500004 PM 9765504 ER PT J AU Conwit, RA Tracy, B Cowl, A McHugh, M Stashuk, D Brown, WF Metter, EJ AF Conwit, RA Tracy, B Cowl, A McHugh, M Stashuk, D Brown, WF Metter, EJ TI Firing rate analysis using decomposition-enhanced spike triggered averaging in the quadriceps femoris SO MUSCLE & NERVE LA English DT Article DE EMG signal decomposition; mean motor unit firing rate; firing rates and force generation ID MOTOR UNITS; PATTERN AB Electromyographic signals detected from the quadriceps femoris during various constant force contractions were decomposed to identify individual motor unit discharges and mean firing rates (FRs). Subject and group mean FRs were calculated for each force level. Mean FR values and FR variability increased with force. Individual, subject, and group mean FRs showed slight increases until 30% of maximum voluntary contraction and larger increases thereafter. Findings are discussed in relation to motor unit recruitment, frequency modulation, and fatigue. (C) 1998 John Wiley & Sons, Inc. C1 Johns Hopkins Bayview Med Ctr, Dept Neurol, Baltimore, MD 21224 USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. Cornell Univ, Ithaca, NY USA. Univ Waterloo, Dept Syst Design Engn, Waterloo, ON N2L 3G1, Canada. New England Med Ctr, Neuromuscular Div, Boston, MA 02111 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Conwit, RA (reprint author), Johns Hopkins Bayview Med Ctr, Dept Neurol, 4940 Ave, Baltimore, MD 21224 USA. NR 6 TC 21 Z9 21 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-639X J9 MUSCLE NERVE JI Muscle Nerve PD OCT PY 1998 VL 21 IS 10 BP 1338 EP 1340 DI 10.1002/(SICI)1097-4598(199810)21:10<1338::AID-MUS17>3.0.CO;2-Y PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 115PA UT WOS:000075672800017 PM 9736067 ER PT J AU Leroy, E Boyer, R Auburger, G Leube, B Ulm, G Mezey, E Harta, G Brownstein, MJ Jonnalagada, S Chernova, T Dehejia, A Lavedan, C Gasser, T Steinbach, PJ Wilkinson, KD Polymeropoulos, MH AF Leroy, E Boyer, R Auburger, G Leube, B Ulm, G Mezey, E Harta, G Brownstein, MJ Jonnalagada, S Chernova, T Dehejia, A Lavedan, C Gasser, T Steinbach, PJ Wilkinson, KD Polymeropoulos, MH TI The ubiquitin pathway in Parkinson's disease SO NATURE LA English DT Letter ID CARBOXYL-TERMINAL HYDROLASE; ALPHA-SYNUCLEIN; PGP 9.5; BODIES C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Hosp Dusseldorf, Dept Neurol, D-40001 Dusseldorf, Germany. Paracelcus Elena Klin, D-34128 Kassel, Germany. NINDS, Basic Neurosci Program, NIH, Bethesda, MD 20892 USA. NIMH, Genet Sect, NIH, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Dept Biochem, Atlanta, GA 30322 USA. Univ Munich, Klinikum Grosshadern, Neurol Klin, D-8000 Munich, Germany. NIH, Ctr Mol Modeling, CIT, Bethesda, MD 20892 USA. RP Leroy, E (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 49 Room 4A66, Bethesda, MD 20892 USA. RI Brownstein, Michael/B-8609-2009 NR 9 TC 1070 Z9 1120 U1 3 U2 48 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD OCT 1 PY 1998 VL 395 IS 6701 BP 451 EP 452 DI 10.1038/26652 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 124ZG UT WOS:000076212200037 PM 9774100 ER PT J AU Xu, JF Meyers, D Freije, D Isaacs, S Wiley, K Nusskern, D Ewing, C Wilkens, E Bujnovszky, P Bova, GS Walsh, P Isaacs, W Schleutker, J Matikainen, M Tammela, T Visakorpi, T Kallioniemi, OP Berry, R Schaid, D French, A McDonnell, S Schroeder, J Blute, M Thibodeau, S Gronberg, H Emanuelsson, M Damber, JE Bergh, A Jonsson, BA Smith, J Bailey-Wilson, J Carpten, J Stephan, D Gillanders, E Amundson, I Kainu, T Freas-Lutz, D Baffoe-Bonnie, A Van Aucken, A Sood, R Collins, F Brownstein, M Trent, J AF Xu, JF Meyers, D Freije, D Isaacs, S Wiley, K Nusskern, D Ewing, C Wilkens, E Bujnovszky, P Bova, GS Walsh, P Isaacs, W Schleutker, J Matikainen, M Tammela, T Visakorpi, T Kallioniemi, OP Berry, R Schaid, D French, A McDonnell, S Schroeder, J Blute, M Thibodeau, S Gronberg, H Emanuelsson, M Damber, JE Bergh, A Jonsson, BA Smith, J Bailey-Wilson, J Carpten, J Stephan, D Gillanders, E Amundson, I Kainu, T Freas-Lutz, D Baffoe-Bonnie, A Van Aucken, A Sood, R Collins, F Brownstein, M Trent, J TI Evidence for a prostate cancer susceptibility locus on the X chromosome SO NATURE GENETICS LA English DT Article ID ANDROGEN-RECEPTOR GENE; LINKAGE ANALYSIS; FAMILY HISTORY; RISK; INHERITANCE; SUPPORT; HUMANS; CAG AB Over 200.000 new prostate cancer cases are diagnosed in the United States each year, accounting for more than 35% of all cancer cases affecting men, and resulting in 40,000 deaths annually(1). Attempts to characterize genes predisposing to prostate cancer have been hampered by a high phenocopy rate, the late age of onset of the disease and, in the absence of distinguishing clinical features, the inability to stratify patients into subgroups relative to suspected genetic locus heterogeneity. We previously performed a genome-wide search for hereditary prostate cancer (HPC) genes, finding evidence of a prostate cancer susceptibility locus on chromosome 1 (termed HPC1; ref. 2). Here we present evidence for the location of a second prostate cancer susceptibility gene, which by heterogeneity estimates accounts for approximately 16% of HPC cases. This HPC locus resides on the X chromosome (Xq27-28), a finding consistent with results of previous population-based studies suggesting an X-linked mode of HPC inheritance. Linkage to Xq27-28 was observed in a combined study population of 360 prostate cancer families collected at four independent sites in North America, Finland and Sweden. A maximum two-point lod score of 4.60 was observed at DXS1113, theta=0.26, in the combined data set. Parametric multipoint and non-parametric analyses provided results consistent with the two-point analysis. Significant evidence for genetic locus heterogeneity was observed, with similar estimates of the proportion of linked families in each separate family collection. Genetic mapping of the locus represents an important initial step in the identification of an X-linked gene implicated in the aetiology of HPC. C1 Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21287 USA. Univ Maryland, Ctr Genet Asthma & Complex Dis, Baltimore, MD 21201 USA. Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Tampere, Finland. Mayo Clin & Mayo Fdn, Dept Lab Med & Pathol, Rochester, MN 55902 USA. Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55902 USA. Mayo Clin & Mayo Fdn, Dept Urol, Rochester, MN 55902 USA. Umea Univ, Dept Oncol, Umea, Sweden. Umea Univ, Dept Urol & Androl, Umea, Sweden. Umea Univ, Dept Pathol, Umea, Sweden. Natl Human Genome Res Inst, Canc Invest Grp, NIH, Bethesda, MD 20892 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19012 USA. RP Isaacs, W (reprint author), Johns Hopkins Med Inst, Dept Urol, Baltimore, MD 21287 USA. EM wisaacs@jhmi.edu RI Brownstein, Michael/B-8609-2009; Kallioniemi, Olli/H-5111-2011; Smith, Jeff/C-3484-2012; Kallioniemi, Olli/H-4738-2012; OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332; Bailey-Wilson, Joan/0000-0002-9153-2920 FU NCI NIH HHS [CA58236, CA72818]; NHGRI NIH HHS [N01-HG-55389] NR 28 TC 336 Z9 339 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1998 VL 20 IS 2 BP 175 EP 179 DI 10.1038/2477 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 125HL UT WOS:000076231300020 PM 9771711 ER PT J AU Brown, SA Warburton, D Brown, LY Yu, CY Roeder, ER Stengel-Rutkowski, S Hennekam, RCM Muenke, M AF Brown, SA Warburton, D Brown, LY Yu, CY Roeder, ER Stengel-Rutkowski, S Hennekam, RCM Muenke, M TI Holoprosencephaly due to mutations in ZIC2, a homologue of Drosophila odd-paired SO NATURE GENETICS LA English DT Article ID SONIC-HEDGEHOG GENE; PROTEIN; DEFINITION; EXPRESSION; REGION; DOMAIN AB Holoprosencephaly (HPE) is the most common structural anomaly of the human brain and is one of the anomalies seen in patients with deletions and duplications of chromosome 13. On the basis of molecular analysis of a series of patients with hemizygous deletions of the long arm of chromosome 13. we have defined a discrete region in band 13q32 where deletion leads to major developmental anomalies (the 13q32 deletion syndrome). This approximately 1-Mb region(1) lies between markers D13S136 and D13S147. Patients in which this region is deleted usually have major congenital malformations, including brain anomalies such as HPE or exencephaly, and digital anomalies such as absent thumbs(2). We now report that human ZIC2 maps to this critical deletion region and that heterozygous mutations in ZIC2 are associated with HPE. Haploinsufficiency for ZIC2 is likely to cause the brain malformations seen in 13q deletion patients. C1 Columbia Univ, Dept Obstet & Gynecol, New York, NY 10027 USA. Columbia Univ, Dept Pediat, New York, NY 10027 USA. Columbia Univ, Dept Genet & Dev, New York, NY 10027 USA. Presbyterian Hosp, New York, NY 10032 USA. Valley Childrens Hosp, Fresno, CA 93703 USA. Kinderzentrum Munchen, Munich, Germany. Univ Amsterdam, Inst Human Genet, NL-1012 WX Amsterdam, Netherlands. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Childrens Hosp Philadelphia, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD USA. RP Brown, SA (reprint author), Columbia Univ, Dept Obstet & Gynecol, New York, NY 10027 USA. EM brown@cuccfa.ccc.columbia.edu FU NICHD NIH HHS [HD28732, HD29862, HD32467] NR 28 TC 315 Z9 319 U1 2 U2 5 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1998 VL 20 IS 2 BP 180 EP 183 DI 10.1038/2484 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 125HL UT WOS:000076231300021 PM 9771712 ER PT J AU Reddy, PH Williams, M Charles, V Garrett, L Pike-Buchanan, L Whetsell, WO Miller, G Tagle, DA AF Reddy, PH Williams, M Charles, V Garrett, L Pike-Buchanan, L Whetsell, WO Miller, G Tagle, DA TI Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA SO NATURE GENETICS LA English DT Article ID HUNTINGTONS-DISEASE GENE; INTRANUCLEAR INCLUSIONS; CAG REPEAT; NEUROLOGICAL PHENOTYPE; WIDESPREAD EXPRESSION; TRINUCLEOTIDE REPEAT; PROTEIN; BRAIN; ONSET; AGE AB Huntington disease (HD) is an adult-onset, autosomal dominant inherited human neurodegenerative disorder characterized by hyperkinetic involuntary movements, including motor restlessness and chorea, slowing of voluntary movements and cognitive impairment. Selective regional neuron loss and gliosis in striatum. cerebral cortex, thalamus, subthalamus and hippocampus(1-4) are well recognized as neuropathological correlates for the clinical manifestations of HD. The underlying genetic mutation is the expansion of CAG trinucleotide repeats (coding for polyglutamines) to 36-121 copies in exon 1 of the HD gene(5-8). The HD mRNA and protein product (huntingtin) show widespread distribution(9-11), and thus much remains to be understood about the selective and progressive neurodegeneration in HD. To create an experimental animal model for HD, transgenic mice were generated showing widespread expression of full-length human HD cDNA with either 16, 48 or 89 CAG repeats. Only mice with 48 or 89 CAG repeats manifested progressive behavioural and motor dysfunction with neuron loss and gliosis in striatum, cerebral cortex, thalamus and hippocampus. These animals represent clinically relevant models for HD pathogenesis, and may provide insights into the underlying pathophysiological mechanisms of other triplet repeat disorders. C1 Natl Human Genome Res Inst, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. Natl Human Genome Res Inst, Lab Genet Dis Res, Bethesda, MD 20892 USA. NIH, Off Res Serv, Vet Resources Program, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. RP Tagle, DA (reprint author), Natl Human Genome Res Inst, Genet & Mol Biol Branch, Bldg 49,Room 3A26,49 Convent Dr MSC 4442, Bethesda, MD 20892 USA. EM datagle@helix.nih.gov FU NINDS NIH HHS [NS-28236] NR 30 TC 301 Z9 304 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1998 VL 20 IS 2 BP 198 EP 202 DI 10.1038/2510 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 125HL UT WOS:000076231300025 PM 9771716 ER PT J AU Majumdar, A Khorlin, A Dyatkina, N Lin, FLM Powell, J Liu, J Feiz, ZZ Khripine, Y Watanabe, KA George, J Glazer, PM Seidman, MM AF Majumdar, A Khorlin, A Dyatkina, N Lin, FLM Powell, J Liu, J Feiz, ZZ Khripine, Y Watanabe, KA George, J Glazer, PM Seidman, MM TI Targeted gene knockout mediated by triple helix forming oligonucleotides SO NATURE GENETICS LA English DT Article ID DOUBLE-STRAND BREAKS; ILLEGITIMATE RECOMBINATION; MAMMALIAN CHROMOSOME; BASE-PAIRS; HPRT GENE; DNA; SEQUENCES; BINDING; RECOGNITION; MUTAGENESIS AB Triple helix forming oligonucleotides (TFOs) recognize and bind sequences in duplex DNA and have received considerable attention because of their potential for targeting specific genomic sites(1-3). TFOs can deliver DNA reactive reagents to specific sequences in purified chromosomal DNA (ref. 4) and nuclei(5). However, chromosome targeting in viable cells has not been demonstrated, and in vitro experiments indicate that chromatin structure is incompatible with tripler formation(6-8) We have prepared modified TFOs, linked to the DNA-crosslinking reagent psoralen. directed at a site in the Hprt gene. We show that stable Hprt-deficient clones can be recovered following introduction of the TFOs into viable cells and photoactivation of the psoralen. Analysis of 282 clones indicated that 85% contained mutations in the tripler target region. We observed mainly deletions and some insertions. These data indicate that appropriately constructed TFOs can find chromosomal targets, and suggest that the chromatin structure in the target region is more dynamic than predicted by the in vitro experiments. C1 NIA, NIH, Baltimore, MD 21224 USA. Codon Pharmaceut, Gaithersburg, MD 20877 USA. Yale Univ, Dept Therapeut Radiol, New Haven, CT 06510 USA. Ribozyme Pharmaceut Inc, Boulder, CO USA. RP Seidman, MM (reprint author), NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 30 TC 149 Z9 150 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD OCT PY 1998 VL 20 IS 2 BP 212 EP 214 DI 10.1038/2530 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 125HL UT WOS:000076231300028 PM 9771719 ER PT J AU Sharkis, S Kanz, L Brugger, N Orlic, D AF Sharkis, S Kanz, L Brugger, N Orlic, D TI The fascinating life of hematopoietic stem cells SO NATURE MEDICINE LA English DT Editorial Material C1 Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA. Univ Klinikum Tubingen, Med Klin & Poliklin, Tubingen, Germany. HNGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. RP Sharkis, S (reprint author), Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 1998 VL 4 IS 10 BP 1118 EP 1119 DI 10.1038/2611 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 125GY UT WOS:000076230100023 PM 9771737 ER PT J AU Bonney, EA Matzinger, P AF Bonney, EA Matzinger, P TI Much IDO about pregnancy SO NATURE MEDICINE LA English DT Editorial Material C1 Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA 30303 USA. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Bonney, EA (reprint author), Emory Univ, Sch Med, Dept Gynecol & Obstet, Atlanta, GA 30303 USA. NR 3 TC 39 Z9 42 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 1998 VL 4 IS 10 BP 1128 EP 1129 DI 10.1038/2624 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 125GY UT WOS:000076230100030 PM 9771744 ER PT J AU Persons, DA Allay, JA Riberdy, JM Wersto, RP Donahue, RE Sorrentino, BP Nienhuis, AW AF Persons, DA Allay, JA Riberdy, JM Wersto, RP Donahue, RE Sorrentino, BP Nienhuis, AW TI Use of the green fluorescent protein as a marker to identify and track genetically modified hematopoietic cells SO NATURE MEDICINE LA English DT Article ID MEDIATED GENE-TRANSFER; BONE-MARROW CELLS; PERIPHERAL-BLOOD LYMPHOCYTES; TITER RETROVIRAL VECTORS; SELECTABLE MARKER; PROGENITOR CELLS; MAMMALIAN-CELLS; T-LYMPHOCYTES; IN-VIVO; EXPRESSION C1 St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Expt Hematol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Immunol, Memphis, TN 38105 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Nienhuis, AW (reprint author), St Jude Childrens Res Hosp, Dept Hematol Oncol, Div Expt Hematol, 332 N Lauderdale Dr, Memphis, TN 38105 USA. FU NCI NIH HHS [P30 CA 21765]; NHLBI NIH HHS [P01 HL 53749] NR 35 TC 89 Z9 92 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD OCT PY 1998 VL 4 IS 10 BP 1201 EP 1205 DI 10.1038/2704 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 125GY UT WOS:000076230100044 PM 9771757 ER PT J AU Mayer, M AF Mayer, M TI Ion-binding sites in NMDA receptors: classical approaches provide the numbers SO NATURE NEUROSCIENCE LA English DT Article ID CALCIUM CHANNELS; AMINO-ACIDS; K+ CHANNEL; CONDUCTANCE; PORE; SELECTIVITY; RINGS; BLOCK AB The structure of glutamate receptor pores is not well defined. A new study reveals multiple Na+ binding sites in NMDA receptors, occupancy of which interferes with channel blockers. C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Mayer, M (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49,Room 5A78, Bethesda, MD 20892 USA. NR 12 TC 3 Z9 3 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD OCT PY 1998 VL 1 IS 6 BP 433 EP 434 DI 10.1038/2149 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 128LE UT WOS:000076406900003 PM 10196537 ER PT J AU Lee, AY Gulnik, SV Erickson, JW AF Lee, AY Gulnik, SV Erickson, JW TI Conformational switching in an aspartic proteinase SO NATURE STRUCTURAL BIOLOGY LA English DT Letter ID HUMAN CATHEPSIN-D; PORCINE PEPSINOGEN; CRYSTAL-STRUCTURES; INHIBITION; RESOLUTION; DESIGN; PROTEASES; PEPTIDES; ENZYME; LIVER AB The crystal structure of a catalytically inactive form of cathepsin D (CatD(hi)) has been obtained at pH 7.5. The N-terminal strand relocates by 30 Angstrom from its position in the interdomain beta-sheet and inserts into the active site cleft, effectively blocking substrate access. CatD(hi) has a five-stranded interdomain beta-sheet anti resembles intermediate 3, a hypothetical structure proposed to be transiently formed during proteolytic activation of the proenzyme precursor. Interconversion between active and inactive forms of CatD is reversible and map be regulated by an ionizable switch involving the carboxylate side chains of Glu 5, Glu 180, and Asp 187. Our findings provide a structural basis for the pH-dependent regulation of aspartic proteinase activity and suggest a novel mechanism for pH-dependent modulation of substrate specificity. C1 NCI, Struct Biochem Program, SAIC Frederick, Frederick, MD 21702 USA. RP Erickson, JW (reprint author), NCI, Struct Biochem Program, SAIC Frederick, POB B, Frederick, MD 21702 USA. EM erickson@ncifcrf.gov FU NCI NIH HHS [N01-CO-56000] NR 35 TC 75 Z9 75 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD OCT PY 1998 VL 5 IS 10 BP 866 EP 871 DI 10.1038/2306 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 126QC UT WOS:000076303800010 PM 9783744 ER PT J AU Cai, M Huang, Y Zheng, R Wei, SQ Ghirlando, R Lee, MS Craigie, R Gronenborn, AM Clore, GM AF Cai, M Huang, Y Zheng, R Wei, SQ Ghirlando, R Lee, MS Craigie, R Gronenborn, AM Clore, GM TI Solution structure of the cellular factor BAF responsible for protecting retroviral DNA from autointegration SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID CRYSTAL-STRUCTURE; PROTEIN NMR; INTEGRATION; RESOLUTION; COUPLINGS; INVITRO; SYSTEM; CORE AB The solution structure of the human barrier-to-autointegration factor, BAF, a 21,000 M, dimer, has been solved by NMR, including extensive use of dipolar couplings which provide a priori long range structural information. BAF is a highly evolutionarily conserved DNA binding protein that is responsible for inhibiting autointegration of retroviral DNA, thereby promoting integration of retroviral DNA into the host chromosome. BAF is largely helical, and each subunit is composed of five helices. The dimer is elongated in shape and the dimer interface comprises principally hydrophobic contacts supplemented by a single salt bridge. Despite the absence of any sequence similarity to any other known protein family, the topology of helices 3-5 is similar to that of a number of DNA binding proteins, with helices 4 and 5 constituting a helix-turn-helix motif. A model for the interaction of BAF with DNA that is consistent with structural and mutagenesis data is proposed. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM gronenborn@vger.niddk.nih.gov; clore@speck.niddk.nih.gov RI Clore, G. Marius/A-3511-2008; Ghirlando, Rodolfo/A-8880-2009 OI Clore, G. Marius/0000-0003-3809-1027; NR 38 TC 104 Z9 108 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD OCT PY 1998 VL 5 IS 10 BP 903 EP 909 DI 10.1038/2345 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 126QC UT WOS:000076303800017 PM 9783751 ER PT J AU Brooks, R Grossberg, S Optican, L AF Brooks, R Grossberg, S Optican, L TI Neural control and robotics: biology and technology SO NEURAL NETWORKS LA English DT Editorial Material C1 MIT, Cambridge, MA 02139 USA. Boston Univ, Boston, MA 02215 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. RP Brooks, R (reprint author), MIT, Cambridge, MA 02139 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD OCT-NOV PY 1998 VL 11 IS 7-8 BP 1147 EP 1147 PG 1 WC Computer Science, Artificial Intelligence SC Computer Science GA 137YH UT WOS:000076944300001 ER PT J AU Lefevre, P Quaia, C Optican, LM AF Lefevre, P Quaia, C Optican, LM TI Distributed model of control of saccades by superior colliculus and cerebellum SO NEURAL NETWORKS LA English DT Article DE saccade; eye movements; superior colliculus; cerebellum; frontal eye fields; parietal cortex; modeling ID NEURAL-NETWORK MODEL; FRONTAL EYE-FIELD; ELECTRICAL-STIMULATION; MOVEMENT CONTROL; ALERT MONKEY; GAZE SHIFTS; MOTOR MAP; GENERATION; SYSTEM; DYNAMICS AB We investigate the role that superior colliculus (SC) and cerebellum (CBLM) might play in controlling saccadic eye movements. Even though strong experimental evidence argues for an important role for the CBLM, the most recent models of the saccadic system have relied mostly on the SC for the dynamic control of saccades. In this study, we propose that saccades are controlled by two parallel pathways, one including the SC and the other including the CBLM. In this model, both SC and CBLM provide part of the drive to the saccade. Furthermore, the CBLM receives direct feedback from the brain stem and keeps track of the residual motor error, so that it can issue appropriate commands to compensate for incorrect heading and to end the movement when the target has been foveated. We present here a distributed model that produces realistic saccades and accounts for a great deal of neurophysiological data. Published by Elsevier Science Ltd. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Catholic Univ Louvain, Neurophysiol Lab, B-1348 Louvain, Belgium. Catholic Univ Louvain, CESAME, B-1348 Louvain, Belgium. Univ Trieste, DEEI, Trieste, Italy. RP NEI, Sensorimotor Res Lab, NIH, Bldg 49,Rm 2A50, Bethesda, MD 20892 USA. EM loptican@nih.gov NR 47 TC 70 Z9 71 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 EI 1879-2782 J9 NEURAL NETWORKS JI Neural Netw. PD OCT-NOV PY 1998 VL 11 IS 7-8 BP 1175 EP 1190 DI 10.1016/S0893-6080(98)00071-9 PG 16 WC Computer Science, Artificial Intelligence; Neurosciences SC Computer Science; Neurosciences & Neurology GA 137YH UT WOS:000076944300004 ER PT J AU Quaia, C Optican, LM Goldberg, ME AF Quaia, C Optican, LM Goldberg, ME TI The maintenance of spatial accuracy by the perisaccadic remapping of visual receptive fields SO NEURAL NETWORKS LA English DT Article DE model; saccades; salience; lateral intraparietal cortex (LIP); frontal eye fields (FEF); superior colliculus (SC) ID SACCADIC EYE-MOVEMENTS; LATERAL INTRAPARIETAL AREA; POSTERIOR PARIETAL CORTEX; MONKEY CEREBRAL-CORTEX; BEHAVIORAL ENHANCEMENT; NEURONS; RESPONSES; MODULATION; GAZE AB Humans and monkeys can direct their eyes to the spatial location of briefly flashed targets even when a saccade intervenes between the stimulus flash and the saccade to acquire its location. It had been proposed that the oculomotor system performs this task by resorting to a supraretinal representation of space. In this paper we review neurophysiological and clinical data suggesting that the brain can use a different strategy that does not require an explicit supraretinal representation of targets. We propose and implement a simple neural model that can keep track continuously of the location of saccade targets in eye-centered coordinates. Finally, based on recent data, we argue that such a neural mechanism is in fact used to keep track not only of saccade targets but of the location of salient areas of the visual scene in general. Published by Elsevier Science Ltd. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Goldberg, ME (reprint author), Georgetown Univ, Sch Med, Dept Neurol, Washington, DC 20007 USA. EM meg@lsr.nei,nih.gov NR 28 TC 67 Z9 67 U1 2 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0893-6080 J9 NEURAL NETWORKS JI Neural Netw. PD OCT-NOV PY 1998 VL 11 IS 7-8 BP 1229 EP 1240 DI 10.1016/S0893-6080(98)00069-0 PG 12 WC Computer Science, Artificial Intelligence SC Computer Science GA 137YH UT WOS:000076944300008 ER PT J AU Grange, E Rabin, O Bell, J Chang, MCJ AF Grange, E Rabin, O Bell, J Chang, MCJ TI Manoalide, a phospholipase A(2) inhibitor, inhibits arachidonate incorporation and turnover in brain phospholipids of the awake rat SO NEUROCHEMICAL RESEARCH LA English DT Article DE phospholipase A(2); manoalide; arachidonic acid; phospholipids; turnover; inhibition; rat; awake; in vivo; fatty acids ID CALCIUM-INDEPENDENT PHOSPHOLIPASE-A2; ACID INCORPORATION; FATTY-ACIDS; METABOLISM; PHOSPHOINOSITIDE; IDENTIFICATION; TRANSLOCATION; ENZYMES; CYTOSOL; ESTERS AB The Fatty Acid method was used to determine whether incorporation of plasma radiolabeled arachidonic acid into brain phospholipids is controlled by phospholipase A(2). Awake rats received an i.v. injection of a phospholipase A(2) inhibitor, manoalide (10 mg/kg), and then were infused i.v. with [I-C-14]arachidonate or [H-3]arachidonate. Animals were killed after infusion by microwave irradiation, and tracer distribution was analyzed in brain phospholipid, neutral lipid and acyl-CoA pools. Calcium-independent phospholipase A(2) activity in brain homogenate was reduced by manoalide, whereas phospholipase C activity was unaffected. At 60 min but not at 20 or 40 min after its injection, manoalide had significantly decreased by 50% incorporation of unesterified arachidonate into and turnover within brain phospholipids, taking into account dilution of the brain arachidonoyl-CoA pool by recycled arachidonate. Manoalide also increased by 100% the net rate of unesterified arachidonate incorporation into brain triacylglycerol. This study indicates that manoalide can be used to inhibit brain phospholipase A(2) in vivo, and that phospholipase A(2) plays a critical role in arachidonate turnover in brain phospholipids and neutral lipids. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP NIA, Neurosci Lab, NIH, Bldg 10,Room 6C-103, Bethesda, MD 20892 USA. EM mcjchang@box-m.nih.gov NR 35 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 EI 1573-6903 J9 NEUROCHEM RES JI Neurochem. Res. PD OCT PY 1998 VL 23 IS 10 BP 1251 EP 1257 DI 10.1023/A:1020788031720 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 131BY UT WOS:000076556900005 PM 9804280 ER PT J AU Heinz, A Knable, MB Wolf, SS Jones, DW Gorey, JG Hyde, TM Weinberger, DR AF Heinz, A Knable, MB Wolf, SS Jones, DW Gorey, JG Hyde, TM Weinberger, DR TI Tourette's syndrome - [I-123]beta-CIT SPECT correlates of vocal tic severity SO NEUROLOGY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; I-123 BETA-CIT; POSITRON EMISSION TOMOGRAPHY; MIDBRAIN INVOLVEMENT; SEROTONIN TRANSPORTER; MONOZYGOTIC TWINS; HUMAN BRAIN; RAT-BRAIN; DOPAMINE; BINDING AB Objective: To examine in vivo the density of brain monoaminergic transporters in Tourette's syndrome (TS). Background: TS is a heritable neuropsychiatric disorder characterized by chronic vocal and motor ties and is often associated with obsessive-compulsive symptoms. Hyperstimulation of dopamine receptors and dysfunction of serotonergic transmission have been implicated in its pathogenesis, but direct evidence of involvement of these neurochemical systems has been limited. Methods: Symptom severity and the availability of presynaptic monoaminergic transporters in the basal ganglia, midbrain, and thalamus were measured using SPECT and the radioligand [I-123]2 beta-carbomethoxy-3 beta-(4-iodophenyl)tropane ([I-123]P-CIT) in 10 patients with TS and in 10 age- and sex-matched normal volunteers. Results: A significant negative correlation was found between a measure of overall tic severity and beta-CIT binding in the midbrain (r = -0.73, p = 0.02) and the thalamus (r = -0.82, p < 0.01). When examined post hoc, these correlations were determined largely by Vocal tic severity. No other significant correlations were found between symptom severity and beta-CIT binding in the striatum or cortex. Conclusions: These findings indicate that serotonergic neurotransmission in the midbrain and serotonergic or noradrenergic neurotransmission in the thalamus may be important factors in the expression of TS and may suggest novel targets for treatment. C1 St Elizabeth Hosp, Ctr Neurosci, NIMH,Intramural Res Program, Clin Brain Disorders Branch,NIH, Washington, DC 20032 USA. Stanley Fdn Res Program, Bethesda, MD USA. RP Weinberger, DR (reprint author), St Elizabeth Hosp, Ctr Neurosci, NIMH,Intramural Res Program, Clin Brain Disorders Branch,NIH, Washington, DC 20032 USA. NR 39 TC 64 Z9 66 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT PY 1998 VL 51 IS 4 BP 1069 EP 1074 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 128HC UT WOS:000076399100029 PM 9781531 ER PT J AU Basso, MA AF Basso, MA TI Cognitive set and oculomotor control SO NEURON LA English DT Review ID SUPERIOR COLLICULUS; EYE-MOVEMENTS; MONKEY; CORTEX; CELLS C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Basso, MA (reprint author), NEI, Sensorimotor Res Lab, Bldg 10, Bethesda, MD 20892 USA. NR 15 TC 7 Z9 8 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 1998 VL 21 IS 4 BP 665 EP 668 DI 10.1016/S0896-6273(00)80583-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 133QM UT WOS:000076697300010 PM 9808453 ER PT J AU Xiao, B Tu, JC Petralia, RS Yuan, JP Doan, A Breder, CD Ruggiero, A Lanahan, AA Wenthold, RJ Worley, PF AF Xiao, B Tu, JC Petralia, RS Yuan, JP Doan, A Breder, CD Ruggiero, A Lanahan, AA Wenthold, RJ Worley, PF TI Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of Homer-related, synaptic proteins SO NEURON LA English DT Article ID ALDRICH-SYNDROME PROTEIN; TRANSGENIC MICE; GENE; SEQUENCE; CYTOSKELETON; EXPRESSION; MEMBRANE; VASP AB Homer is a neuronal immediate early gene (IEG) that is enriched at excitatory synapses and binds group 1 metabotropic glutamate receptors (mGluRs). Here, we characterize a family of Homer-related proteins derived from three distinct genes. Like Homer IEG (now termed Homer 1a), all new members bind group 1 mGluRs. In contrast to Homer 1a, new members are constitutively expressed and encode a C-terminal coiled-coil (CC) domain that mediates self-multimerization. CC-Horners form natural complexes that cross-link mGluRs and are enriched at the postsynaptic density. Homer 1a does not multimerize and blocks the association of mGluRs with CC-Homer complexes. These observations support a model in which the dynamic expression of Homer 1a competes with constitutively expressed CC-Homers to modify synaptic mGluR properties. C1 Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Worley, PF (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. FU NIDA NIH HHS [DA11742, DA10309]; NIMH NIH HHS [KO2 MH01152] NR 27 TC 438 Z9 456 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT PY 1998 VL 21 IS 4 BP 707 EP 716 DI 10.1016/S0896-6273(00)80588-7 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 133QM UT WOS:000076697300015 PM 9808458 ER PT J AU Li, H Rogawski, MA AF Li, H Rogawski, MA TI GluR5 kainate receptor mediated synaptic transmission in rat basolateral amygdala in vitro SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 7th Neuropharmacology Conference CY NOV 05-07, 1998 CL LOS ANGELES, CALIFORNIA DE kainate receptor; 2,3-benzodiazepine; 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX); LY293558; amygdala; synaptic transmission ID NEURONS; GLUTAMATE; AMPA; ACID; NMDA; HIPPOCAMPUS; MECHANISMS; ANTAGONISM; ASPARTATE; NBQX AB A non-NMDA and non-AMPA receptor mediated excitatory synaptic response was identified in intracellularly recorded basolateral amygdala (BLA) neurons in an in vitro slice preparation. Synaptic potentials were evoked by stimulation of either the external capsule (EC) or basal amygdala (BA). NMDA and GABA, receptors were blocked by inclusion of 100 mu M (+/-)-2-amino-5-phosphonopentanoic acid and 10 mu M bicuculline in the perfusion solution. The AMPA receptor-selective allosteric antagonists GYKI 52466 (50 mu M) and GYKI 53655 (50 mu M) partially suppressed depolarizing synaptic responses evoked by single shock EC stimulation, but fully blocked synaptic responses evoked by BA stimulation. In recordings carried out in the presence of the AMPA receptor antagonists, EC stimulation with pulse trains (5-8 pulses at 50-100 Hz) evoked a large increase in the amplitude of synaptic responses. The AMPA receptor-independent component of the train-induced synaptic response had a null potential near 0 mV. Such AMPA receptor-independent, train-evoked synaptic responses were largely blocked by the AMPA/kainate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (20 mu M; 85 +/- 4%). In addition, the responses were blocked by the GluR5-selective kainate receptor antagonist LY293558 (10 mu M; 95 +/- 2%). These results indicate that a component of the EC (but not the BA) synaptic response is mediated by kainate receptors containing the GluR5 subunit. Published by Elsevier Science Ltd. C1 NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bethesda, MD 20892 USA. RP Rogawski, MA (reprint author), NINDS, Neuronal Excitabil Sect, Epilepsy Res Branch, NIH, Bldg 10,Room 5N-250,10 Ctr Dr MSC 1408, Bethesda, MD 20892 USA. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 31 TC 74 Z9 77 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT-NOV PY 1998 VL 37 IS 10-11 BP 1279 EP 1286 DI 10.1016/S0028-3908(98)00109-9 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 142UU UT WOS:000077219400010 PM 9849665 ER PT J AU Petralia, RS Zhao, HM Wang, YX Wenthold, RJ AF Petralia, RS Zhao, HM Wang, YX Wenthold, RJ TI Variations in the tangential distribution of postsynaptic glutamate receptors in Purkinje cell parallel and climbing fiber synapses during development SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 7th Neuropharmacology Conference CY NOV 05-07, 1998 CL LOS ANGELES, CALIFORNIA DE delta glutamate receptors; AMPA; mGluR1; cerebellum; climbing fibers; parallel fibers; immunogold ID CHANNEL DELTA-2 SUBUNIT; DEVELOPING RAT-BRAIN; AMINO-ACID RECEPTOR; NMDA RECEPTOR; NERVOUS-SYSTEM; IMMUNOGOLD LOCALIZATION; DIFFERENTIAL EXPRESSION; CEREBELLAR DEVELOPMENT; MULTIPLE INNERVATION; DENDRITIC SPINES AB Major factors affecting the responses of a neuron to release of glutamate include the kinds and distribution of glutamate receptors in the neuron and their distribution along the surface of the postsynaptic membrane (tangential distribution). The latter distribution pattern is established during the development of the synapse and could be modified during maturation of synapse structure/function and through adult synapse plasticity. Parallel and climbing fiber synapses of cerebellar Purkinje cells are good models for studying this pattern because they contain two major kinds of ionotropic glutamate receptors, alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and delta, that are involved in adult plasticity and show differences in distribution, and because these two synapse types show complex changes in architecture and glutamate receptor distributions during development. In the present study, both AMPA and delta receptors showed variations in tangential distributions during many stages of development from postnatal day 2 to adult; i.e. qualitative assessment showed that receptors are concentrated either near the center or in outer portions of the synapse, while they are rare or absent from the perisynaptic region. Quantitative analysis showed statistically significant nonuniformities at some ages; the most common nonuniformity in these cases appears to be a drop-off in receptor density in the outer 20% of the synapse. Statistical analyses also indicated that distribution patterns did not change significantly with age. In contrast to the ionotropic receptors, the metabotropic glutamate receptor, mGluR1 alpha, was found mainly in the perisynaptic region both during development and in adults. Differences in the distribution of glutamate receptors may be necessary to assure an effective response to glutamate release and may be modified through synaptic plasticity. Our findings show that the basic patterns of distribution of ionotropic and metabotropic glutamate receptors in synapses are established early in development, indicating that the postsynaptic density/membrane region is highly organized even in the immature synapse. Published by Elsevier Science Ltd. C1 NIDCD, NIH, Neurochem Lab, Bethesda, MD 20892 USA. RP Petralia, RS (reprint author), NIDCD, NIH, Neurochem Lab, 36 Convent DR MSC 4162, Bethesda, MD 20892 USA. EM petralia@nidcd.nih.gov NR 61 TC 40 Z9 41 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT-NOV PY 1998 VL 37 IS 10-11 BP 1321 EP 1334 DI 10.1016/S0028-3908(98)00118-X PG 14 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 142UU UT WOS:000077219400013 PM 9849668 ER PT J AU Cu, CH Bahring, R Mayer, ML AF Cu, CH Bahring, R Mayer, ML TI The role of hydrophobic interactions in binding of polyamines to non NMDA receptor ion channels SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 7th Neuropharmacology Conference CY NOV 05-07, 1998 CL LOS ANGELES, CALIFORNIA DE AMPA receptor; spermine; channel block; kainate receptor; polyamines ID RECTIFIER POTASSIUM CHANNELS; INWARD RECTIFICATION; GLUTAMATE RECEPTORS; AMPA; BLOCK; GLYCINE AB Block of kainate subtype glutamate receptor channels by internal polyamines was analysed using outside out patches from HEK 293 cells transiently transfected with GluR6(Q). Tetramines with different numbers and spacing of methylene groups between NH2 groups produced biphasic rectification well fit by the Woodhull model for a weakly permeable ion channel blocker. Such analysis revealed an increase in binding energy of 611 cal M-1 for each methylene group added over the range 6-12 (CH2) suggesting that a major component of block by polyamines involves hydrophobic binding. Isomers with the same number of CH2 groups but different spacing between NH2 groups showed similar affinity. Due to differences in pK(a) values for protonation of NH2 groups, the average charge on the tetramines studied would be expected to vary from 3.98 to 2.22 at physiological pH; despite this, the voltage dependence of block was similar for all tetramines tested, with a mean value for z theta of 1.82, similar to values for polyamines with five or six NH2 groups. In contrast, for 1,3-propane diamine (DA3 z theta 0.83), and the N-propyl- (z theta 1.42) and N,N'-diethyl- (z theta 1.37) analogues of DA3, there was an increase in the voltage dependence of block on addition of hydrophobic groups. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bethesda, MD 20892 USA. RP Mayer, ML (reprint author), NICHD, Lab Cellular & Mol Neurophysiol, NIH, Bldg 49,Convent Dr,Room 5A78, Bethesda, MD 20892 USA. RI Bahring, Robert/F-7146-2010; Mayer, Mark/H-5500-2013 NR 32 TC 14 Z9 14 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD OCT-NOV PY 1998 VL 37 IS 10-11 BP 1381 EP 1391 DI 10.1016/S0028-3908(98)00112-9 PG 11 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 142UU UT WOS:000077219400018 PM 9849673 ER PT J AU Doody, RS Massman, PJ Mawad, M Nance, M AF Doody, RS Massman, PJ Mawad, M Nance, M TI Cognitive consequences of subcortical magnetic resonance imaging changes in Alzheimer's disease: Comparison to small vessel ischemic vascular dementia SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID WHITE-MATTER LESIONS; CLINICAL-DIAGNOSIS; HYPERINTENSITIES; ABNORMALITIES; BRAIN; PATTERNS; CRITERIA; STATE; MRI AB Objective: The objective of this study was to compare psychometric profiles of Alzheimer's disease (AD) patients with subcortical magnetic resonance imaging (MRI) signal abnormalities to those of AD patients without such MRI findings (normal subcortical MRI) and to those of patients with ischemic vascular dementia (IVD) associated with small and primarily subcortical ischemic changes. Background: The cognitive significance of MRI white matter and other subcortical abnormalities in AD is unknown. Prior studies comparing AD patients with white matter changes on MRI have not included IVD patients with comparable MRI findings. If white matter/subcortical changes in AD reflect vascular abnormalities, they might be associated with cognitive profiles similar to those seen in subcortical IVD. Method: We studied 15 AD patients with normal subcortical MRIs, 22 AD patients with subcortical MRI hyperintensities, and 18 IVD (NINCDS-ADRDA and NINDS-AIREN criteria) at the Alzheimer's Disease Research Center of the Baylor College of Medicine. IVD patients had predominantly small and subcortical signal abnormalities, and none had large cortical infarcts. AD patients had only nonspecific subcortical signal abnormalities with or without atrophy (atrophy was not analyzed). We compared the AD group with abnormal MRIs to the AD group with normal subcortical MRIs and the AD group to the IVD group using ANCOVA planned comparisons (dementia severity and education covaried). Results: AD patients with abnormal MRIs did not differ significantly from AD patients with normal subcortical MRIs on any of the neuropsychological measures. AD patients exhibited significantly better attention/concentration, visuospatial/visuoconstructional performance, fetter fluency, motor programming, and simple motor speed than IVD patients as well as significantly worse delayed verbal recognition memory. Because MRT changes were generally more extensive in IVD, a subset of AD patients with abnormal subcortical MRIs was compared to a subset of IVD patients matched for degree of MRI signal abnormalities. These subsets of AD and IVD patients still showed distinctive neuropsychological profiles. Conclusions: AD patients with or without MRI subcortical signal abnormalities have similar neuropsychological profiles, and they differ from IVD patients with comparable MRI changes. Although MRI signal abnormalities in AD patients who have no history or examination findings of cerebrovascular disease overlap with those seen in IVD patients, they do not seem to have the same cognitive significance. Periventricular hyperintensities (PVHs) and deep signal hyperintensities, especially those of a mild to moderate degree, may reflect a different pathophysiologic process in AD than in IVD and do not necessarily have cognitive consequences in AD patients. C1 Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Alzheimers Dis Res Ctr NIH AGO 8664, Houston, TX 77030 USA. Baylor Coll Med, Dept Neuroradiol, Houston, TX 77030 USA. Univ Houston, Dept Psychol, Houston, TX USA. Vet Affairs Med Ctr, Houston, TX 77030 USA. RP Doody, RS (reprint author), Baylor Coll Med, Dept Neurol, 6550 Fannin,Suite 1801, Houston, TX 77030 USA. NR 39 TC 14 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD OCT PY 1998 VL 11 IS 4 BP 191 EP 199 PG 9 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 173JD UT WOS:000078976600003 ER PT J AU Weld, KP Mench, JA Woodward, RA Bolesta, MS Suomi, SJ Higley, JD AF Weld, KP Mench, JA Woodward, RA Bolesta, MS Suomi, SJ Higley, JD TI Effect of tryptophan treatment on self-biting and central nervous system serotonin metabolism in rhesus monkeys (Macaca mulatta) SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE L-tryptophan; behavior; cerebrospinal fluid; 5-hydroxyindoleacetic acid; Macaca mulatta; serotonin ID CEREBROSPINAL-FLUID; 5-HYDROXYINDOLEACETIC ACID; INJURIOUS-BEHAVIOR; AMINE METABOLITES; SOCIAL-BEHAVIOR; VERVET MONKEYS; AGGRESSION; MUTILATION; SUICIDE; 5-HYDROXYTRYPTOPHAN AB Two studies were conducted to examine the effects of oral L-tryptophan (TRP) supplementation as a treatment for self-injurious behavior (SIB) and to investigate behavior and central serotonin turnover of male rhesus monkeys. In Study One, TRP teas administered to seven individually housed rhesus monkeys with a recent history of spontaneous SIE. While the monkeys were on TRP treatment (100 mg/kg twice a day), cisternal cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid increased markedly (p = .0013) above baseline (baseline mean 207.6 pmol/ml +/- 39; TRP mean = 320.3 pmol/ml +/- 83.4), and the duration of self-biting behavior decreased below baseline (p = .03). In Study Two, 14 individually housed rhesus monkeys without a history of SIB were placed on three different doses of TRP in random order (50, 100, and 200 mg/kg twice a day). TRP had no effect on any behavioral or biochemical variables in the normal monkeys. Conclusions: Supplemental tryptophan in well-tolerated noses reduced self-biting and increases serotonin turnover rate in male monkeys with a recent history of SIB, The same doses of TRP do not effect behavior or serotonin metabolism in male monkeys without a history of SIB. Published by Elsevier Science Inc. C1 NIAAA, Anim Ctr, Clin Studies Lab, DICBR,NIH, Poolesville, MD 20837 USA. Adv BioSci Labs Inc, Rockville, MD USA. NICHD, Comparat Ethol Lab, NIH, Bethesda, MD USA. RP Weld, KP (reprint author), NIAAA, Anim Ctr, Clin Studies Lab, DICBR,NIH, POB 529, Poolesville, MD 20837 USA. NR 45 TC 42 Z9 43 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD OCT PY 1998 VL 19 IS 4 BP 314 EP 321 DI 10.1038/sj.npp.1395210 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 109RN UT WOS:000075337100007 PM 9718594 ER PT J AU Ensoli, F Fiorelli, V Vannelli, B Barni, T De Cristofaro, M Ensoli, B Thiele, CJ AF Ensoli, F Fiorelli, V Vannelli, B Barni, T De Cristofaro, M Ensoli, B Thiele, CJ TI Basic fibroblast growth factor supports human olfactory neurogenesis by autocrine/paracrine mechanisms SO NEUROSCIENCE LA English DT Article DE primary neuroblasts; neuronal plasticity; differentiation; FGF; antisense oligomers; growth factors ID SENSORY NEURONS; CELL-LINE; NEUROFILAMENT PROTEIN; EXTRACELLULAR-MATRIX; HIPPOCAMPAL-NEURONS; DIFFUSIBLE FACTORS; ENDOTHELIAL-CELLS; PROGENITOR CELLS; FACTOR PROMOTES; NERVOUS-SYSTEM AB Throughout life, olfactory sensory neurons are renewed from a population of dividing stem cells. Little is known about the molecular mechanisms that regulate the activation, self-renewal and differentiation of olfactory neuronal precursors; however, evidence indicates that soluble mediators may play a central role in olfactory neurogenesis. To identify molecules that regulate olfactory self-renewal and differentiation, we have recently established, cloned and propagated in vitro primary long-term cell cultures from the human Fetal olfactory neuroepithelium. Here we show that primary human olfactory neuroblasts synthesize and release biologically active basic fibroblast growth Factor which, in turn, supports neuroblast growth by autocrine/paracrine mechanisms. The growth-promoting activity of basic fibroblast growth factor is dose dependent and is accompanied by morphological changes of the cells and by an increase in the expression of neuronal-related genes. These observations indicate that endogenous basic fibroblast growth factor participates in controlling olfactory self-renewal and suggest that this cytokine represents a key regulatory element of olfactory neurogenesis. (C) 1998 IBRO. Published by Elsevier Science Ltd. C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Rome La Sapienza, Dept Clin Med Allergy & Immunol, I-00185 Rome, Italy. Univ Florence, Dept Anat, Florence, Italy. Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. RP Ensoli, F (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RI Ensoli, Barbara/J-9169-2016; OI Ensoli, Barbara/0000-0002-0545-8737; BARNI, Tullio/0000-0002-9044-4929 NR 69 TC 28 Z9 28 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT PY 1998 VL 86 IS 3 BP 881 EP 893 DI 10.1016/S0306-4522(98)00104-3 PG 13 WC Neurosciences SC Neurosciences & Neurology GA ZX492 UT WOS:000074521600016 PM 9692724 ER PT J AU Marini, JC AF Marini, JC TI Osteogenesis imperfecta - Managing brittle bones SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HETEROGENEITY; COLLAGEN; THERAPY C1 NIH, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 10 TC 11 Z9 11 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 1 PY 1998 VL 339 IS 14 BP 986 EP 987 DI 10.1056/NEJM199810013391408 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 124MW UT WOS:000076186900008 PM 9753715 ER PT J AU Shrager, RI Weiss, GH Spencer, RGS AF Shrager, RI Weiss, GH Spencer, RGS TI Optimal time spacings for T-2 measurements: Monoexponential and biexponential systems SO NMR IN BIOMEDICINE LA English DT Article DE exponential/biexponential decay curve; relaxation time T-2; spin-echo measurements ID MAGNETIZATION-TRANSFER EXPERIMENTS; LATTICE RELAXATION-TIMES; NMR-MICROSCOPY; OPTIMIZATION; DIFFUSION; TISSUE; MAPS; BRAIN; GELS AB We have developed an optimal design strategy, i.e. a choice of times at which the magnetization should be measured, in spin-echo measurements, when the number of measurements is fixed in advance. Results are given for samples whose relaxation is described by either an exponential or biexponential decay curve. The analysis is based on having an initial estimate of the ranges in which the relaxation times are likely to lie. The optimal design consists of a set of easily parameterized non-uniformly spaced measurement times, as opposed to present implementation of spin-echo experiments. Analysis of the biexponential case shows that an order of magnitude greater signal-to-noise is required to achieve T-2 estimates of comparable precision to monoexponential measurements with the same number of data points. The optimal designs lead to an improved ability to discriminate between two relatively similar relaxation times. (C) 1998 John Wiley & Sons, Ltd. C1 NIH, Div Comp Res & Technol, Ctr Informat Technol, Bethesda, MD 20892 USA. NIA, Nucl Magnet Resonance Unit, Baltimore, MD 21224 USA. RP Weiss, GH (reprint author), NIH, Div Comp Res & Technol, Ctr Informat Technol, Bethesda, MD 20892 USA. NR 24 TC 22 Z9 22 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD OCT PY 1998 VL 11 IS 6 BP 297 EP 305 DI 10.1002/(SICI)1099-1492(199810)11:6<297::AID-NBM531>3.0.CO;2-A PG 9 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 128YB UT WOS:000076435000006 PM 9802472 ER PT J AU Horti, AG Scheffel, U Koren, AO Ravert, HT Mathews, WB Musachio, JL Finley, PA London, ED Dannals, RF AF Horti, AG Scheffel, U Koren, AO Ravert, HT Mathews, WB Musachio, JL Finley, PA London, ED Dannals, RF TI 2-[F-18]fluoro-A-85380, an in vivo tracer for the nicotinic acetylcholine receptors SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE A-85380 derivative; nicotinic receptor; acetylcholine receptor; radiotracer; brain distribution; pharmacology; PET ID POSITRON EMISSION TOMOGRAPHY; BINDING-SITES; CEREBRAL-CORTEX; POISON FROG; BRAIN; EPIBATIDINE; FLUORINE-18-FPH; AFFINITY; LIGAND; PET AB The in vivo brain regional distribution of 2-[F-18]fluoro-A-85380, a novel tracer for positron emission tomographic (PET) studies, followed the regional densities of brain nAChRs reported in the literature. Evidence of binding to nAChRs and high specificity of the binding in vivo was demonstrated by inhibition with nAChR selective ligands as well as with unlabeled 2-fluoro-A-85380. A preliminary toxicology study of the 2-fluoro-A-85380 showed a relatively low biological effect. 2-[F-18]Fluoro-A-85380 holds promise as a useful radiotracer for imaging of nAChRs with PET. (C) 1998 Elsevier Science Inc. C1 Johns Hopkins Med Inst, Div Nucl Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Div Radiat Hlth Sci, Baltimore, MD 21205 USA. NIDA, Intramural Res Program, Brain Imaging Ctr, Baltimore, MD 21224 USA. RP Dannals, RF (reprint author), Johns Hopkins Med Inst, Div Nucl Med, 615 N Wolfe St, Baltimore, MD 21205 USA. NR 31 TC 72 Z9 75 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD OCT PY 1998 VL 25 IS 7 BP 599 EP 603 DI 10.1016/S0969-8051(98)00031-6 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 118RH UT WOS:000075853400003 PM 9804040 ER PT J AU Aravind, L Landsman, D AF Aravind, L Landsman, D TI AT-hook motifs identified in a wide variety of DNA binding proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ZINC-FINGER PROTEIN; IFN-BETA GENE; TRANSCRIPTION FACTOR; SACCHAROMYCES-CEREVISIAE; HOMEODOMAIN PROTEIN; SEQUENCE DATABASES; MOLECULAR-CLONING; ACUTE-LEUKEMIA; PHD-FINGER; DROSOPHILA AB The AT-hook is a small DNA-binding protein motif which was first described in the high mobility group non-histone chromosomal protein HMG-I(Y), Since its discovery, this motif has been observed in other DNA-binding proteins from a wide range of organisms. Using pattern searches and position-dependent matrices, we have extracted the AT-hook motifs present in a non-redundant protein sequence database. We have classified these motifs into three types according to their sequence similarity and have found that they are prevalent in many eukaryotic nuclear proteins in single or multiple copies. Furthermore, AT-hook motifs are frequently associated with known functional domains seen in chromatin proteins and in DNA-binding proteins (e.g. histone folds, homeodomains and zinc fingers). In general, it appears that the AT-hook motif is an auxiliary protein motif cooperating with other DNA-binding activities and facilitating changes in the structure of the DNA either as a polypeptide on its own [e.g. HMG-I(Y)] or as part of a multidomain protein [e.g, Swi2p in Saccharomyces cerevisiae or HRX (ALL-1) in Homo sapiens], It is most interesting that this motif seems to be quite specific to known or predicted chromosomal/DNA-binding proteins, suggesting that it may act as a versatile minor groove tether. C1 NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX USA. RP Landsman, D (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Computat Biol Branch, Bldg 38A,Room 8N807,8600 Rockville Pike, Bethesda, MD 20894 USA. RI Landsman, David/C-5923-2009; OI Landsman, David/0000-0002-9819-6675 NR 75 TC 284 Z9 295 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 1 PY 1998 VL 26 IS 19 BP 4413 EP 4421 DI 10.1093/nar/26.19.4413 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126JF UT WOS:000076289600015 PM 9742243 ER PT J AU Winter, DB Gearhart, PJ Bohr, VA AF Winter, DB Gearhart, PJ Bohr, VA TI Homogeneous rate of degradation of nuclear DNA during apoptosis SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSCRIPTION-COUPLED REPAIR; KILOBASE PAIR FRAGMENTS; PROGRAMMED CELL-DEATH; INTERNUCLEOSOMAL FRAGMENTATION; THYMOCYTE NUCLEI; CLEAVAGE; GENE; UV; ENDONUCLEASE; EXPRESSION AB DNA fragmentation during apoptosis is characterized by endonucleolytic cleavage of chromosomal DNA into an oligonucleosomal ladder. To determine if actively transcribed genes are more susceptible to cleavage during apoptosis than non-transcribed genes, the rate of fragmentation of differentially expressed genes was measured in B-lymphocyte hybridoma cells. Five genes were studied based on their transcriptional activity and/or nuclear localization, and mitochondrial DNA was assayed as a negative control for apoptotic fragmentation. Apoptosis was induced in the hybridoma cells by ultraviolet light, and DNA was prepared at multiple time points after ultraviolet irradiation, Degradation into an oligonucleosomal ladder appeared as early as 2 h after treatment, showing that fragmentation is rapidly activated in hybridoma cells, The DNA was then digested with restriction enzymes, separated by gel electrophoresis and hybridized with the gene-specific probes for Southern blot analyses. Loss of gene-specific signals was measured by quantitation of autoradiographs, The results show all of the nuclear genes were degraded at the same rate regardless of their transcriptional status or nuclear localization. The data suggest that once the cell activates its destruction program, nuclear DNA is rapidly degraded in a homogeneous manner. C1 NIA, Genet Mol Lab, NIH, Baltimore, MD 21224 USA. RP Winter, DB (reprint author), NIA, Genet Mol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov NR 41 TC 11 Z9 13 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 1 PY 1998 VL 26 IS 19 BP 4422 EP 4425 DI 10.1093/nar/26.19.4422 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126JF UT WOS:000076289600016 PM 9742244 ER PT J AU van Beest, M Mortin, M Clevers, H AF van Beest, M Mortin, M Clevers, H TI Drosophila RpS3a, a novel Minute gene situated between the segment polarity genes cubitus interruptus and dTCF SO NUCLEIC ACIDS RESEARCH LA English DT Article ID TRANSFORMATION EFFECTOR GENE; S3A RIBOSOMAL-PROTEIN; SACCHAROMYCES-CEREVISIAE; MOLECULAR ANALYSIS; LOCUS ENCODES; MELANOGASTER; CLONING; MUTATIONS; SEQUENCE; CELL AB Genetic analysis of the small chromosome 4 of Drosophila has been hampered by the virtual lack of recombination, The segment polarity gene cubitus interruptus (ci) maps to the most intensively studied locus on this chromosome. Up to four complementation groups have been found to be associated with ci. We and others have recently characterized a second segment polarity gene, dTCF or pan, 12 kb upstream of ci, in a head-to-head configuration, During the course of these studies we identified a transcription unit in the intergenic region. We report here the cloning of cDNAs from this transcription unit, which encode the Drosophila homologue of the human ribosomal protein S3a (RpS3a), The RpS3a gene is expressed ubiquitously and throughout development. A Minute allele, M(4)101, linked tightly to ci, was found to harbour an integration of a Doc retroposon in the promotor region of RpS3a, Thus, like other Minute loci, M(4)101 encodes a component of the protein synthesis machinery. These data further unravel the complex genetics surrounding the ci and dTCF loci. C1 Univ Hosp, Dept Immunol, Utrecht, Netherlands. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Clevers, H (reprint author), Univ Hosp, Dept Immunol, Utrecht, Netherlands. RI Mortin, Mark/B-4251-2008 NR 32 TC 10 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD OCT 1 PY 1998 VL 26 IS 19 BP 4471 EP 4475 DI 10.1093/nar/26.19.4471 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 126JF UT WOS:000076289600023 PM 9742251 ER PT J AU Sichieri, R Everhart, JE AF Sichieri, R Everhart, JE TI Validity of a Brazilian food frequency questionnaire against dietary recalls and estimated energy intake SO NUTRITION RESEARCH LA English DT Article DE dietary assessment; bias; misclassification; 24-hour recall; food frequency ID VALIDATION; OBESE; WOMEN AB Food frequency questionnaires are commonly used to obtain dietary information in epidemiological studies, but validity studies have primarily been performed in western countries situated in the Northern Hemisphere. A food frequency questionnaire for the Brazilian diet was developed based on a previous survey and expert decision. This questionnaire was compared with four 24-hour recalls among faculty and support staff at the University of Rio de Janeiro, Brazil; and both methods were validated against estimated daily energy requirement. Results of the food frequency questionnaire and the 24-hour recalls were correlated to a similar degree as in studies of other populations. The correlation coefficients varied from 0.55 for calcium to 0.18 for vitamin A, with all but vitamin A being highly significant. The ratio of energy intake to estimated basal metabolism among men was 1.37 for the 24-hour recall and 1.31 for the food frequency; among women the ratio was 1.15 for the 24-hour recall and 1.24 for the food frequency. Women with high predicted energy expenditure often underestimated intake, with a greater discrepancy on the 24-hour recall than the food frequency. (C) 1998 Elsevier Science Inc. C1 UERJ, Inst Social Med, BR-20550900 Rio De Janeiro, Brazil. NIDDK, NIH, Bethesda, MD 20892 USA. RP Sichieri, R (reprint author), UERJ, Inst Social Med, Rua Sao Francisco Xavier 524,7 Andar, BR-20550900 Rio De Janeiro, Brazil. NR 22 TC 132 Z9 161 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD OCT PY 1998 VL 18 IS 10 BP 1649 EP 1659 DI 10.1016/S0271-5317(98)00151-1 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 121NP UT WOS:000076020400001 ER PT J AU Newton, KM Lacroix, AZ Leveille, SG Rutter, C Keenan, NL Anderson, LA AF Newton, KM Lacroix, AZ Leveille, SG Rutter, C Keenan, NL Anderson, LA TI The physician's role in women's decision making about hormone replacement therapy SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID MIDDLE-AGED WOMEN; ESTROGEN REPLACEMENT; AFRICAN-AMERICAN; ATTITUDES; MENOPAUSE; SYMPTOMS; PERIMENOPAUSAL; DETERMINANTS; INFORMATION; PREVALENCE AB Objective: To ascertain the sources of information women use when making decisions about hormone replacement therapy (HRT). Methods: A cross-sectional, population-based computer-assisted telephone survey of 1082 randomly selected women aged 50-80 years (80.3% response rate) was conducted at Group Health Cooperative of Puget Sound, a large staff-model health maintenance organization in Washington state. Results: Overall, 460 participants (42.5%) were current HRT users, 226 (20.9%) were past users,nd 396 (36.6%) were never users. Discussions with physicians dominated as the major source of information used in decision making by current (83.4%) and past (65.5%) users, but were less often cited by never users (44.4%); printed material was used by 44.5% of women. Although 72.1% of current users reported that the amount of information received from their physician about the benefits of HRT was about right, only 48.2% of past users and 33.6% of never users shared this view (P < .001 current versus never), and 13.3% of current users, 32.6% of past users and 58% of never users reported receiving no information from their physician about HRT's benefits. Conclusion: Hormone replacement therapy use is strongly related to interactions between women and their physicians. Many women use written materials to make decisions about HRT. A large proportion of women feel inadequately informed about HRT's risks and benefits. Much work remains to be accomplished toward meeting the goal of the US Preventive Services Task Force that all perimenopausal and postmenopausal women be counseled about the potential benefits and risks of HRT. (Obstet Gynecol 1998;92:580-4. (C) 1998 by The American College of Obstetricians and Gynecologists.). C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. NIA, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Newton, KM (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. FU PHS HHS [U48/CCU009654-04] NR 24 TC 40 Z9 41 U1 5 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1998 VL 92 IS 4 BP 580 EP 584 DI 10.1016/S0029-7844(98)00272-5 PN 1 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 123GY UT WOS:000076118500018 PM 9764632 ER PT J AU Nyirjesy, I Billingsley, FS Forman, MR AF Nyirjesy, I Billingsley, FS Forman, MR TI Evaluation of atypical and low-grade cervical cytology in private practice SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SQUAMOUS CELLS; UNDETERMINED SIGNIFICANCE; MANAGEMENT; SMEARS; NEOPLASIA; WOMEN AB Objective: To evaluate the adequacy of cytology alone for diagnosis of grade of cervical intraepithelial neoplasia (CIN) and to study performance of cytology, human papillomavirus (HPV) testing, and colposcopy in the evaluation of cytologic findings suggesting low-grade squamous intraepithelial lesions (SIL), or atypical squamous (ASCUS) or atypical glandular (AGCUS) cells of undetermined significance. Methods: Standard gynecologic and cytologic evaluation and colposcopic inspection as an additional screening approach were performed on women with no prior hysterectomies screened in a private practice between January 1, 1993, and August 1, 1995. Among these 7651 women, 367 had ASCUS, AGCUS, or SIL cytology or clinically or colposcopically visible cervical lesions. Sensitivity, specificity, and relative risk of CIN in the 367 women were compared by colposcopic, cytologic, histologic and virologic diagnoses. Results: The sensitivity bf all non-negative Papanicolaou smears for CIN 2-3 and cancer was 92%, combined cytologic categories of high- and low-grade SIL were 59%, and high-grade SIL alone was 22%. Colposcopy was performed in all 367 patients, and positive findings led to biopsies in 48%. Colposcopy bf patients with ASCUS increased detection of CIN 2-3 by 32% and CIN 1 by 48%. Cervical cytology was false negative in 8% of patients with CIN 2-3 and in 14% of those with CIN 1. These cases of CIN were detected by screening colposcopic inspection. High-risk HPV DNA was positive in 41% of women with CIN 2-3, and in 25% of those with CIN 1. The positive predictive value of ASCUS cytology increased from 5% to 42% for CIN 2-3 and from 30% to 85% for all grades of CIN in patients carrying high-risk HPV DNA. Virologic studies did not add to an increase in the sensitivity for CIN 2-3 among women in the low- and high-grade SIL cytology groups. Conclusion: Because of the limited sensitivity of the high-grade SIL cytologic category for CIN 2-3, we recommend that all women with ASCUS, AGCUS, low- or high-grade SIL cytology be recalled for colposcopy, with biopsy only when indicated by colposcopic findings. (Obstet Gynecol 1998;92:601-7. (C) 1998 by The American College of Obstetricians and Gynecologists.). C1 NCI, Div Clin Sci, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. RP Nyirjesy, I (reprint author), 5301 Westbard Circle 5, Bethesda, MD 20816 USA. NR 14 TC 15 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD OCT PY 1998 VL 92 IS 4 BP 601 EP 607 DI 10.1016/S0029-7844(98)00274-9 PN 1 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 123GY UT WOS:000076118500022 PM 9764636 ER PT J AU Rothman, N Bechtold, WE Yin, SN Dosemeci, M Li, GL Wang, YZ Griffith, WC Smith, MT Hayes, RB AF Rothman, N Bechtold, WE Yin, SN Dosemeci, M Li, GL Wang, YZ Griffith, WC Smith, MT Hayes, RB TI Urinary excretion of phenol, catechol, hydroquinone, and muconic acid by workers occupationally exposed to benzene SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article DE benzene; phenol; catechol; hydroquinone; muconic acid; biomonitoring ID HUMAN-LYMPHOCYTES; B6C3F1 MICE; METABOLITES; TOXICITY; INVITRO; RATS; DNA; IDENTIFICATION; LEUKEMOGENESIS; MICRONUCLEI AB Objectives-Animal inhalation studies and theoretical models suggest that the pattern of formation of benzene metabolites changes as exposure to benzene increases. To determine if this occurs in humans, benzene metabolites in urine samples collected as part of a cross sectional study of occupationally exposed workers in Shanghai, China were measured. Methods-With organic vapour monitoring badges, 38 subjects were monitored during their full workshift for inhalation exposure to benzene. The benzene urinary metabolites phenol, catechol, hydroquinone, and muconic acid were measured with an isotope dilution gas chromatography mass spectroscopy assay and strongly correlated with concentrations of benzene air. For the subgroup of workers (n=27) with urinary phenol >50 ng/g creatinine (above which phenol is considered to be a specific indicator of exposure to benzene) concentrations of each of the four metabolites were calculated as a ratio of the sum of the concentrations of all four metabolites (total metabolites) and were compared in workers exposed to >25 ppm v less than or equal to 25 ppm. Results-The median, 8 hour time weighted average exposure to benzene was 25 ppm. Relative to the lower exposed workers, the ratio of phenol and catechol to total metabolites increased by 6.0% (p=0.04) and 22.2% (p=0.007), respectively, in the more highly exposed workers. By contrast, the ratio of hydroquinone and muconic acid to total metabolites decreased by 18.8% (p=0.04) and 26.7% (p=0.006), respectively. Similar patterns were found when metabolite ratios were analysed as a function of internal benzene dose (defined as total urinary benzene metabolites), although catechol showed a more complex, quadratic relation with increasing dose. Conclusions-These results, which are consistent with previous animal studies, show that the relative production of benzene metabolites is a function of exposure level. If the toxic benzene metabolites are assumed to be derived from hydroquinone, ring opened products, or both, these results suggests that the risk for adverse health outcomes due to exposure to benzene may have a supralinear relation with external dose, and that linear extrapolation of the toxic effects of benzene in highly exposed workers to lower levels of exposure may underestimate risk. C1 NCI, NIH, Occupat Studies Branch, Div Canc Epidemiol & Genet,EPN 418, Bethesda, MD 20892 USA. Inhalat Toxicol Res Inst, Albuquerque, NM USA. Chinese Acad Prevent Med, Inst Occupat Med, Beijing 100050, Peoples R China. Shanghai Hyg & Antiepidem Ctr, Dept Occupat Hlth, Shanghai, Peoples R China. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Rothman, N (reprint author), NCI, NIH, Occupat Studies Branch, Div Canc Epidemiol & Genet,EPN 418, Bethesda, MD 20892 USA. FU NIEHS NIH HHS [P30ES01896, P42ES04705] NR 40 TC 46 Z9 51 U1 1 U2 4 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD OCT PY 1998 VL 55 IS 10 BP 705 EP 711 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 123GE UT WOS:000076116800010 PM 9930093 ER PT J AU Bates, S Ryan, KM Phillips, AC Vousden, KH AF Bates, S Ryan, KM Phillips, AC Vousden, KH TI Cell cycle arrest and DNA endoreduplication following p21(Waf1/Cip1) expression SO ONCOGENE LA English DT Article DE p21(Waf1/Cip1); cell cycle arrest; cyclin dependent kinase; endoreduplication; senescence ID DEPENDENT-KINASE INHIBITOR; P53-MEDIATED G(1) ARREST; HUMAN CANCER-CELLS; WILD-TYPE P53; S-PHASE; RETINOBLASTOMA PROTEIN; HUMAN FIBROBLASTS; CDK INHIBITORS; GROWTH ARREST; IN-VIVO AB p21(Waf1/Cip1) is a major transcriptional target of p53 and has been shown to be one of the principal mediators of the p53 induced G1 cell cycle arrest. We show that in addition to the G1 block, p21(Waf1/Cip1) can also contribute to a delay in G2 and expression of p21(Waf1/Cip1) gives rise to cell cycle profiles essentially indistinguishable from those obtained following p53 expression. Arrest of cells in G2 likely reflects an inability to induce cyclin B1/cdc2 kinase activity in the presence of p21(Waf1/Cip1), although the inefficient association of p21(Waf1/cip1) and cyclin B1 suggests that the mechanism of inhibition is indirect. Cells released from an S-phase block were not retarded in their ability to progress through S-phase by the presence of p21(Waf1/Cip1), despite efficient inhibition of cyclin E, A and B1 dependent kinase activity, suggesting that p2l(Waf1/Cip1) is inefficient at inhibiting replicative DNA synthesis in vivo. Interestingly, significant numbers of cells released from the p21(Waf1/Cip1) activated G2 block undergo endoreduplication, passing through another S-phase before undergoing mitosis, This supports a function of the mitotic kinases in both entry into mitosis, and also in preventing re-replication of DNA following S-phase and suggests a role for p21(Waf1/Cip1) in coupling DNA synthesis and mitosis, Unlike p53, which induces apoptosis in these cells, extended expression of p21(Waf1/Cip1) resulted in the expression of a senescent-like phenotype in these p53 null, pRB null tumor cells. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Vousden, KH (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Bldg 560,Room 22-96,W 7th St, Frederick, MD 21702 USA. NR 62 TC 124 Z9 126 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 1 PY 1998 VL 17 IS 13 BP 1691 EP 1703 DI 10.1038/sj.onc.1202104 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 124UH UT WOS:000076200100007 PM 9796698 ER PT J AU Sundaresan, V Chung, G Heppell-Parton, A Xiong, J Grundy, C Roberts, I James, L Cahn, A Bench, A Douglas, J Minna, J Sekido, Y Lerman, M Latif, F Bergh, J Li, H Lowe, N Ogilvie, D Rabbitts, P AF Sundaresan, V Chung, G Heppell-Parton, A Xiong, J Grundy, C Roberts, I James, L Cahn, A Bench, A Douglas, J Minna, J Sekido, Y Lerman, M Latif, F Bergh, J Li, H Lowe, N Ogilvie, D Rabbitts, P TI Homozygous deletions at 3p12 in breast and lung cancer SO ONCOGENE LA English DT Article DE DUTT1/Hrobo-1; lung cancer; U2020 deletion; tumour suppressor gene; familial non-specific dementia ID YEAST ARTIFICIAL CHROMOSOMES; MOLECULAR-GENETIC CHANGES; CELL-LINE U2020; SHORT ARM; CLONING; CARCINOMA; SEQUENCES; TUMORS; PCR; DNA AB We have constructed a physical map of the region homozygously deleted in the U2020 cell line at 3p12, including the location of putative CpG islands. Adjacent to one of these islands, we have identified and cloned a new gene (DUTT1) and used probes from this gene to detect two other homozygous deletions occurring in lung and breast carcinomas: the smallest deletion is within the gene itself and would result in a truncated protein. The DUTT1 gene is a member of the neural cell adhesion molecule family, although its widespread expression suggests it plays a less specialized role compared to other members of the family. C1 Med Res Council Ctr, Macclesfield SK10 4TG, Cheshire, England. Zeneca Pharmaceut, Macclesfield SK10 4TG, Cheshire, England. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75235 USA. NCI, Frederick Canc Res Facil, Immunobiol Lab, Frederick, MD 21701 USA. Univ Uppsala, Akad Sjukhuset, Dept Oncol, S-75185 Uppsala, Sweden. RP Rabbitts, P (reprint author), Med Res Council Ctr, Alderley Pk, Macclesfield SK10 4TG, Cheshire, England. RI Sekido, Yoshitaka/P-9756-2015 FU NCI NIH HHS [P50 CA70907] NR 31 TC 84 Z9 87 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 1 PY 1998 VL 17 IS 13 BP 1723 EP 1729 DI 10.1038/sj.onc.1202103 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 124UH UT WOS:000076200100010 PM 9796701 ER PT J AU Cheson, BD AF Cheson, BD TI Current approaches to therapy for indolent non-Hodgkin's lymphoma SO ONCOLOGY-NEW YORK LA English DT Review ID BONE-MARROW TRANSPLANTATION; LOW-GRADE LYMPHOMA; PHASE-II TRIAL; B-CELL LYMPHOMA; RELAPSED LOW-GRADE; 2-CHLORODEOXYADENOSINE 2-CDA THERAPY; RECURRENT FOLLICULAR LYMPHOMA; NODULAR MIXED LYMPHOMA; DETUDE-DES-LYMPHOMES; HIGH-DOSE THERAPY AB Progress in the treatment of indolent non-Hodgkin's lymphoma has been slow and the disease remains incurable despite the relatively long median survival of patients. Decades of clinical trials resulted in standard chemotherapy regimens that produced relatively identical results. Two recent events, however, offer great optimism for future therapeutic progress. First, our understanding of the biology and immunology of lymphoid malignancies has increased remarkably. Second, there are a large number of new and unique chemotherapeutic and biological agents entering into clinical trials. C1 NCI, Med Sect, Bethesda, MD 20892 USA. RP Cheson, BD (reprint author), NCI, Med Sect, Execut Plaza N,Rm 741, Bethesda, MD 20892 USA. NR 122 TC 4 Z9 4 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 1998 VL 12 IS 10 SU 8 BP 25 EP 34 PG 10 WC Oncology SC Oncology GA 140BV UT WOS:000077067600004 PM 9830630 ER PT J AU Magrath, IT AF Magrath, IT TI Management of high-grade lymphomas SO ONCOLOGY-NEW YORK LA English DT Article ID NON-HODGKINS-LYMPHOMA; ACUTE LYMPHOBLASTIC-LEUKEMIA; NONCLEAVED-CELL LYMPHOMA; BONE-MARROW TRANSPLANTATION; CHILDRENS CANCER GROUP; HIGH-DOSE THERAPY; TERM FOLLOW-UP; ADULT PATIENTS; COMBINATION CHEMOTHERAPY; BURKITTS-LYMPHOMA AB High-grade non-Hodgkin's lymphomas generally refer to immunoblastic lymphoma, lymphoblastic lymphoma, and small-noncleaved-cell lymphoma, three histological subtypes that were associated with the worst prognosis at the time of categorization 16 years ago in the Working Formulation for Clinical Usage. Small-noncleaved-cell lymphoma was classified further into Burkitt's lymphoma ann non-Burkitt's lymphoma. The treatment of high-grade lymphomas in adults remains somewhat unfavorable today. In children, however, survival rates of 80% to 90% are being achieved with intensive short duration protocols. In this article, the management of Burkitt, Burkitt-like, and lymphoblastic lymphomas is discussed as is the possibility of improved survival in adults using treatment strategies developed for pediatric patients. C1 NCI, Pediat Branch, Lymphoma Biol Sect, Bethesda, MD 20892 USA. RP Magrath, IT (reprint author), NCI, Pediat Branch, Lymphoma Biol Sect, Bldg 10,Room 13N240, Bethesda, MD 20892 USA. NR 55 TC 11 Z9 11 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD OCT PY 1998 VL 12 IS 10 SU 8 BP 40 EP 48 PG 9 WC Oncology SC Oncology GA 140BV UT WOS:000077067600006 PM 9830632 ER PT J AU Ondrey, FG Juhn, SK Adams, GL AF Ondrey, FG Juhn, SK Adams, GL TI Early-response cytokine expression in adult middle ear effusions SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 29-OCT 02, 1996 CL WASHINGTON, D.C. SP Amer Acad Otolaryngol Head & Neck Surg ID OTITIS-MEDIA AB Various cytokines are presently known to be associated with the regulation of inflammatory responses. In pediatric otitis media, cytokines that correlate with various degrees of inflammation are present in middle ear effusions as inflammatory mediators. The present study was undertaken to examine the potential role of the early-response cytokines, interleukin-1 beta and tumor necrosis factor-alpha, in adult otitis media, Fifty-nine adults with otitis media underwent tympanocentesis, and the effusion specimens were analyzed for the presence of both cytokines by enzyme-linked immunosorbent assay methods, Eighty-eight percent of the effusions were serous in nature. Sixty-seven percent of the patients had a known history of head and neck malignancy and radiation to the temporal bone, Twelve percent of the effusions were positive for interleukin-1 beta expression, compared with 85% of effusions in children with otitis media, Eight percent of the effusions contained tumor necrosis factor-alpha, compared with 85% of those collected in pediatric otitis media. All of the specimens that contained tumor necrosis factor-alpha also contained interleukin-1 beta. In the present study, there was no correlation with head and neck malignancy/radiation or the clinical degree of inflammation with the presence of either cytokine. We conclude that adult otitis media is associated with lower expression of an acute inflammatory response, as judged by the levels of interleukin-1 beta and tumor necrosis factor-alpha in the effusions, Additionally, adult otitis probably represents a less severe and more chronic inflammatory state in comparison with pediatric otitis media. Further analysis of inflammatory mediators in adult otitis media is necessary to evaluate the contribution of cytokines in relation to various etiologic factors. C1 Univ Minnesota, Dept Otolaryngol, Minneapolis, MN 55455 USA. NIDOCD, Tumor Cell Biol Div, Head & Neck Surg Branch, NIH, Bethesda, MD USA. RP Adams, GL (reprint author), Univ Minnesota, Dept Otolaryngol, 420 Delaware St SE,Box 396, Minneapolis, MN 55455 USA. NR 10 TC 20 Z9 20 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 1998 VL 119 IS 4 BP 342 EP 345 DI 10.1016/S0194-5998(98)70075-0 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 127NU UT WOS:000076358100007 PM 9781987 ER PT J AU Kato, T Dong, G Loukinova, E Chen, Z Van Waes, C AF Kato, T Dong, G Loukinova, E Chen, Z Van Waes, C TI Differential expression of the murine Ly-6A/E antigen homolog of human squamous cell carcinoma antigen E48 during malignant transformation and tumor progression of squamous cell carcinoma line Pam 212 SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 101st Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 07-10, 1997 CL SAN FRANCISCO, CALIFORNIA SP Amer Acad Otolaryngol Head & Neck Surg AB The mRNA differential display method detected increased expression of the mRNA of an immune recognition antigen known as Ly-6A/E after malignant transformation of the murine squamous cell carcinoma line Pam 212, Subsequent loss of expression of Ly-6A/E occurred with metastatic tumor progression of Pam in vivo. Ly-6 molecules have been implicated in immune cell recognition and signal transduction and are homologous to the human E48 SCC antigen that has been shown to be involved in cell-cell recognition. These observations suggest that loss of Ly-6A/E antigen may contribute to tumor progression and metastasis of squamous cell carcinoma through decreased tumor-lymphocyte or tumor-tumor recognition. C1 Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bldg 10,Rm 5D55, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [Z01 DC 00016-04] NR 7 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD OCT PY 1998 VL 119 IS 4 BP 408 EP 411 DI 10.1016/S0194-5998(98)70091-9 PG 4 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 127NU UT WOS:000076358100023 PM 9782003 ER PT J AU Lindmark, G Berendes, H Meirik, O AF Lindmark, G Berendes, H Meirik, O TI Antenatal care in developed countries SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Editorial Material C1 Univ Uppsala, Akad Sjukhuset, Sect Int Maternal & Reprod Hlth, Dept Women & Childrens Hlth, S-75185 Uppsala, Sweden. NICHD, NIH, Bethesda, MD USA. WHO, Special Programme Res Dev & Res Training Huma, Epidemiol Unit, CH-1211 Geneva, Switzerland. RP Lindmark, G (reprint author), Univ Uppsala, Akad Sjukhuset, Sect Int Maternal & Reprod Hlth, Dept Women & Childrens Hlth, S-75185 Uppsala, Sweden. NR 0 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD OCT PY 1998 VL 12 SU 2 BP 4 EP 6 DI 10.1046/j.1365-3016.12.s2.5.x PG 3 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 133KZ UT WOS:000076686900004 PM 9805720 ER PT J AU Villar, J Bakketeig, L Donner, A Al-Mazrou, Y Ba'aqeel, H Belizan, JM Carroli, G Farnot, U Lumbiganon, P Piaggio, G Berendes, H AF Villar, J Bakketeig, L Donner, A Al-Mazrou, Y Ba'aqeel, H Belizan, JM Carroli, G Farnot, U Lumbiganon, P Piaggio, G Berendes, H CA WHO Antenatal Care Trial Res Grp TI The WHO antenatal care randomised controlled trial: rationale and study design SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID CLINICAL-TRIALS; PRENATAL-CARE; SCIENTIFIC BASIS; ROUTINE; OUTCOMES; VISITS; PREGNANCIES; ELIMINATE; QUALITY; POWER AB The World Health Organisation and collaborating institutions in developing countries al-e conducting a multicentre randomised controlled trial to evaluate a new antenatal care (ANC) programme, consisting of tests, clinical procedures and follow-up actions scientifically demonstrated to be effective in improving maternal and newborn outcomes. These activities are distributed, for practical reasons, over four visits during the course of pregnancy and are aimed at achieving predetermined goals. The study is taking place in four countries, Argentina, Cuba, Saudi Arabia and Thailand. Recruitment of study subjects started on 1 May 1996. All 53 ANC clinical units had been enrolled by December 1996. Clinics in each country were randomly allocated (cluster randomisation) to provide either the new programme or the traditional programme currently in use. Approximately 24000 women presenting for ANC at these clinics over an average period of 18 months will have been recruited. As women attending the control clinics receive the 'best standard treatment' as currently offered in these clinics, individual informed consent is requested only from nwomen attending the intervention clinics. Authorities of the corresponding health districts and all participating clinics have provided written institutional informed consent before randomisation. The primary outcome of the trial in relation to maternal conditions is the rate of a morbidity indicator index, defined as the presence of at least one of the following conditions for which ANC is relevant: (a) preeclampsia or eclampsia during pregnancy or within 24h of delivery; (b) postpartum anaemia (haemoglobin < 90 g/L); or (c) severe urinary tract infection/pyelonephritis, defined as an episode requiring antibiotic treatment and/or hospitalisation. The primary fetal outcome is the rate of low birthweight (< 2500 g). Adverse maternal and fetal outcomes are expected for approximate to 10% of the control group. Several maternal and perinatal secondary outcomes are also considered. A comprehensive cost-effectiveness analysis and women's and providers' satisfaction evaluation are performed concurrently with the trial. Health-care programmes should be rigorously evaluated by randomised controlled trials, which are feasible in developing countries and should be? conducted before introducing new treatments or health interventions. C1 WHO, World Bank Special Programme Res Dev & Res Traini, UNFPA, UNDP, CH-1211 Geneva 27, Switzerland. Natl Publ Hlth Inst, Oslo, Norway. Univ Western Ontario, London, ON, Canada. Minist Hlth, Riyadh, Saudi Arabia. Natl Guard King Khalid Hosp, Jeddah, Saudi Arabia. CREP, Rosario, Argentina. Hosp Ginecoobstet Amer Arias, Havana, Cuba. Khon Kaen Univ, Khon Kaen, Thailand. NICHHD, NIH, Bethesda, MD USA. RP Villar, J (reprint author), WHO, World Bank Special Programme Res Dev & Res Traini, UNFPA, UNDP, CH-1211 Geneva 27, Switzerland. OI Baaqeel, Hassan/0000-0002-0774-2790; Belizan, Jose/0000-0002-8412-3010 NR 52 TC 41 Z9 45 U1 0 U2 6 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD OCT PY 1998 VL 12 SU 2 BP 27 EP 58 DI 10.1046/j.1365-3016.1998.00006.x PG 32 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 133KZ UT WOS:000076686900006 PM 9805722 ER PT J AU Donner, A Piaggio, G Villar, J Pinol, A Al-Mazrou, Y Ba'aqeel, H Bakketeig, L Belizan, JM Berendes, H Carroli, G Farnot, U Lumbiganon, P AF Donner, A Piaggio, G Villar, J Pinol, A Al-Mazrou, Y Ba'aqeel, H Bakketeig, L Belizan, JM Berendes, H Carroli, G Farnot, U Lumbiganon, P CA WHO Antenatal Care Trial Res Grp TI Methodological considerations in the design of the WHO Antenatal Care Randomised Controlled Trial SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY LA English DT Article ID COMMUNITY INTERVENTION; CLUSTER RANDOMIZATION; PERINATAL DATA; ISSUES; MODELS AB We discuss methodological issues arising in a recent evaluation trial of a new antenatal care programme, as sponsored by the Special Programme of Research, Development and Research Training in Human Reproduction, and WHO's Division of Reproductive Health (Technical Support). The randomisation unit for the trial is the antenatal care clinic, with 53 clinics located in four countries randomly allocated to provide either the new programme or the traditional programme currently in use. Approximately 24 000 women presenting for antenatal care over an average period of 18 months will have been recruited. C1 WHO, Special Programme Res Dev & Res Training Huma, World Bank, UNDP,UNFPA, CH-1211 Geneva 27, Switzerland. Univ Western Ontario, London, ON, Canada. Minist Hlth, Riyadh, Saudi Arabia. Natl Guard King Khalid Hosp, Jeddah, Saudi Arabia. Natl Inst Publ Hlth, Oslo, Norway. CREP, Rosario, Argentina. NICHD, NIH, Bethesda, MD USA. Hosp Gineco Obstet Amer Arias, Havana, Cuba. Khon Kaen Univ, Khon Kaen, Thailand. RP Villar, J (reprint author), WHO, Special Programme Res Dev & Res Training Huma, World Bank, UNDP,UNFPA, CH-1211 Geneva 27, Switzerland. OI Baaqeel, Hassan/0000-0002-0774-2790; Belizan, Jose/0000-0002-8412-3010 NR 24 TC 12 Z9 12 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-5022 J9 PAEDIATR PERINAT EP JI Paediatr. Perinat. Epidemiol. PD OCT PY 1998 VL 12 SU 2 BP 59 EP 74 DI 10.1046/j.1365-3016.1998.00007.x PG 16 WC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics SC Public, Environmental & Occupational Health; Obstetrics & Gynecology; Pediatrics GA 133KZ UT WOS:000076686900007 PM 9805723 ER PT J AU Chen, JH Le, SY Shapiro, BA Maizel, JV AF Chen, JH Le, SY Shapiro, BA Maizel, JV TI Optimization of an RNA folding algorithm for parallel architectures SO PARALLEL COMPUTING LA English DT Article DE dynamic programming; ribonucleic acid (RNA) folding problem; block computation; CRAY Y-MP; Mas Par MP-2; communication cost; performance results ID SECONDARY STRUCTURES; PREDICTION; SEQUENCE; VIRUS; ELEMENTS AB In this paper we describe parallel implementations of a dynamic programming algorithm for predicting ribonucleic acid (RNA) secondary structure based on energy minimization in high performance computers. The computations of the energies for all possible fragments of the molecule consume almost all the computations in the prediction algorithm. The computation ordering and the data placement dictate the performance of the algorithm. Only the diagonal ordering, which starts with short fragments and progresses to successively greater fragments in length, out of three possible computation orderings can take full advantage of the advanced architectures discussed in this study. We have implemented two methods on a GRAY Y-MP. Our results demonstrate that the method with less bank conflict performs better in a single-processor environment. However, the other method utilizes the processors more efficiently in the multiple-processor environment of GRAY Y-MP. An efficient parallel algorithm has also been designed solely for a distributed-memory SIMD architecture. In a distributed memory system, the performance is also affected by the cost of communication between processors. The algorithm significantly reduces the data communication cost. Consequently, our results show that the performance on our MasPar MP-2 system is far better than that on a single-processor GRAY Y-MP as the problem size grows. Our algorithm has been applied to a SMP MIMD architecture (eight-processor GRAY Y-MP) and may be adapted to a distributed MIMD architecture. The methodology described in this study may possibly be applied to other optimization problems using a dynamic programming algorithm. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Frederick Canc Res & Dev Ctr, Math Biol Lab, Div Canc Biol,NIH, Frederick, MD 21702 USA. RP Chen, JH (reprint author), NCI, Frederick Canc Res & Dev Ctr, Math Biol Lab, Div Canc Biol,NIH, Bldg 469,Rm 151, Frederick, MD 21702 USA. NR 15 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8191 J9 PARALLEL COMPUT JI Parallel Comput. PD OCT PY 1998 VL 24 IS 11 BP 1617 EP 1634 DI 10.1016/S0167-8191(98)00054-4 PG 18 WC Computer Science, Theory & Methods SC Computer Science GA 132AJ UT WOS:000076607200002 ER PT J AU Mofenson, LM Yogev, R Korelitz, J Bethel, J Krasinski, K Moye, J Nugent, R Rigau-Perez, JG AF Mofenson, LM Yogev, R Korelitz, J Bethel, J Krasinski, K Moye, J Nugent, R Rigau-Perez, JG CA Natl Inst Child Hlth Human Dev Intravenous Immu TI Characteristics of acute pneumonia in human immunodeficiency virus-infected children and association with long term mortality risk SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE pediatric human immunodeficiency virus infection; pneumonia; mortality; intravenous immunoglobulin prophylaxis ID HIV-INFECTION; BACTERIAL-INFECTIONS; CONTROLLED TRIAL; DISEASE AB Objective. To describe the epidemiologic, clinical, radiologic, laboratory and treatment characteristics of acute pneumonia and its association with mortality in HIV-infected children. Methods. Data were collected during a trial of intravenous immunoglobulin (IVIG) for infection prophylaxis (1988 to 1991); CD4(+) percentage was measured and HIV RNA was assessed on stored sera collected at baseline and every 3 months. Mortality was recorded during the trial and updated through 1996. All reported physician-diagnosed pneumonia episodes underwent blinded review for trial endpoint classification as acute (new radiologic findings and presence of clinical symptoms) or nonacute. Results. On blinded clinical trial endpoint review of all reported pneumonia episodes (n = 281), only 47% were classified as acute. One hundred thirty-one episodes of acute pneumonia were reported in 93 children (47 in 31 IVIG and 84 in 62 placebo patients, P < 0.01). The incidence of acute pneumonia was 24 episodes per 100 patient years. Findings associated with an acute bacterial process were uncommon (leukocytosis greater than or equal to 15 000/mm(3) in 21% and fever greater than or equal to 103 degrees F in 32% of episodes). Multiple acute episodes occurred in 34% of the children and were associated with increased risk of mortality in a univariate analysis (risk ratio, 2.1; 95% confidence interval, 1.3 to 3.4, P = 0.002), but in a multivariate model only baseline HIV RNA copy number and CD4(+) percentage remained independently associated with mortality (relative risk, 2.0 and 1.4, respectively, P < 0.001). Conclusion. Acute pneumonia was a common occurrence in HIV-infected children and was associated with long term mortality risk. Multiple episodes of acute pneumonia likely represent a marker of progressive disease and immunologic dysfunction rather than being causally associated with increased long term mortality. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, Rockville, MD 20852 USA. Northwestern Univ, Childrens Mem Hosp, Dept Pediat, Sch Med, Chicago, IL 60614 USA. WESTAT Corp, Rockville, MD 20850 USA. NYU Med Ctr, Dept Pediat, New York, NY 10016 USA. Ctr Dis Control & Prevent, Dengue Branch, Div Vector Borne Infect Dis, Natl Ctr Infect Dis, San Juan, PR USA. RP Mofenson, LM (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Room 4B11, Rockville, MD 20852 USA. EM LM65D@nih.gov OI Mofenson, Lynne/0000-0002-2818-9808; moye, john/0000-0001-9976-8586 NR 28 TC 15 Z9 16 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD OCT PY 1998 VL 17 IS 10 BP 872 EP 880 DI 10.1097/00006454-199810000-00005 PG 9 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 131CE UT WOS:000076557500004 PM 9802627 ER PT J AU Subar, AF Krebs-Smith, SM Cook, A Kahle, LL AF Subar, AF Krebs-Smith, SM Cook, A Kahle, LL TI Dietary sources of nutrients among US children, 1989-1991 SO PEDIATRICS LA English DT Article DE dietary surveys; nutrients; food; diet; children ID UNITED-STATES POPULATION; NHANES-II SURVEY; FOOD SOURCES; QUANTITATIVE DATA; AMERICAN DIET; FIBER; MACRONUTRIENTS; WOMEN AB Objective. To identify major food sources of nutrients and dietary constituents for US children. Methods. Twenty-four-hour dietary recalls were collected from a nationally representative sample of children age 2 to 18 years (n = 4008) from the US Department of Agriculture's 1989-1991 Continuing Survey of Food Intakes by Individuals. For each of 16 dietary constituents, the contribution of each of 113 food groups was obtained by summing the amount provided by the food group for all individuals and dividing by total intake from all food groups for all individuals. Results. Milk, yeast bread, cakes/cookies/quick breads/donuts, beef, and cheese are among the top 10 sources of energy, fat, and protein. Many of the top 10 sources of carbohydrate (yeast bread, soft drinks/sodas, milk, ready-to-eat cereal, cakes/cookies/quick breads/donuts, sugars/syrups/jams, fruit drinks, pasta, white potatoes); protein (poultry, ready-to-eat cereal, pasta); and fat (potato chips/corn chips/popcorn) also contributed >2% each to energy intakes. Ready-to-eat cereal is among the top contributors to folate, vitamin A, vitamin C, iron, and zinc intakes. Fruit drinks, containing little juice, contribute similar to 14% of total vitamin C intakes. Conclusions. Fortified foods are influential contributors to many vitamins and minerals. Low nutrient-dense foods are major contributors to energy, fats, and carbohydrate. This compromises intakes of more nutritious foods and may impede compliance with current dietary guidance. C1 NCI, Appl Res Branch, Bethesda, MD 20892 USA. USDA ARS, Riverdale, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. RP Subar, AF (reprint author), NCI, Appl Res Branch, 6130 Execut Blvd,MSC 7344,EPN 313, Bethesda, MD 20892 USA. NR 23 TC 153 Z9 155 U1 3 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1998 VL 102 IS 4 BP 913 EP 923 DI 10.1542/peds.102.4.913 PN 1 PG 11 WC Pediatrics SC Pediatrics GA 126DL UT WOS:000076277600007 PM 9755265 ER PT J AU Athreya, BH Cheh, ML Kingsland, LC AF Athreya, BH Cheh, ML Kingsland, LC TI Computer-assisted diagnosis of pediatric rheumatic diseases SO PEDIATRICS LA English DT Article DE computer-assisted diagnosis; multimedia; rheumatic diseases; expert system ID CONSULTANT SYSTEM; AI/RHEUM AB Objective. AI/RHEUM is a multimedia expert system developed originally to assist in the diagnosis of rheumatic diseases in adults. In the present study we evaluated the usefulness of a modified version of this diagnostic decision support system in diagnosing childhood rheumatic diseases. Methodology. AI/RHEUM was modified by the addition of 5 new diseases to the knowledge base of the system. Criteria tables for each of the diseases included in the knowledge base were modified to suit the needs of children. The modified system was tested on 94 consecutive children seen in a pediatric rheumatology clinic. Results. AI/RHEUM made the correct diagnosis in 92% of the cases when the diagnosis was available in the knowledge base of the system. It was also shown to be effective in the education of pedia trainees through;ts multimedia features. Conclusions. AI/RHEUM is an expert system that may be helpful to the nonspecialist as a diagnostic decision support system and as an educational tool. URL: http://www.pediatrics.org/cgi/contentfull/102/4/e48. C1 duPont Hosp Children, Wilmington, DE 19899 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. NIH, Comp Sci Branch, Natl Lib Med, Bethesda, MD 20892 USA. RP Athreya, BH (reprint author), duPont Hosp Children, 1600 Rockland Rd, Wilmington, DE 19899 USA. NR 6 TC 7 Z9 7 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 1998 VL 102 IS 4 BP art. no. EP e48 DI 10.1542/peds.102.4.e48 PN 1 PG 7 WC Pediatrics SC Pediatrics GA 126DL UT WOS:000076277600023 PM 9755285 ER PT J AU Padfield, PJ Elliot, AC Baldassare, JJ AF Padfield, PJ Elliot, AC Baldassare, JJ TI Adenovirus-mediated gene expression in isolated rat pancreatic acini and individual pancreatic acinar cells SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Article DE adenovirus; exocrine pancreas; gene expression; gene transfer ID GLANDS AB In this study we have examined the feasibility of using replication-deficient recombinant adenoviral vectors to transfer and express genes in pancreatic acinar cells in vitro. We infected primary cultures of both isolated pancreatic acini and individual acinar cells with a recombinant adenovirus containing the coding sequence for beta-galactosidase. Our data demonstrate that recombinant adenoviruses readily infect pancreatic acinar cells in vitro. Close to 100% infection and maximal beta-galactosidase expression were obtained, when acini or acinar cells were infected with 5x10(6) or 10(6) plaque-forming units (pfu) of virus per millitre of acini or acinar cell suspension, respectively. Examination of the time-course of beta-galactosidase expression showed that there was a lag of approximately 6 h before beta-galactosidase levels increased. Thereafter beta-galactosidase expression increased rapidly. By 20 h post-infection beta-galactosidase activity had increased from undetectable levels to 2.5-3.0 units/mg of cellular protein. Acini/acinar cells maintained a robust secretory response after adenoviral infection. The cholecystokinin-octapeptide (CCK8) dose/response curves for amylase secretion for acini and acinar cells infected with 5x10(5) and 1x10(5) pfu/ml of virus, respectively, were biphasic, with maximal amylase secretion being stimulated by 1 nM CCK8. In addition, the dose/response curves were identical to those obtained from control, sham-infected, acini/acinar cells. Our findings indicate that replication-deficient recombinant adenoviral vectors will be excellent tools to transfer and express genes in isolated pancreatic acini or acinar cells. C1 St Louis Univ, Hlth Sci Ctr, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA. St Louis Univ, Hlth Sci Ctr, Dept Pathol, St Louis, MO 63104 USA. Univ Manchester, Sch Biol Sci, Cell Physiol Grp, Manchester, Lancs, England. NIDR, Gene Therapy & Therapeut Branch, Bethesda, MD 20892 USA. RP Padfield, PJ (reprint author), St Louis Univ, Hlth Sci Ctr, Dept Pharmacol & Physiol Sci, 1402 S Grand Blvd, St Louis, MO 63104 USA. FU NIDDK NIH HHS [DK46814-01A3] NR 15 TC 13 Z9 13 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD OCT PY 1998 VL 436 IS 5 BP 782 EP 787 DI 10.1007/s004240050702 PG 6 WC Physiology SC Physiology GA 119CG UT WOS:000075877300021 PM 9716713 ER PT J AU Yang, TJ Sai, Y Krausz, KW Gonzalez, FJ Gelboin, HV AF Yang, TJ Sai, Y Krausz, KW Gonzalez, FJ Gelboin, HV TI Inhibitory monoclonal antibodies to human cytochrome P450 1A2: analysis of phenacetin O-deethylation in human liver SO PHARMACOGENETICS LA English DT Article DE inhibitory monoclonal antibodies; human P450 1A2; 2C19; 2A6; phenacetin O-deethylation; human liver microsomes ID CDNA-EXPRESSED HUMAN; MICROSOMES; BACULOVIRUS; METABOLISM; SEQUENCES; CYP1A2; PROBES; 2E1 AB Human cytochrome P450 1A2 metabolizes a large number of common drugs and engages in carcinogen metabolism and activation, Baculovirus-expressed 1A2 was used to immunize mice producing hybridomas yielding monoclonal antibodies (MAbs), Three of 2050 clones assayed yielded the MAbs, MAb 26-7-5, MAb 951-5-1, MAb 1812-2-4, which were specific for 1A2 as assessed by enzyme-linked immunosorbent assay and immunoblots, The three MAbs inhibited 1A2-catalysed metabolism of phenacetin, 7-ethoxycoumarin, chlorzoxazone and phenanthrene by more than 85%, The MAbs were highly specific to 1A2 and did not inhibit 11 other human P450s. The phenancetin O-deethylation activity varied from 0.44-2.49 nmol/min/nmol P450 in eight human liver microsomes samples. MAb 26-7-5 inhibited 1A2-dependent phenacetin O-deethylation in these samples by 64-84% indicating the amount of 1A2 contribution to this reaction and in addition a role for other P450s in the O-deethylation, Independent analysis of recombinant human P450s showed that 1A1, 1A2, 2A6 and 2C19 exhibited phenacetin O-deethylation activity with 1A1 and 1A2 being the most active followed by 2C19 and 2A6. Eight other P450s were inactive towards phenacetin O-deethylation, The role of different P450 in eight liver samples was analysed with specific individual inhibitory MAbs. Inhibitory antibodies to 1A2, 2C8/9/18/19, 2A6, 2D6, 2E1, and 1A1 were combinatorially added to the microsomes, The O-deethylation activity was inhibited by antibodies to 1A2 (64-84%), to 2C19 (4.6-20%) and to 2A6 (0-8.8%), The total activity inhibited by antibodies to P450 2E1, 2D6 and 1A1 was less than 4.5%, indicating a minor role for these P450s in phenancetin metabolism in human liver microsomes, Thus, 1A2, 2C19 and 2A6 are the dominant P450s for phenacetin O-deethylation. These studies demonstrate the use of inhibitory MAbs to P450s for a simple and precise assessment of the quantitative role of each P450 in the metabolism of substrates, including drugs, carcinogens, mutagens, environmental chemicals and endobiotics. Pharmacogenetics 8:375-382 (C) 1998 Lippincott Williams & Wilkins. C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Gelboin, HV (reprint author), NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 29 TC 18 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1998 VL 8 IS 5 BP 375 EP 382 DI 10.1097/00008571-199810000-00002 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 134LE UT WOS:000076743800002 PM 9825829 ER PT J AU Shou, MG Martinet, M Korzekwa, KR Krausz, KW Gonzalez, FJ Gelboin, HV AF Shou, MG Martinet, M Korzekwa, KR Krausz, KW Gonzalez, FJ Gelboin, HV TI Role of human cytochrome P450 3A4 and 3A5 in the metabolism of taxotere and its derivatives: enzyme specificity, interindividual distribution and metabolic contribution in human liver SO PHARMACOGENETICS LA English DT Article DE drug metabolism; cytochrome P450; taxotere; cDNA expression; monoclonal antibody; human liver; high performance liquid chromatography ID CDNA-DIRECTED EXPRESSION; MAJOR HUMAN METABOLITES; HEPATIC CYTOCHROME-P450; MONOCLONAL-ANTIBODIES; DOCETAXEL TAXOTERE; DRUG-INTERACTIONS; TAXOL METABOLISM; IN-VITRO; PURIFICATION; MICROSOMES AB Taxotere, a promising anticancer agent, is metabolized almost exclusively in liver and excreted from bile in all species. To determine which cytochrome P450 is involved in taxotere biotransformation, 11 cDNA-expressed human cytochrome P450s were examined for their activity in the metabolism of taxotere and its derivatives. Of all P450s, cytochrome P450 3A4 and 3A5 were the most active for the oxidation of taxotere to the primary metabolite RPR104952 and for subsequent oxidation of RPR104952 to RPR111059 and RPR111026. RP70617, an epimer of taxotere was also metabolized by both P450 3A enzymes to form metabolite XII. The activity of 3A4/5 enzymes for these substrates was 4-50-fold greater than the other P450s examined. The K(m)s of 3A4 and 3A5 for taxotere were 0.91 and 9.28 mu M, and V-max for the formation of RPR104952 were 1.17 and 1.36 m(-1), respectively. The contribution of the 3A enzyme complex to the metabolism of taxotere in human livers from 21 individuals was assessed with the inhibitory monoclonal antibody and ranged from 64-93%. The primary oxidative metabolism of taxotere by human liver microsomes was well correlated with 3A4-dependent reactions for testosterone 6 beta-hydroxylation (r(2) = 0.84), taxol aromatic hydroxylation (r(2) = 0.67) and aflatoxin B-1 3 alpha-hydroxylation (r(2) = 0.63); whereas a poor correlation was found for reactions specifically catalysed by other P450s (all r(2) less than or equal to 0.17). The extent of taxotere metabolism also closely correlated with levels of 3A4 enzyme in human livers quantified with immunoblot monoclonal antibody (r(2) = 0.61), These results demonstrate that the P450 3A4 and 3A5 enzymes are major determinants in taxotere oxidation and suggest that care must be taken when administering this drug with other drugs that are also substrates for these enzymes. Pharmacogenetics 8:391-401 (C) 1998 Lippincott Williams & Wilkins. C1 NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Rhone Poulenc Rorer, Drug Metab & Pharmacokinet, Antony, France. Univ Pittsburgh, Med Ctr, Dept Clin Pharmacol, Pittsburgh, PA USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Shou, MG (reprint author), Merck Res Labs, Dept Drug Metab, WP26A-2044, W Point, PA 19486 USA. EM magang_shou@merck.com NR 51 TC 125 Z9 128 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD OCT PY 1998 VL 8 IS 5 BP 391 EP 401 DI 10.1097/00008571-199810000-00004 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 134LE UT WOS:000076743800004 PM 9825831 ER PT J AU Chignell, CF Sik, RH AF Chignell, CF Sik, RH TI Effect of magnetite particles on photoinduced and nonphotoinduced free radical processes in human erythrocytes SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID LIPID-PEROXIDATION; FIELD; MAGNETORECEPTION AB Magnetite (Fe3O4) encapsulated in polystyrene microspheres dramatically decreased the time for 50% hemolysis (t(1/2)) of human erythrocytes irradiated (lambda > 300 mm) in the presence of ketoprofen (0.1 mM). The magnetic microspheres were present at a very low concentration (0.002%) such that on average there was only one particle per four erythrocytes. No such effect was seen when nonmagnetic microspheres were employed or when the equivalent concentration of soluble iron (FeCl3) was present. A decrease in t(1/2) was also observed when the magnetic microspheres were added after UVA/ketoprofen treatment or when they were present during hemolysis initiated by thermolysis of 2,2'-azobis(2-amidinopropane). These findings may be attributed to an increase in the membrane concentration of lipid radicals as a result of a magnetic field-induced increase in radicals escaping from triplet radical pairs. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Chignell, CF (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 18 TC 8 Z9 8 U1 2 U2 2 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD OCT PY 1998 VL 68 IS 4 BP 598 EP 601 DI 10.1111/j.1751-1097.1998.tb02520.x PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 130VB UT WOS:000076540100026 PM 9796445 ER PT J AU McCann, UD Eligulashvili, V Ricaurte, GA AF McCann, UD Eligulashvili, V Ricaurte, GA TI Adverse neuropsychiatric events associated with dexfenfluramine and fenfluramine SO PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY LA English DT Review DE adverse effects; dexfenfluramine; fenfluramine; serotonin ID PRIMARY PULMONARY-HYPERTENSION; NEUROTOXICITY; SEROTONIN; PHENTERMINE; BRAIN; MANIA; DRUG; RAT AB 1. There is a large body of evidence indicating that fenfluramines damage brain serotonin neurons in animals. 2. Little is known about potential adverse neuropsychiatric consequences in humans associated with use of fenfluramines that could potentially be related to serotonergic dysfunction. 3. The authors now report numerous cases of severe and, sometimes persistent, neuropsychiatric syndromes associated with fenfluramine use. 4. Thirty one representative cases are presented and summarized in table form. 5. Several of the cases presented suggest long-lasting deleterious effects of fenfluramines on brain serotonin function. 6. Clinicians should be vigilant for disorders of mood, anxiety, cognitive function and impulse control in patients previously exposed to fenfluramines. C1 NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Neurol, Baltimore, MD 21205 USA. RP McCann, UD (reprint author), NIMH, Biol Psychiat Branch, NIH, Bldg 10,Room 3N212,MSC 1272,10 Ctr Dr, Bethesda, MD 20892 USA. FU NIDA NIH HHS [R01DA11226-01] NR 22 TC 13 Z9 14 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-5846 J9 PROG NEURO-PSYCHOPH JI Prog. Neuro-Psychopharmacol. Biol. Psychiatry PD OCT PY 1998 VL 22 IS 7 BP 1087 EP 1102 DI 10.1016/S0278-5846(98)00063-3 PG 16 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 131RK UT WOS:000076588900003 PM 9829290 ER PT J AU Mezinskis, J Dyrenforth, S Goldsmith, RJ Cohen, M Somoza, E AF Mezinskis, J Dyrenforth, S Goldsmith, RJ Cohen, M Somoza, E TI Craving and withdrawal symptoms for various drugs of abuse SO PSYCHIATRIC ANNALS LA English DT Article ID MISUSE AB The authors investigate craving and how it varies with the intensity of the eight mood states commonly associated with withdrawal. They compare craving between subjects dependent on various single drugs to see if cravings for different drugs are quantitatively different and also compare craving for different substances within subjects who have multiple substance dependencies to see if the cravings are qualitatively similar. C1 Dept Vet Affairs Med Ctr, NIDA, VAUC, MDRU, Cincinnati, OH 45220 USA. Univ Cincinnati, Dept Psychiat, Coll Med, Cincinnati, OH 45221 USA. RP Somoza, E (reprint author), Dept Vet Affairs Med Ctr, NIDA, VAUC, MDRU, 3200 Vine St, Cincinnati, OH 45220 USA. NR 15 TC 34 Z9 34 U1 2 U2 5 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 1998 VL 28 IS 10 BP 577 EP + PG 8 WC Psychiatry SC Psychiatry GA 132TQ UT WOS:000076646500006 ER PT J AU Hall, FS Huang, S Fong, GW Pert, A Linnoila, M AF Hall, FS Huang, S Fong, GW Pert, A Linnoila, M TI Effects of isolation rearing on locomotion, anxiety and responses to ethanol in Fawn Hooded and Wistar rats SO PSYCHOPHARMACOLOGY LA English DT Article DE Fawn Hooded rat; Wistar rat; isolation-rearing; ethanol; anxiety; locomotor activity ID ELEVATED PLUS-MAZE; NUCLEUS-ACCUMBENS; SOCIAL-ISOLATION; LABORATORY RATS; PREFERENCE; AMPHETAMINE; RESOCIALIZATION; HYPERACTIVITY; STIMULATION; ENVIRONMENT AB Voluntary ethanol (EtOH) consumption is increased by isolation-rearing in several rat strains. The following experiments examined the effects of isolation-rearing on basal and ethanol-stimulated behavior in Fawn Hooded rats, an alcohol-preferring rat strain, compared to Wistar rats. Locomotor activity and anxiety were examined under both conditions. Basal locomotor activity was higher in isolated subjects of both strains in low light conditions, but under bright light conditions: this difference was only observed in Wistar rats. Locomotor stimulant effects of EtOH were only observed in isolation-reared rats. In the elevated plus maze, Fawn Hooded rats were more anxious than Wistar rats under low light conditions, but under bright light conditions, Wistar socials were less anxious than all of the other groups. Administration of 1.5 mg/kg EtOH produced an anxiolytic response in the elevated plus maze under bright light conditions in Fawn Hooded rats, but to a lesser degree Wistar rats, particularly Wistar isolates. In conclusion, although both strain and isolation-rearing had effects on locomotion and anxiety as well as the stimulatory and anxiolytic effects of EtOH, these effects appeared to be independent. C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Hall, FS (reprint author), NIAAA, Clin Studies Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 42 TC 74 Z9 76 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1998 VL 139 IS 3 BP 203 EP 209 DI 10.1007/s002130050705 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 123NQ UT WOS:000076131600004 PM 9784074 ER PT J AU Hall, FS Huang, S Fong, GW Pert, A Linnoila, M AF Hall, FS Huang, S Fong, GW Pert, A Linnoila, M TI Effects of isolation-rearing on voluntary consumption of ethanol, sucrose and saccharin solutions in Fawn Hooded and Wistar rats SO PSYCHOPHARMACOLOGY LA English DT Article DE isolation-rearing; ethanol; sucrose; saccharin; rat ID SPRAGUE-DAWLEY RATS; NUCLEUS-ACCUMBENS; SOCIAL-ISOLATION; ALCOHOL-CONSUMPTION; HOUSING CONDITIONS; LABORATORY RATS; DOPAMINE; SEROTONIN; DRINKING; STRAINS AB These experiments examined the hypothesis that isolation-rearing and strain influence hedonic mechanisms. In experiment 1, voluntary consumption of ethanol and water was monitored in the home cage of Fawn Hooded (FH) and Wistar rats. FH rats were found to consume more ethanol at low concentrations than Wistar rats, independent of rearing condition, and isolation-reared rats were found to consume more of high ethanol concentrations, independent of strain. In experiment 2, isolation-reared rats were found to consume more sucrose, independent of concentration, than socially reared rats. In experiment 3, Fawn Hooded rats were found to be more sensitive to low concentration solutions of saccharin, and to consume less of the high concentration solutions, while isolation-rearing was found to enhance consumption of high concentrations. Thus, hedonic processes are independently modulated by strain and rearing conditions, although the effects of isolation-rearing appear to be exacerbated in Fawn Wooded rats. C1 NIAAA, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. RP Hall, FS (reprint author), NIAAA, Clin Studies Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. RI Hall, Frank/C-3036-2013 OI Hall, Frank/0000-0002-0822-4063 NR 43 TC 62 Z9 63 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD OCT PY 1998 VL 139 IS 3 BP 210 EP 216 DI 10.1007/s002130050706 PG 7 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 123NQ UT WOS:000076131600005 PM 9784075 ER PT J AU Summers, RM Brune, AM Choyke, PL Chow, CK Patronas, NJ Miller, FW White, PH Malley, JD Rider, LG AF Summers, RM Brune, AM Choyke, PL Chow, CK Patronas, NJ Miller, FW White, PH Malley, JD Rider, LG TI Juvenile idiopathic inflammatory myopathy: Exercise-induced changes in muscle at short inversion time inversion-recovery MR imaging SO RADIOLOGY LA English DT Article DE dermatomyositis; muscles, diseases; muscles, MR; myositis ID MAGNETIC-RESONANCE SPECTROSCOPY; SKELETAL-MUSCLE; TRANSVERSE RELAXATION; LEG MUSCLE; DERMATOMYOSITIS; DISEASE; WORK; T2; CHILDREN; IMAGES AB PURPOSE: To study the effect of exercise on short inversion time inversion-recovery (STIR) magnetic resonance (MR) images of thigh muscles in children with juvenile idiopathic inflammatory myopathy. MATERIALS AND METHODS: Thirty-two MR studies were performed in 19 patients with juvenile idiopathic inflammatory myopathy who performed stair-stepping exercise for up to 10 minutes (mean, 5.7 minutes). Baseline T1-weighted (n = 32) and STIR (n = 32) images and STIR images immediately (n = 32) and at 30 (n = 24) and 60 (n = 29) minutes after exercise were obtained at 0.5 T. Four radiologists graded STIR signal intensity changes, in observer performance experiments in which they were blinded to the order of image acquisition in relation to exercise. RESULTS: Changes in muscle signal intensity were observed on STIR images obtained immediately after exercise in 20 of 32 (63%) studies. The mean signal intensity score immediately after exercise (1.7 +/- 1.0 [SD]) increased compared with the mean baseline score (1.4 +/- 1.1) (P = .0005) and resolved by 30 minutes after exercise. The magnitude of exercise-induced changes correlated with the amount of work performed (r = 0.51, P = .003) but not with disease activity or baseline signal intensity when the changes were corrected for work (r < 0.17, P > .35). Radiologists demonstrated moderate to substantial agreement in the grading of signal intensity changes after exercise (kappa = 0.60-0.84). CONCLUSION: In patients with juvenile idiopathic inflammatory myopathy, stair-stepping exercise induces signal intensity changes on STIR MR studies of muscle for approximately 30 minutes after exercise, in a distribution that may mimic active muscle inflammation. C1 US FDA, Ctr Biol Evaluat & Res, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NIH, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Pediat Rheumatol, Washington, DC 20010 USA. RP Summers, RM (reprint author), US FDA, Ctr Biol Evaluat & Res, Dept Diagnost Radiol, Bldg 10,Rm 1C660,10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 26 TC 17 Z9 18 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD OCT PY 1998 VL 209 IS 1 BP 191 EP 196 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 121QK UT WOS:000076024700032 PM 9769831 ER PT J AU Zeiger, E AF Zeiger, E TI Identification of rodent carcinogens and noncarcinogens using genetic toxicity tests: Premises, promises, and performance SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID HAMSTER OVARY CELLS; NATIONAL-TOXICOLOGY-PROGRAM; SISTER CHROMATID EXCHANGES; UNITED-STATES NTP; SHORT-TERM TESTS; MUTAGENESIS ASSAY; TOX PROGRAM; SALMONELLA-TYPHIMURIUM; MUTAGENICITY ASSAYS; CHEMICAL-STRUCTURE AB The basic premises that guide genetic toxicity testing for identifying carcinogens and to support administrative and regulatory decisions are: the Salmonella mutagenicity test is a necessary component of testing schemes; a chromosome aberration test is needed in addition to a gene mutation test; a mammalian cell mutagenicity test is needed in addition to the Salmonella test; in vivo tests are needed to confirm the results of in vitro tests; and test batteries are more predictive than the individual tests of the battery. Results from the Salmonella mutagenicity, in vitro chromosome aberration, mutations in mouse lymphoma cells, rodent bone marrow micronucleus, and rodent carcinogenicity tests, performed by the U.S. National Toxicology Program, were used to evaluate these premises. A positive Salmonella test was most predictive of carcinogenicity. However, the data do not support using the other tests in addition to Salmonella for predicting carcinogenicity. The genetic toxicity tests did not complement each other, and batteries or combinations of the tests were no more predictive of carcinogenicity than Salmonella alone. If a chemical is mutagenic in Salmonella it should be considered a potential rodent carcinogen, unless ancillary information suggests otherwise. Positive responses in the other in vitro or in vivo tests do not increase the probability that the chemical is a carcinogen, and negative responses in the other tests do not diminish the implications of the positive Salmonella response. C1 NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Zeiger, E (reprint author), NIEHS, Environm Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. NR 67 TC 127 Z9 131 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD OCT PY 1998 VL 28 IS 2 BP 85 EP 95 DI 10.1006/rtph.1998.1234 PG 11 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 167EV UT WOS:000078620300004 PM 9927558 ER PT J AU Marques, AR Straus, SE AF Marques, AR Straus, SE TI Advances in the treatment of chronic hepatitis B virus infection SO REVIEWS IN MEDICAL VIROLOGY LA English DT Review ID RANDOMIZED CONTROLLED TRIAL; ADENINE-ARABINOSIDE MONOPHOSPHATE; PLACEBO-CONTROLLED TRIAL; TERM FOLLOW-UP; LYMPHOBLASTOID INTERFERON; LIVER-TRANSPLANTATION; REVERSE-TRANSCRIPTASE; PREDNISONE WITHDRAWAL; ALPHA-INTERFERON; IN-VITRO AB Recent advances in our understanding of the replicative mechanism of HBV, and the development of potent nucleoside analogues as clinically effective inhibitors of the HIV reverse transcriptase or herpesvirus polymerases has opened a new era in the treatment of chronic HBV infection. Single agent therapies, such as famciclovir, lamivudine or lobucavir, have had some success. There is now a logical basis for combination therapy, because of the clear need for prolonged treatment and the associated possibility that drug resistant strains will emerge with monotherapy, but the choice of agents to combine and the regimens in which they should be employed remain uncertain. (C) 1998 John Wiley & Sons, Ltd. C1 NIAID, Clin Studies Unit, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Marques, AR (reprint author), NIAID, Clin Studies Unit, Clin Invest Lab, NIH, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 77 TC 8 Z9 8 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1052-9276 J9 REV MED VIROL JI Rev. Med. Virol. PD OCT-DEC PY 1998 VL 8 IS 4 BP 223 EP 234 DI 10.1002/(SICI)1099-1654(1998100)8:4<223::AID-RMV229>3.0.CO;2-J PG 12 WC Virology SC Virology GA 146LX UT WOS:000077431500007 ER PT J AU Sherman, CD Portier, CJ AF Sherman, CD Portier, CJ TI Eyes closed: Simple, intuitive, statistically sound, and efficient methods for estimating parameters of clonal growth cancer models SO RISK ANALYSIS LA English DT Letter ID COMPUTER-SIMULATION; MULTISTAGE MODEL; CARCINOGENESIS C1 Radiat Effects Res Fdn, Dept Stat, Minami Ku, Hiroshima 732, Japan. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. RP Sherman, CD (reprint author), Radiat Effects Res Fdn, Dept Stat, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 732, Japan. RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 14 TC 3 Z9 3 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD OCT PY 1998 VL 18 IS 5 BP 529 EP 534 PG 6 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 143ZG UT WOS:000077287000001 PM 9853390 ER PT J AU Kumon, Y Nakauchi, Y Kidawara, K Fukushima, M Kobayashi, S Ikeda, Y Suehiro, T Hashimoto, K Sipe, JD AF Kumon, Y Nakauchi, Y Kidawara, K Fukushima, M Kobayashi, S Ikeda, Y Suehiro, T Hashimoto, K Sipe, JD TI A longitudinal analysis of alteration in lecithin-cholesterol acyltransferase and paraoxonase activities following laparoscopic cholecystectomy relative to other parameters of HDL function and the acute phase response SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID SERUM AMYLOID-A; HIGH-DENSITY-LIPOPROTEIN; RHEUMATOID-ARTHRITIS; PROTEIN; SAA; POLYMORPHISM; ACCUMULATION; MECHANISMS; MORTALITY; GENETICS AB The composition of high-density lipoprotein (HDL) changes during inflammation; however, potential changes of HDL function during inflammation and the effects of acute phase proteins that are either on the HDL particles or in the serum have not been clarified. The concentrations of C-reactive protein (CRP), serum amyloid A protein (apoSAA) isoforms, lipids and apolipoproteins, and the activities of lecithin-cholesterol acyltransferase (LCAT) and paraoxonase (PON) were measured before and after laparoscopic cholecystectomy, in 12 patients with cholecystolithiasis to clarify the function of acute-phase HDL and the relationship between acute-phase proteins and HDL functions. Both acute-phase apoSAA (A-apoSAA) and CRP increased, reached their maximum levels 3-6 days after the operation, and then returned to preoperative levels after 2 weeks. In contrast, apolipoproteins and LCAT decreased reciprocally, reached their minimum levels 3-6 days after the operation, and returned to preoperative levels after 2 weeks. However, PON decreased 3-6 days after the operation, and remained low even after 2 weeks. At the nadir the mean activities of LCAT and PON were 56 and 76% of the preoperative levels, respectively. HDL-cholesterol or constitutive apoSAA did not change significantly. LCAT has been reported to be involved in reverse-cholesterol transport and PON to be preventive for lipid peroxidation of low-density lipoprotein in vitro. Thus, during the acute phase of inflammation, HDL may be altered to an atherogenic state due to a decrease in LCAT and PON activities, Therefore, this longitudinal analysis was carried out to determine whether HDL function is modified in a single episode of inflammation and thus may contribute to the occurrence of atherosclerotic disease in patients with chronic or recurrent acute inflammation. C1 Kochi Med Sch, Dept Internal Med 2, Nankoku, Kochi 7838505, Japan. Kidawara Hosp, Dept Internal Med, Kochi, Japan. Cosmo Biolab Inst, Satte, Saitama, Japan. NIH, Ctr Sci Review, Biochem Sci IRG, Bethesda, MD 20892 USA. RP Kumon, Y (reprint author), Kochi Med Sch, Dept Internal Med 2, Okohcho, Nankoku, Kochi 7838505, Japan. NR 36 TC 32 Z9 33 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD OCT PY 1998 VL 48 IS 4 BP 419 EP 424 PG 6 WC Immunology SC Immunology GA 130RH UT WOS:000076533400013 PM 9790313 ER PT J AU Matzinger, P AF Matzinger, P TI An innate sense of danger SO SEMINARS IN IMMUNOLOGY LA English DT Review ID DELTA T-CELLS; MHC CLASS-I; TRANSGENIC MICE; ANTITUMOR IMMUNITY; DENDRITIC CELLS; VIRUS-INFECTION; TOLERANCE; ANTIGEN; SELF; SYSTEM C1 NIAID, NIH, Bethesda, MD 20894 USA. RP Matzinger, P (reprint author), NIAID, NIH, Bldg 4,Room 111, Bethesda, MD 20894 USA. NR 87 TC 492 Z9 509 U1 1 U2 9 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD OCT PY 1998 VL 10 IS 5 BP 399 EP 415 DI 10.1006/smim.1998.0143 PG 17 WC Immunology SC Immunology GA 133VG UT WOS:000076706800008 PM 9840976 ER PT J AU Korn, EL Graubard, BI AF Korn, EL Graubard, BI TI Variance estimation for superpopulation parameters SO STATISTICA SINICA LA English DT Article DE cluster sampling; finite-population correction factors; probability-proportional-to-size sampling; stratified sampling ID INFERENCE AB In scientific applications, interest usually focuses on the "superpopulation" parameters of a stochastic model hypothesized to underlie the generation of the values in a finite population, rather than finite-population parameters themselves. Variance formulas for sampled data that incorporate finite-population correction factors are not appropriate for these applications. For simple random sampling, it is common practice to ignore these correction factors invariance estimation; this yields correct superpopulation inference under a simple superpopulation model. This is shown to hold true for two-stage simple random sampling of clusters, but not for stratified sampling or probability-proportional-to-size sampling. Asymptotically unbiased variance estimators are provided for these latter two types of sampling that are appropriate for superpopulation inference under a general superpopulation model. An application is given using data from the, 1987 National Health Interview Survey which shows that the difference between classical repeated-sampling variance estimators and a superpopulation variance estimator can be quite large. C1 NCI, Biometr Res Branch EPN739, Bethesda, MD 20892 USA. RP Korn, EL (reprint author), NCI, Biometr Res Branch EPN739, Bethesda, MD 20892 USA. NR 20 TC 12 Z9 12 U1 0 U2 2 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 OCT PY 1998 VL 8 IS 4 BP 1131 EP 1151 PG 21 WC Statistics & Probability SC Mathematics GA 133KN UT WOS:000076685900012 ER PT J AU Hirata, H Asanuma, M Cadet, JL AF Hirata, H Asanuma, M Cadet, JL TI Melatonin attenuates methamphetamine-induced toxic effects on dopamine and serotonin terminals in mouse brain SO SYNAPSE LA English DT Article DE methamphetamine; melatonin; superoxide radicals; DA transporters; 5-HT transporters; striatum; nucleus accumbens ID DISMUTASE TRANSGENIC MICE; NITRIC-OXIDE SYNTHASE; RAT-BRAIN; INDUCED NEUROTOXICITY; STRIATAL DOPAMINE; UPTAKE SITES; 7-NITROINDAZOLE; PROTECTION; INHIBITOR; RADICALS AB Methamphetamine (METH) is a drug of abuse that causes deleterious effects to brain monoaminergic systems. These toxic effects are thought to be due to oxidative stress. The pineal hormone, melatonin, has been shown to have neuroprotective effects against toxic quinones and oxidative stress produced by catecholamines. The present study was thus undertaken to assess possible protective effects of melatonin against METH-induced neurotoxic effects on the striatum and the nucleus accumbens by using autoradiographic techniques. Four dosages (5, 20, 40, 80 mg/kg) of melatonin were administered to mice intraperitoneally 30 minutes prior to the injections of METH (4 x 5 mg/kg) given at 2-hour intervals. The lowest doses of melatonin (5 mg/kg) had no significant effects against METH-induced toxicity. However, the higher doses (40 or 80 mg/kg) of melatonin significantly attenuated METH-induced toxic effects on both dopamine and serotonin systems. These data provide further evidence for a possible role of oxidative stress in METH-induced toxicity. Synapse 30:150-155, 1998. (C) Wiley-Liss, Inc.(dagger) C1 NIDA, Mol Neuropsychiat Sect, NIH, Div Intramural Res, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Mol Neuropsychiat Sect, NIH, Div Intramural Res, POB 5180, Baltimore, MD 21224 USA. NR 28 TC 33 Z9 33 U1 1 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 OCT PY 1998 VL 30 IS 2 BP 150 EP 155 DI 10.1002/(SICI)1098-2396(199810)30:2<150::AID-SYN4>3.3.CO;2-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 110HN UT WOS:000075375500004 PM 9723784 ER PT J AU Cone, EJ Tsadik, A Oyler, J Darwin, WD AF Cone, EJ Tsadik, A Oyler, J Darwin, WD TI Cocaine metabolism and urinary excretion after different routes of administration SO THERAPEUTIC DRUG MONITORING LA English DT Article; Proceedings Paper CT 5th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology CY NOV 10-14, 1997 CL VANCOUVER, CANADA DE cocaine; metabolism; esterases; humans; metabolites ID HUMAN LIVER; METHYL-ESTER; ETHANOL; CARBOXYLESTERASE; BENZOYLECGONINE; DISPOSITION; ALCOHOL; USERS; MICE AB Cocaine abusers frequently self-administer cocaine by different routes of administration. A controlled-dosing study was performed to assess the effect of different routes of administration on the excretion profile of cocaine and metabolites in urine. Single bioequivalent doses of cocaine were administered by the intravenous, intranasal, and smoked routes to six human subjects. Urine specimens were collected for 3 days after drug administration and were analyzed for cocaine, metabolites, and anhydoecogonine methyl ester, the thermal degradation product of cocaine, by gas chromatography-mass spectrometry. Cocaine was rapidly absorbed, metabolized, and excreted in urine. Peak cocaine concentrations were generally present in the first specimen collected; thereafter, concentrations declined quickly and were usually below the limit of detection (approximately 1 ng/ml) within 24 hours. The metabolite benzoylecgonine was present in the highest concentration and represented approximately 39%, 30%, and 16%, of the administered dose by the intravenous, intranasal, and smoked routes, respectively. Combined amounts of ecgonine methyl ester and six minor metabolites (norcocaine, benzoylnorecgonine, m-hydroxycocaine, p-hydroxycocaine, m-hydroxybenzoylecgonine, and p-hydroxybenzoylecgonine) accounted for approximately 18%, 15%, and 8% of the administered dose by the intravenous, intranasal, and smoked routes, respectively. Anhydroecgonine methyl ester was present in trace amounts (0.02% dose) in specimens collected after smoked cocaine administration. Because many of these metabolites exhibit pharmacologic activity, their presence in urine may indicate that they play complex biologic roles in the overall activity of cocaine. C1 NIDA, Addict Res Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Cone, EJ (reprint author), NIDA, Addict Res Ctr, Intramural Res Program, NIH, POB 5180, Baltimore, MD 21224 USA. NR 25 TC 45 Z9 45 U1 4 U2 23 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD OCT PY 1998 VL 20 IS 5 BP 556 EP 560 DI 10.1097/00007691-199810000-00019 PG 5 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 127FD UT WOS:000076339200019 PM 9780135 ER PT J AU Huestis, MA Cone, EJ AF Huestis, MA Cone, EJ TI Urinary excretion half-life of 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol in humans SO THERAPEUTIC DRUG MONITORING LA English DT Article; Proceedings Paper CT 5th International Congress of Therapeutic Drug Monitoring and Clinical Toxicology CY NOV 10-14, 1997 CL VANCOUVER, CANADA DE marijuana; half-life; excretion; tetrahydrocannabinol; cannabinoids ID GC-MS; DELTA-9-TETRAHYDROCANNABINOL; METABOLITES; MARIJUANA; DELTA-1-TETRAHYDROCANNABINOL; TETRAHYDROCANNABINOL; CANNABINOIDS; DISPOSITION; SMOKING; SINGLE AB The excretion of marijuana metabolites occurs over an extended period of time. yet few studies have been designed for accurate estimation of excretion half-lives. The authors monitored excretion of the primary urinary metabolite of marijuana, 11-nor-9-carboxy-Delta 9-tetrahydrocannabinol (THCCOOH), by gas chromatography-mass spectrometry in a controlled clinical study of marijuana smoking that included measurement of the drug in each urine void collected during the 3-week study. Terminal excretion half-lives of THCCOOH were determined in six healthy male subjects with histories of marijuana smoking; the study was conducted on the clinical research unit of a major medical institution. Subjects smoked a single marijuana cigarette (placebo, 1.75% or 3.55% THC) each week. Urine specimens (N = 953) were analyzed under blind conditions for THCCOOH by gas chromatography-mass spectrometry. Mean +/- SEM half-lives calculated by the amount remaining to be excreted method after the low and high doses were 31.5 +/- 1.0 hours (range, 28.4 to 35.3 hours) and 28.6 +/- 1.5 hours (range, 24.9 to 34.5 hours), respectively, when a 7-day monitoring period was used. The amounts of THCCOOH excreted over a 7-day period were 93.9 +/- 24.5 mu g (range, 34.6 to 171.6 mu g) and 197.4 +/- 33.6 mu g after the low- and high-dose sessions. Longer half-lives, 44.3 to 59.9 hours, were obtained with a 14-day sample collection. This study documents the prolonged excretion of THCCOOH in urine and emphasizes the importance of study design in the precise estimation of terminal excretion half-lives. A sensitive analytical method and a prolonged specimen collection period are important study considerations in the monitoring of marijuana excretion. C1 NIDA, Addict Res Ctr, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), NIDA, Addict Res Ctr, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 22 TC 37 Z9 42 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD OCT PY 1998 VL 20 IS 5 BP 570 EP 576 DI 10.1097/00007691-199810000-00021 PG 7 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 127FD UT WOS:000076339200021 PM 9780137 ER PT J AU Shimada, H Takiguchi, M Waalkes, MP AF Shimada, H Takiguchi, M Waalkes, MP TI Modification of the adverse effects of cadmium exposure by steroid compounds in rodents: A review SO TOXIC SUBSTANCE MECHANISMS LA English DT Article ID ISOLATED RAT HEPATOCYTES; INDUCED METALLOTHIONEIN SYNTHESIS; ZINC-INDUCED TOLERANCE; MALE FISCHER F344/NCR; PROGESTERONE PRETREATMENT; LIPID-PEROXIDATION; GLUCOCORTICOID REGULATION; MOUSE METALLOTHIONEIN; INDUCED NEPHROPATHY; TREATED RATS AB Cadmium is ct very important metal toxin and environmental pollutant. In rodents, the acute and chronic toxic effects of cadmium are pronounced in several tissues including the lung, liver, kidney, prostate, and testes. The toxic effects of cadmium can be modulated by pretreatments or concurrent treatments with various metallic and nonmetallic substances. This review focuses on the effects of steroid hormones and steroid antagonists on cadmium toxicity in, vivo. Steroids can have a variety of effects on cadmium toxicity including both mitigation and exacerbation of the adverse effects of this metal. Steroids or steroid antagonists that have been reported to modify cadmium toxicity include testosterone, progesterone, cyproterone, estradiol, and stilbestrol. Some steroids, like dexamethasone and corticosterone, are inducers of metallothionein (MT), a cadmium-binding protein thought to be important in cadmium tolerance. From these reports several possible mechanisms have been proposed to explain the modulating effects of steroids on cadmium toxicity. This article reviews available literature on this topic anal attempts to explore the possible mechanisms of acquired tolerance to cadmium in rodents or enhanced cadmium toxicity produced by exposure to steroid compounds. C1 Natl Inst Environm Hlth Sci, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC USA. NR 91 TC 2 Z9 2 U1 1 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1076-9188 J9 TOX SUBST MECH JI Tox. Subst. Mech. PD OCT-DEC PY 1998 VL 17 IS 4 BP 267 EP 284 DI 10.1080/107691898229260 PG 18 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 131YG UT WOS:000076602400003 ER PT J AU Shimizu, M Hochadel, JF Fulmer, BA Waalkes, MP AF Shimizu, M Hochadel, JF Fulmer, BA Waalkes, MP TI Effect of glutathione depletion and metallothionein gene expression on arsenic-induced cytotoxicity and c-myc expression in vitro SO TOXICOLOGICAL SCIENCES LA English DT Article DE arsenic; arsenite; arsenate; glutathione; metallothionein; c-myc; rat; in vitro ID HAMSTER OVARY CELLS; SODIUM ARSENITE; CYTO-TOXICITY; HEAT-SHOCK; MORPHOLOGICAL TRANSFORMATION; HUMAN-FIBROBLASTS; TRANSGENIC MICE; FREE-RADICALS; EMBRYO CELLS; DNA AB Arsenic exposure is clearly linked to human cancer. In rodent cells, arsenic has been reported to induce aberrant gene expression, including activation of the proto-oncogene c-myc. Abnormal or altered expression of such oncogenes can be involved in the acquisition of a malignant phenotype. Although its mechanism of action is unclear, arsenic is known to exert at least some of its toxic effects through interaction with sulfhydryl groups, and the nonprotein sulfhydryl glutathione (GSH) appears to play an important role in detoxication of arsenic. Similarly, metallothionein (MT), a metal-binding protein with high sulfhydryl content, often functions in defense against metal-induced or oxidative cellular injury. Therefore, we examined the relationship among GSH, MT gene expression, and arsenic-induced toxicity or c-myc expression in cultured rat myoblast (L6) cells. In initial toxicity studies, arsenic was used in both the trivalent (arsenite) and pentavalent (arsenate) forms. The role of GSH was studied by pretreating cells with L-buthionine sulfoximine (BSO), which induces a marked depletion of GSH. In vitro exposure of L6 cells to BSO (1 to 25 mu M) resulted in dose-dependent decreases in GSH. GSH depletion sensitized cells to both arsenite and arsenate. Zinc pretreatment, at levels which highly activated MT expression, had no effect on arsenite-induced cytotoxicity. Arsenite (1 mu M) alone modestly increased c-myc expression from 1 to 4 h after treatment (maximum of 2.0-fold over control). After GSH depletion cells responded to arsenite exposure with much larger increases in c-myc transcription (3.2-fold over control). Zinc pretreatment had no reductive effect on arsenite-induced c-myc expression despite markedly activating the MT gene. Thus, it appears that the cellular levels of GSH, but not MT gene expression, play an important role in resistance to arsenic toxicity and aberrant gene activation. Moreover, depletion of GSH enhances arsenic-induced proto-oncogene activation, which might contribute to subsequent transformation. C1 NIEHS, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. RP Waalkes, MP (reprint author), NIEHS, Comparat Carcinogenesis Lab, NCI, 111 Alexander Dr,POB 12233,MD F0-09, Res Triangle Pk, NC 27709 USA. NR 57 TC 75 Z9 79 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 1998 VL 45 IS 2 BP 204 EP 211 DI 10.1093/toxsci/45.2.204 PG 8 WC Toxicology SC Toxicology GA 136XA UT WOS:000076883300009 PM 9848127 ER PT J AU Alter, HJ Matsumoto, A Yeo, AET Shih, JW AF Alter, HJ Matsumoto, A Yeo, AET Shih, JW TI The role of TT virus in transfusion-associated hepatitis SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1998 VL 38 IS 10 SU S MA P3 BP 1S EP 1S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800004 ER PT J AU Birmingham, GC Carr, JM Martin, CL Leitman, SF AF Birmingham, GC Carr, JM Martin, CL Leitman, SF TI Comparison of mononuclear cell (MNC) collection efficiencies with two single needle discontinuous flow apheresis devices. SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1998 VL 38 IS 10 SU S MA S4 BP 6S EP 6S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800025 ER PT J AU Chun, H Cipolone, K Procter, J Stroncek, D AF Chun, H Cipolone, K Procter, J Stroncek, D TI Granulocyte storage and antigen stability. SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1998 VL 38 IS 10 SU S MA S368 BP 97S EP 97S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800388 ER PT J AU Lazarus, EF Browning, J Oblitas, JM Leitman, SF AF Lazarus, EF Browning, J Oblitas, JM Leitman, SF TI Non-transient decreases in platelet count associated with multiple regular plateletpheresis donations. SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1998 VL 38 IS 10 SU S MA S372 BP 98S EP 98S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800392 ER PT J AU Matsuo, K Procter, J Stroncek, D AF Matsuo, K Procter, J Stroncek, D TI Variations in neutrophil NA1 and NA2 genes. SO TRANSFUSION LA English DT Meeting Abstract C1 NIH, Dept Transfus Med, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1998 VL 38 IS 10 SU S MA S369 BP 98S EP 98S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800389 ER PT J AU Cowley, HW Cipolone, KM Procter, JL Stroncek, DF Woida, U Miller, JL AF Cowley, HW Cipolone, KM Procter, JL Stroncek, DF Woida, U Miller, JL TI Biotinylation modifies the antigenicity of red blood cells. SO TRANSFUSION LA English DT Meeting Abstract C1 NIDDK, Biol Chem Lab, NIH, Bethesda, MD USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1998 VL 38 IS 10 SU S MA S383 BP 101S EP 101S PG 1 WC Hematology SC Hematology GA 124FM UT WOS:000076171800403 ER PT J AU McCullough, J Bianco, C Busch, M Dodd, R Hewlett, IK Jackson, JB Katz, LM McFarland, A Mied, P Page, P Preston, MS Simon, T Stramer, S Stroncek, D Young, CT AF McCullough, J Bianco, C Busch, M Dodd, R Hewlett, IK Jackson, JB Katz, LM McFarland, A Mied, P Page, P Preston, MS Simon, T Stramer, S Stroncek, D Young, CT TI Interagency Genome Amplification Testing Task Force: preliminary report SO TRANSFUSION LA English DT Editorial Material C1 Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. New York Blood Ctr Inc, Med Affairs, New York, NY USA. Pacific Irwin Ctr, Ctr Blood, Res & Sci Serv, San Francisco, CA USA. Amer Red Cross, Blood Serv, Jerome C Holland Lab, Transmissible Dis Dept, Rockville, MD USA. US FDA, Mol Virol Lab, Div Transfus Transmitted Dis, Bethesda, MD 20014 USA. Johns Hopkins Hosp, Dept Pathol, Baltimore, MD 21287 USA. Mississippi Valley Reg Blood Ctr, Davenport, IA USA. Blood Ctr SE Wisconsin Inc, Med Affairs, Milwaukee, WI 53233 USA. Amer Red Cross, Arlington, VA USA. Alpha Therapeut Corp, Qual & Regulatory Affairs, Los Angeles, CA USA. Serol Inc, Med & Sci Affairs, Clarkston, GA USA. Amer Red Cross, Natl Confirmatory Testing Lab, Gaithersburg, MD USA. NIH, Lab Serv Sect, Dept Transfus Med, Bethesda, MD 20892 USA. Rhode Isl Blood Ctr, DNA HLA Reference & Educ Serv, Providence, RI USA. RP McCullough, J (reprint author), Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. NR 3 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD OCT PY 1998 VL 38 IS 10 BP 903 EP 904 DI 10.1046/j.1537-2995.1998.381098440852.x PG 2 WC Hematology SC Hematology GA 124AL UT WOS:000076158100002 PM 9767738 ER PT J AU Aguilera, G AF Aguilera, G TI Corticotropin releasing hormone, receptor regulation and the stress response SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID MESSENGER-RIBONUCLEIC-ACID; ANTERIOR-PITUITARY CORTICOTROPES; PARAVENTRICULAR NUCLEUS; FACTOR CRF; ARGININE-VASOPRESSIN; ACTH-SECRETION; C-FOS; GLUCOCORTICOID REGULATION; DIFFERENTIAL REGULATION; PERIPHERAL-TISSUES AB Corticotropin releasing hormone (CRH) coordinates behavioral, autonomic and hormonal responses to stress, including activation of the hypothalamic-pituitary-adrenal (HPA) axis with stimulation of adrenocorticotropin (ACTH) and glucocorticoids. Differential changes of expression of CRH and vasopressin (VP) in the parvicellular hypothalamic paraventricular nucleus (PVN), as well as regulation of CRH and VP receptors, are critical for the responsiveness of the HPA axis during stress. Pituitary CRH receptor (CRH-R) expression and content is controlled by the coordinated action of CRH, VP and glucocorticoids. Marked changes in hypothalamic and pituitary CRH-R expression support a key regulatory role for CRH in the HPA axis and the integrated stress response. C1 NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Aguilera, G (reprint author), NICHHD, Sect Endocrine Physiol, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NR 65 TC 119 Z9 121 U1 2 U2 14 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD OCT PY 1998 VL 9 IS 8 BP 329 EP 336 DI 10.1016/S1043-2760(98)00079-4 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 128JW UT WOS:000076403500005 PM 18406298 ER PT J AU Bentley, DR Pruitt, KD Deloukas, P Schuler, GD Ostell, J AF Bentley, DR Pruitt, KD Deloukas, P Schuler, GD Ostell, J TI Coordination of human genome sequencing via a consensus framework map SO TRENDS IN GENETICS LA English DT Editorial Material ID RADIATION HYBRID MAP; YAC CONTIG MAP; CHROMOSOME; RESOLUTION; TAGS C1 Sanger Ctr, Cambridge CB10 1SA, England. NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Bentley, DR (reprint author), Sanger Ctr, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. RI Deloukas, Panos/B-2922-2013 OI Deloukas, Panos/0000-0001-9251-070X NR 23 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD OCT PY 1998 VL 14 IS 10 BP 381 EP 384 DI 10.1016/S0168-9525(98)01591-1 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 134NK UT WOS:000076749300002 PM 9820023 ER PT J AU Wen, H Balaban, RS AF Wen, H Balaban, RS TI Ultrasonic imaging of the electroacoustic effect in macromolecular gels SO ULTRASONIC IMAGING LA English DT Article DE biological tissue; colloid; electroacoustic; electrolyte; macromolecular gel; ultrasonic imaging ID ELECTROLYTES AB The electroacoustic effect occurs in electrolytes and colloidal suspensions. It describes the phenomenon in which a voltage applied to the sample produces an acoustic signal or vice versa. The basic mechanism is that charged particles in the sample have various mobilities due to different mosses and viscosities. Under an external voltage they respond differently to the electrical force. This results in an overall acoustic vibration. The electroscoustic effect has been the basis for many measurement tools of solutions and other materials. In this note a method to image macromolecular gel samples using the electroacoustic effect at ultrasound frequencies is presented. Radiofrequency electrical excitation produces ultrasonic signal due to spatial changes in the electroacoustic sonic amplitude of the sample, which is used to construct an image similar to ultrasonography. This method is demonstrated in agar gel and eggwhite protein phantoms. The image contrast mechanism is also discussed. C1 NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. RP Wen, H (reprint author), NHLBI, Cardiac Energet Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009; Wen, Han/G-3081-2010 OI Balaban, Robert/0000-0003-4086-0948; Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [Z01 HL004606-11] NR 13 TC 2 Z9 2 U1 1 U2 4 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0161-7346 J9 ULTRASONIC IMAGING JI Ultrason. Imaging PD OCT PY 1998 VL 20 IS 4 BP 288 EP 297 PG 10 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 181ME UT WOS:000079444500005 PM 10197349 ER PT J AU Nagai, Y Kemper, MK Earley, CJ Metter, EJ AF Nagai, Y Kemper, MK Earley, CJ Metter, EJ TI Blood-flow velocities and their relationships in carotid and middle cerebral arteries SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE blood flow velocity; carotid arteries; cerebral arteries; gender; aging ID TRANSCRANIAL DOPPLER ULTRASOUND; VOLUNTEERS; RACE; SEX AB This study defines normative how velocity (FV) ranges for the common carotid (CCA), internal carotid (ICA) and middle cerebral arteries (MCA), compares them to subjects,vith nonfocal vascular disease (mild to moderate hypertension, diabetes, hyperlipidemia or coronary artery disease), and clarifies the association between carotid and MCA FVs, FVs were measured by carotid and transcranial Doppler ultrasonography in 278 healthy and 190 vascular-disease subjects. Normative FV ranges for CCA, ICA and MCA were large in healthy subjects, with modest gender and age differences. Vascular-disease subjects had similar FVs to healthy controls. MCA FVs were significantly correlated with carotid FVs (r ranged 0.26-0.50), but were only weakly or not significantly associated with them (beta ranged 0.08-0.18) when controlling for age and gender. These findings suggest that normative FVs are not affected by the presence of nonfocal vascular disease, but carotid FVs do not aid in assessing MCA FVs, (C) 1998 World Federation for Ultrasound in Medicine & Biology. C1 NIA, Gerontol Res Ctr, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Bayview Med Ctr, Dept Neurol, Baltimore, MD USA. RP Metter, EJ (reprint author), NIA, Gerontol Res Ctr, Clin Invest Lab, NIH, Box 06,4940 Eastern Ave, Baltimore, MD 21224 USA. NR 20 TC 13 Z9 13 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD OCT PY 1998 VL 24 IS 8 BP 1131 EP 1136 DI 10.1016/S0301-5629(98)00092-1 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 132HH UT WOS:000076623900009 PM 9833581 ER PT J AU Yu, ZY Karem, KL Kanangat, S Manickan, E Rouse, BT AF Yu, ZY Karem, KL Kanangat, S Manickan, E Rouse, BT TI Protection by minigenes: a novel approach of DNA vaccines SO VACCINE LA English DT Article DE epitope; DNA vaccine; HSV ID HERPES-SIMPLEX-VIRUS; SYNTHETIC PEPTIDES; GLYCOPROTEIN-D; T-LYMPHOCYTES; INDUCTION; INVITRO; TYPE-1; CELLS; RECOGNITION; EPITOPES AB To test the principle that genetically engineered epitopes in a plasmid DNA can efficiently induce specific immunity, a minigene cassette encoding cytotoxic T lymphocyte (CTL), helper T and B cell epitopes from herpes simplex virus (HSV) was constructed and placed in an expression vector named pcMini. Following immunizations with pcMini, mice developed epitope-specific CTLs comparable to the response induced by live HSV. Less effective but detectable antibody, lymphoproliferative, and T cell cytokine responses were also produced, In addition, pcMini-primed mice elicited a recall response upon restimulation with recombinant vaccinia virus expressing HSV antigen. The protection provided by minigene vaccination was significant, although not as efficient as live virus vaccine. The DNA minigene approach may prove useful to define and induce immune responses against minimal antigenic determinants. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Heska Corp, Atlanta, GA 30333 USA. Univ Tennessee, Dept Med, Div Pulm & Crit Care, Memphis, TN 38163 USA. NIKKD, Liver Dis Sect, DDB, NIH, Bethesda, MD 20892 USA. Univ Tennessee, Coll Vet Med, Dept Microbiol, Knoxville, TN 37996 USA. RP Yu, ZY (reprint author), Mayo Clin & Mayo Fdn, Dept Immunol, 828 Guggenheim Bldg,200 1st St SW, Rochester, MN 55905 USA. FU NIAID NIH HHS [AI-14981] NR 21 TC 25 Z9 26 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT PY 1998 VL 16 IS 17 BP 1660 EP 1667 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 107RC UT WOS:000075222200011 PM 9713944 ER PT J AU Burka, LT Black, SR Mathews, JM AF Burka, LT Black, SR Mathews, JM TI Disposition of methyl ethyl ketoxime in the rat after oral, intravenous and dermal administration SO XENOBIOTICA LA English DT Article ID CYCLOHEXANONE OXIME; 2-NITROPROPANE; DEHYDRATION; ACETOXIME; TOXICITY; DAMAGE; DNA; RNA AB 1. The disposition of C-14-methyl ethyl ketoxime (MEKO) was determined in the male F344 rat following oral, intravenous (i.v.) and dermal administration. 2. Oral doses of 2.7, 27 and 270 mg/kg were primarily excreted as CO2 (71-49 %) in decreasing percentage as the dose increased. Excretion in urine (13-26 %) and as volatiles (5-18 %) increased as the dose increased. Five to 6 % of the dose remained in the major tissues after 72 h. 3. An i.v. dose of 2.7 mg/kg was also principally excreted as CO2 (48.8 %) with excretion in urine and as expired volatiles accounting for 21.4 and 11.4 %, respectively. About 7 %, of the administered radioactivity remained in the tissues after 72 h. 4. Following dermal administration, 13 and 26 % of a 2.7 and 270 mg/kg dose, respectively, were absorbed. Volatilization from the dose site prior to placement in the metabolism cage may account for the low absorption. 5. MEKO was biotransformed to at least five polar metabolites that could only be partially resolved by anion exchange chromatography. Incubation with glucuronidase, but not sulphatase, changed the urinary metabolic profile. Methyl ethyl ketone was a major component in the volatiles. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Res Triangle Inst, Ctr Biorgan 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 22 TC 2 Z9 2 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0049-8254 J9 XENOBIOTICA JI Xenobiotica PD OCT PY 1998 VL 28 IS 10 BP 1005 EP 1015 DI 10.1080/004982598239065 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 140GN UT WOS:000077079500009 PM 9849647 ER PT J AU Ebb, D Tang, DC Drew, L Chin, K Berg, PE Rodgers, GP AF Ebb, D Tang, DC Drew, L Chin, K Berg, PE Rodgers, GP TI Identification of upstream regulatory elements that repress expression of adult beta-like globin genes in a primitive erythroid environment SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Article DE globin gene; transcription; silencer; mutagenesis; human erythroleukemia cells ID HUMAN GAMMA-GLOBIN; KRUPPEL-LIKE FACTOR; TRANSGENIC MICE; DEVELOPMENTAL REGULATION; DNA INTERACTIONS; TRANSCRIPTION; ACTIVATION; CHROMATIN; SEQUENCE; PROTEIN AB Our investigations have focused on localizing cis-elements responsible for the down regulation of the adult beta-like globin genes (delta and beta) in immature, or primitive erythroid tissues. We studied their activity after transfection into K562 cells, an erythroleukemia cell line with an embryonic-fetal phenotype. Analyzed DNA sequences included delta and beta 5' flanking regions extending from approximately -500 to +50bp (promoter regions), truncated delta and beta 5' flanking regions extending from approximately -250 to +50 bp, and chimeric promoter constructions, which consisted of a distal delta or beta fragment fused to a proximal beta or delta sequence, In CAT reporter constructions no appreciable level of CAT activity was supported by the beta globin promoter, and only low level activity by the delta promoter. Truncation of the beta globin promoter led to a 2-3 fold increase in promoter activity. In contrast, deletion of the upstream portion of the delta promoter led to a 10 fold decrease in expression. Coupling of the upstream beta globin sequence from approximately -500 to -250 bp to the truncated delta promoter fragment led to complete extinction of transcriptional activity, consistent with a negative regulatory effect of the beta globin gene upstream element(s), Fusion of the upstream portion of the delta promoter to the truncated beta globin promoter yielded a modest increase in promoter strength relative to the truncated beta gene promoter, indicating the presence of a positive transcriptional element(s) in the upstream delta globin regulatory region. Site-directed mutagenesis of binding sites for the repressor proteins BP1 and BP2 in the upstream portion of the beta globin gene flanking region led to a 4-6 fold increase in promoter activity, DNase I footprinting of the upstream delta-globin region revealed protected sequences corresponding to consensus binding sites for GATA-1 and BP2. These results confirm that sequences in the upstream promoter region of the adult beta globin gene contribute to its factor-mediated suppression early in development and then may modulate its expression at a later stage. (C) 1998 Academic Press. C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Pediat Hematol Oncol, Boston, MA 02114 USA. Univ Maryland, Sch Med, Dept Pediat Hematol Oncol, Baltimore, MD 21201 USA. RP Rodgers, GP (reprint author), NIDDK, Mol & Clin Hematol Branch, NIH, Bldg 10,Room 9N318,10 Ctr Dr, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [R01 DK53533] NR 36 TC 11 Z9 11 U1 0 U2 0 PU BLOOD CELLS FOUNDATION PI LA JOLLA PA C/O ERNEST BEUTLER SCRIPPS RES INST, DEPT MOLECULAR EXP MEDICINE, LA JOLLA, CA 92037 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD SEP 30 PY 1998 VL 24 IS 18 BP 356 EP 369 DI 10.1006/bcmd.1998.0202 PG 14 WC Hematology SC Hematology GA 124YM UT WOS:000076210400001 PM 10087993 ER PT J AU Chin, H AF Chin, H TI Molecular biology of neuronal voltage-gated calcium channels SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Review ID HYPOKALEMIC PERIODIC PARALYSIS; N-TYPE; FUNCTIONAL EXPRESSION; CA2+ CHANNELS; COMPLEMENTARY-DNA; BETA-SUBUNIT; GENE; SYNTAXIN; ATAXIA; MOUSE C1 NIMH, Genet Res Branch, Div Basic & Clin Neurosci Res, NIH, Bethesda, MD 20892 USA. NR 49 TC 10 Z9 11 U1 0 U2 0 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 SEP 30 PY 1998 VL 30 IS 3 BP 123 EP 130 PG 8 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 126NL UT WOS:000076299900001 PM 9873833 ER PT J AU McKenzie, R O'Fallon, A Dale, J Demitrack, M Sharma, G Deloria, M Garcia-Borreguero, D Blackwelder, W Straus, SE AF McKenzie, R O'Fallon, A Dale, J Demitrack, M Sharma, G Deloria, M Garcia-Borreguero, D Blackwelder, W Straus, SE TI Low-dose hydrocortisone for treatment of chronic fatigue syndrome - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; PITUITARY-ADRENAL AXIS; DEFINITION; EPIDEMIOLOGY; RESPONSES AB Context.-Chronic fatigue syndrome (CFS) is associated with a dysregulated hypothalamic-pituitary adrenal axis and hypocortisolemia. Objective.-To evaluate the efficacy and safety of low-dose oral hydrocortisone as a treatment for CFS. Design.-A randomized, placebo-controlled, double-blind therapeutic trial, conducted between 1992 and 1996. Setting.-A single-center study in a tertiary care research institution. Patients.-A total of 56 women and 14 men aged 18 to 55 years who met the 1988 Centers for Disease Control and Prevention case criteria for CFS and who withheld concomitant treatment with other medications. Intervention.-Oral hydrocortisone, 13 mg/m(2) of body surface area every morning and 3 mg/m(2) every afternoon, or placebo, for approximately 12 weeks. Main Outcome Measures.-A global Wellness scale and other self-rating instruments were completed repeatedly before and during treatment. Resting and cosyntropin-stimulated cortisol levels were obtained before and at the end of treatment. Patients recorded adverse effects on a checklist. Results.-The number of patients showing improvement on the Wellness scale was 19 (54.3%) of 35 placebo recipients vs 20 (66.7%) of 30 hydrocortisone recipients (P=.31). Hydrocortisone recipients had a greater improvement in mean Wellness score (6.3 vs 1.7 points; P=.06), a greater percentage (53% vs 29%; P=.04) recording an improvement of 5 or more points in Wellness score, and a higher average improvement in Wellness score on more days than did placebo recipients (P<.001). Statistical evidence of improvement was not seen with other self-rating scales. Although adverse symptoms reported by patients taking hydrocortisone were mild, suppression of adrenal glucocorticoid responsiveness was documented in 12 patients who received it vs none in the placebo group (P<.001). Conclusions.-Although hydrocortisone treatment was associated with some improvement in symptoms of CFS, the degree of adrenal suppression precludes its practical use for CFS. C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA. NIMH, Clin Psychobiol Branch, NIH, Bethesda, MD 20892 USA. Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Straus, SE (reprint author), NIAID, Clin Invest Lab, NIH, 10 Ctr Dr,Room 11N228, Bethesda, MD 20892 USA. RI Demitrack, Mark/I-7697-2013 NR 34 TC 122 Z9 124 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 30 PY 1998 VL 280 IS 12 BP 1061 EP 1066 DI 10.1001/jama.280.12.1061 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 121FJ UT WOS:000076002400034 PM 9757853 ER PT J AU Chan, PC Hasemani, JK Mahleri, J Aranyi, C AF Chan, PC Hasemani, JK Mahleri, J Aranyi, C TI Tumor induction in F344/N rats and B6C3F1 mice following inhalation exposure to ethylbenzene SO TOXICOLOGY LETTERS LA English DT Article DE carcinogenesis; ethylbenzene ID STATISTICAL ISSUES; CARCINOGENICITY; METABOLISM; BENZENE; CYTOCHROME-P-450; TOXICITY; SOLVENTS; ISOMERS; KIDNEY; ASSAY AB Carcinogenesis studies of ethylbenzene were conducted because of its extensive use as a solvent and because it is structurally similar to the known carcinogen benzene. Groups of 50 male and 50 female Fischer rats and B6C3F1 mice were exposed to ethylbenzene by inhalation at 0, 75, 250, and 750 ppm 6 h per day, 5 days per week, for 2 years. The dose levels were selected based on the results of 13-week studies. In the 750 ppm group of male and female rats, body weights were slightly lower and incidences of renal hyperplasia and tubular neoplasms were significantly increased compared with controls. Incidence of testicular tumors was also significantly increased in male rats. Survival and body weights of the exposed groups of male and female mice and controls were comparable. Incidences of alveolar epithelium metaplasia, alveolar/bronchiolar adenoma, and hepatocyte hypertrophy and necrosis were significantly increased in the 750 ppm male mice and incidences of liver eosinophilic foci and hepatocellular neoplasms were significantly increased in the 750 ppm female mice compared with controls. Ethylbenzene is carcinogenic inducing neoplasms in kidneys and testes in Fischer rats and in lungs in male and liver in female B6C3F1 mice. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 NIEHS, Res Triangle Pk, NC 27709 USA. IIT, Res Inst, Chicago, IL 60616 USA. RP Chan, PC (reprint author), NIEHS, POB 12233, Res Triangle Pk, NC 27709 USA. NR 40 TC 21 Z9 22 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD SEP 30 PY 1998 VL 99 IS 1 BP 23 EP 32 DI 10.1016/S0378-4274(98)00133-7 PG 10 WC Toxicology SC Toxicology GA 131PT UT WOS:000076585000003 PM 9801027 ER PT J AU Heidecker, G Munoz, H Lloyd, P Hodge, D Ruscetti, FW Morton, WR Hu, SL Benveniste, RE AF Heidecker, G Munoz, H Lloyd, P Hodge, D Ruscetti, FW Morton, WR Hu, SL Benveniste, RE TI Macaques infected with cloned simian immunodeficiency virus show recurring nef gene alterations SO VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; CD4 DOWN-REGULATION; LONG-TERM SURVIVOR; HUMAN T-CELLS; HIV-1 NEF; MOLECULAR CHARACTERIZATION; ENVELOPE GLYCOPROTEIN; RHESUS MACAQUES; SH3 DOMAIN; HTLV-III AB We compared nef gene sequences isolated by polymerase chain reaction from peripheral blood lymphocyte DNA of macaques that had been inoculated with either biologically (E11S) or molecularly (clone 8) cloned SIV/Mne Two samples from each animal obtained either early (weeks 2-8) or late (weeks 21-137) after infection were analyzed, Three substitutions in the predicted Nef amino acid sequence were seen in all animals at the late time point and two other substitutions were seen in all except one. Two of the common exchanges are located similar to 40 residues apart in the Nef core sequence but are juxtaposed on the tertiary structure as judged by computer modeling using the structure of the HIV Nef core protein as a guide. Most recurrent in vivo changes replaced a residue found in the cloned Nef sequence with one present in a consensus derived by aligning the Nef sequences of the SIV/Sm clade. Recombinant virus containing a macaque-adapted (MA nef) nef on the clone 8 backbone was 3-fold more infectious on SMAGI cells than the original virus. A lymphocyte line infected with SIV-clone 8-MAnef contained a large proportion of cells carrying provirus with defective nef genes. These findings suggest that the nef gene of the cloned SIV/Mne had undergone attenuating mutations during propagation in tissue culture that were "corrected" in vivo. (C) 1998 Academic Press. C1 NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Lab Leukocyte Biol, Frederick, MD 21702 USA. NCI, Lab Genome Divers, Frederick, MD 21702 USA. Univ Washington, Reg Primate Res Ctr, Seattle, WA 98195 USA. RP Heidecker, G (reprint author), NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RI Hu, Shiu-Lok/A-3196-2008 OI Hu, Shiu-Lok/0000-0003-4336-7964 FU NCI NIH HHS [N01-CO-56000]; NCRR NIH HHS [RR-00166] NR 63 TC 15 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 1998 VL 249 IS 2 BP 260 EP 274 DI 10.1006/viro.1998.9325 PG 15 WC Virology SC Virology GA 128BD UT WOS:000076384600007 PM 9791018 ER PT J AU Horiuchi, M Yamaguchi, Y Gojobori, T Mochizuki, M Nagasawa, H Toyoda, Y Ishiguro, N Shinagawa, M AF Horiuchi, M Yamaguchi, Y Gojobori, T Mochizuki, M Nagasawa, H Toyoda, Y Ishiguro, N Shinagawa, M TI Differences in the evolutionary pattern of feline panleukopenia virus and canine parvovirus SO VIROLOGY LA English DT Article ID MINK ENTERITIS VIRUS; INFLUENZA-A VIRUSES; HOST-RANGE; NUCLEOTIDE-SEQUENCE; OVERDOMINANT SELECTION; MONOCLONAL-ANTIBODIES; CAPSID STRUCTURE; CELL-LINE; GENE; HEMAGGLUTINATION AB Canine parvovirus (CPV) suddenly appeared in the late 1970s after which it showed continuous antigenic changes, Virological and molecular genetic analyses mainly focused on feline panleukopenia virus (FPLV) were conducted in this study because FPLV is the suspected ancestor of CPV, the way in which FPLV evolves may help to explain the emergence of CPV. Analysis of escape mutants against FPLV-specific monoclonal antibody showed that viruses possessing CPV-like properties were not easily detected in FPLV virus stocks. Phylogenetic analysis revealed that the nonstructural protein 1 (NS1) and capsid protein 2 (VP2) genes of FPLV changed with time. A similar tendency, however, was not observed in the FPLV VP2 proteins. In contrast the topology of the phylogenetic tree of VP2 proteins of CPV basically concurred with that of the VP2 genes. Analysis of the ratio of nonsynonymous and synonymous substitutions revealed that synonymous substitutions exceeded nonsynonymous substitutions in both the NS1 and VP2 genes of FPLV, even when the analysis focused on specific regions in the VP2 gene that are known to be located on the capsid surface. Comparison of the CPV VP2 genes revealed that nonsynonymous substitution was found to dominate over synonymous substitution in one specific region in the VP2 gene. These results suggested that FPLV has changed mainly by random genetic drift In contrast after the appearance of CPV, changes in the CPV VP2 gene appear to be partly selected by certain positive selection forces. CPV and FPLV are known to be closely related viruses genetically and biologically, but the evolutionary mechanisms of the two viruses appeared to be different (C) 1998 Academic Press. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Obihiro Univ Agr & Vet Med, Dept Vet Publ Hlth, Obihiro, Hokkaido 080, Japan. Obihiro Univ Agr & Vet Med, Res Ctr Protozoan Mol Immunol, Obihiro, Hokkaido 080, Japan. Natl Inst Genet, Ctr Informat Biol, Shizuoka 411, Japan. Kyoritsu Shoji Co, Lab Clin Microbiol, Chiyoda Ku, Tokyo 102, Japan. RP Horiuchi, M (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM mhoriuchi@atlas.niaid.nih.gov NR 70 TC 18 Z9 25 U1 1 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 1998 VL 249 IS 2 BP 440 EP 452 DI 10.1006/viro.1998.9335 PG 13 WC Virology SC Virology GA 128BD UT WOS:000076384600023 PM 9791034 ER PT J AU Baldwin, WS Barrett, JC AF Baldwin, WS Barrett, JC TI Melatonin attenuates hydrogen peroxide toxicity in MCF7 cells only at pharmacological concentrations SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CARCINOGEN SAFROLE; GLUTATHIONE; ANTIOXIDANT; RADICALS AB Melatonin is proposed to be oncostatic in mammary tissue, and one mechanism by which this hormone may elicit its possible oncostatic effect is as an oxygen radical scavenger. Therefore, we examined melatonin's abilities to act as an oxygen radical scavenger at physiological or pharmacological concentrations. Hydrogen peroxide at 400 mu M killed 97% of treated MCF7 cells within 8 h, and following melatonin at 10(-5) and 10(-4) M concentrations only 76 and 64% of cells, respectively, were killed by hydrogen peroxide. However, melatonin at lower concentrations (10(-7) M) did not protect MCF7 cells. Moreover, pretreatment with melatonin (10(-5) or 10(-7) M) prior to hydrogen peroxide stress offered no further efficacy, and pretreatment with melatonin followed by the withdrawal of melatonin eliminated its protective effect from hydrogen peroxide toxicity. These findings indicate that melatonin acts directly as an antioxidant and does not stimulate antioxidant defenses in MCF7 cells that protect against hydrogen peroxide. Glutathione levels were examined to substantiate this hypothesis and were not altered by melatonin treatment. In conclusion, melatonin is an excellent oxygen radical scavenger at pharmacological concentrations, but not at physiological concentrations. Thus, loss of melatonin is unlikely to be important in oxidative scavenger mechanisms in human mammary cells. (C) 1998 Academic Press. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Baldwin, WS (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NR 19 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 29 PY 1998 VL 250 IS 3 BP 602 EP 605 DI 10.1006/bbrc.1998.9370 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 127TU UT WOS:000076367300015 PM 9784392 ER PT J AU Scherf, U Kalab, P Dasso, M Pastan, I Brinkmann, U AF Scherf, U Kalab, P Dasso, M Pastan, I Brinkmann, U TI The hCSE1/CAS protein is phosphorylated by HeLa extracts and MEK-1: MEK-1 phosphorylation may modulate the intracellular localization of CAS SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE cancer; cell cycle; nuclear transport; apoptosis; importin ID SEGREGATION GENE CSE1; APOPTOSIS SUSCEPTIBILITY GENE; SPINDLE ASSEMBLY CHECKPOINT; CHROMOSOME SEGREGATION; HUMAN HOMOLOG; NUCLEAR-LOCALIZATION; MEDIATED APOPTOSIS; CELL-PROLIFERATION; CANCER-CELLS; MAP KINASE AB hCSE1/CAS (CAS), the human homologue of the yeast chromosome segregation gene CSE1, is a nuclear transport factor that plays a role in proliferation and apoptosis. A MEK-1 phosphorylation sequence in CAS raises the possibility that MER-phosphorylation regulates the function of CAS. CAS protein from cell extracts shows covalent charge modifications; one of these charge variants contains phosphotyrosine. CAS protein can be captured from cell extracts by immobilized anti-phosphotyrosine antibodies. We have produced recombinant protein fragments containing the N-terminal or central portion of CAS and found that the N-terminal fragment, which contains a putative MER phosphorylation site, is phosphorylated by the HeLa extracts and MEK-1. Treatment of cells with an inhibitor of MEK-1 phosphorylation in vivo changes the intracellular localization of CAS from predominantly cytoplasmic to nuclear. This suggests that a function of CAS in nuclear transport may be regulated by phosphorylation. (C) 1998 Academic Press. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. NICHHD, Mol Embryol Lab, NIH, Bethesda, MD 20892 USA. RP Brinkmann, U (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, 37-4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM uli@helix.nih.gov RI Kalab, Petr/B-2478-2009; OI Dasso, Mary/0000-0002-5410-1371 NR 27 TC 18 Z9 18 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 29 PY 1998 VL 250 IS 3 BP 623 EP 628 DI 10.1006/bbrc.1998.9367 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 127TU UT WOS:000076367300019 PM 9784396 ER PT J AU Thatcher, BJ Doherty, AE Orvisky, E Martin, BM Henkin, RI AF Thatcher, BJ Doherty, AE Orvisky, E Martin, BM Henkin, RI TI Gustin from human parotid saliva is carbonic anhydrase VI SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE carbonate dehydratase; saliva; taste; growth factors; zinc; metalloproteins ID ALIMENTARY-TRACT; ISOENZYME-II; PURIFICATION; PHOSPHODIESTERASE; LOCALIZATION; ACTIVATOR; SEQUENCE; GLANDS; BRAIN; TASTE AB Gustin, a zinc-metalloprotein constituting about 3% of human parotid saliva protein was previously isolated and characterized as a single polypeptide chain of 37kDa with one mole of zinc tightly bound to the protein. It exhibited biological activity activating calmodulin dependent bovine brain cAMP phosphodiesterase and was decreased in saliva of patients with loss of taste in whom taste buds showed a specific pathological morphology. Determination of its primary structure by amino acid sequence revealed it was identical with carbonic anhydrase (CA) [EC 4.2.1.1] VI and had two N-linked glycosylation sites. Analysis by reverse phase HPLC and SDS-PAGE before and after deglycosylation confirmed a single peak with molecular weight of the purified protein being 37kDa, the deglycosylated protein, 33kDa. N-linked carbohydrate chains contained N-acetyl glucosamine, galactose, mannose, and fucose interior to di, tri and tetra sialyated termini. By isoelectric focusing five increasingly acidic pi values were determined consistent with addition of sialic acid as the terminal carbohydrate residue on the N-linked glycoforms of the protein. Gustin was found to exhibit CA activity but was inhibited by known CA inhibitors in a different manner than CA I or II. These findings, consistent with analysis of previous investigators, indicate that parotid saliva gustin is CA VI. (C) 1998 Academic Press. C1 NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. Taste & Smell Clin, Washington, DC 20016 USA. RP Thatcher, BJ (reprint author), NIMH, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. NR 32 TC 64 Z9 64 U1 0 U2 14 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 29 PY 1998 VL 250 IS 3 BP 635 EP 641 DI 10.1006/bbrc.1998.9356 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 127TU UT WOS:000076367300021 PM 9784398 ER PT J AU Grimaldi, M Navarra, P Pozzoli, G Preziosi, P Schettini, G AF Grimaldi, M Navarra, P Pozzoli, G Preziosi, P Schettini, G TI Bacterial lipopolysaccharide increases interleukin-6 and prostaglandin release in rat cortical type I astrocytes by different mechanisms: Role of anti-inflammatory agents SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; ALZHEIMERS-DISEASE PATIENTS; FACTOR-ALPHA; FETAL ASTROCYTES; GENE-EXPRESSION; CELL-CULTURES; ENDOTOXIN; INDUCTION; BRAIN AB LPS stimulated IL-6 release in a concentration-dependent manner from rat cortical type I astrocytes. This stimulatory action was completely abolished by Dexamethasone (DEX), but was not affected by indomethacin (IND), a 5-cyclooxigenase inhibitor. LPS-induced IL-6 release was partially inhibited by BW 4AC, a 5-lipoxygenase inhibitor. LPS concentration-dependently increased the release of PGE(2) from type I astrocytes, an effect completely inhibited by IND. To rule out the possibility that DEX was inhibiting LPS-induced IL-6 release by blocking IL-6 gene expression, we tested the effect of DEX on interleukin 1 beta(IL-1)induced IL-6 release. DEX slightly inhibited IL-1-induced IL-6 release, while IL-1 releasing action on IL-6 was significantly reduced by IND. The involvement of nitric oxide (NO) generation on LPS-induced IL-6 release was also studied. We found that L-NO-arginine, an inhibitor of nitric oxide synthase, concentration-dependently reduced LPS-induced IL-6 release in astrocytes. In conclusion, we provide evidence that LPS action on IL-6 and PGE(2) release can be ascribed to the activation of different transduction mechanisms, which can be pharmacologically dissected with the aid of anti-inflammatory drugs. (C) 1998 Academic Press. C1 Univ Naples Federico 2, Sez Farmacol, Dipartimento Neurosci & Comunicaz Interumana, I-80131 Naples, Italy. Univ Cattolica Sacro Cuore, Ist Farmacol, Rome, Italy. Univ Genoa, Ist Farmacol, Ist Nazl Ric Canc, Unita Neurosci,CBA, I-16132 Genoa, Italy. RP Grimaldi, M (reprint author), NINDS, Lab Adapt Syst, NIH, 36 Convent Dr,Bldg 36,Rm 4A22, Bethesda, MD 20892 USA. EM maurizio@codon.nih.gov OI Grimaldi, Maurizio/0000-0002-7331-7055 NR 38 TC 11 Z9 12 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 29 PY 1998 VL 250 IS 3 BP 798 EP 804 DI 10.1006/bbrc.1998.9378 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 127TU UT WOS:000076367300049 PM 9784426 ER PT J AU Hrycyna, CA Airan, LE Germann, UA Ambudkar, SV Pastan, I Gottesman, MM AF Hrycyna, CA Airan, LE Germann, UA Ambudkar, SV Pastan, I Gottesman, MM TI Structural flexibility of the linker region of human P-glycoprotein permits ATP hydrolysis and drug transport SO BIOCHEMISTRY LA English DT Article ID PROTEIN-KINASE-C; MULTIDRUG-RESISTANT CELLS; PSEUDOMONAS EXOTOXIN; INSECT CELLS; TUMOR-CELLS; MDR1 GENE; EXPRESSION; MUTANTS; SITES; PHOSPHORYLATION AB P-Glycoprotein (Pgp), an energy-dependent drug efflux pump responsible for multidrug resistance of many cancer cells, is comprised of two homologous halves connected by a peptide segment approximately 75 amino acids (aa) in length. The effects of length and composition of this connecting region on Pgp cell surface expression and the ability of the two halves to interact were explored using both stable transfections of Pgp mutants in mammalian cell lines and a vaccinia virus transient expression system. A 17 aa insertion of predicted flexible structure between amino acids 681 and 682 resulted in a functional Pgp molecule that was capable of conferring drug resistance. In contrast, an 18 aa peptide insertion with a predicted alpha-helical structure was unstable when expressed transiently. A 34 aa deletion from the central core of the Linker region (Delta 653-686) resulted in a protein expressed at the cell surface in amounts comparable to that of wild-type Pgp but unable to confer drug resistance. No apparent differences in drug or [alpha-P-32]-8-azido-ATP photoaffinity labeling were observed. However, both ATP hydrolysis and drug transport activities of the deletion mutant were completely abrogated, indicating that the linker deletion disconnected substrate binding from ATP hydrolysis and transport. This mutant also failed to exhibit an ATP hydrolysis-dependent enhancement of binding of a conformation-sensitive monoclonal antibody, UIC2. Upon replacement with a 17 aa linker peptide having a predicted flexible secondary structure, but bearing no homology to the deleted 34 aa segment, normal Pgp transport and basal and drug-stimulated ATPase activities were restored along with increased UIC2 binding in the presence of substrate, suggesting a dramatic conformational change between the nonfunctional and functional molecules. Taken together, these data suggest a flexible secondary structure of the connector region is sufficient for the coordinate functioning of the two halves of Pgp, likely specifically required for the proper interaction of the two ATP binding sites. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Div Basic Sci, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 1A-09,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Ambudkar, Suresh/B-5964-2008 NR 60 TC 71 Z9 71 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 29 PY 1998 VL 37 IS 39 BP 13660 EP 13673 DI 10.1021/bi9808823 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127UA UT WOS:000076367900025 PM 9753453 ER PT J AU Ridky, TW Kikonyogo, A Leis, J AF Ridky, TW Kikonyogo, A Leis, J TI Drug-resistant HIV-1 proteases identify enzyme residues important for substrate selection and catalytic rate SO BIOCHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ROUS-SARCOMA VIRUS; DECREASED SENSITIVITY; MOLECULAR-DYNAMICS; ASPARTIC PROTEASE; BINDING POCKETS; TYPE-1 VARIANTS; INHIBITORS; MUTATIONS; MUTANTS AB A series of mutations, first identified in protease inhibitor-resistant HIV-1 viral isolates, were introduced into HIV-1 PR as individual substitutions. Mutants containing R8K, V32I, V82T, 184V, G48V/ L90M, or V82T/184V substitutions were analyzed for differences in substrate preference and catalytic efficiency using a set of single amino acid substituted HIV-I CA-NCa cleavage site peptides. All mutants exhibited wild-type preference for large hydrophobic residues, especially Phe, in the P1' substrate position. Only the R8K and V32I mutants showed significant differences in subsite selection compared to wild-type enzyme. In a parallel study, the individual mutations R10K, L12V, I44V, A60M, I71V, and I108V were introduced into RSV PR. These amino acid positions are structurally equivalent to Arg8, Leu10, Va132, Met46, Ile54, and Ile84 in HIV-1 PR, respectively, which mutate in drug-resistance. The RSV R10K substitution significantly altered substrate specificity and catalytic rate, compared to wild-type, in a manner similar to that of the HIV-1 RsK mutant. Crystal structures of the RSV PR R10K, I44V, I71V, and I108V mutant enzymes presented here indicate that each of these substitutions has little effect on the overall structure of the respective enzymes. Taken together, these data provide an explanation for the reported in vivo predilection for selection of large hydrophobic residues in the P1' substrate position of second locus mutations in the Gag polyprotein PR cleavage sites. The data also suggest that the selection of resistant enzymes is not simply limited to loss of binding to inhibitor but affects other steps in proteolysis. C1 Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. NCI, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. RP Leis, J (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, 2119 Abington Rd, Cleveland, OH 44106 USA. OI Ridky, Todd/0000-0001-8482-1284 FU NCI NIH HHS [CA52047, CA58166]; NIAID NIH HHS [AI41380]; NIGMS NIH HHS [R01 GM062920] NR 33 TC 36 Z9 36 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 29 PY 1998 VL 37 IS 39 BP 13835 EP 13845 DI 10.1021/bi980612k PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 127UA UT WOS:000076367900045 PM 9753473 ER PT J AU Jacobs, AK Kelsey, SF Brooks, MM Faxon, DP Chaitman, BR Bittner, V Mock, MB Weiner, BH Dean, L Winston, C Drew, L Sopko, G AF Jacobs, AK Kelsey, SF Brooks, MM Faxon, DP Chaitman, BR Bittner, V Mock, MB Weiner, BH Dean, L Winston, C Drew, L Sopko, G TI Better outcome for women compared with men undergoing coronary revascularization - A report from the Bypass Angioplasty revascularization Investigation (BARI) SO CIRCULATION LA English DT Article DE coronary disease; angioplasty; surgery; women ID IN-HOSPITAL MORTALITY; LONG-TERM; ARTERY SURGERY; REGISTRY; RISKS; PTCA AB Background-Numerous studies have shown that women undergoing coronary revascularization procedures do so at a higher risk for an adverse outcome compared with men. However, the impact of advances in technology and improvements in techniques on in-hospital and long-term outcome after revascularization in women is unclear. Methods and Results-We evaluated 1829 patients with symptomatic multivessel coronary disease randomized to CABG or PTCA in the Bypass Angioplasty Revascularization Investigation (BARI), of whom 27% were women. As expected, women were older (64.0 versus 60.5 years), with more congestive heart failure (14% versus 7%), hypertension (68% versus 42%), treated diabetes mellitus (31% versus 15%), and unstable angina (67% versus 61%) than men but had similar preservation of left ventricular function and extent of multivessel disease. Women assigned to surgery received the same number of total grafts but fewer internal mammary artery grafts (72% versus 85%, P<0.01), and those assigned to angioplasty had more intended lesions (76% versus 71%, P<0.01) successfully dilated than men. At an average of 5.4 years' follow-up, crude mortality rates were similar in women (12.8%) and men (12.0%). The Cox regression model adjusting for baseline differences revealed that women had a significantly lower risk of death (relative risk, 0.60; 95% CI, 0.43 to 0.84; P=0.003) but not a significantly lower risk of death plus myocardial infarction (relative risk, 0.84; 95% CI, 0.66 to 1.07; P=0.16) than men. Conclusions-Although the unadjusted mortality rate suggests that women and men undergoing CABG and PTCA have a similar 5-year mortality, women have higher risk profiles; consequently, contrary to previous reports, female sex is an independent predictor of improved 5-year survival after we control for multiple risk factors. C1 Boston Med Ctr, Cardiol Sect, Dept Med, Boston, MA 02118 USA. Boston Med Ctr, Evans Mem Dept Clin Res, Boston, MA 02118 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ So Calif, Los Angeles, CA USA. St Louis Univ, St Louis, MO 63103 USA. Univ Alabama, Birmingham, AL USA. Mayo Clin, Rochester, MN USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Duke Univ, Med Ctr, Durham, NC USA. NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Jacobs, AK (reprint author), Boston Med Ctr, Cardiol Sect, Dept Med, 88 E Newton St, Boston, MA 02118 USA. EM alice.jacobs@bmc.org OI Brooks, Maria/0000-0002-2030-7873 FU NHLBI NIH HHS [HL-38493, HL-38504, HL-38509] NR 25 TC 187 Z9 200 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 29 PY 1998 VL 98 IS 13 BP 1279 EP 1285 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 123AC UT WOS:000076102800007 PM 9751675 ER PT J AU Berger, EA Moss, B Pastan, I AF Berger, EA Moss, B Pastan, I TI Reconsidering targeted toxins to eliminate HIV infection: You gotta have HAART SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EXOTOXIN HYBRID PROTEIN; ACTIVE ANTIRETROVIRAL THERAPY; CD4-PSEUDOMONAS EXOTOXIN; ENVELOPE GLYCOPROTEINS; PSEUDOMONAS EXOTOXIN; SOLUBLE CD4; CELLS; IMMUNOTOXINS; RESERVOIR AB The success of highly active anti-retroviral therapy (HAART) has inspired new concepts for eliminating HIV from infected individuals. A major obstacle is the persistence of long-lived reservoirs of latently infected cells that might become activated at some time after cessation of therapy. We propose that, in the context of treatment strategies to deliberately activate and eliminate these reservoirs, hybrid toxins targeted to kill HIV-infected cells be reconsidered in combination with HAART. Such combinations might also prove valuable in protocols aimed at preventing mother-to-child transmission and establishment of infection immediately after exposure to HIV. We suggest experimental approaches in vitro and in animal models to test various issues related to safety and efficacy of this concept. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Berger, EA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 236, Bethesda, MD 20892 USA. NR 33 TC 46 Z9 46 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 SEP 29 PY 1998 VL 95 IS 20 BP 11511 EP 11513 DI 10.1073/pnas.95.20.11511 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200005 PM 9751696 ER PT J AU Czerwinski, G Tarasov, NI Michejda, CJ AF Czerwinski, G Tarasov, NI Michejda, CJ TI Cytotoxic agents directed to peptide hormone receptors: Defining the requirements for a successful drug SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-COLON CANCER; INTERLEUKIN-2 RECEPTOR; GASTRIN RECEPTOR; CELLS; GROWTH; DESIGN; INTERNALIZATION; ENDOCYTOSIS; PROGLUMIDE; CONJUGATE AB In principle, cell surface receptors that are overexpressed in tumor tissue could serve as targets for anticancer drugs attached to receptor ligands. The purpose of this paper is to identify the necessary elements for a successful receptor targeted drug. We used the gastrin/cholecystokinin type B receptor as a model delivery system, and we report on the synthesis, trafficking, and in vitro and in vivo evaluation of heptagastrin, the C-terminal heptapeptide of gastrin, linked via an appropriate linker to a potently cytotoxic ellipticine derivative, 1-[3-[N-(3-aminopropyl)-N-methylamino] propyl] amino-9-methoxy-5,11-dimethyl-6H-pyrido [4,3-b] carbazole, These data, and previous work from our laboratory, show that the drug-complexed ligand is sorted to lysosomes whereas the receptor is recycled to the plasma membrane. The lysosomal processing of the ligand/drug construct depends on the linker between the ligand sequence and the cytotoxic moiety, We show that heptagastrin linked to ellipticine via a succinoyl-substituted pentapeptide, AlaLeuAlaLeuAla, is at least 10(3) more toxic to cholecystokinin type B receptor-positive NIH/3T3 cells than to isogenic NIH/3T3 cells lacking the receptor. The conjugated drug eradicated all receptor-positive tumor cells in vivo without producing any general toxicity, The data indicate that the density of the cell surface receptor, the properties of the cytotoxic moiety, and the correct processing of the drug-conjugated ligand in lysosomes are crucial to the effectiveness of a receptor-targeted drug. C1 NCI, Frederick Canc Res & Dev Ctr, Mol Aspects Drug Design Sect, Macromol Struct Lab,Adv BioSci Labs,Basic Res Pro, Frederick, MD 21702 USA. RP Michejda, CJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Mol Aspects Drug Design Sect, Macromol Struct Lab,Adv BioSci Labs,Basic Res Pro, Frederick, MD 21702 USA. EM michejda@ncifcrf.gov NR 43 TC 29 Z9 29 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 SEP 29 PY 1998 VL 95 IS 20 BP 11520 EP 11525 DI 10.1073/pnas.95.20.11520 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200007 PM 9751698 ER PT J AU Maynard, AT Huang, M Rice, WG Covell, DG AF Maynard, AT Huang, M Rice, WG Covell, DG TI Reactivity of the HIV-1 nucleocapsid protein p7 zinc finger domains from the perspective of density-functional theory SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ACID-BINDING-PROTEINS; ANTI-HIV; ABSOLUTE ELECTRONEGATIVITY; POLYATOMIC-MOLECULES; DISULFIDE BENZAMIDES; INHIBITORS; EJECTION; BENZISOTHIAZOLONES; RETROVIRUSES AB The reaction of the human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein p7 (NCp7) with a variety of electrophilic agents was investigated by experimental measurements of Trp(37) fluorescence decay and compared,vith theoretical measures of reactivity based on density-functional theory in the context of the hard and soft acids and bases principle, Statistically significant correlations were found between rates of reaction and the ability of these agents to function as soft electrophiles. Notably, the molecular propel ty that correlated strongest was the ratio of electronegativity to hardness, chi(2)/eta, a quantity related to the capacity of an electrophile to promote a soft (covalent) reaction. Electronic and steric determinants of the reaction were also probed by Fukui function and frontier-orbital overlap analysis in combination with protein-ligand docking methods. This analysis identified selective ligand docking regions within the conserved zinc finger domains that promoted reaction. The Cys(49) thiolate was found overall to be the NCp7 site most susceptible to electrophilic attack. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC,Mol Struct Sect,LECB, Biomed Supercomp Lab,Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Maynard, AT (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC,Mol Struct Sect,LECB, Biomed Supercomp Lab,Sci Applicat Int Corp, Bldg 430,Room 215, Frederick, MD 21702 USA. EM maynarda@fconqx.ncifcrf.gov; covell@faxpdc.ncifcrf.gov NR 37 TC 196 Z9 196 U1 1 U2 13 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 29 PY 1998 VL 95 IS 20 BP 11578 EP 11583 DI 10.1073/pnas.95.20.11578 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200017 PM 9751708 ER PT J AU Weissman, JD Brown, JA Howcroft, TK Hwang, J Chawla, A Roche, PA Schiltz, L Nakatani, Y Singer, DS AF Weissman, JD Brown, JA Howcroft, TK Hwang, J Chawla, A Roche, PA Schiltz, L Nakatani, Y Singer, DS TI HIV-1 Tat binds TAF(II)250 and represses TAF(II)250-dependent transcription of major histocompatibility class I genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; RNA-POLYMERASE-II; CELL-LINE; TRANSACTIVATOR TAT; DOWN-MODULATION; PROTEIN; EXPRESSION; SUBUNIT; ACTIVATION; PROMOTER AB HIV Tat, a transactivator of viral transcription, represses transcription of major histocompatibility (MHC) class I genes, Repression depends exclusively on the C-terminal domain of Tat, although the mechanism of this repression has not been known. We now show that repression results from the interaction of Tat with the TAF(II)250 component of the general transcription factor, TFIID. The C-terminal domain of Tat binds to a site on TAF(II)250 that overlaps the histone acetyl transferase domain, inhibiting TAF(II)250 histone acetyl transferase activity, Furthermore, promoters repressed by Tat, including the MHC class I promoter, are dependent on TAF(II)250 whereas those that are not repressed by Tat, such as SV40 and MuLV promoters, are independent of functional TAF(II)250. Thus, Tat repression of MHC class I transcription would be one mechanism by which HIV avoids immune surveillance. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B-36, Bethesda, MD 20892 USA. NR 42 TC 126 Z9 127 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 29 PY 1998 VL 95 IS 20 BP 11601 EP 11606 DI 10.1073/pnas.95.20.11601 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200021 PM 9751712 ER PT J AU Kinter, A Catanzaro, A Monaco, J Ruiz, M Justement, J Moir, S Arthos, J Oliva, A Ehler, L Mizell, S Jackson, R Ostrowski, M Hoxie, J Offord, R Fauci, AS AF Kinter, A Catanzaro, A Monaco, J Ruiz, M Justement, J Moir, S Arthos, J Oliva, A Ehler, L Mizell, S Jackson, R Ostrowski, M Hoxie, J Offord, R Fauci, AS TI CC-chemokines enhance the replication of T-tropic strains of HIV-1 in CD4(+) T cells: Role of signal transduction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; BETA-CHEMOKINES; INFECTED INDIVIDUALS; BIOLOGICAL PHENOTYPE; RECEPTORS; ENTRY; PROGRESSION; ASSOCIATION; INHIBITION; AIDS AB This study demonstrates that several CC-chemokines, including those that inhibit entry and replication of macrophage-tropic strains of HIV, increase the replication of T cell (T)-tropic strains in CD4(+) T cells, Enhancement of T-tropic HIV replication is observed at early stages of replication, requires signaling through inhibitory guanine nucleotide-binding regulatory (Gi) proteins, and is associated with increased cell surface colocalization of CD4 and the T-tropic HIV coreceptor CXCR4. These findings may further our understanding of the factors that influence the replication and spread of T-tropic strains of HIV in vivo and suggest that the use of cell signaling CC-chemokines as therapeutic agents for the purpose of limiting HIV replication in vivo should be approached with caution. C1 NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Gryphon Sci, San Francisco, CA 94080 USA. Ctr Med Univ Geneva, Dept Biochim Med, CH-1211 Geneva, Switzerland. RP Kinter, A (reprint author), NIAID, Lab Immunoregulat, NIH, Bldg 10,Room 6A33,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA. NR 41 TC 157 Z9 157 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 SEP 29 PY 1998 VL 95 IS 20 BP 11880 EP 11885 DI 10.1073/pnas.95.20.11880 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200068 PM 9751759 ER PT J AU Moffat, JF Zerboni, L Sommer, MH Heineman, TC Cohen, JI Kaneshima, H Arvin, AM AF Moffat, JF Zerboni, L Sommer, MH Heineman, TC Cohen, JI Kaneshima, H Arvin, AM TI The ORF47 and ORF66 putative protein kinases of varicella-zoster virus determine tropism for human T cells and skin in the SCID-hu mouse SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HERPES-SIMPLEX VIRUS; UNIQUE SHORT REGION; PSEUDORABIES VIRUS; UL13 GENE; IN-VITRO; POSTTRANSLATIONAL MODIFICATION; HERPESVIRUSES ENCODE; VIRAL REPLICATION; DEFICIENT MUTANT; INFECTED-CELLS AB The varicella-zoster virus (VZV) genes ORF47 and ORF66 are predicted to encode serine/threonine protein kinases, which are homologs of herpes simplex virus 1 (HSV-1) UL13, and US3. When mutants were constructed by inserting stop codons into ORF47 and ORF66, the recombinants ROka47S and ROka66S, as well as intact ROka replicated in tissue culture. In contrast, inoculation of human thymus/liver or skin implants in SCID-hu mice showed that ORF47 protein was required for viral growth in human T cells and skin. Eliminating ORF66 expression inhibited VZV infectivity for T cells partially but did not impair replication in skin compared with ROka. Infectivity for T cells and skin was restored when ROka47S virus was complemented by insertion of ORF47 into a distant, noncoding site. The ORF47 gene product is the first VZV protein identified as necessary for T cell tropism. It also is essential for skin infectivity in vivo, as is glycoprotein C. Expression of ORF66 did not compensate for the absence of the ORF47 protein. The requirement for ORF47 expression in T cells and skin indicates that this gene product, which is dispensable in vitro, has a critical role within differentiated cells that are essential targets for VZV pathogenesis in vivo. C1 Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. St Louis Univ, Div Infect Dis & Immunol, St Louis, MO 63110 USA. NIH, Clin Invest Lab, Bethesda, MD 20892 USA. SyStemix Inc, Palo Alto, CA 94304 USA. RP Moffat, JF (reprint author), Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. EM jmoffat@leland.stanford.edu FU NIAID NIH HHS [AI09195, AI36884, F32 AI009195]; NICHD NIH HHS [T32 HD007249, HD07249] NR 50 TC 117 Z9 121 U1 1 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 SEP 29 PY 1998 VL 95 IS 20 BP 11969 EP 11974 DI 10.1073/pnas.95.20.11969 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200083 PM 9751774 ER PT J AU Namkung, Y Smith, SM Lee, SB Skrypnyk, NV Kim, HL Chin, H Scheller, RH Tsien, RW Shin, HS AF Namkung, Y Smith, SM Lee, SB Skrypnyk, NV Kim, HL Chin, H Scheller, RH Tsien, RW Shin, HS TI Targeted disruption of the Ca2+ channel beta(3) subunit reduces N- and L-type Ca2+ channel activity and alters the voltage-dependent activation of P/Q-type Ca2+ channels in neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BULLFROG SYMPATHETIC NEURONS; GATED CALCIUM CHANNELS; ALPHA(1) SUBUNIT; G-PROTEINS; FUNCTIONAL EXPRESSION; INTRACELLULAR LOOP; DOMAIN-II; P-TYPE; INHIBITION; MODULATION AB In comparison to the well characterized role of the principal subunit of voltage-gated Ca2+ channels, the pore-forming, antagonist-binding alpha(1) subunit, considerably less is understood about how beta subunits contribute to neuronal Ca2+ channel function. We studied the role of the Ca2+ channel beta(3) subunit, the major Ca2+ channel beta subunit in neurons, by using a gene-targeting strategy. The beta(3) deficient (beta(3)-/-) animals were indistinguishable from the wild type (wt) with no gross morphological or histological differences. However, in sympathetic beta 3-/- neurons, the L- and N-type current was significantly reduced relative to wt. Voltage-dependent activation of P/Q-type Ca2+ channels was described by two Boltzmann components with different voltage dependence, analogous to the "reluctant" and "willing" states reported for N-type channels. The absence of the beta(3) subunit was associated with a hyperpolarizing shift of the "reluctant" component of activation. Norepinephrine inhibited wt and beta(3)-/- neurons similarly but the voltage sensitive component was greater for N-type than P/Q-type Ca2+ channels, The reduction in the expression of N-type Ca2+ channels in the beta(3)-/- mice may be expected to impair Ca2+ entry and therefore synaptic transmission in these animals. This effect may be reversed, at least in part, by the increase in the proportion of P/Q channels activated at less depolarized voltage levels. C1 Pohang Univ Sci & Technol, Dept Life Sci, Pohang 790784, South Korea. Pohang Univ Sci & Technol, Natl Creat Res Initiat Ctr Calcium & Learning, Pohang 790784, South Korea. Stanford Univ, Howard Hughes Med Inst, Stanford, CA 94305 USA. Stanford Univ, Dept Cellular & Mol Physiol, Stanford, CA 94305 USA. Ewha Womans Univ, Coll Med, Dept Biochem, Yangcheon Ku, Seoul 158056, South Korea. NIMH, Div Basic & Clin Neurosci Branch, NIH, Rockville, MD 20859 USA. RP Shin, HS (reprint author), Pohang Univ Sci & Technol, Dept Life Sci, San 31,Hyoja Dong, Pohang 790784, South Korea. NR 47 TC 63 Z9 66 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 29 PY 1998 VL 95 IS 20 BP 12010 EP 12015 DI 10.1073/pnas.95.20.12010 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 125DM UT WOS:000076222200090 PM 9751781 ER PT J AU Abascal, VM Larson, MG Evans, JC Blohm, AT Poli, K Levy, D AF Abascal, VM Larson, MG Evans, JC Blohm, AT Poli, K Levy, D TI Calcium antagonists and mortality risk in men and women with hypertension in the Framingham Heart Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 69th Annual Scientific Session of the American-Heart-Association CY NOV 09-16, 1996 CL NEW ORLEANS, LOUISIANA SP Amer Heart Assoc, Hoechst Marion Roussel Inc, Kansas City ID ISOLATED SYSTOLIC HYPERTENSION; CORONARY-ARTERY DISEASE; CHANNEL BLOCKERS; MYOCARDIAL-INFARCTION; BLOOD-PRESSURE; DRUG TRIALS; NIFEDIPINE; PLACEBO; STROKE AB Background: Several recent studies have suggested that calcium antagonist drugs, which are widely used for the treatment of hypertension, are associated with increased risk of cardiovascular disease. These studies have cast doubts on the long-term safety of calcium antagonists. Objective: To examine the association of calcium antagonist use with mortality in subjects with hypertension followed up in the Framingham Heart Study. Subjects and Methods: We stratified 3539 subjects (mean +/- SD age, 64 +/- 13 years) from the Framingham Heart Study who had hypertension at routine clinic examinations, according to the use of calcium antagonists and presence of coronary heart disease at the baseline examination. At each follow-up examination (every 2-4 years), subjects were reclassified with regard to the use of calcium antagonists. The end point of the study was all-cause mortality. Hazard ratios and 95% confidence intervals associated with the use of calcium antagonists were obtained using Cox proportional hazards regression models. Results: There were 970 deaths during follow-up. Hazard ratios for mortality associated with the use of calcium antagonists were 0.93 (95% confidence interval, 0.72-1.21; P = .59) for subjects with hypertension without coronary heart disease, and 0.92 (95% confidence interval, 0.69-1.24; P = .58) for those with coronary heart disease at baseline. All models were adjusted for age, sex, current smoking, systolic and diastolic blood pressure, use of P-blockers, and use of other antihypertensive medications. Conclusions: In this cohort of 3539 subjects with hypertension there were no differences in mortality among subjects with hypertension using a calcium antagonist compared with those who were not. Results were similar among subjects with hypertension with and without coronary heart disease. The results of ongoing long-term, randomized clinical trials will provide more definitive data on the safety of calcium antagonists. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Math, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Cardiol & Prevent Med, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 5 Thurber St, Framingham, MA 01702 USA. EM dan@fram.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-38038] NR 35 TC 19 Z9 19 U1 0 U2 1 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 SEP 28 PY 1998 VL 158 IS 17 BP 1882 EP 1886 DI 10.1001/archinte.158.17.1882 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 124DV UT WOS:000076166800003 PM 9759683 ER PT J AU Cohen, RM Carson, RE Aigner, TG Doudet, DJ AF Cohen, RM Carson, RE Aigner, TG Doudet, DJ TI Opiate receptor avidity is reduced in non-motor impaired MPTP-lesioned rhesus monkeys SO BRAIN RESEARCH LA English DT Article DE Parkinson's disease; neurodegeneration; 6-deoxy-6-beta-[F-18]fluoronaltrexone; positron emission tomography; basal ganglia; dopamine ID POSITRON EMISSION TOMOGRAPHY; BASAL GANGLIA; PARKINSONS-DISEASE; HUMAN-BRAIN; ENKEPHALIN; IMMUNOREACTIVITY; EXPOSURE; MODEL; DOPA AB Opiate receptor avidity, roughly equivalent to the ratio of unoccupied receptor density to the receptor dissociation constant (B-max'/K-D), was measured in four MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-lesioned rhesus monkeys and nine normal controls with positron emission tomography (PET) and 6-deoxy-6-beta-[F-18]fluoronaltrexone (cyclofoxy, CF), a mu- and kappa-opiate receptor antagonist. Although the MPTP-lesioned monkeys were dopamine deficient as measured with [F-18]-L-fluorodopa ([F-18]-DOPA) and PET [Doudet et al., 6-[F-18]-L-DOPA imaging of the dopamine neostriatal system in normal and clinically normal-MPTP-treated rhesus monkeys, Exp. Brain Res. 78 (1989) 69-80], they had clinically recovered from the acute motor effects of MPTP exposure. Opiate receptor avidity was found to be reduced by 30-35% in the opiate-receptor rich areas of caudate, anterior putamen, thalamus, and amygdala of the MPTP-lesioned animals. The results suggest that opiate pathways make a significant contribution to the adjustment of cortico-striatal-thalamic pathway activity and thereby to behavior in rhesus monkeys following dopamine loss. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 NIMH, Cerebral Metab Lab, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Cohen, RM (reprint author), NIMH, Cerebral Metab Lab, Bldg 36,Room 1A05,36 Convent Dr MSC 4030, Bethesda, MD 20892 USA. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 20 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 28 PY 1998 VL 806 IS 2 BP 292 EP 296 DI 10.1016/S0006-8993(98)00777-X PG 5 WC Neurosciences SC Neurosciences & Neurology GA 125ML UT WOS:000076241300020 PM 9739155 ER PT J AU Yang, YA Mumy, M Romeo, D Wakefield, LM AF Yang, YA Mumy, M Romeo, D Wakefield, LM TI Identification of the start sites for the 1.9- and 1.4-kb rat transforming growth factor-beta 1 transcripts and their effect on translational efficiency SO GENE LA English DT Article DE 5 ' RACE PCR; RNase protection; translational control; polysome ID FACTOR-BETA; MESSENGER-RNA; EPITHELIAL-CELLS; EXPRESSION; GENE; INDUCTION; PROMOTER; FIBROSIS; ACTIVATION; SEQUENCES AB Three distinct transforming growth factor-beta 1 (TGF-beta 1) transcripts of 2.5, 1.9 and 1.4 kb have been described, but the start sites and functional significance of the shorter transcripts are unknown. Here, we have cloned and sequenced a rat genomic fragment encoding similar to 1250 bases upstream of the start of the TGF-beta 1 open reading frame. Using a combination of ribonuclease protection and 5' RACE-PCR analysis, we have mapped the start sites for the two shorter TGF-beta 1 transcripts in NRP152 cells, a rat prostatic epithelial cell line that expresses all three transcripts at high levels. The 1.4-kb mRNA starts 25 bases upstream of the initiator AUG, whereas the 1.9-kb mRNA has two start sites 366 and 401 bases upstream of the AUG. Polysome analysis of the NRP152 cells indicates that the 1.9-kb transcript is very efficiently translated, whereas the 2.5- and 1.4-kb transcripts appear to be poorly translated. Differential regulation of TGF-beta 1 transcript size may therefore represent an important mechanism for regulating TGF-beta 1 protein levels. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Wakefield, LM (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. NR 35 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD SEP 28 PY 1998 VL 219 IS 1-2 BP 81 EP 89 DI 10.1016/S0378-1119(98)00402-8 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 130DR UT WOS:000076504900010 PM 9757003 ER PT J AU Wahl, PW Savage, PJ Psaty, BM Orchard, TJ Robbins, JA Tracy, RP AF Wahl, PW Savage, PJ Psaty, BM Orchard, TJ Robbins, JA Tracy, RP TI Diabetes in older adults: comparison of 1997 American Diabetes Association classification of diabetes mellitus with 1985 WHO classification SO LANCET LA English DT Article ID GLUCOSE-TOLERANCE; POPULATION; INSULIN; HEALTH; NEED AB Background We aimed to compare the prevalence of abnormal glucose tolerance identified by the 1985 WHO and the 1997 American Diabetes Association (ADA) diagnostic categories based on information collected in the Cardiovascular Health Study, an epidemiological study of elderly people. Methods We measured glucose concentrations during fasting and 2 h after a 75 g oral glucose-tolerance test in participants aged 65-100 years in the Cardiovascular Health Study. From a 1989 cohort, we analysed the glucose measurements of 4515 individuals without a previous diagnosis of diabetes and of 262 additional measurements from an African-American cohort recruited in 1992-93. Findings In the 1989 cohort, the prevalence of untreated diabetes with ADA diagnostic fasting criteria was 7.7% versus a prevalence of 14.8% by the WHO criteria. In the African-American cohort, the prevalence of untreated diabetes was 2.7% with ADA criteria and 11.8% with WHO criteria. 3509 (77.7%) of the 4515 participants in the 1989 cohort had normal glucose concentrations according to ADA fasting criteria, compared with 2401 (53.2%) according to WHO criteria. In the African-American cohort, the corresponding numbers were 239 (91.2%) versus 153 (58.4%). All differences in prevalence of abnormal glucose tolerance between ADA and WHO classifications were significant (p<0.0001). Interpretation Among elderly individuals, there was a significant difference in the prevalence of diabetes identified by the WHO diagnostic criteria based on oral glucose tolerance test and the ADA fasting criteria. Consequently, many individuals currently classified as non-diabetic according to ADA criteria would previously have had a diagnosis of diabetes according to WHO criteria. Longitudinal studies are needed to assess the value of the criteria in the identification of individuals at increased risk of diabetes-associated chronic complications. C1 Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Med & Epidemiol, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Calif, Sch Med, Dept Med, Sacramento, CA USA. Univ Vermont, Sch Med, Dept Pathol, Burlington, VT 05405 USA. Univ Vermont, Sch Med, Dept Biochem, Burlington, VT 05405 USA. RP Wahl, PW (reprint author), Cardiovasc Hlth Study Coordinating Ctr, Century Sq,Suite 2025, Seattle, WA 98101 USA. EM pwahl@u.washington.edu OI orchard, trevor/0000-0001-9552-3215 FU NHLBI NIH HHS [N01-HC-87079] NR 17 TC 134 Z9 141 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 26 PY 1998 VL 352 IS 9133 BP 1012 EP 1015 DI 10.1016/S0140-6736(98)04055-0 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 123JJ UT WOS:000076121800009 PM 9759743 ER PT J AU Brown, P AF Brown, P TI Origins of BSE - Reply SO LANCET LA English DT Letter C1 NINDS, Cent Nervous Syst Studies Lab, Publ Hlth Serv, NIH, Bethesda, MD 20892 USA. RP Brown, P (reprint author), NINDS, Cent Nervous Syst Studies Lab, Publ Hlth Serv, NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 26 PY 1998 VL 352 IS 9133 BP 1068 EP 1069 DI 10.1016/S0140-6736(05)60113-4 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 123JJ UT WOS:000076121800067 ER PT J AU Suffredini, AF AF Suffredini, AF TI Myocardial dysfunction in sepsis: clinical and experimental investigations SO SCHWEIZERISCHE MEDIZINISCHE WOCHENSCHRIFT LA English DT Article; Proceedings Paper CT Annual Meeting of the Swiss-Society-for-Intensive-Care-Medicine CY SEP 25-26, 1997 CL MONTREUX, SWITZERLAND SP Swiss Soc Intensive Med ID HUMAN SEPTIC SHOCK; NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; RAT CARDIAC MYOCYTES; CANINE MODEL; ESCHERICHIA-COLI; CARDIOVASCULAR DYSFUNCTION; VENTRICULAR-FUNCTION; EJECTION FRACTION; IN-VITRO AB Objective: To review the clinical manifestations and mechanisms of cardiac dysfunction in septic shock. Methods: Literature review of selected clinical studies and animal models. Results: Depressed myocardial contractile function is a common consequence of severe infections. Bacterial factors, in conjunction with host inflammatory mediators, produce a profile of reversible cardiac dysfunction manifested by a decrease in ventricular ejection fraction, ventricular dilatation, and increased cardiac output. Global ischemia is not the major mechanism that mediates cardiac dysfunction during sepsis. Inflammatory mediators contribute to myocardial dysfunction by damaging the coronary microcirculation and contributing to myocardial edema and cardiocyte damage. However, trials of anti-inflammatory agents have not prevented or increased the rate of reversal of septic shock or improved survival. The link between nitric oxide and clinical myocardial depression remains unclear, as nonselective nitric oxide synthase inhibition does not block the development of ventricular dysfunction. Conclusions: Serious bacterial infections result in inflammatory injury to the heart manifested by a common profile of cardiac dysfunction. Therapy remains limited to treatment of the infection with antibiotics and supportive care, with fluid resuscitation and selective use of inotropes and vasopressors. Experimental models suggest that new anti-inflammatory strategies (e.g. tyrosine kinase inhibitors) may offer some advantages over those that target a single mediator; these agents remain to be clinically evaluated. C1 NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Suffredini, AF (reprint author), NIH, Dept Crit Care Med, Warren G Magnuson Clin Ctr, Bldg 10,Room 7D-43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. EM anthony_suffredini@nih.gov NR 51 TC 12 Z9 14 U1 0 U2 2 PU SCHWABE & CO AG VERLAG PI MUTTENZ 1 PA FARNSBURGERSTRASSE 8, CH-4132 MUTTENZ 1, SWITZERLAND SN 0036-7672 J9 SCHWEIZ MED WSCHR JI Schweiz. Med. Wochenschr. PD SEP 26 PY 1998 VL 128 IS 39 BP 1444 EP 1452 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 123HR UT WOS:000076120200004 PM 9793163 ER PT J AU Auer, KL Spector, MS Tombes, RM Seth, P Fisher, PB Gao, B Dent, P Kunos, G AF Auer, KL Spector, MS Tombes, RM Seth, P Fisher, PB Gao, B Dent, P Kunos, G TI alpha-Adrenergic inhibition of proliferation in HepG2 cells stably transfected with the alpha(1B)-adrenergic receptor through a p42(MAPkinase)/p21(Cip1/WAF1)-dependent pathway SO FEBS LETTERS LA English DT Article ID MITOGEN-ACTIVATED PROTEIN; CYCLIN-DEPENDENT KINASES; EPIDERMAL GROWTH-FACTOR; RAT HEPATOCYTES; BETA-2-ADRENERGIC RECEPTORS; GENE TRANSCRIPTS; DNA-SYNTHESIS; LIVER-CELLS; EXPRESSION; P21 AB Activation of alpha(1B) adrenergic receptors (alpha(1B)AR) promotes DNA synthesis in primary cultures of hepatocytes, yet expression of alpha(1B)AR in hepatocytes rapidly declines during proliferative events, HepG2 human hepatoma cells, which do not express alpha(1B)AR, were stably transfected with a rat alpha(1B)AR cDNA (TFG2 cells), in order to study the effects of maintained alpha(1B)AR expression on hepatoma cell proliferation. TFG2 cells had a decreased rate of growth compared to mock transfected HepG2 cells as revealed by a decrease in [H-3]thymidine incorporation into DNA, Stimulation of alpha(1B)AR with phenylephrine caused a further large reduction in TFG2 cell growth, whereas no effect on growth was observed in mock transfected cells, Reduced cell growth correlated,vith increased percentages of cells found in G(0)/G(1) and G(2)/M phases of the cell cycle. In TFG2 cells, phenylephrine increased p42(MAPkinase) activity by 1.5- to 2.0-fold for up to 24 h and increased expression of the cyclin dependent kinase inhibitor protein p21(Cip1/WAF1). Treatment of TFG2 cells with the specific MEK1 inhibitor PD98059, or infection with a -/- MEK1 recombinant adenovirus permitted phenylephrine to increase rather than decrease [H-3]thymidine incorporation. In addition, inhibition of MAP kinase signaling by PD98059 or MEK1 -/- blunted the ability of phenylephrine to increase p21(Cip1/WAF1) expression. In agreement with a role for increased p21(Cip1/WAF1) expression in causing growth arrest, infection of TFG2 cells with a recombinant adenovirus to express antisense p21(Cip1/WAF1) mRNA blocked the ability of phenylephrine to increase p21(Cip1/WAF1) expression and to inhibit DNA synthesis. Antisense p21(Cip1/WAF1) permitted phenylephrine to stimulate DNA synthesis in TFG2 cells, and abrogated growth arrest. These results suggest that transformed hepatocytes may turn off the expression of alpha(1B)ARs in order to prevent the activation of a growth inhibitory pathway. Activation of this inhibitory pathway via alpha(1B)AR appears to be p42(MAPkinase) and p21(Cip1/WAF1) dependent. (C) 1998 Federation of European Biochemical Societies. C1 Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Biol, Richmond, VA 23298 USA. NCI, Med Branch, Breast Canc Sect, Bethesda, MD 20892 USA. Columbia Univ Coll Phys & Surg, Dept Urol & Pathol, New York, NY 10032 USA. RP Dent, P (reprint author), Virginia Commonwealth Univ, Med Coll Virginia, Dept Radiat Oncol, Box 980058, Richmond, VA 23298 USA. EM pdent@gems.vcu.edu RI Tombes, Robert/A-7780-2008; Tombes, Rob/B-5224-2011 FU NCI NIH HHS [R01-CA52825, R29-CA72363]; NHLBI NIH HHS [HL-49938] NR 47 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 25 PY 1998 VL 436 IS 1 BP 131 EP 138 DI 10.1016/S0014-5793(98)01074-6 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 127HM UT WOS:000076344900026 PM 9771908 ER PT J AU Mulvaney, PT Stracke, ML Nam, SW Woodhouse, E O'Keefe, M Clair, T Liotta, LA Khaddurah-Daouk, R Schiffmann, E AF Mulvaney, PT Stracke, ML Nam, SW Woodhouse, E O'Keefe, M Clair, T Liotta, LA Khaddurah-Daouk, R Schiffmann, E TI Cyclocreatine inhibits stimulated motility in tumor cells possessing creatine kinase SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID GROWTH; PHOSPHOCREATINE; CHEMOTAXIS; ANALOGS AB Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine), an analog of creatine and a substrate for creatine kinase (EC 2.7.3.2), inhibits the stimulated motility of tumor cells which possess creatine kinase. A2058-055 human melanoma cells, transfected with a creatine kinase gene, showed an 80-90% reduction in chemotactic response to type IV collagen when incubated overnight in the presence of 10 mM cyclocreatine (p < 0.0001 for n = 8 experiments). This inhibitory effect of cyclocreatine can be partially reversed by addition of creatine to the overnight cell treatment. Non-transfected cells, with very low levels of creatine kinase, were not significantly inhibited. Further experiments utilizing type IV collagen as attractant demonstrated that cyclocreatine inhibited the chemokinetic (91%) and the haptotactic (73%) responses and the in vitro invasion of A2058-055 cells through Matrigel-coated membranes (88%). In addition, motility stimulation of A2058-055 cells by either autotaxin or fibronectin was markedly inhibited by cyclocreatine. DU-145 prostatic tumor cells, which express endogenous creatine kinase, also have a reduced motility response to either autotaxin or epidermal growth factor induced motility in the presence of cyclocreatine. Int. J. Cancer 78:46-52, 1998. (C) 1998 Wiley-Liss, Inc. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. AVICENA Grp Inc, Cambridge, MA USA. RP Stracke, ML (reprint author), NCI, Pathol Lab, NIH, Bldg 10 Room 2A33, Bethesda, MD 20892 USA. NR 29 TC 16 Z9 16 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 25 PY 1998 VL 78 IS 1 BP 46 EP 52 DI 10.1002/(SICI)1097-0215(19980925)78:1<46::AID-IJC9>3.0.CO;2-X PG 7 WC Oncology SC Oncology GA 113GY UT WOS:000075543400009 PM 9724093 ER PT J AU Ye, Y Vasavada, S Kuzmin, I Stackhouse, T Zbar, B Williams, BRG AF Ye, Y Vasavada, S Kuzmin, I Stackhouse, T Zbar, B Williams, BRG TI Subcellular localization of the von Hippel-Lindau disease gene product is cell cycle-dependent SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID TUMOR-SUPPRESSOR GENE; ENDOTHELIAL GROWTH-FACTOR; CASEIN KINASE-II; RENAL-CARCINOMA CELLS; NUCLEAR-LOCALIZATION; PROTEIN-KINASE; BINDING; IDENTIFICATION; MUTATIONS; PHOSPHORYLATION AB The von Hippel-Lindau gene product (pVHL) interacts with and inhibits the cellular transcription factor elongin, However, the subcellular localization of pVHL has remained uncertain. Naturally occurring pVHL mutants which fail to interact with elongin have been described in patients with VHL disease or sporadic renal cell carcinoma (RCC), Here, we have examined the cellular expression pattern of endogenous pVHL in different RCC cell lines by immunocytochemistry and confocal microscopy. Both anti-N-terminal and anti-C-terminal pVHL antibodies were able to recognize endogenous wild-type pVHL expressed by the RCC cells studied. A C-terminal truncated VHL mutant expressed by RCC cell line A498 was detected only by the N-terminal antibody but not by the C-terminal antibody as expected. The overall staining patterns of these cell lines are similar, with a predominant nuclear speckled pattern and a moderate cytoplasmic staining in subconfluent cell cultures. Interestingly, when cells reached confluency, more prominent nuclear staining with little or no cytoplasmic expression was observed. By using double labeling with anti-VHL and antibromodeoxyuridine (BrdU) antibodies and cell cycle analyses, we found that in the G(1)/G(0)-phase, pVHL was localized exclusively in the nucleus associated with distinctive large subnuclear structures, whereas the majority of the cells in S-phase of the cell cycle also showed a diffuse cytoplasmic staining. Our results indicate that subcellular localization of pVHL is regulated in a cell cycle-dependent manner. Int. J. Cancer 78:62-69, 1998. (C) 1998 Wiley-Liss. Inc. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. NCI, Immunobiol Lab, Biol Carcinogenesis & Dev Program, Frederick, MD 21701 USA. RP Williams, BRG (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM Williab@cesmtp.ccf.org RI Williams, Bryan/A-5021-2009 OI Williams, Bryan/0000-0002-4969-1151 FU NIDDK NIH HHS [DK47101] NR 37 TC 27 Z9 29 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD SEP 25 PY 1998 VL 78 IS 1 BP 62 EP 69 DI 10.1002/(SICI)1097-0215(19980925)78:1<62::AID-IJC11>3.0.CO;2-7 PG 8 WC Oncology SC Oncology GA 113GY UT WOS:000075543400011 PM 9724095 ER PT J AU Chen, XY Reitman, M Bieker, JJ AF Chen, XY Reitman, M Bieker, JJ TI Chromatin structure and transcriptional control elements of the erythroid Kruppel-like factor (EKLF) gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FETAL LIVER HEMATOPOIESIS; LOCUS-CONTROL REGION; BINDING-FACTOR; DEFINITIVE HEMATOPOIESIS; ERYTHROPOIETIN RECEPTOR; HYPERSENSITIVE SITES; BETA-THALASSEMIA; MICE LACKING; IN-VITRO; C-MYB AB Erythroid Kruppel-like factor (EKLF) is a red cell-specific transcription factor whose activity is critical for the switch in expression from fetal to adult beta-globin during erythroid ontogeny, We have examined its own regulation using a number of approaches. First, the EKLF transcription unit is in an open chromatin configuration in erythroid cells. Second, in vivo transfection assays demonstrate that the more distal of the two erythroid-specific DNase-hypersensitive sites behaves as an enhancer. Although this conserved element imparts high level transcription to a heterologous promoter in all lines examined, erythroid specificity is retained only when it is fused to the proximal EKLF promoter, which contains an important GATA site. Third, extensive mutagenesis of this enhancer element has delimited its in vivo activity to a core region of 49 base pairs. Finally, in vitro footprint and gel shift assays demonstrate that three distinct DNA binding activities in erythroid cell extracts individually interact with three short sequences within this core enhancer element. These analyses reveal that high level erythroid expression of EKLF relies on the interplay between conserved proximal and distal promoter elements that alter chromatin structure and likely provide a target for genetic control via extracellular induction pathways. C1 CUNY Mt Sinai Sch Med, Brookdale Ctr Mol Biol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Biochem, New York, NY 10029 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. RP Bieker, JJ (reprint author), CUNY Mt Sinai Sch Med, Brookdale Ctr Mol Biol, Box 1126,1 Gustave L Levy Pl, New York, NY 10029 USA. RI Reitman, Marc/B-4448-2013 OI Reitman, Marc/0000-0002-0426-9475 FU NIDDK NIH HHS [DK09391, DK48721] NR 62 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1998 VL 273 IS 39 BP 25031 EP 25040 DI 10.1074/jbc.273.39.25031 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 122RN UT WOS:000076085400009 PM 9737959 ER PT J AU Lee, C Yim, MB Chock, PB Yim, HS Kang, SO AF Lee, C Yim, MB Chock, PB Yim, HS Kang, SO TI Oxidation-reduction properties of methylglyoxal-modified protein in relation to free radical generation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCATION END-PRODUCTS; ASCORBIC-ACID; AUTOXIDATIVE GLYCOSYLATION; PHYSIOLOGICAL CONDITIONS; HYDROGEN-PEROXIDE; GLYOXALASE SYSTEM; DIABETES-MELLITUS; MAILLARD REACTION; OXIDANT STRESS; CROSS-LINKING AB Oxidation-reduction properties of methylglyoxal-modified protein in relation to free radical generation were investigated. Glycation of bovine serum albumin by methylglyoxal generated the protein-bound free radical, probably the cation radical of the cross-linked Schiff base, as observed in the reaction of methylglyoxal with L-alanine (Yim, H.-S., Kang, S.-O., Bah, Y. C., Chock, P. B., and Yim, M. B. (1995) J. Biol. Chem. 270, 28228-28233) or with N-alpha-acetyl-L-lysine. The glycated bovine serum albumin showed increased electrophoretic mobility suggesting that the basic residues, such as lysine, were modified by methylglyoxal. The glycated protein reduced ferricytochrome c to ferrocytochrome c in the absence of oxygen or added metal ions. This reduction of cytochrome c was accompanied by a large increase in the amplitude of the electron paramagnetic resonance signal originated from the protein-bound free radical. In addition, the glycated protein catalyzed the oxidation of ascorbate in the presence of oxygen, whereas the protein free radical signal disappeared. These results indicate that glycation of protein generates active centers for catalyzing one-electron oxidation-reduction reactions. This active center, which exhibits enzyme-like characteristic, was suggested to be the cross-linked Schiff base/the cross-linked Schiff base radical cation of the protein. It mimics the characteristics of the metal-catalyzed oxidation system. The glycated bovine serum albumin cross-linked further to the cytochrome c in the absence of methylglyoxal. The cross-linked cytochrome c maintains its oxidation-reduction properties. These results together indicate that glycated proteins accumulated in vivo provide stable active sites for catalyzing the formation of free radicals. C1 Seoul Natl Univ, Coll Nat Sci, Dept Microbiol, Biophys Lab, Seoul 151742, South Korea. Seoul Natl Univ, Res Ctr Mol Microbiol, Seoul 151742, South Korea. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Kang, SO (reprint author), Seoul Natl Univ, Coll Nat Sci, Dept Microbiol, Biophys Lab, Seoul 151742, South Korea. EM kangsaou@plaza.snu.ac.kr NR 33 TC 98 Z9 101 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 25 PY 1998 VL 273 IS 39 BP 25272 EP 25278 DI 10.1074/jbc.273.39.25272 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 122RN UT WOS:000076085400042 PM 9737992 ER PT J AU Zamora, PO Moody, TW John, CS AF Zamora, PO Moody, TW John, CS TI Increased binding to sigma sites of N-[1 '(2-piperidinyl)ethyl]-4-[I-125]-iodobenzamide (I-125-PAB) with onset of tumor cell proliferation SO LIFE SCIENCES LA English DT Article DE sigma receptors; mammary carcinoma; proliferation ID IN-VITRO; MALIGNANT-MELANOMA; SELECTIVE LIGANDS; RECEPTOR LIGAND; BREAST-CANCER; HALOPERIDOL; AFFINITY; EXPRESSION; SUBTYPE; MAMMARY AB This study evaluated if the density of sigma sites was modulated following stimulation of mitosis and progression through the cell cycle. The sigma ligand N-[1'(2-piperidinyl)ethyl)-4-[I-125]-iodobenzamide (I-125-PAB) was a binding probe on the mammary tumor cell lines T47D and MCF-7, and the prostate tumor cell line DU-145. Cells at low density and in log phase growth bound more I-125-IPAB than those at high density at or the near plateau phase. Stimulation of mitosis with insulin or fresh 10% serum increased I-125-IPAB binding in all three cell lines. In cell-cycle synchronized cells, the highest amount of binding was found in cells treated with colcemid to block cells in the M-phase, while the lowest amount of binding was found in cells treated with low serum to block the cells in G(1). Cells treated with aphidicolin to block cells at G(1)/S also bound less than cells block in the M-phase. Collectively, these results support a direct correlation between I-12S-PAB binding and proliferative status, and suggest an up-regulation of sigma binding sites prior to mitosis. C1 George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA. NCI, Med Branch, Rockville, MD 20850 USA. RP Zamora, PO (reprint author), George Washington Univ, Med Ctr, Dept Radiol, Ross Hall,Rm 661,2300 I St, Washington, DC 20037 USA. FU NCI NIH HHS [CA58496] NR 24 TC 18 Z9 18 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD SEP 25 PY 1998 VL 63 IS 18 BP 1611 EP 1618 DI 10.1016/S0024-3205(98)00430-5 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 125EQ UT WOS:000076224800004 PM 9806214 ER PT J AU Lenfant, C AF Lenfant, C TI Salt wars SO SCIENCE LA English DT Letter C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Lenfant, C (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 SEP 25 PY 1998 VL 281 IS 5385 BP 1961 EP 1961 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 124BV UT WOS:000076161800023 PM 9767040 ER PT J AU Rosamond, WD Chambless, LE Folsom, AR Cooper, LS Conwill, DE Clegg, L Wang, CH Heiss, G AF Rosamond, WD Chambless, LE Folsom, AR Cooper, LS Conwill, DE Clegg, L Wang, CH Heiss, G TI Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994 SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID COMMUNITY SURVEILLANCE; ALAMEDA COUNTY; RISK-FACTORS; SURVEY MHS; MINNESOTA; DECLINE; EXPERIENCE; MORBIDITY; PROJECT; DEATH AB Background and Methods To clarify the determinants of contemporary trends in mortality from coronary heart disease (CHD), we conducted surveillance of hospital admissions for myocardial infarction and of in-hospital and out-of-hospital deaths due to CHD among 35-to-74-year-old residents of four communities of varying size in the United States (a total of 352,481 persons in 1994). Between 1987 and 1994, we estimate that there were 11,869 hospitalizations for myocardial infarction (on the basis of 8572 hospitalizations sampled) and 3407 fatal coronary events (3023 sampled). Results The largest average annual decrease in mortality due to CHD occurred among white men (change in mortality, -4.7 percent; 95 percent confidence interval, -2.2 to -7.1 percent), followed by white women (-4.5 percent; 95 percent confidence interval, -0.7 to -8.2 percent), black women (-4.1 percent; 95 percent confidence interval, -10.3 to +2.5 percent), and black men (-2.5 percent; 95 percent confidence interval, -6.9 to +2.2 percent). Overall, in-hospital mortality from CHD fell by 5.1 percent per year, whereas out-of-hospital mortality declined by 3.6 percent per year. There was no evidence of a decline in the incidence of hospitalization for a first myocardial infarction among either men or women; in fact, such hospital admissions increased by 7.4 percent per year (95 percent confidence interval, 0.5 to 14.8 percent) among black women and 2.9 percent per year (95 percent confidence interval, -3.6 to +9.9 percent) among black men. Rates of recurrent myocardial infarction decreased, and survival after myocardial infarction improved. Conclusions From 1987 to 1994, we observed a stable or slightly increasing incidence of hospitalization for myocardial infarction. Nevertheless, there were significant annual decreases in mortality from CHD. The decline in mortality in the four communities we studied may be due largely to improvements in the treatment and secondary prevention of myocardial infarction. (N Engl J Med 1998;339:861-7) (C)1998, Massachusetts Medical Society. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC 27599 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Dept Prevent Med, Div Epidemiol, Jackson, MS 39216 USA. RP Rosamond, WD (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, CB 7400,McGavran-Greenberg Hall, Chapel Hill, NC 27599 USA. FU NHLBI NIH HHS [N01-HC-55018, N01-HC-55015, N01-HC-55016] NR 24 TC 558 Z9 578 U1 1 U2 6 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 24 PY 1998 VL 339 IS 13 BP 861 EP 867 DI 10.1056/NEJM199809243391301 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 121VY UT WOS:000076037400001 PM 9744969 ER PT J AU Arioglu, E Doppman, J Gomes, M Kleiner, D Mauro, D Barlow, C Papanicolaou, DA AF Arioglu, E Doppman, J Gomes, M Kleiner, D Mauro, D Barlow, C Papanicolaou, DA TI Cushing's syndrome caused by corticotropin secretion by pulmonary tumorlets SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Diabet Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Radiol, Bethesda, MD USA. Georgetown Univ Hosp, Dept Thorac & Cardiovasc Surg, Washington, DC 20007 USA. NCI, Dept Pathol, Bethesda, MD USA. Natl Human Genome Res Inst, Lab Genet Dis Res, Bethesda, MD USA. RP Papanicolaou, DA (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10,Rm 10N262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. OI Oral, Elif/0000-0002-9171-1144; Kleiner, David/0000-0003-3442-4453 NR 10 TC 30 Z9 31 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 24 PY 1998 VL 339 IS 13 BP 883 EP 886 DI 10.1056/NEJM199809243391304 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 121VY UT WOS:000076037400004 PM 9744972 ER PT J AU Levy, D Thom, TJ AF Levy, D Thom, TJ TI Death rates from coronary disease - Progress and a puzzling paradox SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEART-DISEASE; RISK-FACTORS; TRENDS; MORTALITY C1 NHLBI, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. RP Levy, D (reprint author), NHLBI, Framingham, MA 01702 USA. NR 16 TC 56 Z9 56 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 24 PY 1998 VL 339 IS 13 BP 915 EP 917 DI 10.1056/NEJM199809243391309 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 121VY UT WOS:000076037400009 PM 9744977 ER PT J AU Burstein, ES Hesterberg, DJ Gutkind, JS Brann, MR Currier, EA Messier, TL AF Burstein, ES Hesterberg, DJ Gutkind, JS Brann, MR Currier, EA Messier, TL TI The ras-related GTPase rac1 regulates a proliferative pathway selectively utilized by G-protein coupled receptors SO ONCOGENE LA English DT Article DE rac; ras; G-protein coupled receptor; tyrosine kinase linked receptor; JAK/STAT linked receptor ID NIH 3T3 CELLS; HETEROTRIMERIC G-PROTEINS; KINASE KINASE KINASE; C-JUN; MUSCARINIC RECEPTORS; SIGNALING PATHWAY; BINDING PROTEINS; TYROSINE PHOSPHORYLATION; ALPHA-SUBUNIT; HA-RAS AB Ras and rac are each members of the superfamily of monomeric GTPases and both function as molecular switches to link cell-surface signals to intracellular responses. Using a novel assay of cellular proliferation called R-SAT(TM) (Receptor Selection and Amplification Technology), we examined the roles of ras and rac in mediating the proliferative responses to a variety of cell-surface receptors, Activated, wild-type and dominant-negative mutants of rac and ras were tested for their effects on cellular proliferation either alone or in combination with receptors, Activated rac (rac Q61L, henceforth rac*) and ras (ras G12V, henceforth ras*) each induced strong proliferative responses. Dominant-negative rac (rac T17N, henceforth rac(-)) dramatically suppressed proliferative responses to G-protein coupled receptors (GPCR's) including the m5 muscarinic receptor and the alpha 1B adrenergic receptor. In contrast, rac(-) had little or no effect upon responses to the tyrosine kinase receptor TrkC, and only partially suppressed responses to the Janus kinase (JAK/STAT) linked granulocyte macrophage colony stimulating factor (GM-CSF) receptor. Dominant-negative ras (ras T17N, henceforth ras(-)) blocked the proliferative responses to all of the tested receptors, Compared to rac(-) and ras(-), wild-type rac and ras had only modest effects on the tested receptors, Overall these results demonstrate that rac mediates the proliferative effects of G-protein coupled receptors through a pathway that is distinct from the proliferative signaling pathway utilized by tyrosine kinase linked and JAK-linked receptors. C1 ACADIA Pharmaceut Inc, San Diego, CA 92121 USA. NIDR, Mol Signaling Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Burstein, ES (reprint author), ACADIA Pharmaceut Inc, 3911 Sorrento Valley Blvd, San Diego, CA 92121 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 58 TC 21 Z9 21 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 24 PY 1998 VL 17 IS 12 BP 1617 EP 1623 DI 10.1038/sj.onc.1202067 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 122UM UT WOS:000076089900014 PM 9794239 ER PT J AU Coxon, AB Ward, JM Geradts, J Otterson, GA Zajac-Kaye, M Kaye, FJ AF Coxon, AB Ward, JM Geradts, J Otterson, GA Zajac-Kaye, M Kaye, FJ TI RET cooperates with RB/p53 inactivation in a somatic multi-step model for murine thyroid cancer SO ONCOGENE LA English DT Article DE mouse model; p53; RB; Ret; thyroid cancer ID GERMLINE MUTATIONS; MICE; RB; TUMORS; SYSTEM; P53 AB Mice bred to carry germline Rb and p53 null alleles are associated with a tumor spectrum that overlaps with the inherited multiple endocrine neoplasia-1 (MEN1) and MEN2 syndromes in humans, including medullary thyroid cancer (MTC). To study the genetic basis for these tumors, we microdissected MTC specimens or obtained fresh MTC tissue from nine independent Rb+/- p53(+/-) mice, amplified the region of the Ret gene known to be mutated in human MTC, and detected acquired missense Ret mutations in four different mice, These mutations were Localized to a group of tandem cysteines which are analogous to activating germline mutations observed in human MEN2A and familial MTC (FMTC), To determine whether the remaining wild type Rb allele was inactivated in these murine MTC samples, we subjected tumor tissue to immunohistochemical staining with an Rb antibody, and demonstrated the absence of RE staining in murine MTC, while normal tissue retained RE nuclear staining. These findings demonstrate the ability of the gene knockout model to recapitulate somatic multi-step tumorigenesis and suggest that the development of a murine neuroendocrine tumor requires mutational dysregulation within both receptor tyrosine kinase and nuclear tumor suppressor gene pathways. C1 NCI, Dept Genet, Bethesda, MD 20889 USA. Natl Naval Med Ctr, Bethesda, MD 20889 USA. Div Basic Sci, Anim Sci Branch, Vet & Tumor Pathol Sect, Frederick, MD 21702 USA. Univ N Carolina, Dept Lab Med & Pathol, Chapel Hill, NC 27599 USA. RP Kaye, FJ (reprint author), Naval Hosp, NCI, Bldg 8-Rm 5101, Bethesda, MD 20889 USA. RI kaye, frederic/E-2437-2011 NR 12 TC 32 Z9 32 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 24 PY 1998 VL 17 IS 12 BP 1625 EP 1628 DI 10.1038/sj.onc.1202381 PG 4 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 122UM UT WOS:000076089900015 PM 9794240 ER PT J AU Zhang, J Yergey, A Kowalak, J Kovac, P AF Zhang, J Yergey, A Kowalak, J Kovac, P TI Linking carbohydrates to proteins using N-(2,2-dimethoxyethyl)-6-hydroxy hexanamide SO TETRAHEDRON LA English DT Article DE neoglycoconjugate; reductive amination; antigen; Vibrio cholerae ID O-SPECIFIC ANTIGEN; METHYL ALPHA-GLYCOSIDES; REDUCTIVE AMINATION; BLOCK SYNTHESIS; SEROTYPE-OGAWA; POLYSACCHARIDE; OLIGOSACCHARIDES; TRISACCHARIDE; DISACCHARIDE; PENTASACCHARIDE AB The title dimethyl acetal 4 and related compounds can be efficiently synthesized by treatment of 6-caprolactone with commercially available dialkyl acetals. Conventional glucosylation using 4 as a glycosyl acceptor gave mainly beta-glycosides which were deprotected to give 13. The latter was converted to the corresponding aldehyde 16, which was used as a hapten in conjugation, by reductive amination, to chicken serum albumin (CSA). Effect of reaction time, concentration and molar ratio of hapten 16 to the number of L-lysine residue in CSA upon incorporation of the hapten was studied using MALDI-TOF spectrometry. High loading of CSA with hapten, up to 22 moles of 16/CSA, could be achieved with 32% efficiency of utilization of the hapten. A glycoconjugate from a derivative, analogous to 16, of the monosaccharide determinant of the O-PS of Vibrio cholerae O:1, serotype Ogawa and CSA was also prepared. The achieved incorporation of the Vibrio cholerae hapten was in remarkable agreement with the value expected, based on the study with the D-glucose derivative. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, Med Chem Lab, NIH, 8 Ctr Dr, Bethesda, MD 20892 USA. NR 31 TC 16 Z9 17 U1 0 U2 4 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 SEP 24 PY 1998 VL 54 IS 39 BP 11783 EP 11792 DI 10.1016/S0040-4020(98)00723-6 PG 10 WC Chemistry, Organic SC Chemistry GA 117GA UT WOS:000075771500007 ER PT J AU Wyszynski, DF Zeiger, J Tilli, MT Bailey-Wilson, JE Beaty, TH AF Wyszynski, DF Zeiger, J Tilli, MT Bailey-Wilson, JE Beaty, TH TI Survey of genetic counselors and clinical geneticists regarding recurrence risks for families with nonsyndromic cleft lip with or without cleft palate SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE cleft lip; cleft palate; oral clefts; genetic counseling; epidemiology; birth defects; congenital malformations ID BIRTH-DEFECTS; ORAL CLEFT; FOLLOW-UP; PROBANDS; TWINS AB Nonsyndromic cleft lip with or without cleft palate (CL/P) is a common congenital malformation affecting about 1/1,000 caucasian infants. Although the familial clustering of CLIP has been studied thoroughly, estimation of recurrence risk for genetic counseling purposes can be difficult, A survey was mailed to 912 board-certified genetic counselors, 542 non-board-certified genetic counselors, and 776 board-certified clinical geneticists to investigate the recurrence risks they would assign to three example families with CL/P, Responses were received from 155 (17%) board-certified genetic counselors, 36 (6.6%) non-board-certified genetic counselors, and 100 (18.5%) board-certified clinical geneticists, No major differences were found in their responses, suggesting that for these three families, geneticists would provide similar estimates of risk, regardless of their amount of experience with oral clefts patients, where they are currently employed, or their board certification status. (C) 1998 Wiley-Liss, Inc. C1 Univ Buenos Aires, Sch Med, Dept Publ Hlth, RA-1428 Buenos Aires, DF, Argentina. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD 21218 USA. NIH, Natl Human Genome Res Inst, Med Genet Branch, Baltimore, MD USA. Western Maryland Coll, Westminster, MD 21157 USA. RP Wyszynski, DF (reprint author), Univ Buenos Aires, Sch Med, Dept Publ Hlth, Conde 1972 1B, RA-1428 Buenos Aires, DF, Argentina. OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU NIDCR NIH HHS [D01-DE10293] NR 32 TC 7 Z9 7 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 23 PY 1998 VL 79 IS 3 BP 184 EP 190 DI 10.1002/(SICI)1096-8628(19980923)79:3<184::AID-AJMG6>3.0.CO;2-N PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 122HC UT WOS:000076065100006 PM 9788558 ER PT J AU Stratakis, CA Lin, JP Rennert, OM AF Stratakis, CA Lin, JP Rennert, OM TI Description of a large kindred with autosomal dominant inheritance of branchial arch anomalies, hearing loss, and ear pits, and exclusion of the branchio-oto-renal (BOR) syndrome gene locus (chromosome 8q13.3) SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE BOR syndrome; branchial arch anomalies; hearing loss; ear pits; chromosome 8q ID BRANCHIOOCULOFACIAL SYNDROME; LINKAGE ANALYSIS; REGION; DELETION; PATIENT; DEFECTS; FAMILY; EYA1; 8Q AB It has been suggested that branchio-oculo-facial (BOF) syndrome, deafness with ear pits, and associated conditions [MIM nos. 125100, 120502], and branchio-oto-renal (BOR) [MIM no. 113650] or Melnick-Fraser syndrome represent phenotypic variants of the BOR syndrome, which is inherited in an autosomal dominant (AD) manner and has variable clinical expression. Recently, the BOR gene was mapped to chromosome region 8q13.3 and its sequence was identified as the human homolog of the Drosophila eyes absent (EYA1) gene. We studied an extended family with AD inheritance of branchial arch anomalies (BAA), hearing loss, and ear pits, whose phenotype differed from that of patients with BOR in that none of the affected members had renal abnormalities or lacrimal duct stenosis, Fifteen affected members were studied; ear pits were present in all of them, whereas hearing loss and other BAA mere present in 40 and 20%, respectively, Blood was collected from 31 patients; DNA was extracted by standard methods and amplified using primers from microsatellite sequences flanking the BOR locus on chromosome 8q13.3 (D8S1807, D8S530, and D8S543). Linkage analysis was performed under two models of AD inheritance with different penetrance: 100% and 80%, In both cases, the logarithm of odds (LOD) scores produced were significantly less than -2; exclusion of the 8q13.3 locus was also confirmed by multipoint LOD score analysis. We conclude that, in one large family with AD inheritance of BAA, hearing loss and ear pits, the BOR locus was excluded. This represents the first documentation of heterogeneity in branchio-oto anomalies, syndromes with phenotypes similar to BOR syndrome. (C) 1998 Wiley-Liss, Inc. C1 NICHHD, UGEN, SPE, DEB,NIH, Bethesda, MD 20892 USA. NIAMSD, Sect Genet Studies, Skin Biol Lab, NIH, Bethesda, MD 20205 USA. Georgetown Univ, Childrens Med Ctr, Dept Pediat, Div Genet, Washington, DC 20007 USA. RP Stratakis, CA (reprint author), NICHHD, UGEN, SPE, DEB,NIH, Bldg 10,Room 10 N 262,10 Ctr Dr,MSC 1862, Bethesda, MD 20892 USA. EM stratakc@cc1.nichd.nih.gov NR 36 TC 25 Z9 26 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 SEP 23 PY 1998 VL 79 IS 3 BP 209 EP 214 DI 10.1002/(SICI)1096-8628(19980923)79:3<209::AID-AJMG12>3.0.CO;2-L PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 122HC UT WOS:000076065100012 PM 9788564 ER PT J AU Srinivasan, J Cheatham, TE Cieplak, P Kollman, PA Case, DA AF Srinivasan, J Cheatham, TE Cieplak, P Kollman, PA Case, DA TI Continuum solvent studies of the stability of DNA, RNA, and phosphoramidate - DNA helices SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; SECONDARY STRUCTURE FORMATION; FREE-ENERGY DETERMINANTS; POISSON-BOLTZMANN EQUATION; PARTICLE MESH EWALD; B-DNA; A-DNA; DIELECTRIC MEDIUM; AQUEOUS-SOLUTIONS; MODELS AB We apply continuum solvent models to investigate the relative stability of A- and B-form helices for three DNA sequences, d(CCAACGTTGG)(2), d(ACCCGCGGGT)(2), and d(CGCGAATTCGCG)(2), a phosphoramidate-modified DNA duplex, p(CGCGAATTCGCG)(2), in which the O3' atom in deoxyribose is replaced with NH, and an RNA duplex, r(CCAACGUUGG)(2). Structures were taken as snapshots from multi-nanosecond molecular dynamics simulations computed in a consistent fashion using explicit solvent and with long-range electrostatics accounted for using the particle-mesh Ewald procedure. The electrostatic contribution to solvation energies were computed using both a finite-difference Poisson-Boltzmann (PB) model and a pairwise generalized Born model; nonelectrostatic contributions were estimated with a surface-area-dependent term. To these solvation free energies were added the mean solute internal energies (determined from a molecular mechanics potential) and estimates of the solute entropy (from a harmonic analysis). Consistent with experiment, the relative energies favor B-form helices for DNA and A-form helices for the NP-modified system and for RNA. Salt effects, modeled at the linear or nonlinear PB level, favor the A-form helices by modest amounts; for d(ACCCGCGGGT)(2), salt is nearly able to switch the conformational preference to "A''. The results provide a physical interpretation for the origins of the relative stabilities of A- and B-helices and suggest that similar analyses might be useful in a variety of nucleic acid conformational problems. C1 Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Univ Warsaw, Dept Chem, PL-02093 Warsaw, Poland. NIH, Div Comp Res & Technol, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. RP Case, DA (reprint author), Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. NR 47 TC 946 Z9 955 U1 6 U2 105 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 SEP 23 PY 1998 VL 120 IS 37 BP 9401 EP 9409 DI 10.1021/ja981844+ PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 123GJ UT WOS:000076117200001 ER PT J AU Balagopalakrishna, C Abugo, OO Horsky, J Manoharan, PT Nagababu, E Rifkind, JM AF Balagopalakrishna, C Abugo, OO Horsky, J Manoharan, PT Nagababu, E Rifkind, JM TI Superoxide produced in the heme pocket of the beta-chain of hemoglobin reacts with the beta-93 cysteine to produce a thiyl radical SO BIOCHEMISTRY LA English DT Article ID INTRAMOLECULAR ELECTRON-TRANSFER; S-NITROSOHEMOGLOBIN; HORSE HEMOGLOBIN; CYTOCHROME-C; OXIDATION; MECHANISM; OXYGEN; AUTOXIDATION; COPPER; METHEMOGLOBIN AB The role of the beta-93 cysteine residue in the hemoglobin autoxidation process has been delineated by electron paramagnetic resonance. At low temperatures (8 K) after incubation at 235 K, free radical signals were detected. An analysis of the free radical spectrum produced implies that, besides the superoxide radical expected to be formed during autoxidation, an isotropic free radical is produced with a g(iso) of 2.0133. This g value is consistent with that expected for a sulfur radical. Blocking the beta-93 sulfhydryl group with N-ethylmaleimide was found to eliminate the formation of the isotropic radical, but not the superoxide. This finding confirms the assignment of the isotropic radical as a thiyl radical originating from the oxidation of the cysteine SH group. A kinetic analysis of the time course for the formation of both the superoxide and thiyl radicals is consistent with a reversible electron transfer process between superoxide in the heme pocket of the beta-chains and the cysteine residue. This reaction is expected to produce both a thiyl radical and a peroxide. Direct evidence for peroxide production comes from the detection of a transient Fe(III) heme peroxide complex. The significance of the electron transfer process producing a thiyl radical is discussed. It is shown that the formation of the thiyl radical decreases the rate of autoxidation for the beta-chain and reduces heme degradation attributed to the reaction of superoxide with the heme. The insights gained from these low-temperature studies are believed to be relevant to room-temperature autoxidation. C1 NIA, Mol Dynam Sect, Cellular & Mol Biol Lab, Gerontol Res Ctr,NIH, Baltimore, MD 21224 USA. Indian Inst Technol, Dept Chem, Reg Sophisticated Instrumentat Ctr, Madras 600036, Tamil Nadu, India. RP Balagopalakrishna, C (reprint author), NIA, Mol Dynam Sect, Cellular & Mol Biol Lab, Gerontol Res Ctr,NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Horsky, Jiri/G-3442-2014 NR 48 TC 46 Z9 46 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 22 PY 1998 VL 37 IS 38 BP 13194 EP 13202 DI 10.1021/bi980941c PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 122TU UT WOS:000076088200018 PM 9748326 ER PT J AU Tawa, GJ Topol, IA Burt, SK Caldwell, RA Rashin, AA AF Tawa, GJ Topol, IA Burt, SK Caldwell, RA Rashin, AA TI Calculation of the aqueous solvation free energy of the proton SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID DENSITY-FUNCTIONAL THEORY; BOUNDARY-ELEMENT METHOD; SMALL WATER CLUSTERS; MOLECULAR-INTERACTIONS; AB-INITIO; VIBRATIONAL-SPECTRA; DIELECTRIC MODEL; EXCHANGE-ENERGY; CONTINUUM MODEL; DIPOLE-MOMENT AB The value of the proton hydration free energy, Delta G(hyd)(H+) has been quoted in the literature to be from -252.6 to -262.5 kcal/mol. In this article, we present a theoretical model for calculating the hydration free energy of ions in aqueous solvent and use this model to calculate the proton hydration free energy, Delta G(hyd)(H+), in an effort to resolve the uncertainty concerning its exact value. In the model we define Delta G(hyd)(H+) as the free energy change associated with the following process: Delta G[H+(gas)+ H2nOn(aq)-->H+(H2nOn)(aq)], where the solvent is represented by a neutral n-water cluster embedded in a dielectric continuum and the solvated proton is represented by a protonated n-water cluster also in the continuum. All solvated species are treated as quantum mechanical solutes coupled to a dielectric continuum using a self consistent reaction field cycle. We investigated the behavior of Delta G(hyd)(H+) as the number of explicit waters of hydration is increased from n = 1 to n = 6. As n increases from 1 to 3, the hydration foe energy decreases dramatically. However, for n = 4-6 the hydration foe energy maintains a relatively constant value of -262.23 kcal/mol. These results indicate that the first hydration shell of the proton is composed of at least four water molecules, The constant value of the hydration free energy for n greater than or equal to 4 strongly suggests that the proton hydration free energy is at the far lower end of the range of values that have been proposed in the literature. (C) 1998 American Institute of Physics. C1 NCI, Frederick Canc Res & Dev Ctr, Frederick Biomed Supercomp Ctr, SAIC Frederick, Frederick, MD 21702 USA. Univ Texas, Dept Chem, Richardson, TX 75083 USA. BioChemComp Inc, Teaneck, NJ 07666 USA. RP Tawa, GJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, Frederick Biomed Supercomp Ctr, SAIC Frederick, POB B, Frederick, MD 21702 USA. EM tawa@nciferf.gov NR 91 TC 230 Z9 230 U1 0 U2 25 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 SEP 22 PY 1998 VL 109 IS 12 BP 4852 EP 4863 DI 10.1063/1.477096 PG 12 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 122CY UT WOS:000076054500017 ER PT J AU Kloczkowski, A Jernigan, RL AF Kloczkowski, A Jernigan, RL TI Transfer matrix method for enumeration ansi generation of compact self-avoiding walks. 1. Square lattices SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID GLOBULAR-PROTEINS; CONFORMATIONS; COPOLYMERS; POLYMERS; SEQUENCE AB The transfer matrix method has been developed to enumerate and generate compact self-avoiding walks in two dimensions on the square lattice within rectangular strips of size m x n. The method is significantly superior to the traditional method of computer generation of self-avoiding walks, because it is attrition-free, i.e., each computation leads to successful conformations, with no failures. The method is generalized to irregular shapes, and the extension of the method to the Monte Carlo sampling of the compact conformational space is proposed. Application of this new method to protein conformation generation is discussed, with the possibility of including several types of constraints. (C) 1998 American Institute of Physics. C1 NCI, Mol Struct Sect, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Kloczkowski, A (reprint author), NCI, Mol Struct Sect, Lab Expt & Computat Biol, NIH, Bldg 12B,Room B116,MSC 5677, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012; Kloczkowski, Andrzej/B-9868-2012 NR 29 TC 20 Z9 20 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 22 PY 1998 VL 109 IS 12 BP 5134 EP 5146 DI 10.1063/1.477128 PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 122CY UT WOS:000076054500049 ER PT J AU Kloczkowski, A Jernigan, RL AF Kloczkowski, A Jernigan, RL TI Transfer matrix method for enumeration and generation of compact self-avoiding walks. II. Cubic lattice SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID CONFORMATIONS; COPOLYMERS; SEQUENCE; PROTEINS AB The transfer matrix method, developed earlier for the 2D square lattice has been generalized to enumerate and generate self-avoiding walks (chains with two ends) and self-avoiding circuits (no ends) in 3D on the cubic lattice. The method has been applied to Hamiltonian paths and circuits within simple geometries, i.e., parallelepipeds of size l x m x n for varying integer numbers l, m, n. The generalization of the method to irregular shapes has also been discussed, We also discussed an extension of this new method to permit random sampling of the conformational space. (C) 1998 American Institute of Physics. C1 NCI, Mol Struct Sect, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. RP Kloczkowski, A (reprint author), NCI, Mol Struct Sect, Lab Expt & Computat Biol, NIH, Bldg 12B,Room B116,MSC 5677, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012; Kloczkowski, Andrzej/B-9868-2012 NR 12 TC 15 Z9 15 U1 0 U2 4 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD SEP 22 PY 1998 VL 109 IS 12 BP 5147 EP 5159 DI 10.1063/1.477129 PG 13 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 122CY UT WOS:000076054500050 ER PT J AU Ploug, T van Deurs, B Ai, H Cushman, SW Ralston, E AF Ploug, T van Deurs, B Ai, H Cushman, SW Ralston, E TI Analysis of GLUT4 distribution in whole skeletal muscle fibers: Identification of distinct storage compartments that are recruited by insulin and muscle contractions SO JOURNAL OF CELL BIOLOGY LA English DT Article DE membrane trafficking; glucose transport; endosomes; exercise; diabetes ID GLUCOSE-TRANSPORTER GLUT4; TRANS-GOLGI NETWORK; PLASMA-MEMBRANE; INTRACELLULAR GLUT4; CELL-SURFACE; APPARENT TRANSLOCATION; TRANSFERRIN RECEPTOR; POTENTIAL MECHANISM; 3T3-L1 ADIPOCYTES; RAT AB The effects of insulin stimulation and muscle contractions on the subcellular distribution of GLUT4 in skeletal muscle have been studied on a preparation of single whole fibers from the rat soleus. The fibers were labeled for GLUT4 by a preembedding technique and observed as whole mounts by immunofluorescence microscopy, or after sectioning, by immunogold electron microscopy. The advantage of this preparation for cells of the size of muscle fibers is that it provides global views of the staining from one end of a fiber to the other and from one side to the other through the core of the fiber. In addition, the labeling efficiency is much higher than can be obtained with ultracryosections. In nonstimulated fibers, GLUT4 is excluded from the plasma membrane and T tubules. It is distributed throughout the muscle fibers with similar to 23% associated with large structures including multivesicular endosomes located in the TGN region, and 77% with small tubulovesicular structures. The two stimuli cause translocation of GLUT4 to both plasma membrane and T tubules. Quantitation of the immunogold electron microscopy shows that the effects of insulin and contraction are additive and that each stimulus recruits GLUT4 from both large and small depots. Immunofluorescence double labeling for GLUT4 and transferrin receptor (TfR) shows that the small depots can be further subdivided into TfR-positive and TfR-negative elements. Interestingly, we observe that colocalization of TfR and GLUT4 is increased by insulin and decreased by contractions. These results, supported by subcellular fractionation experiments, suggest that TfR-positive depots are only recruited by contractions. We do not find evidence for stimulation-induced unmasking of resident surface membrane GLUT4 transporters or for dilation of the T tubule system (Wang, W., P.A. Hansen, B.A. Marshall, J.O. Holloszy, and M. Mueckler. 1996. J. Cell Biol, 135:415-430). C1 Univ Copenhagen, Panum Inst, Dept Med Physiol, DK-2200 Copenhagen N, Denmark. Univ Copenhagen, Panum Inst, Dept Med Anat, Struct Cell Biol Unit, DK-2200 Copenhagen N, Denmark. Rigshosp, Copenhagen Muscle Res Ctr, DK-2200 Copenhagen N, Denmark. NIDDKD, Diabet Branch, Expt Diabet Metab & Nutr Sect, NIH, Bethesda, MD 20892 USA. NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Ploug, T (reprint author), Univ Copenhagen, Panum Inst, Dept Med Physiol, Blegdamsvej 3C, DK-2200 Copenhagen N, Denmark. EM t.ploug@mfi.ku.dk NR 66 TC 183 Z9 192 U1 0 U2 5 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 SEP 21 PY 1998 VL 142 IS 6 BP 1429 EP 1446 DI 10.1083/jcb.142.6.1429 PG 18 WC Cell Biology SC Cell Biology GA 123GA UT WOS:000076116400004 PM 9744875 ER PT J AU Porgador, A Irvine, KR Iwasaki, A Barber, BH Restifo, NP Germain, RN AF Porgador, A Irvine, KR Iwasaki, A Barber, BH Restifo, NP Germain, RN TI Predominant role for directly transfected dendritic cells in antigen presentation to CD8(+)T cells after gene gun immunization SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE dendritic cells; DNA immunization; cytotoxic T lymphocytes; gene gun; antigen presentation ID CYTOTOXIC T-LYMPHOCYTES; MARROW-DERIVED CELLS; NAKED PLASMID DNA; VIRAL PROTEIN; LYMPH-NODES; EXPRESSION; INDUCTION; VACCINES; INVIVO; PROTECTION AB Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes (LNs). Under these conditions, two possible modes of DC antigen presentation to naive CD8(+) T cells might exist: (a) presentation directly by gene-transfected DC trafficking to local lymph nodes, and (b) cross-presentation by untransfected DC of antigen released from or associated with transfected epidermal cells. The relative contributions of these distinct modes of antigen presentation to priming for cytotoxic T cell (CTL) responses have not been clearly established. Here we show that LN cells directly expressing the DNA-encoded antigen are rare; 24 h after five abdominal skin bombardments, the number of these cells does not exceed 50-100 cells in an individual draining LN. However, over this same time period, the total number of CD11c(+) DC increases more than twofold, by an average of 20,000-30,000 DC per major draining node. This augmentation is due to gold bombardment and is independent of the presence of plasmid DNA. Most antigen-bearing cells in the LNs draining the site of DNA delivery appear to be DC and can be depleted by antibodies to an intact surface protein encoded by cotransfected DNA. This finding of predominant antigen presentation by directly transfected cells is also consistent with data from studies on cotransfection with antigen and CD86-encoding DNA, showing that priming of anti-mutant influenza nucleoprotein CTLs with a single immunization is dependent upon coexpression of the DNAs encoding nucleoprotein and B7.2 in the same cells. These observations provide insight into the relative roles of direct gene expression and cross-presentation in CD8+ T cell priming using gene gun immunization, and indicate that augmentation of direct DC gene expression may enhance such priming. C1 NIAID, Immunol Lab, Lymphocyte Biol Sect, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Immunol, Toronto, ON M5S 1A8, Canada. RP Germain, RN (reprint author), Immunol Lab, Bldg 10,Rm 11N311,10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 37 TC 401 Z9 414 U1 0 U2 9 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 SEP 21 PY 1998 VL 188 IS 6 BP 1075 EP 1082 DI 10.1084/jem.188.6.1075 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 123EK UT WOS:000076112700008 PM 9743526 ER PT J AU Wyatt, RJ Karoum, F Masserano, J AF Wyatt, RJ Karoum, F Masserano, J TI Effects of antipsychotics, vitamin E, and MK-801 on dopamine dynamics in the rat brain following discontinuation of cocaine SO PSYCHIATRY RESEARCH LA English DT Review DE schizophrenia; cocaine; haloperidol; clozapine; vitamin E; DOPAC ID VENTRAL TEGMENTAL AREA; FREE-RADICAL MECHANISMS; CENTRAL-NERVOUS-SYSTEM; LONG-TERM REDUCTION; FRONTAL-CORTEX; NUCLEUS-ACCUMBENS; BEHAVIORAL SENSITIZATION; EXTRACELLULAR DOPAMINE; PREFRONTAL CORTEX; METHAMPHETAMINE PSYCHOSIS AB Cocaine, 10 mg/kg, I.P., twice daily, was given to rats for 1 week. At 1 and 4 weeks following discontinuation of cocaine, the initial rate of 3,4-dihydroxyphenylacetic acid (DOPAC) formation was assessed. The initial rate of DOPAC formation was found to be decreased in the frontal and cingulate cortices at 1 week, but was only decreased in the frontal cortex at 4 weeks. When administered in conjunction with cocaine, haloperidol, clozapine, and vitamin E, but not MK-801, were found to prevent cocaine's effects. In addition to the potential value these findings have for further understanding cocaine abuse, it is proposed that the alteration in dopamine metabolism produced by cocaine, and the ability of haloperidol, clozapine and vitamin E to decrease cocaine's effects, model some biochemical aspects of schizophrenia. Published by Elsevier Science Ireland Ltd. C1 NIMH, Neuropsychiat Branch, Intramural Res Program, Washington, DC 20032 USA. RP NIMH, Neuropsychiat Branch, Intramural Res Program, 2700 Martin Luther King Jr Ave SE,Room 536, Washington, DC 20032 USA. EM wyattr@dirpc.nimh.nih.gov NR 101 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD SEP 21 PY 1998 VL 80 IS 3 BP 213 EP 225 DI 10.1016/S0165-1781(98)00080-8 PG 13 WC Psychiatry SC Psychiatry GA 128JK UT WOS:000076402500002 PM 9796937 ER PT J AU Scott, DE Golding, H Huang, LY Inman, J Golding, B AF Scott, DE Golding, H Huang, LY Inman, J Golding, B TI HIV peptide conjugated to heat-killed bacteria promotes antiviral responses in immunodeficient mice SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID MHC CLASS-II; CYTOKINE GENE-EXPRESSION; T-CELL RESPONSES; BRUCELLA-ABORTUS; IFN-GAMMA; IMMUNE-RESPONSES; INTERLEUKIN-12 PRODUCTION; ANTIBODY-RESPONSE; ISOTYPE SELECTION; DEFICIENT MICE AB Enhancement of immunity in the setting of HIV infection is difficult owing to loss of functional CD4(+) T cells, The MHC class II-deficient mouse (II-/-) environment simulates that of the immunocompromised HIV-infected individual, since these mice have low CD4(+) T cell numbers, defective CD4-dependent responses, and are susceptible to opportunistic infection. This strain was used to test whether heat-killed Brucella abortus (BA), covalently conjugated to the V3 peptide of HIV-1 (MN), could elicit anti-HIV responses, V3-BA, but not the T-dependent antigen V3-KLH, induced high levels of IL-12, IFN-gamma, and IL-10 mRNA in both wild-type (WT) and II-/- mice within 24 hr of injection. V3-BA-treated, but not V3-KLH-treated, II-/- mice developed serum IgG and IgA anti-V3 antibodies, with IgG(2b) and IgG(3) as the predominant isotype. Viral neutralization studies, using a syncytium inhibition assay, demonstrated that the antibodies generated by V3-BA in II-/- mice were capable of neutralizing HN. These experiments demonstrate that a heat-inactivated bacterium such as BA, when used as a carrier, can generate a cytokine environment that results in the production of neutralizing antiviral antibodies in an immunodeficient host. Such strategies could be important in the development of immunotherapies and vaccines for HIV-1 patients. C1 US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Div Viral Prod, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Scott, DE (reprint author), Bldg 29,Room 232,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 51 TC 9 Z9 9 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 20 PY 1998 VL 14 IS 14 BP 1263 EP 1269 DI 10.1089/aid.1998.14.1263 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 130YB UT WOS:000076547000006 PM 9764910 ER PT J AU Seok, YJ Zhu, PP Koo, BM Peterkofsky, A AF Seok, YJ Zhu, PP Koo, BM Peterkofsky, A TI Autophosphorylation of enzyme I of the Escherichia coli Phosphoenolpyruvate : Sugar phosphotransferase system requires dimerization SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE monomer-dimer transition; phosphotransferase; autophosphorylation ID N-TERMINAL DOMAIN; FLUORESCENCE ANISOTROPY; TRANSPORT; PROTEIN; HPR; IDENTIFICATION; CLONING; BINDING; GLUCOSE; OPERON AB Enzyme I of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system undergoes a slow monomer-dimer transition. In vitro autophosphorylation of Enzyme I by PEP was studied at limiting concentrations of the protein. Addition to incubation mixtures containing wild-type Enzyme I of inactive or low-activity mutant forms of Enzyme I resulted in stimulation of autophosphorylation activity. The kinetics of the activation fit well. to a model in which the active form of Enzyme I is the dimer. These experiments provide support for the argument that only the dimeric form of Enzyme I can be autophosphorylated. (C) 1998 Academic Press. C1 NHLBI, Lab Biochem Genet, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Nat Sci, Dept Microbiol, Seoul 151742, South Korea. RP Peterkofsky, A (reprint author), NHLBI, Lab Biochem Genet, Bldg 36,Room 4C-11, Bethesda, MD 20892 USA. NR 19 TC 19 Z9 19 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 18 PY 1998 VL 250 IS 2 BP 381 EP 384 DI 10.1006/bbrc.1998.9323 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 122TR UT WOS:000076088000034 PM 9753638 ER PT J AU Kim, J Ault, KT Chen, HD Xu, RH Roh, DH Lin, MC Park, MJ Kung, HF AF Kim, J Ault, KT Chen, HD Xu, RH Roh, DH Lin, MC Park, MJ Kung, HF TI Transcriptional regulation of BMP-4 in the Xenopus embryo: Analysis of genomic BMP-4 and its promoter SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID BONE MORPHOGENETIC PROTEIN-4; TGF-BETA FAMILY; HOMEOBOX GENE; DROSOPHILA EMBRYO; VENTRAL MESODERM; NEURAL INDUCTION; MARGINAL ZONE; RECEPTOR; SIGNALS; ORGANIZER AB Recent experiments in the Xenopus embryo suggest that proper regulation of BMP-4 signaling is critical to the dorsal ventral specification of both mesoderm and ectoderm. Regulation of BMP-4 signaling is known to occur extracellularly by direct binding with chordin, noggin, and follistatin, and intracellularly through the antagonistic signal interaction with dorsalizing TGF-beta family member activin. However, the tight repressional regulation of BMP transcription may also be required to sustain the dorsal and neural status of the induced cells. Here we demonstrate that the dominant negative mutant of the BMP receptor (DN-BR) or the BMP-4 antagonizers, chordin and noggin, negatively regulate BMP-4 transcription in animal cap explants. We suggest that repression of BMP-4 transcription is important in the maintenance of dorsal fate and that continuous input of BMP-4 signaling is required to sustain the expression of BMP-4 transcription in the maintenance of epidermal/ventral fate. Consistent with this postulation, we found that the promoter region of the isolated BMP-4 genomic DNA includes several consensus binding sites for transcriptional regulators functioning under BMP-4 signaling such as GATA binding and ventralizing homeobox genes. In a functional assay we found that the GATA binding and ventral homeobox proteins can positively modulate BMP-4 promoter activity. We also observed that DN-BR decreases BMP-4 promoter activity. This was likely due to a repression of the above-mentioned transcription factors. The significance of these observations to embryonic patterning is discussed. C1 NCI, Lab Biochem Physiol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Frederick, MD 21702 USA. NIDDKD, Lab Biochem & Genet, Bethesda, MD 20892 USA. Kyung Pook Natl Univ, Dept Anat, Taegu, South Korea. RP Kung, HF (reprint author), NCI, Lab Biochem Physiol, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NR 46 TC 19 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 18 PY 1998 VL 250 IS 2 BP 516 EP 530 DI 10.1006/bbrc.1998.9280 PG 15 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 122TR UT WOS:000076088000060 PM 9753664 ER PT J AU Rao, VD Misra, S Boronenkov, IV Anderson, RA Hurley, JH AF Rao, VD Misra, S Boronenkov, IV Anderson, RA Hurley, JH TI Structure of type II beta phosphatidylinositol phosphate kinase: A protein kinase fold flattened for interfacial phosphorylation SO CELL LA English DT Article ID MULTIPLE ISOMORPHOUS REPLACEMENT; CATALYTIC SUBUNIT; CRYSTAL-STRUCTURE; PHOSPHOLIPASE-C; INOSITOL TRISPHOSPHATE; DIFFRACTION DATA; 5-KINASE; FAMILY; 3-KINASE; DOMAIN AB Phosphoinositide kinases play central roles in signal transduction by phosphorylating the inositol ring at specific positions. The structure of one such enzyme, type I1 beta phosphatidylinositol phosphate kinase, reveals a protein kinase ATP-binding core and demonstrates that all phosphoinositide kinases belong to one superfamily. The enzyme is a disc-shaped homodimer with a 33 x 48 Angstrom basic flat face that suggests an electrostatic mechanism for plasma membrane targeting. Conserved basic residues form a putative phosphatidylinositol phosphate specificity site. The substrate-binding site is open on one side, consistent with dual specificity for phosphatidylinositol 3- and 5-phosphates. A modeled complex with membrane-bound substrate and ATP shows how a phosphoinositide kinase can phosphorylate its substrate in situ at the membrane interface. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. RP Hurley, JH (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. OI Misra, Saurav/0000-0002-1385-8554 FU NIGMS NIH HHS [GM51968, GM57549] NR 57 TC 163 Z9 167 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD SEP 18 PY 1998 VL 94 IS 6 BP 829 EP 839 DI 10.1016/S0092-8674(00)81741-9 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 121NX UT WOS:000076021200015 PM 9753329 ER PT J AU Lewin, DA Sheff, D Ooi, CE Whitney, JA Yamamoto, E Chicione, LM Webster, P Bonifacino, JS Mellman, I AF Lewin, DA Sheff, D Ooi, CE Whitney, JA Yamamoto, E Chicione, LM Webster, P Bonifacino, JS Mellman, I TI Cloning, expression, and localization of a novel gamma-adaptin-like molecule SO FEBS LETTERS LA English DT Article DE adaptin; adaptor; Golgi; human; mouse ID MANNOSE 6-PHOSPHATE RECEPTORS; CLATHRIN-COATED VESICLES; PROTEIN COMPLEX; GOLGI MEMBRANES; BREFELDIN-A; TRANSPORT; EPS15; AP-3; ENDOCYTOSIS; RECRUITMENT AB We describe the cloning, expression, and localization of gamma(2)-adaptin, a novel isoform of gamma-adaptin. The predicted human and mouse gamma(2)-adaptin proteins are similar to 90 kDa and 64.4% and 61.7% identical to gamma-adaptin, respectively. gamma(2)-Adaptin was localized to the Golgi, its localization distinct from gamma-adaptin. The membrane association of gamma- and gamma(2)-adaptin could further be distinguished by differential sensitivity to the fungal metabolite brefeldin A, gamma(2)-adaptin binding being insensitive to drug treatment, Together, these results suggest that gamma(2)-adaptin plays a role in membrane transport distinct from that played by gamma-adaptin. (C) 1998 Federation of European Biochemical Societies. C1 Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Mellman, I (reprint author), Yale Univ, Sch Med, Dept Cell Biol, POB 208002, New Haven, CT 06520 USA. EM ira.mellman@quickmail.yale.edu RI Sheff, David/A-1269-2007 NR 34 TC 22 Z9 24 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 SEP 18 PY 1998 VL 435 IS 2-3 BP 263 EP 268 DI 10.1016/S0014-5793(98)01083-7 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 123RL UT WOS:000076138100029 PM 9762922 ER PT J AU Benkirane, M Chun, RF Xiao, H Ogryzko, VV Howard, BH Nakatani, Y Jeang, KT AF Benkirane, M Chun, RF Xiao, H Ogryzko, VV Howard, BH Nakatani, Y Jeang, KT TI Activation of integrated provirus requires histone acetyltransferase - p300 AND P/CAF are coactivators for HIV-1 Tat SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA-POLYMERASE-II; NF-KAPPA-B; PROTEINS SPECIFICALLY ASSOCIATE; CARBOXYL-TERMINAL DOMAIN; TRANSCRIPTIONAL ACTIVATION; CELLULAR PROTEIN; IN-VITRO; CHROMATIN STRUCTURE; HUMAN CHROMOSOME-12 AB A unique aspect of the retrovirus life cycle is the obligatory integration of the provirus into host cell chromosomes. Unlike viruses that do not integrate, retroviruses must conserve an ability to activate transcription from a chromatin context. Human immunodeficiency virus (HIV)-1 encodes an unusual and an unusually potent transcriptional transactivator, Tat, which binds to a nascent viral leader RNA, TAR. The action of Tat has been well studied in various reductive model systems; however, the physiological mechanism through which Tat gains access to chromatin-associated proviral long terminal repeats (LTRs) is not understood. We show here that a nuclear histone acetyltransferase activity associates with Tat. Intracellularly, we found that Tat forms a ternary complex with p300 and P/CAF, two histone acetyltransferases (HATs). A murine cell defect in Tat transactivation of the HIV-1 LTR was linked to the reduced abundance of p300 and P/CAF. Thus, overexpression of p300 and P/CAF reconstituted Tat transactivation of the HIV-1 LTR in NIH3T3 cells to a level similar to that observed for human cells. By using transdominant p300 or P/CAF mutants that lack enzymatic activity, we delineated a requirement for the HAT component from the latter but not the former in Tat function. Finally, we observed that Tat-associated HAT is preferentially important for transactivation of integrated, but not unintegrated, HIV-1 LTR. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. IGH, UPR 1142, Montpellier, France. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bldg 4,Rm 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008; Ogryzko, Vasily/M-6665-2015; Chun, Rene/A-9415-2010 OI Ogryzko, Vasily/0000-0002-8548-1389; Chun, Rene/0000-0002-0190-0807 NR 89 TC 214 Z9 216 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 18 PY 1998 VL 273 IS 38 BP 24898 EP 24905 DI 10.1074/jbc.273.38.24898 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121HL UT WOS:000076007300088 PM 9733796 ER PT J AU Park, K Mukhopadhyay, S Chattoraj, DK AF Park, K Mukhopadhyay, S Chattoraj, DK TI Requirements for and regulation of origin opening of plasmid P1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COPY-NUMBER CONTROL; ESCHERICHIA-COLI; DNA-REPLICATION; INITIATOR PROTEIN; NEGATIVE CONTROL; REPA GENE; BINDING; INCOMPATIBILITY; SEQUESTRATION; MAINTENANCE AB Origin opening is essential for the initiation of DNA replication in the theta mode and requires binding of initiator proteins. Using reactivity to KMnO4 in vivo as an assay, we find that, like initiation, origin opening of the Escherichia coli plasmid P1 requires the host initiators DnaA and HU and the plasmid-encoded initiator RepA. The ability to detect opening at the P1ori in vivo allowed us to study this activity at various copy numbers in chimeric replicons, The opening was prevented when the P1ori was cloned in high copy vectors or when excess RepA binding sites (iterons) mere provided in trans. However, when RepA supply was also increased, the opening was efficient. A further increase in RepA prevented opening. Replication of an incoming pi under these conditions correlated with opening. These results demonstrate that initiation is possible even at abnormally high origin concentrations and that oversupply of RepA, relative to iterons, can prevent replication by blocking origin opening. It appears that plasmid overreplication can be prevented either by limiting RepA or by accumulating RepA at a rate higher than that of the origin. C1 NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NCI, Biochem Lab, NIH, 37-4D-18, Bethesda, MD 20892 USA. NR 37 TC 28 Z9 28 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 18 PY 1998 VL 273 IS 38 BP 24906 EP 24911 DI 10.1074/jbc.273.38.24906 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121HL UT WOS:000076007300089 PM 9733797 ER PT J AU Ellis, RJ Seubert, P Motter, R Galasko, D Deutsch, R Heaton, RK Heyes, MP McCutchan, JA Grant, I AF Ellis, RJ Seubert, P Motter, R Galasko, D Deutsch, R Heaton, RK Heyes, MP McCutchan, JA Grant, I CA HIV Neurobehavioral Res Ctr Grp TI Cerebrospinal fluid tau protein is not elevated in HIV-associated neurologic disease in humans SO NEUROSCIENCE LETTERS LA English DT Article DE HIV/AIDS; tau protein; cerebrospinal fluid; neurological disorders; dementia; cerebrospinal fluid markers ID ALZHEIMERS-DISEASE; AIDS AB We measured the concentrations of the neuron-specific protein, tau, in the cerebrospinal fluid (CSF) of 32 neurologically characterized HIV-infected (HIVpos) subjects and nine matched seronegative (HIVneg) controls using a sensitive ELISA assay. Of 32 HIVpos subjects, nine had HIV-associated neurocognitive disorders, and nine had clinically diagnosed peripheral neuropathies. CSF tau levels in subjects with HIV-associated neurocognitive disorders were similar to those in HIVneg subjects (185 +/- 83 vs. 223 +/- 106 pg/ml; P = 57). CSF tau levels in HIVpos subjects with peripheral neuropathies did not differ from those without neuropathies (320 +/- 190 vs. 251 ri: 185; P = 23). In summary, CSF tau levels were not elevated in patients with HIV-associated neurologic disease. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Calif San Diego, HNRC, Dept Neurosci, San Diego, CA 92103 USA. Athena Neurosci Inc, San Francisco, CA USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. RP Ellis, RJ (reprint author), Univ Calif San Diego, HNRC, Dept Neurosci, 2760 5th Ave, San Diego, CA 92103 USA. EM roellis@ucsd.edu RI Ellis, Ronald/K-3543-2015 OI Ellis, Ronald/0000-0003-4931-752X FU NIMH NIH HHS [MH45294] NR 13 TC 18 Z9 18 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 SEP 18 PY 1998 VL 254 IS 1 BP 1 EP 4 DI 10.1016/S0304-3940(98)00549-7 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 122VC UT WOS:000076091300001 PM 9780077 ER PT J AU Cho, CH Bunch, DO Faure, JE Goulding, EH Eddy, EM Primakoff, P Myles, DG AF Cho, CH Bunch, DO Faure, JE Goulding, EH Eddy, EM Primakoff, P Myles, DG TI Fertilization defects in sperm from mice lacking fertilin beta SO SCIENCE LA English DT Article ID DISINTEGRIN DOMAIN; EGG FUSION; SURFACE PROTEIN; POTENTIAL ROLE; CELL-ADHESION; MOUSE EGG; METALLOPROTEASE; MOTILITY; IDENTIFICATION; TRANSPORT AB Fertilin, a member of the ADAM family, is found on the plasma membrane of mammalian sperm. Sperm from mice tacking fertilin beta were shown to be deficient in sperm-egg membrane adhesion, sperm-egg fusion, migration from the uterus into the oviduct, and binding to the egg zona pellucida. Egg activation was unaffected. The results are consistent with a direct role of fertilin in sperm-egg plasma membrane interaction. Fertilin could also have a direct role in sperm-zona binding or oviduct migration; alternatively, the effects on these functions could result from the absence of fertilin activity during spermatogenesis. C1 Univ Calif Davis, Sect Mol & Cellular Biol, Livermore, CA 95616 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Myles, DG (reprint author), Univ Calif Davis, Sect Mol & Cellular Biol, Livermore, CA 95616 USA. EM dgmyles@ucdavis.edu FU NICHD NIH HHS [U54HD29125, HD16580] NR 24 TC 370 Z9 388 U1 1 U2 9 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 SEP 18 PY 1998 VL 281 IS 5384 BP 1857 EP 1859 DI 10.1126/science.281.5384.1857 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 121HK UT WOS:000076007100055 PM 9743500 ER PT J AU Levine, M Daruwala, RC Park, JB Rumsey, SC Wang, YH AF Levine, M Daruwala, RC Park, JB Rumsey, SC Wang, YH TI Does vitamin C have a pro-oxidant effect? SO NATURE LA English DT Letter ID ASCORBIC-ACID; 8-HYDROXYDEOXYGUANOSINE; VOLUNTEERS; DEPLETION C1 NIDDKD, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. RP Levine, M (reprint author), NIDDKD, Mol & Clin Nutr Sect, NIH, Bldg 10,Room 4D 52,MSC 1372, Bethesda, MD 20892 USA. NR 9 TC 37 Z9 39 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 17 PY 1998 VL 395 IS 6699 BP 231 EP 231 DI 10.1038/26137 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120TZ UT WOS:000075974600032 PM 9751048 ER PT J AU Gutkind, JS AF Gutkind, JS TI Cell growth control by G protein-coupled receptors: from signal transduction to signal integration SO ONCOGENE LA English DT Review DE g proteins; g protein-coupled receptors; Ras; MAP kinases; Rho; cell growth ID BETA-GAMMA-SUBUNITS; TERNARY COMPLEX FACTORS; SMOOTH-MUSCLE CELLS; MAP KINASE CASCADE; FACTOR RAS-GRF; CONSTITUTIVELY ACTIVATING MUTATION; INDUCED TYROSINE PHOSPHORYLATION; VAV PROTOONCOGENE PRODUCT; HETEROTRIMERIC G-PROTEIN; SERUM RESPONSE ELEMENT C1 NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP NIDR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 163 TC 198 Z9 202 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 EI 1476-5594 J9 ONCOGENE JI Oncogene PD SEP 17 PY 1998 VL 17 IS 11 SI SI BP 1331 EP 1342 DI 10.1038/sj.onc.1202186 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 124BW UT WOS:000076161900002 PM 9779981 ER PT J AU Campbell, SL Khosravi-Far, R Rossman, KL Clark, GJ Der, CJ AF Campbell, SL Khosravi-Far, R Rossman, KL Clark, GJ Der, CJ TI Increasing complexity of Ras signaling SO ONCOGENE LA English DT Review DE Ras; review; signal transduction; effector; Ras sub-family ID ACTIVATED PROTEIN-KINASE; NUCLEOTIDE DISSOCIATION STIMULATOR; C-HA-RAS; TUMOR-SUPPRESSOR ACTIVITY; RALGDS-RELATED PROTEIN; CYSTEINE-RICH REGION; NIH 3T3 CELLS; MAP KINASE; ONCOGENIC RAS; R-RAS AB The initial discovery that ras genes endowed retroviruses with potent carcinogenic properties and the subsequent determination that mutated ras genes were present in a wide variety of human cancers, prompted a strong suspicion that the growth-promoting actions of mutated Ras proteins contribute to their aberrant regulation of growth stimulatory signaling pathways. In 1993, a remarkable convergence of experimental observations from genetic analyses of Drosophila, S. cerevisiae and C. elegans as well as biochemical and biological studies in mammalian cells came together to define a clear role for Ras in signal transduction, What emerged was an elegant linear signaling pathway where Ras functions as a relay switch that is positioned downstream of cell surface receptor tyrosine kinases and upstream of a cytoplasmic cascade of kinases that included the mitogen-activated protein kinases (MAPKs). Activated MAPKs in turn regulated the activities of nuclear transcription factors. Thus, a signaling cascade where every component between the cell surface and the nucleus was defined and conserved in worms, flies and man. This was a remarkable achievement in our efforts to appreciate how the aberrant function of Ras proteins may contribute to the malignant growth properties of the cancer cell, However, the identification of this pathway has proven to be just the beginning, rather than the culmination, of our understanding of Ras in signal transduction, Instead, we now appreciate that this simple linear pathway represents but a minor component of a very complex signaling circuitry. Ras signaling has emerged to involve a complex array of signaling pathways, where cross-talk, feedback loops, branch points and multi-component signaling complexes are recurring themes. The simplest concept of a signaling cascade, where each component simply relays the same message to the next, is clearly not the case. In this review, we summarize our current understanding of Ras signal transduction with an emphasis on new complexities associated with the recognition and/or activation of cellular effecters, and the diverse array of signaling, pathways mediated by interaction between Ras and Ras-subfamily proteins with multiple effecters. C1 MIT, Dept Biochem & Biophys, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA. NCI, Dept Cell & Cellular Canc Biol, NIH, Rockville, MD 20850 USA. RP Campbell, SL (reprint author), MIT, Dept Biochem & Biophys, Cambridge, MA 02139 USA. RI Khosravi-Far, Roya/C-3789-2008; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [CA42978, CA52072, CA55008] NR 254 TC 808 Z9 827 U1 4 U2 49 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 17 PY 1998 VL 17 IS 11 SI SI BP 1395 EP 1413 DI 10.1038/sj.onc.1202174 PG 19 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 124BW UT WOS:000076161900008 PM 9779987 ER PT J AU Schwartzberg, PL AF Schwartzberg, PL TI The many faces of Src: multiple functions of a prototypical tyrosine kinase SO ONCOGENE LA English DT Review DE Src; tyrosine kinase; PDGF-R; integrin ID FOCAL ADHESION KINASE; EPIDERMAL GROWTH-FACTOR; C-SRC; SH3 DOMAIN; CELL-TRANSFORMATION; BINDING-SITE; PROTEIN; FAMILY; ACTIVATION; PHOSPHORYLATION AB c-src was first isolated as the normal cellular homologue of v-src, the transforming gene of Rous Sarcoma virus (Stehelin et al., 1976). As the first proto-oncogene described and one of the first molecules demonstrated to have tyrosine kinase activity, Src has provided a prototype for understanding signal transduction involving tyrosine phosphorylation. Comparison between c-src and activated or transforming mutants of Src including v-src, combined with recent data on the structure of Src family kinases has provided new insight into their regulation. In this review, I will discuss the function of the various domains of Src in light of these mutational and structural studies. C1 Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), Natl Human Genome Res Inst, Lab Genet Dis Res, NIH, Bethesda, MD 20892 USA. NR 65 TC 116 Z9 118 U1 0 U2 5 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 17 PY 1998 VL 17 IS 11 SI SI BP 1463 EP 1468 DI 10.1038/sj.onc.1202176 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 124BW UT WOS:000076161900013 PM 9779992 ER PT J AU Rajeswaran, WG Cohen, LA AF Rajeswaran, WG Cohen, LA TI Studies on protection of oxindoles SO TETRAHEDRON LA English DT Article ID CONVENIENT METHOD AB Protection of amide nitrogen of oxindole and methyloxindole using Boc and Z-groups has been described. Sodium carbonate was found to be an effective base for these protections. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rajeswaran, WG (reprint author), Tulane Univ, Med Ctr, Dept Med, Peptide Res Labs SL12, 1430 Tulane Ave, New Orleans, LA 70112 USA. NR 8 TC 19 Z9 19 U1 1 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 SEP 17 PY 1998 VL 54 IS 38 BP 11375 EP 11380 DI 10.1016/S0040-4020(98)00679-6 PG 6 WC Chemistry, Organic SC Chemistry GA 117FZ UT WOS:000075771400003 ER PT J AU Kitayama, S Mitsuhata, C Davis, S Wang, JB Sato, T Morita, K Uhl, GR Dohi, T AF Kitayama, S Mitsuhata, C Davis, S Wang, JB Sato, T Morita, K Uhl, GR Dohi, T TI MPP+ toxicity and plasma membrane dopamine transporter: study using cell lines expressing the wild-type and mutant rat dopamine transporters SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE dopamine; transporter; MPP+; Parkinsonism; neurotoxin; efflux ID PARKINSONISM-INDUCING NEUROTOXIN; NEUROTRANSMITTER TRANSPORTERS; SPECIES SENSITIVITY; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYLPYRIDINIUM; SYNAPTOSOMES; METABOLITE; RELEASE; MPTP AB The Parkinsonism-inducing neurotoxin 1-methyl-4-phenylpyridinium (MPP+) causes specific cell death in dopaminergic neurons after accumulation by the dopamine transporter (DAT). COS cells, a non-neuronal cell line insensitive to high doses of MPP+, becomes sensitive to MPP+ when transfected with the rat DAT cDNA. We analyzed the bi-directional transport of MPP+ and its toxicity in several cell lines expressing wild or mutant DATs. Cell death in COS cells expressing wild DAT by exposure to MPP+ was concentration-dependent and cocaine-reversible. Increased wild DAT expression caused higher sensitivities to the toxin in HeLa cells. Although several mutant DA'Ts demonstrated greater transport activity than the wildtype, they displayed similar or lower sensitivity to MPP+ toxicity. Reverse transport of preloaded [H-3]MPP+ through DAT was facilitated in COS cells expressing certain mutant DATs, which consistently displayed less sensitivity to MPP+ toxicity. These results suggest that re-distribution of MPP+ due to influx/efflux turnover through the transporter is a key factor in MPP+ toxicity. 0167-4889/98/$-see front matter (C) 1998 Elsevier Science B.V. All rights reserved. C1 Hiroshima Univ, Sch Dent, Dept Pharmacol, Minami Ku, Hiroshima 734, Japan. NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Kitayama, S (reprint author), Hiroshima Univ, Sch Dent, Dept Pharmacol, Minami Ku, Kasumi 1-2-3, Hiroshima 734, Japan. NR 18 TC 28 Z9 28 U1 0 U2 2 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 SEP 16 PY 1998 VL 1404 IS 3 BP 305 EP 313 DI 10.1016/S0167-4889(98)00071-8 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124NW UT WOS:000076189500004 PM 9739158 ER PT J AU Rosado, JA Salido, GM Jensen, RT Garcia, LJ AF Rosado, JA Salido, GM Jensen, RT Garcia, LJ TI Are tyrosine phosphorylation of p125(FAK) and paxillin or the small GTP binding protein, Rho, needed for CCK-stimulated pancreatic amylase secretion? SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article DE enzyme secretion; Rho; tyrosine kinase; PKC; small GTP binding protein ID BOTULINUM C3 EXOENZYME; FOCAL ADHESION KINASE; SWISS 3T3 CELLS; ADP-RIBOSYLTRANSFERASE; MAST-CELLS; ACTIN CYTOSKELETON; PHOSPHOLIPASE-C; ACINAR-CELLS; GENE-PRODUCT; CHOLECYSTOKININ AB Studies of a possible role of tyrosine phosphorylation in the secretory process in rat pancreatic acinar cells provide conflicting conclusions. Recent studies show that tyrosine phosphorylation of the focal adhesion kinase, p125(FAK) and the cytoskeletal protein, paxillin. may mediate a number of cellular changes and this phosphorylation is dependent on the activation of the small GTP binding protein, p21(Rho) (Rho). In this work we have investigated the role of tyrosine phosphorylation of each of these proteins and of the activation of Rho in pancreatic enzyme secretion. Pretreatment with genistein, a tyrosine kinase inhibitor, decreased CCK-8-stimulated tyrosine phosphorylation of p125(FAK) and paxillin and CCK-8-stimulated amylase secretion by more than 60%, raising the possibility that tyrosine phosphorylation of these two proteins could be important in the ability of CCK-8 to stimulate amylase release. However, genistein did not alter the amylase release stimulated by TPA but inhibited TPA-stimulated p125(FAK) and paxillin tyrosine phosphorylation by 70%. Pretreatment with C3 transferase, which specifically inactivates Rho, causes a decrease in CCK-8-induced maximal amylase release by 33%. Moreover, C3 transferase pretreatment causes a 48% and a 38% decrease in the tyrosine phosphorylation of p125(FAK) and paxillin by CCR-8, respectively. Pretreat-ment with different concentrations of cytochalasin D, an actin cytoskeleton assembly inhibitor, completely inhibited CCK-8-stimulated tyrosine phosphorylation of p125(FAK) and paxillin without having any effect on either the potency or efficacy of CCK-8 at stimulating amylase release. Furthermore, cytochalasin D completely inhibited TPA-stimulated tyrosine phosphorylation of both proteins without affecting TPA-stimulated amylase release. These results show that tyrosine phosphorylation of p125(FAK) and paxillin is not required for CCK-8 stimulation of enzyme secretion. However, our results suggest Rho is involved in the CCK-S stimulation of amylase release by a parallel pathway to its involvement in the CCK-8-stimulated tyrosine phosphorylation of p125(FAK) and paxillin. 0167-4889/98/$ - see front matter (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Extremadura, Dept Physiol, Caceres 10071, Spain. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA. RI Salido, Gines/A-4292-2009; Garcia-Marin, Luis /L-4680-2014; rosado, juan/H-3488-2015 OI Salido, Gines/0000-0002-8687-2445; Garcia-Marin, Luis /0000-0002-1795-7381; rosado, juan/0000-0002-9749-2325 NR 48 TC 26 Z9 26 U1 0 U2 1 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 SEP 16 PY 1998 VL 1404 IS 3 BP 412 EP 426 DI 10.1016/S0167-4889(98)00072-X PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 124NW UT WOS:000076189500015 PM 9739170 ER PT J AU Ferrucci, L Guralnik, JM Penninx, BWJH Leveille, S AF Ferrucci, L Guralnik, JM Penninx, BWJH Leveille, S TI Cigarette smoke exposure and hearing loss SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 Natl Res Inst, Florence, Italy. NIA, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), Natl Res Inst, Florence, Italy. NR 4 TC 3 Z9 3 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD SEP 16 PY 1998 VL 280 IS 11 BP 963 EP 964 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 119JC UT WOS:000075891400014 PM 9749471 ER PT J AU Paik, SM Bryant, J Park, CH Fisher, B Tan-Chiu, E Hyams, D Fisher, ER Lippman, ME Wickerham, DL Wolmark, N AF Paik, SM Bryant, J Park, CH Fisher, B Tan-Chiu, E Hyams, D Fisher, ER Lippman, ME Wickerham, DL Wolmark, N TI erbB-2 and response to doxorubicin in patients with axillary lymph node-positive, hormone receptor-negative breast cancer SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID SURGICAL ADJUVANT BREAST; TOPOISOMERASE-II-ALPHA; C-ERBB-2 EXPRESSION; CELL-PROLIFERATION; STAGE-II; HER-2/NEU; CARCINOMA; THERAPY; CHEMORESISTANCE; OVEREXPRESSION AB Background: Overexpression of the erbB-2 protein by breast cancer cells has been suggested to be a predictor of response to doxorubicin. A retrospective study was designed to test this hypothesis. Methods: In National Surgical Adjuvant Breast and Bowel Project protocol B-ll, patients with axillary lymph node-positive, hormone receptor-negative breast cancer were randomly assigned to receive either L-phenylalanine mustard plus 5-fluorouracil (PF) or a combination of L-phenylalanine mustard, 5-fluorouracil, and doxorubicin (PAF), Tumor cell expression of erbB-2 was determined by immunohistochemistry for 638 of 682 eligible patients. Statistical analyses were performed to test for interaction between treatment and erbB-2 status (positive versus negative) with respect to disease-free survival (DFS), survival, recurrence-free survival (RFS), and distant disease-free survival (DDFS), Reported P values are two-sided. Results: Overexpression of erbB-2 (i.e., positive immunohistochemical staining) was observed in 239 (37.5%) of the 638 tumors studied. Overexpression was associated with tumor size (P = .02), lack of estrogen receptors (P = .008), and the number of positive lymph nodes (P = .0001), After a mean time on study of 13.5 years, the clinical benefit from doxorubicin (PAF versus PF) was statistically significant for patients with erbB-2-positive tumors-DFS: relative risk of failure (RR) = 0.60 (95% confidence interval [CI] = 0.44-0.83), P = .001; survival: RR = 0.66 (95% CI = 0.47-0.92), P = .01; RFS: RR = 0.58 (95% CI = 0.42-0.82), P = .002; DDFS: RR = 0.61 (95% CI = 0.44-0.85), P = .003, However, it was not significant for patients with erbB-2-negative tumors-DFS: RR = 0.96 (95% CI = 0.75-1.23), P = .74; survival: RR = 0.90 (95% CI = 0.69-1.19), P = .47; RFS: RR = 0.88 (95% CI = 0.67-1.16), P = .37; DDFS: RR = 1.03 (95% CI = 0.79-1.35), P = .84, Interaction between doxorubicin treatment and erbB-2 overexpression was statistically significant for DFS (P = .02) and DDFS (P = .02) but not for survival (P = .15) or RFS (P = .06), Conclusions: These data support the hypothesis of a preferential benefit from doxorubicin in patients with erbB-2-positive breast cancer. C1 Allegheny Univ Hlth Sci, NSABP, Pathol Sect, Pittsburgh, PA 15212 USA. Allegheny Univ Hlth Sci, Dept Human Oncol, Pittsburgh, PA USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. Univ Pittsburgh, Dept Stat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. RP Allegheny Univ Hlth Sci, NSABP, Pathol Sect, E Commons Profess Bldg,4 Allegheny Ctr,5th Floor, Pittsburgh, PA 15212 USA. EM spaik@pgh.auhs.edu FU NCI NIH HHS [U10CA37377, U10CA69651, U10CA12027] NR 24 TC 497 Z9 511 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD SEP 16 PY 1998 VL 90 IS 18 BP 1361 EP 1370 DI 10.1093/jnci/90.18.1361 PG 10 WC Oncology SC Oncology GA 120NT UT WOS:000075963000010 PM 9747867 ER PT J AU Johnson, BE AF Johnson, BE TI Second lung cancers in patients after treatment for an initial lung cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID PRIMARY BRONCHOGENIC CARCINOMAS; SMALL-CELL-CARCINOMA; LONG-TERM SURVIVORS; 2ND PRIMARY CANCERS; INTERNATIONAL STAGING SYSTEM; TUMOR-SUPPRESSOR GENE; HODGKINS-DISEASE; FOLLOW-UP; RADIATION-THERAPY; LATE RECURRENCE AB Background: Prospectively and retrospectively identified patient cohorts that were successfully treated for primary lung cancer have been followed to document the rate of development of and the effectiveness of treatment of second lung cancers. This review was performed to assess rates of second lung cancer development, factors associated with the development of these cancers, and the success of their treatment. Methods: The MEDLINE(R) database was searched to identify articles published in English concerning lung cancers, second primary cancers, treatment of these cancers, and patient survival. Results: The risk of developing a second lung cancer in patients who survived resection of a non-small-cell lung cancer is approximately 1%-2% per patient per year. Approximately one half of the patients who develop second non-small-cell lung cancers can have these tumors resected, The median survival from diagnosis of a second lung cancer in these patients is between 1 and 2 years, with a 5-year survival of approximately 20% (range, 4%-32%). The average risk of developing a second lung cancer in patients who survived small-cell lung cancer is approximately 6% per patient per year. For patients who survived small-cell cancer, the risk increases from approximately 2% to greater than 10% per patient per year 10 years after initial treatment. Only 7% (range, 6%-12%) of patients treated for small-cell lung cancer survive 2 years or more. Survivors who continue to smoke cigarettes have an increased risk of developing a second lung cancer. Conclusions: In patients surviving an initial lung cancer, the cumulative risk for the development of a second primary lung cancer makes this cancer a common cause of death. The high risk of developing a second lung cancer makes patients with these cancers an important population for study of surveillance strategies and chemoprevention agents. C1 NCI, Med Branch, Div Clin Sci, Natl Naval Med Ctr, Bethesda, MD 20889 USA. RP Johnson, BE (reprint author), NCI, Med Branch, Div Clin Sci, Natl Naval Med Ctr, Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM bj16b@nih.gov NR 87 TC 174 Z9 180 U1 0 U2 10 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 16 PY 1998 VL 90 IS 18 BP 1335 EP 1345 DI 10.1093/jnci/90.18.1335 PG 11 WC Oncology SC Oncology GA 120NT UT WOS:000075963000008 PM 9747865 ER PT J AU Fisher, B Costantino, JP Wickerham, DL Redmond, CK Kavanah, M Cronin, WM Vogel, V Robidoux, A Dimitrov, N Atkins, J Daly, M Wieand, S Tan-Chiu, E Ford, L Wolmark, N AF Fisher, B Costantino, JP Wickerham, DL Redmond, CK Kavanah, M Cronin, WM Vogel, V Robidoux, A Dimitrov, N Atkins, J Daly, M Wieand, S Tan-Chiu, E Ford, L Wolmark, N TI Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RECEPTOR-POSITIVE TUMORS; RAT MAMMARY-CARCINOMA; RANDOMIZED TRIAL; POSTMENOPAUSAL WOMEN; SERUM-LIPOPROTEINS; ENDOMETRIAL CANCER; ANTITHROMBIN-III; PLASMA-LIPIDS; THERAPY; INSITU AB Background: The finding of a decrease in contralateral breast cancer incidence following tamoxifen administration for adjuvant therapy led to the concept that the drug might play a role in breast cancer prevention. To test this hypothesis, the National Surgical Adjuvant Breast and Bowel Project initiated the Breast Cancer Prevention Trial (P-l) in 1992. Methods: Women (N = 13388) at increased risk for breast cancer because they 1) were 60 years of age or older, 2) were 35-59 years of age with a 5-year predicted risk for breast cancer of at least 1.66%, or 3) had a history of lobular carcinoma in situ were randomly assigned to receive placebo (n = 6707) or 20 mg/day tamoxifen (n = 6681) for 5 years. Call's algorithm, based on a multivariate logistic regression model using combinations of risk factors, was used to estimate the probability (risk) of occurrence of breast cancer over time. Results: Tamoxifen reduced the risk of invasive breast cancer by 49% (two-sided P<.00001), with cumulative incidence through 69 months of follow-up of 43.4 versus 22.0 per 1000 women in the placebo and tamoxifen groups, respectively. The decreased risk occurred in women aged 49 years or younger (44%), 50-59 years (51%), and 60 years or older (55%); risk was also reduced in women with a history of lobular carcinoma in situ (56%) or atypical hyperplasia (86%) and in those with any category of predicted 5-year risk. Tamoxifen reduced the risk of noninvasive breast cancer by 50% (two-sided P<.002), Tamoxifen reduced the occurrence of estrogen receptor-positive tumors by 69%, hut no difference in the occurrence of estrogen receptor-negative tumors was seen. Tamoxifen administration did not alter the average annual rate of ischemic heart disease; however, a reduction in hip, radius (Colles'), and spine fractures was observed. The rate of endometrial cancer was increased in the tamoxifen group (risk ratio = 2.53; 95% confidence interval = 1.35-4.97); this increased risk occurred predominantly in women aged 50 years or older. All endometrial cancers in the tamoxifen group were stage I(localized disease); no endometrial cancer deaths have occurred in this group. No liver cancers or increase in colon, rectal, ovarian, or other tumors was observed in the tamoxifen group. The rates of stroke, pulmonary embolism, and deep-vein thrombosis were elevated in the tamoxifen group; these events occurred more frequently in women aged 50 years or older. Conclusions: Tamoxifen decreases the incidence of invasive and noninvasive breast cancer. Despite side effects resulting from administration of tamoxifen, its use as a breast cancer preventive agent is appropriate in many women at increased risk for the disease. C1 Allegheny Univ Hlth Sci, Pittsburgh, PA 15212 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Boston Med Ctr, Boston, MA USA. Hotel Dieu, Montreal, PQ, Canada. Michigan State Univ, E Lansing, MI 48824 USA. SE Canc Control Consortium, Winston Salem, NC USA. Fox Chase Canc Ctr, Cheltenham, PA USA. Univ Pittsburgh, NSABP, Ctr Biostat, Pittsburgh, PA 15260 USA. NCI, Bethesda, MD 20892 USA. RP Fisher, B (reprint author), Allegheny Univ Hlth Sci, 4 Allegheny Ctr,Suite 602, Pittsburgh, PA 15212 USA. EM BFISHERl@aherf.edu FU NCI NIH HHS [U10-CA-37377, U10-CA-69974] NR 68 TC 3571 Z9 3647 U1 24 U2 193 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 16 PY 1998 VL 90 IS 18 BP 1371 EP 1388 DI 10.1093/jnci/90.18.1371 PG 18 WC Oncology SC Oncology GA 120NT UT WOS:000075963000011 PM 9747868 ER PT J AU Cannon, RO Curiel, RV Prasad, A Quyyumi, AA Panza, JA AF Cannon, RO Curiel, RV Prasad, A Quyyumi, AA Panza, JA TI Comparison of coronary endothelial dynamics with electrocardiographic and left ventricular contractile responses to stress in the absence of coronary artery disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID SYNDROME-X; ANGINA-PECTORIS; RISK-FACTORS; RESISTANCE VESSELS; FLOW RESERVE; BLOOD-FLOW; DYSFUNCTION; EXERCISE; ANGIOGRAMS; ATHEROSCLEROSIS AB Coronary artery endothelial dysfunction has been proposed as a cause of myocardial ischemia and symptoms in patients with angina-like chest pain despite normal coronary angiograms, especially those with ischemic-appearing ST-segment depression during exercise (syndrome X). We measured coronary vasomotor responses to acetylcholine (3 to 300 mu g/min) in 42 patients (27 women and 15 men) with effort chest pain and normal coronary angiograms who also had normal electrocardiograms and echocardiograms at rest. All patients underwent treadmill exercise testing and measurement of systolic wall thickening responses to dobutamine (40 mu g/kg/min) during transesophageal echocardiography. There were no differences in the acetylcholine-stimulated epicardial coronary diameter (+5 +/- 13% vs +/-1 a 13%, p = 0.386) and flow (+179 +/- 90% vs +169 +/- 96%, p = 0.756), or in the systolic wall thickening responses (+134 +/- 65% vs +118 +/- 57%, p = 0.445) from baseline values in the 12 syndrome X patients compared with the 30 patients with negative exercise test results. In patients in the lowest quartile of coronary flow responses to acetylcholine, dobutamine increased systolic wall thickening by 121 +/- 73%; 3 had ischemic-appearing ST-segment depression during this stress. This contractile response to dobutamine was no different than the increase in systolic wall thickening (129 +/- 48%, p = 0.777) in patients in the highest quartile of coronary flow responses, 3 of whom also had ischemic-appearing ST-segment depression during this stress. Thus, coronary endothelial dysfunction in the absence of coronary artery disease does not account for ischemic-appearing ST-segment depression in patients with chest pain despite normal coronary angiograms. Further, coronary endothelial dysfunction is not associated with myocardial contractile responses to stress consistent with myocardial ischemia. (C) 1998 by Excerpta Medica, Inc. C1 NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiol Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr MSC 1650, Bethesda, MD 20892 USA. NR 29 TC 15 Z9 15 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD SEP 15 PY 1998 VL 82 IS 6 BP 710 EP 714 DI 10.1016/S0002-9149(98)00456-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 122CK UT WOS:000076053100002 PM 9761078 ER PT J AU Gammon, MD Schoenberg, JB Britton, JA Kelsey, JL Stanford, JL Malone, KE Coates, RJ Brogan, DJ Potischman, N Swanson, CA Brinton, LA AF Gammon, MD Schoenberg, JB Britton, JA Kelsey, JL Stanford, JL Malone, KE Coates, RJ Brogan, DJ Potischman, N Swanson, CA Brinton, LA TI Electric blanket use and breast cancer risk among younger women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bedding and linens; breast neoplasms; electromagnetic fields; receptors; estrogen; receptors; progesterone ID MAGNETIC-FIELD EXPOSURE; ELECTROMAGNETIC-FIELDS; UTILITY WORKERS; OCCUPATIONAL EXPOSURE; RESIDENTIAL EXPOSURE; UNITED-STATES; ADULT CANCERS; BRAIN CANCER; MORTALITY; POWER AB To investigate whether use of electric blankets, one of the largest sources of electromagnetic field exposure in the home, is associated with the risk of female breast cancer, the authors analyzed data from a population-based US case-control study. The 2,199 case patients were under age 55 years and had been newly diagnosed with breast cancer between 1990 and 1992. The 2,009 controls were frequency-matched to cases by 5-year age group and geographic area. There was little or no risk associated with ever having used electric blankets, mattress pads, or heated water beds among women under age 45 years (adjusted odds ratio = 1.01, 95% confidence interval 0.86-1.18) or among women aged greater than or equal to 45 years (adjusted odds ratio = 1.12, 95% confidence interval 0.87-1.43). There was no substantial variation in risk with duration of use; with whether the appliance was used only to warm the bed or used throughout the night; with menopausal status; or with the cases' hormone receptor status or stage of disease. Potential breast cancer risk factors that were associated with electric blanket use did not substantially confound the associations under investigation. These data do not support the hypothesis that electric blanket use increases breast cancer risk among women under age 55 years. C1 Columbia Sch Publ Hlth, Div Epidemiol, New York, NY USA. New Jersey Dept Hlth & Senior Serv, Applied Canc Epidemiol Program, Trenton, NJ USA. Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. Ctr Prevention, Atlanta, GA USA. Emory Univ, Rollins Sch Publ Hlth, Dept Biostat, Atlanta, GA USA. Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Gammon, MD (reprint author), Columbia Sch Publ Hlth, Div Epidemiol, New York, NY USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 52 TC 38 Z9 39 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 15 PY 1998 VL 148 IS 6 BP 556 EP 563 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 121XK UT WOS:000076041000005 PM 9753010 ER PT J AU Marx, S Spiegel, AM Skarulis, MC Doppman, JL Collins, FS Liotta, LA AF Marx, S Spiegel, AM Skarulis, MC Doppman, JL Collins, FS Liotta, LA TI Multiple endocrine neoplasia type 1: Clinical and genetic topics SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT National-Institutes-of-Health Clinical Staff Conference CY JUN 04, 1997 CL NIH, BETHESDA, MARYLAND HO NIH ID ZOLLINGER-ELLISON SYNDROME; MEN1 GENE; PARATHYROID TUMORS; PRIMARY HYPERPARATHYROIDISM; POSITIONAL CLONING; CUSHINGS-SYNDROME; CARCINOID-TUMORS; LONG-TERM; 11Q13; LOCALIZATION AB Multiple endocrine neoplasia type 1 (MEN1) consists of benign, and sometimes malignant, tumors (often multiple in a tissue) of the parathyroids, enteropancreatic neuroendocrine system, anterior pituitary, and other tissues. Skin angiofibromas and skin collagenomas are common. Typically, MEN1 tumors begin two decades earlier than sporadic tumors. Because of tumor multiplicity and the tendency for postoperative tumor recurrence, specialized methods have been developed for preoperative and intraoperative localization of many MEN1-associated tumors. The MEN1 gene was recently isolated by positional cloning. This strategy progressively narrows the size of the candidate MEN1 gene interval on the chromosome and then finds and tests many or, if needed, all genes within that interval. The MEN1 gene was finally identified because it was the one gene that contained mutations in most DNAs from a test panel of MEN1 cases. It has been suggested that MEN1, like many hereditary cancer syndromes, is caused by mutation in a tumor suppressor gene that contributes to neoplasia when both gene copies in a tumor precursor cell have been sequentially inactivated ("two-hit" oncogenesis mechanism). Germline MEN1 mutations were found in most families with MEN1 and in most cases of sporadic MEN1. In addition, the MEN1 gene was the gene most likely to show acquired mutation in several sporadic or nonhereditary tumors-parathyroid adenomas, gastrinomas, insulinomas, and bronchial carcinoids. Most germline or acquired MEN1 mutations predicted truncation (and thus likely inactivation) of the encoded protein, supporting expectations for the "first hit" to a tumor suppressor gene. Testing for MEN1 germline mutation is possible in a research setting. Candidates for MEN1 mutation testing include patients with MEN1 or its phenocopies and first-degree relatives of persons with MEN1. C1 NIH, Bethesda, MD 20892 USA. RP Marx, S (reprint author), NIH, Bldg 10,Room 9C-101, Bethesda, MD 20892 USA. NR 60 TC 213 Z9 216 U1 1 U2 5 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 SEP 15 PY 1998 VL 129 IS 6 BP 484 EP 494 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 119JJ UT WOS:000075892100008 PM 9735087 ER PT J AU Klose, TS Ibeanu, GC Ghanayem, BI Pedersen, LG Li, LP Hall, SD Goldstein, JA AF Klose, TS Ibeanu, GC Ghanayem, BI Pedersen, LG Li, LP Hall, SD Goldstein, JA TI Identification of residues 286 and 289 as critical for conferring substrate specificity of human CYP2C9 for diclofenac and ibuprofen SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cytochrome P450; CYP2C9; CYP2C19; site-directed mutagenesis; cDNA expression system; diclofenac; ibuprofen; tolbutamide; sulfaphenazole; substrate binding sites ID CYTOCHROME P4502C9; BINDING SITE; SUBFAMILY; 2C; HYDROXYLASE; EXPRESSION AB Specificity of human CYP2C9 for two substrates, diclofenac and ibuprofen, was studied using chimeras and site-directed mutants of CYP2C9 and the highly related CYP2C19 expressed in Escherichia coli. Data were correlated with the presence of putative substrate recognition sites (SRS). A CYP2C19 chimera containing residues 228-340 (SRS 3 and 4) of 2C9 conferred both diclofenac hydroxylation and 2- and 3-hydroxylation of ibuprofen. The regiospecificity of this construct for metabolism of ibuprofen differed from that of CYP2C9 by favoring 2-hydroxylation over 3-hydroxylation. A CYP2C9 construct containing residues 228-340 of CYP2C19 lacked both diclofenac and ibuprofen hydroxylase activities. When residues 228-282 (containing SRS 3) of CYP2C9 were replaced by those of CYP2C19, the chimera retained appreciable activity for diclofenac and ibuprofen, and tolbutamide activity was inhibited by a specific CYP2C9 inhibitor, sulfaphenazole. This suggested that SRS 3 is not important in conferring specificity. CYP2C9 and CYP2C19 differ in five residues within the region 283-340 (within SRS 4). Mutations to analyze SRS 4 were made on a CYP2C19 chimera containing residues 228-282 of CYP2C9. A single I289N mutation conferred a dramatic increase in diclofenac hydroxylation and a small increase in ibuprofen a-hydroxylation. A second mutation (N286S and I289N) increased diclofenac hydroxylation and conferred a dramatic increase in ibuprofen a-hydroxylation. A V288E mutation did not increase activity toward either substrate and decreased activity toward the two substrates in combination with the I289N or the N286S, I289N mutants. Therefore residues 286 and 289 of CYP2C9 are important in conferring specificity for diclofenac and ibuprofen. (C) 1998 Academic Press. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. Indiana Univ, Sch Med, Div Clin Pharmacol, Indianapolis, IN 46202 USA. RP Goldstein, JA (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. RI Goldstein, Joyce/A-6681-2012; Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 21 TC 58 Z9 58 U1 0 U2 8 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 15 PY 1998 VL 357 IS 2 BP 240 EP 248 DI 10.1006/abbi.1998.0826 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 119UC UT WOS:000075915200007 PM 9735164 ER PT J AU Tauscher, J Fischer, P Neumeister, A Rappelsberger, P Kasper, S AF Tauscher, J Fischer, P Neumeister, A Rappelsberger, P Kasper, S TI Low frontal electroencephalographic coherence in neuroleptic-free schizophrenic patients SO BIOLOGICAL PSYCHIATRY LA English DT Article DE schizophrenia; electroencephalographic coherence analysis; hypofrontality; clinical neurophysiology ID CEREBRAL BLOOD-FLOW; DORSOLATERAL PREFRONTAL CORTEX; EEG COHERENCE; DYSFUNCTION; DENSITY; MODEL AB Background: Electroencephalographic (EEG) coherence analysis is a noninvasive technique for studying corticocortical associations. As there is evidence for a dysfunction of the prefrontal dorsolateral cortex in schizophrenia, we hypothesized to find lower frontal EEG coherence in schizophrenia. Methods: EEG amplitude and coherence analysis was performed in 16 antipsychotic-free schizophrenic patients and 16 healthy controls. EEG recordings were done with 19 gold-plated electrodes placed according to the International 10/20 system against averaged signals from both earlobes. Local coherence was computed for 22 adjacent electrode pairs within the hemispheres and interhemispheric coherence for eight corresponding electrode pairs of both hemispheres in the delta, theta, alpha, and beta-1 band. Results: Amplitude and interhemispheric coherence analysis revealed no differences. Local EEG coherence was significantly lower in schizophrenic patients for Fp1-F7 in the delta (p = .001) and the theta band (p = .002), and at F7-F3 in the alpha band (p = .002). In the delta band coherence of Fp1-F7 was inversely correlated to the Positive and Negative Syndrome Scale positive symptoms subscore (R = -.74, p = .014). Conclusions: Assuming that EEG coherence can be used to index functional coupling between brain areas under the electrodes, the low EEG coherence in Fp1-F7 and F7-F3 in schizophrenic patients might reflect impaired information processing in the left dorsolateral prefrontal cortex. (C) 1998 Society of Biological Psychiatry. C1 Univ Vienna, Dept Gen Psychiat, A-1090 Vienna, Austria. NIMH, Clin Psychobiol Branch, Bethesda, MD 20892 USA. Univ Vienna, Inst Neurophysiol, Vienna, Austria. RP Tauscher, J (reprint author), Univ Vienna, Dept Gen Psychiat, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. RI Tauscher, Johannes/M-5976-2016 NR 30 TC 41 Z9 45 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD SEP 15 PY 1998 VL 44 IS 6 BP 438 EP 447 DI 10.1016/S0006-3223(97)00428-9 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 121LM UT WOS:000076015300011 PM 9777175 ER PT J AU Liu, SJ Sher, YP Ting, CC Liao, KW Yu, CP Tao, MH AF Liu, SJ Sher, YP Ting, CC Liao, KW Yu, CP Tao, MH TI Treatment of B-cell lymphoma with chimeric IgG and single-chain Fv antibody interleukin-2 fusion proteins SO BLOOD LA English DT Article ID COLONY-STIMULATING FACTOR; ACTIVATED KILLER CELLS; ESTABLISHED PULMONARY METASTASES; RECOMBINANT INTERLEUKIN-2; MONOCLONAL-ANTIBODIES; TUMOR-CELLS; MELANOMA METASTASES; BIOLOGICAL-ACTIVITY; EFFECTOR FUNCTIONS; IDIOTYPE THERAPY AB Anti-idiotype (Id) antibodies (Abs) have been shown to be effective in treatment of B-cell lymphoma in animal models and in clinical trials. The combination of interleukin-2 (IL-2) can augment the therapeutic effect of anti-Id Abs. To further improve the power of the combined therapy, a monoclonal anti-Id Ab, S5A8, specifically recognizing a murine B-cell lymphoma 38C13, was genetically modified to contain the IL-2 domain and thus use the unique targeting ability of Abs to direct IL-2 to the tumor site. Two forms of the anti-Id-IL-2 fusion proteins were constructed: one configuration consisting of mouse-human chimeric IgG (chS5A8-IL-2) and the other containing only the variable light (V-L) and variable heavy (V-H) Ab domains covalently connected by a peptide linker (scFvS5A8-IL-2). Both forms of the anti-Id-IL-2 fusion proteins retained IL-2 biological activities and were equivalent in potentiating tumor cell lysis in vitro. In contrast, the antigen-binding ability of scFvS5A8-IL-2 was 30- to 40-fold lower than that of the bivalent chS5A8-IL-2. Pharmacokinetic analysis showed that scFvS5A8-IL-2 was eliminated about 20 times faster than chS5A8-IL-2. Finally, it was shown that chS5A8-IL-2 was very proficient in inhibiting 38C13 tumor growth in vivo, more effectively than a combined therapy with anti-id Abs and IL-2, whereas scFvS5A8-IL-2 did not show any therapeutic effect. These results demonstrate that the anti-Id-IL-2 fusion protein represents a potent reagent for treatment for B-cell lymphoma and that the intact IgG fusion protein is far more effective than its single-chain counterpart. (C) 1998 by The American Society of Hematology. C1 Acad Sinica, Inst Biomed Sci, Div Canc Res, Taipei 11529, Taiwan. Natl Def Med Ctr, TriServ Gen Hosp, Dept Pathol, Taipei, Taiwan. Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan. Natl Taiwan Univ, Grad Inst Med Technol, Taipei 10764, Taiwan. NCI, Lab Immune Cell Biol, Div Basic Sci, NIH, Bethesda, MD USA. RP Tao, MH (reprint author), Acad Sinica, Inst Biomed Sci, Div Canc Res, Taipei 11529, Taiwan. RI Liu, Shih-Jen /E-3942-2010 NR 58 TC 25 Z9 27 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 0006-4971 J9 BLOOD JI Blood PD SEP 15 PY 1998 VL 92 IS 6 BP 2103 EP 2112 PG 10 WC Hematology SC Hematology GA 118HJ UT WOS:000075832200029 PM 9731068 ER PT J AU Bartlett, DL Buell, JF Libutti, SK Reed, E Lee, KB Figg, WD Venzon, DJ Alexander, HR AF Bartlett, DL Buell, JF Libutti, SK Reed, E Lee, KB Figg, WD Venzon, DJ Alexander, HR TI A phase I trial of continuous hyperthermic peritoneal perfusion with tumor necrosis factor and cisplatin in the treatment of peritoneal carcinomatosis SO CANCER LA English DT Article DE peritoneal carcinomatosis; tumor necrosis factor; cisplatin; hyperthermia; mesothelioma ID GASTRIC-CANCER; INTRAPERITONEAL CISPLATIN; FACTOR-ALPHA; INTERFERON-GAMMA; MITOMYCIN-C; CELLS; CHEMOTHERAPY; THIOSULFATE; RECURRENCE; MELPHALAN AB BACKGROUND, Tumor necrosis factor (TNF), hyperthermia, and cisplatin have synergistic cytotoxicity against cancer cells in vitro. This combination may be suited to the regional treatment of peritoneal tumor spread in patients. CHPP with TNF and cisplatin was conducted to define the maximum dose (MTD) for TNF and cisplatin under moderate hyperthermia in the of peritoneal carcinomatosis. METHODS, Twenty-seven patients with peritoneal carcinomatosis underwent exploratory laparotomy and tumor debulking followed by a 90-minute CHPP with cisplatin (100-350 mg/m(2)) and TNF (0-0.3 mg/L). Perfusion parameters included a perfusate volume of 3-9 L, a peritoneal temperature of 42-43 degrees C, and a flow rate of 1.5 L/minute. Sodium thiosulfate was administered systemically during and after the perfusion as a cisplatin binding agent. RESULTS. There was no operative or treatment-related mortality in this study. CHPP resulted in a 14-fold higher area under the concentration versus time curve (AUC) for cisplatin in the perfusate compared with plasma, and a 4854-fold higher AUC for TNF. The MTD was defined as 250 mg/m(2) cisplatin plus 0.1 mg/L TNF. The dose-limiting toxicity was renal insufficiency. No other systemic toxicity was identified, and no significant regional toxicity was identified. The median time to toleration of a regular diet was 8 days (range, 5-20 days). CONCLUSIONS, The favorable regional pharmacologic profile of the combination of cisplatin and TNF suggests that these agents administered via CHPP warrant further evaluation as prophylaxis against or treatment for peritoneal carcinomatosis. (C) 1998 American Cancer Society. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Bartlett, DL (reprint author), NCI, Surg Branch, NIH, Bldg 10,Room 2B17, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008; Figg Sr, William/M-2411-2016 NR 33 TC 59 Z9 59 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD SEP 15 PY 1998 VL 83 IS 6 BP 1251 EP 1261 DI 10.1002/(SICI)1097-0142(19980915)83:6<1251::AID-CNCR27>3.3.CO;2-U PG 11 WC Oncology SC Oncology GA 118GM UT WOS:000075830100027 PM 9740093 ER PT J AU Hussain, SP Harris, CC AF Hussain, SP Harris, CC TI Molecular epidemiology of human cancer: Contribution of mutation spectra studies of tumor suppressor genes SO CANCER RESEARCH LA English DT Review ID WILD-TYPE P53; TATA-BINDING PROTEIN; HEPATITIS-B VIRUS; NONPOLYPOSIS COLORECTAL-CANCER; TRANSCRIPTION-COUPLED REPAIR; NUCLEOTIDE EXCISION-REPAIR; LI-FRAUMENI SYNDROME; BRCA1 BREAST-CANCER; STRANDED-DNA ENDS; C-TERMINAL DOMAIN C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 2C05, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov NR 232 TC 307 Z9 314 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 15 PY 1998 VL 58 IS 18 BP 4023 EP 4037 PG 15 WC Oncology SC Oncology GA 120ZM UT WOS:000075987800002 PM 9751603 ER PT J AU Mongini, PKA Vilensky, MA Highet, PF Inman, JK AF Mongini, PKA Vilensky, MA Highet, PF Inman, JK TI Membrane IgM-stimulated human B lymphocytes succumb to activation-related apoptosis at a G(1)-> S transition: Influence of ligand affinity and valency SO CELLULAR IMMUNOLOGY LA English DT Article ID CELL-CYCLE PROGRESSION; PROTEIN-KINASE-C; ANTI-IGM; CROSS-LINKING; TRANSGENIC MICE; SURFACE-IMMUNOGLOBULIN; INDEPENDENT ANTIGENS; HEMATOPOIETIC-CELLS; MOUSE LYMPHOCYTES; GROWTH-REGULATION AB Culture of human B lymphocytes with polyclonally activating surrogates for type II T-cell-independent antigen, i.e., anti-IgM mAb and anti-IgM:dextran, resulted in both membrane IgM (mIgM)-triggered S/G(2)/M entry and apoptosis. Although high ligand valency could compensate for low affinity, and high affinity could compensate for low valency, in achieving mIgM-triggered apoptosis, the phenomenon was most pronounced when the soluble "antigen" had both high binding site affinity and valency. Most of the mIgM-triggered apoptosis may represent B cells which progress into G(1) but fail to receive a sufficient level of continuous mIgM-mediated signaling during G(1) for passage through a G(1) --> S phase restriction point(s). This was supported by the findings that (a) a lesser proportion of mig-triggered cells enter S phase than G(1); (b) maximal mIgM-triggered apoptosis was noted at 48-72 h of culture and surrounding activated cell clusters; (c) mIgM-triggered apoptosis was not inhibited by pharmacologic blockers of S phase; and (d) a high proportion of viable mIgM-triggered B cell blasts in G(1) succumb to apoptosis rather than enter S phase, if high-affinity multivalent ligand is washed from the cultures. In addition to quantitative aspects of initial receptor engagement, the potential for a protracted period of recurrent mIgM signaling events may in fluence whether apoptosis or cell cycle progression is the functional outcome of B cell encounter with a multivalent antigen. (C) 1998 Academic Press. C1 Hosp Joint Dis & Med Ctr, Dept Rheumatol & Mol Med, New York, NY 10003 USA. NYU, Sch Med, Dept Pathol, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. NIH, Immunol Lab, Bethesda, MD 20892 USA. RP Mongini, PKA (reprint author), Hosp Joint Dis & Med Ctr, Dept Rheumatol & Mol Med, New York, NY 10003 USA. FU NIGMS NIH HHS [R01 GM35174] NR 76 TC 6 Z9 6 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD SEP 15 PY 1998 VL 188 IS 2 BP 137 EP 150 DI 10.1006/cimm.1998.1359 PG 14 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 128GD UT WOS:000076396600008 PM 9756644 ER PT J AU Sidney, S Siscovick, DS Petitti, DB Schwartz, SM Quesenberry, CP Psaty, BM Raghunathan, TE Kelaghan, J Koepsell, TD AF Sidney, S Siscovick, DS Petitti, DB Schwartz, SM Quesenberry, CP Psaty, BM Raghunathan, TE Kelaghan, J Koepsell, TD TI Myocardial infarction and use of low-dose oral contraceptives - A pooled analysis of 2 US studies SO CIRCULATION LA English DT Article DE women; myocardial infarction; epidemiology; risk factors ID CARDIOVASCULAR-DISEASE; INCREASED RISK; WOMEN AB Background-Population-based case-control studies to assess the relationship of low-dose oral contraceptive (OC) use with myocardial infarction (MI) were performed at 2 sites in the United States (California and Washington state). The purpose of the present study was to estimate risk of MI in relation to use of low-dose OCs in a pooled analysis combining results from the 2 sites. Methods and Results-The study included as cases women aged 18 to 44 years with incident MI who had no prior history of ischemic heart disease or cerebrovascular disease. Women in the case and control groups were interviewed in person regarding OC use and cardiovascular risk factors. The analysis included 271 MI cases and 993 controls. Compared with noncurrent users, the adjusted pooled odds ratio for MI in current OC users was 0.94 (95% CI, 0.44, 2.20) after adjustment for major risk factors and sociodemographic factors. Compared with never users, the adjusted pooled odds ratio for MI was 0.56 (0.21, 1.49) in current OC users and 0.54 (0.31, 0.95) in past OC users. Among past OC users, duration and recency of use were unrelated to MI risk as was current hormone replacement therapy. There was no evidence of interaction between OC use and age, presence of cardiovascular risk factors (hypercholesterolemia, hypertension, diabetes), obesity, or smoking. Conclusions-We conclude that low-dose OCs as used in these populations are safe with respect to risk of MI in women. C1 Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Div Gen Internal Med, Seattle, WA 98195 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Biostat, Seattle, WA 98195 USA. Kaiser Permanente Med Care Program, Res & Evaluat, Pasadena, CA USA. NICHHD, Contracept & Reprod Evaluat Branch, Bethesda, MD 20892 USA. RP Sidney, S (reprint author), Kaiser Permanente Med Care Program, Div Res, 3505 Broadway, Oakland, CA 94611 USA. EM sxs@dor.kaiser.org FU NICHD NIH HHS [N01-HD-1-3108, N01-HD-1-3107] NR 24 TC 71 Z9 72 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 15 PY 1998 VL 98 IS 11 BP 1058 EP 1063 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 118UK UT WOS:000075858600004 PM 9736591 ER PT J AU Hara, T Tamura, K de Miguel, MP Mukouyama, Y Kim, HJ Kogo, H Donovan, PJ Miyajima, A AF Hara, T Tamura, K de Miguel, MP Mukouyama, Y Kim, HJ Kogo, H Donovan, PJ Miyajima, A TI Distinct roles of oncostatin M and leukemia inhibitory factor in the development of primordial germ cells and Sertoli cells in mice SO DEVELOPMENTAL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; EMBRYONIC STEM-CELLS; GROWTH-FACTOR; IN-VITRO; MOUSE; RECEPTOR; CULTURE; PROLIFERATION; SURVIVAL; DIFFERENTIATION AB Leukemia inhibitory factor (LIF) stimulates the growth of primordial germ cells (PGCs) in mouse embryo. However, as neither mice lacking LIF nor mice lacking the LH receptor show defects in PGC growth, an alternate cytokine for PGC growth has been postulated. We investigated the role of mouse oncostatin M (mOSM), which is structurally and functionally related to LIF, in germ cell development. While LIF enhanced the survival of migratory as well as postmigratory PGCs, mOSM acted only on the postmigratory PGCs. Consistent with its biological activity, mOSM was found to be expressed in developing gonads. In the male, Sertoli cells in neonatal testis express mOSM; however, its expression is downregulated in adult testes. Moreover, mOSM enhanced the proliferation of Sertoli cells derived from neonatal testes in vitro more than human OSM or LIF. In contrast, postnatal ovaries do not express mOSM. These results indicate that mOSM is a stage- and sex-specific autocrine growth factor for Sertoli cells. (C) 1998 Academic Press. C1 Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan. Tokyo Univ Pharm & Life Sci, Tokyo 1920355, Japan. Univ Alcala de Henares, Dept Cell Biol & Genet, Alcala De Henares 28871, Madrid, Spain. NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RP Hara, T (reprint author), Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, 1-1-1 Yayoi, Tokyo 1130032, Japan. NR 39 TC 55 Z9 57 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD SEP 15 PY 1998 VL 201 IS 2 BP 144 EP 153 DI 10.1006/dbio.1998.8990 PG 10 WC Developmental Biology SC Developmental Biology GA 125QJ UT WOS:000076248300003 PM 9740655 ER PT J AU Weeks, BS Nomizu, M Ramchandran, RS Yamada, Y Kleinman, HK AF Weeks, BS Nomizu, M Ramchandran, RS Yamada, Y Kleinman, HK TI Laminin-1 and the RKRLQVQLSIRT laminin-1 alpha 1 globular domain peptide stimulate matrix metalloproteinase secretion by PC12 cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID NERVE GROWTH-FACTOR; NEURITE OUTGROWTH; SYNTHETIC PEPTIDES; BASEMENT-MEMBRANE; PLASMINOGEN-ACTIVATOR; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; SENSORY NEURONS; BINDING-SITES; A-CHAIN AB Here we have investigated the ability of laminin-1 and specific laminin-l-derived synthetic peptides to stimulate neuronal cell matrix metalloproteinase secretion. Zymographic analysis of conditioned media from laminin-l-treated PC12 and NG108-15 cells revealed a 72-kDa matrix metalloproteinase which was not secreted by untreated cells. Laminin-l alpha 1 chain-derived synthetic peptides, AASIKVAVSADR (LAM-L) and RKRLQVQLSIRT (AG-73), also stimulated PC12 cell secretion of a 72-kDa matrix metalloproteinase. We further investigated the structural requirements of AG-73 for cell attachment, neurite outgrowth, and matrix metalloproteinase secretion using a series of AG-73 analogs that had single amino acids substituted with alanine. At the substrate levels tested, the AG-73 peptide promoted the adhesion of 67% of the PC12 cells and neurite outgrowth in 71% of the PC12 cells. Substitutions in any one of the amino acids within the central LQVQ sequence resulted in a large reduction in cell, attachment whereas substitution in the carboxyl terminal proximal amino acids L, S, and R had little effect on attachment. Alanine substitution of any of the amino terminal proximal LQV amino acids and the carboxyl terminal L, I, and R residues resulted in a 65-91% reduction in neurite outgrowth. These data demonstrate that the sequence requirements for cell attachment and neurite outgrowth were not necessarily coupled but that the sequence requirements for neurite outgrowth and matrix metalloproteinase secretion were identical. We conclude that laminin-l is able to stimulate neuronal cells to secrete a matrix metalloproteinase. Further, this study identifies the LQVXLXIR laminin-l alpha 1 globular domain peptide to be capable of stimulating both neurite outgrowth and matrix metalloproteinase secretion. (C) 1998 Academic Press. C1 Adelphi Univ, Dept Biol, Garden City, NY 11530 USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. RP Weeks, BS (reprint author), Adelphi Univ, Dept Biol, 1 South Ave, Garden City, NY 11530 USA. EM weeks@adlibv.adelphi.edu NR 39 TC 34 Z9 34 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 15 PY 1998 VL 243 IS 2 BP 375 EP 382 DI 10.1006/excr.1998.4157 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 125MQ UT WOS:000076241700017 PM 9743597 ER PT J AU Shneyvays, V Nawrath, H Jacobson, KA Shainberg, A AF Shneyvays, V Nawrath, H Jacobson, KA Shainberg, A TI Induction of apoptosis in cardiac myocytes by an A(3) adenosine receptor agonist SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE adenosine receptors; apoptosis; Feulgen-staining; image analysis; cultured cardiomyocyte; Ca2+ transients; light and electron microscopy ID PROGRAMMED CELL-DEATH; RABBIT CARDIOMYOCYTES; INTRACELLULAR CALCIUM; FLOW-CYTOMETRY; IMAGE-ANALYSIS; RAT-BRAIN; HEART; ACTIVATION; INVOLVEMENT; EXPRESSION AB The effects of the selective adenosine (ADO) A(3) receptor agonist IB-MECA (N-6-(3-iodobenzyl)adenosine-5'-N-methylcarboxamide) on cultured newborn rat cardiomyocytes were examined in comparison with ADO, the ADO A, receptor-selective agonist R-PIA (N-6-R-phenylisopropyladenosine), or the ADO A(3) selective antagonist MRS 1191 (3-ethyl-5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1,4-(+/-)-dihydropyride-3,5 dicarboxylate), using digital image analysis of Feulgen-stained nuclei, At high concentration, IB-MECA (greater than or equal to 10 mu M) and ADO (200 mu M) induced apoptosis; however, R-PIA or MRS 1191 did not have any detectable effects on cardiac cells. In addition, DNA breaks in cardiomyocytes undergoing apoptosis following treatment by IB-MECA were identified in situ using the nick end labeling of DNA ('TUNEL"-like) assay. In the presence of greater than or equal to 10 mu M IB-MECA, disorder in the contraction waves appeared, and a decrease in the frequency of beats was observed. Analysis with light microscopy revealed that the number of contracting cells decreased in a concentration-dependent manner. The A(3) receptor agonist IB-MECA caused an increase in intracellular free calcium concentration ([Ca2+](i)). The drug produced a rapid rise followed by a sustained increase in [Ca2+](i), which lasted for 40-60 s, Finally, cessation of beating and Ca2+ transients were observed, Full recovery of contractile activity and rhythmical Ca2+ transients were observed 15-20 min after IB-MECA treatment. The induction of apoptosis in the cardiocytes by IB-MECA led to the appearance of features of apoptotic nuclei: the onset of condensation, compacting, and margination of nuclear chromatin. These effects were accompanied by the disintegration of the structural framework of the nucleus and nuclear breakdown. The results suggest that activation of the A(3) adenosine receptor may participate in the process of apoptosis in cardiomyocytes. (C) 1998 Academic Press. C1 Bar Ilan Univ, Dept Life Sci, Otto Meyerhoff Drug Receptor Ctr, Ramat Gan, Israel. Univ Mainz, Inst Pharmacol, D-6500 Mainz, Germany. NIH, Mol Recognit Sect, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Shainberg, A (reprint author), Bar Ilan Univ, Dept Life Sci, Otto Meyerhoff Drug Receptor Ctr, Ramat Gan, Israel. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 47 TC 68 Z9 68 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 15 PY 1998 VL 243 IS 2 BP 383 EP 397 DI 10.1006/excr.1998.4134 PG 15 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 125MQ UT WOS:000076241700018 PM 9743598 ER PT J AU Katz, BZ Levenberg, S Yamada, KM Geiger, B AF Katz, BZ Levenberg, S Yamada, KM Geiger, B TI Modulation of cell-cell adherens junctions by surface clustering of the N-cadherin cytoplasmic tail SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE cadherin; cytoplasmic domain; clustering; assembly ID SIGNAL-TRANSDUCTION; PROTEIN INTERACTIONS; ADHESION; MOLECULES; RECEPTORS; CATENINS; CAM AB Cadherins mediate the formation of cell-cell adherens junctions (AJ) by homophilic interactions through their extracellular domains as well as by interacting with the actin cytoskeleton via their cytoplasmic portions. Cadherin clustering initiates cytoplasmic signaling that results in the assembly of structural components into cell-cell AJ. To elucidate the function of the cytoplasmic tail of cadherins in initiating the assembly signal, we generated and characterized a chimeric cadherin tail fused to an inert transmembrane anchor. The chimera enabled us to cluster the cadherin cytoplasmic tail in the absence of extracellular portions of the molecule. The transfected cadherin tail chimera localized to cell-cell AJ of epithelial cells, indicating that the submembrane junctional plaque has the capacity to recruit additional cadherins, with no involvement of their extracellular domains. Expression of the chimera in cells of mesenchymal origin resulted in dominant negative effects on the formation of cell-cell AJ. Surface clustering of cadherin cytoplasmic tails induced the recruitment of components and structural assembly of cell-cell AJ, thereby reversing the initial dominant-negative effects. We conclude that the cadherin cytoplasmic tail contains information required to direct the molecule to cell-cell AJ. Its function as modulator of cell-cell AJ depends on cell type and on whether the tail is clustered. (C) 1998 Academic Press. C1 NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. RP Katz, BZ (reprint author), NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 421,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 23 TC 34 Z9 34 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD SEP 15 PY 1998 VL 243 IS 2 BP 415 EP 424 DI 10.1006/excr.1998.4194 PG 10 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 125MQ UT WOS:000076241700021 PM 9743601 ER PT J AU Sakaguchi, K Herrera, JE Saito, S Miki, T Bustin, M Vassilev, A Anderson, CW Appella, E AF Sakaguchi, K Herrera, JE Saito, S Miki, T Bustin, M Vassilev, A Anderson, CW Appella, E TI DNA damage activates p53 through a phosphorylation-acetylation cascade SO GENES & DEVELOPMENT LA English DT Article DE CBP/p300; PCAF; histone acetyltransferase; DNA-PK; transcriptional activation; checkpoints ID WILD-TYPE P53; BINDING FUNCTION; P300/CBP-ASSOCIATED FACTOR; TERMINAL DOMAIN; UV-LIGHT; PROTEIN; KINASE; MDM2; GENE; TRANSACTIVATION AB Activation of p53-mediated transcription is a critical cellular response to DNA damage. p53 stability and site-specific DNA-binding activity and, therefore, transcriptional activity, are modulated by post-translational modifications including phosphorylation and acetylation. Here we show that p53 is acetylated in vitro at separate sites by two different histone acetyltransferases (HATs), the coactivators p300 and PCAF. p300 acetylates Lys-382 in the carboxy-terminal region of p53, whereas PCAF acetylates Lys-320 in the nuclear localization signal. Acetylations at either site enhance sequence-specific DNA binding. Using a polyclonal antisera specific for p53 that is phosphorylated or acetylated at specific residues, we show that Lys-382 of human p53 becomes acetylated and Ser-33 and Ser-37 become phosphorylated in vivo after exposing cells to UV light or ionizing radiation. In vitro, amino-terminal p53 peptides phosphorylated at Ser-33 and/or at Ser-37 differentially inhibited p53 acetylation by each HAT. These results suggest that DNA damage enhances p53 activity as a transcription factor in part through carboxy-terminal acetylation that, in turn, is directed by amino-terminal phosphorylation. C1 Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. RP Anderson, CW (reprint author), Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RI Bustin, Michael/G-6155-2015 FU NIGMS NIH HHS [GM52825] NR 49 TC 848 Z9 858 U1 7 U2 35 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 15 PY 1998 VL 12 IS 18 BP 2831 EP 2841 DI 10.1101/gad.12.18.2831 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 123ZB UT WOS:000076154600003 PM 9744860 ER PT J AU Pikaart, MI Recillas-Targa, F Felsenfeld, G AF Pikaart, MI Recillas-Targa, F Felsenfeld, G TI Loss of transcriptional activity of a transgene is accompanied by DNA methylation and histone deacetylation and is prevented by insulators SO GENES & DEVELOPMENT LA English DT Article DE insulator; transcription; DNA methylation; histone acetylation; silencing ID POSITION-EFFECT VARIEGATION; CHROMATIN ACCESSIBILITY; GENE-EXPRESSION; DROSOPHILA; ACETYLATION; PROTEIN; DOMAIN; LOCUS; HETEROCHROMATIN; PROBABILITY AB The constitutive DNase I hypersensitive site at the 5' end of the chicken beta-globin locus marks the boundary of the active chromatin domain in erythroid cells. The DNA sequence containing this site has the properties of an insulator, as shown by its ability in stable transformation experiments to block enhancer-promoter interaction when it lies between the two, but not when it lies outside, and to protect against position effects in Drosophila. We now show that the chicken insulator can protect a stably integrated gene, which is otherwise subject to great variability of expression, from chromatin-mediated repression in cell culture. When the integrated reporter gene is surrounded by insulator elements, stably transformed cell lines display consistent enhancer-dependent expression levels, in accord with the strength of the enhancer. In the absence of insulators, long-term nonselective propagation of cells carrying the integrated reporter gene results in gradual extinction of the reporter's expression, with expression patterns from tandemly repeated inserted genes suggesting that the extinction of adjacent genes is coupled. We show that the uninsulated reporter genes, in addition to becoming transcriptionally inactive, lose several epigenetic hallmarks of active chromatin, including nuclease accessibility, DNA hypomethylation, and histone hyperacetylation during time in culture. Treatment with inhibitors of histone deacetylase or DNA methylation reverses the extinction of the uninsulated genes. Extinction is completely prevented by flanking the reporter construct with insulators. Furthermore, in contrast to the uninsulated reporter genes, chromatin over the insulated genes retains nuclease accessibility and histone hyperacetylation. However, there is no clear correlation between the presence of the insulators and the level of DNA methylation. This leads us to propose a model for the insulator's ability to protect against extinction in the transformed cell lines and to function as a chromatin boundary for the chicken beta-globin locus in normal erythroid cells. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Felsenfeld, G (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM GXF@vger.niddk.nih.gov NR 40 TC 300 Z9 306 U1 1 U2 8 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD SEP 15 PY 1998 VL 12 IS 18 BP 2852 EP 2862 DI 10.1101/gad.12.18.2852 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 123ZB UT WOS:000076154600005 PM 9744862 ER PT J AU Nagaraja, R MacMillan, S Jones, C Masisi, M Pengue, G Porta, G Miao, S Casamassimi, A D'Urso, M Brownstein, B Schlessinger, D AF Nagaraja, R MacMillan, S Jones, C Masisi, M Pengue, G Porta, G Miao, S Casamassimi, A D'Urso, M Brownstein, B Schlessinger, D TI Integrated YAC/STS physical and genetic map of 22.5 Mb of human Xq24-q26 at 56-kb inter-STS resolution SO GENOMICS LA English DT Article ID SEQUENCE-TAGGED SITES; DISEASE XLP LOCUS; X-CHROMOSOME; HUMAN GENOME; YAC CONTIG; LYMPHOPROLIFERATIVE SYNDROME; YEAST; CONSTRUCTION; LIBRARY; REGION AB A yeast artificial chromosome sequence-tagged site-based (YAC/STS) physical map of 22.5 Mb of the Xq24-q26 cytogenetic band region of the human X chromosome has been assembled. DNA coverage includes 857 large-insert clones formatted with 405 STSs to provide ninefold depth of DNA At five points, no bridging clones have been recovered from 20 X-chromosome equivalents of human DNA in YACs or bacterial clones, but the placement of 25 ("CA")(n) polymorphic markers permits the ordering of contigs by comparison with the genetic linkage map and radiation hybrid data. The map localizes the X3000 translocation breakpoint and six genes (ANT2, NDUFA1, LAMPS, OCRL, IGSF1, and HDGF) at better than 100-kb resolution. The relatively gene-poor nature of the region is consistent with relatively low uniform 34-42% GC content in STSs across nearly all of the region. (C) 1998 Academic Press. C1 NIA, Genet Lab, IRP, Baltimore, MD 21224 USA. Washington Univ, Sch Med, Ctr Genet Med, St Louis, MO 63110 USA. Univ Pavia, Dept Human Pathol & Genet, Fac Med & Surg 2, Milan, Italy. Int Inst Genet & Biophys, I-80125 Naples, Italy. RP Nagaraja, R (reprint author), NIA, Genet Lab, IRP, Box 31,5600 Nathan Shock Ave, Baltimore, MD 21224 USA. EM NagarajaR@grc.nia.nih.gov FU NHGRI NIH HHS [HG00201]; Telethon [E.0633] NR 37 TC 19 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD SEP 15 PY 1998 VL 52 IS 3 BP 247 EP 266 DI 10.1006/geno.1998.5438 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 130EA UT WOS:000076505900001 PM 9790744 ER PT J AU Djouadi, F Weinheimer, CJ Saffitz, JE Pitchford, C Bastin, J Gonzalez, FJ Kelly, DP AF Djouadi, F Weinheimer, CJ Saffitz, JE Pitchford, C Bastin, J Gonzalez, FJ Kelly, DP TI A gender-related defect in lipid metabolism and glucose homeostasis in peroxisome proliferator-activated receptor alpha-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE fatty acids; estrogens; myocardial diseases; hypoglycemia; cytoplasmic and nuclear receptors ID TISSUE-SPECIFIC EXPRESSION; ACYL-COA DEHYDROGENASE; FATTY-ACID OXIDATION; GENE-EXPRESSION; CLOFIBRIC ACID; RAT; MOUSE; IDENTIFICATION; INDUCTION; ELEMENT AB The peroxisome proliferator-activated receptor alpha (PPAR alpha) is a nuclear receptor implicated in the control of cellular lipid utilization. To test the hypothesis that PPAR alpha is activated as a component of the cellular lipid homeostatic response, the expression of PPAR alpha target genes was characterized in response to a perturbation in cellular lipid oxidative flux caused by pharmacologic inhibition of mitochondrial fatty acid import. Inhibition of fatty acid oxidative flux caused a feedback induction of PPAR alpha target genes encoding fatty acid oxidation enzymes in liver and heart. In mice lacking PPAR alpha (PPAR alpha-/-), inhibition of cellular fatty acid flux caused massive hepatic and cardiac lipid accumulation, hypoglycemia, and death in 100% of male, but only 25% of female PPAR alpha-/- mice. The metabolic phenotype of male PPAR alpha-/- mice was rescued by a 2-wk pretreatment with beta-estradiol. These results demonstrate a pivotal role for PPAR alpha in lipid and glucose homeostasis in vivo and implicate estrogen signaling pathways in the regulation of cardiac and hepatic lipid metabolism. C1 Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Biol & Pharmacol, St Louis, MO 63110 USA. Univ Paris 07, INSERM, U319, Paris, France. NCI, NIH, Met Lab, Bethesda, MD 20892 USA. RP Kelly, DP (reprint author), Washington Univ, Sch Med, Cardiovasc Res Ctr, Dept Med, POB 8086,660 S Euclid Ave, St Louis, MO 63110 USA. RI Bastin, Jean/E-3083-2016 FU NIDDK NIH HHS [DK-45416] NR 27 TC 285 Z9 294 U1 2 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1998 VL 102 IS 6 BP 1083 EP 1091 DI 10.1172/JCI3949 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 122EX UT WOS:000076059900003 PM 9739042 ER PT J AU Sarobe, P Pendleton, CD Akatsuka, T Lau, D Engelhard, VH Feinstone, SM Berzofsky, JA AF Sarobe, P Pendleton, CD Akatsuka, T Lau, D Engelhard, VH Feinstone, SM Berzofsky, JA TI Enhanced in vitro potency and in vivo immunogenicity of a CTL epitope from hepatitis C virus core protein following amino acid replacement at secondary HLA-A2.1 binding positions SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE cytotoxic T lymphocyte; epitope enhancement; major histocompatibility complex class I affinity peptide, synthetic; vaccine ID CYTOTOXIC T-LYMPHOCYTE; CLASS-I MOLECULES; DESIGNING PEPTIDE VACCINES; PAPILLOMAVIRUS TYPE-16 E6; NON-B-HEPATITIS; TRANSGENIC MICE; NUCLEOTIDE-SEQUENCE; NON-A; VIRAL-HEPATITIS; ALPHA-3 DOMAIN AB Since the natural immune response to hepatitis C virus (HCV) is often unable to clear the infection, to enhance immunogenicity we studied substituted peptides from an HCV cytotoxic T lymphocyte (CTL) epitope (C7A2) from a conserved region of the HCV core protein (DLMGYIPLV) recognized by CTL lines from HLA-A2.1(+) HCV-infected patients and HLA-A2.1 transgenic mice. HLA-A2.1 binding, human and murine CTL recognition, and in vivo immunogenicity (using mice transgenic for human HLA-A2 in lieu of immunizing humans) were analyzed to define peptides with enhanced immunogenicity. Peptides substituted at position 1 showed enhanced HLA-A2 binding affinity, but paradoxically poorer immunogenicity. A peptide with Ala substituted at position 8 (8A) showed higher HLA-A2 binding affinity and CTL recognition and was a more potent in vivo immunogen in HLA-A2-transgenic mice, inducing higher CTL responses with higher avidity against native C7A2 than induced by C7A2 itself. These results suggest that peptide 8A is a more potent in vitro antigen and in vivo immunogen than C7A2 and may be useful as a vaccine component. They provide proof of principle that the strategy of epitope enhancement can enhance immunogenicity of a CTL epitope recognized by human CTL. C1 NCI, NIH, Metab Branch, Mol Immunogenet & Vaccine Res Sect, Bethesda, MD 20892 USA. NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Microbiol, Charlottesville, VA 22908 USA. NIH, Div Viral Prod, Lab Hepatitis Viruses, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. RP Berzofsky, JA (reprint author), NCI, NIH, Metab Branch, Mol Immunogenet & Vaccine Res Sect, Bldg 10,Room 6B12, Bethesda, MD 20892 USA. RI Sarobe, Pablo/D-6976-2017 OI Sarobe, Pablo/0000-0003-0503-7905 FU NIAID NIH HHS [AI-21393] NR 69 TC 82 Z9 84 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD SEP 15 PY 1998 VL 102 IS 6 BP 1239 EP 1248 DI 10.1172/JCI3714 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 122EX UT WOS:000076059900019 PM 9739058 ER PT J AU Wu, CY Wang, KN McDyer, JF Seder, RA AF Wu, CY Wang, KN McDyer, JF Seder, RA TI Prostaglandin E-2 and dexamethasone inhibit IL-12 receptor expression and IL-12 responsiveness SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; DIFFERENTIAL MODULATION; INTERLEUKIN-2 SYNTHESIS; CYTOKINE PRODUCTION; INTERFERON-GAMMA; GENE-EXPRESSION; IFN-GAMMA; IN-VITRO; TH1; CAMP AB Regulation of the factors governing IL-12R expression and IL-12 responsiveness has been shown to be important in the generation and stability of Th1- and Th2-type responses. In this regard, cytokines have been shown to have a prominent role in regulating IL-12R expression. In this study, the role that PGE(2) and dexamethasone (DXM) have in regulating IL-12R expression was evaluated. Addition of PGE(2) or DXM to human PBMCs stimulated,vith immobilized anti-CD3 plus IL-12 inhibited the production of IFN-gamma in a dose-responsive manner. Moreover, PBMCs stimulated with immobilized anti-CD3 in the presence of PGE(2) or DXM for 3 days, washed extensively, and restimulated in the presence of IL-12 still did not produce IFN-gamma. This lack of IL-12 responsiveness from cells cultured in either PGE(2) or DXM was correlated with diminished surface expression of IL-12R beta 1, IL-12R beta 2 mRNA expression, and IL-12 binding. Finally, the PGE(2)- and DXM-mediated inhibition of IL-12R expression was not affected significantly by addition of neutralizing Abs against either IL-4, IL-10, or TGF-beta. By contrast, addition of dibutyryl cAMP, 8-bromoadenosine 3:5 cAMP (8-Br-cAMP), or cholera toxin substantially reduced IL-12R expression, suggesting that PGE(2) may be mediating its effects through enhancement of cAMP. C1 NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Clin Immunol Sect, Clin Invest Lab, NIH, Bldg 10,Room 11C215, Bethesda, MD 20892 USA. NR 36 TC 150 Z9 157 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1998 VL 161 IS 6 BP 2723 EP 2730 PG 8 WC Immunology SC Immunology GA 118WU UT WOS:000075864600009 PM 9743329 ER PT J AU Sarin, A Haddad, EK Henkart, PA AF Sarin, A Haddad, EK Henkart, PA TI Caspase dependence of target cell damage induced by cytotoxic lymphocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ACTIVATED KILLER-CELLS; GRANZYME-B; MEDIATED CYTOTOXICITY; CYTOCHROME-C; IN-VIVO; PHOSPHATIDYLSERINE EXPOSURE; FAMILY PROTEASES; APOPTOTIC DEATH; NATURAL-KILLER; INHIBITION AB Since the CTL secreted granule protease granzyme B can activate multiple target caspases, it has been proposed that this pathway is responsible for CTL-induced cytolysis of Fas-negative targets. However, target lysis via the granule exocytosis pathway is completely resistant to caspase inhibitors. To test the possibility that granzymes trigger a postcaspase cytoplasmic apoptotic pathway leading to lysis, we have examined the caspase dependence of several cytoplasmic changes associated with apoptotic death. Rapid prelytic phosphatidylserine externalization was induced in Jurkat target cells by both the Fas ligand (FasL)/Fas and the granule exocytosis effector pathways, This was specifically blocked by peptide ketone caspase inhibitors when induced by the former, but not by the latter, pathway. A rapid prelytic loss of target mitochondrial psi was also induced by both CTL effector pathways, and this was also specifically blocked by caspase inhibitors when induced by the FasL/Fas, but not by the granule exocytosis, pathway. Similarly, target membrane blebbing induced by CTL via the FasL/Fas, but not via the granule exocytosis, effector pathway was specifically blocked by caspase inhibitors. In contrast to the above nonnuclear damage, CTL-induccd target staining by the lipid probe FM1-43 reflecting plasma membrane endocytosis was blocked by caspase inhibitors. Thus, when caspase activation is blocked, the granule exocytosis pathway triggers several parameters of target apoptotic damage in addition to lysis, suggesting that granzymes directly trigger a postcaspase cytoplasmic apoptotic death pathway. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Henkart, PA (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 4B17, Bethesda, MD 20892 USA. NR 51 TC 76 Z9 85 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1998 VL 161 IS 6 BP 2810 EP 2816 PG 7 WC Immunology SC Immunology GA 118WU UT WOS:000075864600020 PM 9743340 ER PT J AU Jakob, T Walker, PS Krieg, AM Udey, MC Vogel, JC AF Jakob, T Walker, PS Krieg, AM Udey, MC Vogel, JC TI Activation of cutaneous dendritic cells by CpG-containing oligodeoxynucleotides: A role for dendritic cells in the augmentation of th1 responses by immunostimulatory DNA SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; BACTERIAL-DNA; FACTOR-ALPHA; IMMUNE ACTIVATION; LEISHMANIA-MAJOR; GAMMA PRODUCTION; LYMPH-NODE; NAKED DNA; ANTIGEN; MURINE AB Genetic vaccination depends at least in part on the adjuvant properties of plasmids, properties that have been ascribed to unmethylated CpG dinucleotides in bacterial DNA, Because dendritic cells (DC) participate in the T cell priming that occurs during genetic vaccination, we reasoned that CpG-containing DNA might activate DC. Thus, we assessed the effects of CpG oligodeoxynucleotides (CpG ODN) on Langerhans cell (LC)-like murine fetal skin-derived DC (FSDDC) in vitro and on LC in vivo. Treatment with CpG ODN as well as LPS induced FSDDC maturation, manifested by decreased E-cadherin-mediated adhesion, up-regulation of MHC class II and costimulator molecule expression, and acquisition of enhanced accessory cell activity. In contrast to LPS, CpG ODN stimulated FSDDC to produce large amounts of IL-12 but only small amounts of IL-6 and TNF-alpha. Injection of CpG ODN into murine dermis also led to enhanced expression of MHC class II and CD86 Ag by LC in overlying epidermis and intracytoplasmic IL-12 accumulation in a subpopulation of activated LC, We conclude that immunostimulatory CpG ODN stimulate DC in vitro and in vivo. Bacterial DNA-based vaccines may preferentially elicit Th1-predominant immune responses because they activate and mobilize DC and induce them to produce large amounts of IL-12. C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Iowa City, IA 52242 USA. Univ Iowa, Coll Med, Dept Internal Med, Iowa City, IA 52242 USA. RP Vogel, JC (reprint author), NCI, Dermatol Branch, NIH, Bldg 10,Room 12N238,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Jakob, Thilo/J-1621-2012 NR 48 TC 405 Z9 415 U1 3 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1998 VL 161 IS 6 BP 3042 EP 3049 PG 8 WC Immunology SC Immunology GA 118WU UT WOS:000075864600049 PM 9743369 ER PT J AU Zhang, YH McCluskey, K Fujii, K Wahl, LM AF Zhang, YH McCluskey, K Fujii, K Wahl, LM TI Differential regulation of monocyte matrix metalloproteinase and TIMP-1 production by TNF-alpha granulocyte-macrophage CSF, and IL-1 beta through prostaglandin-dependent and -independent mechanisms SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN MONONUCLEAR PHAGOCYTES; HUMAN ALVEOLAR MACROPHAGES; INTERSTITIAL COLLAGENASE; TISSUE INHIBITOR; EXPRESSION; INTERLEUKIN-4; BIOSYNTHESIS; SUPPRESSION; GELATINASE; CYTOKINES AB Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) produced by monocytes are believed to be involved in the migration of these cells through the basement membrane and the ensuing destruction of connective tissue in chronic inflammatory lesions. Because monocytes encounter a variety of cytokines at these sites,,ve examined the effect of cytokines either alone or in combination on the production of monocyte MMPs and TIMP-1. TNF-alpha, granulocyte-macrophage-CSF (GM-CSF), or IL-1 beta when added individually enhanced the endogenous levels of 92-kDa gelatinase (MMP-9) and TIMP-1 but failed to induce interstitial collagenase (MMP-1). However, GM-CSF, when added with either TNF-alpha or IL-1 beta, induced MMP-1 and synergistically enhanced MMP-9 and TIMP-1, Th2 cytokines, such as IL-4, inhibited the induction of MMPs and TIMP-1 by TNF-alpha, GM-CSF, and IL-1, Cytokine stimulation of MMP-1 was due, at least in part, to an increase in the release of arachidonic acid and PG E-2 (PGE(2)), because inhibition of MMP-1 by indomethacin could be reversed by exogenous PGE(2). In contrast to MMP-1, cytokine stimulation of MMP-9 and TIMP-1 was unaffected by indomethacin. The PGE(2)-independent induction of monocyte MMP-9 and TIMP-1 by these cytokines differed from stimulation of MMP-9 and TIMP-1 by LPS, which is in large part PG-dependent. In addition, LPS stimulated higher levels of MMP-1 whereas cytokines induced higher levels of MMP-9 and TIMP-1, This is the first demonstration that monocyte MMP-1 can be induced by cytokines and that MMP-1, MMP-9, and TIMP-1 are differentially regulated by cytokines through PG-dependent and -independent mechanisms. C1 NIDR, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. RP Wahl, LM (reprint author), NIDR, Immunopathol Sect, NIH, Bldg 30,Room 325, Bethesda, MD 20892 USA. EM wahl@yoda.nidr.nih.gov NR 30 TC 219 Z9 224 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1998 VL 161 IS 6 BP 3071 EP 3076 PG 6 WC Immunology SC Immunology GA 118WU UT WOS:000075864600053 PM 9743373 ER PT J AU Zaitseva, MB Lee, S Rabin, RL Tiffany, HL Farber, JM Peden, KWC Murphy, PM Golding, H AF Zaitseva, MB Lee, S Rabin, RL Tiffany, HL Farber, JM Peden, KWC Murphy, PM Golding, H TI CXCR4 and CCR5 on human thymocytes: Biological function and role in HIV-1 infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VIRUS TYPE-1 INFECTION; ACQUIRED IMMUNODEFICIENCY SYNDROME; LINE-TROPIC HIV-1; SCID-HU MOUSE; T-CELL; IN-VITRO; HUMAN THYMUS; ENVELOPE GLYCOPROTEIN; PROGENITOR CELLS; PERIPHERAL-BLOOD AB Thymocyte infection with HIV-1 is associated with thymic involution and impaired thymopoiesis, particularly in pediatric patients. To define mechanisms of thymocyte infection,,ve examined human thymocytes for expression and function of CXCR4 and CCR5, the major cell entry coreceptors for T cell line-tropic (T-tropic) and macrophage-tropic (M-tropic) strains of HIV-1, respectively, CXCR4 was detected on the surface of all thymocytes, CXCR4 expression on mature, high level TCR thymocytes was similar to that on peripheral blood T cells, but,vas much lower than that on immature thymocytes, including CD34(+) thymic progenitors. Consistent with this, stroma-derived factor-1 (SDF-1) induced calcium flux primarily in immature thymocytes, with CD34(+) progenitors giving the strongest response, In addition, SDF-1 mRNA was detected in thymic-derived stromal cells, and SDF-1 induced chemotaxis of thymocytes, suggesting that CXCR4; may play a role in thymocyte migration. Infection of immature thymocytes by the T-tropic HIV-1 strain LAI was 10-fold more efficient than that in mature thymocytes, consistent with their relative CXCR4 surface expression. Anti-CXCR4 antiserum or SDF-1 blocked fusion of thymocytes with cells expressing the LAI envelope. In contrast to CXCR4, CCR5 was detected at low levels on thymocytes, and CCR5 agonists did not induce calcium flux of chemotaxis in thymocytes, However, CD4(+) mature thymocytes;were productively infected with the CCR5-tropic strain Ba-L, and this infection was specifically inhibited with the CCR5 agonist, macrophage inflammatory protein-1 beta. Our data provide strong evidence that CXCR4 and CCR5 function as coreceptors for HIV-1. infection of human thymocytes. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Zaitseva, MB (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bldg 29B,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 58 TC 103 Z9 109 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1998 VL 161 IS 6 BP 3103 EP 3113 PG 11 WC Immunology SC Immunology GA 118WU UT WOS:000075864600057 PM 9743377 ER PT J AU Correale, P Walmsley, K Zaremba, S Zhu, MZ Schlom, J Tsang, KY AF Correale, P Walmsley, K Zaremba, S Zhu, MZ Schlom, J Tsang, KY TI Generation of human cytolytic T lymphocyte lines directed against prostate-specific antigen (PSA) employing a PSA oligoepitope peptide SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-INFILTRATING LYMPHOCYTES; MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULES; HUMAN-MELANOMA; CONVERTING ENZYME; IDENTIFICATION; CELLS; EPITOPES; MHC; RECOGNIZE AB Prostate specific Ag (PSA), which is expressed in a majority of prostate cancers, is a potential target for specific immunotherapy. Previous studies have shown that two 10-mer PSA peptides (designated PSA-1 and PSA-3) selected to conform to human HLA class I-A2 motifs can elicit CTL responses in vitro. A longer PSA peptide (30-mer) designated PSA-OP (oligoepitope peptide), which contains both the PSA-1 and PSA-3 HLA-A2 epitopes and an additional potential CTL epitope (designated PSA-9) for the HLA-class I-A3 allele, was investigated for the ability to induce cytotoxic T cell activity. T cell lines from different HLA-A2 and HLA-A3 donors were established by in vitro stimulation with PSA-OP; the CTL lines lysed PSA-OP as well as PSA-1- or PSA-3-pulsed C1R-A2 cells, and PSA-OP and PSA-9-pulsed C1R-A3 cells, respectively. The CTL lines derived from the PSA-OP peptide also lysed PSA-positive prostate cancer cells. PSA-OP-derived T cell lines also lysed recombinant vaccinia-PSA-infected targets but not targets infected with wild-type vaccinia, PSA-OP did not bind HLA-A2 and HLA-A3 molecules. The decrease in cytotoxicity in the presence of protease inhibitors suggests that the PSA-OP is cleaved into shorter peptides, which in turn can interact with HLA-class I molecules and, as a consequence, induce CTL-mediated lysis,We have also demonstrated that it is possible to induce CTL responses in HLA-A2.1/K-b transgenic mice by immunization with PSA-OP with adjuvant. These studies thus provide evidence that oligopeptides such as PSA-OP may be useful candidates for peptide-based cancer vaccines. C1 NCI, Tumor Immunol & Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Div Basic Sci, NIH, 10 Ctr Dr,Bldg 10,Room 8B07, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Correale, Pierpaolo/K-1640-2016 OI Correale, Pierpaolo/0000-0003-2154-6734 NR 59 TC 101 Z9 104 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1998 VL 161 IS 6 BP 3186 EP 3194 PG 9 WC Immunology SC Immunology GA 118WU UT WOS:000075864600067 PM 9743387 ER PT J AU Ostrowski, MA Justement, SJ Catanzaro, A Hallahan, CA Ehler, LA Mizell, SB Kumar, PN Mican, JA Chun, TW Fauci, AS AF Ostrowski, MA Justement, SJ Catanzaro, A Hallahan, CA Ehler, LA Mizell, SB Kumar, PN Mican, JA Chun, TW Fauci, AS TI Expression of chemokine receptors CXCR4 and CCR5 in HIV-1-infected and uninfected individuals SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL ACTIVATION; HIV-1 INFECTION; DISEASE PROGRESSION; FUSION COFACTOR; VIRAL PHENOTYPE; TROPIC HIV-1; RESISTANCE; LYMPHOCYTES; REPLICATION AB The chemokine receptors CXCR4 and CCR5 have been identified as major coreceptors for HIV-1 entry into CD4(+) T cells. The majority of primary HIV-1 isolates in early disease use CCR5 as a coreceptor, whereas during disease progression with the emergence pf syncytium-inducing viruses, CXCR4 is also used. We performed a cross-sectional study in which we evaluated the expression of two HIV-1 coreceptors, CCR5 and CXCR4, in whole blood samples taken from HIV-1-infected and uninfected individuals. We demonstrate that CXCR4 on CD4(+) and CD8(+) T cells, and CD14(+) monocytes is significantly down-regulated, and CCR5 expression on CD4(+) T cells is up-regulated in HIV-infected individuals compared with uninfected controls. Coreceptor expression correlated with the level of cellular activation in vivo in both HIV-infected and uninfected individuals, with CXCR4 being expressed predominantly on quiescent (HLA-DR-) T cells and CCR5 being expressed predominantly on activated (HLA-DR+) T cells, Lower expression of CXCR4 and higher expression of CCR5 on CD4(+) T cells correlated with advancing disease. In addition, a tendency for greater activation of CXCR4(+)CD4(+) T cells in patients with advanced disease was observed. Patients who harbored syncytium-inducing viruses, however, could not be distinguished from those who harbored nonsyncytium-inducing viruses based on the level of CD4(+) T cell activation or chemokine receptor expression. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Div Infect Dis, Washington, DC 20057 USA. RP Ostrowski, MA (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A11,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA. NR 35 TC 153 Z9 167 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD SEP 15 PY 1998 VL 161 IS 6 BP 3195 EP 3201 PG 7 WC Immunology SC Immunology GA 118WU UT WOS:000075864600068 PM 9743388 ER PT J AU Vicario-Abejon, C Collin, C McKay, RDG Segal, M AF Vicario-Abejon, C Collin, C McKay, RDG Segal, M TI Neurotrophins induce formation of functional excitatory and inhibitory synapses between cultured hippocampal neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE synapses; hippocampus; culture; BDNF; NT-3; GABA ID DEVELOPING NEUROMUSCULAR SYNAPSES; SYNAPTIC TRANSMISSION; RAT HIPPOCAMPUS; NERVOUS-SYSTEM; GROWTH-FACTOR; BDNF; RECEPTORS; SYNAPTOGENESIS; NT-3; EXPRESSION AB Cell cultures were used to analyze the role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in the development of synaptic transmission. Neurons obtained from embryonic day 18 (E18) rat hippocampus and cultured for 2 weeks exhibited extensive spontaneous synaptic activity. By comparison, neurons obtained from E16 hippocampus expressed very low levels of spontaneous or evoked synaptic activity. Neurotrophin treatment produced a sevenfold increase in the number of functional synaptic connections in the E16 cultures. BDNF induced formation of both excitatory and inhibitory synapses, whereas NT-3 induced formation of only excitatory synapses. These effects were independent of serum or the age of the glia bed used for the culture. They were not accompanied by significant changes in synaptic-vesicle-associated proteins or glutamate receptors. Treatment of the cultures with the neurotrophins for 3 d was sufficient to establish the maximal level of functional synapses. During this period, neurotrophins did not affect the viability or the morphology of the excitatory neurons, although they did produce an increase in the number and length of dendrites of the GABAergic neurons. Remarkably, only BDNF caused an increase in the number of axonal branches and in the total length of the axons of the GABAergic neurons. These results support a unique and differential role for neurotrophins in the formation of excitatory and inhibitory synapses in the developing hippocampus. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP McKay, RDG (reprint author), NINDS, Mol Biol Lab, NIH, Bldg 36,Room 3DO2, Bethesda, MD 20892 USA. NR 55 TC 254 Z9 260 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1998 VL 18 IS 18 BP 7256 EP 7271 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 119JR UT WOS:000075893000020 PM 9736647 ER PT J AU Basso, MA Wurtz, RH AF Basso, MA Wurtz, RH TI Modulation of neuronal activity in superior colliculus by changes in target probability SO JOURNAL OF NEUROSCIENCE LA English DT Article DE monkey; saccade; motor set; target selection; decision; buildup neurons ID FRONTAL EYE FIELD; VISUAL-SEARCH; BEHAVING MONKEY; MOVEMENTS; ATTENTION; SELECTION; SACCADES; MACAQUE; CORTEX; CELLS AB Complex visual scenes require that a target for an impending saccadic eye movement be selected from a larger number of possible targets. We investigated whether changing the probability that a visual stimulus would be selected as the target for a saccade altered activity of monkey superior colliculus (SC) neurons in two experiments. First, we changed the number of possible targets on each trial. Second, we kept the visual display constant and presented a single saccade target repeatedly so that target probability was established over time. Buildup neurons in the SC, those with delay period activity, showed a consistent reduction in activity as the probability of the saccade decreased, independent of the visual stimulus configuration. Other SC neurons, fixation and burst, were largely unaffected by the changes in saccade target probability. Because we had monkeys making saccades to many locations within the visual field, we could examine activity associated with saccades outside of the movement field of neurons. We found the activity of buildup neurons to be similar across the SC, before the target was identified, and reduced when the number of possible targets increased. The results of our experiments are consistent with a role for this activity in establishing a motor set. We found, consistent with this interpretation, that the activity of these neurons was predictive of the latency of a saccadic eye movement and not other saccade parameters such as end point or peak velocity. C1 NEI, Sensorimotor Res Lab, Bethesda, MD 20892 USA. RP Basso, MA (reprint author), NEI, Sensorimotor Res Lab, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. NR 38 TC 301 Z9 302 U1 1 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD SEP 15 PY 1998 VL 18 IS 18 BP 7519 EP 7534 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 119JR UT WOS:000075893000043 PM 9736670 ER PT J AU Dabestani, R Reszka, KJ Sigman, ME AF Dabestani, R Reszka, KJ Sigman, ME TI Surface catalyzed electron transfer from polycyclic aromatic hydrocarbons (PAH) to methyl viologen dication: evidence for ground-state charge transfer complex formation on silica gel SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY LA English DT Article DE polycyclic aromatic hydrocarbons; methyl viologen dication; electron transfer ID PHOTOREDUCTION YIELD; RADICAL-CATION; SPIN-RESONANCE; CHAIN-LENGTH; ION RADICALS; DRY SILICA; METHYLVIOLOGEN; ALKYLMETHYLVIOLOGENS; PHOTOCHEMISTRY; VESICLES AB Porous silica surfaces are shown to slowly catalyze the oxidation of adsorbed polycyclic aromatic hydrocarbons (PAH) to the corresponding radical cation via Lewis acid sites present on the surface. When a good electron acceptor such as methyl viologen dication (MV++) is co-adsorbed on silica surface, a red-shifted structureless absorption band characteristic of a ground-state charge transfer (CT) complex formed between the PAH and MV++ is observed. Oxygen efficiently competes with MV++ for the trapped electrons on the active sites of silica surface causing a significant decrease in the concentration of ground-state CT complex. The rate of this electron transfer process is enhanced dramatically at the solid/liquid interface when solution of PAH in a non-polar solvent is added to dry silica containing adsorbed MV++. Room temperature electron paramagnetic resonance (EPR) spectra of PAHs adsorbed on silica show a broad unresolved signal (g=2.0031-2.0045) due to PAH(+); radical cation which disappears in the presence of air but can be restored upon evacuation of the sample. The EPR measurements of mixed samples containing PAH and MV++ co-adsorbed on silica show a composite signal with hyperfine structure that may be due to presence of two paramagnetic species corresponding to MV++ and possibly PAH radical cation. (C) 1998 Elsevier Science S.A. All rights reserved. C1 Oak Ridge Natl Lab, Div Chem & Analyt Sci, Oak Ridge, TN 37831 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Dabestani, R (reprint author), Oak Ridge Natl Lab, Div Chem & Analyt Sci, POB 2008,MS-6100, Oak Ridge, TN 37831 USA. NR 42 TC 69 Z9 69 U1 2 U2 14 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1010-6030 J9 J PHOTOCH PHOTOBIO A JI J. Photochem. Photobiol. A-Chem. PD SEP 15 PY 1998 VL 117 IS 3 BP 223 EP 233 DI 10.1016/S1010-6030(98)00327-X PG 11 WC Chemistry, Physical SC Chemistry GA 136AN UT WOS:000076835600009 ER PT J AU Burland, V Shao, Y Perna, NT Plunkett, G Sofia, HJ Blattner, FR AF Burland, V Shao, Y Perna, NT Plunkett, G Sofia, HJ Blattner, FR TI The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157 : H7 SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GRAM-NEGATIVE BACTERIA; GENERAL SECRETORY PATHWAY; PROGRAMMED CELL-DEATH; DIFFICILE TOXIN-B; BASIC REPLICON; NUCLEOTIDE-SEQUENCE; ENCODED HEMOLYSIN; RHO-PROTEINS; HLY OPERON; STRAINS AB The complete DNA sequence of pO157, the large virulence plasmid of EHEC strain O157:H7 EDL 933, is presented. The 92 kb F-like plasmid is composed of segments of putative virulence genes in a framework of replication and maintenance regions, with seven insertion sequence elements, located mostly at the boundaries of the virulence segments. One hundred open reading frames (ORFs) were identified, of which 19 were previously sequenced potential virulence genes. Forty-two ORFs were sufficiently similar to known proteins for suggested functions to be assigned, and 22 had no convincing similarity with any known proteins. Of the newly identified genes, an unusually large ORF of 3169 amino acids has a putative cytotoxin active site shared with the large clostridial toxin (LCT) family and proteins such as ToxA and B of Clostridium difficile. A conserved motif was detected that links the large ORF and the LCT proteins with the OCH1 family of glycosyltransferases, In the complete sequence, the mosaic form can be observed at the levels of base composition, codon usage and gene organization. Insights were obtained from patterns of DNA composition as well as the pathogenic and 'housekeeping' gene segments. Evolutionary trees built from shared plasmid maintenance genes show that even these genes have heterogeneous origins. C1 Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Burland, V (reprint author), Univ Wisconsin, Genet Lab, 445 Henry Mall, Madison, WI 53706 USA. EM ecoli@genetics.wisc.edu RI Plunkett III, Guy/B-8058-2009 OI Plunkett III, Guy/0000-0003-1422-469X NR 75 TC 231 Z9 264 U1 2 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 15 PY 1998 VL 26 IS 18 BP 4196 EP 4204 DI 10.1093/nar/26.18.4196 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121GG UT WOS:000076004500015 PM 9722640 ER PT J AU Aravind, L Leipe, DD Koonin, EV AF Aravind, L Leipe, DD Koonin, EV TI Toprim - a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins SO NUCLEIC ACIDS RESEARCH LA English DT Article ID ESCHERICHIA-COLI PRIMASE; AMINO-ACID-SEQUENCE; STRUCTURAL CLASSIFICATION; RESTRICTION-ENDONUCLEASE; BINDING-PROTEINS; REPLICATION FORK; RECOGNITION; DATABASES; ALIGNMENT; MOTIF AB Iterative profile searches and structural modeling show that bacterial DnaG-type primases, small primase-like proteins from bacteria and archaea, type IA and type It topoisomerases, bacterial and archaeal nucleases of the OLD family and bacterial DNA repair proteins of the RecR/M family contain a common domain, designated Toprim (topoisomerase-primase) domain. The domain consists of similar to 100 amino acids and has two conserved motifs, one of which centers at a conserved glutamate and the other one at two conserved aspartates (DxD), Examination of the structure of Topo IA and Topo II and modeling of the Toprim domains of the primases reveal a compact beta/alpha fold, with the conserved negatively charged residues juxtaposed, and inserts seen in Topo IA and Topo II. The conserved glutamate may act as a general base in nucleotide polymerization by primases and in strand rejoining by topoisomerases and as a general acid in strand cleavage by topoisomerases and nucleases, The role of this glutamate in catalysis is supported by site-directed mutagenesis data on primases and Topo IA. The DxD motif may coordinate Mg2+ that is required for the activity of all Toprim-containing enzymes. The common ancestor of all life forms could encode a prototype Toprim enzyme that might have had both nucleotidyl transferase and polynucleotide cleaving activity. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Texas A&M Univ, Dept Biol, College Stn, TX 77843 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NR 73 TC 215 Z9 220 U1 0 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD SEP 15 PY 1998 VL 26 IS 18 BP 4205 EP 4213 DI 10.1093/nar/26.18.4205 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 121GG UT WOS:000076004500016 PM 9722641 ER PT J AU Bicout, DJ Berezhkovskii, AM Weiss, GH AF Bicout, DJ Berezhkovskii, AM Weiss, GH TI Where do Brownian particles spend their time? SO PHYSICA A LA English DT Article AB We study statistical properties of the fraction of time spent by a Brownian particle in different regions of space. Also treated in our analysis are the effects of one or more constraints on the trajectory at different times. We show that the effects of imposing n constraints can be analyzed in terms of the probability density of the residence time for a single constraint, An analogy to the description of the spatial density of a polymer chain is proposed and applied to evaluate the monomeric density in some specific examples. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NCI, Math & Stat Comp Lab, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. NIDDKD, Chem Phys Lab, Bethesda, MD 20892 USA. RP Weiss, GH (reprint author), NCI, Math & Stat Comp Lab, Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. NR 16 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4371 J9 PHYSICA A JI Physica A PD SEP 15 PY 1998 VL 258 IS 3-4 BP 352 EP 364 DI 10.1016/S0378-4371(98)00247-7 PG 13 WC Physics, Multidisciplinary SC Physics GA 122DW UT WOS:000076057500008 ER PT J AU Westaway, D Telling, G Priola, S AF Westaway, D Telling, G Priola, S TI Prions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article; Proceedings Paper CT 9th Annual Frontiers of Science Symposium CY NOV 07-09, 1997 CL IRVINE, CALIFORNIA SP Natl Acad Sci (NAS) ID PROTEIN; SCRAPIE; PROPAGATION; ISOFORM; YEAST; PRP C1 Univ Toronto, Ctr Res Neurodegenerat Dis, Toronto, ON M5S 3H2, Canada. St Marys Hosp, Imperial Coll Sch Med, Neurogenet Unit, Prion Dis Grp, London W2 1PG, England. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Westaway, D (reprint author), Univ Toronto, Ctr Res Neurodegenerat Dis, Tanz Neurosci Bldg,6 Queens Pk Crescent W, Toronto, ON M5S 3H2, Canada. NR 17 TC 12 Z9 12 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 SEP 15 PY 1998 VL 95 IS 19 BP 11030 EP 11031 DI 10.1073/pnas.95.19.11030 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100003 PM 9736680 ER PT J AU Carosa, E Fanelli, A Ulisse, S Di Lauro, R Rall, JE Jannini, EA AF Carosa, E Fanelli, A Ulisse, S Di Lauro, R Rall, JE Jannini, EA TI Ciona intestinalis nuclear receptor 1: A member of steroid/thyroid hormone receptor family SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID THYROID-HORMONE; DNA-BINDING; GENE; SUPERFAMILY; PROTEINS; RNA; TRANSCRIPTION; ORGANIZATION; FLOUNDER; CLONING AB Nuclear hormone receptors comprise a large family of zinc finger transcription factors, some with hydrophobic Ligands, such as thyroid hormone, vitamin D, steroids, etc., and others for which no ligand has been found. Thyroid hormone receptors (TRs) generally are considered to be confined to the vertebrata that possess a thyroid gland, Tunicates represent the most primitive of the chordates, and there are data supporting a role for thyroid hormone in their metamorphosis, but no data are available on TRs in this genus; hence, we have studied Ciona intestinalis. Screening of a Ciona library with the DNA binding domain of Xenopus laevis TR (xTR) resulted in the isolation of a nuclear hormone receptor, C. intestinalis nuclear receptor 1 (CiNR1), CiNR1 is similar to TRs of more evolved species with a conserved DNA binding domain whereas the ligand binding domain shows poor homology to vertebrate sequences. The C-terminal part of CiNR1 spans approximate to 200 amino acids more than other TRs, lacks the AF2 transactivation domain, and is not able to bind triiodothyronine, Phylogenetically, CiNR1 appears to be close to the common ancestral gene of TRs. Expression of CiNR1 was limited to the developing embryo and the larval stage, which suggests a role during development and metamorphosis, In transfection experiments, CiNR1 down-regulated basal transcription of a reporter gene driven by the TR palindrome responsive element. When CiNR1 was cotransfected with chicken TR alpha, it attenuated the normal thyroid hormone response in a dominant negative fashion. This attenuation required the C-terminal portion of the molecule. C1 Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. Staz Zool Anton Dohrn, I-80121 Naples, Italy. NIDDK, NIH, Bethesda, MD 20892 USA. RP Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. EM joseph_rall@nih.gov RI Di Lauro, Roberto/A-2746-2012; OI Di Lauro, Roberto/0000-0001-9493-3036; Jannini, Emmanuele A./0000-0002-5874-039X; CAROSA, Eleonora/0000-0002-6593-6833; Ulisse, Salvatore/0000-0002-7573-0759 NR 38 TC 26 Z9 27 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 SEP 15 PY 1998 VL 95 IS 19 BP 11152 EP 11157 DI 10.1073/pnas.95.19.11152 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100028 PM 9736705 ER PT J AU Olson, WK Gorin, AA Lu, XJ Hock, LM Zhurkin, VB AF Olson, WK Gorin, AA Lu, XJ Hock, LM Zhurkin, VB TI DNA sequence-dependent deformability deduced from protein-DNA crystal complexes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SITE-SPECIFIC BINDING; B-DNA; ANISOTROPIC FLEXIBILITY; CURVED DNA; TRANSCRIPTION; HELIX; FLUCTUATIONS; TRANSITION; HISTONES; GROOVE AB The deformability of double helical DNA is critical for its packaging in the cell, recognition by other molecules, and transient opening during biochemically important processes. Here, a complete set of sequence-dependent empirical energy functions suitable for describing such behavior is extracted from the fluctuations and correlations of structural parameters in DNA-protein crystal complexes. These elastic functions provide useful stereochemical measures of the local base step movements operative in sequence-specific recognition and protein-induced deformations. In particular, the pyrimidine-purine dimers stand out as the most variable steps in the DNA-protein complexes, apparently acting as flexible "hinges" fitting the duplex to the protein surface. In addition to the angular parameters widely used to describe DNA deformations (i,e,, the bend and twist angles), the translational parameters describing the displacements of base pairs along and across the helical axis are analyzed. The observed correlations of base pair bending and shearing motions are important for nonplanar folding of DNA in nucleosomes and other nucleoprotein complexes. The knowledge-based energies also offer realistic three-dimensional models for the study of long DNA polymers at the global level, incorporating structural features beyond the scope of conventional elastic rod treatments and adding a new dimension to literal analyses of genomic sequences. C1 Rutgers State Univ, Dept Chem, New Brunswick, NJ 08903 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Olson, WK (reprint author), Rutgers State Univ, Dept Chem, New Brunswick, NJ 08903 USA. EM olson@rutchem.rutgers.edu; zhurkin@structure.nci.nih.gov RI Gorin, Andrey/B-1545-2014 FU NCI NIH HHS [N10-CO-74102]; NIGMS NIH HHS [R01 GM020861, GM20861] NR 48 TC 701 Z9 715 U1 4 U2 54 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 SEP 15 PY 1998 VL 95 IS 19 BP 11163 EP 11168 DI 10.1073/pnas.95.19.11163 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100030 PM 9736707 ER PT J AU Verneau, O Catzeflis, F Furano, AV AF Verneau, O Catzeflis, F Furano, AV TI Determining and dating recent rodent speciation events by using L1 (LINE-1) retrotransposons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTERSPERSED REPEATED DNA; MUROID RODENTS; PINK SALMON; RATTUS; ELEMENTS; SEQUENCES; MURIDAE; FAMILY; SINES; AMPLIFICATION AB Phylogenies based on the inheritance of shared derived characters will be ambiguous when the shared characters are not the result of common ancestry. Such characters are called homoplasies. Phylogenetic analysis also can be problematic if the characters have not changed sufficiently, as might be the case for rapid or recent speciations. The latter are of particular interest because evolutionary processes may be more accessible the more recent the speciation. The repeated DNA subfamilies generated by the mammalian L1 (LINE-1) retrotransposon are apparently homoplasy-freee phylogenetic characters. L1 retrotransposons are transmitted only by inheritance and rapidly generate novel variants that produce distinct subfamilies of mostly defective copies, which then "age" as they diverge, Here we show that the L1 character can both resolve and date recent speciation events within the large group of very closely related rats known as Rattus sensu stricto. This lineage arose 5-6 million years ago (Mya) and subsequently underwent two episodes of speciation: an intense one, approximate to 2.7 Mya, produced at least five lineages in <0.3 My; a second began approximate to 1.2 Mya and may still be continuing. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Montpellier 2, Inst Sci Evolut, F-34095 Montpellier, France. RP Furano, AV (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bldg 8,Room 203,8 Ctr Dr,MSC 0830, Bethesda, MD 20892 USA. RI VERNEAU, Olivier/A-6631-2010 NR 42 TC 70 Z9 70 U1 1 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 SEP 15 PY 1998 VL 95 IS 19 BP 11284 EP 11289 DI 10.1073/pnas.95.19.11284 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100051 PM 9736728 ER PT J AU Chavany, C Vicario-Abejon, C Miller, G Jendoubi, M AF Chavany, C Vicario-Abejon, C Miller, G Jendoubi, M TI Transgenic mice for interleukin 3 develop motor neuron degeneration associated with autoimmune reaction against spinal cord motor neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; CENTRAL-NERVOUS-SYSTEM; CULTURED MICROGLIA; DISEASE; CYTOKINES; HEMATOPOIESIS; EXPRESSION; REPAIR AB Interleukin 3 (IL-3) stimulates the proliferation and differentiation of various haematopoietic progenitor cells. Recently, IL-3 and other cytokines were reported to exert a neurotrophic activity and to be associated with neurological disorders, suggesting their complex role in the central nervous system. We now show that overexpression of IL-3 in transgenic mice causes a motor neuron disease with several features of amyotrophic lateral sclerosis and progressive muscular atrophy. These animals exhibit hind limb paralysis at 7 months of age, associated with dendritic and axonal degeneration, loss of motor neurons in the spinal cord, and autoimmune reaction against these cells. We examined the effect of IL-3 on embryonic motor neurons survival in mixed spinal cord cultures. Our results suggest that motor neuronal degeneration is not directly triggered by the high level of expression of IL-3. C1 NINDS, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NIH, Lab Sci Sect, Pathol Unit, Natl Ctr Res Resources,Vet Resources Program, Bethesda, MD 20892 USA. NEI, Genet & Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Jendoubi, M (reprint author), Milagen Inc, 6455 Christie Ave, Emeryville, CA 94608 USA. RI Vicario-Abejon, Carlos/G-2814-2016 NR 30 TC 30 Z9 30 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 SEP 15 PY 1998 VL 95 IS 19 BP 11354 EP 11359 DI 10.1073/pnas.95.19.11354 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100063 PM 9736740 ER PT J AU Murphy, DD Cole, NB Segal, M AF Murphy, DD Cole, NB Segal, M TI Brain-derived neurotrophic factor mediates estradiol-induced dendritic spine formation in hippocampal neurons SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ELEMENT-BINDING PROTEIN; RESPONSE ELEMENT; MESSENGER-RNA; ESTROUS-CYCLE; PLASTICITY; RAT; STIMULATION; INTERNEURONS; EXPRESSION; INCREASES AB Dendritic spines are of major importance in information processing and memory formation in central neurons. Estradiol has been shown to induce an increase of dendritic spine density on hippocampal neurons in vivo and in vitro. The neurotrophin brain-derived neurotrophic factor (BDNF) recently has been implicated in neuronal maturation, plasticity, and regulation of GABAergic interneurons, We now demonstrate that estradiol do,vn-regulates BDNF in cultured hippocampal neurons to 40% of control values within 24 hr of exposure. This, in turn, decreases inhibition and increases excitatory tone in pyramidal neurons, leading to a 2-fold increase in dendritic spine density, Exogenous BDNF blocks the effects of estradiol on spine formation, and BDNF depletion with a selective antisense oligonucleotide mimics the effects of estradiol. Addition of BDNF antibodies also increases spine density, and diazepam, which facilitates GABAergic neurotransmission, blocks estradiol-induced spine formation. These observations demonstrate a functional link between estradiol, BDNF as a potent regulator of GBBAergic interneurons, and activity-dependent formation of dendritic spines in hippocampal neurons. C1 NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Murphy, DD (reprint author), 3rd Floor,Maloney,3600 Spruce St, Philadelphia, PA 19104 USA. EM dianedm@mail.med.upenn.edu NR 27 TC 177 Z9 179 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 SEP 15 PY 1998 VL 95 IS 19 BP 11412 EP 11417 DI 10.1073/pnas.95.19.11412 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100073 PM 9736750 ER PT J AU van Hooft, JA Spier, AD Yakel, JL Lummis, SCR Vijverberg, HPM AF van Hooft, JA Spier, AD Yakel, JL Lummis, SCR Vijverberg, HPM TI Promiscuous coassembly of serotonin 5-HT3 and nicotinic alpha 4 receptor subunits into Ca2+-permeable ion channels SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID FUNCTIONAL EXPRESSION; XENOPUS OOCYTES; PHARMACOLOGICAL CHARACTERIZATION; CA2+ PERMEABILITY; SPLICE VARIANTS; A SUBUNIT; ACETYLCHOLINE; CLONING; BRAIN; HETEROGENEITY AB Serotonin (5-hydroxytryptamine) type 3 receptors (5-HT3R) and nicotinic acetylcholine receptors are structurally and functionally related proteins, yet distinct members of the family of ligand-gated ion channels. For most members of this family a diversity of heteromeric receptors is known at present, In contrast, known 5-HT3R subunits are all homologs of the same 5-HT3R-A subunit and form homopentameric receptors, Here we show, by heterologous expression followed by immunoprecipitation, that 5-HT3R and nicotinic acetylcholine receptor alpha 4 subunits coassemble into a novel type of heteromeric ligand-gated ion channel, which is activated by 5-HT. The Ca2+ permeability of this heteromeric ion channel is enhanced as compared with that of the homomeric 5-HT3R channel. Heteromeric 5-HT3/alpha 4 and homomeric 5-HT(3)Rs have similar pharmacological profiles, but distinct sensitivities to block by the antagonist d-tubocurarine. Coassembly of subunits beyond the boundaries of ligand-gated ion channel families may constitute an important mechanism contributing to the diverse properties and functions of native neurotransmitter receptors. C1 Univ Utrecht, Toxicol Res Inst, NL-3508 TD Utrecht, Netherlands. MRC, Mol Biol Lab, Div Neurobiol, Cambridge CB2 2QH, England. Univ Cambridge, Dept Biochem, Cambridge CB2 1QW, England. NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. RP Vijverberg, HPM (reprint author), Univ Utrecht, Toxicol Res Inst, POB 80176, NL-3508 TD Utrecht, Netherlands. EM h.vijverberg@ritox.vet.uu.nl RI Vijverberg, Henk/J-7490-2012 FU Wellcome Trust NR 32 TC 37 Z9 38 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD SEP 15 PY 1998 VL 95 IS 19 BP 11456 EP 11461 DI 10.1073/pnas.95.19.11456 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 120LD UT WOS:000075957100081 PM 9736758 ER PT J AU Rohlff, C Blagosklonny, MV Kyle, E Kesari, A Kim, IY Zelner, DJ Hakim, F Trepel, J Bergan, RC AF Rohlff, C Blagosklonny, MV Kyle, E Kesari, A Kim, IY Zelner, DJ Hakim, F Trepel, J Bergan, RC TI Prostate cancer cell growth inhibition by tamoxifen is associated with inhibition of protein kinase C and induction of p21(waf1/cip1) SO PROSTATE LA English DT Article DE transforming growth factor beta; retinoblastoma; signal transduction; drug therapy; cell cycle ID FOCAL ADHESION KINASE; BETA TGF-BETA; TRANSFORMING GROWTH-FACTOR-BETA-1; SIGNAL-TRANSDUCTION; ESTROGEN-RECEPTOR; IN-VITRO; EXPRESSION; APOPTOSIS; TUMOR; LINES AB BACKGROUND. Inhibition of protein kinase C (PKC) and modulation of transforming growth factor-beta (TGF-beta) are both associated with tamoxifen treatment, and both appear to be important in the regulation of prostate cancer cell growth. Investigations were performed which sought to measure the efficacy, and to elucidate the mechanism of growth inhibition by tamoxifen, in hormone-refractory prostate cancer. METHODS. Growth assays were performed on PC3, PC3-M, and DU145 prostate cancer cells. TGF-beta was measured by ELISA; p21(waf1/cip1) and retinoblastoma (Rb) protein levels were measured by Western blot; PKC activity was measured by kinase assay; and effects upon cell cycle were measured by flow cytometric analysis. RESULTS. IC(50)s for growth inhibition ranged from 5.5-10 mu M, and were not affected by estrogen. Tamoxifen-mediated growth inhibition was not associated with induction of TGF-beta. However, tamoxifen treatment was associated with inhibition of PKC, which was followed by induction of p2l(waf1/cip1), Rb dephosphorylation, and G1/S phase cell cycle arrest. Similar effects were observed with the known PKC inhibitor, Ro31-8220. CONCLUSIONS. These data suggest that micromolar concentrations of tamoxifen inhibit prostate cancer cell growth by inhibition of PKC, resulting in induction of the p21(waf1/cip1) protein. Prostate 37:51-59, 1998. (C) 1998 Wiley-Liss, Inc.dagger C1 NCI, Med Branch, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Dept Urol, Chicago, IL 60611 USA. RP Bergan, RC (reprint author), NCI, Med Branch, NIH, Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 52 Z9 55 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 0270-4137 J9 PROSTATE JI Prostate PD SEP 15 PY 1998 VL 37 IS 1 BP 51 EP 59 DI 10.1002/(SICI)1097-0045(19980915)37:1<51::AID-PROS8>3.0.CO;2-B PG 9 WC Endocrinology & Metabolism; Urology & Nephrology SC Endocrinology & Metabolism; Urology & Nephrology GA 112FV UT WOS:000075484200008 PM 9721069 ER PT J AU van Toor, AJ AF van Toor, AJ TI Letter to the Editor SO TIJDSCHRIFT VOOR DIERGENEESKUNDE LA Dutch DT Letter C1 NCI, Interim Voorzitter, Bethesda, MD 20892 USA. RP van Toor, AJ (reprint author), NCI, Interim Voorzitter, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROYAL NETHERLANDS VETERINARY ASSOC PI UTRECHT PA PO BOX 14031, 3508 UTRECHT, NETHERLANDS SN 0040-7453 J9 TIJDSCHR DIERGENEESK JI Tijdschr. Diergeneeskd. PD SEP 15 PY 1998 VL 123 IS 18 BP 541 EP 542 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 124JM UT WOS:000076179200003 PM 9764464 ER PT J AU van der Bijl, H Deleu, S AF van der Bijl, H Deleu, S TI Computerization of veterinary practices via the Internet - KNMVD and NCI join hands SO TIJDSCHRIFT VOOR DIERGENEESKUNDE LA Dutch DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP van der Bijl, H (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ROYAL NETHERLANDS VETERINARY ASSOC PI UTRECHT PA PO BOX 14031, 3508 UTRECHT, NETHERLANDS SN 0040-7453 J9 TIJDSCHR DIERGENEESK JI Tijdschr. Diergeneeskd. PD SEP 15 PY 1998 VL 123 IS 18 BP 553 EP 554 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 124JM UT WOS:000076179200007 ER PT J AU Restifo, NP Surman, DR Zheng, HY Palese, P Rosenberg, SA Garcia-Sastre, A AF Restifo, NP Surman, DR Zheng, HY Palese, P Rosenberg, SA Garcia-Sastre, A TI Transfectant influenza A viruses are effective recombinant immunogens in the treatment of experimental cancer SO VIROLOGY LA English DT Article ID ESTABLISHED PULMONARY METASTASES; TUMOR-ASSOCIATED ANTIGEN; CD8(+) T-CELL; VACCINIA VIRUS; DENDRITIC CELLS; IN-VITRO; A VIRUS; EXPRESSION; MODEL; IMMUNIZATION AB Using reverse genetics methods, we constructed three different transfectant influenza A viruses encoding an Ld-restricted, nine amino-acid-long fragment, corresponding to amino-acid residues 876-884, of beta-galactosidase (beta-gal). Sequences encoding this epitope were nested within the hemagglutinin (HA) or neuraminidase (NA) open reading frames. Alternatively, an independent beta-gal mini-gene, preceded by an endoplasmic reticulum insertion signal sequence, was placed in a bicistronic arrangement in the NA RNA segment of the virus. All three transfectants mediated the presentation of the epitope to a beta-gal-specific CTL clone. Furthermore, each of the three transfectant viruses expressing the beta-gal fragment elicited specific cytolytic responses in vivo. Most importantly, these H1N1 transfectants mediated the regression of established murine pulmonary metastases. Tumor regression in mice was also achieved in the presence of preexisting immunity against an H3N2 influenza A virus serotype. Nononcogenic and nonintegrating, transfectant influenza A viruses are attractive candidates for development as antitumor vaccines. (C) 1998 Academic Press. C1 CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. NCI, Labs Surg Branch, NIH, Bethesda, MD 20892 USA. RP Garcia-Sastre, A (reprint author), CUNY Mt Sinai Sch Med, Dept Microbiol, 1 Gustave L Levy Pl, New York, NY 10029 USA. RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580; Palese, Peter/0000-0002-0337-5823; Garcia-Sastre, Adolfo/0000-0002-6551-1827 FU Intramural NIH HHS [NIH0010139353, Z99 TW999999, Z01 BC010763-01] NR 39 TC 22 Z9 22 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 15 PY 1998 VL 249 IS 1 BP 89 EP 97 DI 10.1006/viro.1998.9330 PG 9 WC Virology SC Virology GA 125PM UT WOS:000076246100010 PM 9740780 ER PT J AU Lemaitre, RN Furberg, CD Newman, AB Hulley, SB Gordon, DJ Gottdiener, JS McDonald, RH Psaty, BM AF Lemaitre, RN Furberg, CD Newman, AB Hulley, SB Gordon, DJ Gottdiener, JS McDonald, RH Psaty, BM TI Time trends in the use of cholesterol-lowering agents in older adults - The Cardiovascular Health Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; MYOCARDIAL-INFARCTION; SCREENING GUIDELINES; ELDERLY PATIENTS; COMMON-SENSE; PRAVASTATIN; HYPERCHOLESTEROLEMIA; REDUCTION; PROGRAM AB Objectives: To describe recent temporal patterns of cholesterol-lowering medication use and the characteristics that may have influenced the initiation of cholesterol-lowering therapy among those aged 65 years or older. Subjects and Methods: A cohort of 5201 adults 65 years or older were examined annually between June 1989 and May 196. We added 687 African American adults to the cohort in 1992-1993. We measured blood lipid levels at baseline and for the original cohort in the third year of follow-up. We assessed the use of cholesterol-lowering drugs at each visit. Results: The prevalence of cholesterol-lowering drug use in 1989-1990 was 4.5% among the men and 5.9% among the women; these figures increased over the next 6 years to 8.1% and 10.0%, respectively, in 1995-1996. There was a 4-fold increase in the use of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors during the 6 years of follow-up, from 1.9% of all participants in 1989-1990 to 7.5% in 1995-1996. The use of bile acid sequestrants, nicotinic acid, and probucol declined from initial levels of less than 1% each. Among the participants who were untreated in 1989-1990, but eligible for cholesterol-lowering therapy after a trial of dietary therapy according to the 1993 guidelines of the National Cholesterol Education Panel, less than 20% initiated drug therapy in the 6 years of follow-up, even among subjects with a history of coronary heart disease. Among participants untreated at baseline but eligible for either cholesterol-lowering therapy or dietary therapy, initiation of cholesterol-lowering drug therapy was directly associated with total cholesterol levels, hypertension, and a history of coronary heart disease, and was inversely related to age, high-density lipoprotein cholesterol levels, and difficulties with activities of daily living. Other characteristics that form the basis of the 1993 National Cholesterol Education Panel guidelines-diabetes, smoking, family history of premature coronary heart disease, and total number of risk factors-were not associated with the initiation of cholesterol-lowering drug therapy. Conclusions: Given the clinical trial evidence for benefit, those aged 65 to 75 years and with prior coronary heart disease appeared undertreated with cholesterol-lowering drug therapy. C1 Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Div Cardiol, Washington, DC 20007 USA. RP Lemaitre, RN (reprint author), Cardiovasc Hlth Res Unit, Metropolitan Pk,East Tower,Suite 1360,1730 Minor, Seattle, WA 98101 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NHLBI NIH HHS [N01 HC 85080, N01 HC 85079, N01 HC 85081] NR 36 TC 71 Z9 72 U1 0 U2 2 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 SEP 14 PY 1998 VL 158 IS 16 BP 1761 EP 1768 DI 10.1001/archinte.158.16.1761 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 118GC UT WOS:000075829200004 PM 9738605 ER PT J AU Zhai, J Stewart, RR Friedberg, MW Li, CY AF Zhai, J Stewart, RR Friedberg, MW Li, CY TI Phosphorylation of the GABA(A) receptor gamma 2L subunit in rat sensory neurons may not be necessary for ethanol sensitivity SO BRAIN RESEARCH LA English DT Article DE GABA(A) receptor; ethanol; phosphorylation; patch-clamp; dorsal root ganglion; rat; RT-PCR; potentiation ID PROTEIN-KINASE-C; ROOT GANGLION NEURONS; A RECEPTORS; CHLORIDE CURRENT; XENOPUS OOCYTES; PHORBOL ESTERS; ION CURRENT; ALCOHOLS; EXPRESSION; ACID AB The effect of ethanol on the current activated by 2.5 to 40 mu M gamma-aminobutyric acid (GABA) was studied in freshly isolated rat dorsal root ganglion (DRG) neurons under voltage clamp in the whole-cell and perforated-patch recording configurations. Our results confirmed that GABA(A)-activated current in these neurons was insensitive to ethanol at concentrations from 2.5 to 100 mM [G. White, D.M. Lovinger, F.F. Weight, Ethanol inhibits NMDA-activated current but does not alter GABA-activated current in an isolated adult mammalian neuron, Brain Res. 507 (1990) 332-336.]. In addition, the ethanol sensitivity of GABA receptors was studied under conditions that promote phosphorylation of the PKC site on the gamma 2L subunit. The presence of the gamma 2L and other subunit mRNAs was detected by reverse transcription (RT) of total RNA purified from adult DRG followed by polymerase chain reaction (PCR) using subunit specific primer sets. We found that the GABA response remained insensitive to 2.5-100 mM ethanol despite: (i) the extracellular preapplication of 5, 20 or 500 nM phorbol 12-myristate 13-acetate (PMA); (ii) raising free intracellular Ca2+ ([Ca2+](i)) from 7 to 100 or 600 nM by altering the intracellular Ca2+/EGTA ratio; (iii) intracellular application of PKC (0.247 U ml(-1)); and (iv) combining the intracellular application of 1 mu M okadaic acid and 30 mu M peptide 3 with the extracellular application of 20 nM PMA. These results suggest that phosphorylation of the gamma 2L subunit is not the only requirement for ethanol sensitivity of GABA(A) receptors. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NIAAA, Cellular & Mol Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Zhai, J (reprint author), Columbia Univ, Coll Phys & Surg, Dept Anat & Cell Biol, 630 W 168th St, New York, NY 10032 USA. NR 26 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 14 PY 1998 VL 805 IS 1-2 BP 116 EP 122 DI 10.1016/S0006-8993(98)00689-1 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 124NE UT WOS:000076188000010 PM 9733942 ER PT J AU Zhou, FC Tao-Cheng, JH Segu, L Patel, T Wang, Y AF Zhou, FC Tao-Cheng, JH Segu, L Patel, T Wang, Y TI Serotonin transporters are located on the axons beyond the synaptic junctions: Anatomical and functional evidence SO BRAIN RESEARCH LA English DT Article DE synapse; cocaine; MDMA; methamphetamine; depression; high-affinity uptake; voltammetry; electron microscopy; immunocytochemistry; autoradiography; citalopram; paroxetine ID H-3 PAROXETINE BINDING; ADULT-RAT NEOSTRIATUM; QUANTITATIVE AUTORADIOGRAPHY; DOPAMINE TRANSPORTER; VOLUME TRANSMISSION; UPTAKE SITES; ULTRASTRUCTURAL FEATURES; INNERVATION DENSITY; BRAIN; LOCALIZATION AB The serotonin (5-HT) transporter (5-HTT) is known to play a role in depression and many 5-HT related diseases, and is the target site for drugs of abuse, such as cocaine, MDMA, and methamphetamine. The major role of the 5-HTT has long been considered to be to inactivate serotonin transmission through the elimination of serotonin at release sites. However, immunocytochemistry using an antibody against the N-terminal of the 5-HTT at the light microscopic (LM) level indicates that the 5-HTT is associated not only with 5-HT varicosities but also with axons. Electron microscopy (EM) reveals that the majority of the 5-HTTs exist on the axolemma outside the synaptic junctions. In studying whether axonal 5-HTTs are involved in the uptake of 5-HT, we found with autoradiography that [H-3]citalopram bound to all major 5-HT fibers, not only in the terminal regions, but also in 5-HT axonal bundles such as the cingulum bundle and medial forebrain bundle. Furthermore, voltammetry recordings indicated that serotonin axonal bundles were actively engaged in high affinity serotonin uptake. The evidence indicates that 5-HTTs on 5-HT axons away from the synapse are likely to be functional in a manner similar to the terminal 5-HTT for serotonin uptake. It also suggests that the role of the 5-HTT may not only be for the termination of synaptic transmission, but also for the regulation of 5-HT through extrasynaptic (volume) transmission. Our findings may also impact the understanding of the sites of action of selective serotonin reuptake inhibitors and drug entry into serotonin neurons via the numerous axonal sites. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Indiana Univ, Sch Med, Dept Anat, Indianapolis, IN 46202 USA. NINDS, EM Facil, NIH, Bethesda, MD 20892 USA. Univ Bordeaux 1, CNRS, URA 339, F-33405 Talence, France. Natl Def Med Ctr, Dept Pharmacol, Taipei, Taiwan. RP Indiana Univ, Sch Med, Dept Anat, 635 Barnhill Dr, Indianapolis, IN 46202 USA. EM imce100@iupui.edu FU NIMH NIH HHS [MH 50602] NR 72 TC 127 Z9 132 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD SEP 14 PY 1998 VL 805 IS 1-2 BP 241 EP 254 DI 10.1016/S0006-8993(98)00691-X PG 14 WC Neurosciences SC Neurosciences & Neurology GA 124NE UT WOS:000076188000023 PM 9733975 ER PT J AU Lenz, FA Gracely, RH Baker, FH Richardson, RT Dougherty, PM AF Lenz, FA Gracely, RH Baker, FH Richardson, RT Dougherty, PM TI Reorganization of sensory modalities evoked by microstimulation in region of the thalamic principal sensory nucleus in patients with pain due to nervous system injury SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE human thalamic ventral posterior nucleus; spinothalamic tract; somatosensory plasticity; nervous system injury ID POSTERIOR LATERAL NUCLEUS; SOMATOSENSORY CORTEX; SQUIRREL-MONKEY; VPM NUCLEUS; SOMATOTOPIC ORGANIZATION; SPINOTHALAMIC TRACT; RESPONSE PROPERTIES; SAIMIRI-SCIUREUS; NEURONS; ADULT AB Stimulation of the somatosensory system is more likely to evoke pain in patients with chronic pain after nervous system injury than in patients without somatosensory abnormalities. We now describe results of stimulation through a microelectrode at microampere thresholds (threshold microstimulation; TMIS) in the region of the human thalamic principal sensory nucleus (ventral caudal; Vc) during operations for treatment of movement disorders or of chronic pain. Patients were trained preoperatively to use a standard questionnaire to describe the location (projected field) and quality of sensations evoked by TMIS intraoperatively. The region of Vc was divided on the basis of projected fields into areas representing the part of the body where the patients experienced chronic pain (pain affected) or did not experience chronic pain (pain unaffected) and into a control area located in the thalamus of patients with movement disorders and no experience of chronic pain. The region of the Vc was also divided into a core region and a posterior-inferior region. The core was defined as the region above a standard radiologic horizontal line (anterior commissure-posterior commisure line; ACPC line) where the majority of cells responded to innocuous somatosensory stimulation. The posterior-inferior area was a cellular area posterior and inferior to the core. In both the core and the posterior-inferior regions, the proportion of sites where TMIS evoked pain was larger in pain-affected and unaffected areas than in control areas. The number of sites where thermal (warm or cold) sensations were evoked was correspondingly smaller, so that the total of pain-plus-thermal (sensation of warmth or cold) sites was the same in all areas. Therefore, sites pain where stimulation evoked pain in patients with neuropathic pain (i.e., pain following an injury to the nervous system) may correspond to sites where thermal sensations were evoked by stimulation in patients without somatosensory abnormality. J. Comp. Neurol. 399:125-138, 1998. (C) 1998 Wiley-Liss, Inc. C1 Johns Hopkins Hosp, Dept Neurosurg, Baltimore, MD 21287 USA. NIDR, Pain & Neurosensory Mechanisms Branch, NIH, Bethesda, MD 20892 USA. RP Lenz, FA (reprint author), Johns Hopkins Hosp, Dept Neurosurg, Meyer Bldg 7-113,600 N Wolfe St, Baltimore, MD 21287 USA. EM fal@research.med.jhu.edu OI Dougherty, Patrick/0000-0002-2177-2734 FU NINDS NIH HHS [K08 NS01384, NS28598, P01 NS32386-PROJECT 1] NR 92 TC 48 Z9 50 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 SEP 14 PY 1998 VL 399 IS 1 BP 125 EP 138 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 111BE UT WOS:000075416800010 PM 9725706 ER PT J AU Bengel, D Isaacs, KR Heils, A Lesch, KP Murphy, DL AF Bengel, D Isaacs, KR Heils, A Lesch, KP Murphy, DL TI The appetite suppressant d-fenfluramine induces apoptosis in human serotonergic cells SO NEUROREPORT LA English DT Article DE appetite suppressant; apoptosis; d-fenfluramine; JAR cells; neurodegeneration; neurotoxicity; serotonin transporter ID PULMONARY-HYPERTENSION; P-CHLOROAMPHETAMINE; NONHUMAN-PRIMATES; MDMA ECSTASY; DEXFENFLURAMINE; RAT; TRANSPORTER; DISEASE; 5-HT; NEUROTOXICITY AB FENFLURAMINE is an amphetamine analogue which has been widely used in the treatment of obesity. In rodents, non-human primates, and humans, fenfluramine is associated with some indices of neurotoxicity, as well as pulmonary hypertension and cardiac valve pathology. In the present study, d-fenfluramine was found to be cytotoxic to the serotonin (5-HT) transporter (5-HTT) expressing human placental choriocarcinoma cells. d-Fenfluramine caused DNA fragmentation and apoptosis. Apoptosis was not observed after the 5-HTT had been blocked by fluoxetine, indicating that intact 5-HTT function is required for d-fenfluramine to induce programmed cell death. These observations in a human cell line may reflect a possible mechanism associated with the risks of fenfluramine administration in several species, including humans. NeuroReport 9: 2989-2993 (C) 1998 Lippincott Williams & Wilkins. C1 Univ Wurzburg, Dept Psychiat, D-97080 Wurzburg, Germany. NIMH, Sect Clin Neuropharmacol, NIH, Ctr Clin, Bethesda, MD 20892 USA. NIMH, Sect Histopharmacol, Clin Sci Lab, NIH,Ctr Clin, Bethesda, MD 20892 USA. RP Bengel, D (reprint author), Univ Wurzburg, Dept Psychiat, Fuchsleinstr 15, D-97080 Wurzburg, Germany. RI Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 24 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 14 PY 1998 VL 9 IS 13 BP 2989 EP 2993 DI 10.1097/00001756-199809140-00013 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 131XA UT WOS:000076599500013 PM 9804303 ER PT J AU Liu, QY Schaffner, A Chang, YH Maric, D Barker, JL AF Liu, QY Schaffner, A Chang, YH Maric, D Barker, JL TI Amyloid beta-protein impairs astrocyte-mediated differentiation of hippocampal neurons SO NEUROREPORT LA English DT Article DE amyloid beta-protein; astrocytes; GABA; glycine; hippocampus; kainic acid; neuronal development; neurotrophic effect; NMDA ID GLIA INTERACTIONS; CEREBRAL-CORTEX; RAT; CULTURES; PEPTIDES; CELLS; RELEASE; INVITRO AB EMBRYONIC rat hippocampal neurons were cultured on poly-D-lysine (PDL) or on cortical astrocytes, some of which had been pretreated for 24 h with amyloid beta-protein (beta-AP). Amino acid-induced currents were quantified. Membrane capacitance (C-m), as well as the amplitude and density of amino acid-evoked currents recorded in neurons cultured on untreated astrocytes were all statistically greater than those recorded in neurons grown on PDL. However, compared to untreated astrocytes, those treated with beta-AP led to significantly lower values in neurons for C-m and GABA, kainate- and NMDA-induced currents, while glycine-activated current values were not significantly different. Furthermore, beta-AP treatment abolished spontaneous Ca-c(2+) fluctuations in astrocytes, which may account for their impaired ability to promote the expression of functional transmitter receptors in neurons. NeuroReport 9: 3059-3063 (C) 1998 Lippincott Williams & Wilkins. C1 NINCDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. RP Liu, QY (reprint author), NINCDS, Neurophysiol Lab, NIH, Bldg 36 Rm 2C02,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 26 TC 1 Z9 1 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD SEP 14 PY 1998 VL 9 IS 13 BP 3059 EP 3063 DI 10.1097/00001756-199809140-00026 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 131XA UT WOS:000076599500026 PM 9804316 ER PT J AU McDermott, DH Zimmerman, PA Guignard, F Kleeberger, CA Leitman, SF Murphy, PM AF McDermott, DH Zimmerman, PA Guignard, F Kleeberger, CA Leitman, SF Murphy, PM CA Multicenter AIDS Cohort Study MACS TI CCR5 promoter polymorphism and HIV-1 disease progression SO LANCET LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR; PLASMODIUM-VIVAX; INFECTION; GENE; TRANSMISSION; RESISTANCE; CCR5-DELTA-32; DELETION; ALLELE AB Background The rate of progression to AIDS varies among individuals infected with HIV-1. Factors responsible include two inherited human alleles, CCR5 Delta 32 and CCR2-641, which alter the protein-coding regions for the HIV-1 coreceptors/chemokine receptors CCR5 and CCR2b. We tested the hypothesis that polymorphisms of the CCR5 promoter might affect the rate of progression of HIV-1 infected people to AIDS. Methods We used directed heteroduplex analysis to identify polymorphism in the CCR5 promoter. Promoter-variants were compared in vitro with a chloramphenicol acetyltransferase reporter gene, and in vivo by genotyping HIV-1 seroconvertors discordant at polymorphous loci, Findings An A/G polymorphism was identified at basepair 59029 (Genbank U95626) in the CCR5 promoter. Both promoter alleles were common (43-68% allelic frequency for 59029-A depending on race). When in-vitro promoter activity was measured, 59029-G had 45% lower activity than 59029-A (p=0.05). In a cohort of HIV-1 seroconvertors lacking both CCR5 Delta 32 and CCR2-641, 59029-G/G individuals progressed to AIDS on average 3.8 years more slowly than 59029-A/A individuals (p=0.004). 59029-G/A discordance did not correlate with discordant rates of infection. Interpretation Our results are consistent with the hypothesis that CCR5 is important in HIV-1 pathogenesis, CCR5 59029-G/G appears to be protective relative to CCR5 59029-A/A, and about twice as protective relative to CCR5 Delta 32 or CCR2-641. This effect may be the result of reduced CCR5 mRNA production. These results identify the first site in the CCR5 promoter that may be a useful target for treatment of HIV-1 infection. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Murphy, PM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Rm 11N113, Bethesda, MD 20892 USA. EM pmm@nih.gov OI McDermott, David/0000-0001-6978-0867 FU NCRR NIH HHS [5-M01-RR-00052]; PHS HHS [UO1-A1-35042, UO1-A1-35043] NR 27 TC 299 Z9 306 U1 0 U2 6 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 12 PY 1998 VL 352 IS 9131 BP 866 EP 870 DI 10.1016/S0140-6736(98)04158-0 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 118UA UT WOS:000075857300008 PM 9742978 ER PT J AU Greenberg, BD Ziemann, U Harmon, A Murphy, DL Wassermann, EM AF Greenberg, BD Ziemann, U Harmon, A Murphy, DL Wassermann, EM TI Decreased neuronal inhibition in cerebral cortex in obsessive-compulsive disorder on transcranial magnetic stimulation SO LANCET LA English DT Article C1 NIMH, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. RP Greenberg, BD (reprint author), NIMH, Bethesda, MD 20892 USA. NR 5 TC 47 Z9 50 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 12 PY 1998 VL 352 IS 9131 BP 881 EP 882 DI 10.1016/S0140-6736(05)60009-8 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 118UA UT WOS:000075857300018 PM 9742988 ER PT J AU Goedert, JJ Biggar, RJ AF Goedert, JJ Biggar, RJ TI Spectrum of AIDS-associated malignant disorders - Reply SO LANCET LA English DT Letter C1 NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Rockville, MD 20852 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD SEP 12 PY 1998 VL 352 IS 9131 BP 907 EP 907 DI 10.1016/S0140-6736(05)60049-9 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 118UA UT WOS:000075857300062 ER PT J AU Clifford, GM McCormick, DKT Londos, C Vernon, RG Yeaman, SJ AF Clifford, GM McCormick, DKT Londos, C Vernon, RG Yeaman, SJ TI Dephosphorylation of perilipin by protein phosphatases present in rat adipocytes SO FEBS LETTERS LA English DT Article DE lipolysis; perilipin; protein phosphorylation; protein phosphatase; adipocyte ID HORMONE-SENSITIVE LIPASE; LIPID-METABOLISM; SKELETAL-MUSCLE; ADIPOSE-TISSUE; 3T3-L1 CELLS; INSULIN; KINASE; STIMULATION; LIPOLYSIS; PHOSPHORYLATION AB By incubating P-32-labelled adipocytes, and extracts from these cells, in the presence or absence of specific inhibitors, we evaluated the contribution of protein phosphatases PP1, PP2A and PP2C, to the dephosphorylation of perilipin, an acutely hormone-regulated adipocyte phosphoprotein. Under conditions to completely inhibit PP2A activity, perilipin phosphatase activity in extracts remain unaffected, but PP1 inhibition results in abolition of perilipin phosphatase activity. Inhibition of PP1 (and 2A) in intact adipocytes stimulated lipolysis and increased phosphorylation of perilipin. No involvement of PP2C was found. Hence, PP1 constitutes the predominant if not sole perilipin phosphatase in adipocytes. (C) 1998 Federation of European Biochemical Societies. C1 Univ Newcastle, Sch Med, Dept Biochem & Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. Hannah Res Inst, Ayr KA6 5HL, Scotland. RP Yeaman, SJ (reprint author), Univ Newcastle, Sch Med, Dept Biochem & Genet, Newcastle Upon Tyne NE2 4HH, Tyne & Wear, England. NR 29 TC 20 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD SEP 11 PY 1998 VL 435 IS 1 BP 125 EP 129 DI 10.1016/S0014-5793(98)01052-7 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 122AR UT WOS:000076048700026 PM 9755872 ER PT J AU Okazaki, IJ Moss, J AF Okazaki, IJ Moss, J TI Glycosylphosphatidylinositol-anchored and secretory isoforms of mono-ADP-ribosyltransferases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID NICOTINAMIDE ADENINE-DINUCLEOTIDE; RIBOSYLATING BACTERIAL TOXINS; LYMPHOCYTE ALLOANTIGEN RT6.1; NAD GLYCOHYDROLASE ACTIVITY; SKELETAL-MUSCLE CELLS; POLY(ADP-RIBOSE) POLYMERASE; NITRIC-OXIDE; MOLECULAR CHARACTERIZATION; TURKEY ERYTHROCYTES; ADENYLATE-CYCLASE C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Okazaki, IJ (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10,Rm 5N307,10 Ctr Dr MSC 1434, Bethesda, MD 20892 USA. NR 70 TC 64 Z9 65 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 11 PY 1998 VL 273 IS 37 BP 23617 EP 23620 DI 10.1074/jbc.273.37.23617 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100001 PM 9726960 ER PT J AU Bennett, MK Van Leeuwen, JEM Kearse, KP AF Bennett, MK Van Leeuwen, JEM Kearse, KP TI Calnexin association is not sufficient to protect T cell receptor alpha proteins from rapid degradation in CD4(+)CD8(+) thymocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ASPARAGINE-LINKED OLIGOSACCHARIDES; TCR-BETA PROTEINS; ENDOPLASMIC-RETICULUM; ANTIGEN RECEPTOR; MOLECULAR CHAPERONE; DEVELOPMENTAL REGULATION; MONOCLONAL-ANTIBODY; TRANSGENIC MICE; QUALITY-CONTROL; INITIAL STEP AB During T cell development, assembly of the mutisubunit T cell receptor (TCR) complex is regulated by the differential stability of newly synthesized TCR alpha molecules, having a half-life of approximately 20 min in immature CD4(+)CD8(+) thymocytes compared with >75 min in mature T cells. The molecular basis for TCRa instability in CD4(+)CD8(+) thymocytes is unknown but has been postulated to involve abnormalities in N-glycan processing and calnexin assembly as perturbation of these pathways markedly destabilizes TCR alpha proteins in all other T cell types examined. Here, we compared the processing of TCR alpha glycoproteins and their assembly with calnexin and calreticulin chaperones in CD4(+)CD8(+) thymocytes and splenic T cells, These studies show that TCR alpha glycoproteins synthesized in CD4(+)CD8(+) thymocytes were processed in a similar manner as those made in splenic T cells and that TCR alpha proteins stably associated with calnexin in both cell types. Interestingly, however, TCR alpha association with the calnexin-related molecule calreticulin was decreased in CD4(+)CD8(+) thymocytes compared with splenic T cells. Finally, TCR alpha degradation in CD4(+)CD8(+) thymocytes was impaired by inhibitors of proteasome activity, which was correlated with stabilization of calnexin TCR alpha complexes. These data demonstrate that calnexin association is not sufficient to protect TCR alpha proteins from rapid degradation in CD4(+)CD8(+) thymocytes, suggesting that additional components of the quality control system of the endoplasmic reticulum operate to ensure the proper folding of nascent TCR alpha glycoproteins. C1 E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Kearse, KP (reprint author), E Carolina Univ, Sch Med, Dept Microbiol & Immunol, Greenville, NC 27858 USA. EM kearse@brody.med.ecu.edu RI van Leeuwen, Jeroen/G-3555-2010 FU NIAID NIH HHS [R29 AI42104] NR 42 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 11 PY 1998 VL 273 IS 37 BP 23674 EP 23680 DI 10.1074/jbc.273.37.23674 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100013 PM 9726972 ER PT J AU Rameh, LE Rhee, SG Spokes, K Kazlauskas, A Cantley, LC Cantley, LG AF Rameh, LE Rhee, SG Spokes, K Kazlauskas, A Cantley, LC Cantley, LG TI Phosphoinositide 3-kinase regulates phospholipase C gamma-mediated calcium signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR RECEPTOR-BETA; PROTEIN-KINASE-B; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; LYSOPHOSPHATIDIC ACID; HOMOLOGY DOMAINS; LIPID PRODUCTS; CROSS-LINKING; ACTIVATION; WORTMANNIN AB It has been demonstrated that the lipid products of the phosphoinositide a-kinase (PI3K) can associate with the Src homology 2 (SH2) domains of specific signaling molecules and modify their actions. In the current experiments, phosphatidylinositol 3,4,5-trisphosphate (Pt-dIns-3,4,5-P-3) was found to bind to the C-terminal SH2 domain of phospholipase C gamma (PLC gamma) with an apparent K-d of 2.4 pra and to displace the C-terminal SH2 domain from the activated platelet-derived growth factor receptor (PDGFR). To investigate the in vivo relevance of this observation, intracellular inositol trisphosphate (IP3) generation and calcium release were examined in HepGB cells expressing a series of PDGFR mutants that activate PLC gamma with or without receptor association with PI3K. Coactivation of PLC gamma and PI3K resulted in an similar to 40% increase in both intracellular IF, generation and intracellular calcium release as compared with selective activation of PLC gamma. Similarly, the addition of wortmannin or LY294002 to cells expressing the wild-type PDGFR inhibited the release of intracellular calcium. Thus, generation of PtdIns-3,4,5-P-3 by receptor-associated PI3K causes an increase in IP3 production and intracellular calcium release, potentially via enhanced PtdIns-4,5-P-2 substrate availability due to PtdIns-3,4,5-P-3-mediated recruitment of PLC gamma to the lipid bilayer. C1 Harvard Univ, Sch Med, Div Nephrol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Div Signal Transduct, Boston, MA 02215 USA. Schepens Eye Res Inst, Boston, MA 02114 USA. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Cantley, LG (reprint author), Harvard Univ, Sch Med, Div Nephrol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [DK48871]; NIGMS NIH HHS [GM41890, GM48339, R01 GM041890] NR 28 TC 174 Z9 175 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 11 PY 1998 VL 273 IS 37 BP 23750 EP 23757 DI 10.1074/jbc.273.37.23750 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100024 PM 9726983 ER PT J AU Combadiere, C Salzwedel, K Smith, ED Tiffany, HL Berger, EA Murphy, PM AF Combadiere, C Salzwedel, K Smith, ED Tiffany, HL Berger, EA Murphy, PM TI Identification of CX(3)CR1 - A chemotactic receptor for the human CX3C chemokine fractalkine and a fusion coreceptor for HIV-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTOR; FUNCTIONAL EXPRESSION; HUMAN MONOCYTE; TROPIC HIV-1; CDNA CLONING; COFACTOR; ENTRY; GENE; 7-TRANSMEMBRANE; MIP-1-ALPHA AB Fractalkine is a multimodular human leukocyte chemoattractant protein and a member of the chemokine superfamily. Unlike other human chemokines, the chemokine domain of fractalkine has three amino acids between two conserved cysteines, referred to as the CX3C motif. Both plasma membrane-associated and shed forms of fractalkine have been identified. Here, we show that the recombinant 76-amino acid chemokine domain of fractalkine is a potent and highly specific chemotactic agonist at a human orphan receptor previously named V28 or alternatively CMKBRL1 (chemokine beta receptor-like 1), which was shown previously to be expressed in neutrophils, monocytes, T lymphocytes, and several solid organs, including brain. CMKBRL1/V28 also functioned with CD4 as a coreceptor for the envelope protein from a primary isolate of HIV-1 in a cell-cell fusion assay, and fusion was potently and specifically inhibited by fractalkine. Thus CMKBRL1/V28 is a specific receptor for fractalkine, and we propose to rename it CX(3)CR1 (CX3C chemokine receptor 1), according to an accepted nomenclature system. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. CHU X Bichat, INSERM U479, F-75877 Paris, France. RP Murphy, PM (reprint author), NIAID, Host Def Lab, NIH, Bldg 10,Rm 11N113, Bethesda, MD 20892 USA. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 28 TC 209 Z9 223 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 11 PY 1998 VL 273 IS 37 BP 23799 EP 23804 DI 10.1074/jbc.273.37.23799 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100031 PM 9726990 ER PT J AU Goalstone, ML Leitner, JW Wall, K Dolgonos, L Rother, KI Accili, D Draznin, B AF Goalstone, ML Leitner, JW Wall, K Dolgonos, L Rother, KI Accili, D Draznin, B TI Effect of insulin on farnesyltransferase - Specificity of insulin action and potentiation of nuclear effects of insulin-like growth factor-1, epidermal growth factor, and platelet-derived growth factor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; 3T3-L1 ADIPOCYTES; RAS; RECEPTOR; MEMBRANE AB We have previously demonstrated that insulin activates, farnesyltransferase (FTase) and augments the amounts of farnesylated p21(ras) (Goalstone, NI, L., and Draznin, B. (1996) J. Biol, Chem. 271, 27585-27589). We postulated that this aspect of insulin action might explain the "priming effect" of insulin on the cellular response to other growth factors. In the present study, we show the specificity of the effect of insulin on FTase. Insulin, but not insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), or platelet-derived growth factor (PDGF), stimulated the phosphorylation of the alpha-subunit of FTase and the amounts of farnesylated p21(ras). Even though all four growth factors utilized the Ras pathway to stimulate DNA synthesis, only insulin used this pathway to influence FTase, Insulin failed to stimulate FTase in cells expressing the chimeric insulin/ IGF-I receptor and in cells derived from the insulin receptor knock-out animals. Insulin potentiated the effects of IGF-1, EGF, and PDGF on DNA synthesis in cells expressing the wild type insulin receptor, but this potentiation was inhibited in the presence of the FTase inhibitor, alpha-hydroxyfarnesylphosphonic acid. We conclude that the effect of insulin on FTase is specific, requires the presence of an intact insulin receptor and selves as a conduit for the "priming" influence of insulin on the nuclear effects of other growth factors. C1 Denver Vet Affairs Med Ctr, Res Serv, Denver, CO 80220 USA. Denver Vet Affairs Med Ctr, Dept Med, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80220 USA. NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Draznin, B (reprint author), VA Hosp 151, 1055 Clermont St, Denver, CO 80220 USA. NR 19 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 11 PY 1998 VL 273 IS 37 BP 23892 EP 23896 DI 10.1074/jbc.273.37.23892 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100043 PM 9727002 ER PT J AU Warner, DR Weng, GZ Yu, SH Matalon, R Weinstein, LS AF Warner, DR Weng, GZ Yu, SH Matalon, R Weinstein, LS TI A novel mutation in the switch 3 region of G(s)alpha in a patient with Albright hereditary osteodystrophy impairs GDP binding and receptor activation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GRADIENT GEL-ELECTROPHORESIS; PROTEIN ALPHA-SUBUNITS; GTP-GAMMA-S; ADENYLATE-CYCLASE; ESCHERICHIA-COLI; GS-ALPHA; CRYSTAL-STRUCTURE; G(S-ALPHA); PSEUDOHYPOPARATHYROIDISM; TRANSDUCIN AB Albright hereditary osteodystrophy (AHO), a disorder characterized by skeletal abnormalities and obesity, is associated with heterozygous inactivating mutations in the gene for G(s)alpha. A novel G(s)alpha mutation encoding the substitution of tryptophan for a nonconserved arginine within the switch 3 region (G(s)alpha R258W) was identified in an AHO patient. Although reverse transcription-polymerase chain reaction studies demonstrated that mRNA expression from wild type and mutant alleles was similar, G(s)alpha expression in erythrocyte membranes from the affected patient was reduced by 50%. A G(s)alpha R258W cDNA, as well as one with arginine replaced by alanine (G(s)alpha R258A), was generated, and the biochemical properties of lit vitro transcription/translation products were examined, When reconstituted with cyc(-) membranes, both mutant proteins were able to stimulate adenylyl cyclase normally in the presence of guanosine-5'-O-(3-thiotriphosphate) (GTP gamma S) but had decreased ability in the presence of isoproterenol or AlF4- (a mixture of 10 mu M AlCl3 and 10 mM NaF). The ability of each mutant to bind and be activated by GTP gamma S or AlF4- was assessed by trypsin protection assays. Both mutants were protected normally by GTP gamma S but showed reduced protection in the presence of AlF4-. The addition of excess GDP (2 mM) was able to rescue the ability of AlF4- to protect the mutants, suggesting that they might have reduced affinity for GDP. A G(s)alpha R258A mutant purified from Escherichia coli had decreased affinity for GDP and an apparent rate of GDP release that was 10-fold greater than that of wild type G(s)alpha. Sucrose density gradient analysis demonstrated that both G(s)alpha R258W and G(s)alpha R258A were thermolabile at higher temperatures and that denaturation of both mutants was prevented by the presence of 0.1 mM GTP gamma S or 2 mM GDP. The crystal structure of G(s)alpha demonstrates that Arg(258) interacts with a conserved residue in the helical domain (Gln(170)). Arg(258) substitutions would be predicted to open the cleft between the GTPase and helical domains, allowing for increased GDP release in the inactive state, resulting in enhanced thermolability and reduced AlF4--induced adenylyl cyclase stimulation and trypsin protection, since activation by AlF4- requires bound GDP. C1 NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Dept Pharmacol, New York, NY 10029 USA. Univ Texas, Med Branch, Dept Pediat, Galveston, TX 77555 USA. RP Warner, DR (reprint author), NINDS, Membrane Biochem Sect, Mol & Cellular Neurobiol Lab, NIH, Bldg 49,Rm 2A28, Bethesda, MD 20892 USA. RI Weinstein, Lee/I-5575-2015 NR 38 TC 48 Z9 49 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 11 PY 1998 VL 273 IS 37 BP 23976 EP 23983 DI 10.1074/jbc.273.37.23976 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100054 PM 9727013 ER PT J AU Dey, BR Spence, SL Nissley, P Furlanetto, RW AF Dey, BR Spence, SL Nissley, P Furlanetto, RW TI Interaction of human suppressor of cytokine signaling (SOCS)-2 with the insulin-like growth factor-I receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INDUCED STAT INHIBITOR; PROTEIN; FAMILY; ACTIVATION; CIS; SUBSTRATE; KINASES; CLONING; DOMAIN; SHC AB SOCS (suppressor of cytokine signaling) proteins have been shown to be negative regulators of cytokine receptor signaling via the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway. We have cloned a member of this family (hSOCS-2) by utilizing the insulin-like growth factor I receptor (IGF-IR) cytoplasmic domain as bait in a yeast two-hybrid screen of a human fetal brain library. The hSOCS-2 protein interacted strongly with the activated IGF-IR and not with a kinase negative mutant receptor in the two-hybrid assay. Mutation of receptor tyrosines 950, 1250, 1251, and 1316 to phenylalanine or deletion of the COOH-terminal 93 amino acids did not result in decreased interaction of the receptor with hSOCS-2 protein. hSOCS-1 protein also interacted strongly with IGF-IR in the two-hybrid assay. Glutathione S-transferase-hSOCS-2 associated with activated IGF-IR in lysates of mouse fibroblasts overexpressing IGF-IR, Human embryonic kidney cells (293) were transiently transfected with vectors containing IGF-IR and FLAG epitope-tagged hSOCS-2, After IGF-I stimulation, activated IGF-IR was found in anti-FLAG immunoprecipitates and, conversely, FLAG-hSOCS-2 was found in anti IGF-IR immunoprecipitates. Thus, hSOCS-2 interacted with IGF-IR both in vitro and in vivo. HSOCS-2 mRNA was expressed in many human fetal and adult tissues with particularly high abundance in fetal kidney and adult heart, skeletal muscle, pancreas, and liver, These results raise the possibility that SOCS proteins may also play a regulatory role in IGF-I receptor signaling. C1 NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med & Dent, Dept Pediat, Strong Childrens Res Ctr, Rochester, NY 14642 USA. RP Nissley, P (reprint author), NCI, Metab Branch, NIH, Bldg 10,Rm 4N115, Bethesda, MD 20892 USA. FU NIDDK NIH HHS [1RO1 DK51657] NR 26 TC 148 Z9 154 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 11 PY 1998 VL 273 IS 37 BP 24095 EP 24101 DI 10.1074/jbc.273.37.24095 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 119JT UT WOS:000075893100070 PM 9727029 ER PT J AU Canman, CE Lim, DS Cimprich, KA Taya, Y Tamai, K Sakaguchi, K Appella, E Kastan, MB Siliciano, JD AF Canman, CE Lim, DS Cimprich, KA Taya, Y Tamai, K Sakaguchi, K Appella, E Kastan, MB Siliciano, JD TI Activation of the ATM kinase by ionizing radiation and phosphorylation of p53 SO SCIENCE LA English DT Article ID CELL-CYCLE CHECKPOINT; ATAXIA-TELANGIECTASIA CELLS; PROTEIN-KINASE; DNA-DAMAGE; PATHWAYS; RECOMBINATION; INDUCTION; PRODUCT; DEFECT; MDM2 AB The p53 tumor suppressor protein is activated and phosphorylated on serine-15 in response to various DNA damaging agents. The gene product mutated in ataxia telangiectasia, ATM, acts upstream of p53 in a signal transduction pathway initiated by ionizing radiation. Immunoprecipitated ATM had intrinsic protein kinase activity and phosphorylated p53 on serine-15 in a manganese-dependent manner. Ionizing radiation, but not ultraviolet radiation, rapidly enhanced this p53-directed kinase activity of endogenous ATM. These observations, along with the fact that phosphorylation of p53 on serine-15 in response to ionizing radiation is reduced in ataxia telangiectasia cells, suggest that ATM is a protein kinase that phosphorylates p53 in vivo. C1 Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. Stanford Univ, Sch Med, Dept Mol Pharmacol, Stanford, CA 94305 USA. Natl Canc Ctr, Res Inst, Chuo Ku, Tokyo 104, Japan. MBL Co Ltd, Ina Labs, Nagano 396, Japan. NIH, Cell Biol Lab, Bethesda, MD 20892 USA. RP Kastan, MB (reprint author), St Jude Childrens Res Hosp, Dept Hematol Oncol, 332 N Lauderdale St,D-1034, Memphis, TN 38105 USA. RI Tamai, Katsuyuki/F-4743-2013; Lim, Dae-Sik/C-1599-2011 OI Tamai, Katsuyuki/0000-0003-4094-3911; Lim, Dae-Sik/0000-0003-2356-7555 FU NCI NIH HHS [CA71387]; NIEHS NIH HHS [ES05777] NR 25 TC 1442 Z9 1463 U1 10 U2 60 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 SEP 11 PY 1998 VL 281 IS 5383 BP 1677 EP 1679 DI 10.1126/science.281.5383.1677 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 118TR UT WOS:000075856500048 PM 9733515 ER PT J AU Touloumi, G Hatzakis, A Rosenberg, PS O'Brien, TR Goedert, JJ AF Touloumi, G Hatzakis, A Rosenberg, PS O'Brien, TR Goedert, JJ CA Multicenter Hemophilia Cohort Study TI Effects of age at seroconversion and baseline HIV RNA level on the loss of CD4+ cells among persons with hemophilia SO AIDS LA English DT Article DE age; HIV RNA; CD4 cell counts; hemophilia; longitudinal studies; PCR; statistical linear models ID VIRUS TYPE-1 INFECTION; NATURAL-HISTORY; AIDS; PLASMA; PROGRESSION; COUNTS; LYMPHOCYTES; VIREMIA; MARKERS; NUMBERS AB Objective: To assess the impact of age at seroconversion and HIV RNA level in serum during early chronic infection on the initial values and subsequent trends (slopes) of CD4+ lymphocyte counts. Design and methods: In a cohort of 137 HIV-1-positive hemophiliacs with well-estimated dates of seroconversion, baseline HIV RNA level was measured by reverse transcription PCR in serum specimens collected 12-36 months after the estimated date of seroconversion. Baseline values, 24 months after seroconversion, and slopes of CD4+ lymphocyte counts by age and HIV RNA quartile were examined by fitting random effects models that allowed for intrasubject variability. Results: Both age at seroconversion and HIV RNA level were associated with the CD4+ lymphocyte count at baseline and its subsequent slope. The baseline median CD4+ lymphocyte count was 620 x 10(6)/l. Within each HIV RNA quartile, the median CD4+ cell count of:he oldest subjects (age 30-58 yeats) was about 200 x 10(6)/l lower and at least 350 x 10(6)/l lower than the median counts of the younger (age 11-29) years) and youngest (age 2-10 years) subjects, respectively; Within each age-group, the median CD4+ cell count differed by about 200 x 10(6)/l between subjects in the lowest compared with the highest HIV RNA quartiles. The mean slope of the CD4+ lymphocyte count after month 24 was linear on the square-loot scale, steeper in children, and did not vary significantly by baseline HIV RNA quartile. There was large variation between subjects that was unexplained by differences in age and HIV RNA level. Conclusions: By 24 months after HIV seroconversion, the oldest subjects and those with the highest HIV RNA levels during early chronic infection had experienced the most severe depletion of CD4+ cells. Subsequent declines in CD4+ cells varied little by early chronic HIV RNA level or age. (C) 1998 Lippincott Williams & Wilkins. C1 Univ Athens, Sch Med, Dept Hyg & Epidemiol, GR-11527 Athens, Greece. NCI, Viral Epidemiol Branch, Rockville, MD USA. RP Goedert, JJ (reprint author), 6130 Execut Blvd,Suite 434, Rockville, MD 20852 USA. FU NCI NIH HHS [N01-CP-33002] NR 39 TC 28 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PD SEP 10 PY 1998 VL 12 IS 13 BP 1691 EP 1697 DI 10.1097/00002030-199813000-00018 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 119HR UT WOS:000075890300018 PM 9764790 ER PT J AU Duffy, S Tsao, KL Waugh, DS AF Duffy, S Tsao, KL Waugh, DS TI Site-specific, enzymatic biotinylation of recombinant proteins in Spodoptera frugiperda cells using biotin acceptor peptides SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE enzymatic biotinylation; baculovirus; biotin acceptor peptide; BirA ID ESCHERICHIA-COLI; IN-VIVO; STREPTAVIDIN; PURIFICATION; AVIDIN; CONSTRUCTION; EFFICIENCY; INSERTION; SUBUNIT; GENES AB Site-specific, enzymatic biotinylation of recombinant proteins can be exploited to circumvent many problems associated with the use of biotinylating reagents in vitro and to overcome some of their inherent Limitations. Additionally, biotinyl proteins can be purified to near-homogeneity in a single step under native conditions. Here we report that a biotin acceptor peptide (BAP) substrate for Escherichia coli biotin holoenzyme synthetase (BirA) can be used to label recombinant proteins with biotin in Spodoptera frugiperda (Sf9) cells, and we describe a collection of baculovirus transfer vectors specifically designed for this purpose. These BioBac vectors will greatly expand the range of proteins to which this technology can be applied. (C) 1998 Academic Press. C1 NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Hoffmann La Roche Inc, Roche Res Ctr, Nutley, NJ 07110 USA. RP Waugh, DS (reprint author), NCI, ABL Basic Res Program, Frederick Canc Res & Dev Ctr, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov RI Duffy, Siobain/A-9104-2009 OI Duffy, Siobain/0000-0003-0753-223X NR 30 TC 52 Z9 53 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 EI 1096-0309 J9 ANAL BIOCHEM JI Anal. Biochem. PD SEP 10 PY 1998 VL 262 IS 2 BP 122 EP 128 DI 10.1006/abio.1998.2770 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 127RA UT WOS:000076363300003 PM 9750126 ER PT J AU Hansson, SR Hoffman, BJ Mezey, E AF Hansson, SR Hoffman, BJ Mezey, E TI Ontogeny of vesicular monoamine transporter mRNAs VMAT1 and VMAT2 - I. The developing rat central nervous system SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE biogenic amines; embryonal development; subventricular zone; basal ganglia; sensory nuclei; limbic system; hypothalamus ID FLUORESCENCE HISTOCHEMICAL OBSERVATIONS; IMMUNO-CYTOCHEMICAL LOCALIZATION; DEPENDENT SYNAPTIC PLASTICITY; GROWTH CONE MOTILITY; TYROSINE-HYDROXYLASE; DEVELOPMENTAL CHARACTERISTICS; EARLY EMBRYOGENESIS; AMINE TRANSPORTER; PRENATAL ONTOGENY; ENDOCRINE-CELLS AB We used in situ hybridization histochemistry to study the expression of the mRNA of the two vesicular monoamine transporters (VMAT1 and VMAT2) during embryonic and postnatal development of the central nervous system (CNS) in the rat. In the adult rat, VMAT2 mRNA is present exclusively in monoaminergic cell groups of the CNS and VMAT1 mRNA was reported to be present in the adrenal medulla and certain intestinal epithelial cells. In contrast to the above, the expression of VMAT1 mRNA has previously never been detected in the central nervous system. This study shows the first evidence that both transporter molecules are expressed in CNS during ontogenesis. We here demonstrate four main expression patterns detected during development: 1. VMAT2 mRNA expression in monoaminergic neurons of the brainstem beginning as early as embryonic day E13. 2. Expression of VMAT2 mRNA in all major sensory relay nuclei of central nervous system. 3. Go-expression of VMAT1 and VMAT2 mRNA in most limbic structures, basal ganglia, as well as in some hypothalamic nuclei. 4. Exclusive expression of VMAT1 mRNA in the neocortical subventricular zone, in the amygdala at early (E15-18) and late (P1-P28) timepoints, the granular cell layer of cerebellum, and in several brainstem motor nuclei. Based on their distribution during development we suggest that monoamines, released in a controlled fashion, might affect wiring of sensory and also motor circuits. VMAT1 mRNA expression may reflect a specific effect of monoamines in glial differentiation and cerebellar granule cell migration and/or differentiation. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. NIMH, Unit Mol Pharmacol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NINDS, Basic Neurosci Program, Bldg 36,3D10, Bethesda, MD 20892 USA. NR 42 TC 20 Z9 21 U1 1 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 SEP 10 PY 1998 VL 110 IS 1 BP 135 EP 158 DI 10.1016/S0165-3806(98)00104-7 PG 24 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 122UC UT WOS:000076089000016 ER PT J AU Hansson, SR Mezey, E Hoffman, BJ AF Hansson, SR Mezey, E Hoffman, BJ TI Ontogeny of vesicular monoamine transporter mRNAs VMAT1 and VMAT2 - II. Expression in neural crest derivatives and their target sites in the rat SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE biogenic amines; dorsal root ganglia; sympathetic ganglia; heart; gastrointestinal tract; endocrine; placenta ID NEUROTRANSMITTER TRANSPORTERS; AMINE TRANSPORTER; ENDOCRINE-CELLS; SYSTEM; LOCALIZATION; RECEPTOR; ISOFORMS; NEURONS; MOUSE AB We used in situ hybridization histochemistry to study the expression of the two vesicular monoamine transporters (VMAT1 and VMAT2) during embryonic development in the rat. In the adult rat VMAT2 is present exclusively in neuronal tissues and VMAT1 is present in the adrenal medulla and in certain intestinal endocrine cells. We found that both transporter molecules are more widely expressed during development. We demonstrate a complete overlap of the two VMAT mRNAs in the sympathetic nervous system between E13 and E21 days. In addition, VMAT2 land to some extent VMAT1) mRNA is expressed in ganglionic cells of the parasympathetic nervous system and in cranial ganglia (trigeminal, vestibular and spiral ganglia) between E12 and E21. The sensory neurons of the dorsal root ganglia, which are also neural crest derivatives, express VMAT2 mRNA (E11-E21), exclusively. Bath VMAT mRNAs are found in the developing GI system, but in different cells. VMAT1 mRNA was detected in organs of the endocrine system (pituitary gland, adrenal gland, testis, seminal vesicle), some connective tissue cells, and the thymus. We observed expression of both VMAT mRNAs in two separate cell groups in the placenta (E8-E10). Based on their distribution during development we suggest that monoamines, released in a controlled fashion, might affect migration and differentiation of neural crest derivatives. (C) 1998 Elsevier Science B.V. All rights reserved. C1 NINDS, Basic Neurosci Program, Bethesda, MD 20892 USA. NIMH, Unit Mol Pharmacol, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Mezey, E (reprint author), NINDS, Basic Neurosci Program, Bldg 36,3D10, Bethesda, MD 20892 USA. EM mezey@codon.nih.gov NR 36 TC 14 Z9 16 U1 1 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 SEP 10 PY 1998 VL 110 IS 1 BP 159 EP 174 DI 10.1016/S0165-3806(98)00103-5 PG 16 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 122UC UT WOS:000076089000017 ER PT J AU Koren, AO Horti, AG Mukhin, AG Gundisch, D Kimes, AS Dannals, RF London, ED AF Koren, AO Horti, AG Mukhin, AG Gundisch, D Kimes, AS Dannals, RF London, ED TI 2-, 5-, and 6-halo-3-(2(S)-azetidinylmethoxy)pyridines: Synthesis, affinity for nicotinic acetylcholine receptors, and molecular modeling SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CHOLINERGIC CHANNEL MODULATOR; IN-VIVO; ABT-089 2-METHYL-3(2-(S)-PYRROLIDINYLMETHOXY)PYRIDINE; HUMAN BRAIN; BINDING; LIGAND; EPIBATIDINE; PHARMACOPHORE; TOMOGRAPHY; FACILE AB 3-(2(S)-Azetidinylmethoxy)pyridine (A-85380) has been identified recently as a ligand with high affinity for nicotinic acetylcholine receptors (nAChRs). Here we report the synthesis and in vitro nAChR binding of a series of 10 pyridine-modified analogues of A-85380; The novel compounds feature a halogen substituent at position 2, 5, or 6 of the 3-pyridyl fragment. Those with the substituents at position 5 or 6, as well as the 2-fluoro analogue, possess subnanomolar affinity for nAChRs in membranes from rat brain. For these ligands, K-i values range from 11 to 210 pM, as measured by competition with (+/-)-[H-3]epibatidine. In contrast, 2-chloro, 2-bromo, and 2-iodo analogues exhibit substantially lower affinity. AM1 quantum chemical calculations demonstrate that the bulky substituents at position 2 cause notable changes in the molecular geometry. The high-affinity members of the series and (+)-epibatidine display a tight fit superposition of low-energy stable conformers. The new ligands with high affinity for nAChRs may be of interest as pharmacological probes, potential medications, and candidates for developing radiohalogenated tracers to study nAChRs. C1 NIDA, Intramural Res Program, Brain Imaging Ctr, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Radiol, Div Nucl Med, Baltimore, MD 21287 USA. RP Koren, AO (reprint author), NIDA, Intramural Res Program, Brain Imaging Ctr, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 43 TC 116 Z9 118 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 10 PY 1998 VL 41 IS 19 BP 3690 EP 3698 DI 10.1021/jm980170a PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 119JH UT WOS:000075892000016 PM 9733494 ER PT J AU Kingston, DGI Chaudhary, AG Chordia, MD Gharpure, M Gunatilaka, AAL Higgs, PI Rimoldi, JM Samala, L Jagtap, PG Giannakakou, P Jiang, YQ Lin, CM Hamel, E Long, BH Fairchild, CR Johnston, KA AF Kingston, DGI Chaudhary, AG Chordia, MD Gharpure, M Gunatilaka, AAL Higgs, PI Rimoldi, JM Samala, L Jagtap, PG Giannakakou, P Jiang, YQ Lin, CM Hamel, E Long, BH Fairchild, CR Johnston, KA TI Synthesis and biological evaluation of 2-acyl analogues of paclitaxel (Taxol) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MICROTUBULE-ASSOCIATED PROTEINS; TUBULIN POLYMERIZATION; ANTITUMOR AGENTS; BACCATIN-III; CHEMISTRY; C-2; CYTOTOXICITY; DEACYLATION; HYDROLYSIS; EFFICIENT AB The anticancer drug paclitaxel (Taxol) has been converted to a large number of 2-debenzoyl-2-aroyl derivatives by three different methods. The bioactivities of the resulting analogues were determined in both tubulin polymerization and cytotoxicity assays, and several analogues with enhanced activity as compared with paclitaxel were discovered. Correlation of cytotoxicity in three cell lines with tubulin polymerization activity showed reasonable agreement. Among the cell lines examined, the closest correlation with antitubulin activity was observed with a human ovarian carcinoma cell line. C1 Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. NCI, Div Clin Sci, Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag,Dev Therapeut Program, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. Bristol Myers Squibb Pharmaceut Res Inst, Princeton, NJ USA. RP Kingston, DGI (reprint author), Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. RI Chordia, Mahendra/A-4706-2008; OI Giannakakou, Paraskevi/0000-0001-7378-262X; Kingston, David/0000-0001-8944-246X FU NCI NIH HHS [CA 55131, CA 48974, CA 69571] NR 53 TC 59 Z9 60 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD SEP 10 PY 1998 VL 41 IS 19 BP 3715 EP 3726 DI 10.1021/jm980229d PG 12 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 119JH UT WOS:000075892000019 PM 9733497 ER PT J AU Bates, S Phillips, AC Clark, PA Stott, F Peters, G Ludwig, RL Vousden, KH AF Bates, S Phillips, AC Clark, PA Stott, F Peters, G Ludwig, RL Vousden, KH TI p14(ARF) links the tumour suppressors RB and p53 SO NATURE LA English DT Letter ID APOPTOSIS C1 ABL Basic Res Program, Frederick, MD 21702 USA. Imperial Canc Res Fund Labs, London WC2A 3PX, England. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Bates, S (reprint author), ABL Basic Res Program, Chandler St, Frederick, MD 21702 USA. NR 11 TC 732 Z9 756 U1 2 U2 11 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 10 PY 1998 VL 395 IS 6698 BP 124 EP 125 DI 10.1038/25867 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 118GK UT WOS:000075829900026 PM 9744267 ER PT J AU Gaydos, CA Howell, MR Pare, B Clark, KL Ellis, DA Hendrix, RM Gaydos, JC McKee, KT Quinn, TC AF Gaydos, CA Howell, MR Pare, B Clark, KL Ellis, DA Hendrix, RM Gaydos, JC McKee, KT Quinn, TC TI Chlamydia trachomatis infections in female military recruits SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LIGASE CHAIN-REACTION; PELVIC INFLAMMATORY DISEASE; FIRST-VOID URINE; REACTION ASSAY; UNITED-STATES; WOMEN; DIAGNOSIS; PREVALENCE; ADOLESCENTS; RISK AB Background. Asymptomaticgenital Chlamydia trachomatis infections in women can lead to pelvic inflammatory disease, infertility, and ectopic pregnancy. To design a chlamydia-control program, we conducted a large survey of women in the U.S. military. Methods From January 1996 through December 1997, urine samples from 13,204 new female U.S. Army recruits from 50 states were screened by ligase chain reaction for C. trachomatis infection. Information on potential risk factors was obtained by questionnaire. With multivariate analysis, we identified criteria for a screening program. Results The overall prevalence of chlamydial infection was 9.2 percent, with a peak of 12.2 percent among the 17-year-old recruits. The prevalence was 15 percent or more among the recruits from five southern states. The following risk factors were independently associated with chlamydial infection: having ever had vaginal sex (odds ratio for infection, 5.9), being 25 years of age or less (odds ratio, 3.0), being black (odds ratio, 3.4), having had more than one sex partner in the previous 90 days (odds ratio, 1.4), having had a new partner in the previous 90 days (odds ratio, 1.3), having had a partner in the previous 90 days who did not always use condoms (odds ratio, 1.4), and having ever had a sexually transmitted disease (odds ratio, 1.2). A screening program for subjects 25 years of age or less (87.9 per cent of our sample) would have identified 95.3 percent of the infected women. Conclusions. Among female military recruits, the prevalence of chlamydial infection is high. A control program that screens female recruits who are 25 years old or younger with urine DNA-amplification assays has the potential to reduce infection, transmission, and the sequelae of chlamydial infection. (N Engl J Med 1998;339:739-44.) (C) 1998, Massachusetts Medical Society. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. USA, Med Dept Act, Ft Jackson, SC USA. Henry M Jackson Fdn, Rockville, MD USA. Womack Army Med Ctr, Ft Bragg, NC USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Gaydos, CA (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, 720 Rutland Ave,1159 Ross Res Bldg, Baltimore, MD 21205 USA. RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010 NR 38 TC 179 Z9 183 U1 0 U2 3 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 10 PY 1998 VL 339 IS 11 BP 739 EP 744 DI 10.1056/NEJM199809103391105 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 116RF UT WOS:000075737800005 PM 9731090 ER PT J AU Iglesias, M Yen, K Gaiotti, D Hildesheim, A Stoler, MH Woodworth, CD AF Iglesias, M Yen, K Gaiotti, D Hildesheim, A Stoler, MH Woodworth, CD TI Human papillomavirus type 16 E7 protein sensitizes cervical keratinocytes to apoptosis and release of interleukin-1 alpha SO ONCOGENE LA English DT Article DE apoptosis; cervical carcinoma; human; papillomavirus; interleukin-1; keratinocyte ID EPITHELIAL-CELLS; GENE-EXPRESSION; DIFFERENTIAL REGULATION; GROWTH-FACTOR; DNA; CARCINOMA; RECEPTOR; PROLIFERATION; FIBROBLASTS; INFECTION AB Interleukin-1 alpha. (IL-1 alpha) is a multifunctional cytokine that promotes inflammation, tissue remodeling and epithelial hyperplasia, Keratinocytes produce and sequester large amounts of biologically active IL-1 alpha which can be released after injury or infection. We show that high level expression of human papillomavirus (HPV) type 16 E6 and E7 oncoproteins enhanced release of IL-1 alpha from cultures of normal cervical keratinocytes (relative effectiveness E7>E6/E7 much greater than E6> control). The amount of IL-1 alpha. released was directly related to the ability of E7 or E6/E7 to stimulate apoptosis, E7 proteins that bound the retinoblastoma protein (Rb) strongly (HPV-16 and -18) induced more IL-1 alpha release than those that bound poorly (HPV-6 and an HPV-16 E7 24gly mutant). Furthermore, overexpression of the E2F-1 transcription factor, a downstream target of Rb, induced extensive apoptosis and IL-1 alpha release. Apoptosis and IL-1 alpha release in response to growth factor removal occurred in part through a p53-independent pathway as coexpression of E6 and downregulation of p53 did not prevent either response. Immunohistochemical analyses showed that IL-1 alpha. was expressed by keratinocytes in normal cervical epithelia, low and high grade dysplasias, and cervical carcinomas. However, HPV-16 E6/E7 RNA expression and apoptosis increased in parallel in proliferating keratinocytes in severe dysplasias and carcinomas suggesting that IL-1 alpha release is associated with progression to high grade disease. Thus, high level expression of the HPV-16 E7 protein sensitizes keratinocytes to apoptosis which results in release of IL-1 alpha. C1 NCI, Biol Lab, Bethesda, MD 20892 USA. NCI, Environm Epidemiol Branch, Bethesda, MD 20892 USA. Univ Virginia, Hlth Sci Ctr, Dept Pathol, Charlottesville, VA 22901 USA. RP Woodworth, CD (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bldg 37,Room 3B25, Bethesda, MD 20892 USA. NR 52 TC 44 Z9 46 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 10 PY 1998 VL 17 IS 10 BP 1195 EP 1205 DI 10.1038/sj.onc.1202054 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 117VL UT WOS:000075803300001 PM 9771962 ER PT J AU Zhang, LJ Zhan, SL Navid, F Li, QD Choi, YH Kim, M Seth, P Helman, LJ AF Zhang, LJ Zhan, SL Navid, F Li, QD Choi, YH Kim, M Seth, P Helman, LJ TI AP-2 may contribute to IGF-II overexpression in rhabdomyosarcoma SO ONCOGENE LA English DT Article DE IGF-II; AP-2; tumor cells ID TRANSCRIPTION FACTOR AP-2; GROWTH FACTOR-II; GENE-EXPRESSION; INDUCIBLE ENHANCER; MAMMARY-CARCINOMA; CYCLIC-AMP; CELL-LINE; PROMOTER; EMBRYOGENESIS; ACTIVATION AB The human insulin-like growth factor II gene is regulated in a development-dependent manner and is not expressed in most adult tissues. However, high levels of insulin-like growth factor II mRNA are detected in many human tumors including rhabdomyosarcoma, an embryonal tumor of skeletal muscle origin. In this study, we demonstrate that the developmentally regulated transcription factor AP-2 is expressed at higher levels in human fetal skeletal muscle and rhabdomyosarcoma cells compared to human adult skeletal muscle, Endogenous insulin-like growth factor II mRNA derived from the P3 as well as transfected P3 promoter activity were modestly and consistently increased to the same extent following treatment of the rhabdomyosarcoma cell line RD with forskolin, a compound implicated in AP-2 transactivation, This effect of AP-2 on increased transcriptional activity was confirmed by nuclear run-on assays. Expression of AP-2B, a dominant-negative inhibitor of AP-2, suppressed the P3 promoter activity in AP-2 expressing RD cells. Furthermore, five AP-2 protected regions corresponding to six AP-2 specific binding sites were detected in the insulin-like growth factor II P3 promoter. These data together suggest that AP-2 may contribute to the high expression of IGF-II in rhabdomyosarcoma cells. C1 NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Ovarian Canc Sect, NIH, Bethesda, MD 20892 USA. NCI, Cell Signaling & Oncogenesis Sect, NIH, Bethesda, MD 20892 USA. NCI, Med Breast Canc Sect, Med Branch, NIH, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. NR 31 TC 21 Z9 23 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 10 PY 1998 VL 17 IS 10 BP 1261 EP 1270 DI 10.1038/sj.onc.1202050 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 117VL UT WOS:000075803300008 PM 9771969 ER PT J AU Ramirez, BE Bax, A AF Ramirez, BE Bax, A TI Modulation of the alignment tensor of macromolecules dissolved in a dilute liquid crystalline medium SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID HUMAN UBIQUITIN; NMR; RELAXATION; RESOLUTION C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. NR 24 TC 137 Z9 141 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 9 PY 1998 VL 120 IS 35 BP 9106 EP 9107 DI 10.1021/ja982310b PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 118VA UT WOS:000075860100041 ER PT J AU Witteveen, CFB Giovanelli, J Yim, MB Gachhui, R Stuehr, DJ Kaufman, S AF Witteveen, CFB Giovanelli, J Yim, MB Gachhui, R Stuehr, DJ Kaufman, S TI Reactivity of the flavin semiquinone of nitric oxide synthase in the oxygenation of arginine to N-G-hydroxyarginine, the first step of nitric oxide synthesis SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID HYDROXY-L-ARGININE; ADENINE-DINUCLEOTIDE PHOSPHATE; HEME IRON REDUCTION; CATALYZED CONVERSION; ELECTRON-TRANSFER; CYTOCHROME P-450; ACID SUBSTRATE; ENZYME; BRAIN; CITRULLINE AB Nitric oxide synthase (NOS) is a heme protein that catalyzes the oxygenation of L-arginine in the presence of NADPH to form nitric oxide, L-citrulline and NADP(+), and proceeds via two partial reactions: L-Arginine --> N-G-hydroxy-L-argine N-G-Hydroxy-L-arginine --> L-citrulline + nitric oxide Calmodulin, FAD, FMN and tetrahydrobiopterin are required for both reactions. Reactions 1 and 2 require the input of 2 and 1 electron equivalents, respectively. Under normal multiple turnover conditions, these electrons are ultimately derived from NADPH. We previously reported that NOS contains an endogenous reductant that, in the absence of NADPH, can support the single-turnover oxygenation of L-arginine to N(G_)hydroxy-L-arginine and a relatively small amount of L-citrulline [Campos, K.L., Giovanelli, J., and Kaufman, S. (1995) J. Biol. Chem. 270, 1721-1728]. This reductant has now been identified as the stable flavin semiquinone free radical (FSQ). its oxidation appears to be coupled to the formation of N-G-hydroxy-L-arginine and L-citrulline. The rate of FSQ oxidation is two orders of magnitude slower than the flux of electrons from NADPH through NOS during normal turnover of the enzyme, indicating that FSQ is not the proximal electron donor for heme under these conditions. (C) 1998 Academic Press. C1 NIMH, Neurochem Lab, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Res Inst, Dept Immunol NN1, Cleveland, OH 44195 USA. RP Giovanelli, J (reprint author), NIMH, Neurochem Lab, Bethesda, MD 20892 USA. FU NIGMS NIH HHS [GM 51491] NR 35 TC 22 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 8 PY 1998 VL 250 IS 1 BP 36 EP 42 DI 10.1006/bbrc.1998.8807 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 119RY UT WOS:000075912000008 PM 9735327 ER PT J AU Holst, LS Mulder, H Manganiello, V Sundler, F Ahren, B Holm, C Degerman, E AF Holst, LS Mulder, H Manganiello, V Sundler, F Ahren, B Holm, C Degerman, E TI Protein kinase B is expressed in pancreatic beta cells and activated upon stimulation with insulin-like growth factor I SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PHOSPHATIDYLINOSITOL 3-KINASE; RAT ADIPOCYTES; MOLECULAR-CLONING; SECRETION; TRANSLOCATION; GLUCOSE; PHOSPHORYLATION; ISLETS; AKT; ASSOCIATION AB Protein kinase B (PKB) is involved in signaling to a multitude of important cellular events and is activated by insulin and growth factors, including insulin-like growth factor I (IGF-I), We show here expression of PKB in pancreatic islets and in the beta cell lines HIT-T15, INS-1, and RINm5F. Expression of PKB mRNA and the presence of PKB isoforms (alpha, beta, and gamma) were assessed by Northern blot analysis and RT-PCR, respectively, Antibodies recognizing different parts of PKB isoforms were employed to demonstrate PKB protein expression by immunoblot analysis. By use of immunohistochemistry in rat and mouse pancreatic tissue sections, PKB was localized to predominantly beta cells. Regulation of PKB was examined in INS-1 and RINm5F cells; upon stimulation with IGF-I (5-10 min), PKB was phosphorylated and activated (approximate to 3-fold) by a wortmannin-sensitive mechanism, indicating involvement of phosphatidylinositol-3 kinase. The possible participation of PKB in signal transduction pathways modulating cAMP-dependent insulin secretion and in proliferation of beta cells is discussed. (C) 1998 Academic Press. C1 Univ Lund, Dept Cell & Mol Biol, Sect Mol Signalling, Lund, Sweden. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Lund, Dept Physiol & Neurosci, Lund, Sweden. Univ Lund, Wallenberg Lab, Dept Med, Malmo, Sweden. RP Holst, LS (reprint author), Univ Lund, Dept Cell & Mol Biol, Sect Mol Signalling, Lund, Sweden. RI Mulder, Hindrik/E-1045-2012 NR 36 TC 44 Z9 44 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD SEP 8 PY 1998 VL 250 IS 1 BP 181 EP 186 DI 10.1006/bbrc.1998.9166 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 119RY UT WOS:000075912000034 PM 9735353 ER PT J AU Benjamin, EJ Wolf, PA D'Agostino, RB Silbershatz, H Kannel, WB Levy, D AF Benjamin, EJ Wolf, PA D'Agostino, RB Silbershatz, H Kannel, WB Levy, D TI Impact of atrial fibrillation on the risk of death SO CIRCULATION LA English DT Article DE fibrillation, atrial; mortality; prognosis; stroke; cerebrovascular disorders; risk factors; aging ID ACUTE MYOCARDIAL-INFARCTION; PROGNOSTIC-SIGNIFICANCE; EPIDEMIOLOGIC FEATURES; HEART-FAILURE; FOLLOW-UP; STROKE; POPULATION; PREVALENCE; MORTALITY AB Background-Atrial fibrillation (AF) causes substantial morbidity. It is uncertain whether AF is associated with excess mortality independent of associated cardiac conditions and risk factors. Methods and Results-We examined the mortality of subjects 55 to 94 years of age who developed AF during 40 years of follow-up of the original Framingham Heart Study cohort. Of the original 5209 subjects, 296 men and 325 women (mean ages, 74 and 76 years, respectively) developed AF and met eligibility criteria. By pooled logistic regression, after adjustment for age, hypertension, smoking, diabetes, left ventricular hypertrophy, myocardial infarction, congestive heart failure, valvular heart disease, and stroke or transient ischemic attack, AF was associated with an OR for death of 1.5 (95% CI, 1.2 to 1.8) in men and 1.9 (95% CI, 1.5 to 2.2) in women. The risk of mortality conferred by AF did not significantly vary by age. However, there was a significant AF-sex interaction: AF diminished the female advantage in survival. In secondary multivariate analyses, in subjects free of valvular heart disease and preexisting cardiovascular disease, AF remained significantly associated with excess mortality, with about a doubling of mortality in both sexes. Conclusions-In subjects from the original cohort of the Framingham Heart Study, AF was associated with a 1.5- to 1.9-fold mortality risk after adjustment for the preexisting cardiovascular conditions with which AF was related. The decreased survival. seen with AF was present in men and women and across a wide range of ages. C1 NHLBI, Framingham Heart Study, NIH, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Beth Israel Hosp, Div Cardiol & Clin Epidemiol, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP Benjamin, EJ (reprint author), NHLBI, Framingham Heart Study, NIH, 5 Thurber St, Framingham, MA 01702 USA. EM emelia@fram.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-38038]; NINDS NIH HHS [5-R01-NS-17590-16] NR 39 TC 2153 Z9 2224 U1 10 U2 68 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 8 PY 1998 VL 98 IS 10 BP 946 EP 952 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 116HC UT WOS:000075717600003 PM 9737513 ER PT J AU Feng, J Sobell, JL Heston, LL Goldman, D Cook, E Kranzler, HR Gelernter, J Sommer, SS AF Feng, J Sobell, JL Heston, LL Goldman, D Cook, E Kranzler, HR Gelernter, J Sommer, SS TI Variants in the alpha(2A) adrenergic receptor gene in psychiatric patients SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Article DE schizophrenia; attention deficit hyperactivity disorder; autism; alcohol dependence; cocaine dependence ID CANDIDATE-GENE; MESSENGER-RNA; CLONIDINE; SCHIZOPHRENIA; ASSOCIATION; WITHDRAWAL; EXPRESSION; MUTATIONS; CLOZAPINE; SUBTYPES AB In various studies of psychiatric patients, alterations in adrenergic receptor (AR) expression or function have been suggested. Herein, the alpha(2A) AR gene was screened in 206 patients with schizophrenia, attention deficit hyperactivity disorder (ADHD), autism, alcohol dependence, or cocaine dependence. The entire coding region was examined for single base pair changes, using restriction endonuclease fingerprinting (REF), a screening method that can detect virtually 100% of mutations in 2-kb DNA segments. In the approximately 600 kb of screened sequence, six novel nucleotide changes were identified. The changes resulted in four missense changes (A25G, N251K, R368L, and K370N), and a sequence in the 3' untranslated region. In addition, a silent change (G363G) was found at high frequency in Asians and Native Americans. Of the four missense changes, two found in patients with alcohol/drug dependence occur in highly conserved amino acids, suggesting that these are of likely functional significance. As the alpha(2A) ARs are widely distributed both pre- and postsynaptically, and as many pharmacological agents with multiple effects target these receptors, the novel missense changes described herein may be candidates for involvement in alcohol/drug dependence, in other clinical disorders or traits, or in differential response to pharmacotherapy. (C) 1998 Wiley-Liss, Inc. C1 City Hope Natl Med Ctr, Dept Mol Genet, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Div Mol Med, Duarte, CA 91010 USA. Univ Washington, Dept Psychiat, Seattle, WA 98195 USA. NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Chicago, Dept Child Psychiat, Chicago, IL 60637 USA. Univ Connecticut, Ctr Hlth, Dept Psychiat, Farmington, CT 06032 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. RP Sommer, SS (reprint author), City Hope Natl Med Ctr, Dept Mol Genet, Duarte, CA 91010 USA. RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIAAA NIH HHS [AA00239]; NIDA NIH HHS [DAAO4060]; NIMH NIH HHS [MH44276] NR 27 TC 19 Z9 19 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD SEP 7 PY 1998 VL 81 IS 5 BP 405 EP 410 DI 10.1002/(SICI)1096-8628(19980907)81:5<405::AID-AJMG9>3.0.CO;2-R PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 117MA UT WOS:000075784000009 PM 9754626 ER PT J AU Baumann, MH Horowitz, JM Kristal, MB Torres, G AF Baumann, MH Horowitz, JM Kristal, MB Torres, G TI Effects of cocaethylene on dopamine and serotonin synthesis in Long-Evans and Sprague-Dawley brains SO BRAIN RESEARCH LA English DT Article DE behavior; caudate nucleus; cingulate cortex; cocaine; genotype; nucleus accumbens ID COCAINE; ETHANOL; METABOLITE; PHARMACOLOGY; RAT AB We examined the behavioral and neurochemical effects of cocaethylene treatment in Long-Evans (LE) and Sprague-Dawley (SD) rats. Cocaethylene-induced behaviors were significantly less in LE rats. Cocaethylene caused an inhibition of dopamine synthesis in the caudate nucleus and nucleus accumbens that was equivalent in both rat lines. Serotonin synthesis was also suppressed by cocaethylene treatment, however this phenomenon was less pronounced when compared with the effects on dopamine synthesis. (C) 1998 Published by Elsevier Science B.V. All rights reserved. C1 SUNY Buffalo, Dept Psychol, Behav Neurosci Program, Buffalo, NY 14260 USA. Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Torres, G (reprint author), SUNY Buffalo, Dept Psychol, Behav Neurosci Program, Pk Hall, Buffalo, NY 14260 USA. EM gtorres@acsu.buffalo.edu NR 17 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 7 PY 1998 VL 804 IS 2 BP 316 EP 319 DI 10.1016/S0006-8993(98)00714-8 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 122TL UT WOS:000076087500016 PM 9757074 ER PT J AU Su, H Messer, R Whitmire, W Fischer, E Portis, JC Caldwell, HD AF Su, H Messer, R Whitmire, W Fischer, E Portis, JC Caldwell, HD TI Vaccination against chlamydial genital tract infection after immunization with dendritic cells pulsed ex vivo with nonviable Chlamydiae SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE chlamydia; pulsed dendritic cells; immunization; CD4(+) T cells; mucosal protective immunity ID GENE KNOCKOUT MICE; MOUSE PNEUMONITIS BIOVAR; CD4(+) T-CELLS; PROTECTIVE IMMUNITY; IFN-GAMMA; IN-VIVO; LISTERIA-MONOCYTOGENES; TRACHOMATIS INFECTION; ECTOPIC PREGNANCY; LEISHMANIA-MAJOR AB Chlamydia trachomatis, an obligate intracellular bacterial pathogen of mucosal surfaces, is a major cause of preventable blindness and sexually transmitted diseases for which vaccines are badly needed. Despite considerable effort, antichlamydial vaccines have proven to be elusive using conventional immunization strategies. We report the use of murine bone marrow-derived dendritic cells (DC) pulsed ex vivo with killed chlamydiae as a novel approach to vaccination against chlamydial infection. Our results show that DC efficiently phagocytose chlamydiae, secrete IL-12 p40, and present chlamydial antigen(s) to infection sensitized CD4(+) T cells. Mice immunized intravenously with chlamydial-pulsed DC produce protective immunity against chlamydial infection of the female genital tract equal to that obtained after infection with live organisms. Immunized mice shed similar to 3 logs fewer infectious chlamydiae and are protected from genital tract inflammatory and obstructive disease. Protective immunity is correlated with a chlamydial-specific Th1-biased response that closely mimics the immune response produced after chlamydial infection. Thus, ex vivo antigen-pulsed DC represent a powerful tool for the study of protective immunity to chlamydial mucosal infection and for the identification of chlamydial protective antigens through reconstitution experiments. Moreover, these findings might impact the design of vaccine strategies against other medically important sexually transmitted diseases for which vaccines are sought but which have proven difficult to develop. C1 NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Lab, Hamilton, MT 59840 USA. NIAID, Microscopy Branch, NIH, Rocky Mt Lab, Hamilton, MT 59840 USA. NIAID, Persistent Viral Dis Lab, NIH, Rocky Mt Lab, Hamilton, MT 59840 USA. RP Caldwell, HD (reprint author), NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Lab, Hamilton, MT 59840 USA. NR 52 TC 146 Z9 151 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD SEP 7 PY 1998 VL 188 IS 5 BP 809 EP 818 DI 10.1084/jem.188.5.809 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 119ZR UT WOS:000075929600002 PM 9730883 ER PT J AU van Putten, JPM Duensing, TD Carlson, J AF van Putten, JPM Duensing, TD Carlson, J TI Gonococcal invasion of epithelial cells driven by P.IA, a bacterial ion channel with GTP binding properties SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE Neisseria gonorrhoeae; porin; GTP binding protein; Rmp protein; bacterial invasion ID OUTER-MEMBRANE PROTEIN; NEISSERIA-GONORRHOEAE; ESCHERICHIA-COLI; PHASE VARIATION; MONOCLONAL-ANTIBODIES; ANTIGENIC VARIATION; OPACITY PROTEINS; SERUM RESISTANCE; GENE CONVERSION; INFECTION AB The neisserial porin P.I is a GTP binding protein that forms a voltage-gated channel that translocates into mammalian cell membranes and modulates host cell signaling events. Here, we report that P.I confers invasion of the bacterial pathogen Neisseria gonorrhoeae into Chang epithelial cells and that this event is controlled by GTP, as well as other phosphorus-containing compounds. Bacterial invasion was observed only for strains carrying the P.IA subtype of porin, which is typically associated with the development of disseminated neisserial disease, and did not require opacity outer membrane proteins, previously recognized as gonococcal invasins. Allelic replacement studies showed that bacterial invasiveness cotransferred with the P.IA (por1A) gene. Mutation of the P.I-associated protein Rmp did not alter the invasive properties. Cross-linking of labeled GTP to the porin revealed more efficient GTP binding to the P.IA than P.IB porin subtype. GTP binding was inhibited by an excess of unlabeled GTP, ATP, and GDP, as well as inorganic phosphate, but not by UTP or beta-glycerophosphate, fully in line with the respective invasion-inhibitory activities observed for these compounds. The P.IA-mediated cellular invasion may explain the more invasive behavior of P.IA strains in the natural infection and may broaden the basis for the development of a P.I-based gonococcal vaccine. C1 NIAID, Microbial Struct & Funct Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP van Putten, JPM (reprint author), NIAID, Microbial Struct & Funct Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. OI van Putten, Jos/0000-0002-4126-8172 NR 79 TC 58 Z9 60 U1 9 U2 12 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 SEP 7 PY 1998 VL 188 IS 5 BP 941 EP 952 DI 10.1084/jem.188.5.941 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 119ZR UT WOS:000075929600014 PM 9730895 ER PT J AU Tikoo, R Osterhout, DJ Casaccia-Bonnefil, P Seth, P Koff, A Chao, MV AF Tikoo, R Osterhout, DJ Casaccia-Bonnefil, P Seth, P Koff, A Chao, MV TI Ectopic expression of p27(Kip1) in oligodendrocyte progenitor cells results in cell-cycle growth arrest SO JOURNAL OF NEUROBIOLOGY LA English DT Article DE oligodendrocyte; differentiation; cell cycle; cyclin-dependent kinase ID DIFFERENTIATION; KINASE; ASTROCYTES; INVITRO; CULTURE; CLOCK AB Oligodendrocyte differentiation is a complex process believed to be controlled by an intrinsic mechanism associated with cell-cycle arrest. Recently, the cell-cycle inhibitor protein p27(Kip1) has been proposed as a key element in causing growth arrest of oligodendrocyte precursor cells. To investigate the effects of p27 upon oligodendrocyte cell development, we have introduced the p27 cDNA in oligodendrocyte progenitor cells using an adenovirus vector. Progenitor cells normally express low levels of p27, After adenoviral infection and p27 overexpression, progenitor cells were able to undergo cell-cycle arrest, even in the presence of strong mitogens. The effects of p27 were shown to be directly upon cyclin-dependent kinase-2 (CDK2), the protein kinase complex responsible for G1/S transition, as immunodepletion of oligodendrocyte extracts of p27 protein resulted in the activation of CDK2 activity, However, cells that became growth arrested owing to infection with p27 adenovirus did not display conventional oligodendrocyte differentiation markers, such as O4 or O1, Taken together, these data provide mechanistic evidence indicating that p27 is primarily involved in oligodendroglial progenitor proliferation by inhibiting CDK2 activity and inducing oligodendrocyte cell-cycle arrest. (C) 1998 John Wiley & Sons, Inc. C1 NYU, Med Ctr, Skirball Inst, Mol Neurobiol Program, New York, NY 10016 USA. Cornell Univ Med Coll, Dept Neurol & Neurosci, New York, NY 10012 USA. NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA. RP Chao, MV (reprint author), NYU, Med Ctr, Skirball Inst, Mol Neurobiol Program, 540 1st Ave, New York, NY 10016 USA. FU NICHD NIH HHS [HD232315]; NIGMS NIH HHS [GM52597]; NINDS NIH HHS [NS21072] NR 25 TC 68 Z9 68 U1 0 U2 2 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3034 J9 J NEUROBIOL JI J. Neurobiol. PD SEP 5 PY 1998 VL 36 IS 3 BP 431 EP 440 DI 10.1002/(SICI)1097-4695(19980905)36:3<431::AID-NEU10>3.0.CO;2-E PG 10 WC Neurosciences SC Neurosciences & Neurology GA 112UA UT WOS:000075511500010 PM 9733077 ER PT J AU Liu, DJ Ishima, R Tong, KI Bagby, S Kokubo, T Muhandiram, DR Kay, LE Nakatani, Y Ikura, M AF Liu, DJ Ishima, R Tong, KI Bagby, S Kokubo, T Muhandiram, DR Kay, LE Nakatani, Y Ikura, M TI Solution structure of a TBP-TAF(II)230 complex: Protein mimicry of the minor groove surface of the TATA box unwound by TBP SO CELL LA English DT Article ID RNA-POLYMERASE-II; YEAST TFIIA/TBP/DNA COMPLEX; NUCLEAR-MAGNETIC-RESONANCE; URACIL-DNA GLYCOSYLASE; CRYSTAL-STRUCTURE; BINDING-PROTEIN; TRANSCRIPTION FACTOR; TERNARY COMPLEX; TRANSACTIVATION DOMAIN; PREINITIATION COMPLEX AB General transcription factor TFIID consists of TATA box-binding protein (TBP) and TBP-associated factors (TAF(II)s), which together play a central role in both positive and negative regulation of transcription. The N-terminal region of the 230 kDa Drosophaa TAF(II)(dTAF(II)230) binds directly to TBP and inhibits TBP binding to the TATA box. We report here the solution structure of the complex formed by dTAF(II)230 N-terminal region (residues 11-77) and TBP. dTAF(II)230(11-77) comprises three or helices and a beta hairpin, forming a core that occupies the concave DNA-binding surface of TBP. The TBP-binding surface of dTAF(II)230 markedly resembles the minor groove surface of the partially unwound TATA box in the TBP-TATA complex. This protein mimicry of the TATA element surface provides the structural basis of the mechanism by which dTAF(II)230 negatively controls the TATA box-binding activity within the TFIID complex. C1 Ontario Canc Inst, Div Mol & Struct Biol, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Univ Toronto, Protein Engn Network Ctr Excellence, Dept Med & Mol Genet, Toronto, ON M5S 1A8, Canada. Univ Toronto, Protein Engn Network Ctr Excellence, Dept Biochem, Toronto, ON M5S 1A8, Canada. Univ Toronto, Protein Engn Network Ctr Excellence, Dept Chem, Toronto, ON M5S 1A8, Canada. RP Ikura, M (reprint author), Ontario Canc Inst, Div Mol & Struct Biol, Dept Med Biophys, Toronto, ON M5G 2M9, Canada. NR 67 TC 150 Z9 157 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD SEP 4 PY 1998 VL 94 IS 5 BP 573 EP 583 DI 10.1016/S0092-8674(00)81599-8 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 118QR UT WOS:000075851900005 PM 9741622 ER PT J AU Park, T Davis, CS Li, N AF Park, T Davis, CS Li, N TI Alternative GEE estimation procedures for discrete longitudinal data SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE generalized estimating equations; quasi-likelihood; pearson residuals; anscombe residuals; deviance residuals ID EFFECTS MODELS; ASSOCIATION; REGRESSION AB Liang and Zeger (1986) proposed a generalized estimating equations (GEE) approach to the analysis of longitudinal data. Liang and Zeger's method consists of two estimation steps. One is a quasi-likelihood method for estimating regression parameters. The other is a robust moment method for estimating correlation parameters which incorporates the dependence among outcomes. The estimation of correlation parameters is based upon the Pearson residuals, which are implicitly assumed to be normally distributed. However, the normality assumption of Pearson residuals does not hold for discrete responses such as Poisson and binary outcomes. Instead of Pearson residuals, we consider two alternative types of residuals to estimate correlation parameters: Anscombe and deviance residuals. For Poisson and binary outcomes, the three methods are compared through simulation studies. Our results show that the choice of residual has little or no effect on the properties of the resulting estimates. The simple Pearson residual is thus recommended. (C) 1998 Published by Elsevier Science B.V. All. rights reserved. C1 Hankuk Univ Foreign Studies, Kyungki Do, South Korea. Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Univ Iowa, Iowa City, IA USA. WESTAT, Rockville, MD USA. NR 20 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD SEP 4 PY 1998 VL 28 IS 3 BP 243 EP 256 DI 10.1016/S0167-9473(98)00039-5 PG 14 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 122KH UT WOS:000076070400001 ER PT J AU Lin, Y Fossom, LH Skolnick, P Long, JB AF Lin, Y Fossom, LH Skolnick, P Long, JB TI Sustained exposure to a glycine receptor partial agonist differentially alters NMDA receptor agonist and antagonist potencies in cultured spinal cord neurons SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE ACPC (l-aminocyclopropanecarboxylic acid); neuroprotection; excitotoxicity; NMDA (N-methyl-D-aspartate); neuronal injury; glycine; excitatory amino acid ID 1-AMINOCYCLOPROPANECARBOXYLIC ACID PROTECTS; CEREBRAL-ISCHEMIA; COMPLEX; GLUTAMATE; TOXICITY; SITE; RAT AB Sustained (20 h) exposure to the glycine partial agonist 1-aminocyclopropanecarboxylic acid (ACPC) significantly reduced N-methyl-D-aspartate (NMDA)-induced neurotoxicity in cultured spinal cord neurons when the NMDA (25 and 100 mu M) was added to the cultures 30 min after removal of the ACPC (1 mM). In contrast, ACPC preexposure failed to protect against kainate-induced neuronal injury. The magnitude of neuronal protection against NMDA (100 mu M) was further enhanced if the neurons pretreated with ACPC were reexposed to this drug during the NMDA challenge. In addition, the potencies of both the competitive NMDA antagonist AP5 and the noncompetitive antagonist dizocilpine to block NMDA toxicity were significantly increased following ACPC preexposure, while the potency of the competitive glycine receptor antagonist 7-chlorokynurenate (7-CK) was unchanged. Analysis of Northern blots suggest that ACPC-induced changes in NMDA receptor function were not associated with alterations in the levels of the mRNAs encoding the NMDAR-1, -2A, -2B, or -2C subunits. These results indicate that sustained exposure to ACPC modifies NMDA receptors in a manner that diminishes NMDA receptor-mediated neurotoxicity while selectively enhancing the potencies of several NMDA receptor antagonists. These effects do not appear to be related to changes in expression of specific NMDA receptor subunits, and may instead involve a post-translational modification of one or more subunit proteins. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Neurosci, Washington, DC 20307 USA. NIDDKD, Neurosci Lab, NIH, Bethesda, MD 20892 USA. RP Long, JB (reprint author), Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Neurosci, Washington, DC 20307 USA. NR 20 TC 3 Z9 3 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD SEP 4 PY 1998 VL 356 IS 2-3 BP 255 EP 260 DI 10.1016/S0014-2999(98)00515-9 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 122HF UT WOS:000076065500020 PM 9774257 ER PT J AU Tsumaki, N Kimura, T Tanaka, K Kimura, JH Ochi, T Yamada, Y AF Tsumaki, N Kimura, T Tanaka, K Kimura, JH Ochi, T Yamada, Y TI Modular arrangement of cartilage- and neural tissue-specific cis-elements in the mouse alpha 2(XI) collagen promoter SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID XI COLLAGEN; FIBRILLAR COLLAGEN; GENE; EXPRESSION; ORGANIZATION; CONTRIBUTE; CLONING; REVEALS; COL11A1; CHAINS AB Type XI collagen, a heterotrimer specific to cartilage matrix, plays an important role in cartilage morphogenesis. We analyzed various alpha 2(XI) collagen promoter-lacZ reporter gene constructs in transgenic mice to understand tissue-specific transcriptional regulation. The -530 promoter sequence was sufficient to direct reporter gene expression specifically to cartilage. Further deletion to -500 abolished reporter gene expression iu cartilage but activated the expression specific to neural tissues such as brain and neural tube. An additional 47-base pair deletion resulted in random tissue expression patterns. A 24-base pair sequence from -530 to -507 of the alpha 2(XI) promoter was able to switch the activity of the heterologous neurofilament light gene promoter from neural tissues to cartilage. These results suggest that the alpha 2(XI) collagen gene is regulated by at least three modular elements: a basal promoter sequence distal to -453, a neural tissue-specific element (-454 to -500), and a cartilage-specific element (-501 to -530), which inhibits expression in neural tissues and induces expression in cartilage. C1 Osaka Univ, Sch Med, Dept Orthopaed Surg, Suita, Osaka 5650871, Japan. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Henry Ford Hosp, Ctr Bone & Joint, Biochem Sect, Detroit, MI 48202 USA. RP Tsumaki, N (reprint author), Osaka Univ, Sch Med, Dept Orthopaed Surg, 2-2 Yamadaoka, Suita, Osaka 5650871, Japan. NR 21 TC 26 Z9 26 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 22861 EP 22864 DI 10.1074/jbc.273.36.22861 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100002 PM 9722502 ER PT J AU Xiao, H Jeang, KT AF Xiao, H Jeang, KT TI Glutamine-rich domains activate transcription in yeast Saccharomyces cerevisiae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TATA-BINDING PROTEIN; GENE-EXPRESSION; FUNCTIONAL DISSECTION; UPSTREAM ACTIVATOR; MAMMALIAN-CELLS; PHO5 PROMOTER; IN-VIVO; SP1; SEQUENCE; RECRUITMENT AB Activation domains of eukaryotic transcription factors can be classified into at least three distinct types based on their amino acid composition: acidic, proline-rich, and glutamine-rich, Acidic activators, such as yeast GAL4 and GCN4 and herpes simplex virus VP16, have been shown to stimulate transcription in various higher and lower eukaryotic cells. Similarly, proline-rich activators also function in both mammalian and yeast cells. These activators are regarded to possess "universal" activating potentials. By contrast, several studies have suggested that glutamine-rich activators such as human Spl are active in higher (mammalian) but not lower (yeast) eukaryotic cells. One interpretation is that lower eukaryotic cells lack a critical cofactor necessary for a glutamine-rich domain. This reasoning is counter-intuitive because many native yeast activator proteins contain glutamine-rich domains. Here, we have investigated the activity of a glutamine-rich GAL4-Sp1 domain A (Sp1A) hybrid protein in yeast Saccharomyces cerevisiae. We show that GAL4-Sp1A activated a GAL1-lacZ reporter by more than 200-fold over basal when the reporter was carried on a 2 mu vector. The generality of the Sp1A results is supported by our finding that yeast glutamine-rich domains from HAP2 and MCM1 are also transcriptionally active in S. cerevisiae, Interestingly, we found that glutamine-rich domains are considerably less potent when responsive promoters (i.e. GAL1-lacZ) are integrated into yeast chromosome. Thus our results segregate the inherent transcriptional activity of a glutamine-rich domain in yeast S, cerevisiae from its apparent lack of activity when assayed on chromosomally embedded promoters. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Xiao, H (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM hxiao@atlas.niaid.nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 45 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 22873 EP 22876 DI 10.1074/jbc.273.36.22873 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100005 PM 9722505 ER PT J AU Ghedin, E Charest, H Zhang, WW Debrabant, A Dwyer, D Matlashewski, G AF Ghedin, E Charest, H Zhang, WW Debrabant, A Dwyer, D Matlashewski, G TI Inducible expression of suicide genes in Leishmania donovani amastigotes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID 3'-NUCLEOTIDASE NUCLEASE; THYMIDINE KINASE; PROMASTIGOTES; CLONING; DNA; A2; 5'-NUCLEOTIDASE; INFECTION; PROTEINS; REGION AB This study tests the feasibility of using the A2 gene regulatory system to create a Leishmania cell line in which attenuation is developmentally regulated when the parasite differentiates from promastigotes to amastigotes. The Leishmania donovani- inducible A2 gene regulatory system was used to differentially express in amastigotes two potential suicide genes: a truncated version of the L. donovani 3'-nucleotidase/nuclease expressed in the cytoplasm and the herpes simplex virus thymidine kinase gene. These genes were inserted between A2 noncoding regulatory sequences for up-regulation of expression in amastigotes. The accumulation of toxic products affected L. donovani cell replication and viability both in vitro and in vivo. The inducible expression of toxic gene products represents a valuable tool for the development of safe and effective vaccines. C1 McGill Univ, Inst Parasitol, St Anne Bellevue, PQ H9X 3V9, Canada. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Matlashewski, G (reprint author), McGill Univ, Inst Parasitol, 21111 Lakeshore Rd,Macdonald Campus, St Anne Bellevue, PQ H9X 3V9, Canada. NR 28 TC 20 Z9 21 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 22997 EP 23003 DI 10.1074/jbc.273.36.22997 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100023 PM 9722523 ER PT J AU Worth, L Bader, T Yang, J Clark, S AF Worth, L Bader, T Yang, J Clark, S TI Role of MutS ATPase activity in MutS,L-dependent block of in vitro strand transfer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIRECTED MISMATCH REPAIR; DNA-BASE PAIRS; NEGATIVE MUTATOR MUTATIONS; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; SACCHAROMYCES-CEREVISIAE; GENE; RECOMBINATION; PROTEIN; HOMOLOG AB In addition to mismatch recognition, Escherichia coli MutS has an associated ATPase activity that is fundamental to repair. Hence, we have characterized two MutS mutant gene products to define the role of ATP hydrolysis in homeologous recombination. These mutants, denoted MutS501 and MutS506, have single point mutations within the Walker A motif, and rate constants for ATP hydrolysis are down 60-100-fold as compared with wild type. Both MutS501 and MutS506 retain mismatch binding and,unlike wild type, fail to relinquish this specificity in the presence of ATP, adenosine 5'-O-(thiotriphosphate), and adenosine 5'-(beta,gamma-imino)triphosphate. Both MutS501 and MutS506 blocked the level of strand transfer between M13 and fd DNAs, The level of inhibition varied between the mutants and corresponded with the relative affinities to a G/T mispair. Neither MutS501 nor MutS506, however, would afford complete block of full-length heteroduplex in the presence of MutL. DNase I footprinting data are consistent with these results, as the region of protection by MutS501 and MutS506 was unchanged in the presence of ATP and MutL. Taken together, these studies suggest that 1) MutS impedes RecA-mediated homeologous exchange as a distinct mismatch-provoked event and 2) the role of MutL is coupled to MutS-dependent ATP hydrolysis, These observations are in good agreement with the present model for E. coli methyl-directed mismatch repair. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Inst Mol Pathol, Res Inst Mol Pathol, A-1030 Vienna, Austria. RP Worth, L (reprint author), NIEHS, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 42 TC 43 Z9 43 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 23176 EP 23182 DI 10.1074/jbc.273.36.23176 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100047 PM 9722547 ER PT J AU Hassett, RF Yuan, DS Kosman, DJ AF Hassett, RF Yuan, DS Kosman, DJ TI Spectral and kinetic properties of the Fet3 protein from Saccharomyces cerevisiae, a multinuclear copper ferroxidase enzyme SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ASCORBATE OXIDASE; IRON UPTAKE; CERULOPLASMIN; YEAST; PURIFICATION; LACCASE; GENE; SITE; STELLACYANIN; MECHANISM AB High affinity iron uptake in Saccharomyces cerevisiae requires Fet3p. Fet3p is proposed to facilitate iron uptake by catalyzing the oxidation of Fe(II) to Fe(III) by O-2; in this model, Fe(III) is the substrate for the iron permease, encoded by FTR1. Here, a recombinant Fet3p has been produced in yeast that, lacking the C-terminal membrane-spanning domain, is secreted directly into the growth medium. Solutions of this Fet3p at >1 mg/ml have the characteristic blue color of a type 1 Cu(II)-containing protein, consistent with the sequence homology that placed this protein in the class of multinuclear copper oxidases that includes ceruloplasmin. Fet3p has an intense absorption at 607 nm (epsilon = 5500 M-1 cm(-1)) due to this type 1 Cu(II) and a shoulder in the near UV at 330 nm (epsilon = 5000 M-1 cm(-1)) characteristic of a type 3 binuclear Cu(II) cluster. The EPR spectrum of this Fet3p showed the presence of one type 1 Cu(II) and one type 2. Cu(II) (A(parallel to) = 91 and 190 x 10(-4) cm(-1), respectively). Copper analysis showed this protein to have 3.85 g atom copper/mol, consistent with the presence of one each of the three types of Cu(II) sites found in multinuclear copper oxidases. N-terminal analysis demonstrated that cleavage of a signal peptide occurred after Ala-21 in the primary translation product. Mass spectral and carbohydrate analysis of the protein following Endo H treatment indicated that the preparation was still 15% (w/w) carbohydrate, probably O-linked. Kinetic analysis of the in vitro ferroxidase reaction catalyzed by this soluble Fet3p yielded precise kinetic constants. The K-m values for Fe(II) and O-2 were 4.8 and 1.3 mu M, respectively, while k(cat) values for Fe(II) and O-2 turnover were 9.5 and 2.3 min(-1), consistent with an Fe(II):O-2 reaction stoichiometry of 4:1. C1 SUNY Buffalo, Sch Med & Biomed Sci, Dept Biochem, Buffalo, NY 14214 USA. NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Kosman, DJ (reprint author), SUNY Buffalo, Sch Med & Biomed Sci, Dept Biochem, 140 Farber Hall,3435 Main St, Buffalo, NY 14214 USA. EM camkos@acsu.buffalo.edu FU NIGMS NIH HHS [GM46787] NR 58 TC 74 Z9 75 U1 0 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 23274 EP 23282 DI 10.1074/jbc.273.36.23274 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100059 PM 9722559 ER PT J AU Tarcsa, E Candi, E Kartasova, T Idler, WW Marekov, LN Steinert, PM AF Tarcsa, E Candi, E Kartasova, T Idler, WW Marekov, LN Steinert, PM TI Structural and transglutaminase substrate properties of the small proline-rich 2 family of cornified cell envelope proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN EPIDERMAL-KERATINOCYTES; DIFFERENTIATION-SPECIFIC GENES; INTERMEDIATE FILAMENTS; EPITHELIAL-CELLS; HUMAN LORICRIN; BOND FORMATION; CROSS-LINKING; RETINOIC ACID; SPR1 GENE; EXPRESSION AB The small proline-rich (SPR) proteins are components of the cornified cell envelope of stratified squamous epithelia and become cross-linked to other proteins by transglutaminases (TGases). The SIPR2 family is the most complex, as it consists of several differentially expressed members of the same size. To explore their physical and cross-linking properties, we have expressed in bacteria a human SPR2 family member, and purified it to homogeneity. By circular dichroism, it possesses no alpha or beta structure but has some organized structure associated with the central peptide repeat domain. The TGase 1, 2, and 3 enzymes expressed in epithelia use the recombinant SPR2 protein as a complete substrate in vitro, but with widely differing kinetic efficiencies, and in different ways. With TGase 1, only one glutamine on the head domain and one lysine on the tail domain were used for limited interchain cross-linking. With TGase 3, multiple head and tail domain residues were used for extensive interchain cross-linking. The total usage of glutamine and lysine residues in vitro by TGase 3 was similar to that seen in earlier in vivo studies. We conclude that SPR2 proteins are cross-linked in epithelia primarily by the TGase 3 enzyme, a minor extent by TGase 1, and probably not by TGase 2. C1 NIAMS, Skin Biol Lab, NIH, Bethesda, MD 20892 USA. RP Steinert, PM (reprint author), NIAMS, Skin Biol Lab, NIH, Bldg 6,Room 425,9000 Rockville Pike, Bethesda, MD 20892 USA. EM pemast@helix.nih.gov NR 50 TC 47 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 23297 EP 23303 DI 10.1074/jbc.273.36.23297 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100062 PM 9722562 ER PT J AU Li, QD Gardner, K Zhang, LJ Tsang, B Bostick-Bruton, F Reed, E AF Li, QD Gardner, K Zhang, LJ Tsang, B Bostick-Bruton, F Reed, E TI Cisplatin induction of ERCC-1 mRNA expression in A2780/CP70 human ovarian cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA EXCISION-REPAIR; INTERSTRAND CROSS-LINKS; PROTEIN-KINASE PATHWAY; PIGMENTOSUM GROUP-F; C-JUN; HA-RAS; GENE-EXPRESSION; ACTIVATION DOMAIN; ADDUCT FORMATION; TUMOR-CELLS AB ERCC-1 is a critical gene within the nucleotide excision repair pathway, and cells without a functional ERCC-1 do not perform cisplatin-DNA adduct repair. We therefore investigated the cisplatin effect on ERCC-1 mRNA expression in vitro. In response to a l-h cisplatin exposure, A2780/CP70 human ovarian cancer cells showed a B-fold increase in steady-state level of ERCC-1 mRNA This rise was attributable to increased transcription as measured by nuclear run-on assays and a 60% increase in ERCC-1 mRNA half-life. The increase in ERCC-1 mRNA was preceded by a 4-5-fold rise in mRNA expressions of c-fos and c-jun, a 14-fold increase in c-Jun protein phosphorylation, and an increase in in vitro nuclear extract binding activity to the AP-1-like site of ERCC-1, These data suggest that the induction of ERCC-1 expression in A2780/CP70 cells exposed to cisplatin results from two major factors: (a) an increase in the expression of transactivating factors that bind the AP-1-like site in the 5'-flanking region of ERCC-1 and (b) an increase in the level of c-Jun phosphorylation that enhances its transactivation property. C1 NCI, Med Ovarian Canc Sect, Dept Dev Therapeut, Med Branch,NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Oncol Sect, Pediat Branch, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Reed, E (reprint author), NCI, Med Ovarian Canc Sect, Dept Dev Therapeut, Med Branch,NIH, Bldg 10,Rm 13N248,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 64 TC 91 Z9 93 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 23419 EP 23425 DI 10.1074/jbc.273.36.23419 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100077 PM 9722577 ER PT J AU Greenberg, JR Phan, L Gu, ZY deSilva, A Apolito, C Sherman, F Hinnebusch, AG Goldfarb, DS AF Greenberg, JR Phan, L Gu, ZY deSilva, A Apolito, C Sherman, F Hinnebusch, AG Goldfarb, DS TI Nip1p associates with 40 S ribosomes and the Prt1p subunit of eukaryotic initiation factor 3 and is required for efficient translation initiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-SYNTHESIS INITIATION; INTACT YEAST-CELLS; STEM-LOOP MUTATION; SACCHAROMYCES-CEREVISIAE; BINDING-PROTEIN; RNA-BINDING; AMINOGLYCOSIDE ANTIBIOTICS; INTERNAL INITIATION; COMPLEX-FORMATION; SHUTTLE VECTORS AB Nip1p is an essential Saccharomyces cerevisiae protein that was identified in a screen for temperature conditional (ts) mutants exhibiting defects in nuclear transport. New results indicate that Nip1p has a primary role in translation initiation. Polysome profiles indicate that cells depleted of Nip1p and nip1-1 cells are defective in translation initiation, a conclusion that is supported by a reduced rate of protein synthesis in Nip1p-depleted cells. Nip1p cosediments with free 40 S ribosomal subunits and polysomal preinitiation complexes, but not with free or elongating 80 S ribosomes or 60 S subunits. Nip1p can be isolated in an about 670-kDa complex containing polyhistidine-tagged Prt1p, a subunit of translation initiation factor 3, by binding to Ni2+-NTA-agarose beads in a manner completely dependent on the tagged form of Prt1p. The nip1-1 ts growth defect was suppressed by the deletion of the ribosomal protein, RPL46. Also, nip1-1 mutant cells are hypersensitive to paromomycin. These results suggest that Nip1p is a subunit of eukaryotic initiation factor 3 required for efficient translation initiation. C1 Univ Rochester, Dept Biol, Rochester, NY 14627 USA. NICHD, Lab Eukaryot Gene Regulat, NIH, Bethesda, MD 20892 USA. Univ Rochester, Sch Med, Dept Biochem & Biophys, Rochester, NY 14642 USA. RP Univ Rochester, Dept Biol, Rochester, NY 14627 USA. EM dasg@uhura.cc.rochester.edu FU NIGMS NIH HHS [R01 GM12702] NR 67 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 23485 EP 23494 DI 10.1074/jbc.273.36.23485 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100086 PM 9722586 ER PT J AU Pham, PT Olson, MW McHenry, CS Schaaper, RM AF Pham, PT Olson, MW McHenry, CS Schaaper, RM TI The base substitution and frameshift fidelity of Escherichia coli DNA polymerase III holoenzyme in vitro SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COORDINATED LEADING-STRAND; SPONTANEOUS MUTATION; MISMATCH REPAIR; NUCLEOTIDE MISINCORPORATION; REPLICATION FORK; EPSILON-SUBUNIT; BETA-SUBUNIT; MUTAGENESIS; EXONUCLEASE; COMPLEX AB We have investigated the in vitro fidelity of Escherichia coli DNA polymerase III holoenzyme from a wildtype and a proofreading-impaired mutD5 strain. Exonuclease assays showed the mutD5 holoenzyme to have a 30-50-fold reduced 3'-->5'-exonuclease activity. Fidelity was assayed during gap-filling synthesis across the lacI(d) forward mutational target. The error rate for both enzymes was lowest at low dNTP concentrations (10-50 mu M) and highest at high dNTP concentration (1000 mu M) The mutD5 proofreading defect increased the error rate by only 3-5-fold. Both enzymes produced a high level of (-1)-frameshift mutations in addition to base substitutions. The base substitutions were mainly C-->T, G-->T, and G-->C, but cNTP pool imbalances suggested that these may reflect misincorporations opposite damaged template bases and that, instead, T-->C, G-->A, and C-->T transitions represent the normal polymerase III-mediated base base mispairs. The frequent (-1)-frameshift mutations do not result from direct slippage but may be generated via a mechanism involving "misincorporation plus slippage." Measurements of the fidelity of wild-type and mutD5 holoenzyme during M13 in vivo replication revealed significant differences between the in vivo and in vitro fidelity with regard to both the frequency of frameshift errors and the extent of proofreading. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80262 USA. RP Schaaper, RM (reprint author), NIEHS, Mol Genet Lab, NIH, E3-01,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM schaaper@niehs.nih.gov NR 59 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD SEP 4 PY 1998 VL 273 IS 36 BP 23575 EP 23584 DI 10.1074/jbc.273.36.23575 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117JL UT WOS:000075778100097 PM 9722597 ER PT J AU Bahar, I Jernigan, RL AF Bahar, I Jernigan, RL TI Vibrational dynamics of transfer RNAs: Comparison of the free and synthetase-bound forms SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE tRNA-synthetase complex; vibrational dynamics; recognition and binding; collective motions; B factors ID PHENYLALANINE TRANSFER-RNA; MOLECULAR-DYNAMICS; CRYSTALLOGRAPHIC REFINEMENT; RESTRAINED REFINEMENT; SINGLE-PARAMETER; STRUCTURAL BASIS; PROTEINS; RESOLUTION; MOTIONS; FLUCTUATIONS AB The vibrational dynamics of transfer RNAs, both free, and complexed with the cognate synthetase, are analyzed using a model (Gaussian network model) which recently proved to satisfactorily describe the collective motions of folded proteins. The approach is similar to a normal mode analysis, with the major simplification that no residue specificity is taken into consideration, which permits us (i) to cast the problem into an analytical form applicable to biomolecular systems including about 10(3) residues, and (ii) to acquire information on the essential dynamics of such large systems within computational times at least two orders of magnitude shorter than conventional simulations. On a local scale, the fluctuations calculated for yeast tRNA(Phe) and tRNA(Asp) in the free state, and for tRNA(Gln) complexed with glutaminyl-tRNA synthetase (GlnRS) are in good agreement with the corresponding crystallographic B factors. On a global scale, a hinge-bending region comprising nucleotides US to C12 in the D arm, G20 to G22 in the D loop, and m(7)G46 to C48 in the variable loop (for tRNA(Phe)), is identified in the free tRNA, conforming with previous observations. The two regions subject to the largest amplitude anticorrelated fluctuations in the free form, i.e. the anticodon region and the acceptor arm are, at the same time, the regions that experience the most severe suppression in their flexibilities upon binding to synthetase, suggesting that their sampling of the conformational space facilitates their recognition by the synthetase. Likewise, examination of the global mode of motion of GlnRS in the complex indicates that residues 40 to 45, 260 to 270, 306 to 314, 320 to 327 and 478 to 485, all of which cluster near the ATP binding site, form a hinge-bending region controlling the cooperative motion, and thereby the catalytic function, of the enzyme. The distal beta-barrel and the tRNA acceptor binding domain, on the other hand, are distinguished by their high mobilities in the global modes of motion, a feature typical of recognition sites, also observed for other proteins. Most of the conserved bases and residues of tRNA and GlnRS are severely constrained in the global motions of the molecules, suggesting their having a role in stabilizing and modulating the global motion. (C) 1998 Academic Press. C1 NCI, Mol Struct Sect, Lab Expt & Computat Biol, Div Basic Sci,NIH, Bethesda, MD 20892 USA. Bogazici Univ, Dept Chem Engn, TR-80815 Bebek, Turkey. Bogazici Univ, Polymer Res Ctr, TR-80815 Bebek, Turkey. TUBITAK, Adv Polymer Mat Res Ctr, TR-80815 Bebek, Turkey. RP Jernigan, RL (reprint author), NCI, Mol Struct Sect, Lab Expt & Computat Biol, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RI Jernigan, Robert/A-5421-2012 NR 40 TC 97 Z9 99 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 4 PY 1998 VL 281 IS 5 BP 871 EP 884 DI 10.1006/jmbi.1998.1978 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117FX UT WOS:000075771200010 PM 9719641 ER PT J AU Chowdhury, PS Vasmatzis, G Lee, B Pastan, I AF Chowdhury, PS Vasmatzis, G Lee, B Pastan, I TI Improved stability and yield of a Fv-toxin fusion protein by computer design and protein engineering of the Fv SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE modeling; sequence variability; K1 antibody; immunotoxin; stabilization ID B-CELL LYMPHOMA; MONOCLONAL-ANTIBODY; SINGLE-CHAIN; OVARIAN CANCERS; PSEUDOMONAS EXOTOXIN; COMPLETE REGRESSION; PHAGE DISPLAY; IMMUNOTOXIN; MESOTHELIN; SITE AB The conversion of the anti-mesothelin monoclonal antibody K1 to a single-chain Fv (scFv) that is fused to a truncated form of Pseudomonas exotoxin A (PE) results in a fusion protein (immunotoxin) that is unstable and refolds very inefficiently. We have devised a method that identifies candidate residues in the framework region of K1 Fv that, when mutated, improved the yield and stability of the protein. The method works by initially aligning the framework sequences of KI V-H and V-L with those of other scFvs that are stable and give a good yield as immunotoxins. Then we assigned a character to each residue that indicates its state of exposure based on the known crystal structures of Fabs. This identifies residues that are not compatible with their environment in the folded state of the protein. Next we calculated the frequencies of different amino acids for each position of the Fvs based on the available sequence database. This identifies residues that are not commonly present in the conserved positions. If these residues are compatible with their exposure profile they are left unaltered. Otherwise, they are identified as candidate residues for mutation. We identified two such residues in the V-H (T82 and A85) and hive in the V-L (H36 and V60) of K1 that did not seem appropriate for their respective positions. By mutating these residues in K1 into those that occur most commonly in the sequence database or in stable scFvs, we significantly improved the stability and yield of the K1 scFv immunotoxins. By making single and combined mutations we assessed the relative contribution of mutations at these four sites towards the stability and yield of K1 scFv immunotoxins. The method we devised is probably general and can be used to improve other scFvs. (C) 1998 Academic Press. C1 NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Div Basic Sci, NIH, Bldg 37,Room 4E16,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 31 TC 38 Z9 40 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD SEP 4 PY 1998 VL 281 IS 5 BP 917 EP 928 DI 10.1006/jmbi.1998.1980 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 117FX UT WOS:000075771200013 PM 9719644 ER PT J AU He, TC Sparks, AB Rago, C Hermeking, H Zawel, L da Costa, LT Morin, PJ Vogelstein, B Kinzler, KW AF He, TC Sparks, AB Rago, C Hermeking, H Zawel, L da Costa, LT Morin, PJ Vogelstein, B Kinzler, KW TI Identification of c-MYC as a target of the APC pathway SO SCIENCE LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; HUMAN-COLON-CARCINOMA; LEUKEMIA-CELL-LINE; BETA-CATENIN; COLORECTAL-CANCER; TRANSCRIPTION FACTOR; BURKITT-LYMPHOMA; GENE-EXPRESSION; ONC GENE; AMPLIFICATION AB The adenomatous polyposis coil gene (APC) is a tumor suppressor gene that is inactivated in most colorectal cancers. Mutations of APC cause aberrant accumulation of beta-catenin, which then binds T cell factor-4 (Tcf-4), causing increased transcriptional activation of unknown genes. Here, the c-MYC oncogene is identified as a target gene in this signaling pathway. Expression of c-MYC was shown to be repressed by wild-type APC and activated by beta-catenin, and these effects were mediated through Tcf-4 binding sites in the c-MYC promoter. These results provide a molecular framework for understanding the previously enigmatic overexpression of c-MYC in colorectal cancers. C1 Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. Howard Hughes Med Inst, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Program Human Genet, Baltimore, MD 21205 USA. NIA, Baltimore, MD 21224 USA. RP Kinzler, KW (reprint author), Johns Hopkins Oncol Ctr, 424 N Bond St, Baltimore, MD 21231 USA. FU NCI NIH HHS [CA57345, CA62924]; NIGMS NIH HHS [GM07309] NR 40 TC 3234 Z9 3313 U1 17 U2 141 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 SEP 4 PY 1998 VL 281 IS 5382 BP 1509 EP 1512 DI 10.1126/science.281.5382.1509 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116RJ UT WOS:000075738100041 PM 9727977 ER PT J AU Linke, SP AF Linke, SP TI Cancer - Has the smart bomb been defused? SO NATURE LA English DT Editorial Material ID ADENOVIRUS C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Linke, SP (reprint author), NCI, Human Carcinogenesis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 9 Z9 9 U1 0 U2 1 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON, ENGLAND N1 9XW SN 0028-0836 J9 NATURE JI Nature PD SEP 3 PY 1998 VL 395 IS 6697 BP 13 EP + DI 10.1038/25595 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 116JY UT WOS:000075722200018 PM 9738489 ER PT J AU Sibai, BM Lindheimer, M Hauth, J Caritis, S VanDorsten, P Klebanoff, M MacPherson, C Landon, M Miodovnik, M Paul, R Meis, P Dombrowski, M AF Sibai, BM Lindheimer, M Hauth, J Caritis, S VanDorsten, P Klebanoff, M MacPherson, C Landon, M Miodovnik, M Paul, R Meis, P Dombrowski, M CA Natl Inst Hlth Human Dev Network Maternal Fetal TI Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the Society-of-Perinatal-Obstetricians CY FEB 02-07, 1998 CL MIAMI, FLORIDA SP Soc Perinatal Obstetricians ID LOW-DOSE ASPIRIN; PREGNANT-WOMEN; PROGNOSIS; TRIMESTER; THERAPY; TERM AB Background Women with chronic hypertension who become pregnant have an increased risk of preeclampsia and adverse neonatal outcomes. However, within this group, the risk factors for these adverse events are not known. Methods We analyzed data on outcomes for 763 women with chronic hypertension enrolled in a multicenter trial of low-dose aspirin for the prevention of preeclampsia. Preeclampsia was defined as new-onset proteinuria (urinary protein excretion, greater than or equal to 300 mg per 24 hours) in the 682 women without proteinuria at base line. it was defined according to strict clinical criteria in the 81 women who had proteinuria at base line. The end points were maternal and neonatal outcomes. Results Among the 763 women, 193 (25 percent) had preeclampsia. The frequency of preeclampsia was not affected by the presence of proteinuria at base line (27 percent among women with proteinuria, vs. 25 percent among those without it), but it was greater in women who had had hypertension for at least four years (31 percent vs. 22 percent; odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.2) and in those with preeclampsia during a previous pregnancy (32 percent vs. 23 percent; odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.3). Women with proteinuria at base line were significantly more likely to deliver their babies at less than 35 weeks of gestation (36 percent vs. 16 percent; odds ratio, 3.1; 95 percent confidence interval, 1.8 to 5.3) and to have infants that were small for gestational age (23 percent vs. 10 percent; odds ratio, 2.8; 95 percent confidence interval, 1.6 to 5.0). Conclusions In women with chronic hypertension, the presence of proteinuria early in pregnancy is associated with adverse neonatal outcomes independently of the development of preeclampsia. (N Engl J Med 1998;339:667-71.) (C)1998, Massachusetts Medical Society. C1 Univ Tennessee, Dept Obstet & Gynecol, Memphis, TN 38103 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. NICHHD, Dept Epidemiol, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ So Calif, Los Angeles, CA USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Hutzel Hosp, Detroit, MI 48201 USA. Univ Oklahoma, Oklahoma City, OK USA. Univ Pittsburgh, Pittsburgh, PA USA. NICHHD, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. RP Sibai, BM (reprint author), Univ Tennessee, Dept Obstet, 853 Jefferson Ave,Suite E102, Memphis, TN 38103 USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD19897, HD21410, HD21414] NR 16 TC 194 Z9 203 U1 1 U2 4 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 3 PY 1998 VL 339 IS 10 BP 667 EP 671 DI 10.1056/NEJM199809033391004 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 115WA UT WOS:000075688100004 PM 9725924 ER PT J AU Pearson, SD Sabin, JE Emanuel, EJ AF Pearson, SD Sabin, JE Emanuel, EJ TI Ethical guidelines for physician compensation based on capitation SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MANAGED CARE; RISK; PATIENT; PAYMENT C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. NIH, Bethesda, MD 20892 USA. RP Pearson, SD (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 30 TC 43 Z9 43 U1 0 U2 1 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 3 PY 1998 VL 339 IS 10 BP 689 EP 693 DI 10.1056/NEJM199809033391009 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 115WA UT WOS:000075688100009 PM 9725929 ER PT J AU Taylor, GA Jeffers, M Webb, CP Koo, HM Anver, M Sekiguchi, K Woude, GFV AF Taylor, GA Jeffers, M Webb, CP Koo, HM Anver, M Sekiguchi, K Woude, GFV TI Decreased fibronectin expression in Met/HGF-mediated tumorigenesis SO ONCOGENE LA English DT Article DE Met; HGF; fibronectin; TGF beta ID HEPATOCYTE GROWTH-FACTOR; C-MET RECEPTOR; SCATTER FACTOR; EPITHELIAL-CELLS; EXTRACELLULAR-MATRIX; PROTOONCOGENE; INDUCTION; MUTATIONS; METASTASIS; ADHESION AB The tyrosine kinase receptor Met and its ligand, hepatocyte growth factor (HGF)/scatter factor are involved in the etiology and progression of a number of human cancers. Coexpression of Met and HGF in mesenchymal cells increases the tumorigenic and metastatic potential of the cells. In the studies described here, we used differential display screening to identify changes in gene expression that are initiated by Met/HGF, and that may lead to these phenotypes. We learned that Met/HGF signaling resulted in greatly decreased fibronectin mRNA production in three different human and mouse tumor cell lines; these decreases in fibronectin mRNA were paralleled by decreases in fibronectin protein. We also found a progressive decrease in fibronectin in tumor explants and metastases derived from the Met/HGF transformed cells. The absence of fibronectin expression is a frequent cancer phenotype; our results indicate that decreases in fibronectin correlate with, but are not essential for, MetHGF/SF-mediated tumorigenesis. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. Osaka Med Ctr Maternal & Child Hlth, Inst Res, Osaka 59002, Japan. RP Woude, GFV (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RI Webb, Craig/I-8123-2012 NR 31 TC 13 Z9 13 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD SEP 3 PY 1998 VL 17 IS 9 BP 1179 EP 1183 DI 10.1038/sj.onc.1202004 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 114FL UT WOS:000075598400014 PM 9764829 ER PT J AU Rohan, TE Hartwick, W Miller, AB Kandel, RA AF Rohan, TE Hartwick, W Miller, AB Kandel, RA TI Immunohistochemical detection of c-erbB-2 and p53 in benign breast disease and breast cancer risk SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ONCOPROTEIN EXPRESSION; ONCOGENE EXPRESSION; PROTEIN EXPRESSION; TUMOR SUPPRESSOR; OVARIAN-CANCER; GENE-PRODUCT; CARCINOMA; LESIONS; ANTIBODIES; TISSUE AB Background: We studied the associations between c-erbB-2 protein overexpression and p53 protein accumulation in benign breast tissue and the risk of subsequent breast cancer, Methods: We conducted a case-control study nested within the cohort of 4888 women in the National Breast Screening Study (NBSS) who were diagnosed with benign breast disease during active follow-up. Case subjects were the women who subsequently developed breast cancer (ductal carcinoma ill situ [DCIS] or invasive carcinoma), Control subjects were matched to each case subject on NBSS study arm, screening center, year of birth, and age at diagnosis of benign breast disease. Histologic sec sections of benign and cancerous breast tissues were analyzed immunohistochemically Information on potential confounding factors was obtained by use of a self-administered lifestyle questionnaire. Results: Accumulation of p53 protein was associated with an increased risk of progression to breast cancer (adjusted odds ratio [OR] = 2.55; 95% confidence interval [CI] = 1.01-6.40), whereas c-erbB-2 protein overexpression was not (adjusted OR = 0.65; 95% CI = 0.27-1.53). The findings for c-erbB-2 and p53 did not differ among strata defined by menopausal status, allocation within the NBSS, history of breast disease, and whether the benign breast disease was detected at a scheduled screen or between screens. The results were also similar after exclusion of case subjects whose diagnosis of breast cancer occurred within 1 year of their diagnosis of benign breast disease and after exclusion of subjects with DCIS, Conclusions: p53 protein accumulation, but mot c-erbB-2 protein overexpression, appears to be associated with an increased risk of progression to breast cancer in women with benign breast disease. C1 NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Canc Surveillance Res Program, Div Canc Control & Populat, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. RP NIH, Execut Plaza N,Rm 741, Bethesda, MD 20892 USA. EM tom.rohan@utoronto.ca RI Kandel, Rita/E-2149-2017 OI Kandel, Rita/0000-0003-4047-3913 NR 49 TC 89 Z9 91 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD SEP 2 PY 1998 VL 90 IS 17 BP 1262 EP 1269 DI 10.1093/jnci/90.17.1262 PG 8 WC Oncology SC Oncology GA 115MJ UT WOS:000075668600010 PM 9731732 ER PT J AU Tawa, GJ Topol, IA Burt, SK Erickson, JW AF Tawa, GJ Topol, IA Burt, SK Erickson, JW TI Calculation of relative binding free energies of peptidic inhibitors to HIV-1 protease and its I84V mutant SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID ORALLY BIOAVAILABLE INHIBITOR; BOUNDARY-ELEMENT METHOD; TYPE-1 PROTEASE; CRYSTAL-STRUCTURE; CONTINUUM MODEL; ELECTROSTATIC INTERACTIONS; MOLECULAR ELECTROSTATICS; INCREASED RESISTANCE; COMPLEXES; DESIGN AB A methodology is presented for calculating relative binding free energies of enzyme-inhibitor associations in aqueous solvent. The methodology uses synthesis of semiempirical quantum chemistry to determine the protonation state of important residues in the enzyme active site, molecular mechanics to determine the gas-phase energetic contributions to the relative binding free energy, and dielectric continuum solvation to calculate electrostatic hydration contributions. The methodology is then applied to the calculation of the relative binding free energy of the inhibitors KNI-272, Ro31-8959, L-735,524, and A-77003 to HIV-1 protease and its I84V mutant. The calculated relative binding free energy is sensitive to the active-site protonation state of the aspartic acid residues of HIV-1 protease. The protonation state is inhibitor dependent. Given a particular protonation state, it was found that quantitatively accurate relative binding free energies could only be achieved when solvent effects were included. Three categories of binding were found. In the first, the change in binding free energy due to mutation is mainly due to the change in enthalpic interactions within the inhibitor-enzyme complex (Ro31-8959). In the second (L-735,524 and A-77003), the change in affinity is caused both by a change in enthalpic interactions within the enzyme and by a change in the hydration energy of the enzyme and inhibitor-enzyme complexes. In the third case (KNI-272), the change in affinity is mainly a solvent effect-it is due to changes in hydration of the enzyme only. In all cases, it was found that the I84V mutant enzyme was more stable than the wild-type enzyme. This alone (without consideration of the inhibitor-enzyme complexes) can qualitatively explain the reduction in binding affinity due to mutation. C1 NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick Biomed Supercomp Ctr, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Struct Biochem Program, Frederick, MD 21702 USA. RP Tawa, GJ (reprint author), NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Frederick Biomed Supercomp Ctr, POB B, Frederick, MD 21702 USA. NR 60 TC 25 Z9 26 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD SEP 2 PY 1998 VL 120 IS 34 BP 8856 EP 8863 DI 10.1021/ja9733090 PG 8 WC Chemistry, Multidisciplinary SC Chemistry GA 116TQ UT WOS:000075741300032 ER PT J AU Smith, MA Freidlin, B Ries, LAG Simon, R AF Smith, MA Freidlin, B Ries, LAG Simon, R TI Trends in reported incidence of primary malignant brain tumors in children in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ONSET AQUEDUCTAL STENOSIS; INTRINSIC TECTAL TUMORS; STEM GLIOMAS; CANCER-GROUP; HYPERFRACTIONATED RADIOTHERAPY; NEUROFIBROMATOSIS TYPE-1; SURGICAL INDICATIONS; CHILDHOOD; MANAGEMENT; DIAGNOSIS AB Background: The reported incidence of primary malignant brain tumors among children in the United States increased by 35% during the period from 1973 through 1994. The purpose of our study was twofold: 1) to determine whether the reported incidence rates for this period are better represented by a linear increase over the entire period ("linear model") or, alternatively, by a step function, with a lower rate in the years preceding 1984-1985 and a constant higher rate afterward ("jump model"); and 2) to identify the specific brain regions and histologic subtypes that have increased in incidence. Methods: Incidence data from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the period from 1973 through 1994 for primary malignant brain tumors in children were used to model the number of cases in a year as a random variable from a Poisson distribution by use of either a linear model or a jump model. Results/Conclusions: The increase in reported incidence of childhood primary malignant brain tumors is best explained by the jump model, with a step increase in incidence occurring in the mid-1980s, The brain stem and the cerebrum are the primary sites for which an increase in tumor incidence has been reported. The increase in reported incidence of low-grade gliomas in the cerebrum and the brain stem (unaccompanied by an increase in mortality for these sites) supports the substantial contribution of low-grade gliomas to the overall increase in reported incidence for childhood brain tumors. Implications: The significantly better fit of the data to a jump model supports the hypothesis that the observed increase in incidence somehow resulted from changes in detection and/or reporting of childhood primary malignant brain tumors during the mid-1980s. C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD USA. NCI, Canc Surveillance Res Program, Div Canc Control & Populat, Bethesda, MD USA. Emmes Corp, Rockville, MD USA. RP Smith, MA (reprint author), NIH, Execut Plaza N,Rm 741, Bethesda, MD 20892 USA. EM smithm@ctep.nci.nih.gov NR 55 TC 168 Z9 173 U1 1 U2 4 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 2 PY 1998 VL 90 IS 17 BP 1269 EP 1277 DI 10.1093/jnci/90.17.1269 PG 9 WC Oncology SC Oncology GA 115MJ UT WOS:000075668600011 PM 9731733 ER PT J AU Selik, RM Rabkin, CS AF Selik, RM Rabkin, CS TI Cancer death rates associated with human immunodeficiency virus infection in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HOMOSEXUAL MEN; HIV-INFECTION; CERVICAL-CANCER; SAN-FRANCISCO; RISK; MALIGNANCIES; HEMOPHILIA; LYMPHOMAS C1 Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Selik, RM (reprint author), Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Natl Ctr HIV STD & TB Prevent, Mail Stop E-47, Atlanta, GA 30333 USA. NR 19 TC 38 Z9 39 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD SEP 2 PY 1998 VL 90 IS 17 BP 1300 EP 1302 DI 10.1093/jnci/90.17.1300 PG 3 WC Oncology SC Oncology GA 115MJ UT WOS:000075668600015 PM 9731737 ER PT J AU Friedman, CP Corn, M Krumrey, AJ Perry, DR Stevens, RH AF Friedman, CP Corn, M Krumrey, AJ Perry, DR Stevens, RH TI Managing information technology in academic medical centers: A "multicultural" experience SO ACADEMIC MEDICINE LA English DT Article AB Based on a session at the 1997 conference on Information Resources and Academic Medicine sponsored by the Association of American Medical Colleges, this article illustrates how the beliefs and concerns of academic medicine's diverse professional cultures affect the management of information technology. Two scenarios - one dealing with the standardization of desktop PCs, the other with publication of syllabi on an institutional intranet - from the basis of this exercise. Four prototypical members of a hypoethical medical center community - the chairman of surgery, a senior basic scientist, the chief information officer of an affiliated hospital, and the chief administrative officer - offer their perspectives on each scenario. Their statements illustrate many of the challenges of planning, deploying, and maintaining effective information technology in the "multicultural" environment of academic medical centers. C1 Univ Pittsburgh, Sch Med, UPMC Hlth Syst, Ctr Biomed Informat, Pittsburgh, PA 15213 USA. Natl Lib Med, Div Extramural Programs, Rockville, MD USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Friedman, CP (reprint author), Univ Pittsburgh, Sch Med, UPMC Hlth Syst, Ctr Biomed Informat, 8084 Forges Tower,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD SEP PY 1998 VL 73 IS 9 BP 975 EP 979 DI 10.1097/00001888-199809000-00016 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 119VM UT WOS:000075918900018 PM 9759100 ER PT J AU Bragg, DG AF Bragg, DG TI Radiology research and the NIH: Problems and future prospects SO ACADEMIC RADIOLOGY LA English DT Article C1 NCI, EPN 800, Bethesda, MD 20892 USA. RP Bragg, DG (reprint author), NCI, EPN 800, 6130 Execut Blvd,MSC7440, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD SEP PY 1998 VL 5 SU 2 BP S416 EP S418 DI 10.1016/S1076-6332(98)80371-1 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 115LA UT WOS:000075665200050 PM 9750871 ER PT J AU Hu, PS Trumble, DA Foley, DJ Eberhard, JW Wallace, RB AF Hu, PS Trumble, DA Foley, DJ Eberhard, JW Wallace, RB TI Crash risks of older drivers: A panel data analysis SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE older drivers; highway safety; crash risks ID VEHICLE COLLISION INJURIES; MEDICAL CONDITIONS; ELDERLY DRIVERS AB Considerable progress has been made on understanding older drivers' safely issues. None the less, findings from previous research have been rather inconclusive. Differences in data and research methodology have been suggested as factors that contribute to the discrepancies in previous findings. One of the methodological limitations is the lack of considering temporal order between events (i.e. the time between onset of medical condition, symptom and crash). Without time-series data, a 'snap-shot' of medical conditions and driving patterns were often linked to more than 1 year of crash data, hoping to accumulate enough data on crashes. The interpretation of the results from these studies is difficult in that one cannot explicitly attribute the increase in highway crash rates to medical conditions and/or physical limitations. This paper uses a panel data analysis to identify factors that place older drivers at greater crash risk. Our results show that factors that place female drivers at greater crash risk are different from those influencing male drivers. More risk factors were found to be significant in affecting older men's involvement in crashes than older women. When the analysis controlled for the amount of driving, women who live alone or who experience back pain were found to have a higher crash risk. Similarly, men who are employed, score low on word-recall tests, have a history of glaucoma, or use antidepressant drugs were found to have a higher crash risk. The most influential risk factors in men were the number of miles driven, and use of antidepressants. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Oak Ridge Natl Lab, Ctr Transportat Anal, Oak Ridge, TN 37831 USA. Accustat Inc, Knoxville, TN 37932 USA. NIA, Bethesda, MD 20892 USA. Natl Highway Traff Safety Adm US, Washington, DC 20590 USA. Univ Iowa, Dept Prevent Med, Iowa City, IA 52242 USA. RP Hu, PS (reprint author), Oak Ridge Natl Lab, Ctr Transportat Anal, Bldg 3156,POB 2008, Oak Ridge, TN 37831 USA. NR 20 TC 71 Z9 71 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD SEP PY 1998 VL 30 IS 5 BP 569 EP 581 DI 10.1016/S0001-4575(98)00019-0 PG 13 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA ZZ951 UT WOS:000074785800002 PM 9678211 ER PT J AU Brunger, AT Adams, PD Clore, GM DeLano, WL Gros, P Grosse-Kunstleve, RW Jiang, JS Kuszewski, J Nilges, M Pannu, NS Read, RJ Rice, LM Simonson, T Warren, GL AF Brunger, AT Adams, PD Clore, GM DeLano, WL Gros, P Grosse-Kunstleve, RW Jiang, JS Kuszewski, J Nilges, M Pannu, NS Read, RJ Rice, LM Simonson, T Warren, GL TI Crystallography & NMR system: A new software suite for macromolecular structure determination SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID PROTEIN-STRUCTURE DETERMINATION; INTERPROTON DISTANCE RESTRAINTS; NUCLEAR-MAGNETIC-RESONANCE; FREE R-VALUE; MOLECULAR-DYNAMICS; 3-DIMENSIONAL STRUCTURES; CRYSTAL-STRUCTURES; DIRECT REFINEMENT; MAXIMUM-LIKELIHOOD; CHEMICAL-SHIFTS AB A new software suite, called Crystallography & NMR System (CNS), has been developed for macromolecular structure determination by X-ray crystallography or solution nuclear magnetic resonance (NMR) spectroscopy. In contrast to existing structure-determination programs the architecture of CNS is highly flexible, allowing for extension to other structure - determination methods, such as electron microscopy and solid-state NMR spectroscopy. CNS has a hierarchical structure: a high-level hypertext markup language (HTML) user interface, task-oriented user input files, module files, a symbolic structure-determination language (CNS language), and low-level source code. Each layer is accessible to the user. The novice user may just use the HTML interface, while the more advanced user may use any of the other layers. The source code will be distributed, thus source-code modification is possible. The CNS language is sufficiently powerful and flexible that many new algorithms can be easily implemented in the CNS language without changes to the source code. The CNS language allows the user to perform operations on data structures, such as structure factors, electron-density maps, and atomic properties. The power of the CNS language has been demonstrated by the implementation of a comprehensive set of crystallographic procedures for phasing, density modification and refinement. User-friendly task-oriented input files are available for nearly all aspects of macromolecular structure determination by X-ray crystallography and solution NMR. C1 Yale Univ, Howard Hughes Med Inst, New Haven, CT 06511 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06511 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Grad Grp Biophys, San Francisco, CA 94143 USA. Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands. Brookhaven Natl Lab, Dept Biol, Prot Data Bank, Upton, NY 11973 USA. European Mol Biol Lab, D-69117 Heidelberg, Germany. Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB T6G 2G1, Canada. Univ Alberta, Dept Math Sci, Edmonton, AB T6G 2H7, Canada. Univ Strasbourg 1, Biol Struct Lab, CNRS, IGBMC, F-67401 Illkirch Graffenstaden, France. RP Brunger, AT (reprint author), Yale Univ, Howard Hughes Med Inst, New Haven, CT 06511 USA. EM brunger@laplace.csb.yale.edu RI Clore, G. Marius/A-3511-2008; Simonson, Thomas/A-5733-2008; Nilges, Michael/E-4803-2011; Read, Randy/L-1418-2013; Adams, Paul/A-1977-2013; Gros, Piet/I-5569-2016 OI Clore, G. Marius/0000-0003-3809-1027; Nilges, Michael/0000-0002-1451-8092; Read, Randy/0000-0001-8273-0047; Adams, Paul/0000-0001-9333-8219; Gros, Piet/0000-0002-7782-2585 NR 61 TC 15505 Z9 15573 U1 71 U2 551 PU MUNKSGAARD INT PUBL LTD 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 SEP 1 PY 1998 VL 54 BP 905 EP 921 DI 10.1107/S0907444998003254 PN 5 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 120JA UT WOS:000075952200023 PM 9757107 ER PT J AU Stoner, GL Ryschkewitsch, CF AF Stoner, GL Ryschkewitsch, CF TI Reappraisal of progressive multifocal leukoencephalopathy due to simian virus 40 SO ACTA NEUROPATHOLOGICA LA English DT Article DE JC virus; demyelination; polyomavirus; central nervous system; macaque ID DEFICIENCY SYNDROME AIDS; LARGE TUMOR-ANTIGEN; HUMAN BRAIN; CHOROID-PLEXUS; JC PAPOVAVIRUS; DNA-SEQUENCES; SV40 ETIOLOGY; VIRAL-DNA; DISEASE; TISSUE AB Several cases of progressive multifocal leukoencephalopathy (PML) have been associated with simian virus 40 (SV40), rather than with JC virus (JCV), the polyomavirus originally isolated from PML tissue. PML has, therefore, been defined as a demyelinating syndrome with possible multiple viral etiologies. Tissues from three of the cases thought to be associated with SV40 were available for reexamination. Monoclonal antibodies specific for SV40 capsid antigen VP1, virus-specific biotinylated DNA probes for in situ hybridization, and virus-specific primers in the polymerase chain reaction (PCR) were used. Macaque PML brain served as a positive control tissue for SV40 brain infection. Monoclonal antibodies to SV40 VP1 failed to recognize viral antigen in lesions from all three human PML cases. The biotinylated DNA probe, which reacted with SV40 in macaque PML, failed to detect SV40 in human PML. However, JCV could be detected by in situ hybridization with a JCV-specific DNA probe. Moreover, JCV DNA sequences were amplified by PCR from the human PML tissues, whereas SV40 DNA sequences were amplified only from the macaque brain. Thus, we could not confirm the original reports that the demyelinating agent in these three cases of PML was SV40, rather than JCV. We conclude that SV40 infection of the central nervous system need not be ruled out in the differential diagnosis of PML. C1 NINDS, Neurotoxicol Sect, NIH, Bethesda, MD 20892 USA. RP Stoner, GL (reprint author), NINDS, Neurotoxicol Sect, NIH, 36 Convent Dr,MSC-4126, Bethesda, MD 20892 USA. NR 61 TC 8 Z9 8 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD SEP PY 1998 VL 96 IS 3 BP 271 EP 278 PG 8 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 118FN UT WOS:000075827900010 PM 9754960 ER PT J AU Piscitelli, SC Polis, MA AF Piscitelli, SC Polis, MA TI An update on drug interactions with zidovudine SO AIDS PATIENT CARE AND STDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHARMACOKINETIC INTERACTION; CLINICAL PHARMACOKINETICS; COMBINED GANCICLOVIR; AIDS; EFFICACY; TOXICITY; THERAPY; ACETAMINOPHEN; METABOLISM AB Zidovudine remains one of the most commonly prescribed agents for patients with HIV infection. A variety of drug interactions have been reported that may alter blood levels of zidovudine and concomitantly administered drugs or may involve overlapping toxicities. Several concomitant medications have been shown to alter the plasma concentrations of zidovudine, although most of these interactions are not thought to be clinically important. Use of agents that share the bone marrow-suppressive properties of zidovudine require additional monitoring for the development of hematologic toxicity. An understanding of potential mechanisms and important zidovudine-related interactions will aid in the optimal care of the HIV-infected patient. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Dept Pharm, Ctr Clin, NIH, Bethesda, MD 20892 USA. RP Polis, MA (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 11C103, Bethesda, MD 20892 USA. OI Polis, Michael/0000-0002-9151-2268 NR 25 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD SEP PY 1998 VL 12 IS 9 BP 687 EP 690 DI 10.1089/apc.1998.12.687 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 125JH UT WOS:000076234100004 PM 15468442 ER PT J AU Dybul, M Weissman, D Rubbert, A Machado, E Cohn, M Ehler, L O'Callahan, M Mizell, S Fauci, AS AF Dybul, M Weissman, D Rubbert, A Machado, E Cohn, M Ehler, L O'Callahan, M Mizell, S Fauci, AS TI The role of dendritic cells in the infection of CD4+ T cells with the human immunodeficiency virus: Use of dendritic cells from individuals homozygous for the Delta 32CCR5 allele as a model SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HIV-1 INFECTION; PERIPHERAL-BLOOD; TYPE-1 INFECTION; FUSION COFACTOR; RHESUS MACAQUES; TROPIC HIV-1; IN-VITRO; RECEPTORS; MACROPHAGE; POPULATIONS AB Despite exposure to multiple strains of both macrophage (M)-tropic and T cell (T)-tropic HIV, primary infection is largely restricted to relatively homogeneous M-tropic virus, Since dendritic cells (DCs) play a pivotal role in the early events of HIV infection, several studies have focused on the role of DCs in this restriction. It has been proposed that DCs are more efficiently infected with M-tropic versus T-tropic viruses; however, the infectability of DCs and the relevance of their infectability for inducing productive infection is controversial. It has also been suggested that variability in DC expression of coreceptors for M-tropic versus T-tropic virus could explain the restriction in the transmitting virus. Using HIV-pulsed DCs from individuals with a homozygous deletion in the CCR5 gene as a human "knockout" model, we demonstrate that infection of DCs per se is not necessary to promulgate infection in CD4(+) T cells. The data also suggest that transmission of HIV to CD4(+) T cells is not dependent on DC coreceptor expression. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Dybul, M (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A02,10 Ctr Dr,MSC-1576, Bethesda, MD 20892 USA. NR 45 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD SEP 1 PY 1998 VL 14 IS 13 BP 1109 EP 1113 DI 10.1089/aid.1998.14.1109 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 115UZ UT WOS:000075685400001 PM 9737582 ER PT J AU Allen, J Anton, RF Babor, TF Carbonari, J Carroll, KM Connors, GJ Cooney, NL Del Boca, FK Di-Clemente, CC Donovan, D Kadden, RM Litt, M Longabaugh, R Mattson, M Miller, WR Randall, CL Rounsaville, BJ Rychtarik, RG Stout, RL Tonigan, JS Wirtz, PW Zweben, A AF Allen, J Anton, RF Babor, TF Carbonari, J Carroll, KM Connors, GJ Cooney, NL Del Boca, FK Di-Clemente, CC Donovan, D Kadden, RM Litt, M Longabaugh, R Mattson, M Miller, WR Randall, CL Rounsaville, BJ Rychtarik, RG Stout, RL Tonigan, JS Wirtz, PW Zweben, A CA Project MATCH Res Grp TI Matching alcoholism treatments to client heterogeneity: Project MATCH three-year drinking outcomes SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE long-term outcome; matching; alcoholism treatment; client attributes; Project MATCH ID SCALE; RELIABILITY; PREDICTORS; INSTRUMENT; DRINKERS; PATTERNS AB This study reports 3-year outcomes for clients who had been treated in the five outpatient sites of Project MATCH, a multisite clinical trial designed to test a priori client treatment matching hypotheses. The main purpose of this study was to characterize the status of the matching hypotheses at the 3-year follow-up. This entailed investigating which matching findings were sustained or even strengthened across the 3-year study period, and whether any hypotheses that were not supported earlier eventually emerged at 3 years, or conversely, whether matching findings discerned earlier dissipated at this later time. This research also examines the prognostic effects of the client matching attributes, characterizes the overall outcomes at 37 to 39 months, and explores differential effects of the three treatments at extended follow-up. With regard to the matching effects, client anger demonstrated the most consistent interaction in the trial, with significant matching effects evident at both the 1-year and 3-year follow-ups. As predicted, clients high in anger fared better in Motivational Enhancement Therapy (MET) than in the other two MATCH treatments: Cognitive-Behavioral Therapy (CBT) and Twelve-Step Facilitation (TSF). Among subjects in the highest third of the anger variable, clients treated in MET had on average 76.4% abstinent days, whereas their counterparts in the other two treatments (CBT and TSF) had on average 66% abstinent days. Conversely, clients low in anger performed better after treatment in CBT and TSF than in MET. Significant matching effects for the support for drinking variable emerged in the 3-year outcome analysis, such that clients whose social networks were more supportive of drinking derived greater benefit from TSF treatment than from MET. Among subjects in the highest third of the support for drinking variable, TSF participants were abstinent 16.1% more days than MET participants. At the lower end of this variable, difference in percent days abstinent between MET and TSF was 3%, with MET clients having more abstinent days. A significant matching effect for psychiatric severity that appeared in the first year posttreatment was not observed after 3 years. Of the 21 client attributes used in testing the matching hypotheses, 11 had prognostic value at 3 years. Among these, readiness-to-change and self-efficacy emerged as the strongest predictors of long-term drinking outcome. With regard to the overall outcomes, the reductions in drinking that were observed in the first year after treatment were sustained over the 3-year follow-up period: almost 30% of the subjects were totally abstinent in months 37 to 39, whereas those who did report drinking nevertheless remained abstinent an average of two-thirds of the time. As in the 1-year follow-up, there were few differences among the three treatments, although TSF continued to show a possible slight advantage. C1 Med Univ S Carolina, Charleston, SC 29425 USA. Univ Houston, Houston, TX 77004 USA. Yale Univ, Sch Med, Vet Affairs Connecticut Healthcare Syst, Res Inst Addict, New Haven, CT 06520 USA. Univ S Florida, Tampa, FL 33620 USA. Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. Univ Washington, Seattle, WA 98195 USA. Univ Connecticut, Sch Med & Dent, Vet Affairs Puget Sound Hlth Care Syst, Storrs, CT 06269 USA. Brown Univ, Providence, RI 02912 USA. Univ New Mexico, Albuquerque, NM 87131 USA. George Washington Univ, Washington, DC 20052 USA. Univ Wisconsin, Madison, WI 53706 USA. Univ Connecticut, Sch Med, Farmington, CT USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. Vet Affairs Med Ctr, Charleston, SC 29403 USA. Res Inst Addict, Buffalo, NY 14203 USA. Univ Wisconsin, Milwaukee, WI 53201 USA. RP Allen, J (reprint author), NIAAA, Willco Bldg,Suite 409,6000 Execut Blvd, Bethesda, MD 20892 USA. RI Carroll, Kathleen/A-7526-2009; Cooney, Ned/C-5176-2014; OI Cooney, Ned/0000-0001-6698-8312; Carroll, Kathleen/0000-0003-3263-3374; Litt, Mark/0000-0002-8319-6090 NR 48 TC 141 Z9 146 U1 6 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0145-6008 EI 1530-0277 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 1998 VL 22 IS 6 BP 1300 EP 1311 PG 12 WC Substance Abuse SC Substance Abuse GA 120KV UT WOS:000075956300016 ER PT J AU Mattson, ME Del Boca, FK Carroll, KM Cooney, NL DiClemente, CC Donovan, D Kadden, RM McRee, B Rice, C Rycharik, RG Zweben, A AF Mattson, ME Del Boca, FK Carroll, KM Cooney, NL DiClemente, CC Donovan, D Kadden, RM McRee, B Rice, C Rycharik, RG Zweben, A CA Project MATCH Res Grp TI Compliance with treatment and follow-up protocols in Project MATCH: Predictors and relationship to outcome SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE compliance; alcoholism treatment; clinical trials ID ALCOHOLISM-TREATMENT; PATIENT ATTRITION; CLIENT; ATTENDANCE; PROGRAM; DROPOUT; WOMEN AB Treatment and follow-up session attendance data from Project MATCH, a multisite clinical trial investigating patient-treatment matching, were analyzed to study compliance. High rates of compliance to both therapy and research protocols were achieved, enhancing treatment integrity and data quality. Strong baseline predictors of compliance did not emerge, and the small relationships found were consistent with reports from previous studies. Attendance at therapy sessions was moderately correlated with research follow-up participation. Treatment compliance predicted drinking outcome, underscoring the importance of retaining patients in treatment. Future studies should examine the associations between compliance and structural features of the treatment environment, treatment delivery, and context-features that are often under the control of the clinician/investigator. C1 NIAAA, Rockville, MD 20892 USA. Univ S Florida, Dept Psychol, Tampa, FL 33620 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. Univ Washington, Inst Alcohol & Drug Abuse, Seattle, WA 98195 USA. Univ Connecticut, Sch Med, Dept Psychiat, Storrs, CT 06268 USA. Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. Res Inst Addict, Buffalo, NY 14203 USA. Univ Wisconsin, Sch Social Welf, Milwaukee, WI 53201 USA. RP Mattson, ME (reprint author), NIAAA, 6000 Execut Blvd,Willco Bldg,Suite 505, Rockville, MD 20892 USA. RI Carroll, Kathleen/A-7526-2009; Cooney, Ned/C-5176-2014; OI Cooney, Ned/0000-0001-6698-8312; Carroll, Kathleen/0000-0003-3263-3374 FU NIAAA NIH HHS [U10 AA08428, U10 AA08430, U10 AA08431] NR 62 TC 41 Z9 41 U1 4 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 1998 VL 22 IS 6 BP 1328 EP 1339 DI 10.1097/00000374-199809000-00020 PG 12 WC Substance Abuse SC Substance Abuse GA 120KV UT WOS:000075956300020 PM 9756050 ER PT J AU Weinstein, A Lingford-Hughes, A Martinez-Raga, J Marshall, J AF Weinstein, A Lingford-Hughes, A Martinez-Raga, J Marshall, J TI What makes alcohol-dependent individuals early in abstinence crave for alcohol: Exposure to the drink, images of drinking, or remembrance of drinks past? SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE craving; alcohol dependence; cue exposure; imagery; mood ID CUE REACTIVITY; OPIATE ADDICTS; SMOKING URGES; MANIFESTATIONS; QUESTIONNAIRE; MANIPULATION; RELIABILITY; WITHDRAWAL; RESPONSES; INDUCTION AB Craving is a major factor in addiction, predicting poorer outcome to treatment. To improve our understanding of craving for alcohol, we have compared in the laboratory the effects of inducting craving for alcohol by exposure to the sight and the smell of an alcoholic beverage, imagery of craving scripts, and recall of autobiographical memories of craving. We used subjective measures of craving, together with autonomic measures, in 14 abstinent alcohol-dependent individuals in the first month after detoxification. All subjects reported a significant increase in ratings of urges after exposure to alcoholic drinks, following the imagery of craving and after recalling autobiographical memories of craving. Physiological measures have shown that craving imagery as well as memory induction were equally effective as exposure to alcoholic drinks in modestly increasing autonomic arousal (indicated by systolic blood pressure). Our preliminary findings support the existing evidence in nicotine and opiate dependence that images and memories are as effective as in vivo exposure in eliciting craving for drugs. C1 Univ Bristol, Sch Med, Psychopharmacol Unit, Bristol, Avon, England. Inst Psychiat, London, England. Bethlem & Maudsley NHS Trust, Natl Alcohol Unit, London, England. RP Weinstein, A (reprint author), NIDA, Brain Imaging Ctr, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Martinez-Raga, Jose/B-6251-2017 OI Martinez-Raga, Jose/0000-0002-2856-6562 NR 31 TC 24 Z9 27 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD SEP PY 1998 VL 22 IS 6 BP 1376 EP 1381 DI 10.1097/00000374-199809000-00026 PG 6 WC Substance Abuse SC Substance Abuse GA 120KV UT WOS:000075956300026 PM 9756056 ER PT J AU Cohen, SG AF Cohen, SG TI John F. Kennedy (1917-1963) - 35th President of the United States SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article C1 NIAID, Bethesda, MD 20892 USA. Natl Lib Med, NIH, Bethesda, MD USA. RP Cohen, SG (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1998 VL 19 IS 5 BP 312 EP 317 PG 6 WC Allergy SC Allergy GA 130HX UT WOS:000076515200010 PM 9801746 ER PT J AU Cohen, SG AF Cohen, SG TI Leonard Bernstein (1918-1990) - American musical composer and conductor SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article C1 NIAID, Bethesda, MD 20892 USA. Natl Lib Med, NIH, Bethesda, MD USA. RP Cohen, SG (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1998 VL 19 IS 5 BP 318 EP 323 PG 6 WC Allergy SC Allergy GA 130HX UT WOS:000076515200011 PM 9801747 ER PT J AU Cohen, SG AF Cohen, SG TI Philip K. Dick (1928-1982) - American author SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article C1 NIAID, Bethesda, MD 20892 USA. Natl Lib Med, NIH, Bethesda, MD USA. RP Cohen, SG (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1998 VL 19 IS 5 BP 324 EP 327 PG 4 WC Allergy SC Allergy GA 130HX UT WOS:000076515200012 PM 9801748 ER PT J AU Cohen, SG AF Cohen, SG TI Roger E. C. Altounyan (1922-1987) - British physician and pharmacologist SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article C1 NIAID, Bethesda, MD 20892 USA. Natl Lib Med, NIH, Bethesda, MD USA. RP Cohen, SG (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD SEP-OCT PY 1998 VL 19 IS 5 BP 328 EP 332 PG 5 WC Allergy SC Allergy GA 130HX UT WOS:000076515200013 PM 9801749 ER PT J AU Wu, Z Kinslow, C Pettigrew, KD Rapoport, SI Schapiro, MB AF Wu, Z Kinslow, C Pettigrew, KD Rapoport, SI Schapiro, MB TI Role of familial factors in late-onset Alzheimer disease as a function of age SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; family history; genetics; familial; late-onset ID RELATIVES; RISK; DEMENTIA AB Whereas early-onset Alzheimer disease (AD; usually onset at age < 50 years) has been defined with genetic mutation on chromosomes 1, 14, and 21, the degree of familial contribution to late-onset AD is unclear. Further, it is uncertain if subgroups of late-onset AD exist. To examine the influence of familial factors as a function of age in late-onset AD we investigated lifetime risks and age-specific hazard rates of AD-like illness among late-onset AD probands' and controls' first-degree relatives, using questionnaires and medical records. As part of a longitudinal study on aging and AD, we studied 78 AD probands with age of onset greater than or equal to 50 years (28 "definite" and 50 "probable" AD according to NINCDS/ADRDA criteria) and 101 healthy old controls seen since 1981. Both probands and controls were screened rigorously with medical tests and brain imaging and seen regularly until autopsy. Multiple informants and medical records were used for first-degree relatives. Among first-degree relatives, 49 secondary cases of AD-like illness were found for the AD probands' relatives (391 relatives 40 years old or older) compared with 20 cases among controls' relatives (456 relatives 40 years old or older). Relatives of AD probands had a significantly increased lifetime risk of AD-like illness of 52.8 +/- 11.4% by age 94 years compared with a lifetime risk in relatives of controls of 22.1 +/- 5.8% by age 90 years. Age-specific hazard rates in relatives of AD probands increased until the 75-79-year age interval and then decreased; in contrast the age-specific hazard rates increased in relatives of controls after the 80-84-year age interval. To determine if a dividing line exist among late-onset AD, several cutoff ages were used in our study to compare cumulative risk curves of AD-like illness between relatives of late-onset probands and relatives of late-late-onset probands. Differences in the pattern of cumulative incidence of AD in relatives showed that 67-71 years is the range for a dividing line between late- and late-late-onset AD. Age specific hazard rates of AD in relatives supported a difference between late- and late-late-onset. Whereas these rates increased until the 75-79-year age interval and then decreased in late-onset AD, the rates began increasing after the 65-69-year age interval and through the oldest age interval in both late-late-onset AD and control groups, Our results support the concept that familial factors exist in late-onset AD and that different familial factors may exist in late-onset AD subgroups. C1 NIA, Neurosci Lab, Bethesda, MD 20892 USA. NIMH, Div Epidemiol & Serv, Bethesda, MD USA. RP Schapiro, MB (reprint author), NIA, Neurosci Lab, Bldg 10,Room 6C414, Bethesda, MD 20892 USA. NR 20 TC 6 Z9 6 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD SEP PY 1998 VL 12 IS 3 BP 190 EP 197 DI 10.1097/00002093-199809000-00011 PG 8 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 145DG UT WOS:000077355300011 PM 9772022 ER PT J AU Djousse, L Ellison, RC Zhang, YQ Arnett, DK Sholinsky, P Borecki, I AF Djousse, L Ellison, RC Zhang, YQ Arnett, DK Sholinsky, P Borecki, I TI Relation between dietary fiber consumption and fibrinogen and plasminogen activator inhibitor type 1: The National Heart, Lung, and Blood Institute Family Heart Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE PAI-1; plasminogen activator inhibitor type 1; fibrinogen; dietary fiber; waist-hip ratio; cardiovascular disease ID FOOD FREQUENCY QUESTIONNAIRE; HYPERCHOLESTEROLEMIC MEN; RISK FACTOR; FACTOR-VII; FIBRINOLYTIC-ACTIVITY; OAT-BRAN; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; PLASMA-FIBRINOGEN; 10-YEAR MORTALITY AB Considerable evidence suggests that high plasma concentrations of plasminogen activator inhibitor type 1 (PAI-1) and fibrinogen increase the risk of cardiovascular disease. Recent studies report beneficial effects of dietary fiber on coronary artery disease, although the mechanisms by which high fiber intake reduces the risk of heart disease are not well understood. This study examined the relation of dietary fiber intake to PAI-1 and fibrinogen concentrations in 883 men and 1116 women aged 50.4 +/- 13.8 and 52.1 +/- 13.7 y, respectively, in the National Heart, Lung, and Blood Institute Family Heart Study. Diet was assessed with a semiquantitative food-frequency questionnaire. The natural logarithm was used to transform PAI-1 because of a skewed distribution. In the first through fifth ageand energy-specific quintiles of fiber intake, mean (ln)PAI-1 was 6.09, 5.91, 5.88, 5.82, and 5.67 pmol/L, respectively, for men and 5.50, 5.37, 5.39, 5.23, and 5.18 pmol/L, respectively, for women. Multiple regression showed that when the lowest was compared with the second, third, fourth, and fifth age- and energy-specific quintiles of fiber intake, (ln)PAI-1 was 0.21, 0.25, 0.22, and 0.32 pmol/L lower in men (P for trend = 0.009) and 0.08, 0.06, 0.14, and 0.20 pmol//L lower in women (P for trend = 0.037), respectively, with anthropometric, lifestyle, and metabolic factors adjusted for. No significant association was found between fiber intake and fibrinogen. Waist-hip ratio did not modify the relation of fiber intake to PAI-1 (P for interaction = 0.39 for men and 0.36 for women). These data suggest that higher fiber intake is inversely associated with PAI-1, but not with fibrinogen concentration. C1 Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. RP Djousse, L (reprint author), Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Rppm B-612,88 E Newton St, Boston, MA 02118 USA. RI Djousse, Luc/F-5033-2017 OI Djousse, Luc/0000-0002-9902-3047 NR 63 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 1998 VL 68 IS 3 BP 568 EP 575 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 115CN UT WOS:000075646100011 PM 9734732 ER PT J AU Visser, M Langlois, J Guralnik, JM Cauley, JA Kronmal, RA Robbins, J Williamson, JD Harris, TB AF Visser, M Langlois, J Guralnik, JM Cauley, JA Kronmal, RA Robbins, J Williamson, JD Harris, TB TI High body fatness, but not low fat-free mass, predicts disability in older men and women: The Cardiovascular Health Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE bioelectrical impedance; body composition; obesity; body fat; fat-free mass; fat mass; disability; elderly; Cardiovascular Health Study; humans ID ISOMETRIC MUSCLE STRENGTH; X-RAY ABSORPTIOMETRY; BIOELECTRICAL-IMPEDANCE; FUNCTIONAL ABILITY; ELDERLY SUBJECTS; PEOPLE; SARCOPENIA; MOBILITY; SMOKING; ALCOHOL AB Using data from the Cardiovascular Health Study, we studied the relation between body composition (fat mass and fat-free mass, assessed by bioelectrical impedance) and self-reported, mobility-related disability (difficulty walking or stair climbing) in 2714 women and 2095 men aged 65-100 y. In a cross-sectional analysis at baseline (1989-1990), disability was reported by 26.5% of the women and 16.9% of the men. A positive association was observed between fat mass and disability. The odds ratio for disability in the highest quintile of fat mass was 3.04 (95% CI: 2.18, 4.25) for women and 2.77 (95% CI: 1.82, 4.23) for men compared with those in the lowest quintile. Low fat-free mass was not associated with a higher prevalence of disability. In a longitudinal analysis among persons not reporting disability at baseline, 20.3% of the women and 14.8% Of the men reported disability 3 y later. Fat mass at baseline was predictive of disability 3 y later, with odds ratios of 2.83 (95% CI: 1.80, 4.46) for women and 1.72 (95% CI: 1.03, 2.85) for men in the highest quintile of fat. The increased risk was not explained by age, physical activity, chronic disease, or other potential confounders. Low fat-free mass was not predictive of disability. The results showed that high body fatness is an independent predictor of mobility-related disability in older men and women. These findings suggest that high body fatness in old age should be avoided to decrease the risk of disability. C1 NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Calif Davis, Dept Med, Sacramento, CA 95817 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Visser, M (reprint author), NIA, Epidemiol Demog & Biometry Program, Gateway Bldg,Room 3C309,7201 Wisconsin Ave, Bethesda, MD 20892 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 NR 32 TC 199 Z9 206 U1 0 U2 3 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD SEP PY 1998 VL 68 IS 3 BP 584 EP 590 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 115CN UT WOS:000075646100013 PM 9734734 ER PT J AU Weir, SC Fischer, SH Stock, F Gill, VJ AF Weir, SC Fischer, SH Stock, F Gill, VJ TI Detection of Legionella by PCR in respiratory specimens using a commercially available kit SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Legionella species; polymerase chain reaction; PCR; bronchoalveolar lavages; sputum; DNA extraction ID POLYMERASE CHAIN-REACTION; BRONCHOALVEOLAR LAVAGE FLUIDS; GENE PROBE METHODS; LEGIONNAIRES-DISEASE; PNEUMOPHILA; AMPLIFICATION; DIAGNOSIS; INFECTION; DNA AB Using polymerase chain reaction (PCR)for the detection of pathogens that are difficult to grow, such as Legionella species, may reduce difficulties encountered with culture and immunofluorescent staining. We evaluated a commercial PCR and hybridization kit, designed for environmental samples, for the detection of Legionella in respiratory specimens. Sixteen Legionella species cultures tested positive with the Perkin Elmer Legionella EnviroAmp Amplification and Detection kits (Perkin Elmer; Foster City, Calif) The assay detected as few as 100 colony-forming units per milliliter of spiked bronchoalveolar lavage (BAL)fluid, and no false-negative results were obtained. PCR inhibition by blood in the specimens was removed by washing pelleted specimens in sterile distilled water Of 126 specimens screened with the kit, 1 induced sputum and 3 BAL specimens were positive by PCR. All 4 were validated as true-positive results by culture or serologic testing. The entire PCR and hybridization assay can be completed in less than 6 hours, whereas isolation and identification by culture requires up to 12 days, and serologic conversion may not be demonstrated for weeks. Molecular techniques based on direct extraction and amplification of DNA from respiratory specimens may be useful for the timely diagnosis of legionellosis. C1 NIH, Dept Clin Pathol, Microbiol Serv, Bethesda, MD 20892 USA. RP Weir, SC (reprint author), NIH, Dept Clin Pathol, Microbiol Serv, Bldg 10,Room 2C-385,9000 Rockville Pike, Bethesda, MD 20892 USA. NR 19 TC 16 Z9 21 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS 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 SEP PY 1998 VL 110 IS 3 BP 295 EP 300 PG 6 WC Pathology SC Pathology GA 113DD UT WOS:000075533800003 PM 9728603 ER PT J AU Benichou, J Chow, WH McLaughlin, JK Mandel, JS Fraumeni, JF AF Benichou, J Chow, WH McLaughlin, JK Mandel, JS Fraumeni, JF TI Population attributable risk of renal cell cancer in Minnesota SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE body mass index; case-control studies; dietary proteins; hypertension; kidney neoplasms; parity; smoking ID UNITED-STATES; REPRODUCTIVE FACTORS; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; KIDNEY CANCER; CARCINOMA; WOMEN; DIURETICS; OBESITY; WEIGHT AB A population-based case-control study of renal cell cancer was conducted in Minnesota between 1988 and 1990. It included 690 histologically confirmed incident cases identified through the state cancer surveillance system, and 707 age and sex frequency-matched controls. In this paper, the authors present estimates of the proportion of renal cell cancer cases attributable (or population attributable risk (PAR)) to 1) well-established risk factors, namely smoking, excess weight, and hypertension, and 2) more speculative risk factors, namely elevated protein intake, history of renal disease (i.e,, stone, injury, or infection) and high parity among women. These estimates were based on information obtained from directly interviewed subjects (65% of cases and 100% of controls). The PARs for the three main risk factors were 21% for hypertension (defined by a reported personal history of hypertension or of treatment with antihypertensive or diuretic drugs), 21% for excess weight (defined by an elevation of the usual body mass index above the first quartile), and 18% for smoking (past and current). Overall, these three factors accounted for 49% of cases. The proportion increased to 60% when the three more speculative risk factors were considered as well. Sex-specific analyses revealed a greater impact of smoking among men mainly due to a higher prevalence of past smoking, In contrast, the impact of hypertension and excess weight was greater among women due to higher relative risks. These results suggest that 1) intervention measures aimed at reducing smoking, excess weight, and hypertension could substantially lower the overall incidence of renal cell cancer, and 2) intervention measures may have to be sex-specific. Conversely, because at least 40% of cases remain unexplained by the risk factors under study, further etiologic research is needed into renal cell cancer, an increasingly common form of cancer. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Int Epidemiol Inst, Rockville, MD USA. Univ Minnesota, Sch Publ Hlth, Div Environm & Occupat Hlth, Minneapolis, MN USA. RP Benichou, J (reprint author), Univ Rouen, Sch Med, Rouen, France. NR 53 TC 83 Z9 83 U1 1 U2 1 PU JOHNS HOPKINS UNIV SCHOOL HYGIENE PUB HEALTH PI BALTIMORE PA 111 MARKET PLACE, STE 840, BALTIMORE, MD 21202-6709 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1998 VL 148 IS 5 BP 424 EP 430 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 116KD UT WOS:000075722700003 PM 9737554 ER PT J AU Cook, NR Kumanyika, SK Cutler, JA AF Cook, NR Kumanyika, SK Cutler, JA TI Effect of change in sodium excretion on change in blood pressure corrected for measurement error - The trials of hypertension prevention, phase I SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE blood pressure; longitudinal studies; potassium; regression analysis; sodium ID URINARY ELECTROLYTE EXCRETION; DIETARY SALT; OBSERVATIONAL DATA; REDUCTION; POPULATIONS; INTERSALT; BIAS AB Intraperson variability in both blood pressure (BP) and sodium excretion dilutes associations and leads to underestimates of the dose-response relation, The authors applied statistical correction techniques to data from the Trials of Hypertension Prevention (TOHP), Phase I, carried out 1987-1990, Men and women with high normal diastolic BP (80-89 mmHg) were randomized to sodium reduction (n = 327) or a usual care comparison group (n = 417), Regression estimates of the effects of change in sodium and sodium/potassium ratio (Na/K ratio) on blood pressure change in the pooled sample were corrected for both the within-person variance of the excretion measures and the within-person covariance with blood pressure using a multivariate error correction. The estimated cross-sectional reliability was 0.36 for root Na and 0.42 for root Na/K ratio and that for change was 0.31 and 0.28, respectively, Corrected coefficients suggested a decrease of 4.4 mmHg in systolic BP (95% confidence interval (CI) 0.1-8.8) and 2.8 mmHg in diastolic BP (95% CI -0.2 to 5.8) per 100 mmol/24 hour reduction in sodium, and of 3.4 mmHg in systolic BP (95% CI 0.8-6.1) and 1.7 mmHg in diastolic BP (95% CI 0.0-3.5) per unit decrease in Na/K. These results are comparable with those from the Intersalt Study, and suggest that the true effect of sodium change on blood pressure change in normotensives over 18 months is underestimated by more than half in uncorrected data. C1 Harvard Univ, Div Prevent Med, Brigham & Womens Hosp, Med Sch,Dept Med, Boston, MA 02115 USA. Univ Illinois, Dept Human Nutr & Dietet, Chicago, IL USA. NHLBI, Clin Applicat & Prevent Program, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Cook, NR (reprint author), Harvard Univ, Div Prevent Med, Brigham & Womens Hosp, Med Sch,Dept Med, 900 Commonwealth Ave E, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL37853, HL37849, HL37852] NR 30 TC 36 Z9 36 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD SEP 1 PY 1998 VL 148 IS 5 BP 431 EP 444 PG 14 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 116KD UT WOS:000075722700004 PM 9737555 ER PT J AU Gaudenz, K Roessler, E Quaderi, N Franco, B Feldman, G Gasser, DL Wittwer, B Montini, E Opitz, JM Ballabio, A Muenke, M AF Gaudenz, K Roessler, E Quaderi, N Franco, B Feldman, G Gasser, DL Wittwer, B Montini, E Opitz, JM Ballabio, A Muenke, M TI Opitz G/BBB syndrome in Xp22: Mutations in the MID1 gene cluster in the carboxy-terminal domain SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID RING FINGER; ZINC-FINGER; SEQUENCE MOTIF; GBBB SYNDROME; PROTEIN; FAMILY; CLONING; XNF7 AB The MID1 gene in Xp22 codes for a novel member of proteins containing a RING finger, B-box, coiled-coil and a conserved C-terminal domain. Initially, three mutations in the C-terminal region were found in patients with Opitz G/BBB syndrome, a defect of midline development. Here we have determined the complete gene structure of the MID1 gene and have analyzed all nine exons for mutations in a set of 40 unrelated Opitz G/BBB patients. We now report six additional mutations all clustered in the carboxy-terminal domain of the MID1 protein. These data suggest that this conserved domain of the B-box proteins may play a fundamental role in the pathogenesis of Opitz syndrome and in morphogenetic events at the midline during blastogenesis. C1 Natl Human Genome Res Inst, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Genet, Philadelphia, PA 19104 USA. Telethon Inst Genet & Med, Milan, Italy. Univ Vita Salute, Milan, Italy. Univ Munster, Inst Human Genet, D-4400 Munster, Germany. Univ Utah, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Dept Human Genet, Salt Lake City, UT USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. RP Muenke, M (reprint author), Natl Human Genome Res Inst, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1852,Bldg 10,10C101, Bethesda, MD 20892 USA. OI FRANCO, Brunella/0000-0001-5588-4569; Montini, Eugenio/0000-0003-1771-6067; BALLABIO, Andrea/0000-0003-1381-4604 FU NICHD NIH HHS [HD28732, HD29862]; Telethon [TGM06S01, TGM97000] NR 28 TC 56 Z9 57 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1998 VL 63 IS 3 BP 703 EP 710 DI 10.1086/302010 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 119VN UT WOS:000075919000007 PM 9718340 ER PT J AU Wilkin, DJ Szabo, JK Cameron, R Henderson, S Bellus, GA Mack, ML Kaitila, I Loughlin, J Munnich, A Sykes, B Bonaventure, J Francomano, CA AF Wilkin, DJ Szabo, JK Cameron, R Henderson, S Bellus, GA Mack, ML Kaitila, I Loughlin, J Munnich, A Sykes, B Bonaventure, J Francomano, CA TI Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID OSTEOGENESIS IMPERFECTA; THANATOPHORIC DYSPLASIA; APERT-SYNDROME; NORMAL PARENTS; FGFR3; AGE; MOSAICISM; DWARFISM; DOMAIN AB More than 97% of achondroplasia cases are caused by one of two mutations (G1138A and G1138C) in the fibroblast growth factor receptor 3 (FGFR3) gene, which results in a specific amino acid substitution, G380R. Sporadic cases of achondroplasia have been associated with advanced paternal age, suggesting that these mutations occur preferentially during spermatogenesis. We have determined the parental origin of the achondroplasia mutation in 40 sporadic cases. Three distinct 1-bp polymorphisms were identified in the FGFR3 gene, within close proximity to the achondroplasia mutation site. Ninety-nine families, each with a sporadic case of achondroplasia in a child, were analyzed in this study. In this population, the achondroplasia mutation occurred on the paternal chromosome in all 40 cases in which parental origin was unambiguous. This observation is consistent with the clinical observation of advanced paternal age resulting in new cases of achondroplasia and suggests that factors influencing DNA replication or repair during spermatogenesis, but not during oogenesis, may predispose to the occurrence of the G1138 FGFR3 mutations. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Inst Necker, INSERM, U393, Paris, France. Univ Oxford, John Radcliffe Hosp, Dept Cellular Sci, Inst Mol Med, Oxford OX3 9DU, England. Johns Hopkins Univ, Sch Med, Ctr Med Genet, Baltimore, MD 21205 USA. George Washington Univ, Inst Biomed Sci, Washington, DC USA. Univ Helsinki, Cent Hosp, Dept Clin Genet, Helsinki, Finland. RP Wilkin, DJ (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1267,Bldg 10,Room 3D45, Bethesda, MD 20892 USA. NR 26 TC 113 Z9 117 U1 4 U2 14 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1998 VL 63 IS 3 BP 711 EP 716 DI 10.1086/302000 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 119VN UT WOS:000075919000008 PM 9718331 ER PT J AU Flejter, WL Fergestad, J Gorski, J Varvill, T Chandrasekharappa, S AF Flejter, WL Fergestad, J Gorski, J Varvill, T Chandrasekharappa, S TI A gene involved in XY sex reversal is located on chromosome 9, distal to marker D9S1779 SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID SRY-RELATED GENE; CAMPOMELIC DYSPLASIA; MUTATIONAL ANALYSIS; DETERMINING REGION; FEMALE; SOX9; DELETION; MONOSOMY; POLYMORPHISMS; LOCUS AB The genetic mechanisms involved in sex differentiation are poorly understood, and progress in identification of the genes involved has been slow The fortuitous finding of chromosomal rearrangements in association with a sex-reversed phenotype has led to the isolation of SRY and SOX9, both shown to be involved in the sex-determining pathway. In addition, duplications of the X chromosome, deletions of chromosomes 9 and 10, and translocations involving chromosome 17 have been reported to be associated with abnormal testicular differentiation, leading to male-to-female sex reversal in 46,XY individuals. We present the cytogenetic and molecular analyses of four sex-reversed XY females, each with gonadal dysgenesis and other variable malformations, and with terminal deletions of distal chromosome 9p, resulting from unbalanced autosomal translocations. PCR amplification and DNA sequence analysis of SRY revealed no mutations in the high-mobility-group domain (i.e., HMG box) in any of the four patients. Conventional and molecular cytogenetic analyses of metaphase chromosomes from each patient suggest that the smallest region of overlap (SRO) of deletions involves a very small region of distal band 9p24. Loss-of-heterozygosity studies using 17 highly polymorphic microsatellite markers, as well as FISH using YAC clones corresponding to the most distal markers on 9p, showed that the SRO lies distal to marker D9S1779. These results significantly narrow the putative sex-determining gene to the very terminal region of the short arm of chromosome 9. C1 Univ Utah, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Dept Human Genet, Salt Lake City, UT USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. RP Flejter, WL (reprint author), Wake Forest Univ, Sch Med, Dept Pediat, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM wflejter@wfubmc.edu FU NCI NIH HHS [CA42014-10]; NHGRI NIH HHS [P50HG00199-06] NR 34 TC 70 Z9 75 U1 3 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1998 VL 63 IS 3 BP 794 EP 802 DI 10.1086/302016 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 119VN UT WOS:000075919000017 PM 9718346 ER PT J AU Badner, JA Gershon, ES Goldin, LR AF Badner, JA Gershon, ES Goldin, LR TI Optimal ascertainment strategies to detect linkage to common disease alleles SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETICALLY COMPLEX TRAITS; MODELS AB Traditionally, extended pedigrees with many affected individuals have been studied for the purpose of detection of linkage. For traits caused by a rare susceptibility allele, this is a productive strategy. However, this sampling strategy may not work well for traits determined by multiple loci in which one or more have common susceptibility alleles. We simulated three single-additive-locus models of inheritance and two-locus models with additive or multiplicative interactions, all with rare or common susceptibility alleles. A trait locus was linked, with no recombination, to a marker locus with four equally frequent alleles. Family structure varied, but the total number of affected individuals was held constant. Two generations of individuals were genotyped. We used three nonparametric affected-sib-pair programs and two nonparametric pedigree-analysis programs to perform linkage analysis. For single-locus, additive, and multiplicative models, we found that, when the susceptibility allele was rare, (frequency .0025), extended pedigrees with first or second cousins had the most power for detection of linkage. However, when the susceptibility allele was common in the single-locus, additive, and multiplicative two-locus models (frequency .25), extended pedigrees were no more powerful than nuclear families. There was also a decrease in power when the pedigrees had a greater number of affected individuals, more so for the single-locus and multiplicative models than for the additive model. We conclude that for single-locus, additive, and multiplicative models of qualitative traits with common alleles, there is no benefit to the collection of extended pedigrees, and there may be a loss of power in the collection of pedigrees with many affected individuals. C1 NIMH, Intramural Res Program, Clin Neurogenet Branch, Bethesda, MD 20892 USA. RP Badner, JA (reprint author), NIMH, Intramural Res Program, Clin Neurogenet Branch, Bldg 10,Room 3N218,10 Ctr Dr,MSC 1274, Bethesda, MD 20892 USA. FU NCRR NIH HHS [1 P41 RR03655] NR 20 TC 34 Z9 34 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1998 VL 63 IS 3 BP 880 EP 888 DI 10.1086/302007 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 119VN UT WOS:000075919000027 PM 9718337 ER PT J AU Anikster, Y Nyhan, WL Gahl, WA AF Anikster, Y Nyhan, WL Gahl, WA TI NTBC and alkaptonuria SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Letter ID TYROSINEMIA TYPE-I; 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE; INHIBITOR C1 NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Med Genet Branch, Natl Human Genome Res Inst, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. RP Gahl, WA (reprint author), NICHHD, Sect Human Biochem Genet, Heritable Disorders Branch, NIH, 10 Ctr Dr,MSC 1830,Bldg 10,Room 9S-241, Bethesda, MD 20892 USA. NR 10 TC 22 Z9 24 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD SEP PY 1998 VL 63 IS 3 BP 920 EP 921 DI 10.1086/302027 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 119VN UT WOS:000075919000037 PM 9718357 ER PT J AU Donovan, EF Ehrenkranz, RA Shankaran, S Stevenson, DK Wright, LL Younes, N Fanaroff, AA Korones, SB Stoll, BJ Tyson, JE Bauer, CR Lemons, JA Oh, W Papile, LA AF Donovan, EF Ehrenkranz, RA Shankaran, S Stevenson, DK Wright, LL Younes, N Fanaroff, AA Korones, SB Stoll, BJ Tyson, JE Bauer, CR Lemons, JA Oh, W Papile, LA CA Natl Inst Child Hlth Human Dev Neonatal Res Net TI Outcomes of very low birth weight twins cared for in the National Institute of Child Health and Human Development Neonatal Research Network's intensive care units SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE morbidity; mortality; twins; very low birth weight ID INFANT-MORTALITY; SINGLETONS; COHORT; STATES AB OBJECTIVE: The study's aim was to compare outcomes of very low birth weight twins with those of matched singletons. STUDY DESIGN: With data from the Neonatal Research Network registry (May 1991 to December 1994), univariable and multivariable comparisons of very low birth weight twin pairs and singletons were performed in 2 subgroups: (1) all paired twins and singletons with birth weights between 401 and 1500 g and (2) all paired twins and singletons born at <28 weeks' gestation. RESULTS: Twins constituted 19% of infants admitted with very low birth weight. Mothers of twins were more likely to receive prenatal care, have labor, have cesarean delivery, and receive antenatal glucocorticoids. Twins were more likely to have respiratory disease and to receive surfactant. Second-born twins had more early respiratory disease but similar longer-term outcomes. The risks of death, chronic lung disease, and grade III or IV intracranial hemorrhage were similar in twins and singletons. CONCLUSIONS: Although very low birth weight twins compose a sizable proportion of admissions, in National Institute of Child Health and Human Development Neonatal Research Network intensive care units, twins and singletons have similar outcomes. C1 Univ Cincinnati, Med Ctr, Div Neonatol, Cincinnati, OH 45267 USA. Yale Univ, New Haven, CT 06520 USA. Wayne State Univ, Detroit, MI 48202 USA. Stanford Univ, Stanford, CA 94305 USA. NICHHD, Bethesda, MD 20892 USA. George Washington Univ, Ctr Biostat, Washington, DC 20052 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ Tennessee, Memphis, TN USA. Emory Univ, Atlanta, GA 30322 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Miami, Miami, FL 33152 USA. Indiana Univ, Bloomington, IN 47405 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP Donovan, EF (reprint author), Univ Cincinnati, Med Ctr, Div Neonatol, POB 670541, Cincinnati, OH 45267 USA. FU NICHD NIH HHS [U10 HD21385, U10 HD27853, U10 HD27871] NR 23 TC 62 Z9 64 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD SEP PY 1998 VL 179 IS 3 BP 742 EP 749 DI 10.1016/S0002-9378(98)70075-4 PN 1 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 122RP UT WOS:000076085500031 PM 9757982 ER PT J AU Cooperstock, MS Bakewell, J Herman, A Schramm, WF AF Cooperstock, MS Bakewell, J Herman, A Schramm, WF TI Effects of fetal sex and race on risk of very preterm birth in twins SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE preterm birth; twins; multiple birth; fetal sex; male fetuses ID GESTATIONAL-AGE; MULTIPLE BIRTH; EXCESS MALES; POPULATION; DELIVERY; PREGNANCIES; PARTURITION; COHORT; TERM AB OBJECTIVE: Our purpose was to determine whether the risk of twin preterm birth correlates with the number of male fetuses. STUDY DESIGN: Among 8109 white and 1884 black twin pregnancies in the Missouri Successive Pregnancy Birth/Death Data Set, 1978 through 1990, risk for preterm birth at various gestational ages was determined with 0, 1, or 2 male infants. RESULTS: Studied as individuals, white preterm twins <35 weeks' gestation demonstrated a 9.2% excess of male fetuses (P<.001). Adjusted for monozygosity, risk for preterm birth <35 weeks' gestation was 15.7% in white female-female pairs, 17.9% in unlike-sex white fetuses, and 20.2% in white male-male pairs (r=.999, P=.01). The effect was absent in black pregnancies and was unrelated to birth order, cesarean delivery, parity, twins' weight differential, year, or season. CONCLUSIONS: In white twin gestations the observed linear relationship between the number of male fetuses and the likelihood of preterm birth <35 weeks' gestation suggests a fetal mechanism for preterm birth <35 weeks' gestation linked to fetal sex. Studies of mechanisms for preterm birth must stratify by fetal sex and race. C1 Univ Missouri, Sch Med, Dept Child Hlth, Columbia, MO 65201 USA. Missouri Dept Hlth, Bur Hlth Data Anal, Jefferson City, MO USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. RP Cooperstock, MS (reprint author), Univ Missouri, Sch Med, Dept Child Hlth, Columbia, MO 65201 USA. NR 26 TC 19 Z9 21 U1 0 U2 2 PU MOSBY-YEAR BOOK 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 SEP PY 1998 VL 179 IS 3 BP 762 EP 765 DI 10.1016/S0002-9378(98)70079-1 PN 1 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 122RP UT WOS:000076085500035 PM 9757986 ER PT J AU Parks, RA Oakley, F Fonseca, M AF Parks, RA Oakley, F Fonseca, M TI Play development in children with HIV infection: A pilot study SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE motor performance; pediatrics; social development C1 NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. RP Parks, RA (reprint author), NIH, Dept Rehabil Med, Bldg 10,Room 6S-235,10 Ctr Dr,MSC 1604, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD SEP PY 1998 VL 52 IS 8 BP 672 EP 675 PG 4 WC Rehabilitation SC Rehabilitation GA 111CG UT WOS:000075419300010 PM 9739402 ER PT J AU Edwards, AO Klein, ML Berselli, CB Hejtmancik, JF Rust, K Wirtz, MK Weleber, RG Acott, TS AF Edwards, AO Klein, ML Berselli, CB Hejtmancik, JF Rust, K Wirtz, MK Weleber, RG Acott, TS TI Malattia leventinese: Refinement of the genetic locus and phenotypic variability in autosomal dominant macular drusen SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID HONEYCOMB RETINAL DYSTROPHY; LINKAGE AB PURPOSE: To study the phenotypic variability in patients inheriting the disease gene for malattia leventinese (dominant macular drusen) and refine the localization of the gene. METHODS: A family with dominant radial drusen was ascertained and studied with clinical examination and DNA linkage analysis. Inheritance of the disease gene was determined by DNA analysis and used to document the variability in phenotypic expression. RESULTS: Fifty family members were studied with fundus photography and genotyping. Linkage analysis showed that the disease in this family was linked to chromosome 2p16-21 with a maximum lod score of 3.72 at D2S2153. An affected patient with obligate recombinations allowed refinement of the disease interval to a 6.2-cM region between D2S2227 and D2S378. The phenotype of older affected patients varied from severe geographic atrophy or subretinal fibrosis to a single druse adjacent to the optic disk. Small and medium sized, nonradial, and soft macular drusen seen in four older individuals in the family were not specifically associated with the disease haplotype. CONCLUSIONS: Refinement of the localization of the gene for malattia leventinese will facilitate its positional cloning. Genotypic documentation of the variable expression of the disease shows that a single, large, subretinal druse adjacent to the optic disk is consistent with inheritance of the disease gene. Soft macular drusen in low abundance were not specifically associated with inheritance of the disease gene. These results will facilitate the genetic counseling of patients with malattia leventinese. It is unknown what proportion of age-related macular degeneration arises from mutations in disease genes for dominant drusen. (C) 1998 by Elsevier Science Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Ophthalmol, Casey Eye Inst, Portland, OR 97201 USA. Univ Texas, SW Med Ctr, Dept Ophthalmol, Dallas, TX USA. NEI, NIH, Bethesda, MD 20892 USA. RP Klein, ML (reprint author), Oregon Hlth Sci Univ, Dept Ophthalmol, Casey Eye Inst, 3375 SW Terwilliger Blvd, Portland, OR 97201 USA. NR 23 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD SEP PY 1998 VL 126 IS 3 BP 417 EP 424 DI 10.1016/S0002-9394(98)00097-X PG 8 WC Ophthalmology SC Ophthalmology GA 118UJ UT WOS:000075858500010 PM 9744375 ER PT J AU Fuhrer, MJ AF Fuhrer, MJ TI The national center for medical rehabilitation research - Beyond infancy, looking toward maturity SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-of-Academic-Physiatrists CY FEB 19-20, 1998 CL SAN ANTONIO, TEXAS SP Assoc Acad Physiatrists ID OUTCOMES RESEARCH; AGENDA C1 NICHHD, Natl Ctr Med Rehabil Res, NIH, Rockville, MD 20852 USA. RP Fuhrer, MJ (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, Bldg 61E,Room 2A03,6100 Execut Blvd, Rockville, MD 20852 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD SEP-OCT PY 1998 VL 77 IS 5 BP 437 EP 443 DI 10.1097/00002060-199809000-00017 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 132DA UT WOS:000076613900014 PM 9798837 ER PT J AU French, SA Territo, PR Balaban, RS AF French, SA Territo, PR Balaban, RS TI Correction for inner filter effects in turbid samples: fluorescence assays of mitochondrial NADH SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE optical methods; light scattering; mitochondria; linear least squares; calcium; pig; heart ID REDUCED PYRIDINE-NUCLEOTIDES; RAT-LIVER MITOCHONDRIA; OXIDATIVE-PHOSPHORYLATION; LIGHT-SCATTERING; MATRIX VOLUME; SPECTROSCOPY; CONTRACTION; CELLS AB Fluorescent determinations of NADH in porcine heart mitochondria were subject to significant errors caused by alterations in inner filter effects during numerous metabolic perturbations. These inner filter effects were primarily associated with changes in mitochondrial volume and accompanying light scattering. The observed effects were detected in a standard commercial fluorometer with emission orthogonal to the excitation light path and, to a lesser extent, in a light path geometry detecting only the surface fluorescence. A method was developed to detect and correct for inner filter effects on mitochondrial NADH fluorescence measurements that were independent of the optical path geometry using an internal fluorescent standard and linear least-squares spectral analysis. A simple linear correction with the inner fluorescence reference was found to adequately correct for inner filter effects. This approach may be useful for other fluorescence probes in isolated mitochondria or other light-scattering media. C1 NHLBI, Cardiac Energet Lab, Bethesda, MD 20892 USA. RP Balaban, RS (reprint author), NHLBI, Cardiac Energet Lab, Bldg 10,Rm B1D-161, Bethesda, MD 20892 USA. RI Balaban, Robert/A-7459-2009 OI Balaban, Robert/0000-0003-4086-0948 NR 33 TC 33 Z9 34 U1 1 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 1998 VL 275 IS 3 BP C900 EP C909 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 114QP UT WOS:000075620600033 PM 9730975 ER PT J AU Yang, H Egan, JM Wang, Y Moyes, CD Roth, J Montrose, MH Montrose-Rafizadeh, C AF Yang, H Egan, JM Wang, Y Moyes, CD Roth, J Montrose, MH Montrose-Rafizadeh, C TI GLP-1 action in L6 myotubes is via a receptor different from the pancreatic GLP-1 receptor SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE glycolysis; glycogen synthesis; muscle; transfection; glucagon-like peptide ID GLUCAGON-LIKE PEPTIDE-1; RAT SKELETAL-MUSCLE; POSSIBLE MEDIATORS; 3T3-L1 ADIPOCYTES; CELLS; GLP-1(7-36)AMIDE; BINDING; INOSITOLPHOSPHOGLYCANS; (7-36)AMIDE; METABOLISM AB The incretin hormone glucagon-like peptide-1 (GLP-1)-(7-36) amide is best known for its antidiabetogenic actions mediated via a GLP-1 receptor present on pancreatic endocrine cells. To investigate the molecular mechanisms of GLP-1 action in muscle, we used cultured L6 myotubes. In L6 myotubes, GLP-1 enhanced insulin-stimulated glycogen synthesis by 140% while stimulating CO2 production and lactate formation by 150%. In the presence of IBMX, GLP-1 diminished cAMP levels to 83% of IBMX alone. In L6 myotubes transfected with pancreatic GLP-1 receptor, GLP-1 increased cAMP levels and inhibited glycogen synthesis by 60%. An antagonist of pancreatic GLP-1 receptor, exendin-4-(9-39), inhibited GLP-1-mediated glycogen synthesis in GLP-1 receptor-transfected L6 myotubes. However, in parental L6 myotubes, exendin-4-(9-39) and GLP-1-(1-36) amide, an inactive peptide on pancreatic GLP-1 receptor, displaced I-125-labeled GLP-1 binding and stimulated glycogen synthesis by 186 and 130%, respectively. These results suggest that the insulinomimetic effects of GLP-1 in L6 cells are likely to be mediated by a receptor that is different from the GLP-1 receptor found in the pancreas. C1 NIA, Gerontol Res Ctr, Lab Clin Physiol, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada. RP Montrose-Rafizadeh, C (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Lilly Res Labs, Bldg 88-416,Drop Code 1543, Indianapolis, IN 46285 USA. NR 26 TC 65 Z9 67 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD SEP PY 1998 VL 275 IS 3 BP C675 EP C683 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 114QP UT WOS:000075620600009 PM 9730951 ER PT J AU Koehler-Stec, EM Simpson, IA Vannucci, SJ Landschulz, KT Landschulz, WH AF Koehler-Stec, EM Simpson, IA Vannucci, SJ Landschulz, KT Landschulz, WH TI Monocarboxylate transporter expression in mouse brain SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Neuroscience CY OCT 25-30, 1997 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci DE monocarboxylate transporter-1; monocarboxylate transporter-2; cDNA sequences; in situ hybridization ID PHENOL-CHLOROFORM EXTRACTION; KETONE-BODY UTILIZATION; SINGLE-STEP METHOD; RAT-BRAIN; CDNA CLONING; HIPPOCAMPAL SLICES; RNA ISOLATION; L-LACTATE; ASTROCYTES; NEURONS AB Although glucose is the major metabolic fuel needed for normal brain function, monocarboxylic acids, i.e., lactate, pyruvate, and ketone bodies, can also be utilized by the brain as alternative energy substrates. In most mammalian cells, these substrates are transported either into or out of the cell by a family of monocarboxylate transporters (MCTs), first cloned and sequenced in the hamster. We have recently cloned two MCT isoforms (MCT1 and MCT2) from a mouse kidney cDNA library. Northern blot analysis revealed that MCT1 mRNA is ubiquitous and can be detected in most tissues at a relatively constant level. MCT2 expression is more limited, with high levels of expression confined to testes, kidney, stomach, and liver and lower levels in lung, brain, and epididymal fat. Both MCT1 mRNA and MCT2 mRNA are detected in mouse brain using antisense riboprobes and in situ hybridization. MCT1 mRNA is found throughout the cortex, with higher levels of hybridization in hippocampus and cerebellum. MCT2 mRNA was detected in the same areas, but the pattern of expression was more specific. In addition, MCT1 mRNA, but not MCT2, is localized to the choroid plexus, ependyma, microvessels, and white matter structures such as the corpus callosum. These results suggest a differential expression of the two MCTs at the cellular level. C1 NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bethesda, MD 20892 USA. Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA. Univ Texas, SW Med Ctr, Dallas, TX 75235 USA. RP Koehler-Stec, EM (reprint author), NIDDKD, Expt Diabet Metab & Nutr Sect, Diabet Branch, NIH, Bldg 10,Rm 5N102,10 Ctr Dr,MSC 1420, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD-31521] NR 37 TC 88 Z9 92 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 1998 VL 275 IS 3 BP E516 EP E524 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 116VX UT WOS:000075746700020 PM 9725820 ER PT J AU Snitker, S Hellmer, J Boschmann, M Monroe, MB Ravussin, E AF Snitker, S Hellmer, J Boschmann, M Monroe, MB Ravussin, E TI Whole body fat oxidation is related to in situ adipose tissue lipolytic response to isoproterenol in males SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE indirect calorimetry; microdialysis ID MICRODIALYSIS ETHANOL TECHNIQUE; BETA-ADRENERGIC STIMULATION; 24-HOUR ENERGY-EXPENDITURE; SKELETAL-MUSCLE METABOLISM; OBESE HUMAN-SUBJECTS; BLOOD-FLOW; WEIGHT-GAIN; ACID; INDIVIDUALS; RESISTANCE AB A high 24-h respiratory quotient (RQ), i.e., low fat oxidation, predicts weight gain. To determine whether impaired fat mobilization (lipolysis) may contribute to weight gain, we studied the relation between lipolytic response to nonselective p-adrenergic stimulation and RQ measured in a respiratory chamber in 21 males (11 Caucasians, 10 Pima Indians; age 32 +/- 5 yr, weight 93 +/- 24 kg, body fat 30 +/- 8%; means +/- SD) and 23 females (10 Caucasians, 13 Pima Indians; age 32 +/- 9 yr, weight 95 +/- 26 kg, body fat 44 +/- 8%). Lipolytic response was assessed as the relative increase in dialysate glycerol concentration (% above baseline) when isoproterenol (1 mu mol/l) was added to the perfusate of a microdialysis probe inserted in the abdominal subcutaneous adipose tissue. In males, but not in females, basal RQ measured during sleep from 0500 to 0630 and adjusted for waist circumference was negatively correlated to lipolytic response (r = -0.66, P = 0.001). The results suggest that in males, impaired p-adrenergic-mediated lipolysis may contribute to low rates of fat oxidation, a condition known to predispose to weight gain. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Rockefeller Univ, Human Behav & Metab Lab, New York, NY 10021 USA. RP Snitker, S (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St,Rm 541, Phoenix, AZ 85016 USA. NR 27 TC 5 Z9 5 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD SEP PY 1998 VL 275 IS 3 BP E400 EP E404 PG 5 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 116VX UT WOS:000075746700005 PM 9725805 ER PT J AU Miller, DS Masereeuw, R Henson, J Karnaky, KJ AF Miller, DS Masereeuw, R Henson, J Karnaky, KJ TI Excretory transport of xenobiotics by dogfish shark rectal gland tubules SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE confocal microscopy; elasmobranch; immunostaining; membrane transport; multidrug resistance-associated protein; P-glycoprotein; sulforhodamine 101 ID RESISTANCE-ASSOCIATED PROTEIN; CONJUGATE EXPORT PUMP; MULTIDRUG-RESISTANCE; P-GLYCOPROTEIN; CANALICULAR MEMBRANE; ORGANIC ANION; GENE; MRP; EXPRESSION; CHLORIDE AB Marine elasmobranch rectal gland is a specialized, osmoregulatory organ composed of numerous blind-ended, branched tubules emptying into a central duct. To date, NaCl excretion has been its only described function. Here we use isolated rectal gland tubule fragments from dogfish shark (Squalus acanthias), fluorescent xenobiotics, and confocal microscopy to describe a second function, xenobiotic excretion. Isolated rectal gland tubules rapidly transported the fluorescent organic anion sulforhodamine 101 from bath to lumen. Luminal accumulation was concentrative, saturable, and inhibited by cyclosporin A (CSA), chlorodinitrobenzene, leukotriene C-4, and KCN. Inhibitors of renal organic anion transport (probenecid, p-aminohippurate), organic cation transport (tetraethylammonium and verapamil), and P-glycoprotein (verapamil) were without effect. Cellular accumulation of sulforhodamine 101 was not concentrative, saturable, or inhibitable. Rectal gland tubules did not secrete fluorescein, daunomycin, or a fluorescent CSA derivative. Finally, frozen rectal gland sections stained with an antibody to a hepatic canalicular multispecific organic anion transporter (cMOAT or MRP2) showed heavy and specific staining on the luminal membrane of the epithelial cells. We conclude that rectal gland is capable of active and specific excretion of xenobiotics and that such transport is mediated by a shark analog of MRP2, an ATP-driven xenobiotic transporter, but not by P-glycoprotein. C1 NIEHS, Intracellular Regulat Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME 04672 USA. Univ Nijmegen, Fac Med Sci, Dept Pharmacol, NL-6500 HB Nijmegen, Netherlands. Dickinson Coll, Dept Biol, Carlisle, PA 17013 USA. Med Univ S Carolina, Dept Cell Biol & Anat, Charleston, SC 29425 USA. Med Univ S Carolina, Marine Biomed & Environm Sci Program, Charleston, SC 29425 USA. RP Miller, DS (reprint author), NIEHS, Intracellular Regulat Sect, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. RI Masereeuw, Roos/N-3582-2014 FU NIEHS NIH HHS [P30-ES03828] NR 29 TC 24 Z9 24 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD SEP PY 1998 VL 275 IS 3 BP R697 EP R705 PG 9 WC Physiology SC Physiology GA 117VC UT WOS:000075802500008 PM 9728065 ER PT J AU Hediger, MA Knepper, MA AF Hediger, MA Knepper, MA TI Recent insights into the urinary concentrating mechanism: from cDNA cloning to modeling renal function - Introduction SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Editorial Material C1 Harvard Univ, Inst Med, Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Hediger, MA (reprint author), Harvard Univ, Inst Med, Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 SEP PY 1998 VL 275 IS 3 BP F317 EP F317 PG 1 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 117VE UT WOS:000075802700001 ER PT J AU Knepper, MA AF Knepper, MA TI Long-term regulation of urinary concentrating capacity SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT Experimental Biology 97 Conference CY APR 06-10, 1997 CL NEW ORLEANS, LA DE cortical collecting duct; vasopressin; water permeability ID WATER CHANNEL; VASOPRESSIN; RAT; AQUAPORINS AB Urinary concentrating capacity is regulated in part by a long-term adaptational process involving changes in the absolute abundance of the aquaporin-2 water channel in collecting duct cells. Alterations in aquaporin-2 abundance play key roles in the pathophysiology of several water balance disorders. Escape from the antidiuretic action of vasopressin, e.g. in the syndrome of inappropriate antidiuretic hormone secretion, involves a selective downregulation of aquaporin-2 expression. Excessive water retention causing hyponatremia in volume-expanded states such as congestive heart failure appears to be due in part to a failure of this escape mechanism. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NR 12 TC 17 Z9 17 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 SEP PY 1998 VL 275 IS 3 BP F332 EP F333 PG 2 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 117VE UT WOS:000075802700005 PM 9729504 ER PT J AU Marples, D Christensen, BM Frokiaer, J Knepper, MA Nielsen, S AF Marples, D Christensen, BM Frokiaer, J Knepper, MA Nielsen, S TI Dehydration reverses vasopressin antagonist-induced diuresis and aquaporin-2 downregulation in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE aquaporin-2; vasopressin; antidiuresis; antidiuretic hormone ID WATER CHANNEL EXPRESSION; INDUCED DOWN-REGULATION; COLLECTING DUCT; KIDNEY MEDULLA; OPC-31260; PERMEABILITY; GENE AB To examine the involvement of vasopressin and dehydration in the regulation of aquaporin-2 (AQP2) expression in rat kidney we investigated the effects of treatment for 60 h with the specific V(2)-receptor antagonist OPC-31260 (OPC), alone and in conjunction with dehydration for the last 12 h. Changes in AQP2 protein and mRNA expression in kidney inner medulla were determined by Western and Northern blotting, and AQP2 distribution was analyzed by immunocytochemistry and immunoelectron microscopy. Treatment with OPC increased urine output fourfold, with a reciprocal decrease in urine osmolality. AQP2 expression decreased to 52 +/- 11% of control levels (n = 12, P < 0.05), and AQP2 was found predominantly in intracellular vesicles in collecting duct principal cells. This is consistent with efficient blockade of the vasopressin-induced AQP2 delivery to the plasma membrane and with the observed increased diuresis. Consistent with this, AQP2 mRNA levels mere also reduced in response to prolonged OPC treatment (30 +/- 10% of control levels, n = 9). Five days of treatment with furosemide, despite producing even greater polyuria than OPC, was not associated with downregulation of AQP2 levels, demonstrating that AQP2 do downregulation is not secondary to increased urine flow rate or loss of medullary hypertonicity. During 12-h thirsting in the continued presence of OPC, urine output dropped dramatically, to levels not significantly different from that seen in (nonthirsted) control animals. In parallel with this, AQP2 levels rose to control levels. Control experiments confirmed continued effective receptor blockade. These results indicate that the V(2)-receptor antagonist causes a modest decrease in AQP2 expression that is not a consequence of increased urine flow rate or washout of medullary hypertonicity. However, this decrease is much less marked than that seen in some forms of acquired nephrogenic diabetes insipidus. In conjunction with the effects of thirsting, this suggests that modulation of AQP2 expression is mediated partly but not exclusively, via V(2) receptors. C1 Univ Aarhus, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. Univ Leeds, Dept Physiol, Leeds LS2 9NQ, W Yorkshire, England. Univ Aarhus, Dept Clin Physiol, DK-8000 Aarhus C, Denmark. NHLBI, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Univ Aarhus, Inst Anat, Dept Cell Biol, DK-8000 Aarhus C, Denmark. NR 28 TC 57 Z9 58 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 SEP PY 1998 VL 275 IS 3 BP F400 EP F409 PG 10 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 117VE UT WOS:000075802700014 PM 9729513 ER PT J AU Judd, LL AF Judd, LL TI The fiftieth anniversary of the National Institute of Mental Health: Five decades of contribution to psychiatric practice SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material C1 Univ Calif San Diego, Sch Med, Dept Psychiat, La Jolla, CA 92093 USA. NIMH, Rockville, MD 20857 USA. RP Judd, LL (reprint author), Univ Calif San Diego, Sch Med, Dept Psychiat, Rm 2072,BSB,9500 Gillman Dr, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 SU S BP 1 EP 1 PG 1 WC Psychiatry SC Psychiatry GA 118CN UT WOS:000075821000001 ER PT J AU Brown, BS AF Brown, BS TI NIMH before (1946-1970) and during the tenure of Director Bertram S. Brown, MD (1970-1978): The early years and the public health mission SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on 50th Anniversary of the NIMH - 5 Decades of Contribution to Psychiatric Practice at the 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc C1 NIMH, Rockville, MD 20857 USA. RP Brown, BS (reprint author), NIMH, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 SU S BP 9 EP 13 PG 5 WC Psychiatry SC Psychiatry GA 118CN UT WOS:000075821000003 PM 9736858 ER PT J AU Pardes, H AF Pardes, H TI NIMH during the tenure of Director Herbert Pardes, MD (1978-1984): The President's commission on mental health and the reemergence of NIMH's scientific mission SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on 50th Anniversary of the NIMH - 5 Decades of Contribution to Psychiatric Practice at the 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc C1 NIMH, Rockville, MD 20857 USA. RP Pardes, H (reprint author), NIMH, Rockville, MD 20857 USA. NR 6 TC 1 Z9 1 U1 1 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 SU S BP 14 EP 19 PG 6 WC Psychiatry SC Psychiatry GA 118CN UT WOS:000075821000004 PM 9736859 ER PT J AU Frazier, SH AF Frazier, SH TI NIMH during the tenure of Director Shervert H. Frazier, MD (1984-1986): The mental disorder-based reorganization and research on schizophrenia and severe mental disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on 50th Anniversary of the NIMH - 5 Decades of Contribution to Psychiatric Practice at the 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc C1 NIMH, Rockville, MD 20857 USA. RP Frazier, SH (reprint author), NIMH, Rockville, MD 20857 USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 SU S BP 20 EP 24 PG 5 WC Psychiatry SC Psychiatry GA 118CN UT WOS:000075821000005 PM 9736860 ER PT J AU Judd, LL AF Judd, LL TI NIMH during the tenure of Director Lewis L. Judd, MD (1987-1990): The decade of the brain and the four national research plans SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on 50th Anniversary of the NIMH - 5 Decades of Contribution to Psychiatric Practice at the 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc C1 NIMH, Rockville, MD 20857 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 SU S BP 25 EP 31 PG 7 WC Psychiatry SC Psychiatry GA 118CN UT WOS:000075821000006 PM 9736861 ER PT J AU Hyman, SE AF Hyman, SE TI NIMH during the tenure of Director Steven E. Hyman, M.D. (1996-present): The now and future of NIMH SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT Symposium on 50th Anniversary of the NIMH - 5 Decades of Contribution to Psychiatric Practice at the 150th Annual Meeting of the American-Psychiatric-Association CY MAY 17-22, 1997 CL SAN DIEGO, CALIFORNIA SP Amer Psychiat Assoc C1 NIMH, Rockville, MD 20857 USA. RP Hyman, SE (reprint author), NIMH, Rockville, MD 20857 USA. NR 3 TC 8 Z9 8 U1 0 U2 0 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD SEP PY 1998 VL 155 IS 9 SU S BP 36 EP 40 PG 5 WC Psychiatry SC Psychiatry GA 118CN UT WOS:000075821000008 PM 9736863 ER PT J AU Brookmeyer, R Gray, S Kawas, C AF Brookmeyer, R Gray, S Kawas, C TI Projections of Alzheimer's disease in the United States and the public health impact of delaying disease onset SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ESTROGEN REPLACEMENT THERAPY; RISK; DEMENTIA; PREVALENCE; POPULATION; ASSOCIATION; EDUCATION; WOMEN; DIAGNOSIS; PERIODS AB Objectives. The goal of this study was to project the future prevalence and incidence of Alzheimer's disease in the United States and the potential impact of interventions to delay disease onset. Methods. The numbers of individuals in the United States with AIzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections. Results. In 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: 1.09 to 4.58 million); of these individuals, 68% were female. It is projected that the prevalence will nearly quadruple in the next 50 years, by which time approximately 1 in 45 Americans will be afflicted with the disease. Currently, the annual number of new incident cases is 360 000, If interventions could delay onset of the disease by 2 years, after 50 years there would be nearly 2 million fewer cases than projected; if onset could be delayed by 1 year, there would be nearly 800 000 fewer prevalent cases. Conclusions, As the US population ages, Alzheimer's disease will become an enormous public health problem. Interventions that could delay disease onset even modestly would have a major public health impact. C1 Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. NIA, Bethesda, MD 20892 USA. RP Brookmeyer, R (reprint author), Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, 615 N Wolfe St, Baltimore, MD 21205 USA. EM rbrook@jhsph.edu FU NIA NIH HHS [AG05146, AG08325] NR 56 TC 1002 Z9 1027 U1 9 U2 53 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD SEP PY 1998 VL 88 IS 9 BP 1337 EP 1342 DI 10.2105/AJPH.88.9.1337 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 115PD UT WOS:000075673100010 PM 9736873 ER PT J AU Moss, NE Carver, K AF Moss, NE Carver, K TI The effect of WIC and Medicaid on infant mortality in the United States SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID MATERNAL WEIGHT-GAIN; BIRTH-WEIGHT; PREGNANT-WOMEN; PRENATAL-CARE; HEALTH; PARTICIPATION; OUTCOMES; DEATH; CHILDREN; COVERAGE AB Objectives. This study examined the impact of participation in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) and Medicaid on risk of infant death in the United States. Methods. The 1988 National Maternal and Infant Health Survey was used to consider the risk of endogenous and exogenous deaths among infants of women participating in WIC and Medicaid during pregnancy and the infant's first year. Results. Participation in the WIC program during pregnancy and infancy :vas associated with a reduced risk of endogenous and exogenous infant deaths (odds ratios [ORs] = 0.68 and 0.62. respectively). The risk of endogenous death among infants whose mothers participated in Medicaid during pregnancy was equal to that of the privately insured (OR= 1.04). Uninsured infants faced higher risks of endogenous death (:OR = 1.42). Conclusions. These results show that it is important to consider the net effect of WIC and Medicaid participation and to differentiate both the timing of program receipt and cause of death. Evidence suggests that WIC and Medicaid programs have beneficial effects for poor women and their infants. C1 NICHHD, Bethesda, MD 20892 USA. RP Moss, NE (reprint author), 701 Garland, Palo Alto, CA 94303 USA. NR 51 TC 44 Z9 44 U1 1 U2 4 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 SEP PY 1998 VL 88 IS 9 BP 1354 EP 1361 DI 10.2105/AJPH.88.9.1354 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 115PD UT WOS:000075673100013 PM 9736876 ER PT J AU Kulldorff, M Athas, WF Feuer, EJ Miller, BA Key, CR AF Kulldorff, M Athas, WF Feuer, EJ Miller, BA Key, CR TI Evaluating cluster alarms: A space-time scan statistic and brain cancer in Los Alamos, New Mexico SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID DISEASE AB Objectives. This article presents a space-time scan statistic, useful for evaluating space-time cluster alarms, and illustrates the method on a recent brain cancer cluster alarm in Los Alamos, NM. Methods. The space-time scan statistic accounts for the preselection bias and multiple testing inherent in a cluster alarm. Confounders and time trends can be adjusted for Results. The observed excess of brain cancer in Los Alamos was not statistically significant. Conclusions. The space-time scan statistic is useful as a screening tool for evaluating which cluster alarms merit further investigation and which clusters are probably chance occurrences. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Uppsala Univ, Dept Stat, Uppsala, Sweden. New Mexico Dept Hlth, Div Epidemiol Evaluat & Planning, Santa Fe, NM USA. Univ New Mexico, New Mexico Tumor Registry, Ctr Canc, Albuquerque, NM 87131 USA. RP Kulldorff, M (reprint author), NCI, Div Canc Prevent, EPN 344,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Kulldorff, Martin/H-4282-2011; OI Kulldorff, Martin/0000-0002-5284-2993 FU NCI NIH HHS [N01-CN05228]; NIDCR NIH HHS [DE-FG04-91AL75237] NR 21 TC 265 Z9 276 U1 5 U2 17 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 SEP PY 1998 VL 88 IS 9 BP 1377 EP 1380 DI 10.2105/AJPH.88.9.1377 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 115PD UT WOS:000075673100018 PM 9736881 ER PT J AU Kennedy, T Ghio, AJ Reed, W Samet, J Zagorski, J Quay, J Carter, J Dailey, L Hoidal, JR Devlin, RB AF Kennedy, T Ghio, AJ Reed, W Samet, J Zagorski, J Quay, J Carter, J Dailey, L Hoidal, JR Devlin, RB TI Copper-dependent inflammation and nuclear factor-kappa B activation by particulate air pollution SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; BRONCHOALVEOLAR LAVAGE FLUID; RESPIRATORY SYNCYTIAL VIRUS; OBSTRUCTIVE PULMONARY-DISEASE; BRONCHIAL EPITHELIAL-CELLS; HUMAN ALVEOLAR MACROPHAGES; TUMOR-NECROSIS-FACTOR; SMOOTH-MUSCLE CELLS; OIL FLY-ASH; HOSPITAL ADMISSIONS AB Particulate air pollution causes increased cardiopulmonary morbidity and mortality, but the chemical determinants responsible for its biologic effects are not understood. We studied the effect of total suspended particulates collected in Prove, Utah, an area when an increase in respiratory symptoms in relation to levels of particulate pollution has been well documented. Prove particulates caused cytokine-induced neutrophil chemoattractant-dependent inflammation of rat lungs. Prove particulates stimulated interleukin-6 (IL-6) and IL-8 production, increased IL-8 messenger RNA (mRNA) and enhanced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured BEAS-2B cells, and stimulated IL-8 secretion in primary cultures of human bronchial epithelium. Cytokine secretion was preceded by activation of the transcription factor nuclear factor-kappa B (NF-kappa B) and was reduced by treatment of cultures with superoxide dismutase, deferoxamine, or N-acetylcysteine. These biologic effects were replicated by culturing BEAS cells with quantities of Cu2+ found in Prove extract. IL-8 secretion by BEAS cells could be modified by addition of normal constituents of airway lining fluid to the culture medium. Mucin significantly reduced IL-8 secretion, and ceruloplasmin significantly increased IL-8 secretion and activation of NF-kappa B. These findings suggest that copper ions may cause some of the biologic effects of inhaled particulate air pollution in the Prove region of the United States, and may provide an explanation for the sensitivity of asthmatic individuals to Prove particulates that has been observed in epidemiologic studies. C1 Carolinas Med Ctr, Dept Internal Med, Charlotte, NC 28232 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Ctr Environm Med & Lung Biol, Chapel Hill, NC 27515 USA. Primary Childrens Hosp, Asthma Ctr, Salt Lake City, UT USA. NIDR, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. RP Kennedy, T (reprint author), Carolinas Med Ctr, Dept Internal Med, POB 32861, Charlotte, NC 28232 USA. NR 68 TC 119 Z9 124 U1 0 U2 5 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 1998 VL 19 IS 3 BP 366 EP 378 PG 13 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 120UP UT WOS:000075976000004 PM 9730864 ER PT J AU Dong, WM Selgrade, MK Gilmour, MI Lange, RW Park, P Luster, MI Kari, FW AF Dong, WM Selgrade, MK Gilmour, MI Lange, RW Park, P Luster, MI Kari, FW TI Altered alveolar macrophage function in calorie-restricted rats SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; DIETARY RESTRICTION; AD-LIBITUM; LIFE-SPAN; MICE; OZONE; TRANSPORT; INFECTION; IMMUNITY; CELLS AB Alveolar macrophage functions associated with clearance of bacteria from the lung were assessed in male Fischer 344 rats maintained on a 25% calorie-restricted diet. Calorie-restricted and nd libitum-fed (control) rats were exposed to concentrations of ozone known to compromise phagocytic function of alveolar macrophages. Ozone suppressed alveolar macrophage phagocytosis of latex beads in vitro in nd libitum-fed rats, but not in calorie-restricted rats. In fact, caloric restriction enhanced phagocytic function in both control and ozone-exposed animals. Ad libitum-fed rats exposed to ozone and challenged with Streptococcus zooepidemicus experienced a prolonged infection and influx of polymorphonuclear leukocytes (PMN), whereas calorie-restricted rats exposed to ozone cleared the bacteria in 24 h without an inflammatory response. Bacterial endotoxin-stimulated in vitro production of nitric oxide and tumor necrosis factor (TNF)-alpha as well as expression of TNF-alpha and interleukin-6 messenger RNAs were all lower in alveolar macrophages isolated from calorie-restricted rats. Together, the data suggest that caloric restriction enhances resistance to gram-positive bacteria, while lowering the production of proinflammatory mediators elicited by endotoxin, a component of gram-negative bacteria. Although increased bacterial resistance is considered beneficial, reduction in the lung's ability to induce inflammatory mediators can have both positive and pathophysiologic consequences. C1 NIEHS, Toxicol Lab, Nutr & Toxicol Grp, Res Triangle Pk, NC 27709 USA. NIOSH, Toxicol & Mol Biol Branch, Morgantown, WV USA. Univ N Carolina, Ctr Environm Med & Lung Biol, Chapel Hill, NC 27515 USA. US EPA, Immunotoxicol Branch, Res Triangle Pk, NC 27711 USA. RP Kari, FW (reprint author), NIEHS, Toxicol Lab, Nutr & Toxicol Grp, MD B3-09,POB 12233, Res Triangle Pk, NC 27709 USA. NR 36 TC 41 Z9 41 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD SEP PY 1998 VL 19 IS 3 BP 462 EP 469 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 120UP UT WOS:000075976000014 PM 9730874 ER PT J AU Choyke, PL Siegel, MJ Oz, O Sotelo-Avila, C DeBaun, MR AF Choyke, PL Siegel, MJ Oz, O Sotelo-Avila, C DeBaun, MR TI Nonmalignant renal disease in pediatric patients with Beckwith-Wiedemann syndrome SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CHILDREN; KIDNEYS; TUMOR AB OBJECTIVE, The objective of this retrospective review was to determine the incidence and spectrum of nonmalignant renal disease in patients with Beckwith-Wiedemann syndrome. MATERIALS AND METHODS. Patient records were obtained from the Beckwith-Wiedemann Registry of the National Cancer Institute. Imaging findings and medical records of 152 neonates, infants, children, and adults with Beckwith-Wiedemann syndrome (age range, 1 day to 30 years old; median age, 1 year 3 months old) were retrospectively reviewed by three radiologists. Available pathologic material also was reviewed. RESULTS. Thirty-eight (25%) of 152 patients with Beckwith-Wiedemann syndrome had 45 nonmalignant renal abnormalities, including medullary renal cysts (n = 19, 13%), caliceal diverticula (n = 2, 1%), hydronephrosis (n = 18, 12%), and nephrolithiasis (a = 6, 4%). Thirty three (87%) of the 38 patients with nonmalignant renal disease were asymptomatic. Clinical manifestations of the remaining five patients included urinary tract infections (n = 4) and flank pain due to obstructive stone disease (n = 1). Nonmalignant renal disease was mistaken for Wilms' tumor in two patients, resulting in unnecessary nephrectomies. Seven children (18%) had Wilms' tumor and nonmalignant renal disease. CONCLUSION. Nonmalignant renal abnormalities occur in approximately 25% of patients with Beckwith-Wiedemann syndrome but are generally asymptomatic. Nonmalignant renal abnormalities should be considered in the differential diagnosis of a mass revealed during screening sonography of a patient with Beckwith-Wiedemann syndrome to avoid unnecessary surgery. C1 NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. Edward Mallinckrodt Inst Radiol, St Louis, MO 63110 USA. Univ Texas, SW Med Ctr, Dept Radiol, Dallas, TX 75235 USA. Cardinal Glennon Childrens Hosp, Dept Pathol, St Louis, MO 63104 USA. NCI, Genet Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP DeBaun, MR (reprint author), Washington Univ, Sch Med, Dept Pediat, St Louis, MO 63110 USA. NR 17 TC 30 Z9 31 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 SEP PY 1998 VL 171 IS 3 BP 733 EP 737 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 112LT UT WOS:000075496700040 PM 9725306 ER PT J AU Andriko, JAW Kaldjian, EP Tsokos, M Abbondanzo, SL Jaffe, ES AF Andriko, JAW Kaldjian, EP Tsokos, M Abbondanzo, SL Jaffe, ES TI Reticulum cell neoplasms of lymph nodes - A clinicopathologic study of 11 cases with recognition of a new subtype derived from fibroblastic reticular cells SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE lymph node; stromal cells; interdigitating dendritic cell; follicular dendritic cell; fibroblastic reticular cell; Castleman's disease ID FOLLICULAR DENDRITIC CELLS; INTERDIGITATING CELLS; MALIGNANT HISTIOCYTOSIS; CASTLEMANS DISEASE; SMALL-INTESTINE; SMOOTH-MUSCLE; SARCOMA; TUMOR; FEATURES; FOLLICLES AB Lymph nodes contain nonlymphoid accessory cells including Follicular dendritic cells (FDCs), interdigitating dendritic cells (IDCs) and fibroblastic reticular cells (FBRCs). Neoplasms derived from FDCs are uncommon, and those of IDC origin are even more rare. We report the clinicopathologic features of 11 reticulum cell neoplasms, including 2 of FBRC origin. There were seven male patients and four female patients ranging in age from 13 to 73 years. All cases involved lymph nodes (cervical or supraclavicular-6 cases), (abdominal-2 cases), epitrochlear (1 case); two had more than one site of involvement (cervical lymph node and mediastinum-1 case, cervical and abdominal lymph nodes-1 case). One case of FDC tumor had concomitant Castleman's disease, plasma cell variant. Each neoplasm showed similar histology with oval-to-spindle-shaped cells in a storiform or fascicular pattern. Eased on immunophenotypic findings, the neoplasms were classified as FDC (five cases). LDC (two cases), FBRC ((three cases), and reticulum cell neoplasm, not otherwise specified tone case). The FDC tumors showed immunoreactivity for CD21 or CD35, vimentin, and CD68. The IDC tumors showed strong positivity for S-100 protein and variable positivity for CD68 and CD1a. The cases derived from FBRCs were positive for vimentin, desmin, and smooth-muscle actin. The neoplasm classified as reticulum cell neoplasm, not otherwise specified had similar morphologic features but showed only equivocal positivity for CD68 and vimentin. Follow-up was available for 9 of 11 (82%) cases with a mean of 3.5 years. Four of five patients with FDC tumors were alive with disease when last seen; the fifth is alive and well with no evidence of disease at 4-year follow-up. One patient with IDC tumor had a recurrence in a different nodal site. Two patients with FBRC tumor were disease free at follow-up of 2 years and 8 years, respectively. The patient with reticulum cell neoplasm, not otherwise specified, was alive and disease free 8 years after diagnosis. C1 Armed Forces Inst Pathol, Dept Hematol & Lymphat Pathol, Washington, DC 20306 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. RP Abbondanzo, SL (reprint author), Armed Forces Inst Pathol, Dept Hematol & Lymphat Pathol, Washington, DC 20306 USA. NR 58 TC 78 Z9 87 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD SEP PY 1998 VL 22 IS 9 BP 1048 EP 1058 DI 10.1097/00000478-199809000-00002 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 116VQ UT WOS:000075746100002 PM 9737236 ER PT J AU Djimde, A Plowe, CV Diop, S Dicko, A Wellems, TE Doumbo, O AF Djimde, A Plowe, CV Diop, S Dicko, A Wellems, TE Doumbo, O TI Use of antimalarial drugs in Mali: Policy versus reality SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID WEST-AFRICAN VILLAGE; MALARIA; SEASONALITY; PROPHYLAXIS; COMMUNITY; IMPACT AB Inappropriate use of antimalarial drugs undermines therapeutic efficacy and promotes the emergence and spread of drug-resistant malaria. Strategies for improving compliance require accurate information about current practices. Here we describe Knowledge-Attitude-Practice surveys conducted among health providers and consumers in two Malian villages, one rural and one periurban. All sanctioned providers limited their first choices of antimalarial drug to those recommended by the national malaria control program and reported using correct dosing regimens. However, the majority of consumers in the two villages chose non-recommended treatments for malaria and reported suboptimal treatment regimens when they did use recommended drugs. Antimalarial drugs were also widely available from unsanctioned sources, often accompanied by erroneous advice on dosing regimens. This study demonstrates that even when the most peripheral health providers are well-trained in correct use of antimalarial drugs, additional measures directly targeting consumers will be required to improve drug use practices. C1 Univ Maryland, Sch Med, Div Geog Med, Mol Parasitol & Malaria Field Studies Unit, Baltimore, MD 21201 USA. Fac Med Pharm & Odontostomatol, Malaria Res & Training Ctr, Dept Epidemiol Parasit Dis, Bamako, Mali. NIAID, Malaria Genet Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Plowe, CV (reprint author), Univ Maryland, Sch Med, Div Geog Med, Mol Parasitol & Malaria Field Studies Unit, 685 W Baltimore St,HSF 480, Baltimore, MD 21201 USA. NR 10 TC 42 Z9 43 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 1998 VL 59 IS 3 BP 376 EP 379 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 119RJ UT WOS:000075910700006 PM 9749628 ER PT J AU Toure, YT Doumbo, O Toure, A Bagayoko, M Diallo, M Dolo, A Vernick, KD Keister, DB Muratova, O Kaslow, DC AF Toure, YT Doumbo, O Toure, A Bagayoko, M Diallo, M Dolo, A Vernick, KD Keister, DB Muratova, O Kaslow, DC TI Gametocyte infectivity by direct mosquito feeds in an area of seasonal malaria transmission: Implications for Bancoumana, Mali as a transmission-blocking vaccine site SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID PLASMODIUM-FALCIPARUM MALARIA; SRI-LANKA; CANDIDATE; KATARAGAMA; ANTIBODIES AB Infectivity of gametocytemic volunteers living in Bancoumana, a;village 60 km from Bamako, Mall, was determined by direct feeds of laboratory-reared Anopheles gambiae s. l. Gametocytemic adolescents (10-18 years old) were as infectious to mosquitoes as younger volunteers and appear to be a more suitable population for testing transmission-blocking efficacy as compared with adults (> 18 years old). To begin to validate the membrane-feeding assay, sera collected from these same volunteers were subjected to a standard membrane-feeding assay. The data suggest that areas with intense but seasonal transmission might be feasible sites for testing transmission-blocking vaccines because of the high gametocytemic rates, high mosquito infectivity rates, and lack of pre-existing humoral-mediated transmission-blocking activity. The differences observed between held-based direct mosquito feeds and laboratory-based membrane feeding assays suggests that caution be used in interpreting Phase I study results in which laboratory-based membrane-feeding assays are used as a surrogate for vaccine efficacy. C1 Fac Med Pharm & Odontostomatol, Dept Epimediol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali. NIAID, Malaria Vaccines Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Toure, YT (reprint author), Fac Med Pharm & Odontostomatol, Dept Epimediol Parasit Dis, Malaria Res & Training Ctr, Bamako, Mali. NR 16 TC 37 Z9 37 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD SEP PY 1998 VL 59 IS 3 BP 481 EP 486 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 119RJ UT WOS:000075910700026 PM 9749648 ER PT J AU Radzius, A Gorelick, DA Henningfield, JE AF Radzius, A Gorelick, DA Henningfield, JE TI Cigarette smoking during early cocaine abstinence SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID ALCOHOL AB Use of cocaine has been reported to increase cigarette smoking, but there are no published studies of cigarette smoking during early cocaine abstinence. The authors assessed ad libitum cigarette smoking of 12 cocaine-dependent smokers housed on a closed research ward. Last cocaine use averaged 0.6 grams 1.8 days before admission. Smoking was measured indirectly with computerized cigarette dispensers. There was no significant difference between self-reported daily number of cigarettes smoked before admission and the number of cigarettes dispensed daily for the first 7 full days after admission. These findings suggest that early cocaine abstinence does not significantly alter cigarette smoking. C1 NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Gorelick, DA (reprint author), NIDA, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 13 TC 2 Z9 2 U1 0 U2 1 PU AMER PSYCHIATRIC ASSOCIATION PI WASHINGTON PA 1400 K ST NW, WASHINGTON, DC 20005 USA SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD FAL PY 1998 VL 7 IS 4 BP 305 EP 308 PG 4 WC Substance Abuse SC Substance Abuse GA 136YJ UT WOS:000076886400008 PM 9809135 ER PT J AU Frank, SM Raja, SN Bulcao, C Goldstein, D AF Frank, SM Raja, SN Bulcao, C Goldstein, D TI Determinants of thermal discomfort and the thermoregulatory response: Relative contribution of core and skin-surface temperatures SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Johns Hopkins Med Inst, Dept Anesthesiol Crit Care Med, Baltimore, MD 21205 USA. NINDS, Clin Neurosci Branch, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A312 BP U296 EP U296 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810900312 ER PT J AU Kain, ZN Caramico, L Mayes, L Genevro, J Hofstadter, M AF Kain, ZN Caramico, L Mayes, L Genevro, J Hofstadter, M TI Preoperative preparation programs in children: A hierarchical study SO ANESTHESIOLOGY LA English DT Meeting Abstract C1 Yale Sch Med, Dept Anesthesiol, Ctr Child Study, New Haven, CT USA. Yale Sch Med, Dept Pediat, Ctr Child Study, New Haven, CT USA. NICHHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD SEP PY 1998 VL 89 IS 3A SU S MA A1267 BP U992 EP U992 PG 1 WC Anesthesiology SC Anesthesiology GA 117YR UT WOS:000075810901261 ER PT J AU Kataoka, H Kumagai, H Hanai, H AF Kataoka, H Kumagai, H Hanai, H TI Jugular vein sampling in Cushing disease - In response SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Kataoka, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 13 Z9 13 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD SEP 1 PY 1998 VL 129 IS 5 BP 424 EP 424 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 114RL UT WOS:000075622600018 PM 9735077 ER PT J AU Chen, R Yaseen, Z Cohen, LG Hallett, M AF Chen, R Yaseen, Z Cohen, LG Hallett, M TI Time course of corticospinal excitability in reaction time and self-paced movements SO ANNALS OF NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; MOTOR-EVOKED-POTENTIALS; VOLUNTARY MOVEMENT; ELECTRICAL-STIMULATION; FINGER MOVEMENTS; LIMB MOVEMENTS; HUMAN-BRAIN; CORTEX; SCALP; ACTIVATION AB We used transcranial magnetic stimulation (TMS) to study the time course of corticospinal excitability before and after brisk thumb abduction movements, either in a simple reaction time (RT) paradigm or self-paced. Premovement increase in corticospinal excitability began about 20 msec earlier for self-paced compared with simple RT movements. For both simple RT and self-paced movements after electromyographic (EMG) offset, there was a first period of increased excitability from 0 to 100 msec, followed by a second period from 100 to 160 msec. Corticospinal excitability was decreased from about 500 to 1,000 msec after EMG offset for both types of movements. Our results show that motor preparation that begins 1.5 to 2 seconds before self-paced movement is not associated with increased corticospinal excitability, The first phase of increased corticospinal excitability after EMG offset may be due to activity of motor cortex neuron subthreshold for activating spinal motor neurons, and the second phase may reflect a subthreshold second agonist burst. The period of decreased corticospinal excitability after movement corresponds to the onset of event-related synchronization (ERS) of electroencephalographic signals in the 20-Hz band, and supports the hypothesis that ERS may be related to an inactive, idling state of the motor cortex. C1 NINDS, Human Cort Physiol Unit, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 44 TC 213 Z9 214 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1998 VL 44 IS 3 BP 317 EP 325 DI 10.1002/ana.410440306 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 116VB UT WOS:000075744700005 PM 9749597 ER PT J AU Zipp, F Martin, R Dichgans, J Weller, M AF Zipp, F Martin, R Dichgans, J Weller, M TI CD95 (APO-1/Fas) and Parkinson's disease - Reply SO ANNALS OF NEUROLOGY LA English DT Letter C1 Univ Tubingen, Dept Neurol, D-7400 Tubingen, Germany. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Zipp, F (reprint author), Univ Tubingen, Dept Neurol, Hoppe Seyler Str 3, D-7400 Tubingen, Germany. NR 4 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1998 VL 44 IS 3 BP 426 EP 426 DI 10.1002/ana.410440331 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 116VB UT WOS:000075744700030 ER PT J AU Polymeropoulos, MH AF Polymeropoulos, MH TI Autosomal dominant Parkinson's disease and alpha-Synuclein SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT Symposium on Neuroprotection in Parkinsons Disease CY OCT 31-NOV 02, 1997 CL CANNES, FRANCE ID ALZHEIMERS-DISEASE; GENE; BRAIN AB Multiple factors have been hypothesized over the years to be contributory and/or causative for Parkinson's disease (PD). Hereditary factors, although originally discounted, have recently emerged in the focus of PD research. The study of a large Italian family with PD using a genome scan approach led to the mapping of a PD susceptibility gene to the 4q21-q23 genomic region, where the gene for alpha-synuclein was previously mapped. Mutation analysis of the alpha-synuclein in four unrelated families with PD revealed a missense mutation segregating with the illness. alpha-Synuclein is an abundant presynaptic protein in the human brain with unknown function. It is conceivable that the mutation identified in the PD families may result in self-aggregation and/or decreased degradation of the protein, leading to the development of intracytoplasmic inclusion bodies and eventually to neuronal cell death. Moreover, the discovery of a mutation in the synuclein gene may offer us new insights in the understanding of the pathways that lead to neuronal degeneration. C1 NIH, Lab Genet Dis Res, Natl Human Genome Res Inst, Bethesda, MD 20892 USA. RP Polymeropoulos, MH (reprint author), NIH, Lab Genet Dis Res, Natl Human Genome Res Inst, Bldg 49,Rm 4A66, Bethesda, MD 20892 USA. NR 19 TC 37 Z9 38 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD SEP PY 1998 VL 44 IS 3 SU 1 BP S63 EP S64 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 118BX UT WOS:000075818800009 PM 9749575 ER PT J AU Rosenberg, SA Yang, JC White, DE Steinberg, SM AF Rosenberg, SA Yang, JC White, DE Steinberg, SM TI Durability of complete responses in patients with metastatic cancer treated with high-dose interleukin-2 - Identification of the antigens mediating response SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 118th Annual Scientific Session of the American-Surgical-Association CY APR, 1998 CL PALM BEACH, FLORIDA SP Amer Surg Assoc ID TUMOR-INFILTRATING LYMPHOCYTES; RENAL-CELL CARCINOMA; RECOMBINANT INTERLEUKIN-2; AUTOLOGOUS TUMOR; MELANOMA; GENE; REGRESSION; IMMUNOTHERAPY; RECOGNITION; TYROSINASE AB Objective To determine the durability of complete responses in patients with metastatic melanoma or renal cancer treated with high-dose bolus interleukin-2 (IL-2) as well as the factors associated with the development of a complete response and the antigens mediating clinical responses. Methods A consecutive series of 409 patients with either metastatic, melanoma or renal cancer who were treated with high-dose bolus IL-2 in the Surgery Branch, National Cancer institute, between September 1985 and November 1996 have been analyzed with a median potential follow-up of 7.1 years. All patients were treated with 720,000 IU/kg administered by 15-minute intravenous infusions every 8 hours for up to 5 days as clinically tolerated per cycle. Two cycles constituted a treatment course. Tumor-infiltrating lymphocytes (TIL) from melanoma patients were used to clone the genes encoding the tumor antigens responsible for clinical responsiveness. Results Thirty-three of 409 (8.1%) patients treated with high-dose bolus IL-2 achieved a complete response and 37 (9%) achieved a partial response. Complete regression was seen in 6.6% and 9.3% of patients with metastatic melanoma and renal cancer, respectively. Twenty-seven of these 33 completely responding patients (82%) remain in ongoing continuous complete response from 39 to more than 148 months from the onset of treatment. Tumor regressions were seen at virtually all organ sites. The absence of prior treatment with immunotherapy, the total dose of IL-2 administered, and the maximal rebound lymphocytosis after cessation of IL-2 correlated with achieving a complete response. Expression cloning techniques have identified a series of tumor antigens that are recognized by TIL grown from resected melanomas, These antigens are mainly melanoma/melanocyte differentiation antigens, although mutated intracellular proteins can also serve as antigens. Conclusions Treatment with high-dose bolus IL-2 mediates complete cancer regression in approximately 8% of patients with metastatic renal cancer and melanoma. The great majority of these patients will enter durable complete regressions and appear to be cured of their metastatic cancer. Thus, immunotherapy with high-dose bolus IL-2 should be considered as initial therapy io;appropriately selected patients with metastatic melanoma and renal cell cancer, identification of the tumor antigens mediating clinical response is opening new therapeutic possibilities for cancer treatment. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Biostat, NIH, Bethesda, MD 20892 USA. NCI, Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Div Clin Sci, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 2B42, Bethesda, MD 20892 USA. NR 29 TC 299 Z9 305 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD SEP PY 1998 VL 228 IS 3 BP 307 EP 317 DI 10.1097/00000658-199809000-00004 PG 11 WC Surgery SC Surgery GA 119VJ UT WOS:000075918600006 PM 9742914 ER PT J AU Temeck, BK Wexler, LH Steinberg, SM McClure, LL Horowitz, MA Pass, HI AF Temeck, BK Wexler, LH Steinberg, SM McClure, LL Horowitz, MA Pass, HI TI Reoperative pulmonary metastasectomy for sarcomatous pediatric histologies SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Southern-Thoracic-Surgical-Association CY NOV 06-09, 1997 CL NAPLES, FLORIDA SP So Thorac Surg Assoc ID SOFT-TISSUE SARCOMA; METASTATIC OSTEOGENIC-SARCOMA; PROGNOSTIC FACTORS; RESECTION; SURVIVAL AB Background. The role for reoperative pulmonary metastasectomy in patients with "pediatric sarcomas" (osteosarcoma, nonrhabdomyosarcoma-soft tissue sarcoma, and E-wing's sarcoma) is undefined. Methods. We reviewed our results for patients with these histologic presentations (median age, 17.5 years; range, 6 to 32 years) having two (70), three (27), or four (10) metastasectomies between January 1965 and March 1995 to define postresection survival and potential prognostic factors. Simple wedges (88 thoracotomies, 84%) were performed more frequently than anatomic (17 thoracotomies, 16%) resections. Results. With a median potential follow-up of 12.7 years, median survival was 2.25, 3.60, and 0.96 years from the second, third, and fourth explorations, respectively, Primary tumor site, sex, histology, age, maximal metastasis size, and systemic chemotherapy did not influence survival. Resectability was the most important prognostic factor (5.6 versus 0.7 years, 5.2 versus 2.5 years, 2.2 versus 0.2 years, resectable versus unresectable, median survival from second, third,and fourth thoracotomy, respectively). Unresectability, disease-free interval less than 6 months between initial (ie, first) pulmonary resection and the second thoracotomy, and two or more preoperative nodules noted on the right were simultaneously negatively associated with survival from the second thoracotomy. Unresectability or finding two or more metastases negatively affected survival from the third thoracotomy. Conclusions. These data imply that repeat metastasectomy can salvage a subset of patients with sarcomatous pediatric histologic presentations who retain favorable prognostic determinants. (Ann Thorac Surg 1998;66:908-13) (C) 1998 by The Society of Thoracic Surgeons. C1 NCI, Thorac Oncol Sect, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Pass, HI (reprint author), Dept Surg & Oncol, 3990 John R,Suite 2102, Detroit, MI 48201 USA. NR 25 TC 10 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD SEP PY 1998 VL 66 IS 3 BP 908 EP 912 DI 10.1016/S0003-4975(98)00666-3 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 124DM UT WOS:000076166100056 PM 9768950 ER PT J AU Parshad, R Sanford, KK Price, FM Steele, VE Tarone, RE Kelloff, GJ Boone, CW AF Parshad, R Sanford, KK Price, FM Steele, VE Tarone, RE Kelloff, GJ Boone, CW TI Protective action of plant polyphenols on radiation-induced chromatid breaks in cultured human cells SO ANTICANCER RESEARCH LA English DT Article DE UV; DNA damage; human cells; plant polyphenols; black and green tea extracts; curcumin ID PHASE-X-IRRADIATION; G2 PHASE; DNA-REPAIR; FIBROBLASTS; CANCER; DAMAGE; RADIOSENSITIVITY; INDIVIDUALS; LYMPHOCYTES; GENE AB The present study was performed to determine whether plant polyphenols can protect human cells against radiation-induced DNA damage manifested as chromatid breaks Since each chromatid contains a single continuous molecule of double-stranded DNA, chromatid breaks represent unrepaired DNA strand breaks. The addition of green or black tea extracts, their polyphenols or curcumin to cultures of human skin fibroblasts or PHA-stimulated blood lymphocytes significantly reduced the frequencies of radiation-induced chromatid breaks. An exception to this general finding was that the green tea polyphenol, (-)epigallocatechin gallate, had no effect. The protective action of these plant polyphenols seems to result from their known antioxidant properties, particularly the scavaging of hydroxyl free radicals. Frequencies of chromatid breaks in cells arrested immediately after irradiation or 0.5 to 1.5 hours post-irradiation in the presence or absence of a DNA repair inhibitor, provide a measure of DNA damage. The results of the present study show that tea and other plant polyphenols can protect human cells against radiation-induced DNA damage. C1 NCI, Mol & Cellular Biol Lab, Bethesda, MD 20892 USA. NCI, Chemoprevent Branch, Bethesda, MD 20892 USA. NCI, Stat Branch, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Dept Pathol, Washington, DC 20059 USA. RP Sanford, KK (reprint author), 101 Stuart Dr, Sagamiko, Kanagawa 19901, Japan. NR 21 TC 47 Z9 48 U1 1 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD SEP-OCT PY 1998 VL 18 IS 5A BP 3263 EP 3266 PG 4 WC Oncology SC Oncology GA 145MT UT WOS:000077376000017 PM 9858893 ER PT J AU Khan, AA Nasr, M Araujo, FG AF Khan, AA Nasr, M Araujo, FG TI Two 2-hydroxy-3-alkyl-1,4-naphthoquinones with in vitro and in vivo activities against Toxoplasma gondii SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID HYDROXYNAPHTHOQUINONE 566C80; MURINE TOXOPLASMOSIS; INVIVO ACTIVITIES; INVITRO; TROVAFLOXACIN; COMBINATION AB Two 3-alkyl-substituted 2-hydroxy-1,4-naphthoquinones, NSC 113452 (NSC52) and NSC 113455 (NSC55), were evaluated for activity against Toxoplasma gondii in vitro and in murine models of acute toxoplasmosis. In vitro, both NSC52 and NSC55 significantly inhibited intracellular replication of T. gondii. In vivo, each compound was examined alone and in combination with other drugs currently used for treatment of human toxoplasmosis. Although none of the compounds protected mice against death when administered orally, both were significantly protective when administered intraperitoneally, In addition, a significant increase in survival was observed when suboptimal doses of each compound were used in combination with suboptimal doses of pyrimethamine or sulfadiazine. These results indicate that combinations of NSC52 or NSC55 with pyrimethamine or sulfadiazine have promising activity against T. gondii. C1 Palo Alto Med Fdn, Res Inst, Dept Immunol & Infect Dis, Palo Alto, CA 94301 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Dept Med, Div Infect Dis & Geog Med, Stanford, CA 94305 USA. RP Araujo, FG (reprint author), Palo Alto Med Fdn, Res Inst, Dept Immunol & Infect Dis, 860 Bryant St, Palo Alto, CA 94301 USA. FU NIAID NIH HHS [N01-AI-35174] NR 14 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1998 VL 42 IS 9 BP 2284 EP 2289 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 116RB UT WOS:000075737400024 PM 9736550 ER PT J AU McSharry, JJ Lurain, NS Drusano, GL Landay, AL Notka, M O'Gorman, MRG Weinberg, A Shapiro, HM Reichelderfer, PS Crumpacker, CS AF McSharry, JJ Lurain, NS Drusano, GL Landay, AL Notka, M O'Gorman, MRG Weinberg, A Shapiro, HM Reichelderfer, PS Crumpacker, CS TI Rapid ganciclovir susceptibility assay using flow cytometry for human cytomegalovirus clinical isolates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ZIDOVUDINE RESISTANCE; MUTATIONS; THERAPY; PREVALENCE; ACYCLOVIR; FOSCARNET; DISEASE; DRUGS; UL97 AB Rapid, quantitative, and objective determination of the susceptibilities of human cytomegalovirus (HCMV) clinical isolates to ganciclovir has been assessed by an assay that uses a fluorochrome-labeled monoclonal antibody to an HCMV immediate-early antigen and flow cytometry. Analysis of the ganciclovir susceptibilities of 25 phenotypically characterized clinical isolates by Bow cytometry demonstrated that the 50% inhibitory concentrations (IC(50)s) of ganciclovir for 19 of the isolates were between 1.14 and 6.66 mu M, with a mean of 4,32 mu M (+/-1.93) (sensitive; IC50 less than 7 mu M), the IC(50)s for 2 isolates were 8.48 and 9.79 mu M (partially resistant), and the IC(50)s for 3 isolates were greater than 96 mu M (resistant). Comparative analysis of the drug susceptibilities of these clinical isolates by the plaque reduction assay gave IC(50)s of less than 6 mu M, with a mean of 2.88 mu M (+/-1.40) for the 19 drug-sensitive isolates, IC(50)s of 6 to 8 mu M for the partially resistant isolates, and IC(50)s of greater than 12 mu M for the four resistant clinical isolates. Comparison of the IC(50)s for the drug-susceptible and partially resistant clinical isolates obtained by the flow cytometry assay with the IC(50)s obtained by the plaque reduction assay showed an acceptable correlation (r(2) = 0.473; P = 0.001), suggesting that the Bow cytometry assay could substitute for the more labor-intensive, subjective, and time-consuming plaque reduction assay. C1 Albany Med Coll, Dept Microbiol Immunol & Mol Genet, Albany, NY 12208 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Colorado, Med Ctr, Denver, CO 80262 USA. NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP McSharry, JJ (reprint author), Albany Med Coll, Dept Microbiol Immunol & Mol Genet, A-68,47 New Scotland Ave, Albany, NY 12208 USA. FU NIAID NIH HHS [AI41690, AI32367]; NICHD NIH HHS [N01 HD033162, N01-HD33162] NR 34 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1998 VL 42 IS 9 BP 2326 EP 2331 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 116RB UT WOS:000075737400031 PM 9736557 ER PT J AU Walsh, TJ Yeldandi, V McEvoy, M Gonzalez, C Chanock, S Freifeld, A Seibel, NI Whitcomb, PO Jarosinski, P Boswell, G Bekersky, I Alak, A Buell, D Barret, J Wilson, W AF Walsh, TJ Yeldandi, V McEvoy, M Gonzalez, C Chanock, S Freifeld, A Seibel, NI Whitcomb, PO Jarosinski, P Boswell, G Bekersky, I Alak, A Buell, D Barret, J Wilson, W TI Safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) in neutropenic patients SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; BONE-MARROW TRANSPLANT; RECENT PROGRESS; TOXICITY; INFUSION; EXPERIENCE; MORTALITY; EFFICACY; RABBITS; TRIAL AB The safety, tolerance, and pharmacokinetics of a small unilamellar liposomal formulation of amphotericin B (AmBisome) administered for empirical antifungal therapy were evaluated for 36 persistently febrile neutropenic adults receiving cancer chemotherapy and bone marrow transplantation. The protocol was an open-label, sequential-dose-escalation, multidose pharmacokinetic study which enrolled a total of 8 to 12 patients in each of the four dosage cohorts. Each cohort received daily doses of either 1.0, 2.5, 5.0, or 7.5 mg of amphotericin B in the form of AmBisome/kg of body weight. The study population consisted of patients between the ages of 13 and 80 years with neutropenia (absolute neutrophil count, <500/mm(3)) who were eligible to receive empirical antifungal therapy. Patients were monitored for safety and tolerance by frequent laboratory examinations and the monitoring of infusion-related reactions. Efficacy was assessed by monitoring for the development of invasive fungal infection. The pharmacokinetic parameters of AmBisome were measured as those of amphotericin B by high-performance liquid chromatography. Noncompartmental methods were used to calculate pharmacokinetic parameters. AmBisome administered as a l-h infusion in this population was well tolerated and was seldom associated with infusion-related toxicity. Infusion-related side effects occurred in 15 (5%) of all 331 infusions, and only two patients (5%) required premedication. Serum creatinine, potassium, and magnesium levels,were not significantly changed from baseline in any of the dosage cohorts, and there was no net increase in serum transaminase levels. AmBisome followed a nonlinear dosage relationship that was consistent with reticuloendothelial uptake and redistribution. There were no breakthrough fungal infections during empirical therapy with AmBisome. AmBisome administered to febrile neutropenic patients in this study was well tolerated, was seldom associated,vith infusion-related toxicity, was characterized by nonlinear saturation kinetics, and was effective in preventing breakthrough fungal infections. C1 NCI, POB, IHS, Dept Nursing, Bethesda, MD 20892 USA. NCI, Med Branch, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Loyola Univ, Med Ctr, Chicago, IL 60611 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Walsh, TJ (reprint author), NCI, POB, IHS, Dept Nursing, Bldg 10,Rm 13N-240, Bethesda, MD 20892 USA. NR 30 TC 93 Z9 97 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1998 VL 42 IS 9 BP 2391 EP 2398 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 116RB UT WOS:000075737400043 PM 9736569 ER PT J AU Gonzalez, CE Groll, AH Giri, N Shetty, D Al-Mohsen, I Sein, T Feuerstein, E Bacher, J Piscitelli, S Walsh, TJ AF Gonzalez, CE Groll, AH Giri, N Shetty, D Al-Mohsen, I Sein, T Feuerstein, E Bacher, J Piscitelli, S Walsh, TJ TI Antifungal activity of the pradimicin derivative BMS 181184 in the treatment of experimental pulmonary aspergillosis in persistently neutropenic rabbits SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; BMS-181184; INFECTION; PROGRESS; INVITRO AB The activity of the pradimicin derivative EMS 181184 was evaluated in a model of invasive pulmonary aspergillosis in persistently neutropenic rabbits and compared with that of amphotericin B deoxycholate. EMS 181184 at total daily doses of 50 and 150 mg/kg of body weight was at least as effective as amphotericin B at 1 mg/kg once a day in conferring survival and had comparable activity in reducing organism-mediated tissue injury and excess lung weight. Although treatment at all dosing regimens of EMS 181184 resulted in significant reductions in fungal tissue burden compared to untreated controls, equivalence to amphotericin B occurred only at the higher dosage level. Similar observations were made in bronchoalveolar lavage fluid cultures obtained postmortem. Monitoring of the animals through ultrafast computerized tomography scan revealed a marked resolution of pulmonary lesions during treatment with EMS 181184. The compound was well tolerated at all dosing regimens, and no toxicity was noted. Pharmacokinetic studies revealed nonlinear drug disposition with increased clearance at higher dosages and some evidence for extravascular drug accumulation. EMS 181184 had excellent activity in the treatment of experimental invasive pulmonary aspergillosis in persistently neutropenic rabbits, thus underscoring the potential of pradimicin derivatives in therapy of invasive aspergillosis in the neutropenic host. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. Warren Grant Magnuson Clin Ctr, Pharmacokinet Res Lab, Dept Pharm, Bethesda, MD 20892 USA. NIH, Natl Ctr Res Resources, Surg Branch, Vet Resources Program, Bethesda, MD 20892 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bldg 10,room 13N240,10 Ctr Dr, Bethesda, MD 20892 USA. EM twalsh@pbmac.nci.nih.gov NR 31 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD SEP PY 1998 VL 42 IS 9 BP 2399 EP 2404 PG 6 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 116RB UT WOS:000075737400044 PM 9736570 ER PT J AU Liu, SY Redmond, TM AF Liu, SY Redmond, TM TI Role of the 3 '-untranslated region of RPE65 mRNA in the translational regulation of the RPE65 gene: Identification of a specific translation inhibitory element SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE retinal pigment epithelium; translational regulation; mRNA stability; 3 '-untranslated region; translation inhibitory element ID 3' UNTRANSLATED REGION; RETINAL-PIGMENT EPITHELIUM; MESSENGER-RNA STABILITY; IRON-RESPONSIVE ELEMENTS; BINDING-PROTEIN; MICROSOMAL PROTEIN; RICH SEQUENCES; STEM-LOOP; C-FOS; RECEPTOR AB Previously, we demonstrated that explanted bovine retinal pigment epithelium (RPE) cells lose RPE65 protein, a major microsomal protein specific to RPE, while the RPE65 mRNA remains, suggesting posttranscriptional regulation of RPE65 expression in vitro. Accordingly, we analyze here the effect of the 5'- and 3'-untranslated regions (UTRs) of RPE65 mRNA on translational efficiency using in vitro translation systems. We compared the levels of translation products and mRNA stability among RPE65 transcripts containing deletions of the 5'- and 3'-UTRs. First, the 5'-UTR does not affect translational efficiency, However, the 3'-UTR does influence translation efficiency. A putative translation inhibitory element (TIE) is contained within the 170-nucleotide (nt) sequence downstream of the stop codon, There is also a weak destabilizing effect that is associated with the region 3' to the putative TIE. But the effect of this is much less than that of the TIE. This TIE, however, does not inhibit translation of the heterologous chloramphenicol acetyltransferase gene, suggesting that a specific interaction with the upstream RPE65 coding sequence, or its product, may be required. Thus, the posttranscriptional regulation of RPE65 mRNA expression observed in cultured RPE may be via a mechanism of translational inhibition. C1 NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Liu, SY (reprint author), NEI, Retinal Cell & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM redmond@helix.nih.gov OI Redmond, T. Michael/0000-0002-1813-5291 NR 39 TC 18 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1998 VL 357 IS 1 BP 37 EP 44 DI 10.1006/abbi.1998.0817 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 116UB UT WOS:000075742300006 PM 9721181 ER PT J AU Luo, G Zeldin, DC Blaisdell, JA Hodgson, E Goldstein, JA AF Luo, G Zeldin, DC Blaisdell, JA Hodgson, E Goldstein, JA TI Cloning and expression of murine CYP2Cs and their ability to metabolize arachidonic acid SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cytochrome P450; CYP2Cs; mouse; cDNA cloning; cDNA expression; arachidonic acid metabolism; liver; extrahepatic; mRNA expression ID HUMAN LIVER-MICROSOMES; 12-HYDROXY-5,8,10,14-EICOSATETRAENOIC ACID; (S)-MEPHENYTOIN 4'-HYDROXYLASE; CYTOCHROME-P450 MONOOXYGENASE; ENANTIOFACIAL SELECTIVITY; EPOXYEICOSATRIENOIC ACIDS; MOLECULAR-CLONING; ESCHERICHIA-COLI; MEPHENYTOIN; SUBFAMILY AB Five murine cytochrome P450 (CYP) 2C cDNAs were cloned and characterized, including four new members of this subfamily: CYP2C37, CYP2C38, CYP2C39, and CYP2C40. The cDNAs ranged from 1716 to 1812 bp in length and encoded polypeptides of 490 amino acid residues except for CYP2C40, which contained an additional glutamic acid residue at the carboxyl terminus. The amino acid identity of the murine CYP2Cs ranged from 69 to 92%, while the overall amino acid identity was 60%; however, within the six putative substrate recognition sites the identity was only 25 to 41%, suggesting possible differences in substrate specificity and product profiles. The CYP2C cDNAs were expressed in Escherichia coli following modification of the N-terminus. All five recombinant CYP2Cs metabolized arachidonic acid, but with different metabolic profiles and catalytic rates. Based on coelution with authentic standards on reverse-phase HPLC, the major metabolites were tentatively identified as follows: CYP2C29 and CYP2C39 produced 14,15-cis-epoxyeicosatrienoic acid (EET); CYP2C37 produced 12-hydroxyeicosatetraenoic acid (HETE); CYP2C38 produced 11,12-EET; and CYP2C40 produced an unidentified metabolite that coeluted with 16-,17-, and 18-HETEs. The turnover numbers for CYP2C29, CYP2C37, CYP2C38, CYP2C39, and CYP2C40 were 0.34, 1.12, 5.15, 0.51, and 0.15 nmol/nmol/min, respectively. Reverse transcriptase-polymerase chain reaction demonstrated the presence of CYP2C29 mRNA in liver as well as in extrahepatic tissues including brain, kidney, lung, heart, and intestine. CYP2C38 and CYP2C40 were found in liver, brain, kidney, and intestine, with trace amounts in lung and heart, while CYP2C37 and CYP2C39 appeared to be liver specific. (C) 1998 Academic Press. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Pulm Pathobiol Lab, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27606 USA. RP NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. EM goldstein@niehs.nih.gov NR 62 TC 78 Z9 82 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1998 VL 357 IS 1 BP 45 EP 57 DI 10.1006/abbi.1998.0806 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 116UB UT WOS:000075742300007 PM 9721182 ER PT J AU Fang, B Hanover, JA Miller, MW AF Fang, B Hanover, JA Miller, MW TI An evaluation of sialation of the nucleoporin p62 SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE nuclear pore complex; N-acetylglucosamine; sialic acid; p62 ID NUCLEAR-PORE COMPLEX; LINKED N-ACETYLGLUCOSAMINE; INVITRO TRANSFER; PROTEIN P62; GLYCOPROTEINS; PHOSPHORYLATION; IDENTIFICATION; GLYCOSYLATION; SEQUENCE; EXTRACTS AB Many nuclear and cytosolic proteins are modified by single residues of O-linked N-acetyl-D-glucosamine. These include many proteins found in nuclear pore complexes required for transport of macromolecules between the nucleus and the cytoplasm. The best characterized pore glycoprotein, p62, mediates its function as one component of a protein complex essential for nuclear transport. Although p62 sugar residues are not essential for nuclear transport, they appear to oppose protein phosphorylation occurring at sites predicted to destabilize protein-protein interactions of the p62 complex. Recently, a p62-like protein isolated from mouse neuroblastoma cells was reported to be modified by both GlcNAc and sialic acid. As there is little precedent for nucleoplasmic sialation, the finding that a characterized nuclear pore protein is sialated is significant because it may regulate pore function. To assess the biological importance of p62 sialation, GlcNAc and sialic acid-specific lectins were used to examine the state of p62 glycosylation in cells commonly used to study nuclear transport: frog eggs and normal rat kidney and HeLa fibroblasts, In addition, four mouse neuroblastoma cell lines derived from the same tumor were examined. The glycosylation of p62 in these cells appears to involve only single O-linked GlcNAc moieties; no significant sialation was detected. (C) 1998 Academic Press. C1 Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Miller, MW (reprint author), Wright State Univ, Dept Biol Sci, Dayton, OH 45435 USA. EM mwmiller@wright.edu NR 32 TC 5 Z9 5 U1 1 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1998 VL 357 IS 1 BP 95 EP 100 DI 10.1006/abbi.1998.0767 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 116UB UT WOS:000075742300012 PM 9721187 ER PT J AU Peterkofsky, B Gosiewska, A Wilson, S Kim, YR AF Peterkofsky, B Gosiewska, A Wilson, S Kim, YR TI Phosphorylation of rat insulin-like growth factor binding protein-1 does not affect its biological properties SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE insulin-like growth factor; insulin-like growth factor binding proteins; phosphorylation; ligand affinity; DNA synthesis ID HUMAN AMNIOTIC-FLUID; VITAMIN-C-DEFICIENT; FASTED GUINEA-PIGS; CASEIN KINASE; BREFELDIN-A; IGF-I; GOLGI-APPARATUS; MAMMARY-GLAND; CELLS; IDENTIFICATION AB Insulin-like growth factors (IGFs) I and II stimulate growth and expression of specific genes through binding to cell membrane receptors. IGF binding proteins also bind IGF-1 with higher affinity than the receptor. They are found in the circulation and tissues and can modulate IGF actions. Human IGFBP-1 is phosphorylated on serine residues, which increases its affinity for IGF-1. An acidic, presumably phosphorylated, form of human IGFBP-1 inhibits IGF-1-stimulated DNA synthesis in cultured cells, while a less acidic, unphosphorylated form potentiates this function. Phosphorylation of human IGFBP-3, however, does not affect its affinity for IGF-1. Previously we found that multiple forms of rat IGFBP-1 are obtained by anion-exchange chromatography, raising the possibility that it also is phosphorylated, which led us to examine its properties. Phosphopeptide analysis of P-32-labeled, immunoprecipitated rat IGFBP-1 synthesized by H-4-II-EC3 rat hepatoma cells indicated that it is phosphorylated on two sites that were deduced to be ser107 and ser132 in the central nonconserved domain. Dephosphorylation of purified phosphorylated rat IGFBP-1 did not affect its affinity for IGF-1 or its specific binding activity, and the dephosphorylated form inhibited DNA synthesis in 3T3 cells. Incubation of cells labeled with radioactive proline in the presence of monensin and brefeldin A, which inhibit secretion at different sites, led to intracellular accumulation of the least phosphorylated form of rat IGFBP-1, but prevented further phosphorylation. The results suggested that phosphorylation occurs at two sites in cells, the cis-Golgi and the trans-Golgi network. In summary, these studies have shown that rat IGFBP-1 is phosphorylated on two sites by reactions that occur in different secretory organelles and that similar to human IGFBP-3, but unlike human IGFBP-1, phosphorylation does not affect its affinity for IGF-1. (C) 1998 Academic Press. C1 NCI, Biochem Lab, Bethesda, MD 20982 USA. RP NCI, Biochem Lab, Bethesda, MD 20982 USA. EM peterkob@dc37a.nci.nih.gov NR 40 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 1998 VL 357 IS 1 BP 101 EP 110 DI 10.1006/abbi.1998.0797 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 116UB UT WOS:000075742300013 PM 9721188 ER PT J AU Bradley, EH Wetle, T Horwitz, SM AF Bradley, EH Wetle, T Horwitz, SM TI The Patient Self-Determination Act and advance directive completion in nursing homes SO ARCHIVES OF FAMILY MEDICINE LA English DT Article ID CONTROLLED TRIAL; DURABLE POWER; HEALTH-CARE; LIFE; ATTITUDES; END; IMPLEMENTATION; OUTPATIENTS; PHYSICIANS; CAPACITY AB Objectives: To assess the prevalence of advance directives among nursing home residents before and after passage of the Patient Self-Determination Act (PSDA) and to identify factors associated with advance directive completion. Design: Prestudy and poststudy of nursing home admissions using medical record reviews and a companion cross-sectional survey of alert and oriented residents. Setting: Six nursing homes in Connecticut. Participants: Residents (N = 635) from 6 randomly chosen nursing homes in the greater Hartford and greater New Haven areas. Main Outcome Measures: The existence of a documented advance directive, the timing of advance directive completion, and reported reasons for completion and noncompletion. Results: The prevalence of advance directives documentation in nursing home medical records has increased significantly since the implementation of the PSDA (4.7% [14/300] before vs 34.7% [104/300] after PSDA; odds ratio, 10.84; P<.001). The increase in documented advance directives was significant after controlling for sociodemographic and health status factors (odds ratio, 11.5; P<.001). Residents admitted to the nursing homes from hospitals (vs from their home or other source), residents with more education, and residents paying privately for nursing home care (vs using Medicare or Medicaid benefits) were more likely to have documented advance directives. Younger residents (aged (75 years) were less likely than older residents to have completed a directive. Among the 35 interviewed residents, the most common reason for completing an advance directive was experience with a prolonged death of a friend or family member. Only 1 of the interviewed residents reported that the information provided under the PSDA at the time of admission was an important factor in choosing to complete an advance directive. Conclusions: Nearly 35% of the residents in the post-PSDA cohort had an advance directive documented in the medical record. Most residents with advance directives had completed them more than 6 months before the nursing home admission. The major effect of the PSDA for nursing homes has been to enhance the documentation of existing advance directives. Little evidence exists that providing advance directive information at the time of nursing home admission has enhanced the completion of an advance directive after admission. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Bradley, EH (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St, New Haven, CT 06520 USA. EM elizabeth.bradley@yale.edu FU AHRQ HHS [1T32HS00052] NR 49 TC 31 Z9 32 U1 6 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1063-3987 J9 ARCH FAM MED JI Arch. Fam. Med. PD SEP-OCT PY 1998 VL 7 IS 5 BP 417 EP 423 DI 10.1001/archfami.7.5.417 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 119TB UT WOS:000075912300007 PM 9755733 ER PT J AU Longstreth, WT Bernick, C Manolio, TA Bryan, N Jungreis, CA Price, TR AF Longstreth, WT Bernick, C Manolio, TA Bryan, N Jungreis, CA Price, TR CA Cardiovascular Hlth Study Collaborative Res Grp TI Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people - The cardiovascular health study SO ARCHIVES OF NEUROLOGY LA English DT Article ID SILENT CEREBRAL INFARCTION; RISK-FACTORS; DIABETES-MELLITUS; BRAIN INFARCTION; CAROTID STENOSIS; OLDER ADULTS; STROKE; DISEASE; ABNORMALITIES; HYPOTHESIS AB Objective: To identify risk factors for and functional consequences of lacunar infarct in elderly people. Methods: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years or older, in which 3660 participants underwent cranial magnetic resonance imaging (MRI). Neuroradiologists read scans in a standard fashion without any clinical information. lacunes were defined as subcortical areas consistent with infarcts measuring 3 to 20 mm. In cross-sectional analyses, clinical correlates were contrasted among groups defined by MRI findings. Results: Of the 3660 subjects who underwent MRI, 2529 (69%) were free of infarcts of any kind and 841 (23%) had 1 or more lacunes without other types present, totaling 1270 lacunes. For most of these 841 subjects, their lacunes were single (66%) and silent (89%), namely without a history of transient ischemic attack or stroke. In multivariate analyses, factors independently associated with lacunes were increased age, diastolic blood pressure, creatinine, and pack-years of smoking (listed in descending order of strength of association; for all, P<.005), as well as maximum internal carotid artery stenosis of more than 50% (odds ratio [OR], 1.81; P<.005), male sex (OR, 0.74; P<.005), and history of diabetes at entrance into the study (OR, 1.33; P<.05). Models for subgroups of single, multiple, silent, and symptomatic lacunes differed only minimally. Those with silent lacunes had more cognitive, upper extremity, and lower extremity dysfunction not recognized as stroke than those whose MRIs were free of infarcts. Conclusions: In this group of older adults, lacunes defined by MRI are common and associated with factors that likely promote or reflect small-vessel disease. Silent lacunes are also associated with neurologic dysfunction. C1 Univ Washington, Harborview Med Ctr, Dept Neurol, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. Univ Calif Davis, Dept Neurol, Davis, CA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Neuroradiol Div, Baltimore, MD 21205 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Neurol Surg, Pittsburgh, PA USA. Univ Maryland, Dept Neurol, Baltimore, MD 21201 USA. RP Longstreth, WT (reprint author), Univ Washington, Harborview Med Ctr, Dept Neurol, Box 359775,325 9th Ave, Seattle, WA 98104 USA. FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85086] NR 50 TC 312 Z9 323 U1 3 U2 10 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 SEP PY 1998 VL 55 IS 9 BP 1217 EP 1225 DI 10.1001/archneur.55.9.1217 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 117HD UT WOS:000075775100008 PM 9740116 ER PT J AU Tomita, H Egashira, K Kubo-Inoue, M Usui, M Koyanagi, M Shimokawa, H Takeya, M Yoshimura, T Takeshita, A AF Tomita, H Egashira, K Kubo-Inoue, M Usui, M Koyanagi, M Shimokawa, H Takeya, M Yoshimura, T Takeshita, A TI Inhibition of NO synthesis induces inflammatory changes and monocyte chemoattractant protein-1 expression in rat hearts and vessels SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE endothelium-derived factors; nitric oxide; remodeling; monocyte chemoattractant protein-1; macrophages ID ANGIOTENSIN-CONVERTING ENZYME; NITRIC-OXIDE SYNTHESIS; VASCULAR ENDOTHELIAL-CELLS; FACTOR-KAPPA-B; L-ARGININE; ATHEROSCLEROTIC LESIONS; CORONARY-ARTERY; SMOOTH-MUSCLE; MACROPHAGE INFILTRATION; CARDIOVASCULAR-SYSTEM AB We recently showed that chronic inhibition of NO synthesis by N-omega-nitro-L-arginine methyl ester (L-NAME) causes coronary vascular remodeling (ie, vascular fibrosis and medial thickening) in rats. To test the hypothesis that the inhibition of NO synthesis induces inflammatory changes in the heart, we characterized the inflammatory lesions that occurred during L-NAME administration and determined whether inflammation involved the induction of monocyte chemoattractant protein-1 (MCP-1) in vivo. During the first week of L-NAME administration to Wistar-Kyoto rats, we observed a marked infiltration of mononuclear leukocytes (ED1-positive macrophages) and fibroblast-like cells (alpha-smooth muscle actin-positive myofibroblasts) into the coronary vessels and myocardial interstitial areas. These inflammatory changes were associated with the expression of proliferating cell nuclear antigen and MCP-1 (both mRNA and protein). The areas affected by inflammatory changes, as well as the expression of MCP-1 mRNA, declined after longer (28 days) treatment with L-NAME and were replaced by vascular and myocardial remodeling. Our results support the hypothesis that the inhibition of NO synthesis induces inflammatory changes in coronary vascular and myocardial tissues and involves MCP-1 expression. Results also suggest that the early stages of inflammatory changes are important in the development of later-stage structural changes observed in rat hearts. C1 Kyushu Univ, Sch Med, Angiocardiol Res Inst, Fac Med,Higashi Ku, Fukuoka 8128582, Japan. Kumamoto Univ, Sch Med, Dept Pathol 2, Kumamoto 860, Japan. Natl Canc Inst, Immunobiol Lab, Immunopathol Sect, Frederick, MD USA. RP Egashira, K (reprint author), Kyushu Univ, Sch Med, Angiocardiol Res Inst, Fac Med,Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan. EM egashira@cardiol.med.kyushu-u.ac.jp RI U-ID, Kyushu/C-5291-2016 NR 48 TC 92 Z9 95 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD SEP PY 1998 VL 18 IS 9 BP 1456 EP 1464 PG 9 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 119VL UT WOS:000075918800014 PM 9743235 ER PT J AU Langford, CA Sneller, MC AF Langford, CA Sneller, MC TI Pulse versus oral cyclophosphamide in the treatment of Wegener's granulomatosis: comment on the article by Guillevin et al SO ARTHRITIS AND RHEUMATISM LA English DT Letter ID THERAPY C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Langford, CA (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 BP 1706 EP 1707 DI 10.1002/1529-0131(199809)41:9<1706::AID-ART29>3.0.CO;2-Z PG 2 WC Rheumatology SC Rheumatology GA 122HQ UT WOS:000076066400028 PM 9751111 ER PT J AU Baldwin, CT Joost, O Chaisson, C McAlindon, T Farrer, L Ordovas, J Schaefer, E Levy, D Myers, R Felson, D AF Baldwin, CT Joost, O Chaisson, C McAlindon, T Farrer, L Ordovas, J Schaefer, E Levy, D Myers, R Felson, D TI The type II collagen vitamin D receptor locus and osteoarthritis: The Framingham osteoarthritis study. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1915 BP S352 EP S352 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601914 ER PT J AU Caricchio, R D'Adamio, L Cohen, PL AF Caricchio, R D'Adamio, L Cohen, PL TI Fas, ceramide and serum withdrawal share a common apoptotic pathway. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAID, LCMI, NIH, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 22 BP S36 EP S36 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600023 ER PT J AU Casciola-Rosen, L Pluta, A Plotz, P Nagaraju, K Cox, A Morris, S Rosen, A AF Casciola-Rosen, L Pluta, A Plotz, P Nagaraju, K Cox, A Morris, S Rosen, A TI hPMS1 is a novel, frequently targeted myositis autoantigen which is cleaved by granzyme B but not by caspases during apoptosis. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. NIAMSD, Arthrit & Rheumatism Branch, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 570 BP S127 EP S127 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600571 ER PT J AU Centola, M Wood, G Farrell, C Kingma, DW Horwitz, M Mansfield, E Samuels, J Rosenberg, HF Malech, HL Kastner, D AF Centola, M Wood, G Farrell, C Kingma, DW Horwitz, M Mansfield, E Samuels, J Rosenberg, HF Malech, HL Kastner, D TI Tissue specificity and kinetics of FMF gene expression during hematopoiesis SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAID, LHD, Bethesda, MD 20892 USA. NIAMSD, ARB, Bethesda, MD 20892 USA. NCI, LP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1198 BP S232 EP S232 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601199 ER PT J AU Chen, EH Gadina, M O'Shea, JJ AF Chen, EH Gadina, M O'Shea, JJ TI Regulation of cell-mediated immunity: The role of STAT4 in IL-12 signaling. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMSD, Lymphocyte Cell Biol Sect, Arthrit & Rheumatism Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1582 BP S296 EP S296 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601581 ER PT J AU Clancy, RM Varneika, B Rediske, J Stoyanovsky, D Wink, D Abramson, SB AF Clancy, RM Varneika, B Rediske, J Stoyanovsky, D Wink, D Abramson, SB TI The nitric oxide (NO) paradox resolved by Angeli's salt: Tissue injury depends upon NO redox state. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. Hosp Joint Dis, New York, NY 10003 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Navartis Pharm Corp, Summit, NJ 07901 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 664 BP S143 EP S143 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215600665 ER PT J AU Danning, CL Illei, GG Lee, EG Boumpas, DT McInnes, IB AF Danning, CL Illei, GG Lee, EG Boumpas, DT McInnes, IB TI Characterization of psoriatic arthritis synovial membrane (PsA SM): Cytokine and cell activation marker expression. SO ARTHRITIS AND RHEUMATISM LA English DT Meeting Abstract C1 NIAMS, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD SEP PY 1998 VL 41 IS 9 SU S MA 1806 BP S333 EP S333 PG 1 WC Rheumatology SC Rheumatology GA 125AQ UT WOS:000076215601805 ER EF