FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lau, D Kleiner, DK Park, Y Vergalla, J Hoofnagle, JH AF Lau, D Kleiner, DK Park, Y Vergalla, J Hoofnagle, JH TI Flare of hepatitis B during alpha interferon therapy. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, PATHOL LAB, NIH, BETHESDA, MD 20892 USA. NIDDK, LIVER DIS SECT, BETHESDA, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1246 EP A1246 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704962 ER PT J AU Li, XM Jeffers, LJ Liu, HP Bernstein, D Garon, C Fischer, ER Scheffel, J Moore, B Reddy, KR deMedina, M Schiff, ER AF Li, XM Jeffers, LJ Liu, HP Bernstein, D Garon, C Fischer, ER Scheffel, J Moore, B Reddy, KR deMedina, M Schiff, ER TI Human megakaryoblastic leukemia cell line (MEG-01) is shedding hepatitis C virus. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV MIAMI, SCH MED, VAMC, DIV HEPATOL, MIAMI, FL USA. NIAID, ROCKY MT LABS, HAMILTON, MT 59840 USA. ABBOTT LABS, ABBOTT PK, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1251 EP A1251 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704979 ER PT J AU Marth, T Strober, W Kelsall, BL AF Marth, T Strober, W Kelsall, BL TI Systemic administration of antibodies to IL-12 enhances oral tolerance by augmentation of TGF beta secretion and T cell apoptosis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIAID, MUCOSAL IMMUN SECT, NIH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A958 EP A958 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73703812 ER PT J AU Martinez, V Cuttitta, F Tache, Y AF Martinez, V Cuttitta, F Tache, Y TI Central action of adrenomedullin to inhibit gastric emptying in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV CALIF LOS ANGELES, BRAIN RES INST, LOS ANGELES, CA 90024 USA. UNIV CALIF LOS ANGELES, DEPT MED, LOS ANGELES, CA 90024 USA. VET ADM MED CTR, CURE DIG DIS RES CTR, LOS ANGELES, CA 91343 USA. NCI, NIH, DCPC, BIOMARKERS & PREVENT RES BRANCH, ROCKVILLE, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1097 EP A1097 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704370 ER PT J AU Neurath, MF Kollias, G Duchmann, R Fuss, I Strober, W Meyer, KH AF Neurath, MF Kollias, G Duchmann, R Fuss, I Strober, W Meyer, KH TI Effects of antibodies to TNF-alpha on acute and chronic experimental colitis in mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV MAINZ, MED CLIN 1, IMMUNOL LAB, W-6500 MAINZ, GERMANY. HELLEN INST PASTEUR, ATHENS, GREECE. NIAID, NIH, LCI, MUCOSAL IMMUN SECT, BETHESDA, MD 20892 USA. RI Kollias, George/A-7079-2012 OI Kollias, George/0000-0003-1867-3150 NR 0 TC 5 Z9 5 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A979 EP A979 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73703897 ER PT J AU Pisegna, JR Tarasova, NI Kopp, JA Asico, LD Jose, P Farnsworth, DW Michejda, CJ Wank, SA AF Pisegna, JR Tarasova, NI Kopp, JA Asico, LD Jose, P Farnsworth, DW Michejda, CJ Wank, SA TI Postprandial changes in renal function are mediated by elevated serum gastrin acting at cholecystokinin type B receptors (CCKB--R) in the kidney SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, DIGEST DIS BRANCH, BETHESDA, MD USA. NIDDK, NIH, METAB DIS BRANCH, BETHESDA, MD USA. GEORGETOWN UNIV, WASHINGTON, DC USA. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD USA. NR 0 TC 10 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1106 EP A1106 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704406 ER PT J AU Pohl, M Poirot, SS Pisegna, JR Tarasova, NI Wank, SA AF Pohl, M Poirot, SS Pisegna, JR Tarasova, NI Wank, SA TI The carboxy-terminus of the cholecystokinin type B receptor (CCKBR), unlike that of the type A receptor (CCKAR) is essential for ligand-induced internalization SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, NIH, DDB, BETHESDA, MD USA. NCI, ABL, FREDERICK, MD 21701 USA. RI Poirot, Sandrine/D-5448-2017 NR 0 TC 1 Z9 1 U1 2 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1107 EP A1107 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704409 ER PT J AU Sonnenberg, A Everhart, JE AF Sonnenberg, A Everhart, JE TI Health impact of peptic ulcer in the United States. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDKD, BETHESDA, MD 20892 USA. UNIV NEW MEXICO, VET ADM MED CTR, ALBUQUERQUE, NM 87131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A40 EP A40 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73700155 ER PT J AU Stettler, C Tarasova, NI Farnsworth, DW Friess, H Zimmermann, A Flogerzi, B Halter, F Schmassmann, A AF Stettler, C Tarasova, NI Farnsworth, DW Friess, H Zimmermann, A Flogerzi, B Halter, F Schmassmann, A TI Gastrin/CCKB receptors are predominantly expressed in gastric cancer of the intestinal type. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 UNIV HOSP BERN, GASTROINTESTINAL UNIT, CH-3010 BERN, SWITZERLAND. UNIV HOSP BERN, DEPT VISCERAL SURG & TRANSPLANTAT, CH-3010 BERN, SWITZERLAND. UNIV BERN, INST PATHOL, BERN, SWITZERLAND. NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1122 EP A1122 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704470 ER PT J AU Stewart, CA Termanini, B Sutliff, VE Gibril, F Jensen, RT AF Stewart, CA Termanini, B Sutliff, VE Gibril, F Jensen, RT TI Assessment of the risk of iron malabsorption occurring in patients with Zollinger-Ellison syndrome (ZES) treated with long-term gastric antisecretory therapy. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, DIGEST DIS BRANCH, BETHESDA, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A264 EP A264 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73701050 ER PT J AU Sutliff, VE Doppman, JL Gibril, F Terminini, B Stewart, CA Jensen, RT AF Sutliff, VE Doppman, JL Gibril, F Terminini, B Stewart, CA Jensen, RT TI Growth rates of hepatic metastasis in patients with Zollinger-Ellison syndrome (ZES). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, BETHESDA, MD USA. NIH, DEPT RADIOL, BETHESDA, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A433 EP A433 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73701722 ER PT J AU Tarasova, N Czerwinski, G Wank, S Schmidt, B Hernandez, L Michejda, C AF Tarasova, N Czerwinski, G Wank, S Schmidt, B Hernandez, L Michejda, C TI Delivery of cytotoxic chemical agents into cells through gastrin/CCK-B and CCK-A receptors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, MOLEC ASPECTS DRUG DESIGN SECT, FREDERICK, MD 21702 USA. NIDDK, NIH, BETHESDA, MD USA. CARNEGIE MELLON UNIV, PITTSBURGH, PA 15213 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1125 EP A1125 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704481 ER PT J AU Tarasova, NI Shen, RL Oskarsson, M Hudson, EA Resau, JH Smoot, D daSilva, PP Michejda, CJ Woude, GV AF Tarasova, NI Shen, RL Oskarsson, M Hudson, EA Resau, JH Smoot, D daSilva, PP Michejda, CJ Woude, GV TI Cellular localization of met and its ligand hepatocyte growth factor scatter factor in human stomach epithelium. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NCI, FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. HOWARD UNIV HOSP, DEPT MED, DIV GASTROENTEROL, WASHINGTON, DC USA. NCI, FREDERICK CANC RES & DEV CTR, MEMBRANE BIOL SECT, FREDERICK, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1125 EP A1125 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704480 ER PT J AU Termanini, B Gibril, F Doppman, JH Stewart, CA Sutliff, VE Jensen, RT AF Termanini, B Gibril, F Doppman, JH Stewart, CA Sutliff, VE Jensen, RT TI Somatostatin receptor scintigraphy (SRS), a new method to distinguish hepatic hemangiomas from vascular liver metastases in pancreatic endocrine tumors (PET). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIH, BETHESDA, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A437 EP A437 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73701739 ER PT J AU Tsuda, T Jensen, RT AF Tsuda, T Jensen, RT TI Neuromedin B causes tyrosine phosphorylation (TYR-P) of p125 focal adhesion kinase (p125(FAK)) through a Ca2+- and PKC-independent mechanism which is partially mediated by the small GTP-binding protein SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDDK, DIGEST DIS BRANCH, NIH, BETHESDA, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1127 EP A1127 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704489 ER PT J AU Weber, HC Battey, JF Jensen, RT AF Weber, HC Battey, JF Jensen, RT TI Cyclic AMP and dexamethasone can regulate the promoter activity of the murine gastrin-releasing peptide receptor gene in Swiss 3T3 cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NIDCD, NIH, BETHESDA, MD USA. NIDDK, DIGEST DIS BRANCH, BETHESDA, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1132 EP A1132 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73704509 ER PT J AU Wiener, SM Hoyt, RF DeLeonardis, JR Clevenger, RR Eckhaus, M Owens, J Kotin, RM Safer, B AF Wiener, SM Hoyt, RF DeLeonardis, JR Clevenger, RR Eckhaus, M Owens, J Kotin, RM Safer, B TI Organ-specific gene transfer to murine hepatobiliary and pancreatic tissues in vivo. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 NHLBI, BETHESDA, MD 20892 USA. NIH, NATL CTR RES RESOURCES, BETHESDA, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1996 VL 110 IS 4 SU S BP A1360 EP A1360 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UF737 UT WOS:A1996UF73705416 ER PT J AU Dawsey, SM Fleischer, DE Wang, GQ Kidwell, JA Zhou, B Lewin, KJ AF Dawsey, SM Fleischer, DE Wang, GQ Kidwell, JA Zhou, B Lewin, KJ TI Lugol's staining improves endoscopic detection of esophageal squamous dysplasia and cancer in high-risk Chinese patients. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. UNIV CALIF LOS ANGELES,CTR HLTH SCI,LOS ANGELES,CA 90024. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1996 VL 43 IS 4 BP 169 EP 169 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UH281 UT WOS:A1996UH28100169 ER PT J AU Fleischer, DE Wang, GQ Dawsey, SM Tio, TL Kidwell, JA AF Fleischer, DE Wang, GQ Dawsey, SM Tio, TL Kidwell, JA TI Endoscopic therapy for early esophageal cancer (EEC) and dysplasia (D). SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. CHCAMS,BEIJING,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1996 VL 43 IS 4 BP 180 EP 180 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UH281 UT WOS:A1996UH28100180 ER PT J AU Roth, M Liu, S Solomon, D Zhou, B Copeland, C Wang, G Dawsey, S AF Roth, M Liu, S Solomon, D Zhou, B Copeland, C Wang, G Dawsey, S TI Cytologic detection of esophageal squamous dysplasia and cancer using esophageal balloon and sponge samplers in Linxian, China. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. CHINESE ACAD MED SCI,INST CANC,BEIJING 100021,PEOPLES R CHINA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1996 VL 43 IS 4 BP 215 EP 215 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UH281 UT WOS:A1996UH28100215 ER PT J AU Weber, HC Lubensky, I Jensen, RT Tucker, M Lin, A AF Weber, HC Lubensky, I Jensen, RT Tucker, M Lin, A TI Endoscopic and histopathologic features of gastrointestinal polyps in Cowden's disease. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 NIDDK,DIGEST DIS BRANCH,BETHESDA,MD. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1996 VL 43 IS 4 BP 282 EP 282 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UH281 UT WOS:A1996UH28100282 ER PT J AU Tio, TL Dawsey, SM WAng, GO Fleischer, DE Roth, MJ Xio, YX Kidwell, JA Wang, H AF Tio, TL Dawsey, SM WAng, GO Fleischer, DE Roth, MJ Xio, YX Kidwell, JA Wang, H TI Endoscopic ultrasonography (EUS) in staging of early esophageal cancer (EEC) in Linxian, China: Preliminary results. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 GEORGETOWN UNIV,MED CTR,WASHINGTON,DC 20007. NCI,BETHESDA,MD 20892. CHINESE ACAD MED SCI,CANC HOSP,BEIJING 100037,PEOPLES R CHINA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1996 VL 43 IS 4 BP 562 EP 562 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UH281 UT WOS:A1996UH28100562 ER PT J AU Schrock, E Blume, C Meffert, MC duManoir, S Bersch, W Kiessling, M Lozanowa, T Thiel, G Witkowski, R Ried, T Cremer, T AF Schrock, E Blume, C Meffert, MC duManoir, S Bersch, W Kiessling, M Lozanowa, T Thiel, G Witkowski, R Ried, T Cremer, T TI Recurrent gain of chromosome arm 7q in low-grade astrocytic tumors studied by comparative genomic hybridization SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN GLIOMAS; GENE AB Consistent tumor-specific chromosomal aberrations have not been described in low-grade astrocytic tumors. The most frequent genetic alterations are mutations of the TP53 tumor suppressor gene and/or loss of heterozygosity (LOH) on 17p that occur in about 30% of the cases in adult patients but that are uncommon in childhood tumors. We used comparative genomic hybridization (CGH) to map DNA copy number alterations in 18 primary low-grade astrocytic tumors (ten adult patients and eight children). A gain of chromosome arm 79 was the most frequent event detected in five of ten astrocytomas (50%) from adult patients, followed by DNA amplification on chromosome arm 8q and gain on 12p (two cases). Loss of chromosomal regions on 1p, 4q, and the X chromosome was observed in two of ten cases each [including one patient afflicted with Turner syndrome (45,X)]. In contrast, no consistent changes were observed in low-grade astrocytomas in children. A loss of the X chromosome was the sole aberration detected in two of eight cases using DNA extracted from normal brain tissue. The findings suggest that a gain of 79 is an early event in the initiation of astrocytomas in adult patients. The discrepant findings in low-grade astrocytic tumors in adults compared to tumors in children support the hypothesis that there might be different mechanisms responsible for tumor development. (C) 1996 Wiley-Liss, Inc. C1 UNIV HEIDELBERG,INST HUMAN GENET,HEIDELBERG,GERMANY. INST PATHOL,SPEYER,GERMANY. UNIV HEIDELBERG,INST NEUROPATHOL,HEIDELBERG,GERMANY. HUMBOLDT UNIV BERLIN,INST MED GENET,BERLIN,GERMANY. RP Schrock, E (reprint author), NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,49 CONVENT DR,BETHESDA,MD 20892, USA. NR 16 TC 79 Z9 80 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 1996 VL 15 IS 4 BP 199 EP 205 DI 10.1002/(SICI)1098-2264(199604)15:4<199::AID-GCC1>3.0.CO;2-X PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UD383 UT WOS:A1996UD38300001 PM 8703845 ER PT J AU Ried, T Knutzen, R Steinbeck, R Blegen, H Schrock, E Heselmeyer, K duManoir, S Auer, G AF Ried, T Knutzen, R Steinbeck, R Blegen, H Schrock, E Heselmeyer, K duManoir, S Auer, G TI Comparative genomic hybridization reveals a specific pattern of chromosomal gains and losses during the genesis of colorectal tumors SO GENES CHROMOSOMES & CANCER LA English DT Article ID MOLECULAR CYTOGENETIC ANALYSIS; INSITU HYBRIDIZATION; KIDNEY TISSUE; SOLID TUMORS; IDENTIFICATION; CARCINOMA; CANCERS AB Comparative genomic hybridization was used to screen the DNA extracted from histologically defined tissue sections from consecutive stages of colorectal carcinogenesis for chromosomal aberrations. No aberrations were detected in normal epithelium (n = 14). Gain of chromosome 7 occurred as a single event in low-grade adenomas (n = 14). In high-grade adenomas (n = 12), an overrepresentation of chromosomes 7 and 20 was present in 30% of the cases analyzed. The transition to colon carcinomas (n = 16) was characterized by the emergence of multiple chromosomal aberrations. Chromosomes 1, 13, and 20 and chromosome arms 7p and 8q were frequently gained, whereas chromosome 4 and chromosome arms 8p and 18q were recurrently underrepresented. The same tissue sections that were used for CGH were analyzed by means of DNA-ploidy measurements and immunohistochemical staining to quantify proliferative activity and p21/WAF-I and TP53 expression. We observed that crude aneuploidy and increased proliferative activity are early events in colorectal carcinogenesis, followed by TP53 overexpression and the acquisition of recurrent chromosomal gains and losses during the progression from high-grade adenomas to invasive carcinomas. (C) 1996 Wiley-Liss, Inc. C1 KAROLINSKA HOSP & INST,DEPT PATHOL,STOCKHOLM,SWEDEN. INST PATHOL,FLENSBURG,GERMANY. RP Ried, T (reprint author), NIH,NCHGR,DIAGNOST DEV BRANCH,BLDG 49,RM 4A28,49 CONVENT DR,MSC 4470,BETHESDA,MD 20892, USA. NR 30 TC 292 Z9 298 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 1996 VL 15 IS 4 BP 234 EP 245 DI 10.1002/(SICI)1098-2264(199604)15:4<234::AID-GCC5>3.3.CO;2-Y PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA UD383 UT WOS:A1996UD38300005 PM 8703849 ER PT J AU Godley, LA Kopp, JB Eckhaus, M Paglino, JJ Owens, J Varmus, HE AF Godley, LA Kopp, JB Eckhaus, M Paglino, JJ Owens, J Varmus, HE TI Wild-type p53 transgenic mice exhibit altered differentiation of the ureteric bud and possess small kidneys SO GENES & DEVELOPMENT LA English DT Article DE p53; transgenic mice; kidney development; ureteric bud ID BINDING-PROTEIN; APOPTOSIS; GLOMERULOSCLEROSIS; TRANSFORMATION; TRANSCRIPTION; EXPRESSION; MUTANT; GENE AB Transgenic mice expressing wild-type murine p53 under the control of the mouse mammary tumor virus long terminal repeat (MMTV LTR) undergo progressive renal failure due to abnormal kidney development. Similar phenotypes are observed in two transgenic lines that express wild-type p53 within the ureteric bud but not in transgenic animals expressing a dominant-negative p53 mutant allele. Defective differentiation of the ureteric bud, as evidenced by altered marker expression during development, accompanies expression of the p53 transgene. At E17.5-18.5, metanephric mesenchymal cells undergo high rates of apoptosis, and fewer cells than normal are converted to tubular epithelium. As a result, p53 transgenic kidneys grow to only half of their expected size and contain about half of the normal number of nephrons, with compensatory hypertrophy of the glomeruli. In this setting, rather than arrest the cell cycle or induce apoptosis directly, abnormally high levels of wild-type p53 appear to alter cellular differentiation in embryonic ureteric buds and cause secondary effects (apoptosis and inefficient conversion to epithelium) in the adjacent undifferentiated mesenchyme. C1 NCI,VARMUS LAB,NIH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM & BIOPHYS,SAN FRANCISCO,CA 94143. NIDDKD,METAB DIS BRANCH,KIDNEY DIS SECT,NIH,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL & IMMUNOL,SAN FRANCISCO,CA 94143. NIH,NATL CTR RES RESOURCES,VET RESOURCES PROGRAM,BETHESDA,MD 20892. NIH,OFF DIRECTOR,BETHESDA,MD 20892. NR 54 TC 99 Z9 101 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 1996 VL 10 IS 7 BP 836 EP 850 DI 10.1101/gad.10.7.836 PG 15 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA UE558 UT WOS:A1996UE55800006 PM 8846920 ER PT J AU McGuire, RE Jordan, SA Braden, VV Bouffard, GG Humphries, P Green, ED Daiger, SP AF McGuire, RE Jordan, SA Braden, VV Bouffard, GG Humphries, P Green, ED Daiger, SP TI Mapping the RP10 locus for autosomal dominant retinitis pigmentosa on 7q: Refined genetic positioning and localization within a well-defined YAC contig SO GENOME RESEARCH LA English DT Article ID ARTIFICIAL-CHROMOSOME VECTORS; HUMAN GENOME; YEAST; CONSTRUCTION; LIBRARY; DNA AB Retinitis pigmentosa is a genetically heterogeneous disease that has autosomal dominant, autosomal recessive and X-linked forms. Autosomal dominant retinitis pigmentosa (adRP) has thus far been associated with eight distinct loci, including the rhodopsin and peripherin/RDS genes as well as unidentified genes on chromosomes 7p, 7q, 8q, 17p, 17q, and 19q, The RP10 locus for adRP on chromosome 7q was first mapped in a Spanish family; later, an unrelated American family was identified that also showed linkage to 7q. By combining the linkage results from both families, we are able to assign the disease gene to a 5-cM interval on 7q. Based on extensive physical mapping of this region, the genetic interval is now fully contained within a similar to 5-Mb segment on a well-defined YAC contig. These studies significantly reduce the size of the RP10 critical region, exclude a number of possible candidate genes, and provide the necessary cloned DNA For the positional cloning of the RP10 gene. C1 UNIV TEXAS, HLTH SCI CTR, SCH PUBL HLTH, CTR HUMAN GENET, HOUSTON, TX 77030 USA. UNIV TEXAS, HLTH SCI CTR, DEPT OPHTHALMOL & VISUAL SCI, HOUSTON, TX 77030 USA. UNIV DUBLIN TRINITY COLL, DEPT GENET, WELLCOME OCULAR GENET UNIT, DUBLIN 2, IRELAND. NIH, NATL CTR HUMAN GENOME RES, BETHESDA, MD 20892 USA. FU NEI NIH HHS [R01 EY007142, EY07024] NR 28 TC 16 Z9 16 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD APR PY 1996 VL 6 IS 4 BP 255 EP 266 DI 10.1101/gr.6.4.255 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UJ014 UT WOS:A1996UJ01400003 PM 8723719 ER PT J AU Pathak, BG Shaughnessy, JD Meneton, P Greeb, J Shull, GE Jenkins, NA Copeland, NG AF Pathak, BG Shaughnessy, JD Meneton, P Greeb, J Shull, GE Jenkins, NA Copeland, NG TI Mouse chromosomal location of three epithelial sodium channel subunit genes and an apical sodium chloride cotransporter gene SO GENOMICS LA English DT Article ID EXPRESSION AB The amiloride-sensitive epithelial sodium channel alpha, beta, and gamma subunit genes, Scnn1a, Scnn1b, and Scnn1g, and the thiazide-sensitive sodium chloride cotransporter gene, Slc12a1, have been mapped in the mouse using an interspecific backcross panel. These loci map to previously defined homologous regions between human and mouse chromosomes and provide additional information regarding human/mouse comparative mapping. (C) 1996 Academic Press, Inc. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. UNIV CINCINNATI,COLL MED,DEPT MOLEC GENET BIOCHEM & MICROBIOL,CINCINNATI,OH 45267. FU NHLBI NIH HHS [HL 41496] NR 18 TC 18 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1996 VL 33 IS 1 BP 124 EP 127 DI 10.1006/geno.1996.0168 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UF102 UT WOS:A1996UF10200016 PM 8617496 ER PT J AU Mahata, SK Kozak, CA Szpirer, J Szpirer, C Modi, WS Gerdes, HH Huttner, WB OConnor, DT AF Mahata, SK Kozak, CA Szpirer, J Szpirer, C Modi, WS Gerdes, HH Huttner, WB OConnor, DT TI Dispersion of chromogranin secretogranin secretory protein family loci in mammalian genomes SO GENOMICS LA English DT Article ID A GENE; MOUSE; RAT; ASSIGNMENT; PEPTIDES; HYBRIDIZATION; CHROMOSOME-14; ORGANIZATION; ALZHEIMER; SEQUENCE AB Chromogranin A, chromogranin B, and secreto-granin II, members of the chromogranin/secretogranin secretory protein family, are overexpressed in some human hereditary maladies and may have arisen, in part, from common ancestor genes. To understand better the mammalian chromosomal dispersion of this gene family and to facilitate studies of these genes in human illnesses and their animal models, we positioned the locus of each member in the rat, mouse, and human genomes. Our results indicate that each locus lies in a region of locally syntenic chromosomal homology across the three species. (C) 1996 Academic Press, Inc. C1 UNIV CALIF SAN DIEGO,DEPT MED 9111H,SAN DIEGO,CA 92161. UNIV CALIF SAN DIEGO,CTR GENET MOLEC,SAN DIEGO,CA 92161. DEPT VET AFFAIRS MED CTR,SAN DIEGO,CA 92161. FREE UNIV BRUSSELS,DEPT BIOL MOLEC,B-1640 RHODE ST GENESE,BELGIUM. NIAID,MOLEC MICROBIOL LAB,NIH,BETHESDA,MD 20892. NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,FCRDC,FREDERICK,MD 21701. UNIV HEIDELBERG,INST NEUROBIOL,HEIDELBERG,GERMANY. NR 46 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1996 VL 33 IS 1 BP 135 EP 139 DI 10.1006/geno.1996.0171 PG 5 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UF102 UT WOS:A1996UF10200019 PM 8617499 ER PT J AU Lennon, G Auffray, C Polymeropoulos, M Soares, MB AF Lennon, G Auffray, C Polymeropoulos, M Soares, MB TI The IMAGE consortium: An integrated molecular analysis of genomes and their expression SO GENOMICS LA English DT Article ID HYBRIDIZATION C1 CNRS,F-94801 VILLEJUIF,FRANCE. GENEXPRESS,EVRY,FRANCE. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. COLUMBIA UNIV,DEPT PSYCHIAT,NEW YORK,NY 10032. RP Lennon, G (reprint author), LAWRENCE LIVERMORE NATL LAB,CTR HUMAN GENOME,L452,LIVERMORE,CA 94550, USA. NR 8 TC 1074 Z9 1081 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD APR 1 PY 1996 VL 33 IS 1 BP 151 EP 152 DI 10.1006/geno.1996.0177 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UF102 UT WOS:A1996UF10200025 PM 8617505 ER PT J AU Riley, MW AF Riley, MW TI Discussion: What does it all mean? SO GERONTOLOGIST LA English DT Editorial Material DE life-course reductionism; aging and society paradigm; dialectical interplay AB Offsetting the current tendency toward ''life-course reductionism,'' insights from these papers illustrate a broader (''aging and society'') paradigm - one that includes the life-course perspective, but also complements it with deeper understanding of the dialectical interplay between changes in lives and changes in the surrounding social structures. RP Riley, MW (reprint author), NIA,NIH,7201 WISCONSIN AVE,BETHESDA,MD 20892, USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD APR PY 1996 VL 36 IS 2 BP 256 EP 258 PG 3 WC Gerontology SC Geriatrics & Gerontology GA UL780 UT WOS:A1996UL78000018 PM 8920097 ER PT J AU PerezOtano, I McMillian, NK Chen, J Bing, GY Hong, JS Pennypacker, KR AF PerezOtano, I McMillian, NK Chen, J Bing, GY Hong, JS Pennypacker, KR TI Induction of NF-kB-like transcription factors in brain areas susceptible to kainate toxicity SO GLIA LA English DT Article DE NF-kB; astrocytes; gliosis; hippocampus; transcription ID FACTOR KAPPA-B; GENE-EXPRESSION; MAMMALIAN BRAIN; KAINIC ACID; RAT CORTEX; ASTROCYTES; INTERLEUKIN-1; CELLS; SEIZURES; DISEASE AB Administration of kainate (KA), a glutamate receptor agonist, to rats causes neuronal damage in the CA1/CA3 fields of the hippocampus and in the pyriform/ entorhinal cortex. Reactive gliosis also occurs and activated astrocytes upregulate their expression of a large number of molecules. Since NF-kB transcription factors are involved in cellular responses to diverse pathogenic stimuli and have been shown to be induced in astrocytes in vitro in response to cytokines and growth factors, we investigated their possible involvement in the changes in gene expression subsequent to KA-induced lesions. Immunoreactivity to the p65 subunit of NF-kB was markedly increased in non-neuronal cells 2 days after KA administration (8 mg/kg i.p.) in the areas pf selective neuronal degeneration. This increase was not observed 3 h or 1 day after injection, but was still present 7-10 days after KA injection. By gel mobility-shift assay, a protein complex binding to the kB consensus sequence was found to be induced by 2 days after KA, which correlated with immunohistochemical findings. This NF-kB-protein complex seemed to be localized in reactive astrocytes, as indicated by the morphological similarity of NF-kB-positive cells and reactive astrocytes stained with glial fibrillary acidic protein (GFAP) antibody, and the parallelism between the time course of NF-kB induction and appearance of gliosis after KA treatment. Double immunocytochemistry experiments demonstrated the colocalization of NF-kB positive cells and reactive astrocytes. Our results suggest that activated NF-kB in astrocytes participates in delayed and long-term responses of glia to injury. (C) 1996 Wiley-Liss, Inc. C1 NIEHS,NEUROPHARMACOL SECT,NIH,RES TRIANGLE PK,NC 27709. RI Pennypacker, Keith/I-5092-2012; OI Bing, Guoying/0000-0003-0609-8152 NR 38 TC 67 Z9 67 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0894-1491 J9 GLIA JI Glia PD APR PY 1996 VL 16 IS 4 BP 306 EP 315 DI 10.1002/(SICI)1098-1136(199604)16:4<306::AID-GLIA3>3.0.CO;2-Y PG 10 WC Neurosciences SC Neurosciences & Neurology GA UC631 UT WOS:A1996UC63100003 PM 8721671 ER PT J AU Trimble, EL Rubinstein, LV Menck, HR Hankey, BF Kosary, C Giusti, RM AF Trimble, EL Rubinstein, LV Menck, HR Hankey, BF Kosary, C Giusti, RM TI Vaginal clear cell adenocarcinoma in the United States SO GYNECOLOGIC ONCOLOGY LA English DT Article ID CERVIX; DIETHYLSTILBESTROL; CANCER AB We elected to examine available information from several sources to approximate the annual number of cases of vaginal adenocarcinoma in the United States for recent years. Data were obtained from the Registry on Hormonal Transplacental Carcinogenesis, the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute, the National Cancer Databank of the American College of Surgeons Commission on Cancer, and a survey of gynecologic oncologists practicing in the United States. In 1990 a total of 33 new cases and 11 recurrences were reported, while in 1991 23 new cases and 8 recurrences were reported. Neither SEER nor the Registry appear to provide adequate surveillance for this rare disease. Phase III clinical trials are not feasible, given the small number of patients. Statistically effective phase II one-armed studies to investigate new agents in the treatment of advanced or recurrent vaginal clear cell cancer may be possible. Effective mobilization of patients and physicians will be required for such trials to be completed in a timely manner. (C) 1996 Academic Press, Inc. C1 AMER COLL SURGEONS,COMMISS CANC,CHICAGO,IL. RP Trimble, EL (reprint author), NCI,6130 EXECUT BLVD,SUITE 241,ROCKVILLE,MD 20852, USA. NR 13 TC 9 Z9 9 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 1996 VL 61 IS 1 BP 113 EP 115 DI 10.1006/gyno.1996.0107 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA UC961 UT WOS:A1996UC96100022 PM 8626097 ER PT J AU McFall, SL Warnecke, RB Kaluzny, AD Ford, L AF McFall, SL Warnecke, RB Kaluzny, AD Ford, L TI Practice setting and physician influences on judgments of colon cancer treatment by community physicians SO HEALTH SERVICES RESEARCH LA English DT Article DE colonic neoplasms; therapy; practice characteristics; medical decision making ID ADJUVANT THERAPY; IMPACT AB Objective. This article compares judgments about the treatment of Dukes' B2 and C colon cancer made by general surgeons to those of internists and family practitioners. Physician and practice variables were specialty, affiliation with a Community Clinical Oncology Program (CCOP) hospital, time in practice, professional centrality (level of participation in cancer information networks), solo practice, and number of colon cancer patients. Data Collection Methods. Data are combined from national probability samples of CCOP- and non-CCOP-affiliated physicians. This study focused on 1,138 internists, family physicians, and general surgeons who participated in decision making for patients diagnosed with Dukes' B2 or C stage colon cancer. Judgments were elicited using brief vignettes. Methods of Analysis. Judgments of adjuvant therapy are classified as (a) consistent with the National Institutes of Health Consensus Conference recommendations (experimental for Dukes' B2, accepted for Dukes' C); (b) accepted treatment for both stages; or (c) experimental for both stages. Multinomial legit analyses were used to examine the association of practice setting and physician characteristics to judgments of treatment. Results. Surgeons and CCOP-affiliated physicians were more likely to endorse the NIH consensus conference position. Surgeons, younger physicians, and those in group practice were more likely to approve of chemotherapy for both cancer stages. The most common position (chemotherapy experimental) was more likely from nonsurgeons, solo practitioners, and non-CCOP physicians. Conclusion. Physician and practice setting characteristics, including organized structures such as the CCOP, are possible mediating structures that can facilitate dissemination of standards of treatment. C1 UNIV ILLINOIS,SURVEY RES LAB,CHICAGO,IL. UNIV N CAROLINA,SCH PUBL HLTH,CHAPEL HILL,NC. UNIV N CAROLINA,CECIL G SHEPS CTR HLTH SERV RES,CHAPEL HILL,NC. NATL CANC INST,DIV CANC PREVENT & CONTROL,COMMUNITY ONCOL & REHABIL BRANCH,BETHESDA,MD. RP McFall, SL (reprint author), UNIV OKLAHOMA,HLTH SCI CTR,HLTH PROMOT SCI DEPT,POB 26901,OKLAHOMA CITY,OK 73190, USA. NR 21 TC 18 Z9 18 U1 0 U2 3 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 1996 VL 31 IS 1 BP 5 EP 19 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA UG616 UT WOS:A1996UG61600002 PM 8617610 ER PT J AU Mizuta, K Iwasa, KH Simonds, WF Tachibana, M AF Mizuta, K Iwasa, KH Simonds, WF Tachibana, M TI Ultrastructural localization of G-protein G(s) in the lateral wall of the guinea pig cochlear duct SO HEARING RESEARCH LA English DT Article DE G(s) protein; C-terminal peptide (RMHLRQYELL); immunocytochemistry; post-embedding immunogold; Lowicryl K4M; stria vascularis; Reissner's membrane ID ADENYLATE-CYCLASE; INNER-EAR; NONSELECTIVE CATION; STRIA VASCULARIS; ALPHA-SUBUNITS; BINDING-SITES; CL CHANNELS; RAT-KIDNEY; VASOPRESSIN; STIMULATION AB Immunocytochemical localization of a GTP-binding protein, G(s), in the various cells of the-lateral wall of guinea pig cochlear duct was investigated using a post-embedding immunogold method with antibody raised against a synthetic decapeptide (RMHLRQYELL) encoding the C-terminus of the alpha-subunit of G(s). In the stria vascularis, labeling was observed on the basolateral membrane infoldings of marginal cells, on the juxtaposed membrane of intermediate cells, and on the cell membrane of basal cell. In contrast, no significant labeling was observed on the luminal membrane of marginal cells. Immunoreactivity also was detected on the cell membranes of various other cells. These include spiral prominence epithelial cells, fibrocytes of spiral ligament, external sulcus cells, and epithelial and mesothelial cells of Reissner's membrane. Adenylylcyclase has been functionally implicated in some of the cell types with membranes labeled in this study. The significance of these findings is briefly discussed. C1 NIDOCD,LAB CELLULAR BIOL,BETHESDA,MD 20892. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NIDOCD,MOLEC GENET LAB,BETHESDA,MD 20892. OI Iwasa, Kuni/0000-0002-9397-7704 NR 35 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD APR PY 1996 VL 93 IS 1-2 BP 111 EP 119 DI 10.1016/0378-5955(95)00202-2 PG 9 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA UL655 UT WOS:A1996UL65500007 PM 8735072 ER PT J AU Tiberghien, P Cahn, JY Contassot, E Ferrand, C Reynolds, CW Herve, P AF Tiberghien, P Cahn, JY Contassot, E Ferrand, C Reynolds, CW Herve, P TI Gene transfer applied to the modulation of alloreactivity SO HEMATOLOGY AND CELL THERAPY LA English DT Article; Proceedings Paper CT 4th Cell Therapy Workshop CY OCT 19-20, 1995 CL MARSEILLE, FRANCE SP AMGEN ROCHE ID MARROW TRANSPLANTATION; HOST-DISEASE; ACUTE GRAFT; LEUKEMIA; DONORS AB Allogeneic hematopoietic stem cell transplantation is associated with a severe complication induced by the T-cells present in the graft: graft-vs-host disease (GVHD). While effectively preventing GVHD, ex vivo T-lymphocyte depletion of the graft unfortunately increases graft rejection and reduces the graft-vs-leukemia (GVL) effect. The ex vivo transfer of the herpes simplex thymidine kinase (HS-tk) suicide gene into T-cells before their infusion with the hematopoietic stem cells should allow for selective in vivo depletion of these T-cells with ganciclovir (GCV) if subsequent GVHD was to occur. In patients not experiencing GVHD, and therefore at a higher risk of relapse, one could preserve the beneficial effects of the donor T-cells on tumor control. Lastly, the early presence of donor T-cells in all patients should contribute to successful engraftment. We have demonstrated that retroviral-mediated transfer of HS-tk and Neomycine resistance genes in T-lymphocytes, followed by G418 selection, results in T-cells specifically inhibited by GCV with no bystander effect. In a phase I study, escalating amounts of HS-tk expressing T-cells will be infused in conjunction with a T-cell depleted marrow graft to allogeneic HLA identical recipients. Toxicity, survival, alloreactivity and GCV-sensitivity of the gene-modified cells will be monitored. If successful, such an approach could significantly contribute to expanding the use of alloreactivity as a treatment modality. C1 NCI,FREDERICK CANC RES & DEV CTR,BIOL RESOURCES BRANCH,FREDERICK,MD 21702. RP Tiberghien, P (reprint author), CHU BESANCON,ETABLISSEMENT TRANSFUS SANGUINE FRANCHE COMTE,SERV HEMATOL,F-25000 BESANCON,FRANCE. NR 25 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 1430-2772 J9 HEMATOL CELL THER JI Hematol. Cell Ther. PD APR PY 1996 VL 38 IS 2 BP 221 EP 224 DI 10.1007/s00282-996-0221-7 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA UT911 UT WOS:A1996UT91100015 PM 8932011 ER PT J AU Goad, KE Gralnick, HR AF Goad, KE Gralnick, HR TI Coagulation disorders in cancer SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Review ID ACUTE PROMYELOCYTIC LEUKEMIA; HEPARIN-INDUCED THROMBOCYTOPENIA; DISSEMINATED INTRAVASCULAR COAGULATION; FACTOR-X DEFICIENCY; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACQUIRED VONWILLEBRAND DISEASE; MONOCYTE PROCOAGULANT ACTIVITY; PLATELET-AGGREGATING ACTIVITY; FIBRIN DEGRADATION PRODUCTS; HEMOLYTIC-UREMIC SYNDROME AB Cancer and its treatment launch many attacks on megakaryocyte and platelet production. This article focuses on the hematopoietic cytokines that affect this process. Frier to the cloning of thrombopoietin, at least two of these cytokines, IL-11 and PIXY 321, displayed promising clinical effects. To determine how these agents will compare to the physiologic regulator of platelet production will require carefully controlled clinical trials. The next few years most certainly will see the resolution of many of the complications of thrombocytopenia. RP Goad, KE (reprint author), NIH,WARREN G MAGNUSON CLIN CTR,DEPT CLIN PATHOL,SERV HEMATOL,9000 ROCKVILLE PIKE,BLDG 10,BETHESDA,MD 20892, USA. NR 308 TC 72 Z9 77 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD APR PY 1996 VL 10 IS 2 BP 457 EP & DI 10.1016/S0889-8588(05)70347-6 PG 29 WC Oncology; Hematology SC Oncology; Hematology GA UC649 UT WOS:A1996UC64900009 PM 8707764 ER PT J AU Ardehali, H Tiller, GE Printz, RL Mochizuki, H Prochazka, M Granner, DK AF Ardehali, H Tiller, GE Printz, RL Mochizuki, H Prochazka, M Granner, DK TI A novel (TA)(n) polymorphism in the hexokinase II gene: Application to noninsulin-dependent diabetes mellitus in the Pima Indians SO HUMAN GENETICS LA English DT Article ID GLUCOKINASE GENE; INSULIN; LINKAGE; NIDDM; PATHOGENESIS AB Hexokinase II, one member of a family of structurally similar enzymes that catalyze the phosphorylation of glucose in the 6-position, has been suggested to play a role in the pathophysiology of noninsulin-dependent diabetes mellitus (NIDDM). The gene for hexokinase II, HK2, has been previously mapped to human chromosome 2p13 by fluorescence in situ hybridization, and two-point linkage analysis has placed it near the locus for transforming growth factor alpha, TGFA. We now report the characterization of a (TA)(n) polymorphism in intron 12 of HK2. Using multipoint analysis of CEPH family genotypes, we have determined the most likely locus order to be cen-D2S169-[D2S286-HK2]-[D2S145-D2S291]-[D2S45-D2S101-TGFA]-tel. As HKII is a candidate gene that could contribute to the manifestation of insulin resistance and NIDDM, we genotyped 1152 Pima Indians, a Native American tribe that has the highest reported prevalence of NIDDM in the world. Although we did not detect any linkage or association of HK2 with insulin resistance or NIDDM in the Pima Indians, the polymorphism and detailed mapping of HK2 described in this report should prove useful in the assessment of the role of this gene in the predisposition to NIDDM in other populations. C1 VANDERBILT UNIV,SCH MED,DEPT PHYSIOL & MOLEC BIOPHYS,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT PEDIAT,NASHVILLE,TN 37232. VANDERBILT UNIV,SCH MED,DEPT MED,NASHVILLE,TN 37232. NIDDKD,NIH,PHOENIX EPIDEMIOL & CLIN RES BRANCH,PHOENIX,AZ 85016. FU NIDDK NIH HHS [DK42502, DK46867, DK35107] NR 23 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 1996 VL 97 IS 4 BP 482 EP 485 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA TZ783 UT WOS:A1996TZ78300015 PM 8834247 ER PT J AU Setini, A Beretta, A DeSantis, C Meneveri, R Martayan, A Mazzilli, MC Appella, E Siccardi, AG Natali, PG Giacomini, P AF Setini, A Beretta, A DeSantis, C Meneveri, R Martayan, A Mazzilli, MC Appella, E Siccardi, AG Natali, PG Giacomini, P TI Distinctive features of the alpha(1)-domain alpha helix of HLA-C heavy chains free of beta(2)-microglobulin SO HUMAN IMMUNOLOGY LA English DT Article ID ONE-DIMENSIONAL IEF; CLASS-I ANTIGENS; MONOCLONAL-ANTIBODIES; PEPTIDE-BINDING; LOCUS ANTIGENS; GENE-PRODUCTS; EXPRESSION; BLANK; POLYMORPHISM; RECOGNITION AB Only a few monoclonal antibodies are available with a restricted specificity to HLA-C products. In the present report, we demonstrate that antibody L31, previously shown to react with beta 2m-less (free) class I MHC heavy chains [23], binds to an epitope (residues 66-68 of the alpha(1) domain alpha helix) present on all the HLA-C alleles corresponding to the accepted (CW1 through CW8) serologic specificities, and on a few HLA-B heavy chains sharing with HLA-C an aromatic residue at position 67. Extensive IEF blot testing of HLA homozygous, EBV-transformed B-lymphoid cells indicates that HLA-C molecules are present at significantly lower levels than HLA-B polypeptides not only at cell surface, as previously demonstrated, but also in total cellular extracts. Testing of metabolically labeled HLA-CW1, -CW5, and -CW6 transfectants and HLA homozygous lymphoid cells, particularly HLA-CW1-expressing cells, demonstrates that the L31 epitope is present on a subpopulation of naturally occurring HLA-C molecules distinct from that identified by antibody W6/32 to beta 2m-associated heavy chains. Pulse-chase experiments demonstrate that this epitope is transiently made available to antibody binding at early biosynthetic stages, but becomes hidden upon assembly with beta 2m. Thus, free HLA-C and other Y/F67(+) heavy chains are characterized by distinctive antibody binding features in a region (residues 66-68) included in a previously identified HLA-C restricted motif [17], which has been suggested to be the primary cause of distinctive features of the antigen-binding groove, low affinity for endogenous peptide antigens and beta 2m, acid preferential uptake of exogenous peptides, possibly of viral origin. We also show that HLA-CW1 heavy chains, both free and beta 2m associated, acquire sialilation. Free HLA-CW1 heavy chains are expressed at the cell surface even when unsialilated, albeit at low levels. C1 IST REGINA ELENA,CTR EXPTL RES,IMMUNOL LAB,I-00158 ROME,ITALY. HOSP SAN RAFFAELE,DEPT BIOL & BIOTECHNOL RES,I-20132 MILAN,ITALY. UNIV MILAN,DEPT BIOL & GENET MED SCI,MILAN,ITALY. UNIV ROMA LA SAPIENZA,DEPT EXPTL MED,ROME,ITALY. NCI,CELL BIOL LAB,NIH,BETHESDA,MD 20892. RI Giacomini, Patrizio/K-5217-2016 OI Giacomini, Patrizio/0000-0001-6109-1709 NR 30 TC 57 Z9 57 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD APR 1 PY 1996 VL 46 IS 2 BP 69 EP 81 DI 10.1016/0198-8859(96)00011-0 PG 13 WC Immunology SC Immunology GA UM273 UT WOS:A1996UM27300001 PM 8727205 ER PT J AU Pandya, A Xia, XJ Landa, BL Arnos, KS Israel, J Lloyd, J James, AL Diehl, SR Blanton, SH Nance, WE AF Pandya, A Xia, XJ Landa, BL Arnos, KS Israel, J Lloyd, J James, AL Diehl, SR Blanton, SH Nance, WE TI Phenotypic variation in Waardenburg syndrome: Mutational heterogeneity, modifier genes or polygenic background? SO HUMAN MOLECULAR GENETICS LA English DT Article ID SYNDROME TYPE-I; PAX3 GENE; PAIRED DOMAIN; CHROMOSOME-2; DEFECTS; BOX AB We have identified 11 mutational changes in the PAX3 gene in patients with type 1 Waardenburg syndrome (WS1) including three in the paired domain, six within or immediately adjacent to the homeodomain and two previously described polymorphic variants in exons 2 and 6. The affected members of one family carried substitutions involving two base pairs separated by one unaltered codon. Two of the deleterious mutations were identical and three others were identical to previously reported mutations. A comparison of clinical findings in families carrying substitutions in the same codon failed to reveal conspicuous similarities. Although subtle mutation-specific effects may well exist, allelic heterogeneity clearly cannot account for within family variation. However, the striking concordance of a pair of monozygotic twins with Waardenburg syndrome (WS) and previous reports of similar pairs indicate that phenotypic variation in WS has a genetic basis, If the genetic effects are mediated by oligogenic epistasis, as studies in the mouse suggest, it may ultimately be possible to predict clinically relevant aspects of the Waardenburg phenotype. C1 GALLAUDET UNIV,WASHINGTON,DC 20002. NIDR,NIH,DEODP,MOLEC EPIDEMIOL & DIS INDICATORS BRANCH,BETHESDA,MD 20892. UNIV VIRGINIA,DEPT PEDIAT,CHARLOTTESVILLE,VA 22908. RP Pandya, A (reprint author), VIRGINIA COMMONWEALTH UNIV MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298, USA. FU NIDCD NIH HHS [5 R01 DC 00038-05] NR 38 TC 31 Z9 35 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD APR PY 1996 VL 5 IS 4 BP 497 EP 502 DI 10.1093/hmg/5.4.497 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA UC637 UT WOS:A1996UC63700009 PM 8845842 ER PT J AU Tagaya, Y Bamford, RN DeFilippis, AP Waldmann, TA AF Tagaya, Y Bamford, RN DeFilippis, AP Waldmann, TA TI IL-15: A pleiotropic cytokine with diverse receptor/signaling pathways whose expression is controlled at multiple levels SO IMMUNITY LA English DT Review ID RECEPTOR GAMMA-CHAIN; MESSENGER-RNA; INTERLEUKIN-7; TRANSLATION; SEQUENCES; GENE RP Tagaya, Y (reprint author), NCI,METAB BRANCH,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 42 TC 346 Z9 351 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1996 VL 4 IS 4 BP 329 EP 336 DI 10.1016/S1074-7613(00)80246-0 PG 8 WC Immunology SC Immunology GA UH522 UT WOS:A1996UH52200001 PM 8612127 ER PT J AU Matechak, EO Killeen, N Hedrick, SM Fowlkes, BJ AF Matechak, EO Killeen, N Hedrick, SM Fowlkes, BJ TI MHC class II-specific T cells can develop in the CD8 lineage when CD4 is absent SO IMMUNITY LA English DT Article ID RECEPTOR TRANSGENIC MICE; ANTIGEN RECEPTOR; THYMOCYTE DEVELOPMENT; IMMATURE THYMOCYTES; NEGATIVE SELECTION; THYMIC SELECTION; DEFICIENT MICE; LYMPHOCYTES; EXPRESSION; MOLECULES AB The generation of mature CD4 T cells from CD4(+)CD8(+) precursor thymocytes usually requires corecognition of class II MHC by a TCR and CD4, while the production of mature CD8 T cells requires corecognition of class I MHC by a TCR and CD8. To assess the role of the CD4 coreceptor in development and lineage commitment, we generated CD4-deficient mice expressing a transgenic class Ii-specific TCR. Surprisingly, in the absence of CD4 a large number of T cells mature, but these cells appear in the CD8 lineage. Thus, when CD4 is present, the majority of immature T cells with this class Ii-specific TCR choose the CD4 lineage but develop in the CD8 pathway when CD4 is absent. The results indicate that even for TCRs that are not dependent on coreceptor for MHC recognition, the coreceptor can influence the lineage choice. These findings are considered in terms of a quantitative signaling model for CD4/CD8 lineage commitment. C1 UNIV CALIF SAN FRANCISCO,DEPT MICROBIOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT IMMUNOL,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT BIOCHEM,SAN FRANCISCO,CA 94143. UNIV CALIF SAN FRANCISCO,DEPT BIOPHYS,SAN FRANCISCO,CA 94143. UNIV CALIF SAN DIEGO,DEPT BIOL,LA JOLLA,CA 92093. UNIV CALIF SAN DIEGO,CTR CANC,LA JOLLA,CA 92093. RP Matechak, EO (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,NATL INST HLTH,BETHESDA,MD 20892, USA. NR 53 TC 186 Z9 187 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 1996 VL 4 IS 4 BP 337 EP 347 DI 10.1016/S1074-7613(00)80247-2 PG 11 WC Immunology SC Immunology GA UH522 UT WOS:A1996UH52200002 PM 8612128 ER PT J AU Rabin, O Piciotti, M Drieu, K Bourre, JM Roux, F AF Rabin, O Piciotti, M Drieu, K Bourre, JM Roux, F TI Effect of anoxia and reoxygenation on antioxidant enzyme activities in immortalized brain endothelial cells SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE anoxia; immortalized endothelial cell; antioxidant enzymes; cell culture; rat brain endothelium ID PULMONARY-ARTERY; DISMUTASE; RAT; CULTURE; OXYGEN; BOVINE AB The effects of anoxia and reoxygenation on major antioxidant enzyme activities were investigated in vitro in immortalized rat brain endothelial cells (RBE(4) cells). A sublethal anoxic period of 12 h was assessed for RBE(4) cells using the neutral red uptake test. Anoxia markedly influenced the specific activity of catalase and superoxide dismutase, with no major effect on glutathione peroxidase or glutathione reductase. After 24 h postanoxia, the superoxide dismutase activity modulated by the presence or absence of oxygen returned to control value. Damage and recovery of RBE(4) immortalized rat brain endothelial cells in culture after exposure to free radicals and other oxygen-derived species provides a useful in vitro model to study anoxia-reoxygenation trauma at the cellular level. C1 HOP FERNAND WIDAL,INSERM U26,F-75010 PARIS,FRANCE. INST HENRI BEAUFOUR,F-75016 PARIS,FRANCE. RP Rabin, O (reprint author), NIA,NEUROSCI LAB,NIH,BLDG 10,ROOM 6C103,BETHESDA,MD 20892, USA. NR 27 TC 3 Z9 3 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD APR PY 1996 VL 32 IS 4 BP 221 EP 224 PG 4 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA UQ430 UT WOS:A1996UQ43000008 PM 8727046 ER PT J AU Lavrovsky, V Dong, Z Ma, WY Colburn, N AF Lavrovsky, V Dong, Z Ma, WY Colburn, N TI Drug-induced reversion of progression phenotype is accompanied by reversion of AP-1 phenotype in JB6 cells SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Article DE transformed cells; revertant cells; AP-1 activity ID ANCHORAGE INDEPENDENCE; TRANSFORMATION; PROMOTION; TUMORIGENICITY; SUPPRESSION; EXPRESSION; GROWTH; GENES AB Transformed JB6 cells can be stably reverted to nontransformed phenotype by AP-1 inhibiting glucocorticoid fluocinolone (FA) and cAMP elevator forskolin (FN), yielding stable revertants of promotion resistant (P-) and promotion sensitive (P+) phenotypes. AP-I activity of nontransformed P- and P+ revertant clones was decreased under a variety of experimental conditions compared with their transformed counterparts. Moreover, AP-1 activity in P+ cells under anchorage-independent conditions was induced by 12-0-tetradecanoyl-phorbol-13-acetate (TPA) while AP-1 activity in the reverted P- cells was not induced, just as observed for the original P+ and P- variants. Taken together these data suggest that changes in AP-1 activity may be one key mediator not only of forward progression but also of reversion of tumor cells to nontransformed phenotype. In addition, the higher transfection efficiency of the new reverted P- and P+ cells renders them useful for studying the role of transcription factors in tumor promotion. C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. UNIV MINNESOTA,HORMEL INST,AUSTIN,MN 55912. RUSSIAN ACAD SCI,INST CYTOL & GENET,NOVOSIBIRSK 630090,RUSSIA. NR 15 TC 12 Z9 12 U1 0 U2 0 PU SOC IN VITRO BIOLOGY PI COLUMBIA PA 8815 CENTRE PARK DRIVE SUITE 210, COLUMBIA, MD 21045 SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD APR PY 1996 VL 32 IS 4 BP 234 EP 237 PG 4 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA UQ430 UT WOS:A1996UQ43000010 PM 8727048 ER PT J AU Yi, ES Remick, DG Lim, Y Tang, W Nadzienko, CE Bedoya, A Yin, SM Ulich, TR AF Yi, ES Remick, DG Lim, Y Tang, W Nadzienko, CE Bedoya, A Yin, SM Ulich, TR TI The intratracheal administration of endotoxin .10. Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo SO INFLAMMATION LA English DT Article ID ACUTE-INFLAMMATION; MESSENGER-RNA; NECROSIS; INTERLEUKIN-1 AB Intratracheal instillation of endotoxin (LPS causes acute pulmonary inflammation characterized by the accumulation of plasma proteins and leukocytes within the pulmonary airways. The synthetic glucocorticoid dexamethasone 1) inhibits the LPS-initiated vascular leak of plasma proteins into the ai;space, 2) inhibits the LPS-initiated emigration of neutrophils and lymphocytes into the airspace in a dose-dependent fashion, and 3) inhibits LPS-initiated mRNA and/or bronchoalveolar lavage protein expression of cytokines (TNF, IL-1 and IL-6) and chemokines (MIP-1 alpha, MIP-2 and MCP-1). In conclusion, dexamethasone inhibits both the vascular and cellular aspects of acute inflammation by downregulation of a broad spectrum of inflammatory cytokines and chemokines. C1 UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48109. NCI,MOLEC IMMUNOREGULAT LAB,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. AMGEN INC,THOUSAND OAKS,CA 91320. UNIV CALIF IRVINE,SCH MED,DEPT PATHOL,IRVINE,CA 92717. RP Yi, ES (reprint author), UNIV CALIF SAN DIEGO,SCH MED,DEPT PATHOL,SAN DIEGO,CA 92103, USA. NR 22 TC 38 Z9 38 U1 0 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0360-3997 J9 INFLAMMATION JI Inflammation PD APR PY 1996 VL 20 IS 2 BP 165 EP 175 DI 10.1007/BF01487403 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA UF304 UT WOS:A1996UF30400004 PM 8728019 ER PT J AU Kaden, DA Warren, J Ryan, L Boorman, G Mellick, P AF Kaden, DA Warren, J Ryan, L Boorman, G Mellick, P TI The NTP/HEI collaborative ozone project on the health effects of chronic ozone inhalation SO INHALATION TOXICOLOGY LA English DT Article ID COLLAGEN-METABOLISM; AMBIENT LEVELS; LUNG COLLAGEN; ADULT-RATS; PPM OZONE; EXPOSURE; BRONCHIOLITIS; CONSEQUENCES; EPITHELIUM; RESPONSES AB Although many people are exposed to ozone, the effects of chronic exposure to this ubiquitous pollutant, especially low-level chronic exposure, are not well understood. The U.S. Environmental Protection Agency (EPA) current national ambient air quality standard for ozone is exceeded in many communities, especially during the summer. The standard is attained when the number of days per calendar year with maximum hourly average concentrations above 0.12 ppm is equal to or less than 1. The U.S. EPA estimates that 67 million people in the United States, or slightly more than a quarter of the residents, live in areas that were out of compliance with the current National Ambient Air Quality Standard (NAAQS) for ozone in 1989. Although there have been some studies of long-term exposure to ozone, many important questions remain about the health effects of chronic ozone exposure. The Health Effects Institute (HEI), in conjunction with the National Toxicology Program (NTP) carcinogenesis studies, has completed a major effort to help answer these questions. NTP included additional animals in its study for HEI investigators. Included in this effort is a set of studies examining histopathological, biochemical, morphological, and functional alterations in rats exposed to 0, 0.12, 0.5 or 1.0 ppm ozone for 20 mo. This article describes several aspects of this effort. This project can serve as a model for other large toxicological studies for which cancer may not be the only endpoint of concern. The additional animals required for the NTP/HEI Collaborative Ozone Project only represented a modest incremental cost, yet provided information on a much broader range of potential effects of ozone than the basic NTP carcinogenesis studies. C1 HARVARD UNIV, SCH PUBL HLTH, DANA FARBER CANC INST, BOSTON, MA 02115 USA. NIEHS, RES TRIANGLE PK, NC 27709 USA. PACIFIC NW LAB, RICHLAND, WA 99352 USA. RP Kaden, DA (reprint author), HLTH EFFECTS INST, 141 PORTLAND ST, SUITE 7300, CAMBRIDGE, MA 02139 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 47 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD APR PY 1996 VL 8 IS 3 BP 213 EP 227 DI 10.3109/08958379609005431 PG 15 WC Toxicology SC Toxicology GA UJ171 UT WOS:A1996UJ17100001 ER PT J AU Dietert, R Hedge, A Luster, MI Qureshi, MA AF Dietert, R Hedge, A Luster, MI Qureshi, MA TI Factors influencing indoor air quality, immunity and health SO INHALATION TOXICOLOGY LA English DT Editorial Material C1 CORNELL UNIV,DEPT IMMUNOL & MICROBIOL,ITHACA,NY 14853. CORNELL UNIV,DEPT DESIGN & ENVIRONM ANAL,ITHACA,NY 14853. NIEHS,ENVIRONM IMMUNOL & NEUROBIOL SECT,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,COLL AGR & LIFE SCI,DEPT POULTRY SCI,RALEIGH,NC 27695. US EPA,NATL HLTH & ENVIRONM EFFECTS RES LAB,EXPT TOXICOL DIV,RES TRIANGLE PK,NC 27711. RP Dietert, R (reprint author), CORNELL UNIV,INST COMPARAT & ENVIRONM TOXICOL,213 RICE HALL,ITHACA,NY 14853, USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU TAYLOR & FRANCIS PI BRISTOL PA 1900 FROST ROAD, SUITE 101, BRISTOL, PA 19007-1598 SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD APR PY 1996 VL 8 IS 3 BP 299 EP 301 DI 10.3109/08958379609005437 PG 3 WC Toxicology SC Toxicology GA UJ171 UT WOS:A1996UJ17100007 ER PT J AU Okada, T Metcalfe, DD Ito, Y AF Okada, T Metcalfe, DD Ito, Y TI Purification of mast cells with an improved nonsynchronous flow-through coil planet centrifuge SO INTERNATIONAL ARCHIVES OF ALLERGY AND IMMUNOLOGY LA English DT Article DE cell separation; mast cells; centrifuges; IgE receptor; histamine release ID COMPOUND 48/80; RAT AB A method for cell purification was designed without using high-density media which may impair membrane receptors. Rat and mouse mast cells were separated with an improved nonsynchronous flow-through coil planet centrifuge. Peritoneal cells were suspended at a concentration of 2-3 x 10(7) cells/ml in conditioned RPMI 1640, supplemented with 50% heat-inactivated FCS and 0.32% sodium citrate. In each separation 3 ml of cell suspension were loaded into the coiled column and elutriated at 4 degrees C. Several conditions, including the centrifugal force, revolution/rotation ratio, density of separation media, flow speed, and designs of both coiled column and flow tubes, were examined and optimized for mast cell purification. Rat mast cells were separated at the purity of 99.2%, with an average yield of 40% under sterile conditions. Nearly 90% pure mouse mast cells were harvested, despite a very low population of mast cells available in murine peritoneal cells. Purified cells were morphologically intact and discharged granules by exocytosis as indicated by electron-microscopic observations. The average histamine release with antigenic specificity was 34 and 61%, in passive sensitization in vitro and in vivo, respectively. Mast cells sensitized with mouse monoclonal IgE antibody released histamine, similar to cells sensitized with homologous antibody. This newly devised method of cell separation will be useful to purify biologically intact mast cells. C1 NIAID,LAB ALLERG DIS,BETHESDA,MD 20892. NHLBI,NIH,BIOPHYS CHEM LAB,BETHESDA,MD 20892. NR 24 TC 6 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1018-2438 J9 INT ARCH ALLERGY IMM JI Int. Arch. Allergy Immunol. PD APR PY 1996 VL 109 IS 4 BP 376 EP 382 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA UB509 UT WOS:A1996UB50900011 PM 8634523 ER PT J AU Pearce, EJ Cheever, A Leonard, S Covalesky, M FernandezBotran, R Kohler, G Kopf, M AF Pearce, EJ Cheever, A Leonard, S Covalesky, M FernandezBotran, R Kohler, G Kopf, M TI Schistosoma mansoni in IL-4-deficient mice SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE granuloma; Schistosoma; T(h)2 ID GRANULOMA-FORMATION; T-CELLS; CYTOKINE PRODUCTION; DOWN-REGULATION; INFECTED MICE; TH2 RESPONSE; IL-4; INTERLEUKIN-4; ANTIGEN; INVIVO AB Immunopathology and immune responses to Schistosoma mansoni were examined in IL-4 -/- mice. IL-5 and IL-10 production by lymphoid cells stimulated with soluble egg antigen (SEA), peripheral eosinophilia and serum levels of soluble IL-4 receptor but not IgE were all significantly elevated over background normal levels in IL-4 -/- mice as a result of infection. Additionally, IL-10 and IL-5 in addition to IL-2 and IFN-gamma-transcripts were equally evident in diseased liver tissue from infected IL-4 -/- and wild-type mice. Nevertheless, analysis of antigen-stimulated IL-2, IL-4, IL-5, IL-10 and IFN-gamma production by lymphoid organ cells from infected or egg-injected IL-4 -/- mice revealed a more T(h)1-like pattern of cytokine production (IFN-gamma > IL-5) than in (wild-type) mice in which a stronger type 2 response to SEA was detectable (IL-4, IL-5 > IFN-gamma). Despite this, at 8 and 16 weeks after infection, liver pathology, as indicated by the size, cellularity, cellular composition and collagen content of granulomas, was similar in IL-4 -/- and wild-type animals, As in wild-type animals, granuloma size at week 16 was smaller than at week 8, indicating that modulation had occurred in the absence of IL-4. Differences in pathology were seen only when eggs were experimentally embolized to the lungs, in which case IL-4 -/- mice made smaller granulomatous responses than did wild-type animals. These data clearly show that IL-4 is not necessary for the hepatic granuloma formation which occurs during experimental schistosomiasis. C1 NIAID,PARASIT DIS LAB,NATL INST HLTH,BETHESDA,MD 20892. UNIV LOUISVILLE,SCH MED,DEPT PATHOL,LOUISVILLE,KY 40292. MAX PLANCK INST IMMUNBIOL,D-79108 FREIBURG,GERMANY. RP Pearce, EJ (reprint author), CORNELL UNIV,NEW YORK STATE COLL VET MED,DEPT IMMUNOL & MICROBIOL,ITHACA,NY 14853, USA. RI Fernandez-Botran, Rafael/J-3659-2016 OI Fernandez-Botran, Rafael/0000-0001-8138-8745 FU NIAID NIH HHS [AI32573] NR 43 TC 108 Z9 108 U1 0 U2 1 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD APR PY 1996 VL 8 IS 4 BP 435 EP 444 DI 10.1093/intimm/8.4.435 PG 10 WC Immunology SC Immunology GA UG691 UT WOS:A1996UG69100001 PM 8671630 ER PT J AU Karavanov, AA SaintJeannet, JP Karavanova, I Taira, M Dawid, IB AF Karavanov, AA SaintJeannet, JP Karavanova, I Taira, M Dawid, IB TI The LIM homeodomain protein Lim-1 is widely expressed in neural, neural crest and mesoderm derivatives in vertebrate development SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL BIOLOGY LA English DT Article DE LIM domain; homeodomain; Xenopus; Lim-1 antibody ID CAENORHABDITIS-ELEGANS; FLOOR PLATE; INSULIN GENE; DOMAIN; INDUCTION; NOTOCHORD; CELLS; ISL-1; TUBE; DIFFERENTIATION AB Polyclonal antibodies to Xlim-1 homeodomain protein of Xenopus laevis were used to study the developmental expression pattern of this protein in Xenopus, rat and mouse. Western blotting of embryo extracts injected with different Xlim-1 constructs confirmed the specificity of the antibody. Beginning at the gastrula stage, Xlim-1 protein was detected in three cell lineages: (i) notochord, (ii) pronephros and (iii) certain regions of the central nervous system, in agreement with earlier studies of the expression of Xlim-1 RNA (Taira et at, Development 120:1525-1536, 1994a). In addition, several new locations of Xlim-1 expression were found, including the olfactory organ, retina, otic vesicle, dorsal root ganglia and adrenal gland. Similar expression patterns were seen for the Lim-1 protein in frog and rodent tissues. These observations implicate the Xlim-1 gene in the specification of multiple cell lineages, particularly within the nervous system, and emphasize the conserved nature of the role of this gene in different vertebrate animals. C1 NICHHD,GENET MOLEC LAB,NIH,BETHESDA,MD 20892. NCI,COMPARAT CARCINOGENESIS LAB,NIH,FREDERICK,MD 21701. NR 43 TC 28 Z9 31 U1 0 U2 0 PU UNIV BASQUE COUNTRY PRESS PI BILBAO PA POST BOX 1397, E-48080 BILBAO, SPAIN SN 0214-6282 J9 INT J DEV BIOL JI Int. J. Dev. Biol. PD APR PY 1996 VL 40 IS 2 BP 453 EP 461 PG 9 WC Developmental Biology SC Developmental Biology GA UP322 UT WOS:A1996UP32200002 PM 8793615 ER PT J AU Gladen, BC AF Gladen, BC TI Matched-pair case-control studies when risk factors are correlated within the pairs SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bias (epidemiology); odds ratio; selection bias; epidemiological methods ID SELECTION BIAS; FRIEND CONTROLS; DISEASE AB Background. if pair members are independent, simple matched-pair case-control studies are known to yield consistent estimates of the population odds ratio. If pair members are not independent, this is not necessarily true, It has been shown previously that the usual matched-pair estimate remains consistent if the exposure of interest is correlated within the pairs. However, the effect of correlation of unmeasured risk factors within the pairs has not been studied. Methods. We examine the effect of within-pair correlation of unmeasured risk factors independent of the measured exposure. This is done within the context of a simple matched-pair case-control study. We compare the large-sample expectation of the usual matched-pair estimate to the population odds ratio. Results. We show that the usual estimate may be inconsistent in the presence of this correlation. However, if the disease is rare, the magnitude of the bias will be negligible. Conclusions. Correlation of unmeasured risk factors independent of the measured exposure is not a practical problem in this setting. RP Gladen, BC (reprint author), NIEHS,STAT & BIOMATH BRANCH,MAIL DROP A3-03,POB 12233,RES TRIANGLE PK,NC 27709, USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 1996 VL 25 IS 2 BP 420 EP 425 DI 10.1093/ije/25.2.420 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA VE063 UT WOS:A1996VE06300023 PM 9119569 ER PT J AU DeNictolis, M Garbisa, S Lucarini, G Goteri, G Masiero, L Ciavattini, A Garzetti, GG Stetlerstevenson, WG Fabris, G Biagini, G Prat, J AF DeNictolis, M Garbisa, S Lucarini, G Goteri, G Masiero, L Ciavattini, A Garzetti, GG Stetlerstevenson, WG Fabris, G Biagini, G Prat, J TI 72-KiloDalton type IV collagenase, type IV collagen, and Ki 67 antigen in serous tumors of the ovary: A clinicopathologic, immunohistochemical, and serological study SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovarian serous tumors; MMP-2; type IV collagen; Ki 67 ID CELL-PROLIFERATION; CANCER; MICROINVASION; METASTASIS; CARCINOMA; INVASION; SECTIONS; LAMININ; TISSUE AB The immunohistochemical expression of 72-kDa type IV collagenase [matrix-metalloproteinase (MMP)-2], basement membrane component type IV collagen and proliferation-related antigen Ki 67 were investigated in 43 benign, borderline, and malignant serous tumors of the ovary. The results were compared with the histotypes of ovarian serous tumors and with their clinical behavior. Serum evaluation of MMP-2 was performed in 14 patients with cystadenocarcinoma and the data compared with that of a control group. The basement membrane (BM) was continuous in benign cystadenomas and in some borderline tumors, whereas it was discontinuous or absent in other borderline tumors, in borderline tumors with microinvasion, and in cystadenocarcinomas. The percentage of MMP-2- and Ki 67-expressing cells increased from cystadenomas to borderline tumors, being the highest in malignant tumors; a frequent basal disposition of the MMP-2 cytoplasmic granules also was observed in cystadenocarcinomas. Statistical analysis demonstrated that MMP-2 expression was inversely related to BM integrity. Serum MMP-2 values did not differ from that of the control group. Cox regression analysis showed that tumor stage and grade were significant prognostic factors, whereas MMP-2 and Ki 67 immunohistochemical expression added no further significant information to the prognosis. The investigators conclude that the correlation between increasing MMP-2 expression and BM alteration gives support to the hypothesis of a direct role of the metalloproteinase in the process of destructive stromal invasion. MMP-2, type IV collagen, and Ki 67 immunodetection varied according to the histologic classification of ovarian serous tumors. However, neither these factors nor the serum evaluation of MMP-2 appear useful as prognostic predictors in this series. C1 UNIV ANCONA,FAC MED,DIV PATHOL,ANCONA,ITALY. UNIV ANCONA,FAC MED,INST HUMAN MORPHOL,ANCONA,ITALY. UNIV PADUA,FAC MED,INST HIST & GEN EMBRYOL,PADUA,ITALY. NIH,PATHOL LAB,BETHESDA,MD. AUTONOMOUS UNIV BARCELONA,DEPT PATHOL,BARCELONA,SPAIN. RI Prat, Jaime/G-4679-2011; Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 NR 29 TC 36 Z9 36 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD APR PY 1996 VL 15 IS 2 BP 102 EP 109 PG 8 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA UE290 UT WOS:A1996UE29000003 PM 8786198 ER PT J AU Kim, SN Lee, GR ChoChung, YS Park, SD Hong, SH AF Kim, SN Lee, GR ChoChung, YS Park, SD Hong, SH TI Overexpression of RII beta regulatory subunit of protein kinase A induces growth inhibition and reverse-transformation in SK-N-SH human neuroblastoma cells SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE cAMP-dependent protein kinase; RII beta subunit; RI alpha subunit; neuroblastoma cell line; growth inhibition ID SELECTIVE CAMP ANALOGS; AMINO-ACID SEQUENCE; CYCLIC-AMP; MOLECULAR-CLONING; CATALYTIC SUBUNIT; HUMAN TESTIS; ANTISENSE OLIGODEOXYNUCLEOTIDE; ADENOSINE-MONOPHOSPHATE; GENE-EXPRESSION; HL-60 LEUKEMIA AB SK-N-SH human neuroblastoma cell line was employed to test whether direct introduction of the RII beta subunit of PKA could induce growth inhibition and reverse-transformation of cancer cells. We infected SK-N-SH cells with an RII beta expression construct and the clonal line with the highest expression level was selected to examine the effect of RII beta overexpression. Elevation of RII beta was accompanied by marked reduction of RI alpha level and increase of C alpha level. Since the mRNA levels of RI alpha and C alpha were not altered by increased RII beta, the changes in the level of RI alpha and C alpha protein seem to be due to a post-transcriptional event. The RII beta-overexpressing cell line, SK-RII beta, exhibited retarded monolayer growth, decreased DNA synthesis, inability to grow in soft agar, and reduced viability in serum-free or low-serum condition as compared to parental cell, SK-N-SH. These characteristics of SK-RII beta disappeared when the RII beta expression was not fully induced. These results showed that the elevation of RII beta and/or the decrease of RI alpha is closely related to the suppression of cell proliferation and the status of transformation of SK-N-SH neuroblastoma cell line. C1 SEOUL NATL UNIV,INST MOLEC BIOL & GENET,CELL BIOL LAB,SEOUL 151742,SOUTH KOREA. SEOUL NATL UNIV,COLL NAT SCI,DEPT MOLEC BIOL,SEOUL 151742,SOUTH KOREA. SEOUL NATL UNIV,COLL NAT SCI,RES CTR CELL DIFFERENTIAT,SEOUL 151742,SOUTH KOREA. NCI,NIH,TUMOR IMMUNOL & BIOL LAB,CELLULAR BIOCHEM SECT,BETHESDA,MD 20892. NR 33 TC 7 Z9 7 U1 0 U2 0 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 APR PY 1996 VL 8 IS 4 BP 663 EP 668 PG 6 WC Oncology SC Oncology GA UB251 UT WOS:A1996UB25100003 PM 21544410 ER PT J AU Federau, T Schubert, U Flossdorf, J Henklein, P Schomburg, D Wray, V AF Federau, T Schubert, U Flossdorf, J Henklein, P Schomburg, D Wray, V TI Solution structure of the cytoplasmic domain of the human immunodeficiency virus type 1 encoded virus protein U (Vpu) SO INTERNATIONAL JOURNAL OF PEPTIDE AND PROTEIN RESEARCH LA English DT Article DE association behaviour; human immunodeficiency virus type 1 (HIV-1); nuclear magnetic resonance (NMR); protein structure; Vpu ID HIV-1; CD4; IDENTIFICATION; DEGRADATION; GENE AB The HIV-1-specific Vpu protein is an 81 amino acid class I integral membrane phosphoprotein that induces degradation of the virus receptor CD4 in the endoplasmic reticulum and enhances the release of virus particles from infected cells. Vpu is of amphipathic nature and consists of a hydrophobic N-terminal membrane anchor proximal to a polar C-terminal cytoplasmic domain. In our recent work, focussed on the structural analysis of the cytoplasmic tail, we established an alpha-helix-flexible-alpha-helix-turn model. Now we present the experimental solution structure of the Vpu cytoplasmic domain which has been elucidated in aqueous 50% trifluoroethanol solution by 2D H-1 NMR spectroscopy, and restrained molecular dynamics and energy minimization calculations. Under these conditions the peptide, Vpu(32-81), is predominantly monomeric and adopts a well defined helix-interconnection-helix-turn conformation, in which the four regions are bounded by residues 37-51, 52-56, 57-72 and 73-78. The presence of the cis isomer of Pro-75 manifests itself as a doubling of cross peaks of neighbouring residues in the 2D spectra. A related variant peptide, Vpum(32-81), in which the Vpu-phosphoacceptor sites Ser(52) and Ser(56) were exchanged for Asn, adopts a very similar structure and, taken together, provides evidence that the second helix and the turn form a comparatively rigid region. Both helices are amphipathic in character, but show different charge distributions. In general the cytoplasmic region is N-terminally positively charged, passes through a region of alternating charges in helix 1 and then becomes negatively charged. The flexibility of the interconnection permits orientational freedom of the two helices. The motif found here is the first experimentally refined solution structure of the cytoplasmic domain of Vpu, and it is conceivable that these alpha-helices are important for a previously defined physical interaction with an alpha-helical Vpu-responsive element located within the cytoplasmic tail of CD4. (C) Munksgaard 1996. C1 GESELL BIOTECHNOL FORSCH MBH, ABT MOL STRUKTURFORSCH, D-38124 BRAUNSCHWEIG, GERMANY. HUMBOLDT UNIV BERLIN, MED FAK CHARITE, INST KLIN IMMUNOL, O-1086 BERLIN, GERMANY. NIAID, MOLEC MICROBIOL LAB, NIH, BETHESDA, MD 20892 USA. HUMBOLDT UNIV BERLIN, MED FAK CHARITE, INST PHARMAKOL & TOXIKOL, O-1086 BERLIN, GERMANY. NR 35 TC 59 Z9 59 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0367-8377 J9 INT J PEPT PROT RES JI Int. J. Pept. Protein Res. PD APR PY 1996 VL 47 IS 4 BP 297 EP 310 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UK859 UT WOS:A1996UK85900011 PM 8738656 ER PT J AU Sullivan, DM Chung, DC Anglade, E Nussenblatt, RB Csaky, KG AF Sullivan, DM Chung, DC Anglade, E Nussenblatt, RB Csaky, KG TI Adenovirus-mediated gene transfer of ornithine amino transferase in cultured human retinal pigment epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE gene therapy; metabolic diseases; mitochondria; ornithine; retina ID GYRATE ATROPHY; AMINOTRANSFERASE; HYPERORNITHINEMIA; HETEROGENEITY; MUTATIONS; TISSUES AB Purpose, To evaluate the efficacy of adenovirus mediated transfer of ornithine delta-aminotransferase (OAT) into human retinal pigment epithelial (RPE) cells. Methods, Adenovirus-mediated gene transfer into primary cultures of human RPE was evaluated by measurement of enzyme activity in whole cell extracts and by Western blot analysis, To assess mitochondrial integrity, succinate dehydrogenase activity was measured in transduced RPE cells. Expression of adenovirus early genes was evaluated using reverse transcription-polymerase chain reaction. Results, OAT activity, which was 65 nmol/mg hour in untrasduced cells, could be increased to levels in excess of 20,000 nmol/mg hour using an adenovirus vector carrying the OAT cDNA. There was, however, a significant reduction in succinate dehydrogenase activity associated with OAT activity greater than 12,000 nmol/mg hour. Transduced human RPE displayed an altered morphology that appears to be a response to the vector because similar changes could be induced by an adenovirus vector that does not carry the OAT cDNA. Adenovirus early gene expression was detected in transduced RPE. Conclusions, This study represents a first step in the development of intraocular gene replacement therapy for the treatment of gyrate atrophy. The authors demonstrate that adenovirus is an efficient vehicle for the delivery of OAT into human RPE and that RPE will tolerate greater than a 150-fold increase in OAT-specific activity. Evidence for disruption of mitochondria when OAT activity exceeds 12,000 nmol/mg hour and vector-induced toxicity indicate that more controlled transgene expression and refinement of the vector systems is needed. C1 NEI,NIH,IMMUNOL LAB,BETHESDA,MD 20895. NR 30 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1996 VL 37 IS 5 BP 766 EP 774 PG 9 WC Ophthalmology SC Ophthalmology GA UD853 UT WOS:A1996UD85300008 PM 8603861 ER PT J AU Detrick, B Rhame, J Wang, Y Nagineni, CN Hooks, JJ AF Detrick, B Rhame, J Wang, Y Nagineni, CN Hooks, JJ TI Cytomegalovirus replication in human retinal pigment epithelial cells - Altered expression of viral early proteins SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article DE cytomegalovirus; flow cytometry; immediate early genes; retinal pigment epithelium ID GENE-EXPRESSION; RETINITIS PIGMENTOSA; VIRUS RETINITIS; LYMPHOCYTES-T; INFECTION; ANTIGEN; LINE; DIFFERENTIATION; TRANSCRIPTION; PERSISTENCE AB Purpose. Cytomegalovirus (CMV) infections are frequent complications in patients who have undergone kidney and bone marrow transplant and in patients with acquired immune deficiency syndrome. The mechanism by which CMV is activated and replicated within the retina is unknown. The authors evaluated the ability of human CMV to initiate replication in human retinal pigment epithelial (RPE) cells and compared this system with CMV replication in human fibroblasts (HEL-299, MRC-5) and human amnion epithelial (WISH) cells. Methods. Human RPE cells were obtained from donor eyes and propagated in vitro. Cells were infected, and CMV replication was evaluated in three ways: the detection of viral antigen by immunofluorescent, flow cytometry, and Western blot assays; the detection of virus-induced cytopathic effect (cpe), and the detection of infectious virus. Results, No evidence of viral replication in the epithelial (WISH) cells was found. Although CMV does not usually replicate in vitro in epithelial cells, CMV replication was detected in RPE cells. There are a number of distinct differences in CMV replication in RPE cells compared to replication in human fibroblasts. Virus-induced cpe and the production of infectious virus by RPE cells were delayed when compared to virus infection in either HEL or MRC 5 cells. At a multiplicity of infection of 0.1 and 1, cpe and infectious virus yield reached maximum levels at days 4 to 5 in fibroblasts and at days 19 to 46 in RPE cells, respectively. Nevertheless, infectious virus produced by RPE cells (10(6.5) TCID50/0.1 ml) significantly surpassed levels produced by HEL cells (10(5.5) TCID50/0.1 ml). The permissive infection in RPE cells consisted of a prolonged period (5 to 6 days) of virus production in the absence of cytopathology. Virus protein expression evaluated by indirect immunofluorescence assays, Western blot analysis, and flow cytometry revealed a delay in viral protein expression in RPE cells compared to viral protein expression in fibroblasts. The pattern of viral protein evaluated by flow cytometry was noticeably different in the two cell types. At the middle phase of CMV replication in RPE cells, a low percentage of cells express immediate early (IE) protein at a time when a high percentage of the cells express early (E) proteins. This IE-1 protein is a stable protein found concurrently with E protein in fibroblasts. This difference in percentage of cells expressing specific CMV proteins is transient, that is, it does not remain apparent at 100% cpe. Conclusions. Retinal pigment epithelial cells appear to demonstrate a distinct pattern of CMV infection. The low frequency of expression of IE viral protein in RPE cells, the subsequent slow replication of CMV, and the altered expression of IE viral proteins may be critical variables that impact on their relationship to viral persistence and activation within the retina. Alterations in the IE gene product may indicate the existence of positive or negative nuclear transcription factors within infected RPE cells. C1 NEI,NIH,IMMUNOL LAB,IMMUNOL & VIROL SECT,BETHESDA,MD 20892. RP Detrick, B (reprint author), GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,ROSS HALL,ROOM 502,2300 EYE ST NW,WASHINGTON,DC 20037, USA. NR 49 TC 42 Z9 42 U1 1 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 1996 VL 37 IS 5 BP 814 EP 825 PG 12 WC Ophthalmology SC Ophthalmology GA UD853 UT WOS:A1996UD85300013 PM 8603866 ER PT J AU Jensen, PS Watanabe, HK Richters, JE Roper, M Hibbs, ED Salzberg, AD Liu, S AF Jensen, PS Watanabe, HK Richters, JE Roper, M Hibbs, ED Salzberg, AD Liu, S TI Scales, diagnoses, and child psychopathology .2. Comparing the CBCL and the DISC against external validators SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article ID BEHAVIOR PROBLEM SYNDROMES; PSYCHIATRIC-DIAGNOSIS; VALIDITY; CONVERGENCE; IMPAIRMENT; COMMUNITY; ANXIETY AB Using a multimethod multistage screening procedure, the authors interviewed 201 parents and their children with the Diagnostic Interview Schedule for Children (DISC 2.1), In addition, parents completed the Child Behavior Checklist (CBCL) and other survey measures, while their children completed self-report scales. Receiver operating characteristic (ROC) analyses were done to determine optimal cutpoints on the CBCL, referenced to DISC diagnostic ''caseness.'' DISC diagnoses, DISC ''stem'' symptoms, CBCL scores, and CBCL ROC-cutpoints were compared against ''external validators,'' in order to determine the comparative advantages of each approach for assessing child psychopathology. Overall findings suggest that the controversies about ''best'' assessment strategies may be artificial: When both assessment approaches are compared using similar methods, they are reasonably comparable. However, highly specific diagnostic categories may show fewer relationships with external validators and may therefore need more systematic validational studies. C1 WALTER REED ARMY INST RES,DEPT MIL PSYCHIAT,DIV NEUROPSYCHIAT,WASHINGTON,DC 20005. NIMH,DIV EPIDEMIOL & SERV RES,EPIDEMIOL & PSYCHOPATHOL RES BRANCH,ROCKVILLE,MD 20857. RP Jensen, PS (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,DIV CLIN & TREATMENT RES,ROOM 18C-17,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 30 TC 79 Z9 79 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD APR PY 1996 VL 24 IS 2 BP 151 EP 168 DI 10.1007/BF01441482 PG 18 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA UK194 UT WOS:A1996UK19400002 PM 8743242 ER PT J AU Dickler, HB Collier, E AF Dickler, HB Collier, E TI Vaccines: New approaches and concepts SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Editorial Material ID MULTIPLE-SCLEROSIS; CELL; RECOGNITION; ANTIBODIES; INJECTION; REOVIRUS; IMMUNITY; EPITOPE; PROTEIN; MICE RP Dickler, HB (reprint author), NIAID, CLIN IMMUNOL BRANCH, NIH, SOLAR BLDG, ROOM 4A-19, BETHESDA, MD 20892 USA. NR 41 TC 3 Z9 3 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 1996 VL 97 IS 4 BP 896 EP 906 DI 10.1016/S0091-6749(96)80063-7 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA UG086 UT WOS:A1996UG08600003 PM 8655884 ER PT J AU Jacot, JL Laver, NM Glover, JP Lazarous, DF Unger, EF Robison, WG AF Jacot, JL Laver, NM Glover, JP Lazarous, DF Unger, EF Robison, WG TI Histological evaluation of the canine retinal vasculature following chronic systemic administration of basic fibroblast growth factor SO JOURNAL OF ANATOMY LA English DT Article DE dog; proliferative retinopathy; neovascularisation; bFGF ID DIABETIC-RETINOPATHY; ENDOTHELIAL-CELLS; INVIVO AB The purpose of the present study was to determine if prolonged systemic arterial administration of basic fibroblast growth factor (bFGF) at a dose sufficient to enhance collateral vessel formation in the ischaemic hearts of dogs would produce retinal neovascularisation in these same animals. Adult dogs (15-25 kg) were subjected to gradual occlusion of a coronary artery and randomised to receive 1 of 3 treatments via an indwelling left atrial catheter: (1) bFGF 1.74 mg/d, 5 d/wk for 63 d (n = 7); (2) bFGF 1.74 mg/d, 5 d/wk, for 35 d followed by physiological saline, 5 d/wk, for 28 d (n = 10); or (3) physiological saline, 5 d/wk, for 63 d (n = 10). After 63 d the retinal vasculatures from these dogs were isolated and examined for capillary varicosity, neovascularisation and other histopathological signs of angiopathy. All data were collected under masked conditions. The results suggest that chronic, systemic arterial administration of bFGF stimulates neovascularisation in the ischemic myocardium, but has no significant structural or vasoproliferative effect on the nonischaemic retina of the same animal. C1 NEI,LAB MECHANISMS OCULAR DIS,NIH,BETHESDA,MD 20892. NHLBI,EXPT PHYSIOL & PHARMACOL SECT,CARDIOL BRANCH,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,SCH MED,DEPT PATHOL,WASHINGTON,DC. NR 22 TC 3 Z9 3 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 SN 0021-8782 J9 J ANAT JI J. Anat. PD APR PY 1996 VL 188 BP 349 EP 354 PN 2 PG 6 WC Anatomy & Morphology SC Anatomy & Morphology GA UK190 UT WOS:A1996UK19000011 PM 8621333 ER PT J AU Bristol, M Volkmar, FR AF Bristol, M Volkmar, FR TI Autism research report from the National Institutes of Health - Preface SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Editorial Material C1 YALE UNIV,CTR CHILD STUDY,NEW HAVEN,CT 06520. NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 1996 VL 26 IS 2 BP 115 EP 116 DI 10.1007/BF02172000 PG 2 WC Psychology, Developmental SC Psychology GA UH449 UT WOS:A1996UH44900001 ER PT J AU Alexander, D Cowdry, RW Hall, ZW Snow, JB AF Alexander, D Cowdry, RW Hall, ZW Snow, JB TI The state of the science in autism: A view from the National Institutes of Health SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article; Proceedings Paper CT Working Conference on the State of the Science in Autism CY APR, 1995 CL NIH, WASHINGTON, DC HO NIH C1 NICHHD,BETHESDA,MD 20892. NIMH,ROCKVILLE,MD 20857. NINCDS,BETHESDA,MD 20892. NIDOCD,BETHESDA,MD 20892. NR 0 TC 5 Z9 5 U1 0 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 1996 VL 26 IS 2 BP 117 EP 119 DI 10.1007/BF02172001 PG 3 WC Psychology, Developmental SC Psychology GA UH449 UT WOS:A1996UH44900002 ER PT J AU Smalley, SL Collins, F AF Smalley, SL Collins, F TI Brief report: Genetic, prenatal, and immunologic factors SO JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS LA English DT Article; Proceedings Paper CT Working Conference on the State of the Science in Autism CY APR, 1995 CL NIH, WASHINGTON, DC HO NIH ID AUTISM C1 NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RP Smalley, SL (reprint author), UNIV CALIF LOS ANGELES,INST NEUROPSYCHIAT,760 WESTWOOD PLAZA,LOS ANGELES,CA 90024, USA. NR 16 TC 10 Z9 10 U1 2 U2 2 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0162-3257 J9 J AUTISM DEV DISORD JI J. Autism Dev. Disord. PD APR PY 1996 VL 26 IS 2 BP 195 EP 198 DI 10.1007/BF02172011 PG 4 WC Psychology, Developmental SC Psychology GA UH449 UT WOS:A1996UH44900012 PM 8744484 ER PT J AU Martin, RG Jair, KW Wolf, RE Rosner, JL AF Martin, RG Jair, KW Wolf, RE Rosner, JL TI Autoactivation of the marRAB multiple antibiotic resistance operon by the MarA transcriptional activator in Escherichia coli SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SUPEROXIDE RESPONSE REGULON; OXIDATIVE STRESS; POSITIVE CONTROL; REDOX STRESS; PROTEIN; LOCUS; GENES; MUTATIONS; COMPLEX; FUSIONS AB Transcriptional activation of the promoters of the mar/soxRS regulons by the sequence-related but independently inducible MarA and SoxS proteins renders Escherichia coli resistant to a broad spectrum of antibiotics and superoxide generators. Here, the effects of MarA and SoxS on transcription of the marRAB promoter itself were assayed in vitro by using a minimal transcription system and in vivo by assaying beta-galactosidase synthesized from marR::lacZ fusions. Purified MarA and MalE-SoxS proteins stimulated mar transcription about 6- and 15-fold, respectively, when the RNA polymerase/DNA ratio was 1. Purified MarA bound as a monomer to a 16-bp ''marbox'' located 69 to 54 nucleotides upstream of a putative RNA initiation site. Deletion of the marbox reduced MarA-mar binding 100-fold, abolished the stimulatory effects of MarA and SoxS on transcription in vitro, and reduced marR::lacZ synthesis about 4-fold in vivo. Deletion of upstream DNA adjoining the marbox reduced MarA binding efficiency 30-fold and transcriptional activation 2- to 3-fold, providing evidence for an accessory marbox. Although MarA and the mar operon repressor, MarR, bound to independent sites, they competed for promoter DNA in band shift experiments. Assays of marR::lacZ transcriptional fusions in marRAB deletion or soxRS deletion strains showed that the superoxide generator paraquat stimulates mar transcription via soxRS and that salicylate stimulates mar transcription both by antagonizing MarR and by a MarR-independent mechanism. Thus, transcription of the marRAB operon is autorepressed by MarR and autoactivated by MarA at a site that also can be activated by SoxS. C1 NIDDKD, MOLEC BIOL LAB, BETHESDA, MD 20892 USA. UNIV MARYLAND, DEPT BIOL SCI, BALTIMORE, MD 21228 USA. FU NIGMS NIH HHS [GM27113] NR 44 TC 98 Z9 99 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1996 VL 178 IS 8 BP 2216 EP 2223 PG 8 WC Microbiology SC Microbiology GA UF036 UT WOS:A1996UF03600008 PM 8636021 ER PT J AU Flatow, U Rajendrakumar, GV Garges, S AF Flatow, U Rajendrakumar, GV Garges, S TI Analysis of the spacer DNA between the cyclic AMP receptor protein binding site and the lac promoter SO JOURNAL OF BACTERIOLOGY LA English DT Article ID COLI RNA-POLYMERASE; ESCHERICHIA-COLI; TRANSCRIPTION ACTIVATION; REGULATORY REGION; ALPHA-SUBUNIT; CAP PROTEIN; GENE; CRP; CAMP; MUTANTS AB The role of the spacer region DNA between the cyclic AMP receptor protein (CRP) site and the RNA polymerase in the lac promoter was examined. We wanted to determine whether the wild-type DNA sequence of this region was an absolute requirement for CRP activation of inc transcription. The sequence of a 9-bp stretch of the spacer, from -41 to -49 relative to the start of transcription, was randomized, and the effect of randomization on inc expression was investigated in vitro and in vivo. We found that the spacer contains no specific sequence determinants for CRP activation of lac transcription; fewer than 1% of the mutants displayed greater than a 50% decrease in CRP activation of lac transcription. C1 NCI,DEV GENET SECT,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. NR 34 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1996 VL 178 IS 8 BP 2436 EP 2439 PG 4 WC Microbiology SC Microbiology GA UF036 UT WOS:A1996UF03600039 PM 8636052 ER PT J AU Mannella, CA Neuwald, AF Lawrence, CE AF Mannella, CA Neuwald, AF Lawrence, CE TI Detection of likely transmembrane beta-strand regions in sequences of mitochondrial pore proteins using the Gibbs sampler SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article ID VDAC ION CHANNEL; MEMBRANE AB The mitochondrial channel VDAC is presumed to fold as a beta-barrel although the number and identity of transmembrane beta-strands in the protein are controversial. Previously, a novel multiple alignment algorithm called the Gibbs sampler was used to detect a residue-frequency motif in sequences of bacterial outer-membrane proteins that corresponds to transmembrane beta-strands in bacterial porins of known structure (Neuwald et al., 1995, Protein Science, 4, 1618. In the present study, this bacterial motif has been used to screen sets of mitochondrial membrane protein sequences, with matches occurring in only two classes of proteins: VDACs and the outer-membrane protein import pore (ISP42, MOM38). These results suggest a structural (and perhaps evolutionary) relatedness between the bacterial and mitochondrial pore proteins; with the mitochondrial subsequences that match the bacterial motif corresponding to transmembrane beta-strands as in the porins. C1 SUNY ALBANY,SCH PUBL HLTH,DEPT BIOMED SCI,ALBANY,NY 12201. NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894. RP Mannella, CA (reprint author), WADSWORTH CTR,EMPIRE STATE PLAZA,ALBANY,NY 12201, USA. NR 24 TC 68 Z9 69 U1 1 U2 1 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD APR PY 1996 VL 28 IS 2 BP 163 EP 169 DI 10.1007/BF02110647 PG 7 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA UH176 UT WOS:A1996UH17600011 PM 9132415 ER PT J AU Geetha, V Munson, PJ AF Geetha, V Munson, PJ TI Simplified representation of proteins SO JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS LA English DT Article ID HOMOLOGOUS PROTEINS; PLEATED SHEETS; BETA-TURNS; CONFORMATION; GEOMETRY AB The conventional methods for characterizing the secondary structures of proteins based on hydrogen bonding patterns and phi,phi torsions are not fully specific in determining the spatial arrangements of various secondary structural elements. This fact motivates a search for an efficient description of the various secondary structures and their interactions. The successive identical repeating units of a polypeptide chain, namely the atoms of the peptide plane may be superposed using a method based on the mathematical quaternion. The superposition angle then characterizes different secondary structures. The distortions in protein alpha-helices such as kinks and bends are also precisely determined. The twist in beta-sheets is quantified and reverse turns are found to have characteristic variations. This new representation might pave the way for a better understanding of the final folding conformation of the polypeptide chain. RP Geetha, V (reprint author), NIH,DIV COMP RES & TECHNOL,STRUCT BIOL LAB,ANALYT BIOSTAT SECT,BETHESDA,MD 20892, USA. NR 29 TC 5 Z9 7 U1 0 U2 1 PU ADENINE PRESS INC PI GUILDERLAND PA PO BOX 355/340, GUILDERLAND, NY 12084 SN 0739-1102 J9 J BIOMOL STRUCT DYN JI J. Biomol. Struct. Dyn. PD APR PY 1996 VL 13 IS 5 BP 781 EP 793 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UJ090 UT WOS:A1996UJ09000005 PM 8723773 ER PT J AU Warmerdam, PAM Long, EO Roche, PA AF Warmerdam, PAM Long, EO Roche, PA TI Isoforms of the invariant chain regulate transport of MHC class II molecules to antigen processing compartments SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HLA-DR MOLECULES; MANNOSE 6-PHOSPHATE RECEPTORS; BETA-CHAIN; LINKED OLIGOSACCHARIDES; PEPTIDE COMPLEXES; ALPHA-CHAIN; EXPRESSION; CELLS; GLYCOSYLATION; LOCALIZATION AB Newly synthesized class II molecules of the major histocompatibility complex must be transported to endosomal compartments where antigens are processed for presentation to class II-restricted T cells, The invariant chain (Ii), which assembles with newly synthesized class II alpha- and beta-chains in the endoplasmic reticulum, carries one or more targeting signals for transport to endosomal compartments where Ii dissociates from alpha beta Ii complexes. Here we show that the transport route of alpha beta Ii complexes is regulated selectively by two forms of Ii (p33 and p35) that are generated by the use of alternative translation initiation sites. Using a novel quantitative surface arrival assay based on labeling with [6-H-3]-D-galactose combined with biochemical modification at the cell surface with neuraminidase, we demonstrate that newly synthesized alpha beta Ii molecules containing the Ii-p33 isoform can be detected on the cell surface shortly after passage through the Golgi apparatus/trans-Golgi network, A substantial amount of these alpha beta Ii complexes are targeted to early endosomes either directly from the trans-Golgi network or after internalization from the cell surface before their delivery to antigen processing compartments, The fraction of alpha beta Ii complexes containing the p35 isoform of Ii with a longer cytosolic domain was not detected at the cell surface as determined by iodination of intact cells and the lack of susceptibility to neuraminidase trimming on ice, However, treatment with neuraminidase at 37 degrees C did reveal that some of the alpha beta Ii-p35 complexes traversed early endosomes. These results demonstrate that a fraction of newly synthesized class II molecules arrive at the cell surface as alpha beta Ii complexes before delivery to antigen processing compartments and that class II alpha beta Ii complexes associated with the two isoforms of Ii are sorted to these compartments by different transport routes. C1 NCI,EXPTL IMMUNOL BRANCH,NIH,BETHESDA,MD 20892. NIAID,IMMUNOGENET LAB,NIH,ROCKVILLE,MD 20852. RI Long, Eric/G-5475-2011 OI Long, Eric/0000-0002-7793-3728 NR 53 TC 59 Z9 65 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR PY 1996 VL 133 IS 2 BP 281 EP 291 DI 10.1083/jcb.133.2.281 PG 11 WC Cell Biology SC Cell Biology GA UG037 UT WOS:A1996UG03700007 PM 8609162 ER PT J AU Jung, G Wu, XF Hammer, JA AF Jung, G Wu, XF Hammer, JA TI Dictyostelium mutants lacking multiple classic myosin I isoforms reveal combinations of shared and distinct functions SO JOURNAL OF CELL BIOLOGY LA English DT Article ID HEAVY-CHAIN ISOFORM; DISCOIDEUM; ENDOCYTOSIS; ACTIN; AMEBAS; LOCALIZATION; RECEPTORS; MOTILITY; SURFACE; CELLS AB Dicryostelium cells that lack the myoB isoform were previously shown to exhibit reduced efficiencies of phagocytosis and chemotactic aggregation (''streaming'') and to crawl at about half the speed of wild-type cells. Of the four other Dictyostelium myosin I isoforms identified to date, myoC and myoD are the most similar to myoB in terms of tail domain sequence. Furthermore, we show here that myoC, like myoB and myoD, is concentrated in actin-rich cortical regions like the leading edge of migrating cells. To look for evidence of functional overlap between these isoforms, we analyzed myoB, myoC, and myoD single mutants, myoB/myoD double mutants, and myoB/myoC/myoD triple mutants, which were created using a combination of gene targeting techniques and constitutive expression of antisense RNA. With regard to the speed of locomoting, aggregation-stage cells, of the three single mutants, only the myoB mutant was significantly slower. Moreover, double and triple mutants were only slightly slower than the myoB single mutant. Consistent with this, the protein level of myoB alone rises dramatically during early development, suggesting that a special demand is placed on this one isoform when cells become highly motile. We also found, however, that the absolute amount of myoB protein in aggregation-stage cells is much higher than that for myoC and myoD, suggesting that what appears to be a case of nonoverlapping function could be the result of large differences in the amounts of functionally overlapping isoforms. Streaming assays also suggest that myoC plays a significant role in some aspect of motility other than cell speed. With regard to phagocytosis, both myoB and myoC single mutants exhibited significant reductions in initial rate, suggesting that these two isoforms perform nonredundant roles in supporting the phagocytic process. In triple mutants these defects were not additive, however. Finally, because double and triple mutants exhibited significant and progressive decreases in doubling times, we also measured the kinetics of fluid phase endocytic flux (uptake, transit time, efflux). Not only do all three isoforms contribute to this process, but their contributions are synergistic. While these results, when taken together, refute the simple notion that these three ''classic'' myosin I isoforms perform exclusively identical functions, they do reveal that all three share in supporting at least one cellular process (endocytosis), and they identify several other processes (motility, streaming, and phagocytosis) that are supported to a significant extent by either individual isoforms or various combinations of them. C1 NHLBI,CELL BIOL LAB,SECT MOL CELL BIOL,NIH,BETHESDA,MD 20892. NR 61 TC 140 Z9 143 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD APR PY 1996 VL 133 IS 2 BP 305 EP 323 DI 10.1083/jcb.133.2.305 PG 19 WC Cell Biology SC Cell Biology GA UG037 UT WOS:A1996UG03700009 PM 8609164 ER PT J AU You, J Aznavoorian, S Liotta, LA Dong, C AF You, J Aznavoorian, S Liotta, LA Dong, C TI Responses of tumor cell pseudopod protrusion to changes in medium osmolality SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID SIGNAL TRANSDUCTION; AMEBOID CHEMOTAXIS; MYOSIN-II; ACTIN; METASTASIS; MECHANISMS; INVASION; MOTILITY; FIBROBLASTS; LOCOMOTION AB The potential involvement of osmotically generated force in protrusion of tumor cell pseudopods was examined during a micropipette assay. Experiments were performed on single A2058 melanoma cells activated by a micropipette filled with soluble type IV collagen. Previous observations suggested that tumor cell pseudopod protrusion induced by type IV collagen took place in distinct, separable phases: an initial bleb (first phase) caused by localized Ca2+-activated actin filament severing resulting in an osmotic flux followed by an extension with an irregular shape (second phase) which required G protein-mediated actin polymerization (Dong et al., 1994, Microvasc. Res., 47:55-67). Presently we studied cell pseudopod protrusion in response to the changes in chemoattractant osmolality. Reduction of attractant osmolality by 20-25% from its baseline value (297 mmol/kg) resulted in an increase in pseudopod length by 50% apparent in the initial phase. Increases in attractant osmolality by 25-30% from the baseline value arrested pseudopod protrusion significantly during both initial and later phases. Using a dual-pipette method, such osmotic influence on the cell pseudopod protrusion was shown to be only a local effect in a small region where the cell surface was stimulated by the micropipette. While forces derived from actin polymerization and osmotic pressure have been proposed to cause protrusion in general, our results suggested that osmotically generated force is more apparent in the initial phase of the pseudopod formation. (C) 1996 Wiiey-Liss, Inc. C1 PENN STATE UNIV,BIOENGN PROGRAM,CELLULAR BIOMECH LAB,UNIVERSITY PK,PA 16802. NCI,NIH,PATHOL LAB,BETHESDA,MD 20892. NR 32 TC 8 Z9 11 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 1996 VL 167 IS 1 BP 156 EP 163 DI 10.1002/(SICI)1097-4652(199604)167:1<156::AID-JCP18>3.0.CO;2-9 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA UA977 UT WOS:A1996UA97700018 PM 8698833 ER PT J AU Lijinsky, W Kovatch, RM AF Lijinsky, W Kovatch, RM TI Similar carcinogenic actions of nitrosoalkylureas of varying structure given to rats by gavage SO JOURNAL OF CLEAN TECHNOLOGY ENVIRONMENTAL TOXICOLOGY AND OCCUPATIONAL MEDICINE LA English DT Article ID METHYL-N-NITROSOUREA; MOUSE SKIN; F344 RATS; INDUCTION AB To relate the tumorigenic effects of directly acting alkylating nitrosoalkylureas to their chemical structure, a series of these compounds was given to F344 rats by gavage at approximately equimolar doses. In some cases, more than one dose rate was used. Potency, as measured by time to death with tumors, was similar for nitrosomethylurea and nitrosoethylurea, although the tumor pattern was different between the two. Nitrosoallylurea was of similar potency, and induced a spectrum of tumors similar to nitrosoethylurea. Nitroso-n-butyl-, n-amyl- and n-hexyl-ureas were less potent than nitrosoethylurea, but induced a similar pattern of tumors. All of the nitrosoureas induced tumors of the forestomach, usually in high incidence, except nitroso-2-hydroxyprophlurea, which caused death of the rats with thymic lymphoma within 6 months. Nitroso-3-hydroxypropylurea was much less potent than its 2-isomer, but induced no tumors of the thymus and was the only one of this group to induce tumors of the glandular stomach. Only nitrosomethylurea induced a high incidence of tumors of the nervous system, but no mammary carcinomas, which most of the other nitrosoureas induced in high incidence in females. Tumors of the lung, duodenum, colon and intestines were induced by several of the compounds, more commonly in males than in females, but a high incidence of liver tumors was found only in rats of both sexes given nitroso-2-phenylethylurea. RP Lijinsky, W (reprint author), NCI,FREDERICK CANC RES FACIL,BASIC RES PROGRAM,FREDERICK,MD 21701, USA. NR 20 TC 0 Z9 0 U1 0 U2 1 PU PRINCETON SCIENTIFIC PUBL INC PI PRINCETON PA PO BOX 2155, PRINCETON, NJ 08543 SN 1052-1062 J9 J CLEAN TECHNOL E T JI J. Clean Technol. Environ. Toxicol. Occup. Med. PD APR-JUN PY 1996 VL 5 IS 2 BP 155 EP 165 PG 11 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA WL781 UT WOS:A1996WL78100005 ER PT J AU Davidson, RA Smith, BD Tamny, TR Fedio, P AF Davidson, RA Smith, BD Tamny, TR Fedio, P TI Emotional arousal in temporal lobectomy: Autonomic and performance effects of success and failure feedback SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID ELECTRODERMAL ACTIVITY; REACTION-TIME; LOBE EPILEPSY; HEMISPHERIC ASYMMETRIES; MEMORY PERFORMANCE; DEPRESSION; ATTENTION; ANXIETY; PHYSIOLOGY; MEDIATION AB Both theory and evidence suggest that right temporal lobectomy (RTL) patients show hypoarousal and left temporal lobectomy (LTL) patients show relative hyperarousal (Davidson, Fedio, Smith, Aurielle, & Martin, 1992). However, we hypothesized that these differences occur only under passive, nonevaluative stimulus conditions. The present study employed, instead, conditions of performance evaluation. We recorded the skin conductance responses (SCRs) and reaction times (RTs) of RTLs, LTLs, and normal controls (NCs) during easy and difficult trial blocks on a target-detection task, with auditory success/failure feedback. We found that LTLs exhibited relative hypoarousal and retarded RTs and that RTLs were normally aroused following success feedback. These results demonstrated that the arousal level of LTLs is contingent on stimulus conditions, thus calling into question the theory that this group is generally subject to hyperarousal. The two-dimensional theory of the neural processing of emotional experience partially explains our data. C1 UNIV MARYLAND,DEPT PSYCHOL,COLLEGE PK,MD 20742. UNIV MARYLAND,CROWNSVILLE HOSP CTR,NINDS,NIH,COLLEGE PK,MD 20742. UNIV MARYLAND,CROWNSVILLE HOSP CTR,NEUROPSYCHOL SERV,COLLEGE PK,MD 20742. CUNY CITY COLL,NEW YORK,NY 10031. NR 43 TC 2 Z9 2 U1 2 U2 3 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 APR PY 1996 VL 18 IS 2 BP 249 EP 258 DI 10.1080/01688639608408279 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA UR524 UT WOS:A1996UR52400008 PM 8780959 ER PT J AU Harlow, BL Frigoletto, FD Cramer, DW Evans, JK LeFevre, ML Bain, RP McNellis, D AF Harlow, BL Frigoletto, FD Cramer, DW Evans, JK LeFevre, ML Bain, RP McNellis, D TI Determinants of preterm delivery in low-risk pregnancies SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE prospective studies; epidemiological methods; infant-premature; risk factors; labor-premature; pregnancy complications ID SERUM ALPHA-FETOPROTEIN; BIRTH; MEMBRANES; RUPTURE; SYSTEM; LABOR; WOMEN AB From 14,948 low-risk singleton pregnancies, we calculated incidence, risk ratios, and attributable risks for characteristics associated with spontaneous and medically induced preterm delivery. There were 754 women who gave birth prior to 37 weeks of gestation (50.4/1000 deliveries). The greatest fraction of the incidence of prematurity among low-risk pregnancies was due to unknown factors associated with carrying a first live birth, regardless of preterm delivery mechanism (i.e., spontaneous Labor, FROM, medical intervention), with population-attributable risk percents (PAR%) ranging from 16.0 to 30.5%. Other than nulliparity, male sex of the fetus accounted for the greatest fraction of spontaneous labor-induced prematurity incidence (PAR% 13.6%), and maternal age greater than 30 years or a positive urine culture accounted for the greatest fraction of FROM-induced prematurity incidence (PAR% = 7.9 and 6.7, respectively). All other risk factors for either preterm labor or FROM accounted for less than 5% of the incidence. Three characteristics explained a large fraction of medically induced prematurity: women over 150 pounds at the onset of pregnancy (PAR% = 23.8), a greater than or equal to 2+ prenatal urine protein (PAR% = 18.7%), and cigarette smoking during the first trimester (PAR% = 8.6). Our results suggest that known risk factors may explain only a small fraction of spontaneous preterm delivery incidence in low-risk pregnancies. C1 HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,DEPT OBSTET GYNECOL & REPROD BIOL,BOSTON,MA 02115. GEORGE WASHINGTON UNIV,CTR BIOSTAT,DEPT STAT COMP & INFORMAT SYST,ROCKVILLE,MD. UNIV MISSOURI,SCH MED,DEPT FAMILY & COMMUNITY MED,COLUMBIA,MO. NICHHD,WASHINGTON,DC. RP Harlow, BL (reprint author), HARVARD UNIV,BRIGHAM & WOMENS HOSP,SCH MED,CTR OBSTET & GYNECOL EPIDEMIOL,BOSTON,MA 02115, USA. FU NICHD NIH HHS [HD 19897, HD 21017, HD 21140] NR 26 TC 35 Z9 35 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 1996 VL 49 IS 4 BP 441 EP 448 DI 10.1016/0895-4356(95)00566-8 PG 8 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA UH716 UT WOS:A1996UH71600007 PM 8621995 ER PT J AU Aneman, A Eisenhofer, G Olbe, L Dalenback, J Nitescu, P Fandriks, L Friberg, P AF Aneman, A Eisenhofer, G Olbe, L Dalenback, J Nitescu, P Fandriks, L Friberg, P TI Sympathetic discharge to mesenteric organs and the liver - Evidence for substantial mesenteric organ norepinephrine spillover SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE sympathetic nervous system; splanchnic circulation; portal system; portal vein; liver ID ALCOHOLIC CIRRHOSIS; NERVOUS ACTIVITY; INHIBITION; HUMANS; CATECHOLAMINES; NORADRENALINE; METABOLISM; ANESTHESIA; KINETICS; RELEASE AB This study used sampling of blood from the portal vein, in addition to arterial and hepatic sites, to estimate separately spillovers of norepinephrine from mesenteric organs and the liver in seven patients undergoing upper abdominal surgery, Conventional measurements in arterial and hepatic venous plasma provided a measure of net hepatomesenteric NE spillover (403 pmol/ml) that indicated a 13% contribution of these organs to total body spillover of NE into systemic plasma (3,071+/-518 pmol/min), The net hepatomesenteric spillover of NE into systemic plasma was much lower than the spillover of NE from mesenteric organs into portal venous plasma (1,684+/-418 pmol/min). This and the hepatic spillover of NE into systemic plasma (212+/-72 pmol/min) indicated a considerable combined spillover of NE from hepatomesenteric organs (1,896+/-455 pmol/min). The sum of the latter estimate with the difference between total body and net hepatomesenteric NE spillovers provided an adjusted total body spillover of NE into both systemic and portal venous plasma (4,564+/-902 pmol/min). Mesenteric organs made a 37% contribution, and the liver made a 5% contribution to the adjusted total body spillover of NE, Thus, a substantial proportion of total body sympathetic outflow is directed towards mesenteric organs; this is obscured by efficient hepatic extraction of NE (86+/-6%) when measurements are restricted to arterial and hepatic venous plasma. C1 NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. GOTHENBURG UNIV,DEPT ANESTHESIOL & INTENS CARE,S-41345 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT SURG,S-41345 GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT PHYSIOL,S-41345 GOTHENBURG,SWEDEN. NR 26 TC 52 Z9 53 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 1 PY 1996 VL 97 IS 7 BP 1640 EP 1646 DI 10.1172/JCI118590 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UD916 UT WOS:A1996UD91600012 PM 8601629 ER PT J AU Rehermann, B Lau, D Hoofnagle, JH Chisari, FV AF Rehermann, B Lau, D Hoofnagle, JH Chisari, FV TI Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HBV; CTL; interferon; HLA-A2; limiting dilution analysis ID ALPHA-INTERFERON THERAPY; NUCLEOCAPSID ANTIGEN; HBSAG-CARRIERS; CONTROLLED TRIAL; CELL RESPONSES; EXPRESSION; DNA; RECOGNIZE; PROTEINS; EPITOPE AB Clearance of the hepatitis B virus (HBV) during acute hepatitis is associated with a strong, polyclonal, multispecific cytotoxic T lymphocyte (CTL) response to the viral envelope, nucleocapsid and polymerase proteins that persists for decades after clinical recovery, In contrast, chronically infected patients usually fail to mount a strong CTL response to this virus, In this study we demonstrate that chronically infected patients who experience a spontaneous or interferon-induced remission develop a CTL response to HBV that is similar in strength and specificity to patients who have recovered from acute hepatitis, The results suggest that specific immunotherapeutic enhancement of the CTL response to HBV should be possible in chronically infected patients, and that it could lead to viral clearance in these individuals with resolution of chronic liver disease. C1 SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, LA JOLLA, CA 92037 USA. NIDDKD, LIVER DIS SECT, DIGEST DIS BRANCH, NIH, BETHESDA, MD 20892 USA. RI Chisari, Francis/A-3086-2008; OI Chisari, Francis/0000-0002-4832-1044 FU NCRR NIH HHS [RR00833]; NIAID NIH HHS [AI20001] NR 28 TC 211 Z9 222 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 1 PY 1996 VL 97 IS 7 BP 1655 EP 1665 DI 10.1172/JCI118592 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UD916 UT WOS:A1996UD91600014 PM 8601631 ER PT J AU Ward, RL Kapikian, AZ Goldberg, KM Knowlton, DR Watson, IW Rappaport, R AF Ward, RL Kapikian, AZ Goldberg, KM Knowlton, DR Watson, IW Rappaport, R TI Serum rotavirus neutralizing-antibody titers compared by plaque reduction and enzyme-linked immunosorbent assay-based neutralization assays SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VACCINE; WC3; IMMUNOGENICITY; REASSORTANT; PROTECTION; INFANTS AB Comparisons in rotavirus neutralizing-antibody responses were made with sera collected from vaccinated infants. The methods were a plaque reduction assay and a new enzyme-linked immunosorbent assay-based neutralization assay. Agreement of 94% was found in detecting at least fourfold seroresponses, and correlation coefficients between titers obtained by the two methods showed excellent agreement, indicating that either could be used reliably. C1 JAMES N GAMBLE INST MED RES,CINCINNATI,OH 45219. NIAID,BETHESDA,MD 20892. WYETH AYERST RES,PHILADELPHIA,PA 19101. NR 19 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1996 VL 34 IS 4 BP 983 EP 985 PG 3 WC Microbiology SC Microbiology GA UA683 UT WOS:A1996UA68300043 PM 8815124 ER PT J AU Tolcher, AW Cowan, KH Solomon, D Ognibene, F Goldspiel, B Chang, R Noone, MH Denicoff, AM Barnes, CS Gossard, MR Fetsch, PA Berg, SL Balis, FM Venzon, DJ OShaughnessy, JA AF Tolcher, AW Cowan, KH Solomon, D Ognibene, F Goldspiel, B Chang, R Noone, MH Denicoff, AM Barnes, CS Gossard, MR Fetsch, PA Berg, SL Balis, FM Venzon, DJ OShaughnessy, JA TI Phase I crossover study of paclitaxel with r-verapamil in patients with metastatic breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID P-GLYCOPROTEIN EXPRESSION; BACTERIAL TRANSPORT PROTEINS; MULTIDRUG RESISTANCE; DOXORUBICIN RESISTANCE; OVARIAN-CANCER; CELLS; PHARMACOKINETICS; TRIAL; CHEMOTHERAPY; VINCRISTINE AB Purpose: We conducted a phase I crossover study of escalating doses of both paclitaxel (Taxol; Bristol-Myers Squibb, Princeton, NJ) and r-verapamil, the less cardiotoxic stereoisomer, in heavily pretreated patients with metastatic breast cancer. Patients and Methods: Twenty-nine patients refractory to paclitaxel by 3-hour infusion were treated orally with r-verapamil every 4 hours starting 24 hours before the same-dose 3-hour paclitaxel infusion and continuing for a total of 12 doses. Once the maximum-tolerated dose (MTD) of the combination was determined, seven additional patients who held not been treated with either drug were evaluated to determine whether the addition of r-verapamil altered the pharmacokinetics of paclitaxel. Consenting patients had tumor biopsies for P-glycoprotein (Pgp) expression before receiving paclitaxel and after becoming refractory to paclitaxel therapy. Results: The MTD of the combination was 225 mg/m(2) of r-verapamil every 4 hours with paclitaxel 200 mg/m(2) by 3-hour infusion. Dose-limiting hypotension and bradycardia were observed in three of five patients treated at 250 mg/m(2) r-verapamil. Fourteen patients received 32 cycles of r-verapamil at the MTD as outpatient therapy without developing cardiac toxicity. The median peak and trough serum verapamil concentrations at the MTD were 5.1 mu mol/L (range, 4.1 to 12.7) and 3.2 mu mol/L (range, 1.9 to 6.3), respectively, which are within the range necessary for in vitro modulation of Pgp-mediated multidrug resistance (MDR). Increased serum verapamil concentrations and cardiac toxicity were observed more frequently in patients with elevated hepatic transaminases and bilirubin levels. Hematologic toxicity from combined paclitaxel and r-verapamil was significantly worse compared with the previous cycle of paclitaxel without r-verapamil. In the pharmacokinetic analysis, r-verapamil delayed mean paclitaxel clearance and increased mean peak paclitaxel concentrations. Conclusion: r-Verapamil at 225 mg/m(2) orally every 4 hours can be given safely with paclitaxel 260 mg/m(2) by 3-hour infusion as outpatient therapy and is associated with serum levels considered active for Pgp inhibition. The addition of r-verapamil significantly alters the toxicity and pharmacokinetics of paclitaxel. C1 NCI,MED BRANCH,BETHESDA,MD 20892. NCI,DETECT & CTR,DIV CANC BIOL,BETHESDA,MD 20892. NCI,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. RI Venzon, David/B-3078-2008 NR 44 TC 58 Z9 59 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1996 VL 14 IS 4 BP 1173 EP 1184 PG 12 WC Oncology SC Oncology GA UF068 UT WOS:A1996UF06800018 PM 8648372 ER PT J AU Dahut, W Harold, N Takimoto, C Allegra, C Chen, A Hamilton, JM Arbuck, S Sorensen, M Grollman, F Nakashima, H Lieberman, R Liang, M Corse, W Grem, J AF Dahut, W Harold, N Takimoto, C Allegra, C Chen, A Hamilton, JM Arbuck, S Sorensen, M Grollman, F Nakashima, H Lieberman, R Liang, M Corse, W Grem, J TI Phase I and pharmacologic study of 9-aminocamptothecin given by 72-hour infusion in adult cancer patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID TOPOISOMERASE-I; MALIGNANT-MELANOMA; CAMPTOTHECIN; TOPOTECAN; NSC-100880; XENOGRAFTS; INHIBITION; ANALOGS; TRIAL AB Purpose: To conduct a phase I and pharmacologic study of the new topoisomerase I inhibitor, 9-aminocamptothecin (9-AC). Patients and Methods: A 72-hour infusion of 9-AC was administered every 14 days to 48 solid-tumor patients at doses of 5 to 59 mu g/m(2)/h without granulocyte colony-stimulating factor (G CSF) and 47 to 74 mu g/m(2)/ h with G-CSF. Results: Without G-CSF, two of eight patients who received 47 mu g/m(2)/h had dose-limiting neutropenia in their initial cycle, as did both patients who received 59 mu g/m(2)/h (with a platelet count < 25,000/mu L in one). With G-CSF, zero of seven patients treated with 47 mu g/ m(2)/h had dose-limiting neutropenia in their first cycle, while dose-limiting neutropenia occurred in six of 14 patients (with platelet count < 25,000/mu L in five) entered at 59 mu g/m(2)/h. Among 39 patients entered at greater than or equal to 25 mu g/ m(2)/h 9-AC with or without G CSF, fatigue, diarrhea, and navsea/vomiting of grade 2 severity ultimately occurred in 54%, 30%, and 38%, respectively, while grade 3 toxicity of each type occurred in 8% of patients. Steady-state 9-AC lactone concentration (Css) increased linearly from 0.89 to 10.6 nmol/L, and correlated strongly with leukopenia (r = .85). Conclusion: The recommended phase II dose of 9-AC given by 72-hour infusion every 2 weeks is 35 mu g/m(2)/h without G-CSF or 47 mu g/m(2)/h with G-CSF support. Dose escalation in individual patients may be possible according to their tolerance. C1 NATL NAVAL MED CTR, NAVY MED ONCOL BRANCH, DEPT RADIOL, BETHESDA, MD 20889 USA. NCI, DIV CANC TREATMENT,CANC THERAPY EVALUAT PROGRAM, CLIN ONCOL PROGRAM,NCI,NAVY MED ONCOL BRANCH, BETHESDA, MD USA. US FDA, CTR DRUG EVALUAT & RES, ROCKVILLE, MD 20857 USA. NR 26 TC 66 Z9 67 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1996 VL 14 IS 4 BP 1236 EP 1244 PG 9 WC Oncology SC Oncology GA UF068 UT WOS:A1996UF06800025 PM 8648379 ER PT J AU Grasing, K Murphy, MG Lin, JI Swigar, M Freedholm, D Clarke, L Zhang, J Wolkowitz, OM Weingartner, H Putnam, K Seibold, JR AF Grasing, K Murphy, MG Lin, JI Swigar, M Freedholm, D Clarke, L Zhang, J Wolkowitz, OM Weingartner, H Putnam, K Seibold, JR TI Human pharmacokinetics and tolerability of L-365,260, a novel cholecystokinin-B antagonist SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID PREVENTS MORPHINE-TOLERANCE; BRAIN CCK RECEPTORS; SELECTIVE ANTAGONIST; PANIC DISORDER; RAT; POTENT; PERFORMANCE; RELEASE; ATTACKS; ANXIETY AB A study was conducted to examine the tolerability and pharmacokinetics of single and multiple oral doses of L-365,260, a novel antagonist for type B cholecystokinin (CCK) receptors and to quantify effects of selective blockade of type B CCK receptors through treatment with L-365,260 on measures of anxiety, hunger, and cognitive performance. Healthy volunteers were given single oral doses of up to 50 mg of L-365,260 and multiple oral doses of up to 25 mg every 6 hours for 10 days. Plasma concentrations of L-365,260 were quantified by means of high-performance liquid chromatography. Anxiety and hunger were assessed by visual analog scale and the Spielberger State Anxiety Index. Cognitive testing was used to evaluate attention level and short-term memory. L-365,260 was rapidly absorbed and a biphasic pattern of elimination was demonstrated with a terminal half-life (t(1/2)) of 8 to 12 hours. The mean (n = 6) values for peak plasma concentration (C-max) and time to peak concentration (t(max)) of L-365,260 were 503 ng/mL and 1.25 hours, respectively, after a single 50-mg oral dose. Accumulation of L-365,260 plasma concentrations was seen after the prescribed multiple-dose regimens. Steady state was achieved after 3 days of oral administration. L-365,260 had an acceptable tolerability profile after oral administration. No changes in measures of anxiety, hunger, or short-term memory were observed at doses of L-365,260 shown to have antagonist activity at the CCK-B receptor. C1 MERCK SHARP & DOHME RES LABS,W POINT,PA. UNIV CALIF SAN FRANCISCO,DEPT PSYCHIAT,SAN FRANCISCO,CA 94143. NATL INST ALCOHOL ABUSE,COGNIT NEUROSCI SECT,BETHESDA,MD. RP Grasing, K (reprint author), UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,CLIN RES CTR,DEPT MED,NEW BRUNSWICK,NJ 08903, USA. NR 36 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 1996 VL 36 IS 4 BP 292 EP 300 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UG281 UT WOS:A1996UG28100003 PM 8728342 ER PT J AU Bowden, CL Brady, KT Forster, PL Goodwin, K Tohen, M AF Bowden, CL Brady, KT Forster, PL Goodwin, K Tohen, M TI Current concepts in treating bipolar disorder SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Editorial Material ID PSYCHIATRIC EMERGENCIES; ACUTE MANIA; LITHIUM; DISCONTINUATION; VALPROATE; QUALITY C1 MED UNIV S CAROLINA,DEPT PSYCHIAT & BEHAV SCI,CHARLESTON,SC 29425. MED UNIV S CAROLINA,CTR DRUG & ALCOHOL PROGRAMS,CHARLESTON,SC 29425. UNIV CALIF SAN FRANCISCO,SAN FRANCISCO,CA 94143. ALAMEDA CTY MED CTR,DEPT PSYCHIAT,SAN LEANDRO,CA. GEORGE WASHINGTON UNIV,DEPT PSYCHIAT,CTR NEUROSCI BEHAV & SOC,WASHINGTON,DC. NIMH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138. HARVARD UNIV,SCH PUBL HLTH,CAMBRIDGE,MA 02138. MCLEAN HOSP,GEN ADULT PSYCHIAT PROGRAM,BELMONT,MA 02178. INST MED STUDIES,LAGUNA NIGUEL,CA. ABBOTT LABS,N CHICAGO,IL 60064. RP Bowden, CL (reprint author), UNIV TEXAS,HLTH SCI CTR,DEPT BIOL PSYCHIAT,7703 FLOYD CURL DR,SAN ANTONIO,TX, USA. NR 19 TC 1 Z9 1 U1 1 U2 1 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 1996 VL 57 IS 4 BP A1 EP A12 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA UF768 UT WOS:A1996UF76800003 ER PT J AU Potter, WZ AF Potter, WZ TI Key issues in the diagnosis and treatment of bipolar disorder SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Editorial Material RP Potter, WZ (reprint author), NIMH,BETHESDA,MD 20892, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 1996 VL 16 IS 2 SU 1 BP S1 EP S3 DI 10.1097/00004714-199604001-00001 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA UE552 UT WOS:A1996UE55200002 PM 8707995 ER PT J AU Keefe, KA Gerfen, CR AF Keefe, KA Gerfen, CR TI D1 dopamine receptor-mediated induction of zif268 and c-fos in the dopamine-depleted striatum: Differential regulation and independence from NMDA receptors SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE in situ hybridization; c-fos; zif268; glutamate antagonists; SKF 38393 ID IDENTIFIED STRIATONIGRAL NEURONS; SUBSTANTIA-NIGRA; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; STRIATOPALLIDAL NEURONS; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; DENDRITIC SPINES; CORTICAL INPUTS; FACTOR CREB AB Excitatory amino acid afferents from cerebral cortex and dopamine afferents from the substantia nigra synapse on common projection neurons in the striatum. Activation of D1 dopamine receptors increases immediate early gene expression in the striatum and conductance through the N-methyl-d-aspartate (NMDA) receptor. To examine the contribution of NMDA receptor activation to dopamine receptor-mediated responses, we determined the effects of intrastriatal administration of NMDA antagonists on immediate early gene expression in the striatum and rotational behavior induced by stimulation of the D1 receptor in rats with unilateral dopamine depletions. Systemic administration of SKF 38393 increased c-fos and zif268 mRNAs in the striatum and induced contralateral rotation. Intrastriatal infusion of the competitive NMDA receptor antagonist (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid caused a dose-dependent attenuation of SKF 38393-induced rotation and partially decreased c-fos mRNA expression. However, D1-mediated increases in zif268 mRNA were not affected, except by the highest concentration of antagonist used (10 mM). Another competitive antagonist, 2-amino-5-phosphonovaleric acid, had similar effects. Like the competitive antagonists, intrastriatal infusion of the non-competitive NMDA antagonist MK-801 partially decreased c-fos, but not zif268, mRNA in the area around the microdialysis probe. However, unlike competitive antagonists, local infusion of 1 mM MK-801 potentiated D1-mediated increases in c-fos and zif268 mRNAs in lateral striatum. These data suggest that 1) some D1 dopamine receptor-mediated effects on striatal function are independent of ongoing NMDA receptor activation, whereas other effects are at least partially mediated by NMDA receptor activity in the striatum, and 2) competitive and non-competitive antagonists of the NMDA receptor differently affect D1-mediated immediate early gene expression in the striatum. (C) 1996 Wiley-Liss, Inc. C1 NIMH,NEUROPHYSIOL LAB,BETHESDA,MD 20892. NR 62 TC 65 Z9 65 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 1 PY 1996 VL 367 IS 2 BP 165 EP 176 DI 10.1002/(SICI)1096-9861(19960401)367:2<165::AID-CNE1>3.0.CO;2-3 PG 12 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA UC714 UT WOS:A1996UC71400001 PM 8708002 ER PT J AU delCarmen, R Huffman, L AF delCarmen, R Huffman, L TI Epilogue: Bridging the gap between research on attachment and psychopathology SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID PREDICTORS; BEHAVIOR AB Clinicians and researchers are beginning to acknowledge the importance of integrating a developmental perspective into the understanding of clinical disorders. The application of findings from basic attachment research to this understanding of psychopathology is a prototype for interdisciplinary research. However, major gaps continue to exist between basic research on attachment processes and clinical issues of assessment, classification, and treatment of mental disorders from infancy through adolescence. This epilogue highlights the importance of more integrative research. As a reflection of growth in this direction, National Institute of Mental Health funding patterns are reviewed, and promising areas for future research are suggested. The field is well positioned for conceptual advancement if more integrative approaches are used. RP delCarmen, R (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,18C-17,ROCKVILLE,MD 20857, USA. NR 33 TC 2 Z9 2 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 1996 VL 64 IS 2 BP 291 EP 294 PG 4 WC Psychology, Clinical SC Psychology GA UH154 UT WOS:A1996UH15400007 PM 8871413 ER PT J AU Rosby, O Stromme, P Sandsmark, M Ramstad, K Ormerod, E vanderHagen, CB Kubota, T Ledbetter, DH Orstavik, KH AF Rosby, O Stromme, P Sandsmark, M Ramstad, K Ormerod, E vanderHagen, CB Kubota, T Ledbetter, DH Orstavik, KH TI Unilateral cleft lip in a boy with Angelman syndrome SO JOURNAL OF CRANIOFACIAL GENETICS AND DEVELOPMENTAL BIOLOGY LA English DT Article DE mentally retarded; seizures ataxia; delayed motor milestones; FISH; DNA analysis; 15 q11-13 deletion ID DIAGNOSIS; PALATE; DISOMY AB We report on a mentally retarded boy with epileptic seizures, microcephaly, ataxia. and developmental delay. His clinical features were consistent with Angelman syndrome, Fluorescent in situ hybridization and DNA analysis showed a deletion of chromosome 15 q11-13 and thus confirmed the diagnosis. In addition, thr patient had a unilateral, incomplete cleft lip, a feature which has not previously been reported in Angelman syndrome. C1 UNIV OSLO,ULLEVAL HOSP,DEPT MED GENET,N-0315 OSLO,NORWAY. UNIV OSLO,RIKSHOSP,CTR MENTLA RETARDAT,DEPT PEDIAT,N-0316 OSLO,NORWAY. UNIV OSLO,RIKSHOSP,DEPT PLAST SURG,N-0027 OSLO,NORWAY. BUSKERUD HABILITAT CTR,DRAMMEN,NORWAY. NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,NIH,BETHESDA,MD. NR 13 TC 2 Z9 2 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0270-4145 J9 J CRAN GENET DEV BIO JI J. Craniofac. Genet. Dev. Biol. PD APR-JUN PY 1996 VL 16 IS 2 BP 122 EP 125 PG 4 WC Anatomy & Morphology; Developmental Biology; Genetics & Heredity SC Anatomy & Morphology; Developmental Biology; Genetics & Heredity GA UM596 UT WOS:A1996UM59600006 PM 8773903 ER PT J AU Sander, CA Kaudewitz, P Kutzner, H Simon, M Schirren, CG Sioutos, N Cossman, J Plewig, G Kind, P Jaffe, ES AF Sander, CA Kaudewitz, P Kutzner, H Simon, M Schirren, CG Sioutos, N Cossman, J Plewig, G Kind, P Jaffe, ES TI T-cell rich B-cell lymphoma presenting in skin - A clinicopathologic analysis of six cases SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article AB We reviewed our experience with six T-cell-rich B-cell lymphomas (TRBL) presenting in skin. Immunohistochemical studies were performed on all biopsies. The lymphoid population consisted mainly of CD3 and/or UCHL-1 (CD45RO) positive T cells. 5 to 15% of the lymphoid cells stained for the B-cell marker L26 (CD20). Monoclonality of the B-cell component was demonstrated in all cases, utilizing either light chain restriction (5 cases) or clonal immunoglobulin heavy chain gene rearrangement by polymerase chain reaction (PCR) (2 cases). One case tvas confirmed to be monoclonal by both techniques. Additionally, no clonal rearrangements of the T-cell receptor gamma gene were observed. There was considerable morphological variety in these cases. In H&E stained sections, the differential diagnosis included pseudolymphoma, peripheral T-cell lymphoma, Hodgkin's disease, Lennert's lymphoma and a MALT lymphoma. A significant component of monoclonal plasma cells was present in 3 of 6 cases, suggesting a possible origin from cutaneous immunocytoma. In fact, one of our cases was a biphasic lymphoma displaying TRBL with a small focus of immunocytoma. We conclude that immunophenotypic analysis is necessary for the diagnosis of TRBL. Pathologists should be aware of this type of cutaneous B-cell lymphoma to avoid misinterpretation as a pseudolymphoma. C1 LAB DERMATOHISTOPATHOL,FRIEDRICHSHAFEN,GERMANY. GEORGETOWN UNIV,DEPT PATHOL,WASHINGTON,DC 20007. NCI,PATHOL LAB,HEMATOPATHOL SECT,NIH,BETHESDA,MD. RP Sander, CA (reprint author), UNIV MUNICH,DEPT DERMATOL,FRAUENLOBSTR 9-11,D-80337 MUNICH,GERMANY. NR 25 TC 23 Z9 23 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD APR PY 1996 VL 23 IS 2 BP 101 EP 108 DI 10.1111/j.1600-0560.1996.tb01282.x PG 8 WC Dermatology; Pathology SC Dermatology; Pathology GA UD477 UT WOS:A1996UD47700001 PM 8721443 ER PT J AU Scott, DB AF Scott, DB TI The early days of electron microscopy in dental research SO JOURNAL OF DENTAL RESEARCH LA English DT Editorial Material C1 NIDR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 1996 VL 75 IS 4 BP 962 EP 965 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VA158 UT WOS:A1996VA15800004 PM 8708136 ER PT J AU Monma, Y Chen, ZJ Mayama, H Kamiyama, K Shimizu, F AF Monma, Y Chen, ZJ Mayama, H Kamiyama, K Shimizu, F TI Highly virulent strains of herpes simplex virus fail to kill mice following infection via gingival route SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE gamma delta T-cells; gingiva; herpes simplex virus; mice; virulence ID INFLAMED HUMAN GINGIVA; TYPE-1; INTERFERON; CELLS AB Virulence of herpes simplex virus (HSV) in mice has been demonstrated to be dependent on the site of infection. In this experiment, pathogenesis of HSV was studied in 2 different routes of infection in a mouse model system. When BALB/c mice were infected with 5 x 10(3) plaque-forming units (PFU) of virulent HSV type 1 Miyama GC(+) strain (HSV-1-GC(+)) intraperitoneally, all mice were dead in 6 to 9 days. HSV-1-GC(+) was recovered from organs such as the cerebrum, cerebellum, brainstem, and spleen 2 to 5 days after infection, but not from other organs such as trigeminal ganglia. However, if mice were infected in the maxillary gingiva with 1.0 x 10(7) PFU of HSV-1-GC(+), all mice survived. HSV-1-GC(+) was recovered from the trigeminal ganglia and brainstem 2 to 5 days after infection, but not from other organs tested. When mice were infected in maxillary gingiva with HSV-1-GC(+), followed by the intraperitoneal injection of 6 mg of cyclophosphamide 72 hrs after virus infection, all mice were dead within days. Immunofluorescent and hematoxylin-eosin staining of gingival tissue sections revealed that when mice were infected in maxillary gingiva with HSV-1-GC(+), 3 times as many gamma delta T-cells and 5 times as many polymorphonuclear cells can be detected in sections of maxillary gingiva when compared with non-infected mice. These data show that the gingiva of mice is considerably more resistant to infection with HSV, compared with the peritoneal cavity, and suggest the possible presence of an oral defense mechanism which might be different from that in the peritoneal cavity. C1 TOKYO MED & DENT UNIV,SCH MED,DEPT MICROBIOL,TOKYO 113,JAPAN. NIDR,ORAL MED LAB,NIH,BETHESDA,MD 20892. TOHOKU UNIV,SCH DENT,DEPT PEDIAT DENT,SENDAI,MIYAGI 980,JAPAN. NR 17 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC DENTAL RESEARCH PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314 SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD APR PY 1996 VL 75 IS 4 BP 974 EP 979 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA VA158 UT WOS:A1996VA15800006 PM 8708138 ER PT J AU Boyd, MR AF Boyd, MR TI The position of intellectual property rights in drug discovery and development from natural products SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium on Intellectual Property Rights, Naturally Derived Bioactive Compounds and Resource Conservation, at the 1994 Interim Annual Meeting of the American-Society-of-Pharmacognosy CY OCT 20-22, 1994 CL SAN JOSE, COSTA RICA SP Amer Soc Pharmacognosy, Coll Pharmacy, Dept Medicinal Chem & Pharmacognosy, Program Collaborat Res, Pharm Sci, Univ Illinois Chicago, Ctr Investigac Prod Nat, Univ Costa Rica, San Jose, Inst Nacl Biodiversidad, San Jose DE intellectual property; intellectual property rights; intellectual property contributions to drug discovery and development; protection of intellectual property; intellectual property agreements; patents; licenses; biodiversity; biodiversity treaty AB Some practical working definitions and perspectives are offered here as to 'intellectual property' (IP) and 'intellectual property rights' (IPR), particularly as they may pertain to the essential contributions of the parties to an international cooperation or collaboration in drug discovery and development from natural products. Existing and new intellectual properties are examined particularly in respect to feasible ways in which they may be appropriately recognized and protected. It is further illustrated how such suitable recognition and protection may provide the basis to insure fair and appropriate compensation for contributions of existing intellectual property essential for the creation of new intellectual property. The importance of an adequate mutual understanding, and shared realistic perspective, of the overall process and probability of outcome of any given drug discovery and development venture, is emphasized. RP Boyd, MR (reprint author), NCI,FREDERICK CANC RES & DEV CTR,DIV CANC TREATMENT,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702, USA. NR 12 TC 13 Z9 15 U1 0 U2 7 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD APR PY 1996 VL 51 IS 1-3 BP 17 EP 25 DI 10.1016/0378-8741(95)01346-6 PG 9 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UC676 UT WOS:A1996UC67600004 PM 9213613 ER PT J AU Cragg, G Boyd, MR AF Cragg, G Boyd, MR TI The position of intellectual property rights in drug discovery and development from natural products - Discussion SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Editorial Material RP Cragg, G (reprint author), NCI,FREDERICK CANC RES & DEV CTR,BLDG 1052,RM 121,FREDERICK,MD 21702, USA. NR 0 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD APR PY 1996 VL 51 IS 1-3 BP 25 EP 27 PG 3 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UC676 UT WOS:A1996UC67600005 ER PT J AU Mays, T Mazan, KD AF Mays, T Mazan, KD TI Legal issues in sharing the benefits of biodiversity prospecting SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Article; Proceedings Paper CT Symposium on Intellectual Property Rights, Naturally Derived Bioactive Compounds and Resource Conservation, at the 1994 Interim Annual Meeting of the American-Society-of-Pharmacognosy CY OCT 20-22, 1994 CL SAN JOSE, COSTA RICA SP Amer Soc Pharmacognosy, Coll Pharmacy, Dept Medicinal Chem & Pharmacognosy, Program Collaborat Res, Pharm Sci, Univ Illinois Chicago, Ctr Investigac Prod Nat, Univ Costa Rica, San Jose, Inst Nacl Biodiversidad, San Jose DE biodiversity; intellectual property rights; indigenous rights; contracts ID ANTITUMOR AB The National Cancer Institute (NCI) is the US Government's principal agency for research on the prevention, diagnosis and treatment of cancer. A critical component of the Institute's mission is the identification and development of new and promising treatments for cancer and AIDS. For many years these efforts have included a program to investigate natural products for potential new therapeutic agents. In 1986, with the advent of new screening techniques, the National Cancer Institute stepped up its exploration of natural products and began world-wide collections of plants in tropical and subtropical regions. In recognition of the principles of the Biodiversity Treaty, NCI appreciates that continued access to the natural products of these countries depends on the Institute's ability to recognize the contributions of these source countries and their indigenous peoples, and to provide them adequate incentives to conserve their natural resources for the purposes of drug discovery. Accomplishing this goal presented several legal issues for the National Cancer Institute. As an agency of the US government, the NCI has an adjunct statutory mission to facilitate the transfer of technology developed through the Institute's programs into the private sector for further development and commercialization, and NCI operates under a national policy to use the patent system to transfer Federally supported research to the private domestic sector. Reliance on patent law may limit the Institute's ability to recognize the rights of source countries and their indigenous people and provide compensation for their contributions. However, other legal instruments, such as contracts, can serve as interim measures to provide compensation to source countries and indigenous populations. The National Cancer Institute's Letter of Collection agreement (LOG, formerly the 'Letter of Intent'), is an example of an alternative means that 'fills-in the gaps' created by patent law and through which source countries may share in the benefits of natural product development. C1 NCI,OFF TECHNOL DEV,NIH,BETHESDA,MD 20892. NR 14 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD APR PY 1996 VL 51 IS 1-3 BP 93 EP 102 DI 10.1016/0378-8741(95)01352-0 PG 10 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UC676 UT WOS:A1996UC67600013 PM 9213633 ER PT J AU Aalbersberg, WGL Mazan, RD Soejarto, DD Farnsworth, NR Garcia, R McChesney, JD Cragg, GM Jato, J Sittenfeld, A AF Aalbersberg, WGL Mazan, RD Soejarto, DD Farnsworth, NR Garcia, R McChesney, JD Cragg, GM Jato, J Sittenfeld, A TI Legal issues in sharing the benefits of biodiversity prospecting - Discussion SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Editorial Material C1 NCI,OFF TECHNOL DEV,NAT PROD PROGRAM,NAT PROD UNIT,BETHESDA,MD 20892. UNIV ILLINOIS,CHICAGO,IL 60612. JARDIN BOT NACL,SANTO DOMINGO,DOMINICAN REP. UNIV MISSISSIPPI,UNIVERSITY,MS 38677. NCI,FREDERICK CANC RES & DEV CTR,FAIRVIEW CTR,FREDERICK,MD 21702. FAC MED & BIOCHEM SCI,YAOUNDE,CAMEROON. INBIO,HEREDIA,COSTA RICA. RP Aalbersberg, WGL (reprint author), UNIV S PACIFIC,SCH PURE & APPL SCI,SUVA,FIJI. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD APR PY 1996 VL 51 IS 1-3 BP 102 EP 105 PG 4 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UC676 UT WOS:A1996UC67600014 ER PT J AU Cragg, GM Elisabetsky, E McChesney, JD AF Cragg, GM Elisabetsky, E McChesney, JD TI Medicinal plant genetic resources and international cooperation: The Brazilian perspective - Discussion SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Editorial Material C1 UNIV FED RIO GRANDE SUL,BR-90041970 PORTO ALEGRE,RS,BRAZIL. UNIV MISSISSIPPI,UNIVERSITY,MS 38677. RP Cragg, GM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FAIRVIEW CTR,SUITE 206,FREDERICK,MD 21702, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD APR PY 1996 VL 51 IS 1-3 BP 119 EP 120 PG 2 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UC676 UT WOS:A1996UC67600016 ER PT J AU Calle, R Cragg, GM King, SR Sittenfeld, A AF Calle, R Cragg, GM King, SR Sittenfeld, A TI Juridical and sociocultural problems on the definition of a law concerning property, usage and access to genetic resources in Colombia - Discussion SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Editorial Material C1 NCI,FREDERICK CANC RES & DEV CTR,FAIRVIEW CTR,FREDERICK,MD 21702. SHAMAN PHARMACEUT INC,S SAN FRANCISCO,CA 94080. INBIO,HEREDIA,COSTA RICA. RP Calle, R (reprint author), UNIV ANTIOQUIA,FAC LAW,MEDELLIN,COLOMBIA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD APR PY 1996 VL 51 IS 1-3 BP 142 EP 145 PG 4 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UC676 UT WOS:A1996UC67600019 ER PT J AU Conte, L AF Conte, L TI Intellectual property rights, naturally derived bioactive compounds and resource conservation - Discussions SO JOURNAL OF ETHNOPHARMACOLOGY LA English DT Editorial Material C1 UNIV FED RIO GRANDE SUL,PORTO ALEGRE,RS,BRAZIL. GLAXO GRP RES LTD,GREENFORD UB6 0HE,MIDDX,ENGLAND. UNIV CHICAGO,CHICAGO,IL 60637. UNIV ANTIOQUIA,MEDELLIN,COLOMBIA. NCI,BETHESDA,MD. AUSTRALIAN INST MARINE SCI,TOWNSVILLE,QLD 4810,AUSTRALIA. UNIV MISSISSIPPI,UNIVERSITY,MS 38677. UNIV ILLINOIS,CHICAGO,IL. UNIV YAOUNDE,YAOUNDE,CAMEROON. UNIV CENT ECUADOR,QUITO,ECUADOR. NEW YORK BOT GARDEN,NEW YORK,NY. NEW YORK MED COLL,VALHALLA,NY 10595. RP Conte, L (reprint author), SHAMAN PHARMACEUT INC,213 E GRAND AVE,S SAN FRANCISCO,CA 94080, USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-8741 J9 J ETHNOPHARMACOL JI J. Ethnopharmacol. PD APR PY 1996 VL 51 IS 1-3 BP 255 EP 278 DI 10.1016/S0378-8741(96)90034-3 PG 24 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA UC676 UT WOS:A1996UC67600035 ER PT J AU Henkart, PA Grinstein, S AF Henkart, PA Grinstein, S TI Apoptosis: Mitochondria resurrected? SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID BCL-2 C1 HOSP SICK CHILDREN,DIV CELL BIOL,TORONTO,ON M5G 1X8,CANADA. RP Henkart, PA (reprint author), NCI,LYMPHOCYTE CYTOTOX SECT,EXPTL IMMUNOL BRANCH,NIH,BLDG 10,ROOM 4B17,BETHESDA,MD 20892, USA. NR 35 TC 43 Z9 46 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1996 VL 183 IS 4 BP 1293 EP 1295 DI 10.1084/jem.183.4.1293 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UH144 UT WOS:A1996UH14400002 PM 8666886 ER PT J AU Mayordomo, JI Loftus, DJ Sakamoto, H DeCesare, CM Appasamy, PM Lotze, MT Storkus, WJ Appella, E DeLeo, AB AF Mayordomo, JI Loftus, DJ Sakamoto, H DeCesare, CM Appasamy, PM Lotze, MT Storkus, WJ Appella, E DeLeo, AB TI Therapy of murine tumors with p53 wild-type and mutant sequence peptide-based vaccines SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CHEMICALLY-INDUCED SARCOMAS; DENDRITIC CELLS; MOUSE; INDUCTION; MUTATIONS; MOLECULES; CULTURES; ANTIGENS; BINDING AB The BALB/c Meth A sarcoma carries a p53 missense mutation at codon 234, which occurs in a peptide, termed 234CM, capable of being presented to cytotoxic T lymphocytes (CTL) by H-2K(d) molecules (Noguchi, Y., E.C. Richards, Y.-T. Chen, and L.J. Old. 1994. Proc. Natl. Acad. Sci. USA. 91:3171-3175). Immunization of BALB/c mice with bone marrow-derived dendritic cells (DC), generated in the presence of granulocyte macrophage colony-stimulating factor and interleukin 4, and prepulsed with the Meth A p53 mutant peptide, induced CTL that specifically recognized peptide-pulsed P815 cells, as well as Meth A cells naturally expressing this epitope. Immunization with this vaccine also protected naive mice from a subsequent tumor challenge, and it inhibited tumor growth in mice bearing day 7 subcutaneous Meth A tumors. We additionally determined that immunization of BALB/c mice with DC pulsed with the p53 peptide containing the wild-type residue at position 234, 234CW, induced peptide-specific CTL that reacted against several methylcholanthrene-induced BALB/c sarcomas, including CMS4 sarcoma, and rejection of CMS4 sarcoma in vaccination and therapy (day 7) protocols. These results support the efficacy of DC-based, p53-derived peptide vaccines for the immunotherapy of cancer. The translational potential of this strategy is enhanced by previous reports showing that DC can readily be generated from human peripheral blood lymphocytes. C1 UNIV PITTSBURGH,INST CANC,DIV BASIC RES,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DEPT MOLEC GENET & BIOCHEM,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DEPT PATHOL,PITTSBURGH,PA 15213. UNIV PITTSBURGH,SCH MED,DEPT SURG,PITTSBURGH,PA 15213. NCI,BETHESDA,MD 20892. RI Sakamoto, Hiroshi/A-3181-2011; Mayordomo, Jose/K-3453-2013; OI Storkus, Walter/0000-0001-8961-4444 FU NCI NIH HHS [CA 57840]; NIAID NIH HHS [AI 31515] NR 41 TC 223 Z9 225 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1996 VL 183 IS 4 BP 1357 EP 1365 DI 10.1084/jem.183.4.1357 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UH144 UT WOS:A1996UH14400010 PM 8666894 ER PT J AU Junghans, RP Waldmann, TA AF Junghans, RP Waldmann, TA TI Metabolism of Tac (IL2R alpha): Physiology of cell surface shedding and renal catabolism, and suppression of catabolism by antibody binding SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN INTERLEUKIN-2 RECEPTOR; MOLECULAR-WEIGHT PROTEINS; CARCINOEMBRYONIC-ANTIGEN; MEMBRANE-PROTEINS; LIGAND-BINDING; SERUM LEVELS; EXPRESSION; LEUKEMIA; PHARMACOKINETICS; MANAGEMENT AB The interleukin 2 receptor alpha (IL2R alpha; CD25; Tac) is the prototypic model For soluble receptor studies. It exists in vivo as a transmembrane complete molecule (TM-Tac) on cell surfaces and as a truncated soluble form (sTac; sIL2R alpha). sTac has been used as a serum marker of T cell activation in immune disorders and of tumor burden in Tac-exprsssing malignancies. In vivo, serum levels of all soluble proteins depend oil the balance between production and catabolism, but little is known about the metabolic features of this class of molecules. We have developed a model for Tac metabolism that incorporates new insights in its production and catabolism. Tac was shed from the surface of malignant and activated human T cells with a modal half-life (t(1/2)) of 2-6 h, but which was prolonged under certain circumstances. The rate of shedding is first order overall and nonsaturable over a two order of magnitude range of substrate (TM-Tac) expression. Once shed from cells, sTac is subject to catabolic activities in the host. In vivo studies in mice showed that 90% of sTac was catabolized by the kidney with a t(1/2) of 1 h and a filtration fraction of 0.11 relative to creatinine. The remaining 10% of catabolism was mediated by other tissues with a t(1/2) of 10 h. Approximately 1-3% of sTac is excreted intact as proteinuria with the remaining 97-99% catabolized to amino acids. Antibody to the receptor induced a marked delay in sTac catabolism by preventing filtration of the smaller protein through the renal glomerulus and additionally suppressing other nonrenal catabolic mechanisms. A discrepancy between the catabolic rates for Tac and anti-Tac in the same complex was interpreted as a previously unrecognized differential catabolic mechanism, suggesting features of the Brambell hypothesis and immunoglobulin G transport and catabolism, in which the antigen-in-complex in intracellular vesicles is relatively less protected from catabolism than the associated antibody. In light of the pivotal role played by the kidney in sTac catabolism and the impact of administered antibody, the serum concentration of Tac in the settings of renal dysfunction or antibody therapy is not a suitable surrogate of activated T cells or of the body burden of tumor. These results provide parameters for assessing soluble receptor-ligand interactions generally. C1 NCI, METAB BRANCH, NCI, BETHESDA, MD 20892 USA. RP Junghans, RP (reprint author), HARVARD UNIV, NEW ENGLAND DEACONESS HOSP, SCH MED, DIV HEMATOL ONCOL, BIOTHERAPEUT DEV LAB, BOSTON, MA 02215 USA. NR 59 TC 45 Z9 45 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1996 VL 183 IS 4 BP 1587 EP 1602 DI 10.1084/jem.183.4.1587 PG 16 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UH144 UT WOS:A1996UH14400033 PM 8666917 ER PT J AU Gazzinelli, RT Sher, A Cheever, A Gerstberger, S Martin, MA Dickie, P AF Gazzinelli, RT Sher, A Cheever, A Gerstberger, S Martin, MA Dickie, P TI Infection of human immunodeficiency virus 1 transgenic mice with Toxoplasma gondii stimulates proviral transcription in macrophages in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID TUMOR-NECROSIS-FACTOR; IMMUNE-DEFICIENCY SYNDROME; FACTOR-ALPHA; MONONUCLEAR PHAGOCYTES; KAPPA-B; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; CEREBRAL TOXOPLASMOSIS; HUMAN CHROMOSOME-12; AIDS VIRUS AB Human immunodeficiency virus (HIV) 1 transgenic mice expressing low or undetectable levels of viral mRNA in lymphoid tissue were infected with the intracellular protozoan Toxoplasma gondii. Exposure to this parasite resulted in an increase in HIV-1 transcripts in lymph nodes, spleens, and lungs during the acute phase of infection and in the central nervous system during the chronic stage of disease. In vivo and ex vivo experiments identified macrophages as a major source of the induced HIV-1 transcripts. In contrast, T. gondii infection failed to stimulate HIV-1 transcription in tissues of two HIV-1 transgenic mouse strains harboring a HIV-1 proviral DNA in which the nuclear factor (NF) kappa B binding motifs from the viral long terminal repeats had been replaced with a duplicated Moloney murine leukemia virus core enhancer. A role for NF-kappa B in the activation of the HIV-1 by T. gondii was also suggested by the simultaneous induction of NF-kappa B binding activity and tumor necrosis factor alpha synthesis in transgenic mouse macrophages stimulated by exposure to parasite extracts. These results demonstrate the potential of all opportunistic pathogen to induce HIV-1 transcription in vivo and suggest a mechanism for the in vivo dissemination of HIV-1 by macrophages. C1 NIAID, NIH, IMMUNOL SECT, PARASIT DIS LAB, BETHESDA, MD 20892 USA. NIAID, NIH, LAB IMMUNOREGULAT, BETHESDA, MD 20892 USA. NIAID, NIH, MOLEC MICROBIOL LAB, BETHESDA, MD 20892 USA. UNIV FED MINAS GERAIS, DEPT BIOCHEM & IMMUNOL, BR-31270 BELO HORIZONTE, MG, BRAZIL. NR 51 TC 50 Z9 51 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1996 VL 183 IS 4 BP 1645 EP 1655 DI 10.1084/jem.183.4.1645 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UH144 UT WOS:A1996UH14400038 PM 8666922 ER PT J AU Di, JA Lenardo, MJ ZunigaPflucker, JC AF Di, JA Lenardo, MJ ZunigaPflucker, JC TI p53 prevents maturation to the CD4(+)CD8(+) stage of thymocyte differentiation in the absence of T cell receptor rearrangement SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MICE; MUTATIONS; RESTORATION; IRRADIATION; RADIATION; MOUSE; BLOCK; GENE AB Rearrangement of the immunoglobulin (Ig) and T cell receptor (TCR) gene loci allows for the generation of B and T lymphocytes with antigen-specific receptors. Complete rearrangement and expression of the TCR-beta chain enables immature thymocytes to differentiate from the CD4(-)CD8(-) to the CD4(+)CD8(+) stage. Mice in which rearrangement is impaired, such as severe combined immunodeficient (SCID) mice or recombinase activating gene-deficient (RAG(-/-)) mice, lack mature B and T lymphocytes. Thymocytes from these mice are attested at the CD4(-)CD8(-) stage of T cell development. We previously observed that thymocytes from RAG-2(-/-) mice exposed to gamma radiation differentiate front CD4(-)CD8(-) into CD4(+)CD8(+) without TCR-P chain rearrangement. We now report that irradiated RAG-2(-/-) thymocytes undergo direct somatic mutations at the p53 gene locus, and that p53 inactivation is associated with maturation of RaG-2(-/-) thymocytes to the CD4(+)CD8(+) stage. Generation of RAG-2(-/-) and p53(-/-) double-deficient mice revealed that, in the absence of TCR-beta chain rearrangement, loss of p53 function is sufficient for CD4(-)CD8(-) thymocytes to differentiate into the CD4(+)CD8(+) stage of T cell development. Our data provide evidence for a novel p53-mediated checkpoint in early thymocyte development that regulates the transition of CD4(-)CD8(-) into CD4(+)CD8(+) thymocytes. C1 UNIV TORONTO,DEPT IMMUNOL,TORONTO,ON M5S 1A8,CANADA. NIAID,IMMUNOL LAB,BETHESDA,MD 20892. OI Zuniga-Pflucker, Juan Carlos/0000-0003-2538-3178 NR 30 TC 3 Z9 3 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 1 PY 1996 VL 183 IS 4 BP 1923 EP 1928 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UH144 UT WOS:A1996UH14400066 ER PT J AU Westergaard, GC Suomi, SJ AF Westergaard, GC Suomi, SJ TI Hand preference for stone artefact production and tool-use by monkeys: Possible implications for the evolution of right-handedness in hominids SO JOURNAL OF HUMAN EVOLUTION LA English DT Article DE hand preference; tool-use; monkeys; right-handedness ID PLEISTOCENE; CHIMPANZEES; BEHAVIOR AB This research examined hand preference for stone artefact production and tool-use in monkeys. We presented capuchins (Cebus apella) with stones and an apparatus that accommodated the use of stones as cutting tools. The monkeys were preferentially right-handed for striking stones against hard surfaces and for using stones as cutting tools. These results fut ther demonstrate that primates exhibit lateral bias for tool-related activities, and indicate that handedness for the production and use of stone tools may have pre-dated the earliest known occurrence of lateral bias in hominids. (C) 1996 Academic Press Limited RP Westergaard, GC (reprint author), NICHHD,COMPARAT ETHOL LAB,POB 529,POOLESVILLE,MD 20837, USA. NR 34 TC 34 Z9 34 U1 1 U2 4 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0047-2484 J9 J HUM EVOL JI J. Hum. Evol. PD APR PY 1996 VL 30 IS 4 BP 291 EP 298 DI 10.1006/jhev.1996.0024 PG 8 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA UJ376 UT WOS:A1996UJ37600001 ER PT J AU Ciernik, IF Berzofsky, JA Carbone, DP AF Ciernik, IF Berzofsky, JA Carbone, DP TI Induction of cytotoxic T lymphocytes and antitumor immunity with DNA vaccines expressing single T cell epitopes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; GENETIC IMMUNIZATION; PEPTIDE; PROTECTION; ANTIGEN; INVIVO; RECOGNITION; INFECTION; RESPONSES; PROTEIN AB Delivery of genetic expression constructs into living animals can effectively induce both humoral and cellular immunity to the expressed proteins. Here we test the effectiveness of genetic immunization with a minigene coding for single epitopes derived from mutant p53 or from HIV gp120. We show that when these constructs are delivered by particle bombardment-mediated DNA transfer into the skin of mice, it results in efficient induction of tumor protective CTL, The immunogenicity of the epitope derived from mutant p53 is significantly enhanced if the epitope sequence is fused in frame with the adenovirus E3 leader sequence to target the epitope to the endoplasmic reticulum, thus acting like a ''genetic adjuvant.'' We conclude that genetic T cell epitope immunization is an alternative to peptide-based techniques for eliciting an effective immune response targeted against a single defined epitope, In some cases, the fusion of the gene product of the DNA vaccine vector with an endoplasmic reticulum targeting sequence may enhance immune induction. C1 UNIV TEXAS, SW MED CTR, SIMMONS CANC CTR, DALLAS, TX 75235 USA. NCI, METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NR 43 TC 157 Z9 158 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1996 VL 156 IS 7 BP 2369 EP 2375 PG 7 WC Immunology SC Immunology GA UB155 UT WOS:A1996UB15500007 PM 8786293 ER PT J AU Seder, RA AF Seder, RA TI High-dose IL-2 and IL-15 enhance the in vitro priming of naive CD4(+) T cells for IFN-gamma but have differential effects on priming for IL-4 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MEDIATED-IMMUNITY; INTERLEUKIN-2 DEFICIENT; MONOCLONAL-ANTIBODIES; PHENOTYPE DEVELOPMENT; TRANSGENIC MICE; RECEPTOR; TH1; MACROPHAGES; CYTOKINES; INDUCTION AB Cytokines play an important role for the in vitro differentiation of naive CD4(+) T cells into IL-4- or IFN-gamma-producing cells. The presence of both IL-4 and IL-2 is required to prime cells for IL-4 in vitro, Using purified CD4(+)/LECAM-1(high) T cells from TCR transgenic mice as naive responder cells, the role of IL-15 was studied to see if it functioned similarly to IL-2 with regard to IL-4 priming. Purified CD4(+) T cells cultured in the presence of IL-4 and anti-IL-2 failed to prime cells for IL-4 production. Addition of IL-15 to these same cultures could not restore priming for IL-4, suggesting that IL-2 and IL-15 may have different functional properties during the in vitro differentiation of IL-4-producing cells. The role of IL-15 in priming for IFN-gamma was also examined. The addition of high doses of IL-15 to priming cultures resulted in a striking increase in the amount of IFN-gamma produced following restimulation. Similarly, addition of a relatively high dose of IL-2 also produced a significant enhancement of IFN-gamma production; however, as previously reported, the presence of IL-12 in priming cultures induced the greatest increase in IFN-gamma production, leaving it as the predominant controller of Th1 differentiation in physiologic situations. Finally, IL-15 was shown to increase proliferation of activated CD4(+) T cell blasts but not of naive CD4(+) T cells. Moreover, cultures containing both IL-12 and IL-15 showed greater proliferation than either cytokine alone, suggesting an additive effect between these cytokines. RP Seder, RA (reprint author), NIAID,NIH,LYMPHOKINE REGULAT UNIT,CLIN INVEST LAB,BLDG 10,ROOM 11C215,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 52 TC 63 Z9 64 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1996 VL 156 IS 7 BP 2413 EP 2422 PG 10 WC Immunology SC Immunology GA UB155 UT WOS:A1996UB15500013 PM 8786299 ER PT J AU Kuprash, DV Osipovich, OA Pokholok, DK Alimzhanov, MB Biragyn, A Turetskaya, RL Nedospasov, SA AF Kuprash, DV Osipovich, OA Pokholok, DK Alimzhanov, MB Biragyn, A Turetskaya, RL Nedospasov, SA TI Functional analysis of the lymphotoxin-beta promoter - Sequence requirements for PMA activation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR TNF-ALPHA; T-CELL HYBRIDOMA; HETEROMERIC COMPLEX; 33-KDA GLYCOPROTEIN; KAPPA-B; SURFACE; GENES; MONOCYTOGENES; MACROPHAGES AB Membrane lymphotoxin (LT) complex is a trimer composed of two subunits, LT-alpha and LT-beta, of which the latter is a 33-kDa transmembrane protein. The LT-beta gene is expressed in lymphoid cells and organs, but little is known about its inducible regulation, Previously, the surface expression of LT-beta in jurkat cells has been shown to increase in response to PMA. In this report, we used this model to study the transcriptional control of the human and murine LT-beta genes, PMA strongly induced the expression of LT-beta mRNA, and the level of induction was not changed markedly by cycloheximide (CHX) treatment, The LT-beta promoter region contains conserved Egr-1, nuclear factor (NF)-kappa B, and Ets binding sites, and PMA-inducible factors bound to these sites were detected by the gel-retardation technique (electrophoretic mobility shift assay (EMSA)). To identify sequences involved in transcriptional control, sets of human and mouse promoter-chloramphenicol acetyltransferase (CAT) constructs were generated and assayed by transient transfections. The PMA response was lost after deletion of the distal Ets binding site at -110, Mutations at either the Ets or NF-kappa B sites that prevented factor binding dramatically reduced PMA-inducible promoter activity, suggesting cooperative interaction between corresponding transcription factors in PMA activation, Mutation at the Egr-1 site also resulted insubstantial loss of promoter activity, and the residual activity may be attributed to binding of constitutively expressed Sp-1 to the same site, We propose that the interaction between the members of NF-kappa B and Ets families of transcription factors and their cognate sites in the promoter is the major determinant of inducible expression of the LT-beta gene in Jurkat cells. C1 MOSCOW MV LOMONOSOV STATE UNIV,BELOZERSKY INST PHYSICOCHEM BIOL,MOSCOW,RUSSIA. SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,MOLEC IMMUNOREGULAT LAB,DIV BASIC SCI,FREDERICK,MD 21702. RP Kuprash, DV (reprint author), VA ENGELHARDT MOLEC BIOL INST,LAB CYTOKINE MOLEC BIOL,32 VAVILOV STR,MOSCOW 117984,RUSSIA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; NR 32 TC 34 Z9 34 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1996 VL 156 IS 7 BP 2465 EP 2472 PG 8 WC Immunology SC Immunology GA UB155 UT WOS:A1996UB15500020 PM 8786306 ER PT J AU Crowe, JE Bui, PT Firestone, CY Connors, M Elkins, WR Chanock, RM Murphy, BR AF Crowe, JE Bui, PT Firestone, CY Connors, M Elkins, WR Chanock, RM Murphy, BR TI Live subgroup B respiratory syncytial virus vaccines that are attenuated, genetically stable, and immunogenic in rodents and nonhuman primates SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID F-GLYCOPROTEIN; COTTON RATS; CHILDREN; RSV; PURIFICATION; INFECTIONS; IMMUNITY; INFANTS; PROTEIN AB Optimal immunization of neonates against disease caused by respiratory syncytial virus (RSV) probably will require multiple doses of a vaccine containing viruses of both subgroups A and B, Live subgroup B RSV mutants were generated containing multiple attenuating mutations, ts (temperature-sensitive) and non-ts (host range), that were introduced by prolonged passage in cell culture or by chemical mutagenesis, The cold-passaged (cp)-52 mutant was restricted in replication compared to wild type virus in rodents and nonhuman primates, In addition, the attenuation phenotype of cp-52 was stable after prolonged replication in immunosuppressed rodents, One or two ts mutations were then introduced into the cp-52 mutant to generate additional candidate vaccine strains that were more attenuated in vivo than the cp-52 parental virus, Tests in humans are being done to determine if one or more of the RSV B-1 mutants exhibit a satisfactory balance between attenuation and immunogenicity. C1 NIAID,NIH,INFECT DIS LAB,RESP VIRUSES SECT,BETHESDA,MD 20892. RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 NR 31 TC 41 Z9 42 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1996 VL 173 IS 4 BP 829 EP 839 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UB274 UT WOS:A1996UB27400007 PM 8603960 ER PT J AU Kovacs, JA Bechtel, C Davey, RT Falloon, J Polis, MA Walker, RE Metcalf, JA Davey, V Piscitelli, SC Baseler, M Dewar, R Salzman, NP Masur, H Lane, HC AF Kovacs, JA Bechtel, C Davey, RT Falloon, J Polis, MA Walker, RE Metcalf, JA Davey, V Piscitelli, SC Baseler, M Dewar, R Salzman, NP Masur, H Lane, HC TI Combination therapy with didanosine and interferon-alpha in human immunodeficiency virus-infected patients: Results of a phase I/II trial SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNE-DEFICIENCY SYNDROME; PLACEBO-CONTROLLED TRIAL; KAPOSIS-SARCOMA; COMBINED ZIDOVUDINE; TYPE-1 INFECTION; SYNDROME AIDS; INVITRO; HIV; REPLICATION AB A nonrandomized trial was undertaken to evaluate the combination of didanosine and interferon-alpha (IFN-alpha) in human immunodeficiency virus (HIV)-infected patients, Thirty-six volunteers with >200 x 10(6) CD4 cells/L received didanosine (one 100-, 250-, or 375-mg sachet twice daily) for at least 6 weeks, following which IFN-alpha (1, 5, 10, or 15 MU/day) was begun. Didanosine (one 375-mg sachet twice daily) was substituted for zidovudine in 14 additional patients who had received IFN-alpha and zidovudine for 7-45 months. Thirty-five patients completed the 34-week study, Clinical or chemical pancreatitis was the most common (6 patients) dose-limiting toxicity, CD4 cell counts increased with didanosine but declined following the addition of IFN-alpha; CD4 cell percents tended to increase and remain elevated. Thus, combination therapy with didanosine and IFN-alpha can be safely administered to patients with HIV infection, The clinical benefit of this combination therapy will require further evaluation. C1 NIAID,NIH,CTR CLIN,DEPT CRIT CARE MED,BETHESDA,MD 20892. NIAID,NIH,CTR CLIN,DEPT PHARM,BETHESDA,MD 20892. NIAID,NIH,LAB IMMUNOREGULAT,BETHESDA,MD 20892. SCI APPLICAT INT CORP,FREDERICK,MD. OI Polis, Michael/0000-0002-9151-2268 NR 30 TC 21 Z9 21 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1996 VL 173 IS 4 BP 840 EP 848 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UB274 UT WOS:A1996UB27400008 PM 8603961 ER PT J AU Cohen, OJ Pantaleo, G Holodniy, M Fox, CH Orenstein, JM Schnittman, S Niu, M Graziosi, C Pavlakis, GN Lalezari, J Bartlett, JA Steigbigel, RT Cohn, J Novak, R McMahon, D Bilello, J Fauci, AS AF Cohen, OJ Pantaleo, G Holodniy, M Fox, CH Orenstein, JM Schnittman, S Niu, M Graziosi, C Pavlakis, GN Lalezari, J Bartlett, JA Steigbigel, RT Cohn, J Novak, R McMahon, D Bilello, J Fauci, AS TI Antiretroviral monotherapy in early stage human immunodeficiency virus disease has no detectable effect on virus load in peripheral blood and lymph nodes SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ASYMPTOMATIC HIV-INFECTION; FOLLICULAR DENDRITIC CELLS; POLYMERASE CHAIN-REACTION; PLACEBO-CONTROLLED TRIAL; LYMPHADENOPATHY SYNDROME; CLINICAL PROGRESSION; CUBIC MILLIMETER; VIRAL BURDEN; DOUBLE-BLIND; TYPE-1 AB Initiation of antiretroviral monotherapy early in the course of infection with human immunodeficiency virus may result in a temporary slowing in the rate of disease progression; however, little is known about the virologic effects of early therapy, Virus load was measured in peripheral blood and lymph nodes from 16 antiretroviral-naive patients with a mean CD4 T lymphocyte count of 659 cells/mu L at baseline and after 8 weeks of either no treatment or zidovudine therapy, CD4 T lymphocyte counts and all virologic parameters examined remained unchanged regardless of zido-vudine treatment status, Histopathology and virus distribution within lymph nodes remained constant between baseline and week 8 in each patient, indicating that the virologic and histologic parameters examined in a single lymph node are representative of a systemic process, Early antiretroviral monotherapy with zidovudine had no effect on virologic parameters in this group of patients with relatively high CD4 T lymphocyte counts and low measures of virus load at baseline. C1 NIAID,DIV AIDS,BETHESDA,MD 20892. MOLEC HISTOL LABS,GAITHERSBURG,MD. NCI,ADV BIOSCI LABS,BASIC RES PROGRAM,HUMAN RETROVIRUS SECT,FREDERICK,MD 21701. UNIV MARYLAND,MED CTR,DIV INFECT DIS,BALTIMORE,MD 21201. UNIV CALIF SAN FRANCISCO,MT ZION MED CTR,DEPT MED,SAN FRANCISCO,CA 94120. DEPT VET AFFAIRS MED CTR,CTR AIDS RES,PALO ALTO,CA. GEORGE WASHINGTON UNIV,MED CTR,DEPT PATHOL,WASHINGTON,DC 20037. DUKE UNIV,MED CTR,DIV INFECT DIS,DURHAM,NC. SUNY STONY BROOK,MED CTR,DIV INFECT DIS,STONY BROOK,NY 11794. ALBANY MED COLL,DEPT MED,ALBANY,NY. UNIV ILLINOIS,MED CTR,DIV INFECT DIS,CHICAGO,IL. UNIV PITTSBURGH,MED CTR,DIV INFECT DIS,PITTSBURGH,PA. RP Cohen, OJ (reprint author), NIAID,LAB IMMUNOREGULAT,10 CTR DR,MSC 1876,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016 FU NCI NIH HHS [CO-46000] NR 45 TC 25 Z9 25 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1996 VL 173 IS 4 BP 849 EP 856 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UB274 UT WOS:A1996UB27400009 PM 8603962 ER PT J AU Berkower, I Mostowski, H Bull, TE Murphy, D AF Berkower, I Mostowski, H Bull, TE Murphy, D TI CD4-IgG binding threshold for inactivation of human immunodeficiency virus type 1 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; RECOMBINANT SOLUBLE CD4; ENVELOPE GLYCOPROTEIN-GP120; NEUTRALIZING ANTIBODIES; CELL RECEPTORS; AIDS VIRUS; HTLV-III; T-CELLS; GP120; HIV AB The stoichiometry of human immunodeficiency virus type 1 (HIV-1) inactivation by soluble receptor CD4-IgG hybrid dimers (CD4-IgG) was examined. The extent of HIV-1 inactivation was measured in a sensitive plaque-forming assay, and the corresponding level of CD4-IgG binding was determined by immunofluorescence of infected cells, Ninety percent virus inactivation occurred at relatively low levels of CD4-IgG binding (10% of the saturating level). At even lower binding levels (1.4% of maximum binding), virus survival was 44%. Over a broad range of binding conditions, the survival curve followed a model in which viruses binding more than a threshold level of CD4-IgG were completely inactivated, while viruses binding less remained infectious, The data indicate that CD4-IgG binding to 1.4% of gp120 binding sites equals the threshold for inactivation, Thus, virus inactivation can begin when 3 CD4-IgG (of similar to 216 gp120 sites) bind per virion. C1 NIH,BIOPHYS LAB,OFF VACCINE RES,CTR BIOL,FDA,BETHESDA,MD 20892. RP Berkower, I (reprint author), NIH,IMMUNOREGULAT LAB,OFF VACCINE RES,CTR BIOL,FDA,BLDG 29,ROOM 523,NIH CAMPUS,BETHESDA,MD 20892, USA. NR 34 TC 4 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1996 VL 173 IS 4 BP 863 EP 869 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UB274 UT WOS:A1996UB27400011 PM 8603964 ER PT J AU Weiss, SM Roblin, PM Gaydos, CA Cummings, P Patton, DL Schulhoff, N Shani, J Frankel, R Penney, K Quinn, TC Hammerschlag, MR Schachter, J AF Weiss, SM Roblin, PM Gaydos, CA Cummings, P Patton, DL Schulhoff, N Shani, J Frankel, R Penney, K Quinn, TC Hammerschlag, MR Schachter, J TI Failure to detect Chlamydia pneumoniae in coronary atheromas of patients undergoing atherectomy SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ARTERY DISEASE; HEART-DISEASE; STRAIN TWAR; INFECTION; ASSOCIATION AB To further investigate a proposed relationship between Chlamydia pneumoniae and coronary heart disease, coronary atheromas were collected from patients undergoing percutaneous atherectomy, Fifty-eight atheroma specimens were examined by culture and polymerase chain reaction (PCR) and 22 by electron microscopy, All were negative for C. pneumoniae, except a single specimen that was PCR-positive, These results differ from studies in other populations, in which this organism was identified by nonculture methods within coronary atheromas obtained at autopsy, Anti-C, pneumoniae antibody titers from 65 of the patients were compared with those of 28 asymptomatic controls, IgG titers were higher in controls than in patients, There is no evidence that C. pneumoniae exists within atheromas in this study population, nor does seroprevalence correlate with the presence of coronary disease in these patients. C1 SUNY HLTH SCI CTR,DEPT MED,DIV INFECT DIS,BROOKLYN,NY 11203. SUNY HLTH SCI CTR,DEPT PEDIAT,DIV INFECT DIS,BROOKLYN,NY 11203. MAIMONIDES HOSP,DIV CARDIOL,BROOKLYN,NY 11219. JOHNS HOPKINS UNIV,SCH MED,DEPT MED,DIV INFECT DIS,BALTIMORE,MD. NIAID,IMMUNOREGULAT LAB,BETHESDA,MD 20892. WASHINGTON UNIV,DEPT OBSTET & GYNECOL,SEATTLE,WA. UNIV CALIF SAN FRANCISCO,DEPT LAB MED,SAN FRANCISCO,CA 94143. RI Gaydos, Charlotte/E-9937-2010; Quinn, Thomas/A-2494-2010 NR 16 TC 162 Z9 163 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 S WOODLAWN AVE, CHICAGO, IL 60637 SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1996 VL 173 IS 4 BP 957 EP 962 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA UB274 UT WOS:A1996UB27400024 PM 8603977 ER PT J AU Bhakuni, V Singha, UK Dutta, GP Levy, HB Maheshwari, RK AF Bhakuni, V Singha, UK Dutta, GP Levy, HB Maheshwari, RK TI Killing of Leishmania donovani amastigotes by poly ICLC in hamsters SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID NITRIC-OXIDE; L-ARGININE; MURINE LEISHMANIASIS; INTERFERON-GAMMA; NITROGEN-OXIDES; HOST DEFENSE; MACROPHAGES; PARASITES; INVITRO; INVIVO AB In vitro as well as in vivo studies suggest that cytokine-induced synthesis of nitric oxide (NO) from L-arginine is a major effector mechanism against intracellular pathogens. In this study, we demonstrate that golden hamsters infected with Leishmania donovani amastigotes upon treatment with polyinosinic-polycytidylic acid stabilized with polylysine and carboxymethylcellulose (poly ICLC), a potent interferon inducer and immune enhancer, in combination with L-arginine, develop the capacity to eliminate intracellular pathogens, This antileishmanial activity of poly ICLC was suppressed by N-w nitro-L-arginine (N-w NLA), an inhibitor of inducible NO synthase. Furthermore, prolonged treatment of infected animals with L-arginine alone for 5 days more after 5 day treatment with poly ICLC plus L-arginine increased the antileishmanial activity compared with 5 day treatment with poly ICLC plus L-arginine, suggesting that inducible NO synthase, once activated, produces NO for 5 days more. Our results suggest that an L-arginine-dependent, NO-mediated mechanism is probably responsible for the antileishmanial action of poly ICLC. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. NIAID,NIH,BETHESDA,MD 20892. CENT DRUG RES INST,LUCKNOW 226001,UTTAR PRADESH,INDIA. NR 29 TC 7 Z9 7 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR PY 1996 VL 16 IS 4 BP 321 EP 325 DI 10.1089/jir.1996.16.321 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA UH506 UT WOS:A1996UH50600008 PM 9162526 ER PT J AU Hengge, UR Walker, SP Foster, RA Himmler, A Vogel, JC AF Hengge, UR Walker, SP Foster, RA Himmler, A Vogel, JC TI Eradication of canine papillomatosis via intralesional injection of naked DNA encoding interferon-A. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,NIH,DERMATOL BRANCH,BETHESDA,MD 20892. BENDER & CO,VIENNA,AUSTRIA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 3 EP 3 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700044 ER PT J AU Morasso, MI Feledy, JA Sargent, TD AF Morasso, MI Feledy, JA Sargent, TD TI Role of the Distal-less(Dlx-3) homeobox gene in the process of skin differentiation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NICHHD,NIH,GENET MOLEC LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 28 EP 28 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700071 ER PT J AU Walker, PS SchartonKersten, TM Hengge, U Udey, MC Vogel, JC AF Walker, PS SchartonKersten, TM Hengge, U Udey, MC Vogel, JC TI Direct targeting of skin and muscle for genetic immunization in a murine model of leishmaniasis. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NIAID,NIH,PARASIT DIS LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 29 EP 29 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700069 ER PT J AU Dlugosz, AA Hansen, L Cheng, C Denning, MF Threadgill, DW Magnuson, T Coffey, RJ Yuspa, SH AF Dlugosz, AA Hansen, L Cheng, C Denning, MF Threadgill, DW Magnuson, T Coffey, RJ Yuspa, SH TI Targeted disruption of EGFR impairs keratinocyte responses to the v-ras(Ha) oncogene in vitro and in vivo. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,CLEVELAND,OH 44106. VANDERBILT UNIV,NASHVILLE,TN. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 31 EP 31 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700073 ER PT J AU Wienecke, R Maize, JC Lowy, DR DeClue, JE AF Wienecke, R Maize, JC Lowy, DR DeClue, JE TI The tuberous sclerosis gene TSC2 is a tumor suppressor gene whose protein product co-localizes with its putative substrate RAP1 in the cis medial Golgi. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 32 EP 32 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700076 ER PT J AU DeLaurenzi, V Rogers, GR Hamrock, DJ DeLaurenzi, F Marekov, LN Compton, JG Markova, N Steinert, PM Rizzo, WB AF DeLaurenzi, V Rogers, GR Hamrock, DJ DeLaurenzi, F Marekov, LN Compton, JG Markova, N Steinert, PM Rizzo, WB TI Sjogren-Larsson syndrome (SLS) is caused by mutations in the fatty aldehyde dehydrogenase gene. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD. UNIV ROMA TOR VERGATA,DEPT EXPTL MED,BIOCHEM LAB,IRCCS,IDI,I-00187 ROME,ITALY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 33 EP 33 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700074 ER PT J AU Lazarova, Z Yee, C Cheng, P Yancey, K AF Lazarova, Z Yee, C Cheng, P Yancey, K TI Anti-laminin 5 IgG induces subepidermal blisters in adult murine skin as well as human skin grafted onto SCID mice. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 40 EP 40 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700083 ER PT J AU Hertl, M Amagai, M Ishii, K Karr, R Katz, SJ AF Hertl, M Amagai, M Ishii, K Karr, R Katz, SJ TI The HLA-DR11-restricted T cell response to the extracellular portion (ECL-5) of the pemphigus vulgaris antigen (PVA) is modulated by polymorphisms of the beta 1-chain. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 RHEIN WESTFAL TH AACHEN,DEPT DERMATOL,W-5100 AACHEN,GERMANY. KEIO UNIV,TOKYO,JAPAN. GD SEARLE & CO,ST LOUIS,MO. NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 44 EP 44 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700088 ER PT J AU Asada, H Katz, SI AF Asada, H Katz, SI TI Cytokine gene expression during the elicitation phase of contact sensitivity: Regulation by endogenous SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 49 EP 49 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700091 ER PT J AU Steinert, PM MareKov, LN AF Steinert, PM MareKov, LN TI Assembly of the cornified cell envelope of terminally differentiating keratinocytes is initiated by the attachment of involucrin to desmoplakin at the site of the desmosome. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 59 EP 59 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700099 ER PT J AU Kim, SY Chung, SI Steinert, PM AF Kim, SY Chung, SI Steinert, PM TI The transglutaminase 1 enzyme in keratinocytes is controlled during differentiation by transcription, proteolytic processing, and posttranslational acylation with myristate and palmitate. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. KOREAN GREEN CROSS CORP,KYONGGI DO,SOUTH KOREA. PACIFIC CORP,KYONGGI DO,SOUTH KOREA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 62 EP 62 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700106 ER PT J AU Tennenbaum, T Denning, MF Belanger, AB Szallaski, Z Kazanietz, M Blumberg, PM Yuspa, SH AF Tennenbaum, T Denning, MF Belanger, AB Szallaski, Z Kazanietz, M Blumberg, PM Yuspa, SH TI Down regulation of alpha 6 beta 4 integrin in keratinocyte differentiation is mediated by protein kinase SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 67 EP 67 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700109 ER PT J AU Markova, NG Lang, SI DeLaurenzi, V Lee, JH Steinert, PM Andreoli, JM AF Markova, NG Lang, SI DeLaurenzi, V Lee, JH Steinert, PM Andreoli, JM TI Regulatory function for ETS transcription factors in the epidermis. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20205. CHUNGNAM NATL UNIV,SCH MED,DEPT DERMATOL,TAEJON,SOUTH KOREA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 71 EP 71 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700111 ER PT J AU Andreoli, JM Jang, SI Lee, SC Tarcsa, E Steinert, PM Markova, NG AF Andreoli, JM Jang, SI Lee, SC Tarcsa, E Steinert, PM Markova, NG TI The regulation of expression of the human trichohyalin gene in vitro and in transgenic mice in vivo. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 74 EP 74 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700118 ER PT J AU Hansen, LA Tennenbaum, T Threadgill, DW Magnuson, T Yuspa, SH AF Hansen, LA Tennenbaum, T Threadgill, DW Magnuson, T Yuspa, SH TI Altered hair follicle morphogenesis in epidermal growth factor receptor deficient mice. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 87 EP 87 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700128 ER PT J AU Fleischmajer, R Utani, A Ninomiya, Y Sado, Y MacDonald, ED Perlish, JS Yamada, Y AF Fleischmajer, R Utani, A Ninomiya, Y Sado, Y MacDonald, ED Perlish, JS Yamada, Y TI Differential epidermal dermal expression of collagen IV (C-IV) and laminin chains (La) during the development of the basal lamina zone (BLZ). SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 MT SINAI SCH MED,DEPT DERMATOL,NEW YORK,NY. OKAYAMA UNIV,SCH MED,OKAYAMA 700,JAPAN. NIDR,DEV BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 95 EP 95 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700135 ER PT J AU Blauvelt, A Saville, MW Asada, H KlausKovtun, V Altman, DJ Yarchoan, R Katz, SI AF Blauvelt, A Saville, MW Asada, H KlausKovtun, V Altman, DJ Yarchoan, R Katz, SI TI Productive infection of Langerhans cell-like dendritic cells by HIV and their ability to capture virus are mediated through separate pathways. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 107 EP 107 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700147 ER PT J AU Jakob, T Lawrence, TJ vanDyke, BJ McFarland, V Schwarzenberger, K Udey, MC AF Jakob, T Lawrence, TJ vanDyke, BJ McFarland, V Schwarzenberger, K Udey, MC TI Propagation and characterization of Langerhans cell (LC)-like dendritic cells (FSDC) from fetal murine skin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 109 EP 109 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700151 ER PT J AU Jakob, T Udey, MC AF Jakob, T Udey, MC TI E-cadherin-associated proteins in Langerhans cell-like dendritic cells (FSDC) propagated from fetal murine skin SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. RI Jakob, Thilo/J-1621-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 111 EP 111 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700152 ER PT J AU Medrano, EE Liao, F Arnheiter, H AF Medrano, EE Liao, F Arnheiter, H TI Correlation of end-stage differentiation of human melanocytes with suppression of cyclin D1 and induction of MITF, p21 and p27. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 BAYLOR COLL MED,HOUSTON,TX 77030. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 128 EP 128 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700172 ER PT J AU Tarcsa, E Mei, G Melino, G Marekov, LN Steinert, PM AF Tarcsa, E Mei, G Melino, G Marekov, LN Steinert, PM TI Peptidylarginine deiminase modification of proteins: Evidence that the enzyme functions as an anti-chaperonin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV ROMA TOR VERGATA,DEPT EXPTL MED,I-00167 ROME,ITALY. IST DERMOPAT IMMACOLATA,IRCCS,IDI,I-00167 ROME,ITALY. NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 131 EP 131 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700171 ER PT J AU Marekoy, LN Steinert, PM AF Marekoy, LN Steinert, PM TI Evidence that the lipids of the epidermal cornified cell envelope are attached directly to involucrin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 133 EP 133 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700175 ER PT J AU Bouloc, A Walker, P Grivel, JC Vogel, J Katz, SI AF Bouloc, A Walker, P Grivel, JC Vogel, J Katz, SI TI A role for epidermal Langerhans cells in intracutaneous DNA immunization. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 150 EP 150 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700192 ER PT J AU Skalli, O Goldman, RD Steinert, PM AF Skalli, O Goldman, RD Steinert, PM TI IFAP-300 is associated with the anchorage of keratin intermediate filaments to desmoplakin at desmosomal junctions in epidermal cells. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV ILLINOIS,DEPT ANAT & CELL BIOL,CHICAGO,IL 60680. NORTHWESTERN UNIV,CMS BIOL,CHICAGO,IL 60601. NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 176 EP 176 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700220 ER PT J AU Rutberg, SE Saez, E Spiegelman, B Yuspa, SH AF Rutberg, SE Saez, E Spiegelman, B Yuspa, SH TI Negative regulation of AP-1 transcriptional activity in differentiating mouse keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20205. HARVARD UNIV,SCH MED,DANA FARBER CANC INST,BOSTON,MA 02115. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 196 EP 196 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700239 ER PT J AU Jang, SL Steinert, PM Markova, NG AF Jang, SL Steinert, PM Markova, NG TI Activity regulates the specificity of expression from the proximal promoter of the human profilaggrin gene in cultured keratinocytes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 199 EP 199 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700241 ER PT J AU Darling, T McGrath, JA Yee, C Gatalica, B Hametner, R Bauer, J PohlaGubo, G Christiano, AM Uitto, J Hintner, H Yancey, K AF Darling, T McGrath, JA Yee, C Gatalica, B Hametner, R Bauer, J PohlaGubo, G Christiano, AM Uitto, J Hintner, H Yancey, K TI Mutations in the bullous pemphigoid antigen 2 (BPAG2) gene in five Austrian families with generalized atrophic benign epidermolysis bullosa (GABEB). SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIH,DERMATOL BRANCH,BETHESDA,MD 20892. JEFFERSON MED COLL,PHILADELPHIA,PA. DEPT DERMATOL,SALZBURG,AUSTRIA. RI McGrath, John/D-6824-2012 OI McGrath, John/0000-0002-3708-9964 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 219 EP 219 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700260 ER PT J AU Korge, BP Richard, G Punter, C Mauch, C Junginger, H Lin, JP Rogers, M Winter, H Hamm, H Schweizer, J Krieg, T Traupe, H AF Korge, BP Richard, G Punter, C Mauch, C Junginger, H Lin, JP Rogers, M Winter, H Hamm, H Schweizer, J Krieg, T Traupe, H TI Monilethrix links to the keratin type II cluster at 12q13 and cloning of a possible candidate gene. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV COLOGNE,DEPT DERMATOL & VENEROL,W-5000 COLOGNE,GERMANY. UNIV MUNSTER,DEPT DERMATOL & VENEROL,MUNSTER,GERMANY. UNIV WURZBURG,DEPT DERMATOL & VENEROL,WURZBURG,GERMANY. GERMAN CANC RES CTR,W-6900 HEIDELBERG,GERMANY. NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD 20205. RI Rogers, Michael/J-9803-2012 OI Rogers, Michael/0000-0002-3728-2107 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 227 EP 227 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700267 ER PT J AU Russell, LJ Whyte, YM DiGiovanna, JJ Hashem, N Bale, SJ Compton, JG AF Russell, LJ Whyte, YM DiGiovanna, JJ Hashem, N Bale, SJ Compton, JG TI Mutation screening of the transglutaminase 1 gene in patients with lamellar ichthyosis (LI) and other congenital recessive ichthyoses using dideoxy fingerprinting. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,DERMATOL CLIN RES UNIT,BETHESDA,MD. AINSHAMS MED GENET CLIN,CAIRO,EGYPT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 228 EP 228 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700270 ER PT J AU Kirnbauer, R ONeil, B Grindlay, J Armstrong, A Lowy, D Schiller, J Campo, S AF Kirnbauer, R ONeil, B Grindlay, J Armstrong, A Lowy, D Schiller, J Campo, S TI Immunization with virus-like particles prevents bovine papillomavirus type 4 mucosal infection of calves. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,DIV IMMUNOL ALLERGY & INFECT DIS,DEPT DERMATOL,A-1010 VIENNA,AUSTRIA. UNIV GLASGOW,DEPT VET PATHOL,GLASGOW,LANARK,SCOTLAND. BEATSON INST CANC RES,GLASGOW G61 1BD,LANARK,SCOTLAND. NCI,LAB CELL ONCOL,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 234 EP 234 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700276 ER PT J AU Fenjves, ES Schwartz, PM Blaese, RM Taichman, LB AF Fenjves, ES Schwartz, PM Blaese, RM Taichman, LB TI Epidermal gene therapy for inherited metabolic disorders SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 SUNY STONY BROOK,DEPT ORAL BIOL & PATHOL,STONY BROOK,NY 11794. W HAVEN VET AFFAIRS MED CTR,DEPT DERMATOL,NEW HAVEN,CT. YALE UNIV,NEW HAVEN,CT. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 368 EP 368 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700412 ER PT J AU Idler, WW Kartasova, T Mei, G Melino, G Steinert, PM Tarcsa, E AF Idler, WW Kartasova, T Mei, G Melino, G Steinert, PM Tarcsa, E TI Characterization of human and mouse SPRs: Biochemical and structural properties SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. UNIV ROMA TOR VERGATA,DEPT EXPTL MED,ROME,ITALY. IRCCS,IDI,I-00167 ROME,ITALY. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 370 EP 370 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700413 ER PT J AU Kartasova, T Darwich, N Kuroki, T Steinert, PM AF Kartasova, T Darwich, N Kuroki, T Steinert, PM TI Sequence and expression pattern of mouse SPR2 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. NCI,NIH,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. UNIV TOKYO,INST MED SCI,DEPT CANC CELL RES,TOKYO,JAPAN. RI Kuroki, Toshio/A-9500-2011 OI Kuroki, Toshio/0000-0001-6369-4351 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 371 EP 371 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700411 ER PT J AU Saitoh, A Udey, MC AF Saitoh, A Udey, MC TI Expression of WNT genes in murine epidermis. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 399 EP 399 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700440 ER PT J AU Anzano, MA Jang, SI Markova, NG Woodworth, CD Steinert, PM AF Anzano, MA Jang, SI Markova, NG Woodworth, CD Steinert, PM TI Effects of retinoids and deltanoids on papilloma virus transformed human epidermal keratinocytes in vitro. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. NCI,NIH,BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 405 EP 405 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700446 ER PT J AU Jarnik, M Kartasova, T Steinert, PM Lichti, U Steven, AC AF Jarnik, M Kartasova, T Steinert, PM Lichti, U Steven, AC TI Differential expression and localization of SPR1 in cornified epithelia. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,STRUCT BIOL RES LAB,BETHESDA,MD 20892. NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. NCI,NIH,CELL CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 407 EP 407 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700447 ER PT J AU Yoneda, K Imamura, S Lee, JH Steinert, PM Kim, SY AF Yoneda, K Imamura, S Lee, JH Steinert, PM Kim, SY TI The expression of loricrin and transglutaminase 1 in hair follicle. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 KYOTO UNIV,DEPT DERMATOL,KYOTO,JAPAN. NIAMS,NIH,SKIN BIOL BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 419 EP 419 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700459 ER PT J AU Guerra, L Tosti, A DeDoucker, P Cameli, N Pellegrini, G AF Guerra, L Tosti, A DeDoucker, P Cameli, N Pellegrini, G TI Effects of itraconazole on normal keratinocytes cultivated from human nail matrix. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NATL CANC INST,ADV BIOTECHNOL CTR,GENOA,ITALY. JANSSEN RES FDN,DEPT CLIN RES,BEERSE,BELGIUM. UNIV BOLOGNA,DEPT DERMATOL,BOLOGNA,ITALY. RI Pellegrini, Graziella/E-1189-2015; Guerra, Liliana/G-8849-2016 OI Pellegrini, Graziella/0000-0001-9861-0736; NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 433 EP 433 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700475 ER PT J AU Turner, ML Darling, TN Skarulis, M AF Turner, ML Darling, TN Skarulis, M TI Facial angiofibromas and collagenomas in patients with multiple endocrine neoplasia type 1. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NIDDK,METAB DIS BRANCH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 499 EP 499 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700540 ER PT J AU Son, IY Yang, JM Yeo, EC Steinert, PW Lee, BS AF Son, IY Yang, JM Yeo, EC Steinert, PW Lee, BS TI Arg to Glu mutation in the 1A domain of keratin 9 in sporadic case of epidermolytic palmoplantar keratoderma. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 SAMSUNG MED CTR,DEPT DERMATOL,SEOUL,SOUTH KOREA. NIAMSD,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 561 EP 561 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700600 ER PT J AU Yang, JM Park, KB Kim, WS Moon, KC Koh, JK Steinert, PM Lee, BS AF Yang, JM Park, KB Kim, WS Moon, KC Koh, JK Steinert, PM Lee, BS TI Mutations of keratin 1/10 genes in epidermolytic hyperkeratosis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 SAMSUNG MED CTR,DEPT DERMATOL,SEOUL,SOUTH KOREA. ASAN MED CTR,DEPT DERMATOL,SEOUL,SOUTH KOREA. NIAMSD,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 562 EP 562 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700603 ER PT J AU Rossi, A Ceci, R Iang, SI Steinert, PM Markova, NG AF Rossi, A Ceci, R Iang, SI Steinert, PM Markova, NG TI The keratinocyte-specific effect of the AP1 site in the loricrin proximal promoter region is exerted through interactions with c-jun and c-fos transcription factors. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 581 EP 581 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700619 ER PT J AU Richard, G Whyte, YM Itin, P Hohl, D Giroux, JM Chamas, L Epstein, E Lin, JP Smith, L Bale, SJ AF Richard, G Whyte, YM Itin, P Hohl, D Giroux, JM Chamas, L Epstein, E Lin, JP Smith, L Bale, SJ TI Erythrokeratodermia variabilis (EKV) maps to a 5cM region on chromosome 1p. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 KANTONSSPITAL BASEL,DERMATOL KLIN & POLIKLIN,BASEL,SWITZERLAND. NIAMS,SKIN BIOL LAB,NIH,GENET STUDIES SECT,BETHESDA,MD 20205. BEAUMONT HOSP,DEPT DERMATOL,LAUSANNE,SWITZERLAND. HOP HOTEL DIEU,DEPT MED,DERMATOL SECT,MONTREAL,PQ,CANADA. SAN FRANCISCO GEN HOSP,SAN FRANCISCO,CA 94110. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 586 EP 586 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700627 ER PT J AU Itin, P Bon, A Bale, SJ Richard, G AF Itin, P Bon, A Bale, SJ Richard, G TI Evidence for genetic heterogeneity in monilethrix. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV BASEL,DEPT DERMATOL,CH-4003 BASEL,SWITZERLAND. NIAMS,NIH,SKIN BIOL LAB,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 587 EP 587 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700625 ER PT J AU Bale, SJ Russell, LJ Lee, ML Compton, JG DiGiovanna, JJ AF Bale, SJ Russell, LJ Lee, ML Compton, JG DiGiovanna, JJ TI Congenital recessive ichthyosis unlinked to transglutaminase-1, 2, or 3. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,GENET STUDIES SECT,BETHESDA,MD 20205. NIAMS,IRP,DERMATOL CLIN RES UNIT,BETHESDA,MD 20205. RI Lee, Minjoo/A-9720-2008 OI Lee, Minjoo/0000-0002-3151-3808 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 588 EP 588 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700628 ER PT J AU Rogers, GR DeLaurenzi, V Bale, SJ Markova, N Rizzo, WB Compton, JG AF Rogers, GR DeLaurenzi, V Bale, SJ Markova, N Rizzo, WB Compton, JG TI Genomic organization of the fatty aldehyde dehydrogenase gene for DNA-based mutation analysis in Sjogren-Larrson Syndrome SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIAMS,SKIN BIOL LAB,NIH,BETHESDA,MD 20205. NIAMS,GENET STUDIES SECT,NIH,BETHESDA,MD 20205. UNIV ROMA TOR VERGATA,IRCCS,IDI,I-00167 ROME,ITALY. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT PEDIAT,RICHMOND,VA 23298. VIRGINIA COMMONWEALTH UNIV,MED COLL VIRGINIA,DEPT HUMAN GENET,RICHMOND,VA 23298. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 589 EP 589 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700629 ER PT J AU Hengge, UR Walker, PS Kazaks, EL Williams, M Vogel, JC AF Hengge, UR Walker, PS Kazaks, EL Williams, M Vogel, JC TI Expression of naked DNA in human, pig, and mouse skin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,DERMATOL BRANCH,BETHESDA,MD 20892. NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 590 EP 590 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700632 ER PT J AU Jones, DO Zimonjic, D Popescu, N Bowden, PE AF Jones, DO Zimonjic, D Popescu, N Bowden, PE TI Sequencing and chromosomal localisation of two human hair-specific type II keratin genes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,NIH,BIOL LAB,BETHESDA,MD 20892. UNIV WALES COLL MED,DEPT DERMATOL,CARDIFF CF4 4XN,S GLAM,WALES. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 611 EP 611 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700649 ER PT J AU Klement, JF Rice, NR Car, BD Abbondanzo, SJ Bhatt, H Chen, CH Powers, G Rosen, CA Stewart, CL AF Klement, JF Rice, NR Car, BD Abbondanzo, SJ Bhatt, H Chen, CH Powers, G Rosen, CA Stewart, CL TI I kappa B alpha is essential for terminating NF-kappa B response and is crucial in modulating inflammation as animals deficient in I kappa B alpha develop a severe dermatitis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 ROCHE INST MOLEC BIOL,NUTLEY,NJ 07110. THOMAS JEFFERSON UNIV,JEFFERSON MED COLL,DEPT DERMATOL & CUTANEOUS BIOL,PHILADELPHIA,PA 19107. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. DUPONT MERCK PHARMACEUT CO,RES & DEV,STINE HASKELL RES CTR,NEWARK,DE 19714. HOFFMANN LAROCHE,NUTLEY,NJ. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 616 EP 616 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700657 ER PT J AU Marikovsky, M Vogt, P Eriksson, E Rubin, JS Taylor, WG Sasse, J Klagsbrun, M AF Marikovsky, M Vogt, P Eriksson, E Rubin, JS Taylor, WG Sasse, J Klagsbrun, M TI Wound fluid-derived heparin-binding EGF-like growth factor (HB-EGF) is synergistic with insulin-like growth factor-I for Balb/MK keratinocyte proliferation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE epidermal growth factor; insulin; re-epithelialization; wound repair ID HUMAN EPIDERMAL-KERATINOCYTES; RECEPTOR DISTRIBUTION; MONOCLONAL-ANTIBODY; MOUSE KERATINOCYTES; FACTOR EXPRESSION; EPITHELIAL-CELLS; FACTOR-ALPHA; HUMAN-SKIN; IGF-I; SERUM AB Epidermal cell proliferation is required for re-epithelialization during wound repair. Re-epithelialization of partial thickness excisional wounds in pigs is complete by 6 days after injury. The presence of insulin-like growth factor-I (IGF-I) and heparin-binding molecules that are mitogenic for keratinocytes was examined in wound fluid obtained daily from these wounds, Two significant heparin-binding growth factor activities for Balb/MK keratinocytes were detected, a major one that was eluted from a heparin affinity column with 1.1 M NaCl and a minor one with 0.5 M NaCl. These activities appeared 1 day after injury, were maximal by 2-3 days later, and disappeared by 6 days after injury, The molecule eluting with 1.1 M NaCl was heparin-binding EGF-like (HB-EGF), The levels of IGF-I in wound fluid were 45-90 ng/ml during the first 3 days following injury, decreased thereafter, and were not detectable 6 days after injury. IGF-I at 100 ng/ml, increased HB-EGF mitogenic activity for Balb/MK keratinocytes by 40-50-fold, We conclude that the synergism between IGF-I and HB-EGF and their relative concentrations at the various days after injury may be important variables for regulating re-epithelialization during wound repair. C1 BRIGHAM & WOMENS HOSP,DEPT PLAST SURG,BOSTON,MA 02115. NIH,BETHESDA,MD 20892. SHRINERS INST CRIPPLED CHILDREN,TAMPA,FL. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT SURG,BOSTON,MA 02115. RP Marikovsky, M (reprint author), WEIZMANN INST SCI,DEPT CELL BIOL,POB 26,IL-76100 REHOVOT,ISRAEL. FU NCI NIH HHS [CA 37392]; NIGMS NIH HHS [GM 47397] NR 46 TC 34 Z9 37 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 616 EP 621 DI 10.1111/1523-1747.ep12345413 PG 6 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700006 PM 8617994 ER PT J AU Denning, MF Dlugosz, AA Cheng, C Threadgill, DW Magnuson, T Yuspa, SH AF Denning, MF Dlugosz, AA Cheng, C Threadgill, DW Magnuson, T Yuspa, SH TI Tyrosine phosphorylation of protein kinase C delta during calcium-induced keratinocyte differentiation involves activation of epidermal growth factor receptor. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. CASE WESTERN RESERVE UNIV,DEPT GENET,CLEVELAND,OH 44106. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 618 EP 618 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700658 ER PT J AU Roden, RBS Okun, MM Androphy, E Lowy, DR Schiller, JT AF Roden, RBS Okun, MM Androphy, E Lowy, DR Schiller, JT TI Papillomavirus generation requires L1 and L2 capsid proteins and E2 transcription/replication protein. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NCI,CELLULAR ONCOL LAB,BETHESDA,MD 20892. TUFTS UNIV,DEPT DERMATOL,BOSTON,MA 02111. TUFTS UNIV NEW ENGLAND MED CTR,BOSTON,MA 02111. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 641 EP 641 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700678 ER PT J AU Owens, DM Zainal, TA Jetten, AM Smart, RC AF Owens, DM Zainal, TA Jetten, AM Smart, RC TI Localization and expression of cornifin-alpha/SPRR1 in mouse epidermis, anagen hair follicles, and skin neoplasms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE heratinocytes; cornified envelope; cornifin; SPRR ID KERATIN GENE-EXPRESSION; CROSS-LINKED ENVELOPE; ORNITHINE DECARBOXYLASE ACTIVITY; TUMOR PROMOTION; RETINOIC ACID; TERMINAL DIFFERENTIATION; PHORBOL ESTER; CELL-ENVELOPE; 12-O-TETRADECANOYLPHORBOL-13-ACETATE; PROTEINS AB Recently, cornifin-alpha/SPRR1 has been identified as a putative precursor protein of the cornified cell envelope, In this study, the expression and localization of cornifin-alpha/SPRR1 was examined in untreated and tumor promoter-treated mouse skin, hair follicles, and skin neoplasms, Western analysis with antiserum (SQ37A) to a rabbit cornifin-alpha peptide or antiserum (SQ37C) to a human SPRR1 peptide demonstrated a 31-kDa immunoreactive protein in mouse epidermis and Northern analysis revealed the presence of a 1-kb mRNA, Immunohistochemical staining of mouse skin with SQ37A or SQ37C revealed intense apd specific staining of the infundibulum, isthmus, and of Henle's layer of the inner roof sheath of the lower anagen hair follicle and weak staining of the telogen follicle and the suprabasal layers of the epidermis, Treatment of mouse skin with 12-O-tetradecanoylphorbol-13-acetate (TPA) produced a large increase in cornifin-alpha/SPRR1 protein and mRNA, Immunohistochemical localization of cornifin-alpha/SPRR1 in TPA-treated skin indicated that cornifin-alpha/SPRR1 was increased in the suprabasal epidermis but not in the follicle, sn-1,2-Didecanoylglycerol, a model lipid second messenger, produced an increase in cornifin-alpha/SPRR1 protein similar to that of TPA, while Mirex, a non-phorbol ester-type promoter had no effect. Topical doses of retinoic acid did not repress TPA-induced cornifin-alpha/SPRR1 expression, Papillomas demonstrated a 10- and 100-fold increase in cornifin-alpha/SPRR1 protein and mRNA, and expression was restricted to suprabasal cells, Squamous cell carcinomas exhibited an intermediate level of cornifin-alpha protein, and expression was restricted to keratinized areas, These data indicate: i) cornifin-alpha/SPRR1 is expressed in mouse skin; ii) cornifin-alpha/SPRR1 is localized to specific areas of the anagen hair follicle with weak staining in the telogen follicle and epidermis; iii) epidermal cornifin-alpha/SPRR1 expression is induced by phorbol ester and sn-1,2-didecanoylglycerol but pot mirex; and iv) papillomas and squamous Cell carcinomas demonstrate a constitutive increase in cornifin-alpha/SPRR1 in differentiated areas of the neoplasms. C1 N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. NIEHS,NIH,CELL BIOL SECT,PULM PATHOBIOL LAB,RES TRIANGLE PK,NC 27709. OI Jetten, Anton/0000-0003-0954-4445 FU NCI NIH HHS [CA46637]; NIEHS NIH HHS [ES07046] NR 54 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 647 EP 654 DI 10.1111/1523-1747.ep12345463 PG 8 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700011 PM 8617999 ER PT J AU Okada, T Sugiyama, H Nitta, Y Metcalfe, DD AF Okada, T Sugiyama, H Nitta, Y Metcalfe, DD TI Adhesion to human skin fibroblasts promotes differentiation of human mast cells to MC(TC) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 AICHI MED UNIV,DEPT PHYSIOL & DERMATOL,NAGAKUTE,AICHI 48011,JAPAN. NIAID,NIH,LCI,ALLERG DIS SECT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 717 EP 717 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700755 ER PT J AU Maurer, D Ebner, C Reininger, B Fiebiger, E Fischer, GF Wichlas, S Kinet, JP Stingl, G AF Maurer, D Ebner, C Reininger, B Fiebiger, E Fischer, GF Wichlas, S Kinet, JP Stingl, G TI Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and use this receptor for IgE-mediated allergen presentation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 UNIV VIENNA,SCH MED,DEPT DERMATOL GEN & EXP PATHOL,DIAID,VIENNA,AUSTRIA. UNIV VIENNA,SCH MED,INST BLOOD GRP SEROL,VIENNA,AUSTRIA. NIAID,NIH,MOL ALL & IMMUNOL SECT,ROCKVILLE,MD. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 739 EP 739 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700778 ER PT J AU McGrath, JA Darling, T Gatalica, B PohlaGubo, G Hintner, H Christiano, AM Yancey, K Uitto, J AF McGrath, JA Darling, T Gatalica, B PohlaGubo, G Hintner, H Christiano, AM Yancey, K Uitto, J TI A homozygous deletion mutation in the gene encoding the 180-kDa bullous pemphigoid antigen (BPAG2) in a family with generalized atrophic benign epidermolysis bullosa SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article ID RAPID DETECTION; SKIN DISEASES; DIAGNOSIS; HETERODUPLEXES AB The 180-kDa bullous pemphigoid antigen (BPAG2) is a candidate gene/protein for mutations in some forms of junctional epidermolysis bullosa. In this study, we searched for mutations in BPAG2 in a large Austrian pedigree with generalized atrophic benign epidermolysis bullosa, a distinct nonlethal form of junctional epidermolysis bullosa, using polymerase chain reaction amplification of genomic DNA, heteroduplex analysis of the polymerase chain reaction products, and direct nucleotide sequencing. We identified a homozygous 2-bp deletion within the coding region of BPAG2 in the affected individuals. This mutation results in a frameshift and downstream stop codons on both alleles, predicting an absence of functional protein. These findings illustrate the molecular basis of the skin fragility in this family and attest to the importance of the 180-kDa bullous pemphigoid antigen in the attachment of the epidermis to the underlying dermoepidermal basement membrane. C1 THOMAS JEFFERSON UNIV,JEFFERSON INST MOLEC MED,MOLEC DERMATOL SECT,PHILADELPHIA,PA 19107. NCI,NIH,DERMATOL BRANCH,BETHESDA,MD 20892. GEN HOSP,DEPT DERMATOL,SALZBURG,AUSTRIA. RP McGrath, JA (reprint author), JEFFERSON MED COLL,DEPT DERMATOL & CUTANEOUS BIOL,233 S 10TH ST,SUITE 450 BLSB,PHILADELPHIA,PA 19107, USA. RI McGrath, John/D-6824-2012; OI McGrath, John/0000-0002-3708-9964; Darling, Thomas/0000-0002-5161-1974 FU NIAMS NIH HHS [P01-AR38923]; PHS HHS [T32-07561] NR 25 TC 59 Z9 60 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 771 EP 774 DI 10.1111/1523-1747.ep12345821 PG 4 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700031 PM 8618019 ER PT J AU Steinert, PM Chung, SI Yoneda, K Kim, SY AF Steinert, PM Chung, SI Yoneda, K Kim, SY TI Expression of transglutaminase 1 in keratinocytes - Reply SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Letter C1 GREEN CROSS CO,KYONGGI DO,SOUTH KOREA. KYOTO UNIV,FAC MED,DEPT DERMATOL,KYOTO 606,JAPAN. PACIFIC CORP,KYONGGI DO,SOUTH KOREA. RP Steinert, PM (reprint author), NIAMSD,NIH,SKIN BIOL LAB,BETHESDA,MD 20892, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 802 EP 803 DI 10.1111/1523-1747.ep12346465 PG 2 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700042 ER PT J AU Lange, RW Luster, MI AF Lange, RW Luster, MI TI The generation of reactive oxidants by anthralin is a model of environmental dermatotoxicants and inflammation in normal human epidermal keratinocytes SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 NIEHS,ENVIRONM IMMUNOL & NEUROBIOL BRANCH,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,DEPT TOXICOL,RALEIGH,NC 27695. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI CAMBRIDGE PA 238 MAIN ST, CAMBRIDGE, MA 02142 SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1996 VL 106 IS 4 BP 822 EP 822 PG 1 WC Dermatology SC Dermatology GA UC787 UT WOS:A1996UC78700861 ER PT J AU Horti, A Ravert, HT London, ED Dannals, RF AF Horti, A Ravert, HT London, ED Dannals, RF TI Synthesis of a radiotracer for studying nicotinic acetylcholine receptors: (+/-)-Exo-2-(2-[F-18]fluoro-5-pyridyl)-7-azabicyclo[2.2.1]heptane SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE radiotracer; epibatidine; F-18; fluorination; halogen-exchange; nicotinic receptors; acetylcholine; positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; RAT-BRAIN MEMBRANES; BINDING-SITES; CHOLINERGIC RECEPTORS; ALZHEIMERS-DISEASE; CEREBRAL-CORTEX; MOUSE-BRAIN AB The radiochemical synthesis of (+/-)-exo-2-(2-[F-18]fluoro-5-pyridyl)-7-azabicyclo[2.2.1] heptane ([F-18]1) was accomplished by Kryptofix(R) 222 assisted nucleophilic no-carrier-added [F-18]fluorination of (+/-)-exo-2-(2-bromo-5-pyridyl)-7-azabicyclo[2.2.1] heptane (3a). The average radiochemical yield of the final product was 10% and the average specific activity was greater than >2000 mCi/mu mol, calculated at end-of-synthesis. The stable fluorine ligand ([F-19]1) was prepared by Kryptofix(R) 222 assisted nucleophilic fluorination of (+/-)-exo-2-(2-bromo-5-pyridyl)-7-methoxycarbonyl-7-azabicyclo [2.2.1]heptane (3b) followed by acid deprotection. C1 JOHNS HOPKINS MED INST,DIV NUCL MED,BALTIMORE,MD 21205. NIDA,INTRAMURAL RES PROGRAM,NEUROIMAGING & DRUG ACT SECT,BALTIMORE,MD 21224. UNIV MARYLAND,SCH MED,DEPT PHARMACOL & EXPTL THERAPEUT,BALTIMORE,MD 21201. JOHNS HOPKINS MED INST,DIV RADIAT HLTH SCI,BALTIMORE,MD 21205. NR 44 TC 58 Z9 58 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD APR PY 1996 VL 38 IS 4 BP 355 EP 365 DI 10.1002/(SICI)1099-1344(199604)38:4<355::AID-JLCR842>3.0.CO;2-3 PG 11 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA UD879 UT WOS:A1996UD87900005 ER PT J AU Miller, SPF Zirzow, GC Doppelt, SH Brady, RO Barton, NW AF Miller, SPF Zirzow, GC Doppelt, SH Brady, RO Barton, NW TI Analysis of the lipids of normal and Gaucher bone marrow SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID MACROPHAGE-TARGETED GLUCOCEREBROSIDASE; ENZYME REPLACEMENT THERAPY; SKELETAL COMPLICATIONS; MAGNETIC-RESONANCE; DISEASE; INVOLVEMENT; LEUKEMIA; CT AB Quantitative chemical shift magnetic resonance imaging (QCSI) is currently being utilized for measuring the extent of bone marrow involvement and its response to enzyme replacement therapy in patients with Gaucher's disease. Quantitation of the major lipid species in human bone marrow is required to accurately interpret QCSI data on bone marrow composition. The major lipid species in bone marrow specimens from normal individuals and from patients with type 1 Gaucher's disease were analyzed by thin-layer and high-pressure liquid chromatography. In normal marrow (N = 5), triglycerides were by far the most abundant lipid (278 +/- 70 mg/gm wet wt), with other non-polar lipids and phospholipids totaling less than 20 mg/gm wet weight.-The concentration of glucocerebroside in normal marrow was 0.061 +/- 0.06 mg/gm wet weight. Gaucher marrow (N = 9) had dramatically lower triglyceride levels (51 +/- 53 mg/gm wet wt), and as expected, it had markedly elevated levels of glucocerebroside (7.1 +/- 3.4 mg/gm wet wt). The other major non-polar lipids and phospholipids were measured in selected specimens, but none were found that differed so profoundly between normal and Gaucher's disease. These data support a model of bone marrow alteration in Gaucher's disease in which triglyceride rich adipocytes are progressively replaced by storage cells, leading to an overall reduction in total lipid content. This phenomenon provides an explanation for the changes in proton signal intensity observed in QCSI studies of Gaucher bone marrow. C1 NINCDS,NIH,DEV & METAB NEUROL BRANCH,BETHESDA,MD 20892. MASSACHUSETTS GEN HOSP,DEPT ORTHOPED SURG,BOSTON,MA 02114. NR 37 TC 26 Z9 26 U1 1 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD APR PY 1996 VL 127 IS 4 BP 353 EP 358 DI 10.1016/S0022-2143(96)90183-3 PG 6 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA UC790 UT WOS:A1996UC79000007 PM 8656038 ER PT J AU Bamford, RN Battiata, AP Waldmann, TA AF Bamford, RN Battiata, AP Waldmann, TA TI IL-15: The role of translational regulation in their expression SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article; Proceedings Paper CT 3rd International-Cytokine-Society Conference CY SEP 12-15, 1995 CL HARROGATE, ENGLAND SP Int Cytokine Soc DE adult T cell leukemia; HTLV-I; mRNA translation ID T-CELL LEUKEMIA; MESSENGER-RNA; HTLV-I; SEQUENCES AB We previously reported that the human T cell lymphotropic virus type I (HTLV-I)-associated adult T cell leukemia (ATL) line HuT-102 produces a cytokine designated interleukin (IL) -T. Using anticytokine antibodies we demonstrated that IL-T is identical to the simultaneously described IL-15. The observation of a discordance between IL-15 message expression and IL-15 synthesis led us to examine normal and aberrant IL-15 mRNA for post-transcriptional controls that inhibit protein production at the level of RNA translation. When compared to activated monocytes, IL-15 mRNA expression was 6-to 10-fold greater in HuT-102 T cells. The predominant IL-15 message from HuT-102 is a chimeric mRNA joining a segment of the R region of the long terminal repeat of HTLV-I and the 5' untranslated region (UTR) of 1L-15, R segment introduction eliminated over 200 nucleotides of IL-15 5' UTR including 8 of 10 upstream AUGs that are present in the normal 1L-15 message. On analysis of the 5' UTR of normal 1L-15, we demonstrated that these 10 upstream AUGs interfere with IL-15 mRNA translation. Thus, IL-15 synthesis by the ATL cell Line HuT-102 involves an increase in IL-15 mRNA transcription and translation secondary to the production of an HTLV-I-R fusion message that lacks many upstream AUGs. C1 NCI,METAB BRANCH,NIH,BETHESDA,MD 20892. NR 28 TC 46 Z9 46 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 1996 VL 59 IS 4 BP 476 EP 480 PG 5 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA UG063 UT WOS:A1996UG06300002 PM 8613692 ER PT J AU Sommers, CL AF Sommers, Connie L. TI The Role of Cadherin-Mediated Adhesion in Breast Cancer SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE Breast cancer; E-cadherin; catenins; adhesion; invasion; metastasis AB The cell adhesion molecule E-cadherin is expressed on the basolateral surfaces of normal mammary epithelial cells and is lost in a subset of breast cancers. Loss of E-cadherin expression has been postulated to facilitate tumor cell detachment from a primary tumor ultimately leading to metastasis. In this paper, I review the published in vitro data that initially supported this "invasion suppressor" role for E-cadherin as well as more recent in vitro and in vivo data showing that E-cadherin-positive tumor cells can metastasize. I examine other molecules required for E-cadherin function and discuss how defects in the expression or function of these molecules might alter E-cadherin function in E-cadherin-positive tumor cells. For example, loss of expression or function of catenins, intracellular molecules that interact with E-cadherin, can result in the loss of E-cadherin-mediated adhesion and a more invasive phenotype. Altered phosphorylation of E-cadherin or catenins can also influence E-cadherin function. Finally, expression of other cell surface molecules such as mucins may interfere with E-cadherin function. The collective effect of these molecules on the adhesive phenotype of breast cancer cells may be one determinant of metastatic potential. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Sommers, CL (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. EM connies@helix.nih.gov NR 81 TC 25 Z9 26 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS 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 APR PY 1996 VL 1 IS 2 BP 219 EP 229 DI 10.1007/BF02013645 PG 11 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA V25HC UT WOS:000208468100009 PM 10887495 ER PT J AU Foy, CA McCormack, LJ Knowler, WC Barrett, JH Catto, A Grant, PJ AF Foy, CA McCormack, LJ Knowler, WC Barrett, JH Catto, A Grant, PJ TI The angiotensin-I converting enzyme (ACE) gene I/D polymorphism and ACE levels in Pima Indians SO JOURNAL OF MEDICAL GENETICS LA English DT Article DE angiotensin-I converting enzyme; insertion deletion polymorphism; ethnicity ID INSERTION DELETION POLYMORPHISM; CORONARY HEART-DISEASE; MYOCARDIAL-INFARCTION; HIGH PREVALENCE AB An insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene is associated with plasma ACE levels in white populations. The occurrence of the I/D polymorphism and relationship to ACE levels was examined in a Pima Indian group (n=305). The frequency of the D allele was lower in Pimas than whites (0.29 v 0.52 respectively). ACE levels were significantly associated with genotype in both groups (p = 0.0001), which accounted for 6.5% of the variation in ACE levels in Pimas and 18% in whites. The association of the I/D polymorphism with ACE levels confirms the relationship across ethnic groups. The low frequency of the D allele in Pima Indians shows that ethnic differences should be accounted for when studying the ACE gene. C1 UNIV LEEDS,DEPT CLIN MED,DIABET THROMBOSIS RES GRP,LEEDS,W YORKSHIRE,ENGLAND. NIDDK,PHOENIX,AZ. OI Barrett, Jenny/0000-0002-1720-7724 NR 13 TC 30 Z9 33 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 1996 VL 33 IS 4 BP 336 EP 337 DI 10.1136/jmg.33.4.336 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UD877 UT WOS:A1996UD87700016 PM 8730292 ER PT J AU Lin, SL Nussinov, R AF Lin, SL Nussinov, R TI Molecular recognition via face center representation of a molecular surface SO JOURNAL OF MOLECULAR GRAPHICS LA English DT Article DE molecular recognition; molecular shape; surface representation; complementary docking ID SHAPE COMPLEMENTARITY; DOCKING; COMPLEX AB While docking methodologies are now frequently being developed, a careful examination of the molecular surface representation, which necessarily is employed by them, is largely overlooked. There are two important aspects here that need to be addressed: how the surface representation quantifies surface complementarity, and whether a minimal representation is employed. Although complementarity is an accepted concept regarding molecular recognition, its quantification for computation is not trivial, and requires verification. A minimal representation is important because docking searches a conformational space whose extent and/or dimensionality grows quickly with the size of surface representation, making it especially costly with big molecules, imperfect interfaces, and changes of conformation that occur in binding. It is essential for a docking methodology to establish that it employs an accurate, concise molecular surface representation. Here we employ the face center representation of molecular surface, developed by Lin et al.,(1) to investigate the complementarity of molecular interface. We study a wide variety of complexes: protein/small ligand, oligomeric chain-chain interfaces, proteinase/protein inhibitors, antibody/antigen, NMR structures, and complexes built from unbound, separately solved structures. The complementarity is examined at different levels of reduction, and hence roughness, of the surface representation, from one that describes subatomic details to a very sparse one that captures only the prominent features on the surface. Our simulation of molecular recognition indicates that in all cases, quality interface complementarity is obtained. We show that the representation is powerful in monitoring the complementarity either in its entirety, or in selected subsets that maintain a fraction of the face centers, and is capable of supporting molecular docking at high fidelity and efficiency. Furthermore, we also demonstrate that the presence of explicit hydrogens in molecular structures may not benefit docking, and that the different classes of protein complexes may hold slightly different degrees of interface complementarity. C1 SAIC,MATH BIOL LAB,FREDERICK,MD. TEL AVIV UNIV,SACKLER INST MOL MED,IL-69978 TEL AVIV,ISRAEL. RP Lin, SL (reprint author), NCI,FREDERICK CANC RES FACIL,MATH BIOL LAB,BLDG 469,RM 151,FREDERICK,MD 21702, USA. FU NCI NIH HHS [1-CO-74102] NR 24 TC 27 Z9 27 U1 0 U2 1 PU BUTTERWORTH-HEINEMANN PI WOBURN PA 225 WILDWOOD AVE #UNITB PO BOX 4500, WOBURN, MA 01801-2084 SN 0263-7855 J9 J MOL GRAPHICS JI J. Mol. Graph. PD APR PY 1996 VL 14 IS 2 BP 78 EP & DI 10.1016/0263-7855(96)00030-6 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Computer Science, Interdisciplinary Applications; Crystallography; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Computer Science; Crystallography; Mathematical & Computational Biology GA UX564 UT WOS:A1996UX56400004 PM 8835775 ER PT J AU Sellers, JR AF Sellers, JR TI Kinesin and NCD, two structural cousins of myosin SO JOURNAL OF MUSCLE RESEARCH AND CELL MOTILITY LA English DT Editorial Material ID PROTEIN; DROSOPHILA; MOTOR; SEGREGATION; MOVEMENT RP Sellers, JR (reprint author), NHLBI,MOLEC CARDIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 23 TC 5 Z9 5 U1 0 U2 1 PU CHAPMAN HALL LTD PI LONDON PA 2-6 BOUNDARY ROW, LONDON, ENGLAND SE1 8HN SN 0142-4319 J9 J MUSCLE RES CELL M JI J. Muscle Res. Cell Motil. PD APR PY 1996 VL 17 IS 2 BP 173 EP 175 DI 10.1007/BF00124239 PG 3 WC Cell Biology SC Cell Biology GA UQ643 UT WOS:A1996UQ64300001 PM 8793719 ER PT J AU Sasagasako, N Toda, K Hollis, M Quarles, RH AF Sasagasako, N Toda, K Hollis, M Quarles, RH TI Myelin gene expression in immortalized schwann cells: Relationship to cell density and proliferation SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE cell density; cellular proliferation; myelin-associated glycoprotein; peripheral myelin protein-22; P-o glycoprotein; Schwann cells; immortalized cells ID CYCLIC-AMP; GROWTH; GLYCOPROTEIN; COMPONENTS; PHENOTYPE; PROTEINS; CULTURE; CAMP AB Myelin gene expression was investigated in the immortalized S16 Schwann cell line grown in the presence and absence of serum and at different densities. Protein expression was monitored by western blotting, and message levels were determined by RNase protection assays. To study cell proliferation rates at different cell densities and serum conditions, [H-3]thymidine uptake assays and cell counts were performed. Although serum deprivation decreased cell proliferation as expected, the proliferation of S16 cells was unchanged or slightly increased at high density under the conditions of our experiments in either serum-containing or serum-free medium. This increased cell division at high density appeared to be due to greater release of an autocrine growth factor to the medium by dense cell populations, For both sparse and dense cells, substantially more P-0 glycoprotein (P-0) and myelin-associated glycoprotein (MAG) per milligram of total cellular protein were expressed when the cells were proliferating slowly in defined medium in comparison with more rapidly proliferating cells in serum-containing medium. Furthermore, in both serum-containing and defined media, dense cell populations expressed more MAG and P-0 than sparse ones. P-0 mRNA and MAG mRNA levels generally paralleled protein levels. The level of mRNA for peripheral myelin protein-22 (PMP-22) was also increased at high cell density but did not change much when proliferation was decreased by serum deprivation. PMP-22 protein was not detected under any of the growth conditions, The changes in expression of these genes with growth conditions may be specific for myelin proteins, because the expression of a nonmyelin glycoprotein, L1, remained constant, The level of cyclic AMP in the cells did not change with the different growth conditions tested. The results indicate that the S16 Schwann cell line mimics primary or secondary Schwann cells by down-regulating myelin gene expression when it proliferates more rapidly in the presence of serum. Furthermore, in both the presence and absence of serum, there was greater expression of myelin genes at high cell density that was not associated with a decreased proliferative rate. Because evidence for a role of secretory factors in affecting myelin gene expression was not obtained by treating sparse S16 cells with medium conditioned by dense S16 cells, the results suggest that the higher expression of myelin genes at high density may be mediated by cell-to-cell contact. C1 NINCDS,NIH,CELLULAR & MOLEC NEUROBIOL LAB,MYELIN & BRAIN DEV SECT,BETHESDA,MD 20892. NR 30 TC 29 Z9 32 U1 1 U2 2 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1996 VL 66 IS 4 BP 1432 EP 1439 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UA119 UT WOS:A1996UA11900012 PM 8627295 ER PT J AU MincGolomb, D Yadid, G Tsarfaty, I Resau, JH Schwartz, JP AF MincGolomb, D Yadid, G Tsarfaty, I Resau, JH Schwartz, JP TI In vivo expression of inducible nitric oxide synthase in cerebellar neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE nitric oxide; nitric oxide synthase; neuronal induction; cerebellum; endotoxin; cytokine; in situ hybridization; immunohistochemistry ID NADPH-DIAPHORASE; RELEASE; MESSENGER; GLUTAMATE; MECHANISM; ISCHEMIA; CYCLASE; INVIVO; CNS AB In the CNS, nitric oxide (NO) functions as both neuromodulator and neurotoxic agent. In vivo neuronal expression of NO synthase (NOS) has been attributed to constitutive NOS-both the neuronal and the endothelial types. The other class of NOS-the inducible NOS (iNOS)-is known to mediate toxic effects of NO in various tissues. In this study, we show for the first time that direct intracerebellar injection of endotoxin and cytokine (lipopolysaccharide and interferon-gamma) induced in vivo neuronal expression of the iNOS gene, as demonstrated by fluorescent in situ hybridization and immunohistochemical staining analyzed by confocal laser-scanning microscopy. This raises the possibility that neuronal iNOS might contribute significantly to the vulnerability of the brain to various insults. C1 NINCDS,NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. NCI,NIH,ABL,FREDERICK,MD 21701. NR 31 TC 77 Z9 77 U1 0 U2 0 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1996 VL 66 IS 4 BP 1504 EP 1509 PG 6 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UA119 UT WOS:A1996UA11900022 PM 8627305 ER PT J AU Poltorak, M Frye, MA Wright, R Hemperly, JJ George, MS Pazzaglia, PJ Jerrels, SA Post, RM Freed, WJ AF Poltorak, M Frye, MA Wright, R Hemperly, JJ George, MS Pazzaglia, PJ Jerrels, SA Post, RM Freed, WJ TI Increased neural cell adhesion molecule in the CSF of patients with mood disorder SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE neural cell adhesion molecule; cell recognition molecule; cerebrospinal fluid; bipolar mood disorder; depression ID IMMUNOELECTRON MICROSCOPIC LOCALIZATION; MYELIN-ASSOCIATED GLYCOPROTEIN; N-CAM; CEREBROSPINAL-FLUID; MAGNETIC-RESONANCE; CHRONIC-SCHIZOPHRENIA; EXTRACELLULAR-MATRIX; SCIATIC-NERVE; EXPRESSION; PROTEIN AB Neural cell adhesion molecule (N-CAM) is involved in cell-cell interactions during synaptogenesis, morphogenesis, and plasticity of the nervous system, Disturbances in synaptic restructuring and neural plasticity may be related to the pathogenesis of several neuropsychiatric diseases, including mood disorders and schizophrenia. Disturbances in brain cellular function may alter concentrations of N-CAM in the CSF. Soluble human N-CAM proteins are detectable in the CSF but are minor constituents of serum. We have recently found an increase in N-CAM content in the CSF of patients with schizophrenia. Although the pathogenesis of both schizophrenia and mood disorders is unknown, ventriculomegaly, decreased temporal lobe volume, and subcortical structural abnormalities have been reported for both disorders. We have therefore measured N-CAM concentrations in the CSF of patients with mood disorder. There were significant increases in amounts of N-CAM immunoreactive proteins, primarily the 120-kDa band, in the CSF of psychiatric inpatients with bipolar mood disorder type I and recurrent unipolar major depression. There were no differences in bipolar mood disorder type II patients as compared with normals. There were no significant effects of medication treatment on N-CAM concentrations. It is possible that the 120-kDa N-CAM band present in the CSF is derived from CNS cells as a secreted soluble NCAM isoform. Our results suggest the possibility of latent state-related disturbances in N-CAM cellular function, i.e., residue from a previous episode, or abnormal N-CAM turnover in the CNS of patients with mood disorder. C1 NIMH,BIOL PSYCHIAT BRANCH,BETHESDA,MD 20892. BECTON DICKINSON RES CTR,RES TRIANGLE PK,NC. NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,SECT PROCLIN NEUROSCI,WASHINGTON,DC 20032. NR 56 TC 61 Z9 62 U1 1 U2 3 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1996 VL 66 IS 4 BP 1532 EP 1538 PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UA119 UT WOS:A1996UA11900026 PM 8627309 ER PT J AU Eisenhofer, G Aneman, A Hooper, D Rundqvist, B Friberg, P AF Eisenhofer, G Aneman, A Hooper, D Rundqvist, B Friberg, P TI Mesenteric organ production, hepatic metabolism, and renal elimination of norepinephrine and its metabolites in humans SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE norepinephrine; sympathetic nerves; metabolism; liver; kidneys ID 4-HYDROXY-3-METHOXYMANDELIC ACID; CATECHOLAMINE METABOLISM; PLASMA; CONVERSION AB This study used regional differences in plasma concentrations of norepinephrine and its metabolites to examine how production of the transmitter by sympathetic nerves, in particular, those innervating mesenteric organs, is integrated with metabolism by the liver and elimination by the kidneys. Higher concentrations of norepinephrine, its glycol metabolites 3,4-dihydroxyphenyl-glycol and 3-methoxy-4-hydroxyphenylglycol and their sulfate conjugates in portal venous than arterial plasma indicate substantial production of norepinephrine by mesenteric organs (15.5 nmol/min). Much lower concentrations of norepinephrine and its glycol metabolites in plasma leaving than entering the liver indicate their efficient hepatic removal (20 nmol/min). Higher concentrations of vanillylmandelic acid in the hepatic outflow than inflow indicate that this metabolic end product is produced largely from the norepinephrine and glycol metabolites removed by the liver. Renal elimination of vanillylmandelic acid (18-20 nmol/min), produced mainly by the liver (17 nmol/min), and of 3-methoxy-4-hydroxyphenylglycol sulfate (7-9 nmol/min), produced largely by mesenteric organs (7 nmol/min), comprised 86-91% of the total renal elimination of norepinephrine metabolites. The results show that mesenteric organs produce about one-half of the norepinephrine formed in the body. The liver removes substantial amounts of circulating norepinephrine and its glycol metabolites and converts these compounds to vanillylmandelic acid, which is then eliminated from the body by the kidneys. The sulfate conjugates are also metabolic end products eliminated by the kidneys. However, these metabolites are produced by extrahepatic tissues, in particular, mesenteric organs, which represent a significant source of sulfate-conjugated norepinephrine and 3,4-dihydroxyphenylglycol, and the main source of sulfate-conjugated 3-methoxy-4-hydroxyphenylglycol. C1 GOTHENBURG UNIV,DEPT PHYSIOL,GOTHENBURG,SWEDEN. GOTHENBURG UNIV,DEPT CLIN PHYSIOL,GOTHENBURG,SWEDEN. RP Eisenhofer, G (reprint author), NINCDS,NIH,CLIN NEUROSCI BRANCH,BLDG 10,ROOM 5N214,10 CTR DR,MSC 1424,BETHESDA,MD 20892, USA. NR 32 TC 68 Z9 68 U1 0 U2 1 PU LIPPINCOTT-RAVEN PUBL PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1996 VL 66 IS 4 BP 1565 EP 1573 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA UA119 UT WOS:A1996UA11900029 PM 8627312 ER PT J AU Busettini, C Miles, FA Krauzlis, RJ AF Busettini, C Miles, FA Krauzlis, RJ TI Short-latency disparity vergence responses and their dependence on a prior saccadic eye movement SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MACAQUE VISUAL-CORTEX; OCULAR FOLLOWING RESPONSES; SLOW OCULOMOTOR CONTROL; RANDOM-DOT STEREOGRAMS; MOTION SELECTIVITY; NEURAL MECHANISMS; BINOCULAR VISION; SMOOTH-PURSUIT; MONKEY; EXPECTATIONS AB 1. A dichoptic viewing arrangement was used to study the initial vergence eye movements elicited by brief horizontal disparity steps applied to large textured patterns in three rhesus monkeys. Disconjugate steps (range, 0.2-10.9 degrees) were applied to the patterns at selected times (range, 13-303 ms) after 10 degrees leftward saccades into the center of the pattern. The horizontal and vertical positions of both eyes were recorded with the electromagnetic search coil technique. 2. Without training or reinforcement, disparity steps of suitable amplitude consistently elicited vergence responses at short latencies. For example, with 1.8 degrees crossed-disparity steps applied 26 ms after the centering saccade, the mean latency of onset of convergence for each of the three monkeys was 52.2 +/- 3.8 (SD) ms, 52.3 +/- 5.2 ms, and 53.4 +/- 4.1 ms. 3. Experiments in which the disparity step was confined to only one eye indicated that each eye was not simply tracking the apparent motion that it saw. For example, when crossed-disparity steps were confined to the right eye (which saw leftward steps), the result was (binocular) convergence in which the left eye moved to the right even though that eye had seen only a stationary scene. This movement of the left eye cannot have resulted from independent monocular tracking and indicates that the vergence here derived from the binocular misalignment of the two retinal images. 4. The initial vergence responses to crossed-disparity steps had the following main features. 1) They were always in the correct (i.e., convergent) direction over the full range of stimuli tested, the initial vergence acceleration increasing progressively with increases in disparity until reaching a peak with steps of 1.4-2.4 degrees and declining thereafter to a nonzero asymptote as steps exceeded 5-7 degrees. 2) They showed transient postsaccadic enhancement whereby steps applied in the immediate wake of a saccadic eye movement resulted in much higher initial vergence accelerations than the same steps applied some time later. The response decline in the wake of a saccade was roughly exponential with time constants of 67 +/- 5 (SD) ms, 35 +/- 2 ms, and 54 +/- 4 ms for the three animals. 3) That the postsaccadic enhancement might have resulted in part from the visual stimulation associated with the prior saccade was suggested by the finding that enhancement could also be observed when the disparity steps were applied in the wake of (conjugate) saccadelike shifts of the textured pattern. However, this visual enhancement did not reach a peak until 17-37 ms after the end of the ''simulated'' saccade, and the peak enhancement averaged only 45% of that after a ''real'' saccade. 4) Qualitatively similar transient enhancements in the wake of real and simulated saccades have also been reported for the initial ocular following responses elicited by conjugate drifts of the visual scene. We replicated the enhancement effects on ocular following to allow a direct comparison with the enhancement effects on disparity vergence using the same animals and visual stimulus patterns and, despite some clear quantitative differences, we suggest that the enhancement effects share a similar etiology. 5. Initial vergence responses to uncrossed-disparity steps had the following main features. 1) They were in the correct (i.e., divergent) direction only for very small steps (<1.5-2-5 degrees), and then only when postsaccadic delays were small; when the magnitude of the steps was increased beyond these levels, responses declined to zero and thereafter reversed direction, eventually reaching a nonzero (convergent) asymptote similar to that seen with large crossed-disparity steps; convergent responses were also seen with larger vertical disparity steps, suggesting that they represent default responses to any disparity exceeding a few degrees. 2) As the postsaccadic delay was increased, responses to small steps (1.8 degrees) declined to zero and thereafter reversed direction. Thus here the effect of a prior saccade was to transiently enhance the correctly directed (divergent) responses, albeit weakly. Again, these effects seemed to depend at least in part on the visual stimulation associated with the saccade because similar, although not identical, changes were observed when uncrossed-disparity steps were applied in the wake of saccadelike shifts of the textured pattern. 6. We suggest that these short-latency vergence responses are mediated by the so-called disparity-selective neurons in the visual cortex. The fact that these neurons are sensitive to disparities only up to a degree or two and that some of them also respond to uncorrelated patterns might explain why initial vergence responses were always appropriate for reducing small imposed disparity errors but often not appropriate for reducing large errors. We also hypothesize that the transient enhancement of correctly directed vergence responses in the wake of saccades will help speed the binocular realignment of the eyes when gaze is transferred to new depth locations. C1 NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. NR 49 TC 60 Z9 61 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 1996 VL 75 IS 4 BP 1392 EP 1410 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA UE798 UT WOS:A1996UE79800007 PM 8727386 ER PT J AU Pluta, RM Thompson, G Dawson, TM Snyder, SH Boock, RJ Oldfield, EH AF Pluta, RM Thompson, G Dawson, TM Snyder, SH Boock, RJ Oldfield, EH TI Loss of nitric oxide synthase immunoreactivity in cerebral vasospasm SO JOURNAL OF NEUROSURGERY LA English DT Article DE nitric oxide; nitric oxide synthase; cerebrovascular regulation; vasospasm; monkey ID ANEURYSMAL SUBARACHNOID HEMORRHAGE; RELAXING FACTOR; CEREBROSPINAL-FLUID; GUANYLATE-CYCLASE; BASILAR ARTERY; SMOOTH-MUSCLE; BLOOD-FLOW; ENDOTHELIUM; HEMOGLOBIN; INHIBITION AB To determine the distribution of nitric oxide synthase (NOS) in the primate cerebral artery nervi vasorum and to examine the potential role of NOS in cerebral vasospasm after subarachnoid hemorrhage (SAH) in primates, the distribution of NOS immunoreactivity (NOS-IR) in the major cerebral arteries was examined immunohistochemically in cynomolgus monkeys by the use of whole, mounted preparations of the circle of Willis. In four normal monkeys, NOS-IR was localized to the endothelial and adventitial layers of the large cerebral arteries. On the abluminal side, NOS-IR staining was densely concentrated in perivascular nerve fibers (nervi vasorum) of the anterior circulation. Staining was less prominent in the posterior circulation. In six monkeys with vasospasm on Day 7 after placement of preclotted arterial blood to form an SAH around the right middle cerebral artery (MCA) (42% +/- 8.3% decrease of MCA area, mean +/- standard deviation), NOS-IR was virtually absent in nerve fibers around the spastic right MCA but was normal on the contralateral side. In five monkeys in which vasospasm resolved by Day 14 after SAH (36% +/- 14% decrease of right MCA area on Day 7, and 5% +/- 14% decrease on Day 14), NOS-IR was also absent in the right MCA adventitial nerve fibers and remained normal in the left MCA. Adventitial NOS-IR was also normal in cerebral vessels of a sham-operated, nonspastic monkey. These findings provide further evidence that nitric oxide (NO) functions as a neuronal transmitter to mediate vasodilation in primates and indicate a role for adventitial NO in the pathogenesis of cerebral vasospasm after SAH in humans. C1 NINCDS,NIH,SURG NEUROL BRANCH,BETHESDA,MD 20892. JOHNS HOPKINS SCH MED,DEPT NEUROL,BALTIMORE,MD. JOHNS HOPKINS SCH MED,DEPT NEUROSCI,BALTIMORE,MD. FU NINDS NIH HHS [NS33277, NS01578] NR 56 TC 108 Z9 111 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD APR PY 1996 VL 84 IS 4 BP 648 EP 654 DI 10.3171/jns.1996.84.4.0648 PG 7 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA UC211 UT WOS:A1996UC21100015 PM 8613858 ER PT J AU Sumner, C Shinohara, T Durham, L Traub, R Major, EO Amemiya, K AF Sumner, C Shinohara, T Durham, L Traub, R Major, EO Amemiya, K TI Expression of multiple classes of the nuclear factor-1 family in the developing human brain: Differential expression of two classes of NF-1 genes SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE human brain; nuclear factor-1; DNA binding; cloning; transcription ID ADENOVIRUS DNA-REPLICATION; BOX-BINDING-PROTEINS; HUMAN PAPILLOMAVIRUS TYPE-16; CELL-SPECIFIC TRANSCRIPTION; HUMAN CYTOMEGALO-VIRUS; HUMAN POLYOMAVIRUS-JC; FACTOR-I; COLLAGEN PROMOTER; RECOGNITION SITE; GLIAL-CELLS AB Nuclear factor-1 (NF-1) is a multifunctional protein that participates in both transcription and replication. NF-1 proteins exist as a family of proteins that share some common structural and functional features but also demonstrate organ and cell type specific expression. Based upon these characteristics, the family of NF-1 proteins is divided into four classes, A, B, C and D. Several NF-1 binding sites have been identified in the regulatory sequences of the human polyomavirus, JCV, which multiplies most efficiently in glial cells derived from human fetal brain. Nuclear proteins from these cultures bind specifically to these NF-1 sites. It is not known, however, which member(s) of the NF-1 family is expressed in cells susceptible to JCV infection. We have examined glial cells as well as HeLa cells, which are not permissive to JCV, for NF-1 expression. By RT-PCR analysis, ail four classes of NF-1 are expressed in human fetal glial cells and HeLa cells. However, by Northern analysis the expression of class D gene is much higher in the glial cells than HeLa cells. Expression of the class C gene, first identified in HeLa cells as NF-1/CTF1, is barely detectable in glial cells but highly expressed in HeLa cells. The screening of cDNA libraries from two early human brain tissues resulted in the identification of a number of clones which appear to be related and belong to a single class of the NF-1 family, class D. Nucleotide sequence of one clone, designated NF-1/AT1, confirms this. The NF-1/AT1 protein was overexpressed in E coli and found tl, bind specifically to an NF-1 probe by gel shift analysis. Southern analysis of human fetal glial cells indicates that the NF-1/AT1 gene, class D, is derived from a different gene than NF-1/CTF1. These results suggest the possibility that genes or viruses, like JCV, which use NF-1 for their expression in human brain derived cells may preferentially use the NF-1 class D protein. C1 NINCDS,LAB MOLEC MED & NEUROSCI,NIH,BETHESDA,MD 20892. IGEN INC,ROCKVILLE,MD 20852. NR 66 TC 41 Z9 42 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 1996 VL 2 IS 2 BP 87 EP 100 DI 10.3109/13550289609146542 PG 14 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA UL929 UT WOS:A1996UL92900005 PM 8799200 ER PT J AU Martin, RE Henken, DB Hill, JM AF Martin, RE Henken, DB Hill, JM TI Altered expression and changing distribution of the nerve growth associated protein GAP-43 during ocular HSV-1 infection in the rabbit SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE HSV latency and reactivation; dexamethastone; neuronal immunohistochemistry; sensory ganglia; immunosuppression; cornea ID AXONALLY TRANSPORTED PROTEINS; CALMODULIN BINDING-PROTEIN; CEREBRAL-CORTEX; GENE-EXPRESSION; B-50 GAP-43; NEURONS; PHOSPHOPROTEIN; REGENERATION; MECHANISM; RELEASE AB This research examines changes that occur in neurons during corneal herpes simplex virus (HSV-1) infection and focuses on the nerve growth associated protein GAP-43. Cornea and trigeminal ganglion (TG) of New Zealand white rabbits were examined after inoculation of the McKrae and 17 Syn(+) strains of HSV-1 to the cornea. Rabbit tissues were taken during acute, latent and induced reactivation stages of infection. Systemic immunosuppression (intravenous injections of cyclophosphamide and dexamethasone) was used to induce reactivation. Western blotting, immunoblotting and autoradiography with the same antibody were used respectively to verify antibody specificity, measure changes in GAP-43 concentration and localize GAP-43 to neurons in the TG. During acute infection, corneal GAP-43 increased significantly while no change was seen in the TG. GAP-43 content was elevated in TG and cornea during viral latency (post-inoculation days 84-154) for both HSV-1 strains. When latent virus was reactivated, the corneal concentration of GAP-43 was more than double that of normal rabbits and the concentration of GAP-43 in TG was reduced compared to the non-reactivated, latently-infected TG. In summary, HSV-1 infected TG neurons expressed more GAP-43 than control neurons and immunosuppressive therapy led not only to viral reactivation and increased GAP-43 concentrations in cornea but also to decreased GAP-43 concentrations in TG. These results suggest that factors which maintain HSV-1 latency and induce reactivation could be linked to elements regulating GAP-43 expression. C1 NINCDS, NIH, EXPTL NEUROPATHOL LAB, BETHESDA, MD 20892 USA. LOUISIANA STATE UNIV, COLL MED, LSU EYE CTR, NEW ORLEANS, LA 70112 USA. RP UNIV OKLAHOMA, COLL MED, DEPT ANAT SCI, 940 STANTON YOUNG BLVD, RM 517, OKLAHOMA CITY, OK 73104 USA. FU NEI NIH HHS [EY02377, EY06311] NR 49 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 EI 1538-2443 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 1996 VL 2 IS 2 BP 127 EP 135 DI 10.3109/13550289609146546 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA UL929 UT WOS:A1996UL92900009 PM 8799204 ER PT J AU Esposito, G VanHorn, JD Weinberger, DR Berman, KF AF Esposito, G VanHorn, JD Weinberger, DR Berman, KF TI Gender differences in cerebral blood flow as a function of cognitive state with PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE cerebral blood flow; PET; cognitive stimulation; gender differences; frontal lobe ID GLUCOSE METABOLIC RATES; SEX-DIFFERENCES; EMISSION TOMOGRAPHY; VERBAL FUNCTIONS; BRAIN; HANDEDNESS; LESIONS; HUMANS; MALES; AGE AB This study explored the role of cognitive states in gender-based differences in brain function, Methods: We used the O-15-water bolus method to measure cerebral blood flow (CBF) in 14 young normal volunteers with PET. Each subject was scanned six times, three during different neuropsychological tasks linked to the prefrontal cortex and three others during customized sensorimotor control tasks, The prefrontal tasks were the Wisconsin Card Sorting (WCS) Test, Delayed Alternation task (DA) and Spatial Delayed Response task (DR), Results: A significant main influence of sex on global CBF (ml/min/100g) was seen, with higher values in women, as viewed across all six conditions (means: 60.9 versus 53.2, ANOVA F = 9.35, p < 0.01), Post-hoc contrasts, however, showed that this finding was not uniform in all conditions, Differences between men and women were seen during performance of the frontal lobe tasks, but not during the sensorimotor control tasks. Even within the three frontal lobe tasks, results tended to vary: the differences between the sexes were most significant during the DA and just reached traditional levels of significance during the WCS, Therefore, if we had utilized a single task condition to determine whether men and women have different global CBFs, disparate conclusions would have been reached depending upon the task chosen, Conclusion: Although clear sex differences in global CBF can be demonstrated, the cognitive state of the subjects must be controlled and considered when interpreting the differences, Also, variations in the cognitive state might explain some of the discrepancies in gender studies in the rCBF and cerebral glucose metabolism literature. C1 NIMH,INTRAMURAL RES PROGRAM,CLIN BRAIN DISORDERS BRANCH,WASHINGTON,DC 20032. NR 55 TC 73 Z9 74 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 1996 VL 37 IS 4 BP 559 EP 564 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UD634 UT WOS:A1996UD63400006 PM 8691239 ER PT J AU Freedman, NMT Bacharach, SL Carson, RE Price, JC Dilsizian, V AF Freedman, NMT Bacharach, SL Carson, RE Price, JC Dilsizian, V TI Effect of smoothing during transmission processing on quantitative cardiac PET scans SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; transmission smoothing; cardiac studies ID POSITRON EMISSION TOMOGRAPHY; ATTENUATION CORRECTION AB The effects of attenuation in cardiac PET are large and are produced by varied and inhomogeneous attenuating media. Although a measured attenuation correction can potentially provide an exact correction for attenuation, it introduces noise into the attenuation-corrected emission scan, Transmission smoothing reduces this noise but can introduce errors of its own, This study investigates these errors in absolute and relative quantitation and estimates their magnitude in a clinical setting. Methods: Fluorodeoxyglucose cardiac PET scans of 24 subjects were processed using measured attenuation correction with different levels of transmission smoothing. Mean activity concentrations were determined in septal, anterior and lateral regions of the left ventricle at each level of transmission smoothing. A theoretical derivation of the effects of transmission smoothing is presented, so that the observed effects could be compared with theory-based predictions. Results: In addition to the reduction of noise, transmission smoothing produced two further effects: (a) a previously unreported reduction in noise-induced bias, which is beneficial acid (b) introduction of errors due to bad estimates of attenuation correction factors resulting from smoothing over regions where attenuation changes. The first effect was observed over all regions of the left ventricle, whereas the second reduced counts primarily in the lateral wall. Twenty-millimeter smoothing reduced noise-induced bias by an average of 4% (compared with 6-mm smoothing). This same smoothing caused an additional 9% decrease in the lateral wall as a result of the adjacent lung-lateral wall boundary. Conclusion: Transmission smoothing reduces both noise and noise-induced bias, but near transitions between differently attenuating media (e.g., lung-myocardial borders) may produce errors in absolute acid relative quantitation, The data presented here document the magnitudes of these effects, permitting one to ensure that artifactually introduced inhomogeneities are kept small. C1 NIH,DEPT NUCL MED,BETHESDA,MD 20892. RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 11 TC 19 Z9 19 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 22090-5316 SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 1996 VL 37 IS 4 BP 690 EP 694 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UD634 UT WOS:A1996UD63400035 PM 8691268 ER PT J AU Pawlosky, RJ Salem, N AF Pawlosky, RJ Salem, N TI Is dietary arachidonic acid necessary for feline reproduction? SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 1995 American-Institute-of-Nutrition Annual Meeting CY APR 09-13, 1995 CL ATLANTA, GA SP Amer Inst Nutr DE arachidonic acid; polyunsaturated fatty acids; corn oil; feline reproduction ID CAT AB A study was carried out to determine whether corn oil-based diets devoid of arachidonic acid, 20:4(n-6), are capable of supporting feline reproduction. One group of four adult female felines were acclimated to a 10 weight% (wt%) fat diet consisting of 1 wt% corn oil and 9 wt% hydrogenated coconut oil for 1 mo before mating. One female produced two live offspring, and the other three females delivered either stillborn fetuses or offspring that were severely deformed and died shortly after birth. Two of these females were subsequently placed on a 1 wt% corn oil diet that was supplemented with 20:4(n-6) (200 mg/kg of diet), and after 2 mo they were mated. Offspring resulting from the second mating were healthy. A third group of females that were maintained on a 10 wt% fat diet consisting of 3 wt% corn oil were also mated. The offspring from these matings appeared healthy at birth. Neonates from each diet group were killed, and the fatty acyl composition of the livers, plasma and brains was analyzed. In the offspring livers and plasma, the level of 20:4(n-6) from both the 1 wt% or 3 wt% corn oil diet groups was about half that of offspring from those receiving 20:4(n-6) in the diet. There were no differences in the level of 20:4(n-6) in the neonate brains,among any of the groups, This study suggests that nutritional factors unrelated to the tissue accumulation of arachidonic acid in the offspring may be responsible for the high percentage of stillbirths and deformities associated with maternal diets containing low amounts of essential fatty acids but that diets that contain a higher percentage of corn oil can support feline reproduction. C1 NIAAA,DIV INTRAMURAL CLIN & BIOL RES,ROCKVILLE,MD 20852. NR 12 TC 11 Z9 11 U1 1 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 1996 VL 126 IS 4 SU S BP S1081 EP S1085 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UD167 UT WOS:A1996UD16700017 ER PT J AU Schwartz, JL AF Schwartz, JL TI The dual roles of nutrients as antioxidants and prooxidants: Their effects on tumor cell growth SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 1995 American-Institute-of-Nutrition Annual Meeting CY APR 09-13, 1995 CL ATLANTA, GA SP Amer Inst Nutr DE carotenoids; tocopherols; ascorbic acid; retinoids; chemoprevention; tumor suppressor genes ID VITAMIN-E; ALPHA-TOCOPHEROL; BETA-CAROTENE; EXPERIMENTAL CANCER; INHIBITION; REGRESSION AB The development of a beneficial or a detrimental cellular response by a nutrient will depend on the nutrient's antioxidant or prooxidant characteristics, which in turn are a product of the cellular oxygen environment. Nutrients such as carotenoids, tocopherols or ascorbate derivatives will demonstrate an antioxidant or prooxidant characteristic depending on the redox potential of the individual molecule and the inorganic chemistry of the cell. Nutrients acting as chemopreventives, inhibit the continual growth of transformed clones of cells through their prooxidant activity. In contrast, when an antioxidant activity occurs in transformed cells an enhanced growth may result. In addition, when an inappropriate prooxidant activity develops in normal cells, the reactive oxygen metabolites generated could damage the DNA and cellular membranes. The cellular response is usually a loss of normal regulatory function and activity, depressing cellular intergrity. Therefore, the labile redox character of each nutrient must be considered in terms of the extracellular and intracellular microoxygen environment. To predict if a specific nutrient will have a beneficial or detrimental effect on a particular tissue or cell, it is important to identify markers that will characterize the biologic activities of each nutrient and elucidate a possible mechanism of action for that nutrient. In various tissues chemopreventive agents derived from nutrients have been shown in laboratory animal studies and in some human intervention trials to inhibit the growth and development of premalignant or malignant lesions. Examples of these tissues include oral tissues, esophagus, gastric cardia and lung tissues. Recently, some clinical studies demonstrated no reduction in the incidence of premalignant change, but, to the contrary, statistical evidence indicated an increase in cancer development. In general, the results of clinical intervention trials remains equivocal. The use of chemopreventive agents without considering their pharmacologic, oxygen-responsive characteristics will produce unwanted iatrogenic side effects or further cloud evidence of these nutrients' biologic activities. RP Schwartz, JL (reprint author), NIH,MOL EPIDEMIOL BIOL INDICATORS BRANCH,NAVAL DENT RES BLDG 1,4TH FLOOR,ROOM 4416,8901 WI,BETHESDA,MD 20889, USA. NR 42 TC 86 Z9 89 U1 2 U2 7 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 1996 VL 126 IS 4 SU S BP S1221 EP S1227 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UD167 UT WOS:A1996UD16700040 ER PT J AU Selhub, J Jacques, PF Bostom, AG DAgostino, RB Wilson, PWF Belanger, AJ OLeary, DH Wolf, PA Rush, D Schaefer, EJ Rosenberg, IH AF Selhub, J Jacques, PF Bostom, AG DAgostino, RB Wilson, PWF Belanger, AJ OLeary, DH Wolf, PA Rush, D Schaefer, EJ Rosenberg, IH TI Relationship between plasma homocysteine, vitamin status and extracranial carotid-artery stenosis in the Framingham study population SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT 1995 American-Institute-of-Nutrition Annual Meeting CY APR 09-13, 1995 CL ATLANTA, GA SP Amer Inst Nutr DE homocysteine; folic acid; pyridoxal phosphate; vitamin B-6; vitamin B-12; arteriosclerosis ID VASCULAR-DISEASE; RISK FACTOR; FOLIC-ACID; HOMOCYST(E)INE; HYPERHOMOCYSTEINEMIA; ATHEROSCLEROSIS; QUESTIONNAIRE; METABOLISM; THERAPY; FOLATE AB Recent studies demonstrated associations between occlusive vascular disease and hyperhomocysteinemia of both genetic and nutritional origin. In the present study we analyzed plasma samples from the 20th biannual examination of the Framingham Heart Study cohort to determine distribution of plasma homocysteine concentrations with emphasis on relationships to B vitamins and prevalence of carotid artery stenosis. Results showed that homocysteine exhibited strong inverse association with plasma folate and weaker associations with plasma vitamin B-12 and pyridoxal-5'-phosphate (PLP). Homocysteine was also inversely associated with intakes of folate and vitamin B-6, but not vitamin B-12. prevalence of high homocysteine (>14 mu mol/l) was 29.3% in this cohort, and inadequate plasma concentrations of one or more B vitamins appear to contribute to 67% of the cases of high homocysteine, Prevalence of stenosis greater than or equal to 25% was 43% in men and 34% in women with an odds ratio of 2.0 for individuals in the highest homocysteine quartile (greater than or equal to 14.4 mu mol/l) compared with those in the lowest quartile (less than or equal to 9.1 mu mol/l), after adjustment for sex, age, high density lipoprotein cholesterol, systolic blood pressure and cigarette smoking (P-trend < 0.001). plasma concentrations of folate and pyridoxal-5'-phosphate and folate intake were inversely associated with extracranial carotid stenosis after adjustment for age, sex and other risk factors. C1 NHLBI,FRAMINGHAM HEART DIS EPIDEMIOL STUDY,FRAMINGHAM,MA 01701. BOSTON UNIV,DEPT MATH,STAT & CONSULTING UNIT,BOSTON,MA 02111. GEISINGER MED CTR,DEPT RADIOL,DANVILLE,PA 17821. BOSTON UNIV,SCH MED,DEPT NEUROL,BOSTON,MA 02111. UNIV BOSTON HOSP,EVANS MEM DEPT CLIN RES,PREVENT MED & EPIDEMIOL SECT,BOSTON,MA 02111. UNIV BOSTON HOSP,DEPT MED,BOSTON,MA 02111. RP Selhub, J (reprint author), TUFTS UNIV,USDA,JEAN MAYER HUMAN NUTR RES CTR AGING,711 WASHINGTON ST,BOSTON,MA 02111, USA. NR 32 TC 69 Z9 70 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 1996 VL 126 IS 4 SU S BP S1258 EP S1265 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UD167 UT WOS:A1996UD16700047 ER PT J AU Ahluwalia, GS Driscoll, JS Ford, H Johns, DG AF Ahluwalia, GS Driscoll, JS Ford, H Johns, DG TI Comparison of the DNA incorporation in human MOLT-4 cells of two 2'-beta-fluoronucleosides, 2'-beta-fluoro-2',3'-dideoxyadenosine and fialuridine SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID HIV AB Incorporation of 2'-beta-fluoro-2',3'-dideoxyadenosine (F-ddA), a recently developed anti-HIV agent, into the cellular DNA of human MOLT-4 cells has been compared with the DNA incorporation seen with fialuridine (FIAU; 1-[2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl]-5-iodouracil), a potent anti-hepatitis B (anti-HBV) nucleoside analogue recently found to cause severe hepatic toxicity in human subjects. At equimolar concentrations (10 mu M), incorporation of F-ddA was less than 1% of that for FIAU, a difference attributable to the lack of a 3'-hydroxyl group in the former compound and a consequent inability of F-ddA, unlike FIAU, to form DNA internucleotide linkages. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 13 TC 4 Z9 4 U1 0 U2 0 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD APR PY 1996 VL 85 IS 4 BP 454 EP 455 DI 10.1021/js950494b PG 2 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA UD668 UT WOS:A1996UD66800022 PM 8901088 ER PT J AU Witkin, JM Acri, JB Wong, G Gleeson, S Barrett, JE AF Witkin, JM Acri, JB Wong, G Gleeson, S Barrett, JE TI Behavioral and biochemical characterization of benzodiazepine receptor partial agonists in pigeons SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DISCRIMINATIVE STIMULUS PROPERTIES; AMINOBUTYRIC ACID(A) RECEPTOR; RO 16-6028; DRUG DISCRIMINATION; ANXIOLYTIC DRUGS; FULL AGONISTS; ANTAGONIST RO-15-1788; INTRINSIC EFFICACIES; PHYSICAL-DEPENDENCE; BETA-CARBOLINES AB The ability of benzodiazepine receptor partial agonists to exhibit full efficacy in preclinical anxiolytic tests, in conjunction with initial clinical results, has suggested the possibility of a reduced clinical side-effect profile compared to benzodiazepine receptor full agonists like diazepam. Because punished behavior of pigeons has been useful in detecting effects of novel anxiolytic drugs, effects of imidazobenzodiazepine and beta-carboline benzodiazepine receptor partial agonists and some related compounds were evaluated in this species. The abilities of these compounds to substitute for the discriminative stimulus effects of the full agonist midazolam also was determined. Intrinsic efficacy was assessed by the degree to which gamma-aminobutyric acid increased ligand potency to displace [H-3]Ro 15-1788 (flumazinil) from membranes of pigeon cerebrum, and ranged from full agonist-like efficacy {Ro 19-5470; 7-(3-cyclopropyl-1,2,4-oxodiazol-5-yl)-5,6-dihydro-5-methyl-4H- imidazo[1,5a]-thieno[3,2-f]diazin-4-one} to minimal gamma-aminobutyric acid potentiations close to that of the antagonist flumazenil {abecarnil and Ro 41-7812; 7-chloro-4,5-dihydro-3-(3-hydroxy-1-propynyl)-5-methyl-6H-imidazo[1,5-a]-[1,4]benzodiazepine-6-one}. Punished responding was increased markedly by midazolam and by all partial agonists, except Ro 41-7812 and Ro 42-8773 {7-chloro-3-[3-(cylclopropylmethoxy)-1-propynyl]-4,5-dihyro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepine-6-one}, at doses that did not affect nonpunished responding. In contrast to the full substitution generally observed in mammals, all of the partial agonists produced incomplete substitution (40-70%) in the midazolam drug discrimination procedure in pigeons. A positive relationship was observed between the degree of substitution and intrinsic efficacy. The benzodiazepine antagonists, flumazenil and ZK 93,426 {ethyl-5-isopropoxy-4-methoxymethyl-beta-carboline-3- carboxylate}, neither increased punished responding nor substituted for midazolam. The results of the present study suggest that benzodiazepine receptor partial agonists and related compounds may provide full anxiolytic activity at doses that do not fully reproduce the subjective effect profile of full agonists. C1 NIDDKD, NEUROSCI LAB, NIH, BETHESDA, MD 20892 USA. UNIFORMED SERV UNIV HLTH SCI, DEPT PSYCHIAT, BETHESDA, MD 20814 USA. RP Witkin, JM (reprint author), NATL INST DRUG ABUSE, DRUG DEV GRP,PSYCHOBIOL SECT,ADDICT RES CTR,NIH, POB 5180, BALTIMORE, MD 21224 USA. NR 93 TC 15 Z9 15 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1996 VL 277 IS 1 BP 87 EP 96 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UE585 UT WOS:A1996UE58500013 PM 8613971 ER PT J AU Acri, JB Seidleck, BK Witkin, JM AF Acri, JB Seidleck, BK Witkin, JM TI Effects of benztropine on behavioral and toxic effects of cocaine: Comparison with atropine and the selective dopamine uptake inhibitor 1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-propyl)-piperazine SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SCHEDULE-CONTROLLED BEHAVIOR; NONHUMAN-PRIMATES; BINDING-SITES; PHARMACOLOGICAL CHARACTERIZATION; ANTIPARKINSONIAN DRUGS; INDUCED HYPERACTIVITY; REUPTAKE INHIBITORS; SQUIRREL-MONKEYS; CAUDATE-PUTAMEN; UPTAKE COMPLEX AB Behavioral effects of cocaine that are relevant to its abuse have been associated with pharmacological actions at the dopamine uptake carrier. Benztropine (Cogentin) is an antiparkinson agent that has limited abuse despite its ability to block dopamine uptake, and has been suggested as a candidate for the treatment of cocaine dependence. Preclinical studies were conducted to assess the behavioral and toxic effects of benztropine alone and in conjunction with cocaine, Because of the mixed pharmacology of benztropine which includes antimuscarinic as well as dopaminergic actions, results obtained from parallel experiments with atropine and the selective dopamine uptake inhibitor, GBR 12935 {1-[2-(diphenylmethoxy)ethyl]-4-(3-phenyl-propyl)-piperazine}, were performed, All of the drugs stimulated locomotor activity of mice, but atropine and benztropine had much lower efficacy. Nonstimulatory doses of GBR 12935 enhanced the locomotor stimulant effects of cocaine, whereas benztropine and atropine did not share this effect. GBR 12935, benztropine and cocaine increased fixed-interval responding, whereas atropine decreased fixed-interval response rates in rats. Only GBR 12935 and cocaine increased responding during timeout periods. GBR 12935, but not benztropine or atropine, fully reproduced the discriminative stimulus effects of cocaine (10 mg/kg). GBR 12935 and atropine augmented the discriminative stimulus effects of lower cocaine doses in rats. Only GBR 12935 and cocaine had convulsant effects and only GBR 12935 significantly enhanced the convulsant effects of cocaine in mice. These results document a behavioral and toxicity profile for benztropine distinct from that of classical dopamine uptake blockers. The data underscore further the potential of benztropine as a candidate for clinical evaluation in the treatment of cocaine dependence. C1 NIDA,DRUG DEV GRP,ADDICT RES CTR,NIH,BALTIMORE,MD. NR 70 TC 25 Z9 25 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1996 VL 277 IS 1 BP 198 EP 206 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UE585 UT WOS:A1996UE58500027 PM 8613919 ER PT J AU Shoaf, SE Schmall, B AF Shoaf, SE Schmall, B TI Pharmacokinetics of alpha-methyl-L-tryptophan in rhesus monkeys and calculation of the lumped constant for estimating the rate of serotonin synthesis SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID SYNTHESIS INVIVO; METHYLTRYPTOPHAN; BRAIN AB We have determined several kinetic and pharmacokinetic parameters of L-tryptophan (Trp) and alpha-methyl-L-tryptophan (alpha MTrp) in the rhesus monkey from which the lumped constant for the alpha MTrp method of estimating serotonin synthesis rates is calculated. alpha MTrp was isolated from DL-alpha MTrp using a chiral separation column with high performance liquid chromatography. alpha MTrp (50 mu g/kg) was administered i.v. to four adult male rhesus monkeys and arterial blood samples were collected for a 4-hr period. Plasma concentrations, as determined by high performance liquid chromatography with electrochemical detection, were best fitted by a tri-exponential equation. Plasma protein binding of Trp and alpha MTrp was determined by measuring concentrations in ultrafiltrates obtained at 30 degrees C. After a 2-hr adjusted rate infusion of alpha MTrp designed to establish steady-state plasma concentrations, three adult male rhesus monkeys were killed by exsanguination with perfused ice-cold saline. Brain/arterial plasma concentration ratios of Trp and alpha MTrp and the Michaelis-Menten parameters for tryptophan hydroxylase, EC 1.14.16.4, with Trp and alpha MTrp as initiating substrates, were determined for seven brain regions. The lumped constants determined for the different brain regions were not significantly different from each other and indicate, that for modeling purposes, the brain may be treated as a homogeneous area and the lumped constant given a single value, 0.18 +/- 0.05. C1 NIH,CTR CLIN,PET DEPT,BETHESDA,MD 20892. RP Shoaf, SE (reprint author), NIAAA,CLIN STUDIES LAB,10 CTR DR,MSC-1256,BETHESDA,MD 20892, USA. NR 14 TC 18 Z9 18 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1996 VL 277 IS 1 BP 219 EP 224 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UE585 UT WOS:A1996UE58500030 PM 8613922 ER PT J AU Elmer, GI George, FR AF Elmer, GI George, FR TI The role of specific eicosanoids in mediating the acute narcotic effects of ethanol SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID PANCREATIC PHOSPHOLIPASE A2; BRAIN MEMBRANES; PROSTAGLANDIN SYNTHETASE; MESSENGER-RNA; RAT-BRAIN; PHOSPHATIDYLCHOLINE; INHIBITION; HYDROLYSIS; BINDING; ACID AB The pharmacological effects of ethanol may be in part due to increased membrane fluidity, resulting in increased phospholipase A(2) activity and the subsequent conversion of released arachidonic acid (AA) into pharmacologically relevant eicosanoids (prostaglandins/leukotrienes). A significant correlation between the in vivo and in vitro potency of prostaglandin synthetase (PES) inhibitors to antagonize PES activity and their ability to antagonize the acute narcotic and rate-depressant effects of ethanol support this hypothesis. However, inhibition of PES not only decreases the production of at least five prostaglandins and thromboxane but may shunt free AA into the lipoxygenase cascade with subsequent formation of leukotrienes. The purpose of the present study was to systematically investigate numerous points in the AA cascade to determine the eicosanoid products relevant to the acute narcotic effects of ethanol. Ethanol-induced loss of the righting reflex in mice was used as the behavioral endpoint. The relative importance of PES metabolites vs. lipoxygenase metabolites was determined via administration of specific enzyme inhibitors (phospholipase, lipoxygenase and dual PES/lipoxygenase inhibitors) and receptor agonists/antagonists (prostaglandin and leukotriene). Pretreatment with specific lipoxygenase inhibitors, dual PES/lipoxygenase inhibitors and leukotriene antagonists suggest a negligible role for lipoxygenase metabolites in acute ethanol-induced narcosis. Pretreatment with prostaglandin agonists and antagonists suggest a significant role for prostaglandin E (PGE) and a minor role for prostaglandin D in mediating the acute effects of ethanol. The PGE agonist 16,16-dimethyl PGE significantly enhanced the narcotic effects of ethanol (> 400%), whereas the prostaglandin receptor antagonist L-640,035 significantly decreased the effects of ethanol (-54%). These results further support the hypothesis that eicosanoid formation is important in the biochemical and behavioral effects of ethanol. C1 AMETHYST TECHNOL INC,DIV RES,SCOTTSDALE,AZ. RP Elmer, GI (reprint author), NIDA,BEHAB PHARMACOL & GENET SECT,PRECLIN PHARMACOL LAB,DIV INTRAMURAL RES,ADDICT RES CTR,NIH,BALTIMORE,MD 21224, USA. FU NIAAA NIH HHS [AA-07754] NR 49 TC 10 Z9 10 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1996 VL 277 IS 1 BP 308 EP 315 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UE585 UT WOS:A1996UE58500041 PM 8613935 ER PT J AU Bilsky, EJ Bernstein, RN Hruby, VJ Rothman, RB Lai, J Porreca, F AF Bilsky, EJ Bernstein, RN Hruby, VJ Rothman, RB Lai, J Porreca, F TI Characterization of antinociception to opioid receptor selective agonists after antisense oligodeoxynucleotide-mediated ''knock-down'' of opioid receptors in vivo SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NCX BINDING-SITES; DELTA-RECEPTOR; RAT-BRAIN; NALTRINDOLE 5'-ISOTHIOCYANATE; DIFFERENTIAL ANTAGONISM; FUNCTIONAL EXPRESSION; H-3 NALTRINDOLE; MOUSE-BRAIN; SUBTYPES; CLONING AB Pharmacological studies in vivo and in vitro have suggested the existence of subtypes of the delta opioid receptor termed delta(1) and delta(2) (delta(1) and delta(2)). The hypothesis of subtypes of delta receptors was further explored by assessing the effects of administration of antisense or mismatch oligodeoxynucleotides (ODN) in vivo to the cloned DOR, or to a conserved region of the cloned opioid receptors, on the antinociceptive responses elicited by selective mu, kappa and delta opioid receptor agonists in mice. Additionally, the density of opioid delta receptors in brain after delta opioid receptor (DOR) ODN treatment was investigated. Repeated twice daily intracerebroventricular (i.c.v.) administration of DOR antisense, but not mismatch, ODN, produced a dose- and time-related blockade of i.c.v. [D-Ala(2), Glu(4)]deltorphin (delta(2) agonist), but not [D-Pen(2), D-Pen(5)]enkephalin (delta(1) agonist), antinociception. The antinociceptive responses to selective CL and kappa opioid agonists were unaffected by DOR antisense or mismatch ODN treatments. The antinociceptive effect of an A(90) dose of [D-Ala(2), Glu(4)]deltorphin was significantly reduced by the third day of DOR antisense ODN administration and persisted over a treatment period of 6 days with recovery by the third posttreatment day. Saturation studies in mouse whole brain preparations with the selective delta-radioligand [H-3]naltrindole showed that DOR antisense, but not mismatch, ODN treatment produced a significant time-related reduction in B-max values of approximately 30 to 40% by day 6, without changing the K-d value. The reduction in DOR density was reversible and returned to control levels within 3 days after cessation of antisense ODN treatment. The i.c.v. administration of an antisense, but not mismatch, ODN directed to a conserved region of the cloned opioid receptors, termed common opioid receptor antisense ODN, inhibited the antinociceptive effects of i.c.v. mu, kappa and delta agonists, including [D-Pen(2), D-Pen(5)]enkephalin. These data further support the hypothesis of subtypes of opioid delta receptors. C1 UNIV ARIZONA,COLL MED,DEPT PHARMACOL,HLTH SCI CTR,TUCSON,AZ 85724. UNIV ARIZONA,DEPT CHEM,HLTH SCI CTR,TUCSON,AZ 85724. NIDA,ADDICT RES CTR,BALTIMORE,MD 21224. FU NIDA NIH HHS [K02 DA 00185] NR 44 TC 44 Z9 45 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 1996 VL 277 IS 1 BP 491 EP 501 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UE585 UT WOS:A1996UE58500062 PM 8613959 ER PT J AU Masi, AT Chrousos, GP AF Masi, AT Chrousos, GP TI Hypothalamic-pituitary-adrenal-glucocorticoid axis function in rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID IMMUNE C1 NICHHD,SECT PEDIAT CARDIOL,DEV ENDOCRINOL BRANCH,BETHESDA,MD 20892. RP Masi, AT (reprint author), UNIV ILLINOIS,COLL MED,1 ILLINI DR,PEORIA,IL 61605, USA. OI Masi, Alfonse/0000-0002-9695-6634 NR 19 TC 82 Z9 83 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO ON M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 1996 VL 23 IS 4 BP 577 EP 581 PG 5 WC Rheumatology SC Rheumatology GA UE520 UT WOS:A1996UE52000001 PM 8730107 ER PT J AU Jensen, PS Martin, D Watanabe, H AF Jensen, PS Martin, D Watanabe, H TI Children's response to parental separation during Operation Desert Storm SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE parental absence; father absence; military children; stress ID MANIFEST ANXIETY; MILITARY FAMILY; I THINK; STRESS; RISK; FEEL; WAR AB Objective: Commonly held attitudes concerning the effects of parental wartime deployment on children have usually been guided by stereotype, rather than scientific data. To determine the effects of Operation Desert Storm on military children and their parents, the authors compared children and families with and without a deployed soldier-parent prior to and during Operation Desert Storm. Method: Three hundred eighty-three children and the remaining caretaking parent completed self- and parent-report instruments concerning child and family functioning and life stressors. Children of deployed and nondeployed personnel were compared cross-sectionally, as well as longitudinally, using data collected prior to any knowledge of Operation Desert Storm. Results: Children of deployed personnel experienced elevated self-reported symptom levels of depression, as did their parents. Likewise, families of deployed personnel reported significantly more intervening stressors, compared with children and families of nondeployed personnel. However, deployment per se rarely provoked pathological levels of symptoms in otherwise healthy children. Conclusions: Generally, the factors shaping differential outcomes among children of deployed personnel do not differ from the variables affecting outcomes of children of nondeployed parents. However, boys and younger children appear to be especially vulnerable to deployment effects, and increased monitoring of these children is warranted. Adequate treatment of children requires treatment of the effects of the deployment on other family members. For children showing more persistent or pervasive psychopathology, factors other than simple deployment should be considered. C1 CITADEL COLL,CHARLESTON,SC. WALTER REED ARMY INST RES,DIV NEUROPSYCHIAT,DEPT MIL PSYCHIAT,WASHINGTON,DC. RP Jensen, PS (reprint author), NIMH,CHILD & ADOLESCENT DISORDERS RES BRANCH,5600 FISHERS LANE,ROCKVILLE,MD 20857, USA. OI Jensen, Peter/0000-0003-2387-0650 NR 24 TC 93 Z9 93 U1 5 U2 10 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1996 VL 35 IS 4 BP 433 EP 441 DI 10.1097/00004583-199604000-00009 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA UB759 UT WOS:A1996UB75900009 PM 8919705 ER PT J AU Slavkin, HC AF Slavkin, HC TI The war on oral cavity and pharyngeal cancer SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article RP Slavkin, HC (reprint author), NIDR,31 CTR DR,MSC 2290,BLDG 31,ROOM 2C892,BETHESDA,MD 20892, USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 1996 VL 127 IS 4 BP 517 EP 520 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA UD665 UT WOS:A1996UD66500027 PM 8655875 ER PT J AU Hayes, CR Ropka, ME Sebring, NG Anderson, RE AF Hayes, CR Ropka, ME Sebring, NG Anderson, RE TI Recent food intake did not influence precision of body composition estimates by bioelectrical impedance analysis in men with HIV infection SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article C1 VIRGINIA COMMONWEALTH UNIV,SCH NURSING,ADULT HLTH DEPT,RICHMOND,VA. NIH,CTR CLIN,DEPT NUTR,BETHESDA,MD 20892. NIH,NATL INST NURSING RES,BETHESDA,MD 20892. RP Hayes, CR (reprint author), DIV HIV SERV,5600 FISHERS LANE,RM 7A-39,ROCKVILLE,MD 20857, USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER DIETETIC ASSN PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD APR PY 1996 VL 96 IS 4 BP 386 EP 388 DI 10.1016/S0002-8223(96)00105-8 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA UE274 UT WOS:A1996UE27400015 PM 8598442 ER PT J AU Levey, AS Bosch, JP Coggins, CH Greene, T Mitch, WE Schluchter, MD Schwab, SJ AF Levey, AS Bosch, JP Coggins, CH Greene, T Mitch, WE Schluchter, MD Schwab, SJ TI Effects of diet and antihypertensive therapy on creatinine clearance and serum creatinine concentration in the modification of diet in renal disease study SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article DE renal function measurement; glomerular filtration rate; creatinine secretion; creatinine excretion; progression of renal disease ID FILTRATION RATE MEASUREMENTS; PROTEIN RESTRICTION; PROGRESSION; FAILURE; INSUFFICIENCY; TRIAL AB Factors other than the glomerular filtration rate (GFR) can affect creatinine clearance (C-cr) and serum creatinine concentration (P-cr). The effect of dietary protein and antihypertensive therapy on C-cr, the reciprocal of the P-cr (1/P-cr), and their determinants (GFR, creatinine clearance from tubular secretion (C-TScr), and creatinine excretion (UcrV) values) was assessed in patients participating in the Modification of Diet in Renal Disease (MDRD) Study. This study compared the effects of assignment to a low versus usual-protein diet and to a low versus usual-blood pressure goal on the decline in these measurements over 3 yr in 585 patients with baseline GFR of 25 to 55 mL/min per 1.73 m(2) (Study A). This study also assessed correlations and associations of these measurements with each other and with protein intake, blood pressure, class of antihypertensive agents, and renal diagnosis in 840 patients with baseline GFR of 13 to 55 mL/min per 1.73 m(2) (Studies A and B). In Study A, the estimated mean decline in GFR at 3 yr did not differ significantly between the low and usual-protein diet groups (-10.9 versus -12.1 mL/min). In contrast, C-TScr declined more in the low-protein diet group (-7.8 versus -3.6 mL/min, P < .05). Consequently, the low-protein diet group had a greater decline in C-cr (-17.6 versus -14.4 mL/min, P < .05). The low-protein diet group also had a greater decline in UcrV (-306 versus -92 mg/day, P < .05). The decline in UcrV was proportionately greater than the decline in C-TScr, hence the decline in 1/P-cr was less in the low-protein diet group (-0.091 versus -0.122 dL/mg, P < .05). Similarly, in Study A, there was no significant difference in the decline in GFR at 3 yr between the low and usual-blood pressure groups (-10.7 versus -12.3 mL/min). However, there was a lesser decline in C-TScr in the low blood pressure group (-4.7 versus -6.7 mL/min, P < .05). Consequently, the decline in C-cr was less in the low blood pressure group (-14.2 versus -17.8 mL/min, P < .05). There was no significant difference in UcrV between the blood pressure groups (-192 versus -205 mg/day). Hence, the decline in 1/P-cr paralleled the decline in C-cr; it was less in the low blood pressure group (-0.091 versus -0.122 dL/mg, P < .05). In Studies A and B, correlations of rates of decline in C-cr and GFR were 0.64 and 0.79, respectively (P < 0.001). Correlations of rates of decline in 1/P-cr and GFR were 0.79 and 0.85, respectively (P < 0.001). In Studies A and B combined, baseline GFR, C-TScr, and UcrV correlated significantly with protein intake (r = 0.45, 0.47, and 0.36, respectively; Pt intake (r = 0.45, 0.47, and 0.36, respectively; P < 0.001), but not with blood pressure. Baseline C-TScr was significantly lower in patients with polycystic kidney disease and tubulointerstitial diseases or urinary tract diseases, compared with glomerular and other diseases (P < 0.05). It was also lower in patients who were taking calcium channel blockers, compared with patients not taking these agents, and in patients not taking diuretics, compared with patients taking diuretics (P < 0.05). These results show that creatinine secretion and excretion are affected by protein intake. Creatinine secretion is also affected by antihypertensive therapy and renal diagnosis. In the MDRD Study, the low-protein diet reduced creatinine secretion and excretion, and the low blood pressure goal slowed the decline in creatinine secretion. These effects caused differences between the diet groups and between the blood pressure groups in C-cr and 1/P-cr that were not the result of differences in GFR. Studies assessing the effects of these interventions on the progression of renal disease should measure GFR in addition to C-cr and P-cr. C1 NIDDKD,NIH,BETHESDA,MD 20892. NR 36 TC 58 Z9 60 U1 0 U2 2 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 1996 VL 7 IS 4 BP 556 EP 566 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA UF243 UT WOS:A1996UF24300005 ER PT J AU DeBellis, MD Burke, L Trickett, PK Putnam, FW AF DeBellis, MD Burke, L Trickett, PK Putnam, FW TI Antinuclear antibodies and thyroid function in sexually abused girls SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE antinuclear antibodies; thyroid function; childhood sexual abuse; psychoneuroimmunology ID STRESS-DISORDER; AUTOANTIBODIES AB Sexually abused girls manifest dysregulation of physiological stress response systems. In this exploratory investigation, 14 sexually abused and 13 control girls, ages 8-15 years, recruited from a prospective, longitudinal study, underwent plasma antinuclear antibody and thyroid function tests. Thyroid function tests and plasma antinuclear antibody titers did not differ between sexually abused and control girls. However a significantly higher incidence of plasma antinuclear antibody titers was seen in abused subjects when compared with the frequency of positive antinuclear antibody titers in a sample of 22 adult healthy female volunteers, ages 20-58 years. These findings suggest that sexually abused girls may show evidence of an alteration in normal immune homeostatic function. C1 NCI,BIOCHEM LAB,NIH,BETHESDA,MD 20892. UNIV SO CALIF,DEPT PSYCHOL,LOS ANGELES,CA 90089. NIMH,LAB DEV PSYCHOL,NIH,BETHESDA,MD 20892. RP DeBellis, MD (reprint author), UNIV PITTSBURGH,WESTERN PSYCHIAT INST & CLIN,DEPT CHILD & ADOLESCENT PSYCHIAT,3811 OHARA ST,PITTSBURGH,PA 15213, USA. RI Burke, Lillian/A-7334-2008 FU NIMH NIH HHS [5 T32 MH18951] NR 24 TC 26 Z9 26 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 1996 VL 9 IS 2 BP 369 EP 378 DI 10.1002/jts.2490090218 PG 10 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA UG493 UT WOS:A1996UG49300017 PM 8731555 ER PT J AU Newbound, GC Andrews, JM ORourke, J Brady, JN Lairmore, MD AF Newbound, GC Andrews, JM ORourke, J Brady, JN Lairmore, MD TI Human T-cell lymphotropic virus type 1 tax mediates enhanced transcription in CD4(+) T lymphocytes SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; HUMAN-IMMUNODEFICIENCY-VIRUS; LEUKEMIA-VIRUS; HTLV-I; DNA-SYNTHESIS; 3' END; ACTIVATION; INFECTION; BINDING; GENE AB Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia/lymphoma and is associated with a variety of immunoregulatory disorders. HTLV-1 has been shown to bind to and infect a variety of hematopoietic and nonhematopoietic cells. However, both in vivo and in vitro, the provirus is mostly detected in and preferentially transforms CD4(+) T cells. The molecular mechanism that determines the CD4(+) T-cell tropism of HTLV-1 has not been determined. Using cocultures of purified CD4(+) and CD8(+) T cells with an HTLV-1-producing cell line, we measured viral transcription by using Northern (RNA) blot analysis, protein production by using a p24 antigen capture assay and how cytometric analysis for viral envelope, and proviral integration by using DNA slot blot analysis. We further measured HTLV-1 long terminal repeat-directed transcription in purified CD4(+) and CD8(+) T cells by using transient transfection assays and in vitro transcription. We demonstrate a higher rate of viral transcription in primary CD4(+) T cells than in CD8(+) T cells. HTLV-1 protein production was 5- to 25-fold greater in CD4(+) cocultures and mRNA levels were 5-fold greater in these cultures than in the CD8(+) cocultures. Transient transfection and in vitro transcription indicated a modest increase in basal transcription in CD4(+) T cells, whereas there was a 20-fold increase in reporter gene activity in CD4(+) T cells cotransfected with tax. These data suggest that unique or activated transcription factors, particularly Tax-responsive factors in CD4(+) T cells, recognize regulatory sequences within the HTLV-1 long terminal repeat, and this mediates the observed enhanced viral transcription and ultimately the cell tropism and leukemogenic potential of the virus. C1 OHIO STATE UNIV,DEPT VET BIOSCI,COLUMBUS,OH 43210. OHIO STATE UNIV,CTR RETROVIRUS RES,COLUMBUS,OH 43210. OHIO STATE UNIV,ARTHUR JAMES CANC HOSP & RES INST,CTR COMPREHENS CANC,COLUMBUS,OH 43210. NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. FU NCI NIH HHS [CA55185]; NIAID NIH HHS [K11 AI01190-02] NR 55 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1996 VL 70 IS 4 BP 2101 EP 2106 PG 6 WC Virology SC Virology GA UA397 UT WOS:A1996UA39700004 PM 8642630 ER PT J AU Flory, E Hoffmeyer, A Smola, U Rapp, UR Bruder, JT AF Flory, E Hoffmeyer, A Smola, U Rapp, UR Bruder, JT TI Raf-1 kinase targets GA-binding protein in transcriptional regulation of the human immunodeficiency virus type 1 promoter SO JOURNAL OF VIROLOGY LA English DT Article ID SERUM RESPONSE ELEMENT; LONG TERMINAL REPEAT; KAPPA-B SITE; GENE-EXPRESSION; DNA-BINDING; REQUIRES RAF-1; FACTOR EF-1A; C-FOS; ACTIVATION; ENHANCER AB The serine/threonine protein kinase Raf-1 is a component of a conserved intracellular signaling cascade that controls responses to various extracellular stimuli. Transcription from several promoters, including the oncogene-responsive element in the polyomavirus enhancer, the c-fos promoter, as well as other AP-1- and Ets-dependent promoters, can be induced by Raf-1 kinase. Previously, we have shown that activated Raf-1 kinase transactivates the human immunodeficiency virus type 1 (HIV-1) long terminal repeat and have identified the NF-kappa B binding motif as a Raf-1-responsive element (RafRE). We now report that Raf-1 kinase-induced transactivation from the HIV RafRE involves the purine-rich-repeat-binding protein (GABP), which is composed of two distinct subunits (alpha and beta). GABP alpha is an Ets oncogene-related DNA-binding protein, and GABP beta contains four ankyrin-like repeats that have been shown to be essential in protein-protein interactions. In electrophoretic mobility shift assays using nuclear extracts from human Jurkat T cells, a protein-DNA complex which was supershifted with antiserum against GABP alpha and GABP beta was observed. Purified recombinant GABP alpha and beta interact with the HIV RafRE as judged from DNA binding assays. Cotransfection experiments with GABP alpha and beta and Raf-1 kinase demonstrate synergistic transactivation of the HIV-1 promoter. Point mutations in the HIV RafRE abolished the Raf-1 kinase- as well as GABP alpha- and beta-induced transactivation. The observed Raf-1-GABP synergism presumably involves phosphorylation of GABP subunits, as treatment of cells with Raf-1 kinase activators serum and 12-O-tetradecanoylphorbol-13-acetate increases phosphorylation of GABP in vivo. However, GABP is not a target of Raf-1 kinase, instead, it is a substrate of mitogen-activated protein kinase (MAPK/ERK), since in vitro phosphorylation of GABP alpha and beta was achieved by the reconstituted protein kinase cascade but not with purified Raf-1 or MEK. These results suggest that Raf-1 kinase-induced activation of the HIV-1 promoter is mediated by the classical cytoplasmic cascade resulting in MAPK/ERK-mediated phosphorylation of GABP alpha and beta. Because the HIV RafRE corresponds to a region within the promoter which is essential for regulation of HIV-1 expression, the data indicate that in addition to NF-kappa B, GABP transcription factors are important for induced expression of HIV. C1 UNIV WURZBURG,INST RADIOBIOL & CELL RES,D-97078 WURZBURG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N0I-CO-74102] NR 52 TC 74 Z9 74 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1996 VL 70 IS 4 BP 2260 EP 2268 PG 9 WC Virology SC Virology GA UA397 UT WOS:A1996UA39700025 PM 8642652 ER PT J AU Weitzman, MD Kyostio, SRM Carter, BJ Owens, RA AF Weitzman, MD Kyostio, SRM Carter, BJ Owens, RA TI Interaction of wild-type and mutant adeno-associated virus (AAV) Rep proteins on AAV hairpin DNA SO JOURNAL OF VIROLOGY LA English DT Article ID LARGE-T-ANTIGEN; DOMINANT-NEGATIVE MUTANT; ESCHERICHIA-COLI; REPLICATION INVITRO; HUMAN-CELLS; BINDING; ORIGIN; IDENTIFICATION; GENE; HELICASE AB Both the Rep68 and Rep78 proteins of adeno-associated virus type 2 (AAV) bind to AAV terminal repeat hairpin DNA and can mediate site-specific nicking in vitro at the terminal resolution site (trs) within the terminal repeats. To define the regions of the Rep proteins required for these functions, a series of truncated Rep78 derivatives was created. Wild-type and mutant proteins were synthesized by in vitro translation and analyzed for AAV hairpin DNA binding, trs endonuclease activity, and interaction on hairpin DNA. Amino-terminal deletion mutants which lacked the first 29 or 79 amino acid residues of Rep78 did not bind hairpin DNA, which is consistent with our previous identification of a DNA-binding domain in this region. Progressive truncation of the carboxyl-terminal region of Rep78 di not eliminate hairpin DNA binding until the deletion reached amino acid 443. The electrophoretic mobility of the Rep-specific protein-DNA complexes ws inversely related to the molecular weight of the Rep derivative. Analysis of the C-terminal deletion mutants by the trs endonuclease assay identified a region (amino acids 467 to 476) that is essential for nicking but is not necessary for DNA binding. When endonuclease-positive, truncated Rep proteins that bound hairpin DNA were mixed with full-length Rep78 or Rep68 protein in electrophoretic mobility shift assays, a smear of protein-DNA complexes was observed. This smear migrated at an intermediate position with respect to the bands generated by the proteins individually. An antibody recognizing only the full-length protein produced a novel supershift band when included in a mixed binding assay containing Rep68 and a truncated Rep mutant. These experiments suggest that the Rep proteins can form hetero-oligomers on the AAV hairpin DNA. C1 NIDDK,NIH,MOL & CELLULAR BIOL LAB,BETHESDA,MD 20892. NR 56 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1996 VL 70 IS 4 BP 2440 EP 2448 PG 9 WC Virology SC Virology GA UA397 UT WOS:A1996UA39700045 PM 8642672 ER PT J AU Lindholm, PF Tamami, M Makowski, J Brady, JN AF Lindholm, PF Tamami, M Makowski, J Brady, JN TI Human T-cell lymphotropic virus type 1 Tax(1) activation of NF-kappa B: Involvement of the protein kinase C pathway SO JOURNAL OF VIROLOGY LA English DT Article ID LONG TERMINAL REPEAT; HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; LEUKEMIA-VIRUS; HTLV-I; GENE-EXPRESSION; INTERLEUKIN-2 RECEPTOR; TRANSCRIPTION FACTOR; SIGNAL TRANSDUCTION; RESPONSIVE ELEMENT AB Human T-cell lymphotropic virus type 1 Tax(1) induces the activation and nuclear localization of the cellular transcription factor, NF-kappa B. Treatment of cells with calphostin C, a protein kinase C (PKC) inhibitor, blocked induction of NF-kappa B DNA binding activity in human T-cell lymphotropic virus type 1-transformed C81 cells and Tax(1)-stimulated murine pre-B cells, suggesting that PKC was an important intermediate in the NF-kappa B induction pathway. We further demonstrate that Tax(1) associates with, and activates, PKC. PKC was coimmunoprecipitated with anti-Tax(1) sera from Tax(1)-expressing MT4 extracts and Jurkat extracts in the presence of exogenous Tax(1) protein. In addition, the glutathione-S-transferase-Tax(1) protein bound specifically to the alpha, delta, and eta PKC isoenzymes synthesized in rabbit reticulocyte lysates. The addition of Tax(1) to in vitro kinase reaction mixtures leads to the phosphorylation of Tax(1) and an 18-fold increase in the autophosphorylation of PKC. Transfection of Jurkat cells with wild-type Tax(1) stimulated membrane translocation of PKC. In contrast, Tax(1) mutant M22, which fails to stimulate NF-kappa B-dependent transcription, failed to stimulate membrane translocation of PKC. Tax(1) did not directly increase PKC phosphorylation of I kappa B alpha. Our results are consistent with a model in which Tax(1) interacts with PKC and stimulates membrane translocation and triggering of the PKC pathway. Subsequent steps in the PKC cascade likely stimulate phosphorylation of I kappa B alpha. C1 NCI,MOLEC VIROL LAB,BETHESDA,MD 20892. NR 82 TC 33 Z9 33 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1996 VL 70 IS 4 BP 2525 EP 2532 PG 8 WC Virology SC Virology GA UA397 UT WOS:A1996UA39700056 PM 8642682 ER PT J AU Gorelick, RJ Chabot, DJ Ott, DE Gagliardi, TD Rein, A Henderson, LE Arthur, LO AF Gorelick, RJ Chabot, DJ Ott, DE Gagliardi, TD Rein, A Henderson, LE Arthur, LO TI Genetic analysis of the zinc finger in the Moloney murine leukemia virus nucleocapsid domain: Replacement of zinc-coordinating residues with other zinc-coordinating residues yields noninfectious particles containing genomic RNA SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN; RETROVIRUSES; MUTATIONS; SEQUENCES; TYPE-1; INFECTIVITY; MOUSE; CELLS; ASSAY; HIV-1 AB The effect of changing zinc (Zn2+)-coordinating residues in the nucleocapsid protein of Moloney murine leukemia virus was investigated by introducing a His-34-to-Cys or Cys-39-to-His mutation into the putative Zn2+ finger. Mutant virions contained normal levels of properly processed Gag and Env proteins and wild-type levels of full-length viral RNA. However, the specific infectivity of the mutants was similar to 4 x 10(-4) that of wild-type particles. They were probably noninfectious because of the inability of the particles to synthesize cDNA transcripts, since full-length viral DNA could not be detected in Hirt supernatants of NIH 3T3 cells infected with the CCCC or CCHH virus. These mutants will provide an extremely valuable tool for analysis of the role of retroviral Zn2+ fingers in infection processes, independent of viral RNA recognition and packaging. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,LAB MOLEC VIROL & CARCINOGENESIS,FREDERICK,MD 21702. RP Gorelick, RJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,AIDS VACCINE PROGRAM,SAIC FREDERICK,FREDERICK,MD 21702, USA. FU NCI NIH HHS [N01-CA-56000] NR 37 TC 89 Z9 89 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1996 VL 70 IS 4 BP 2593 EP 2597 PG 5 WC Virology SC Virology GA UA397 UT WOS:A1996UA39700065 PM 8642691 ER PT J AU Gazit, A Mashiah, P Kalinski, H Gast, A RosinAbersfeld, R Tronick, SR Yaniv, A AF Gazit, A Mashiah, P Kalinski, H Gast, A RosinAbersfeld, R Tronick, SR Yaniv, A TI Two species of Rev proteins, with distinct N termini, are expressed by caprine arthritis encephalitis virus SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS; VISNA VIRUS; SUBCELLULAR-LOCALIZATION; IDENTIFICATION; TRANSLATION; TRANSCRIPTS; INITIATION; CAEV AB Several cDNA clones representing alternatively spliced Rev-specific transcripts were isolated from a cDNA library prepared from Himalayan tahr cells infected with caprine arthritis encephalitis virus (CAEV). We previously characterized two rev-like cDNA species, d1 and d2, and a tat e1 cDNA containing the rev coding sequence downstream to the tat. In these cDNAs, the rev coding domain derives its amino terminus from the N terminus of env, which is spliced the 3' open reading frame encoding the putative Rev protein. In this study, we report the genetic structure of a fourth rev-like cDNA (designated g1), which lacks the 5' env-derived sequences. All of these rev transcripts, including cDNA g1, increased the level of chloramphenicol acetyltransferase expression when cotransfected with a reporter plasmid containing the CAEV Rev-responsive element-spanning region downstream of the cat coding sequences. Western blot (immunoblot) analysis showed that each transfected cDNA species gave rise to a 16-kDa protein lacking env-encoded amino-terminal epitopes. In contrast, CAEV-infected Himalayan tahr cells expressed only a 20-kDa protein, whose N terminus, in contrast, is derived from the env. Moreover only the 20-kDa protein was also detected in the mature CAEV virions. These observations suggest that the transcripts d1, d2, and e1 can potentially, in appropriate cellular contest, encode two Rev isoforms differing in their N termini, whereas the g1 transcript encodes only the 16-kDa species. Elucidation of the significance of the 16-kDa Rev protein in CAEV biology must await further studies. C1 TEL AVIV UNIV,SACKLER SCH MED,DEPT HUMAN MICROBIOL,IL-69978 TEL AVIV,ISRAEL. NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. NR 27 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1996 VL 70 IS 4 BP 2674 EP 2677 PG 4 WC Virology SC Virology GA UA397 UT WOS:A1996UA39700080 PM 8642706 ER PT J AU Nash, EA Ludlow, CL AF Nash, EA Ludlow, CL TI Laryngeal muscle activity during speech breaks in adductor spasmodic dysphonia SO LARYNGOSCOPE LA English DT Article ID BOTULINUM TOXIN INJECTION; SPASTIC DYSPHONIA; DYSTONIA AB To determine the laryngeal muscle activation abnormalities that are associated with speech symptoms in adductor spasmodic dysphonia (ADSD), electromyographic measures of extrinsic and intrinsic laryngeal muscles during speech compared 1) muscle activity when ADSD patients had breaks in words with when they produced the same words without breaks; and 2) muscle activity in ADSD patients during speech without voice breaks with normal controls producing phonetically similar words. Simultaneous electromyographic recordings were made from the thyroarytenoid (TA), cricothyroid (CT), sternothyroid (ST), thyrohyoid (TH) and the posterior cricoarytenoid (PCA) muscles during speech testing in 11 ADSD patients and 10 control subjects. Speech breaks were identified and mean muscle activity measured starting 100 ms preceding a voice break and for the remainder of the word. Mean muscle activity level was significantly greater on break than non break words in ADSD patients only for the thyroarytenoid muscle (p<.001). No significant differences were found between the ADSD and control subjects during non break words for any of the laryngeal muscles studied. The results demonstrated that 1) only the thyroarytenoid, of the muscles tested, was affected in ADSD, 2) that muscle activation abnormalities were spasmodic, only appearing when symptoms occurred and 3) no imbalances of muscle tone were evident when speech disruptions did not appear. C1 NIDOCD,VOICE & SPEECH SECT,BETHESDA,MD. OI Ludlow, Christy/0000-0002-2015-6171 NR 23 TC 42 Z9 44 U1 1 U2 2 PU LARYNGOSCOPE CO PI ST LOUIS PA 10 S BROADWAY 14TH FLOOR, ST LOUIS, MO 63102-1741 SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 1996 VL 106 IS 4 BP 484 EP 489 DI 10.1097/00005537-199604000-00017 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA UM980 UT WOS:A1996UM98000032 PM 8614226 ER PT J AU Thorgeirsson, UP Gomez, DE Lindsay, CK Sinha, CC Adamson, RH AF Thorgeirsson, UP Gomez, DE Lindsay, CK Sinha, CC Adamson, RH TI Liver tumors and possible preneoplastic lesions, induced by a food-derived heterocyclic amine in cynomolgus monkeys; A study of histology and cytokeratin expression SO LIVER LA English DT Article DE carcinoma; cytokeratins; heterocyclic amines; histology; liver; monkey ID RAT-LIVER; METABOLIC-ACTIVATION; N-NITROSOMORPHOLINE; BROILED SARDINE; CELL DYSPLASIA; BEEF EXTRACT; HEPATOCARCINOGENESIS; CARCINOGENICITY; 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE; HEPATOCYTES AB A food-derived mutagenic heterocyclic aromatic amine, 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), is a potent hepatocarcinogen in cynomolgus monkeys. In an ongoing carcinogenesis study, 34 out of 40 monkeys dosed with IQ have developed malignant liver tumors. The histology and cytokeratin expression was examined in a total of 94 tumors and non-neoplastic lesions obtained from 34 cases. The majority of the tumors were classified as hepatocellular carcinoma. In some cases, a striking difference in the histological features between individual tumor nodules was suggestive of a multicentric origin. Intrahepatic vascular invasion was seen in 14 (41.2%) and metastases in 6 (17.6%) of the hepatocellular carcinoma cases. There was no evidence of regenerative hyperplasia or fibrosis in the parenchyma of the tumor-bearing livers. Clear-cell foci composed of glycogen-rich hepatocytes were the only macroscopic lesions detected prior to gross tumor development. Other liver lesions included dysplastic hepatocyte foci and areas of proliferating bile ductular like (oval) cells, located around the periportal areas and along the portal tracts. Expression of bile duct type cytokeratin 7 was observed in a few of the oval cells and non-malignant hepatocytes, as well as in some of the hepatocellular carcinoma nodules. This aberrant cytokeratin expression raises questions concerning the histogenesis of the IQ-induced hepatocellular carcinoma. RP Thorgeirsson, UP (reprint author), NCI, TUMOR BIOL & CARCINOGENESIS SECT,OFF DIRECTOR, DIV CANC ETIOL,NIH,BLDG 37, ROOM 2D02, BETHESDA, MD 20892 USA. OI Gomez, Daniel E/0000-0002-8629-0787 FU NCI NIH HHS [N01-CP-51013] NR 41 TC 11 Z9 11 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0106-9543 J9 LIVER JI Liver PD APR PY 1996 VL 16 IS 2 BP 71 EP 83 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA UG568 UT WOS:A1996UG56800001 PM 8740838 ER PT J AU Mariano, TM Muthukumaran, G Donnelly, RJ Wang, N Adamson, MC Pestka, S Kozak, CA AF Mariano, TM Muthukumaran, G Donnelly, RJ Wang, N Adamson, MC Pestka, S Kozak, CA TI Genetic mapping of the gene for the mouse interferon-gamma receptor signaling subunit to the distal end of Chromosome 16 SO MAMMALIAN GENOME LA English DT Article C1 NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT MOLEC GENET & MICROBIOL,PISCATAWAY,NJ 08854. FU NCI NIH HHS [CA46465] NR 11 TC 4 Z9 4 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1996 VL 7 IS 4 BP 321 EP 322 DI 10.1007/s003359900093 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UH896 UT WOS:A1996UH89600017 PM 8661709 ER PT J AU Lyu, MS Kozak, CA Chin, H AF Lyu, MS Kozak, CA Chin, H TI Genetic mapping of the gene encoding the alpha1 subunit of neuronal calcium channels SO MAMMALIAN GENOME LA English DT Article ID MOUSE; MAPS C1 NINCDS,NEUROCHEM LAB,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 11 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0938-8990 J9 MAMM GENOME JI Mamm. Genome PD APR PY 1996 VL 7 IS 4 BP 326 EP 327 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA UH896 UT WOS:A1996UH89600024 PM 8661716 ER PT J AU Johnson, ES Griswold, CM AF Johnson, ES Griswold, CM TI Oncogenic retroviruses of cattle, chickens and turkeys: Potential infectivity and oncogenicity for humans SO MEDICAL HYPOTHESES LA English DT Article ID MEAT INDUSTRY; LUNG-CANCER; MORTALITY; BUTCHERS; VIRUS AB Reticuloendotheliosis virus naturally infects and cause lymphoid leukosis in chickens and turkeys. We investigated whether it can infect/transfect a variety of human cells in vitro. Successful infection and transfection were achieved with limited replication of virus. These findings, together with the knowledge that other oncogenic retroviruses of chickens and cattle, viz. The avian leukosis/sarcoma viruses and bovine leukemia virus show similar infectivity/oncogencity in vitro for humans, and the recent demonstration of antibodies to avian leukosis/sarcoma virus and reticuloendotheliosis virus in human sera, suggest that these viruses may have a role in the etiology of certain cancers in humans. There is now urgent need to investigate this, particularly because recent epidemiological studies consistently demonstrate excess of cancers in groups occupationally exposed to these viruses. C1 NIEHS,RES TRIANGLE PK,NC 27709. N CAROLINA STATE UNIV,DEPT GENET,RALEIGH,NC 27695. NR 19 TC 17 Z9 21 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD APR PY 1996 VL 46 IS 4 BP 354 EP 356 DI 10.1016/S0306-9877(96)90186-3 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UJ554 UT WOS:A1996UJ55400012 PM 8733164 ER PT J AU Rockey, DD Chesebro, BB Heinzen, RA Hackstadt, T AF Rockey, DD Chesebro, BB Heinzen, RA Hackstadt, T TI A 28 kDa major immunogen of Chlamydia psittaci shares identity with Mip proteins of Legionella spp and Chlamydia trachomatis - Cloning and characterization of the C-psittaci mip-like gene SO MICROBIOLOGY-UK LA English DT Article DE Chlamydia; Mip-like protein; chlamydial antigen; intracellular pathogen; intracellular survival ID OUTER-MEMBRANE PROTEIN; GUINEA-PIGS; GENITAL-INFECTION; INTRACELLULAR INFECTION; CYCLOSPORINE-A; DNA-SEQUENCE; PNEUMOPHILA; INITIATION; HYPERSENSITIVITY; CONJUNCTIVITIS AB Chlamydia psittaci strain guinea-pig inclusion conjunctivitis (GPIC) produces a self-limiting ocular infection of guinea-pigs, and this condition is a representative animal model of ocular chlamydial disease. Convalescent guinea-pigs, which are resistant to reinfection, produce antibodies to several elementary-body proteins, including an uncharacterized antigen of 28 kDa. Convalescent guinea-pig sera were used to identify, from a lambda expression library, two overlapping GPIC genomic clones that produced the 28 kDa antigenic protein, Nucleotide sequence analysis revealed that the gene coding for the 28 kDa protein was similar to the mip (macrophage infectivity potentiator) genes from Legionella pneumophila and Chlamydia trachomatis, The GPIC gene and its product were accordingly designated mip and Mip, respectively. Analysis of the regions flanking mip identified three tightly linked open reading frames coding for predicted products with sequence similarity to asparagine tRNA ligase (AspS), rRNA methylase (SpoU), and thioredoxin (TrxA), The arrangement of these genes in GPIC was aspS-mip-spoU-trxA, Sequence analysis of PCR products produced using genomic DNA from an ovine abortion strain of C. psittaci and from C. trachomatis strain LGV-434 demonstrated that the arrangement of mip, spoU and trxA is common among these chlamydiae. RP Rockey, DD (reprint author), NIAID,ROCKY MT LABS,INTRACELLULAR PARASITES LAB,HAMILTON,MT 59840, USA. NR 40 TC 20 Z9 22 U1 0 U2 0 PU SOC GENERAL MICROBIOLOGY PI READING PA HARVEST HOUSE 62 LONDON ROAD, READING, BERKS, ENGLAND RG1 5AS SN 1350-0872 J9 MICROBIOL-UK JI Microbiology-(UK) PD APR PY 1996 VL 142 BP 945 EP 953 PN 4 PG 9 WC Microbiology SC Microbiology GA UH163 UT WOS:A1996UH16300030 PM 8936321 ER PT J AU Henson, DE AF Henson, DE TI Is the meaning of science changing in the practice of medicine? SO MODERN PATHOLOGY LA English DT Editorial Material RP Henson, DE (reprint author), NCI,BETHESDA,MD 20892, USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD APR PY 1996 VL 9 IS 4 BP 353 EP 354 PG 2 WC Pathology SC Pathology GA UE851 UT WOS:A1996UE85100001 PM 8729970 ER PT J AU Kimura, T Sakamoto, H Appella, E Siraganian, RP AF Kimura, T Sakamoto, H Appella, E Siraganian, RP TI Conformational changes induced in the protein tyrosine kinase p72(syk) by tyrosine phosphorylation or by binding of phosphorylated immunoreceptor tyrosine-based activation motif peptides SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; GROWTH-FACTOR RECEPTOR; BASOPHILIC LEUKEMIA-CELLS; AFFINITY IGE RECEPTOR; T-CELL; SIGNAL-TRANSDUCTION; ZETA-CHAIN; SH2 DOMAINS; MONOCLONAL-ANTIBODIES; HISTAMINE-RELEASE AB A critical event in signaling in immune cells is the interaction of Syk or ZAP-70 protein tyrosine kinases with multisubunit receptors that contain an similar to 18-amino-acid domain called the immunoreceptor tyrosine-based activation motif (ITAM), Tyrosine-phosphorylated Syk from activated cells was in a conformation different from that in nonstimulated cells as demonstrated by changes in immunoreactivity, The addition of tyrosine-diphosphorylated ITAM peptides resulted in a similar conformational change in Syk from nonactivated cells. The peptides based on Fc epsilon RI gamma were more active than those based on Fc epsilon RI beta, In vitro autophosphorylation of Syk was dramatically enhanced by the addition of the diphosphorylated ITAM peptides, The conformational change and the enhanced autophosphorylation required the presence of both phosphorylated tyrosines on the same molecule. These conformational changes in Syk by tyrosine phosphorylation or binding to diphosphorylated ITAM could be critical for Syk activation and downstream propagation of intracellular signals. C1 NIDR,IMMUNOL LAB,NIH,BETHESDA,MD 20892. NCI,CELL BIOL LAB,BETHESDA,MD 20892. RI Sakamoto, Hiroshi/A-3181-2011 NR 59 TC 99 Z9 99 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1996 VL 16 IS 4 BP 1471 EP 1478 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UB562 UT WOS:A1996UB56200020 PM 8657120 ER PT J AU Hatton, KS Mahon, K Chin, L Chiu, FC Lee, HW Peng, DM Morgenbesser, SD Horner, J DePinho, RA AF Hatton, KS Mahon, K Chin, L Chiu, FC Lee, HW Peng, DM Morgenbesser, SD Horner, J DePinho, RA TI Expression and activity of L-Myc in normal mouse development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AVIAN MYELOCYTOMATOSIS VIRUS; PUTATIVE TRANSFORMING GENE; HUMAN N-MYC; C-MYC; DNA-BINDING; NEOPLASTIC TRANSFORMATION; MAMMALIAN NEUROFILAMENTS; DIFFERENTIAL EXPRESSION; EMBRYONIC LETHALITY; TARGETED DISRUPTION AB To determine the role of L-Myc in normal mammalian development and its functional relationship to other members of the Myc family, we determined the normal patterns of L-myc gene expression in the developing mouse by RNA in situ hybridization and assessed the phenotypic impact of L-Myc deficiency produced through standard gene targeting methodology, L-myc transcripts were detected in the developing kidney and lung as well as in both the proliferative and the differentiative zones of the brain and neural tube, Despite significant expression of L-myc in developing mouse tissues, homozygous null L-myc mice were found to be viable, reproductively competent, and represented in expected frequencies from heterozygous matings, A detailed histological survey of embryonic and adult tissues, characterization of an embryonic neuronal marker, and measurement of cellular proliferation in situ did not reveal any congenital abnormalities. The lack of an apparent phenotype associated with L-Myc deficiency indicates that L-Myc is dispensable for gross morphological development and argues against a unique role for L-Myc in early central nervous system development as had been previously suggested, Although overlapping expression patterns among myc family members raise the possibility of complementation of L-Myc deficiency by other Myc oncoproteins, compensatory changes in the levels of c- and/or N-myc transcripts were not detected in homozygous null L-myc mice. C1 YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MED,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DIV DERMATOL,BRONX,NY 10461. YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT NEUROL,BRONX,NY 10461. TEMPLE UNIV,SCH MED,DEPT BIOCHEM,PHILADELPHIA,PA 19140. TEMPLE UNIV,SCH MED,FELS INST CANC RES & MOLEC BIOL,PHILADELPHIA,PA 19140. NICHHD,LAB MAMMALIAN GENES & DEV,BETHESDA,MD 20892. FU NCI NIH HHS [2P30CA13330, CA09173]; NINDS NIH HHS [NS23840] NR 76 TC 57 Z9 60 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1996 VL 16 IS 4 BP 1794 EP 1804 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UB562 UT WOS:A1996UB56200055 PM 8657155 ER PT J AU Sithanandam, G Latif, F Duh, FM Bernal, R Smola, U Li, H Kuzmin, I Wixler, V Geil, L Shrestha, S Lloyd, PA Bader, S Sekido, Y Tartof, KD Kashuba, VI Zabarovsky, ER Dean, M Klein, G Lerman, MI Minna, JD Rapp, UR Allikmets, R AF Sithanandam, G Latif, F Duh, FM Bernal, R Smola, U Li, H Kuzmin, I Wixler, V Geil, L Shrestha, S Lloyd, PA Bader, S Sekido, Y Tartof, KD Kashuba, VI Zabarovsky, ER Dean, M Klein, G Lerman, MI Minna, JD Rapp, UR Allikmets, R TI 3pK, a new mitogen-activated protein kinase-activated protein kinase located in the small cell lung cancer tumor suppressor gene region (vol 16, pg 868, 1996) SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Correction, Addition C1 NCI,FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,PRI DYNCORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,IMMUNOBIOL LAB,FREDERICK,MD 21702. UNIV TEXAS,SW MED CTR,HAMON CTR THERAPEUT ONCOL RES,DALLAS,TX 75235. FOX CHASE CANC CTR,PHILADELPHIA,PA 19111. KAROLINSKA INST,CTR MICROBIOL & TUMOR BIOL,STOCKHOLM,SWEDEN. NR 1 TC 0 Z9 0 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 1996 VL 16 IS 4 BP 1880 EP 1880 PG 1 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UB562 UT WOS:A1996UB56200064 ER PT J AU Cole, NB Sciaky, N Marotta, A Song, J LippincottSchwartz, J AF Cole, NB Sciaky, N Marotta, A Song, J LippincottSchwartz, J TI Golgi dispersal during microtubule disruption: Regeneration of Golgi stacks at peripheral endoplasmic reticulum exit sites SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID MEMBRANE-PROTEINS; BREFELDIN-A; HELA-CELLS; RECYCLING PATHWAY; EPITHELIAL-CELLS; PLASMA-MEMBRANE; APPARATUS; TRANSPORT; COLCHICINE; COMPLEX AB Microtubule disruption has dramatic effects on the normal centrosomal localization of the Golgi complex, with Golgi elements remaining as competent functional units but undergoing a reversible ''fragmentation'' and dispersal throughout the cytoplasm. In this study we have analyzed this process using digital fluorescence image processing microscopy combined with biochemical and ultrastructural approaches. After microtubule depolymerization, Golgi membrane components were found to redistribute to a distinct number of peripheral sites that were not randomly distributed, but corresponded to sites of protein exit from the ER. Whereas Golgi enzymes redistributed gradually over several hours to these peripheral sites, ERGIC-53 (a protein which constitutively cycles between the ER and Golgi) redistributed rapidly (within 15 minutes) to these sites after first moving through the ER. Prior to this redistribution, Golgi enzyme processing of proteins exported from the ER was inhibited and only returned to normal levels after Golgi enzymes redistributed to peripheral ER exit sites where Golgi stacks were regenerated. Experiments examining the effects of microtubule disruption on the membrane pathways connecting the ER and Golgi suggested their potential role in the dispersal process. Whereas clustering of peripheral pre-Golgi elements into the centrosomal region failed to occur after microtubule disruption, Golgi-to-ER membrane recycling was only slightly inhibited. Moreover, conditions that impeded Golgi-to-ER recycling completely blocked Golgi fragmentation. Based on these findings we propose that a slow but constitutive flux of Golgi resident proteins through the same ER/Golgi cycling pathways as ERGIC-53 underlies Golgi dispersal upon microtubule depolymerization. Both ERGIC-53 and Golgi proteins would accumulate at peripheral ER exit sites due to failure of membranes at these sites to cluster into the centrosomal region. Regeneration of Golgi stacks at these peripheral sites would re-establish secretory flow from the ER into the Golgi complex and result in Golgi dispersal. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NR 61 TC 342 Z9 351 U1 1 U2 8 PU AMER SOC CELL BIOL PI BETHESDA PA PUBL OFFICE 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 1996 VL 7 IS 4 BP 631 EP 650 PG 20 WC Cell Biology SC Cell Biology GA UE440 UT WOS:A1996UE44000011 PM 8730104 ER PT J AU Puro, DG Hwang, JJ Kwon, OJ Chin, HM AF Puro, DG Hwang, JJ Kwon, OJ Chin, HM TI Characterization of an L-type calcium channel expressed by human retinal Muller (glial) cells SO MOLECULAR BRAIN RESEARCH LA English DT Article DE calcium channel subunits; retina; glia; potassium homeostasis; conotoxin; potassium currents ID VOLTAGE-DEPENDENT CALCIUM; BETA-SUBUNIT; FUNCTIONAL EXPRESSION; SKELETAL-MUSCLE; ALPHA-1 SUBUNIT; BRAIN; ALPHA-2-SUBUNIT; ALPHA-1-SUBUNIT; CLONING; GENE AB The traditional notion that glial cells are permeable only to potassium has been revised. For example, glia from various parts of the nervous system have calcium-permeable ion channels. Since characterization of the calcium channels in glia is limited, the purpose of this study was to determine the molecular identity and examine the functional properties of a voltage-gated calcium channel expressed by Muller cells, the predominant glia of the retina. Whole-cell and perforated-patch recordings of human Muller cells in culture revealed a high threshold voltage-activated calcium current that is blocked by dihydropyridines, but not by omega-conotoxin GVIA or omega-conotoxin MWC. RT-PCR of cultured human Muller cells using primers specific for the calcium channel subunits demonstrated the expression of an L-type channel composed of the alpha(1)D, alpha(2) and beta(3) subunits. The alpha(2) subunit of the Muller cell calcium channel is a splice variant which is distinct from either the skeletal muscle alpha(2)s or the brain alpha(2)b. Our electrophysiological experiments indicate that the alpha(1)D/alpha(2)/beta(3) calcium channel is functionally linked with the activation of a potassium channel that may serve as one of the pathways for the redistribution by Muller cells of excess retinal potassium. C1 NINCDS,NIH,NEUROCHEM LAB,BETHESDA,MD 20892. RP Puro, DG (reprint author), UNIV MICHIGAN,WK KELLOGG EYE CTR,DEPT OPHTHALMOL & PHYSIOL,1000 WALL ST,ANN ARBOR,MI 48105, USA. NR 32 TC 42 Z9 42 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 APR PY 1996 VL 37 IS 1-2 BP 41 EP 48 DI 10.1016/0169-328X(96)80478-5 PG 8 WC Neurosciences SC Neurosciences & Neurology GA UL348 UT WOS:A1996UL34800005 ER PT J AU Johren, O Inagami, T Saavedra, JM AF Johren, O Inagami, T Saavedra, JM TI Localization of AT(2) angiotensin II receptor gene expression in rat brain by in situ hybridization histochemistry SO MOLECULAR BRAIN RESEARCH LA English DT Article DE angiotensin II; receptor subtypes; brain development; [I-125]Sar(1)-ANG II binding ID SUBTYPES; BINDING; HETEROGENEITY; SENSITIVITY; CLONING; NUCLEUS; AT2 AB To localize the gene expression of AT(2) angiotensin II receptors in rat brain we performed in situ hybridization histochemistry using S-35-labeled antisense riboprobes. The AT(2) receptor mRNA expression pattern was compared in consecutive brain sections, from 2 week old rats, with the receptor expression by means of [I-125]Sar(1)-ANG II binding and displacement with AT(2) selective ligands followed by autoradiography. Expression of AT(2) receptor mRNA was found in several thalamic nuclei (ventral posterolateral, mediodorsal, central medial, paracentral, and paraventricular), the medial geniculate nuclei, the nucleus of the optic tract, the subthalamic nucleus, the interposed nucleus of the cerebellum, and in the inferior olive. In these areas the AT(2) receptor gene expression corresponds well with [I-125]Sar(1)-ANG II binding. In addition, AT(2) receptor mRNA expression was found in the red nucleus where no [I-125]Sar(1)-ANG II binding was present. No significant hybridization of the AT(2) receptor antisense probe was found in septal nuclei, the locus coeruleus, the dorsolateral geniculate nucleus, or the cerebellar cortex, areas rich in [I-125]Sar(1)-ANG II binding. Our results indicate that some brain regions may be involved in AT(2) receptor formation, transporting the receptor protein to other brain areas. However, in most structures, both the formation and expression of receptors occur, suggesting the existence of local AT(2) receptor circuits, or that of AT(2) autoreceptors. Other structures express only the receptor protein, indicating that these AT(2) receptors are produced elsewhere. Our present data are the basis for further studies on the clarification of AT(2) receptor pathways in the brain. C1 VANDERBILT UNIV,SCH MED,DEPT BIOCHEM,NASHVILLE,TN 37232. RP Johren, O (reprint author), NIMH,CLIN SCI LAB,PHARMACOL SECT,9000 ROCKVILLE PIKE,BLDG 10,ROOM 2D-45,BETHESDA,MD 20892, USA. RI Johren, Olaf/G-6967-2011 NR 30 TC 44 Z9 44 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 APR PY 1996 VL 37 IS 1-2 BP 192 EP 200 DI 10.1016/0169-328X(95)00309-G PG 9 WC Neurosciences SC Neurosciences & Neurology GA UL348 UT WOS:A1996UL34800022 ER PT J AU Inoue, K Sato, K Tohyama, M Shimada, S Uhl, GR AF Inoue, K Sato, K Tohyama, M Shimada, S Uhl, GR TI Widespread brain distribution of mRNA encoding the orphan neurotransmitter transporter v7-3 SO MOLECULAR BRAIN RESEARCH LA English DT Article DE sodium- and chloride-dependent neurotransmitter transporter family; v7-3; mRNA expression; hybridization, in situ; widespread brain distribution ID RAT-BRAIN; GLYCINE TRANSPORTER; FUNCTIONAL EXPRESSION; DOPAMINE TRANSPORTER; MOUSE-BRAIN; CLONING; SYSTEM AB Orphan transporter v7-3 is a member of a new subfamily of Na+, Cl- dependent neurotransmitter transporters with two large extracellular loops. Distribution of v7-3 mRNA was investigated in the rat brain. In situ hybridization study revealed that v7-3 mRNA was widely distributed in the rat central nervous system, including the olfactory bulb, the hypothalamus, the cerebral cortex, the hippocampus, and the cerebellum. In addition, intense v7-3 mRNA expression was found in the motor nuclei including the oculomotor nucleus, abducens nucleus, trigeminal motor nucleus, facial nucleus, hypoglossal nucleus and ventral horn of spinal cord. Intense hybridization signals were also observed in the nuclei containing monoaminergic neurons, such as locus coeruleus, the substantia nigra pars compacta, the ventral tegmental area, the dorsal raphe nucleus and the median raphe nucleus. This multifocal and broad nature of the v7-3 distribution suggests widespread roles for this gene product in neurons mediating several important brain function. C1 NATL INST DRUG ABUSE,INTRAMURAL RES PROGRAM,MOL NEUROBIOL BRANCH,BALTIMORE,MD 21224. OSAKA UNIV,SCH MED,DEPT ANAT & NEUROSCI,OSAKA,JAPAN. JOHNS HOPKINS UNIV,SCH MED,DEPT NEUROL & NEUROSCI,BALTIMORE,MD 21224. NR 19 TC 15 Z9 16 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 APR PY 1996 VL 37 IS 1-2 BP 217 EP 223 DI 10.1016/0169-328X(95)00298-7 PG 7 WC Neurosciences SC Neurosciences & Neurology GA UL348 UT WOS:A1996UL34800025 ER PT J AU Pennypacker, KR Hong, JS Mullis, SB Hudson, PM McMillian, MK AF Pennypacker, KR Hong, JS Mullis, SB Hudson, PM McMillian, MK TI Transcription factors in primary glial cultures: Changes with neuronal interactions SO MOLECULAR BRAIN RESEARCH LA English DT Article DE astrocyte; cell culture; gene regulation; neuron-glia interaction; AP-1 DNA binding activity ID FIBRILLARY ACIDIC PROTEIN; CELL-ADHESION MOLECULES; DNA-BINDING ACTIVITY; RESPONSE-ELEMENT; LEUCINE ZIPPER; C-JUN; CYCLIC-AMP; FOS JUN; AP-1; PROENKEPHALIN AB Several astrocyte gene products, such as enkephalin and glial fibrillary acidic protein (GFAP), are expressed at higher levels under in vitro conditions relative to in vivo. We have observed that cultured glial cells express high basal levels of transcription factors, such as fos-related antigens (Fra), c-Jun, JunD, and cAMP responsive element binding protein (CREB). When neuronal cells are plated on top of the monolayers, the expression of Fra, c-Jun, JunD, and GFAP decreases in the astroglial cells. The DNA binding activity to the AP-l-Like sites of the GFAP and proenkephalin genes was examined in these cultures. The protein complex from glial cultures which recognizes the GFAP AP-1 element contained Fra immunoreactivity while the DNA binding from mixed neuronal/glial cultures consists of CREB-immunoreactive proteins. In glial cultures, no binding occurred to the proenkephalin AP-1-Iike element but a CREB-immunoreactive complex recognized this sequence in the mixed cultures. Thus, with the addition of neurons, both transcription factors and target gene products decrease in astroglial cells. The proteins that compose gene modulatory complexes also change suggesting that regulation of astroglial gene expression is modulated by neurons. C1 NIEHS,NIH,LAB ENVIRONM NEUROSCI,RES TRIANGLE PK,NC 27709. RI Pennypacker, Keith/I-5092-2012 NR 47 TC 22 Z9 22 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 APR PY 1996 VL 37 IS 1-2 BP 224 EP 230 DI 10.1016/0169-328X(95)00318-M PG 7 WC Neurosciences SC Neurosciences & Neurology GA UL348 UT WOS:A1996UL34800026 ER PT J AU Su, YA Hutter, CM Trent, JM Meltzer, PS AF Su, YA Hutter, CM Trent, JM Meltzer, PS TI Complete sequence analysis of a gene (OS-9) ubiquitously expressed in human tissues and amplified in sarcomas SO MOLECULAR CARCINOGENESIS LA English DT Article DE neoplasm; genetics; chromosome 12q ID AMPLIFICATION; IDENTIFICATION; MDM2; GLI AB Amplification and overexpression of genes involved in cellular growth control occur frequently in human tumors. Using a chromosome microdissection-based hybrid-selection strategy, we recently identified two novel genes (OS-9 and OS-4) within 12q13-15, a region frequently amplified in human cancers. We now report further characterization of the full-length OS-9 cDNA sequence. This cDNA sequence consists of 2785 bp from which an open reading frame (ORF) with 667 amino-acid residues was deduced. The predicted polypeptide was water soluble and acidic. We also demonstrate that the OS-9 gene encoded a 2.8-kb mRNA transcribed in all 16 human tissues examined, suggesting that OS-9 is ubiquitously expressed in human tissues. OS-9 was coamplified with CDK4 in three of five sarcoma tissues. Homology analysis of the amino-acid sequence reveals significant similarities between OS-9 and two ORFs deduced from genomic sequences in Caenorhabditis elegans and Saccharomyces cerevisiae. The region of similarity extended over 200 residues (approximately one-third of each ORF), and eight cysteines were conserved in all three ORFs. These observations suggest that this region comprises a functional domain present in a novel evolutionarily conserved gene family defined by OS-9. (C) 1996 Wiley-Liss, Inc.* C1 NATL CTR HUMAN GENOME RES,CANC GENET LAB,NIH,BETHESDA,MD 20892. NR 22 TC 43 Z9 48 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD APR PY 1996 VL 15 IS 4 BP 270 EP 275 DI 10.1002/(SICI)1098-2744(199604)15:4<270::AID-MC4>3.0.CO;2-K PG 6 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA UF724 UT WOS:A1996UF72400004 PM 8634085 ER PT J AU Mazumder, A Neamati, N Sommadossi, JP Gosselin, G Schinazi, RF Imbach, JL Pommier, Y AF Mazumder, A Neamati, N Sommadossi, JP Gosselin, G Schinazi, RF Imbach, JL Pommier, Y TI Effects of nucleotide analogues on human immunodeficiency virus type 1 integrase SO MOLECULAR PHARMACOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; DNA POLYMERASE; CELLULAR PHARMACOLOGY; ANTI-HIV; 3'-AZIDO-3'-DEOXYTHYMIDINE; INHIBITION; 3'-AMINO-3'-DEOXYTHYMIDINE; 3'-FLUOROTHYMIDINE; PHOSPHORYLATION; TOPOISOMERASE AB We extended our previous study with 3'-azido-3'-deoxythymidine nucleotides [Proc. Natl. Acad. Sci. USA 91:5771-5775 (1994)] and examined the effects on human immunodeficiency virus type 1 (HIV-1) integrase of the nucleotides of three nucleoside analogues currently under evaluation in clinical trials: beta-D-2',3'-didehydro-3'-deoxythymidine, beta-D-2'-ara-fluoro-2', 3'-dideoxyadenosine, and beta-L-2',3'-dideoxy-3'-thiacytidine. beta-D-2',3'-Didehydro-3'-deoxythymidine and beta-D-2'-ara-fluoro-2',3'-dideoxyadenosine nucleotides had IC50 values for strand transfer of 100 and 200 mu M, respectively, whereas the corresponding 2',3'-dideoxynucleoside triphosphates, ddT triphosphate and ddA triphosphate, did not inhibit the integrase at 800 and 200 mu M, respectively. beta-L-2',3'-Dideoxy-3'-thiacytidine triphosphate had no effect up to 500 mu M. The L-enantiomers of 5-fluoro-2',3'-dideoxycytidine monophosphate and triphosphate had IC50 values of similar to 40 mu M, whereas their D-enantiomer isomers showed no inhibition at 200 mu M. NAD, pyridoxal phosphate, and coumermycin A1, which exhibit no antiviral activity but are typically used to probe nucleotide binding sites, were also tested. NAD was inactive, and its etheno derivative exhibited activity at 1 mM. In contrast, pyridoxal phosphate (IC50 = 18 mu M) and coumermycin A1 (IC50 = 5 mu M) were potent inhibitors. None of the coumermycin monomeric derivatives were active integrase inhibitors. The physiological ribonucleotides ATP and GTP inhibited HIV-1 integrase at or near cellular concentrations, suggesting that they may regulate HIV-1 integrase activity in cells. In general, the active nucleotides tested inhibited binding of HIV-1 integrase to its substrate DNA and inhibited an integrase deletion mutant containing only amino acids 50-212, indicating that nucleotides bind to the enzyme catalytic core. Consistently, the choice of nucleophile in the 3'- processing reaction was blocked to the same extent regardless of the nucleotide used (water, glycerol, or the viral DNA hy droxyl) by the enzyme. These observations suggest new strategies for antiviral drug development that could be based on nucleotide analogues as inhibitors of HIV-1 integrase. C1 NCI,MOLEC PHARMACOL LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. UNIV ALABAMA,CTR COMPREHENS CANC,CTR AIDS RES,DEPT PHARMACOL,BIRMINGHAM,AL 35294. UNIV MONTPELLIER 2,CHIM BIOORGAN LAB,CNRS,URA 488,F-34095 MONTPELLIER 5,FRANCE. VET AFFAIRS MED CTR,DECATUR,GA 30033. EMORY UNIV,SCH MED,DEPT PEDIAT,BIOCHEM PHARMACOL LAB,ATLANTA,GA 30322. RI Schinazi, Raymond/B-6777-2017 FU NIAID NIH HHS [AI-25899, AI-33239] NR 41 TC 63 Z9 63 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1996 VL 49 IS 4 BP 621 EP 628 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UD689 UT WOS:A1996UD68900006 PM 8609889 ER PT J AU Kim, JH Jiang, QL Glashofer, M Yehle, S Wess, J Jacobson, KA AF Kim, JH Jiang, QL Glashofer, M Yehle, S Wess, J Jacobson, KA TI Glutamate residues in the second extracellular loop of the human A(2a) adenosine receptor are required for ligand recognition SO MOLECULAR PHARMACOLOGY LA English DT Article ID ADENYLATE-CYCLASE; RAT STRIATUM; ACTIVATION; EXPRESSION; CGS-21680; BINDING; CELLS AB The A(2a) adenosine receptor, a member of the G protein-coupled receptor family, is important in the regulation of dopaminergic pathways of the brain and in platelet and cardiovascular functions. In this study, the role of extracellular loops in ligand binding to the human A(2a) receptor was explored through site-directed mutagenesis. Four glutamate/aspartate residues (Glu(151), Glu(161), Glu(169), and Asp(170)) in the second extracellular loop (E2) and a cysteine residue (Cys(262)) in the third extracellular loop (E3) were individually replaced with alanine and other amino acids. A proline residue (Pro(173)) in E2 was mutated to arginine, the homologous amino acid in A(3) receptors. The binding properties of the resultant mutant receptors were determined in transfected COS-7 cells. The mutant receptors were tagged at their amino terminus with a hemagglutinin epitope, thus allowing their detection in the plasma membrane with immunological techniques. High affinity specific binding of [H-3]2-[4-[(2-carboxyethyl)phenyl]ethyl-amino]-5'-N- ethylcarboxamidoadenosine (15 nM) and [H-3]8-[4-[[[[(2-aminoethyl)-amino]carbonyl]methyl]oxy]phenyl]- 1,3- dipropylxanthine (4 nM), an A(2a) agonist and antagonist, respectively, was not observed with four of the mutant receptors, E(151)A, E(151)Q, E(151)D, and E(169)A, although they were well expressed at the cell surface. The E(151)A and E(169)A mutant receptors showed nearly full stimulation of adenylyl cyclase at similar to 10(3)-fold higher concentrations of 2-[4-[(2-carboxyethyl)phenyl]ethyl-amino ethylcarboxamidoadenosine. The E(161)A mutant receptor showed an increase in affinity for the nonxanthine adenosine antagonist 9-chloro-2-(furyl)[1,2,4]triazolo[1,5-c]quinazolin-5-amine (6-fold) but not for other ligands. An E(169)Q mutant gained affinity (5-22-fold) for adenosine derivatives (agonists) substituted at N6 but not at C2 or C5' positions. Mutant receptors (DK)-K-170 and P(173)R were similar to wild-type receptors in binding of both agonist and antagonist radioligands. A C(262)G mutant also resembled the wild-type receptor in radioligand binding, indicating that a potential disulfide bridge with another cysteine residue in proximity is not required for the structural integrity of the receptor. Our data suggest that certain amino acids in the second extracellular loop may be directly or indirectly involved in ligand binding. C1 NIDDK,BIOORGAN CHEM LAB,MOL RECOGNIT SECT,NIH,BETHESDA,MD 20892. NIDDK,BIOORGAN CHEM LAB,DRUG RECEPTOR INTERACT SECT,NIH,BETHESDA,MD 20892. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 39 TC 95 Z9 96 U1 0 U2 3 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 1996 VL 49 IS 4 BP 683 EP 691 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UD689 UT WOS:A1996UD68900014 PM 8609897 ER PT J AU Peters, R Sikorski, R AF Peters, R Sikorski, R TI Thermocycling on the Web: A user's guide SO NATURE BIOTECHNOLOGY LA English DT Editorial Material C1 NCI,BETHESDA,MD 20892. RP Peters, R (reprint author), HARVARD UNIV,SCH MED,CAMBRIDGE,MA 02138, USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 1996 VL 14 IS 4 BP 517 EP 517 DI 10.1038/nbt0496-517 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA UL588 UT WOS:A1996UL58800040 PM 9630932 ER PT J AU Ginns, EI Ott, J Egeland, JA Allen, CR Fann, CSJ Pauls, DL Weissenbach, J Carulli, JP Falls, KM Keith, TP Paul, SM AF Ginns, EI Ott, J Egeland, JA Allen, CR Fann, CSJ Pauls, DL Weissenbach, J Carulli, JP Falls, KM Keith, TP Paul, SM TI A genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish SO NATURE GENETICS LA English DT Letter ID LINKAGE; RELIABILITY; MARKERS; GENE C1 COLUMBIA UNIV,NEW YORK,NY 10032. NEW YORK STATE PSYCHIAT INST & HOSP,NEW YORK,NY 10032. UNIV MIAMI,SCH MED,DEPT PSYCHIAT,MIAMI,FL 33136. YALE UNIV,SCH MED,CTR CHILD STUDY,NEW HAVEN,CT 06520. HUMAN GENOME RES CTR,EVRY,FRANCE. GENOME THERAPEUT CORP,WALTHAM,MA 02154. ELI LILLY & CO,LILLY RES LABS,INDIANAPOLIS,IN 46285. UNIV INDIANAPOLIS,SCH MED,DEPT PSYCHIAT,INDIANAPOLIS,IN 46285. UNIV INDIANAPOLIS,SCH MED,DEPT PHARMACOL,INDIANAPOLIS,IN 46285. UNIV INDIANAPOLIS,SCH MED,DEPT TOXICOL,INDIANAPOLIS,IN 46285. RP Ginns, EI (reprint author), NIMH,CLIN NEUROSCI BRANCH,IRP,NIH,BLDG 49,RM B1EE16,49 CONVENT DR,MSC 4405,BETHESDA,MD 20892, USA. FU NIH HHS [NH28287]; NIMH NIH HHS [MH44292] NR 37 TC 146 Z9 147 U1 1 U2 3 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1996 VL 12 IS 4 BP 431 EP 435 DI 10.1038/ng0496-431 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA UC553 UT WOS:A1996UC55300025 PM 8630500 ER PT J AU Schulze, A Hansen, C Skakkebaek, NE BrondumNielsen, K Ledbetter, DH Tommerup, N AF Schulze, A Hansen, C Skakkebaek, NE BrondumNielsen, K Ledbetter, DH Tommerup, N TI Exclusion of SNRPN as a major determinant of Prader-Willi syndrome by a translocation breakpoint SO NATURE GENETICS LA English DT Letter ID ANGELMAN; CHROMOSOME-15; 15Q11-13; ORIGIN C1 JOHN F KENNEDY INST,DANISH CTR HUMAN GENOME RES,DK-2600 GLOSTRUP,DENMARK. RIGSHOSP,DEPT GROWTH & REPROD,COPENHAGEN,DENMARK. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. NR 19 TC 52 Z9 52 U1 0 U2 2 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1996 VL 12 IS 4 BP 452 EP 454 DI 10.1038/ng0496-452 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA UC553 UT WOS:A1996UC55300030 PM 8630505 ER PT J AU Kaslow, RA Carrington, M Apple, R Park, L Munoz, A Saah, AJ Goedert, JJ Winkler, C OBrien, SJ Rinaldo, C Detels, R Blattner, W Phair, J Erlich, H Mann, DL AF Kaslow, RA Carrington, M Apple, R Park, L Munoz, A Saah, AJ Goedert, JJ Winkler, C OBrien, SJ Rinaldo, C Detels, R Blattner, W Phair, J Erlich, H Mann, DL TI Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection SO NATURE MEDICINE LA English DT Article ID CLASS-I MOLECULES; MULTICENTER AIDS COHORT; HLA; POLYMORPHISM; ANTIGENS; INVITRO; PEPTIDE; REGION AB Major histocompatibility complex (MHC) genes (HLA in humans) regulate the immune response to foreign antigens. Molecular and serologic techniques were used to identify products of HLA class I, class II and transporter (TAP) genes (also part of the MHC) in homosexual seroconverters to human immunodeficiency virus type 1 (HIV-1). Comprehensive statistical analysis produced an HLA profile that predicted time from HIV-1 infection to the onset of AIDS. The profile was developed in a cohort of 139 men and evaluated in a second unrelated cohort of 102 men. In the evaluation cohort, the profile discriminated a sixfold difference between groups with the shortest and longest times to AIDS (P = 0.001). These findings support current theory about control of antigen processing by HLA genes and have implications for immunopathogenesis of HIV-1 and other infections. C1 NCI,BCDP SAIC,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. ROCHE MOL SYST INC,DEPT HUMAN GENET,ALAMEDA,CA 94501. JOHNS HOPKINS UNIV,SCH HYG & PUBL HLTH,DEPT EPIDEMIOL,BALTIMORE,MD 21205. NCI,VIRAL EPIDEMIOL BRANCH,DIV CANC ETIOL,ROCKVILLE,MD 20852. FREDERICK CANC RES & DEV CTR,VIRAL CARCINOGENESIS LAB,FREDERICK,MD 21702. UNIV PITTSBURGH,DEPT PATHOL,PITTSBURGH,PA 15261. UNIV CALIF LOS ANGELES,SCH PUBL HLTH,HLTH SCI CTR,DEPT EPIDEMIOL,LOS ANGELES,CA 90024. NORTHWESTERN UNIV,SCH MED,DEPT MED,COMPREHENS AIDS CTR,CHICAGO,IL 60611. RP Kaslow, RA (reprint author), UNIV ALABAMA,SCH PUBL HLTH,DEPT EPIDEMIOL,212C TIDWELL HALL,720 20TH ST S,BIRMINGHAM,AL 35294, USA. RI apple, raymond/I-4506-2012 OI apple, raymond/0000-0002-8007-0345 FU NIAID NIH HHS [N01-AI-72631, N01-AI-72632, N01-AI-72634] NR 43 TC 703 Z9 716 U1 0 U2 16 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1996 VL 2 IS 4 BP 405 EP 411 DI 10.1038/nm0496-405 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UD314 UT WOS:A1996UD31400041 PM 8597949 ER PT J AU Paxton, WA Martin, SR Tse, D OBrien, TR Skurnick, J VanDevanter, NL Padian, N Braun, JF Kotler, DP Wolinsky, SM Koup, RA AF Paxton, WA Martin, SR Tse, D OBrien, TR Skurnick, J VanDevanter, NL Padian, N Braun, JF Kotler, DP Wolinsky, SM Koup, RA TI Relative resistance to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures SO NATURE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; IMMUNE-RESPONSE; REPLICATION; ANTIGEN; ENTRY; DECLINE; CELLS AB Some individuals remain uninfected with human immunodeficiency virus type-1 (HIV-1) despite multiple high-risk sexual exposures. We studied a cohort of 25 subjects with histories of multiple high-risk sexual exposures to HIV-1 and found that their CD8(+) lymphocytes had greater anti-HIV-1 activity than did CD8(+) lymphocytes from nonexposed controls. further studies indicated that their purified CD4(+) lymphocytes were less susceptible to infection with multiple primary isolates of HIV-1 than were CD4(+) lymphocytes from the nonexposed controls. This relative resistance to HIV-1 infection did not extend to T-cell line-adapted strains, was restricted by the envelope glycoprotein, was not explained by the cell surface density of CD4 molecules, but was associated with the activity of the C-C chemokines RANTES, MIP-1 alpha, and MIP-1 beta. This relative resistance of CD4(+) lymphocytes may contribute to protection from HIV-1 in multiply exposed persons. C1 AARON DIAMOND AIDS RES CTR,NEW YORK,NY 10016. NYU,SCH MED,NEW YORK,NY 10016. NCI,VIRAL EPIDEMIOL BRANCH,NIH,ROCKVILLE,MD 20852. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,DEPT PREVENT MED & COMMUNITY HLTH,NEWARK,NJ 07103. COLUMBIA UNIV,SCH PUBL HLTH,DIV SOCIOMED SCI,NEW YORK,NY 10032. UNIV CALIF SAN FRANCISCO,DEPT OBSTET GYNECOL & REPROD SCI,SAN FRANCISCO,CA 94110. ST LUKES ROOSEVELT HOSP,GASTROINTESTINAL IMMUNOL DIV,NEW YORK,NY 10025. NORTHWESTERN UNIV,DIV INFECT DIS,CHICAGO,IL 60611. RI Wolinsky, Steven/B-2893-2012; OI Wolinsky, Steven/0000-0002-9625-6697 FU NIAID NIH HHS [AI 35522, AI 30358, AI 45218] NR 48 TC 553 Z9 562 U1 0 U2 4 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1996 VL 2 IS 4 BP 412 EP 417 DI 10.1038/nm0496-412 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UD314 UT WOS:A1996UD31400042 PM 8597950 ER PT J AU Lacorazza, HD Flax, JD Snyder, EY Jendoubi, M AF Lacorazza, HD Flax, JD Snyder, EY Jendoubi, M TI Expression of human beta-hexosaminidase alpha-subunit gene (the gene defect of Tay-Sachs disease) in mouse brains upon engraftment of transduced progenitor cells SO NATURE MEDICINE LA English DT Article ID TRANSPLANTATION; BIOSYNTHESIS; FIBROBLASTS; LINE AB In humans, beta-hexosaminidase alpha-subunit deficiency prevents the formation of a functional beta-hexosaminidase A heterodimer resulting in the severe neurodegenerative disorder, Tay-Sachs disease. To explore the feasibility of using ex vivo gene transfer in this lysosomal storage disease, we produced ecotropic retroviruses encoding the human beta-hexosaminidase alpha-subunit cDNA and transduced multipotent neural cell lines. Transduced progenitors stably expressed and secreted high levels of biologically active beta-hexosaminidase A in vitro and cross-corrected the metabolic defect in a human Tay-Sachs fibroblasts cell line in vitro. These genetically engineered CNS progenitors were transplanted into the brains of both normal fetal and newborn mice. Engrafted brains, analyzed at various ages after transplant, produced substantial amounts of human beta-hexosaminidase alpha-subunit transcript and protein, which was enzymatically active throughout the brain at a level reported to be therapeutic in Tay-Sachs disease. These results have implications for treating neurologic diseases characterized by inherited single gene mutations. C1 NEI,GENET & MOLEC IMMUNOL SECT,IMMUNOL LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT PEDIAT,BOSTON,MA 02115. HARVARD UNIV,CHILDRENS HOSP,SCH MED,DEPT NEUROL,BOSTON,MA 02115. NR 24 TC 149 Z9 153 U1 0 U2 5 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1996 VL 2 IS 4 BP 424 EP 429 DI 10.1038/nm0496-424 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA UD314 UT WOS:A1996UD31400044 PM 8597952 ER PT J AU Grzesiek, S Bax, A Clore, GM Gronenborn, AM Hu, JS Kaufman, J Palmer, I Stahl, SJ Wingfield, PT AF Grzesiek, S Bax, A Clore, GM Gronenborn, AM Hu, JS Kaufman, J Palmer, I Stahl, SJ Wingfield, PT TI The solution structure of HIV-1 Nef reveals an unexpected fold and permits delineation of the binding surface for the SH3 domain of Hck tyrosine protein kinase SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID GENE; SEQUENCES; NMR AB The solution structure of HIV-1 Nef has been solved by multidimensional heteronuclear NMR spectroscopy. The construct employed to circumvent problems associated with aggregation was a double-deletion mutant (Delta 2-39, Delta 159-173) in which conformationally disordered regions of the protein at the N terminus and in a long solvent-exposed flexible loop were removed, without affecting the properties or structural integrity of the remainder of the protein. Despite the absence of any sequence similarity, the overall fold of Nef is reminiscent of that of the family of winged helix-turn-helix DNA binding proteins. The binding surface of Nef for the SH3 domain of Hck tyrosine protein kinase has been mapped and reveals a non-contiguous (in terms of amino-acid sequence) interaction surface. This unique feature may suggest possible avenues for drug design aimed at inhibiting the interaction between Nef and SH3 domains. C1 NIAMSD,NIH,PROT EXPRESS LAB,BETHESDA,MD 20892. RP Grzesiek, S (reprint author), NIDDKD,NIH,PHYS CHEM LAB,BLDG 5,BETHESDA,MD 20892, USA. RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 34 TC 274 Z9 275 U1 2 U2 9 PU NATURE PUBLISHING CO PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 1996 VL 3 IS 4 BP 340 EP 345 DI 10.1038/nsb0496-340 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UD310 UT WOS:A1996UD31000012 PM 8599760 ER PT J AU Liu, ZH Striker, LJ Hattori, M Yang, CW Striker, GE AF Liu, ZH Striker, LJ Hattori, M Yang, CW Striker, GE TI Localization of glutamic acid decarboxylase in the kidneys of nonobese diabetic mice SO NEPHRON LA English DT Article DE glutamic acid decarboxylase; nonobese diabetic mice; insulin-dependent diabetes mellitus; kidney; polymerase chain reaction; tubulointerstitial disease; glomerulus ID PANCREATIC BETA-CELLS; SYNAPTIC-LIKE MICROVESICLES; MOUSE; IDENTIFICATION; AUTOIMMUNITY; EXPRESSION; MELLITUS; TISSUES; ENZYME; FORMS AB Antibodies to glutamic acid decarboxylase (GAD), a pancreatic islet beta-cell antigen, are present in >80% of newly diagnosed insulin-dependent diabetes mellitus (IDDM), and are found in nonobese diabetic (NOD) mice, a murine model of spontaneous IDDM. To determine whether GAD is a target antigen in the kidney damage of NOD mice, we studied GAD mRNAs (GAD(65) and GAD(67)) by RT-PCR in mesangial cells, isolated glomeruli, and kidney cortex and medulla in NOD and SJL/C57BL mice. GAD mRNAs were detected in the cortex of both diabetic and nondiabetic NOD and SJL/C57BL mice and GAD antigen was present in proximal and distal tubules by immunofluorescence microscopy. Neither GAD antigen nor mRNA were present in mesangial cells or glomeruli of diabetic or nondiabetic mice. Thus, the expression of GAD in renal tubules raises the possibility that GAD antigens may play a role in diabetic tubulointerstitial disease, whereas the absence of these antigens in glomeruli suggests that CAD-triggered autoimmunity is not directly involved in the glomerular lesions. C1 NIDDKD,NIH,METAB DIS BRANCH,RENAL CELL BIOL SECT,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,JOSLIN DIABET CTR,SECT IMMUNOL & IMMUNOGENET,BOSTON,MA 02115. FU NIDDK NIH HHS [R01DK36836, R01DK43613] NR 31 TC 8 Z9 9 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-2766 J9 NEPHRON JI Nephron PD APR PY 1996 VL 72 IS 4 BP 662 EP 666 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA UD213 UT WOS:A1996UD21300028 PM 8730438 ER PT J AU Eriksson, M Ceccatelli, S UvnasMoberg, K Iadarola, M Hokfelt, T AF Eriksson, M Ceccatelli, S UvnasMoberg, K Iadarola, M Hokfelt, T TI Expression of Fos-related antigens, oxytocin, dynorphin and galanin in the paraventricular and supraoptic nuclei of lactating rats SO NEUROENDOCRINOLOGY LA English DT Article DE oxytocin; dynorphin; immunocytochemistry; in situ hybridization; c-fos; galanin; galanin, message associated peptide; suckling ID MILK-EJECTION REFLEX; HYPOTHALAMIC MAGNOCELLULAR NEURONS; CORTICOTROPIN-RELEASING FACTOR; VASOPRESSIN GENE-EXPRESSION; ENDOGENOUS OPIOID-PEPTIDES; INSITU HYBRIDIZATION; MESSENGER-RNA; CHEMICAL MESSENGERS; PORCINE PITUITARY; NEURAL LOBE AB The magnocellular oxytocin neurons within the paraventricular and supraoptic nuclei (PVN and SON) of the hypothalamus are important relays in the milk ejection reflex in lactating animals, and are activated by suckling. It has been suggested that proto-oncogene transcription factors such as Fos/Jun act as early nuclear transducers of sensory stimuli in neurons. Therefore, we have studied with immunohistochemistry Fos-related antigens (FRAs) as a marker for neuronal activity in the PVN and SON during suckling in lactating rats. In nonlactating rats, only few cells exhibiting FRAs were observed in these nuclei. Also in lactating rats subjected to continuous suckling Fos-like activity was low. In contrast, lactating rats separated from their pups for 4 h and then exposed to suckling for 1 h expressed strong Fos-like immunoreactivity, both in vasopressin and oxytocin neurons. Using in situ hybridization and immunohistochemistry we have also investigated the expression of the mRNAs for oxytocin, dynorphin, galanin and galanin message-associated peptide and of oxytocin and dynorphin in the PVN of lactating and nonlactating rats. In lactating rats, an increase in oxytocin and dynorphin and their mRNAs was observed, whereas mRNAs for galanin and galanin message-associated peptide were downregulated. With the help of immunohistochemistry and double-staining methods, a substantial coexistence between oxytocin- and dynorphin-like immunoreactivities was shown in magnocellular neurons. These results indicate that FRAs are activated in the PVN in the beginning of a suckling period, while this response cannot be seen after continuous stimulation. Furthermore, in the PVN of lactating rats, an upregulation of oxytocin and dynorphin occurs while galanin expression decreases. Finally, the coexistence between oxytocin and dynorphin is more pronounced in lactating rats and nonlactating female rats than has previously been described in male rats. C1 KAROLINSKA INST,DEPT NEUROSCI,S-17177 STOCKHOLM,SWEDEN. KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,S-17177 STOCKHOLM,SWEDEN. NIDR,NEUROBIOL & ANESTHESIOL BRANCH,NIH,BETHESDA,MD 20892. NR 82 TC 41 Z9 41 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0028-3835 J9 NEUROENDOCRINOLOGY JI Neuroendocrinology PD APR PY 1996 VL 63 IS 4 BP 356 EP 367 DI 10.1159/000126976 PG 12 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA UH560 UT WOS:A1996UH56000006 PM 8739891 ER PT J AU Rueckert, L Lange, N Partiot, A Appollonio, I Litvan, I LeBihan, D Grafman, J AF Rueckert, L Lange, N Partiot, A Appollonio, I Litvan, I LeBihan, D Grafman, J TI Visualizing cortical activation during mental calculation with functional MRI SO NEUROIMAGE LA English DT Article ID TIME; LOCALIZATION; RETRIEVAL; NETWORKS; CORTEX AB Cortical activation during arithmetic calculation (silent subtraction by sevens) was compared to that observed during a control condition for which subjects were required to count forward by ones. Nine normal subjects underwent 1.5-T functional magnetic resonance imaging while performing these tasks. All subjects showed bilateral premotor, posterior parietal, and prefrontal cortex activation during serial calculation. There was a large degree of individual variation in activation outside of these areas. These results confirm the role of posterior parietal cortex in arithmetic calculation and implicate other regions, including prefrontal cortex. (C) 1996 Academic Press, Inc. C1 NINCDS,COGNIT NEUROSCI SECT,MNB,BETHESDA,MD 20892. NINCDS,BIOMETRY BRANCH,BETHESDA,MD 20892. NINCDS,NEUROEPIDEMIOL BRANCH,BETHESDA,MD 20892. NIH,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. OSPED SAN GERARDO,MONZA,ITALY. OI Grafman, Jordan H./0000-0001-8645-4457; Litvan, Irene/0000-0002-3485-3445 NR 44 TC 130 Z9 136 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR PY 1996 VL 3 IS 2 BP 97 EP 103 DI 10.1006/nimg.1996.0011 PG 7 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA UJ239 UT WOS:A1996UJ23900003 PM 9345480 ER PT J AU Litvan, I Agid, Y Jankovic, J Goetz, C Brandel, JP Lai, EC Wenning, G DOlhaberriague, L Verny, M Chaudhuri, KR McKee, A Jellinger, K Bartko, JJ Mangone, CA Pearce, RKB AF Litvan, I Agid, Y Jankovic, J Goetz, C Brandel, JP Lai, EC Wenning, G DOlhaberriague, L Verny, M Chaudhuri, KR McKee, A Jellinger, K Bartko, JJ Mangone, CA Pearce, RKB TI Accuracy of clinical criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) SO NEUROLOGY LA English DT Article ID LEWY BODY DISEASE; ALZHEIMERS-DISEASE; GAZE PALSY; DEMENTIA; PARKINSONISM; DEGENERATION; TANGLES AB We assessed the validity and interrater reliability of neurologists who, using four different sets of previously published criteria for the clinical diagnosis of progressive supranuclear palsy (PSP), also called Steele-Richardson-Olszewski syndrome, rated 105 autopsy-proven cases of PSP (n = 24), Lewy body disease (n = 29), corticobasal ganglionic degeneration (n = 10), postencephalitic parkinsonism (n = 7), multiple system atrophy (n = 16), Pick's disease (n = 7), and other parkinsonian or dementia disorders (n = 12). Cases were presented in random order to six neurologists. Information from each patient's first and last visits to the medical center supplying the case was presented sequentially to the rater, and the rater's diagnosis was compared with the neuropathologic diagnosis of each case. Interrater agreement for the diagnosis of PSP varied from substantial to near perfect, but none of the criteria had both high sensitivity and high predictive value. Because of these limitations, we used a logistic regression analysis to identify the variables from the data set that would best predict the diagnosis. This analysis identified vertical supranuclear palsy with downward gaze abnormalities and postural instability with unexplained falls as the best features for predicting the diagnosis. From the results of the regression analysis and the addition of exclusionary features, we propose optimal criteria for the clinical diagnosis of PSP. C1 HOP LA PITIE SALPETRIERE,INSERM,U289,F-75651 PARIS,FRANCE. HOP LA PITIE SALPETRIERE,FEDERAT NEUROL,PARIS,FRANCE. BAYLOR COLL MED,DEPT NEUROL,HOUSTON,TX 77030. RUSH MED COLL,DEPT NEUROL,CHICAGO,IL 60612. INST NEUROL,PARKINSONS DIS SOC BRAIN TISSUE BANK,LONDON WC1N 3BG,ENGLAND. INST PSYCHIAT,DEPT NEUROL,LONDON SE5 8AF,ENGLAND. HOP LA PITIE SALPETRIERE,RAYMOND ESCOUROLLE NEUROPATHOL LAB,INSERM U360,PARIS,FRANCE. MASSACHUSETTS GEN HOSP,DEPT NEUROPATHOL,BOSTON,MA 02114. LUDWIG BOLTZMANN INST CLIN NEUROBIOL,VIENNA,AUSTRIA. NIMH,DIV EPIDEMIOL & SERV RES,BETHESDA,MD 20892. RP Litvan, I (reprint author), NINCDS,NEUROEPIDEMIOL BRANCH,NIH,FED BLDG,ROOM 714,BETHESDA,MD 20814, USA. OI Litvan, Irene/0000-0002-3485-3445; Ray Chaudhuri, K/0000-0003-2815-0505 NR 58 TC 237 Z9 240 U1 0 U2 1 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1996 VL 46 IS 4 BP 922 EP 930 PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA UG635 UT WOS:A1996UG63500007 PM 8780065 ER PT J AU Morens, DM Davis, JW Grandinetti, A Ross, GW Popper, JS White, LR AF Morens, DM Davis, JW Grandinetti, A Ross, GW Popper, JS White, LR TI Epidemiologic observations on Parkinson's disease: Incidence and mortality in a prospective study of middle-aged men SO NEUROLOGY LA English DT Article ID PREVALENCE; CITY AB We determined age-specific and age-adjusted incidence rates and mortality rates of idiopathic Parkinson's disease (PD)in a cohort of men followed for 29 years. Since enrollment in 1965, the Honolulu Heart Study has followed 8,006 American men of Japanese or Okinawan ancestry. Rescreening of the entire cohort, completed in 1994, included attempts to detect all prevalent and incident cases of PD, parkinsonism, and related conditions. PD incidence rates and age-incidence patterns were similar to rates previously published for Caucasian men in Europe and the United States, and were higher than incidence rates published for Asian men living in Asian nations; Prevalence patterns appeared to correspond more closely to patterns observed in developed nations than in Asian nations. PD was associated with markedly increased mortality that appeared to result from effects of both absolute age and disease duration. There was no firm evidence for differences in birth cohort risks of PD. These data may have implications for maturational and environmental theories of PD etiology. C1 UNIV HAWAII,SCH MED,HONOLULU,HI 96822. HAWAII OSTEOPOROSIS CTR,HONOLULU,HI. EAST WEST CTR,HONOLULU,HI 96822. UNIV HAWAII,PACIFIC BIOMED RES CTR,HONOLULU,HI 96822. HONOLULU ASIA AGING STUDY,HONOLULU,HI 96822. US DEPT VET AFFAIRS,HONOLULU,HI 96822. NIA,NIH,HONOLULU,HI 96822. RP Morens, DM (reprint author), UNIV HAWAII,SCH PUBL HLTH,PROGRAM EPIDEMIOL,BIOMED D103,1960 EAST WEST RD,HONOLULU,HI 96822, USA. FU NINDS NIH HHS [NS-30371] NR 26 TC 105 Z9 111 U1 0 U2 6 PU LITTLE BROWN CO PI BOSTON PA 34 BEACON STREET, BOSTON, MA 02108-1493 SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1996 VL 46 IS 4 BP 1044 EP 1050 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA UG635 UT WOS:A1996UG63500030 PM 8780088 ER PT J AU Brownstein, MJ Hughes, J AF Brownstein, MJ Hughes, J TI A new beginning SO NEUROPEPTIDES LA English DT Editorial Material C1 ADDENBROOKES HOSP,PARKE DAVIS NEUROSCI RES CTR,CAMBRIDGE CB2 2QB,ENGLAND. RP Brownstein, MJ (reprint author), NIMH,CELL BIOL LAB,BLDG 36,ROOM 3A-17,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH, MIDLOTHIAN, SCOTLAND EH1 3AF SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 1996 VL 30 IS 2 BP 115 EP 115 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA UN984 UT WOS:A1996UN98400001 ER PT J AU Chen, K Kokate, TG Donevan, SD Carroll, FI Rogawski, MA AF Chen, K Kokate, TG Donevan, SD Carroll, FI Rogawski, MA TI Ibogaine block of the NMDA receptor: In vitro and in vivo studies SO NEUROPHARMACOLOGY LA English DT Article DE Ibogaine; voltage clamp recording; [H-3]dizocilpine binding; NMDA receptor; hippocampus; maximal electroshock (MES) test; seizure ID D-ASPARTATE RECEPTOR; HIPPOCAMPAL-NEURONS; PARASAGITTAL ZONES; ACTIVATED CURRENT; CHANNELS; RATS; HARMALINE; RESPONSES; DOPAMINE; BINDING AB Ibogaine is an hallucinogenic indole alkaloid claimed to have anti-addictive properties. Although its mechanism of action is unknown, binding studies have indicated that the drug may interact with N-methyl-D-aspartate (NMDA) receptors. We further investigated the nature of the interaction between ibogaine and NMDA receptors in voltage clamp and binding studies, and sought to confirm that the drug has NMDA receptor blocking activity in vivo. In whole-cell recordings from cultured rat hippocampal neurons, ibogaine caused a slow, concentration-dependent block of NMDA-induced currents (IC50, 3.1 mu M at -60 mV). In contrast, ibogaine failed to affect either kainate- or gamma-aminobutyric acid-evoked currents. The blockade of NMDA currents was use- and voltage-dependent, and the long lasting ibogaine block could be occluded by co-application of Mg2+. Ibogaine also inhibited equilibrium [H-3]dizocilpine binding to NMDA receptors in rat forebrain membranes (IC50, 3.2 mu M). We conclude that ibogaine is an open channel NMDA receptor antagonist. Administration of ibogaine to mice resulted in complete protection in the maximal electroshock test (ED(50), 31 mg/kg, i.p.) and partial protection against NMDA-induced lethality, confirming that ibogaine can block NMDA receptors in vivo. Published by Elsevier Science Ltd 1996. C1 NINCDS,NEURONAL EXCITABIL SECT,EPILEPSY RES BRANCH,NIH,BETHESDA,MD. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 32 TC 26 Z9 26 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD APR PY 1996 VL 35 IS 4 BP 423 EP 431 DI 10.1016/0028-3908(96)84107-4 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA UT502 UT WOS:A1996UT50200005 PM 8793904 ER PT J AU FureyKurkjian, ML Pietrini, P GraffRadford, NR Alexander, GE Freo, U Szczepanik, J Schapiro, MB AF FureyKurkjian, ML Pietrini, P GraffRadford, NR Alexander, GE Freo, U Szczepanik, J Schapiro, MB TI Visual variant of Alzheimer disease: Distinctive neuropsychological features SO NEUROPSYCHOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; POSTERIOR CORTICAL ATROPHY; BALINTS SYNDROME; DISCONNECTION; DEMENTIA; MEMORY AB A subgroup of patients with probable Alzheimer disease (AD) reported a history of isolated visual disturbances (VS) early in the course of disease, without the characteristic memory complaints. Brain imaging and neuropathologic studies indicated that this subgroup had larger involvement of visual cortical areas and relative sparing of temporal, frontal, and limbic structures compared with classic AD. Consistent with these findings, the authors hypothesized that the cognitive deficits in this subgroup would be distinctly different from those seen in more typical AD patients. The authors studied 10 probable AD patients with VS (AD+VS), 22 patients without VS (AD-), and 25 healthy controls with a neuropsychological test battery. Compared with AD-, AD+VS patients performed significantly better on tests of verbal memory and had greater impairment on tests of visuospatial skills, suggesting a distinct pattern of cognitive dysfunction consistent with metabolic and neuropathologic reports. C1 MAYO CLIN JACKSONVILLE, DEPT NEUROL, JACKSONVILLE, FL 32224 USA. RP FureyKurkjian, ML (reprint author), NIA, NEUROSCI LAB, BLDG 10, ROOM 6C414, 9000 ROCKVILLE PIKE, BETHESDA, MD 20892 USA. NR 39 TC 8 Z9 8 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 EI 1931-1559 J9 NEUROPSYCHOLOGY JI Neuropsychology PD APR PY 1996 VL 10 IS 2 BP 294 EP 300 PG 7 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA UD704 UT WOS:A1996UD70400015 ER PT J AU Brauer, LH Johanson, CE Schuster, CR Rothman, RB deWit, H AF Brauer, LH Johanson, CE Schuster, CR Rothman, RB deWit, H TI Evaluation of phentermine and fenfluramine, alone and in combination, in normal, healthy volunteers SO NEUROPSYCHOPHARMACOLOGY LA English DT Article ID TERM WEIGHT CONTROL; D-AMPHETAMINE; DISCRIMINATIVE STIMULUS; ABUSE LIABILITY; DRUG PREFERENCE; HUMANS; COCAINE; RATS; MOOD; PHENMETRAZINE AB Recent clinical reports indicate that combined administration of phentermine and fenfluramine may have useful effects in the treatment of drug abuse. The present study was designed to evaluate the subjective and mood-altering effects of these drugs, alone and in combination, in normal healthy volunteers. Seven male and five female volunteers participated in an eight-session, double-blind study in which each subject received each of the following drug conditions: d-amphetamine (10 and 20 mg), phentermine (30 mg), fenfluramine (40 and 80 mg), phentermine (30 mg) with fenfluramine (40 mg), phentermine (30 mg) with fenfluramine (80 mg), and placebo. Sessions were conducted in a laboratory setting two or three days a week. Subjects completed standardized self-report questionnaires and psychomotor tests before and at regular intervals after each drug administration. Phentermine produced effects that were similar to those of d-amphetamine, whereas fenfluramine produced different and apparently aversive effects (e.g., it increased measures of anxiety and confusion). Phentermine reduced the apparently aversive effects of fenfluramine when the two drugs were given together. These results suggest that the combination of phentermine and fenfluramine would have a low potential for abuse. C1 UNIV CHICAGO,DEPT PSYCHIAT,CHICAGO,IL 60637. WAYNE STATE UNIV,DEPT PSYCHIAT & BEHAV NEUROSCI,DETROIT,MI. NATL INST DRUG ABUSE,DIV INTRAMURAL RES,BALTIMORE,MD. OI de Wit, Harriet/0000-0002-7211-8994 FU NIDA NIH HHS [DA02812] NR 55 TC 43 Z9 43 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 1996 VL 14 IS 4 BP 233 EP 241 DI 10.1016/0893-133X(95)00113-R PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA UB303 UT WOS:A1996UB30300002 PM 8924191 ER PT J AU Petralia, RS Wang, YX Niedzielski, AS Wenthold, RJ AF Petralia, RS Wang, YX Niedzielski, AS Wenthold, RJ TI The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations SO NEUROSCIENCE LA English DT Article DE excitatory amino acids; ultrastructure; immunocytochemistry; hippocampus; cortex; striatum ID CENTRAL-NERVOUS-SYSTEM; AMINO-ACID RECEPTORS; RAT OLFACTORY-BULB; IMMUNOCYTOCHEMICAL LOCALIZATION; SIGNAL TRANSDUCTION; MESSENGER-RNA; BRAIN; NEURONS; HIPPOCAMPUS; MODULATION AB Glutamate neurotransmission involves numerous ionotropic and metabotropic glutamate receptor types in postsynaptic, presynaptic and glial locations. Distribution of the metabotropic glutamate receptors mGluR2 and mGluR3 was studied with an affinity-purified, characterized polyclonal antibody made from a C-terminus peptide. This antibody, mGluR2/3, recognized both mGluR2 and mGluR3, but did not cross-react with any other type of metabotropic glutamate receptor except for a very slight recognition of mGluR5. Light microscope distribution of the antibody binding sites in the nervous system matched the combined distributions of messenger RNA for mGluR2 and mGluR3. For example, dense staining seen in the accessory olfactory bulb and cerebellar Golgi cells matched high levels of mGluR2 messenger RNA in these structures, while moderately dense staining in the reticular nucleus of the thalamus and light to moderate staining in glia throughout the brain matched significant levels of mGluR3 messenger RNA in these structures. In the rostral olfactory structures, the densest stained neurons belonged to presumptive ''necklace olfactory glomeruli.'' In the hippocampus, staining was densest in the neuropil of the stratum lucidum/pyramidale, stratum lacunosum/moleculare, hilus and middle third of the molecular layer of the dentate gyrus. Ultrastructural studies of the cerebral cortex, hippocampus and caudate-putamen revealed significant staining in postsynaptic and presynaptic structures and glial wrappings of presumptive excitatory synapses; frequently, this staining was concentrated in discrete patches at or near active zones. In the hippocampus, presynaptic staining appeared to be concentrated in terminals of two populations of presumptive glutamatergic axons: messy fibers originating from granule cells and perforant path fibers originating from the entorhinal cortex. These data suggest that populations of mGluR2 and/or mGluR3 receptors are localized differentially in synapses, i.e. those in and near the postsynaptic and presynaptic membranes and in glial wrappings of synapses, in several regions of the brain. In addition, we provide immunocytochemical evidence of mGluR2 or mGluR3 receptors in presynaptic terminals of glutamatergic synapses. Thus, mGluR2 and mGluR3 are found in various combinations of presynaptic, postsynaptic and glial localizations that may reflect differential modulation of excitatory amino acid transmission. RP Petralia, RS (reprint author), NIDCD,NIH,NEUROCHEM LAB,BETHESDA,MD 20892, USA. NR 74 TC 451 Z9 457 U1 0 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR PY 1996 VL 71 IS 4 BP 949 EP 976 DI 10.1016/0306-4522(95)00533-1 PG 28 WC Neurosciences SC Neurosciences & Neurology GA UC068 UT WOS:A1996UC06800005 PM 8684625 ER PT J AU Tallent, M Liapakis, G OCarroll, AM Lolait, SJ Dichter, M Reisine, T AF Tallent, M Liapakis, G OCarroll, AM Lolait, SJ Dichter, M Reisine, T TI Somatostatin receptor subtypes SSTR2 and SSTR5 couple negatively to an L-type Ca2+ current in the pituitary cell line AtT-20 SO NEUROSCIENCE LA English DT Article DE somatostatin; calcium current; neurotransmitter; somatostatin antagonist ID RAT NEOCORTICAL NEURONS; RELEASE-INHIBITING HORMONE; DEPENDENT CALCIUM CURRENT; GTP-BINDING-PROTEINS; TUMOR-CELLS; ADRENOCORTICOTROPIN HORMONE; MOLECULAR-CLONING; ADENYLATE-CYCLASE; GASTRIC-ACID; K+ CHANNELS AB The somatostatin receptor subtypes SSTR2 and SSTR5 mediate distinct endocrine and exocrine functions of somatostatin and may also be involved in mediating the neuromodulatory actions of somatostatin in the brain. To investigate whether these receptors couple to voltage-sensitive Ca2+ channels, SSTR2 and SSTR5 selective agonists were tested for their effects on AtT-20 cells using whole cell patch clamp techniques. The SSTR2 selective agonist MK 678 inhibited Ca2+ currents in AtT-20 cells. The effects of MK 678 were reversible and blocked by pertussis toxin pretreatment, suggesting that SSTR2 couples to the L-type Ca2+ channels via G proteins. Other SSTR2-selective agonists, including BIM 23027 and NC8-12, were able to inhibit the Ca2+ current in these cells. The SSTR5 selective agonist BIM 23052 also inhibited the Ca2+ currents in these cells and this effect was reversible and blocked by pertussis toxin treatment. The ability of SSTR5 to mediate inhibition of the Ca2+ current was greatly attenuated by pretreatment with the SSTR5-selective agonist BIM 23052, whereas SSTR2-mediated inhibition of the Ca2+ current was not altered by pretreatment with the SSTR2-selective agonist MK 678. Thus, the SSTR2 and SSTR5 couplings to the Ca2+ current are differentially regulated. The peptide L362,855, which we previously have shown to have high affinity for the cloned SSTR5, had minimal effects on Ca2+ currents in AtT-20 cells at concentrations up to 100 nM and did not alter the ability of MK 678 to inhibit Ca2+ currents. However, it completely antagonized the effects of the SSTR5-selective agonist BIM 23052 on the Ca2+ currents. L362,855 is an antagonist/partial agonist at SSTR5 since it can reduce Ca2+ currents in these cells at concentrations above 100 nM. L362,855 is also an antagonist/partial agonist at the cloned rat SSTR5 expressed in CHO cells since it is able to block the inhibition of cAMP accumulation induced by somatostatin at concentrations below 100 nM but at higher concentrations can inhibit cAMP formation itself. Structural analysis of L362,855 reveals that only a single hydroxyl group at residue seven in the peptide is needed to convert the compound from an antagonist/partial agonist to a full agonist at SSTR5. These studies reveal that two different somatostatin receptor subtypes, SSTR2 and SSTR5, can mediate the inhibition of an L-type Ca2+ channel in AtT-20 cells by somatostatin. The receptor subtype responses can be distinguished by selective agonists and antagonists and are regulated differently by agonist pretreatment. The inhibition of Ca2+ influx into endocrine cells and neurons may be a major cellular mechanism by which somatostatin modulates hormone and neurotransmitter release. Our results reveal that at least two receptor subtypes can mediate this cellular response. C1 UNIV PENN,SCH MED,DEPT PHARMACOL,PHILADELPHIA,PA 19104. UNIV PENN,SCH MED,DEPT NEUROL,PHILADELPHIA,PA 19104. NIMH,CELL BIOL LAB,BETHESDA,MD 20892. FU NIMH NIH HHS [MH45533, MH48518] NR 66 TC 63 Z9 64 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR PY 1996 VL 71 IS 4 BP 1073 EP 1081 DI 10.1016/0306-4522(95)00510-2 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UC068 UT WOS:A1996UC06800016 PM 8684611 ER PT J AU Jucker, M Tian, M Norton, DD Sherman, C Kusiak, JW AF Jucker, M Tian, M Norton, DD Sherman, C Kusiak, JW TI Laminin alpha 2 is a component of brain capillary basement membrane: Reduced expression in dystrophic dy mice SO NEUROSCIENCE LA English DT Article DE merosin; M-chain; laminin-2; endothelial cell; vasculature; smooth muscle cell ID MURINE MUSCULAR-DYSTROPHY; CENTRAL-NERVOUS-SYSTEM; NEUROMUSCULAR-JUNCTION; MONOCLONAL-ANTIBODIES; EXTRACELLULAR-MATRIX; ENDOTHELIAL-CELLS; PERIPHERAL-NERVES; NEURITE OUTGROWTH; SCHWANN-CELLS; COLLAGEN-IV AB In the present study we demonstrate low level expression of the laminin alpha 2 chain in brain and localize the alpha 2 protein to the capillary basement membrane. While in peripheral basement membranes the laminin alpha 1 and alpha 2 chains have an almost mutually exclusive distribution, the present results suggest both alpha 1 and alpha 2 in the cerebral capillary basement membrane. Towards elucidating the function of alpha 2 in brain, we have performed ultrastructural analysis of the capillary basement membrane in dystrophic dy mice, which show a 70-90% and >95% reduction of alpha 2 messenger RNA compared to heterozygous and wild-type mice, respectively, and show a nearly total absence of the alpha 2 protein by immunofluorescence. In contrast to the muscle and Schwann cell basement membrane, where alpha 2 deficiency causes structural basement membrane abnormalities, the present results show that the lack of the alpha 2 subunit in the cerebral capillary basement membrane is not detrimental to its structure. This observation might be explained by the fact that the cerebral capillary basement membrane expresses both a chains and therefore exhibits structural redundancy. C1 NIA,NIH,GERONTOL RES CTR,CELLULAR & MOLEC BIOL LAB,BALTIMORE,MD 21224. RP Jucker, M (reprint author), NIA,NIH,GERONTOL RES CTR,MOLEC NEUROBIOL UNIT,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 46 TC 46 Z9 46 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD APR PY 1996 VL 71 IS 4 BP 1153 EP 1161 DI 10.1016/0306-4522(95)00496-3 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UC068 UT WOS:A1996UC06800024 PM 8684619 ER PT J AU Kawai, K Ohta, H Kubodera, A Channing, MA Eckelman, WC AF Kawai, K Ohta, H Kubodera, A Channing, MA Eckelman, WC TI Synthesis and evaluation of radioiodinated 6-Iodo-L-DOPA as a cerebral L-amino acid transport marker SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE 6-iodo-L-DOPA; cerebral L-amino acid transport; radiopharmaceutical; SPECT; 6-mercuric trifluoroacetate protected DOPA ID BRAIN; 6-FLUORO-L-DOPA; METABOLISM; PANCREAS; BLOOD; RAT AB Regioselective radioiodination of N-trifluoroacetyl 3,4 -dimethoxy-6-trifluoroacetoxymercurio-L-phenylalanine ethyl ester 1 under no-carrier-added condition gave 6-[I-125]iodo protected L-DOPA with a labeling efficiency of more than 85%, and no-carrier-added 6 [I-125]I-L-DOPA was obtained with a radio chemical purity of over 95% after hydrolysis and chromatography. A nonradioactive standard of 6-iodo protected L DOPA was synthesized by the iododemercuration of 6-mercuric trifluoroacetate protected L DOPA 1 using I, in chloroform. 6-[I]I-L-DOPA showed high brain accumulation and rapid blood clearance in mice. The rat brain slice studies indicated high affinity of 6[I-125]I-L-DOPA for carrier-mediated and stereoselective active transport systems. The tissue homogenate analysis revealed that most of the accumu lated radioactivity was intact 6-[I-125]T-L-DOPA. Thus, 6-[I-123]I-L-DOPA appears to be a suitable single photon emission computed tomography (SPECT) tracer for the selective measurement of cerebral L-amino acid transport, having no affinity for dopamine metabolism. C1 NATL INST HLTH,WARREN GRANT MAGNUSON CLIN CTR,PET DEPT,BETHESDA,MD 20892. RP Kawai, K (reprint author), UNIV TOKYO,FAC PHARMACEUT SCI,DEPT RADIOPHARMACEUT CHEM,12 ICHIGAYA FUNAGAWARA MACHI,TOKYO 162,JAPAN. NR 20 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 1996 VL 23 IS 3 BP 251 EP 255 DI 10.1016/0969-8051(95)02054-3 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UH948 UT WOS:A1996UH94800009 PM 8782233 ER PT J AU Schmall, B Conti, PS Alauddin, MM AF Schmall, B Conti, PS Alauddin, MM TI Synthesis of [C-11-methyl]-alpha-aminoisobutyric acid (AIB) SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE carbon-11; alpha-aminoisobutyric acid; AIB ID ALPHA-AMINOISOBUTYRIC-ACID; AMINO-ACIDS; ROUTINE SYNTHESIS; TUMOR-DETECTION; TRANSPORT; MELANOMA; CELLS AB Alpha-aminoisobutyric acid (ATE) labeled with the cyclotron-produced, positron-emitting radionuclide C-11 has been synthesized with the label in the alpha-methyl group. Our previously published synthesis of [C-11] AIB in the carboxyl position from [C-11] HCN requires a rigorous quality assurance program to ensure that the concentration of cyanide in the final product is below certain levels, This can be avoided using the method described here with [C-11] CH3I. The radiochemical yield calculated to end of bombardment (EOB) was 45-55% from [C-11] CO2 with radiochemical purity of [C-11 methyl] AIB exceeding 99%. Synthesis times from [C-11] CO2 were about 55 min. Specific activities of 1 Ci/mu mol were achieved on average. It has been shown that [C-11-carboxyl] AIB is a useful imaging agent in patients with soft tissue cancers and melanoma, and it demonstrates tumor uptake in a spectrum of other animal tumor models. Because AIB is a nonmetabolized amino acid, [C-11 methyl] AIB should be equally as useful. Either agent can be employed for the quantification of the A type amino acid transport system in vivo with PET. C1 NATL INST HLTH,WARREN G MAGNUSON CLIN CTR,DEPT NUCL MED,BETHESDA,MD 20892. UNIV SO CALIF,PET IMAGING SCI CTR,DEPT RADIOL,LOS ANGELES,CA 90033. NR 26 TC 8 Z9 8 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 1996 VL 23 IS 3 BP 263 EP 266 DI 10.1016/0969-8051(95)02065-9 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UH948 UT WOS:A1996UH94800011 PM 8782235 ER PT J AU Lever, JR Scheffel, U Stathis, M Seltzman, HH Wyrick, CD Abraham, P Parham, K Thomas, BF Boja, JW Kuhar, MJ Carroll, FI AF Lever, JR Scheffel, U Stathis, M Seltzman, HH Wyrick, CD Abraham, P Parham, K Thomas, BF Boja, JW Kuhar, MJ Carroll, FI TI Synthesis and in vivo studies of a selective ligand for the dopamine transporter: 3 beta-(4-[I-125]iodophenyl)tropan-2 beta-carboxylic acid isopropyl ester ([I-125]RTI-121) SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE dopamine transporter; tadiotracer; RTI-121; radioiodine; amphetamine; metabolism ID COCAINE ANALOGS; INVIVO BINDING; H-3 GBR-12783; I-125 RTI-55; RAT-BRAIN; STRIATUM; SITES; RECEPTORS; RELEASE; AGENTS AB A selective ligand for the dopamine transporter 3 beta-(4-iodophenyl)tropan-2 beta-carboxylic acid isopropyl ester (RTI-121) has been labeled with iodine-125 by electrophilic radioiododestannylation. The [I-125]RTI-121 was obtained in good yield (86 +/- 7%, n = 3) with high radiochemical purity(>99%) and specific radioactivity (1210-1950 mCi/mu mol). After i.v. administration of [I-125]Rn-121 to mice, the rank order of regional brain tissue radioactivity (striatum > olfactory tubercles much greater than cortex, hippocampus, thalamus, hypothalamus, cerebellum) was consistent with dopamine transporter labeling, Specific in pike binding in striatum and olfactory tubercles was saturable, and was blocked by the dopamine transporter ligands GBR 12,909 and (+/-)-nomifensine. By contrast, binding was not reduced by paroxetine, a serotonin transporter inhibitor, or desipramine, a norepinephrine transporter inhibitor. A variety of additional drugs having high affinities for recognition sites other than the neuronal dopamine transporter also had no effect, The [I-125]RTI-121 binding in striatum and olfactory tubercles was inhibited by d-amphetamine in dose-dependent fashion. Nonmetabolized radioligand represents 85% of the signal observed in extracts of whole mouse brain. Thus, [I-125]RTI-121 is readily prepared, and is a useful tracer for dopamine transporter studies in vivo. C1 JOHNS HOPKINS UNIV,DEPT RADIOL,BALTIMORE,MD 21205. RES TRIANGLE INST,RES TRIANGLE PK,NC 27709. NIDA,ADDICT RES CTR,NEUROSCI BRANCH,BALTIMORE,MD 21224. RP Lever, JR (reprint author), JOHNS HOPKINS UNIV,DEPT ENVIRONM HLTH SCI,BALTIMORE,MD 21205, USA. FU NIDA NIH HHS [DA 05477, DA 08816, DA 08870] NR 39 TC 22 Z9 22 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 1996 VL 23 IS 3 BP 277 EP 284 DI 10.1016/0969-8051(95)02074-8 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UH948 UT WOS:A1996UH94800013 PM 8782237 ER PT J AU Hume, SP Luthra, SK Brown, DJ OpackaJuffry, J Osman, S Ashworth, S Myers, R Brady, F Carroll, FI Kuhar, MJ Brooks, DJ AF Hume, SP Luthra, SK Brown, DJ OpackaJuffry, J Osman, S Ashworth, S Myers, R Brady, F Carroll, FI Kuhar, MJ Brooks, DJ TI Evaluation of [C-11]RTI-121 as a selective radioligand for PET studies of the dopamine transporter SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE dopamine transporter; RTI-121; positron emission tomography ID POSITRON EMISSION TOMOGRAPHY; COCAINE ANALOGS; REUPTAKE SITES; UPTAKE INHIBITOR; I-125 RTI-55; HUMAN BRAIN; BETA-CIT; BINDING; INVIVO; AUTORADIOGRAPHY AB The cocaine analogue RTI-121 (3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid isopropyl ester), when labeled with carbon-11, was evaluated in rats as a potential PET ligand for the dopamine transporter. The compound gave in vivo striatum:cerebellum ratios that were similar to those obtained with the related ligand [C-11]RTI-55 (2 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester) but showed a much greater selectivity for the dopamine compared with the 5-HT uptake site, The results indicate that [C-11]RTI-121 could be used in preference to [C-11]RTI-55 in man. Experimentally, [C-11]RTI-121 has potential in the quantification of dopamine terminal function in rat models of disease, using a combination of autoradiography, postmortem sampling, and in vivo tomography. C1 HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,MRC CLIN SCI CTR,CYCLOTRON UNIT,NEUROSCI GRP,LONDON W12 0NN,ENGLAND. RES TRIANGLE INST,DEPT ORGAN & MED CHEM,RES TRIANGLE PK,NC 27709. NIDA,NEUROSCI BRANCH,ADDICT RES CTR,BALTIMORE,MD 21224. RP Hume, SP (reprint author), HAMMERSMITH HOSP,ROYAL POSTGRAD MED SCH,MRC CLIN SCI CTR,CYCLOTRON UNIT,PET METHODOL GRP,LONDON W12 0NN,ENGLAND. RI Opacka-Juffry, Jolanta/B-7835-2009 NR 44 TC 16 Z9 16 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0883-2897 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 1996 VL 23 IS 3 BP 377 EP 384 DI 10.1016/0969-8051(96)00019-4 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UH948 UT WOS:A1996UH94800027 PM 8782251 ER PT J AU Sherer, DM Divon, MY AF Sherer, DM Divon, MY TI Prenatal ultrasonographic assessment of the ductus arteriosus: A review SO OBSTETRICS AND GYNECOLOGY LA English DT Review ID VELOCITY WAVE-FORMS; RANDOMIZED COMPARATIVE TRIAL; ABSENT PULMONARY VALVE; PRETERM LABOR; DOPPLER ECHOCARDIOGRAPHY; INDOMETHACIN TREATMENT; UMBILICAL ARTERY; GESTATIONAL-AGE; FETAL; FLOW AB Objective: To review current data pertaining to prenatal ultrasonography of the ductus arteriosus. Data Sources: We reviewed manuscripts published in the English language regarding prenatal ultrasonography and the fetal ductus arteriosus obtained from a MEDLINE search for 1966 onward. Additional sources were identified through cross-referencing. Methods of Study Selection: Data regarding morphology, physiology, pathophysiology of fetal disease, and hemodynamic changes after administration of various maternal medications and structural congenital anomalies of the ductus arteriosus were selected. Data Extraction and Synthesis: Knowledge of the function of the ductus arteriosus in both normal and abnormal fetal conditions is enhanced by prenatal ultrasonographic findings. Detailed analyses of ductus arteriosus hemodynamics are indicated in well-defined medical conditions, including maternal medication and established structural or functional fetal cardiac disease. Conclusion: The fetal ductus arteriosus is a vascular structure of major functional importance. Knowledge of physiologic hemodynamic changes of blood Row in this vessel obtained by prenatal ultrasonography in conjunction with increasing gestational age, maternal medication, fetal growth restriction, as well as the detection of structural anomalies, may assist in clinical management of complicated pregnancies. C1 NICHHD,PERINATOL RES FACIL,INTRAMURAL DIV,NIH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,WASHINGTON,DC 20007. RP Sherer, DM (reprint author), MONTEFIORE MED CTR,ALBERT EINSTEIN COLL MED,DEPT OBSTET & GYNECOL,DIV MATERNAL FETAL MED,BRONX,NY 10461, USA. NR 50 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 1996 VL 87 IS 4 BP 630 EP 637 DI 10.1016/0029-7844(95)00484-X PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA UB873 UT WOS:A1996UB87300028 PM 8602322 ER PT J AU Waters, AP Wirth, DF Wellems, TE delPortillo, HA AF Waters, AP Wirth, DF Wellems, TE delPortillo, HA TI Transfection of malaria parasites SO PARASITOLOGY TODAY LA English DT Editorial Material C1 HARVARD UNIV,SCH PUBL HLTH,DEPT TROP PUBL HLTH,BOSTON,MA 02115. NIAID,NIH,PARASIT DIS LAB,BETHESDA,MD 20892. UNIV SAO PAULO,DEPT PARASITOL,BR-05508 SAO PAULO,BRAZIL. RP Waters, AP (reprint author), LEIDEN UNIV,DEPT PARASITOL,POSTBUS 9605,2300 RC LEIDEN,NETHERLANDS. RI Waters, Andy/C-9377-2009; del Portillo, Hernando /L-2131-2014 OI Waters, Andy/0000-0001-8900-2982; del Portillo, Hernando /0000-0002-5278-3452 NR 10 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD APR PY 1996 VL 12 IS 4 BP 129 EP 132 DI 10.1016/0169-4758(96)30002-1 PG 4 WC Parasitology SC Parasitology GA UB396 UT WOS:A1996UB39600002 ER PT J AU Domachowske, JB Rafferty, SP Singhania, N Mardiney, M Malech, HL AF Domachowske, JB Rafferty, SP Singhania, N Mardiney, M Malech, HL TI Nitric oxide post-transcriptionally alters the expression of transferrin receptor, ferritin and globin in human K562 cells. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,HOST DEF LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 44 EP 44 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800044 ER PT J AU Fisher, GH Wong, J Kim, PK Straus, SE Dale, JK Middleton, L Strober, W Lenardo, MJ Puck, JM AF Fisher, GH Wong, J Kim, PK Straus, SE Dale, JK Middleton, L Strober, W Lenardo, MJ Puck, JM TI Defective FAS mediated apoptosis in a human autoimmune lymphoproliferative syndrome SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 DUKE UNIV,SCH MED,DURHAM,NC. NIAID,NIH,BETHESDA,MD. NCHGR,NIH,BETHESDA,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 46 EP 46 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800046 ER PT J AU Liu, T Zhu, OL Blaese, RM Junker, SK Winkelstein, J Ochs, HD AF Liu, T Zhu, OL Blaese, RM Junker, SK Winkelstein, J Ochs, HD TI Splice site mutations in the Wiskott Aldrich syndrome. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UNIV WASHINGTON,DEPT PEDIAT,SEATTLE,WA 98195. NIH,CLIN GENE THERAPY BRANCH,NCHCR,BETHESDA,MD. UNIV BRITISH COLUMBIA,DEPT PEDIAT,VANCOUVER,BC V6T 1W5,CANADA. JOHNS HOPKINS UNIV,SCH MED,DEPT PEDIAT,BALTIMORE,MD 21205. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 59 EP 59 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800059 ER PT J AU Taylor, N Smith, S Isakov, J Jahn, T Puck, J Weinberg, K AF Taylor, N Smith, S Isakov, J Jahn, T Puck, J Weinberg, K TI Differential signaling through the IL-2 and IL-4 receptors in lymphocytes from patients with X-SCID: Evidence for a Y-c independent IL-4 receptor SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 CHILDRENS HOSP LOS ANGELES,DIV IMMUNOL RES,LOS ANGELES,CA 90027. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. RI Taylor, Naomi/H-4016-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 73 EP 73 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800073 ER PT J AU Trawoeger, R Kolobow, T Cereda, M Giacomini, M AF Trawoeger, R Kolobow, T Cereda, M Giacomini, M TI Mucus is not deposited within endotracheal tubes during intratracheal pulmonary ventilation (ITPV). SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NHLBI,P CCM,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 313 EP 313 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800313 ER PT J AU Green, JE Maroulakou, JG Shibata, MA Anver, M AF Green, JE Maroulakou, JG Shibata, MA Anver, M TI Heterotopic endochondral ossification associated with mixed tumor formation in C3(1)/Tag transgenic mice. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. NCI,OFF LAB ANIM SCI,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,PHL,SAIC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 340 EP 340 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800340 ER PT J AU Ramayya, MS Driggers, PH Segars, JH Chrousos, GP AF Ramayya, MS Driggers, PH Segars, JH Chrousos, GP TI Steroidogenic Factor-1 mRNA expression in human tissues: Basic and clinical implications. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 385 EP 385 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800385 ER PT J AU Mirochnick, M Sullivan, J Cort, S McNamara, J Fenton, T Sperling, R AF Mirochnick, M Sullivan, J Cort, S McNamara, J Fenton, T Sperling, R TI Safety and pharmacokinetics (PK) of nevirapine (NVP) in HIV-1 infected pregnant women and their newborns. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 BOSTON UNIV,SCH MED,DEPT PEDIAT,BOSTON,MA 02118. UNIV MASSACHUSETTS,SCH MED,DEPT PEDIAT,WORCESTER,MA. BOEHRINGER INGELHEIM PHARMACEUT INC,RIDGEFIELD,CT 06877. NIAID,BETHESDA,MD 20892. FSTRF,BROOKLINE,MA. MT SINAI MED CTR,SCH MED,DEPT OBSTET & GYNECOL,NEW YORK,NY 10029. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 444 EP 444 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800444 ER PT J AU Biesecker, LG Kang, SM Allen, JC Grebe, TA Clericuzio, CL Olney, AH Graham, JM AF Biesecker, LG Kang, SM Allen, JC Grebe, TA Clericuzio, CL Olney, AH Graham, JM TI Clinical and genetic analysis of Pallister-Hall syndrome. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,NCHGR,BETHESDA,MD. NYU,MED CTR,DEPT PEDIAT NEUROL,NEW YORK,NY 10016. UNIV NEW MEXICO,SCH MED,DEPT PEDIAT,ALBUQUERQUE,NM 87131. UNIV ARIZONA,SCH MED,DEPT PEDIAT,PHOENIX,AZ. UNIV NEBRASKA,SCH MED,DEPT PEDIAT,OMAHA,NE 68198. UNIV CALIF LOS ANGELES,CEDARS SINAI HOSP,SCH MED,DEPT PEDIAT,LOS ANGELES,CA 90048. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 470 EP 470 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800470 ER PT J AU Biesecker, LG AF Biesecker, LG TI Detection of subtle chromosomal aberrations in children with undiagnosed anomaly syndromes by STRP analysis. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,NCHGR,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 471 EP 471 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800471 ER PT J AU DeLuca, F Mancilla, EE Winer, KK Cutler, GB Baron, J AF DeLuca, F Mancilla, EE Winer, KK Cutler, GB Baron, J TI Ca2+-sensing receptor mutations in sporadic hypoparathyroidism. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 507 EP 507 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800507 ER PT J AU Furlanetto, RW Day, B Lopaczynski, W Nissley, SP AF Furlanetto, RW Day, B Lopaczynski, W Nissley, SP TI Use of the yeast two-hybrid system to investigate IGF-I signal transduction. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UNIV ROCHESTER,MED CTR,DEPT PEDIAT,ROCHESTER,MI. NCI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 516 EP 516 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800516 ER PT J AU Leschek, EW Jones, J Barnes, KM Hill, SC Cutler, GB AF Leschek, EW Jones, J Barnes, KM Hill, SC Cutler, GB TI Long-term treatment of familial male precocious puberty (FMPP) with spironolactone, testolactone, and deslorelin. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,DEV ENDOCRINOL BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 536 EP 536 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800537 ER PT J AU Ross, J Feuillan, P Long, L Cutler, G AF Ross, J Feuillan, P Long, L Cutler, G TI Appropriate bone density for height in estrogen-treated adolescent girls with Turner syndrome. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 THOMAS JEFFERSON UNIV,DEPT PEDIAT,PHILADELPHIA,PA 19107. NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 570 EP 570 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800570 ER PT J AU Stratakis, CA Aksentijevich, I Kastner, DL Carney, JA Chrousos, GP AF Stratakis, CA Aksentijevich, I Kastner, DL Carney, JA Chrousos, GP TI Carney complex: Confirmation of the chromosome 2p16 locus, exclusion of the hMSH-2, -6, & CALNB1 genes and construction of a genetic and physical map of the region SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MAYO CLIN,ROCHESTER,MN. GEORGETOWN UNIV,WASHINGTON,DC 20057. NIAMS,ARB,NIH,BETHESDA,MD 20892. NICHHD,DEB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 584 EP 584 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800584 ER PT J AU Yanovski, J Yanovski, S Cutler, G Chrousos, G Filmer, K AF Yanovski, J Yanovski, S Cutler, G Chrousos, G Filmer, K TI Differences in the hypothalamic-pituitary-adrenal (HPA) axis of black and white girls. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,DEB,NIH,BETHESDA,MD 20892. NICHHD,DDDN,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 591 EP 591 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800591 ER PT J AU Yanovski, JA Rose, SR Filmer, KM Municchi, G Pescovitz, OH Hill, SC Cassorla, FG Cutler, GB AF Yanovski, JA Rose, SR Filmer, KM Municchi, G Pescovitz, OH Hill, SC Cassorla, FG Cutler, GB TI Deslorelin-induced delay of puberty increases adult height of adolescents with short stature: Results of a randomized, placebo-controlled trial. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 2 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 592 EP 592 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800592 ER PT J AU Kercsmar, C Crain, E Mitchell, H Lynn, H Weiss, K AF Kercsmar, C Crain, E Mitchell, H Lynn, H Weiss, K TI Site-specific variation in access to health care for inner city children with asthma. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIAID,NIH,NATL COOPERAT INNER CITY ASTHMA STUDY,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 619 EP 619 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800620 ER PT J AU Klebanoff, M Read, J Clemens, J AF Klebanoff, M Read, J Clemens, J TI Maternal smoking during pregnancy and childhood cancer. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 623 EP 623 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800624 ER PT J AU Malloy, MH Berendes, H AF Malloy, MH Berendes, H TI Does Breastfeeding affect IQ at 9 and 10 years of age? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UNIV TEXAS,MED BRANCH,GALVESTON,TX 77550. NICHHD,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 635 EP 635 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800636 ER PT J AU Mitchell, H Lynn, H Crain, E Kercsmar, C Weiss, K AF Mitchell, H Lynn, H Crain, E Kercsmar, C Weiss, K TI An index of access to care for inner city children with asthma. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,NIAID,NCICAS,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 639 EP 639 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800640 ER PT J AU DeBaun, M Choyke, P AF DeBaun, M Choyke, P TI The relationship between nephromegaly and Wilms tumor in children with Beckwith Wiedemamn syndrome. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 849 EP 849 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800849 ER PT J AU Forlino, A Wang, Q Marini, JC AF Forlino, A Wang, Q Marini, JC TI Alternative splicing caused by a large deletion in COL1A1 gene is responsible for a severe case of osteogenesis imperfecta type III. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,HERITABLE DISORDER BRANCH,NIH,BETHESDA,MD 20892. RI Forlino, Antonella/H-5385-2015 OI Forlino, Antonella/0000-0002-6385-1182 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 853 EP 853 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800853 ER PT J AU Gerber, L Chaudbry, U DeBaun, MR AF Gerber, L Chaudbry, U DeBaun, MR TI Musculoskeletal abnormalities in 53 children with Beckwith Wiedemann syndrome. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 855 EP 855 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800855 ER PT J AU Grassi, G Marini, JC AF Grassi, G Marini, JC TI Hammerhead ribozymes achieve allele-specific cleavage of collagen mRNA in vitro from patients affected by osteogenesis imperfecta. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,HERITABLE DISORDERS BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 857 EP 857 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800857 ER PT J AU Kaler, SG Holmes, CS Kirshman, R Goldstein, DS AF Kaler, SG Holmes, CS Kirshman, R Goldstein, DS TI Comparison of plasma catechol levels from cord blood and infant venous blood in the neonatal diagnosis of menkes disease. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 CHILDRENS HOSP,WASHINGTON,DC. NINCDS,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 861 EP 861 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800861 ER PT J AU Kimonis, VE Goldstein, AM Pastakia, B Yang, ML Kase, R DiGiovanna, JJ Bale, AE Bale, SJ AF Kimonis, VE Goldstein, AM Pastakia, B Yang, ML Kase, R DiGiovanna, JJ Bale, AE Bale, SJ TI Clinical features in children with nevoid basal cell carcinoma syndrome. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIAMS,IRP,BETHESDA,MD. NCI,GENET EPIDEMIOL BRANCH,BETHESDA,MD 20892. NIH,CTR CLIN,WASHINGTON,DC. VET ADM MED CTR,WASHINGTON,DC. WESTAT CORP,ROCKVILLE,MD. YALE UNIV,SCH MED,NEW HAVEN,CT. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 863 EP 863 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800863 ER PT J AU Krasnewich, D Bernardini, I Rouhani, F Brantly, M Holt, G Gahl, W AF Krasnewich, D Bernardini, I Rouhani, F Brantly, M Holt, G Gahl, W TI Biochemical heterogeneity in type 1 carbohydrate-deficient glycoprotein syndrome (CDGS). SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIMH,NIH,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD 20892. NHLBI,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 864 EP 864 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800864 ER PT J AU Sidransky, E Cushner, S Tayebi, N AF Sidransky, E Cushner, S Tayebi, N TI Use of long template PCR to differentiate the glucocerebrosidase gene from pseudogene: Implications for Gaucher disease. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 870 EP 870 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800870 ER PT J AU Sonies, BC Scheib, D Cowan, B DeBaun, M AF Sonies, BC Scheib, D Cowan, B DeBaun, M TI Oral facial, speech and swallowing functioning in 56 children with Beckwith Wiedemann syndrome. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 871 EP 871 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800871 ER PT J AU Stratakis, CA Vottero, A Mitsiades, CS Abbassi, V AF Stratakis, CA Vottero, A Mitsiades, CS Abbassi, V TI Autosomal dominant inheritance of Schimd's metaphyseal chondrodysplasia: Description of a new family, and investigation of the COL10A1 gene. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 GEORGETOWN UNIV,CHILDRENS MED CTR,WASHINGTON,DC 20007. NICHHD,DEB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 874 EP 874 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800874 ER PT J AU Tayebi, N Stubblefield, BK DamschroderWilliams, P Cushner, S Lau, E Sidransky, E AF Tayebi, N Stubblefield, BK DamschroderWilliams, P Cushner, S Lau, E Sidransky, E TI Different sites of recombination between the glucocerebrosidase gene and pseudogene in patients with Gaucher disease. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIMH,CLIN NEUROSCI BRANCH,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 875 EP 875 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800875 ER PT J AU Lehmann, HP DeBaun, MR AF Lehmann, HP DeBaun, MR TI Pre-morbid bone-marrow transplant v post-stroke transfusion or BMT in patients with sickle cell disease: A decision analytic approach SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV,SCH MED,BALTIMORE,MD. NCI,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 931 EP 931 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800931 ER PT J AU Mackall, CL Gress, RE AF Mackall, CL Gress, RE TI Skewing of the T cell repertoire toward a target antigen during a period of T cell immune reconstitution. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 935 EP 935 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800935 ER PT J AU Maroulakou, IG Schindler, K Anver, M Green, JE AF Maroulakou, IG Schindler, K Anver, M Green, JE TI Hormone effects on prostate and mammary tumor progression in transgenic mice: Alterations in oncogene expression. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NCI,MOLEC ONCOL LAB,FREDERICK,MD 21702. FREDERICK CANC RES & DEV CTR,SAIC,PHL,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 938 EP 938 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800938 ER PT J AU Nicholson, HS Fears, TR Sklar, C Robison, LL Haupt, R Reaman, GH Meadows, AT Byrne, J Mills, JL AF Nicholson, HS Fears, TR Sklar, C Robison, LL Haupt, R Reaman, GH Meadows, AT Byrne, J Mills, JL TI The health status of adults treated for acute lymphoblastic leukemia (ALL) during childhood SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. NCI,BETHESDA,MD 20892. CHILDRENS CANC GRP,ARCADIA,CA. RI Haupt, Riccardo/C-2237-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 945 EP 945 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800945 ER PT J AU Stein, DT Mackall, CL Bare, CV Brown, MR Carter, CS Casey, N Yu, MY Fleisher, TA Leitman, SF Shearer, GM Wexler, L Gress, RE AF Stein, DT Mackall, CL Bare, CV Brown, MR Carter, CS Casey, N Yu, MY Fleisher, TA Leitman, SF Shearer, GM Wexler, L Gress, RE TI Impaired immune reconstitution post sequential high-dose chemotherapy and peripheral blood progenitor cell (PBPC) infusion. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NCI,DEPT TRANSFUS MED,BETHESDA,MD 20892. NIH,DEPT CLIN PATHOL,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 962 EP 962 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23800962 ER PT J AU DHeilly, SJ Sloas, MM Steinberg, SM Pizzo, PA Lewis, LL AF DHeilly, SJ Sloas, MM Steinberg, SM Pizzo, PA Lewis, LL TI The incidence and risk factors associated with transaminitis in HIV infected children. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MAYO CLIN & MAYO FDN,MAYO MED SCH,ROCHESTER,MN 55905. NCI,PEDIAT BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1001 EP 1001 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801001 ER PT J AU Greco, D Salmaso, S Mastrantonio, P Giuliano, M Giammanco, A Stefanelli, P Anemona, A Tozzi, AE Atti, MCD Panei, P Wassilak, SG AF Greco, D Salmaso, S Mastrantonio, P Giuliano, M Giammanco, A Stefanelli, P Anemona, A Tozzi, AE Atti, MCD Panei, P Wassilak, SG TI A difference in relative efficacy of two DTaP vaccines in continued blinded observation of children following a clinical trial. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 IST SUPER SANITA,I-00161 ROME,ITALY. NIAID,NIH,BETHESDA,MD 20892. RI Tozzi, Alberto Eugenio/F-9494-2012; STEFANELLI, PAOLA/B-8729-2016 OI Tozzi, Alberto Eugenio/0000-0002-6884-984X; STEFANELLI, PAOLA/0000-0003-1620-4385 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1021 EP 1021 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801021 ER PT J AU Pichichero, ME Deloria, MA Rennels, MB Anderson, EL Edwards, KM Englund, JA Decker, MD Steinhoff, MC Deforest, A Meade, BD AF Pichichero, ME Deloria, MA Rennels, MB Anderson, EL Edwards, KM Englund, JA Decker, MD Steinhoff, MC Deforest, A Meade, BD TI A comparison of whole cell DPT (DTwP) with 12 acellular pertussis vaccines (DTaP) as a booster in 15- to 20-month-old children. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 UNIV ROCHESTER,ROCHESTER,NY. NIAID,BETHESDA,MD 20892. UNIV MARYLAND,BALTIMORE,MD 21201. ST LOUIS UNIV,ST LOUIS,MO 63103. VANDERBILT UNIV,NASHVILLE,TN. BAYLOR UNIV,HOUSTON,TX 77030. JOHNS HOPKINS UNIV,BALTIMORE,MD. TEMPLE UNIV,PHILADELPHIA,PA 19122. US FDA,BETHESDA,MD 20014. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1075 EP 1075 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801075 ER PT J AU Pikis, A Keith, JM Rodriquez, WJ Donkersloot, JA AF Pikis, A Keith, JM Rodriquez, WJ Donkersloot, JA TI Molecular mechanism of trimethoprim (TMP) resistance in Streptococcus pneumoniae. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIDR,MICROBIAL ECOL LAB,NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT INFECT DIS,WASHINGTON,DC 20010. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1078 EP 1078 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801078 ER PT J AU Zeichner, SL Dimitrov, DS Mueller, BU Pizzo, PA AF Zeichner, SL Dimitrov, DS Mueller, BU Pizzo, PA TI Oscillations of HIV-1 RNA in pediatric patients: Implications for pathogenesis and therapy. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NCI,PEDIAT BRANCH,NIH,BETHESDA,MD 20892. NCI,MATH BIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1117 EP 1117 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801117 ER PT J AU Donovan, EF Ehrenkranz, RA Tyson, JE Wright, LL Verter, JI AF Donovan, EF Ehrenkranz, RA Tyson, JE Wright, LL Verter, JI TI Inaccuracy of Ballard scores in estimating gestational age (GA) of 24-27 weeks infants of women with known menstrual history. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1219 EP 1219 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801219 ER PT J AU Donovan, EF Fanaroff, AA Ehrenkranz, RA Shankaran, S Stevenson, DK Stoll, BJ Wright, LL Verter, JI Younes, N AF Donovan, EF Fanaroff, AA Ehrenkranz, RA Shankaran, S Stevenson, DK Stoll, BJ Wright, LL Verter, JI Younes, N TI Outcomes of 24 to 27 week twins cared for in neonatal intensive care units. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1220 EP 1220 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801220 ER PT J AU Ehrenkranz, RA Younes, N Fanaroff, AA Donovan, EF Lemons, JA Wright, LL Verter, JI AF Ehrenkranz, RA Younes, N Fanaroff, AA Donovan, EF Lemons, JA Wright, LL Verter, JI TI Velocity growth curves for VLBW infants. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1224 EP 1224 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801224 ER PT J AU Lemons, J STevenson, D Verter, J Bauer, C Papile, LA Korones, S Stoll, B Oh, W Wright, L AF Lemons, J STevenson, D Verter, J Bauer, C Papile, LA Korones, S Stoll, B Oh, W Wright, L TI In utero magnesium exposure: Risk of death and of intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1336 EP 1336 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801337 ER PT J AU Martin, RJ AF Martin, RJ TI Risk of prematurity and neonatal respiratory disease associated with maternal HIV infection. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NHLBI,PEDIAT PULM & CARDIOVASC COMPLICAT VERTICALLY TRA,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1354 EP 1354 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801355 ER PT J AU Oh, W Fanaroff, AA Verter, J Stevenson, DK Papile, LA Stoll, BJ Lemons, JS Bauer, CR Wright, LL AF Oh, W Fanaroff, AA Verter, J Stevenson, DK Papile, LA Stoll, BJ Lemons, JS Bauer, CR Wright, LL TI Neonatal mortality and morbidities in very low birth weight (VLBW) infants: A seven-year trend analysis of the Neonatal Research Network Data. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1392 EP 1392 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801393 ER PT J AU Papile, LA Stoll, B Donovan, E Tyson, J Bauer, C Wright, L KrauseSteinrauf, H Verter, J AF Papile, LA Stoll, B Donovan, E Tyson, J Bauer, C Wright, L KrauseSteinrauf, H Verter, J TI Dexamethasone therapy in infants at risk for chronic lung disease (CLD): A multi-center, randomized, double-masked trial. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1399 EP 1399 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801400 ER PT J AU Shankaran, S Papile, LA Wright, LL Ehrenkranz, R Verter, J Mele, L AF Shankaran, S Papile, LA Wright, LL Ehrenkranz, R Verter, J Mele, L TI Does antenatal phenobarbital prevent neonatal intracranial hemorrhage in preterm infants? Randomized controlled trial. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 3 Z9 2 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1452 EP 1452 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801453 ER PT J AU Taylor, GA Seibert, JJ DiPietro, MA Wright, LL Verter, J Melee, L Shankaran, S Papile, LA Ehrenkranz, RA AF Taylor, GA Seibert, JJ DiPietro, MA Wright, LL Verter, J Melee, L Shankaran, S Papile, LA Ehrenkranz, RA TI Effect of local versus central reading and image quality on sonographic diagnosis of intracranial hemorrhage. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1481 EP 1481 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801482 ER PT J AU Wright, LL Merenstein, GB Goldenberg, RL Cliver, SP Rowe, M AF Wright, LL Merenstein, GB Goldenberg, RL Cliver, SP Rowe, M TI Impact of the NIH consensus development conference on corticosteroids for fetal maturation: Change in obstetric attitudes. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,BETHESDA,MD 20892. UNIV COLORADO,DENVER,CO 80202. UNIV ALABAMA,BIRMINGHAM,AL. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1506 EP 1506 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801507 ER PT J AU Wright, LL Verter, J Stevenson, DK Korones, SA Bauer, CR Oh, W Papile, LA Tyson, J Lemons, JA Stoll, B AF Wright, LL Verter, J Stevenson, DK Korones, SA Bauer, CR Oh, W Papile, LA Tyson, J Lemons, JA Stoll, B TI Impact of the NIH consensus development conference on corticosteroids for fetal maturation: Increased antenatal steroid use in NICHD network VLBW infants. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1507 EP 1507 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801508 ER PT J AU Bada, HS Bauer, CR Shankaran, S Lester, B Wright, LL Smeriglio, VL Finnegan, LP Maza, PL Verter, J AF Bada, HS Bauer, CR Shankaran, S Lester, B Wright, LL Smeriglio, VL Finnegan, LP Maza, PL Verter, J TI Maternal lifestyle study (MLS): Central and autonomic nervous systems (CNS/ANS) signs associated with in utero exposure to cocaine/opiates (C/O). SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,NIDA,CSAT,ACYF,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1523 EP 1523 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801523 ER PT J AU Bada, HS Verter, J Bauer, CR Shankaran, S Lester, B Wright, LL Smeriglio, VL Finnegan, LP Maza, PL AF Bada, HS Verter, J Bauer, CR Shankaran, S Lester, B Wright, LL Smeriglio, VL Finnegan, LP Maza, PL TI Maternal lifestyle study (MCS): Intrauterine growth of infants exposed to cocaine/opiates (C/O) in utero. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,NIDA,CSAT,ACYF,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1524 EP 1524 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801524 ER PT J AU Bauer, CR Shankaran, S Bada, HS Lester, B Wright, LL KrauseSteinrauf, H Smeriglio, VL Finnegan, LP Maza, PL Verter, J AF Bauer, CR Shankaran, S Bada, HS Lester, B Wright, LL KrauseSteinrauf, H Smeriglio, VL Finnegan, LP Maza, PL Verter, J TI Maternal lifestyles study (MLS): Effects of substance exposure during pregnancy on acute maternal outcomes. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,NIDA,ACYF,CSAT,BETHESDA,MD 20892. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1527 EP 1527 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801527 ER PT J AU Bauer, CR Shankaran, S Bada, HS Lester, B Wright, LL KrauseSteinrauf, H Smeriglio, VL Finnegan, LP Maza, PL Verter, J AF Bauer, CR Shankaran, S Bada, HS Lester, B Wright, LL KrauseSteinrauf, H Smeriglio, VL Finnegan, LP Maza, PL Verter, J TI Maternal lifestyles study (MLS): The effects of substance exposure during pregnancy on acute infant outcomes. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,NIDA,ACYF,CSAT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1528 EP 1528 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801528 ER PT J AU ElMohandes, AAE Katz, K Abedin, M ElKhorazaty, NM Herman, A AF ElMohandes, AAE Katz, K Abedin, M ElKhorazaty, NM Herman, A TI Substance abuse is a significant marker for perinatal morbidity in a population of women with poor prenatal care in Washington DC SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 GEORGETOWN UNIV,NEWBORN SERV,WASHINGTON,DC 20057. GEORGETOWN UNIV,DEPT PEDIAT,WASHINGTON,DC 20057. DIST COLUMBIA GEN HOSP,DEPT PEDIAT,WASHINGTON,DC 20057. RES TRIANGLE INST,WASHINGTON,DC. NICHHD,ROCKVILLE,MD. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1560 EP 1560 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801560 ER PT J AU Lester, B Tronick, EZ LaGasse, LL Seifer, R Mayes, L Wright, LL Smeriglio, VL Bauer, CR Shankaran, S Bada, HS Katsikiotis, V AF Lester, B Tronick, EZ LaGasse, LL Seifer, R Mayes, L Wright, LL Smeriglio, VL Bauer, CR Shankaran, S Bada, HS Katsikiotis, V TI The maternal lifestyles study (MLS): Cocaine/opiate exposure and 1 month neurobehavioral outcome. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NIDA,ACYF,CSAT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1610 EP 1610 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801610 ER PT J AU Lester, BM ElSohly, M Walls, C Wright, LL Smeriglio, VL Bauer, CR Shankaran, S Bada, HS Verter, J AF Lester, BM ElSohly, M Walls, C Wright, LL Smeriglio, VL Bauer, CR Shankaran, S Bada, HS Verter, J TI The maternal lifestyles study (MLS): Meconium toxicology assay, what does it add? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NIDA,ACYF,CSAT,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1611 EP 1611 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801611 ER PT J AU Maza, PL Wright, LL Bauer, CR Shankaran, S Bada, HS Lester, B KrauseSteinrauf, H Smeriglio, VL Bowler, A Katsikiotis, V AF Maza, PL Wright, LL Bauer, CR Shankaran, S Bada, HS Lester, B KrauseSteinrauf, H Smeriglio, VL Bowler, A Katsikiotis, V TI Maternal lifestyles study (MLS): Caretaking environment and stability of substance-exposed infants at one-month corrected age. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,ACYF,NIDA,CSAT,BETHESDA,MD 20892. NICHHD,ACYF,NIDA,CSAT,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1620 EP 1620 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801620 ER PT J AU Shankaran, S Bauer, CR Bada, HS Lester, B Wright, LL Katsikiotis, V AF Shankaran, S Bauer, CR Bada, HS Lester, B Wright, LL Katsikiotis, V TI Maternal lifestyles study: Patterns of cocaine use in term pregnancy and effect on birthweight. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1660 EP 1660 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801661 ER PT J AU Shankaran, S Bauer, CR Bada, HS Lester, B Wright, LL Verter, J AF Shankaran, S Bauer, CR Bada, HS Lester, B Wright, LL Verter, J TI Maternal lifestyles study (MLS): Health care resource utilization following cocaine/opiate exposure. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1661 EP 1661 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801662 ER PT J AU Wright, LL Bauer, CR Shankaran, S Bada, HS Lester, B Katsikiotis, V Smeriglio, VL Finnegan, LP Maza, P KrauseSteinrauf, H AF Wright, LL Bauer, CR Shankaran, S Bada, HS Lester, B Katsikiotis, V Smeriglio, VL Finnegan, LP Maza, P KrauseSteinrauf, H TI Maternal lifestyles study (MLS): Health status of substance exposed infants at one-month corrected age. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NIDA,CSAT,ACYF,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1692 EP 1692 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801693 ER PT J AU Ehrenkranz, RA Younes, N Fanaroff, AA Donovan, EF Lemon, JA Wright, LL Verter, JI AF Ehrenkranz, RA Younes, N Fanaroff, AA Donovan, EF Lemon, JA Wright, LL Verter, JI TI Effect of nutritional practices on daily weight gain in VLBW infants. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1834 EP 1834 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801834 ER PT J AU Lemons, J Stevenson, D Vreman, H Oh, W FAnaroff, A Mele, L Wright, L AF Lemons, J Stevenson, D Vreman, H Oh, W FAnaroff, A Mele, L Wright, L TI Serum bilirubin, bilirubin production and weight loss in breast-fed only or formula-fed only well term infants. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 1871 EP 1871 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23801871 ER PT J AU Sokol, GM VanMeurs, KP Thorn, WT Rivera, O Wright, LL Sams, RL AF Sokol, GM VanMeurs, KP Thorn, WT Rivera, O Wright, LL Sams, RL TI Nitrogen dioxide kinetics in a neonatal continuous flow ventilatory circuit. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NATL INST STAND & TECHNOL,NICHD,NEONATAL RES NETWORK,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 2084 EP 2084 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23802083 ER PT J AU VanMeurs, KP Sokol, GM Wright, LL Rivera, O Thom, WJ AF VanMeurs, KP Sokol, GM Wright, LL Rivera, O Thom, WJ TI Minimizing nitrogen dioxide exposure during inhaled nitric oxide therapy. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NICHHD,NEONATAL RES NETWORK,BETHESDA,MD 20892. NATL INST STAND & TECHNOL,BOULDER,CO 80303. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 2105 EP 2105 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23802104 ER PT J AU Velarde, CA Short, BL Rivera, O Seale, W Kolobow, T AF Velarde, CA Short, BL Rivera, O Seale, W Kolobow, T TI A comparison of intratracheal pulmonary ventilation (ITPV) to conventional ventilation on a surfactant deficient animal model. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NIH,BETHESDA,MD 20892. CHILDRENS NATL MED CTR,DEPT NEONATOL,WASHINGTON,DC. CHILDRENS NATL MED CTR,DEPT BIOMED ENGN,WASHINGTON,DC. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 2106 EP 2106 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23802105 ER PT J AU Ray, PE Saavedra, JM AF Ray, PE Saavedra, JM TI Activation of brain ANP receptors during chronic ECF volume contraction in young rats. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 CHILDREN RES INST,CTR I,WASHINGTON,DC. NIMH,LAB CLIN PHARMACOL,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 2192 EP 2192 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23802191 ER PT J AU Schnaper, HW Hubchak, SC Kopp, JB AF Schnaper, HW Hubchak, SC Kopp, JB TI Characterization of a mesangial cell phenotype associated with extracellular matrix (ECM) accumulation. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 NORTHWESTERN UNIV,SCH MED,DEPT PEDIAT,DIV RENAL,CHICAGO,IL 60611. NIDDKD,METAB DIS BRANCH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 2197 EP 2197 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23802196 ER PT J AU McCune, SK Hill, JM Hurn, PD AF McCune, SK Hill, JM Hurn, PD TI Alpha-1 adrenergic receptor mRNA expression in the rat CNS after focal ischemia. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 JOHNS HOPKINS UNIV HOSP,DIV NEONATOL,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV HOSP,DIV ANESTHESIA & CRIT CARE MED,BALTIMORE,MD 21205. NICHHD,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 1996 VL 39 IS 4 BP 2246 EP 2246 PN 2 PG 1 WC Pediatrics SC Pediatrics GA UD238 UT WOS:A1996UD23802246 ER PT J AU Popik, P Skolnick, P AF Popik, P Skolnick, P TI The NMDA antagonist memantine blocks the expression and maintenance of morphine dependence SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE NMDA receptor antagonists; morphine; dependence; addiction; withdrawal; memantine; NPC 17742; glycine ID ASPARTATE RECEPTOR ANTAGONIST; INDUCED HYPERACTIVITY; PARKINSONS-DISEASE; OPIATE WITHDRAWAL; D-SERINE; TOLERANCE; RATS; PHENCYCLIDINE; MK-801; GLYCINE AB The ability of memantine (1-amino-3,5-dimethyladamantane) to block the expression and maintenance of morphine dependence was examined in mice. When administered to morphine-dependent mice 45 min prior to naloxone challenge, memantine (7.5-30 mg/kg IP) in a dose-dependent manner reduced jumping behavior (a manifestation of the expression of dependence). The ability of memantine to attenuate naloxone-precipitated jumping was reversed by administration of glycine, an observation consistent with electrophysiological studies indicating that memantine is a use-dependent (uncompetitive) N-methyl-D-aspartate (NMDA) antagonist. In an independent series of experiments, the effect of memantine on a preestablished morphine dependence was investigated. A residual dependence to morphine was present 3 days after cessation of morphine administration. Repeated administration of memantine (10 mg/kg, IP) or the competitive NMDA antagonist NPC 17742 [2R,4R,5S-(2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid)] (6 mg/kg, IP) during this 3-day period abolished subsequent naloxone-precipitated jumping. In contrast, when administered concurrently with morphine after dependence had already been well established, memantine (10 and 20 mg/kg, IP) did not affect the maintenance of morphine dependence. Based on these findings, NMDA antagonists appear to inhibit the maintenance of opioid dependence, an action distinct from their acute inhibitory effects on the expression of dependence. Nonetheless, these regimen-dependent effects of memantine indicate that the most efficacious use of NMDA antagonists would be in detoxified subjects, rather than in individuals with an established dependence who are currently abusing opioids. C1 NIDDK,NATL INST HLTH,NEUROSCI LAB,BETHESDA,MD 20892. RP Popik, P (reprint author), POLISH ACAD SCI,INST PHARMACOL,SMETNA 12,PL-31343 KRAKOW,POLAND. RI Popik, Piotr/R-5383-2016 OI Popik, Piotr/0000-0003-0722-1263 NR 57 TC 82 Z9 82 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD APR PY 1996 VL 53 IS 4 BP 791 EP 797 DI 10.1016/0091-3057(95)02163-9 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA UC055 UT WOS:A1996UC05500006 PM 8801580 ER PT J AU Elmer, GI Brockington, A Gorelick, DA Carrol, FI Rice, KC Matecka, D Goldberg, SR Rothman, RB AF Elmer, GI Brockington, A Gorelick, DA Carrol, FI Rice, KC Matecka, D Goldberg, SR Rothman, RB TI Cocaine cross-sensitization to dopamine uptake inhibitors: Unique effects of GBR12909 SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE sensitization; cocaine; mazindol; RTI-55; GBR12909 ID DISCRIMINATIVE STIMULUS PROPERTIES; BEHAVIORAL SENSITIZATION; AMPHETAMINE; MORPHINE; APOMORPHINE; INJECTIONS; ADDICTION; MONKEYS; CONTEXT AB Repeated administration of cocaine will cross-sensitize the locomotor response to a variety of psychomotor stimulants. The ability of cocaine to cross-sensitize the locomotor effects of other psychomotor stimulants provides information relevant to the pharmacological mechanisms underlying the sensitization process. The purpose of the current experiment was to investigate the ability of cocaine to cross-sensitize the locomotor effects of several dopamine uptake blockers with unique pharmacological profiles. Cocaine (40 mg/kg, IP) or saline was administered prior to a locomotor session on day one. On day 2, a full dose-effect curve was established for the locomotor effects of cocaine, RTI-55, mazindol, and GBR12909. Previous exposure to Cocaine significantly affected locomotor activity and stereotopy-like behavior produced by cocaine, mazindol, RTI-55, and GBR12909. However, GBR12909 was unique in that the maximal stimulant effect and slope of the dose-effect curve was significantly depressed and the stereotopy-like behavior was unchanged. Thus, despite the similarity of these compounds in their ability to inhibit dopamine uptake, cocaine-induced sensitization did not generalize to GBR12909. This study further demonstrates the unique pharmacology of GBR12909 and supports the further study of this compound as a potential treatment medication for cocaine abuse. C1 NIAID,CLIN PSYCHOPHARMACOL SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. NIAID,BEHAV PHARMACOL & GENET SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. NIAID,PHARMACOTHERAPY SECT,DIV INTRAMURAL RES,NIH,BALTIMORE,MD 21224. NIDDK,MED CHEM LAB,NIH,BETHESDA,MD 20892. NR 38 TC 26 Z9 26 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD APR PY 1996 VL 53 IS 4 BP 911 EP 918 DI 10.1016/0091-3057(95)02143-4 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA UC055 UT WOS:A1996UC05500023 PM 8801597 ER PT J AU Paruszewski, R RostafinskaSuchar, G Strupinska, M Jaworski, P Winiecka, I Stables, JP AF Paruszewski, R RostafinskaSuchar, G Strupinska, M Jaworski, P Winiecka, I Stables, JP TI Synthesis and anticonvulsant activity of some amino acid derivatives .2. Derivatives of Gly, Ala, Leu, Pro, Trp, Phe(4 Cl), Ala(alpha-Me)(3) SO PHARMAZIE LA English DT Article AB Fourteen amides of N-substituted natural and anatural amino acids have been designed and synthesized as potential anticonvulsants. They were evaluated in the maximal electroshock seizure (MES) test, the subcutaneous Metrazol seizure threshold (sc Met) test and the rotorod neurotoxicity (Tox) test. According to the classification of the Anticonvulsant Screening Project (ASP) of the Antiepileptic Drug Development Program (ADDP) eight of synthesized compounds received class I, two class II and four class III. One of the compounds classified in class I (18) was tested quantitatively after i.p. administration in mice. It showed MES ED(50) = 67.41 mg/kg and protective index (PI) = 4.5. Conformational models of the synthesized compounds were compared to one another, as well as to models of some standard compounds. C1 MED UNIV WARSAW,DEPT PHARMACEUT CHEM,WARSAW,POLAND. NINCDS,DIV CONVULS DEV & NEUROMUSCULAR DISORDERS,NIH,BETHESDA,MD 20892. NR 7 TC 16 Z9 17 U1 0 U2 2 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD APR PY 1996 VL 51 IS 4 BP 212 EP 215 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA UF469 UT WOS:A1996UF46900003 PM 8628738 ER PT J AU Kraemer, KH AF Kraemer, KH TI Lessons learned from xeroderma pigmentosum SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID SHUTTLE VECTOR PLASMID; SKIN-CANCER; DNA-REPAIR; P53 GENE; CELLS; MUTATIONS; FREQUENCY; SPECTRUM; SUNLIGHT; PATIENT RP Kraemer, KH (reprint author), NCI,MOLEC CARCINOGENESIS LAB,BLDG 37,BETHESDA,MD 20892, USA. FU Intramural NIH HHS [Z01 BC004517-31] NR 19 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 1996 VL 63 IS 4 BP 420 EP 422 DI 10.1111/j.1751-1097.1996.tb03060.x PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE400 UT WOS:A1996UE40000021 PM 8934754 ER PT J AU Rothstein, J Kelly, SP McGarvey, C May, BJ Mueller, MJ AF Rothstein, J Kelly, SP McGarvey, C May, BJ Mueller, MJ TI The influence of lower-extremity muscle force on gait characteristics in individuals with below-knee amputations secondary to vascular disease - Conference SO PHYSICAL THERAPY LA English DT Editorial Material C1 NIH,CTR CLIN,BETHESDA,MD 20892. MED COLL GEORGIA,DEPT PHYS THERAPY,AUGUSTA,GA 30912. PHYSIOTHERAPY INT PC,ATLANTA,GA. WASHINGTON UNIV,PROGRAM PHYS THERAPY,ST LOUIS,MO 63110. PHYS MED ASSOCIATES,INDIANAPOLIS,IN 46224. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYS THER ASSN PI ALEXANDRIA PA 1111 N FAIRFAX ST, ALEXANDRIA, VA 22314 SN 0031-9023 J9 PHYS THER JI Phys. Ther. PD APR PY 1996 VL 76 IS 4 BP 378 EP 385 PG 8 WC Orthopedics; Rehabilitation SC Orthopedics; Rehabilitation GA UG654 UT WOS:A1996UG65400007 ER PT J AU Anderson, DE Fedorova, OV French, AW AF Anderson, DE Fedorova, OV French, AW TI Preavoidance hypercapnia and decreased hematocrit in micropigs SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE behavior; blood pressure; pCO(2); potassium; respiration; sodium AB Previous studies found that regular confinement of dogs in an experimental environment preceding onset of an avoidance task was associated with increases in blood pressure and decreases in heart rate and respiration rate that were not prevented by adrenergic antagonists. The present study investigated a) whether divergent changes in blood pressure and heart rate also occur in micropigs preceding onset of an avoidance task, and b) the nature of changes in blood gases, plasma pH, plasma bicarbonate, hematocrit, and plasma electrolytes observed under these conditions. Blood pressure increased and heart rate decreased during 2-h preavoidance periods, whereas both blood pressure and heart rate were elevated during 20-min avoidance periods. During preavoidance periods, pO(2) plasma pH, and plasma potassium pCO(2) were decreased below home kennel levels during early preavoidance, whereas pCO, and plasma bicarbonate were persistently increased and hematocrit was persistently decreased for the duration of the preavoidance periods. Each of these changes was reversed during the avoidance sessions. These findings suggest that behaviorally induced hypercapnia might participate in blood pressure regulation via increased renal sodium/hydrogen exchange and renal sodium retention. C1 NIA,GERONTOL RES CTR,RES RESOURCES BRANCH,BALTIMORE,MD 21224. RP Anderson, DE (reprint author), NIA,GERONTOL RES CTR,BEHAV SCI LAB,4940 EASTERN AVE,BALTIMORE,MD 21224, USA. NR 19 TC 9 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0031-9384 J9 PHYSIOL BEHAV JI Physiol. Behav. PD APR-MAY PY 1996 VL 59 IS 4-5 BP 857 EP 861 DI 10.1016/0031-9384(95)02165-5 PG 5 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA UC955 UT WOS:A1996UC95500040 PM 8778877 ER PT J AU Mcmurtry, JP Richards, MP Brocht, DM Schoen, T Waldbillig, R AF Mcmurtry, JP Richards, MP Brocht, DM Schoen, T Waldbillig, R TI Developmental changes in serum insulin-like growth factor-I and insulin-like growth factor binding proteins in the turkey embryo SO POULTRY SCIENCE LA English DT Article DE growth; poultry; insulin; ligand ID SHELL-LESS CULTURE; CHICKEN; ACID AB The ontogeny of insulin-like growth factor-I (IGF-I) and ontogeny as well as the molecular nature of the insulin-like growth factor binding proteins (IGFBP) as they relate to embryogenesis and posthatch growth in the turkey have not been reported. In this study, serum samples were harvested from turkey embryos incubated under shell-less and shelled conditions from Day 12 to 28 of incubation. Samples from 3, 6, and 8 wk posthatch were also evaluated. Significant changes in serum IGF-I in shelled embryos were observed in that IGF-I was low in early incubation, peaked at mid-incubation, and returned to levels equivalent to early incubation at hatching. No mid-embryogenesis (Days 14 to 18) increase in serum IGF-I was noted in the shell-less cultures. Embryo weights diverge at Day 18 of incubation, with shell-less embryos being significantly lighter than their age-matched shelled embryos, suggesting a possible relationship between total circulating IGF-I and body weight gain. Three distinct IGFBP were identified in serum from turkey embryos, exhibiting molecular weights of 27, 29, and 69 kDa. During embryonic development, the 29 kDa IGFBP appeared to be the predominant species, with levels peaking on Day 24 of incubation, and being minimally detectable at hatching. Ontogeny of the 29 kDa IGFBP was similar in the shelled and shell-less embryos. The 69-kDa IGFBP-Like protein did not appear in the circulation until late in embryogenesis, Day 22 in shell-less and Day 26 in shelled embryos. The 27-kDa IGFBP appeared in late incubation. Similar IGFBP (28, 30, and 69 kDa) were observed in the growing male turkey. The 69-kDa protein did not vary across ages studied, whereas the 28-kDa IGFBP appeared to increase with age. This is the first report describing serum IGF-I and IGFBP in the developing turkey. Turkey IGFBP appear to be regulated by independent events during incubation and posthatch growth. C1 NEI,NIH,RETINAL CELL & MOLEC BIOL LAB,BETHESDA,MD 20892. RP Mcmurtry, JP (reprint author), ARS,USDA,GROWTH BIOL LAB,BELTSVILLE,MD 20705, USA. NR 26 TC 14 Z9 14 U1 0 U2 1 PU POULTRY SCIENCE ASSN INC PI CHAMPAIGN PA 309 W CLARK ST, CHAMPAIGN, IL 61802 SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD APR PY 1996 VL 75 IS 4 BP 563 EP 569 PG 7 WC Agriculture, Dairy & Animal Science SC Agriculture GA UE391 UT WOS:A1996UE39100020 PM 8786950 ER PT J AU Christian, SL Smith, ACM Macha, M Black, SH Elder, FFB Johnson, JMP Resta, RG Surti, U Suslak, L Verp, MS Ledbetter, DH AF Christian, SL Smith, ACM Macha, M Black, SH Elder, FFB Johnson, JMP Resta, RG Surti, U Suslak, L Verp, MS Ledbetter, DH TI Prenatal diagnosis of uniparental disomy 15 following trisomy 15 mosaicism SO PRENATAL DIAGNOSIS LA English DT Article DE Prader-Willi syndrome; uniparental disomy 15; prenatal diagnosis; trisomy 15 mosaicism; advanced maternal age; confined placental mosaicism ID PRADER-WILLI SYNDROME; MOLECULAR DIAGNOSIS; ANGELMAN AB Maternal uniparental disomy 15 (UPD15), responsible for approximately 25 per cent of Prader-Willi syndrome cases, is usually caused by maternal meiosis I non-disjunction associated with advanced maternal age. These cases may initially be detected as mosaic trisomy 15 during routine prenatal,diagnostic studies. In such cases, PCR (polymerase chain reaction) microsatellite analysis of uncultured cells makes prospective prenatal diagnosis for UPD15 possible with results available in 2-4 days. We have performed molecular analyses on a series of seven cases of mosaic trisomy 15 identified in amniotic fluid (AF, n=3) or chorionic villus samples (CVS, n=4) from patients initially referred for advanced maternal age or abnormal triple screen. In all cases, the maternal ages were greater than or equal to 35 years and maternal meiosis I non-disjunction was documented as the cause of the trisomy in all informative cases (n=5). Of the three cases with mosaic trisomy 15 at amniocentesis, two showed the presence of the trisomy in the fetus. Molecular analysis showed one case with maternal UPD15 in the euploid cell, line and one case with biparental inheritance. Both of these families elected to terminate the pregnancies based on the presence of true fetal mosaicism. In the third case, low-level trisomy 15 mosaicism in the amniotic fluid was not confirmed in a follow-up amniotic fluid sample and molecular analysis indicated biparental inheritance in the fetus. For the four trisomy 15 mosaics detected at CVS, molecular analysis was performed on direct amniotic fluid cell lysates for prospective diagnosis of UPD at 14-16 weeks' gestation. Follow-up cytogenetic analysis of the amniotic fluid in all four cases was normal, indicating confirmed placental mosaicism. Molecular analysis showed one of these four cases to have maternal heterodisomy 15. Based on the likelihood of Prader-Willi syndrome due to maternal UPD15, the couple chose to terminate the pregnancy. The total of two of seven cases of trisomy 15 mosaicism resulting in UPD15 is consistent with the theoretical expectation of one-third and indicates a high risk of UPD in such pregnancies. Therefore, UPD testing should be offered in all cases of mosaic trisomy 15 encountered in CVS dr amniocentesis. C1 NIH,NATL CTR HUMAN GENOME RES,DIAGNOST DEV BRANCH,BETHESDA,MD 20892. GEORGETOWN UNIV,MED CTR,DEPT OBSTET & GYNECOL,WASHINGTON,DC 20007. GENET & IVF INST,FAIRFAX,VA 22039. UNIV TEXAS,SCH MED,DEPT PATHOL,HOUSTON,TX 77030. WAYNE STATE UNIV,HUTZEL HOSP,DIV REPROD GENET,DETROIT,MI. SWEDISH MED CTR,CTR PERINATAL STUDIES,SEATTLE,WA. MAGEE WOMENS HOSP,DEPT GENET,PITTSBURGH,PA. UNIV MED & DENT NEW JERSEY,NEW JERSEY MED SCH,CTR HUMAN & MOLEC GENET,NEWARK,NJ 07103. UNIV CHICAGO,DEPT OBSTET & GYNECOL,CHICAGO,IL 60637. OI Resta, Robert/0000-0001-7120-0673 NR 32 TC 44 Z9 44 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX, ENGLAND PO19 1UD SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD APR PY 1996 VL 16 IS 4 BP 323 EP 332 DI 10.1002/(SICI)1097-0223(199604)16:4<323::AID-PD856>3.3.CO;2-X PG 10 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA UL506 UT WOS:A1996UL50600006 PM 8734806 ER PT J AU Unser, M Aldroubi, A AF Unser, M Aldroubi, A TI A review of wavelets in biomedical applications SO PROCEEDINGS OF THE IEEE LA English DT Review ID ORTHONORMAL BASES; TRANSFORM; MULTIRESOLUTION; IMAGES; COMPRESSION; DISCRETE; SIGNALS; CORTEX AB In this paper we present an overview of the various uses of the wavelet transform (WT) in medicine and biology. We start by describing the wavelet properties that are the most important for biomedical applications. In particular, we provide an interpretation of the continuous wavelet transform (CWT) as a prewhitening multiscale matched filter. Me also briefly indicate the analogy between the WT and some of the biological processing that occurs in the early components of the auditory and visual system. We then review the rises of the WT for the analysis of 1-D physiological signals obtained by phonocardiography, electrocardiography (ECC), and electroencephalography (EEG), including evoked response Next, we provide a survey of recent wavelet developments in medical imaging. These include biomedical image processing algorithms (e.g., noise reduction, image enhancement, and detection of microcalcifications in mammograms), image reconstruction and acquisition schemes (tomography, and magnetic resonance imaging (MRI)), and multiresolution methods for the registration and statistical analysis of functional images of the brain (positron emission tomography (PET) and functional MRI (fMRI)). In each case, we provide the reader with some general background information and a brief explanation of how the methods work. RP NIH, NATL CTR RES RESOURCES, BIOMED ENGN & INSTRUMENTAT PROGRAM, BETHESDA, MD 20892 USA. RI Unser, Michael/A-1550-2008; Aldroubi, Akram/J-7186-2012 NR 115 TC 368 Z9 389 U1 3 U2 49 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9219 EI 1558-2256 J9 P IEEE JI Proc. IEEE PD APR PY 1996 VL 84 IS 4 BP 626 EP 638 DI 10.1109/5.488704 PG 13 WC Engineering, Electrical & Electronic SC Engineering GA UD746 UT WOS:A1996UD74600010 ER PT J AU Grobler, JA Hurley, JH AF Grobler, JA Hurley, JH TI Expression, characterization, and crystallization of the catalytic core of rat phosphatidylinositide-specific phospholipase C delta(1) SO PROTEIN SCIENCE LA English DT Article DE CD spectra; crystallization; expression and purification; kinetics; phosphatidylinositol-specific phospholipase C ID PROTEINS; ISOZYMES; FORMS; GQ AB Phosphatidylinositide-specific phospholipase Cs (PI-PLCs) catalyze the calcium-dependent hydrolysis of phosphatidylinositides in response to diverse stimuli in higher eukaryotes. Mammalian PI-PLCs contain divergent regulatory regions, but all share three conserved regions: an N-terminal pleckstrin homology (PH) domain, X, and Y. We report the high-level expression and characterization of a recombinant ''catalytic core'' of rat PI-PLC delta(1) that contains the catalytically essential X and Y regions, but not the PH domain. The expressed protein, PI-PLC delta(Delta 1-134), is catalytically active versus phosphatidylinositol 4,5-bisphosphate in deoxycholate micelles with a K-m of 182 mu M and a V-max of 27 mu mol/min/mg. PI-PLC delta(Delta 1-134) is monomeric and monodisperse as judged by dynamic light scattering. Far-UV CD indicates a structure with approximately 35% alpha-helix. A reversible change in the near-UV CD spectrum is observed on addition of calcium, suggesting that calcium can bind PI-PLC delta(Delta 1-134) in the absence of phospholipid. Triclinic crystals of PI-PLC delta(Delta 1-134) have been obtained that diffract beyond 2.4 Angstrom resolution under cryogenic conditions. Based on V-m = 2.72 Da/Angstrom(3) and on the self-rotation function, there are two PI-PLC delta(Delta 1-134) molecules per asymmetric unit that are related to each other by a noncrystallographic axis of approximate twofold symmetry parallel to a. C1 NIDDKD, MOLEC BIOL LAB, NIH, BETHESDA, MD 20892 USA. NR 27 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0961-8368 EI 1469-896X J9 PROTEIN SCI JI Protein Sci. PD APR PY 1996 VL 5 IS 4 BP 680 EP 686 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UD304 UT WOS:A1996UD30400012 PM 8845757 ER PT J AU Schulkin, J AF Schulkin, J TI Pragmatism and the cognitive and neural sciences SO PSYCHOLOGICAL REPORTS LA English DT Article ID PHYSIOLOGICAL-PSYCHOLOGY AB Two prominent intellectual disciplines dominate the discipline of psychology, the cognitive and neural sciences. Separate departments for both are now commonplace at major universities across America. I suggest, however, that the discipline of psychology asks key questions about experience, mind, or central stales not found in other disciplines. Psychology is embodied in both the cognitive and neural sciences, and an important common thread is the Jamesian-Deweyian emphasis on experience. The Jamesian-Deweyian tradition emphasized the sense of experience in problem-solving and functional adaptations. The pragmatists' sense of experience is the way by which one engages the world, is inherently cognitive, and orchestrated by central states of the brain. Any attempt within the neural and cognitive sciences to capture human experience will need to resurrect this tradition. RP Schulkin, J (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BEHAV NEUROSCI UNIT,BLDG 10,3S231,6000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 62 TC 2 Z9 2 U1 1 U2 1 PU PSYCHOLOGICAL REPORTS PI MISSOULA PA P O BOX 9229, MISSOULA, MT 59807 SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD APR PY 1996 VL 78 IS 2 BP 499 EP 506 PG 8 WC Psychology, Multidisciplinary SC Psychology GA UG143 UT WOS:A1996UG14300027 PM 9148308 ER PT J AU Altemus, M Hetherington, M Kennedy, B Licinio, J Gold, PW AF Altemus, M Hetherington, M Kennedy, B Licinio, J Gold, PW TI Thyroid function in bulimia nervosa SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE bulimia; binge eating; thyroid hormone; TSH; TSH surge ID THYROTROPIN-RELEASING-HORMONE; RESTING METABOLIC-RATE; ANOREXIA-NERVOSA; SERUM TRIIODOTHYRONINE; CENTRAL HYPOTHYROIDISM; NONTHYROIDAL ILLNESS; NOCTURNAL SURGE; FREE-THYROXINE; REVERSE T3; TSH SURGE AB Basal thyroid-stimulating hormone (TSH) and thyroid hormone levels were evaluated in 18 women with bulimia nervosa during a period of active bingeing and vomiting and again after 7 weeks of abstinence from these behaviors and compared to measures in 27 control women. In 10 of the patients and 11 of the controls, the TSH nocturnal surge was calculated from hourly TSH measurements obtained in the afternoon from 1500 to 1900h and in the night from 2300 to 0400h. During the bingeing phase of the illness patients had lower total triiodothyronine (T3) values than controls (p<.001). After 7 weeks without binge eating or purging, patients had lower T3, total thyroxine (T4), free triiodothyronine, free thyroxine (FT4), reverse triiodothyronine and thyroid-binding globulin (TBG) values compared to controls (p<.01) and significant reductions in T3, T4, FT4 and TBG compared to themselves in the active phase of the illness (p<.02). The reduction in thyroid hormone levels was not due to a reduction in the nocturnal thyrotropin surge, since surge values did not differ between normals and patients at either phase of the illness. Bulimics in the bingeing phase of the illness showed a positive correlation between caloric intake and TSH values (p<.01), suggesting that food bingeing may stimulate thyroid activity. In sum, these results show a substantial reduction in thyroid hormone levels after 7 weeks of abstinence from bingeing and vomiting behaviors. C1 UNIV DUNDEE, DEPT PSYCHOL, DUNDEE DD1 4HN, SCOTLAND. NIMH, CLIN NEUROENDOCRINOL BRANCH, DIRP, BETHESDA, MD 20892 USA. NIMH, CLIN SCI LAB, DIRP, BETHESDA, MD 20892 USA. RI Hetherington, Marion/A-4397-2013; Licinio, Julio/L-4244-2013 OI Licinio, Julio/0000-0001-6905-5884 NR 69 TC 12 Z9 12 U1 3 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 1996 VL 21 IS 3 BP 249 EP 261 DI 10.1016/0306-4530(96)00002-9 PG 13 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA UY598 UT WOS:A1996UY59800001 PM 8817724 ER PT J AU Rosenstein, DL Kalogeras, KT Kalafut, M Malley, J Rubinow, DR AF Rosenstein, DL Kalogeras, KT Kalafut, M Malley, J Rubinow, DR TI Peripheral, measures of arginine vasopressin, atrial natriuretic peptide and adrenocorticotropic hormone in premenstrual syndrome SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE AVP; ANP; ACTH; PMS; menstrual; mood ID PLASMA BETA-ENDORPHIN; CEREBROSPINAL-FLUID VASOPRESSIN; OBSESSIVE-COMPULSIVE DISORDER; MENSTRUAL-CYCLE; RENIN-ACTIVITY; PHARMACOLOGICAL CHARACTERIZATION; BIOCHEMICAL MANIFESTATIONS; PRIMARY DYSMENORRHEA; HEALTHY-SUBJECTS; SECRETION AB Because of the unique combination of physical (e.g. bloating, water retention) and psychological (e.g. mood, memory) symptoms associated with premenstrual syndrome (PMS), various hypothalamic and pituitary hormones have been implicated in the pathophysiology of PMS. We measured plasma adrenocorticotropic hormone (ACTH), arginine vasopressin (AW) and atrial natriuretic peptide (ANP) across the menstrual cycle in 19 women with PMS and 12 normal women. AVP concentrations were lower throughout the menstrual cycle in symptomatic PMS patients compared with PMS patients during asymptomatic cycles and normal women. No differences in ACTH and ANP were observed between patients and controls. However, ACTH and ANP were positively and significantly correlated with each other in women with PMS but not in controls. These findings contribute to a growing list of menstrual cycle-independent findings in women with PMS and suggest that there may be an underlying neurobiological vulnerability that predisposes some women to experience somatic and mood dysregulation in the luteal phase of the menstrual cycle. Copyright (C) 1996 Elsevier Science Ltd. C1 NIMH, CLIN NEUROENDOCRINOL BRANCH, BETHESDA, MD 20892 USA. UNIV CALIF LOS ANGELES, SCH MED, DEPT NEUROL, LOS ANGELES, CA 90024 USA. NIH, PERSONAL COMP BRANCH, DIV COMP RES & TECHNOL, BETHESDA, MD 20892 USA. RP Rosenstein, DL (reprint author), NIMH, SECT BEHAV ENDOCRINOL,BIOL PSYCHIAT BRANCH, BLDG 10,ROOM 3N238, 10 CTR DR MSC 1276, BETHESDA, MD 20892 USA. NR 72 TC 12 Z9 12 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD APR PY 1996 VL 21 IS 3 BP 347 EP 359 DI 10.1016/0306-4530(95)00035-6 PG 13 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA UY598 UT WOS:A1996UY59800009 PM 8817732 ER PT J AU Shi, YB Stolow, M PuzianowskaKuznicka, M Wong, JM AF Shi, YB Stolow, M PuzianowskaKuznicka, M Wong, JM TI Genes of metamorphosis SO RECHERCHE LA French DT Article ID AMPHIBIAN METAMORPHOSIS; THYROID-HORMONE; RECEPTOR; CELLS RP Shi, YB (reprint author), NICHHD,MOLEC EMBRYOL LAB,BETHESDA,MD 20892, USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU SOC ED SCIENTIFIQUES PI PARIS 06 PA 57 RUE DE SEINE, 75280 PARIS 06, FRANCE SN 0029-5671 J9 RECHERCHE JI Recherche PD APR PY 1996 IS 286 BP 58 EP 64 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UC624 UT WOS:A1996UC62400029 ER PT J AU Fitzgerald, D AF Fitzgerald, D TI Therapy targeted to surface antigens and receptors .2. Introduction and future goals SO SEMINARS IN CANCER BIOLOGY LA English DT Editorial Material RP Fitzgerald, D (reprint author), NCI,MOLEC BIOL LAB,BETHESDA,MD 20892, USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD APR PY 1996 VL 7 IS 2 BP 55 EP 55 DI 10.1006/scbi.1996.0008 PG 1 WC Oncology SC Oncology GA UH848 UT WOS:A1996UH84800001 ER PT J AU King, CR Fischer, PH Rando, RF Pastan, I AF King, CR Fischer, PH Rando, RF Pastan, I TI The performance of e23(Fv)PEs, recombinant toxins targeting the erbB-2 protein SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE erbB2; neu; oncoprotein; therapy; preclinical ID HUMAN-BREAST-CANCER; TUMOR-CELL GROWTH; MONOCLONAL-ANTIBODIES; PSEUDOMONAS EXOTOXIN; C-ERBB-2 ONCOGENE; LUNG-CANCER; EXPRESSION; RECEPTOR; AMPLIFICATION; PROTOONCOGENE AB The overexpression of the erbB-2 (HER-2, neu) gene has attracted significant interest as a molecular target for the rational design of cancer therapies. This review examines the design and preclinical testing phase for one such experimental therapy, recombinant toxins targeted to the erbB-2 protein, termed e23(Fv)PEs. C1 GEN VEC INC,ROCKVILLE,MD 20852. ARONEX PHARMACEUT CORP,THE WOODLANDS,TX 77380. NCI,MOLEC BIOL LAB,BETHESDA,MD 20892. RP King, CR (reprint author), GEORGETOWN UNIV,MED CTR,LOMBARDI CANC CTR,ROOM E508,3970 RESERVOIR RD NW,WASHINGTON,DC 20007, USA. NR 48 TC 14 Z9 14 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD APR PY 1996 VL 7 IS 2 BP 79 EP 86 PG 8 WC Oncology SC Oncology GA UH848 UT WOS:A1996UH84800005 PM 8740563 ER PT J AU Fitzgerald, D AF Fitzgerald, D TI Why toxins! SO SEMINARS IN CANCER BIOLOGY LA English DT Article DE toxin; immunotoxin; cancer; receptor; endocytosis; translocation ID RICIN-A-CHAIN; PSEUDOMONAS EXOTOXIN-A; GROWTH-FACTOR-ALPHA; DIPHTHERIA-TOXIN; FUSION PROTEIN; MONOCLONAL-ANTIBODIES; ANTITUMOR-ACTIVITY; RECOMBINANT FORM; TRANSFERRIN RECEPTOR; DIFFERENT EPITOPES AB Toxins are potent cytotoxic proteins which gain access to the interior of mammalian cells by receptor-mediated endocytosis. However, the trafficking pathways within mammalian cells are complex and toxins must be processed to active forms while avoiding degradation by the lysosomal system. Once delivered to an appropriate intracellular location, the active toxin fragment translocates to the cell cytosol and inhibits protein synthesis. Chimeric toxins are constructed by removing the toxins natural binding domain and replacing it with an antibody or cell-binding ligand that redirects cell killing activity to cancer cells. Gaining an understanding of how toxins manoeuvre within cells is vital for improving the effectiveness of chimeric toxins. RP Fitzgerald, D (reprint author), NCI,MOLEC BIOL LAB,DBS,BLDG 37,4B-03,37 CONVENT DR,MSC 4255,BETHESDA,MD 20892, USA. NR 67 TC 21 Z9 21 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD APR PY 1996 VL 7 IS 2 BP 87 EP 95 DI 10.1006/scbi.1996.0013 PG 9 WC Oncology SC Oncology GA UH848 UT WOS:A1996UH84800006 PM 8740564 ER PT J AU Bard, JBL Davies, JA Karavanova, I Lehtonen, E Sariola, H Vainio, S AF Bard, JBL Davies, JA Karavanova, I Lehtonen, E Sariola, H Vainio, S TI Kidney development: The inductive interactions SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE branching morphogenesis; induction; kidney function; nephrogenesis; stem cells; WT1 ID EMBRYONIC KIDNEY; METANEPHRIC KIDNEY; GROWTH-FACTOR; MOUSE; DIFFERENTIATION; EXPRESSION; CELLS; POLARIZATION; MESENCHYME; TUBULES AB The kidney derives from a set of inductive interactions between two tissues, a blastema of metanephric mesenchyme (MM) that arises from within the intermediate mesoderm, and the ureteric bud, a diverticulum off the nephric duct. The first of these interactions (probably long range) derives from the MM and the signal, almost certainly chemotactic and under the indirect control of WT1, causes the bud to sprout off the duct. The second (again probably long range) is from the bud to the MM and causes it to divide and enter a stem-cell phase rather than undergo apoptosis. The third is also from the bud and causes groups of stem cells to aggregate, epithelialize and form nephrons; this is likely to be a short-range interaction. The fourth is from the stem cells; it supplements the initial interaction underpinning bud growth and leads to bud bifurcation; together, these two interactions regulate the formation of the collecting duct system. There are almost certainly other inductive interactions involved in the later stages of nephrogenesis, but, in this review, we focus on the molecular basis of the four prime inductive steps and their downstream effects. (C) 1996 Academic Press Ltd C1 NCI, FREDERICK CANC RES & DEV CTR, FREDERICK, MD 21702 USA. HELSINKI UNIV, DEPT PATHOL, FIN-00014 HELSINKI, FINLAND. INST BIOTECHNOL, BIOCTR 1A, FIN-00014 HELSINKI, FINLAND. HARVARD UNIV, DEPT BIOL, CAMBRIDGE, MA 02136 USA. RP Bard, JBL (reprint author), UNIV EDINBURGH, SCH MED, DEPT ANAT, TEVIOT PL, EDINBURGH EH8 9AG, MIDLOTHIAN, SCOTLAND. NR 49 TC 21 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD APR PY 1996 VL 7 IS 2 BP 195 EP 202 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA UR626 UT WOS:A1996UR62600007 ER PT J AU Holman, GD Cushman, SW AF Holman, GD Cushman, SW TI Subcellular trafficking of GLUT4 in insulin target cells SO SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY LA English DT Review DE GLUT4; insulin; photolabel; trafficking ID REGULATABLE GLUCOSE TRANSPORTER; RAT ADIPOSE-CELLS; PLASMA-MEMBRANE; INTRACELLULAR SEQUESTRATION; 3T3-L1 ADIPOCYTES; INDUCED TRANSLOCATION; PHORBOL ESTER; NH2 TERMINUS; STIMULATION; PHOSPHORYLATION AB Insulin stimulates glucose transport in its target tissues primarily by inducing a translocation of GLUT4 from intracellular membranes to the plasma membrane. The kinetics of subcellular trafficking of GLUT4 between these compartments have been investigated using a bis-mannose photolabel. Since this reagent is impermeant, it has been used to selectively tag cell surface GLUT4. Subsequent examination of the changes in distribution of the tagged transporter allows resolution of the sites of insulin action in the subcellular trafficking pathway. This approach indicates that insulin mainly increases the rate constant for exocytosis of GLUT4. In addition, these kinetic studies have lean! to the suggestion that GLUT4 trafficks through at least two intracellular compartments during its cycling and that an occluded plasma membrane compartment may be an intermediate in insulin-stimulated exocytosis. Some of the key proteins that catalyse the vesicle trafficking steps are now being resolved. Phosphatidylinositol 3-kinase may have a regulatory role in GLUT4 vesicle budding and fission at several intracellular membrane sites while the N-ethylmaleimide sensitive fusion protein (NSF) complex may have a role in regulation of GLUT4 vesicle docking and fusion at the plasma membrane. (C) 1996 Academic Press Ltd C1 NIDDKD,DIABET BRANCH,NIH,BETHESDA,MD 20892. RP Holman, GD (reprint author), UNIV BATH,DEPT BIOCHEM,BATH BA2 7AY,AVON,ENGLAND. NR 58 TC 7 Z9 7 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1084-9521 J9 SEMIN CELL DEV BIOL JI Semin. Cell Dev. Biol. PD APR PY 1996 VL 7 IS 2 BP 259 EP 268 DI 10.1006/scdb.1996.0034 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA UR626 UT WOS:A1996UR62600015 ER PT J AU Rotman, M Laven, D Levine, G AF Rotman, M Laven, D Levine, G TI Radiopharmaceutical regulation and food and drug administration policy SO SEMINARS IN NUCLEAR MEDICINE LA English DT Article AB The regulatory policy of the Food and Drug Administration (FDA) on radiopharmaceuticals flows from a rigid, traditional, drug-like interpretation of the FDC Act on the licensing of radiopharmaceuticals. This contributes to significant delays in the drug-approval process for radiopharmaceuticals, which are very costly to the nuclear medicine community and the American public. It seems that radiopharmaceuticals would be better characterized as molecular devices. Good generic rulemaking principles include: use of a risk/benefit/cost analysis; intent based on sound science; performance standards prepared by outside experts; a definite need shown by the regulatory agency; to live with the consequences of any erroneous cost estimates; and design individual credential requirements so that additional training results in enhanced professional responsibility. When these common elements are applied to current FDA policy, it seems that the agency is out of sync with the stated goals for revitalizing federal regulatory policies as deemed necessary by the Clinton administration. Recent FDA rulings on positron-emission tomography, Patient Package Inserts, and on medical device service accentuate the degree of such asynchronization. Radiopharmaceutical review and licensing flexibility could be dramatically improved by excluding radiopharmaceuticals from the drug category and reviewing them as separate entities. This new category would take into account their excellent record of safety and their lack of pharmacological action. Additionally, their evaluation of efficacy should be based on their ability to provide useful scintiphotos, data, or responses of the physiological system it portends to image, quantitate, or describe. To accomplish the goal of transforming the FDA's rigid, prescriptive policy into a streamlined flexible performance-based policy, the Council on Radionuclides and Radiopharmaceuticals proposal has been presented. In addition, it is suggested that the United States Pharmacopeia write radiopharmaceutical review standards, that an independent scientific body review the data submitted, and that the FDA either accept or reject the recommendation. Copyright (C) 1996 by W.B. Saunders Company. C1 VET ADM MED CTR,NUCL PHARM PROGRAM,BAY PINES,FL. RP Rotman, M (reprint author), NIH,RADIOLABELLING UNIT,DEPT NUCL MED,BETHESDA,MD 20892, USA. NR 20 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 SN 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD APR PY 1996 VL 26 IS 2 BP 96 EP 106 DI 10.1016/S0001-2998(96)80031-6 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA UG731 UT WOS:A1996UG73100005 PM 8723504 ER PT J AU Mulshine, JL Scott, F Zhou, J Avis, I Vos, M Miller, MJ Szabo, E Martinez, A Treston, AM Cuttitta, F Tockman, M AF Mulshine, JL Scott, F Zhou, J Avis, I Vos, M Miller, MJ Szabo, E Martinez, A Treston, AM Cuttitta, F Tockman, M TI Development of molecular approaches to early lung cancer detection SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID LOCALIZATION; ACID C1 JOHNS HOPKINS UNIV, SCH HYG & PUBL HLTH, BALTIMORE, MD USA. RP NCI, BIOMARKERS & PREVENT RES BRANCH, KWC 300, 9610 MED CTR DR, ROCKVILLE, MD 20850 USA. RI Martinez, Alfredo/A-3077-2013 OI Martinez, Alfredo/0000-0003-4882-4044 NR 18 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1053-4296 EI 1532-9461 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD APR PY 1996 VL 6 IS 2 BP 72 EP 75 DI 10.1016/S1053-4296(96)80002-6 PG 4 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA VV680 UT WOS:A1996VV68000002 ER PT J AU Pantaleo, G Vaccarezza, M Graziosi, C Cohen, OJ Fauci, AS AF Pantaleo, G Vaccarezza, M Graziosi, C Cohen, OJ Fauci, AS TI Antiviral immunity in HIV-1 infected longterm non-progressors (LTNPs) SO SEMINARS IN VIROLOGY LA English DT Article DE immune response; immune activation; viral load; lymphoid tissue; long term non-progressors ID IMMUNODEFICIENCY-VIRUS INFECTION; CD4+ LYMPHOCYTE COUNTS; T-CELL LEVELS; AIDS AB Now that the acquired immunodeficiency syndrome (AIDS) epidemic is well into its second decade, it has become evident that a small percentage (approximately 5%) of HIV-infected individuals do not experience progression of HIV disease even after several years of being infected with HIV. These individuals have been designated as 'long term non-progressors' (LTNPs). From a virologic standpoint, these LTNPs have low viral burden in mononuclear cells, but persistent virus replication as manifested by chronic and generally low levels of plasma viremia. From an immunologic standpoint, immune functions including CD8(+) T-cell- and CD4(+) T-cell-mediated functions are preserved. In addition, they show a vigorous humoral immune response. More importantly, lymphoid tissue structure and function are preserved in LTNPs. Despite persistent low-level virus replication and chronic stimulation of the immune system, immune activation is qualitatively and quantitatively different in LTNPs compared to that observed in HIV-infected individuals whose HIV disease has progressed. (C)1996 Academic Press Ltd RP Pantaleo, G (reprint author), NIAID,IMMUNOREGULAT LAB,NIH,BETHESDA,MD 20892, USA. RI Pantaleo, Giuseppe/K-6163-2016; OI VACCAREZZA, Mauro/0000-0003-3060-318X NR 27 TC 4 Z9 4 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 1044-5773 J9 SEMIN VIROL JI Semin. Virol. PD APR PY 1996 VL 7 IS 2 BP 131 EP 138 DI 10.1006/smvy.1996.0017 PG 8 WC Virology SC Virology GA UF923 UT WOS:A1996UF92300007 ER PT J AU Steyn, K Rossouw, JE Weight, MJ Fourie, JM Benade, AJS Jooste, PL Chalton, DO Wolmarans, P AF Steyn, K Rossouw, JE Weight, MJ Fourie, JM Benade, AJS Jooste, PL Chalton, DO Wolmarans, P TI Apolipoprotein B levels and related factors in a rural white south African community - The CORIS study SO SOUTH AFRICAN MEDICAL JOURNAL LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; FAMILIAL DEFECTIVE APOLIPOPROTEIN-B-100; CORONARY-ARTERY DISEASE; ISCHEMIC-HEART-DISEASE; MYOCARDIAL-INFARCTION; RISK-FACTORS; A-I; PHYSICAL-FITNESS; CHOLESTEROL; HYPERCHOLESTEROLEMIA AB Objective. In a survey of the Coronary Risk Factor Study (CORIS), apolipoprotein B (apoB) levels were determined to ascertain their impact on coronary heart disease (CHD) risk Other CHD risk factors associated with apoB were also identified. Design. Cross-sectional analytical study, which included CHD risk factor and dietary questionnaires, electrocardiography, anthropometric and blood pressure measurements, and a blood sample for a lipid profile. Setting and participants. The three districts of Riversdale, Robertson and Swellendam in the southwestern Cape; a 25% random sample of 1 528 white respondents aged 15-68 years. Results. Men tended to have higher mean apoe levels than women. Classification of CHD risk by apoB levels and total cholesterol (TC) levels did not correspond, as only 61% of men and 58.5% of women were classified in the same risk categories. Respondents in the highest apoB risk category reported a medical history of hypercholesterolaemia and hypertension more frequently than those in lower categories. There was a significant increase from the low to the high apoB risk category of TC, low-density lipoprotein (LDL) cholesterol, triglyceride levels, body mass index and percentage body fat. Using stepwise multiple regression, 84.9% of the variation in apoe of men and 85.8% in apoB of women were accounted for by significantly associated variables. Conclusion. Although apoB may be a better predictor of CHD than TC or LDL cholesterol concentrations, its easy approximation with the formula (TC-HDLC)/2+20, high cost, measurement variability and an approach in management similar to that for raised TC discourage its routine use in the screening of patients for CHD. C1 S AFRICAN MRC,NATL RES PROGRAMME NUTR INTERVENT,PAROWVALLEI,WESTERN CAPE,SOUTH AFRICA. NIH,WOMENS HLTH INITIAT,BETHESDA,MD 20892. RP Steyn, K (reprint author), S AFRICAN MRC,CHRON DIS LIFESTYLE PROGRAMME,PAROWVALLEI,WESTERN CAPE,SOUTH AFRICA. NR 41 TC 3 Z9 3 U1 0 U2 0 PU MED ASSOC S AFRICA PI JOHANNESBURG PA MED HOUSE CENTRAL SQ 7430 PINELANDS JOHANNESBURG, SOUTH AFRICA SN 0038-2469 J9 S AFR MED J JI S. Afr. Med. J. PD APR PY 1996 VL 86 IS 4 BP 359 EP 364 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA UF595 UT WOS:A1996UF59500015 PM 8693373 ER PT J AU Jeong, LS Marquez, VE AF Jeong, LS Marquez, VE TI Use of a cyclic sulfite as an epoxide surrogate in the regioselective synthesis of a carbocyclic ring-enlarged 4',1'a-methano oxetanocin analogue SO TETRAHEDRON LETTERS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYCLOBUT-A; SULFATES; HIV; NUCLEOSIDES; INFECTIVITY; INHIBITORS; ESTERS AB Although cyclic sulfites are less reactive than their cyclic sulfate counterparts, the present work shows that cyclic sulfite 15a is a useful synthon for the convergent synthesis of carbocyclic nucleosides. Target compound 6, which represents a rigid carbocyclic nucleoside mimic of anti-HIV active 9-[2',3'-dideoxy-3'-C- (hydroxymethyl)-beta-erythro-pentofuranosyl]adenine (3), was obtained after regioselective ring opening of 15a with adenine and radical-induced deoxygenation of the extra hydroxyl group. C1 NCI,MED CHEM LAB,DIV BASIC SCI,NIH,BETHESDA,MD 20892. NR 24 TC 23 Z9 23 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD APR 1 PY 1996 VL 37 IS 14 BP 2353 EP 2356 DI 10.1016/0040-4039(96)00289-4 PG 4 WC Chemistry, Organic SC Chemistry GA UD578 UT WOS:A1996UD57800014 ER PT J AU Zimmerman, PA Steiner, LL Titanji, VPK Nde, PN Bradley, JE Pogonka, T Begovich, AB AF Zimmerman, PA Steiner, LL Titanji, VPK Nde, PN Bradley, JE Pogonka, T Begovich, AB TI Three new DPB1 alleles identified in a Bantu-speaking population from central Cameroon SO TISSUE ANTIGENS LA English DT Article DE Cameroon; directed heteroduplex analysis; DNA sequence; HLA-DPB1; MHC class II; sequence motifs; sequence-specific ID DNA AB HLA-DPB1 genotyping of 241 individuals from an African Bantu-speaking population in central Cameroon using sequence-specific oligonucleotide probes identified five individuals with novel probe hybridization patterns. DNA sequence analysis of the second exon of the DPB1 alleles from these five individuals identified three new alleles, *6001, *6101N, and *6201. DPB1*6001, found in two individuals, contains a single nucleotide change that results in a polar amino acid, asparagine, at residue 65; this position in the pr domain is occupied by a nonpolar amino acid in all other reported DPB1 alleles. DPB1*6101N, found in one individual, contains a single base mutation that results in a premature termination codon at position 67. DPB1*6201, found in two individuals, is characterized by the apparent motif shuffling that has been hypothesized to be responsible for the majority of DPB1 sequence polymorphism. These new sequences shed additional light on the potential mechanisms by which allelic diversity is generated at the HLA-DPB1 locus. C1 ROCHE MOL SYST,DEPT HUMAN GENET,ALAMEDA,CA. UNIV LONDON IMPERIAL COLL SCI TECHNOL & MED,DEPT BIOL,LONDON,ENGLAND. UNIV HOHENHEIM,FACHGEBIET PARASITOL,W-7000 STUTTGART,GERMANY. RP Zimmerman, PA (reprint author), NIAID,PARASIT DIS LAB,NIH,BLDG 4,ROOM 126,BETHESDA,MD 20892, USA. OI Bradley, Janette/0000-0003-3973-7977 FU NIAID NIH HHS [AI-29042] NR 13 TC 20 Z9 21 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD APR PY 1996 VL 47 IS 4 BP 293 EP 299 DI 10.1111/j.1399-0039.1996.tb02556.x PG 7 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA UM540 UT WOS:A1996UM54000004 PM 8773318 ER PT J AU Busch, MP Alter, HJ AF Busch, MP Alter, HJ TI Cost-effectiveness of p24 antigen testing in preventing transfusion transmission of human immunodeficiency virus infection - Reply SO TRANSFUSION LA English DT Letter ID BLOOD C1 NIH,BETHESDA,MD 20892. RP Busch, MP (reprint author), UNIV CALIF SAN FRANCISCO,IRWIN MEM BLOOD CTR,SAN FRANCISCO,CA 94143, USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 1996 VL 36 IS 4 BP 382 EP 383 PG 2 WC Hematology SC Hematology GA UK637 UT WOS:A1996UK63700020 ER PT J AU Koonin, EV Bork, P AF Koonin, EV Bork, P TI Ancient duplication of DNA polymerase inferred from analysis of complete bacterial genomes SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Article ID ALIGNMENT C1 EUROPEAN MOLEC BIOL LAB,W-6900 HEIDELBERG,GERMANY. MAX DELBRUCK CTR MOLEC MED,BERLIN,GERMANY. RP Koonin, EV (reprint author), NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,NIH,BETHESDA,MD 20894, USA. RI Bork, Peer/F-1813-2013 OI Bork, Peer/0000-0002-2627-833X NR 14 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 1996 VL 21 IS 4 BP 128 EP 129 DI 10.1016/S0968-0004(96)80165-4 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UE372 UT WOS:A1996UE37200004 PM 8701468 ER PT J AU Hengen, PN AF Hengen, PN TI Methods and reagents - Is there any sense in antisense terminology? SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material AB Methods and reagents is a unique monthly column that highlights current discussions in the newsgroup bionet.molbio.methds-reagnts, available on the Internet. This month's column reviews a recent debate held over the present sense and antisense terminology when referring to DNA. For details on how to partake in the newsgroup, see the accompanying box. RP Hengen, PN (reprint author), NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. NR 10 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 1996 VL 21 IS 4 BP 153 EP 154 DI 10.1016/S0968-0004(96)80171-X PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UE372 UT WOS:A1996UE37200010 PM 8701474 ER PT J AU Klein, DC Roseboom, PH Coon, SL AF Klein, DC Roseboom, PH Coon, SL TI New light is shining on the melatonin rhythm enzyme - The first postcloning view SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID N-ACETYLTRANSFERASE ACTIVITY; PROTEIN KINASE-C; RAT PINEAL-GLAND; ADENOSINE-3',5'-MONOPHOSPHATE; 3',5'-MONOPHOSPHATE; EXPRESSION; ACTIVATION; DECREASE; INFLUX; CELLS AB One of the most interesting molecules in circadian biology is serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT), the enzyme that controls the daily rhythm in pineal melatonin production and blood melatonin. The recent cloning of AANAT cDNA has led to the characterization of the human gene; the realization that AANAT represents a unique gene family; the discovery of circadian rhythms in AANAT mRNA; the determination of the basis of transsynaptic and cellular regulation of expression of the AANAT gene; a new understanding of the relationship of AANAT mRNA and activity; and the surprising finding of strong expression of the AANAT gene in the retina and significant levels in select brain regions, the pituitary gland, and testes. The cloning of AANAT cDNA has not only made it possible to answer longstanding questions in circadian biology, but has also raised stimulating new issues. RP Klein, DC (reprint author), NICHHD,SECT NEUROENDOCRINOL,DEV NEUROBIOL LAB,NIH,BETHESDA,MD 20892, USA. NR 39 TC 73 Z9 75 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 1996 VL 7 IS 3 BP 106 EP 112 DI 10.1016/1043-2760(96)00033-1 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA UJ713 UT WOS:A1996UJ71300005 PM 18406734 ER PT J AU Rudd, KE AF Rudd, KE TI Escherichia coli K-12 on the Internet SO TRENDS IN GENETICS LA English DT Article ID GENOME RP Rudd, KE (reprint author), NIH,NATL LIB MED,NATL CTR BIOTECHNOL INFORMAT,BETHESDA,MD 20894, USA. NR 11 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD APR PY 1996 VL 12 IS 4 BP 156 EP 157 DI 10.1016/0168-9525(96)60012-2 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UC599 UT WOS:A1996UC59900010 PM 8901421 ER PT J AU Hunyady, L Balla, T Catt, KJ AF Hunyady, L Balla, T Catt, KJ TI The ligand binding site of the angiotensin AT(1) receptor SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID II TYPE-1 RECEPTOR; PROTEIN-COUPLED RECEPTORS; MOLECULAR-CLONING; EXPRESSION; SUBTYPE; MUTAGENESIS; AGONISTS; ISOFORM; CORTEX AB The angiotensin AT(1) receptor mediates numerous physiological actions of the octapeptide hormone, angiotensin II, in its cardiovascular and other target tissues. The binding of angiotensin II to the AT(1) receptor is dependent on both intramembrane and extracellular regions of the receptor molecule. Non-peptide antagonists that block angiotensin binding and action interact exclusively with residues located within the intramembrane binding pocket of the AT(1) receptor. However, peptide ligands also interact with extracellular residues to form additional bonds that stabilize their binding to the receptor. Here, Laszlo Hunyady, Tames Balla and Kevin Catt describe how these and other studies have shown that interaction of ligands with residues in the intramembrane binding pocket is the conserved mechanism required for agonist activation of G protein-coupled receptors. C1 NICHHD,NATL INST HLTH,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. RP Hunyady, L (reprint author), SEMMELWEIS UNIV,SCH MED,DEPT PHYSIOL,POB 259,H-1444 BUDAPEST,HUNGARY. OI Balla, Tamas/0000-0002-9077-3335 NR 52 TC 101 Z9 101 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD APR PY 1996 VL 17 IS 4 BP 135 EP 140 DI 10.1016/0165-6147(96)81588-4 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UG758 UT WOS:A1996UG75800005 PM 8984739 ER PT J AU Berencsi, K Gonczol, E Endresz, V Kough, J Takeda, S Gyulay, Z Plotkin, SA Rando, RF AF Berencsi, K Gonczol, E Endresz, V Kough, J Takeda, S Gyulay, Z Plotkin, SA Rando, RF TI The N-terminal 303 amino acids of the human cytomegalovirus envelope glycoprotein B (UL55) and the exon 4 region of the major immediate early protein 1 (UL123) induce a cytotoxic T-cell response SO VACCINE LA English DT Article DE CTL epitope; HCMV; IE1 exon 4; Ad-HCMV recombinants ID IMMUNE-RESPONSES; LYMPHOCYTE-T; NEUTRALIZING ANTIBODY; GENE-EXPRESSION; VIRUS; GB; RECOMBINANT; INFECTION; ADENOVIRUS; CORRELATE AB We reported earlier that an adenovirus (Ad) recombinant expressing the full-length human cytomegalovirus (HCMV) glycoprotein B (gB) gene induces gB-specific cytotoxic T lymphocyte (CTL) responses in CBA (H-2(k)) mice (Berencsi et al., J. Gen. Virol. 74, 257-2512, 1993). Here we show that mice immunized with Ad recombinant viruses expressing truncated forms of the gB gene containing the first 700 (Ad-700), 465 (Ad-465) or 303 (Ad-303) amino acids of gB or an Ad construct containing exon 4 (E4) of the HCMV immediate early 1 (IE1) gene (Ad-IE1 (E4)) demonstrate HCMV-specific CTL responses, These data suggest the importance of the first 303 amino acids of the gB polypeptide and the IE1 E4 product in designing a vaccine to induce anti-HCMV CTL responses. Copyright (C) 1996 Elsevier Science Ltd. C1 UNIV PENN, WISTAR INST, PHILADELPHIA, PA 19104 USA. US EPA, WASHINGTON, DC 20460 USA. NAGOYA UNIV, SCH MED, DEPT SURG 2, SHOWA KU, NAGOYA, AICHI 466, JAPAN. NIDR, NIH, F-92430 MARNES LA COQUETTE, FRANCE. OI waluyo, imam/0000-0002-1813-9487 FU NICHD NIH HHS [HD 18957] NR 37 TC 5 Z9 5 U1 0 U2 3 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 APR PY 1996 VL 14 IS 5 BP 369 EP 374 DI 10.1016/0264-410X(95)00227-R PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UK974 UT WOS:A1996UK97400002 PM 8735546 ER PT J AU Klugman, KP Koornhof, HJ Robbins, JB LeCam, NN AF Klugman, KP Koornhof, HJ Robbins, JB LeCam, NN TI Immunogenicity, efficacy and serological correlate of protection of Salmonella typhi Vi capsular polysaccharide vaccine three years after immunization SO VACCINE LA English DT Article DE Salmonella typhi; Vi capsular polysaccharide; typhoid vaccine ID FEVER AB The protective efficacy and immunogenicity of Vi capsular polysaccharide vaccine against typhoid fever was measured 3 years after its administration in a double-blind randomized trial. Vaccine efficacy was not significantly different during each year of the trial and was 55% (95% CI: 30-71%) over the 3 year period In a case-control study at 3 years after vaccination, recipients of Vi had higher levels of Vi antibodies than controls, as measured by radio-immunoassay (GMT 1.28 vs 0.76 mu g ml(-1), P=0.0004) and by passive haemagglutination assay (GMT 10.46 vs 3.52, P=0.0001). The serological correlate of protection has been estimated using the relative risks of typhoid fever in the 2 groups and the relative ratio of antibody levels. The estimated protective level is I mu g ml(-1) suggesting that at a mean age of 9 years, 64% of vaccinates and 40% of controls had protective antibody against typhoid fever in this endemic area. Copyright (C) 1996 Elsevier Science Ltd. C1 NIHHD,DEV & MOLEC IMMUN LAB,NIH,BETHESDA,MD. PASTEUR MERIEUX SERUMS & VACCINS,F-92430 MARNES COQUETTE,FRANCE. RP Klugman, KP (reprint author), UNIV WITWATERSRAND,SAIMR,SCH PATHOL,DEPT MED MICROBIOL,JOHANNESBURG,SOUTH AFRICA. NR 9 TC 137 Z9 142 U1 0 U2 4 PU BUTTERWORTH-HEINEMANN LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, OXON, ENGLAND OX5 1GB SN 0264-410X J9 VACCINE JI Vaccine PD APR PY 1996 VL 14 IS 5 BP 435 EP 438 DI 10.1016/0264-410X(95)00186-5 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA UK974 UT WOS:A1996UK97400012 PM 8735556 ER PT J AU Delahunty, MD Rhee, I Freed, EO Bonifacino, JS AF Delahunty, MD Rhee, I Freed, EO Bonifacino, JS TI Mutational analysis of the fusion peptide of the human immunodeficiency virus type 1: Identification of critical glycine residues SO VIROLOGY LA English DT Article ID TRANSMEMBRANE ALPHA-HELICES; HTLV-III/LAV ENVELOPE; SYNCYTIUM FORMATION; GP120 GLYCOPROTEIN; MEMBRANE-FUSION; CELL-FUSION; RECEPTOR; SEQUENCE; PROTEIN; DOMAIN AB The ability of human immunodeficiency virus type 1 (HIV-1) to fuse its membrane with the membrane of the target cell is a function of a similar to 23-amino-acid amino-terminal segment of the gp41 subunit of the envelope glycoprotein complex, known as the fusion peptide. The sequence of the fusion peptide is highly conserved among different variants of HIV-1 and is also very similar to that of HIV-2 and SIV. The fusion peptide is very hydrophobic and has a high content of glycine and alanine residues. Representation of the fusion peptide of HIV-1 as an alpha-helix predicts that most glycine residues would be found on one face of the alpha-helix. To assess the importance of the glycine residues for the fusogenic activity of the envelope glycoprotein complex, we mutagenized each glycine residue in the fusion peptide individually to a valine residue. The mutant envelope constructs were tested for their ability to induce syncytia (cell/cell fusion) and to mediate infection (virus/cell fusion) of CD4-positive cells. The results of our analyses show that two glycine residues (G(10) and G(13)) located within the sequence FLGFLG in the middle of the fusion peptide are critical for syncytium formation and for the establishment of a productive infection, whereas other glycine residues (G(3), G(5), and G(20)) are more permissive to substitutions. Mutation of each of the two phenylalanines (F-8 and F-11) of the FLGFLG sequence to valine also decreased fusion, although to a lesser extent than mutation of G(10) and G(13), These observations demonstrate that G(10) and G(13) are critical elements of the fusion peptide and suggest that, in addition to hydrophobicity, the exact amino acid composition and structure of the fusion peptide are critical for function. (C) 1996 Academic Press, Inc. C1 NICHHD,CELL BIOL & METAB BRANCH,BETHESDA,MD 20892. NIAID,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. OI Bonifacino, Juan S./0000-0002-5673-6370 NR 47 TC 78 Z9 80 U1 1 U2 3 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD APR 1 PY 1996 VL 218 IS 1 BP 94 EP 102 DI 10.1006/viro.1996.0169 PG 9 WC Virology SC Virology GA UD495 UT WOS:A1996UD49500010 PM 8615045 ER PT J AU Devico, A Silver, A Thornton, AM Sarngadharan, MG Pal, R AF Devico, A Silver, A Thornton, AM Sarngadharan, MG Pal, R TI Covalently crosslinked complexes of human immunodeficiency virus type 1 (HIV-1) gp120 and CD4 receptor elicit a neutralizing immune response that includes antibodies selective for primary virus isolates SO VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODY; SOLUBLE CD4; ENVELOPE GLYCOPROTEIN-GP120; BINDING; EPITOPES; CELLS; INFECTION; FUSION; IMMUNIZATION AB Specific conformational changes in the envelope glycoprotein gp120 of the human immunodeficiency virus type-1 (HIV-1) may be critical for eliciting a broadly neutralizing immune response against primary virus isolates. Since the interaction of gp120 with its receptor, CD4, induces conformational perturbations in both molecules, gp120-CD4 complexes should present unique immunogenic features that may include novel epitopes for broadly neutralizing antibodies. To test this hypothesis, we raised polyclonal antiserum against covalently crosslinked gp120-CD4 complexes in a goat and examined the ability of the anti-complex antibodies to neutralize primary and laboratory-adapted HIV-1 isolates, In cell-free neutralization assays with HIV-1(MN), the antiserum demonstrated the ability to neutralize primary virus more effectively than the laboratory-adapted isolate. The neutralizing capacity of the anti-complex serum extended to primary isolates from distant genetic clades A, D, and E, although the degree of neutralization was found to vary among the clades. The neutralizing activity of the serum was composed of two components. The first component included anti-CD4 antibodies that recognized epitopes outside the gp120 binding site; the second was independent of CD4 reactivity and was retained after removal of cell surface anti-CD4 reactivity by repeated absorption with CD4-positive cells. These results demonstrate that gp120-CD4 complexes can elicit a unique polyclonal antibody response that is relevant to the neutralization of primary isolates of HIV-1. (C) 1996 Academic Press, Inc. C1 ADV BIOSCI LABS INC,KENSINGTON,MD 20895. NIAID,NIH,BETHESDA,MD 20892. NR 46 TC 42 Z9 42 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0042-6822 J9 VIROLOGY JI Virology PD APR 1 PY 1996 VL 218 IS 1 BP 258 EP 263 DI 10.1006/viro.1996.0188 PG 6 WC Virology SC Virology GA UD495 UT WOS:A1996UD49500029 PM 8615032 ER PT J AU Walther, MM Jennings, SB Choyke, PL Andrich, M Hurley, K Linehan, WM Rosenberg, SA Alexander, RB AF Walther, MM Jennings, SB Choyke, PL Andrich, M Hurley, K Linehan, WM Rosenberg, SA Alexander, RB TI Isolated perfusion of the kidney with tumor necrosis factor for localized renal-cell carcinoma SO WORLD JOURNAL OF UROLOGY LA English DT Article ID VONHIPPEL-LINDAUS DISEASE; FACTOR-ALPHA; INTERFERON-GAMMA; PHASE-I; SPARING SURGERY; CANCER-PATIENTS; COMBINATION; ENDOTOXIN; MELANOMA; MODEL AB Patients with localized renal-cell carcinoma who are candidates for renal parenchymal sparing surgery are being treated with isolated renal perfusion with recombinant human tumor necrosis factor (TNF). Isolated organ perfusion is a surgical technique that allows a cancer-bearing organ or region of the body to be treated with high doses of chemotherapy or biologic, agents that would not be tolerated systemically. In patients with in-transit melanoma or unresectable sarcoma, treatment with hyperthermic isolated limb perfusion using TNF, interferon-gamma, and melphalan has resulted in response rates exceeding 90%. Because preclinical studies suggest that TNF may induce regression of tumors by causing hemorrhagic necrosis mediated by effects on tumor-related vascular endothelium, a vascular tumor such as renal-cell carcinoma could potentially be very responsive. A phase I study of escalating TNF doses delivered via isolated renal perfusion is currently being conducted. C1 NCI,UROL ONCOL SECT,SURG BRANCH,NIH,BETHESDA,MD 20892. NIH,WARREN GRANT MAGNUSON CLIN CTR,DEPT DIAGNOST RADIOL,BETHESDA,MD 20892. NCI,RADIAT ONCOL BRANCH,NIH,BETHESDA,MD 20892. UNIV MARYLAND,SCH MED,DIV UROL,BALTIMORE,MD 21201. NR 49 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD APR PY 1996 VL 14 SU 1 BP S2 EP S7 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA UP313 UT WOS:A1996UP31300002 PM 8738402 ER PT J AU Walther, MM Figg, WD Linehan, WM AF Walther, MM Figg, WD Linehan, WM TI Intravesical suramin: A novel agent for the treatment of superficial transitional-cell carcinoma of the bladder SO WORLD JOURNAL OF UROLOGY LA English DT Article ID EPIDERMAL GROWTH-FACTOR; CYTOTOXICITY INVITRO; BIOLOGICAL-ACTIVITY; PROSTATE-CANCER; MITOMYCIN-C; PHARMACOKINETICS; INHIBITION; EXPRESSION; DRUG; ADRIAMYCIN AB Patients with recurrent or high-grade superficial transitional-cell carcinoma of the bladder that has recurred after intravesical chemotherapy are at increased risk for tumor invasion and metastases. Intravesical chemotherapy is a minimally invasive technique that allows high doses of therapeutic agents to be delivered directly to the malignancy, doses that would not be tolerated systemically. In vitro studies demonstrate suramin's significant efficacy against transitional-cell carcinoma cell lines at relatively low doses. Humans treated with similar doses delivered in a systemic fashion have experienced no bladder toxicity. Suramin has been shown to block the binding of epidermal growth factor (EGF) to its receptors, which are found in large amounts in bladder cancers. Because a significant association has been found between the number of EGF receptors on a bladder-cancer cell and its sensitivity to suramin, transitional-cell carcinoma could potentially be very responsive to such therapy. On the basis of these findings, a phase I escalating-suramin-dose study is currently being conducted. C1 NCI,UROL ONCOL SECT,SURG BRANCH,BETHESDA,MD 20892. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. RI Figg Sr, William/M-2411-2016 NR 31 TC 18 Z9 18 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 SN 0724-4983 J9 WORLD J UROL JI World J. Urol. PD APR PY 1996 VL 14 SU 1 BP S8 EP S11 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA UP313 UT WOS:A1996UP31300003 PM 8738403 ER PT J AU Kim, SF Kim, B Jeng, JJ Soh, YJ Bak, CI Huh, JW Song, BJ AF Kim, SF Kim, B Jeng, JJ Soh, YJ Bak, CI Huh, JW Song, BJ TI Nucleotide sequence of rat transketolase and liver specific pretranslational activation during postnatal development SO JOURNAL OF BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE cDNA cloning; nucleotide sequence; Rattus norvegicus; tissue-specific gene expression; transketolase ID WERNICKE-KORSAKOFF SYNDROME; ALZHEIMERS-DISEASE; DEPENDENT ENZYME; GENE; ABNORMALITY; CLONING; BRAIN; DEFICIENCY AB A 2.1 kb cDNA clone for mt transketolase was isolated from mt liver lambda gt11 cDNA library and its sequence was determined. The predicted mt transketolase (655 amino acids with M(r) 71,186) is highly similar (92%) to that of the human enzyme except that it contains an extra 32 amino acids at its N-terminus. Although it is less similar (<27%) to transketolases from non-mammalian species, the functional motifs such as the catalytic sites and thiamine binding domain are well conserved in the mt enzyme. Southern blot analysis of genomic DNA verified that transketolase appears to be derived from a single gene. Immunoblot and Northern blot analyses suggested that hepatic transketolase was activated pretranslationally by a 2.1-fold while little change was observed in brain enzyme, indicating a tissue-specific pretranslational activation during postnatal development. C1 KOREA GREEN CROSS CORP,CENT RES INST,KYUNGKIDO 449900,SOUTH KOREA. NIAAA,NIH,NEUROGENET LAB,ROCKVILLE,MD 20852. NR 24 TC 1 Z9 1 U1 0 U2 0 PU BIOCHEMICAL SOC REPUBLIC KOREA PI SEOUL PA 538 DOWHA-DONG, SUNG-JEE BLDG B705, MAPO-KU, SEOUL 121-743, SOUTH KOREA SN 1225-8687 J9 J BIOCHEM MOL BIOL JI J. Biochem. Mol. Biol. PD MAR 31 PY 1996 VL 29 IS 2 BP 146 EP 150 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC460 UT WOS:A1996UC46000010 ER PT J AU Brown, P AF Brown, P TI Bovine spongiform encephalopathy and Creutzfeldt-Jakob disease - The link is unproved, but no better explanation is presently forthcoming SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material RP Brown, P (reprint author), NINCDS,CENT NERVOUS SYST STUDIES LAB,NIH,BETHESDA,MD 20892, USA. NR 3 TC 22 Z9 22 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON, ENGLAND WC1H 9JR SN 0959-8138 J9 BRIT MED J JI Br. Med. J. PD MAR 30 PY 1996 VL 312 IS 7034 BP 790 EP 791 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UD378 UT WOS:A1996UD37800002 PM 8608273 ER PT J AU Pacelli, R Taira, J Cook, JA Wink, DA Krishna, MC AF Pacelli, R Taira, J Cook, JA Wink, DA Krishna, MC TI Hydroxyurea reacts with heme proteins to generate nitric oxide SO LANCET LA English DT Letter RP Pacelli, R (reprint author), NCI,RADIAT BIOL BRANCH,NIH,BETHESDA,MD 20892, USA. NR 5 TC 64 Z9 66 U1 0 U2 1 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAR 30 PY 1996 VL 347 IS 9005 BP 900 EP 900 DI 10.1016/S0140-6736(96)91378-1 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UC450 UT WOS:A1996UC45000043 PM 8622413 ER PT J AU Rogan, PK Mascari, MJ Ladda, RL Woodage, T Trent, RJ Smith, A Lai, LW Erickson, RP Cassidy, SB Petersen, MB Mikkelsen, M Driscoll, DJ Nicholls, RD Butler, MG AF Rogan, PK Mascari, MJ Ladda, RL Woodage, T Trent, RJ Smith, A Lai, LW Erickson, RP Cassidy, SB Petersen, MB Mikkelsen, M Driscoll, DJ Nicholls, RD Butler, MG TI Coinheritance of other chromosome 15 abnormalities with Prader-Willi syndrome: Genetic risk estimation and mapping SO AMERICAN JOURNAL OF MEDICAL GENETICS LA English DT Meeting Abstract C1 PENN STATE UNIV,COLL MED,HERSHEY,PA. NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892. ROYAL PRINCE ALFRED HOSP,CAMPERDOWN,NSW 2050,AUSTRALIA. CHILDRENS HOSP,CAMPERDOWN,NSW,AUSTRALIA. UNIV ARIZONA,HLTH SCI CTR,TUCSON,AZ. CASE WESTERN RESERVE UNIV,SCH MED,CLEVELAND,OH. CHILDRENS HOSP,ATHENS,GREECE. JOHN F KENNEDY INST,DK-2600 GLOSTRUP,DENMARK. UNIV FLORIDA,COLL MED,GAINESVILLE,FL. VANDERBILT UNIV,SCH MED,NASHVILLE,TN 37212. RI Petersen, Michael Bjorn/D-1483-2017 OI Petersen, Michael Bjorn/0000-0003-0316-8207 NR 0 TC 0 Z9 1 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0148-7299 J9 AM J MED GENET JI Am. J. Med. Genet. PD MAR 29 PY 1996 VL 62 IS 3 BP 6 EP 6 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA UC681 UT WOS:A1996UC68100007 ER PT J AU Chen, W Steenbergen, C Levy, LA Vance, J London, RE Murphy, E AF Chen, W Steenbergen, C Levy, LA Vance, J London, RE Murphy, E TI Measurement of free Ca2+ in sarcoplasmic reticulum in perfused rabbit heart loaded with 1,2-bis(2-amino-5,6-difluorophenoxy)ethane-N,N,N',N'-tetraacetic acid by F-19 NMR SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM-CONCENTRATION; INTRACELLULAR CA2+; SKELETAL-MUSCLE; ATP-HYDROLYSIS; ELECTRON-PROBE; FREE-ENERGY; CALSEQUESTRIN; RELEASE; CA-2+; MYOCYTES AB Measurements of free calcium ion concentration in the sarcoplasmic reticulum ([Ca2+](SR)) and an evaluation of its relationship to changes in cytosolic free calcium and energy state of the cell, as well as heterogeneity of the SR calcium pool, were performed using F-19 NMR in Langendorff perfused rabbit hearts loaded with acetoxymethyl ester of 1,2-bis(2-amino-5,6-difiuorophenoxy)ethane-N,N,N',N'-tetraacetic acid. We report a base-line time-average [Ca2+](SR) value of 1.5 mM (n = 13) in the beating heart, similar to the value measured at diastole. We further report that [Ca2+](SR) decreases by similar to 30% at the start of systole and that there is no evidence of spacial heterogeneity in [Ca2+](SR) during the contraction cycle. However, there appears to be a heterogeneous response to SR calcium channel release activator (caffeine) and SR calcium-ATPase inhibitor (cyclopiazonic acid), consistent with studies suggesting that there are subpopulations of SR. Raising cytosolic free calcium by depolarizing the cell with 30 mM extracellular KCl, resulted in an increase in [Ca2+](SR); however, the calcium gradient was unchanged. Lowering cell phosphorylation potential, which would reduce the free energy available for the SR Ca2+-ATPase, leads to a decrease in the calcium gradient across the SR, but this reduced gradient was primarily due to an increase in cytosolic free calcium and not a net release of SR calcium. C1 DUKE UNIV,MED CTR,DEPT PATHOL,DURHAM,NC 27710. RP Chen, W (reprint author), NIEHS,LAB MOLEC BIOPHYS,MD 4A-01,POB 12233,RES TRIANGLE PK,NC 27709, USA. FU NHLBI NIH HHS [R01-HL39752, R01 HL039752] NR 35 TC 80 Z9 80 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 1996 VL 271 IS 13 BP 7398 EP 7403 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC774 UT WOS:A1996UC77400032 PM 8631764 ER PT J AU Helm, BA Sayers, I Higginbottom, A Machado, DC Ling, Y Ahmad, K Padlan, EA Wilson, APM AF Helm, BA Sayers, I Higginbottom, A Machado, DC Ling, Y Ahmad, K Padlan, EA Wilson, APM TI Identification of the high affinity receptor binding region in human immunoglobulin E SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PRAUSNITZ-KUSTNER REACTION; IGE-RECEPTOR; ESCHERICHIA-COLI; FC FRAGMENTS; SITE; INHIBITION; CHAIN; PURIFICATION; DOMAIN AB We have investigated the capacity of N- and C-terminally truncated and chimeric human (h) IgE-derived peptides to inhibit the binding of I-125-labeled hIgE, and to engage cell lines expressing high and low affinity receptors (Fc epsilon RI/II). The peptide sequence Pro(343)-Ser(353) of the hC epsilon 3 domain is common to all he-chain peptides that recognize hFc epsilon RI. This region in IgE is homologous to the A loop in C gamma 2 that engages the rat neonatal IgG receptor. Optimum Fc epsilon RI occupancy by hIgE occurs at pH 6.4, with a second peak at 7.4. N- or C-terminal truncation has little effect on the association rate of the ligands with this receptor. Dissociation markedly increases following C-terminal deletion, and hFc epsilon RI occupancy at pH 6.4 is diminished. His residue(s) in the C-terminal region of the epsilon-chain may thus contribute to the high affinity of interaction. Grafting the homologous rat epsilon-chain sequence into hIgE maintains Fc epsilon RI interaction without conferring binding to rat Fc epsilon RI. hFc epsilon RII interaction is lost, suggesting that these residues also contribute to hFc epsilon RII binding. h epsilon-chain peptides comprising only this sequence do not block hIgE/hFc epsilon RI interaction or engage the receptor. Therefore, sequences N- or C-terminal to this core peptide provide structures necessary for receptor recognition. C1 NIDDK,NIH,BETHESDA,MD 20892. EURO DPC LTD,LLANBERIS LL55 4EL,GWYNEDD,WALES. RP Helm, BA (reprint author), UNIV SHEFFIELD,KREBS INST BIOMOLEC RES,MBB,SHEFFIELD S10 2UH,S YORKSHIRE,ENGLAND. RI Machado, Denise/G-2852-2014 OI Machado, Denise/0000-0002-9371-5886 NR 36 TC 37 Z9 38 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 1996 VL 271 IS 13 BP 7494 EP 7500 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC774 UT WOS:A1996UC77400047 PM 8631779 ER PT J AU Williamson, LC Halpern, JL Montecucco, C Brown, JE Neale, EA AF Williamson, LC Halpern, JL Montecucco, C Brown, JE Neale, EA TI Clostridial neurotoxins and substrate proteolysis in intact neurons - Botulinum neurotoxin C acts on synaptosomal-associated protein of 25 kDa SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINAL-CORD NEURONS; TETANUS-TOXIN; NEUROTRANSMITTER RELEASE; SYNAPTIC TRANSMISSION; MEMBRANE-PROTEIN; CULTURE; SNAP-25; FUSION; IDENTIFICATION; SYNAPTOBREVIN AB Clostridial neurotoxins are zinc endopeptidases that block neurotransmission and have been shown to cleave, in vitro, specific proteins involved in synaptic vesicle docking and/or fusion. We have used immunohistochemistry and immunoblotting to demonstrate alterations in toxin substrates in intact neurons under conditions of toxin-induced blockade of neurotransmitter release. Vesicle-associated membrane protein, which colocalizes with synaptophysin, is not detectable in tetanus toxin-blocked cultures. Syntaxin, also concentrated in synaptic sites, is cleaved by botulinum neurotoxin C. Similarly, the carboxyl terminus of the synaptosomal-associated protein of 25 kDa (SNAP-25) is not detectable in botulinum neurotoxin A-treated cultures. Unexpectedly, tetanus toxin exposure causes an increase in SNAP-25 immunofluorescence, reflecting increased accessibility of antibodies to antigenic sites rather than increased expression of the protein. Furthermore, botulinum neurotoxin C causes a marked loss of the carboxyl terminus of SNAP-25 when the toxin is added to living cultures, whereas it has no action on SNAP-25 in in vitro preparations, This study is the first to demonstrate in functioning neurons that the physiologic response to these toxins is correlated with the proteolysis of their respective substrates, Furthermore, the data demonstrate that botulinum neurotoxin C, in addition to cleaving syntaxin, exerts a secondary effect on SNAP-25. C1 US FDA,CTR BIOL EVALUAT & RES,BETHESDA,MD 20892. UNIV PADUA,CTR CNR BIOMEMBRANE,I-35121 PADUA,ITALY. UNIV PADUA,DIPARTIMENTO SCI BIOMED SPERIMENTALI,I-35121 PADUA,ITALY. USA,INST INFECT DIS,FT DETRICK,MD 21701. RP Williamson, LC (reprint author), NICHHD,DEV NEUROBIOL LAB,NIH,BLDG 49,RM 5A38,BETHESDA,MD 20892, USA. FU Telethon [473] NR 43 TC 155 Z9 157 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 1996 VL 271 IS 13 BP 7694 EP 7699 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC774 UT WOS:A1996UC77400076 PM 8631808 ER PT J AU Ghosh, P Sica, A Cippitelli, M Subleski, J Lahesmaa, R Young, HA Rice, NR AF Ghosh, P Sica, A Cippitelli, M Subleski, J Lahesmaa, R Young, HA Rice, NR TI Activation of nuclear factor of activated T cells in a cyclosporin A-resistant pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VERSUS-HOST DISEASE; REGULATORY ELEMENTS; ANTIGEN RECEPTOR; IDENTIFICATION; CALCINEURIN; EXPRESSION; PROMOTER; BINDING AB The mechanism of action of the immunosuppressive drug cyclosporin A (CsA) is the inactivation of the Ca2+/calmodulin-dependent serine-threonine phosphatase calcineurin by the drug-immunophilin complex, Inactive calcineurin is unable to activate the nuclear factor of activated T cells (NFAT), a transcription factor required for expression of the interleukin 2 (IL-2) gene. IL-2 production by CsA-treated cells is therefore dramatically reduced, We demonstrate here, however, that NFAT can be activated, and significant levels of IL-2 can be produced by the CsA-resistant CD28-signaling pathway. In transient transfection assays, both multicopy NFAT- and IL-2 promoter-beta-galactosidase reporter gene constructs could be activated by phorbol 12-myristate 13-acetate (PMA)/alpha CD28 stimulation, and this activation was resistant to CsA. Electrophoretic mobility shift assay showed the induction of a CsA-resistant NFAT complex in the nuclear extracts of peripheral blood T cells stimulated with PMA plus alpha CD28. Peripheral blood T cells stimulated with PMA/alpha CD28 produced IL-2 in the presence of CsA. Collectively, these data suggest that NFAT can be activated and IL-2 can be produced in a calcineurin independent manner. C1 SAIC,EXPTL IMMUNOL LAB,DIV BASIC SCI,FREDERICK,MD 21702. SAIC,BIOL CARCINOGENESIS DEV PROGRAM,FREDERICK,MD 21702. SYNTEX RES,DEPT LEUKOCYTE BIOL,PALO ALTO,CA 94304. NCI,MOLEC BASIS CARCINOGENESIS LAB,ABL BASIC RES PROGRAM,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. OI CIPPITELLI, Marco/0000-0002-9620-538X NR 27 TC 49 Z9 49 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 1996 VL 271 IS 13 BP 7700 EP 7704 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC774 UT WOS:A1996UC77400077 PM 8631809 ER PT J AU Jenkins, TM Engelman, A Ghirlando, R Craigie, R AF Jenkins, TM Engelman, A Ghirlando, R Craigie, R TI A soluble active mutant of HIV-1 integrase - Involvement of both the core and carboxyl-terminal domains in multimerization SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; RETROVIRAL INTEGRATION; ESCHERICHIA-COLI; DNA INTEGRATION; PROTEIN INVITRO; RNA-POLYMERASE; IDENTIFICATION; MUTAGENESIS; REGION; TYPE-1 AB Structural studies of human immunodeficiency virus type 1 (HIV-1) integrase have been impeded by the low solubility of the protein. By systematic replacement of hydrophobic residues, we previously identified a single amino acid change (F185K) that dramatically improved the solubility of the catalytic domain of HIV-1 integrase and enabled the structure to be determined by x-ray crystallography. We have introduced the same mutation into full-length HIV-1 integrase. The resulting recombinant protein is soluble and fully active in vitro, whereas, HIV-1 carrying the mutation is replication-defective due to improper virus assembly. Analysis of the recombinant protein by gel filtration and sedimentation equilibrium demonstrate a dimer-tetramer self-association. We find that the regions involved in multimerization map to both the catalytic core and carboxyl-terminal domains. The dramatically improved solubility of this protein make it a good candidate for structural studies. C1 NIDDKD,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. RI Ghirlando, Rodolfo/A-8880-2009 NR 42 TC 239 Z9 248 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 1996 VL 271 IS 13 BP 7712 EP 7718 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC774 UT WOS:A1996UC77400079 PM 8631811 ER PT J AU Kitaura, M Nakajima, T Imai, T Harada, S Combadiere, C Tiffany, HL Murphy, PM Yoshie, O AF Kitaura, M Nakajima, T Imai, T Harada, S Combadiere, C Tiffany, HL Murphy, PM Yoshie, O TI Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; FUNCTIONAL EXPRESSION; RANTES; CYTOKINE; 1-ALPHA; GENE; CDNA AB The CC chemokine eotaxin is a selective chemoattractant for guinea pig eosinophils, first purified from bronchoalveolar lavage fluid in a guinea pig model of allergic airway inflammation. We have now isolated the gene and cDNA for a human counterpart of eotaxin. The gene maps to chromosome 17 and is expressed constitutively at high levels in small intestine and colon, and at lower levels in various other tissues. The deduced mature protein sequence is 66% identical to human monocyte chemoattractant protein-1, and 60% identical to guinea pig eotaxin. Recombinant human eotaxin produced in insect cells induced a calcium flux response in normal human eosinophils, but not in neutrophils or monocytes. The response could not be desensitized by pretreatment of eosinophils with other CC chemokines, suggesting a unique receptor. In this regard, we show that human eotaxin is a potent and highly specific agonist for CC chemokine receptor 3, a G protein-coupled receptor selectively expressed in human eosinophils. Thus eotaxin and CC chemokine receptor 3 may be host factors highly specialized for eosinophil recruitment in inflammation, and may be good targets for the development of selective drugs for inflammatory diseases where eosinophils contribute to pathogenesis, such as asthma. C1 NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892. SHIONOGI INST MED SCI,SETTSU,OSAKA 566,JAPAN. RI Combadiere, Christophe/I-5639-2013 OI Combadiere, Christophe/0000-0002-1755-4531 NR 37 TC 299 Z9 305 U1 0 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 1996 VL 271 IS 13 BP 7725 EP 7730 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC774 UT WOS:A1996UC77400081 PM 8631813 ER PT J AU Bang, OS Ruscetti, FW Lee, MH Kim, SJ BirchenallRoberts, MC AF Bang, OS Ruscetti, FW Lee, MH Kim, SJ BirchenallRoberts, MC TI Transforming growth factor-beta 1 modulates p107 function in myeloid cells - Correlation with cell cycle progression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RETINOBLASTOMA GENE-PRODUCT; TRANSCRIPTION FACTOR E2F; FACTOR-BETA; TGF-BETA; NEGATIVE REGULATION; CATALYTIC SUBUNIT; DEPENDENT KINASE; MAMMALIAN-CELLS; PROTEIN-KINASE; DNA-SYNTHESIS AB Transforming growth factor-beta 1 (TGF-beta 1) is a potent inhibitor of hematopoietic cell growth. Here we report that TGF-beta 1 signals inhibition of IL-3-dependent 32D-123 murine myeloid cell growth by modulating the activities of cyclin E and cyclin-dependent kinase 2 (cdk2) proteins and their complex formation in the G(1) phase of the cell cycle. Whereas the cyclin E protein was hyperphosphorylated in TGF-beta 1-treated cells, TGF-beta 1 decreased both the phosphorylation of cdk2 and the kinase activity of the cyclin E-cdk2 complex. Decreased cyclin E-cdk2 kinase activity correlated with decreased phosphorylation of the retinoblastoma-related protein p107. In support of these observations, transient overexpression of p107 inhibited the proliferation of the myeloid cells, and expression of antisense oligo deoxynucleotides to p107 mRNA blocked TGF-beta 1 inhibition of myeloid cell growth. Furthermore, as reported previously, in 32D-123 TGF-beta 1-treated cells, c-Myc protein expression was decreased. TGF-beta 1 increased the binding of p107 to the transcription factor E2F, leading to decreased c-Myc protein levels, p107 inhibited E2F transactivation activity and was also found to bind the c-Myc protein, suggesting p107 negative regulation of c-Myc protein function. These studies demonstrate the modulation of p107 function by TGF-beta 1 and suggest a novel mechanism by which TGF-beta 1 blocks cell cycle progression in myeloid cells. C1 NCI,CHEMOPREVENT LAB,NIH,BETHESDA,MD 20892. HARVARD UNIV,SCH MED,MASSACHUSETTS GEN HOSP CANC CTR,MOLEC ONCOL LAB,BOSTON,MA 02129. NCI,BIOL CARCINOGENESIS & DEV PROGRAM,SAIC FREDERICK,NIH,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,LAB LEUKOCYTE BIOL,DIV BASIC SCI,NIH,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NCI,DIV CANC TREATMENT,NIH,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. NR 73 TC 9 Z9 10 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 29 PY 1996 VL 271 IS 13 BP 7811 EP 7819 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC774 UT WOS:A1996UC77400093 PM 8631825 ER PT J AU Cho, SJ Tropsha, A Suffness, M Cheng, YC Lee, KH AF Cho, SJ Tropsha, A Suffness, M Cheng, YC Lee, KH TI Antitumor agents .163. Three-dimensional quantitative structure-activity relationship study of 4'-O-demethylepipodophyllotoxin analogs using the modified CoMFA/q(2)-GRS approach SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID DNA TOPOISOMERASE-II; MOLECULAR-FIELD ANALYSIS; POTENT INHIBITORS; DERIVATIVES; BINDING; PODOPHYLLOTOXIN; MECHANISM; ETOPOSIDE; TUBULIN; COMFA AB Analogs of 4'-O-demethylepipodophyllotoxin are considered as potential anticancer agents. We have applied comparative molecular field analysis (CoMFA) and a novel CoMFA/q(2)-GRS technique recently developed in our group to identify the essential structural requirements for increasing the ability of these compounds to form cellular protein-DNA complex. In addition, a new method to incorporate different types of probe atoms as part of q(2)-GRS routine has been developed. The best final model with 101 compounds using a combination of four different sets of probe atoms and charges [C (sp(3), +1), C (sp(3), 0), H (+1), and O (sp(3), -1)] yielded a q(2) of 0.584 and the standard error of prediction of 0.660 at 5 principal components. The steric and electrostatic contour plots of the final model were compared with the DNA phosphate backbone environment of the DNA-4'-O-demethylepipodophyllotoxin analog complex, which was generated using the X-ray structure of the DNA-nogalamycin complex. The comparison reveals that the CoMFA steric and electrostatic fields are compatible with stereochemical properties of the DNA backbone. The results obtained from this study shall guide our future synthetic efforts. C1 UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,CHAPEL HILL,NC 27599. NCI,DIV CANC TREATMENT,BETHESDA,MD 20892. YALE UNIV,SCH MED,DEPT PHARMACOL,NEW HAVEN,CT 06510. RI Tropsha, Alexander/G-6245-2014 NR 32 TC 78 Z9 78 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 29 PY 1996 VL 39 IS 7 BP 1383 EP 1395 DI 10.1021/jm9503052 PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UC705 UT WOS:A1996UC70500007 PM 8691468 ER PT J AU Kuo, SC Ibuka, T Huang, LJ Lien, JC Yean, SR Huang, SC Lednicer, D MorrisNatschke, S Lee, KH AF Kuo, SC Ibuka, T Huang, LJ Lien, JC Yean, SR Huang, SC Lednicer, D MorrisNatschke, S Lee, KH TI Synthesis and cytotoxicity of 1,2-disubstituted naphth[2,3-d]imidazole-4,9-diones and related compounds SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTICANCER AGENTS; QUINONES AB As part of our continuing search for potential anticancer drug candidates that are selective against slowly growing solid tumors, we have synthesized several series of 1- and a-substituted derivatives of the lead structure, 1-ethyl-2-methylnaphth[2,3-d]imidazole-4,9-dione (5). Their cytotoxic activity in the National Cancer Institute's in vitro cancer cell line panel is reported. In general, substitution of various alkyl, phenyl, or benzyl moieties did not improve activity, and compound 5 remains the most active naphth[2,3-d]imidazole-4,9-dione derivative. However, high levels of activity and selectivity were found with several related 2-(acylamino)-3-chloro-1,4-naphthoquinone, (2f-j). Compound 2i, 2-[(2-fluorophenyl)acetamido]-3-chloro-1,4-naphthoquinone, has been selected for further in vivo testing and as an additional lead compound for further structural modification. C1 NCI,NIH,DRUG SYNTH & CHEM BRANCH,DEV THERAPEUT PROGRAM,DIV CANC TREATMENT,BETHESDA,MD 20892. UNIV N CAROLINA,SCH PHARM,DIV MED CHEM & NAT PROD,NAT PROD LAB,CHAPEL HILL,NC 27599. RP Kuo, SC (reprint author), CHINA MED COLL,GRAD INST PHARMACEUT CHEM,TAICHUNG 400,TAIWAN. FU NCI NIH HHS [CA 17625] NR 18 TC 25 Z9 25 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 29 PY 1996 VL 39 IS 7 BP 1447 EP 1451 DI 10.1021/jm950247k PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UC705 UT WOS:A1996UC70500014 PM 8691475 ER PT J AU Aronson, B Enmon, JL Izenwasser, S Katz, JL Kelkar, SV Luo, LB Nolan, SP Trudell, ML AF Aronson, B Enmon, JL Izenwasser, S Katz, JL Kelkar, SV Luo, LB Nolan, SP Trudell, ML TI Synthesis and ligand binding of eta(6)-(2 beta-carbomethoxy-3 beta-phenyltropane) transition metal complexes SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID COCAINE RECEPTOR; DOPAMINE UPTAKE; ANALOGS; INHIBITORS; ARENE AB The transition metal complexes [eta(6)-(2 beta-carbomethoxy-3 beta-phenyltropane)]tricarbonylchromium (3) and [eta(6)-(2 beta-carbomethoxy-3 beta-phenyltropane)][eta(5)-(phentamethylcyclopentadienyl)]ruthenium(II) triflate (4) were synthesized from 2 beta-carbomethoxy-3 beta-phenyltropane (2, WIN 35,065) to further elucidate the influence of substituents on the 3 beta-aryl on the affinity of the ligand for cocaine-binding sites at the dopamine transporter. The compounds were tested for their ability to displace bound [H-3]WIN 35,428 (5) from rat caudate putamen tissue and for their ability to inhibit [H-3]dopamine uptake. The binding affinity for 3 was a-fold greater than those observed for cocaine (1) and 2, while the binding affinity for 4 was found to be 100-fold less than those of 1 and 2. In addition, 3 was equipotent with 1 and 2 in [H-3]dopamine uptake inhibition studies, while 4 was 10-fold less potent. The potencies of the complexes 3 and 4 correlated; well with the structure-activity relationships of other 2 beta-carbomethoxy-3 beta-aryltropane derivatives. These data further support a pharmacophore model in which the region occupied by the aryl ring is a lipophilic pocket with electropositive character. C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIDA,DIV INTRAMURAL RES,BALTIMORE,MD 21224. RI Izenwasser, Sari/G-9193-2012; Nolan, Steven/C-8465-2013 OI Nolan, Steven/0000-0001-9024-2035 FU NIDA NIH HHS [DA08055] NR 26 TC 14 Z9 14 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 29 PY 1996 VL 39 IS 7 BP 1560 EP 1563 DI 10.1021/jm9508797 PG 4 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UC705 UT WOS:A1996UC70500028 PM 8691489 ER PT J AU Shippenberg, TS Heidbreder, C Lefevour, A AF Shippenberg, TS Heidbreder, C Lefevour, A TI Sensitization to the conditioned rewarding effects of morphine: Pharmacology and temporal characteristics SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE sensitization; morphine; opioid; psychostimulant; conditioned reward; place preference conditioning ID PLACE; RATS; AMPHETAMINE; TOLERANCE; ABUSERS; COCAINE; DRUGS AB An unbiased place preference conditioning procedure was used to determine whether the repeated administration of morphine results in sensitization to its conditioned rewarding effects. Rats received once daily injections of saline or morphine (5.0 mg/kg; i.p.) for 5 days in a room distinct from that where conditioning would occur. Place preference conditioning commenced 72 h later. A minimum of three drug conditioning sessions was necessary for the establishment of morphine-induced conditioned place preferences in saline-pretreated rats. The minimum dose producing this effect was 5.0 mg/kg. in animals pre-exposed to morphine, significant place preferences occurred after only two drug conditioning sessions and in response to doses of 3.0 mg/kg and greater. The augmented response to morphine was apparent when conditioning commenced 3, 10 or 21 days after the cessation of morphine pretreatment. It was not apparent when conditioning commenced 1 day after treatment cessation. An enhanced response to morphine was also observed in rats which had previously received either fentanyl(0.016 mg/kg/day) or nicotine (0.4 mg/kg/day) for 5 days. Animals which received morphine or fentanyl in combination with naloxone (0.5 mg/kg; s.c.) for 5 days failed to exhibit a conditioned response to morphine. When, however, naloxone was administered in combination with nicotine, significant morphine-induced place preferences were still seen. These data demonstrate that both sensitization and cross-sensitization develop to the conditioned rewarding effects of morphine. Furthermore, they indicate that the sensitization induced by morphine and fentanyl, but not nicotine, is opioid-receptor mediated. RP Shippenberg, TS (reprint author), NIDA, NIH, PRECLIN PHARMACOL LAB, DIV INTRAMURAL RES, POB 5180, BALTIMORE, MD 21224 USA. NR 30 TC 149 Z9 152 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 MAR 28 PY 1996 VL 299 IS 1-3 BP 33 EP 39 DI 10.1016/0014-2999(95)00852-7 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UD276 UT WOS:A1996UD27600006 PM 8901005 ER PT J AU Szallasi, A Acs, G Cravotto, G Blumberg, PM Lundberg, JM Appendino, G AF Szallasi, A Acs, G Cravotto, G Blumberg, PM Lundberg, JM Appendino, G TI A novel agonist, phorbol 12-phenylacetate 13-acetate 20-homovanillate, abolishes positive cooperativity of binding by the vanilloid receptor SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE vanilloid receptor; binding cooperativity; resiniferatoxin; capsaicin; PPAHV (phorbol 12-phenylacetate 13-acetate 20-homovanillate) ID PRIMARY SENSORY NEURONS; CAPSAICIN RECEPTOR; RESINIFERATOXIN BINDING; ACETYLCHOLINE-RECEPTOR; ESTROGEN-RECEPTOR; MODULATION; REDUCTION; ANALOGS AB Capsaicin binds to a specific recognition site, referred to as the vanilloid receptor, which it shares with the natural, ultrapotent agonist resiniferatoxin and with the competitive antagonist capsazepine. Upon binding to its receptor, capsaicin opens a cation channel leading to Ca2+ influx. The binding of capsaicin or resiniferatoxin by the vanilloid receptor follows a sigmoidal saturation curve, indicative of positive cooperativity, The biological significance of this positive cooperative behaviour is unknown, as is the mechanism responsible for it. We have developed a novel ligand, phorbol 12-phenylacetate 13-acetate 20-homovanillate (PPAHV), which binds to cultured rat sensory neurons (with a K-i of 3.1 +/- 0.4 mu M), and induces Ca2+ uptake by them (with an ED(50) of 1.8 +/- 0.3 mu M) with similar affinities and in a non-cooperative manner (Hill coefficients are 0.99 and 1.06 for binding and Ca2+ uptake, respectively). The behaviour of PPAHV thus contrasts with resiniferatoxin or capsaicin not only in the lack of cooperativity but also in the relative potencies for resiniferatoxin binding versus Ca2+ uptake (resiniferatoxin is less potent and capsaicin is more potent for induction of Ca2+ uptake than for binding). In further experiments in which the concentration of [H-3]resiniferatoxin was varied, 1 mu M PPAHV likewise reduced the cooperativity index that characterizes resiniferatoxin binding to rat spinal cord membranes from 2.3 +/- 0.1 to 1.1 +/- 0.2; in parallel experiments, neither capsaicin nor capsazepine (both at a concentration of 2 mu M) affected binding cooperativity. Moreover, PPAHV (1 mu M) turned the bi-phasic dissociation curve of resiniferatoxin into a monophasic curve, eliminating the second, slow-dissociation phase. The present results suggest that positive cooperativity is a ligand-induced feature rather than an inherent property of vanilloid receptors. A comparison of the spectrum of biological activity of ligands which bind to vanilloid receptors with different degrees of cooperativity may provide an approach to explore the functional significance of this binding behaviour. C1 NCI,BETHESDA,MD 20892. UNIV TURIN,DIPARTIMENTO SCI & TECHNOL FARMACO,I-10125 TURIN,ITALY. RP Szallasi, A (reprint author), KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,DIV PHARMACOL,S-17177 STOCKHOLM,SWEDEN. RI Appendino, Giovanni/O-4832-2015 OI Appendino, Giovanni/0000-0002-4170-9919 NR 37 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD MAR 28 PY 1996 VL 299 IS 1-3 BP 221 EP 228 DI 10.1016/0014-2999(95)00864-0 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UD276 UT WOS:A1996UD27600027 PM 8901026 ER PT J AU Anderson, LM Souliotis, VL Chhabra, SK Moskal, TJ Harbaugh, SD Kyrtopoulos, SA AF Anderson, LM Souliotis, VL Chhabra, SK Moskal, TJ Harbaugh, SD Kyrtopoulos, SA TI N-nitrosodimethylamine-derived O-6-methylguanine in DNA of monkey gastrointestinal and urogenital organs and enhancement by ethanol SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HUMAN CANCER; RAT; METABOLISM; ALKYLTRANSFERASE; EXPOSURE; ALCOHOL; TISSUES; REPAIR AB N-nitrosodimethylamine (NDMA) is a human cancer initiator suspect. Ethanol, a cancer risk factor, may synergize with nitrosamines by suppressing hepatic clearance, to increase internal exposure. A limitation to these hypotheses is lack of activation of NDMA by many rodent tissues. However, systematic primate studies are lacking. Patas monkeys were utilized to investigate NDMA activation by primate tissues in vivo, generating the promutagenic DNA lesion O-6-methylguanine (O-6-meG). Adult monkeys received 0.1 mg/kg NDMA by gavage, in some cases preceded by ethanol. Four hours after NDMA only, O-6-meG was detected in DNA from all tissues. Levels were highest in gastric mucosa and liver and were only about 50% lower in DNA from white blood cells, esophagus, ovary, pancreas, urinary bladder and uterus. With ethanol co-exposure, amounts of O-6-meG increased at least 2-fold in all tissues except liver. The largest effect was in esophagus (17-fold increase), followed by ovary, large intestine, urinary bladder, spleen and cerebellum (9- to 13-fold increases), and uterus, cerebrum and brain stem (7- to 8-fold increases). Alkylguanine alkyltransferase activities varied over a 30-fold range and were highest in liver and stomach. Thus primate tissues, especially those of the gastrointestinal and urogenital organs, are sensitive targets for DNA adduct damage due to NDMA, and ethanol co-exposure leads to striking increases in adducts. Our data support epidemiology implicating nitrosamines in causation of cancers of stomach and other organs, and alcohol as enhancing internal exposure to nitrosamines. (C) 1996 Wiley-Liss, Inc. C1 NATL HELLEN RES FDN,ATHENS,GREECE. BIOQUAL INC,ROCKVILLE,MD. RP Anderson, LM (reprint author), NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,BLDG 538,FT DETRICK,FREDERICK,MD 21702, USA. NR 21 TC 41 Z9 41 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 28 PY 1996 VL 66 IS 1 BP 130 EP 134 DI 10.1002/(SICI)1097-0215(19960328)66:1<130::AID-IJC22>3.0.CO;2-G PG 5 WC Oncology SC Oncology GA UB751 UT WOS:A1996UB75100022 PM 8608956 ER PT J AU Xie, XL Kokubo, T Cohen, SL Mirza, UA Hoffmann, A Chait, BT Roeder, RG Nakatani, Y Burley, SK AF Xie, XL Kokubo, T Cohen, SL Mirza, UA Hoffmann, A Chait, BT Roeder, RG Nakatani, Y Burley, SK TI Structural similarity between TAFs and the heterotetrameric core of the histone octamer SO NATURE LA English DT Article ID TRANSCRIPTION FACTOR; PREINITIATION COMPLEX; CRYSTAL-STRUCTURE; NUCLEOSOME; RESOLUTION; INITIATION; INTERACTS; DOMAIN; DNA AB A complex of two TFIID TATA hox-binding protein-associated factors (TAF(II)s) is described at 2.0 Angstrom resolution. The amino-terminal portions of dTAF(II)42 and dTAF(II)62 from Drosophila adopt the canonical histone fold, consisting of two short alpha-helices flanking a long central alpha-helix. Like histones H3 and H4, dTAF(II)42 and dTAF(II)62 form an intimate heterodimer by extensive hydrophobic contacts between the paired molecules. In solution and in the crystalline state, the dTAF(II)42/dTAF(II)62 complex exists as a heterotetramer, resembling the (H3/H4), heterotetrameric core of the histone octamer, suggesting that TFIID contains a histone octamer-like substructure. C1 ROCKEFELLER UNIV,LAB MOLEC BIOPHYS,NEW YORK,NY 10021. ROCKEFELLER UNIV,MASS SPECTROMETRY & GASEOUS ION CHEM LAB,NEW YORK,NY 10021. ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10021. NICHHD,NIH,BETHESDA,MD 20892. NR 50 TC 211 Z9 215 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAR 28 PY 1996 VL 380 IS 6572 BP 316 EP 322 DI 10.1038/380316a0 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UC379 UT WOS:A1996UC37900050 PM 8598927 ER PT J AU Busettini, C Masson, GS Miles, FA AF Busettini, C Masson, GS Miles, FA TI A role for stereoscopic depth cues in the rapid visual stabilization of the eyes SO NATURE LA English DT Article ID OCULAR-FOLLOWING RESPONSES; DEPENDENCE AB PRIMATES have visual tracking systems that help stabilize the eyes on the surroundings by responding to retinal image motion at ultra-short latencies(1,2). However, as the observer moves through the environment, the image motion on the retina depends on the three-dimensional structure of the scene(3,4). We report here that the very earliest of these tracking responses is elicited only by objects moving in the immediate vicinity of the plane of fixation: objects nearer or farther are ignored. This selectivity is achieved by means of a stereoscopic depth mechanism which uses the fact that the two eyes have differing viewpoints, so only objects in the plane of fixation have images that occupy corresponding positions on the two retinae. Such behaviour is readily explained by the known binocular properties of some motion-selective neurons in the visual cortex(5). Some (stereoanomalous) subjects showed highly specific tracking deficits as though lacking one subtype of these neurons. C1 NEI,SENSORIMOTOR RES LAB,NIH,BETHESDA,MD 20892. RI MASSON, Guillaume/G-4615-2012 NR 11 TC 42 Z9 42 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAR 28 PY 1996 VL 380 IS 6572 BP 342 EP 345 DI 10.1038/380342a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UC379 UT WOS:A1996UC37900059 PM 8598928 ER PT J AU Hoffmann, A Chiang, CM Oelgeschlager, T Xie, XL Burley, SK Nakatani, Y Roeder, RG AF Hoffmann, A Chiang, CM Oelgeschlager, T Xie, XL Burley, SK Nakatani, Y Roeder, RG TI A histone octamer-like structure within TFIID SO NATURE LA English DT Article ID IMMEDIATE EARLY PROTEIN; RNA POLYMERASE-II; TATA BOX; PROMOTER INTERACTIONS; PREINITIATION COMPLEX; TRANSCRIPTION FACTOR; INITIATION; BINDING AB THE general transcription factor TFIID nucleates initiation complex formation through direct core promoter binding(1,2), commits promoters within chromatin to transcription(3), and mediates the action of transcriptional activators, a phenomenon that may correlate with enhanced TFIID recruitment(4-7) or conformational changes in TFIID-promoter complexes(8,9). Molecular studies of the multiprotein TFIID complex have identified a primary TATA binding subunit (TBP)(2), TBP-associated factors (TAFs) that interact with and mediate the function of activators(2,7,10,11) and intersubunit interactions(2) but have yielded relatively little insight into the structural organization of the complete or the actual mechanism of transcriptional activation. Here we present biochemical evidence for the structural relevance of histone homologies in the human TFIID subunits hTAF80, hTAF31 and hTAF20/15. Together with analyses of native TFIID complexes and accompanying crystallographic studies(12), the results suggest that there is a histone octamer-like TAF complex within TFIID. C1 ROCKEFELLER UNIV,BIOCHEM & MOLEC BIOL LAB,NEW YORK,NY 10021. ROCKEFELLER UNIV,LABS MOL BIOPHYS,NEW YORK,NY 10021. ROCKEFELLER UNIV,HOWARD HUGHES MED INST,NEW YORK,NY 10021. NINCDS,NIH,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD 20892. NR 30 TC 144 Z9 146 U1 0 U2 3 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAR 28 PY 1996 VL 380 IS 6572 BP 356 EP 359 DI 10.1038/380356a0 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UC379 UT WOS:A1996UC37900063 PM 8598932 ER PT J AU Kwon, TK Buchholz, MA Nordin, AA AF Kwon, TK Buchholz, MA Nordin, AA TI The cdk2 binding domain of p27(Kip) correlates with the inhibition of the kinase activity of cdk2/cyclin complexes SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID CYCLINS AB The cyclin-dependent kinase inhibitor p27(Kip) binds to cyclin/cyclin-dependent kinases and preferentially inhibits the catalytic activity of cdk2 and cdk4. The cdk2 binding domain of p27(Kip) was determined using a series of N-terminal truncated and point mutations of GST-p27(Kip). The binding domain was contained within amino acid residues 53-85. The inhibition of the catalytic activity of preformed functional cdk2/cyclin complexes by p27(Kip) was also associated with the binding domain. C1 NIA,CLIN IMMUNOL SECT,CTR GERONTOL RES,NIH,BALTIMORE,MD 21224. NR 23 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1996 VL 220 IS 3 BP 703 EP 709 DI 10.1006/bbrc.1996.0468 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE853 UT WOS:A1996UE85300039 PM 8607829 ER PT J AU Shastry, BS Hejtmancik, FJ Margherio, RT Trese, MT AF Shastry, BS Hejtmancik, FJ Margherio, RT Trese, MT TI Linkage mapping of new X-linked juvenile retinoschisis kindreds using microsatellite markers SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID GENE AB X-linked retinoschisis (RS) is an inherited bilateral eye disorder with variable clinical manifestations. Previous studies have localized RS locus to the region Xp22.1-p22.3 on the short arm of the X-chromosome. In an attempt to map the RS locus more precisely, we have performed linkage analysis in four previously unreported kindreds of different geographic origins using six microsatellite markers-DXS987, DXS207, DXS999, DXS443, DXS365 and DXS274-all located in the region Xp22.1-p22.3. Two point analysis suggests linkage to DXS207 (Z(max) = 1.8 at theta(max) = 0) and DXS999, DXS443, DXS365 and DXS274 (Z(max) = 1.2 at theta(max) = 0). Multipoint analysis has confirmed this linkage with these same markers (Z(max) = 2.107 at theta = 0). There are no recombinants between the disease phenotype and the above markers. These results indicate that RS gene in our families is located in the same inclusion interval (between DXS987 and DXS274) reported for other RS families. Furthermore, they confirm the lack of genetic/locus heterogeneity of RS. (C) 1996 Academic Press, Inc. C1 WILLIAM BEAUMONT HOSP,DEPT OPHTHALMOL,ROYAL OAK,MI 48073. NEI,BETHESDA,MD 20892. RP Shastry, BS (reprint author), OAKLAND UNIV,EYE RES INST,ROCHESTER,MI 48309, USA. FU NEI NIH HHS [EY05230] NR 17 TC 4 Z9 4 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1996 VL 220 IS 3 BP 824 EP 827 DI 10.1006/bbrc.1996.0488 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE853 UT WOS:A1996UE85300059 PM 8607849 ER PT J AU Wu, YM Tirindelli, R Ryba, NJP AF Wu, YM Tirindelli, R Ryba, NJP TI Evidence for different chemosensory signal transduction pathways in olfactory and vomeronasal neurons SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MOLECULAR-CLONING; ADENYLYL CYCLASE; EXPRESSION; PROTEIN; SYSTEM AB Both the olfactory and vomeronasal epithelia mediate chemosensory reception. Here we report that several molecules that are highly expressed in the olfactory epithelium and therefore are likely to be important mediators of olfactory signal transduction (Golf alpha, adenylyl cyclase III and the olfactory cyclic nucleotide gated ion channel) are nor present in the vomeronasal epithelium. Therefore it appears that distinct molecules mediate chemosensory signal transduction in the olfactory and vomeronasal epithelia. The genes for Golf alpha, adenylyl cyclase III, the olfactory cyclic nucleotide gated ion channel, G gamma 8 and olfactory marker protein which are all expressed in the olfactory epithelium have consensus Olf-1 binding sites. The transcription factor Olf-1 was found to be highly expressed in the olfactory epithelium and was detected at a similar level in the vomeronasal epithelium. The expression pattern of Olf-1 did not correlate with that of molecules involved in olfactory signaling but was more similar to the expression pattern of G gamma 8 and olfactory marker protein which are found both in olfactory and vomeronasal neurons. Therefore, expression of Olf-1 in the olfactory epithelium and the presence of Olf-1 binding sites in a number of different genes found to be expressed in the olfactory epithelium are not sufficient to explain the observed gene expression patterns. (C) 1996 Academic Press, Inc. C1 NIDR,NIH,BETHESDA,MD 20892. UNIV PARMA,IST FISIOL UMANA,I-43100 PARMA,ITALY. NR 16 TC 21 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1996 VL 220 IS 3 BP 900 EP 904 DI 10.1006/bbrc.1996.0503 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE853 UT WOS:A1996UE85300074 PM 8607864 ER PT J AU Baler, R Coon, S Klein, DC AF Baler, R Coon, S Klein, DC TI Orphan nuclear receptor RZR beta: Cyclic AMP regulates expression in the pineal gland SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID RETINOIC ACID; THYROID-HORMONE; GENE-EXPRESSION; SUPERFAMILY; SITE AB The nuclear orphan receptor RZR beta is highly expressed in the rat pineal gland. Recent studies proposed that melatonin, the pineal hormone which regulates a wide variety of circadian-linked phenomena, may be the natural ligand of this receptor. These provocative reports prompted us to learn more about RZR beta and how it might function in circadian physiology. Here we confirm high expression of this receptor in the pineal gland, and report that pineal RZR beta expression exhibits a strong daily rhythm. Expression is under photoneural regulation and involves an adrenergic --> cAMP mechanism. (C) 1996 Academic Press, Inc. C1 NICHHD,NIH,DEV NEUROBIOL LAB,SECT NEUROENDOCRINOL,BETHESDA,MD 20892. NR 16 TC 34 Z9 35 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1996 VL 220 IS 3 BP 975 EP 978 DI 10.1006/bbrc.1996.0517 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE853 UT WOS:A1996UE85300088 PM 8607878 ER PT J AU Rafferty, S Malech, HL AF Rafferty, S Malech, HL TI High reductase activity of recombinant NOS2 flavoprotein domain lacking the calmodulin binding regulatory sequence SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID NITRIC-OXIDE SYNTHASE; PURIFICATION; ENZYME AB Nitric oxide synthases (NOSs) represent a special case of the cytochrome P450: cytochrome P450 reductase system in which the two redox partners occur as distinct domains on the same polypeptide chain and are linked by a calmodulin binding regulatory sequence. We expressed the carboxy-terminal, flavoprotein domain (residues 527-1144) of murine NOS2 in E. coli. The UV-visible spectrum of this domain resembles those of other flavoproteins, and the protein catalyses the reduction of ferricytochrome c by NADPH [V-max = 3.1 +/- .1 mol cytochrome reduced/minute/mmol flavoprotein domain, K-m (cytochrome c) = 23 +/- 2 mu M, K-m (NADPH) = 0.30 +/- .06 mu M]. The high reductase activity of this NOS2 flavoprotein domain, which lacks a calmodulin binding site, precludes a role for this site in mediating electron transfer within the flavoprotein domain of the intact enzyme. This is in contrast to the case of NOS1 and suggests that electron transfer is regulated differently in the two isoforms. C1 NIAID,NIH,HOST DEF LAB,BETHESDA,MD 20892. NR 12 TC 14 Z9 14 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1996 VL 220 IS 3 BP 1002 EP 1007 DI 10.1006/bbrc.1996.0522 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE853 UT WOS:A1996UE85300093 PM 8607781 ER PT J AU Matsrafi, L Aflalo, E Blair, DG Priel, E AF Matsrafi, L Aflalo, E Blair, DG Priel, E TI Isolation of an 11-kDa protein associated with the topoisomerase I activity from equine infectious anemia virus SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA VIRUS; DNA TOPOISOMERASE; CAMPTOTHECIN; REPLICATION; RNA; INHIBITION; MUTANTS; ENZYME; GENE AB We have previously demonstrated the presence of topoisomerase I (topo I) activity in purified retroviral particles (i.e., human immunodeficiency virus type 1, equine infectious anemia virus-EIAV and moloney murine leukemia virus). In our present work, an attempt was made to determine the nature and origin of the protein that is associated with this activity. For that purpose we have isolated the topo I activity from equine infectious anemia virus cores and showed that a major protein band of an 11 kDa is present in the topo I active fractions. It was able to form a DNA-protein cleavable complex, which is one of the characteristics of topoisomerases. This protein was recognized by anti-EIAV p11 nucleocapsid protein (NC) antibodies that can also specifically remove the topo I activity from the purified topo I active fractions. Therefore, our present findings, which are compatible with our previous data concerning the HIV NC protein, suggest that the 11 kDa protein which is associated with the topo I activity in EIAV is the nucleocapsid protein. (C) 1996 Academic Press, Inc. C1 BEN GURION UNIV NEGEV,FAC HLTH SCI,CTR CANC RES,DEPT MICROBIOL & IMMUNOL,BEER SHEVA,ISRAEL. NCI,FREDERICK CANC RES & DEV CTR,MICROBIOL SECT,MOLEC ONCOL LAB,FREDERICK,MD 21702. NR 35 TC 4 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1996 VL 220 IS 3 BP 1028 EP 1035 DI 10.1006/bbrc.1996.0527 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE853 UT WOS:A1996UE85300098 PM 8607786 ER PT J AU Yano, K Kohn, LD Saji, M Kataoka, N Okuno, A Cutler, GB AF Yano, K Kohn, LD Saji, M Kataoka, N Okuno, A Cutler, GB TI A case of male-limited precocious puberty caused by a point mutation in the second transmembrane domain of the luteinizing hormone choriogonadotropin receptor gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID DNA AB We describe a Japanese patient with male-limited precocious puberty who has a heterozygous thymine to cytosine (T to C) transition at nucleotide 1193; the mutation encodes a methionine to threonine substitution in residue 398 (M398T) of transmembrane helix 2 of the luteinizing hormone/choriogonadotropin receptor. Transfected into COS-7 cells, M398T exhibited constitutively high basal cAMP levels but retained an agonist-induced cAMP response. The constitutively higher cAMP levels caused by M398T are consistent with Leydig cell activation and precocious puberty in the patient. By comparison to wild type receptor, M398T transfectants have significantly lower agonist-induced inositol phosphate (IF) levels at >10(-10) M hCG concentrations and a higher apparent affinity for binding hCG. These data suggest that the M398T substitution alters Gq coupling and phospholipase-C activation, as well as G(s) coupling and adenylyl cyclase activity, and changes the conformation of the extracellular domain of the receptor. (C) 1996 Academic Press, Inc. C1 NIDDKD,NIH,BETHESDA,MD 20892. NICHHD,NIH,BETHESDA,MD 20892. KAWASAKI MED UNIV,DEPT PEDIAT,KURASHIKI,OKAYAMA,JAPAN. RP Yano, K (reprint author), ASAHIKAWA MED COLL,DEPT PEDIAT,NISHIKAGURA 4-5-3-11,ASAHIKAWA,HOKKAIDO 078,JAPAN. NR 17 TC 41 Z9 43 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1996 VL 220 IS 3 BP 1036 EP 1042 DI 10.1006/bbrc.1996.0528 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UE853 UT WOS:A1996UE85300099 PM 8607787 ER PT J AU Warren, JL Harris, T AF Warren, JL Harris, T TI Dehydration in older adults SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIA,BETHESDA,MD 20892. RP Warren, JL (reprint author), US HLTH CARE FINANCING ADM,BALTIMORE,MD 21207, USA. NR 2 TC 3 Z9 3 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 27 PY 1996 VL 275 IS 12 BP 912 EP 912 DI 10.1001/jama.275.12.912 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA UA563 UT WOS:A1996UA56300029 PM 8598617 ER PT J AU Weller, JL Jaffe, H Roseboom, PH Zylka, MJ Klein, DC AF Weller, JL Jaffe, H Roseboom, PH Zylka, MJ Klein, DC TI 2D-PAGE Analysis: Adrenergically regulated pineal protein AIP 37/6 is a phosphorylated isoform of cytosolic malate dehydrogenase SO BRAIN RESEARCH LA English DT Article DE pineal; cyclic AMP; malate dehydrogenase; phosphorylation; aspartate/malate shuttle ID N-ACETYLTRANSFERASE ACTIVITY; HYDROXYINDOLE-O-METHYLTRANSFERASE; RAT PINEAL; SEQUENCE-ANALYSIS; CIRCADIAN-RHYTHM; MEKA PHOSDUCIN; GLAND; BETA; 3',5'-MONOPHOSPHATE; RESOLUTION AB The adrenergic transmitter norepinephrine (NE) dramatically increases the prominence of only two out of the hundreds of [S-35]methionine-labeled pineal proteins resolved by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE). One of these regulated proteins is AIP 37/6 (37 kDa, pI similar to 6). The labeling of this protein is increased similar to 100-fold by NE. In the study presented here the identity of AIP 37/6 was investigated. The results of microsequencing, immunochemical analysis of 2D-PAGE blots and size exclusion chromatography indicate that AIP 37/6 is an isoform of cytosolic malate dehydrogenase (cMDH; similar to 36.3 kDa; pI similar to 6.5). Associated studies indicate that this isoform is phosphorylated whereas the bulk of cMDH is not. Cotranslational phosphorylation of cMDH is discussed. C1 NICHHD,SECT NEUROENDOCRINOL,DEV NEUROBIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NINCDS,CELLULAR & DEV NEUROBIOL SECT,NEUROCHEM LAB,BASIC NEUROSCI PROGRAM,NATL INST HLTH,BETHESDA,MD 20892. NR 30 TC 1 Z9 1 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 MAR 25 PY 1996 VL 713 IS 1-2 BP 8 EP 16 DI 10.1016/0006-8993(95)01412-8 PG 9 WC Neurosciences SC Neurosciences & Neurology GA UE900 UT WOS:A1996UE90000002 PM 8724970 ER PT J AU Saunders, PA Hough, CJ Chuang, DM AF Saunders, PA Hough, CJ Chuang, DM TI Antagonists have a greater selectivity for muscarinic receptor subtypes in intact cerebellar granule cells than in membranes SO BRAIN RESEARCH LA English DT Article DE muscarinic antagonist; selectivity; intact cerebellar granule cell; intrinsic activity ID INDUCED DOWN-REGULATION; PHOSPHOINOSITIDE TURNOVER; ACETYLCHOLINE-RECEPTORS; MESSENGER-RNA; BINDING; AGONIST; EXPRESSION; LIGANDS; PROTEIN; M2 AB A comparison of muscarinic acetylcholine receptor (mAChR) antagonist binding properties was made between intact cerebellar granule cell cultures and membranes prepared from these cells. [H-3]quinuclidinyl benzylate (QNB) binding displacement by four mAChR antagonists was measured and the selectivities for m(2)- or m(3)-mAChRs estimated by curve fitting. For each antagonist, the preparation of membranes caused a subtype selective decrease in receptor affinity, as compared to intact cell binding. The m(2)-selective antagonists had lower affinities in membranes for m(2)- but not for m(3)-mAChR, while the m(3)-selective antagonists had lower affinities for m(3)- but not for m(2)-mAChR. As a result, the m(2)-mAChR selectivity of AF-DX 116 and methoctramine in membranes was 66- and 1.7 -fold less than in intact cells, and the m(3)-mAChR selectivity of 4-DAMP and pFHHSiD was 2.4- and 3.9-fold less in membranes than in intact cells. The m(3)-mAChR selectivity of 4-DAMP in intact cells was unaffected by cytoskeletal depolymerization with cytochalasins and colchicine. We suggest that the changes in selectivity seen with cell disruption may be due to a loss of cellular factors which regulate receptor properties. Antagonists binding to receptors on intact cells may cause subtype-specific changes in the interaction of the mAChR with these factors. These data suggest that mAChR antagonist binding selectivity needs to be re-examined in intact cell systems. C1 NIMH,MOLEC NEUROBIOL SECT,BIOL PSYCHIAT BRANCH,NATL INST HLTH,BETHESDA,MD 20892. NR 30 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 25 PY 1996 VL 713 IS 1-2 BP 29 EP 35 DI 10.1016/0006-8993(95)01458-6 PG 7 WC Neurosciences SC Neurosciences & Neurology GA UE900 UT WOS:A1996UE90000004 PM 8724972 ER PT J AU Fukuyama, R Hatanpaa, K Rapoport, SI Chandrasekaran, K AF Fukuyama, R Hatanpaa, K Rapoport, SI Chandrasekaran, K TI Gene expression of ND4, a subunit of complex I of oxidative phosphorylation in mitochondria, is decreased in temporal cortex of brains of Alzheimer's disease patients SO BRAIN RESEARCH LA English DT Article DE cloning; northern blot; selective vulnerability; human brain; energy metabolism; Alzheimer's disease ID OXIDASE COX ACTIVITY; CYTOCHROME-OXIDASE; NADH DEHYDROGENASE; ENTORHINAL CORTEX; MESSENGER-RNA; MONKEY BRAIN; DNA; LOCALIZATION; HIPPOCAMPUS; RAT AB Gene expression of mitochondrial DNA-encoded ND4 in brains of Alzheimer's disease (AD) patients and age-matched controls was measured using Northern blot. The level of ND4 message in temporal cortex of control subjects was higher than in motor cortex, whereas the level of ND4 gene expression in temporal cortex of AD brains was decreased compared with that in temporal cortex of controls. A control probe showed no difference in expression between the two areas of AD and control brains. These and previous data suggest that neurons vulnerable to AD express higher levels of enzymes of oxidative phosphorylation than do spared neurons, and that this difference may promote selective neuronal vulnerability of AD. C1 NIA,NEUROSCI LAB,NIH,BLDG 10,RM 6C103,BETHESDA,MD 20892. NR 29 TC 33 Z9 33 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 25 PY 1996 VL 713 IS 1-2 BP 290 EP 293 DI 10.1016/0006-8993(95)01517-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UE900 UT WOS:A1996UE90000035 PM 8725003 ER PT J AU Ledgerwood, EC Brennan, SO Cawley, NX Loh, YP George, PM AF Ledgerwood, EC Brennan, SO Cawley, NX Loh, YP George, PM TI Yeast aspartic protease 3 (Yap3) prefers substrates with basic residues in the P-2, P-1 and P-2' positions SO FEBS LETTERS LA English DT Article DE proalbumin processing; yeast; aspartic protease; Yap3 ID CONVERTING ENZYME; HUMAN PROALBUMINS; KEX2 PROTEASE; CLEAVAGE; ALBUMIN; PURIFICATION; PROTEINS; SITES; GENE AB The yeast aspartic protease Yap3 is localised to the secretory pathway and correctly cleaves pro-alpha-mating factor at its dibasic sites, We determined the specificity of Yap3 for mono-, di- and multi-basic cleavage sites in the context of 15 residue synthetic proalbumin peptides. Yap3 cleaved after dibasic ArgArg and LysArg sites but not after monobasic Arg sites even when there was an additional arginine at -6 and/or -4. Yap3 did not cleave a tetra-arginine site and tribasic sites (RRR and RRK) were poor substrates. Cleavage always occurred C-terminal to the last arginine in the di- or tri-basic sequence. The optimal cleavage site sequence was RR down arrow DR and this substrate was cleaved 8-9-fold faster than the normal RR down arrow DA sequence. In contrast to Kex2, Yap3 did not remove the propeptide from normal proalbumin or a range of natural or recombinant proalbumin variants, However at pH 4.0 Yap3 slowly cleaved proalbumin and albumin between domains 2 and 3. C1 NICHHD,DEV NEUROBIOL LAB,BETHESDA,MD 20892. RP Ledgerwood, EC (reprint author), CHRISTCHURCH HOSP,MOLEC PATHOL LAB,CHRISTCHURCH,NEW ZEALAND. OI Ledgerwood, Elizabeth/0000-0002-4956-6043 NR 25 TC 24 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 MAR 25 PY 1996 VL 383 IS 1-2 BP 67 EP 71 DI 10.1016/0014-5793(96)00219-0 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UC956 UT WOS:A1996UC95600016 PM 8612794 ER PT J AU DaSilva, L Rui, H Erwin, RA Howard, OMZ Kirken, RA Malabarba, MG Hackett, RH Larner, AC Farrar, WL AF DaSilva, L Rui, H Erwin, RA Howard, OMZ Kirken, RA Malabarba, MG Hackett, RH Larner, AC Farrar, WL TI Prolactin recruits STAT1, STAT3 and STAT5 independent of conserved receptor tyrosines TYR402, TYR479, TYR515 and TYR580 SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE prolactin; prolactin receptor; janus kinase; STAT transcription factor; signal transduction ID ERYTHROPOIETIN RECEPTOR; HUMAN MONOCYTES; EXPRESSION; REGION; GENE AB The present study of prolactin (PRL) receptor-mediated recruitment of signal transducers and activators of transcription (STATs) demonstrates that PRL activates STAT3, in addition to STAT1 and STAT5 as previously reported, and that STAT1, STAT3 and STAT5 are mediators of PRL effects in cells whether of lymphoid, myeloid or mammary epithelial origin. Furthermore, receptor mutants M240 and T280 that do not mediate PRL-induced JAK2 activation and cell proliferation, are also unable to mediate STAT activation, supporting the proposed model of JAK2 as the initial effector protein used by PRL receptors. On the other hand, tyrosine phosphorylation analysis and electrophoretic mobility shift assays showed that receptor mutant G328, which lacks four of the five conserved cytoplasmic tyrosine residues of PRL receptors, retained the ability to activate JAK2 and STAT1, STAT3 and STAT5. These results support the notion that phosphotyrosyl residues other than those of the receptor, i.e., JAK2, are involved in recruiting STAT proteins to the activated PRL receptor complex. C1 UNIFORMED SERV UNIV HLTH SCI,DEPT PATHOL,BETHESDA,MD 20814. NCI,MOLEC IMMUNOREGULAT LAB,CYTOKINE MOL MECHANISMS SECT,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702. US FDA,CTR BIOL EVALUAT & RES,DIV CYTOKINE BIOL,BETHESDA,MD 20814. RP DaSilva, L (reprint author), NCI,SAIC FREDERICK,FREDERICK CANC RES & DEV CTR,FREDERICK,MD 21702, USA. RI Howard, O M Zack/B-6117-2012; Malabarba, Maria Grazia/L-4805-2015 OI Howard, O M Zack/0000-0002-0505-7052; Malabarba, Maria Grazia/0000-0002-9457-2047 NR 46 TC 121 Z9 122 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 25 PY 1996 VL 117 IS 2 BP 131 EP 140 DI 10.1016/0303-7207(95)03738-1 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA UF453 UT WOS:A1996UF45300002 PM 8737372 ER PT J AU Scaldaferri, L Arora, K Lee, SH Catt, KJ Moretti, C AF Scaldaferri, L Arora, K Lee, SH Catt, KJ Moretti, C TI Expression of PACAP and its type-I receptor isoforms in the rat ovary SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE pituitary adenylate cyclase-activating polypeptide (PACAP); receptors; PACAP; PACAP receptor, type I isoforms; ovary ID CYCLASE-ACTIVATING POLYPEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; 38-AMINO ACID FORM; ADENYLATE-CYCLASE; MOLECULAR-CLONING; TISSUE DISTRIBUTION; BINDING-SITES; PITUITARY; CELLS; OUTGROWTH AB Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the secretin/glucagon/vasoactive intestinal peptide (VIP)/growth hormone releasing hormone (GHRH) family of neuropeptides, several of which stimulate steroidogenesis in ovarian granulosa cells. PACAP receptors are of two major subtypes; the type I receptor (PACAP-I-R) has much higher affinity for PACAP than VIP, and the type II receptor (PACAP-II-R) has similar affinity for both peptides. In the rat ovary, expression of the PACAP gene was demonstrated by amplification of ovarian RNA by the reverse transcription/polymerase chain reaction (RT-PCR). In addition, hybridization of Northern blots of rat ovarian poly(A)(+) RNA with a 706-nt rat hypothalamic PACAP-I-R cDNA probe revealed the presence of a 7.0 kb PACAP receptor transcript, similar to that detected in brain and hypothalamus. RT-PCR using specific primers for the PACAP-I-R gene yielded products of the expected size with RNA obtained from ovarian tissue, brain, and hypothalamus. The authenticity of the PCR products was confirmed by Southern blotting and nested PCR, which revealed at least three splice variants of the PACAP-I-R in the rat ovary. These findings demonstrate that both PACAP and PACAP-I-R isoforms are expressed in the rat ovary, where they could exert autocrine or paracrine actions on granulosa cell function. C1 UNIV ROMA TOR VERGATA,DEPT INTERNAL MED,SECT ENDOCRINOL & ANDROL,ROME,ITALY. NICHHD,ENDOCRINOL & REPROD RES BRANCH,NIH,BETHESDA,MD 20892. OI MORETTI, COSTANZO/0000-0003-4006-2575 NR 30 TC 38 Z9 39 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 25 PY 1996 VL 117 IS 2 BP 227 EP 232 DI 10.1016/0303-7207(95)03752-7 PG 6 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA UF453 UT WOS:A1996UF45300014 PM 8737384 ER PT J AU Randad, RS Lubkowska, L Bhat, TN Silva, A Gulnik, S Yu, B Erickson, JW AF Randad, RS Lubkowska, L Bhat, TN Silva, A Gulnik, S Yu, B Erickson, JW TI Iterative structure-based design of achiral, non-peptidic anthranilamide and benzamide-containing HIV protease inhibitors as antiviral agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 14 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500014 ER PT J AU Pommier, Y AF Pommier, Y TI DNA topoisomerases and their inhibitors. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,MOLEC PHARMACOL LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 25 EP CARB PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200716 ER PT J AU Beatrice, MG AF Beatrice, MG TI The role of pilot facilities in biologics manufacturing SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,CTR BIOL EVALUAT & RES,ROCKVILLE,MD 20852. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 37 EP BIOT PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48200492 ER PT J AU Walters, DB AF Walters, DB TI The pro's and con's of safety certification. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIEHS,NATL TOXICOL PROGRAM,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 40 EP CHAS PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48201787 ER PT J AU Zaharevitz, DW Gussio, R Pattabiraman, N Kellogg, GE Yang, S Bader, JP AF Zaharevitz, DW Gussio, R Pattabiraman, N Kellogg, GE Yang, S Bader, JP TI Combination of 3D QSAR and 3D database searching in the discovery of novel inhibitors of HIV-1 reverse transcriptase. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,DCTDC,DTP,ITB,ROCKVILLE,MD 20892. NCI,FCRDC,FBSC,FREDERICK,MD 21701. VIRGINIA COMMONWEALTH UNIV,DEPT MED CHEM,RICHMOND,VA. NCI,DCTDC,DTP,AVEB,ROCKVILLE,MD. RI Kellogg, Glen/A-8008-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 41 EP CINF PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48201829 ER PT J AU Ananthan, S Clayton, SD Kussner, CL Harris, B Hu, RJ Skolnick, P AF Ananthan, S Clayton, SD Kussner, CL Harris, B Hu, RJ Skolnick, P TI GABA(A)/benzodiazepine receptor ligands: Synthesis and structure-activity SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SO RES INST,BIRMINGHAM,AL 35255. NIDDK,NIH,NEUROSCI LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 54 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500054 ER PT J AU Chen, Z Izenwasser, S Katz, JL Trudell, ML AF Chen, Z Izenwasser, S Katz, JL Trudell, ML TI Synthesis and structure-activity studies of 9-azabicyclo[3.3.1]nonane cocaine analogs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 63 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500063 ER PT J AU Turnbull, SP Izenwasser, S Katz, JL Trudell, ML AF Turnbull, SP Izenwasser, S Katz, JL Trudell, ML TI Synthesis and activity of novel tricyclic cocaine analogs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL LAB,BALTIMORE,MD 21224. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 64 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500064 ER PT J AU Xu, L Kelkar, SV Lomenzo, SA Izenwasser, S Katz, JL Klein, CL Zhu, N Trudell, ML AF Xu, L Kelkar, SV Lomenzo, SA Izenwasser, S Katz, JL Klein, CL Zhu, N Trudell, ML TI Synthesis and biological evaluation of 2 beta-substituted 3 beta-aryltropanes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV NEW ORLEANS,DEPT CHEM,NEW ORLEANS,LA 70148. NIDA,INTRAMURAL RES PROGRAM,PSYCHOBIOL LAB,BALTIMORE,MD 21224. XAVIER UNIV,DEPT CHEM,NEW ORLEANS,LA 70125. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 65 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500065 ER PT J AU Stadtman, TC AF Stadtman, TC TI Biochemical roles of selected specific selenoenzymes and effects of non-specific incorporation of selenium in proteins. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,BIOCHEM LAB,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 102 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500102 ER PT J AU Sadler, BR Ishaq, KS AF Sadler, BR Ishaq, KS TI Synthesis and biological evaluation of probes for the estrogen receptor. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV N CAROLINA,SCH PHARM,CHAPEL HILL,NC 27599. NIEHS,REPROD & DEV TOXICOL LAB,RES TRIANGLE PK,NC 27709. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 152 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500151 ER PT J AU Carrasquillo, KG Hurley, JH AF Carrasquillo, KG Hurley, JH TI Crystallization of 3-isopropylumalate dehydrogenase in complex with NAD(+) and the transition state analogue O-isobutenyl oxalylhydroxamate. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIDDKD,MOLEC BIOL LAB,NATL INST HLTH,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 157 EP CHED PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48201169 ER PT J AU Para, KS Prasad, JVNV Sawyer, T Ferguson, D Tummino, PJ Erickson, JW Lunney, EA AF Para, KS Prasad, JVNV Sawyer, T Ferguson, D Tummino, PJ Erickson, JW Lunney, EA TI Comparative analysis of nonpeptide HIV-1 protease inhibitors containing a pyran-2-one ring using X-ray crystal structures SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 PARKE DAVIS PHARMACEUT RES,ANN ARBOR,MI 48106. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,FREDERICK BIOMED SUPERCOMP CTR,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 159 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500158 ER PT J AU Smith, MBK Michejda, CJ Smith, RH AF Smith, MBK Michejda, CJ Smith, RH TI Molecular modeling studies of complexes TIBO derivatives: Analysis of binding energy and structure as a key to understanding drug efficacy SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 164 EP MEDI PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500163 ER PT J AU Srinivasan, A Saavedra, JE Keefer, LK AF Srinivasan, A Saavedra, JE Keefer, LK TI Photolysis of O-2-alkyl diazeniumdiolates are they photochemically triggered nitric oxide donors? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,COMPARAT CARCINOGENESIS LAB,FREDERICK,MD 21702. NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BCDP,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 196 EP ORGN PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500551 ER PT J AU Tawa, GJ AF Tawa, GJ TI Dielectric continuum solvation combined with molecular mechanics, ab initio, and semi-empirical molecular orbital treatments of the solute. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PROGRAM,SAIC,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 226 EP PHYS PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48501159 ER PT J AU Brechbiel, MW Tsoupas, NM Ye, N Planalp, RP Bauer, CB Rogers, RD AF Brechbiel, MW Tsoupas, NM Ye, N Planalp, RP Bauer, CB Rogers, RD TI Facile synthesis of cis,cis-1,3,5-triaminocyclohexane and its use in synthesis of novel hexadentate chelating agents as radiopharmaceuticals. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NIH,CHEM SECT,BETHESDA,MD 20892. UNIV NEW HAMPSHIRE,DEPT CHEM,DURHAM,NH 03824. NO ILLINOIS UNIV,DEPT CHEM,DE KALB,IL 60115. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 236 EP ORGN PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48500591 ER PT J AU Rick, SW Burt, SK Erickson, JW AF Rick, SW Burt, SK Erickson, JW TI Large scale motions of HIV-1 protease: The free energy of flap opening for wild type and mutant enzymes SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 SAIC,FREDERICK NATL CANC INST,FREDERICK BIOMED SUPERCOMP CTR,STRUCT BIOCHEM PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 256 EP PHYS PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA485 UT WOS:A1996UA48501191 ER PT J AU Adamczeski, M Nwokekeh, NU Stange, A Bakus, BT Newman, DJ AF Adamczeski, M Nwokekeh, NU Stange, A Bakus, BT Newman, DJ TI Isolation and characterization of bioactive agents from leaves of Polygonum cuspidatum. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 AMERICAN UNIV,DEPT CHEM,WASHINGTON,DC 20016. US EPA,WASHINGTON,DC 20460. NCI,FREDERICK CANC RES & DEV CTR,LAB DRUG DISCOVERY RES & DEV,DEV THERAPEUT PROGRAM,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 276 EP CHED PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48201288 ER PT J AU Lesaca, EE Yeudall, WA AF Lesaca, EE Yeudall, WA TI Transforming growth factor-beta 1 inhibits cell growth & induces p21 (WAF-1) expression in human squamous carcinoma cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MT ST MARYS COLL,LOS ANGELES,CA 90049. NIDR,NIH,MOLEC CARCINOGENESIS GRP,LCDO,BETHESDA,MD 20892. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 279 EP CHED PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48201291 ER PT J AU Tsoupas, NM Ye, N Planalp, RP Bauer, CB Rogers, RD Brechbiel, MW AF Tsoupas, NM Ye, N Planalp, RP Bauer, CB Rogers, RD Brechbiel, MW TI Metal complexes of novel hexadentate ligands based on the cis-1,3,5-triaminocyclohexane framework: Synthesis, structure and stability under biological conditions. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 UNIV NEW HAMPSHIRE,DEPT CHEM,DURHAM,NH 03824. NO ILLINOIS UNIV,DEPT CHEM,DE KALB,IL 60115. NIH,RADIAT ONCOL BRANCH,CHEM SECT,BETHESDA,MD 20892. RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 559 EP INOR PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48203576 ER PT J AU Keefer, LK AF Keefer, LK TI Nitric oxide-releasing complexes as pharmaceutical agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 NCI,FREDERICK CANC RES & DEV CTR,COMPARAT CARCINOGENESIS LAB,CHEM SECT,FREDERICK,MD 21702. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 24 PY 1996 VL 211 BP 575 EP INOR PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA UA482 UT WOS:A1996UA48203592 ER PT J AU Wassermann, EM Cohen, LG Flitman, SS Chen, R Hallett, M AF Wassermann, EM Cohen, LG Flitman, SS Chen, R Hallett, M TI Seizures in healthy people with repeated ''safe'' trains of transcranial magnetic stimuli SO LANCET LA English DT Letter RP Wassermann, EM (reprint author), NINCDS,NIH,MED NEUROL BRANCH,BETHESDA,MD 20892, USA. RI Chen, Robert/B-3899-2009 OI Chen, Robert/0000-0002-8371-8629 NR 4 TC 74 Z9 79 U1 0 U2 3 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON, ENGLAND WC1B 3SL SN 0140-6736 J9 LANCET JI Lancet PD MAR 23 PY 1996 VL 347 IS 9004 BP 825 EP 826 DI 10.1016/S0140-6736(96)90898-3 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA UB153 UT WOS:A1996UB15300038 PM 8622349 ER PT J AU Bacon, BE Cherniak, R KwonChung, KJ Jacobson, ES AF Bacon, BE Cherniak, R KwonChung, KJ Jacobson, ES TI Structure of the O-deacetylated glucuronoxylomannan from Cryptococcus neoformans Cap70 as determined by 2D NMR spectroscopy SO CARBOHYDRATE RESEARCH LA English DT Article DE Cryptococcus neoformans; 2D NMR spectroscopy; capsular polysaccharide ID MAGNETIC-RESONANCE SPECTROSCOPY; CHROMATOGRAPHY MASS-SPECTROMETRY; SEROTYPE-A; CAPSULAR POLYSACCHARIDE; ROTATING-FRAME; SPECTRA; PROTEINS; H-1-NMR; PHASE; SEPARATION AB Cryptococcus neoformans, an opportunistic pathogen, is the fourth leading cause of death among AIDS patients. The yeast's capsule is a major virulence factor, and serotype is related to the chemical structure of glucuronoxylomannan (GXM), its capsular polysaccharide. The GXM from Cap70, a hypocapsular mutant of serotype D isolate B-3501, was investigated by chemical analysis and 2D NMR spectroscopy, The assignment of H-1 and C-13 chemical shifts for the O-deacetylated polysaccharide was accomplished from the analysis of DQF-COSY, TOCSY, and gradient-enhanced HSQC spectra. The sequence and linkage positions of glycosyl residues were determined by NOESY and ROESY spectra. Two repeating polysaccharide components were identified as having the following structures in approximately equal proportions: [GRAPHICS] It is not known if these repeating units comprise a single or two separate polymer chains. Pentasaccharide 2 has been known to be the major GXM polymer of B-3501 and other serotype D isolates. Hexasaccharide 1 is identified for the first time although it has subsequently been identified in other C. neoformans isolates. The presence of 1 in the GXM of Cap70 is consistent with the extra xylose found relative to that in isolate B-3501. The mannose:xylose:glucuronic acid:O-acetyl molar ratio of Cap70 GXM is 3.00: 1.73:0.78:1.75, while the same ratio for B-3501 and other serotype D isolates is approximately 3.00:1.00:0.80:1.75. Methylation analysis confirmed that the GXM of Cap70 contains unsubstituted, monosubstituted (2-linked), and disubstituted (2- and 4-linked) mannose in a ratio of 0.87:1.75:0.38. Dot blot immunoassay indicates that Cap70 is a serotype D isolate like its parent strain. C1 GEORGIA STATE UNIV,LBCS,DEPT CHEM,ATLANTA,GA 30303. NIAID,NIH,BETHESDA,MD 20205. VET AFFAIRS MED CTR,RES SERV,RICHMOND,VA 23249. FU NIAID NIH HHS [AI-31769] NR 48 TC 20 Z9 20 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAR 22 PY 1996 VL 283 BP 95 EP 110 DI 10.1016/0008-6215(95)00397-5 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA UC890 UT WOS:A1996UC89000007 PM 8901265 ER PT J AU Wolffe, AP Pruss, D AF Wolffe, AP Pruss, D TI Targeting chromatin disruption: Transcription regulators that acetylate histones SO CELL LA English DT Review ID YEAST RP Wolffe, AP (reprint author), NICHHD,MOLEC EMBRYOL LAB,NIH,BLDG 6,RM B1A-13,BETHESDA,MD 20892, USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 14 TC 327 Z9 332 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 SN 0092-8674 J9 CELL JI Cell PD MAR 22 PY 1996 VL 84 IS 6 BP 817 EP 819 DI 10.1016/S0092-8674(00)81059-4 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UC381 UT WOS:A1996UC38100002 PM 8601304 ER PT J AU Nakatani, Y Bagby, S Ikura, M AF Nakatani, Y Bagby, S Ikura, M TI The histone folds in transcription factor TFIID SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA POLYMERASE-II; TATA BOX-BINDING; PREINITIATION COMPLEX; PROMOTER INTERACTIONS; INITIATION; PURIFICATION; DOWNSTREAM; PROTEIN; DNA AB The transcription factor TFIID is a multimeric protein complex containing the TATA box-binding polypeptide (TBP) and TBP-associated factors. We have previously reported that the N-terminal regions of dTAF(II)62 and dTAF(II)42 have sequence similarities with histones H4 and H3. Here, we demonstrate that the histone-homologous regions of dTAF(II)62 and dTAF(II)42 form a heteromeric complex both in vitro and in a yeast two-hybrid system. Neither dTAF(II)62 nor dTAF(II)42 forms a homomeric complex, in agreement with a nucleosomal histone character. Moreover, circular dichroism measurements show that the heteromeric complex is dominated by cy-helical secondary structure. These results strongly suggest the existence of a histone-like surface on TFIID. C1 UNIV TORONTO,ONTARIO CANC INST,DIV MOLEC & STRUCT BIOL,TORONTO,ON M5G 2M9,CANADA. UNIV TORONTO,DEPT MED BIOPHYS,TORONTO,ON M5G 2M9,CANADA. UNIV TSUKUBA,CTR TSUKUBA ADV RES ALLIANCE,TSUKUBA,IBARAKI 305,JAPAN. UNIV TSUKUBA,INST APPL BIOCHEM,TSUKUBA,IBARAKI 305,JAPAN. RP Nakatani, Y (reprint author), NICHHD,NIH,LAB MOLEC GROWTH REGULAT,BLDG 6,RM 416,6 CTR DR,MSC 2753,BETHESDA,MD 20892, USA. NR 27 TC 29 Z9 30 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 22 PY 1996 VL 271 IS 12 BP 6575 EP 6578 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700004 PM 8636069 ER PT J AU Wolfe, PC Chang, EY Rivera, J Fewtrell, C AF Wolfe, PC Chang, EY Rivera, J Fewtrell, C TI Differential effects of the protein kinase C activator phorbol 12-myristate 13-acetate on calcium responses and secretion in adherent and suspended RBL-2H3 mucosal mast cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BASOPHILIC LEUKEMIA-CELLS; HISTAMINE-RELEASE; IMMUNOGLOBULIN-E; 2H3 CELLS; TYROSINE PHOSPHORYLATION; CROSS-LINKING; RECEPTOR; INFLUX; EXOCYTOSIS; SIGNALS AB Adhesion of RBL-2H3 mucosal mast cells to fibronectin-coated surfaces has been linked to changes in secretion and tyrosine kinase activity, me now show that adhesion affects the sensitivity of RBL cells to the protein kinase C activator phorbol 12-myristate 13-acetate (PMA). In suspended cells, PMA inhibited antigen-induced calcium influx (as measured by manganese influx) and changes in intracellular free calcium and had complex effects on antigen-stimulated secretion, However, in adherent cells PMA had little effect on these responses, Suspended cells only secreted in response to thapsigargin if they were co-treated with PMA, while adherent cells secreted in response to thapsigargin alone, The thapsigargin-induced secretion in adherent cells was inhibited by protein kinase C down-regulation and by the protein kinase C inhibitor GF 109203X, but not by calphostin C, We suggest that protein kinase C is constitutively activated in adherent cells, possibly due to modification of the regulatory domain of the enzyme. C1 NIAMS,NIH,SECT CHEM IMMUNOL,BETHESDA,MD 20892. RP Wolfe, PC (reprint author), CORNELL UNIV,DEPT PHARMACOL,ITHACA,NY 14853, USA. RI Wan, Daniel/F-4689-2010 FU NIAID NIH HHS [AI 19910]; NIGMS NIH HHS [GM 08210] NR 44 TC 32 Z9 32 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 22 PY 1996 VL 271 IS 12 BP 6658 EP 6665 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700018 PM 8636083 ER PT J AU Bird, GSJ Putney, JW AF Bird, GSJ Putney, JW TI Effect of inositol 1,3,4,5-tetrakisphosphate on inositol trisphosphate-activated Ca2+ signaling in mouse lacrimal acinar cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER; ENTRY; CA-2+ AB In mouse lacrimal acinar cells, microinjection of the metabolically stable analog of inositol 1,4,5-trisphosphate, inositol 2,4,5-trisphosphate ((2,4,5)IP3), stimulated both intracellular Ca2+ mobilization and Ca2+ entry. Microinjection of inositol 1,3,4,5-tetrakisphosphate ((1,3,4,5)IP4), the inositol 1,4,5-trisphosphate-3-kinase product, was ineffective at mobilizing intracellular Ca2+ or activating Ca2+ entry. In lacrimal cells previously microinjected with submaximal levels of (2,4,5)IP3, the subsequent microinjection of low to moderate concentrations of (1,3,4,5)IP4 did not result in additional release of intracellular Ca2+, nor did it potentiate the Ca2+ entry phase attributable to (2,4,5)IP3. However, as previously demonstrated (Bird, G. S. J., Rossier, M. F., Hughes, A. R., Shears, S. B., Armstrong, D. L., and Putney, J. W., Jr. (1991) Nature 352, 162-165), additional injections of (2,4,5)IP3 induced further mobilization of intracellular Ca2+ and increased the elevated and sustained Ca2+ entry phase. Introduction of high concentrations of (1,3,4,5)IP4 appeared to inhibit or block the (2,4,5)IP3-induced Ca2+ entry phase. These results were consistent with the observed effect of (1,3,4,5)IP4 in permeabilized lacrimal cells, where (1,3,4,5)IP4 did not release cellular Ca-45(2+) but at high concentrations inhibited the ability of submaximal concentrations of (2,4,5)IP3 to release Ca-45(2+). Likewise, injection of a high concentration of (1,3,4,5)IP4 prior to injection of (2,4,5)IP3 blocked both release and influx of Ca2+. The inhibitory action of (1,3,4,5)IP4 on Ca2+ signaling observed in intact cells occurred at concentrations that might be obtained in agonist-stimulated cells. However, in permeabilized cells, (1,3,4,5)IP4 inhibited Ca2+ mobilization at concentrations exceeding those likely to occur in agonist-stimulated cells. These results suggest that physiologically relevant levels of (1,3,4,5)IP4, in the cell cytoplasm do not release Ca2+, nor do they potentiate inositol trisphosphate-induced Ca2+ entry across the plasma membrane. Rather, the possibility is raised that (1,3,4,5)IP4 or one of its metabolites could function as a negative feedback on Ca2+ mobilization by inhibiting inositol 1,4,5-trisphosphate-induced Ca2+ release. RP NIEHS, CELLULAR & MOLEC PHARMACOL LAB, CALCIUM REGULAT SECT, NIH, POB 12233, RES TRIANGLE PK, NC 27709 USA. NR 24 TC 45 Z9 45 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 MAR 22 PY 1996 VL 271 IS 12 BP 6766 EP 6770 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700033 PM 8636098 ER PT J AU Tozser, J Bagossi, P Weber, IT Copeland, TD Oroszlan, S AF Tozser, J Bagossi, P Weber, IT Copeland, TD Oroszlan, S TI Comparative studies on the substrate specificity of avian myeloblastosis virus proteinase and lentiviral proteinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ROUS-SARCOMA VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 PROTEINASE; RETROVIRAL PROTEASE; CLEAVAGE SITES; MOLECULAR-DYNAMICS; FORCE-FIELD; AMINO-ACID; REQUIREMENTS; SIMULATIONS AB The retroviral proteinase (PR) seems to play crucial roles in the viral life cycle, therefore it is an attractive target for chemotherapy. Previously we studied the specificity of human immunodeficiency virus (HIV) type 1 and type 2 as well as equine infectious anemia virus PRs using oligopeptide substrates. Here a similar approach is used to characterize the specificity of avian myeloblastosis virus (AMV) PR and to compare it with those of the previously characterized lentiviral PRs. All peptides representing naturally occurring Gag and Gag-Pol cleavage sites were substrates of the AMV PR. Only half of these peptides were substrates of HIV-1 PR. The K-m values for AMV PR were in a micromolar range previously found for the lentiviral PRs; however, the K-cat values were in a 10-30-fold lower range. A series of peptides containing single amino acid substitutions in a sequence representing a naturally occurring HIV cleavage site was used to characterize the seven substrate binding subsites of the AMV PR. The largest differences were found at the P4 and P2 positions of the substrate. Detailed analysis of the results by molecular modeling and comparison with previously reported data revealed the common characteristics of the specificity of the retroviral PRs as well as its strong dependence on the sequence context of the substrate. C1 THOMAS JEFFERSON UNIV, JEFFERSON CANC INST, DEPT PHARMACOL, PHILADELPHIA, PA 19107 USA. NCI, FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM, MOLEC VIROL & CARCINOGENESIS LAB,NIH, FREDERICK, MD 21702 USA. RP Tozser, J (reprint author), DEBRECEN UNIV MED, SCH MED, DEPT BIOCHEM, POB 6, H-4012 DEBRECEN, HUNGARY. RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU NCI NIH HHS [CA58166] NR 43 TC 21 Z9 23 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 MAR 22 PY 1996 VL 271 IS 12 BP 6781 EP 6788 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700035 PM 8636100 ER PT J AU Malek, SN Yang, CH Earnshaw, WC Kozak, CA Desiderio, S AF Malek, SN Yang, CH Earnshaw, WC Kozak, CA Desiderio, S TI p150(TSP), conserved nuclear phosphoprotein that contains multiple tetratricopeptide repeats and binds specifically to SH2 domains SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE-PHOSPHORYLATED PEPTIDES; AFFINITY PHOSPHOTYROSYL PEPTIDE; NUCLEOTIDE EXCHANGE; ADAPTER PROTEIN; RECEPTOR; GRB2; SOS; TRANSFORMATION; RECOGNITION; ACTIVATOR AB Src homology 2 (SH2) domains are structural modules that function in the assembly of multicomponent signaling complexes by binding to specific phosphopeptides. The tetratricopeptide repeat (TPR) is a distinct structural motif that has been suggested to mediate protein-protein interactions, Among SH2-binding phosphoproteins purified from the mouse B cell lymphoma A20, a 150-kDa species was identified and the corresponding complementary DNA (cDNA) was molecularly cloned, This protein encoded by this cDNA, which we have termed p150(TSP) (for TPR-containing, SH2-binding phosphoprotein), is located predominantly in the nucleus and is highly conserved in evolution, The gene encoding p150(TSP) (Tsp) was mapped to chromosome 7 of the mouse with gene order: centromere-Tyr-Wnt11-Tsp-Zp2. The amino-terminal two-thirds of p150(TSP) consist almost entirely of tandemly arranged TPR units, which mediate specific, homotypic protein interactions in transfected cells. The carboxyl-terminal third of p150(TSP) which is serine- and glutamic acid-rich, is essential for SH2 binding; this interaction is dependent on serine/threonine phosphorylation but independent of tyrosine phosphorylation, The sequence and binding properties of p150(TSP) suggest that it may mediate interactions between TPR-containing and SH2-containing proteins. C1 JOHNS HOPKINS UNIV,SCH MED,DEPT MOLEC BIOL & GENET,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,HOWARD HUGHES MED INST,BALTIMORE,MD 21205. JOHNS HOPKINS UNIV,SCH MED,DEPT CELL BIOL & ANAT,BALTIMORE,MD 21205. NIAID,NIH,MOLEC MICROBIOL LAB,BETHESDA,MD 20892. NR 36 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 22 PY 1996 VL 271 IS 12 BP 6952 EP 6962 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700059 PM 8636124 ER PT J AU Paz, K Voliovitch, H Hadari, YR Roberts, CT LeRoith, D Zick, Y AF Paz, K Voliovitch, H Hadari, YR Roberts, CT LeRoith, D Zick, Y TI Interaction between the insulin receptor and its downstream effectors - Use of individually expressed receptor domains for structure function analysis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH FACTOR-I; TYROSINE PHOSPHORYLATION; JUXTAMEMBRANE REGION; KINASE-ACTIVITY; INTACT-CELLS; BETA-SUBUNIT; PROTEINS; STIMULATE AB A structural analysis has been carried out to determine which part of the intracellular domain of the insulin receptor (IR) beta subunit is involved in direct interaction with the receptor substrates IRS-1 and She. Toward this end, the juxtamembrane (JM) domain (amino acids 943-984) and the carboxyl-terminal (CT) region (amino acids 1245-1331) of IR were expressed in bacteria as (His)(6)-fusion peptides, and their interaction with IRS-1 and She was studied, We could demonstrate that the CT region of IR was sufficient to bind She, although significant, but much lower binding of She to the JM region could be detected as well. Furthermore, in vitro Tyr phosphorylation of the CT region potentiated its interactions with She 2-fold. In contrast, the JM region, but not the CT domain of the IR, was sufficient to mediate interactions between the IR and IRS-1. These interactions did not involve the pleckstrin homology (PH) region of IRS-1, since an IRS-I mutant, in which four ''blocks'' of the PH domain (pro(5)-pro(65)) were deleted, interacted with the JM region of IR with the same efficiency as native IRS-l, These results suggest that the IR interacts with its downstream effecters through distinct receptor regions, and that autophosphorylation of Tyr residues located at the CT domain of the IR can modulate these interactions. C1 WEIZMANN INST SCI,DEPT CHEM IMMUNOL,IL-76100 REHOVOT,ISRAEL. NIH,DIABET BRANCH,BETHESDA,MD 20982. OI Roberts, Charles/0000-0003-1756-5772 NR 49 TC 44 Z9 45 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 22 PY 1996 VL 271 IS 12 BP 6998 EP 7003 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700064 PM 8636129 ER PT J AU Nightingale, KP Pruss, D Wolffe, AP AF Nightingale, KP Pruss, D Wolffe, AP TI A single high affinity binding site for histone H1 in a nucleosome containing the Xenopus borealis 5 S ribosomal RNA gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID POLYMERASE-II TRANSCRIPTION; DNA; CHROMATIN; H-1; ORGANIZATION; INVITRO; PROTEIN; NUCLEI; CORE; H5 AB We have reconstituted nucleosomes containing the Xenopus borealis 5 S rRNA gene, a single histone octamer, and 1 or 2 molecules of histone H1. We determine that the 1st molecule of histone H1 to associate with the 5 S nucleosome binds with high affinity (K-D similar to 2 nM), and the 2nd molecule of H1 binds with a reduced affinity (K-D similar to 10 nM). This latter binding is comparable with the association of histone H1 with naked DNA. Neither molecule of histone al alters the helical periodicity of DNA in the nucleosome as revealed by hydroxyl radical cleavage. We conclude that although multiple molecules of histone H1 can associate with nucleosomal DNA, there is only a single high affinity binding site for histone H1 within the 5 S nucleosome. C1 NICHHD,NIH,MOLEC EMBRYOL LAB,BETHESDA,MD 20892. NR 47 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 22 PY 1996 VL 271 IS 12 BP 7090 EP 7094 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700078 PM 8636143 ER PT J AU Panchenko, MV StetlerStevenson, WG Trubetskoy, OV Gacheru, SN Kagan, HM AF Panchenko, MV StetlerStevenson, WG Trubetskoy, OV Gacheru, SN Kagan, HM TI Metalloproteinase activity secreted by fibrogenic cells in the processing of prolysyl oxidase - Potential role of procollagen C-proteinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STROMELYSIN CATALYTIC DOMAIN; PURIFIED LYSYL OXIDASE; AMINO-ACID-SEQUENCE; MATRIX METALLOPROTEINASES; TISSUE INHIBITOR; INTERSTITIAL COLLAGENASE; PARTIAL-PURIFICATION; VACCINIA VIRUS; SMOOTH-MUSCLE; MESSENGER-RNA AB Lysyl oxidase is secreted from fibrogenic cells as a 50-kDa proenzyme that is proteolytically processed to the mature enzyme in the extracellular space. To characterize the secreted proteinase activity, a truncated, recombinant form of lysyl oxidase was prepared as a proteinase substrate containing the sequence of the propeptide cleavage region, The processing proteinase activity secreted by cultured fibrogenic cells resists inhibitors of serine or aspartyl proteinases as well as tissue inhibitor of matrix metalloproteinases-2 (MMP-2) but is completely inhibited by metal ion chelators. Known metalloproteinases were tested for their activity toward this substrate. Carboxyl-terminal procollagen proteinase (C-proteinase), MMP-2, and conditioned fibrogenic cell culture medium cleave the lysyl oxidase substrate to the size of the mature enzyme. The NH2-terminal sequence generated by arterial smooth muscle conditioned medium and the C-proteinase but not by MMP-2, i.e. Asp-Asp Pro-Tyr, was identical to that previously identified in mature lysyl oxidase isolated from connective tissue, The C-proteinase activity against the model substrate was inhibited by a synthetic oligopeptide mimic of the cleavage sequence (Ac-Met-Val-Gly-Asp-Asp-Pro-Tyr-Asn-amide), whereas this peptide also inhibited the generation of lysyl oxidase activity in the medium of fetal rat lung fibroblasts in culture. In toto, these results identify a secreted metalloproteinase activity participating in the activation of prolysyl oxidase, identify inhibitors of the processing activity, and implicate procollagen C-proteinase in this role. C1 BOSTON UNIV,SCH MED,DEPT BIOCHEM,BOSTON,MA 02118. NCI,NIH,PATHOL LAB,BETHESDA,MD 20892. OSTEOARTHRITIS SCI INC,CAMBRIDGE,MA 02139. RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NHLBI NIH HHS [HL 13262, HL 46902] NR 42 TC 137 Z9 141 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 22 PY 1996 VL 271 IS 12 BP 7113 EP 7119 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700081 PM 8636146 ER PT J AU Hammer, JA Jung, G AF Hammer, JA Jung, G TI The sequence of the Dictyostelium myo J heavy chain gene predicts a novel, dimeric, unconventional myosin with a heavy chain molecular mass of 258 kDa SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACANTHAMOEBA MYOSIN; LOCALIZATION; DISCOIDEUM; CALMODULIN; PROTEIN; ISOFORM; MUSCLE; DISRUPTION; ALIGNMENT; MOTILITY AB The complete sequence of the Dictyostelium myo J heavy chain gene has been determined hom overlapping genomic clones. The gene spans similar to 7400 base pairs, is split by two small introns, and encodes a 2241-residue, 258-kDa heavy chain polypeptide that that is composed of an N-terminal 944-residue myosin head domain, a central 863-residue domain that is predicted to form an cu helical coiled-coil containing six hinges, and a C-terminal 434-residue globular domain. The head domain is notable in that it contains a similar to 30 residue insert near the nucleotide binding pocket, and five potential calmodulin/myosin light chain binding sites at the head/tail junction. The existence within the Myo J tail domain of both an extensive coiled-coil structure and a large globular domain suggests that this myosin is dimeric and incapable of self-assembly into filaments. While these properties, as well as the overall predicted structure of the Myo J protein, are reminiscent of class V myosins, the sequence of the 434-residue globular tail piece of Myo J shows no similarity to that of either yeast or vertebrate myosins V. Consistent with this, phylogenetic analyses based on myosin head sequence comparisons do not classify Myo J as a type V myosin. These and other sequence comparisons indicate that Myo J and two as-yet-unclassified unconventional myosins from Arabidopsis represent members of the newest class within the myosin superfamily (class XI). Northern blots analyses suggest that Myo J may function predominantly in vegetative Dictyostelium cells. Finally, Southern blot analyses suggest that Dictyostelium possesses another myosin that is very closely related to Myo J. RP Hammer, JA (reprint author), NHLBI,CELL BIOL LAB,NIH,SECT MOLEC CELL BIOL,BLDG 3,RM B1-22,BETHESDA,MD 20892, USA. NR 55 TC 19 Z9 20 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 22 PY 1996 VL 271 IS 12 BP 7120 EP 7127 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UB157 UT WOS:A1996UB15700082 PM 8636147 ER PT J AU Ridge, JP Fuchs, EJ Matzinger, P AF Ridge, JP Fuchs, EJ Matzinger, P TI Neonatal tolerance revisited: Turning on newborn T cells with dendritic cells SO SCIENCE LA English DT Article ID ANTIGEN-PRESENTING FUNCTION; SMALL B-CELLS; TRANSPLANTATION TOLERANCE; SELF-TOLERANCE; PROTEIN ANTIGENS; IMMUNE-SYSTEM; LYMPHOCYTE-T; INDUCTION; MICE; INVIVO AB For some time it has been thought that antigenic challenge in neonatal life is a tolerogenic rather than immunogenic event. Reexamination of the classic neonatal tolerance experiments of Billingham, Brent, and Medawar showed that tolerance is not an intrinsic property of the newborn immune system, but that the nature of the antigen-presenting cell determines whether the outcome is neonatal tolerance or immunization. RP Ridge, JP (reprint author), NIAID,CELLULAR & MOLEC IMMUNOL LAB,SECT T CELL TOLERANCE & MEMORY,GHOST LAB,BETHESDA,MD 20892, USA. NR 62 TC 594 Z9 607 U1 1 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 22 PY 1996 VL 271 IS 5256 BP 1723 EP 1726 DI 10.1126/science.271.5256.1723 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UB151 UT WOS:A1996UB15100045 PM 8596932 ER PT J AU Fukasawa, K Choi, T Kuriyama, R Rulong, S VandeVoude, GF AF Fukasawa, K Choi, T Kuriyama, R Rulong, S VandeVoude, GF TI Abnormal centrosome amplification in the absence of p53 SO SCIENCE LA English DT Article ID WILD-TYPE P53; HAMSTER OVARY CELLS; GENE AMPLIFICATION; FRIEND-VIRUS; CYCLE; EXPRESSION; TRANSCRIPTION; PROTEIN; BINDING; CANCER AB The centrosome plays a vital role in mitotic fidelity, ensuring establishment of bipolar spindles and balanced chromosome segregation. Centrosome duplication occurs only once during the cell cycle and is therefore highly regulated. Here, it is shown that in mouse embryonic fibroblasts (MEFs) lacking the p53 tumor suppressor protein, multiple copies of functionally competent centrosomes are generated during a single cell cycle. In contrast, MEFs prepared from normal mice or mice deficient in the retinoblastoma tumor suppressor gene product do not display these abnormalities. The abnormally amplified centrosomes profoundly affect mitotic fidelity, resulting in unequal segregation of chromosomes. These observations implicate p53 in the regulation of centrosome duplication and suggest one possible mechanism by which the loss of p53 may cause genetic instability. C1 NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. UNIV MINNESOTA,SCH MED,DEPT CELL BIOL & NEUROANAT,MINNEAPOLIS,MN 55455. NR 57 TC 672 Z9 690 U1 1 U2 12 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 22 PY 1996 VL 271 IS 5256 BP 1744 EP 1747 DI 10.1126/science.271.5256.1744 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UB151 UT WOS:A1996UB15100052 PM 8596939 ER PT J AU Venanzoni, MC Robinson, LR Hodge, DR Kola, I Seth, A AF Venanzoni, MC Robinson, LR Hodge, DR Kola, I Seth, A TI ETS1 and ETS2 in p53 regulation: Spatial separation of ETS binding sites (EBS) modulate protein: DNA interaction SO ONCOGENE LA English DT Article DE ETS1; ETS2; p53 promoter; transactivation; gene regulation ID TRANSCRIPTION FACTORS; ONCOGENIC ACTIVITY; GENE; PROTOONCOGENE; FAMILY; CELLS; EMBRYOGENESIS; EXPRESSION; PROMOTER AB p53 is an extensively studied tumor suppressor gene implicated in the genesis of a large number of varied tumours. However, the pathways of regulation for the wild-type p53 gene and its product are as yet unknown. In situ hybridization analyses of ETS1 and ETS2 expression during mouse embryogenesis, have shown a pattern similar to that of p53 gene expression. Significantly, we have identified several ETS-binding sites (EBS) in the promoter regions of the human and mouse p53 genes. In the human promoter two of these EBS are present in the form of a palindrome, with the two EBS cores being separated by four nucleotides. This report shows that the EBS palindrome of the human p53 promoter has a high affinity for ETS1 and ETS2, and that such binding interaction intracellularly is able to activate the transcription of a CAT reporter gene by 5-10-fold using COS cells. To investigate whether the spacing between the two EBS cores influences the DNA binding activity, we synthesized oligonucleotides with increasing distances (4,12,16 and 20 bases respectively) between the two EBS cores of the palindrome. We observed an inverse correlation between an increasing distance in the two EBS cores of the palindrome and the ETS1 and ETS2 DNA binding activity respectively. Interestingly, optimal DNA binding activity was observed when the distance between the two EBS cores was four bases, identical to that which occurs in the natural promoter. Furthermore we show that the p53 mRNA is expressed at higher levels in NIH3T3 cells over-expressing ETS2 gene product, suggesting that the ETS2 transcription factor is a likely candidate for regulating the expression of p53 in vivo. C1 UNIV TORONTO, FAC MED, DEPT PATHOL, TORONTO, ON M5S 1B2, CANADA. NCI, FREDERICK CANC RES & DEV CTR, MOLEC ONCOL LAB, FREDERICK, MD 21702 USA. FREDERICK CANC RES & DEV CTR, ABL BASIC RES PROGRAM, FREDERICK, MD 21702 USA. MONASH UNIV, MOL GENET & DEV GRP, MELBOURNE, VIC 3168, AUSTRALIA. UNIV TORONTO, FAC DENT, TORONTO, ON M5S 1B2, CANADA. WOMENS COLL HOSP, TORONTO, ON M5S 1B2, CANADA. RI Kola, Ismail/C-5254-2013 NR 35 TC 52 Z9 52 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 21 PY 1996 VL 12 IS 6 BP 1199 EP 1204 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UC067 UT WOS:A1996UC06700004 PM 8649821 ER PT J AU Chan, AML Takai, S Yamada, K Miki, T AF Chan, AML Takai, S Yamada, K Miki, T TI Isolation of a novel oncogene, NET1, from neuroepithelioma cells by expression cDNA cloning SO ONCOGENE LA English DT Article DE oncogene; expression cloning; neuroepithelioma; GEF; RAS; RHO ID INSITU HYBRIDIZATION; GENE-PRODUCT; CDC24; BCR; PROTEINS; SYSTEM; CYCLE; VAV; RAS; DNA AB We generated a cDNA expression library from a human neuroepithelioma cell line for detection of novel oncogenes by focus formation assay in NIH3T3 cells. A morphologically unique focus was identified upon transfection and the transforming plasmid was isolated. The transforming gene, designated NET1, encoded a predicted protein species of 54 kDa containing the Dbl-Homology (DH) motif. This motif is also present in other growth regulatory molecules including Bcr, Cdc24, Vav, Ras-Grf, Ect2, Ost, Tim and Tiam1, which have been implicated as regulators of small GTP-binding proteins. NIH3T3 cells transfected with NET1 expression plasmid showed altered growth properties in vitro and were tumorigenic when injected into nude mice. In addition, a 2.5 kb cDNA was isolated from a normal human cDNA library which represented the NET1 proto-oncogene contained a 5' extended open reading frame. The fact that the proto-oncogene failed to induce transformation in NIH3T3 cells suggested that the original NET1 oncogene was activated by 5'-truncation. The 3.0 and 2.4 kilobasepair (kb) transcripts of the NET1 gene was ubiquitously expressed in all tissues examined. Using fluorescence in situ hybridization, we localized the NET1 gene to the short arm of human chromosome 10 at band p15. C1 NCI,CELLULAR & MOLEC BIOL LAB,BETHESDA,MD 20892. INT MED CTR JAPAN,RES INST,DEPT GENET,SHINJUKU KU,TOKYO 162,JAPAN. NR 35 TC 66 Z9 70 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 21 PY 1996 VL 12 IS 6 BP 1259 EP 1266 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA UC067 UT WOS:A1996UC06700011 PM 8649828 ER PT J AU Franchini, G Benson, J Gallo, R Paoletti, E Tartaglia, J AF Franchini, G Benson, J Gallo, R Paoletti, E Tartaglia, J TI Attenuated poxvirus vectors as carriers in vaccines against human T cell leukemia-lymphoma virus type I SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article; Proceedings Paper CT Workshop on Comparative Approach to Retroviral Vaccines CY JUN 23-24, 1995 CL LES PENSIERES CONF CTR, VEYRIER DU LAC, FRANCE SP Fdn Marcel Merieux HO LES PENSIERES CONF CTR ID HTLV-I; RETROVIRUS; INFECTION; TRANSMISSION; RECOMBINANT; PROTECTION; PARTICLES; PATIENT; VARIANT; LINE C1 VIROGENET CORP,TROY,NY 12180. RP Franchini, G (reprint author), NCI,TUMOR CELL BIOL LAB,37 CONVENT DR,MSC 4255,BLDG 37,ROOM 6A01,BETHESDA,MD 20892, USA. NR 21 TC 6 Z9 6 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR 20 PY 1996 VL 12 IS 5 BP 407 EP 408 DI 10.1089/aid.1996.12.407 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA UA592 UT WOS:A1996UA59200012 PM 8882320 ER PT J AU Judde, JG Spangler, G Magrath, I Bhatia, K AF Judde, JG Spangler, G Magrath, I Bhatia, K TI Use of Epstein-Barr virus nuclear antigen-1 in targeted therapy of EBV-associated neoplasia SO HUMAN GENE THERAPY LA English DT Article ID CYTOSINE DEAMINASE; COLORECTAL-CARCINOMA; GENE-EXPRESSION; CELLS; CANCER; 5-FLUOROCYTOSINE; ORIGIN; SITES AB To target expression of toxic genes to Epstein-Barr virus (EBV)-associated tumor cells, we have developed an EBV-driven enzyme prodrug system (EDEPS) that takes advantage of the trans-activating properties of EBNA1, a latent protein expressed in all EBV-containing cells, to direct expression of cytosine deaminase (CD) at high levels in those cells only, Plasmids were constructed in which the CD gene or a luciferase reporter gene were cloned downstream of the herpes simplex virus thymidine kinase (tk) promoter and the family of repeats (FR) sequence from the oriP region of EBV, Analysis of luciferase activity after transient transfection into a panel of EBV-negative or -positive human cell lines showed that the presence of the FR element enhanced transcription from the tk promoter in all EBV-positive cell lines, whereas transcription from tk was repressed in all EBV-negative cell lines, including B, T, and fibroblast cell lines, In clonogenicity assays following transfection with the CD vector, the presence of 5-fluorocytosine (5-FC) in the culture medium completely abolished cell growth in EBV-positive cell lines, but did not affect the growth of EBV-negative cell lines, This vector system should have wide applicability in that it allows targeted expression of any gene of interest to tumors that carry EBV, irrespective of the role EBV plays in their pathogenesis. RP Judde, JG (reprint author), NCI,PEDIAT BRANCH,LYMPHOMA BIOL SECT,NIH,BLDG 10,RM 13N240,9000 ROCKVILLE PIKE,BETHESDA,MD 20892, USA. NR 35 TC 30 Z9 30 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD MAR 20 PY 1996 VL 7 IS 5 BP 647 EP 653 DI 10.1089/hum.1996.7.5-647 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA UG395 UT WOS:A1996UG39500008 PM 8845390 ER PT J AU Gloth, FM Tobin, JD AF Gloth, FM Tobin, JD TI Vitamin D deficiency in homebound elderly persons - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID POPULATION C1 NIA,BALTIMORE,MD 21224. RP Gloth, FM (reprint author), UNION MEM HOSP,201 E UNIV PKWY,BALTIMORE,MD 21218, USA. NR 3 TC 0 Z9 0 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 20 PY 1996 VL 275 IS 11 BP 839 EP 839 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA TZ971 UT WOS:A1996TZ97100021 ER PT J AU Walther, MM Linehan, WM AF Walther, MM Linehan, WM TI Von Hippel-Lindau disease and pheochromocytoma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter RP Walther, MM (reprint author), NIH, BETHESDA, MD 20892 USA. NR 5 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 20 PY 1996 VL 275 IS 11 BP 839 EP 840 DI 10.1001/jama.275.11.839 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA TZ971 UT WOS:A1996TZ97100022 PM 8596219 ER PT J AU Harris, CC AF Harris, CC TI Molecular epidemiology of basal cell carcinoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID GORLIN SYNDROME; P53 MUTATIONS; SKIN-CANCER; GENE; SUNLIGHT RP Harris, CC (reprint author), NCI,NIH,HUMAN CARCINOGENESIS LAB,DIV BASIC SCI,BLDG 37,RM 2C07,BETHESDA,MD 20892, USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 20 PY 1996 VL 88 IS 6 BP 315 EP 317 DI 10.1093/jnci/88.6.315 PG 3 WC Oncology SC Oncology GA UA361 UT WOS:A1996UA36100001 PM 8609637 ER PT J AU Rossi, SC Srivastava, S AF Rossi, SC Srivastava, S TI National Cancer Institute Workshop on Genetic Screening for Colorectal Cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FAMILIAL ADENOMATOUS POLYPOSIS; COLON CANCER; MUTATIONS; INSTABILITY; PREVENTION; TUMORS; FAP C1 NCI,DIV CANC PREVENT & CONTROL,EARLY DETECT BRANCH,EARLY DETECT & COMMUN ONCOL PROGRAM,NIH,BETHESDA,MD 20892. NR 50 TC 5 Z9 5 U1 1 U2 1 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 20 PY 1996 VL 88 IS 6 BP 331 EP 339 DI 10.1093/jnci/88.6.331 PG 9 WC Oncology SC Oncology GA UA361 UT WOS:A1996UA36100010 PM 8609641 ER PT J AU RobertGuroff, M Stern, TL Richardson, ES Giovanella, BC Michaels, FH AF RobertGuroff, M Stern, TL Richardson, ES Giovanella, BC Michaels, FH TI Presence of Mason-Pfizer monkey virus in some stocks of the human HBL-100 mammary epithelial cell line SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HUMAN-BREAST-MILK; RETROVIRUS; AIDS; ORGANIZATION; PARTICLES; PATIENT; GROWTH RP RobertGuroff, M (reprint author), NCI,TUMOR CELL BIOL LAB,NIH,BLDG 37,RM 6A09,BETHESDA,MD 20892, USA. NR 30 TC 2 Z9 2 U1 0 U2 0 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 20 PY 1996 VL 88 IS 6 BP 372 EP 374 DI 10.1093/jnci/88.6.372 PG 3 WC Oncology SC Oncology GA UA361 UT WOS:A1996UA36100016 PM 8609647 ER PT J AU Downing, GJ Kim, S Nakanishi, S Catt, RJ Balla, T AF Downing, GJ Kim, S Nakanishi, S Catt, RJ Balla, T TI Characterization of a soluble adrenal phosphatidylinositol 4-kinase reveals wortmannin sensitivity of type III phosphatidylinositol kinases SO BIOCHEMISTRY LA English DT Article ID PURIFICATION; YEAST; 3-KINASE; CELLS; BRAIN AB Phosphorylation of phosphatidylinositol (PtdIns) by PtdIns 4-kinases is the first step in the synthesis of polyphosphoinositides, the lipid precursors of intracellular signaling molecules. We have recently identified a cytosolic PtdIns 4-kinase (cPI4K) in the bovine adrenal cortex that is distinguished from previously known PtdIns 4-kinases by its sensitivity to the PtdIns 3-kinase inhibitor wortmannin (WT). The present study has further characterized this soluble enzyme and compared its properties to those of the membrane-bound, type II PtdIns 4-kinase activity of the adrenal cortex and the type III enzyme of bovine brain. The enzymatic activity of adrenal cPI4K was inhibited not only by WT (IC50 similar to 50 nM) but also by LY-294002 (IC50 similar to 100 mu M), another inhibitor of PtdIns 3-kinase, and neither compound affected type II PtdIns 4-kinase at concentrations that inhibited cPI4K. In contrast to the type II enzyme, cPI4K had a significantly higher K-m for ATP, was relatively insensitive to inhibition by adenosine (K-i similar to 800 mu M vs similar to 40 mu M), had lower affinity for PtdIns, and was not inhibited by Ca2+ ions. These properties identify the WT-sensitive adrenal cPI4K as a type III PtdIns 4-kinase that is distinct from the tightly membrane-bound, Ca2+- and adenosine-sensitive, type II PtdIns 4-kinase. The type III PtdIns 4-kinase prepared from bovine brain exhibited similar kinetic parameters as the adrenal cPI4K, and was also inhibited by WT with an IC50 of 30-50 nM. Since WT inhibits the synthesis of agonist-regulated phosphoinositide pools in intact cells at micromolar concentrations, these findings indicate that type III rather than type II PtdIns 4-kinases are responsible for the maintenance of the precursor phospholipids required for intracellular signaling through the inositol phosphate/Ca2+ pathway. C1 NICHHD,NIH,ENDOCRINOL & REPROD RES BRANCH,BETHESDA,MD 20892. OI Balla, Tamas/0000-0002-9077-3335 NR 43 TC 100 Z9 101 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 19 PY 1996 VL 35 IS 11 BP 3587 EP 3594 DI 10.1021/bi9517493 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UA989 UT WOS:A1996UA98900028 PM 8639510 ER PT J AU Lu, J Li, Q Xie, H Chen, ZJ Borovitskaya, AE Maclaren, NK Notkins, AL Lan, MS AF Lu, J Li, Q Xie, H Chen, ZJ Borovitskaya, AE Maclaren, NK Notkins, AL Lan, MS TI Identification of a second transmembrane protein tyrosine phosphatase, IA-2 beta, as an autoantigen in insulin-dependent diabetes mellitus: Precursor of the 37-kDa tryptic fragment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ISLET; ANTIBODIES; DISTINCT; DECARBOXYLASE; ANTIGEN; CLONING AB A novel cDNA, IA-2 beta, was isolated from a mouse neonatal brain library, The predicted protein sequence revealed an extracellular domain, a transmembrane region, and an intracellular domain. The intracellular domain is 376 amino acids long and 74% identical to the intracellular domain of IA-2, a major autoantigen in insulin-dependent diabetes mellitus (IDDM). A partial sequence of the extracellular domain of IA-2 beta indicates that it differs substantially (only 26% identical) from that of IA-2. Both molecules are expressed in islets and brain tissue, Forty-six percent (23 of 50) of the IDDM sera but none of the sera from normal controls (0 of 50) immunoprecipitated the intracellular domain of IA-2 beta. Competitive inhibition experiments showed that IDDM sera have autoantibodies that recognize both common and distinct determinants on IA-2 and IA-2 beta. Many IDDM sera are known to immunoprecipitate 37-kDa and 40-kDa tryptic fragments from islet cells, but the identity of the precursor protein(s) has remained elusive. The current study shows that treatment of recombinant IA-2 beta and IA-2 with trypsin yields a 37-kDa fragment and a 40-kDa fragment, respectively, and that these fragments can be immunoprecipitated with diabetic sera, Absorption of diabetic sera with unlabeled recombinant IA-2 or IA-2 beta, prior to incubation with radiolabeled 37-kDa and 40-kDa tryptic fragments derived from insulinoma or glucagonoma cells, blocks the immunoprecipitation of both of these radiolabeled tryptic fragments. We conclude that IA-2 beta and IA-2 are the precursors of the 37-kDa and 40-kDa islet cell autoantigens, respectively, and that both IA-2 and IA-2 beta are major autoantigens in IDDM. C1 NIDR,NIH,ORAL MED LAB,BETHESDA,MD 20892. UNIV FLORIDA,COLL MED,DEPT PATHOL & LAB MED,GAINESVILLE,FL 32610. NR 17 TC 163 Z9 168 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 19 PY 1996 VL 93 IS 6 BP 2307 EP 2311 DI 10.1073/pnas.93.6.2307 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UB121 UT WOS:A1996UB12100013 PM 8637868 ER PT J AU Jucovic, M Hartley, RW AF Jucovic, M Hartley, RW TI Protein-protein interaction: A genetic selection for compensating mutations at the barnase-barstar interface SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PROMOTER INVERSION INVIVO; EXPRESSION; MUTAGENESIS; SITE; RIBONUCLEASE; CONSTRUCTION; STABILITY AB Barnase and barstar are trivial names of the extracellular RNase and its intracellular inhibitor produced by Bacillus amyloliquefaciens. Inhibition involves the formation of a very tight one-to-one complex of the two proteins. With the crystallographic solution of the structure of the barnase-barstar complex and the development of methods for measuring the free energy of binding, the pair can be used to study protein-protein recognition in detail. In this report, we describe the isolation of suppressor mutations in barstar that compensate for the loss in interaction energy caused by a mutation in barnase. Our suppressor search is based on in vivo selection for barstar variants that are able to protect host cells against the RNase activity of those barnase mutants not properly inhibited by wild-type barstar. This approach utilizes a plasmid system in which barnase expression is tightly controlled to keep the mutant barnase gene silent. When expression of barnase is turned on, failure to form a complex between the mutant barnase and barstar has a lethal effect on host cells unless overcome by substitution of the wild-type barstar by a functional suppressor derivative. A set of barstar suppressors has been identified for barnase mutants with substitutions in two amino acid positions (residues 102 and 59), which are critically involved in both RNase activity and barstar binding. The mutations selected as suppressors could not have been predicted on the basis of the known protein structures. The single barstar mutation with the highest information content for inhibition of barnase (H102K) has the substitution Y30W. The reduction in binding caused by the R59E mutation in barnase can be partly reversed by changing Glu-76 of barstar, which forms a salt bridge with the Arg-59 in the wild-type complex, to arginine, thus completing an interchange of the two charges. RP Jucovic, M (reprint author), NIDDK,NIH,CELLULAR & DEV BIOL LAB,BETHESDA,MD 20892, USA. NR 22 TC 31 Z9 31 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 19 PY 1996 VL 93 IS 6 BP 2343 EP 2347 DI 10.1073/pnas.93.6.2343 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UB121 UT WOS:A1996UB12100020 PM 8637875 ER PT J AU Forrester, K Ambs, S Lupold, SE Kapust, RB Spillare, EA Weinberg, WC FelleyBosco, E Wang, XW Geller, DA Tzeng, E Billiar, TR Harris, CC AF Forrester, K Ambs, S Lupold, SE Kapust, RB Spillare, EA Weinberg, WC FelleyBosco, E Wang, XW Geller, DA Tzeng, E Billiar, TR Harris, CC TI Nitric oxide-induced p53 accumulation and regulation of inducible nitric oxide synthase expression by wild-type p53 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE tumor suppressor gene; mutagenesis; carcinogenesis ID DNA-DAMAGE; ULCERATIVE-COLITIS; INDUCED APOPTOSIS; INTERFERON-GAMMA; BINDING-SITE; PROMOTERS; PROTEIN; CELLS; GENE; TRANSCRIPTION AB The tumor suppressor gene product p53 plays an important role in the cellular response to DNA damage from exogenous chemical and physical mutagens. Therefore, we hypothesized that p53 performs a similar role in response to putative endogenous mutagens, such as nitric oxide (NO). We report here that exposure of human cells to NO generated from an NO donor or from overexpression of inducible nitric oxide synthase (NOS2) results in p53 protein accumulation, In addition, expression of wild-type (WT) p53 in a variety of human tumor cell lines, as well as murine fibroblasts, results in down-regulation of NOS2 expression through inhibition of the NOS2 promoter, These data are consistent with the hypothesis of a negative feedback loop in which endogenous NO-induced DNA damage results in WT p53 accumulation and provides a novel mechanism by which p53 safeguards against DNA damage through p53-mediated transrepression of NOS2 gene expression, thus reducing the potential for NO-induced DNA damage. C1 NCI,HUMAN CARCINOGENESIS LAB,NATL INST HLTH,BETHESDA,MD 20892. NCI,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,NATL INST HLTH,BETHESDA,MD 20892. INST PHARMACOL & TOXICOL,CH-1007 LAUSANNE,SWITZERLAND. UNIV PITTSBURGH,DEPT SURG,PITTSBURGH,PA 15261. RI Weinberg, Wendy/A-8920-2009; Wang, Xin/B-6162-2009; Felley-Bosco, Emanuela/E-7484-2017 OI Felley-Bosco, Emanuela/0000-0002-3408-0294 FU NIGMS NIH HHS [GM-44100, GM-52021] NR 59 TC 318 Z9 328 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 19 PY 1996 VL 93 IS 6 BP 2442 EP 2447 DI 10.1073/pnas.93.6.2442 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UB121 UT WOS:A1996UB12100038 PM 8637893 ER PT J AU Chadwick, RS Dimitriadis, EK Iwasa, KH AF Chadwick, RS Dimitriadis, EK Iwasa, KH TI Active control of waves in a cochlear model with subpartitions SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE wave dispersion and energy; outer hair cell activity; asymptotics ID OUTER HAIR CELL; MECHANICS; MEMBRANE; MOTILITY AB Multiscale asymptotic methods developed previously to study macromechanical wave propagation in cochlear models are generalized here to include active control of a cochlear partition having three subpartitions, the basilar membrane, the reticular lamina, and the tectorial membrane, Activation of outer hair cells by stereocilia displacement and/or by lateral wall stretching result in a frequency-dependent force acting between the reticular lamina and basilar membrane, Wavelength-dependent fluid loads are estimated by using the unsteady Stokes' equations, except in the narrow gap between the tectorial membrane and reticular lamina, where lubrication theory is appropriate. The local wavenumber and subpartition amplitude ratios are determined from the zeroth order equations of motion. A solvability relation for the first order equations of motion determines the subpartition amplitudes, The main findings are as follows: The reticular lamina and tectorial membrane move in unison with essentially no squeezing of the gap; an active force level consistent with measurements on isolated outer hair cells can provide a 35-dB amplification and sharpening of subpartition waveforms by delaying dissipation and allowing a greater structural resonance to occur before the wave is cut off; however, previously postulated activity mechanisms for single partition models cannot achieve sharp enough tuning in subpartitioned models. C1 NATL INST DEAFNESS & OTHER COMMUNICAT DISORDERS,NIH,LAB CELLULAR BIOL,BIOPHYS SECT,BETHESDA,MD 20892. RP Chadwick, RS (reprint author), NATL INST DEAFNESS & OTHER COMMUNICAT DISORDERS,NIH,NATL CTR RES RESOURCES,BETHESDA,MD 20892, USA. OI Iwasa, Kuni/0000-0002-9397-7704 NR 26 TC 26 Z9 26 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 19 PY 1996 VL 93 IS 6 BP 2564 EP 2569 DI 10.1073/pnas.93.6.2564 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA UB121 UT WOS:A1996UB12100059 PM 8637914 ER PT J AU Kyostio, SRM Owens, RA AF Kyostio, SRM Owens, RA TI Identification of mutant adeno-associated virus rep proteins which are dominant-negative for DNA helicase activity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID INVITRO RESOLUTION; WILD-TYPE; REPLICATION; SEQUENCE; GENOME; ORIGIN; ENDS; SITE; GENE AB Adeno-associated virus type 2 (AAV) Rep proteins have been postulated to play a role in unwinding the 145-bp inverted terminal repeats during AAV DNA replication. Previous studies showed that AAV Rep78 and Rep68 could unwind a DNA partial duplex of 26 bp. In this work it is demonstrated that nuclear extracts of human 293 cells containing wild-type Rep68 can unwind partial DNA duplexes up to 160 bp long. Mutant Rep proteins with either a histidine substituted for lysine 340 or a deletion of methionine 225 had no detectable helicase activity and inhibited the helicase activity of wild-type Rep68 protein. This observation is consistent with the model that the functional form of the Rep proteins is a multimer. C1 NIDDKD,CELLULAR & MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. NR 23 TC 16 Z9 16 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 18 PY 1996 VL 220 IS 2 BP 294 EP 299 DI 10.1006/bbrc.1996.0399 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UC940 UT WOS:A1996UC94000010 PM 8645299 ER PT J AU DenisHenriot, D Lacasa, D Goldsmith, PK DeMazancourt, P Giudicelli, Y AF DenisHenriot, D Lacasa, D Goldsmith, PK DeMazancourt, P Giudicelli, Y TI Site-related differences in G-protein alpha subunit expression during adipogenesis in vitro: Possible key role for Gq/11 alpha in the control of preadipocyte differentiation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID REGIONAL FAT DISTRIBUTION; BETA-GAMMA-SUBUNITS; NIH 3T3 CELLS; PERTUSSIS TOXIN; PHOSPHOLIPASE-C; ADIPOSE-TISSUE; PRECURSOR CELLS; PRIMARY CULTURE; KINASE; TRANSFORMATION AB G protein alpha subunits were compared by immunoblotting in preadipocytes and adipocytes from rat subcutaneous and epididymal adipose tissue at three steps of adipogenesis. The most striking difference concerned the Gq/11 alpha subunits whose expression decreased during preadipocyte differentiation in subcutaneous cells while it remained constant in epididymal cells. The PKC inhibitor CGP 41251 increased glycerol 3-phosphate dehydrogenase activity (EC 1.1.1.8), a late marker of differentiation, in epididymal preadipocytes but not in subcutaneous cells. There was no difference in the proliferation capacities between subcutaneous and epididymal preadipocytes: in both cells, CGP 41251 led to the same decrease in [H-3]thymidine incorporation and, at confluence, the amounts of Gq/11 alpha subunits were equivalent. No major site-related difference was found in the amounts of Gs and Gi alpha subunits during adipogenesis. Thus, compared to epididymal preadipocytes, the higher capacity of subcutaneous preadipocyte to differentiate stems to be correlated with the decrease in Gq/11 alpha expression and the decreased Gq/11 mediated PKC activation. (C) 1996 Academic Press, Inc. C1 UNIV PARIS 05,HOP POISSY,INSERM,CFJ 9402,DEPT BIOCHEM,F-78303 POISSY,FRANCE. NIDDK,METAB DIS BRANCH,BETHESDA,MD 20892. HOP RAY POINCARE,F-92380 GARCHES,FRANCE. NR 39 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 18 PY 1996 VL 220 IS 2 BP 443 EP 448 DI 10.1006/bbrc.1996.0392 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UC940 UT WOS:A1996UC94000035 PM 8645324 ER PT J AU Gnarra, JR Duan, DR Weng, YK Humphrey, JS Chen, DYT Lee, S Pause, A Dudley, CF Latif, F Kuzmin, I Schmidt, L Duh, FM Stackhouse, T Chen, F Kishida, T Wei, MH Lerman, MI Zbar, B Klausner, RD Linehan, WM AF Gnarra, JR Duan, DR Weng, YK Humphrey, JS Chen, DYT Lee, S Pause, A Dudley, CF Latif, F Kuzmin, I Schmidt, L Duh, FM Stackhouse, T Chen, F Kishida, T Wei, MH Lerman, MI Zbar, B Klausner, RD Linehan, WM TI Molecular cloning of the von Hippel-Lindau tumor suppressor gene and its role in renal carcinoma SO BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER LA English DT Review ID CELL CARCINOMA; SHORT ARM; DISEASE; CANCER; TRANSLOCATION; CHROMOSOME-3; DELETIONS; IDENTIFICATION; LOCUS; HETEROZYGOSITY C1 NCI, SURG BRANCH, UROL ONCOL SECT, BETHESDA, MD 20892 USA. NICHHD, CELL BIOL & METAB BRANCH, BETHESDA, MD 20892 USA. NCI, IMMUNOBIOL LAB, FREDERICK, MD 21702 USA. NCI, FREDERICK CANC RES & DEV CTR, BIOL CARCINOGENESIS & DEV PROGRAM, FREDERICK, MD 21702 USA. NR 60 TC 95 Z9 97 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-419X EI 0006-3002 J9 BBA-REV CANCER JI Biochim. Biophys. Acta-Rev. Cancer PD MAR 18 PY 1996 VL 1242 IS 3 BP 201 EP 210 DI 10.1016/0304-419X(95)00012-5 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Oncology SC Biochemistry & Molecular Biology; Biophysics; Oncology GA UE610 UT WOS:A1996UE61000006 PM 8603073 ER PT J AU Heidbreder, C Shoaib, M Shippenberg, TS AF Heidbreder, C Shoaib, M Shippenberg, TS TI Differential role of delta-opioid receptors in the development and expression of behavioral sensitization to cocaine SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; enkephalin; delta-opioid receptor; naltrindole; sensitization ID MESSENGER-RNA EXPRESSION; VENTRAL TEGMENTAL AREA; FREELY MOVING RATS; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; ANTAGONIST NALTRINDOLE; MOTOR-ACTIVITY; MU; INVOLVEMENT; AMPHETAMINE AB The present study was designed to determine whether the selective delta-opioid receptor antagonist naltrindole hydrochloride can prevent the expression and development of sensitization to the locomotor-activating effects of cocaine. Rats were sensitized to the motor stimulant effects of cocaine (20 mg/kg i.p. x 3 days). 48 h after withdrawal of pretreatment, rats were pretreated with naltrindole (0.1-1.0 mg/kg s.c.) or its vehicle and 15 min later challenged with either saline or the sensitizing dose of cocaine. In a second set of experiments, naltrindole (0.1-1.0 mg/kg s.c.) or its vehicle were given in combination with either saline or cocaine (20 mg/kg i.p.) for 3 days. Activity in response to saline and to cocaine (20 mg/kg i.p.) was assessed on days 4 and 5, respectively. Additional experiments determined whether naltrindole prevents the development of sensitization to the locomotor-activating effects of nicotine: naltrindole (0.3, 1.0 mg/kg s.c.) or its vehicle were given in combination with nicotine (0.6 mg/kg s.c.) for 3 days. Naltrindole blocked the development but not expression of sensitization to the locomotor-activating effects of cocaine. In contrast, naltrindole failed to modify nicotine-induced sensitization in nicotine-treated animals. These data suggest that delta-opioid receptors are involved in the development but not expression of behavioral sensitization to cocaine. RP Heidbreder, C (reprint author), NIDA,NIH,PRECLIN PHARMACOL LAB,BEHAV PHARMACOL & GENET SECT,POB 5180,BALTIMORE,MD 21224, USA. NR 55 TC 35 Z9 35 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 MAR 18 PY 1996 VL 298 IS 3 BP 207 EP 216 DI 10.1016/0014-2999(95)00815-2 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UC549 UT WOS:A1996UC54900001 PM 8846818 ER PT J AU Szallasi, A Nilsson, S Blumberg, PM Hokfelt, T Lundberg, JM AF Szallasi, A Nilsson, S Blumberg, PM Hokfelt, T Lundberg, JM TI Binding of neuroleptic drugs (trifluoperazine and rimcazole) to vanilloid receptors in porcine dorsal horn SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE [H-3]resiniferatoxin; vanilloid receptor; capsazepine; neuroleptic; cooperative binding ID RESINIFERATOXIN BINDING; POSITIVE COOPERATIVITY; CAPSAICIN RECEPTOR; SPINAL-CORD; PAIN; PIG; MODULATION; ANALOGS; CELLS; RAT AB Neuroleptic drugs were reported to modulate [H-3]resiniferatoxin binding to vanilloid receptors in the spinal cord, with marked differences between rat and man. In the present study, we have used a [H-3]resiniferatoxin binding assay using porcine dorsal horn membranes to explore further species differences in the interaction of neuroleptic drugs at spinal vanilloid receptors. Specific binding of 13 pM [H-3]resiniferatoxin to porcine dorsal horn membranes (corresponding to a 7% fractional receptor occupancy) was affected by trifluoperazine in a bi-phasic fashion, with an initial 90% enhancement of binding preceding inhibition: a fit to the modified Hill equation yielded a cooperativity index of 1.8 and a K-i of 5 mu M. Under similar conditions, rimcazole, by contrast, had a monophasic effect: it enhanced but, up to 100 mu M, did not inhibit [H-3]resiniferatoxin binding. These results are in accord with previous findings in human spinal cord but contrast with those in the rat. In experiments in which the concentration of [H-3]resiniferatoxin was varied, 20 mu M trifluoperazine reduced the B-max by 33% (from 181 +/- 9 fmol/mg protein to 121 +/- 5 fmol/mg protein) without a measurable change in affinity or cooperativity. In parallel experiments, by contrast, neither capsaicin nor capsazepine (both at a concentration of 10 mu M) affected the B-max or cooperativity but, as expected, reduced the affinity from 61 +/- 8 pM to 120 +/- 11 pM or to 101 +/- 7 pM, respectively. Whereas vanilloid receptor agonists (resiniferatoxin and capsaicin) affected [H-3]resiniferatoxin binding at low (approximately 7%) fractional receptor occupancies by the radioligand in a bi-phasic fashion, the competitive vanilloid receptor antagonist capsazepine failed to induce the initial binding enhancement. Thus, capsazepine appears to bind to vanilloid receptors in a non-cooperative fashion, or at least with much reduced positive cooperativity in this system. The mechanism by which neuroleptic drugs modulate resiniferatoxin binding is yet to be clarified and is clearly complicated as well as species-dependent; nonetheless, the reduced B-max at higher concentrations suggests that it may at least in part be non-competitive. C1 KAROLINSKA INST,DEPT NEUROSCI,S-17177 STOCKHOLM,SWEDEN. NCI,MOL MECH TUMOR PROMOT SECT,CELLULAR CARCINOGENESIS & TUMOR PROMOT LAB,BETHESDA,MD 20892. RP Szallasi, A (reprint author), KAROLINSKA INST,DEPT PHYSIOL & PHARMACOL,DIV PHARMACOL,S-17177 STOCKHOLM,SWEDEN. NR 37 TC 6 Z9 6 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 MAR 18 PY 1996 VL 298 IS 3 BP 321 EP 327 DI 10.1016/0014-2999(95)00805-5 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA UC549 UT WOS:A1996UC54900016 PM 8846833 ER PT J AU Singh, P Zottola, M Huang, SQ Shaw, BR Pedersen, LG AF Singh, P Zottola, M Huang, SQ Shaw, BR Pedersen, LG TI 2'-deoxycytidine-N(3)-cyanoborane monohydrate SO ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS LA English DT Article ID NUCLEOSIDES; NUCLEOTIDES AB The structure of the title compound, [4-amino-1-(2-deoxy-beta-D-ribofuranosyl)-2-oxo-1H-3-pyrimidinio]-(cyano)borate, C10H15BN4O4.H2O, features an interaction of 2.05 (4) Angstrom between an H atom of the -BH2CN group and an H atom of the -NH2 group. The -C=N group does not lie in the cytosine plane, the N atom being 2.24 Angstrom away from the plane. The cytosine rings are stacked with almost complete overlap along the twofold screw axis with an interplanar separation of 4.03 Angstrom. The sugar is in the T-3(4) puckering mode, the C(5')-O(5') bond has the gg conformation and the relative orientation of the sugar and the base is anti. C1 NIEHS,QUANTITAT & COMPUTAT BIOL LAB,RES TRIANGLE PK,NC 27709. UNIV N CAROLINA,DURHAM,NC 27706. UNIV N CAROLINA,DEPT CHEM,CHAPEL HILL,NC 27514. RP Singh, P (reprint author), N CAROLINA CENT UNIV,DEPT CHEM,DURHAM,NC 27707, USA. RI Pedersen, Lee/E-3405-2013 OI Pedersen, Lee/0000-0003-1262-9861 NR 13 TC 6 Z9 6 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0108-2701 J9 ACTA CRYSTALLOGR C JI Acta Crystallogr. Sect. C-Cryst. Struct. Commun. PD MAR 15 PY 1996 VL 52 BP 693 EP 696 DI 10.1107/S0108270195013412 PN 3 PG 4 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA UF187 UT WOS:A1996UF18700088 ER PT J AU Schmidt, HHJ Hill, S Makariou, EV Feuerstein, IM Dugi, KA Hoeg, JM AF Schmidt, HHJ Hill, S Makariou, EV Feuerstein, IM Dugi, KA Hoeg, JM TI Relation of cholesterol-year score to severity of calcific atherosclerosis and tissue deposition in homozygous familial hypercholesterolemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACHILLES-TENDON XANTHOMAS; COMPUTED-TOMOGRAPHY; HEART-DISEASE; THICKNESS AB The high concentrations of low-density lipoprotein cholesterol in plasma lead to accelerated atherosclerosis in patients homozygous for familial hypercholesterolemia (FH). We addressed the hypothesis that lipid deposition in the arterial vasculature and in nonvascular tissues in these patients correlates with both the duration and severity of their hypercholesterolemia. The severity of calcific atherosclerosis was defined by calcification scores and a calcified volume determined by electron beam tomography, The extent of tendinous xanthomatosis was quantitated by computed tomography. A cholesterol-year score was calculated based on the age and the yearly mean serum cholesterol concentration of each patient, Seventeen patients homozygous for FH were followed up. The average total cholesterol concentration in the study group was 780 +/- 231 mg/dl 120.2 mmol/L), and the cholesterol-year scores ranged from 2,172 mg-year/dl (56 mmol-year/L) to 32,260 mg-year/dl (834 mmol-year/L). Achilles tendon width (r = 0.86) and cross-sectional area (r = 0.81; both p <0.001) were best correlated with the cholesterol-year score, In addition, the coronary (r = 0.61; p <0.05), ostial (r = 0.45; p <0.05), and total (r = 0.77; p <0.001) calcification atherosclerosis scores all were best correlated with the cholesterol-year score. Calcific atherosclerosis was not observed in these patients until the cholesterol-year score exceeded 10,000 mg-year/dl (260 mmol-year/L). These findings establish a direct association of cholesterol-year with extravascular lipid deposition in tissues of patients with FH. The cholesterol-year score may be useful in defining the risk of atherosclerosis in patients with more common forms of hypercholesterolemia. C1 NHLBI,SECT CELL BIOL,MOLEC DIS BRANCH,NIH,BETHESDA,MD 20892. NIH,WARREN G MAGNUSON CLIN CTR,DEPT RADIOL,BETHESDA,MD 20892. UNIFORMED SERV UNIV HLTH SCI,HENRY M JACKSON FDN ADVANCEMENT MIL MED,BETHESDA,MD 20814. NR 23 TC 53 Z9 54 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 1996 VL 77 IS 8 BP 575 EP 580 DI 10.1016/S0002-9149(97)89309-5 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UD083 UT WOS:A1996UD08300005 PM 8610605 ER PT J AU Kronmal, RA Smith, VE OLeary, DH Polak, JF Gardin, JM Manolio, TA AF Kronmal, RA Smith, VE OLeary, DH Polak, JF Gardin, JM Manolio, TA TI Carotid artery measures are strongly associated with left ventricular mass in older adults (A report from the Cardiovascular Health study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RISK-FACTORS; HYPERTENSION; HYPERTROPHY; ATHEROSCLEROSIS; POPULATIONS; PREVALENCE AB Associations of carotid artery diameter and intimal-medial thickness by ultrasound with echocardiographic left ventricular (LV) structure were examined in 3,409 participants in the Cardiovascular Health Study, a population-based study of risk factors for coronary heart disease and stroke in men and women aged greater than or equal to 65 years, At baseline, sector-guided M-mode echocardiography and B-mode ultrasound were used to evaluate the left ventricle and carotid arteries, respectively. Common carotid artery diameter and intimal-medial thickness were significantly related to LV mass in correlational analysis (r = 0.40 and 0.20, respectively, p < 0.01), and each was independently associated with LV mass after adjustment for age, gender, weight, systolic and diastolic blood pressure, antihypertensive medication use, prior coronary heart disease, electrocardiographic abnormalities, high-density lipoprotein, and factor VH. We speculate that changes in the arterial wall affect impedance to LV ejection leading to increases in LV mass. further follow-up of this cohort is in progress and will help to determine whether such carotid artery measures could, by exacerbating LV hypertrophy, constitute another important risk factor for adverse cardiovascular outcomes. C1 UNIV WASHINGTON,DEPT BIOSTAT,SEATTLE,WA 98195. ALBANY MED COLL,DIV CARDIOL,ALBANY,NY. GEISINGER MED CTR,DIV RADIOL,DANVILLE,PA 17822. BRIGHAM & WOMENS HOSP,DIV RADIOL,BOSTON,MA 02115. UNIV CALIF IRVINE,IRVINE MED CTR,DIV CARDIOL,IRVINE,CA 92717. NHLBI,EPIDEMIOL & BIOMETRY PROGRAM,DIV EPIDEMIOL & CLIN APPLICAT,BETHESDA,MD 20892. FU NHLBI NIH HHS [N01-HC-85080, N01-HC-85081, N01-HC-85079] NR 33 TC 35 Z9 36 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 1996 VL 77 IS 8 BP 628 EP 633 DI 10.1016/S0002-9149(97)89319-8 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA UD083 UT WOS:A1996UD08300015 PM 8610615 ER PT J AU Shelhamer, JH Gill, VJ Quinn, TC Crawford, SW Kovacs, JA Masur, H Ognibene, FP AF Shelhamer, JH Gill, VJ Quinn, TC Crawford, SW Kovacs, JA Masur, H Ognibene, FP TI The laboratory evaluation of opportunistic pulmonary infections SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; PNEUMOCYSTIS-CARINII PNEUMONIA; BONE-MARROW TRANSPLANTATION; ACQUIRED IMMUNODEFICIENCY SYNDROME; BRONCHOALVEOLAR LAVAGE FLUID; PERIPHERAL-BLOOD LEUKOCYTES; HUMAN CYTOMEGALOVIRUS-INFECTION; RESPIRATORY SYNCYTIAL VIRUS; RAPID DETECTION; MONOCLONAL-ANTIBODY AB The patient population at risk for opportunistic pulmonary infections has increased during the last decade. The spectrum of organisms causing opportunistic infections has also grown. With an ever broader list of potential therapeutic options and a growing differential diagnosis, a specific diagnosis of the cause of pulmonary disease becomes more important. Recent microbiologic advances have helped to facilitate the laboratory diagnosis of some of these agents. Immunoassays are available for the detection of antigen in nasopharyngeal secretions (respiratory syncytial virus, influenza), in serum (Cryptococcus species), and in urine (Legionella or Histoplasma species). Rapid-culture techniques are available for the culture a nd detection of various viruses, including cytomegalovirus. Molecular probes can now assist in the rapid identification of Mycobacterium tuberculosis and some fungi. In the near future, polymerase chain reaction-based techniques may assist in the detection of Pneumocystis carinii and Legionella, Chlamydia, Mycoplasma, and Mycobacteria species. An expeditious evaluation of pulmonary disease requires an understanding of the differential diagnosis of likely causes of pulmonary disease in specific immunosuppressed patient populations, an understanding of the most appropriate specimens to process for these diagnoses, and an understanding of the limitations (sensitivity and specificity) of these diagnostic tests. An understanding of the most appropriate specimens and tests in a given institution should allow for early, relatively specific treatment of many potentially life-threatening infections. C1 NIH,CTR CLIN,DEPT CLIN PATHOL,BETHESDA,MD 20892. FRED HUTCHINSON CANC RES CTR,SEATTLE,WA 98104. RP Shelhamer, JH (reprint author), NIH,CTR CLIN,DEPT CRIT CARE MED,BLDG 10,ROOM 7-D-43,BETHESDA,MD 20892, USA. NR 93 TC 44 Z9 45 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 15 PY 1996 VL 124 IS 6 BP 585 EP 599 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA TZ529 UT WOS:A1996TZ52900009 PM 8597323 ER PT J AU Schulze, B Mann, K Poschl, E Yamada, Y Timpl, R AF Schulze, B Mann, K Poschl, E Yamada, Y Timpl, R TI Structural and functional analysis of the globular domain IVa of the laminin alpha 1 chain and its impact on an adjacent RGD site SO BIOCHEMICAL JOURNAL LA English DT Article ID CALCIUM-DEPENDENT BINDING; GLY-ASP SEQUENCE; COLLAGEN TYPE-IV; A-CHAIN; BASEMENT-MEMBRANES; NIDOGEN-BINDING; PROTEIN BM-40; PROTEOGLYCANS; EXPRESSION; COMPLEX AB The globular domain IVa (about 250 residues) of the laminin alpha 1 chain was obtained in recombinant form from mammalian cell clones. It was prepared either with (alpha 11Va-R) or without (alpha IIVa) an adjacent cell-adhesive RGD site which seems to be masked in laminin-1. The recombinant products could be visualized as globular structures by rotary shadowing, were resistant to trypsin and shared immunological epitopes with laminin-l, indicating folding into a native structure. Sequence analysis of pepsin fragments demonstrated the insertion of the globular domain into an epidermal growth factor-like scaffold which is characteristic of the extracellular laminin domain IV (L4) module. Only little immunological cross-reaction was found, however, with other L4 modules from perlecan and different laminin isoforms. Fragment alpha 11Va-R, but not fragment alpha 11Va, bound to alpha V beta 3 integrin, although to a distinctly lower level than a laminin fragment where the RGD site is fully exposed. The fragments also had no or only little cell attachment activity. This confirmed previous predictions that the globular domain alpha 11Va masks the RGD site in laminin-l. Domain alpha 11Va showed, in addition, a weak binding activity for the basement-membrane protein fibulin-1. C1 MAX PLANCK INST BIOCHEM,D-82152 MARTINSRIED,GERMANY. NIDR,NIH,BETHESDA,MD 20892. RI Mann, Karlheinz/C-4254-2008; Poschl, Ernst /E-2103-2011 NR 33 TC 19 Z9 19 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON, ENGLAND W1N 3AJ SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 15 PY 1996 VL 314 BP 847 EP 851 PN 3 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UC245 UT WOS:A1996UC24500020 PM 8615779 ER PT J AU Dwyer, SC Legendre, L Low, PS Leto, TL AF Dwyer, SC Legendre, L Low, PS Leto, TL TI Plant and human neutrophil oxidative burst complexes contain immunologically related proteins SO BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS LA English DT Article DE neutrophil; oxidative burst; signal transduction; (plant) ID CHRONIC GRANULOMATOUS-DISEASE; NADPH OXIDASE; HYPERSENSITIVE RESPONSE; DEFENSE RESPONSE; CELLS; COMPONENTS; ACTIVATION; ELICITOR; STIMULATION; ELICITATION AB Generation of the microbicidal oxidative burst in human neutrophils requires participation of four proteins, a membrane bound flavocytochrome b-558, two soluble proteins termed p47-phox and p67-phox, and the Ras-related GTPase Rac. Because plant cells exposed to pathogens produce a similar oxidative burst, we have looked for similarities between the oxidase complexes of the two systems. Antibodies against human neutrophil p47-phox and p67-phox were used to immunoblot cell extracts from several plant cell lines and were found to cross-react with proteins of the same molecular weight. Furthermore, plant cell lines not previously shown to produce an oxidative burst, yet found to express these immunoreactive proteins, rapidly generated hydrogen peroxide in response to elicitation. Finally, diphenylene iodonium (DPI) and alpha-naphthol, known specific inhibitors of the NADPH oxidase in neutrophils, also inhibited the oxidative burst in soybean cell suspensions with similar K-i values (about 15 mu M and 30 mu M, respectively). These results provide evidence for involvement of proteins related to the neutrophil oxidase complex in the defense-related oxidative burst of plants. C1 PURDUE UNIV,DEPT CHEM,W LAFAYETTE,IN 47907. NIAID,HOST DEF LAB,BETHESDA,MD 20892. UNIV REIMS,LAB BIOL PHYSIOL VEGETALES,UFR SCI,F-51062 REIMS,FRANCE. OI Low, Philip/0000-0001-9042-5528 NR 45 TC 108 Z9 108 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4165 J9 BBA-GEN SUBJECTS JI Biochim. Biophys. Acta-Gen. Subj. PD MAR 15 PY 1996 VL 1289 IS 2 BP 231 EP 237 DI 10.1016/0304-4165(95)00156-5 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UB810 UT WOS:A1996UB81000010 PM 8600979 ER PT J AU VanHorn, JD Berman, KF Weinberger, DR AF VanHorn, JD Berman, KF Weinberger, DR TI Functional lateralization of the prefrontal cortex during traditional frontal lobe tasks SO BIOLOGICAL PSYCHIATRY LA English DT Review DE positron emission tomography; regional cerebral blood flow; frontal lobes; functional lateralization ID CEREBRAL BLOOD-FLOW; CARD SORTING TEST; MONOZYGOTIC TWINS DISCORDANT; SPATIAL WORKING-MEMORY; COMPARATIVE NEUROPSYCHOLOGY; CHRONIC-SCHIZOPHRENIA; KORSAKOFFS SYNDROME; DELAYED-RESPONSE; BRAIN-FUNCTION; PHYSIOLOGICAL DYSFUNCTION AB We attempted to identify brain regions functionally lateralized during cognitive tacks traditionally linked to the prefrontal cortex (PFC) by measuring regional cerebral blood flow with (H2O)-O-15 positron emission tomography (PET). Fourteen normal subjects were scanned six times while performing six different cognitive conditions comprising three task paradigms putatively sensitive to PFC integrity: the Wisconsin Card Sort (WCS), Delayed Response Alternation (DA), and the Spatial Delayed Response (SDR) Tasks, and three matched sensorimotor control tasks. Multivariate and repeated measures analyses indicated that for all three cognitive paradigms there were no significant hemisphere, hemisphere-by-condition, or hemisphere-by-region effects. However with move liberal statistical comparison (paired t tests), the superior frontal gyrus showed lateralization during both the WCS and SDR tasks (both R > L). These results suggest that, although some asymmetries may be found using liberal analyses, there is less evidence of lateralized brain function during performance of these tasks of PFC function, than in language and motor systems. Implications for testing PFC function in neuropsychiatric groups are discussed. RP VanHorn, JD (reprint author), NIMH, NIH,CLIN BRAIN DISORDERS BRANCH,UNIT PET,BLDG 10, 4N-317, ROCKVILLE, MD 20892 USA. NR 103 TC 21 Z9 21 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 1996 VL 39 IS 6 BP 389 EP 399 DI 10.1016/0006-3223(95)00249-9 PG 11 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UC693 UT WOS:A1996UC69300001 PM 8679784 ER PT J AU Kajimura, N Kato, M Okuma, T Sekimoto, M Watanabe, T Takahashi, K AF Kajimura, N Kato, M Okuma, T Sekimoto, M Watanabe, T Takahashi, K TI Relationship between delta activity during all-night sleep and negative symptoms in schizophrenia: A preliminary study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE polysomnogram; period-amplitude analysis; delta activity; schizophrenia; negative symptoms; pathophysiology ID SLOW-WAVE SLEEP C1 NATL CTR NEUROL & PSYCHIAT,TOKYO,JAPAN. NIMH,BETHESDA,MD 20892. RP Kajimura, N (reprint author), NATL CTR HOSP MENTAL NERVOUS & MUSCULAR DISORDERS,NATL CTR NEUROL & PSYCHIAT,KODAIRA,TOKYO 187,JAPAN. NR 29 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 1996 VL 39 IS 6 BP 451 EP 454 DI 10.1016/0006-3223(95)00376-2 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UC693 UT WOS:A1996UC69300009 PM 8679792 ER PT J AU Wyatt, RJ Karoum, F Casanova, MF AF Wyatt, RJ Karoum, F Casanova, MF TI Power to the cingulate - Response SO BIOLOGICAL PSYCHIATRY LA English DT Letter RP Wyatt, RJ (reprint author), NIMH,NEUROSCI CTR ST ELIZABETHS,NEUROPSYCHIAT BRANCH,WASHINGTON,DC 20032, USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 1996 VL 39 IS 6 BP 464 EP 465 DI 10.1016/0006-3223(95)00528-5 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA UC693 UT WOS:A1996UC69300015 ER PT J AU OShaughnessy, JA Tolcher, A Riseberg, D Venzon, D Zujewski, J Noone, M Gossard, M Danforth, D Jacobson, J Chang, V Goldspiel, B Keegan, P Giusti, R Cowan, KH AF OShaughnessy, JA Tolcher, A Riseberg, D Venzon, D Zujewski, J Noone, M Gossard, M Danforth, D Jacobson, J Chang, V Goldspiel, B Keegan, P Giusti, R Cowan, KH TI Prospective, randomized trial of 5-fluorouracil, leucovorin, doxorubicin, and cyclophosphamide chemotherapy in combination with the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein (PIXY321) versus GM-CSF in patients with advanced breast cancer SO BLOOD LA English DT Article ID INTERLEUKIN-3; HEMATOPOIESIS; PRIMATES; THERAPY AB We conducted a prospective randomized trial to evaluate the ability of the interleukin-3/granulocyte-macrophage colony-stimulating factor (GM-CSF) fusion protein, PIXY321, to ameliorate cumulative thrombocytopenia after multiple cycles of 5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide (FLAG) chemotherapy compared with GM-CSF in patients with advanced breast cancer. Fifty-three patients were randomized to receive either PIXY321. 375 mu g/m(2) twice a day subcutaneously, or GM-CSF, 250 mu g/m(2) daily subcutaneously after FLAG chemotherapy. PIXY321 was less well tolerated than GM-CSF, with more patients developing chills and local skin reactions and more patients stopping PIXY321 due to intolerance. While no difference in the neutrophil nadirs was seen with the two cytokines, the duration of the absolute neutrophil count less than 1,000/mu L for all cycles was significantly longer with PIXY321 than with GM-CSF. Fifty percent of patients treated with multiple cycles of FLAG chemotherapy on both study arms developed dose-limiting thrombocytopenia. No differences in platelet nadirs, duration of thrombocytopenia, or need for platelet transfusions were observed with PIXY321 versus GM-CSF. The average delivered doses of FLAG chemotherapy were somewhat higher in the GM-CSF study arm. PIXY321 was not superior to GM-CSF in ameliorating the cumulative thrombocytopenia observed with multiple cycles of FLAG chemotherapy and was less well tolerated. C1 NIH,MED BRANCH,BETHESDA,MD 20892. NIH,BIOSTAT & DATA MANAGEMENT SECT,BETHESDA,MD 20892. NIH,SURG BRANCH,BETHESDA,MD 20892. NIH,RADIAT ONCOL BRANCH,BETHESDA,MD 20892. NIH,DEPT RADIOL,BETHESDA,MD 20892. NIH,DEPT PHARM,BETHESDA,MD 20892. NIH,CTR CLIN,BETHESDA,MD 20892. RP OShaughnessy, JA (reprint author), NCI,NIH,9000 ROCKVILLE PIKE,BLDG 10,ROOM 12N226,BETHESDA,MD 20892, USA. RI Venzon, David/B-3078-2008 NR 19 TC 20 Z9 22 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1996 VL 87 IS 6 BP 2205 EP 2211 PG 7 WC Hematology SC Hematology GA UA957 UT WOS:A1996UA95700009 PM 8630380 ER PT J AU Lukacs, NW Kunkel, SL Strieter, RM Evanoff, HL Kunkel, RG Key, ML Taub, DD AF Lukacs, NW Kunkel, SL Strieter, RM Evanoff, HL Kunkel, RG Key, ML Taub, DD TI The role of stem cell factor (c-kit ligand) and inflammatory cytokines in pulmonary mast cell activation SO BLOOD LA English DT Article ID LYMPHOCYTES-T; BONE-MARROW; ASTHMA; DIFFERENTIATION; PROLIFERATION; INTERLEUKIN-4; BASOPHILS; RECEPTOR; INVIVO AB Mast cells play a critical role in allergic airway responses via IgE-specific activation and release of potent inflammatory mediators, In the present study, we have isolated and characterized primary mast cell lines derived from the upper airways of normal mice, The primary mast cell lines were grown and maintained by incubation with interleukin-3 (IL-3) and stem cell factor (SCF) and shown to be c-kit (SCF receptor) positive by flow cytometry, Subsequently, we examined the proliferation of both airway and bone marrow-derived mast cell lines in response to inflammatory and hematopoietic cytokines, including SCF, IL-1, IL-3, interferon-gamma, IL-4, and IL-10. The results from the pulmonary mast cell lines were compared with those from bone marrow-derived mast cells. Pulmonary mast cell lines were capable of proliferating in response to IL-3, IL-4, IL-10, and SCF, whereas the combination of SCF with the other cytokines did not increase the response over SCF alone. In contrast, the bone marrow-derived mast cells proliferated strongest to SCF or IL-3, but only modestly to IL-4 and IL-10. Furthermore, the combination of SCF with IL-3, but not the other cytokines, exhibited an increase in bone marrow-derived mast cell proliferation. Cytokine-specific stimulation of histamine release in the airway-derived and bone marrow-derived mast cells showed parallel results. SCF was the only cytokine shown to induce substantial histamine release. However, when certain nonhistamine releasing cytokines were combined with SCF, a synergistic increase in histamine release was induced in upper airway, but not bone marrow-derived mast cells. The results of these studies suggest that cytokines differentially modulate induction of proliferation and degranulation of bone marrow and upper airway-derived mast cells and may further indicate a cytokine activational cascade in tissue mast cells. (C) 1996 by The American Society of Hematology. C1 UNIV MICHIGAN,DEPT INTERNAL MED,SCH MED,DIV PULM & CRIT CARE,ANN ARBOR,MI 48109. NCI,FREDERICK CANC RES & DEV CTR,FREDERICK,MD. RP Lukacs, NW (reprint author), UNIV MICHIGAN,DEPT PATHOL,SCH MED,DIV PULM & CRIT CARE,1301 CATHERINE,ANN ARBOR,MI 48109, USA. FU NHLBI NIH HHS [HL31963]; NIA NIH HHS [AG36302] NR 30 TC 51 Z9 51 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1996 VL 87 IS 6 BP 2262 EP 2268 PG 7 WC Hematology SC Hematology GA UA957 UT WOS:A1996UA95700015 PM 8630386 ER PT J AU Giardina, SL Coffman, JD Young, HA Potter, SJ Frey, JL Ortaldo, JR Anderson, SK AF Giardina, SL Coffman, JD Young, HA Potter, SJ Frey, JL Ortaldo, JR Anderson, SK TI Association of the expression of an SR-cyclophilin with myeloid cell differentiation SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; HL-60 CELLS; PROTEINS; MECHANISM; GENES AB The role of a 150-kD SR-cyclophilin (NK-TR1) in monocyte differentiation was investigated. Using an antipeptide monoclonal antibody, we have detected NK-TR1 in human peripheral blood monocytes and HL-60 cells. Unstimulated monocytes showed a low intracellular level of NK-TR1 protein that increased over 3 days of lipopolysaccharide + interferon-gamma treatment, consistent with the kinetics of monocyte differentiation. Normal HL-60 cells also had a low level of NK-TR1 protein, and exposure to 1.25% dimethyl sulfoxide (DMSO) resulted in a marked transient increase in expression that returned to basal levels before the development of granulocyte differentiation-associated biochemical changes. Phorbol myristate acetate, a promoter of monocytic differentiation in HL-60 cells, also caused a significant increase in NK-TR1 over basal levels. Transfection of a vector expressing NK-TR1 antisense RNA into HL-60 cells suppressed DMSO-mediated growth arrest. In addition, the development of a more mature phenotype, as measured by expression of CD16, and the ability to reduce nitroblue tetrazoleum dye was inhibited in transfectants when compared with controls. These results are consistent with the hypothesis that the NK-TR1 gene product is required for the progression towards a mature differentiated phenotype. C1 NCI,FREDERICK CANC RES & DEV CTR,EXPTL IMMUNOL LAB,DIV BASIC SCI,FREDERICK,MD 21702. SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD. RI Anderson, Stephen/B-1727-2012 OI Anderson, Stephen/0000-0002-7856-4266 NR 24 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1996 VL 87 IS 6 BP 2269 EP 2274 PG 6 WC Hematology SC Hematology GA UA957 UT WOS:A1996UA95700016 PM 8630387 ER PT J AU Comerci, JT Runowicz, CD Flanders, KC DeVictoria, C Fields, AL Kadish, AS Goldberg, GL AF Comerci, JT Runowicz, CD Flanders, KC DeVictoria, C Fields, AL Kadish, AS Goldberg, GL TI Altered expression of transforming growth factor-beta 1 in cervical neoplasia as an early biomarker in carcinogenesis of the uterine cervix SO CANCER LA English DT Article DE transforming growth factor-beta 1; cervical dysplasia; cervical cancer; neoplastic transformation ID TRANS-RETINOIC ACID; FACTOR-BETA; GENE-EXPRESSION; TGF-BETA; TAMOXIFEN TREATMENT; COLLAGEN SPONGE; MESSENGER-RNA; CELLS; KERATINOCYTES; INHIBITION AB BACKGROUND. Transforming growth factor-beta 1 (TGF-beta 1) is a potent growth inhibitor of epithelial cell growth, but can also stimulate stromal cell growth. Loss of responsiveness to TGF-beta 1 or loss of TGF-beta 1 itself may be important in the progression of cervical intraepithelial neoplasia (CIN) to invasive cervical carcinoma. METHODS. To examine the expression of TGF-beta in early stages of malignant transformation of the uterine cervix, paraffin embedded tissue samples from 11 patients with normal cervical epithelium, 15 with CIN I-III, 12 with microinvasive, and 18 with invasive squamous cell carcinoma were examined using an immunohistochemical technique. Tissues were immunostained with polyclonal antibodies that react with intracellular and extracellular forms of TGF-beta 1. RESULTS. Percent positive staining for the intracellular form of TGF-beta 1 was 100% for normal epithelium, 73.3% for CIN, and 44.1% for invasive carcinomas (P = 0.002). Percent positive staining for the extracellular form of TGF-beta 1 was 63.6% for stroma underlying normal epithelium, 60% for stroma associated with GIN, and 94.1% for stroma surrounding invasive cancer (P = 0.007). CONCLUSIONS. Decreased expression of intracellular TGF-beta 1 in neoplastic epithelium and increased expression of extracellular TGF-beta 1 in stroma associated with invasive cervical carcinoma suggest that an early event in the neoplastic transformation of cervical epithelial cells may involve the loss of TGF-beta 1. Tumor progression may be indirectly promoted by TGF-beta 1 secreted into or produced by supporting stromal elements. (C) 1996 American Cancer Society. C1 MONTEFIORE MED CTR,BRONX,NY 10467. NCI,CHEMOPREVENT LAB,BETHESDA,MD 20892. ALBERT EINSTEIN COLL MED,DEPT PATHOL,BRONX,NY 10467. RP Comerci, JT (reprint author), ALBERT EINSTEIN COLL MED,DEPT OBSTET & GYNECOL,DIV GYNECOL ONCOL,1695 EASTCHESTER RD,BRONX,NY 10461, USA. NR 47 TC 43 Z9 45 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 1996 VL 77 IS 6 BP 1107 EP 1114 DI 10.1002/(SICI)1097-0142(19960315)77:6<1107::AID-CNCR16>3.0.CO;2-5 PG 8 WC Oncology SC Oncology GA TY621 UT WOS:A1996TY62100016 PM 8635131 ER PT J AU Seth, P Brinkmann, U Schwartz, GN Katayose, D Gress, R Pastan, I Cowan, K AF Seth, P Brinkmann, U Schwartz, GN Katayose, D Gress, R Pastan, I Cowan, K TI Adenovirus-mediated gene transfer to human breast tumor cells: An approach for cancer gene therapy and bone marrow purging SO CANCER RESEARCH LA English DT Article ID AUTOLOGOUS TRANSPLANTATION; EXPRESSION; DELIVERY AB To examine the potential use of adenovirus vectors in cancer gene therapy as a mechanism for purging bone marrow cells of possible breast cancer contaminants, we compared the infection efficiency of adenovirus and the transfection efficiency of plasmid DNA in the presence of adenovirus in human breast cancer and bone marrow cells. Following infection of breast cancer cells with an adenovirus expressing beta-galactosidase gene, high levels of beta-galactosidase activity were observed. No beta-galactosidase activity was observed in low-density human bone marrow cells. A replication-deficient adenovirus mutant dI312 enhanced the transfection efficiency of a plasmid DNA-expressing beta-galactosidase gene into breast cancer cells, and addition of a liposome, lipofectamine, further enhanced the transfection efficiency. In contrast, human bone marrow cells treated under the same conditions expressed very low levels of the transfected beta-galactosidase DNA. Transfection of cells with plasmid DNA expressing a truncated but fully active Pseudomonas exotoxin gene in the presence of dI312 and lipofectamine resulted in marked breast cancer cell killing, whereas colony-forming unit granulocyte-macrophage (CFU-GM) were relatively resistant to these treatments. A recombinant adenovirus expressing human wild-type p53 protein (AdWTp53) was also highly cytotoxic to breast tumor cells. Infection of breast cancer cells with AdWTp53 (100 plaque-forming units/cell) resulted in 100% loss of the clonogenicity of breast tumor cells. However, colony formation from CFU-GM was relatively resistant to the cytotoxic effects of AdWTp53 alone or in the presence of pULI100 plasmid and lipofectamine. On the basis of these results, it is proposed that human adenoviruses are potentially useful for cancer gene therapy and bone marrow purging. C1 NCI,MOLEC BIOL LAB,NIH,BETHESDA,MD 20892. RP Seth, P (reprint author), NCI,MED BRANCH,NIH,BLDG 10,ROOM 12 N 226,BETHESDA,MD 20892, USA. NR 28 TC 81 Z9 83 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA PUBLIC LEDGER BLDG, SUITE 816, 150 S. INDEPENDENCE MALL W., PHILADELPHIA, PA 19106 SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 1996 VL 56 IS 6 BP 1346 EP 1351 PG 6 WC Oncology SC Oncology GA TZ527 UT WOS:A1996TZ52700033 PM 8640824 ER PT J AU Zhang, LJ Kashanchi, F Zhan, QM Zhan, SL Brady, JN Fornace, AJ Seth, P Helman, LJ AF Zhang, LJ Kashanchi, F Zhan, QM Zhan, SL Brady, JN Fornace, AJ Seth, P Helman, LJ TI Regulation of insulin-like growth factor II p3 promoter by p53: A potential mechanism for tumorigenesis SO CANCER RESEARCH LA English DT Article ID WILD-TYPE P53; DNA-DAMAGING AGENTS; GENE-EXPRESSION; MESSENGER-RNA; CELL-LINE; INITIAL CHARACTERIZATION; CANCER-CELLS; BINDING-SITE; TRANSCRIPTION; PROTEIN AB Human insulin-like growth factor (IGF)-II mRNA has been shown to be expressed at high levels in a variety of tumors, including rhabdomyosarcomas, In addition, many tumors have alterations in p53 expression. To investigate whether p53 regulates IGF-II gene expression, we transfected wild-type p53 expression vectors and luciferase constructs driven by IGF-II P3 promoters into multiple cell lines. We found that p53 reduced, in a dose-dependent manner, both endogenous IGF-II P3 transcripts and transfected P3 luciferase expression. The inhibition of P3 luciferase expression by p53 was more pronounced in the two cell lines that expressed mutant p53 protein, RD, and HTB114. The element responsible for this inhibition was mapped to the minimal promoter region. We also transfected an HPV-16 E6 expression plasmid into CCL13 cells containing functional p53 and found that E6 up-regulated IGF-II P3 activity. Wildtype, but not mutant, p53 interfered with the binding of TATA-binding protein to the TATA motif of P3, although both could directly associate with human TATA-binding protein. Our results suggest that p53 may play a role in regulation of IGF-II gene expression. C1 NCI, PEDIAT BRANCH, MOL ONCOL SECT, BETHESDA, MD 20892 USA. NCI, MOLEC VIROL LAB, BETHESDA, MD 20892 USA. NCI, MOLEC PHARMACOL LAB, BETHESDA, MD 20892 USA. NCI, MED BREAST CANC SECT, BETHESDA, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 59 TC 74 Z9 75 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 1996 VL 56 IS 6 BP 1367 EP 1373 PG 7 WC Oncology SC Oncology GA TZ527 UT WOS:A1996TZ52700036 PM 8640827 ER PT J AU Dix, DJ RosarioHerrle, M Gotoh, H Mori, C Goulding, EH Barrett, CV Eddy, EM AF Dix, DJ RosarioHerrle, M Gotoh, H Mori, C Goulding, EH Barrett, CV Eddy, EM TI Developmentally regulated expression of Hsp70-2 and a Hsp70-2/lacZ transgene during spermatogenesis SO DEVELOPMENTAL BIOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; SEQUENCE-ANALYSIS; GENE FAMILY; MOUSE; CELLS; TESTIS; IDENTIFICATION; LOCALIZATION; CLONING; MEMBER AB Germ cells synthesize large amounts of HSP70-2 protein during the meiotic phase of spermatogenesis. This developmentally regulated expression of HSP70-2 contrasts with the constitutive or inducible expression of other 70-kDa heat shock proteins (HSP70s). To better understand the genetic regulation of Hsp70-2, we used mRNA primer-extension, reverse transcriptase PCR (RT-PCR), and cDNA sequencing to determine that transcription began as far as 353 bp upstream of the start codon. We also identified a previously unrecognized 239-bp intron which is spliced out of the pre-mRNA transcript to leave a 114 nt 5'-untranslated region. Transgenic mice were then produced to delimit the upstream regulatory region required for developmental expression of Hsp70-2 during spermatogenesis. Results with multiple lines of transgenic mice containing promoter-reporter transgenes with varying lengths of Hsp70-2 sequence indicate that promoter sequences up to 640 bp upstream of the start codon and 287 bp upstream of the transcription start site are required for Hsp70-2/lacZ expression in spermatocytes. Histochemical detection of transgene p-galactosidase activity was coincident with immunohistochemical detection of HSP70-2 protein, both in the fist wave of spermatogenesis in juvenile mice and in ongoing spermatogenesis of adult mice. The distribution of Hsp70-2 and Hsp70-2/lacZ mRNAs was determined by Northern blot, in situ hybridization, and RT-PCR, and it was found that upregulation of expression of both Hsp70-2 and Hsp70-2/lacZ was specific to the meiotic phase of spermatogenesis. (C) 1996 Academic Press, Inc. C1 NIEHS,NIH,REPROD & DEV TOXICOL LAB,GAMETE BIOL SECT,RES TRIANGLE PK,NC 27709. NATL INST GENET,DEPT CELL GENET,MISHIMA,SHIZUOKA 411,JAPAN. KYOTO UNIV,FAC MED,DEPT ANAT,KYOTO,JAPAN. RP Dix, DJ (reprint author), US EPA,RTD,NATL HLTH & ENVIRONM EFFECTS RES LAB,GAMETE & EARLY EMBRYO BIOL BRANCH,MAIL DROP 72,RES TRIANGLE PK,NC 27711, USA. NR 32 TC 66 Z9 67 U1 0 U2 4 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 15 PY 1996 VL 174 IS 2 BP 310 EP 321 DI 10.1006/dbio.1996.0076 PG 12 WC Developmental Biology SC Developmental Biology GA UB021 UT WOS:A1996UB02100013 PM 8631503 ER PT J AU deMendez, I Adams, AG Sokolic, RA Malech, HL Leto, TL AF deMendez, I Adams, AG Sokolic, RA Malech, HL Leto, TL TI Multiple SH3 domain interactions regulate NADPH oxidase assembly in whole cells SO EMBO JOURNAL LA English DT Article DE NADPH oxidase; proline-rich; p47(phox); p67(phox); SH3 domains ID CHRONIC GRANULOMATOUS-DISEASE; FREE SYSTEM; NEUTROPHIL; TRANSLOCATION; PHOSPHORYLATION; CYTOCHROME-B558; COMPONENTS; ACTIVATION; P67-PHOX; P47-PHOX AB Src homology 3 (SH3) domains mediate specific protein-protein interactions crucial for signal transduction and protein subcellular localization, Upon phagocyte stimulation, two SH3 domain-containing cytosolic components of the NADPH oxidase, p47(phox) and p67(phox), are recruited to the membrane where they interact with flavocytochrome b(558) to form an activated microbicidal oxidase, Deletion analysis of p47(phox) and p67(phox) in transfected K562 cells demonstrated multiple SH3-mediated interactions between p47(phox) and the transmembrane flavocytochrome b(558) and also between the cytosolic components themselves, The core region of p47(phox) (residues 151-284), spanning both SH3 domains, was required for flavocytochrome-dependent translocation and oxidase activity in whole cells, Furthermore, translocation of p67(phox) occurred through interactions of its N-terminal domain (residues 1-246) with p47(phox) SH3 domains. Both of these interactions were promoted by PMA activation of cells and were influenced by the presence of other domains in both cytosolic factors, Deletion analysis also revealed a third SH3 domain-mediated interaction involving the C-termini of both cytosolic factors, which also promoted p67(phox) membrane translocation, These data provide evidence for a central role for p47(phox) in regulation of oxidase assembly through several SH3 domain interactions. RP deMendez, I (reprint author), NIAID,HOST DEF LAB,NIH,BETHESDA,MD 20892, USA. RI Sokolic, Robert/I-6072-2012 NR 41 TC 85 Z9 87 U1 1 U2 2 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 15 PY 1996 VL 15 IS 6 BP 1211 EP 1220 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UD377 UT WOS:A1996UD37700002 PM 8635453 ER PT J AU Schoneberg, T Yun, JN Wenkert, D Wess, J AF Schoneberg, T Yun, JN Wenkert, D Wess, J TI Functional rescue of mutant V2 vasopressin receptors causing nephrogenic diabetes insipidus by a co-expressed receptor polypeptide SO EMBO JOURNAL LA English DT Article DE co-expression experiments; nephrogenic diabetes insipidus; receptor mutagenesis; receptor peptide; V2 vasopressin receptor ID BINDING; COEXPRESSION; CLONING; LIGAND; GENES AB Inactivating mutations in distinct G protein-coupled receptors (GPCRs) are currently being identified as the cause of a steadily growing number of human diseases, Based on previous studies showing that GPCRs are assembled from multiple independently stable folding units, we speculated that such mutant receptors might be functionally rescued by 'supplying' individual folding domains that are lacking or misfolded in the mutant receptors, by using a co-expression strategy, To test the feasibility of this approach, a series of nine mutant V2 vasopressin receptors known to be responsible for X-linked nephrogenic diabetes insipidus were used as model systems, These mutant receptors contained nonsense, frameshift, deletion or missense mutations in the third intracellular loop or the last two transmembrane helices, Studies with transfected COS-7 cells showed that none of these mutant receptors, in contrast to the wild-type V2 receptor, was able to bind detectable amounts of the radioligand, [H-3]arginine vasopressin, or to activate the G(s)/adenylyl cyclase system, Moreover, immunological studies demonstrated that the mutant receptors were not trafficked properly to the cell surface, However, several of the nine mutant receptors regained considerable functional activity upon co-expression with a C-terminal V2 receptor peptide spanning the sequence where the various mutations occur, In many cases, the restoration of receptor activity by the co-expressed receptor peptide was accompanied by a significant increase in cell surface receptor density, These findings may lead to the design of novel strategies in the treatment of diseases caused by inactivating mutations in distinct GPCRs. C1 NIDDKD, BIOORGAN CHEM LAB, BETHESDA, MD 20892 USA. NIDDKD, METAB DIS BRANCH, BETHESDA, MD 20892 USA. NR 38 TC 125 Z9 126 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAR 15 PY 1996 VL 15 IS 6 BP 1283 EP 1291 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UD377 UT WOS:A1996UD37700010 PM 8635461 ER PT J AU Muffler, A Fischer, D Altuvia, S Storz, G HenggeAronis, R AF Muffler, A Fischer, D Altuvia, S Storz, G HenggeAronis, R TI The response regulator RssB controls stability of the sigma(S) subunit of RNA polymerase in Escherichia coli SO EMBO JOURNAL LA English DT Article DE osmoregulation; proteolysis; rpoS; sigma factor; stationary phase ID HEAT-SHOCK RESPONSE; GENE-EXPRESSION; RPOS; KATF; PROTEINS; DNAK; TRANSCRIPTION; SIGMA-32; BINDING AB The rpoS-encoded sigma(S) subunit of RNA polymerase is a central regulator in a regulatory network that governs the expression of many stationary phase-induced and osmotically regulated genes in Escherichia coli. sigma(S) is itself induced under these conditions due to an increase in rpoS transcription (only in rich media) and rpoS translation as well as a stabilization of sigma(S) protein which in growing cells is subject to rapid turnover. We demonstrate here that a response regulator, RssB, plays a crucial role in the control of the cellular sigma(S) content. rssB null mutants exhibit nearly constitutively high levels of sigma(S) and are impaired in the post-transcriptional growth phase-related and osmotic regulation of sigma(S). Whereas rpoS translational control is not affected, sigma(S) is stable in rssB mutants, indicating that RssB is essential for sigma(S) turnover, RssB contains a unique C-terminal output domain and is the first known response regulator involved in the control of protein turnover. C1 UNIV KONSTANZ, DEPT BIOL, D-78434 CONSTANCE, GERMANY. NICHHD, CELL BIOL & METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NR 34 TC 186 Z9 190 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0261-4189 EI 1460-2075 J9 EMBO J JI Embo J. PD MAR 15 PY 1996 VL 15 IS 6 BP 1333 EP 1339 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UD377 UT WOS:A1996UD37700015 PM 8635466 ER PT J AU Kalebic, T AF Kalebic, T TI Human fetal glial cells constitutively produce HIV-inducing cytokines SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TUMOR-NECROSIS-FACTOR; INFECTED MONOCYTIC CELLS; GROWTH-FACTOR-BETA; FACTOR-ALPHA; N-ACETYLCYSTEINE; MICROGLIAL CELLS; BRAIN-TISSUE; JC-VIRUS; EXPRESSION AB The capacity of two human fetal glial cell lines, SVG and POJ, to increase the expression of human immunodeficiency virus (HIV) was investigated. As a cellular model for HIV latency, a chronically infected promonocytic cell line U1 was used. This cell line constitutively expresses a low level of viral activity. To monitor the level of HIV expression in U1 cells, reverse transcriptase (RT) activity was measured in the supernatant and the level of total HIV proteins was determined in cellular lysates. It was observed that the conditioned media from SVG and POJ cells increased RT activity in U1 cells in a dose-dependent fashion. In addition, the conditioned media from fetal glial cells caused an increase in total HIV protein synthesis. The capacity of conditioned media from both fetal glial cell lines to induce the expression of HIV was reduced by 45% in the presence of antibodies against human tumor necrosis factor alpha (TNF alpha), suggesting that one of the HIV-activating factors released by these cells was TNF alpha. The presence of TNF alpha and two other HIV-activating cytokines, IL-6 and IL-1, was confirmed by ELISA. It was also observed that glutathione increased the HN-inducing capacity of the fetal glial cell-derived conditioned media. The finding that fetal glial cells constitutively secrete soluble factors which increase the expression of HN in vitro suggests that in vivo, during perinatally acquired infection, similar events may occur. Fetal glial cells may play an important role in the pathogenesis of HIV-related encephalopathy. (C) 1996 Academic Press, Inc. RP Kalebic, T (reprint author), NCI,PEDIAT BRANCH,MOLEC ONCOL LAB,NATL INST HLTH,BLDG 10-13N240,BETHESDA,MD 20892, USA. NR 50 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR 15 PY 1996 VL 223 IS 2 BP 452 EP 458 DI 10.1006/excr.1996.0101 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA UA590 UT WOS:A1996UA59000029 PM 8601423 ER PT J AU Bernstein, SL Borst, DE Neuder, ME Wong, P AF Bernstein, SL Borst, DE Neuder, ME Wong, P TI Characterization of a human fovea cDNA library and regional differential gene expression in the human retina SO GENOMICS LA English DT Article ID HEAT-SHOCK PROTEINS; HUMAN BRAIN; HSP86 AB The primate fovea is the region of the retina responsible for acute vision. This region constitutes less than 5% of the total area of the retina and has not been intensely studied at the molecular level. As a first step in the molecular characterization of the fovea, we have constructed a primary human fovea cDNA library, Experiments confirm that our cDNA library reflects a nonbiased distribution of foveal expressed sequences, Single-pass sequencing was performed on 209 randomly isolated clones from this library, Analysis of the sequences generated reveals that the distributions of fovea clones with either human mitochondrial gene sequences or repetitive elements are different than those observed in cDNA libraries made from other tissues. A significant number of the fovea expressed sequence tags (ESTs) (88, 42.1%) represent novel human ESTs. This suggests that the library will be useful in identifying new human genes, Northern analysis of specific fovea ESTs defined in this study suggests that there are significant quantitative differences in gene expression that distinguish the fovea from the rest of the retina. (C) 1996 Academic Press, Inc. C1 UNIFORMED SERV UNIV HLTH SCI,BETHESDA,MD 20814. GEORGE WASHINGTON UNIV,SCH MED,WASHINGTON,DC 20005. RP Bernstein, SL (reprint author), NEI,NIH,9000 ROCKVILLE PIKE,BLDG 6,ROOM 337,BETHESDA,MD 20892, USA. NR 28 TC 42 Z9 42 U1 0 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 1996 VL 32 IS 3 BP 301 EP 308 DI 10.1006/geno.1996.0123 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UA298 UT WOS:A1996UA29800001 PM 8838792 ER PT J AU Schmitt, J Hotten, G Jenkins, NA Gilbert, DJ Copeland, NG Pohl, J Schrewe, H AF Schmitt, J Hotten, G Jenkins, NA Gilbert, DJ Copeland, NG Pohl, J Schrewe, H TI Structure, chromosomal localization, and expression analysis of the mouse inhibin/activin beta(c) (Inhbc) gene SO GENOMICS LA English DT Article ID ACTIVIN-A; INSITU HYBRIDIZATION; RAT HEPATOCYTES; LINKAGE MAP; DIFFERENTIATION; CELLS; STIMULATION; INHIBITOR; PRECURSOR; SUBUNITS AB The mouse inhibin/activin beta(c) gene (Inhbc), a member of the transforming growth factor-beta (TGF-beta) superfamily, was cloned, mapped, and characterized. The gene spans approximately 14 kb, is composed of two exons, and maps to the distal region of mouse chromosome 10, which is syntenic to chromosome 12q13.1, where the human inhibin/activin beta(c) gene (INHBC) maps. The primary translation product is a preproprotein of 352 amino acids. The mature C-terminal domain of 116 amino acids shares 94% identity with its human homolog. Primer extension analysis shows that transcription starts approximately 130 bp upstream of the translation initiation site, and no TATA box was found in the promoter. Ribonuclease protection analyses reveal that mouse Inhbc is predominantly expressed in adult liver. Embryonic expression is detected beginning from Day 14.5 of gestation. (C) 1996 Academic Press, Inc. C1 MAX PLANCK INST IMMUNBIOL,DEPT DEV BIOL,D-79108 FREIBURG,GERMANY. BIOPHARM GMBH,D-69115 HEIDELBERG,GERMANY. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. NR 49 TC 46 Z9 49 U1 1 U2 2 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 1996 VL 32 IS 3 BP 358 EP 366 DI 10.1006/geno.1996.0130 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UA298 UT WOS:A1996UA29800008 PM 8838799 ER PT J AU Li, X Zimmerman, A Copeland, NG Gilbert, DJ Jenkins, NA Yin, HL AF Li, X Zimmerman, A Copeland, NG Gilbert, DJ Jenkins, NA Yin, HL TI The mouse thymosin beta 4 gene: Structure, promoter identification, and chromosome localization SO GENOMICS LA English DT Article ID ACTIN-SEQUESTERING PEPTIDE; RESPONSIVE ELEMENT; CELL-PROLIFERATION; BINDING-SITE; EXPRESSION; INDUCTION; PROTEINS; LYMPHOCYTES; THYMOCYTES; RNA AB Thymosin beta 4 (T beta 4) is an actin monomer sequestering protein that may have a critical role in modulating the dynamics of actin polymerization and depolymerization in nonmuscle cells. Its regulatory role is consistent with the many examples of transcriptional regulation of T beta 4 and of tissue-specific expression. Furthermore, lymphocytes have a unique T beta 4 transcript relative to the ubiquitous transcript found in many other tissues and cells. To determine how T beta 4 gene expression is regulated and how the alternative transcripts are derived, we cloned the mouse T beta 4 gene. We established that there is a single mouse TP beta gene and found that the lymphoid-specific transcript is generated by extending the ubiquitous exon 1 with an alternate downstream splice site. The transcription start site is defined by primer extension analysis, and the 5'-flanking region has many of the characteristics of a promoter. It is pyrimidine-rich and contains typical promoter elements, including a GC box, an initiator site, and consensus transcription factor binding sites. The mouse T beta 4 gene locus (Ptmb4) is located by interspecific backcross mapping to the distal region of the mouse X chromosome, linked to Btk and Gja6. (C) 1996 Academic Press, Inc. C1 UNIV TEXAS,SW MED CTR,DEPT PHYSIOL,DALLAS,TX 75235. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NCI NIH HHS [N01-CO-46000]; NIGMS NIH HHS [R01-GM51112]; NINDS NIH HHS [R01-NS31430] NR 38 TC 28 Z9 30 U1 0 U2 1 PU ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 1996 VL 32 IS 3 BP 388 EP 394 DI 10.1006/geno.1996.0133 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA UA298 UT WOS:A1996UA29800011 PM 8838802 ER PT J AU Rusin, MR Okamoto, A Chorazy, M Czyzewski, K Harasim, J Spillare, EA Hagiwara, K Hussain, SP Xiong, Y Demetrick, DJ Harris, CC AF Rusin, MR Okamoto, A Chorazy, M Czyzewski, K Harasim, J Spillare, EA Hagiwara, K Hussain, SP Xiong, Y Demetrick, DJ Harris, CC TI Intragenic mutations of the p16(INK4), p15(INK4B) and p18 genes in primary non-small-cell lung cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article AB The p15(INK4B), p(16INK4) and p18 genes are members of the gene family coding for inhibitors of cyclin-dependent kinases 4 and 6. p15(INK4B) and p16(INK4) are located at 9p21, a chromosomal region frequently deleted in many human neoplasms. To examine the role of these 3 genes in lung carcinogenesis, somatic mutations within the genes were analyzed by single-strand conformation polymorphism and DNA sequencing in 71 non-small-cell lung cancer (NSCLC) samples. Six somatic mutations in the p16(INK4) gene and 3 cases with a polymorphic allele were observed. Loss of heterozygosity in the p18 gene was found in I sample. We did not find any intragenic mutations in the p15(INK4B) Or p18 genes. We conclude that p16(INK4) mutations play a role in the formation of some NSCLCs, whereas the involvement of p15(INK4B) and p18 is uncommon. (C) 1996 Wiley-Liss, Inc.* C1 NCI,HUMAN CARCINOGENESIS LAB,NIH,BETHESDA,MD 20892. INST ONCOL,DEPT TUMOR BIOL,PL-44100 GLIWICE,POLAND. L WARYNSKI SILESIAN MED ACAD,DEPT THORAC MED,PL-41800 ZABRZE,POLAND. UNIV N CAROLINA,CHAPEL HILL,NC 27599. COLD SPRING HARBOR LAB,COLD SPRING HARBOR,NY 11724. FU FIC NIH HHS [5FO5.TW04836-03] NR 21 TC 54 Z9 54 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 15 PY 1996 VL 65 IS 6 BP 734 EP 739 DI 10.1002/(SICI)1097-0215(19960315)65:6<734::AID-IJC4>3.0.CO;2-# PG 6 WC Oncology SC Oncology GA UB749 UT WOS:A1996UB74900004 PM 8631583 ER PT J AU Adami, J Glimelius, B Cnattingius, S Ekbom, A Zahm, SH Linet, M Zack, M AF Adami, J Glimelius, B Cnattingius, S Ekbom, A Zahm, SH Linet, M Zack, M TI Maternal and perinatal factors associated with non-Hodgkin's lymphoma among children SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID CHILDHOOD-CANCER; BURKITTS-LYMPHOMA; PREGNANCY; SMOKING AB This nested case-control study based on 1.7 million live births in Sweden explores the associations between maternal and perinatal factors and the occurrence of childhood non-Hodgkin's lymphoma (NHL). The National Swedish Cancer Registry ascertained 168 cases in successive birth cohorts from 1973 through 1989 recorded in the Swedish Medical Birth Registry. From the nationwide Birth Registry, 5 controls without NHL and alive at the date the case was diagnosed were randomly selected from the pool of children, with each case matched by gender, birth year and birth month. Standardized information on selected maternal and perinatal factors up to one month after delivery were recorded in the Medical Birth Registry. Mothers of children with NHL were more likely than mothers of controls to have undergone Cesarean section [Odds ratio (OR) 1.6] and to have been exposed to paracervical anesthesia during delivery (OR 1.8). Children with NHL were more likely than controls to have endocrine-metabolic disorders (OR 3.3). This study is one of the largest focusing on the etiology of childhood NHL. Most of the maternal and perinatal characteristics studied did not markedly affect risk for childhood NHL, which may be due to maternal and perinatal factors not included in these data or to exposures later in life. (C) 1996 Wiley-Liss, Inc. C1 UNIV UPPSALA HOSP,DEPT ONCOL,S-75185 UPPSALA,SWEDEN. UNIV UPPSALA HOSP,DEPT OBSTET & GYNECOL,S-75185 UPPSALA,SWEDEN. HARVARD UNIV,SCH MED,DEPT EPIDEMIOL,BOSTON,MA. CTR DIS CONTROL,ATLANTA,GA 30333. NCI,BETHESDA,MD 20892. RP Adami, J (reprint author), UNIV UPPSALA HOSP,DEPT CANC EPIDEMIOL,S-75185 UPPSALA,SWEDEN. RI Zahm, Shelia/B-5025-2015 NR 24 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 SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 15 PY 1996 VL 65 IS 6 BP 774 EP 777 DI 10.1002/(SICI)1097-0215(19960315)65:6<774::AID-IJC11>3.0.CO;2-4 PG 4 WC Oncology SC Oncology GA UB749 UT WOS:A1996UB74900011 PM 8631590 ER PT J AU Zdanovsky, AG Zdanovskaia, MV Strickland, D Fitzgerald, DJ AF Zdanovsky, AG Zdanovskaia, MV Strickland, D Fitzgerald, DJ TI Ligand-toxin hybrids directed to the alpha(2)-macroglobulin receptor/low density lipoprotein receptor-related protein exhibit lower toxicity than native Pseudomonas exotoxin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PLASMINOGEN-ACTIVATOR-INHIBITOR; ALPHA-2-MACROGLOBULIN RECEPTOR; DIPHTHERIA-TOXIN; ESCHERICHIA-COLI; MEDIATED ENDOCYTOSIS; HIGH-AFFINITY; BINDING; GENE; EXPRESSION; SEQUENCE AB Pseudomonas exotoxin (PE) binds the heavy chain of the alpha(2)-macroglobulin receptor/low density lipoprotein receptor-related protein (LRP). To understand the significance of this interaction, novel toxin-derived gene fusions were constructed with two ligands that also bind this receptor. A 39-kDa cellular protein, termed RAP, binds LRP with high affinity and often co-purifies with it. Two RAP toxins were constructed, one with PE and one with diphtheria toxin (DT). RAP, which replaced the toxins binding domains, was combined with each of the corresponding translocating and ADP-ribosylating domains. Both RAP-toxins bound LRP with an apparent higher affinity than native PE. Despite this, RAP-PE and DT-RAP were less toxic than native PE. Apparently, RAP-toxin molecules bound and entered cells but used a pathway that afforded only low efficiency of toxin transport to the cytosol. This was evident because co-internalization with adenovirus increased the toxicity of RAP-toxins by 10-fold. We speculate that the high affinity of RAP binding may not allow the toxin's translocating and ADP-ribosylating domains to reach the cytosol but rather causes the toxin to take another pathway, possibly one that leads to lysosomes. To test this hypothesis, additional RAP-PE fusions were constructed. N-terminal or C-terminal fragments of RAP were joined to PE to produce two novel fusion proteins which were likely to have reduced affinity for LRP. Both of these shorter fusion proteins exhibited greater toxicity than full-length RAP-PE. A second ligand-toxin gene fusion was constructed between plasminogen activator inhibitor type 1 and DT. DT-plasminogen activator inhibitor type I formed a complex with tissue-type plasminogen activator and inhibited its proteolytic activity. However, like the RAP-toxins, this hybrid was less toxic for cells than native PE. C1 NCI,MOLEC BIOL LAB,DIV CANC BIOL DIAG & CTR,NIH,BETHESDA,MD 20892. AMER RED CROSS,BIOCHEM LAB,ROCKVILLE,MD 20855. NR 39 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 15 PY 1996 VL 271 IS 11 BP 6122 EP 6128 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UA363 UT WOS:A1996UA36300028 PM 8626399 ER PT J AU Liu, J Blin, N Conklin, BR Wess, J AF Liu, J Blin, N Conklin, BR Wess, J TI Molecular mechanisms involved in muscarinic acetylcholine receptor-mediated G protein activation studied by insertion mutagenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BETA-ADRENERGIC-RECEPTOR; TERNARY COMPLEX MODEL; ADENYLATE-CYCLASE; COUPLED RECEPTORS; BINDING; HYDROLYSIS; SUBTYPES; IDENTIFICATION; SPECIFICITY; G(Q)ALPHA AB We have recently shown that a four-amino acid epitope (VTIL) on the m2 muscarinic receptor (corresponding to Val(385), Thr(386), Ile(389), and Leu(390)) is essential for G(i/o) coupling specificity and G(i/o) activation (Liu, J., Conklin, B. R., Blin, N., Yun, J., and Wess, J. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 11642-11646). Because this sequence element is thought to be located at the junction between the third intracellular loop and the sixth transmembrane helix (TM VI), we speculated that agonist binding to the m2 receptor protein results in conformational changes that enable the VTIL motif to interact with G(i/o) proteins. To test the hypothesis that such structural changes might involve a relative movement of TM VI toward the cytoplasm, we created a series of mutant m2 muscarinic receptors in which one to four extra Ala residues were inserted into TM VI immediately after Leu(390). Based on the geometry of an alpha-helix, such mutations are predicted to ''push'' the VTIL sequence away from the lipid bilayer. Consistent with our working hypothesis, second messenger assays with transfected COS-7 cells showed that all mutant m2 receptors containing extra Ala residues C-terminal of Leu(390) could activate the proper G proteins even in the absence of agonist. However, replacement of the VTIL motif in such constitutively active m2 receptors with the corresponding m3 muscarinic receptor sequence (AALS) or deletion of Ala(391) from the wild type m2 receptor completely abolished G protein coupling. Interestingly, introduction of extra Ala residues C-terminal of the AALS motif in the m3 muscarinic receptor completely abolished functional activity. Mutant m2 and m3 receptors that contained extra Ala residues immediately N-terminal of the VTIL and AALS motif, respectively, displayed wild type-like coupling properties. Our data are consistent with a model in which agonist binding to the m2 muscarinic receptor leads to a relative movement of TM VI toward the cytoplasm, thus enabling the adjacent VTIL sequence to interact with the C terminus of G alpha(i/o) subunits. C1 NIDDK,NIH,BIOORGAN CHEM LAB,BETHESDA,MD 20892. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,DEPT MED,SAN FRANCISCO,CA 94141. UNIV CALIF SAN FRANCISCO,GLADSTONE INST CARDIOVASC DIS,DEPT PHARMACOL,SAN FRANCISCO,CA 94141. NR 47 TC 71 Z9 72 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 15 PY 1996 VL 271 IS 11 BP 6172 EP 6178 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UA363 UT WOS:A1996UA36300035 PM 8626406 ER PT J AU Puzianowska-Kuznicka, M Shi, YB AF Puzianowska-Kuznicka, M Shi, YB TI Nuclear factor I as a potential regulator during postembryonic organ development SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DNA-BINDING PROTEIN; AMPHIBIAN METAMORPHOSIS; GENE-EXPRESSION; TRANSCRIPTION; REPLICATION; PROMOTER; INVITRO; LARVAL; SITE; PURIFICATION AB Nuclear factor I (NFI) family members are transcription factors that are believed to also participate in DNA replication. We have cloned two Xenopus laevis NFIs that are up-regulated by thyroid hormone. They are 84-95% identical to their counterparts in birds and mammals. In contrast, the two Xenopus NFIs are much less homologous to each other, sharing only 58% homology, which largely resides in the DNA binding domain at the amino terminus. However, both NFIs can bind to a consensus NFI binding site and activate the transcription of a promoter bearing the site. Northern blot reveals that both NFI genes are regulated in tissue- and developmental stage-dependent manners. They are first activated, independently of thyroid hormone, to low levels at stages 23/24, around the onset of larval organogenesis. After stage 54, their mRNA levels are dramatically upregulated by endogenous thyroid hormone, and high levels of their expression correlate with organ-specific metamorphosis. Furthermore, gel mobility shift assay indicates that the NFI proteins are present in different organs and that their levels are regulated similarly to the mRNA levels. These results strongly suggest that NFIs play important roles during postembryonic organ development, in contrast to the general belief that NFIs are ubiquitous factors. C1 NICHHD, MOLEC EMBRYOL LAB, NIH, BETHESDA, MD 20892 USA. NR 52 TC 34 Z9 34 U1 1 U2 3 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 MAR 15 PY 1996 VL 271 IS 11 BP 6273 EP 6282 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UA363 UT WOS:A1996UA36300050 PM 8626421 ER PT J AU Chu, YF Solski, PA KhosraviFar, R Der, CJ Kelly, K AF Chu, YF Solski, PA KhosraviFar, R Der, CJ Kelly, K TI The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMEDIATE-EARLY GENE; TYROSINE PHOSPHATASE; T-CELLS AB Mitogen-activated protein (MAP) kinases can be grouped into three structural families, ERK, JNK, and p38, which are thought to carry out unique functions within cells. We demonstrate that ERK, JNK, and p38 are activated by distinct combinations of stimuli in T cells that simulate full or partial activation through the T cell receptor. These kinases are regulated by reversible phosphorylation on Tyr and Thr, and the dual specific phosphatases PAC1 and MKP-1 previously have been implicated in the in vivo inactivation of ERK or of ERK and JNK respectively. Here we characterize a new MAP kinase phosphatase, MKP-2, that is induced in human peripheral blood T cells with phorbol 12-myristate 13-acetate and is expressed in a variety of nonhematopoietic tissues as well. We show that the in vivo substrate specificities of individual phosphatases are unique, PAC1, MKP-2, and MKP-1 recognize ERK and p38, ERK and JNK, and ERK, p38, and JNK, respectively. Thus, individual MAP kinase phosphatases can differentially regulate the potential for cross-talk between the various MAP kinase pathways. A hyperactive allele of ERK2 (D319N), analogous to the Drosophila sevenmaker gain-of-function mutation, has significantly reduced sensitivity to all three MAP kinase phosphatases in vivo. C1 NCI,PATHOL LAB,NIH,BETHESDA,MD 20892. UNIV N CAROLINA,SCH MED,DEPT PHARMACOL,CHAPEL HILL,NC 27599. UNIV N CAROLINA,SCH MED,CURRICULUM GENET & MOLEC BIOL,CHAPEL HILL,NC 27599. RI Khosravi-Far, Roya/C-3789-2008 NR 34 TC 352 Z9 356 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 15 PY 1996 VL 271 IS 11 BP 6497 EP 6501 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UA363 UT WOS:A1996UA36300081 PM 8626452 ER PT J AU Scita, G Darwiche, N Greenwald, E Rosenberg, M Politi, K De Luca, LM AF Scita, G Darwiche, N Greenwald, E Rosenberg, M Politi, K De Luca, LM TI Retinoic acid down-regulation of fibronectin and retinoic acid receptor alpha proteins in NIH-3T3 cells - Block of this response by ras transformation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-LEUKEMIA CELLS; MESSENGER-RNA; TERATOCARCINOMA CELLS; CYCLIC-AMP; VITAMIN-A; EXPRESSION; GENE; DIFFERENTIATION; GAMMA; IMMUNODETECTION AB All trans-retinoic acid (RA) markedly reduced the level of intracellular fibronectin (FN) in a time- and concentration-dependent fashion in NIH-3T3 cells, but not in NIH-3T3 cells transformed by an activated Ha-ras oncogene. Pulse/chase experiments indicated that RA affects FN biosynthesis rather than its turnover rate. Steady state levels of FN transcripts did not change after treatment of the cells with RA for various times or concentrations, suggesting that RA acts at the translational level. Similar effects were observed in other fibroblasts. In NIH-3T3 cells, RA had distinct effects on different receptors; it down-modulated retinoic acid receptor (RAR) alpha protein and transcript levels, it up-regulated RAR beta transcripts, and it had no effect on RAR gamma. Transformation of NIH-3T3 cells with an activated Ha-ras oncogene down-modulated RAR expression and abolished responsiveness to RA. We identified the retinoid signal transduction pathways responsible for the effects of RA on FN and RAR alpha proteins by the use of the retinoid X receptor-selective compound, SR11237, by stable overexpression of a truncated form of the RAR alpha gene, RAR alpha 403, with strong RAR dominant negative activity, and by overexpression of RAR alpha. We conclude that: 1) RA-dependent FN down-modulation is mediated by RARs, 2) retinoid X receptors mediate the observed reduction of RAR alpha by RA, and 3) the block of RA responsiveness in Ha-ras cells cannot be overcome by overexpression of RAR alpha. These studies have defined fibronectin and RAR alpha as targets of RA in fibroblast cells and have shown that oncogenic transformation renders the cells resistant to RA action. C1 NCI, LAB CELLULAR CARCINOGENESIS & TUMOR PROMOT, NIH, BETHESDA, MD 20892 USA. RI Scita, GIORGIO/J-9670-2012; OI Darwiche, Nadine/0000-0002-1862-5426; Scita, Giorgio/0000-0001-7984-1889 NR 54 TC 36 Z9 36 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 15 PY 1996 VL 271 IS 11 BP 6502 EP 6508 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UA363 UT WOS:A1996UA36300082 PM 8626453 ER PT J AU Mincione, G Bianco, C Kannan, S Colletta, G Ciardiello, F Sliwkowski, M Yarden, Y Normanno, N Pramaggiore, A Kim, N Salomon, DS AF Mincione, G Bianco, C Kannan, S Colletta, G Ciardiello, F Sliwkowski, M Yarden, Y Normanno, N Pramaggiore, A Kim, N Salomon, DS TI Enhanced expression of heregulin in c-erb B-2 and c-Ha-ras transformed mouse and human mammary epithelial cells SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE heregulin; transformation; erb B-2; c-Ha-ras; mammary cells ID FACTOR RECEPTOR FAMILY; GROWTH-FACTOR; MULTIPLE FORMS; BREAST-CANCER; MEMBER; LIGAND; ALPHA; GENE; PROTEIN; HER4/P180(ERBB4) AB Heregulin beta 1 was found to stimulate the anchorage-dependent, serum-free growth of nontransformed human MCF-10A mammary epithelial cells. Unlike epidermal growth factor, transforming growth factor alpha, or amphiregulin, heregulin beta 1 was also able to induce the anchorage-independent growth of MCF-10A cells. In contrast, the anchorage-dependent, serum-free growth of c-Ha-ras or c-erb B-2 transformed MCF-10A cells was unaffected by heregulin beta 1, whereas heregulin beta 1 was able to stimulate the anchorage-independent growth of these cells. c-Ha-ras or c-erb B-2 (c-neu) transformed MCF-10A or mouse NOG-8 mammary epithelial cells express elevated levels of 2.5, 5.0, 6.5, 6.8, and 8.5 kb heregulin mRNA transcripts and/or synthesize cell-associated 25, 29, 50, and 115 kDa isoforms of heregulin. Since the MCF-10A cells and transformants also express c-erb B-3, these data suggest that endogenous heregulin might function as an autocrine growth factor for Ha-ras or erb B-2 transformed mammary epithelial cells. (C) 1996 Wiley-Liss, Inc.* C1 NCI,TUMOR GROWTH FACTORS SECT,TUMOR IMMUNOL & BIOL LAB,NIH,BETHESDA,MD 20892. UNIV G DANNUNZIO,FAC MED & CHIRURG,IST PATOL UMANA & MED SOCIALE,CHIETI,ITALY. UNIV NAPLES,FAC MED & CHIRURG,CATTEDRA ONCOL MED,I-80131 NAPLES,ITALY. GENENTECH INC,DEPT PROT BIOCHEM,S SAN FRANCISCO,CA 94080. WEIZMANN INST SCI,DEPT CHEM IMMUNOL,REHOVOT,ISRAEL. IST NAZL STUDIO & CURA TUMORI,FDN PASCALE,NAPLES,ITALY. RI YARDEN, YOSEF/K-1467-2012; OI Normanno, Nicola/0000-0002-7158-2605 NR 52 TC 18 Z9 18 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC 605 THIRD AVE, NEW YORK, NY 10158-0012 SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD MAR 15 PY 1996 VL 60 IS 4 BP 437 EP 446 DI 10.1002/(SICI)1097-4644(19960315)60:4<437::AID-JCB1>3.0.CO;2-T PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA UC703 UT WOS:A1996UC70300001 PM 8707884 ER PT J AU Blauvelt, A Chougnet, C Shearer, GM Katz, SI AF Blauvelt, A Chougnet, C Shearer, GM Katz, SI TI Modulation of T cell responses to recall antigens presented by langerhans cells in HIV-discordant identical twins by anti-interleukin (IL)-10 antibodies and IL-12 SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE dendritic cells; antigen presenting cells; cytokines; immunotherapy; AIDS ID IMMUNODEFICIENCY-VIRUS TYPE-1; BLOOD DENDRITIC CELLS; INFECTED PATIENTS; IMMUNE-RESPONSES; HUMAN-EPIDERMIS; AIDS; DYSFUNCTION; EXPRESSION; SUPPRESSION; INDIVIDUALS AB Decreased antigen (Ag)-specific T cell (TC) proliferation and IL-2 production are detected in all stages of HIV disease. To determine whether dendritic cell dysfunction and/or abnormal cytokine production contribute to HIV-induced immune dysregulation, we studied TC responses to recall Ags (influenza virus and tetanus toroid) presented by Langerhans cells (LC) in sir pairs of HIV-discordant identical twins, and the modulation of these responses by anti-IL-10 (alpha IL-10) mAbs and IL-12, LC from HIV+ twins induced IL-2 comparable to normal LC in cultures containing TC from uninfected twins. In contrast, IL-2 production was markedly decreased in cultures containing TC from HIV+ twins. IL-12 enhanced Ag-specific IL-2 production by TC from two patients with CD4(+) counts > 600. In contrast, alpha IL-10 mAbs enhanced IL-2 production in influenza virus-stimulated cultures containing TC from two patients with CD4(+) counts < 20, Thus, these findings suggest that immunologic dysfunction of dendritic cells does not contribute to impaired secondary immune responses in HIV+ individuals. Although few patients were studied, partial immune reconstitution in vitro, as demonstrated here, may help to predict those individuals who might benefit from cytokines or antibodies against cytokines as immunotherapy for HIV disease. C1 NCI,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. RP Blauvelt, A (reprint author), NCI,DERMATOL BRANCH,BLDG 10,ROOM 12N238,10 CTR DR,MSC 1908,BETHESDA,MD 20892, USA. NR 65 TC 28 Z9 28 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 222 E 70TH STREET, NEW YORK, NY 10021 SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 15 PY 1996 VL 97 IS 6 BP 1550 EP 1555 DI 10.1172/JCI118578 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA UB756 UT WOS:A1996UB75600026 PM 8617889 ER PT J AU Taub, DD TurcovskiCorrales, SM Key, ML Longo, DL Murphy, WJ AF Taub, DD TurcovskiCorrales, SM Key, ML Longo, DL Murphy, WJ TI Chemokines and T lymphocyte activation .1. beta chemokines costimulate human T lymphocyte activation in vitro SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; CELL GROWTH-FACTOR; CYTOKINE FAMILY; INTERLEUKIN-7; MIP-1-ALPHA; MIP-1-BETA; MONOCYTES; RECEPTORS AB While chemokines primarily promote chemotaxis, it is apparent that these cytokines also modulate a number of other biologic activities, including adhesion, degranulation, cytotoxicity, and enzyme release. We demonstrate here that the beta chemokines, recombinant human macrophage inflammatory protein-1 alpha and -1 beta, RANTES (regulated upon activation, normally T cell expressed and secreted), and macrophage chemotactic peptide-1, are capable of directly costimulating purified human T cell and human T cell clone proliferation and IL-2 production in the presence of anti-CD3 mAb, but not phorbol esters, in vitro. This costimulatory activity was dose and donor dependent and required the presence of free extracellular calcium as well as endogenously produced IL-2. Chemokine treatment of human T cells in vitro increased the level of cell surface CD25 and soluble CD25. In addition, these chemokines enhanced both Ag- and alloantigen-specific T cell and T cell clone proliferation. This activity was further augmented in the presence of the CD28 ligand, B7-1. Neutralization analyses using chemokine-specific Abs revealed that endogenously produced chemokines are important costimulatory mediators in human T cell activation. Together, these results suggest that chemokines not only play an important role in lymphocyte recruitment to inflammatory sites, but also participate in T cell activation. C1 SCI APPLICAT INT CORP,CLIN SERV,FREDERICK,MD 21702. SCI APPLICAT INT CORP,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. NIA,BALTIMORE,MD 21702. NR 39 TC 265 Z9 277 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1996 VL 156 IS 6 BP 2095 EP 2103 PG 9 WC Immunology SC Immunology GA TZ281 UT WOS:A1996TZ28100010 PM 8690897 ER PT J AU Murphy, WJ Tian, ZG Asai, O Funakoshi, S Rotter, P Henry, M Strieter, RM Kunkel, SL Longo, DL Taub, DD AF Murphy, WJ Tian, ZG Asai, O Funakoshi, S Rotter, P Henry, M Strieter, RM Kunkel, SL Longo, DL Taub, DD TI Chemokines and T lymphocyte activation .2. Facilitation of human T cell trafficking in severe combined immunodeficiency mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ENDOTHELIAL-CELLS; CYTOKINE FAMILY; MIP-1-ALPHA; ENGRAFTMENT; MIP-1-BETA; MONOCYTES AB Previous studies from this laboratory have demonstrated that the chemokines RANTES (recombinant human regulated upon activation, normally T cell expressed and presumably secreted), macrophage chemotactic peptide-1, recombinant human macrophage inflammatory protein-1 alpha (rhMIP-1 alpha), IL-8, and IP-10 are capable of inducing human T cell infiltration into the injection site of severe combined immunodeficiency (SCID) mice reconstituted with human P&L, However, the ability of these chemokines to facilitate T cell homing into various lymphoid tissues has not been examined, Initial studies focused on the ability of rhMIP-1 beta to induce human T cell infiltration into injection sites in human PBL-SCID mice, SCID mice received s.c, injections of rhMIP-1 beta or PBS (1 mu g/injection) in the hindflank for 4 h or sequential injections for 3 days, Biopsies of the MIP-1 beta injection site revealed the presence of significant mononuclear cell accumulation 72 h after injection, Immunohistologic evaluation determined that significant numbers of human CD3(+) T cells were recruited in response to MIP-1 beta injections, and this infiltration could be specifically blocked by co-administration of anti-MIP-1 beta antiserum. We subsequently examined these chemokine-injected mice for the effect of trafficking of human T cells to peripheral lymphoid organs, Flow cytometric analysis of the thymus in human PBL-SCID mice revealed that treatment with rhMIP-1 beta or rhRANTES, but not platelet factor-4, resulted in improved thymic homing of the human T cells after 72 h, This trafficking effect was shown to be direct, as pretreatment of the human T cells with the chemokines in vitro also improved peripheral lymphoid trafficking of the human cells, In addition, co-injection of rhMIP-1 beta with anti-MIP-1 beta antiserum abrogated the increase in T cell homing to the thymus, These data demonstrate that MIP-1 beta and RANTES directly augment human T cell trafficking to peripheral murine lymphoid tissues. Chemokines may, therefore, under either isogeneic or xenogeneic conditions, play a role in normal lymphocyte recirculation and homing, and may be of potential clinical use in promoting immune cell trafficking and function. C1 SCI APPLICAT INT CORP,CLIN SERV PROGRAM,FREDERICK,MD. NCI,FREDERICK CANC RES & DEV CTR,LAB LEUKOCYTE BIOL,FREDERICK,MD 21702. UNIV MICHIGAN,SCH MED,DEPT PATHOL,ANN ARBOR,MI 48109. UNIV MICHIGAN,SCH MED,DEPT MED,ANN ARBOR,MI 48109. NIA,BALTIMORE,MD 21224. RP Murphy, WJ (reprint author), NCI,FREDERICK CANC RES & DEV CTR,SAIC FREDERICK,BIOL CARCINOGENESIS & DEV PROGRAM,BLDG 567,FREDERICK,MD 21702, USA. RI Tian, Zhigang/J-3512-2013 NR 27 TC 49 Z9 51 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1996 VL 156 IS 6 BP 2104 EP 2111 PG 8 WC Immunology SC Immunology GA TZ281 UT WOS:A1996TZ28100011 PM 8690898 ER PT J AU Palmer, LD Saha, B Hodes, RJ Abe, R AF Palmer, LD Saha, B Hodes, RJ Abe, R TI The role of CD28 costimulation in immune-mediated responses against mouse mammary tumor viruses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; SIGNAL TRANSDUCTION; LYMPHOCYTES-T; CLASS-II; B-CELLS; SUPERANTIGEN; INFECTION; PROLIFERATION; INTERLEUKIN-2; STIMULATION AB Infectious mouse mammary tumor viruses (MMTV) encode superantigens (SAg) which, when presented in association with permissive class II MHC molecules, are recognized by those T cells that express appropriate TCRs. Recent findings have indicated that expression of a permissive MHC class II product and of a specific TCR are also critical to susceptibility of newborn mice to infection with milk-borne MMTV, suggesting that SAg-mediated T cell activation may play a facilitating role in viral infection. Because effective Ag-specific T cell activation can require costimulatory signals in addition to TCR-mediated recognition, the role of the CD28 costimulatory receptor was analyzed in responses of neonatal and adult mice to MMTV challenge. Mice that were deficient in CD28 expression as a result of gene targeting were compared with CD28-intact littermates, In response to parenteral challenge with MMTV, CD28-deficient adult mice exhibited reduced expansion of MMTV SAg-reactive T cells in draining LNs, decreased cytokine production, and decreased B cell activation and Ig secretion, These results indicate that optimal T and B cell responses to MMTV challenge, as reflected in the parameters measured, are CD28 dependent, In contrast, CD28 absence did not impair TCR-V beta-specific clonal deletion induced by neonatal exposure to MMTV, Further, analysis of susceptibility to viral infection in neonatally exposed mice revealed that CD28 deficiency did not interfere with SAg-dependent MMTV infection, Failure to identify CD28 dependence of MMTV infection suggests either the absence of a costimulatory requirement in the events that lead to viral infection or a redundancy in costimulatory signals that support infection. C1 USN,MED RES INST,IMMUNE CELL BIOL PROGRAM,BETHESDA,MD 20889. SCI UNIV TOKYO,RES INST BIOL SCI,TOKYO 162,JAPAN. NIA,NIH,BETHESDA,MD 20892. RP Palmer, LD (reprint author), NCI,NIH,DCBDC,EIB,BLDG 10,ROOM 4B10,10 CTR DR,MSC1360,BETHESDA,MD 20892, USA. NR 39 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1996 VL 156 IS 6 BP 2112 EP 2118 PG 7 WC Immunology SC Immunology GA TZ281 UT WOS:A1996TZ28100012 PM 8690899 ER PT J AU Flavin, MT Rizzo, JD Khilevich, A Kucherenko, A Sheinkman, AK Vilaychack, V Lin, L Chen, W Greenwood, EM Pengsuparp, T Pezzuto, JM Hughes, SH Flavin, TM Cibulski, M Boulanger, WA Shone, RL Xu, ZQ AF Flavin, MT Rizzo, JD Khilevich, A Kucherenko, A Sheinkman, AK Vilaychack, V Lin, L Chen, W Greenwood, EM Pengsuparp, T Pezzuto, JM Hughes, SH Flavin, TM Cibulski, M Boulanger, WA Shone, RL Xu, ZQ TI Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; ALPHA,BETA-UNSATURATED CARBONYL-COMPOUNDS; AIDS-RELATED COMPLEX; PHASE-I TRIAL; SELECTIVE REDUCTION; NATURAL-PRODUCTS; 2',3'-DIDEOXYINOSINE DDI; CONJUGATE REDUCTION; SODIUM-BOROHYDRIDE; ESCHERICHIA-COLI AB The anti-HIV agent (+/-)-calanolide A (1) has been synthesized in a five-step approach starting with phloroglucinol [--> 5 --> 6 --> 11 --> 18 --> (+/-)-1], which includes Pechmann reaction, Friedel-Crafts acylation, chromenylation with 4,4-dimethoxy-2-methylbutan-2-ol, cyclization, and Luche reduction. Cyclization of chromene 11 to chromanone 18 was achieved by employing either acetaldehyde diethyl acetal or paraldehyde in the presence of trifluoroacetic acid and pyridine or PPTS. Luche reduction of chromanone 18 at lower temperature preferably yielded (+/-)-1. Reduction of chromone 12, synthesized by Kostanecki-Robinson reaction from chromene 11, failed to afford (+/-)-1. The synthetic (+/-)-1 has been chromatographically resolved into its optically active forms, (+)- and (-)-1. The anti-HIV activities for synthetic (+/-)-1, as well as resultant (+)- and (-)-1, have been determined. Only (+)-1 accounted for anti-HIV activity, which was similar to the data reported for the natural product, and (-)-1 was inactive. C1 MEDICHEM RES INC,LEMONT,IL 60439. UNIV ILLINOIS,DEPT MED CHEM & PHARMACOGNOSY,PROGRAM COLLABORAT RES PHARMACEUT SCI,CHICAGO,IL 60612. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,FREDERICK,MD 21702. FU NIAID NIH HHS [1R43 AI34805, 2R44 AI34805] NR 76 TC 101 Z9 110 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 15 PY 1996 VL 39 IS 6 BP 1303 EP 1313 DI 10.1021/jm950797i PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA UA577 UT WOS:A1996UA57700014 PM 8632437 ER PT J AU Naor, D Fischer, D Jernigan, RL Wolfson, HJ Nussinov, R AF Naor, D Fischer, D Jernigan, RL Wolfson, HJ Nussinov, R TI Amino acid pair interchanges at spatially conserved locations SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE structural motifs; geometric hashing; structure comparison; amino acid conservation; amino acid interchanges ID SUBSTITUTION MATRICES; SEQUENCES; RECOGNITION; PROTEINS AB Here we study the pattern of amino acid pair interchanges at spatially, locally conserved regions in globally dissimilar and unrelated proteins. By using a method which completely separates the amino acid sequence from its respective structure, this work addresses the question of which properties of the amino acids are the most crucial for the stability of conserved structural motifs. The proteins are taken from a structurally non-redundant dataset. The spatially conserved substructural motifs are defined as consisting of a ''large enough'' number of C-alpha atoms found to provide a geometric match between two proteins, regardless of the order of the C-alpha atoms in the sequence, or of the sequence composition of the substructures. This approach can apply to proteins with little or no sequence similarity but with sufficient structural similarity, and is unique in its ability to handle local, non-topological matches between pairs of dissimilar proteins. The method uses a computer-vision based algorithm, the Geometric Hashing. Since the Geometric Hashing ignores sequence information it lends itself to answer the question posed above. The interchanges at geometrically similar positions that have been obtained with our method demonstrate the expected behaviour. Yet, a closer inspection reveals some distinct characteristics, as compared with interchanges based upon sequence-order based techniques, or from energy-contact-based considerations. First, a pronounced division of the amino acids into two classes is displayed: Lys, Glu, Arg, Gin, Asp, Asn, Pro, Gly, Thr, Ser and His on the one hand, and Ile, Val, Leu, Phe, Met, Tyr, Trp, Cys and Ala on the other. These groups further cluster into subgroups: Lys, Glu, Arg, Gin; Asp Asn; Pro, Gly; lie, Val, Leu, Phe. The other amino acids stand alone. Analysis of the conservation among amino acids indicates proline to be consistently by far, the most conserved. Next are Asp, Glu, Lys and Gly. Cys is also highly conserved. Interestingly, oppositely charged amino acids are interchanged roughly as frequently as those of the same charge. These observations can be explained in terms of the three-dimensional structures of the proteins. Most of all, there is a clear distinction between residues which prefer to be on the protein surfaces, compared to those frequently buried in the interiors. Analysis of the interchanges indicates their low information content. This, together with the separation into two groups, suggests that the predictive value of the spatial positions of the C-alpha atoms is not much greater than the sequence alone, aside from their hydrophobicity/hydrophillicity classification. (C) 1996 Academic Press Limited C1 NCI,FREDERICK CANC RES FACIL,SAIC,MATH BIOL LAB,FREDERICK,MD 21702. TEL AVIV UNIV,SCH MATH SCI,DEPT COMP SCI,IL-69978 TEL AVIV,ISRAEL. NCI,NIH,MATH BIOL LAB,BETHESDA,MD 20892. TEL AVIV UNIV,FAC MED,SACKLER INST MOLEC MED,IL-69978 TEL AVIV,ISRAEL. RI Wolfson, Haim/A-1837-2011; Jernigan, Robert/A-5421-2012 FU NCI NIH HHS [1-CO-74102] NR 23 TC 24 Z9 26 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON, ENGLAND NW1 7DX SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 15 PY 1996 VL 256 IS 5 BP 924 EP 938 DI 10.1006/jmbi.1996.0138 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA TY699 UT WOS:A1996TY69900013 PM 8601843 ER PT J AU Wenthold, RJ Petralia, RS Blahos, J Niedzielski, AS AF Wenthold, RJ Petralia, RS Blahos, J Niedzielski, AS TI Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons SO JOURNAL OF NEUROSCIENCE LA English DT Article DE glutamate receptor; excitatory amino acids; AMPA; hippocampus pyramidal neurons; immunoprecipitation; receptor subunit ID SELECTIVE GLUTAMATE RECEPTORS; SUBUNIT-SPECIFIC ANTIBODIES; RAT-BRAIN; ACETYLCHOLINE-RECEPTOR; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; KAINATE RECEPTORS; OPERATED CHANNELS; GLIAL-CELLS; LOCALIZATION AB The AMPA receptor, which is involved in most fast glutamatergic transmission in the mammalian brain and is expressed in most neurons, is made up of four subunits, GluR1-4. In situ hybridization, immunocytochemistry studies, and single-cell PCR analyses show that the number and type of AMPA receptor subunits expressed vary among neuronal populations and that two to four subunits usually are expressed in each neuron, Neurons that express two or more subunits theoretically could produce multiple pentameric receptor complexes that differ in their subunit compositions, and these complexes could be targeted to different synaptic populations. To determine whether a single neuronal population produces multiple AMPA receptor complexes, we used a preparation of CA1/CA2 hippocampal pyramidal neurons and immunoprecipitation with subunit-specific antibodies to characterize the receptor complexes, The CA1/CA2 pyramidal neurons express high levels of GluR1-3 and receive multiple excitatory inputs, offering the possibility that distinct receptor complexes may be assembled ii and expressed selectively at different synaptic populations, Our results suggest the presence of two major populations of AM PA receptor complexes: those made up of GluR1 and GluR2 and those made up of GluR2 and GluR3. Very few complexes contained both GluR1 and GluR3, whereas similar to 8% of the total AMPA receptor complexes was homomeric GluR1. The integrity of the receptor complex was verified by measuring [H-3]AMPA binding activity in the immunoprecipitated fractions. These results show that AMPA receptor complexes with different subunit compositions are present in CA1/CA2 pyramidal neurons and suggest an additional mechanism to regulate receptor expression in neurons. RP Wenthold, RJ (reprint author), NIDCD,NIH,NEUROCHEM LAB,BLDG 36,ROOM 5D08,36 CONVENT DR,BETHESDA,MD 20892, USA. RI Blahos, Jaroslav/G-4397-2014 NR 47 TC 502 Z9 516 U1 3 U2 14 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 1996 VL 16 IS 6 BP 1982 EP 1989 PG 8 WC Neurosciences SC Neurosciences & Neurology GA TY536 UT WOS:A1996TY53600003 PM 8604042 ER PT J AU Davenport, RW Thies, E Nelson, PG AF Davenport, RW Thies, E Nelson, PG TI Cellular localization of guidance cues in the establishment of retinotectal topography SO JOURNAL OF NEUROSCIENCE LA English DT Article DE retinotectal; topographic projection; growth cone; neuronal development; filopodia; navigation; guidance; repulsion; retraction ID CAUDAL TECTAL MEMBRANES; GROWTH-CONE COLLAPSE; CHICKEN OPTIC TECTUM; RETINAL AXONS; GLYCOSYL-PHOSPHATIDYLINOSITOL; MONOCLONAL-ANTIBODIES; SUPERIOR COLLICULUS; INVITRO EXPERIMENTS; NEURITE OUTGROWTH; DIRECTIONAL CUES AB Topographic projections of the nervous system are essential to numerous brain functions, They arise during development as a result of encounters between projecting growth cones and particular target cells. Cellular localization of guidance cues can indicate the sequential processes involved in establishment of such topography. The map formed by retinal ganglion cells on their target nuclei has served widely as a model system to investigate mechanisms underlying the highly precise and stereotypic connectivity of the nervous system, To investigate cellular localization of guidance cues in the developing retinotectal system, a three-compartment chamber was created to delimit areas where cultured embryonic chick retinal ganglion axons and tectal cells encounter one another and guidance behavior could be readily assessed, Whereas explants from nasal retinae extended fibers across their natural target population, fibers from temporal regions of retinae failed to invade areas of growing posterior tectal cells, This preservation of relevant guidance information on living cell populations enabled an evaluation of retinal ganglion cell growth cone behavior after encounter with individual tectal cells, Posterior tectal neurons appeared selectively repulsive for temporal retinal ganglion cell growth cones, causing growth cone collapse and retraction, On the contrary, neuroepithelial cells from all regions of the tectum attenuated retinal ganglion axon extension, without inducing sudden retraction. Nasal growth cones traversed or tracked more often along neuroepithelial cells from their natural target area, potentially indicating a second set of guidance cues possibly localized to posterior glia, Together, these differential interactions suggest that development of retinotectal topography critically depends on cell-specific cues, which are distributed selectively on particular populations of target cells. RP Davenport, RW (reprint author), NICHHD,NIH,DEV NEUROBIOL LAB,49-5A32,BETHESDA,MD 20892, USA. NR 70 TC 28 Z9 28 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 1996 VL 16 IS 6 BP 2074 EP 2085 PG 12 WC Neurosciences SC Neurosciences & Neurology GA TY536 UT WOS:A1996TY53600013 PM 8604052 ER PT J AU Yao, DL Liu, X Hudson, LD Webster, HD AF Yao, DL Liu, X Hudson, LD Webster, HD TI Insulin-like growth factor-I given subcutaneously reduces clinical deficits, decreases lesion severity and upregulates synthesis of myelin proteins in experimental autoimmune encephalomyelitis SO LIFE SCIENCES LA English DT Article DE insulin-like growth factor-I; experimental autoimmune encephalomyelitis; multiple sclerosis; myelin regeneration; oligodendroglia ID SURVIVAL; INVITRO AB To extend our evaluation of insulin-like growth factor-I (IGF-I) treatment for human demyelinating diseases, we compared effects of s.c. and i.v. IGF-I in an in vivo model with lesions resembling those seen in multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) was induced in Lewis rats with an emulsion containing guinea pig spinal cord and treatment with placebo or with s.c. or i.v. IGF-I was started when definite clinical weakness was present. IGF-I given subcutaneously significantly reduced clinical deficits and lesion severity. The clinical improvement, as measured by clinical deficit scores, stride lengths and exercise wheel rotations, was evident in 48 hrs and was comparable to that produced by the same IGF-I dose administered intravenously. Subcutaneously administered IGF-I also increased relative mRNA levels of myelin basic protein (MBP), proteolipid protein (PLP) and 2',3' cyclic nucleotide 3'-phosphodiesterase (CNP), thereby promoting myelin regeneration. We conclude that s.c. IGF-I produces dramatic improvement in acute, demyelinating EAE. Our results also suggest that this growth factor may be useful in treating multiple sclerosis patients with active demyelination. C1 NINCDS,NIH,EXPTL NEUROPATHOL LAB,BETHESDA,MD 20892. NINCDS,NIH,LAB DEV NEUROGENET,BETHESDA,MD 20892. NR 19 TC 49 Z9 49 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAR 15 PY 1996 VL 58 IS 16 BP 1301 EP 1306 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UA675 UT WOS:A1996UA67500001 PM 8614286 ER PT J AU Misiewicz, B Griebler, C Gomez, M Raybourne, R Zelazowska, E Gold, PW Sternberg, EM AF Misiewicz, B Griebler, C Gomez, M Raybourne, R Zelazowska, E Gold, PW Sternberg, EM TI The estrogen antagonist tamoxifen inhibits carrageenan induced inflammation in LEW/N female rats SO LIFE SCIENCES LA English DT Letter DE carrageenan; tamoxifen; inflammation; LEW/N rat hypothalamus ID WALL INDUCED POLYARTHRITIS; BREAST-CANCER; ANTIESTROGENS; CELLS AB Carrageenan induces a measurable inflammatory response in susceptible animals, and mature females are more responsive to carrageenan, than males. In the present study, we tested whether the estrogen antagonist tamoxifen influences carrageenan-induced inflammatory responses. Female LEW/N rats were treated with tamoxifen and compared to a control group of animals injected with vehicle. Tamoxifen significantly reduced estrous phase of estrous cycle during treatment, consistent with its functional anti-estrogen effects. Moreover, tamoxifen significantly decreased exudate volume but did not significantly influence relative white blood cell counts in the exudate. Interestingly, tamoxifen induced differential dose-dependent alterations in peripheral blood lymphocyte subpopulations. Low dose of tamoxifen increased CD25 cells. The high tamoxifen dose significantly increased CD8 blood lymphocyte counts. Our data indicate that tamoxifen treatment decreases carrageenan-induced inflammatory response in female LEW/N rats and suggest therefore that this inflammatory response is, at least in part, estrogen related. Moreover, our results suggest a possible role for tamoxifen in,treatment of inflammatory disorders. C1 US FDA,LAUREL,MD 20708. RP Misiewicz, B (reprint author), NIMH,CLIN NEUROENDOCRINOL BRANCH,BETHESDA,MD 20892, USA. NR 20 TC 9 Z9 9 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD, ENGLAND OX5 1GB SN 0024-3205 J9 LIFE SCI JI Life Sci. PD MAR 15 PY 1996 VL 58 IS 16 BP PL281 EP PL286 PG 6 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA UA675 UT WOS:A1996UA67500012 ER PT J AU Saito, K Suyama, K Nishida, K Sei, Y Basile, AS AF Saito, K Suyama, K Nishida, K Sei, Y Basile, AS TI Early increases in TNF-alpha, IL-6 and IL-1 beta levels following transient cerebral ischemia in gerbil brain SO NEUROSCIENCE LETTERS LA English DT Article DE cytokines; cerebral ischemia; inflammation; macrophages; gerbil; brain ID NECROSIS-FACTOR-ALPHA; KYNURENINE PATHWAY METABOLISM; FOREBRAIN ISCHEMIA; QUINOLINIC ACID; MESSENGER-RNA; ASTROCYTES; INTERLEUKIN-1-BETA; EXPRESSION; MICROGLIA; CELLS AB The effects of transient global ischemia using bilateral carotid artery occlusion on regional cytokine levels in gerbil brain were investigated using enzyme-linked immunoassay techniques. Brain concentrations of interleukin-6 (IL-6), interleukin-1 beta (IL-1 beta), and tumor necrosis factor-alpha (TNF-alpha) were increased during the early recirculation period (<6 h) after 10 min of ischemia, with lesser degrees of elevation following only 5 min of ischemia. TNF-alpha levels in the hippocampus and striatum were significantly increased as early as 1 h after recirculation, declining sharply to control levels by 12 h, then transiently increasing at 24 h. Elevated levels of IL-1 beta and IL-6 were not seen until 3-6 h post-occlusion. No significant increases in cytokine concentrations were observed in the cerebellum or thalamus. These results suggest that regionally selective increases in cytokines may be involved in the pathophysiological changes in hippocampus and striatum following transient cerebral ischemia. C1 NAGASAKI UNIV,SCH MED,DEPT NEUROSURG,NAGASAKI 852,JAPAN. NIMH,CLIN SCI LAB,BETHESDA,MD 20892. NIDDK,NEUROSCI LAB,BETHESDA,MD 20892. RP Saito, K (reprint author), GIFU UNIV,SCH MED,DEPT LAB MED,GIFU 500,JAPAN. NR 29 TC 205 Z9 225 U1 1 U2 8 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 MAR 15 PY 1996 VL 206 IS 2-3 BP 149 EP 152 DI 10.1016/S0304-3940(96)12460-5 PG 4 WC Neurosciences SC Neurosciences & Neurology GA UC069 UT WOS:A1996UC06900020 PM 8710173 ER PT J AU Hoeppner, MA Gilbert, DJ Copeland, NG Jenkins, NA Linzer, DIH Wu, B AF Hoeppner, MA Gilbert, DJ Copeland, NG Jenkins, NA Linzer, DIH Wu, B TI Cloning and characterization of mouse CCAAT binding factor SO NUCLEIC ACIDS RESEARCH LA English DT Article ID HUMAN HSP70 PROMOTER; TRANSCRIPTIONAL ACTIVATION; CELL-CYCLE; EXPRESSION; PROTEIN; GENE; P53; CONTAINS; LEVEL; MAP AB Isolation of cDNA clones for the mouse CCAAT binding factor (mCBF) has revealed the expression of two distinct forms of mCBF that are generated by alternative splicing of a single primary transcript from a gene that maps to chromosome 17, The mCBF1 mRNA encodes a protein of 997 amino acids, whereas the mCBF2 protein is predicted to be only 461 amino acids in length; mCBF1 and human CBF (hCBF) share > 80% amino acid sequence identity, Analysis of adult mouse tissue RNAs has revealed that the mCBF1 and mCBF2 mRNAs are ubiquitously expressed, but that mCBF1 mRNA is 5- to 10-fold more abundant than mCBF2 mRNA, Similarly, mCBF mRNA was detected throughout the placenta and in all tissues of the developing embryo from day 8 to day 18 of gestation, Overexpression of the two forms of mCBF in mammalian cells has demonstrated that the mCBF1 and mCBF2 proteins localize to different cellular compartments, with mCBF1 found predominantly in the nucleus and mCBF2 restricted to the cytoplasm, Co-expression of these two forms influences their localization, however, indicating that CBF activity can be regulated by the relative amounts of the two forms expressed in a cell. C1 NORTHWESTERN UNIV,DEPT BIOCHEM MOLEC BIOL & CELL BIOL,EVANSTON,IL 60208. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. FU NICHD NIH HHS [HD28048, HD29962]; NIGMS NIH HHS [GM42465] NR 23 TC 7 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS UNITED KINGDOM PI OXFORD PA WALTON ST JOURNALS DEPT, OXFORD, ENGLAND OX2 6DP SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD MAR 15 PY 1996 VL 24 IS 6 BP 1091 EP 1098 DI 10.1093/nar/24.6.1091 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA UD010 UT WOS:A1996UD01000016 PM 8604343 ER PT J AU Rosenberg, PS AF Rosenberg, PS TI AIDS and ethnicity - Response SO SCIENCE LA English DT Letter RP Rosenberg, PS (reprint author), NCI,6130 EXECUT BLVD,ROCKVILLE,MD 20852, USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 15 PY 1996 VL 271 IS 5255 BP 1480 EP 1481 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TZ983 UT WOS:A1996TZ98300005 ER PT J AU Stearman, R Yuan, DS YamaguchiIwai, Y Klausner, RD Dancis, A AF Stearman, R Yuan, DS YamaguchiIwai, Y Klausner, RD Dancis, A TI A permease-oxidase complex involved in high-affinity iron uptake in yeast SO SCIENCE LA English DT Article ID WILSON DISEASE GENE; SACCHAROMYCES-CEREVISIAE; ESCHERICHIA-COLI; FERRIC REDUCTASE; PROTEIN; ATPASE AB Iron must cross biological membranes to reach essential intracellular enzymes. Two proteins in the plasma membrane of yeast-a multicopper oxidase, encoded by the FET3 gene, and a permease, encoded by the FTR1 gene-were shown to mediate high-affinity iron uptake. FET3 expression was required for FTR1 protein to be transported to the plasma membrane. FTR1 expression was required for apo-FET3 protein to be loaded with copper and thus acquire oxidase activity. FTR1 protein also played a direct role in iron transport. Mutations in a conserved sequence motif of FTR1 specifically blocked iron transport. C1 NICHHD, CELL BIOL & METAB BRANCH, NIH, BETHESDA, MD 20892 USA. NR 57 TC 489 Z9 502 U1 4 U2 22 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAR 15 PY 1996 VL 271 IS 5255 BP 1552 EP 1557 DI 10.1126/science.271.5255.1552 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TZ983 UT WOS:A1996TZ98300032 PM 8599111 ER PT J AU vanGent, DC Mizuuchi, K Gellert, M AF vanGent, DC Mizuuchi, K Gellert, M TI Similarities between initiation of V(D)J recombination and retroviral integration SO SCIENCE LA English DT Article ID DNA STRAND TRANSFER; MECHANISM; SITE; PROTEIN AB In the first step of V(D)J recombination, the RAG1 and RAG2 proteins cleave DNA between a signal sequence and the adjacent coding sequence, generating a blunt signal end and a coding end with a closed hairpin structure. These hairpins are intermediates leading to the formation of assembled antigen receptor genes. It is shown here that the hairpins are formed by a chemical mechanism of direct trans-esterification, very similar to the early steps of transpositional recombination and retroviral integration. A minor variation in the reaction is sufficient to divert the process from transposition to hairpin formation. C1 NIDDKD,NIH,MOLEC BIOL LAB,BETHESDA,MD 20892. NR 23 TC 213 Z9 215 U1 1 U2 6 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 SN 0036-8075 J9 SCIENCE JI Science PD MAR 15 PY 1996 VL 271 IS 5255 BP 1592 EP 1594 DI 10.1126/science.271.5255.1592 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TZ983 UT WOS:A1996TZ98300044 PM 8599117 ER PT J AU Adams, DH Hubscher, S Fear, J Johnston, J Shaw, S Afford, S AF Adams, DH Hubscher, S Fear, J Johnston, J Shaw, S Afford, S TI Hepatic expression of macrophage inflammatory protein-1 alpha and macrophage inflammatory protein-1 beta after liver transplantation SO TRANSPLANTATION LA English DT Article ID T-CELL ADHESION; ENDOTHELIAL-CELLS; LEUKOCYTE ADHESION; CHEMOTACTIC FACTORS; CYTOKINE FAMILY; REJECTION; LYMPHOCYTES; ALLOGRAFTS; MIP-1-BETA; ACTIVATION AB Two local events that are crucial for T cell emigration into tissue are (1) activation of T cell integrins to permit binding to endothelial counter-receptors and (2) directed migration through the endothelium and into tissue in response to chemotactic factors. Because the chemokines macrophage inflammatory protein-1 alpha (MIP-1 alpha) and MIP-1 beta can activate adhesion and induce migration of T cells in vitro, we investigated their expression in human liver allografts to determine whether they might be involved in regulating the recruitment of T cells to allografts in vivo. Both chemokines were expressed strongly by infiltrating leukocytes during rejection and could be detected immunohistochemically on biliary epithelium, an important target for T cell mediated graft damage. Both chemokines, but particularly MIP-1 beta, were detected on the vascular and sinusoidal endothelium of rejecting liver allografts, where they were coexpressed with the T cell beta 1-integrin receptor vascular cell. adhesion molecule-1, In situ hybridization with complementary ribonucleic acid probes showed no MIP-1 alpha or MIP-1 beta mRNA in normal liver but dramatic expression of both chemokines in infiltrating leukocytes and graft endothelium during rejection, Expression was reduced after successful corticosteroid treatment of rejection but persisted in patients progressing to chronic rejection, Increased MLP-1 alpha and MIP-1 beta mRNA expression was already found in biopsies taken at the end of the transplant operation, suggesting that early induction of chemokines, possibly in response to graft reperfusion, might promote the subsequent development of graft rejection. These data demonstrate for the first time that MIP-1 alpha and MIP-1 beta are (1) expressed in human liver allografts, (2) produced by endothelial cells in vivo, and (3) induced early after transplantation. They suggest that MIP-1 alpha and MIP-1 beta produced by graft infiltrating leukocytes and graft endothelium might play a crucial role in regulating T cell recruitment to liver allografts in vivo. C1 UNIV BIRMINGHAM,DEPT PATHOL,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND. NCI,NIH,EXPTL IMMUNOL BRANCH,BETHESDA,MD 20892. NCI,FREDERICK CANC RES & DEV CTR,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 20892. RP Adams, DH (reprint author), QUEEN ELIZABETH HOSP,LIVER UNIT,RES LABS,CLIN RES BLOCK,BIRMINGHAM B15 2TH,W MIDLANDS,ENGLAND. RI Adams, David/C-9092-2009 NR 45 TC 73 Z9 73 U1 0 U2 0 PU WILLIAMS & WILKINS PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 1996 VL 61 IS 5 BP 817 EP 825 DI 10.1097/00007890-199603150-00024 PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA UA768 UT WOS:A1996UA76800024 PM 8607189 ER PT J AU Jordan, E Collins, FS AF Jordan, E Collins, FS TI Human genome project - A march of genetic maps SO NATURE LA English DT Editorial Material RP Jordan, E (reprint author), NIH,NATL CTR HUMAN GENOME RES,BETHESDA,MD 20892, USA. NR 9 TC 13 Z9 13 U1 0 U2 0 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAR 14 PY 1996 VL 380 IS 6570 BP 111 EP 112 DI 10.1038/380111a0 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TZ978 UT WOS:A1996TZ97800027 PM 8600381 ER PT J AU Dietrich, WF Miller, J Steen, R Merchant, MA DamronBoles, D Husain, Z Dredge, R Daly, MJ Ingalls, KA OConnor, TJ Evans, CA DeAngelis, MM Levinson, DM Kruglyak, L Goodman, N Copeland, NG Jenkins, NA Hawkins, TL Stein, L Page, DC Lander, ES AF Dietrich, WF Miller, J Steen, R Merchant, MA DamronBoles, D Husain, Z Dredge, R Daly, MJ Ingalls, KA OConnor, TJ Evans, CA DeAngelis, MM Levinson, DM Kruglyak, L Goodman, N Copeland, NG Jenkins, NA Hawkins, TL Stein, L Page, DC Lander, ES TI A comprehensive genetic map of the mouse genome SO NATURE LA English DT Article ID LINKAGE MAP AB The availability of dense genetic linkage maps of mammalian genomes makes feasible a wide range of studies, including positional cloning of monogenic traits, genetic dissection of polygenic traits, construction of genome-wide physical maps, rapid marker-assisted construction of congenic strains, and evolutionary comparisons(1,2). We have been engaged for the past five years in a concerted effort to produce a dense genetic map of the laboratory mouse(3-6). Here we present the final report of this project. The map contains 7,377 genetic markers, consisting of 6,580 highly informative simple sequence length polymorphisms integrated with 797 restriction fragment length polymorphisms in mouse genes. The average spacing between markers is about 0.2 centimorgans or 400 kilobases. C1 WHITEHEAD INST BIOMED RES,WHITEHEAD MIT CTR GENOME RES,CAMBRIDGE,MA 02142. NCI,FREDERICK CANC RES & DEV CTR,ABL BASIC RES PROGRAM,MAMMALIAN GENET LAB,FREDERICK,MD 21702. MIT,DEPT BIOL,CAMBRIDGE,MA 02139. MIT,HOWARD HUGHES MED INST,CAMBRIDGE,MA 02139. RI DeAngelis, e/J-7863-2015 NR 19 TC 708 Z9 737 U1 1 U2 8 PU MACMILLAN MAGAZINES LTD PI LONDON PA 4 LITTLE ESSEX STREET, LONDON, ENGLAND WC2R 3LF SN 0028-0836 J9 NATURE JI Nature PD MAR 14 PY 1996 VL 380 IS 6570 BP 149 EP 152 DI 10.1038/380149a0 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA TZ978 UT WOS:A1996TZ97800047 PM 8600386 ER PT J AU Liang, WW Shi, XL Deshpande, D Malanga, CJ Rojanasakul, Y AF Liang, WW Shi, XL Deshpande, D Malanga, CJ Rojanasakul, Y TI Oligonucleotide targeting to alveolar macrophages by mannose receptor-mediated endocytosis SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE oligonucleotide; macrophage; uptake; endocytosis; mannose receptor; endosome ID HUMAN IMMUNODEFICIENCY VIRUS; ANTISENSE OLIGONUCLEOTIDES; MESSENGER-RNA; GENE-EXPRESSION; INFLUENZA-VIRUS; CELLULAR UPTAKE; CELLS; INHIBITION; INVITRO; DNA AB Antisense oligonucleotides (ONs) have proven useful for selective inhibition of gene expression. However, their effective use is limited by inefficient cellular uptake and lack of cellular targeting. In this paper, we report a drug targeting system which utilizes mannose receptor-mediated endocytosis to enhance cellular uptake of ONs in alveolar macrophages (AMs). The system employs a molecular complex consisting of partially substituted mannosylated poly(L-lysine) (MPL), electrostatically linked to a 5' fluorescently labeled ON. Upon recognition by the macrophage mannose receptors, the MPL was internalized by the receptor-mediated pathway co-transporting the ON. Om results indicated that the AMs treated with the MPL:ON complex exhibited a significant increase in ON uptake (up to 17-fold) over free ON-treated controls. Effective ON uptake was shown to require the recognition of the mannose moiety since unmodified polylysine was much less effective in promoting ON uptake. Specific internalization of the ON:MPL complex by the mannose receptor pathway was verified by competitive inhibition using mannosylated albumin. Under this condition, the ON complex uptake was inhibited. The requirement of mannose receptors for complex uptake was further demonstrated using a macrophage cell line, J774.1, which expresses a low level of mannose receptors. When treated with the complex, these cells showed no susceptibility to ON uptake, thus suggesting the targeting ability of the carrier system to the AMs. Following cellular internalization, the ON complex appeared largely accumulated in endocytic vesicles. Enhanced endosomal exit of the ON was achieved using a fusogenic peptide derived from the amino terminal sequence of influenza virus hemagglutinin HA2. Cytotoxicity studies showed that at the concentrations effectively enhancing ON uptake, both MPL and the fusogenic peptide caused no toxic effects to the cells, thereby suggesting their potential safety and utilization in vivo. C1 W VIRGINIA UNIV,HLTH SCI CTR,DEPT BASIC PHARMACEUT SCI,MORGANTOWN,WV 26506. NCI,LAB EXPTL PATHOL,BETHESDA,MD 20892. RI Shi, Xianglin/B-8588-2012; OI Rojanasakul, Yon/0000-0002-8839-6462 FU NHLBI NIH HHS [HL54291] NR 31 TC 65 Z9 67 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD MAR 13 PY 1996 VL 1279 IS 2 BP 227 EP 234 DI 10.1016/0005-2736(95)00237-5 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA UA113 UT WOS:A1996UA11300016 PM 8603091 ER PT J AU Luepker, RV Perry, CL McKinlay, SM Nader, PR Parcel, GS Stone, EJ Webber, LS Elder, JP Feldman, HA Johnson, CC Kelder, SH Wu, M AF Luepker, RV Perry, CL McKinlay, SM Nader, PR Parcel, GS Stone, EJ Webber, LS Elder, JP Feldman, HA Johnson, CC Kelder, SH Wu, M TI Outcomes of a field trial to improve children's dietary patterns and physical activity - The Child and Adolescent Trial for Cardiovascular Health (CATCH) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CIGARETTE-SMOKING; EDUCATION-PROGRAM; PREVENTION; PROMOTION; ATHEROSCLEROSIS; LIPOPROTEINS; INTERVENTION; TRACKING; BEHAVIOR; LIPIDS AB Objective.-To assess the outcomes of health behavior interventions, focusing on the elementary school environment, classroom curricula, and home programs, for the primary prevention of cardiovascular disease. Design.-A randomized, controlled field trial at four sites with 56 intervention and 40 control elementary schools. Outcomes were assessed using prerandomization measures (fall 1991) and follow-up measures (spring 1994). Participants.-A total of 5106 initially third-grade students from ethnically diverse backgrounds in public schools located in California, Louisiana, Minnesota, and Texas. Intervention.-Twenty-eight schools participated in a third-grade through fifth-grade intervention including school food service modifications, enhanced physical education (PE), and classroom health curricula. Twenty-eight additional schools received these components plus family education. Main Outcome Measures.-At the school level, the two primary end points were changes in the fat content of food service lunch offerings and the amount of moderate-to-vigorous physical activity in the PE programs. At the level of the individual student, serum cholesterol change was the primary end point and was used for power calculations for the study. individual level secondary end points included psychosocial factors, recall measures of eating and physical activity patterns, and other physiologic measures. Results.-In intervention school lunches, the percentage of energy intake from fat fell significantly more (from 38.7% to 31.9%) than in control lunches (from 38.9% to 36.2%)(P<.001). The intensity of physical activity in PE classes during the Child and Adolescent Trial for Cardiovascular Health (CATCH) intervention increased significantly in the intervention schools compared with the control schools (P<.02). Self-reported daily energy intake from fat among students in the intervention schools was significantly reduced (from 32.7% to 30.3%) compared with that among students in the control schools (from 32.6% to 32.2%)(P<.001). Intervention students reported significantly more daily vigorous activity than controls (58.6 minutes vs 46.5 minutes; P<.003). Blood pressure, body size, and cholesterol measures did not differ significantly between treatment groups. No evidence of deleterious effects of this intervention on growth or development was observed. Conclusion.-The CATCH intervention was able to modify the fat content of school lunches, increase moderate-to-vigorous physical activity in PE, and improve eating and physical activity behaviors in children during 3 school years. C1 NEW ENGLAND RES INST,WATERTOWN,MA 02172. UNIV CALIF SAN DIEGO,DEPT PEDIAT,COMMUNITY PEDIAT DIV,LA JOLLA,CA 92093. UNIV TEXAS,HLTH SCI CTR,CTR HLTH PROMOT RES & DEV,HOUSTON,TX. NHLBI,PROJECT OFF,BETHESDA,MD 20892. TULANE UNIV,SCH PUBL HLTH & TROP MED,NEW ORLEANS,LA 70118. RP Luepker, RV (reprint author), UNIV MINNESOTA,SCH PUBL HLTH,DIV EPIDEMIOL,1300 S 2ND ST,SUITE 300,MINNEAPOLIS,MN 55455, USA. FU NHLBI NIH HHS [U01-HL-39852, U01-HL-39880, U01-HL-39906] NR 61 TC 628 Z9 635 U1 11 U2 97 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 13 PY 1996 VL 275 IS 10 BP 768 EP 776 DI 10.1001/jama.275.10.768 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA TY886 UT WOS:A1996TY88600024 PM 8598593 ER PT J AU Wang, AC Bax, A AF Wang, AC Bax, A TI Determination of the backbone dihedral angles phi in human ubiquitin from reparametrized empirical Karplus equations SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID VICINAL COUPLING-CONSTANTS; NUCLEAR-MAGNETIC-RESONANCE; SPIN-SPIN COUPLINGS; ACCURATE MEASUREMENTS; NMR-SPECTRA; SECONDARY STRUCTURE; MOLECULAR-DYNAMICS; ENRICHED PROTEINS; TORSION ANGLES; C-13 AB The backbone dihedral angle phi in polypeptides is characterized by four different J couplings: (3)J(HNH alpha), (3)J(HNC'), (3)J(HNC beta), and (3)J(H alpha C'). E.COSY and quantitative J correlation techniques have been used to measure these couplings in the protein human ubiquitin, uniformly enriched in C-13 and N-15. Assuming that the dihedral backbone angles in solution are identical to those in the X-ray structure of this protein and that H-N is located in the C'-N-C-alpha plane, Karplus relations for (3)J(HNH alpha), (3)J(H alpha C'), and (3)J(HNC beta), have been reparametrized. The root-mean-square (rms) difference between measured values of (3)J(HNH alpha), (3)J(H alpha C beta), (3)J(HNC') and their corresponding Karplus curves are 0.53, 0.25, 0.24, and 0.36 Hz, respectively, whereas the precision of these measurements is considerably better. For any given residue, the differences between the four measured J couplings and values predicted by their Karplus curves on the basis of the X-ray structure-derived phi angle are highly correlated with one another. On average, a root-mean-square change of 5.7 degrees in the X-ray derived phi angles is needed to obtain optimal agreement with all four measured J couplings. There is no clear correlation between the phi angle correction needed and the out-of-plane position of the amide proton predicted by ab initio calculations. The small differences in phi angles therefore presumably result from small uncertainties in the atomic positions of the 1.8 Angstrom X-ray structure. However, they may also be caused by genuine differences between the structure of the protein in solution and in the crystalline state or contain a contribution resulting from deviations from the assumption that the H-N-N-C-alpha-H-alpha dihedral angle equals phi - 60 degrees. C1 NIDDKD,NIH,CHEM PHYS LAB,BETHESDA,MD 20892. NR 66 TC 172 Z9 173 U1 0 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 13 PY 1996 VL 118 IS 10 BP 2483 EP 2494 DI 10.1021/ja9535524 PG 12 WC Chemistry, Multidisciplinary SC Chemistry GA UA029 UT WOS:A1996UA02900021 ER PT J AU WassertheilSmoller, S Applegate, WB Berge, K Chang, CJ Davis, BR Grimm, R Kostis, J Pressel, S Schron, E AF WassertheilSmoller, S Applegate, WB Berge, K Chang, CJ Davis, BR Grimm, R Kostis, J Pressel, S Schron, E TI Change in depression as a precursor of cardiovascular events SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; VITAL EXHAUSTION; OLDER ADULTS; MORTALITY; SYMPTOMS; HEALTH; CATECHOLAMINES; ASSOCIATION; PREDICTORS; POPULATION AB Objective: To determine the relationship between increasing depressive symptoms and cardiovascular events or mortality. Design: Cohort analytic study of data from randomized placebo-controlled double-blind clinical trial of antihypertensive therapy. Depressive symptoms were assessed semiannually with the Center for Epidemiological Studies-Depression (CES-D) scale during an average follow-up of 4.5 years. Setting: Ambulatory patients in 16 clinical centers of the Systolic Hypertension in the Elderly Program. Patients: Generally healthy men and women aged 60 years or older randomized to active antihypertensive drug therapy or placebo who were 79% white and 53% women and had follow-up CES-D scores and no outcome events during the first 6 months (N=4367). Main Outcome Measures: All-cause mortality, fatal or nonfatal stroke, or myocardial infarction. Results: Baseline depressive symptoms were not related to subsequent events; however, an increase in depression was prognostic. Cox proportional hazards regression analyses with the CES-D scale as a time-dependent variable, controlling for multiple covariates, indicated a 25% increased risk of death per 5-unit increase in the CES-D score (relative risk [RR], 1.25; 95% confidence interval [CI], 1.15 to 1.36). The RR for stroke or myocardial infarction was 1.18 (95% CI, 1.08 to 1.30). increase in CES-D score was an independent predictor in both placebo and active drug groups, and it was strongest as a risk factor for stroke among women (RR, 1.29; 95% CI, 1.07 to 1.34). Conclusions: Among elderly persons, a significant and substantial excess risk of death and stroke or myocardial infarction was associated with an increase in depressive symptoms over time, which may be a marker for subsequent major disease events and warrants the attention of physicians to such mood changes. However, further studies of causal pathways are needed before widespread screening for depression in clinical practice is to be recommended. C1 MAYO CLIN & MAYO FDN,MAYO MED SCH,ROCHESTER,MN 55905. UNIV TENNESSEE,MEMPHIS,TN. UNIV TEXAS,HLTH SCI CTR,HOUSTON,TX. UNIV MINNESOTA,MINNEAPOLIS,MN 55455. UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,NEW BRUNSWICK,NJ. NIH,BETHESDA,MD 20892. RP WassertheilSmoller, S (reprint author), YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT EPIDEMIOL SOCIAL MED,1312 BELFER,1300 MORRIS PK AVE,BRONX,NY 10461, USA. FU NHLBI NIH HHS [N01-HC-35130] NR 44 TC 226 Z9 240 U1 2 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 11 PY 1996 VL 156 IS 5 BP 553 EP 561 DI 10.1001/archinte.156.5.553 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA TY353 UT WOS:A1996TY35300010 PM 8604962 ER PT J AU Nedvidkova, J Pacak, K Nedvidek, J Goldstein, DS Schreiber, V AF Nedvidkova, J Pacak, K Nedvidek, J Goldstein, DS Schreiber, V TI Triiodothyronine attenuates estradiol-induced increases in dopamine D-2 receptor number in rat anterior pituitary SO BRAIN RESEARCH LA English DT Article DE T3; estrogen; pituitary D-2 receptor; prolactin; thyroxine; thyrotrophin; cAMP ID ESTROGENIZED RATS; PROLACTIN; TUMORS; INHIBITION; BINDING; BROMOCRIPTINE; RELEASE; SYSTEM; GLAND; CELLS AB Estrogens promote adenohypophyseal enlargement and tumor transformation, and thyroid hormones antagonize these effects. Hormone-induced pituitary enlargement may be mediated by alterations in pituitary dopaminergic function. The present study examined the effects of chronic (20 days) administration of estradiol benzoate (EB), triiodothyronine (T3), or EB and T3 (T3 + EB) on dopamine (D-2) receptors in rat anterior pituitary. D-2 receptor number increased after EB without altered receptor affinity. T3 alone did not affect D-2 receptor number in the anterior pituitary but significantly attenuated the effect of EB. T3 administration also inhibited EB-induced anterior pituitary hyperplasia. D-2 receptor upregulation by EB more likely could reflect a compensatory response to decreased receptor occupation. The present results suggest that D-2 receptors could play an important role in estrogen-induced adenohypophyseal tumor formation and hyperprolactinemia and that thyroid hormones may inhibit estrogen-induced pituitary tumor development via adenohypophyseal D-2 receptors. C1 NINCDS,NIH,CLIN NEUROSCI BRANCH,BETHESDA,MD 20892. INST ENDOCRINOL,PRAGUE,CZECH REPUBLIC. ACAD SCI CZECH REPUBL,INST PHYSIOL,PRAGUE,CZECH REPUBLIC. FAC MED 1,DEPT MED 3,PRAGUE,CZECH REPUBLIC. NR 29 TC 11 Z9 11 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 MAR 11 PY 1996 VL 712 IS 1 BP 148 EP 152 DI 10.1016/0006-8993(95)01524-8 PG 5 WC Neurosciences SC Neurosciences & Neurology GA UC688 UT WOS:A1996UC68800020 PM 8705298 ER PT J AU Dracheva, S Bose, S Hendler, RW AF Dracheva, S Bose, S Hendler, RW TI Chemical and functional studies on the importance of purple membrane lipids in bacteriorhodopsin photocycle behavior SO FEBS LETTERS LA English DT Article DE bacteriorhodopsin photocycle; membrane lipid; membrane protein; photocycle regulation AB In native purple membrane (PM), there are approximately 1 squalene, 2 glycolipid sulfate (GLS), and 6 phospholipid (PL) molecules per bacteriorhodopsin (BR) monomer [10], Brief (similar to 2 min) exposure to 0.1% Triton X-100 removes about 25%, 20%, and 6% of squalenes, GLS, and FL, respectively (this paper) while causing profound changes in the BR photocycle, including the loss of 'photocooperativity' [1]. The BR photocycle in Triton-treated PM can be restored to near normal behavior by reconstitution with native PM lipids, Isolated squalenes are not effective whereas PL alone partially restores normal photocycle characteristics. C1 NHLBI,NIH,CELL BIOL LAB,BETHESDA,MD 20892. NR 11 TC 37 Z9 37 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 11 PY 1996 VL 382 IS 1-2 BP 209 EP 212 DI 10.1016/0014-5793(96)00181-0 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA UA257 UT WOS:A1996UA25700045 PM 8612754 ER PT J AU Jarvis, CD Geiman, T VilaStorm, MP Osipovich, O Akella, U Candeias, S Nathan, I Durum, SK Muegge, K AF Jarvis, CD Geiman, T VilaStorm, MP Osipovich, O Akella, U Candeias, S Nathan, I Durum, SK Muegge, K TI A novel putative helicase produced in early murine lymphocytes SO GENE LA English DT Article DE gene rearrangement; thymus; lsh; T-cell receptor; immunoglobulin ID TRANSCRIPTIONAL ACTIVATION; BINDING PROTEIN; GENE; RECOMBINATION; SEQUENCE; RECEPTOR; REPAIR; DNA; REARRANGEMENT; CONTAINS AB DNA helicases (Hel) play a role in a number of processes involving DNA strand separation, including replication, repair, recombination and transcription. Rearrangement of receptor genes, which occurs in immature lymphocytes, could also be mediated by Hel. We report here the cloning from murine fetal thymus tissue of a novel putative Hel containing seven conserved Hel domains and belonging to the DEGH subclass of DNA Hel. We term the encoding gene lsh (lymphoid-specific Hel), since the gene is expressed in early thymocytes, but not in heart, liver, lung, muscle, brain or kidney, as judged by Northern analysis. Spleen cells expressed lsh following activation. T- and B-cell lines, at both the immature and mature stage, expressed lsh. To examine the earliest stages of lymphopoiesis, mouse embryonic tissues were examined; lsh was not detected in the yolk sac of day 12 of gestation, but was expressed in fetal liver and at high levels in fetal thymus at day 15 of gestation. C1 NCI,FREDERICK CANC RES & DEV CTR,SAIC,BIOL CARCINOGENESIS & DEV PROGRAM,FREDERICK,MD 21702. HAMPSHIRE COLL,SCH NAT SCI,AMHERST,MA 01002. NCI,LMI,BIOL RESPONSE MODIFIERS PROGRAM,FREDERICK,MD 21702. NR 23 TC 37 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD MAR 9 PY 1996 VL 169 IS 2 BP 203 EP 207 DI 10.1016/0378-1119(95)00843-8 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA UC059 UT WOS:A1996UC05900009 PM 8647447 ER EF