FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Brezinski, ME Pitris, C Boppart, SA Fujimoto, JG AF Brezinski, ME Pitris, C Boppart, SA Fujimoto, JG TI Micron scale imaging of the gastrointestinal tract with optical coherence tomography. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. MIT, Cambridge, MA 02139 USA. RI Boppart, Stephen/C-7338-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2334 BP A570 EP A570 DI 10.1016/S0016-5085(98)82320-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602320 ER PT J AU Chen, D Koh, T Zhao, CM Hakanson, R Wang, TC AF Chen, D Koh, T Zhao, CM Hakanson, R Wang, TC TI ECL cells and gastric acid secretion in gastrin-deficient mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Lund, Dept Pharmacol, Lund, Sweden. NR 1 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4646 BP A1135 EP A1135 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604616 ER PT J AU Chen, MC Yang, HT Walsh, JH Soll, AH AF Chen, MC Yang, HT Walsh, JH Soll, AH TI Helicobacter pylori urease activity induces tight junction injury in canine gastric mucosa monolayers. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, CURE, Los Angeles, CA 90073 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0364 BP A89 EP A89 DI 10.1016/S0016-5085(98)80361-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600361 ER PT J AU Chu, S Tanaka, S Kaunitz, JD Montrose, MH AF Chu, S Tanaka, S Kaunitz, JD Montrose, MH TI Surface pH of rat stomach is regulated by luminal pH and hormonal agonists. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0378 BP A93 EP A93 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600375 ER PT J AU Chu, S Tanaka, S Kaunitz, JD Montrose, MH AF Chu, S Tanaka, S Kaunitz, JD Montrose, MH TI Correlation of surface pH versus mucus gel thickness by in vivo confocal microscopy of rat gastric mucosa. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0377 BP A93 EP A93 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600374 ER PT J AU Chung, DC Brown, SB Graeme-Cook, F Warshaw, AL Seto, M Jensen, RT Arnold, A AF Chung, DC Brown, SB Graeme-Cook, F Warshaw, AL Seto, M Jensen, RT Arnold, A TI Overexpression of cyclin D1 protein in pancreatic endocrine tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Connecticut, Ctr Hlth, Ctr Mol Med, Farmington, CT USA. Aichi Canc Ctr, Lab Chemotherapy, Nagoya, Aichi 464, Japan. NIH, Digest Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1821 BP A448 EP A448 DI 10.1016/S0016-5085(98)81810-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601810 ER PT J AU Chung, RT Kaplan, LM AF Chung, RT Kaplan, LM TI Identification of cellular proteins that bind selectively to the conserved 3 ' terminus of the hepatitis C virus genome. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0117 BP A1227 EP A1227 DI 10.1016/S0016-5085(98)84979-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604979 ER PT J AU Ciacci, C Di Vizio, D Insabato, L Savino, G Mazzacca, G Podolsky, DK AF Ciacci, C Di Vizio, D Insabato, L Savino, G Mazzacca, G Podolsky, DK TI Low expression of intestinal trefoil factor in celiac disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Naples Federico II, Naples, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA USA. RI ciacci, carolina/A-2594-2012 OI ciacci, carolina/0000-0002-7426-1145 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1469 BP A360 EP A360 DI 10.1016/S0016-5085(98)81459-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601459 ER PT J AU Coskun, T Gong, P Zong, Y Solomon, TE AF Coskun, T Gong, P Zong, Y Solomon, TE TI Exogenous cholecystokinin (CCK) does not stimulate pancreatic secretion through capsaicin-sensitive afferent or atropine-sensitive efferent vagal pathways in anesthetized rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Marmara Univ, Sch Med, Dept Physiol, TR-81326 Istanbul, Turkey. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. CURE, Los Angeles, CA 90073 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4656 BP A1138 EP A1138 DI 10.1016/S0016-5085(98)84626-X PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604626 ER PT J AU Coskun, T Gong, P Zong, Y Solomon, TE AF Coskun, T Gong, P Zong, Y Solomon, TE TI Endogenous cholecystokinin (CCK) does not stimulate pancreatic enzyme secretion via capsaicin-sensitive afferent pathways in anesthetized rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Marmara Univ, Sch Med, Dept Physiol, TR-81326 Istanbul, Turkey. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. CURE, Los Angeles, CA 90073 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4655 BP A1137 EP A1137 DI 10.1016/S0016-5085(98)84625-8 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604625 ER PT J AU Dangler, CA Fox, JG Wang, TC AF Dangler, CA Fox, JG Wang, TC TI Helicobacter felis-infected C57BL/6 mice develop an altered mucin phenotype consistent with intestinal metaplasm. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2390 BP A583 EP A583 DI 10.1016/S0016-5085(98)82374-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602374 ER PT J AU Dienstag, J Schiff, E Wright, T Perrillo, R Hann, HW Crowther, L Woessner, M Rubin, M Brown, N AF Dienstag, J Schiff, E Wright, T Perrillo, R Hann, HW Crowther, L Woessner, M Rubin, M Brown, N CA US Lamivudine Investigator Grp TI Lamivudine treatment for one year in previously untreated US hepatitis B patients: Histologic improvement and hepatitis Be-antigen (HBeAg) seroconversion. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, US Lamivudine Investigator Grp, Boston, MA 02114 USA. Miami Univ, Miami, FL USA. VA Med Ctr, San Francisco, CA USA. Alton Ochsner Med Fdn & Ochsner Clin, New Orleans, LA 70121 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. NR 0 TC 13 Z9 14 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0148 BP A1235 EP A1235 DI 10.1016/S0016-5085(98)85010-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605010 ER PT J AU El-Zimaity, HMT Gurer, IE Graham, DY Kim, JG AF El-Zimaity, HMT Gurer, IE Graham, DY Kim, JG TI The distribution of intestinal metaplasia in duodenal ulcer, gastric ulcer, and gastric cancer in Korea questions current hypotheses regarding gastric cancer SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Korea Univ, Coll Med, Guro Hosp, Seoul 136701, South Korea. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Dept Med, Houston, TX USA. VA Med Ctr, Dept Pathol, Houston, TX USA. RI Gurer, Inanc Elif/C-3042-2016 NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2423 BP A591 EP A591 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602406 ER PT J AU El-Zimaity, HMT Malaty, HM Graham, DY Gutierrez, O AF El-Zimaity, HMT Malaty, HM Graham, DY Gutierrez, O TI For biopsies targeted to the cardia, corpus, and antrum in gastric malt lymphoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Nacl Colombia, Hosp San Juan de Dios, Bogota, Colombia. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Dept Med, Houston, TX USA. VA Med Ctr, Dept Pathol, Houston, TX USA. RI Gurer, Inanc Elif/C-3042-2016 NR 0 TC 4 Z9 4 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 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2422 BP A591 EP A591 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602405 ER PT J AU El-Zimaity, HMT Ota, H Graham, DY AF El-Zimaity, HMT Ota, H Graham, DY TI Diversity of mucin expression related to high iron diamine typing of intestinal metaplasia. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Dept Med, Houston, TX USA. VA Med Ctr, Dept Pathol, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2421 BP A590 EP A590 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602404 ER PT J AU Encke, J Putlitz, JZ Geissler, M Wands, JR AF Encke, J Putlitz, JZ Geissler, M Wands, JR TI Genetic immunization generates broad-based cellular and humoral immune responses against the nonstructural proteins of hepatitis C virus SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc,Mol Hepatol Lab, Charlestown, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0162 BP A1238 EP A1238 DI 10.1016/S0016-5085(98)85023-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605023 ER PT J AU Ennes, HS Young, SH Goliger, J McRoberts, J Mayer, EA AF Ennes, HS Young, SH Goliger, J McRoberts, J Mayer, EA TI Gap junction-mediated intercellular communication between DRG neurons and three target cell types. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, UCLA CURE Neuroenter Dis Program, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, UCLA CURE Neuroenter Dis Program, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Inst Brain Res, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4668 BP A1141 EP A1141 DI 10.1016/S0016-5085(98)84638-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604638 ER PT J AU Fox, JG Shen, Z Feng, F Dufover, J Kaplan, MM Dewhirst, F AF Fox, JG Shen, Z Feng, F Dufover, J Kaplan, MM Dewhirst, F TI Hepatobiliary Helicobacter spp. identified from patients with primary sclerosing cholangitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tufts Univ, Boston, MA 02111 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4009 BP A978 EP A978 DI 10.1016/S0016-5085(98)83983-8 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603982 ER PT J AU Freedman, SD Bhaskar, KR Lewandrowski, KB Brugge, W Warshaw, AL Katz, MH Parker, EM Waxman, I AF Freedman, SD Bhaskar, KR Lewandrowski, KB Brugge, W Warshaw, AL Katz, MH Parker, EM Waxman, I TI A diagnostic marker for cystic lesions of the pancreas. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Beth Israel Deaconess Med Ctr,Div Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Gastroenterol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2452 BP A597 EP A597 DI 10.1016/S0016-5085(98)82434-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602434 ER PT J AU Freedman, SD Katz, MH Parker, EM Laposata, M Urman, MY Alvarez, JG AF Freedman, SD Katz, MH Parker, EM Laposata, M Urman, MY Alvarez, JG TI Cystic fibrosis may be explained by a primary defect in fatty acid metabolism. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Ob Gyn, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1864 BP A458 EP A458 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601853 ER PT J AU Fullerton, S Anton, P Chang, L Naliboff, B Bernstein, CN Mayer, EA AF Fullerton, S Anton, P Chang, L Naliboff, B Bernstein, CN Mayer, EA TI Prevalence of extraintestinal symptoms in patients with irritable bowel syndrome and inflammatory bowel disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Neuroenter Biol Grp, Digest Dis Res Ctr,CURE, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Manitoba, Winnipeg, MB, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0059 BP A15 EP A15 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600060 ER PT J AU Fullerton, S Mayer, EA AF Fullerton, S Mayer, EA TI International economic impact of functional gastrointestinal disorders. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Neuroenter Biol Grp, Digest Dis Res Ctr,CURE, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0058 BP A15 EP A15 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600059 ER PT J AU Fullerton, S Naliboff, B Mayer, EA AF Fullerton, S Naliboff, B Mayer, EA TI Gender specific predictors of health care utilization for patients with irritable bowel syndrome. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Neuroenter Biol Grp, Digest Dis Res Ctr,CURE, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0057 BP A14 EP A14 DI 10.1016/S0016-5085(98)80058-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600058 ER PT J AU Fusunyan, RD Quinn, JJ Fujimoto, M MacDermott, RP Sanderson, IR AF Fusunyan, RD Quinn, JJ Fujimoto, M MacDermott, RP Sanderson, IR TI Butyrate regulates chemokine secretion by intestinal epithelial (Caco-2) cells through histone acetylation. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Combined Program Pediat Gastroenterol & Nutr, Boston, MA 02114 USA. Lahey Hitchcock Clin, Gastrointestinal Sect, Burlington, MA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3605 BP A879 EP A879 DI 10.1016/S0016-5085(98)83580-4 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603579 ER PT J AU Gong, PX Reeve, JR Walsh, JH Zong, YM Ho, FJ Solomon, TE AF Gong, PX Reeve, JR Walsh, JH Zong, YM Ho, FJ Solomon, TE TI Comparison of secretin-NH2, secretin-Gly, and secretin-OH on pancreatic and gastric secretion indicates the existence of a secretin receptor subtype. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, CURE, Digest Dis Res Ctr, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4693 BP A1146 EP A1146 DI 10.1016/S0016-5085(98)84663-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604662 ER PT J AU Gong, PX Walsh, JH Zong, YM Solomon, TE AF Gong, PX Walsh, JH Zong, YM Solomon, TE TI Physiological doses of secretin inhibit only very low levels of stimulated gastric acid secretion in urethane anesthetized rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 CURE Dig Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dig Dis Div, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0556 BP A136 EP A136 DI 10.1016/S0016-5085(98)80553-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600553 ER PT J AU Gschossmann, JM Miller, JC Mayer, EA AF Gschossmann, JM Miller, JC Mayer, EA TI Evidence for role of vagal innervation in activation of opioidergic antinociceptive systems in response to colorectal distension (CRD) in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, UCLA CURE Neuroenter Dis Program, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, UCLA CURE Neuroenter Dis Program, Dept Physiol, Los Angeles, CA USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 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 15 PY 1998 VL 114 IS 4 SU S MA G4698 BP A1148 EP A1148 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604671 ER PT J AU Gschossmann, JM Mayer, EA AF Gschossmann, JM Mayer, EA TI Role of spinal receptors for NMDA, NK-1 and CGRP in visceral pain response to colorectal distension (CRD). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, UCLA CURE Neoroenter Dis Program, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, UCLA CURE Neoroenter Dis Program, Dept Physiol, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 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 15 PY 1998 VL 114 IS 4 SU S MA G4699 BP A1148 EP A1148 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604668 ER PT J AU Gschossmann, JM Miller, JC Plourde, V Wong, HC Walsh, JH Mayer, EA AF Gschossmann, JM Miller, JC Plourde, V Wong, HC Walsh, JH Mayer, EA TI Involvement of calcitonin gene-related peptide (CGRP) in the development of acute visceral hyperalgesia in the rat. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Dept Med, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Montreal, Andre Viallet Clin Res Ctr, Neurobiol & Digest Motil Unit, Montreal, PQ, Canada. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3123 BP A757 EP A757 DI 10.1016/S0016-5085(98)83099-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603099 ER PT J AU Gschossmann, JM Goliger, J Raybould, HE Ennes, H Young, SH Mayer, EA AF Gschossmann, JM Goliger, J Raybould, HE Ennes, H Young, SH Mayer, EA TI Mechanically-induced calcium transients in DRG neurons are amiloride sensitive. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, UCLA CURE Neuroenter Dis Program, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3124 BP A758 EP A758 DI 10.1016/S0016-5085(98)83100-4 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603100 ER PT J AU Guan, RJ Zhang, JB Martin, K Ford, H Fu, Y Pardee, A AF Guan, RJ Zhang, JB Martin, K Ford, H Fu, Y Pardee, A TI Down-regulation of a homocysteine-induced novel gene in metastatic human colon cancer. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Beth Israel Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2482 BP A604 EP A604 DI 10.1016/S0016-5085(98)82464-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602464 ER PT J AU Hartwig, W Werner, J Carter, EA Jimenez, RE Kupa, S Warshaw, AL Fernandez-del Castillo, C AF Hartwig, W Werner, J Carter, EA Jimenez, RE Kupa, S Warshaw, AL Fernandez-del Castillo, C TI Pancreatic proteases in lymph and blood of rats with cerulein pancreatitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1903 BP A468 EP A468 DI 10.1016/S0016-5085(98)81892-1 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601892 ER PT J AU Henihan, RDJ Colucci, R Zhang, ZS Wang, TC AF Henihan, RDJ Colucci, R Zhang, ZS Wang, TC TI Somatostatin type 2 receptor (SSTR2) inhibition of histidine decarboxylase (HDC) transcription is not mediated through a phosphatase pathway in the human gastric cancer cell line AGS-B. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4702 BP A1149 EP A1149 DI 10.1016/S0016-5085(98)84672-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604675 ER PT J AU Hocker, M Raychowhury, R Wu, HJ O'Connor, DT Riecken, EO Rosewicz, S Wang, TC AF Hocker, M Raychowhury, R Wu, HJ O'Connor, DT Riecken, EO Rosewicz, S Wang, TC TI SP1 and CREB mediate gastrin-dependent regulation of chromogranin A promoter activity. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Free Univ Berlin, Klinikum Benjamin Franklin, D-12200 Berlin, Germany. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4706 BP A1150 EP A1150 DI 10.1016/S0016-5085(98)84676-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604678 ER PT J AU Hocker, M Plath, T Wiedenmann, B Riecken, EO Rosewicz, S Wang, TC AF Hocker, M Plath, T Wiedenmann, B Riecken, EO Rosewicz, S Wang, TC TI CAMP-dependent signaling pathways regulate the human histidine decarboxylase promoter through activation of MAPK/ERK-cascades in gastric cancer cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Free Univ Berlin, Klinikum Benjamin Franklin, D-12200 Berlin, Germany. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4705 BP A1149 EP A1149 DI 10.1016/S0016-5085(98)84675-1 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604673 ER PT J AU Itoh, H Inoue, N Podolsky, DK AF Itoh, H Inoue, N Podolsky, DK TI Goblet cell-specific transcription of the intestinal trefoil factor results from collaboration of distinctive positive and negative regulatory elements. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4713 BP A1151 EP A1151 DI 10.1016/S0016-5085(98)84683-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604681 ER PT J AU Itoh, H Beck, PL Rosenberg, IM Podolsky, DK AF Itoh, H Beck, PL Rosenberg, IM Podolsky, DK TI Targeted transgenic ablation of goblet cells: Paradoxical reduction in susceptibility to dextran sodium sulfate- and acetic acid-induced experimental colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3625 BP A884 EP A884 DI 10.1016/S0016-5085(98)83600-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603599 ER PT J AU Jasper, MS Gulick, T Davis, P Kaplan, LM AF Jasper, MS Gulick, T Davis, P Kaplan, LM TI Leptide, a rate leptin receptor antagonist, is a rapid and potent stimulator of insulin secretion in vivo. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Obes Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3626 BP A884 EP A884 DI 10.1016/S0016-5085(98)83601-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603600 ER PT J AU Jenkins, TD Opitz, OG Okano, J Rustgi, AK AF Jenkins, TD Opitz, OG Okano, J Rustgi, AK TI Trans-activation of the esophageal, squamous epithelial specific human keratin 4 and Epstein-Barr virus ED-12 promoters by gut-enriched Kruppel-like factor. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2535 BP A616 EP A617 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602517 ER PT J AU Jenkins, TD Mueller, A Odze, R Shahsafaei, A Zukerberg, L Stoner, G Rustgi, AK AF Jenkins, TD Mueller, A Odze, R Shahsafaei, A Zukerberg, L Stoner, G Rustgi, AK TI Cooperation between the cyclin D1 oncogene and the chemical carcinogen N-nitrosometylbenzylamine in the induction of esophageal dysplasia in transgenic mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Ohio State Univ, Arthur James Canc Res Inst, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2534 BP A616 EP A616 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602516 ER PT J AU Jimenez, RE Z'graggen, K Warshaw, AL Graeme-Cook, F Hartwig, W Kupa, S Rivera, JA Rattner, DW Fernandez-del Castillo, C AF Jimenez, RE Z'graggen, K Warshaw, AL Graeme-Cook, F Hartwig, W Kupa, S Rivera, JA Rattner, DW Fernandez-del Castillo, C TI Immunohistochemical characterization of pancreatic tumors induced by DMBA in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1920 BP A472 EP A472 DI 10.1016/S0016-5085(98)81909-4 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601909 ER PT J AU Kim, YI Puchyr, M Medline, A Salomon, RN Graeme-Cook, F Choi, SW Mason, JB AF Kim, YI Puchyr, M Medline, A Salomon, RN Graeme-Cook, F Choi, SW Mason, JB TI The effect of dietary folate on p53 mutations in the dimethylhydrazine rat model of colon cancer. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Univ Toronto, Dept Med, Toronto, ON, Canada. Univ Toronto, Dept Pathol, Toronto, ON, Canada. NR 2 TC 1 Z9 1 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2571 BP A625 EP A625 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602553 ER PT J AU Klein, PD Malaty, HM Graham, DY Czinn, S Emmons, S Martin, R AF Klein, PD Malaty, HM Graham, DY Czinn, S Emmons, S Martin, R TI Urea hydrolysis rate (UHR) calculation normalizes the 13C-urea breath test for age, sex, height, and weight. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Meretek Diagnost Inc, Nashville, TN USA. Rainbow Babies & Childrens Hosp, Cleveland, OH USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Marchern Associates Inc, Concord, MA USA. Meretek Diagnost Inc, Houston, TX USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0731 BP A179 EP A179 DI 10.1016/S0016-5085(98)80725-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600725 ER PT J AU Koh, TJ Dockray, GJ Varro, A Chen, D Wang, TC AF Koh, TJ Dockray, GJ Varro, A Chen, D Wang, TC TI The targeted disruption of the gastrin gene in mice results in decreased proliferation of the stomach and colon in response to refeeding SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Lund, Dept Pharmacol, Lund, Sweden. Univ Liverpool, Physiol Lab, Liverpool L69 3BX, Merseyside, England. Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3644 BP A889 EP A889 DI 10.1016/S0016-5085(98)83619-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603621 ER PT J AU Kumagai, T Hosogaya, S Misawa, K Furihata, K Ota, H Sei, C Tanaka, E Akamatsu, T Shimizu, T Kiyosawa, K Katsuyama, T AF Kumagai, T Hosogaya, S Misawa, K Furihata, K Ota, H Sei, C Tanaka, E Akamatsu, T Shimizu, T Kiyosawa, K Katsuyama, T TI Acquisition and loss of Helicobacter pylori infection in Japan: Results from an 8-year birth cohort study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Shinshu Univ, Sch Med, Dept Lab Med, Matsumoto, Nagano, Japan. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0779 BP A190 EP A190 DI 10.1016/S0016-5085(98)80773-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600773 ER PT J AU Li, W Rosenzweig, A Grand, RJ AF Li, W Rosenzweig, A Grand, RJ TI Adenovirus mediated enterocyte specific expression of a beta-galactosidase green fluorescence protein chimeric reporter using an intestinal fatty acid binding protein promoter. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Tufts Univ, New England Med Ctr, GRASP Ctr, Div Pediat Gastroenterol & Nutr, Boston, MA 02111 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1597 BP A391 EP A391 DI 10.1016/S0016-5085(98)81586-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601586 ER PT J AU Mashimo, H He, XD Goyal, RK AF Mashimo, H He, XD Goyal, RK TI Pyloric dysfunction of inhibitory neurotransmission in knockout mice lacking neuronal nitric oxide synthase. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. VAMC, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3286 BP A799 EP A799 DI 10.1016/S0016-5085(98)83261-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603261 ER PT J AU Mashimo, H Kjellin, AP Ashegh, EJ Goyal, RK AF Mashimo, H Kjellin, AP Ashegh, EJ Goyal, RK TI Delayed liquid and solid gastric emptying in gene knockout mice lacking neuronal nitric oxide synthase. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. VAMC, W Roxbury, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3285 BP A798 EP A799 DI 10.1016/S0016-5085(98)83260-5 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603260 ER PT J AU McKaig, B Makh, S Hawkey, CJ Podolsky, DK Mahida, YR AF McKaig, B Makh, S Hawkey, CJ Podolsky, DK Mahida, YR TI Human colonic subepithelial myofibroblasts enhance epithelial restitution. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Univ Nottingham Hosp, Div Gastroenterol, Nottingham NG7 2UH, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4244 BP A1036 EP A1036 DI 10.1016/S0016-5085(98)84217-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604217 ER PT J AU Mizoguchi, A Mizoguchi, E Smith, RN Higaki, K Bhan, AK AF Mizoguchi, A Mizoguchi, E Smith, RN Higaki, K Bhan, AK TI Pathogenic role of IL-4, but not IFN-gamma in colitis of TCR alpha knockout mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4261 BP A1041 EP A1041 DI 10.1016/S0016-5085(98)84234-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604234 ER PT J AU Mizoguchi, E Mizoguchi, A Smith, RN Higaki, K Bhan, AK AF Mizoguchi, E Mizoguchi, A Smith, RN Higaki, K Bhan, AK TI Hyperreactivity of B cells in the appendix lymphoid follicle of TCR alpha-mutant mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4262 BP A1041 EP A1041 DI 10.1016/S0016-5085(98)84235-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604235 ER PT J AU Morales, V Christ, A Watt, S Russell, G Bahn, AK Mizoguchi, A Freeman, G Blumberg, RS AF Morales, V Christ, A Watt, S Russell, G Bahn, AK Mizoguchi, A Freeman, G Blumberg, RS TI Biliary glycoprotein (BGP;CD66a) functions as an inhibitory coreceptor for activation of human intestinal intraepithelial lymphocytes (iIEL). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 John Radcliffe Hosp, Oxford OX3 9DU, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4271 BP A1044 EP A1044 DI 10.1016/S0016-5085(98)84244-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604244 ER PT J AU Munakata, J Silverman, DHS Naliboff, B Liu, M Chang, L Mandelkern, M Mayer, EA AF Munakata, J Silverman, DHS Naliboff, B Liu, M Chang, L Mandelkern, M Mayer, EA TI Altered cortical and subcortical brain activation associated with autonomic responses to visceral pain in irritable bowel syndrome (IBS). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, CURE Neuroenter Dis Program, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Nucl Med, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4773 BP A1167 EP A1167 DI 10.1016/S0016-5085(98)84743-4 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604746 ER PT J AU Nakamura, Y Kinoshita, K Hashida, H Iwata, S Takabayashi, A AF Nakamura, Y Kinoshita, K Hashida, H Iwata, S Takabayashi, A TI Analysis of the mechanism of inhibition of liver metastasis from colon cancer: The role of interleukin 2 receptor of the liver sinusoidal mononuclear cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Kitano Hosp, Tazuke Kofukai Med Res Inst, Dept Surg, Osaka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA S0174 BP A1413 EP A1413 DI 10.1016/S0016-5085(98)85745-4 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605745 ER PT J AU Napadow, VJ Chen, Q Wedeen, VJ Gilbert, RJ AF Napadow, VJ Chen, Q Wedeen, VJ Gilbert, RJ TI Regional lingual mechanics during swallowing: A synergistic model involving intrinsic and extrinsic muscle activity SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NMR Ctr, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA USA. MIT, Dept Mech Engn, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3328 BP A810 EP A810 DI 10.1016/S0016-5085(98)83303-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603303 ER PT J AU Nishiyama, R Podolsky, DK Reinecker, HC AF Nishiyama, R Podolsky, DK Reinecker, HC TI Regulation of tight junction formation in intestinal epithelial cells by the IL-15 ligand-receptor system SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3680 BP A898 EP A898 DI 10.1016/S0016-5085(98)83655-X PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603658 ER PT J AU Obhrai, JS Anand, BS AF Obhrai, JS Anand, BS TI Assessment of fatigue in chronic liver disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0473 BP A1314 EP A1314 DI 10.1016/S0016-5085(98)85331-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605331 ER PT J AU Ohning, GV Curi, A Lyu, RM Zeng, N Wong, HC Sachs, G Walsh, JH Pisegna, JR AF Ohning, GV Curi, A Lyu, RM Zeng, N Wong, HC Sachs, G Walsh, JH Pisegna, JR TI PACAP stimulates gastric acid secretion during somatostatin immunoneutralization in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4788 BP A1170 EP A1171 DI 10.1016/S0016-5085(98)84758-6 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604756 ER PT J AU Opitz, OG Jenkins, TD Inomoto, T Rustgi, AK AF Opitz, OG Jenkins, TD Inomoto, T Rustgi, AK TI The human keratin 4 promoter is regulated by esophageal-specific and ubiquitous transcriptional activators. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Hematol Oncol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2713 BP A658 EP A658 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602693 ER PT J AU Opitz, OG Compton, CC Warland, G Nakagawa, H Togawa, K Rustgi, AK AF Opitz, OG Compton, CC Warland, G Nakagawa, H Togawa, K Rustgi, AK TI Cellular characterization and successful transfection of serially subcultured normal human esophageal keratinocytes. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Shriners Burn Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2712 BP A658 EP A658 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602692 ER PT J AU Puschmann, AJ Dehne, K Page, S Classen, M Schepp, W AF Puschmann, AJ Dehne, K Page, S Classen, M Schepp, W TI In purified rat parietal cells NF-kappa B is activated by proinflammatory cytokines and H2O2. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4799 BP A1173 EP A1173 DI 10.1016/S0016-5085(98)84769-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604769 ER PT J AU Raychowdhury, R Zhang, ZS Wang, TC AF Raychowdhury, R Zhang, ZS Wang, TC TI Activation of human histidine decarboxylase (HDC) gene transcription by gastrin is mediated by two distinct nuclear factors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4800 BP A1173 EP A1173 DI 10.1016/S0016-5085(98)84770-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604768 ER PT J AU Realdi, G Dore, MP Carta, M Atzei, A Manca, A Piana, A Idda, M Are, B Massarelli, G Mura, I Maida, A Sepulveda, AR Graham, DY AF Realdi, G Dore, MP Carta, M Atzei, A Manca, A Piana, A Idda, M Are, B Massarelli, G Mura, I Maida, A Sepulveda, AR Graham, DY TI Failure of Bazzoli's regimen (omeprazole-metronidazole-clarithromycin) therapy for H-pylori infection in Sardinia. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Med, Inst Hyg & Prevent Med, Sassari, Italy. Univ Med, Inst Histopathol, Sassari, Italy. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Univ Med, Inst Internal Med, Sassari, Italy. NR 0 TC 6 Z9 6 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1091 BP A266 EP A266 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601081 ER PT J AU Reeve, JR Gong, PX Coskun, T Zong, YM Ho, FJ Solomon, TE AF Reeve, JR Gong, PX Coskun, T Zong, YM Ho, FJ Solomon, TE TI Comparison of synthetic rat CCK-58 and CCK-8 reveals dissociation of pancreatic fluid and enzyme secretion and greater potency of CCK-58 in vivo. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, CURE Dig Dis Res Ctr, Div Digest Dis, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4801 BP A1174 EP A1174 DI 10.1016/S0016-5085(98)84771-9 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604774 ER PT J AU Reinecker, HC Podolsky, DK Li, DJ AF Reinecker, HC Podolsky, DK Li, DJ TI Novel human IL-17 receptors expressed in intestinal epithelial cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4802 BP A1174 EP A1174 DI 10.1016/S0016-5085(98)84772-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604773 ER PT J AU Rioux, KP Beck, PL Hoppin, AG Le, T Swain, MG AF Rioux, KP Beck, PL Hoppin, AG Le, T Swain, MG TI Leptin does not mediate the anorexia associated with biliary obstruction in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calgary, Liver Unit, Calgary, AB, Canada. Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0531 BP A1328 EP A1328 DI 10.1016/S0016-5085(98)85389-4 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605389 ER PT J AU Sarkar, S Aziz, Q Woolf, CJ Hobson, A Thompson, DG AF Sarkar, S Aziz, Q Woolf, CJ Hobson, A Thompson, DG TI The relationship between oesophageal acid exposure and secondary allodynia: Central sensitizsation contributes to visceral hypersensitivity in man. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Hope Hosp, Dept Med, Salford M6 8HD, Lancs, England. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3411 BP A831 EP A831 DI 10.1016/S0016-5085(98)83386-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603386 ER PT J AU Savard, CE Blinman, TA Pandol, SJ Lee, SP AF Savard, CE Blinman, TA Pandol, SJ Lee, SP TI Lipopolysaccharide stimulates cytokine production by mouse gallbladder epithelial cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Seattle VA Med Ctr, Seattle, WA USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4411 BP A1077 EP A1077 DI 10.1016/S0016-5085(98)84382-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604382 ER PT J AU Sebastian, J Huerta, S Blinman, T Livingston, EH AF Sebastian, J Huerta, S Blinman, T Livingston, EH TI Interleukin-10 (IL-10) results in loss of neural cell adhesion molecule (NCAM) expression in colon carcinoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, W Los Angeles Vet Affairs Med Ctr, Sch Med, Div Gen Surg,Surg Mol Biol Res Lab, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2793 BP A676 EP A677 DI 10.1016/S0016-5085(98)82773-X PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602773 ER PT J AU Shiraki, K Takahashi, H AF Shiraki, K Takahashi, H TI Expression of Fas and Fas ligand in doxorubicin-induced cardiac injury in rat. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA L0593 BP A1342 EP A1342 DI 10.1016/S0016-5085(98)85451-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605451 ER PT J AU Singh, P Velasco, M Given, R Owlia, A Wargovich, M Wang, TC AF Singh, P Velasco, M Given, R Owlia, A Wargovich, M Wang, TC TI High levels of progastrin significantly increase premalignant changes in colonic mucosa of mice in response to the chemical carcinogen, AOM. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Galveston, TX 77555 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2810 BP A680 EP A680 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602790 ER PT J AU Solomon, TE Reeve, JR Grandt, D Bussjaeger, L Varga, G Walsh, JH AF Solomon, TE Reeve, JR Grandt, D Bussjaeger, L Varga, G Walsh, JH TI Different receptor subtypes mediate PYY-induced inhibition of gastric acid and pepsin secretion. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dig Dis Div, Los Angeles, CA USA. CURE, Dig Dis Res Ctr, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1193 BP A290 EP A291 DI 10.1016/S0016-5085(98)81183-9 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601183 ER PT J AU Taupin, D Jeon, WK Wang, TC Podolsky, DK AF Taupin, D Jeon, WK Wang, TC Podolsky, DK TI Egf receptor- and map kinase-dependent inter-regulation within the immediate-early trefoil gene family SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G3731 BP A910 EP A910 DI 10.1016/S0016-5085(98)83706-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089603705 ER PT J AU Taylor, NS Fox, JG Dangler, CA Wang, T AF Taylor, NS Fox, JG Dangler, CA Wang, T TI High salt diet increases Helicobacter pylori colonization in C57B1/6 mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2841 BP A687 EP A687 DI 10.1016/S0016-5085(98)82820-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602820 ER PT J AU Tsuji, N Tsuji, A Shiraki, K Takahashi, H AF Tsuji, N Tsuji, A Shiraki, K Takahashi, H TI Fas ligand expression determines liver colonization competence of colonic adenocarcinoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2865 BP A692 EP A693 DI 10.1016/S0016-5085(98)82844-8 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602844 ER PT J AU Tsuji, N Frederick, D Takahashi, H AF Tsuji, N Frederick, D Takahashi, H TI Induction of human colonic intestinal epithelial cell death by interferon-gamma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Gastrointestinal Unit, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1732 BP A425 EP A425 DI 10.1016/S0016-5085(98)81721-6 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601721 ER PT J AU Wang, K Nourbakhsh, A Nishioka, N Kelsey, P Cass, O AF Wang, K Nourbakhsh, A Nishioka, N Kelsey, P Cass, O TI Optical biopsy of colonic polyps using laser-induced fluorescence (LIF). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2892 BP A699 EP A699 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602870 ER PT J AU Weber, HC Marsh, D Lubensky, I Lin, A Eng, C AF Weber, HC Marsh, D Lubensky, I Lin, A Eng, C TI Germline PTEN/MMAC1/TEP1 mutations and association with gastrointestinal manifestations in Cowden disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Dana Farber Canc Inst, Human Canc Genet Unit, Boston, MA 02115 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2902 BP A702 EP A702 DI 10.1016/S0016-5085(98)82880-1 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602880 ER PT J AU Wong, H Slice, L Zeng, N Walsh, JH AF Wong, H Slice, L Zeng, N Walsh, JH TI Internalization and recycling of galanin-1 receptors by clathrin-mediated pathway. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, DDRC, CURE, Los Angeles, CA 90073 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 15 PY 1998 VL 114 IS 4 SU S MA G4870 BP A1191 EP A1191 DI 10.1016/S0016-5085(98)84840-3 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604838 ER PT J AU Wu, SV Yang, M Avedian, D Walsh, JH AF Wu, SV Yang, M Avedian, D Walsh, JH TI Inhibition of cell growth by CCK requires activation of cyclic AMP signaling in HEK-293 cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, CURE, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4872 BP A1192 EP A1192 DI 10.1016/S0016-5085(98)84842-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604844 ER PT J AU Xavier, RJ Beck, PL Lu, NF Podolsky, DK Seed, B AF Xavier, RJ Beck, PL Lu, NF Podolsky, DK Seed, B TI Mice with decreased E-,P and L-selectin ligand biosynthesis are more resistant to dextran sodium sulfate-induced colitis but have more severe TNBS colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4569 BP A1116 EP A1117 DI 10.1016/S0016-5085(98)84539-3 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604539 ER PT J AU Yoon, SS Carroll, NM Chiocca, EA Tanabe, KK AF Yoon, SS Carroll, NM Chiocca, EA Tanabe, KK TI Influence of p53 status on the efficacy of HSV-mediated cancer gene therapy. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA S0276 BP A1435 EP A1435 DI 10.1016/S0016-5085(98)85844-7 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089605844 ER PT J AU Young, SH Ennes, HS Mayer, EA AF Young, SH Ennes, HS Mayer, EA TI Evidence for efferent function of dorsal root ganglion (DRG) neurons onto colonic smooth muscle cells in primary culture. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Dept Med, CURE,Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, CURE,Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4881 BP A1194 EP A1195 DI 10.1016/S0016-5085(98)84851-8 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604849 ER PT J AU Young, SH Ennes, HS Mayer, EA AF Young, SH Ennes, HS Mayer, EA TI Mechanically insensitive dorsal root ganglion cell (DRG) neurites show chemical excitability. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Dept Med,CURE,Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Dept Physiol,CURE,Neuroenter Dis Program, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Brain Res Inst, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4882 BP A1195 EP A1195 DI 10.1016/S0016-5085(98)84852-X PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604855 ER PT J AU Z'graggen, K Centeno, BA Werner, J Warshaw, AL Jimenez, RE Kupa, S Fernandez-del Castillo, C AF Z'graggen, K Centeno, BA Werner, J Warshaw, AL Jimenez, RE Kupa, S Fernandez-del Castillo, C TI Detection of tumor cells in peripheral blood and bone marrow in patients with pancreatic cancer. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2089 BP A512 EP A513 DI 10.1016/S0016-5085(98)82078-7 PN 2 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602078 ER PT J AU Zaninovic, V Gukovskaya, AS Gukovsky, I Kim, S Pandol, SJ AF Zaninovic, V Gukovskaya, AS Gukovsky, I Kim, S Pandol, SJ TI Adhesion molecule ICAM-1 is present and functions in rat pancreatic acinar cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G2088 BP A512 EP A512 DI 10.1016/S0016-5085(98)82077-5 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089602077 ER PT J AU Zeng, N Kang, T Athmann, C Wen, Y Walsh, JH Sachs, G AF Zeng, N Kang, T Athmann, C Wen, Y Walsh, JH Sachs, G TI Identification of gastric endocrine cells as the target sites of neuropeptides in regulation of gastric secretion by semi-quantitative RT-PCR and video imaging. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, W Los Angeles VA, DDRC, CURE, Los Angeles, CA 90024 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4887 BP A1196 EP A1196 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604858 ER PT J AU Zong, YM Reeve, JR Walsh, JH Gong, PX Ho, FJ Solomon, TE AF Zong, YM Reeve, JR Walsh, JH Gong, PX Ho, FJ Solomon, TE TI Secretin-GLY is a major product of preprosecretin processing in rat small intestine: Identification and quantitation by HPLC and radioimmunoassay. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, CURE, Digest Dis Res Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Div Digest Dis, Los Angeles, CA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G4892 BP A1197 EP A1197 DI 10.1016/S0016-5085(98)84862-2 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089604860 ER PT J AU Lindeman, GJ Dagnino, L Gaubatz, S Xu, YH Bronson, RT Warren, HB Livingston, DM AF Lindeman, GJ Dagnino, L Gaubatz, S Xu, YH Bronson, RT Warren, HB Livingston, DM TI A specific, nonproliferative role for E2F-5 in choroid plexus function revealed by gene targeting SO GENES & DEVELOPMENT LA English DT Article DE E2F-5; gene-targeting; hydrocephalus; choroid plexus; transcription; cell cycle ID S-PHASE ENTRY; CELL-CYCLE; GROWTH SUPPRESSION; FAMILY MEMBERS; P130; PROTEIN; MICE; EXPRESSION; APOPTOSIS; LETHALITY AB Homozygous E2F-5 knockout embryos and mice have been generated. Although embryonic development appeared normal, newborn mice developed nonobstructive hydrocephalus, suggesting excessive cerebrospinal fluid (CSF) production. Although the CSF-producing choroid plexus displayed normal cellular organization, it contained abundant electron-lucent epithelial cells, consistent with excessive CSF secretory activity. Moreover, E2F-5 CNS expression in normal animals was largely confined to the choroid plexus, Cell cycle kinetics were not perturbed in homozygous knockout embryo fibroblasts. Thus, E2F-5 is not essential for cell proliferation, Rather, it affects the secretory behavior of a differentiated neural tissue. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Ottawa Gen Hosp, Res Inst, Ottawa, ON K1H 8L6, Canada. Tufts Univ, Sch Vet Med, Boston, MA 02111 USA. Harvard Univ, Sch Med, Ctr Anim Resources & Comparat Med, Boston, MA 02115 USA. RP Livingston, DM (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. NR 33 TC 130 Z9 131 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 1998 VL 12 IS 8 BP 1092 EP 1098 DI 10.1101/gad.12.8.1092 PG 7 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ZK236 UT WOS:000073299000003 PM 9553039 ER PT J AU Maheswaran, S Englert, C Zheng, G Lee, SB Wong, J Harkin, DP Bean, J Ezzell, R Garvin, AJ McCluskey, RT DeCaprio, JA Haber, DA AF Maheswaran, S Englert, C Zheng, G Lee, SB Wong, J Harkin, DP Bean, J Ezzell, R Garvin, AJ McCluskey, RT DeCaprio, JA Haber, DA TI Inhibition of cellular proliferation by the Wilms tumor suppressor WT1 requires association with the inducible chaperone Hsp70 SO GENES & DEVELOPMENT LA English DT Article DE WT1; hsp70; p21; Wilms tumor; renal development; cell cycle arrest ID HEAT-SHOCK PROTEINS; TRANSCRIPTION FACTOR; GENE-PRODUCT; SUBNUCLEAR LOCALIZATION; MOLECULAR CHAPERONES; ATPASE ACTIVITY; EXPRESSION; BINDING; DNA; CELLS AB The Wilms tumor suppressor WT1 encodes a zinc finger transcription factor that is expressed in glomerular podocytes during a narrow window in kidney development. By immunoprecipitation and protein microsequencing analysis, we have identified a major cellular protein associated with endogenous WT1 to be the inducible chaperone Hsp70, WT1 and Hsp70 are physically associated in embryonic rat kidney cells, in primary Wilms turner specimens and in cultured sells with inducible expression of WT1. Colocalization of WT1 and Hsp70 is evident within podocytes of the developing kidney, and Hsp70 is recruited to the characteristic subnuclear clusters that contain WT1. The amino-terminal transactivation domain of WT1 is required for binding to Hsp70, and expression of that domain itself is sufficient to induce expression of Hsp70 through the heat shock element (HSE). Substitution of a heterologous Hsp70-binding domain derived from human DNAJ is sufficient to restore the functional properties of a WT1 protein with an amino-terminal deletion, an effect that is abrogated by a point mutation in DNAJ that reduces binding to Hsp70. These observations indicate that Hsp70 is an important cofactor for the function of WT1, and suggest a potential role for this chaperone during kidney differentiation. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Pathol Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Surg Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27157 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. FU NCI NIH HHS [R37 CA058596, CA 58596, R01 CA058596] NR 79 TC 74 Z9 76 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 1998 VL 12 IS 8 BP 1108 EP 1120 DI 10.1101/gad.12.8.1108 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ZK236 UT WOS:000073299000005 PM 9553041 ER PT J AU McClatchey, AI Saotome, I Mercer, K Crowley, D Gusella, JF Bronson, RT Jacks, T AF McClatchey, AI Saotome, I Mercer, K Crowley, D Gusella, JF Bronson, RT Jacks, T TI Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors SO GENES & DEVELOPMENT LA English DT Article DE merlin; NF2; tumor suppressor; cytoskeleton; osteosarcoma; metastasis ID TRANSGENIC MICE; NEUROFIBROMATOSIS TYPE-2; GENE-PRODUCT; T-ANTIGEN; PROTEIN; MERLIN; EZRIN; MOESIN; CELLS; SCHWANNOMIN AB A role for the membrane/cytoskeleton interface in the development and progression of cancer is established, yet poorly understood. The neurofibromatosis type II (NF2) turner suppressor gene encodes a member of the ezrin/radixin/moesin (ERM) family of membrane/cytoskeleton linker proteins thought to be important for cell adhesion and motility. We report that in contrast to the narrow spectrum of benign tumors in human NF2 patients, Nf2 heterozygous mice develop a variety of malignant tumors. Using the fact that Nf2 is linked to the p53 tumor suppressor locus in the mouse we have also investigated the effects of genetic linkage of cancer-predisposing mutations on tumorigenesis and examined the genetic pathway to tumor formation involving Nf2 loss. Importantly, we observed a very high rate of metastasis associated with Nf2 deficiency, with or without loss of p53 function, and we provide experimental evidence supporting a role for Nf2 loss in metastatic potential. Together, our results suggest an important role for the NF2 tumor suppressor, and perhaps the ERM family in tumor formation and metastasis. C1 Dept Biol, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Tufts Univ, Sch Vet Med, Dept Pathol, USDA,Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Massachusetts Gen Hosp E, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP McClatchey, AI (reprint author), Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. NR 51 TC 253 Z9 258 U1 2 U2 11 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 1998 VL 12 IS 8 BP 1121 EP 1133 DI 10.1101/gad.12.8.1121 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ZK236 UT WOS:000073299000006 PM 9553042 ER PT J AU Tsang, AP Fujiwara, Y Hom, DB Orkin, SH AF Tsang, AP Fujiwara, Y Hom, DB Orkin, SH TI Failure of megakaryopoiesis and arrested erythropoiesis in mice lacking the GATA-1 transcriptional cofactor FOG SO GENES & DEVELOPMENT LA English DT Article DE friend of GATA-1 (FOG); GATA-1; cofactor gene targeting; hematopoiesis ID EMBRYONIC STEM-CELLS; ZINC-FINGER PROTEIN; MEGAKARYOCYTIC DIFFERENTIATION; ERYTHROID DEVELOPMENT; HEMATOPOIETIC-CELLS; FACTOR NF-E2; DNA-BINDING; EXPRESSION; GENE; PRECURSORS AB GATA transcription factors are required for the differentiation of diverse cell types in several species. Recent evidence suggests that their biologic activities may be modulated through interaction with multitype zinc finger proteins, such as Friend of GATA-1 (FOG) and U-shaped (Ush). In cell culture, FOG; cooperates with the hematopoietic transcription faster GATA-1 to promote erythroid and megakaryocytic differentiation. We show here that mice lacking FOG die during mid-embryonic development With severe anemia. FOG(-/-) erythroid cells display a marked, But partial, blockage of maturation, reminiscent of GATA-1(-) erythroid precursors. In contrast to GATA-1 deficiency, however, megakaryocytes fail to develop in the absence of FOG. Although the FOG(-/-) erythroid phenotype supports the proposed role of FOG as a GATA-1 cofactor in vivo, the latter finding points to a pivotal, GATA-1-independent requirement Ear FOG in megakaryocyte development from the bipotential erythroid/megakaryocytic progenitor. We speculate that FOG and other FOG-like proteins serve as complex cofactors that act through both GATA-dependent and GATA-independent mechanisms. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM orkin@rascal.med.harvard.edu FU NIGMS NIH HHS [T32 GM007753, T32-GM07753-18] NR 55 TC 258 Z9 265 U1 1 U2 5 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 15 PY 1998 VL 12 IS 8 BP 1176 EP 1188 DI 10.1101/gad.12.8.1176 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ZK236 UT WOS:000073299000011 PM 9553047 ER PT J AU Lo Nigro, C Venesio, T Reymond, A Meroni, G Alberici, P Cainarca, S Enrico, F Stack, M Ledbetter, DH Liscia, DS Ballabio, A Carrozzo, R AF Lo Nigro, C Venesio, T Reymond, A Meroni, G Alberici, P Cainarca, S Enrico, F Stack, M Ledbetter, DH Liscia, DS Ballabio, A Carrozzo, R TI The human ROX gene: Genomic structure and mutation analysis in human breast tumors SO GENOMICS LA English DT Article ID C-MYC; SUPPRESSOR GENE; DNA-BINDING; EPIDERMAL DIFFERENTIATION; ONCOGENIC ACTIVITY; REPRESSOR SIN3; MAX; CANCER; MXI1; HYPERMETHYLATION AB We have recently isolated a human gene, ROX, encoding a new member of the basic helix-loop-helix leucine zipper protein family. ROX is capable of heterodimerizing with Max and acts as a transcriptional repressor in an E-box-driven reporter gene system, while it was found to activate transcription in HeLa cells, ROX expression levels vary during the cell cycle, being down-regulated in proliferating cells. These biological properties of ROX suggest a possible involvement of this gene in cell proliferation and differentiation. The ROX gene maps to chromosome 17p13.3, a region frequently deleted in human malignancies. Here we report the genomic structure of the human ROX gene, which is composed of six exons and spans a genomic region of less than 40 kb, In an attempt to identify possible inactivating mutations in the ROX gene in human breast cancer, we performed a single-strand conformation polymorphism analysis of its coding region in 16 sporadic breast carcinomas showing loss of heterozygosity in the 17p13.3 region. No mutations were found in this analysis. Five nucleotide polymorphisms were identified in the ROX gene, three of which caused an amino acid substitution. These nucleotide changes were present in the peripheral blood DNAs of both the patients and the control individuals. In vitro translated assays did not show a significant decrease in the ability of the ROX mutant proteins to bind DNA or to repress transcription of a driven reporter gene in HEK293 cells. Despite experimental evidence that ROX might act as a tumor suppressor gene, our data suggest that mutations in the coding region of ROX are uncommon in human breast tumorigenesis. (C) 1998 Academic Press. C1 Hosp San Raffaele, Gen Med Serv, I-20132 Milan, Italy. Hosp San Raffaele, Lab Citogenet, I-20132 Milan, Italy. TIGEM, Milan, Italy. Osped San Giovanni Ant Seda, Dipartimento Oncol, USL 1, Serv Anat Patol, Turin, Italy. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA. Univ Chicago, Ctr Med Genet, Chicago, IL 60637 USA. Christie Hosp, Paterson Inst Canc Res, CRC, Dept Canc Genet, Manchester, Lancs, England. RP Carrozzo, R (reprint author), Hosp San Raffaele, Gen Med Serv, Via Olgettina 58, I-20132 Milan, Italy. EM carrozzo@tigem.it OI BALLABIO, Andrea/0000-0003-1381-4604 FU Telethon [TGM06S01, TGM97000] NR 45 TC 3 Z9 3 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1998 VL 49 IS 2 BP 275 EP 282 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZN543 UT WOS:000073656400013 PM 9598315 ER PT J AU Ikeuchi, T Sanpei, K Takano, H Sasaki, H Tashiro, K Cancel, G Brice, A Bird, TD Schellenberg, GD Pericak-Vance, MA Welsh-Bohmer, KA Clark, LN Wilhelmsen, K Tsuji, S AF Ikeuchi, T Sanpei, K Takano, H Sasaki, H Tashiro, K Cancel, G Brice, A Bird, TD Schellenberg, GD Pericak-Vance, MA Welsh-Bohmer, KA Clark, LN Wilhelmsen, K Tsuji, S TI A novel long and unstable CAG/CTG trinucleotide repeat on chromosome 17q SO GENOMICS LA English DT Article ID CAG REPEAT; HUMAN GENOME; EXPANSION; INSTABILITY; MECHANISM; DEMENTIA; DISEASE; GENE AB Using the direct identification of repeat expansion and cloning technique, we cloned a novel long CAG/ CTG trinucleotide repeat on chromosome 17. Using radiation hybrid panels, the CAG/CTG repeat was mapped to chromosome 17q. The CAG/CTG repeat is highly polymorphic, with a heterozygosity of 85%, and exhibits a bimodal distribution (allele S, 10-26 repeat units, and allele L, 50-92 repeat units). The CAG/CTG repeat of allele L exhibited intergenerational instabilities, which are more prominent in maternal transmission than in paternal transmission. Analyses of Northern blot and RT-PCR indicate that the repeat is transcribed. Although the size of the CAG/CTG repeat of allele L is within the range of the expanded CAG repeat of disease-causing genes, we did not detect any association of allele L with various neurodegenerative diseases, including frontotemporal dementia and parkinsonism, mapped to 17q21-q23. (C) 1998 Academic Press. C1 Niigata Univ, Brain Res Inst, Dept Neurol, Niigata 951, Japan. Hokkaido Univ, Sch Med, Dept Neurol, Sapporo, Hokkaido 060, Japan. Hop La Pitie Salpetriere, Federat Neurol, Paris, France. Hop La Pitie Salpetriere, INSERM, U289, Paris, France. VA Puget Sound Hlth Care Syst, Neurol Sect, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA 98108 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94110 USA. RP Tsuji, S (reprint author), Niigata Univ, Brain Res Inst, Dept Neurol, 1 Asahimachi, Niigata 951, Japan. EM tsuji@cc.niigata-u.ac.jp FU NINDS NIH HHS [NS26630, NS31153] NR 22 TC 35 Z9 35 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1998 VL 49 IS 2 BP 321 EP 326 DI 10.1006/geno.1998.5266 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZN543 UT WOS:000073656400021 PM 9598323 ER PT J AU Shelley, CS Da Silva, N Georgakis, A Chomienne, C Arnaout, MA AF Shelley, CS Da Silva, N Georgakis, A Chomienne, C Arnaout, MA TI Mapping of the human CD11c (ITGAX) and CD11d (ITGAD) genes demonstrates that they are arranged in tandem separated by no more than 11.5 kb SO GENOMICS LA English DT Article ID ALPHA-SUBUNIT; P150,95; LFA-1; MAC-1 C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Leukocyte Biol & Inflammat Program, Boston, MA 02115 USA. Hop St Louis, Inst Hematol, CNRS, EP 107, Paris, France. RP Shelley, CS (reprint author), Massachusetts Gen Hosp, Renal Unit, Leukocyte Biol & Inflammat Program, 149 13th St, Charlestown, MA 02129 USA. NR 5 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD APR 15 PY 1998 VL 49 IS 2 BP 334 EP 336 DI 10.1006/geno.1998.5232 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZN543 UT WOS:000073656400024 PM 9598326 ER PT J AU Kroll, MH Shandera, WX AF Kroll, MH Shandera, WX TI AIDS-associated Kaposi's sarcoma SO HOSPITAL PRACTICE LA English DT Article AB In less than two decades, the disease mechanisms have been elucidated and hypotheses for innovative treatments have been developed, Our understanding of the sarcoma's pathogenesis has led directly to general knowledge of the physiology and pathology of angiogenesis, Hence, it can be expected that new treatments for all cancer patients may someday emerge from clinical intervention trials for the AIDS-related disease. C1 Baylor Coll Med, Houston, TX 77030 USA. RP Kroll, MH (reprint author), VA Med Ctr, Houston, TX 77211 USA. NR 6 TC 4 Z9 4 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 8750-2836 J9 HOSP PRACT JI Hosp. Pract. PD APR 15 PY 1998 VL 33 IS 4 BP 85 EP + PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA ZH329 UT WOS:000073097100010 PM 9562835 ER PT J AU Hisada, M Garber, JE Fung, CY Fraumeni, JF Li, FP AF Hisada, M Garber, JE Fung, CY Fraumeni, JF Li, FP TI Multiple primary cancers in families with Li-Fraumeni syndrome SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID ADRENAL-CORTICAL CARCINOMA; 2ND MALIGNANT NEOPLASMS; TUMOR-SUPPRESSOR GENE; LONG-TERM SURVIVORS; BREAST-CANCER; P53 GENE; GERMLINE MUTATIONS; HODGKINS-DISEASE; OVARIAN-CANCER; MORTALITY AB Background: Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, sarcomas, and other cancers in children and young adults, Members of families with this syndrome also develop multiple primary cancers, but the frequency is unknown. To approach this issue, we quantified the incidence of second and third primary cancers in individuals from 24 Li-Fraumeni kindreds originally diagnosed with cancer during the period from 1968 through 1986, Methods: The relative risk (RR) of subsequent cancers and 95% confidence intervals (CIs) were calculated by use of population-based incidence data from the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative probability (+/- standard error) of subsequent cancers. Results: Among 200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while four (2%) eventually developed a fourth cancer. Overall, the RR of occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer occurrence of 57% (+/-10%) at 30 years after diagnosis of a first cancer. RRs of second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of Li-Fraumeni syndrome. Conclusions: Compared with the general population, members of Li-Fraumeni syndrome families have an exceptionally high risk of developing multiple primary cancers. The excess risk of additional primary cancers is mainly for cancers that are characteristic of Li-Fraumeni syndrome, with the highest risk observed for survivors of childhood cancers. Cancer survivors in these families should be closely monitored for early manifestations of new cancers. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Div Canc Epidemiol & Control, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Div Canc Epidemiol & Control, 44 Binney St,SM202, Boston, MA 02115 USA. FU NHGRI NIH HHS [5RO1HG00725] NR 53 TC 264 Z9 271 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD APR 15 PY 1998 VL 90 IS 8 BP 606 EP 611 DI 10.1093/jnci/90.8.606 PG 6 WC Oncology SC Oncology GA ZH325 UT WOS:000073096700012 PM 9554443 ER PT J AU Wilson, IB Sullivan, LM Weissman, JS AF Wilson, IB Sullivan, LM Weissman, JS TI Costs and outcomes of AIDS care: Comparing a health maintenance organization with fee-for-service systems in the Boston health study SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HMO; FFS; AIDS care costs ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; INTRAVENOUS-DRUG-USERS; HIV-INFECTED PATIENTS; QUALITY-OF-LIFE; MEDICAL OUTCOMES; MANAGED CARE; PROPENSITY SCORE; CONTROLLED TRIAL; SPECIALTIES; SURVIVAL AB Objective: A I-month observational cohort study was performed to compare the performance of one health maintenance organization (HMO) with two fee-for-service (FFS) systems in Boston. Massachusetts in treating 255 patients with AIDS. Main Outcome Measures: Total I-month costs; cost subcomponents, including inpatient, outpatient, home care, and zidovudine costs; functional status (difficulties with activities of daily living), and satisfaction with care. Results: Compared with FFS patients, HMO patients were better educated. more often white, less often on Medicaid, and more often reported homosexual or bisexual behaviors as HIV risk factors (all factors, p = .001). Both groups had similar duration of AIDS, baseline hemoglobin levels, and leukocyte counts. Total 4-month costs at the HMO were significantly lower than those in the FFS settings ($4799 U.S., versus $8540 U.S.; p = .013), as were outpatient costs ($1131 U.S. versus $1614 U.S.; p = .001), after adjustment for sociodemographic factors, baseline functioning, main HIV risk factor, and other clinical variables. Adjusted physical functioning (p = .32) and patient satisfaction (p = .82). were similar between systems. Conclusions: The HMO had significantly lower total costs without any observable decrement in functional outcomes or patient satisfaction. The largest component of these cost savings came from reduced spending on inpatient care, but the HMO also spent less on outpatient and home care. Better coordination of care at the HMO may have been responsible for these lower costs. C1 New England Med Ctr, Primary Care Outcomes Res Inst, Boston, MA 02111 USA. New England Med Ctr, Dept Med, Boston, MA 02111 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Massachusetts Gen Hosp, Hlth Policy Res & Dev Unit, Boston, MA 02114 USA. RP Wilson, IB (reprint author), New England Med Ctr, Primary Care Outcomes Res Inst, 750 Washington St, Boston, MA 02111 USA. RI Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X FU AHRQ HHS [R01-HS06239] NR 38 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 15 PY 1998 VL 17 IS 5 BP 424 EP 432 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZH483 UT WOS:000073115600007 PM 9562045 ER PT J AU Spergel, JM Mizoguchi, E Brewer, JP Martin, TR Bhan, AK Geha, RS AF Spergel, JM Mizoguchi, E Brewer, JP Martin, TR Bhan, AK Geha, RS TI Epicutaneous sensitization with protein antigen induces localized allergic dermatitis and hyperresponsiveness to methacholine after single exposure to aerosolized antigen in mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE mice; atopic dermatitis; epicutaneous sensitization; cytokines; asthma ID HOUSE-DUST MITE; CD4+ T-CELLS; ATOPIC-DERMATITIS; ADHESION MOLECULES; IGE PRODUCTION; PATCH TEST; EOSINOPHILS; SKIN; RESPONSIVENESS; AEROALLERGEN AB Our understanding of the pathogenesis of atopic dermatitis (AD) and its relationship to asthma remains incomplete. Herein, we describe a murine model of epicutaneous (EC) sensitization to the protein allergen, chicken egg albumin, ovalbumin (OVA), which results in a rice in total and OVA-specific serum IgE and leads to the development of a dermatitis characterized by infiltration of CD3(+) T cells, eosinophils, and neutrophils and by local expression of MRNA for the cytokines IL-4, IL-5, and interferon-gamma. A single exposure of the EC sensitized mice to aerosolized OVA induced eosinophilia in the bronchoalveolar lavage fluid and airway hyperresponsiveness to intravenous methacholine as assessed by measurement of pulmonary dynamic compliance (C-dyn). These results suggest a possible role for EC exposure to antigen in atopic dermatitis and in the development of allergic asthma. C1 Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pathol, Dept Immunopathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Pulm Med, Boston, MA 02115 USA. RP Geha, RS (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Div Immunol, 300 Longwood Ave,Enders 8, Boston, MA 02115 USA. FU NICHD NIH HHS [P30 HD27805]; NIDDK NIH HHS [DK43551, DK47677] NR 50 TC 350 Z9 361 U1 0 U2 6 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 15 PY 1998 VL 101 IS 8 BP 1614 EP 1622 DI 10.1172/JCI1647 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZJ234 UT WOS:000073193000011 PM 9541491 ER PT J AU Pratley, RE Thompson, DB Prochazka, M Baier, L Mott, D Ravussin, E Sakul, H Ehm, MG Burns, DK Foroud, T Garvey, WT Hanson, RL Knowler, WC Bennett, PH Bogardus, C AF Pratley, RE Thompson, DB Prochazka, M Baier, L Mott, D Ravussin, E Sakul, H Ehm, MG Burns, DK Foroud, T Garvey, WT Hanson, RL Knowler, WC Bennett, PH Bogardus, C TI An autosomal genomic scan for loci linked to prediabetic phenotypes in Pima Indians SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE type 2 diabetes mellitus; glucose tolerance; insulin secretion; insulin action; genetics ID DEPENDENT DIABETES-MELLITUS; SUSCEPTIBILITY LOCUS; QUANTITATIVE TRAITS; VARIANCE-COMPONENTS; INSULIN-RESISTANCE; GENETIC-LINKAGE; WIDE SEARCH; MUTATIONS; OBESITY; NIDDM AB Type 2 diabetes mellitus is a common chronic disease that is thought to have a substantial genetic basis. Identification of the genes responsible has been hampered by the complex nature of the syndrome. Abnormalities in insulin secretion and insulin action predict the development of type 2 diabetes and are, themselves, highly heritable traits. Since fewer genes may contribute to these precursors of type 2 diabetes than to the overall syndrome, such genes may be easier to identify. We, therefore, undertook an autosomal genomic scan to identify loci linked to prediabetic traits in Pima Indians, a population with a high prevalence of type 2 diabetes. 363 nondiabetic Pima Indians were genotyped at 516 polymorphic microsatellite markers on all 22 autosomes, Linkage analyses were performed using three methods (single-marker, nonparametric multipoint [MAPMAKER/SIBS], and variance components multipoint). These analyses provided evidence for linkage at several chromosomal regions, including 3q21-24 linked to fasting plasma insulin concentration and in vivo insulin action, 4p15-q12 linked to fasting plasma insulin concentration, 9q21 linked to 2-h insulin concentration during oral glucose tolerance testing, and 22q12-13 linked to fasting plasma glucose concentration. These results suggest loci that may harbor genes contributing to type 2 diabetes in Pima Indians. None of the linkages exceeded a LOD score of 3.6 (a 5% probability of occurring in a genome-wide scan). These findings must, therefore, be considered tentative until extended in this population or replicated in others. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85016 USA. Sequana Therapeut Inc, Dept Stat Genet, La Jolla, CA 92037 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. Indiana Univ, Sch Med, Dept Med Genet, Indianapolis, IN 46202 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Dept Med, Charleston, SC 29425 USA. RP Pratley, RE (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16Th St, Phoenix, AZ 85016 USA. RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NCRR NIH HHS [1P41-RR-03655]; NIDDK NIH HHS [DK-47461] NR 43 TC 173 Z9 183 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 15 PY 1998 VL 101 IS 8 BP 1757 EP 1764 DI 10.1172/JCI1850 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZJ234 UT WOS:000073193000027 PM 9541507 ER PT J AU Barger, AJ Hart, AC Kaplan, JM AF Barger, AJ Hart, AC Kaplan, JM TI G alpha(s)-induced neurodegeneration in Caenorhabditis elegans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cell death; neurodegeneration; necrosis; signal transduction; G-protein; cAMP; mutant; Caenorhabditis elegans ID DEPENDENT PROTEIN-KINASE; PROGRAMMED CELL-DEATH; NUCLEOTIDE-GATED CHANNEL; GLR-1 GLUTAMATE-RECEPTOR; BETA-TUBULIN GENE; C-ELEGANS; SYNAPTIC TRANSMISSION; NEURONAL DEGENERATION; CALCIUM-CHANNEL; DROSOPHILA AB We describe a genetic model for neurodegeneration in the nematode Caenorhabditis elegans. Constitutive activation of the GTP-binding protein G alpha(s) induces neurodegeneration. Neuron loss occurs in two phases whereby affected cells undergo a swelling response in young larvae and subsequently die sometime during larval development. Different neural cell types vary greatly in their susceptibility to G alpha(s)-induced cytotoxicity, ranging from 0 to 88% of cells affected. Mutations that prevent programmed cell death do not prevent G alpha(s)-induced killing, suggesting that these deaths do not occur by apoptosis. Mutations in three genes protect against G alpha(s)-induced cell deaths. The acy-1 gene is absolutely required for neurodegeneration, and the predicted ACY-1 protein is highly similar (40% identical) to mammalian adenylyl cyclases. Thus, G(s)-induced neurodegeneration is mediated by the second messenger cAMP. Mutations in the unc-36 and eat-4 genes are partially neuroprotective, which indicates that endogenous signaling modulates the severity of the neurotoxic effects of G alpha(s). These experiments define an intracellular signaling cascade that triggers a necrotic form of neurodegeneration. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Kaplan, JM (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 361 Life Sci Addit, Berkeley, CA 94720 USA. FU NINDS NIH HHS [NS32196] NR 72 TC 87 Z9 113 U1 1 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD APR 15 PY 1998 VL 18 IS 8 BP 2871 EP 2880 PG 10 WC Neurosciences SC Neurosciences & Neurology GA ZF788 UT WOS:000072933300008 PM 9526004 ER PT J AU Kelly, K AF Kelly, K TI The power of perimenopause: A woman's guide to physical and emotional health during the transitional decade. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD APR 15 PY 1998 VL 123 IS 7 BP 106 EP 106 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA ZH489 UT WOS:000073116200164 ER PT J AU Bozkurt, B Kribbs, SB Clubb, FJ Michael, LH Didenko, VV Hornsby, PJ Seta, Y Oral, H Spinale, FG Mann, DL AF Bozkurt, B Kribbs, SB Clubb, FJ Michael, LH Didenko, VV Hornsby, PJ Seta, Y Oral, H Spinale, FG Mann, DL TI Pathophysiologically relevant concentrations of tumor necrosis factor-alpha promote progressive left ventricular dysfunction and remodeling in rats SO CIRCULATION LA English DT Article DE heart failure; remodeling; contractility; cytokines ID CHRONIC HEART-FAILURE; SUPRAVENTRICULAR TACHYCARDIA; FACTOR CHALLENGES; CONSCIOUS DOGS; NITRIC-OXIDE; INFUSION; ENDOTHELIN; RECEPTORS; ENDOTOXIN; CYTOKINES AB Background-Although patients with heart failure express elevated circulating levels of tumor necrosis factor-alpha (TNF-alpha) in their peripheral circulation, the structural and functional effects of circulating levels of pathophysiologically relevant concentrations of TNF-alpha on the heart are not known. Methods and Results-Osmotic infusion pumps containing either diluent or TNF-alpha were implanted into the peritoneal cavity of rats. The rate of TNF-alpha infusion was titrated to obtain systemic levels of biologically active TNF-alpha comparable to those reported in patients with heart failure (approximate to 80 to 100 U/mL), and the animals were examined serially for 15 days. Two-dimensional echocardiography was used to assess changes in left ventricular (LV) structure (remodeling) and LV function. Video edge detection was used to assess isolated cell mechanics, and standard histological techniques were used to assess changes in the volume composition of LV cardiac myocytes and the extracellular matrix, The reversibility of cytokine-induced effects was determined either by removal of the osmotic infusion pumps on day 15 or by treatment of the animals with a soluble TNF-alpha antagonist (TNFR:Fc). The results of this study show that a continuous infusion of TNF-alpha led to a time-dependent depression in LV function, cardiac myocyte shortening, and LV dilation that were at least partially reversible by removal of the osmotic infusion pumps or treatment of the animals with TNFR:Fc. Conclusions-These studies suggest that pathophysiologically relevant concentrations of TNF-alpha are sufficient to mimic certain aspects of the phenotype observed in experimental and clinical models of heart failure. C1 Vet Adm Med Ctr, Dept Med, Cardiol Sect, Houston, TX 77211 USA. Baylor Coll Med, Huffington Ctr Aging, Dept Cell Biol, Houston, TX 77030 USA. Med Univ S Carolina, Dept Surg, Charleston, SC 29425 USA. Texas Heart Inst, Houston, TX 77025 USA. RP Mann, DL (reprint author), VA Med Ctr, Cardiol Res 151C, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM dmann@bcm.tmc.edu OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [R29-HL-52910, P50-HL-06H] NR 55 TC 541 Z9 583 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 14 PY 1998 VL 97 IS 14 BP 1382 EP 1391 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZG811 UT WOS:000073042200010 PM 9577950 ER PT J AU Casasnovas, JM Stehle, T Liu, JH Wang, JH Springer, TA AF Casasnovas, JM Stehle, T Liu, JH Wang, JH Springer, TA TI A dimeric crystal structure for the N-terminal two domains of intercellular adhesion molecule-1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN RHINOVIRUS; ICAM-1; BINDING; RECEPTOR; INTEGRIN; LFA-1; SURFACE; SITE; NEUTRALIZATION; RESIDUES AB The 3.0-Angstrom structure of a 190-residue fragment of intercellular adhesion molecule-1 (ICAM-1, CD54) reveals two tandem Ig-superfamily (IgSF) domains. Each of two independent molecules dimerizes identically with a symmetry-related molecule over a hydrophobic interface on the BED sheet of domain 1, in agreement with dimerization of ICAM-1 on the cell surface. The residues that bind to the integrin LFA-1 are well oriented for bivalent binding in the dimer, with the critical Glu-34 residues pointing away from each other on the periphery. Residues that bind to rhinovirus are in the flexible BC and FG loops at the tip of domain 1, and these and the upper half of domain 1 are web exposed in the dimer for docking to virus. By contrast, a residue important for binding to Plasmodium falciparum-infected erythrocytes is in the dimer interface. The presence of A' strands in both domains 1 and 2, conserved hydrogen bonds at domain junctions, and elaborate hydrogen bond networks around the key integrin binding residues in domain 1 make these domains suited to resist tensile forces during adhesive interactions. A subdivision of the intermediate (I) set of IgSF domains is proposed in which domain 1 of ICAM-1 and previously described I set domains belong to the I1 set and domain 2 of ICAM-1, ICAM-2, and vascular cell adhesion molecule-1 belong to the I2 set. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Springer, TA (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. RI Casasnovas, Jose/L-6299-2014 OI Casasnovas, Jose/0000-0002-2873-6410 FU NHLBI NIH HHS [HL-48675, P01 HL048675]; NIAID NIH HHS [AI31921] NR 40 TC 159 Z9 162 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 1998 VL 95 IS 8 BP 4134 EP 4139 DI 10.1073/pnas.95.8.4134 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800014 PM 9539702 ER PT J AU Kim, JB Wright, HM Wright, M Spiegelman, BM AF Kim, JB Wright, HM Wright, M Spiegelman, BM TI ADD1/SREBP1 activates PPAR gamma through the production of endogenous ligand SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fatty acid metabolism; nuclear hormone receptor; adipocyte differentiation ID ENHANCER-BINDING-PROTEIN; PROMOTES ADIPOCYTE DIFFERENTIATION; STEROL REGULATORY ELEMENT; LEUCINE ZIPPER PROTEIN; TRANSCRIPTION FACTOR; GENE-EXPRESSION; ECTOPIC EXPRESSION; ADIPOGENESIS; ALPHA; PROGRAM AB Adipose differentiation is an important part of the energy homeostasis system of higher organisms. Recent data have suggested that this profess is controlled by an interplay of transcription factors including PPAR gamma, the C/EBPs, and ADD1/SREBP1. Although these factors interact functionally to initiate the program of differentiation, there are no data concerning specific mechanisms of interaction. We show here that the expression of ADD1/SREBP1 specifically increases the activity of PPAR gamma but not other isoforms, PPAR alpha, or PPAR delta. This activation occurs through the ligand-binding domain of PPAR gamma when it is fused to the DNA-binding domain of Gal4. The stimulation of PPAR gamma by ADD1/SREBP1 does not require coexpression in the same cells; supernatants from cultures that express ADD1/SREBP1 augment the transcriptional activity of PPAR gamma, Finally, we demonstrate directly that cells expressing ADD1/SREBP1 produce and secrete lipid molecule(s) that hind directly to PPAR gamma, displacing the binding of radioactive thiazolidinedione ligands, These data establish that ADD1/SREBP1 can control the production of endogenous ligand(s) for PPAR gamma and suggest a mechanism for coordinating the actions of these adipogenic factors. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Bruce-Spiegelman@dfci.harvard.edu FU NIDDK NIH HHS [2R37DK31405, R37 DK031405] NR 28 TC 399 Z9 427 U1 2 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 1998 VL 95 IS 8 BP 4333 EP 4337 DI 10.1073/pnas.95.8.4333 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800049 PM 9539737 ER PT J AU Hobbs, SK Monsky, WL Yuan, F Roberts, WG Griffith, L Torchilin, VP Jain, RK AF Hobbs, SK Monsky, WL Yuan, F Roberts, WG Griffith, L Torchilin, VP Jain, RK TI Regulation of transport pathways in tumor vessels: Role of tumor type and microenvironment SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VASCULAR-PERMEABILITY FACTOR; ENDOTHELIAL GROWTH-FACTOR; HUMAN ADENOCARCINOMA LS174T; MICROVASCULAR PERMEABILITY; BLOOD-VESSELS; SOLID TUMORS; SCID MICE; ANGIOGENESIS; ALBUMIN; HYPERPERMEABILITY AB Novel anti-neoplastic agents such as gene targeting vectors and encapsulated carriers are quite large (approximately 100-300 nm in diameter). An understanding of the functional size and physiological regulation of transvascular pathways is necessary to optimize delivery of these agents. Here we analyze the functional limits of transvascular transport and its modulation by the microenvironment. One human and five murine tumors including mammary and colorectal carcinomas, hepatoma, glioma, and sarcoma were implanted in the dorsal skin-fold chamber or cranial window, and the pore cutoff size, a functional measure of transvascular gap size, was determined. The microenvironment was modulated: (i) spatially, by growing tumors in subcutaneous or cranial locations and (ii) temporally, by inducing vascular regression in hormone-dependent tumors. Tumors grown subcutaneously exhibited a characteristic pore cutoff size ranging from 200 nm to 1.2 mu m. This pore cutoff size was reduced in tumors grown in the cranium or in regressing tumors after hormone withdrawal. Vessels induced in basic fibroblast growth factor containing gels had a pore cutoff size of 200 nm. Albumin permeability was independent of pore cutoff size. These results have three major implications for the delivery of therapeutic agents: (i) delivery may be less efficient in cranial tumors than in subcutaneous tumors, (ii) delivery may be reduced during tumor regression induced by hormonal ablation, and (iii) permeability to a molecule is independent of pore cutoff size as long as the diameter of the molecule is much less than the pore diameter. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA 02138 USA. Beth Israel Deaconess Med Ctr, Dept Radiol Sci, Boston, MA 02215 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab, 100 Blossom St,Cox-7, Boston, MA 02114 USA. RI Yuan, Fan/A-1287-2011 FU NCI NIH HHS [R35-CA56591] NR 41 TC 1257 Z9 1317 U1 24 U2 179 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 14 PY 1998 VL 95 IS 8 BP 4607 EP 4612 DI 10.1073/pnas.95.8.4607 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZH535 UT WOS:000073120800097 PM 9539785 ER PT J AU Shuler, CL Allison, N Holcomb, S Harlan, M McNeill, J Robinett, G Bagby, SP AF Shuler, CL Allison, N Holcomb, S Harlan, M McNeill, J Robinett, G Bagby, SP TI Accuracy of an automated blood pressure device in stable inpatients - Optimum vs routine use SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HYPERTENSION AB Background: Despite widespread use of the automated blood pressure (BP) device (IVAC model +200, IVAC Corporation, San Diego, Calif), there is little formal validation in the literature on its accuracy. Objective: To assess the accuracy of the IVAC 4200 device, both under standardized conditions and as routinely used by ward staff, compared with the true indirect BP measured by mercury manometer (MM). Methods: One hundred forty-five stable inpatients were randomly selected for BP measurements by 3 randomly ordered protocols: (1) MM performed by certified investigators, (2) IVAC 4200 BP performed by trained investigators (research automated [RA]), and (3) IVAC 4200 BP performed by ward personnel (ward automated [WA]). Results: For RA compared with MM ("true" indirect BP), 59% of systolic and 54% of diastolic readings were within 5 mm Hg and 83% of systolic and 86% of diastolic were within 10 mm Hg for a British Hypertension Society grade C for both. For WA compared with MM, 40% of systolic and 50% of diastolic readings were within 5 mm Hg and 70% of systolic and 80% of diastolic readings were within 10 mm Hg for British Hypertension Society grades D and C, respectively. The presence of arrhythmias and/or low K5 values (fifth phase of Korotkoff sounds <30 mm Hg) significantly increased the inaccuracy for diastolic values. Inappropriate cuff selection significantly increased inaccuracy of systolic BP (WA vs MM). Conclusions: The IVAC 4200 yields substandard estimates of systolic and diastolic BP even under standardized, thus optimum conditions. The presence of arrythmias or low K5 values and the selection of inappropriate cuff size by the ward staff also contributed to inaccuracy. C1 Dept Vet Affairs, Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Bagby, SP (reprint author), Portland Vet Affairs Med Ctr, Dept Med, 111C,3710 SW Vet Hosp Rd,POB 1034, Portland, OR 97207 USA. NR 12 TC 23 Z9 23 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD APR 13 PY 1998 VL 158 IS 7 BP 714 EP 721 DI 10.1001/archinte.158.7.714 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZH209 UT WOS:000073083800005 PM 9554677 ER PT J AU Takeshita, H Kusuzaki, K Ashihara, T Gebhardt, MC Mankin, HJ Hirasawa, Y AF Takeshita, H Kusuzaki, K Ashihara, T Gebhardt, MC Mankin, HJ Hirasawa, Y TI Actin organization associated with the expression of multidrug resistant phenotype in osteosarcoma cells and the effect of actin depolymerization on drug resistance SO CANCER LETTERS LA English DT Article DE differentiation; microfilament; multidrug resistance; osteosarcoma; P-glycoprotein ID P-GLYCOPROTEIN EXPRESSION; GENE AB We have previously reported that P-glycoprotein (Pgp)-overexpressing, multidrug resistant (MDR) osteosarcoma cells were functionally more differentiated than their parent cells. The present study showed that in the parent cells, the actin filaments were sparsely distributed or were diffusely spread throughout the cytoplasm, whereas the MDR osteosarcoma cells exhibited a remarkable increase in well-organized actin stress fibers. Furthermore, dihydrocytochalasin B, a specific inhibitor of actin polymerization, dramatically disrupted this network of stress fibers, increased the intracellular accumulation of doxorubicin (DOX) and modified the resistance against DOX. These results indicate that the organization of actin filaments associated with cellular differentiation may be involved in the expression of Pgp function in the MDR osteosarcoma cells. (C) 1998 Elsevier Science ireland Ltd. C1 Otsu Municipal Hosp, Dept Orthopaed Surg, Otsu, Shiga 520, Japan. Kyoto Prefectural Univ Med, Dept Orthopaed Surg, Kyoto 602, Japan. Kyoto Prefectural Univ Med, Dept Pathol 1, Kyoto 602, Japan. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Takeshita, H (reprint author), Otsu Municipal Hosp, Dept Orthopaed Surg, 2 Chome, Otsu, Shiga 520, Japan. NR 20 TC 25 Z9 26 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD APR 10 PY 1998 VL 126 IS 1 BP 75 EP 81 DI 10.1016/S0304-3835(97)00539-9 PG 7 WC Oncology SC Oncology GA ZD970 UT WOS:000072744000011 PM 9563651 ER PT J AU Pahlavani, MA Harris, MD Richardson, A AF Pahlavani, MA Harris, MD Richardson, A TI Activation of p21(ras)/MAPK signal transduction molecules decreases with age in mitogen-stimulated T cells from rats SO CELLULAR IMMUNOLOGY LA English DT Article ID PROTEIN-TYROSINE KINASE; MURINE LYMPHOCYTES-T; ANTIGEN RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; MAP KINASES; OLD MICE; PHOSPHORYLATION; RAS; PROLIFERATION; EXPRESSION AB Signal transduction is ubiquitously involved in the initiation of physiological signals that lead to growth and proliferation of cells. The signaling cascade mediated by the mitogen-activated protein kinase (MAPK) is considered essential for T cell growth and function. Therefore, it was of interest to determine the influence of age on the induction of MAPK in mitogen-activated T cells. T cells from young (4-6 months) and old (24-26 months) rats responded to concanavalin A (Con A) stimulation by increasing MAPK, c-jun amino terminal kinase (JNK), and p21(ras) activities. The time course of induction of MAPK/JNK and p21(ras) activities was similar in T cells isolated from young and old rats. The induction of JNK activity did not change significantly with age; however, the induction of MAPK and p21(ras) activities was significantly less (50 to 65%) in T cells from old rats than in T cells from young rats. Although the relative protein levels of p42 and p44 MAPK did not change with age, the proportion of the phosphorylated p44 MAPK decreased with age. In addition, it was found that the in vitro kinase activities of the T cell receptor-associated protein tyrosine kinase Lck (p56(Lck)) and ZAP-70 but not Fyn (p59(Fyn)) were lower in T cells from old rats than in T cells from young rats. The decline in activities of these signaling molecules with age was not associated with changes in their corresponding protein levels. Thus, our results demonstrate that aging alters the activation of the signal transduction cascade that leads to T cell activation. (C) 1998 Academic Press. C1 Audie L Murphy Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Pahlavani, MA (reprint author), Audie L Murphy Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG00677, AG14088] NR 76 TC 37 Z9 38 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD APR 10 PY 1998 VL 185 IS 1 BP 39 EP 48 DI 10.1006/cimm.1998.1274 PG 10 WC Cell Biology; Immunology SC Cell Biology; Immunology GA ZU259 UT WOS:000074178700004 PM 9636681 ER PT J AU Richard, L Velasco, P Detmar, M AF Richard, L Velasco, P Detmar, M TI A simple immunomagnetic protocol for the selective isolation and long-term culture of human dermal microvascular endothelial cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID LEUKOCYTE ADHESION MOLECULE-1; NECROSIS-FACTOR-ALPHA; GROWTH-FACTOR; KERATINOCYTES INVITRO; TYROSINE KINASE; PROLIFERATION; EXPRESSION; RECEPTOR; IDENTIFICATION; MICROVESSELS AB Endothelial cells involved in tumor angiogenesis, wound healing, and inflammation are predominantly of microvascular origin and are functionally distinct from large vessel-derived endothelial cells which have been largely used for in vitro vascular research. To overcome the problems commonly involved in the culture of microvascular endothelial cells, including unreliable isolation techniques and low cell yields, we developed a simplified protocol for the selective cultivation of human dermal microvascular endothelial cells (HDMEC) obtained from neonatal foreskins, based on the transient, endothelial cell-specific induction of E-selectin by tamer necrosis factor-alpha (TNF-alpha). Subconfluent primary cultures, consisting of a mixture of endothelial cells, fibroblasts, and keratinocytes, were treated with TNF-alpha for 6 h, and HDMEC were isolated by their selective binding to magnetic beads coupled with anti-E-selectin monoclonal antibody. After two immunomagnetic purification steps, a homogenous population of HDMEC was obtained which showed typical cobblestone morphology, expressed CD31 and von Willebrand factor, proliferated in response to vascular endothelial growth factor, upregulated the expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1 in response to TNF-alpha and formed capillary-like tubes in a three-dimensional collagen type I matrix. This simple technique may facilitate a more widespread use of microvascular endothelial cell cultures obtained from different human or animal organs for functional in vitro studies. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Detmar, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp E, CBRC,Dept Dermatol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM mdetmar@cbrc.mgh.harvard.edu FU NCI NIH HHS [CA69184] NR 29 TC 100 Z9 107 U1 2 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 10 PY 1998 VL 240 IS 1 BP 1 EP 6 DI 10.1006/excr.1998.3936 PG 6 WC Oncology; Cell Biology SC Oncology; Cell Biology GA ZK186 UT WOS:000073294000001 PM 9570915 ER PT J AU Bartzokis, G Altshuler, LL Greider, T Curran, J Keen, B Dixon, WJ AF Bartzokis, G Altshuler, LL Greider, T Curran, J Keen, B Dixon, WJ TI Reliability of medial temporal lobe volume measurements using reformatted 3D images SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE magnetic resonance imaging; methodology; temporal horn; hippocampus; amygdala ID ALZHEIMERS-DISEASE; HIPPOCAMPAL-FORMATION; COMPUTED-TOMOGRAPHY; BRAIN STRUCTURES; LONGITUDINAL CT; MR IMAGES; SCHIZOPHRENIA; ATROPHY; ABNORMALITIES; AMYGDALA AB The study assessed whether standardizing the angle of image display and controlling for head position in three planes affects the scan-rescan reliability of medial temporal lobe volume measures when very thin (1.5 mm) slices are used. Five volunteers were scanned two times oil consecutive days. A three-dimensional MRI sequence acquired whole brain data in 1.4 mm thick coronal slices. The data were displayed as 1.5 mm thick images and were rated both in the originally acquired coronal plane, and after reformatting to correct for head tilt and display the brain in the coronal plane perpendicular to the long axis of the left anterior hippocampus. One rater measured five brain regions (temporal lobe, anterior and posterior hippocampus, amygdala, and temporal horn) on the left and right sides of the two non-reformatted and two reformatted scans to obtain inter-scan variance. Furthermore, most scans were remeasured, to obtain 'reread' variances. All data were log-transformed in order to produce comparable variability across brain regions of different sizes. For all the regions, except the temporal horn, the non-reformatted scans showed significantly larger scan-rescan variability than the reformatted scans. A typical standard deviation for a non-reformatted pair of scans was 0.10, corresponding to 26% error, while a typical value for a reformatted pair of scans was 0.04, corresponding to 10% error. For all the regions, the reread data (intra-rater reliability) gave similar results for both reformatted and non-reformatted images with similar standard deviations (typical value for reread standard deviation was 0.020, corresponding to 5% error). The data suggest that, even when very thin slices are acquired, volume measurement accuracy of gray matter structures in the temporal lobe is considerably improved by controlling for image orientation in three planes. For these structures, the sample size needed to detect a small (5%) within-subject volume change would be halved if reformatted images were used. Image contrast is an additional important factor since the reformatted T-1 weighted images used in this study, which have suboptimal CSF/brain contrast, worsened measurement accuracy in the temporal horn. (C) 1998 Elsevier Science Ireland Ltd. C1 W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90074 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA 90074 USA. Gen Elect Med Syst, Milwaukee, WI 53188 USA. RP Bartzokis, G (reprint author), W Los Angeles Vet Affairs Med Ctr, Res Serv, 11301 Wilshire Blvd,Mail Code B-151H,Bldg 210,Rm, Los Angeles, CA 90073 USA. RI Bartzokis, George/K-2409-2013 NR 60 TC 52 Z9 53 U1 2 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 10 PY 1998 VL 82 IS 1 BP 11 EP 24 DI 10.1016/S0925-4927(98)00007-9 PG 14 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZT798 UT WOS:000074128500002 PM 9645547 ER PT J AU van Kammen, DP Petty, F Kelley, ME Kramer, GL Barry, EJ Yao, JK Gurklis, JA Peters, JL AF van Kammen, DP Petty, F Kelley, ME Kramer, GL Barry, EJ Yao, JK Gurklis, JA Peters, JL TI GABA and brain abnormalities in schizophrenia SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE ventricle-brain ratio (VBR); prefrontal sulcus; computed tomography; plasma; CSF ID GAMMA-AMINOBUTYRIC-ACID; MATTER VOLUME DEFICITS; POST-MORTEM BRAINS; PREFRONTAL CORTEX; BASAL GANGLIA; UPTAKE SITES; FUNCTIONAL ARCHITECTURE; ANTIPSYCHOTIC-DRUGS; AFFECTIVE-DISORDER; NUCLEUS-ACCUMBENS AB Some recent autopsy studies indicate that alpha-aminobutyric acid (GABA) function is decreased in brain areas that involve some of the well-described structural changes observed in schizophrenia. The current study examined the relationship between CSF and plasma GABA levels and brain structural measures in schizophrenia. Sixty-two drug-free, physically healthy male patients with schizophrenia (DSM-IIIR) were evaluated for plasma and CSF GABA, as well as brain structural measures on CT scans. Plasma levels of GABA were associated with prefrontal sulcal widening and VBRs, but not global sulcal widening in the schizophrenic patients. CSF GABA measures were not associated with brain structural measures, but were associated with age and age of onset. The significant relationship between plasma GABA, but not CSF GABA, and specific brain morphology measures in schizophrenic patients suggests that if GABA transmission is impaired in schizophrenia, it is a local, but not global, phenomenon. (C) 1998 Elsevier Science Ireland Ltd. C1 VA Pittsburgh Healthcare Syst, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. VA N Texas Healthcare Syst, Dallas, TX 75216 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75216 USA. RP van Kammen, DP (reprint author), VA Pittsburgh Healthcare Syst, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM dpvk@pitt.edu FU NIMH NIH HHS [MH-41115, MH-44841] NR 86 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 10 PY 1998 VL 82 IS 1 BP 25 EP 35 DI 10.1016/S0925-4927(98)00006-7 PG 11 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZT798 UT WOS:000074128500003 PM 9645548 ER PT J AU Kharbanda, S Pandey, P Morris, PL Whang, Y Xu, YH Sawant, S Zhu, LJ Kumar, N Yuan, ZM Weichselbaum, R Sawyers, CL Pandita, TK Kufe, D AF Kharbanda, S Pandey, P Morris, PL Whang, Y Xu, YH Sawant, S Zhu, LJ Kumar, N Yuan, ZM Weichselbaum, R Sawyers, CL Pandita, TK Kufe, D TI Functional role for the c-Abl tyrosine kinase in meiosis I SO ONCOGENE LA English DT Article DE meiosis; c-Abl; spermatogenesis ID ACTIVATED PROTEIN-KINASE; STRESS-RESPONSE; CELLS; MOUSE; GENE; MICE; P53; RECOMBINATION; EXPRESSION; LETHALITY AB The c-Abl tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents. The DNA-dependent protein kinase (DNA-PK) and the ataxia telangiectasia mutated (ATM) gene product, effecters in the DNA damage response, contribute to the induction of c-Abl activity. The present study demonstrates that c-Abl is expressed in mouse and rat testes, and predominantly in pachytene spermatocytes of meiosis I. The results also demonstrate that c-Abl interacts directly with meiotic chromosomes. In concert with a requirement for c-Abl at the pachytene stage, me show that, in contrast to wild-type mice, testes from Abl(-/-) mice exhibit defects in spermatogenesis. These findings provide the first demonstration that c-Abl plays a functional role in meiosis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Populat Council, Ctr Biomed Res, New York, NY 10021 USA. Rockefeller Univ, New York, NY 10021 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90095 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Columbia Univ, Ctr Radiol Res, New York, NY 10032 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Sawyers, Charles/G-5327-2016 FU NCI NIH HHS [CA42802, CA55241, CA75216] NR 33 TC 32 Z9 35 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 9 PY 1998 VL 16 IS 14 BP 1773 EP 1777 DI 10.1038/sj.onc.1201934 PG 5 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZG368 UT WOS:000072994600001 PM 9583675 ER PT J AU Huang, MS Adebanjo, O Moonga, BS Goldstein, S Lai, FA Lipschitz, DA Zaidi, M AF Huang, MS Adebanjo, O Moonga, BS Goldstein, S Lai, FA Lipschitz, DA Zaidi, M TI Upregulation of functional ryanodine receptors during in vitro aging of human diploid fibroblasts SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID INTRACELLULAR CALCIUM; INOSITOL TRISPHOSPHATE; ALZHEIMER DONORS; AGE; SENESCENCE; CHANNEL; MUSCLE; CELLS AB We demonstrate for the first time that cellular aging in vitro is accompanied by a dramatic elevation in the levels of ryanodine receptor-bearing Ca2+ channels. These channels normally reside within microsomal membranes and gate Ca2+ release from intracellular stores. We therefore measured cytosolic Ca2+ levels in 'young' (30 mean population doublings, MPDs) and 'senescent' (53 to 58 MPDs) human diploid fibroblasts (HDFs). Application of the known. ryanodine receptor modulators, caffeine or cyclic adenosine diphosphate-ribose (cADPr), triggered cytosolic Ca2+ signals in both young and senescent cells. The signal magnitude however was significantly greater in senescent compared with young HDFs. In parallel, incubation with a highly specific anti-ryanodine receptor antiserum resulted in specific immunofluorescence only in senescent HDPs. We envisage that elevated levels of functional ryanodine receptors may underlie the defective Ca2+ handling and cellular degeneration that occurs with aging. (C) 1998 Academic Press. C1 Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. Vet Affairs Med Ctr, Ctr Osteoporosis & Skeletal Aging, Philadelphia, PA 19104 USA. Allegheny Univ Hlth Sci, Med Coll Penn Hahnemann Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. Natl Inst Med Res, MRC, London NW7 1AA, England. RP Huang, MS (reprint author), Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. FU NIA NIH HHS [R01 AG14917-02] NR 18 TC 5 Z9 5 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 7 PY 1998 VL 245 IS 1 BP 50 EP 52 DI 10.1006/bbrc.1998.8392 PG 3 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZK045 UT WOS:000073279400009 PM 9535781 ER PT J AU Stafford, RS Singer, DE AF Stafford, RS Singer, DE TI Recent national patterns of warfarin use in atrial fibrillation SO CIRCULATION LA English DT Article DE atrial fibrillation; anticoagulants; physician practice patterns ID ANTICOAGULATION; PREVENTION AB Background-Studies of selected populations suggest that anticoagulation in atrial fibrillation is underused and that nonclinical factors influence the use of this stroke-preventing therapy. We wished to examine recent national trends and predictors of warfarin sodium use in atrial fibrillation. Methods and Results-A nationally representative sample of office visits from the 1989 to 1996 National Ambulatory Medical Care Surveys was used. We selected 1125 visits by patients with atrial fibrillation, including 877 visits to cardiologists and primary care physicians in which apparent contraindications for anticoagulation were absent. The principal outcome measure was the proportion of visits with warfarin reported. We analyzed trends in warfarin use and statistically evaluated the predictors of warfarin use. Warfarin use increased from 13% of atrial fibrillation visits in 1989 to 40% in 1993 (P for trend <.001) in patients without contraindications. Between 1993 and 1996, however, there was no change in warfarin use. Independent of other factors, warfarin was significantly more likely to be reported in patients with a history of stroke and in patients residing outside of the South. Conclusions-Warfarin use in atrial fibrillation has not increased recently, indicating inadequate implementation of this highly effective therapy. Barriers to anticoagulation in real-world clinical practice need to be identified and addressed. C1 Massachusetts Gen Hosp, Med Serv, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Stafford, RS (reprint author), 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM stafford@sol.mgh.harvard.edu FU NHLBI NIH HHS [K08-HL-03548] NR 23 TC 163 Z9 166 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 7 PY 1998 VL 97 IS 13 BP 1231 EP 1233 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZF824 UT WOS:000072936900005 PM 9570191 ER PT J AU Jones, SD Marasco, WA AF Jones, SD Marasco, WA TI Antibodies for targeted gene therapy: extracellular gene targeting and intracellular expression SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE antibody engineering; targeted immunotherapy; gene delivery; intracellular immunization ID SINGLE-CHAIN ANTIBODY; RICIN-A-CHAIN; HEMATOPOIETIC STEM-CELLS; GROWTH-FACTOR RECEPTOR; POLYMERIC IMMUNOGLOBULIN RECEPTOR; AMYOTROPHIC-LATERAL-SCLEROSIS; SIMPLEX VIRUS VECTORS; LONG-TERM CULTURE; TRANSFER IN-VIVO; BONE-MARROW AB Antibody genes of human origin and human antibodies directed against human proteins have become widely available in recent years. These are valuable reagents for gene therapy applications, in which the use of human proteins and genes allows for increased therapeutic benefit. Engineered human antibodies can be used in gene therapy both as a component of a gene delivery system and as a therapeutic gene. As the targeting moiety of a gene delivery system, the antibody should meet certain criteria that have been previously determined from other clinical applications of antibodies. These include bioavailability, specificity for the target cell, and rapid clearance. In addition, if repeat delivery of therapeutic genes is going to be needed, then gene delivery vectors should be non-immunogenic to allow repeated administration. The use of human antibodies in this application should therefore be superior to approaches which use rodent-derived antibodies. Another application of antibodies in gene therapy is the use of antibodies expressed inside the cell (intrabodies) as therapeutic agents. The power of the immune system to rearrange a limited set of genes to create recognition sites for any known molecule is well documented. The ability to harness this information and use these highly specific binding molecules as medicines to inhibit an unwanted cellular function is a promising advance in the field of molecular medicine, and in particular, in the field of intracellular immunization. (C) 1998 Elsevier Science B.V. C1 Intraimmune Therapies Inc, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. RP Jones, SD (reprint author), Intraimmune Therapies Inc, POB 15599, Boston, MA 02215 USA. NR 100 TC 11 Z9 13 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD APR 6 PY 1998 VL 31 IS 1-2 BP 153 EP 170 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZL317 UT WOS:000073420500010 ER PT J AU Schwartz, PJ Reaume, A Scott, R Coyle, JT AF Schwartz, PJ Reaume, A Scott, R Coyle, JT TI Effects of over- and under-expression of Cu,Zn-superoxide dismutase on the toxicity of glutamate analogs in transgenic mouse striatum SO BRAIN RESEARCH LA English DT Article DE excitotoxicity; oxidative stress; glutamate toxicity; superoxide dismutase ID CU/ZN-SUPEROXIDE-DISMUTASE; AMYOTROPHIC-LATERAL-SCLEROSIS; FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE; GENE-EXPRESSION; PC12 CELLS; MICE; NEUROTOXICITY; PEROXYNITRITE; NEURONS AB Considerable evidence suggests that reactive oxygen species mediate the neurotoxic effects of ionotropic glutamate receptor activation. Accordingly, we have examined neuronal degeneration resulting from intrastriatal injection of quinolinic acid, an NMDA receptor agonist, and kainic acid in gene targeted and transgenic mice that under-or over-express copper, zinc superoxide dismutase (Cu,Zn-SOD; SOD-1), Elevated SOD-1 activity significantly protects against quinolinic acid and kainic acid neurotoxicity in the mouse striatum whereas reduced activity appears to potentiate neurotoxicity. Thus a 'gene-dose' effect of SOD-1 has been demonstrated with regard to excitotoxic mechanisms. (C) 1998 Elsevier Science B.V. C1 Massachusetts Gen Hosp, Lab Mol & Dev Neurosci, CNY 2, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Cephalon, W Brandywine, PA USA. RP Coyle, JT (reprint author), Harvard Univ, McLean Hosp, Sch Med, Dept Psychiat, 115 Mill St, Belmont, MA 02178 USA. FU NIMH NIH HHS [P01-MH46529-02]; NINDS NIH HHS [R01-NS13584-15, R01-NS18414-10] NR 49 TC 41 Z9 41 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 APR 6 PY 1998 VL 789 IS 1 BP 32 EP 39 DI 10.1016/S0006-8993(97)01469-8 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZL056 UT WOS:000073394400004 PM 9602043 ER PT J AU Mannion, RJ Doubell, TP Gill, H Woolf, CJ AF Mannion, RJ Doubell, TP Gill, H Woolf, CJ TI Deafferentation is insufficient to induce sprouting of A-fibre central terminals in the rat dorsal horn SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE sensory neuron; rhizotomy; denervation; spinal cord; pain ID PRIMARY SENSORY NEURONS; NERVE GROWTH-FACTOR; LUMBAR SPINAL-CORD; CHOLERAGENOID-HORSERADISH-PEROXIDASE; PRIMARY AFFERENT NEURONS; GENE-RELATED PEPTIDE; SCIATIC-NERVE; ADULT-RAT; PERIPHERAL-NERVE; LAMINA-II AB The mechanism by which A-fibres sprout into lamina II of the dorsal horn of the adult rat after peripheral nerve injury, a region which normally receives input from noci- and thermoreceptive C-fibres alone, is not known. Recent findings indicating that selective C-fibre injury and subsequent degenerative changes in this region are sufficient to induce sprouting of uninjured A-fibres have raised the possibility that the structural reorganisation of A-fibre terminals is an example of collateral sprouting, in that deafferentation of C-fibre terminals alone in lamina II may be sufficient to cause A-fibre sprouting. Primary afferents of the sciatic nerve have their cell bodies located predominantly in the L4 and L5 dorsal root ganglia (DRGs), and the A-fibres of each DRG have central termination fields that show an extensive rostrocaudal overlap in lamina III in the L4 and L5 spinal segments. In this study, we have found that C-fibres from either DRG have central terminal fields that overlap much less in lamina II than A-fibres in lamina III. We have exploited this differential terminal organisation to produce deafferentation in lamina II of the L5 spinal segment, by an L5 rhizotomy, and then test whether A-fibres of the intact L4 dorsal root ganglion, which terminate within the L5 segment, sprout into the denervated lamina II in the L5 spinal segment. Neither intact nor peripherally injured A-fibres were seen to sprout into denervated lamina II after L5 rhizotomy. Sprouting was only ever seen into regions of lamina II containing the terminals of peripherally injured C-fibres. Therefore, it seems that the creation of synaptic space within lamina II is not the explanation for A-fibre sprouting after peripheral nerve section or crush, emphasising that injury-induced changes in C-fibres and subsequent chemotrophic effects in the superficial dorsal horn are the likely explanation. (C) 1998 Wiley-Liss, Inc. C1 Univ London Univ Coll, Dept Anat & Dev Biol, London WC1E 6BT, England. RP Woolf, CJ (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 4309, Charlestown, MA 02129 USA. OI doubell, timothy/0000-0003-1054-5592 NR 63 TC 29 Z9 31 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 6 PY 1998 VL 393 IS 2 BP 135 EP 144 DI 10.1002/(SICI)1096-9861(19980406)393:2<135::AID-CNE1>3.0.CO;2-3 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA ZC820 UT WOS:000072621400001 PM 9548693 ER PT J AU Gandhi, RT Chen, BK Straus, SE Dale, JK Lenardo, MJ Baltimore, D AF Gandhi, RT Chen, BK Straus, SE Dale, JK Lenardo, MJ Baltimore, D TI HIV-1 directly kills CD4(+) T cells by a Fas-independent mechanism SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVATION-INDUCED APOPTOSIS; LYMPHOPROLIFERATIVE SYNDROME; NORMAL INDIVIDUALS; LIGAND EXPRESSION; LYMPH-NODES; IN-VIVO; LYMPHOCYTES; INFECTION; DEATH AB The mechanism by which HIV-1 induces CD4(+) T cell death is not known. A fundamental issue is whether HIV-1 primarily induces direct killing of infected cells or indirectly causes death of uninfected bystander cells. This question was studied using a reporter virus system in which infected cells are marked with the cell surface protein placental alkaline phosphatase (PLAP). Infection by HIV-PLAP of peripheral blood mononuclear cells (PBMCs) and T cell lines leads to rapid depletion of CD4(+) T cells and induction of apoptosis. The great majority of HIV-induced T cell death in vitro involves direct loss of infected cells rather than indirect effects on uninfected bystander cells. Because of its proposed role in HIV-induced cell death, we also examined die Fas (CD95/Apo1) pathway in killing of T cells by HIV-1. Infected PBMCs or CEM cells display no increase in surface Fas relative to uninfected cells. In addition, HIV-1 kills CEM and Jurkat T cells in the presence of a caspase inhibitor that completely blocks Fas-mediated apoptosis. HIV-1 also depletes CD4(+) T cells in PBMCs from patients who have a genetically defective Fas pathway. These results suggest that HIV-1 induces direct apoptosis of infected cells and kills T cells by a Fas-independent mechanism. C1 CALTECH, Pasadena, CA 91125 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Rockefeller Univ, New York, NY 10021 USA. NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Baltimore, D (reprint author), CALTECH, Pasadena, CA 91125 USA. FU NIAID NIH HHS [1 K08 AI-01443-01]; NIGMS NIH HHS [GM07739, T32 GM007739] NR 47 TC 138 Z9 142 U1 1 U2 8 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 6 PY 1998 VL 187 IS 7 BP 1113 EP 1122 DI 10.1084/jem.187.7.1113 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZH131 UT WOS:000073075900014 PM 9529327 ER PT J AU Le Doux, JM Morgan, JR Yarmush, ML AF Le Doux, JM Morgan, JR Yarmush, ML TI Removal of proteoglycans increases efficiency of retroviral gene transfer SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE recombinant retroviruses; gene therapy; proteoglycans; glycosaminoglycans; transduction efficiency; virus concentration ID VESICULAR-STOMATITIS-VIRUS; HERPES-SIMPLEX VIRUS; HEPARAN-SULFATE PROTEOGLYCANS; HUMAN-IMMUNODEFICIENCY-VIRUS; PACKAGING CELL-LINES; APE LEUKEMIA-VIRUS; RECOMBINANT RETROVIRUSES; THERAPY; BINDING; VECTOR AB We have previously shown that medium conditioned by virus producer cells inhibits retrovirus transduction, and that a portion of the inhibitory activity is sensitive to chondroitinase ABC. In this study, we have quantitatively evaluated the fraction of the inhibitory activity that is due to chondroitinase ABC-sensitive material and partially characterized the inhibitors. The kinetics of chondroitinase ABC digestion of glycosaminoglycans and virus inhibitory activity in cell culture medium were measured, and the results used to estimate the amount of the chondroitinase ABC-sensitive virus inhibitory activity that was initially in the medium. We found that up to 76% of the inhibitory activity of medium conditioned by packaging cells derived from NIH 3T3 cells is sensitive to chondroitinase ABC. The remainder of the inhibitory activity is not sensitive to other glycosaminoglycan lyases (heparitinase I or heparinase I), which suggests that substances other than glycosaminoglycans or proteoglycans are present in virus stocks and inhibit transduction. To further characterize the inhibitors, proteoglycans from conditioned medium were purified by batch anion exchange and size exclusion chromatography. Two major size groups (100 kDa and 950 kDa) of proteoglycans were isolated. Transduction was inhibited 50% by 0.6 mu g/mL of the high-molecular-weight proteoglycan or by 1.7 mu g/mL of the low-molecular-weight proteoglycan. Significantly, the proteoglycans, because of their large size and poor sieving properties, coconcentrated with virus particles concentrated by ultrafiltration and prevented any significant increases in transduction efficiency. Transduction efficiencies of virus stocks were increased more than tenfold by ultrafiltration, but only when the concentrated virus was treated with chondroitinase ABC. (C) 1998 John Wiley & Sons, Inc. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Surg Serv, Boston, MA 02114 USA. Rutgers State Univ, Dept Chem & Biochem Engn, Piscataway, NJ USA. Massachusetts Gen Hosp, Shriners Burns Inst, Boston, MA 02114 USA. RP Yarmush, ML (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Bigelow 1401, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 FU NIAMS NIH HHS [R29 AR42012]; NICHD NIH HHS [P01 HD28528]; NIGMS NIH HHS [GM-08339] NR 35 TC 34 Z9 34 U1 0 U2 1 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD APR 5 PY 1998 VL 58 IS 1 BP 23 EP 34 DI 10.1002/(SICI)1097-0290(19980405)58:1<23::AID-BIT3>3.0.CO;2-W PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA YY231 UT WOS:000072126400003 PM 10099258 ER PT J AU Rose, DJ Babich, J Fischman, A Graham, W Zubieta, J AF Rose, DJ Babich, J Fischman, A Graham, W Zubieta, J TI X-ray crystal structure and biodistribution of NS3 complexes of In and Ga SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02214 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 332-INOR BP U796 EP U796 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414402559 ER PT J AU Yuan, ZM Utsugisawa, T Ishiko, T Nakada, S Huang, YY Kharbanda, S Weichselbaum, R Kufe, D AF Yuan, ZM Utsugisawa, T Ishiko, T Nakada, S Huang, YY Kharbanda, S Weichselbaum, R Kufe, D TI Activation of protein kinase C delta by the c-Abl tyrosine kinase in response to ionizing radiation SO ONCOGENE LA English DT Article DE protein kinase C delta; c-Abl tyrosine kinase; ionizing radiation; genotoxic stress ID STRESS-RESPONSE; SH3 DOMAINS; PHOSPHORYLATION; GROWTH; DNA; CELL; PATHWAY; ARREST; GENE; P53 AB The c-Abl protein tyrosine kinase is activated by ionizing radiation (IR) and certain other DNA-damaging agents. The present studies demonstrate that c-Abl associates constitutively with protein kinase C delta (PkC delta). The results show that the SH3 domain of c-Abl interacts directly with PKC delta. c-Abl phosphorylates and activates PKC delta in vitro. We also show that IR treatment of cells is associated with c-Abl-dependent phosphorylation of PKC delta and translocation of PKC delta to the nucleus. These findings support a functional interaction between c-Abl and PKC delta in the cellular response to genotoxic stress. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Pharmacol, Boston, MA 02115 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Yuan, ZM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Canc Pharmacol, 44 Binney St, Boston, MA 02115 USA. NR 46 TC 122 Z9 123 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 2 PY 1998 VL 16 IS 13 BP 1643 EP 1648 DI 10.1038/sj.onc.1201698 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZE573 UT WOS:000072807600001 PM 9582011 ER PT J AU Feilotter, HE Nagai, MA Boag, AH Eng, C Mulligan, LM AF Feilotter, HE Nagai, MA Boag, AH Eng, C Mulligan, LM TI Analysis of PTEN and the 10q23 region in primary prostate carcinomas SO ONCOGENE LA English DT Article DE prostate carcinoma; 10q23; PTEN; loss of heterozygosity ID ALLELIC LOSS; DELETION; CHROMOSOME-10; ADENOCARCINOMA; GLIOMAS; CANCER; GENES; MAP AB Deletions involving chromosome 10q23 occur frequently in prostatic carcinomas. Recently, a novel tumour suppressor gene, PTEN, mapping to this interval, has been identified, Mutation or deletion of PTEN has been observed in a proportion of prostate cancer cell lines; however, primary prostate carcinomas have not been studied, We have investigated the involvement of PTEN in primary prostatic adenocarcinomas using a panel of 51 matched normal and prostate tumour DNAs, Wie first determined the proportion of tumours with allele loss at loci in 10q23 which span the region containing the PTEN gene. Our results show that LOH involving 10q23 is common in primary prostate carcinomas. Twenty-five of 51 (49%) tumours showed loss of heterozygosity (LOH) over the region spanning the PTEN locus, We next directly analysed the PTEN gene for mutations of the coding region using single strand conformation polymorphism (SSCP) and sequence analyses, Of those tumours with LOH, only a single tumour nas found to carry a missense mutation in PTEN, No mutations in PTEN were identified in tumours without LOH. Our results suggest either that mutation of PTEN is a late event in prostate tumorigenesis, or that another tumour suppressor gene important in prostate cancer mag Lie close to PTEN in 10q23. C1 Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. USP, Fac Med, Dept Radiol, Disciplina Oncol, BR-09500900 Sao Paulo, Brazil. Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Human Canc Genet Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med,Program Populat Sci, Boston, MA 02115 USA. RP Mulligan, LM (reprint author), Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. RI Nagai, Maria/C-6162-2012; OI Nagai, Maria/0000-0002-0728-4937; Eng, Charis/0000-0002-3693-5145 NR 28 TC 152 Z9 159 U1 0 U2 3 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 2 PY 1998 VL 16 IS 13 BP 1743 EP 1748 DI 10.1038/sj.onc.1200205 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZE573 UT WOS:000072807600012 PM 9582022 ER PT J AU Harisinghani, MG Saini, S Hahn, PF Weissleder, R Mueller, PR AF Harisinghani, MG Saini, S Hahn, PF Weissleder, R Mueller, PR TI MR imaging of lymph nodes in patients with primary abdominal and pelvic malignancies using ultrasmall superparamagnetic iron oxide (Combidex) SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Contrast Media Research CY MAY 18-22, 1997 CL KYOTO, JAPAN SP Bracco SpA, Milan, Italy, Bracco Res USA Inc, Princeton, NJ, Guerbet SA, Roissy, France, Mallinckrodt Med Inc, St Louis, MO, Nycomed Amersham AS, Olso, Norway, Schering AG, Berlin, Germany, Adv Magnet Inc, Princeton, NJ, ImaRx Pharm Corp, Tucson, AZ, DuPont Merck Pharm Co, N Billerica, Massachusetts, Alliance Pharm Corp, San Diego, Calif, Berlex Lab, Wayne, NJ, Bracco Res SA, Geneva, Switzerland, Ctr Invest Justesa Imagen SA, Madrid, Spain, EPIX Med Inc, Cambridge, Massachusetts, Molec Biosyst Inc, San Diego, Calif, Nycomed Amersham Imaging, Wayne, NJ ID HODGKIN DISEASE; CONTRAST AGENT; LYMPHOGRAPHY; METASTASES; HEAD; NECK C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Saini, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 17 TC 23 Z9 24 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 1998 VL 5 SU 1 BP S167 EP S169 DI 10.1016/S1076-6332(98)80095-0 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ367 UT WOS:000073207400054 PM 9561072 ER PT J AU Wolf, GL Rogowska, J Bessin, G Trocha, M Whiteman, K Wolf, D Shore, MT AF Wolf, GL Rogowska, J Bessin, G Trocha, M Whiteman, K Wolf, D Shore, MT TI Visualizing renal anatomy and function with 1-10,000-nm radiocontrast agents SO ACADEMIC RADIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Contrast Media Research CY MAY 18-22, 1997 CL KYOTO, JAPAN SP Bracco SpA, Milan, Italy, Bracco Res USA Inc, Princeton, NJ, Guerbet SA, Roissy, France, Mallinckrodt Med Inc, St Louis, MO, Nycomed Amersham AS, Olso, Norway, Schering AG, Berlin, Germany, Adv Magnet Inc, Princeton, NJ, ImaRx Pharm Corp, Tucson, AZ, DuPont Merck Pharm Co, N Billerica, Massachusetts, Alliance Pharm Corp, San Diego, Calif, Berlex Lab, Wayne, NJ, Bracco Res SA, Geneva, Switzerland, Ctr Invest Justesa Imagen SA, Madrid, Spain, EPIX Med Inc, Cambridge, Massachusetts, Molec Biosyst Inc, San Diego, Calif, Nycomed Amersham Imaging, Wayne, NJ ID TOMOGRAPHY; KIDNEY; CT C1 Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. RP Wolf, GL (reprint author), Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, 149 13th St, Charlestown, MA 02129 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 2021 SPRING RD, STE 600, OAK BROOK, IL 60521 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 1998 VL 5 SU 1 BP S127 EP S130 DI 10.1016/S1076-6332(98)80081-0 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZJ367 UT WOS:000073207400040 PM 9561062 ER PT J AU Gorski, PA AF Gorski, PA TI Perinatal outcome and the social contract: Interrelationships between health and society SO ACTA PAEDIATRICA JAPONICA LA English DT Article DE economy; infant mortality; perinatal outcome; prematurity; social inequality; society ID LOW-BIRTH-WEIGHT; INFANT-MORTALITY AB Rates of infant mortality and prematurity or low birthweight serve as indirect measures of the health of a nation. This paper presents current population data documenting the still serious problem of perinatal outcome in the USA as well as in other economically developed countries. International comparisons suggest that nations which have the greatest inequality of income and social opportunity also have the most adverse perinatal, child and adult health outcomes. Furthermore, the data assert that these effects are independent of average national wealth or gross national economic productivity. Health status differs by social class and race, even among the most affluent sectors of the population. All social classes, even the wealthiest, suffer the health consequences of social inequalities. An explanatory socio-psychological theory of causality is proposed. C1 Boston Childrens Hosp, Massachusetts Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Gorski, PA (reprint author), Massachusetts Caring Children Fdn Inc, 100 Summer St,14th Floor, Boston, MA 02110 USA. NR 26 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0374-5600 J9 ACTA PAEDIATR JAPON JI Acta Pediatr. Jpn. PD APR PY 1998 VL 40 IS 2 BP 168 EP 172 PG 5 WC Pediatrics SC Pediatrics GA ZH672 UT WOS:000073135700015 PM 9581312 ER PT J AU Ling, W Charuvastra, C Collins, JF Batki, S Brown, LS Kintaudi, P Wesson, DR McNicholas, L Tusel, DJ Malkerneker, U Renner, JA Santos, E Casadonte, P Fye, C Stine, S Wang, RIH Segal, D AF Ling, W Charuvastra, C Collins, JF Batki, S Brown, LS Kintaudi, P Wesson, DR McNicholas, L Tusel, DJ Malkerneker, U Renner, JA Santos, E Casadonte, P Fye, C Stine, S Wang, RIH Segal, D TI Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial SO ADDICTION LA English DT Article ID OPIOID DEPENDENCE; METHADONE-MAINTENANCE; DETOXIFICATION; PHARMACOLOGY; BLOCKADE; ABUSE AB Aims. To evaluate the safety and efficacy of an 8 mg/day sublingual dose of buprenorphine in the maintenance treatment of heroin addicts by comparison with a 1 mg/day dose over a 16-week treatment period. As a secondary objective, outcomes were determined concurrently for patients treated with two other dose levels. Design. Patients were randomized to four dosage groups and treated double-blind. Setting. Twelve outpatient opiate maintenance treatment centers throughout the United States. Participants. Two hundred and thirty-nine women and 497 men who met the DSM-III-R criteria for opioid dependence and were seeking treatment. Intervention. Patients received either 1, 4, 8 or 16 mg/day of buprenorphine and were treated in the usual clinical context, including a 1-hour weekly clinical counseling session. Measurement. Retention in treatment, illicit opioid use as determined by urine toxicology, opioid craving and global ratings by patient and staff. Safety outcome measures were provided by clinical monitoring and by analysis of the reported adverse events. Findings. Outcomes in the 8 mg group were significantly better than in the 1 mg group in all four efficacy domains. No deaths occurred in either group. The 8 mg group did not show an increase in the frequency of adverse events. Most reported adverse effects were those commonly seen in patients treated with opioids. Conclusions. The findings support the safety and efficacy of buprenorphine and suggest that an adequate dose of buprenorphine will be a useful addition to pharmacotherapy. C1 Los Angeles Addict Treatment Res Ctr, Los Angeles, CA 90025 USA. San Francisco Gen Hosp, San Francisco, CA USA. Med Coll Wisconsin, Milwaukee, WI USA. Univ Penn, Philadelphia, PA 19104 USA. US Dept Vet Affairs, Washington, DC 20420 USA. US Natl Inst Drug Abuse, Lexington, KY USA. RP Ling, W (reprint author), Los Angeles Addict Treatment Res Ctr, 10350 Santa Monica Blvd,Suite 340, Los Angeles, CA 90025 USA. OI Stine, Susan/0000-0001-5426-4448 NR 32 TC 225 Z9 229 U1 1 U2 9 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 0965-2140 J9 ADDICTION JI Addiction PD APR PY 1998 VL 93 IS 4 BP 475 EP 486 DI 10.1046/j.1360-0443.1998.9344753.x PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA ZJ556 UT WOS:000073228600003 PM 9684386 ER PT J AU Ruprecht, RM Baba, TW Liska, V Ayehunie, S Andersen, J Montefiori, DC Trichel, A Murphey-Corb, M Martin, L Rizvi, TA Bernacky, BJ Buchl, SJ Keeling, M AF Ruprecht, RM Baba, TW Liska, V Ayehunie, S Andersen, J Montefiori, DC Trichel, A Murphey-Corb, M Martin, L Rizvi, TA Bernacky, BJ Buchl, SJ Keeling, M TI Oral SIV, SHIV, and HIV type 1 infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article; Proceedings Paper CT Conference on the Reproductive Tract and HIV-1 Transmission CY FEB 11-12, 1997 CL BETHESDA, MARYLAND SP Natl Inst Child Hlth & Human Dev, Off Res Womens Hlth, Natl Inst Allery & Infect Dis, Natl Inst Diabet & Digest & Kidney Dis, Off AIDS Res, Soc Adv Womens Hlth Res ID SIMIAN IMMUNODEFICIENCY VIRUS; FRANCISCO MENS HEALTH; CELL-FREE SIV; RHESUS-MONKEYS; HOMOSEXUAL MEN; MUCOSAL INFECTION; SEXUAL PRACTICES; ATTENUATED SIV; ACID-SECRETION; NEF GENE AB Several strains of simian immunodeficiency virus (SIV), including uncloned and molecularly cloned SIV strains, can cross intact mucosal surfaces after oral exposure in both adult and neonatal rhesus macaques, resulting in viremia and disease, Cell-free SIV strains as well as infected whole blood have resulted in systemic infection after oral inoculation. Neonatal macaques, exposed orally to the chimeric SHIV-vpu(+), a derivative of SIVmac239 that encodes the env gene of the T cell-tropic HIV-IIIB, have also become persistently infected. These data indicate that oral exposure to various virus strains, including T cell-tropic variants, leads to infection. After nontraumatic inoculation, the oral route was more efficient than the rectal route in permitting SIV entry in adult macaques, Infection and AIDS resulting from oral exposure of adult macaques have implications for the transmission of the human immunodeficiency virus type 1 (HIV-1) during oral-genital contact. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Tulane Univ, Reg Primate Res Ctr, Covington, LA 70433 USA. MD Anderson Cancer Ctr, Dept Vet Sci, Bastrop, TX 78602 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [U01-AI24345, R01-AI32330, R01-AI34266] NR 46 TC 26 Z9 26 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR PY 1998 VL 14 SU 1 BP S97 EP S103 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZJ673 UT WOS:000073240600021 PM 9581893 ER PT J AU Chronos, N Vahanian, A Betriu, A Emanuelsson, H Goldberg, S Gulba, D van Hout, BA AF Chronos, N Vahanian, A Betriu, A Emanuelsson, H Goldberg, S Gulba, D van Hout, BA TI Use of abciximab in interventional cardiology SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Meeting on Use of GP IIb/IIIa Inhibitors in Coronary Syndromes - State of the Art CY FEB 15-16, 1997 CL DAVOS, SWITZERLAND SP Eli Lilly & Co, Indianapolis ID PERCUTANEOUS CORONARY INTERVENTION; DIRECTIONAL ATHERECTOMY; MYOCARDIAL-INFARCTION; CLINICAL RESTENOSIS; IIB/IIIA INTEGRIN; RANDOMIZED TRIAL; ARTERY LESIONS; ANGIOPLASTY; ANTIBODY; COMPLICATIONS AB The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed the landscape of interventional cardiology. Given the commercial availability of abciximab and expected regulatory approvals for other receptor blockers, defining appropriate use of these agents in the interventional setting is mandated. One key issue is selection of patients who may benefit From GP IIb/IIIa receptor blockade. Focusing specifically on abciximab, data from three large-scale, randomized trials demonstrate that abciximab is appropriate for all patients undergoing percutaneous transluminal coronary angioplasty, regardless of risk stratum. Other important issues to consider when prescribing this therapy include benefits in conjunction with stents and new devices, dosing and timing of administration, and the role of prophylactic versus "bailout" administration. This article reflects a distillation of the views and consensus regarding the use of GP IIb/IIIa inhibitors in patients undergoing coronary intervention expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation. C1 Emory Univ Hosp, Atlanta, GA 30322 USA. Hop Tenon, F-75970 Paris, France. Orebro Med Ctr, Orebro, Sweden. Univ Barcelona, Barcelona, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. Franz Volhard Klin, Berlin, Germany. Erasmus Univ, Rotterdam, Netherlands. RP Chronos, N (reprint author), Emory Univ Hosp, Suite F606,1364 Clifton Rd NE, Atlanta, GA 30322 USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD APR PY 1998 VL 135 IS 4 BP S67 EP S76 DI 10.1016/S0002-8703(98)70299-6 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZE813 UT WOS:000072833900034 PM 9539497 ER PT J AU George, CJ Baim, DS Brinker, JA Fischman, DL Goldberg, S Holubkov, R Kennard, ED Veltri, L Detre, KM AF George, CJ Baim, DS Brinker, JA Fischman, DL Goldberg, S Holubkov, R Kennard, ED Veltri, L Detre, KM TI One-year follow-up of the Stent Restenosis (STRESS I) Study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; BALLOON ANGIOPLASTY AB We present the completed 1-year follow-up results of the original Stent Restenosis Study (STRESS I), in which 407 patients with symptomatic ischemic heart disease and new lesions of the native coronary circulation were randomly assigned to treatment with either the Palmaz-Schatz coronary stent or conventional percutaneous transluminal coronary angioplasty (PTCA). The present study compares the safety of elective stenting to balloon angioplasty (PTCA) in terms of freedom from clinical events up to 1 year after treatment. Patients were enrolled and treated from January 1991 through February 1993, and follow-up data were collected and verified until July 1995, Ninety-seven percent of all patients had complete follow-up (deceased or alive with known clinical status) beyond 8 months, and 94% beyond 11 months, Anginal status between 9 to 15 months post-procedure was available for 78% of patients, At 1 year, 154 patients (75%) assigned to stent implantation and 141 (70%) to PTCA were free of all clinical events (death, myocardial infarction, or any revascularization procedure), and 162 stent patients (79%) and 149 PTCA patients (74%) were free from death, myocardial infarction, or target lesion revascularization, Symptom-driven target lesion revascularization occurred in 12% of the stent group versus 17% of the PTCA group, None of these differences in clinical events was statistically significant, Only 2 patients in the stent group and 7 in the PTCA group had a first event after 239 days, and freedom from angina at 1 year was reported in equal frequency in both groups (84%). There appear to be no late adverse effects of stent implantation. However, these results are limited by low statistical power, narrow patient selection, and the anticoagulation regimen used in the early experience with this device. (C) 1998 by Excerpta Medica, Inc. C1 Univ Pittsburgh, Pittsburgh, PA 15261 USA. Beth Israel Hosp, Boston, MA 02215 USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Detre, KM (reprint author), Univ Pittsburgh, 130 De Soto St, Pittsburgh, PA 15261 USA. NR 6 TC 49 Z9 50 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 1 PY 1998 VL 81 IS 7 BP 860 EP 865 DI 10.1016/S0002-9149(98)00004-6 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZF712 UT WOS:000072924500009 PM 9555775 ER PT J AU Kabakibi, A Vamvakas, EC Cannistraro, PA Szczepiorkowski, ZM Laposata, M AF Kabakibi, A Vamvakas, EC Cannistraro, PA Szczepiorkowski, ZM Laposata, M TI Collagen-induced whole blood platelet aggregation in patients undergoing surgical procedures associated with minimal to moderate blood loss SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE whole blood platelet aggregation; collagen; estimated blood loss; invasiveness; surgery AB wIntraoperative bleeding due to platelet disorders is a persistent problem. Therefore, a screening assay to identify patients who are likely to bleed as a result of platelet dysfunction would be useful in formulating decisions about patient care. A previous study indicated that preoperative collagen-induced whole blood platelet aggregation predicts bleeding in patients undergoing surgery with cardiopulmonary bypass, a procedure associated with substantial blood loss. In the current study we assessed the ability of the same whole blood platelet aggregation test to predict blood loss in patients undergoing surgical procedures not associated with substantial blood loss. The study included 369 adult patients (165 men and 204 women). Patients were categorized in three groups depending on the invasiveness of the operation and the expected blood loss. The intraoperative estimated blood loss value, obtained from the operative report in the patient record, increased significantly with increasing surgical invasiveness. Patients with excessive blood loss (defined as blood loss at or above the 75th or 90th percentile of the estimated blood loss values of patients undergoing procedures of similar invasiveness) had similar platelet aggregation values as patients who did not experience excessive blood loss. Thus, for patients undergoing operations not associated with substantial blood loss, the results of preoperative collagen-induced whole blood platelet aggregation are not effective in identifying patients likely to experience excessive blood loss. C1 Massachusetts Gen Hosp, Div Clin Labs, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Laposata, M (reprint author), Massachusetts Gen Hosp, Div Clin Labs, Dept Pathol, Room 235,Gray Bldg, Boston, MA 02114 USA. RI Szczepiorkowski, Zbigniew/A-1359-2007 OI Szczepiorkowski, Zbigniew/0000-0003-2357-9564 FU NIDDK NIH HHS [R01DK37454] NR 7 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLIN PATHOLOGISTS PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD APR PY 1998 VL 109 IS 4 BP 392 EP 398 PG 7 WC Pathology SC Pathology GA ZD075 UT WOS:000072648900005 PM 9535391 ER PT J AU Konstam, V Surman, O Hizzazi, KH Fierstein, J Konstam, M Turbett, A Dec, GW Keck, S Mudge, G Flavell, C McCormack, M Hurley, L AF Konstam, V Surman, O Hizzazi, KH Fierstein, J Konstam, M Turbett, A Dec, GW Keck, S Mudge, G Flavell, C McCormack, M Hurley, L TI Marital adjustment in heart transplantation patients and their spouses: A longitudinal perspective SO AMERICAN JOURNAL OF FAMILY THERAPY LA English DT Article ID QUALITY-OF-LIFE; DYADIC ADJUSTMENT; SATISFACTION; ILLNESS; COUPLES; STRESS AB Marital adjustment and its relationship to health-related quality of life (HRQL) in the patient member of the couple was studied in thirty-six couples pre-and post-heart transplantation. All participants completed the Dyadic Adjustment Scale, whereas the patient member of the couple completed the Sickness Impact Profile, a HRQL measure. Both members of the couple reported mild marital distress. The spouse member consistently reported lower marital adjustment scores. Multiple regression analysis revealed the importance of assessing marital adjustment from the perspective of both members of the couple. Implications for assessment and intervention are discussed. C1 Univ Massachusetts, Grad Coll Educ, Dept Counseling & Sch Psychol, Boston, MA 02125 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Simmons Coll, Dept Nursing, Boston, MA 02115 USA. New England Med Ctr, Dept Cardiol, Boston, MA 02111 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Konstam, V (reprint author), Univ Massachusetts, Grad Coll Educ, Dept Counseling & Sch Psychol, Harbor Campus, Boston, MA 02125 USA. NR 24 TC 5 Z9 5 U1 1 U2 2 PU BRUNNER/MAZEL INC PI BRISTOL PA 1900 FROST RD, STE 101, BRISTOL, PA 19007-1598 USA SN 0192-6187 J9 AM J FAM THER JI Am. J. Fam. Ther. PD APR-JUN PY 1998 VL 26 IS 2 BP 147 EP 158 DI 10.1080/01926189808251094 PG 12 WC Psychology, Clinical; Family Studies SC Psychology; Family Studies GA ZF435 UT WOS:000072897200005 ER PT J AU Henihan, RDJ Stuart, RC Nolan, N Gorey, TF Hennessy, TPJ O'Morain, CA AF Henihan, RDJ Stuart, RC Nolan, N Gorey, TF Hennessy, TPJ O'Morain, CA TI Barrett's esophagus and the presence of Helicobacter pylori SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CAMPYLOBACTER-PYLORI; GASTRIC-CANCER; INFECTION; PREVALENCE; CARCINOMA; STOMACH AB Objective: Although the role of Helicobacter pylori in the pathogenesis of peptic ulcer disease and antral gastritis has been well documented, the role of H. pylori in esophageal disease has not been clearly defined. To clarify this issue, we analyzed 141 patients with histologically confirmed esophageal disease. Methods: The study group consisted of 82 patients with Barrett's esophagus, 19 with adenocarcinoma of the esophagus arising in columnar epithelium and 40 patients with reflux esophagitis without columnar metaplasia of the esophagus, In each of these cases the presence or absence of H, pylori was assessed histologically, Results: H, pylori was present in 19 of 82 patients (23 %) with Barrett's esophagus,but was absent in all patients with adenocarcinoma of the esophagus and in patients with reflux esophagitis without Barrett's metaplasia, H, pylori was found only in areas of gastric type metaplasia in the patients with Barrett's esophagus, All of the 19 Barrett's esophagus group with H. pylori had chronic inflammation, and in 16 the inflammation was severe, H. pylori was significantly associated with severity of inflammation in patients with Barrett's esophagus (p < 0.001), Members of the Barrett's group with evidence of moderate to severe dysplasia were negative for H, pylori. Conclusion: These data confirm that the presence of gastric type mucosa within the esophagus is a prerequisite for H. pylori colonization, and that H. pylori may contribute to the severity of inflammation in Barrett's epithelium. (C) 1998 by Am. Coll. of Gastroenterology. C1 St James Hosp, Trinity Coll, Dept Surg, Dublin 8, Ireland. St James Hosp, Trinity Coll, Dept Pathol, Dublin 8, Ireland. Meath Hosp, Dept Gastroenterol, Dublin 8, Ireland. RP Henihan, RDJ (reprint author), Massachusetts Gen Hosp, GI Unit, GRJ 724, Boston, MA 02114 USA. NR 37 TC 34 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 1998 VL 93 IS 4 BP 542 EP 546 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZT265 UT WOS:000074067300015 PM 9576445 ER PT J AU Steigh, C Glassman, PA Fajardo, F AF Steigh, C Glassman, PA Fajardo, F TI Physician and dietitian prescribing of a commercially available oral nutritional supplement SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID PROTEIN-CALORIE UNDERNUTRITION; DIETARY-SUPPLEMENT; ELDERLY PATIENTS; MALNUTRITION; MORTALITY; INTERVENTION; POPULATION; PREVALENCE AB We examined whether a policy change transferring prescribing privileges for oral nutritional supplements to dietitians resulted in fewer inappropriate outpatient prescriptions. This was a pre/post study design using a retrospective review of physician and dietitian prescribing for ambulatory patients during two separate time periods: physician prescribing, October to December, 1994; dietitian prescribing, April to June, 1995. Inappropriate prescriptions during each period were defined as those given to patients with normal nutritional status or with a contraindication to a high-energy, electrolyte-containing solution. The study was conducted in outpatient clinics at a Veterans Affairs teaching hospital. We found that dietitians gave fewer prescriptions to outpatients who were not malnourished or to outpatients who had a contraindication to receiving a supplement (11% vs 34%; P = 0.002). In addition, dietitians more often completed relevant laboratory assessments (75% vs 43%; P = 0.001: and more frequently arranged follow-up dietetic evaluations (84% vs 30%, P < 0.001) for ambulatory patients receiving supplements, We conclude that transferring nutritional supplement prescribing privileges to dietitians led to fewer inappropriate outpatient prescriptions and to more comprehensive nutritional assessments, as measured by relevant laboratory use and dietetic follow-up. Physicians more frequently prescribed supplements to outpatients who were not malnourished or who had contraindications to receiving supplements. Our results suggest that physicians would benefit from assistance with and/or education concerning oral nutritional supplements. C1 W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med 1116, Los Angeles, CA 90073 USA. RP Glassman, PA (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Gen Internal Med 1116, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 19 TC 5 Z9 6 U1 0 U2 1 PU AMER MED PUBLISHING, M W C COMPANY PI OLD BRIDGE PA 1816 ENGLISHTOWN RD, STE 101, OLD BRIDGE, NJ 08857 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD APR PY 1998 VL 4 IS 4 BP 567 EP 572 PG 6 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA ZN869 UT WOS:000073691600006 PM 10179915 ER PT J AU Gulley, ML Nicholls, JM Schneider, BG Amin, MB Ro, JY Geradts, J AF Gulley, ML Nicholls, JM Schneider, BG Amin, MB Ro, JY Geradts, J TI Nasopharyngeal carcinomas frequently lack the p16/MTS1 tumor suppressor protein but consistently express the retinoblastoma gene product SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; P16(INK4A) EXPRESSION; HUMAN CANCERS; P16 GENE; HEAD; INACTIVATION; HETEROZYGOSITY; METHYLATION AB The p16/MTS1 gene is altered by deletion, mutation, or hypermethylation in a wide variety of human cancers. As a result of deficient p16 protein, these cancers lack a critical mechanism for halting G1/S cell cycle progression. In the current study, 59 cases of nasopharyngeal carcinoma were evaluated for expression of the p16 tumor suppressor protein by immunohistochemical analysis of paraffin-embedded tissue. There was no detectable p16 in 38/59 cases (64%), which implies a very high rate of p16 inactivation in this type of cancer. On the other hand, the retinoblastoma gene product, which also regulates the G1 to S phase transition of the cell cycle, was consistently expressed in nasopharyngeal carcinomas by immunohistochemical analysis. These results implicate p16 inactivation but not Rb alteration in the stepwise progression of nasopharyngeal carcinogenesis. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, Dept Pathol, San Antonio, TX 78284 USA. Univ Hong Kong, Hong Kong, Hong Kong. Louisiana State Univ, Med Ctr, New Orleans, LA USA. Stanley Scott Canc Ctr, New Orleans, LA USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Texas, MD Anderson Cancer Ctr, Houston, TX 77030 USA. Univ N Carolina, Chapel Hill, NC USA. RP Gulley, ML (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCI NIH HHS [P30-CA54174] NR 26 TC 44 Z9 49 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1998 VL 152 IS 4 BP 865 EP 869 PG 5 WC Pathology SC Pathology GA ZF714 UT WOS:000072924700003 PM 9546345 ER PT J AU Chandrasekar, B Melby, PC Troyer, DA Colston, JT Freeman, GL AF Chandrasekar, B Melby, PC Troyer, DA Colston, JT Freeman, GL TI Temporal expression of pro-inflammatory cytokines and inducible nitric oxide synthase in experimental acute chagasic cardiomyopathy SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; TRYPANOSOMA-CRUZI; FACTOR-ALPHA; CARDIOVASCULAR-RESPONSE; MYOCARDIAL-FUNCTION; CONSCIOUS DOGS; INDUCTION; ENDOTOXIN; INTERLEUKIN-1; DISEASE AB To characterize the kinetics of myocardial cytokine and inducible nitric oxide synthase (iNOS) expression in acute Chagasic cardiomyopathy, we studied a rat model of acute Trypanosoma cruzi infection, Rats were euthanized 36 hours and 5, 10, and 15 days after infection, and hearts were collected for histology, mRNA, and protein analyses, Histological analysis of myocardium showed a progressive increase in the number of amastigotes and mononuclear inflammatory cells, Organisms were first detected 5 days after intraperitoneal inoculation as isolated nests and became numerous by day 15. Northern blot analysis of total RNA revealed no signal for interleukin (IL)-1 beta or tumor necrosis factor (TNF)-alpha and a weak signal for IL-6 in control hearts, High levels of expression for the three genes mere detected in the infected animals at 36 hours after infection, Although IL-1 beta and IL-6 levels increased steadily up to 10 days, TNF-alpha levels were the highest at 5 days, remained high at 10 days, and declined thereafter, Western blot analysis showed similar results to that of mRNA expression, No signal was detected for iNOS in the controls, but both its mRNA and protein were found in the infected animals, with levels being highest at 15 days after infection, Immunohistochemistry revealed no iNOS immunoreactivity in uninfected animals, but intense iNOS staining was detected in blood vessels of infected animals, which decreased progressively with period of infection, Positive staining for iNOS in cardiomyocytes was first detected at 36 hours after infection Cat a time when there was no histological inflammatory reaction), which steadily increased, being the highest at 15 days after infection, These results indicate that, in addition to mechanical damage by T. cruzi, substantial pro-inflammatory cytokine production within the myocardium is Likely to participate in the pathophysiology of acute Chagasic cardiomyopathy. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Freeman, GL (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 49 TC 55 Z9 56 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1998 VL 152 IS 4 BP 925 EP 934 PG 10 WC Pathology SC Pathology GA ZF714 UT WOS:000072924700011 PM 9546353 ER PT J AU Gravallese, EM Harada, Y Wang, JT Gorn, AH Thornhill, TS Goldring, SR AF Gravallese, EM Harada, Y Wang, JT Gorn, AH Thornhill, TS Goldring, SR TI Identification of cell types responsible for bone resorption in rheumatoid arthritis and juvenile rheumatoid arthritis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID RESISTANT ACID-PHOSPHATASE; CARTILAGE PANNUS JUNCTION; PARATHYROID-HORMONE BINDING; HEMATOPOIETIC BLAST CELLS; CALCITONIN RECEPTOR; MOUSE BONE; HUMAN OSTEOCLAST; VITRONECTIN RECEPTOR; MARROW CULTURES; MESSENGER-RNA AB Focal resorption of bone at the bone-pannus interface is common in rheumatoid arthritis (RA) and juvenile rheumatoid arthritis (JRA) and can result in significant morbidity, However, the specific cellular and hormonal mechanisms involved in this process are not well established, We examined tissue sections from areas of bone erosion in patients with RA and JRA, Multinucleated cells (MNCs) were present in resorption lacunae in areas of calcified cartilage and in subchondral bone immediately adjacent to calcified cartilage, as previously described. mRNA for the calcitonin receptor (CTR) was localized to these MNCs in bone resorption lacunae, a finding that definitively identifies these cells as osteoclasts. These MNCs were also positive for tartrate-resistant acid phosphatase (TRAP) mRNA and TRAP enzymatic activity, Occasional mononuclear cells on the bone surface were also CTR positive, Mononuclear cells and MNCs not on bone surfaces were CTR negative, The restriction of CTR-positive cells to the surface of mineralized tissues suggests that bone and/or calcified cartilage provide signals that are critical for the differentiation of hematopoietic osteoclast precursors to fully differentiated osteoclasts, Some MNCs and mononuclear cells off bone and within invading tissues were TRAP positive. These cells likely represent the precursors of the CTR-TRAP-positive cells on bone, Parathyroid hormone receptor mRNA was present in cells with the phenotypic appearance of osteoblasts, in close proximity to MNCs, and in occasional cells within pannus tissue, but not in the MNCs in bone resorption lacunae, These findings demonstrate that osteoclasts within the rheumatoid lesion do not express parathyroid hormone receptor, In conclusion, the resorbing cells in RA exhibit a definitive osteoclastic phenotype, suggesting that pharmacological agents that inhibit osteoclast recruitment or activity are rational targets for blocking focal bone erosion in patients with RA and JRA. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Rheumatol, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, New England Baptist Bone & Joint Inst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. RP Goldring, SR (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Rheumatol, 110 Francis St, Boston, MA 02215 USA. FU NIAMS NIH HHS [P01 AR03564]; NIDDK NIH HHS [R01-DK46773] NR 49 TC 311 Z9 321 U1 1 U2 7 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 1998 VL 152 IS 4 BP 943 EP 951 PG 9 WC Pathology SC Pathology GA ZF714 UT WOS:000072924700013 PM 9546355 ER PT J AU Koopmans, SJ Mandarino, L DeFronzo, RA AF Koopmans, SJ Mandarino, L DeFronzo, RA TI Time course of insulin action on tissue-specific intracellular glucose metabolism in normal rats SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE lipid metabolism; insulin resistance; glycogen synthesis; glycolysis; hepatic glucose production ID DIABETIC RATS; GLYCOGEN-SYNTHESIS; IN-VIVO; CONSCIOUS RATS; HUMAN MUSCLE; HYPERGLYCEMIA; RESISTANCE; CLAMP; LIVER; STIMULATION AB We investigated the time course of insulin action in conscious rats exposed to constant physiological hyperinsulinemia (similar to 100 mU/l) while maintaining euglycemia (similar to 100 mg/dl) for 0, 0.5, 2, 4, 8, or 12 h. [3-H-3]glucose was infused to quantitate whole body glucose disposal (rate of disappearance, R-d), glycolysis (generation of (H2O)-H-3 in plasma), hepatic glucose production (HGP), and skeletal muscle and liver glycogen synthesis ([3-H-3]glucose incorporation into glycogen and time-dependent change in tissue glycogen concentration). The basal R-d, which equals HGP, was 6.0 +/- 0.3 mg.kg(-1).min(-1). With increased duration of hyperinsulinemia from 0 to 0.5 to 2 to 4 h, R-d increased from 6.0 +/- 0.3 to 21.0 +/- 1.1 to 24.1 +/- 1.5 to 26.6 +/- 0.6 mg.kg(-1).min(-1) (P < 0.05 for 2 and 4 h vs. 0.5 h). During the first 2 h the increase in R-d was explained by parallel increases in glycolysis and glycogen synthesis. From 2 to 4 h the further increase in R-d was entirely due to an increase in glycolysis without change in glycogen synthesis. From 4 to 8 to 12 h of hyperinsulinemia, R-d decreased by 19% from 26.6 +/- 0.6 to 24.1 +/- 1.1 to 21.6 +/- 1.8 mg.kg(-1).min(-1) (P < 0.05 for 8 h vs. 4 h and 12 h vs. 8 h). The progressive decline in R-d, in the face of constant hyperinsulinemia, occurred despite a slight increase (8-14%) in glycolysis and was completely explained by a marked decrease (64%) in muscle glycogen synthesis. In contrast, liver glycogen synthesis increased fourfold, indicating an independent regulation of muscle and liver glycogen synthesis by long-term hyperinsulinemia. In the liver, during the entire 12-h period of insulin stimulation, the contribution of the direct (from glucose) and the indirect (from C-3 fragments) pathways to net glycogen formation remained constant at 77 +/- 5 and 23 +/- 5%, respectively. HGP remained suppressed throughout the 12-h period of hyperinsulinemia. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Diabet, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Affairs Hosp, San Antonio, TX 78284 USA. Leiden Univ Hosp, Dept Endocrinol & Metab Dis, NL-2333 AA Leiden, Netherlands. RP DeFronzo, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Diabet, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 34 TC 16 Z9 16 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 1998 VL 274 IS 4 BP E642 EP E650 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA ZG359 UT WOS:000072993700010 PM 9575825 ER PT J AU Ludwig, DS Mountjoy, KG Tatro, JB Gillette, JA Frederich, RC Flier, JS Maratos-Flier, E AF Ludwig, DS Mountjoy, KG Tatro, JB Gillette, JA Frederich, RC Flier, JS Maratos-Flier, E TI Melanin-concentrating hormone: a functional melanocortin antagonist in the hypothalamus SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE obesity; eating ID MELANOCYTE-STIMULATING-HORMONE; NEUROPEPTIDE-Y; LEPTIN RECEPTOR; FEEDING-BEHAVIOR; AGOUTI GENE; RAT-BRAIN; MICE; EXPRESSION; CLONING; IDENTIFICATION AB Melanin-concentrating hormone (MCH) and alpha-melanocyte-stimulating hormone (alpha-MSH) demonstrate opposite actions on skin coloration in teleost fish. Both peptides are present in the mammalian brain, although their specific physiological roles remain largely unknown. In this study, we examined the interactions between MCH and alpha-MSH after intracerebroventricular administration in rats. MCH increased food intake in a dose-dependent manner and lowered plasma glucocorticoid levels through a mechanism involving ACTH. In contrast, alpha-MSH decreased food intake and increased glucocorticoid levels. MCH, at a twofold molar excess, antagonized both actions of alpha-MSH. alpha-MSH, at a threefold molar excess, blocked the orexigenic properties of MCH. MCH did not block alpha-MSH binding or the ability of alpha-MSH to induce cAMP in cells expressing either the MC3 or MC4 receptor, the principal brain alpha-MSH receptor subtypes. These data suggest that MCH and alpha-MSH exert opposing and antagonistic influences on feeding behavior and the stress response and may function in a coordinate manner to regulate metabolism through a novel mechanism mediated in part by an MCH receptor. C1 Joslin Diabet Ctr, Elliott P Joslin Res Lab, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol & Metab, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Tufts Univ, Sch Med, New England Med Ctr,Tupper Res Inst, Dept Med,Div Endocrinol Metab & Mol Med, Boston, MA 02111 USA. Univ Auckland, Res Ctr Dev Med, Auckland 1, New Zealand. RP Maratos-Flier, E (reprint author), Joslin Diabet Ctr, Elliott P Joslin Res Lab, 1 Joslin Pl,Rm 620, Boston, MA 02215 USA. FU NIDDK NIH HHS [R08-DK-02440]; NIMH NIH HHS [MH-44694] NR 44 TC 123 Z9 125 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD APR PY 1998 VL 274 IS 4 BP E627 EP E633 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA ZG359 UT WOS:000072993700008 PM 9575823 ER PT J AU Klerman, EB Rimmer, DW Dijk, DJ Kronauer, RE Rizzo, JF Czeisler, CA AF Klerman, EB Rimmer, DW Dijk, DJ Kronauer, RE Rizzo, JF Czeisler, CA TI Nonphotic entrainment of the human circadian pacemaker SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE activity; circadian rhythms; light; blindness ID BLIND MAN; BRIGHT LIGHT; RHYTHMS; PHASE; MELATONIN; CLOCK; EXERCISE; TEMPERATURE; SECRETION; EXPOSURE AB In organisms as diverse as single-celled algae and humans, light is the primary stimulus mediating entrainment of the circadian biological dock. Reports that some totally blind individuals appear entrained to the 24-h day have suggested that nonphotic stimuli may also be effective circadian synchronizers in humans, although the nonphotic stimuli are probably comparatively weak synchronizers, because the circadian rhythms of many totally blind individuals "free run" even when they maintain a 24-h activity-rest schedule. To investigate entrainment by nonphotic synchronizers, we studied the endogenous circadian melatonin and core body temperature rhythms of 15 totally blind subjects who lacked conscious light perception and exhibited no suppression of plasma melatonin in response to ocular bright-light exposure. Nine of these fifteen blind individuals were able to maintain synchronization to the 24-h day, albeit often at an atypical phase angle of entrainment. Nonphotic stimuli also synchronized the endogenous circadian rhythms of a totally blind individual to a non-24-h schedule while living in constant near darkness. We conclude that nonphotic stimuli can entrain the human circadian pacemaker in some individuals lacking ocular circadian photoreception. C1 Brigham & Womens Hosp, Dept Med, Endocrinol Hypertens Div, Circadian Neuroendocrine & Sleep Disorders Sect, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Div Appl Sci, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Klerman, EB (reprint author), Brigham & Womens Hosp, Dept Med, Endocrinol Hypertens Div, Circadian Neuroendocrine & Sleep Disorders Sect, 221 Longwood Ave, Boston, MA 02115 USA. RI Dijk, Derk-Jan/D-8387-2011 FU NIA NIH HHS [K01 AG000661, K01 AG000661-05] NR 45 TC 120 Z9 120 U1 0 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD APR PY 1998 VL 274 IS 4 BP R991 EP R996 PG 6 WC Physiology SC Physiology GA ZE788 UT WOS:000072831000015 PM 9575961 ER PT J AU McGlynn, EA Asch, SM AF McGlynn, EA Asch, SM TI Developing a clinical performance measure SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article; Proceedings Paper CT Conference on Prevention in Managed Care - Joining Forces for Value and Quality CY JAN 15-16, 1997 CL ATLANTA, GEORGIA DE quality assessment measurement; health care; chronic disease; task performance and analysis ID HYPERTENSION; POPULATION AB Background: Clinical performance measurement is an increasingly important way for public and private purchasers alike to compare the value of health services provided by competing health delivery systems. The widespread use of performance measures has increased the demand for development of new measures that cover previously unevaluated aspects of care. Methods: Four steps required to develop a clinical performance measure that is suitable for-making comparisons among health delivery systems are discussed: (1) choosing clinical areas to measure, (2) selecting performance indicators within each area, (3) designing specifications for consistent implementation of a measure, and (4) evaluating the scientific strength of a measure, Results: The application of these steps to developing measures of quality for hyper-tension is provided, with an emphasis on a measure of adequacy of control of blood pressure. Conclusions: Developing useful clinical performance measures requires careful attention to methodologic issues, Following the steps outlined in this paper should enhance the quality of future measurement development. (C) 1998 American Journal of Preventive Medicine. C1 RAND, Hlth Program, Santa Monica, CA 90401 USA. RAND Hlth, Ctr Res Qual & Hlth Care, Santa Monica, CA 90401 USA. W Los Angeles Vet Adm, Hlth Serv & Dev, Santa Monica, CA 90401 USA. RP McGlynn, EA (reprint author), RAND, Hlth Program, 1700 Main St, Santa Monica, CA 90401 USA. NR 12 TC 123 Z9 127 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 1998 VL 14 IS 3 SU S BP 14 EP 21 DI 10.1016/S0749-3797(97)00032-9 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA ZG459 UT WOS:000073004700005 PM 9566932 ER PT J AU Vollmer, WM Osborne, ML Buist, AS AF Vollmer, WM Osborne, ML Buist, AS TI 20-year trends in the prevalence of asthma and chronic airflow obstruction in an HMO SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID HEALTH MAINTENANCE ORGANIZATION; ACUTE CHILDHOOD ASTHMA; GENDER DIFFERENCES; MORTALITY; HOSPITALIZATION; CARE; POPULATION; MORBIDITY; SEVERITY; DEATHS AB Although asthma is on the rise in the United States and elsewhere, data on age-sex-specific patterns of change in various types of health care utilization are scarce. We report on 20-yr trends in the treated prevalence of asthma among members of a large health maintenance organization. Data are presented separately for each of six age-sex categories, and include both the treated prevalence of asthma as well as the treated prevalence of the broader category of chronic airflow obstruction (CAO), defined as asthma, chronic bronchitis, or emphysema. During the period 1967-1987 the treated prevalence of asthma and CAO increased significantly in all age-sex categories except males aged 65 and older. These patterns are in contrast to previous studies of this population that showed that increases in asthma hospitalizations and hospital-based episodes of care were limited primarily to young boys. Not only do these findings support other evidence of a real increase in asthma prevalence, but they also highlight the risks associated with drawing inferences about changing disease epidemiology based on a single type of health care utilization. C1 Kaiser Permanente Ctr Hlth Res, Portland, OR 97227 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. RP Vollmer, WM (reprint author), Kaiser Permanente Ctr Hlth Res, 3800 N Kaiser Ctr Dr, Portland, OR 97227 USA. EM vollmerwi@chr.mts.kpnw.org FU NHLBI NIH HHS [HL41039] NR 35 TC 75 Z9 77 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 1998 VL 157 IS 4 BP 1079 EP 1084 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZG643 UT WOS:000073024500012 PM 9563722 ER PT J AU Asch, S Leake, B Anderson, R Gelberg, L AF Asch, S Leake, B Anderson, R Gelberg, L TI Why do symptomatic patients delay obtaining care for tuberculosis? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID IMMUNODEFICIENCY-VIRUS INFECTION; SEEKING CARE; MORTALITY; DIAGNOSIS; ACCESS AB The resurgence of tuberculosis (TB) has coincided with deteriorating access to care for high-risk populations. We sought to determine what perceived access barriers delayed symptomatic TB patients from obtaining care. In order to do this, we conducted a survey in Los Angeles County, California, using a consecutive sample of patients with active TB as confirmed by the county TB control authority. The measures used in the study were a self-reported delay in seeking care of more than 60 d from symptom onset, a period sufficient to cause skin-test conversion in exposed contacts, and self-reported access barriers. The county TB registry provided supplementary clinical data. We found that one in five of the 248 symptomatic respondents (response rate: 60%) delayed obtaining care for > 60 d (mean = 74 d, SD = 216 d). During the delay, patients exposed an average of eight contacts. As compared with the rest of the sample, delay was more common in those who were unemployed (25% versus 14%), concerned about cost (27% versus 14%), anticipated prolonged waiting-room time (26% versus 14%), believed they could treat themselves (31% versus 14%), anticipated difficulty in getting an appointment (28% versus 16%), were uncertain about where to get care (33% versus 16%), and feared immigration authorities (47% versus 18%) (p < 0.05). Logistic regression revealed that uncertainty about where to get care, unemployment, and belief in the efficacy of self-treatment independently predicted delay > 60 d. Illness severity as measured by chest radiography, sputum smears, and symptoms had little impact on delay. We conclude that because access variables such as lack of employment and knowledge about where to obtain care were more closely associated with clinically significant delay than was severity of illness, these results raise concerns about the equity of access to care among TB patients. The results suggest that improving the availability of services for high-risk groups may substantially reduce TB patients' delay in obtaining care, and thus may limit the spread of the disease. C1 W Los Angeles Vet Adm Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Asch, S (reprint author), W Los Angeles Vet Adm Med Ctr, Dept Med, Mail Code 111G,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 28 TC 86 Z9 87 U1 0 U2 6 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 1998 VL 157 IS 4 BP 1244 EP 1248 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZG643 UT WOS:000073024500036 PM 9563746 ER PT J AU Quinn, DA Du, HK Thompson, BT Hales, CA AF Quinn, DA Du, HK Thompson, BT Hales, CA TI Amiloride analogs inhibit chronic hypoxic pulmonary hypertension SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID VASCULAR SMOOTH-MUSCLE; NA+-H+ EXCHANGE; CELL-PROLIFERATION; PH REGULATION; GROWTH; RATS; HEPARINS; INJURY; NHE-1 AB Na+/H+ exchange regulation of intracellular pH may play a permissive role in pulmonary artery smooth muscle cell (PASM) proliferation. Our laboratory has demonstrated that dimethyl amiloride (DMA), an amiloride derivative with enhanced selectivity as an inhibitor of the Na+/H+ antiporter, can inhibit bovine PASM proliferation in vitro. We hypothesized that DMA would inhibit development of hypoxic pulmonary hypertension by interfering with PASM growth in vivo. Sprague-Dawley rats were exposed to 10% O-2 for 14 d without (n = 9) or with (n = 7) DMA continuous infusion 3 mg/kg/d. The animals treated with DMA had significant reductions in pulmonary artery pressure and total pulmonary vascular resistance index (TPVRI) when compared with hypoxic control rats (p < 0.05). Pulmonary vascular remodeling was significantly reduced in animals treated with DMA as measured by percent wall thickness and percentage of thick-walled intra-acinous vessels (p < 0.05). We used a second Na+/H+ exchange inhibitor, ethylisopropyl amiloride (EIPA, 3 mg/kg/d, n = 9), and found similar reductions in pulmonary artery pressure, TPVRI, and pulmonary vascular remodeling. Polycythemia during hypoxia was unchanged by treatment with DMA or EIPA. In conclusion, despite the hypertensive effects of polycythemia, DMA and EIPA can significantly reduce pulmonary vascular remodeling induced by chronic hypoxia. C1 Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hales, CA (reprint author), Massachusetts Gen Hosp, Dept Med, Pulm Crit Care Unit, Fruit St, Boston, MA 02114 USA. EM hales@helix.mgh.harvard.edu FU NHLBI NIH HHS [HL-39150, HL-09572] NR 27 TC 41 Z9 51 U1 1 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 1998 VL 157 IS 4 BP 1263 EP 1268 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZG643 UT WOS:000073024500039 PM 9563749 ER PT J AU Ermert, L Ermert, M Goppelt-Struebe, M Walmrath, D Grimminger, F Steudel, W Ghofrani, HA Homberger, C Duncker, HR Seeger, W AF Ermert, L Ermert, M Goppelt-Struebe, M Walmrath, D Grimminger, F Steudel, W Ghofrani, HA Homberger, C Duncker, HR Seeger, W TI Cyclooxygenase isoenzyme localization and mRNA expression in rat lungs SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID ENDOPEROXIDE SYNTHASE CYCLOOXYGENASE; HYPOXIC PULMONARY VASOCONSTRICTION; MITOGEN-INDUCIBLE CYCLOOXYGENASE; ARACHIDONIC-ACID METABOLISM; ESCHERICHIA-COLI HEMOLYSIN; PROSTAGLANDIN-H SYNTHASE-2; HUMAN ALVEOLAR MACROPHAGES; BLOOD-FLOW DISTRIBUTION; NECROSIS-FACTOR-ALPHA; MESSENGER-RNA AB Prostanoid generation may proceed via both isoforms of cyclooxygenase, Cox-1 and Cox-2. Cox-1 is thought to be ubiquitously expressed, whereas Cox-2 is mostly assumed to be dynamically regulated, responding to inflammatory stimuli. The cellular localization of Cox-1 and Cox-2 in the lung, an organ with high cyclooxygenase activity, is not known. In normal rat lungs the expression and localization of Cox-1 and Cox-2 were examined with immunogold-silver staining and the RT-PCR technique. Quantitative image analysis of the staining intensity was performed by measuring mean gray values of digitized epipolarization images. Expression of both Cox-1 and Cox-2 was readily detectable in rat lungs. Cox-1 immunoreactivity localized predominantly to bronchial epithelial cells, smooth muscle cells of large hilum veins, and (with lower expression) to alveolar macrophages and pulmonary artery endothelial cells. The most intense Cox-2 staining was noted in macrophage-and mast cell-like cells, detected in close vicinity to the bronchial epithelium and in the connective tissue surrounding the vessels. In addition, strong Cox-2 expression was found in smooth muscle cells of partially muscular vessels and large veins of the hilum. Bronchial epithelial cells displayed Cox-2 immunoreactivity with limited intensity. Alveolar macrophages and alveolar septal cells were only occasionally stained with anti-Cox-2 antibodies. Both Cox-1 and Cox-2 are constitutively expressed in several cell types of normal rat lung, but display clearly different patterns of cellular localization. Cox-2 may not be related only to lung inflammation, but is suggested to be implicated in regulatory processes under physiological conditions as well. C1 Universitat Giessen, Inst Anat & Cell Biol, D-35385 Giessen, Germany. Universitat Giessen, Dept Internal Med, D-35385 Giessen, Germany. Universitat Giessen, Dept Pathol, D-35385 Giessen, Germany. Univ Erlangen Nurnberg, Dept Internal Med 4, Res Labs Nephrol, D-8520 Erlangen, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA USA. RP Ermert, L (reprint author), Universitat Giessen, Inst Anat & Cell Biol, Aulweg 123, D-35385 Giessen, Germany. NR 56 TC 74 Z9 74 U1 0 U2 1 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1998 VL 18 IS 4 BP 479 EP 488 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA ZH292 UT WOS:000073092700004 PM 9533935 ER PT J AU Willett, CG Wang, MH Emanuel, RL Graham, SA Smith, DI Shridhar, V Sugarbaker, DJ Sunday, ME AF Willett, CG Wang, MH Emanuel, RL Graham, SA Smith, DI Shridhar, V Sugarbaker, DJ Sunday, ME TI Macrophage-stimulating protein and its receptor in non-small-cell lung tumors: Induction of receptor tyrosine phosphorylation and cell migration SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; FACTOR SCATTER FACTOR; GENE-EXPRESSION; HAMSTER LUNG; CANCER-CELLS; II CELLS; IDENTIFICATION; PROLIFERATION; FAMILY; P53 AB Previously, we identified macrophage-stimulating protein (MSP) as being expressed during hamster lung injury induced by nitrosamine carcinogens. Transient, generalized epithelial-cell hyperplasia during the preneoplastic period, and eventually nonneuroendocrine (non-NE) lung tumors, are known to develop in these nitrosamine-treated hamsters. We wished to test the hypothesis that MSP and its tyrosine kinase receptor, RON, might represent an autocrine/paracrine system involved in the pathogenesis of human nonneuroendocrine lung tumors, the non-small-cell carcinomas (NSCLCs). We found that this occurred in a paracrine fashion in three of eight primary human NSCLCs that expressed messenger RNA (mRNA) for MSP at high levels in histologically normal lung adjacent to the tumor, but not in the primary tumor, together with mRNA for RON in both normal and tumor tissue. MSP and RON could also constitute an autocrine/paracrine system in human NSCLC cell lines: five of 16 cell lines (squamous and adenosquamous) expressed both MSP and RON; and an additional five of 16 cell lines expressed RON without detectable MSP. Although three cases of primary squamous-cell carcinomas expressed MSP (two of three in the tumor and one of three in nonneoplastic lung), mRNA for RON was not detectable in these cases. RON was functional in all tested RON mRNA-positive cell lines, with exogenous MSP inducing RON-mediated tyrosine phosphorylation. Treatment of a RON-positive adenosquamous carcinoma cell line with MSP additionally resulted in increased motility in a cell-migration assay, suggesting that MSP might promote cell migration of some NSCLCs. In conclusion, MSP and RON might represent an autocrine/paracrine system involved in the pathogenesis of lung cancer, although the nature of the biologic responses in different cell types might vary considerably. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Internal Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Mol Biol & Genet, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Dept Expt Pathol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Wayne State Univ, Dept Med, Div Pulm & Crit Care Med, Detroit, MI 48202 USA. Childrens Hosp, Dept Med, Boston, MA 02115 USA. RP Sunday, ME (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, 75 Francis St, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL44984] NR 38 TC 48 Z9 50 U1 0 U2 3 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD APR PY 1998 VL 18 IS 4 BP 489 EP 496 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA ZH292 UT WOS:000073092700005 PM 9533936 ER PT J AU Duerinckx, AJ Lipton, MJ AF Duerinckx, AJ Lipton, MJ TI Noninvasive coronary artery imaging using CT and MR imaging SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID BREATH-HOLD; ANGIOGRAPHY; STENOSIS; ECHO C1 Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Lipton, MJ (reprint author), Univ Chicago, Dept Radiol, MC 2026,5841 S Maryland Ave, Chicago, IL 60637 USA. NR 33 TC 14 Z9 14 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1998 VL 170 IS 4 BP 900 EP 902 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZC706 UT WOS:000072608400012 PM 9530030 ER PT J AU Yeow, KM Kaufman, JA Rieumont, MJ Geller, SC Waltman, AC AF Yeow, KM Kaufman, JA Rieumont, MJ Geller, SC Waltman, AC TI Axillary vein puncture over the second rib SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID VENOUS CATHETERS; MANAGEMENT; PLACEMENT; ACCESS C1 Chang Gung Mem Hosp, Chang Gung Coll Med & Technol, Dept Diagnost Radiol 1, Tao Yuan, Hsien, Taiwan. RP Kaufman, JA (reprint author), Massachusetts Gen Hosp, Dept Radiol, 32 Fruit St,GRB 290, Boston, MA 02114 USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1998 VL 170 IS 4 BP 924 EP 926 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZC706 UT WOS:000072608400017 PM 9530035 ER PT J AU Boland, GW Gazelle, GS Girard, MJ Mueller, PR AF Boland, GW Gazelle, GS Girard, MJ Mueller, PR TI Asymptomatic hydropneumothorax after therapeutic thoracentesis for malignant pleural effusions SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID INTERVENTIONS; SPACE AB OBJECTIVE. The purpose of this study was to document in a historical cohort the incidence and clinical observations of pneumothorax ex vacuo after therapeutic thoracentesis for malignant pleural effusions in patients with underlying parenchymal lung disease. MATERIALS AND METHODS. Forty pneumothoraces resulted from 512 therapeutic thoracenteses performed for malignant pleural effusions over a 3-year period. Twenty-nine patients with pneumothoraces underwent catheter placement in the pleural space for treatment. Of these, 12 pneumothoraces resolved and 17 remained unchanged. We reviewed the charts of these 17 patients to document the cause of malignant pleural effusion, presence of underlying malignant parenchymal disease, volume of fluid aspirated, and improvement in symptoms. Clinical outcome was then evaluated, including size of residual pneumothorax, duration of catheter drainage, and reaccumulation of effusion. RESULTS. No patients' lungs reexpanded despite insertion of large-bore (16- to 35-French) chest tubes. All had pneumothoraces that occupied at least 30% of the hemithorax; all were asymptomatic; all had underlying parenchymal disease and noncompliant lungs. Pleural effusion reaccumulated in all 17 after removal of the chest tube. CONCLUSION. A subgroup of patients with malignant lung parenchymal disease who undergo therapeutic thoracentesis will develop asymptomatic hydropneumothoraces due to poor lung compliance, These patients do not require further catheter drainage. Pleural effusion will reaccumulate in the residual space over a variable period of time. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Boland, GW (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 9 TC 24 Z9 24 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1998 VL 170 IS 4 BP 943 EP 946 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZC706 UT WOS:000072608400022 PM 9530040 ER PT J AU Mueller, PR AF Mueller, PR TI Percutaneous drainage of pancreatic necrosis: Is it ecstasy or agony? SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Mueller, PR (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 7 TC 13 Z9 14 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1998 VL 170 IS 4 BP 976 EP 977 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZC706 UT WOS:000072608400029 PM 9530047 ER PT J AU Goldberg, SN Gazelle, GS Solbiati, L Livraghi, T Tanabe, KK Hahn, PF Mueller, PR AF Goldberg, SN Gazelle, GS Solbiati, L Livraghi, T Tanabe, KK Hahn, PF Mueller, PR TI Ablation of liver tumors using percutaneous RF therapy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Roentgen-Ray-Society CY MAY, 1997 CL BOSTON, MASSACHUSETTS SP Amer Roentgen Ray Soc ID TISSUE ABLATION; RADIOFREQUENCY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Osped Gen, Dept Radiol, I-21052 Busto Arsizio, Italy. Osped Civile, Dept Radiol, I-20059 Vimercate, Italy. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Goldberg, SN (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. OI Solbiati, Luigi/0000-0002-3109-1449 NR 8 TC 184 Z9 201 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 1998 VL 170 IS 4 BP 1023 EP 1028 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZC706 UT WOS:000072608400036 PM 9530053 ER PT J AU Nakatani, Y Kitamura, H Inayama, Y Kamijo, S Nagashima, Y Shimoyama, K Nakamura, N Sano, J Ogawa, N Shibagaki, T Resl, M Mark, EJ AF Nakatani, Y Kitamura, H Inayama, Y Kamijo, S Nagashima, Y Shimoyama, K Nakamura, N Sano, J Ogawa, N Shibagaki, T Resl, M Mark, EJ TI Pulmonary adenocarcinomas of the fetal lung type - A clinicopathologic study indicating differences in histology, epidemiology, and natural history of low-grade and high-grade forms SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE adenocarcinoma of fetal lung type; pulmonary blastoma; pulmonary endodermal tumor resembling fetal lung; pleuropulmonary blastoma; alpha-fetoprotein ID NEUROENDOCRINE DIFFERENTIATION; PLEUROPULMONARY BLASTOMA; TUMOR; CELL; P53; CARCINOMA; ACCUMULATION; CHILDHOOD; PROGNOSIS; FEATURES AB Seven cases of high-grade adenocarcinoma of fetal lung type (H-FLAC) are compared with nine cases of pulmonary endodermal tumor resembling fetal lung or low-grade adenocarcinoma of fetal lung type (L-FLAC). Of the seven patients with of H-FLAC, four were men and three were women. All of the patients but one were in their 60s or 70s. Five patients were smokers. After resection of the tumor, three patients died of metastases, two patients are alive with no evidence of disease, and two patients died of a postoperative complication. Histologically, H-FLAC and L-FLAC have both complex glandular structures resembling fetal lung and neuroendocrine differentiation. Two cases of H-FLAC had stromal proliferation typical of biphasic pulmonary blastoma. The H-FLAC was distinguished from L-FLAC by the presence of disorganized glands, large vesicular nuclei, prominent nucleoli, pronounced aniso-nucleosis, absence of morules, transition to conventional adenocarcinoma, broad areas of necrosis, desmoplastic stroma, overexpression of p53 protein, and production of alpha-fetoprotein. High and low grades of FLAG explain discrepancies in previously reported clinicopathologic features of FLAG. The H-FLAC needs to be distinguished from L-FLAC. Both forms may have stromal components, so both have been referred to as blastomas. The H-FLAC represents the prototype of so-called pulmonary blastoma predominantly seen in the elderly, whereas L-FLAC and its biphasic form predominate in the middle-aged population. C1 Hosp Yokohama City Univ, Sch Med, Div Anat & Surg Pathol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Urafune Hosp, Dept Pathol & Lab Med, Yokohama, Kanagawa 232, Japan. Yokohama City Univ, Sch Med, Dept Pathol, Yokohama, Kanagawa 232, Japan. Yokohama Citizens Hosp, Dept Pathol, Yokohama, Kanagawa, Japan. Kanagawa Prefectural Cardiovasc & Resp Ctr, Dept Pathol, Yokohama, Kanagawa, Japan. Kanagawa Prefectural Cardiovasc & Resp Ctr, Dept Surg, Yokohama, Kanagawa, Japan. Charles Univ, Sch Med, Dept Pathol, CS-50165 Hradec Kralove, Czech Republic. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Nakatani, Y (reprint author), Hosp Yokohama City Univ, Sch Med, Div Anat & Surg Pathol, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. NR 44 TC 54 Z9 56 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD APR PY 1998 VL 22 IS 4 BP 399 EP 411 DI 10.1097/00000478-199804000-00003 PG 13 WC Pathology; Surgery SC Pathology; Surgery GA ZF020 UT WOS:000072854700003 PM 9537466 ER PT J AU Franco, L Najvar, L Gomez, BL Restrepo, S Graybill, JR Restrepo, A AF Franco, L Najvar, L Gomez, BL Restrepo, S Graybill, JR Restrepo, A TI Experimental pulmonary fibrosis induced by Paracoccidioides brasiliensis conidia, measurement of local host responses SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INTERSTITIAL LUNG-DISEASES; LOWER RESPIRATORY-TRACT; GROWTH-FACTOR; CHRONIC INFLAMMATION; UNKNOWN CAUSE; HISTOPLASMOSIS; FIBROBLASTS; CYTOKINES; SECRETION; ALPHA AB Pulmonary fibrosis was induced following inoculation of Paracoccidioides brasiliensis conidia intranasally in BALB/c mice. Fibrosis was associated with formation of granulomas, increase in lung hydroxyproline, and sustained increases in tissue tumor necrosis factor-alpha and transforming growth factor-beta. This study suggests a role for these cytokines in generation of pulmonary fibrosis associated with chronic granulomatous infectious diseases. C1 Corp Invest Biol, Medellin, Colombia. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Franco, L (reprint author), Corp Invest Biol, Medellin, Colombia. NR 36 TC 22 Z9 22 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DRIVE SUITE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 1998 VL 58 IS 4 BP 424 EP 430 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA ZK139 UT WOS:000073289300006 PM 9574786 ER PT J AU Meigs, JB Nathan, DM Wilson, PWF Cupples, LA Singer, DE AF Meigs, JB Nathan, DM Wilson, PWF Cupples, LA Singer, DE TI Metabolic risk factors worsen continuously across the spectrum of nondiabetic glucose tolerance - The Framingham Offspring Study SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE glucose intolerance; diabetes mellitus, non-insulin-dependent; cardiovascular diseases; risk factors; insulin resistance ID CORONARY HEART-DISEASE; UNITED-STATES POPULATION; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; PIMA-INDIANS; ASYMPTOMATIC HYPERGLYCEMIA; PRECIPITATION PROCEDURE; DIAGNOSTIC-CRITERIA; ORIGINAL COHORT AB Background: Categorical definitions for glucose intolerance imply that risk thresholds exist, but metabolic risk for type 2 diabetes mellitus or cardiovascular disease may increase continuously as glucose intolerance increases. Objective: To examine the distributions of the following meta belie risk factors across the spectrum of glucose tolerance: overall and central obesity, hypertension, low levels of high-density lipoprotein cholesterol, and increased triglyceride and insulin levels. Design: Cross-sectional analysis. Setting: The community-based Framingham Offspring Study. Participants: 2583 adults without previously diagnosed diabetes. Measurements: Clinical data; fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken 2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance was determined by 1980 World Health Organization criteria. Patients with normal glucose tolerance were categorized into quintiles of fasting glucose. The distributions of each metabolic risk factor and the metabolic sum of the six risk factors were assessed across seven categories from the lowest quintile of normal fasting glucose level through impaired glucose tolerance and previously undiagnosed diabetes. Results: The mean age of patients was 54 years (range, 26 to 82 years); 52.7% of patients were women. Glucose tolerance testing found that 12.7% of patients had impaired glucose tolerance and 4.8% had previously undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and odds ratios for obesity, elevated waist-to-hip ratio, hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and hyperinsulinemia showed continuous increases across the spectrum of nondiabetic glucose tolerance. Although a threshold effect near the upper range of nondiabetic glucose tolerance could not be ruled out for triglyceride levels in men and for insulin levels Z hours after oral challenge in men and women, no other metabolic risk factors showed clear evidence of thresholds for increased risk. Conclusions: Metabolic risk factors for type 2 diabetes mellitus and for cardiovascular disease worsen continuously across the spectrum of glucose tolerance categories, beginning in the lowest quintiles of normal fasting glucose level. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. NHLBI, Framingham, MA USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Staniford 50-9, Boston, MA 02114 USA. FU NHLBI NIH HHS [N01-HC-38083] NR 68 TC 136 Z9 141 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 1 PY 1998 VL 128 IS 7 BP 524 EP + PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA ZE539 UT WOS:000072803500002 PM 9518396 ER PT J AU Curhan, GC Willett, WC Speizer, FE Stampfer, MJ AF Curhan, GC Willett, WC Speizer, FE Stampfer, MJ TI Beverage use and risk for kidney stones in women SO ANNALS OF INTERNAL MEDICINE LA English DT Article DE kidney calculi; beverages; fluid intake; coffee; alcoholic beverages ID FOOD FREQUENCY QUESTIONNAIRE; DIETARY CALCIUM; CONSUMPTION; REPRODUCIBILITY; VALIDITY; NEPHROLITHIASIS; UROLITHIASIS; PREVENTION; DISEASE; JUICE AB Background: An increase in fluid intake is routinely recommended for patients who have had kidney stones to decrease the likelihood of recurrence. However, data on the effect of particular beverages on stone formation in women are limited. Objective: To examine the association between the intake of 17 beverages and risk for kidney stones in women. Design: Prospective cohort study with 8 years of follow-up. Setting: United States. Participants: 81093 women in the Nurses' Health Study who were 40 to 65 years of age in 1986 and had no history of kidney stones. Measurements: Beverage use and diet were assessed in 1986 and 1990 with a validated, self-administered food-frequency questionnaire. The main outcome measure was incident symptomatic kidney stones. Results: During 553081 person-years of follow-up over an 8-year period, 719 cases of kidney stones were documented. After risk factors other than fluid intake were controlled for, the relative risk for stone formation for women in the highest quintile of total fluid intake compared with women in the lowest quintile was 0.62 (95% CI, 0.48 to 0.80). Inclusion of consumption of specific beverages in the multivariate model significantly added to prediction of risk for kidney stones (P < 0.001). In a multivariate model that adjusted simultaneously for the 17 beverages and other possible risk factors, risk for stone formation decreased by the following amount for each 240-mL (8-oz) serving consumed daily: 10% (CI, 5% to 15%) for caffeinated coffee, 9% (CI, 2% to 15%) for decaffeinated coffee, 8% (CI, 1% to 15%) for tea, and 59% (CI, 32% to 75%) for wine. In contrast, a 44% (CI, 9% to 92%) increase in risk was seen for each 240-mL serving of grapefruit juice consumed daily. Conclusions: An increase in total fluid intake can reduce risk for kidney stones, and the choice of beverage may be meaningful. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA40356]; NIDDK NIH HHS [DK45362] NR 32 TC 141 Z9 144 U1 1 U2 9 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 1 PY 1998 VL 128 IS 7 BP 534 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA ZE539 UT WOS:000072803500003 PM 9518397 ER PT J AU Minassian, BA DeLorey, TM Olsen, RW Philippart, M Bronstein, Y Zhang, QW Guerrini, R Van Ness, P Livet, MO Delgado-Escueta, AV AF Minassian, BA DeLorey, TM Olsen, RW Philippart, M Bronstein, Y Zhang, QW Guerrini, R Van Ness, P Livet, MO Delgado-Escueta, AV TI Angelman syndrome: Correlations between epilepsy phenotypes and genotypes SO ANNALS OF NEUROLOGY LA English DT Article ID HAPPY PUPPET SYNDROME; UNIPARENTAL DISOMY; DELETION; EEG; CHROMOSOME-15; DIAGNOSIS; 15Q11-13; CLONING; GENE AB We compared epilepsy phenotypes with genotypes of Angelman syndrome (AS), including chromosome 15q11-13 deletions (class I), uniparental disomy (class II), methylation imprinting abnormalities (class III), and mutation in the UBE3A gene (class IV). Twenty patients were prospectively selected based on clinical cytogenetic and molecular diagnosis of AS. All patients had 6 to 72 hours of closed-circuit television videotaping and digitized electroencephalogrpahic (EEG) telemetry. Patients from all genotypic classes had characteristic EEGs with diffuse bifrontally dominant high-amplitude 1- to 3-Hz notched or triphasic or polyphasic slow waves, or slow and sharp waves. Class I patients had severe intractable epilepsy, most frequently with atypical absences and myoclonias and less frequently with generalized extensor tonic seizures or flexor spasms. Epileptic spasms were recorded in AS patients as old as 41 years. Aged-matched class II, III, and IV patients had either no epilepsy or drug-responsive mild epilepsy with relatively infrequent atypical absences, myoclonias, or atonic seizures. In conclusion, maternally inherited chromosome 15q11-13 deletions produce severe epilepsy. Loss-of-function UBE3A mutations, uniparental disomy, or methylation imprint abnormalities in AS are associated with relatively mild epilepsy. Involvement of other genes in the chromosome 15q11-13 deletion, such as GABRB3, may explain severe epilepsy in AS. C1 Univ Calif Los Angeles, Comprehens Epilepsy Program, Sch Med, Dept Neurol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Div Pediat Neurol, Los Angeles, CA USA. W Los Angeles DVA Med Ctr, Neurol Serv, Los Angeles, CA USA. W Los Angeles DVA Med Ctr, Res Serv, Los Angeles, CA USA. Univ Toronto, Hosp Sick Children, Dept Pediat, Div Neurol, Toronto, ON M5G 1X8, Canada. Univ Toronto, Bloorview Epilepsy Program, Toronto, ON, Canada. Univ Pisa, Inst Child Neurol & Psychiat, Pisa, Italy. IRCCS, Stella Maris Fdn, Pisa, Italy. Univ Texas, Dept Neurol, Dallas, TX 75230 USA. Hop Enfants La Timone, Dept Child Neurol, Marseille, France. RP Delgado-Escueta, AV (reprint author), Univ Calif Los Angeles, Comprehens Epilepsy Program, Sch Med, Dept Neurol, Bldg 500,Room 3405,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NINDS NIH HHS [NS21908, NS28772] NR 29 TC 117 Z9 118 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD APR PY 1998 VL 43 IS 4 BP 485 EP 493 DI 10.1002/ana.410430412 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZF997 UT WOS:000072954400011 PM 9546330 ER PT J AU Cherukupally, SR Merchant, SN Rosowski, JJ AF Cherukupally, SR Merchant, SN Rosowski, JJ TI Correlations between pathologic changes in the stapes and conductive hearing loss in otosclerosis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE conductive hearing loss; otosclerosis; pathology; stapes; temporal bone AB The goal of this temporal bone study was to quantify the relationship between specific histologic changes at the stapes footplate and the magnitude of the air-bone gap in otosclerosis. The study material comprised 26 specimens with otosclerosis and 37 age-matched controls. Detailed anatomic measurements were made on each histologic section through the stapes footplate in each bone, resulting in 30 different measurement parameters for each bone. For frequencies 250 to 2,000 Hz, the conductive hearing loss correlated highly with (p < .01) and appeared to be caused primarily by narrowing and loss of the annular ligament, especially at the posterior stapediovestibular joint space. The size of the air-bone gap appeared to be determined by the extent and degree of this pathologic change. Schuknecht's hypothesis that bony ankylosis of the footplate would be associated with an air-bone gap of >30 dB was supported by our data. However, the degree and extent of bony footplate ankylosis could not be reliably predicted by the size of the air-bone gap. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Merchant, SN (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [K08-DC00088, P01-DC00119] NR 11 TC 22 Z9 24 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD APR PY 1998 VL 107 IS 4 BP 319 EP 326 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA ZH205 UT WOS:000073083400010 PM 9557767 ER PT J AU Foster, GP Isselbacher, EM Rose, GA Torchiana, DF Akins, CW Picard, MH AF Foster, GP Isselbacher, EM Rose, GA Torchiana, DF Akins, CW Picard, MH TI Accurate localization of mitral regurgitant defects using multiplane transesophageal echocardiography SO ANNALS OF THORACIC SURGERY LA English DT Article ID VALVE REPAIR; RECONSTRUCTION; MOTION AB Background. Appropriate patient selection for surgical repair of the mitral valve depends on the specific location and mechanism of regurgitation, which, in turn, has necessitated a more detailed method to accurately describe mitral pathology. This study tests a strategy of using multiplane transesophageal echocardiography to systematically localize mitral regurgitant defects and compares these results with the surgical findings. Methods. Fifty patients with mitral regurgitation underwent intraoperative transesophageal echocardiography for the evaluation of mitral pathology and potential repair. Mitral regurgitant defects were localized using a systematic strategy and a simple nomenclature that divides each mitral valve into six sections (three sections per leaflet) and each prosthetic sewing ring into six sections (60 radial degrees = one section). Results. Thirty-nine patients with native mitral valves were studied, for a total of 234 sections evaluated. Eighty-seven of these sections contained regurgitant defects by transesophageal echocardiography (mean number of regurgitant defects per valve, 2.2; range, 1 through 6). There was agreement between the transesophageal echocardiographic and surgical localizations in 96% (224/234; p < 0.0001) of the sections. Eleven patients with prosthetic mitral valves were studied, for a total of 66 sections evaluated. Twenty-three of these sections contained paravalvular leaks by transesophageal echocardiography (mean number of leaks per prosthesis, 2.1; range, 1 through 6). There was agreement between the transesophageal echocardiographic and surgical localizations in 88% (58/66; p < 0.001) of the sections. Conclusions. This transesophageal echocardiographic strategy provides a systematic method to accurately localize mitral regurgitant lesions and has the potential to improve the preoperative assessment of patients with significant mitral regurgitation. (C) 1998 by The Society of Thoracic Surgeons. C1 Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Foster, GP (reprint author), Cardiol Consultants PC, 520 Med Ctr Dr,Suite 100, Medford, OR 97504 USA. OI Picard, Michael/0000-0002-9264-3243 NR 23 TC 90 Z9 94 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD APR PY 1998 VL 65 IS 4 BP 1025 EP 1031 DI 10.1016/S0003-4975(98)00084-8 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA ZH911 UT WOS:000073160100030 PM 9564922 ER PT J AU Kohn, SE Melvold, J Shipper, V AF Kohn, SE Melvold, J Shipper, V TI The preservation of sonority in the context of impaired lexical-phonological output SO APHASIOLOGY LA English DT Article ID CONDUCTION APHASIA AB The single word repetition of two fluent aphasics was evaluated to explore the nature of their lexical-phonological deficit. Phonological theory postulates that features, subcomponents of segments, are organized hierarchically according to their acoustic and articulatory properties and their role in the phonological system. This study hypothesized that the higher a feature sits in the hierarchy, the more stable it will be following neurological damage, and the less likely it is to be substituted independently of other features. Analyses focused on the status of the feature sonorant, for the following two reasons: (1) this feature is located at the top of the feature hierarchy; and (2) unlike other consonant features, it plays an important role in syllable structure by constraining the ordering of consonants within syllables. The pattern of feature substitutions produced by the two subjects in this study was identical, with the order of least to most affected type conforming to the predictions based on the feature hierarchy: consonant substitution errors due to a change in the value of the feature sonorant were rare, and when this feature changed, it generally occurred in conjunction with changes to other features. By contrast, place of articulation, a feature that: sits low in the hierarchy, was the most frequent feature substituted, and was typically altered without changing the other feature values of the affected consonant. Moreover, when sonorant feature substitutions and consonant omissions did occur, they most often produced a syllable with a less complex sonority pattern. These findings strengthen the notion that the relative preservation of sonority, both at the segmental and syllabic levels, contributes to the normal sounding quality of the neologisms produced by even the most severe jargonaphasics. C1 Moss Rehabil Res Inst, Philadelphia, PA 19141 USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Kohn, SE (reprint author), Moss Rehabil Res Inst, 1200 W Tabor Rd, Philadelphia, PA 19141 USA. NR 34 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0268-7038 J9 APHASIOLOGY JI Aphasiology PD APR-MAY PY 1998 VL 12 IS 4-5 BP 375 EP 398 DI 10.1080/02687039808249539 PG 24 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ162 UT WOS:000073185700007 ER PT J AU Stewart, JW Quitkin, FM McGrath, PJ Amsterdam, J Fava, M Fawcett, J Reimherr, F Rosenbaum, J Beasley, C Roback, P AF Stewart, JW Quitkin, FM McGrath, PJ Amsterdam, J Fava, M Fawcett, J Reimherr, F Rosenbaum, J Beasley, C Roback, P TI Use of pattern analysis to predict differential relapse of remitted patients with major depression during 1 year of treatment with fluoxetine or placebo SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TRUE DRUG RESPONSE; ANTIDEPRESSANT DRUGS; DOWN-REGULATION; RECEPTOR; RATS; PHARMACOLOGY; DESIPRAMINE; IMIPRAMINE AB Background: Delayed and persistent ("true drug") improvement characterizes the response to antidepressant medication. Early or nonpersistent ("placebo") benefit is typical of a placebo response. The prediction was that patients with a true drug response would sustain their benefit best if they continued to receive the drug and that patients with a placebo response would have an equivalent prognosis whether they continued to receive the drug or were switched to placebo. Methods: Patients with major depression who met the study's response criteria (a modified Hamilton Depression Rating Scale score less than or equal to 7 and failure to meet major depression criteria after each of the last 3 weeks following 12 to 14 weeks of treatment with fluoxetine hydrochloride, 20 mg/d) were enrolled in a 50-week randomized placebo substitution trial during which the return of depressive symptoms defined relapse. The timing and persistency of response during initial treatment defined true drug or placebo response patterns. Results: Patients with a true drug response pattern relapsed significantly more frequently if they were switched to placebo than if they continued to receive fluoxetine (P<.001 for weeks 12-26, P<.005 for weeks 26-50, and P<.41 for weeks 50-62). Patients with a placebo response pattern had an equivalent outcome whether maintained on fluoxetine therapy or placebo (P<.20 for weeks 12-26, test invalid for weeks 26-50, and P<.67 for weeks 50-62). Patients with a placebo response pattern relapsed more often when they continued to receive fluoxetine than patients with a true drug response pattern (P<.01 for weeks 12-26, P<.10 for weeks 26-50, and P<.36 for weeks 50-62). Conclusions: These findings confirm that pattern analysis validly differentiates true drug from nonspecific initial responses and extend its use to the continuation and maintenance phases of treatment for depression. Investigations into the mechanisms of antidepressant activity might best be limited to those that can account for delayed efficacy. Fluoxetine's efficacy during the continuation and maintenance phases of treatment may be limited to patients with a true drug pattern of initial response. C1 New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Rush Presbyterian St Lukes Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. Univ Utah, Dept Psychiat, Salt Lake City, UT USA. Eli Lilly Corp, Indianapolis, IN USA. Colorado State Univ, Dept Stat, Ft Collins, CO 80523 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. RP Stewart, JW (reprint author), Unit 35, 1051 Riverside Dr, New York, NY 10032 USA. RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Beasley, Charles/0000-0001-8743-7691 NR 25 TC 83 Z9 86 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD APR PY 1998 VL 55 IS 4 BP 334 EP 343 DI 10.1001/archpsyc.55.4.334 PG 10 WC Psychiatry SC Psychiatry GA ZG355 UT WOS:000072993300008 PM 9554429 ER PT J AU Gade-Andavolu, R MacMurray, JP Blake, H Muhleman, D Tourtellotte, W Comings, DE AF Gade-Andavolu, R MacMurray, JP Blake, H Muhleman, D Tourtellotte, W Comings, DE TI Association between the gamma-aminobutyric acid A(3) receptor gene and multiple sclerosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID BENZODIAZEPINE RECEPTORS; DECARBOXYLASE; LYMPHOCYTES; DOPAMINE; NEURONS; SCREEN; GROWTH; BRAIN; LOCUS; GABA AB Background: In a prior study we observed an association between the dopamine D-2 receptor gene (DRD2) and the age of onset and/or diagnosis of multiple sclerosis (MS). We hypothesized that this effect was mediated through the dopaminergic control of the release of prolactin, a modulator of immune response. Since gamma-aminobutyric acid also modulates the release of prolactin, we examined the possible association between alleles of the GABRA3 (gamma-aminobutyric acid A, receptor) gene and MS. Design: We examined the GABRA3 alleles of 189 subjects with MS who died of their disease. They were divided into test group 1 (n=64) and retest group 2 (n=56). Each group had a separate set of controls (group 1, n=109; group 2, n=430). All subjects were white. All were tested at a dinucleotide cytosine-adenosine repeat polymorphism with 6 alleles representing 11 to 16 repeats. Results: In the first group there was a significant difference in the frequency of the GABRA3 alleles (P<.002), with the most notable difference being an increase in the frequency of the 16-repeat allele in subjects with MS and a relative decrease in the other alleles. In the replication group there was again a significant difference in the distribution of the GABRA3 alleles (P<.001), and again the greatest difference was an increase in the frequency of the 16-repeat allele in subjects with MS. For both groups combined, a significant difference in the frequency of the 16-repeat allele was noted (chi(2)=46.30; P<.001). Conclusions: These results suggest the GABRA3 gene may be a risk factor for MS. As with the DRD2 gene, the effect may be mediated through its regulation of prolactin release. C1 City Hope Natl Med Ctr, Dept Med Genet, Duarte, CA 91910 USA. Loma Linda Univ, Dept Psychiat, Loma Linda, CA 92350 USA. W Los Angeles Vet Affairs Med Ctr, Dept Neurol, Los Angeles, CA 90073 USA. RP Comings, DE (reprint author), City Hope Natl Med Ctr, Dept Med Genet, 1500 E Duarte Rd, Duarte, CA 91910 USA. NR 36 TC 10 Z9 10 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD APR PY 1998 VL 55 IS 4 BP 513 EP 516 DI 10.1001/archneur.55.4.513 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA ZG859 UT WOS:000073047200011 PM 9561979 ER PT J AU Weissgold, DJ Gragoudas, ES Green, JP Kent, CJ Rubin, PAD AF Weissgold, DJ Gragoudas, ES Green, JP Kent, CJ Rubin, PAD TI Eye-sparing treatment of massive extrascleral extension of choroidal melanoma SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID CILIARY BODY MELANOMAS; ORBITAL EXTENSION C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Gragoudas, ES (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 8 TC 3 Z9 3 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 1998 VL 116 IS 4 BP 531 EP 533 PG 3 WC Ophthalmology SC Ophthalmology GA ZG802 UT WOS:000073041200020 PM 9565057 ER PT J AU Jellinek, M Little, M AF Jellinek, M Little, M TI Supporting child psychiatric services using current managed care approaches - You can't get there from here SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID MENTAL-HEALTH; UNITED-STATES; PREVALENCE; DISORDERS; COMORBIDITY; ADOLESCENTS; MARKETPLACE; RISK AB For-profit behavioral health care companies have transformed the way mental health services are provided for children. Using marketplace approaches, companies have "carved out" mental health services for many patients receiving care from pediatricians. This report details specific approaches used by these firms to maximize profits, minimize the role of child and adolescent psychiatrists, and limit clinical services. Understanding for-profit carveouts will help primary care pediatricians appreciate the likely consequences of such reimbursement incentives for the care of children and their families. C1 Massachusetts Gen Hosp, Child Psychiat Serv, Child Psychiat Dept, Boston, MA 02114 USA. RP Jellinek, M (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, Child Psychiat Dept, 55 Fruit St,Bulfinch 351, Boston, MA 02114 USA. NR 60 TC 12 Z9 12 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 1998 VL 152 IS 4 BP 321 EP 326 PG 6 WC Pediatrics SC Pediatrics GA ZH194 UT WOS:000073082300002 PM 9559705 ER PT J AU Pecha, MD Able, AC Barber, DB Willingham, AC AF Pecha, MD Able, AC Barber, DB Willingham, AC TI Outcome after spontaneous spinal epidural hematoma in children: Case report and review of the literature SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Review ID EXTRADURAL HEMATOMA; HEMORRHAGE AB Objective: Spontaneous spinal epidural hematoma (SSEH) is an idiopathic accumulation of blood in the vertebral epidural space without identifiable predisposing factors. First reported in 1869, the clinical outcome in children younger than 18 years old has not been clearly delineated. Design: A comprehensive review of the English language literature revealed 26 patients younger than 18 years old with reported clinical outcomes. The 27th case is presented. Results: Complete neurologic recovery occurred in 14 of 27 (52%) patients, partial recovery in 12 of 27 (44%) patients, and death in 1 of 27 (4%) patients. Conclusion: There is an overall good prognosis for neurologic recovery in children who experience SSEH. (C) 1998 by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation. C1 Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX 78284 USA. S Texas Vet Healthcare Syst, Audie L Murphy Div, Spinal Cord Injury Sect, San Antonio, TX USA. Warm Springs Baptist Rehabil Hosp, San Antonio, TX USA. RP Able, AC (reprint author), Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 38 TC 21 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 1998 VL 79 IS 4 BP 460 EP 463 DI 10.1016/S0003-9993(98)90151-4 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA ZG317 UT WOS:000072989400018 PM 9552116 ER PT J AU Makary, MA Warshaw, AL Centeno, BA Willett, CG Rattner, DW Fernandez-del Castillo, C AF Makary, MA Warshaw, AL Centeno, BA Willett, CG Rattner, DW Fernandez-del Castillo, C TI Implications of peritoneal cytology for pancreatic cancer management SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the New-England-Surgical-Society CY SEP 19-20, 1997 CL BOLTON LANDING, NEW YORK SP New England Surg Soc ID PROGNOSTIC VALUE; GASTRIC-CANCER; OVARIAN-CARCINOMA; WASHINGS; CELLS; ADENOCARCINOMA; LAPAROSCOPY; DISEASE; HEAD AB Objective: To assess the implications of positive cytology for malignant cells (positive results) from peritoneal washings in the management of patients with pancreatic cancer. Design: Retrospective cohort study. Setting: Referral practice in a university hospital. Patients: A total of 32 consecutive pancreatic cancer patients with positive results from peritoneal washings during a 4-year period, 17 with visible biopsy-proven intraabdominal metastases at the time of laparoscopy or laparotomy and 15 without visible metastases. A treatment-matched control group of 30 patients was randomly selected from a group of 105 patients with negative cytology for malignant cells (negative results) from peritoneal-fluid cytology. Interventions: Eight of 17 patients with visible metastases underwent treatment with chemotherapy, radiation, or both; 13 of the 15 patients with no visible metastases underwent further treatment, including pancreatic resection in 2 patients and external beam radiation in 13 patients (3 with intraoperative radiation therapy). Main Outcome Measures: Time to metastases and mortality. Results: Median survival among patients with and without visible metastasis was 7.8 months and 8.6 months, respectively (P=.95), despite the fact that patients without visible metastases received more treatment. Patients without visible metastases at presentation were found to have metastatic disease as documented by computed tomographic scan or subsequent laparotomy at a median time of 2.9 months. The survival of treatment-matched patients with negative cytology was significantly longer (median, 13.5 months; P=.04). Conclusions: Pancreatic cancer patients with peritoneal micrometastases have a dismal outcome even without macroscopic metastases. Since these patients do not benefit from local therapy, the finding of a positive result from peritoneal-fluid cytologic testing contraindicates further irradiation or surgery, except for specific complications. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, WACC 464,15 Parkman St, Boston, MA 02114 USA. NR 33 TC 47 Z9 47 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1998 VL 133 IS 4 BP 361 EP 364 DI 10.1001/archsurg.133.4.361 PG 4 WC Surgery SC Surgery GA ZH294 UT WOS:000073092900003 PM 9565114 ER PT J AU Z'graggen, K Fernandez-del Castillo, C Rattner, DW Sigala, H Warshaw, AL AF Z'graggen, K Fernandez-del Castillo, C Rattner, DW Sigala, H Warshaw, AL TI Metastases to the pancreas and their surgical extirpation SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the New-England-Surgical-Society CY SEP 19-20, 1997 CL BOLTON LANDING, NEW YORK SP New England Surg Soc ID RENAL-CELL CARCINOMA; FOLLOW-UP; CHONDROSARCOMA; SOLITARY; MANIFESTATION; NEPHRECTOMY; MANAGEMENT; RECURRENCE; SARCOMAS; TUMORS AB Background: The pancreas is an unusual but occasionally favored site for metastases, notably from carcinomas of the kidney and lung. The pancreas may be the only identified locus of spread, and therefore may provide an opportunity for significant palliation or even cure using pancreatectomy. Objective: To report the treatment and outcome of patients presenting with metastases to the pancreas. Design: Five-year survey. Setting: Tertiary referral center. Patients: Ten patients with apparently isolated metastases to the pancreas were identified from January 1, 1991, to December 31, 1995. All patients were followed up until death or to September 1997. Results: The patients had been treated previously for carcinoma of the lung (n=4), renal cell carcinoma (n=2), sarcoma (n=2), breast carcinoma (n=1), and endometrial carcinoma (n=1). The interval between primary treatment and presentation of the metastases averaged 70 months (14-24 months for lung cancer, 10 and 22 years for renal cell carcinoma, 4 and 6 years for sarcoma, 8 years for breast cancer, and 36 months for endometrial carcinoma). Metastases were initially misdiagnosed as primary pancreatic cancers in 7 patients. In 4 patients (those with renal cell cancer and sarcomas), the tumor was completely resected using total pancreatectomy (n=3) or Whipple resection (n=1). Survival after diagnosis averaged 22 months. Two of the 4 patients undergoing pancreatic resection remain alive and well 20 and 25 months after pancreatectomy. Conclusions: The pancreas may be the presenting and perhaps sole locus for metastasis, typically years after treatment for certain extrapancreatic malignant neoplasms. Recognition and surgical treatment can provide worthwhile palliation and long-term survival. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Warshaw, AL (reprint author), Massachusetts Gen Hosp, Dept Surg, White 506,55 Fruit St, Boston, MA 02114 USA. NR 35 TC 113 Z9 117 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1998 VL 133 IS 4 BP 413 EP 416 DI 10.1001/archsurg.133.4.413 PG 4 WC Surgery SC Surgery GA ZH294 UT WOS:000073092900020 PM 9565122 ER PT J AU Ferguson, CM AF Ferguson, CM TI Laparoscopic common bile duct exploration - Practical application SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the New-England-Surgical-Society CY SEP 19-20, 1997 CL BOLTON LANDING, NEW YORK SP New England Surg Soc ID ENDOSCOPIC SPHINCTEROTOMY; MANAGEMENT; CHOLEDOCHOLITHIASIS; SURGERY AB Objective: To evaluate the effectiveness of laparoscopic common bile duct exploration in unselected patients. Design: Consecutive sample. Setting: Tertiary care general hospital. Patients: Three hundred and two patients with symptomatic cholelithiasis presenting to a single surgeon during a 5-year period. Interventions: Laparoscopic cholecystectomy, cholangiography and common bile duct exploration. Main Outcome Measures: Successful laparoscopic cholecystectomy. and common bile duct exploration. Results: Three hundred and two consecutive patients underwent cholecystectomy for symptomatic cholelithiasis; 280 of the procedures were successfully completed laparoscopically. Cholangiography was attempted in 269 patients, was successful in 239, and revealed evidence of choledocholithiasis in 25. Preoperative ultrasonography and liver function tests predicted the presence of common bile duct stones in 24% and 32% of patients, respectively. Seven of the patients with choledocholithiasis presented with biliary colic, 7 with biliary colic and jaundice, 8 with acute cholecystitis (3 with gallbladder perforation), 1 with acute cholecystitis and jaundice, and 2 with gallstone pancreatitis. Four of 5 patients underwent successful transcystic exploration with a biliary-Fogarty catheter, 12 of 16 patients underwent successful transcystic choledochoscopy and stone basket extraction, and all 4 attempts at choledochotomy and choledochoscopic stone basket extraction were successful, for a total success rate of 80% with laparoscopic common bile duct exploration. One of the failures was converted to an open procedure, and 4 of the failures had successful postoperative endoscopic retrograde cholangiopancreatography and extraction of stones. Conclusions: Laparoscopic cholecystectomy and common bile duct exploration is a highly successful procedure for the management of common duct stones in an unselected group of patients. Choledochotomy with choledochoscopy is the preferred method of common bile duct exploration. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Ferguson, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 15 Parkman St,Suite 465, Boston, MA 02114 USA. NR 13 TC 18 Z9 18 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1998 VL 133 IS 4 BP 448 EP 451 DI 10.1001/archsurg.133.4.448 PG 4 WC Surgery SC Surgery GA ZH294 UT WOS:000073092900033 PM 9565128 ER PT J AU Ko, DSC Lerner, R Klose, G Cosimi, AB AF Ko, DSC Lerner, R Klose, G Cosimi, AB TI Effective treatment of lymphedema of the extremities SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 78th Annual Meeting of the New-England-Surgical-Society CY SEP 19-20, 1997 CL BOLTON LANDING, NEW YORK SP New England Surg Soc ID LYMPHATIC MICROSURGERY; GREATER OMENTUM AB Objective: To define the immediate and long-term volumetric reduction following complete decongestive physiotherapy (CDP) for lymphedema. Design: Prospective study of consecutively treated patients. Setting: Freestanding outpatient referral centers. Patients: Two hundred ninety-nine patients referred for evaluation of lymphedema of the upper (2% primary, 98% secondary) or lower (61.3% primary, 38.7% secondary) extremities were treated with CDP for an average duration of 15.7 days. Lymphedema reduction was measured following completion of treatment and at 6- and 12-month follow-up visits. Intervention: Complete decongestive physiotherapy is a 2-phase noninvasive therapeutic regimen. The first phase consists of manual lymphatic massage, multilayered inelastic compression bandaging, remedial exercises, and meticulous skin care. Phase 2 focuses on self-care by means of daytime elastic sleeve or stocking compression, nocturnal wrapping, and continued exercises. Main Outcome Measures: Average limb volumes in milliliters were calculated prior to treatment, at the end of phase 1, and at 6- to 12-month intervals during phase 2 to assess percent volume reduction. Results: Lymphedema reduction averaged 59.1% after upper-extremity CDP and 67.7% after lower-extremity treatment. With an average follow-up of 9 months, this improvement was maintained in compliant patients (86%) at 90% of the initial reduction for upper extremities and lower extremities. Noncompliant patients lost a part (33%) of their initial reduction. The incidence of infections decreased from 1.10 infections per patient per year to 0.65 infections per patient per year after a complete course of CDP. Conclusions: Complete decongestive physiotherapy is a highly effective treatment for both primary and secondary lymphedema. The initial reductions in volume achieved are maintained in the majority of the treated patients. These patients typically report a significant recovery from their previous cosmetic and functional impairments, and also from the psychosocial limitations they experienced from a physical stigma they felt was often trivialized by the medical and payor communities. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Surg Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Lerner Lymphedema Serv, Boston, MA USA. RP Ko, DSC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gen Surg Serv, 55 Fruit St,Blake 655, Boston, MA 02114 USA. NR 26 TC 130 Z9 135 U1 2 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 1998 VL 133 IS 4 BP 452 EP 457 DI 10.1001/archsurg.133.4.452 PG 6 WC Surgery SC Surgery GA ZH294 UT WOS:000073092900035 PM 9565129 ER PT J AU Rider, LG Gurley, RC Pandey, JP Garcia-de la Torre, I Kalovidouris, AE O'Hanlon, TP Love, LA Hennekam, RCM Baumbach, LL Neville, HE Garcia, CA Klingman, J Gibbs, M Weisman, MH Targoff, IN Miller, FW AF Rider, LG Gurley, RC Pandey, JP Garcia-de la Torre, I Kalovidouris, AE O'Hanlon, TP Love, LA Hennekam, RCM Baumbach, LL Neville, HE Garcia, CA Klingman, J Gibbs, M Weisman, MH Targoff, IN Miller, FW TI Clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INCLUSION-BODY MYOSITIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; DEPENDENT DIABETES-MELLITUS; SIGNAL RECOGNITION PARTICLE; RHEUMATOID-ARTHRITIS; GENETIC SUSCEPTIBILITY; OLIGONUCLEOTIDE PROBES; IRANIAN JEWS; DISEASE; HLA AB Objective. To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM. Methods. Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected and 28 unaffected members of 16 unrelated families in which 2 or more blood relatives developed an IIM. In addition, findings in patients with familiar IIM were compared with those in 181 patients with sporadic IIM, The families included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with other siblings or relatives with polymyositis or dermatomyositis, and 3 families with inclusion body myositis. Results, The clinical features of familial IIM were similar to those of sporadic IIM, although the frequency of myositis-specific autoantibodies tvas lon cr in familial than in sporadic IIM. DRB1*0301 mas a common genetic risk factor for familial and sporadic IIM, but contributed less to the genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic IIM), Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P = 0.002), Conclusion. These findings emphasize that 1) familial muscle weakness is not always due to inherited metabolic defects or dystrophies, but may be the result of the development of IIM in several members of the same family, and 2) multiple genetic factors are likely important in the etiology and disease expression of familial IIM, as is also the case for sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial IIM. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Guadalajara, Guadalajara 44430, Jalisco, Mexico. Hosp Gen Occidente SS, Guadalajara, Jalisco, Mexico. US FDA, Ctr Food & Special Nutr, Washington, DC 20204 USA. Amsterdam Med Coll, Dept Pediat, Amsterdam, Netherlands. Amsterdam Med Coll, Inst Human Genet, Amsterdam, Netherlands. Univ Miami, Sch Med, Miami, FL 33152 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Denver VA Med Ctr, Denver, CO USA. Louisiana State Univ, Sch Med, New Orleans, LA USA. So Calif Permanente Med Grp, Walnut Creek, CA USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Univ Oklahoma, Med Sci Ctr, VA Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Indiana Univ, VA Med Ctr, Indianapolis, IN 46204 USA. RP Rider, LG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, NIH, Bldg 29B,Room 2G11,HFM-561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 58 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 1998 VL 41 IS 4 BP 710 EP 719 DI 10.1002/1529-0131(199804)41:4<710::AID-ART19>3.0.CO;2-K PG 10 WC Rheumatology SC Rheumatology GA ZG163 UT WOS:000072972800018 PM 9550481 ER PT J AU Spiro, RG Bhoyroo, VD AF Spiro, RG Bhoyroo, VD TI Characterization of a spleen sulphotransferase responsible for the 6-O-sulphation of the galactose residue in sialyl-N-acetyl-lactosamine sequences SO BIOCHEMICAL JOURNAL LA English DT Article ID LINKED CARBOHYDRATE CHAINS; LEUKOCYTE ADHESION MOLECULE; PORCINE ZONA-PELLUCIDA; L BARK LECTIN; L-SELECTIN; SULFATED OLIGOSACCHARIDES; GLYCOPROTEIN HORMONES; LEWIS-X; LIGANDS; ACETYLGLUCOSAMINE AB An enzyme which catalyses the transfer of sulphate from 3'-phosphoadenosine 5'-phosphosulphate (PAPS) to C-6 of galactose in the NeuAc alpha 2-3Gal beta 1-4GlcNAc (3'SLN) sequence has been found in rat spleen microsomes and its specificity indicates that it is well suited to participate in the assembly of 3'-sialyl-6'-sulpho-LacNAc [NeuAc alpha 2-3Gal(6-SO4)beta 1-4GlcNAc] and 3'-sialyl-6'-sulpho-Lewis(x) [NeuAc alpha 2-3Gal(6-SO4)beta 1-4(Fuc alpha 1-3)GlcNAc] saccharide groups which have been implicated as selectin ligands, This sulphotransferase has a strict requirement for oligosaccharide accepters which are capped by an alpha 2-3-linked sialic acid residue, although GlcNAc in 3'SLN can be substituted by Glc, and Gal beta 1-4GlcNAc can be replaced by Gal beta 1-3GlcNAc without loss of activity. The finding that 3'-sialyl Lewis(x) was inert as an acceptor suggested that fucosylation, in contrast with sialylation, follows the addition of the sulphate group, Since fetuin glycopeptides containing the NeuAc alpha 2-3Gal beta 1-4GlcNAc sequence had a similar affinity for the enzyme as the unattached 3'SLN, it would appear that the acceptor determinants reside primarily in the peripheral trisaccharide constellation. The position of the sulphate on C-6 of galactose was elucidated by Smith periodate oxidation, hydrazine/nitrous acid/NaBH4 treatment and elder (Sambucus nigra) bark lectin chromatography of the desialylated [S-35]sulphate-labelled products of the enzyme. Assays carried out with 3'SLN as acceptor indicated that the sulphotransferase had a pH optimum between 6.5 and 7.0 and a dependence on a bivalent cation best met by Mn2+ (12-25 mM); Triton X-100 (0.02 to 0.35 %) brought about maximal stimulation. Tentative K-m values determined for this enzyme were 4.7 mu M for PAPS, and 0.72 mM and 1.16 mM for 3'SLN and fetuin glycopeptides respectively, A survey of several rat organs indicated that the PAPS: 3'SLN-6-O-sulphotransferase is selectively distributed with maximal activity occurring in spleen which was substantially greater than thymus or lymph nodes, In contrast, other enzymes (i.e. PAPS:Gal-3-O- and GlcNAc-6-O-sulphotransferases) involved in the sulphation of sialyl-lactosamine and lactosamine sequences, which in the sulphated form are believed to also be selectin ligands, were more evenly distributed in lymphoid tissues, Relatively high activities for all three enzymes were found in brain. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med & Biol Chem, Boston, MA 02215 USA. RP Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK17325, DK17477] NR 39 TC 13 Z9 13 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND SN 0264-6021 EI 1470-8728 J9 BIOCHEM J JI Biochem. J. PD APR 1 PY 1998 VL 331 BP 265 EP 271 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG161 UT WOS:000072972500035 PM 9512489 ER PT J AU Kobayashi, T Sugimoto, T Kanzawa, M Chihara, K AF Kobayashi, T Sugimoto, T Kanzawa, M Chihara, K TI Identification of an enhancer sequence in 5 '-flanking region of 1A exon of mouse liver/bone/kidney-type alkaline phosphatase gene SO BIOCHEMISTRY AND MOLECULAR BIOLOGY INTERNATIONAL LA English DT Article DE alkaline phosphatase; osteoblast; differentiation; BMP-2 ID BONE MORPHOGENETIC PROTEIN-2; ELEMENTS CONTROL; EXPRESSION; PROMOTER; CELLS AB The 5'-flanking region of the 1A exon of the mouse liver/bone/kidney-type alkaline phosphatase (L/B/K ALP) gene was analyzed for the promoter activity. Luciferase assays revealed that a segment containing a 9 bp inverted repeat (nt -1212 to -1179, designated as IRS for inverted repeat segment) had an enhancer activity. Though an E-box at nt -234 did not have a prominent promoter activity, the effect of IRS required its presence. Both transcriptional activity and IRS binding to the nuclear proteins were similarly observed even in cells that did not express ALP. Bone morphogenetic protein-2 (BMP-2) induced the ALP expression in pluripotent C3H10T1/2 cells, but it did not increase the transcriptional activity of the promoter region. Though they do not determine cell specific or BMP-2 inducible ALP expression, IRS and the E-box at position -241 seem to be important for the basic transcriptional activity of ALP gene. C1 Kobe Univ, Sch Med, Dept Med,Div 3, Chuo Ku, Kobe, Hyogo 650, Japan. RP Kobayashi, T (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02174 USA. NR 16 TC 9 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS AUST PI MARRICKVILLE PA LOCKED BAG 16, MARRICKVILLE, NSW 2204, AUSTRALIA SN 1039-9712 J9 BIOCHEM MOL BIOL INT JI Biochem. Mol. Biol. Int. PD APR PY 1998 VL 44 IS 4 BP 683 EP 691 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK099 UT WOS:000073284800005 PM 9584982 ER PT J AU Bogdanov, A Simonova, M Weissleder, R AF Bogdanov, A Simonova, M Weissleder, R TI Design of metal-binding green fluorescent protein variants SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Article DE green fluorescent protein; imaging; PCR; fusion peptide; Tc-99m; technetium; oxotechnetate; covalent chromatography ID SINGLE-CHAIN FV; THYMIDINE KINASE; GENE-THERAPY; EXPRESSION; TC-99M; RADIOPHARMACEUTICALS; STABILITY AB Diglycylcysteine motifs bind reduced oxo-compounds of technetium-99m, an important isotope in nuclear imaging. We suggested a system for detecting gene expression employing the effect of oxo[Tc-99m]technetate (Tc(V)O3+) transchelation and coordination with redox amino acid motifs. DNA fragments encoding diglycylcysteine (GGC) binding motifs were prepared by PCR and positioned downstream from the green fluorescent protein (GFP) cDNA insert. Using a Bluescript (+) vector with the fusion protein positioned under the control of a lac promoter, we obtained several E. coli clones expressing the following GFP fusion peptides: (1) GFP-P1 bearing a 'hydrophilic' C-terminal peptide (LEGGGCEGGC) containing two residues of glutamic acid and C-terminal cysteine (2) GFP-P2 carrying a 'hydrophobic' (LGGGGCGG-GCGI) peptide (3) a control GFP fusion peptide with deleted C-terminal portion. Bacterial lysates obtained from the corresponding clones were tested for oxo[Tc-99m]technetate transchelation from a glucoheptonate complex. We found, using a solid phase assay, that radioactivity associated with protein lysates obtained from clones expressing GFP-P2 fusions were 3-4 fold higher than lysates prepared from a clone expressing a truncated GFP fusion protein lacking the C-terminal GGC motifs. High expression of GFP fusions (5-21% of total protein) was demonstrated by electrophoresis and verified by immunoblotting. Specific association of the isotope with GFP-P2 fusion proteins was detected upon incubation of gels in the presence of [Tc-99m]glucoheptonate, while no binding of oxo[Tc-99m]technetate to GFP-P1 was revealed. We demonstrated, by using semi-quantitative autoradiography, that there is a 10-fold higher binding of oxotechnetate to GFP-P2 than to a control GFP fusion protein. The implications of the study for in vivo gene expression imaging are discussed. (C) 1998 Elsevier Science B.V. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02129 USA. RP Bogdanov, A (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Rm 5420,Bldg 149,13th St, Boston, MA 02129 USA. FU NINDS NIH HHS [1RO1 NS35258-01] NR 33 TC 22 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD APR 1 PY 1998 VL 1397 IS 1 BP 56 EP 64 DI 10.1016/S0167-4781(97)00221-2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZG100 UT WOS:000072965600008 PM 9545533 ER PT J AU Schoepf, U Marecos, EM Melder, RJ Jain, RK Weissleder, R AF Schoepf, U Marecos, EM Melder, RJ Jain, RK Weissleder, R TI Intracellular magnetic labeling of lymphocytes for in vivo trafficking studies SO BIOTECHNIQUES LA English DT Article ID SUPERPARAMAGNETIC IRON-OXIDE; POSITRON EMISSION TOMOGRAPHY; T-CELLS; MACROPHAGES; PARTICLES; BIODISTRIBUTION; AGENT AB Lymphocyte adhesion and trafficking is difficult to observe in vivo over time. We used magnetic resonance imaging (MRI) to identify magnetically labeled lymphocytes in phantom experiments and in tissue. A method of lymphocyte labeling was developed that is based on fluid-phase endocytosis of nanometer-sized biocompatible superparamagnetic particles. The maximum cell uptake in culture was 0.11 ng Fe/cell corresponding to 5 x 10(6) particles/lymphocyte. Cells stably retained the label and were fully viable for at least 3 days. Labeled lymphocytes showed adhesion to human endothelial cells similar to unlabeled cells, indicating no effect of labeling on cell surface expression of adhesion proteins. No particle-mediated cytotoxicity could be observed. The detection threshold of MRI for detecting labeled lymphocytes in the current study was 2.5 x 10(6) cells/30 mu L sampling volume. Following intravenous injection of labeled lymphocytes into rats, cells accumulated in spleen, lymph nodes and liver with a similar bio-distribution as unlabeled cells. Lymphocyte accumulation in the spleen resulted in MRI signal intensity changes readily detectable by MRI. These findings suggest that intracellular lymphocyte labeling with superparamagnetic particles is feasible, does not alter the viability or tissue distribution of labeled cells and allows the detection of labeled lymphocytes by MRI. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, 149 13th St,Rm 5403, Boston, MA 02114 USA. FU NCI NIH HHS [2 RO1 CA 54886-04A1, 5 RO1 CA 59649-04]; NINDS NIH HHS [1 RO1 NS 35258-81] NR 24 TC 103 Z9 109 U1 1 U2 6 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD APR PY 1998 VL 24 IS 4 BP 642 EP + PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH111 UT WOS:000073073300027 PM 9564539 ER PT J AU Viola, JPB Kiani, A Bozza, PT Rao, A AF Viola, JPB Kiani, A Bozza, PT Rao, A TI Regulation of allergic inflammation and eosinophil recruitment in mice lacking the transcription factor NFAT1: Role of interleukin-4 (IL-4) and IL-5 SO BLOOD LA English DT Article ID ACTIVATED T-CELLS; AIRWAY HYPERREACTIVITY; DIFFERENTIATION FACTOR; ATOPIC-DERMATITIS; PERIPHERAL-BLOOD; DEFICIENT MICE; BONE-MARROW; ASTHMA; LYMPHOCYTES; EXPRESSION AB Transcription factors of the NFAT (nuclear factor of activated T cells) family regulate the expression of many genes encoding immunoregulatory cytokines and cell surface proteins during the immune response. The NFAT protein NFAT1 (NFATp) is expressed and functional in T cells, B cells, mast cells, and natural killer cells. Here we report a detailed analysis of the enhanced eosinophil responses of NFAT1-deficient mice, observed in an in vivo model of allergic inflammation. In addition to the pleural eosinophilia described previously, NFAT1(-/-) mice that have been sensitized with antigen display a significant increase, relative to wildtype mice. in the numbers of eosinophils in bone marrow end peripheral blood, After restimulation with antigen in vitro, antigen-responsive T cells from the draining lymph nodes of NFAT1(-/-) mice show increased expression of mRNA encoding the Th2 cytokines interleukin-4 (IL-4), IL-5, and IL-13. Consistent with this finding, there is a pronounced increase in the levels of IL-5 and IL-13 in the pleural cavities of sensitized NFAT1(-/-)mice after allergen challenge in vivo. Furthermore, development of eosinophilia depends on overexpression of IL-4 and IL-5. because it is strongly inhibited by administration of neutralizing antibodies to either of these cytokines. These results indicate that NFAT1-deficient mice are prone to develop a classically allergic phenotype characterized by eosinophilia and increased production of Th2 cytokines. Thus, the presence of NFAT1 might inhibit the allergic response, perhaps by interfering with the development of Th2 immune responses, and the lack or dysfunction of NFAT1 could potentially underlie certain cases of atopic disease. (C) 1998 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Fundacao Oswaldo Cruz, Dept Fisiol & Farmacodinam, Rio De Janeiro, Brazil. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. OI Bozza, Patricia/0000-0001-8349-9529; Viola, Joao/0000-0002-0698-3146 FU NCI NIH HHS [R01 CA42471]; NIAID NIH HHS [P01 AI35297] NR 47 TC 60 Z9 60 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1998 VL 91 IS 7 BP 2223 EP 2230 PG 8 WC Hematology SC Hematology GA ZD305 UT WOS:000072671900002 PM 9516119 ER PT J AU Guy, LG Mei, Q Perkins, AC Orkin, SH Wall, L AF Guy, LG Mei, Q Perkins, AC Orkin, SH Wall, L TI Erythroid Kruppel-like factor is essential for beta-globin gene expression even in absence of gene competition, but is not sufficient to induce the switch from gamma-globin to beta-globin gene expression SO BLOOD LA English DT Article ID DOMINANT CONTROL REGION; LOCUS-CONTROL REGION; TRANSCRIPTION FACTOR; TRANSGENIC MICE; DEVELOPMENTAL REGULATION; FACTOR EKLF; ACTIVATION; INACTIVATION; THALASSEMIA; PROMOTERS AB Different genes in the beta-like globin locus are expressed at specific times during development, This is controlled, in part, by competition between the genes for activation by the locus control region, In mice, gene inactivation of the erythroid Kruppel-like factor (EKLF) transcription factor results in a lethal anemia due to a specific and substantial decrease in expression of the fetal/adult-stage-specific beta-globin gene. In transgenic mice carrying the complete human beta-globin locus, EKLF ablation not only impairs human beta-globin-gene expression but also results in increased expression of the human gamma-globin genes during the fetal/adult stages. Hence. it may appear that EKLF is a determining factor for the developmental switch from gamma-globin to beta-globin transcription. However, we show here that the function of EKLF for beta-globin-gene expression is necessary even in absence of gene competition, Moreover, EKLF is not developmental specific and is present and functional before the switch from gamma-globin to beta-globin-gene expression occurs. Thus. EKLF is not the primary factor that controls the switch. We suggest that autonomous repression of gamma-globin transcription that occurs during late fetal development is likely to be the initiating event that induces the switch. (C) 1998 by The American Society of Hematology. C1 Ctr Hosp Univ Montreal, Ctr Rech, Quebec City, PQ H2L 4M1, Canada. Inst Canc Montreal, Quebec City, PQ, Canada. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Montreal, Dept Med, Quebec City, PQ, Canada. Monash Univ, Dept Physiol, Clayton, Vic 3168, Australia. RP Wall, L (reprint author), Ctr Hosp Univ Montreal, Ctr Rech, Room 4605,Pavillon Notre Dame,1560 Sherbrooke E, Quebec City, PQ H2L 4M1, Canada. RI Perkins, Andrew/M-3216-2014 OI Perkins, Andrew/0000-0003-3644-7093 NR 34 TC 23 Z9 23 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1998 VL 91 IS 7 BP 2259 EP 2263 PG 5 WC Hematology SC Hematology GA ZD305 UT WOS:000072671900006 PM 9516123 ER PT J AU Greipp, PR Leong, T Bennett, JM Gaillard, JP Klein, B Stewart, JA Oken, MM Kay, NE Van Ness, B Kyle, RA AF Greipp, PR Leong, T Bennett, JM Gaillard, JP Klein, B Stewart, JA Oken, MM Kay, NE Van Ness, B Kyle, RA TI Plasmablastic morphology - An independent prognostic factor with clinical and laboratory correlates: Eastern Cooperative Oncology Group (ECOG) myeloma trial E9486 report by the ECOG Myeloma Laboratory Group SO BLOOD LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 1995 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol ID MULTIPLE-MYELOMA; BONE-MARROW; CELLULAR MORPHOLOGY; RAS ONCOGENES; SURVIVAL; CLASSIFICATION; RELEVANCE; ESTABLISHMENT; IMMATURE; NETWORK AB We studied the prognostic significance of plasmablastic (PB) multiple myeloma (MM) in Eastern Cooperative oncology Group Phase ill trial E9486. Two reviewers independently reviewed 453 cases. They agreed on 37 PB (8.2%) cases and 416 non-PB cases, achieving an 85% concordance (P < .0001). These PB eases had significantly lower hemoglobin and serum albumin levels, higher calcium and beta 2-microglobuin levels, and higher percentage BM plasma cells (PC) by immunofluorescence. They had higher bone marrow PC labeling indices, higher serum soluble interleukin-6 receptor (sIL-6R) levels, and a higher probability of ras mutations. Three treatment regimens were used: vincristine, bis-chloro-ethyl nitrosourea (BCNU) melphalan, cyclophosphamide. and prednisone (VBMCP) alone; VBMCP with added cyclophosphamide (HiCy); or recombinant interferon alpha 2 (rIFN alpha 2). Although the numbers are low patients with PB had a significantly lower response rate versus non-PB MM when treated with VBMCP (treated, 47.1% v nontreated, 66.5% [P = .015]). Patients with nonresponding PB had a significantly higher progression rate than non-PB cases (30.6% v 11.8% [P < .0001]), especially with VBMCP alone (35.3% v 15.8% [P = .002]), and with added HiCy (37.5% v 9.8% [P < .0001]), but not with added rIFN alpha 2. Event-free and overall survival of PB MM was shorter (median years, 1.1 v 2.7 and 1.9 v 3.7, respectively [P < .0001 for both]). In multivariate analysis, PB classification was also highly prognostic. There is no survival difference between the patients who were classified as PB by both reviewers versus patients classified as PB by only one reviewer. We conclude that PB MM is a discrete entity associated with more aggressive disease and shortened survival. Tumor cell ras mutations and increased sIL-6R may contribute to a higher proliferation rate and reduced survival. There were significant improvements in response and progression with the addition of HiCy and rIFN alpha 2 to VBMCP, but the numbers were small and improved survival could not be shown. (C) 1998 by The American Society of Hematology. C1 Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Rochester, NY 14627 USA. Univ Nantes, F-44035 Nantes, France. Univ Wisconsin, Madison, WI 53706 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Kentucky, Lexington, KY 40506 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Greipp, PR (reprint author), Mayo Clin & Mayo Fdn, Div Hematol, Hilton Room 920,200 1st Ave SW, Rochester, MN 55905 USA. FU NCI NIH HHS [CA 13650, CA 21076, CA 23318] NR 31 TC 107 Z9 114 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1998 VL 91 IS 7 BP 2501 EP 2507 PG 7 WC Hematology SC Hematology GA ZD305 UT WOS:000072671900034 PM 9516151 ER PT J AU Waters, TM Bennett, CL Pajeau, TS Sobocinski, KA Klein, JP Rowlings, PA Horowitz, MM AF Waters, TM Bennett, CL Pajeau, TS Sobocinski, KA Klein, JP Rowlings, PA Horowitz, MM TI Economic analyses of bone marrow and blood stem cell transplantation for leukemias and lymphoma: what do we know? SO BONE MARROW TRANSPLANTATION LA English DT Article DE cost-effectiveness; economics; stem cell transplantation ID COST-EFFECTIVENESS; CLINICAL-TRIALS; RECOMMENDATIONS; CHEMOTHERAPY; MEDICINE; THERAPY; HEALTH; RECALL; POLICY; CARE AB The use of blood and/or bone marrow stem cell transplantation (SCT) grew extensively in the last decade as technological advances led to improved outcomes and wider availability, The first study of SCT costs, however, was not published until 1989, This paper summarizes current knowledge about costs and cost-effectiveness of allogeneic and autologous SCT for leukemias and lymphoma, Methodological issues in cost studies such as types of costs, methods of data collection, and time horizons are discussed, and studies are evaluated with regard to these issues, Considerations specific to economic analyses of SCT are considered, including the potential impact of technological changes, learning curve effects, and inter-institutional differences. C1 Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Evanston, IL 60208 USA. Northwestern Univ, Inst Hlth Serv Res & Policy Studies, Chicago, IL 60611 USA. Northwestern Univ, Lurie Canc Ctr, Chicago, IL 60611 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Midwest Ctr Hlth Serv & Policy Res, Hines, IL 60141 USA. Chicago Vet Adm Hlth Syst, Lakeside Div, Chicago, IL USA. Med Coll Wisconsin, Ctr Stat, Int Bone Marrow Transplant Registry Autologous Bl, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Hlth Policy Inst, Milwaukee, WI 53226 USA. RP Waters, TM (reprint author), Northwestern Univ, Inst Hlth Serv Res & Policy Studies, 629 Noyes St, Evanston, IL 60208 USA. RI Bennett, Charles/C-2050-2008 FU NHLBI NIH HHS [103HR951181P000-0000] NR 30 TC 34 Z9 34 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 1998 VL 21 IS 7 BP 641 EP 650 DI 10.1038/sj.bmt.1701160 PG 10 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA ZF263 UT WOS:000072880000001 PM 9578302 ER PT J AU Daily, J Werner, B Soiffer, R Fingeroth, J AF Daily, J Werner, B Soiffer, R Fingeroth, J TI IGIV: a potential role for hepatitis B prophylaxis in the bone marrow peritransplant period SO BONE MARROW TRANSPLANTATION LA English DT Article DE hepatitis B virus; bone marrow transplant; HBIG; IGIV ID LIVER-TRANSPLANTATION; VIRUS-INFECTION; REACTIVATION; CARRIERS; DONORS; CELLS AB Prevention of hepatitis B virus infection in transplant recipients can be difficult. Patients may be unresponsive to vaccination and intolerant of the intramuscular injections required to administer hepatitis B immune globulin (HBIG). A recipient of HBsAg-positive donor cells for a bone marrow transplant received multiple i.m. injections of HBIG, This mode of antibody delivery was limited by his thrombocytopenia and neutropenia and alternative forms of passive immunization were sought, Four lots of IGIV were investigated for anti-hepatitis B surface antibody (anti-HBs) content and all were found to contain significant antibody titer, Moreover, IGIV that was administered to four bone marrow transplant recipients for medical purposes unrelated to HBV transmission produced protective anti-HBs titers in all, These studies suggest IGIV may be useful for HBV prophylaxis in the appropriate setting or if HBIG is unavailable. The optimum regimen for HBV prevention in distinct transplant settings needs to be determined. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Div Infect Dis,Lab Infect Dis, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis,Dept Med, Boston, MA 02115 USA. Massachusetts Dept Publ Hlth, State Lab Inst, Boston, MA USA. RP Daily, J (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dana Farber Canc Inst, Div Infect Dis,Lab Infect Dis, 75 Francis St, Boston, MA 02115 USA. NR 20 TC 6 Z9 6 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD APR PY 1998 VL 21 IS 7 BP 739 EP 742 DI 10.1038/sj.bmt.1701148 PG 4 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA ZF263 UT WOS:000072880000017 PM 9578318 ER PT J AU Schmahmann, JD Sherman, JC AF Schmahmann, JD Sherman, JC TI The cerebellar cognitive affective syndrome SO BRAIN LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-Neuroscience CY OCT 25-30, 1997 CL NEW ORLEANS, LOUISIANA SP Soc Neurosci DE cerebellum; cognition; intellect; affect; behaviour ID POSITRON-EMISSION TOMOGRAPHY; CEREBRAL BLOOD-FLOW; RHESUS-MONKEY; BASIS PONTIS; CORTICOPONTINE PROJECTIONS; HORSERADISH-PEROXIDASE; MENTAL SKILLS; MOTOR IMAGERY; CORTEX; BRAIN AB Anatomical, physiological and functional neuroimaging studies suggest that the cerebellum participates in the organization of higher order function, but there are very few descriptions of clinically relevant cases that address this possibility. We performed neurological examinations, bedside mental state rests, neuropsychological studies and anatomical neuroimaging on 20 patients with diseases confined to the cerebellum, and evaluated the nature and severity of the changes in neurological and mental function. Behavioural changes were clinically prominent in patients with lesions involving the posterior lobe of the cerebellum and the vermis, and in some cases they were the most noticeable aspects of the presentation. These changes were characterized by: impairment of executive functions such as planning, set shifting, verbal fluency, abstract reasoning and working memory; difficulties with spatial cognition including visual-spatial organization and memory; personality change with blunting of affect or disinhibited and inappropriate behaviour; and language deficits including agrammatism and dysprosodia. Lesions of the anterior lobe of the cerebellum produced only minor changes in executive and visual-spatial functions. We have called this newly defined clinical entity the 'cerebellar cognitive affective syndrome'. The constellation of deficits is suggestive of disruption of the cerebellar modulation of neural circuits that link prefrontal, posterior parietal. superior temporal and limbic cortices with the cerebellum. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, VBK 915,Fruit St, Boston, MA 02114 USA. NR 115 TC 1268 Z9 1301 U1 14 U2 59 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD APR PY 1998 VL 121 BP 561 EP 579 DI 10.1093/brain/121.4.561 PN 4 PG 19 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZK380 UT WOS:000073314700003 PM 9577385 ER PT J AU Cobbers, JMJL Wolter, M Reifenberger, J Ring, GU Jessen, F An, HX Niederacher, D Schmidt, EE Ichimura, K Floeth, F Kirsch, L Borchard, F Louis, DN Collins, VP Reifenberger, G AF Cobbers, JMJL Wolter, M Reifenberger, J Ring, GU Jessen, F An, HX Niederacher, D Schmidt, EE Ichimura, K Floeth, F Kirsch, L Borchard, F Louis, DN Collins, VP Reifenberger, G TI Frequent inactivation of CDKN2A and rare mutation of TP53 in PCNSL SO BRAIN PATHOLOGY LA English DT Article ID NON-HODGKINS-LYMPHOMA; POLYMERASE CHAIN-REACTION; NERVOUS-SYSTEM LYMPHOMA; EPSTEIN-BARR-VIRUS; TUMOR-SUPPRESSOR GENE; GLIOMA CELL-LINES; RETINOBLASTOMA GENE; HUMAN CANCERS; BCL-2 GENE; P53 GENE AB Twenty primary central nervous system lymphomas (PCNSL) from immunocompetent patients (nineteen B-cell lymphomas and one T-cell lymphoma) were investigated for genetic alterations and/or expression of the genes BCL2, CCND1, CDK4, CDKN1A, CDKN2A, MDM2, MYC, RBI, REL, and TP53. The gene found to be altered most frequently was CDKN2A. Eight tumors (40%) showed homozygous and two tumors (10%) hemizygous CDKN2A deletions. Furthermore, methylation analysis of six PCNSL without homozygous CDKN2A loss revealed methylation of the CpG island within exon 1 of CDKN2A in three instances. Reverse transcription PCR analysis of CDKN2A mRNA expression was performed for 11 tumors and showed either no or weak signals. Similarly, immunocytochemistry for the CDKN2A gene product (p16) remained either completely negative or showed expression restricted to single tumor cells. None of the PCNSL showed amplification of CDK4. Similarly, investigation of CCND1 revealed no amplification, rearrangement or overexpression. The retinoblastoma protein was strongly expressed in ail tumors. Only one PCNSL showed a mutation of the TP53 gene, i.e., a missense mutation at codon 248 (CGG to TGG: Arg to Trp). No evidence of BCL2 gene rearrangement was found in 11 tumors investigated. The bcl-2 protein, however, was strongly expressed in most tumors. None of the 20 PCNSL demonstrated gene amplification of MDM2, MYC or REL. In summary, inactivation of CDKN2A by either homozygous deletion or DNA methylation represents an important molecular mechanism in PCNSL. Mutation of the TP53 gene and alterations of the other genes investigated appear to be of minor significance in these tumors. C1 Univ Dusseldorf, Dept Neuropathol, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Dept Dermatol, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Dept Gynecol, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Dept Neurosurg, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Dept Pathol, D-40225 Dusseldorf, Germany. Univ Dusseldorf, Ctr Biol & Med Res BMFZ, D-40225 Dusseldorf, Germany. Evangel & Johanniter Krankenanstalten Duisburg No, Neurosurg Clin, Oberhausen, Germany. Karolinska Hosp, Inst Oncol & Pathol, Div Tumor Pathol, S-10401 Stockholm, Sweden. Karolinska Hosp, Ludwig Inst Canc Res, S-10401 Stockholm, Sweden. Massachusetts Gen Hosp, Mol Neurooncol Lab, Dept Pathol Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Reifenberger, G (reprint author), Univ Dusseldorf, Dept Neuropathol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM reifenb@rz.uni-duesseldorf.de RI Jessen, Frank/E-7655-2012 NR 77 TC 46 Z9 46 U1 1 U2 2 PU INT SOC NEUROPATHOLOGY PI PITTSBURGH PA 200 LOTHROP ST A506, PITTSBURGH, PA 15213 USA SN 1015-6305 J9 BRAIN PATHOL JI Brain Pathol. PD APR PY 1998 VL 8 IS 2 BP 263 EP 276 PG 14 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZD549 UT WOS:000072697700004 PM 9546285 ER PT J AU Yang, H Li, WP Reeve, JR Rivier, J Tache, Y AF Yang, H Li, WP Reeve, JR Rivier, J Tache, Y TI PYY-preferring receptor in the dorsal vagal complex and its involvement in PYY stimulation of gastric acid secretion in rats SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE neuropeptide Y; PYY3-36; [Pro(34)]PYY; pancreatic polypeptide; Y1 receptor agonists; Y2 receptor agonists ID PEPTIDE-YY RECEPTORS; PANCREATIC-POLYPEPTIDE RECEPTOR; NEUROPEPTIDE-Y; BINDING-SITES; FUNCTIONAL EXPRESSION; ANESTHETIZED RATS; BRAIN; IDENTIFICATION; CLONING; SUBTYPE AB 1 Microinjection of peptide YY (PYY, 7-46 pmol) into the dorsal vagal complex (DVC) stimulated gastric acid secretion in urethane-anaesthetized rats. Using a variety of neuropeptide Y (NPY) and PYY derivatives, we characterized the pharmacological profile of the receptor mediating the acid secretory response to PYY. 2 [Pro(34)]rat(r)/porcine(p)PYY and [Pro(34)]human(h)PYY (23-117 pmol), microinjected unilaterally into the DVC resulted in a similar maximal increase in net acid secretion reaching 68+/-11 and 89+/-31 mu mol 90 min(-1) respectively. 3 Rat/hNPY and pNPY (47 pmol) microinjected into the DVC induced a similar net gastric acid secretion (27+/-8 and 23+/-8 mu mol 90 min(-1) respectively) and a higher dose (116 pmol) tended to reduce the response. 4 Pancreatic polypeptide (PP, 4-46pmol), [Leu(31),Pro(34)]r/hNPY (47 and 117 pmol) and the Y2 selective agonists, hPYY(3-36), PNPY5-36 and pNPY(13-36) (25-168 pmol) microinjected into the DVC failed to influence basal gastric acid secretion. 5 The rank order of potency of PYY greater than or equal to[Pro(34)]r/pPYY=[Pro(34)]hPYY>r/hNPY=pNPY to stimulate gastric acid secretion upon injection into the DVC and the ineffectiveness of PP, [Leu(31),Pro(34)]NPY and C-terminal NPY/PYY fragments suggest that a PYY-preferring receptor subtype may be involved in mediating the stimulating effect. C1 W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Peptide Biol, La Jolla, CA 92037 USA. RP Yang, H (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-50255, DK-30110]; NIMH NIH HHS [MH-00663] NR 53 TC 22 Z9 22 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD APR PY 1998 VL 123 IS 8 BP 1549 EP 1554 DI 10.1038/sj.bjp.0701767 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZJ171 UT WOS:000073186600011 PM 9605560 ER PT J AU van Dijk, S Dean, DD Liu, Y Zhao, Y Chirgwin, JM Schwartz, Z Boyan, BD AF van Dijk, S Dean, DD Liu, Y Zhao, Y Chirgwin, JM Schwartz, Z Boyan, BD TI Purification, amino acid sequence, and cDNA sequence of a novel calcium-precipitating proteolipid involved in calcification of Corynebacterium matruchotii SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE microbial calcification; proteolipid; dental calculus; amino acid sequence; cDNA nucleotide sequence ID PHOSPHOLIPID-PHOSPHATE COMPLEXES; CARTILAGE MATRIX VESICLES; POLYACRYLAMIDE-GEL ELECTROPHORESIS; SECONDARY-STRUCTURE; BRUSH-BORDER; PROTEINS; GROWTH; MEMBRANES; ION; IDENTIFICATION AB Corynebacterium matruchotii is a microbial inhabitant of the oral cavity associated with dental calculus formation. It produces membrane-associated proteolipid capable of inducing hydroxyapatite formation in vitro. This proteolipid was purified from chloroform:methanol extracts by chromatography on Sephadex LH-20 and migrated on SDS-polyacrylamide gel electrophoresis at 6-9 kDa. Removal of covalently attached acyl moieties by methanolic KOH decreased its molecular mass to approximately 5.5 kDa. The amino acid sequence of the apoproteolipid indicated a peptide of 50 amino acids, a calculated molecular weight of 5354 Da, and an isoelectric point of 4.28. Sequence analysis revealed an 8 amino acid sequence with homology to human phosphoprotein phosphatase 2A as well as several potential acylation sites and one phosphorylation site. The purified proteolipid induced calcium precipitation in vitro. Deacylation of the proteolipid by hydroxylamine treatment resulted in >50% loss of calcium-precipitating activity, suggesting that covalently attached Lipids are required. Degenerate oligonucleotide primers, based on the amino acid sequence, were used to amplify the gene for the 5.5 kDa proteolipid from total chromosomal DNA of C. matruchotii by PCR. A 166 bp cDNA was isolated and sequenced, confirming the amino acid sequence of the proteolipid. Thus, we have sequenced a unique bacterial proteolipid that is involved in the formation of dental calculus by precipitating Ca2+ and possibly in transport of inorganic phosphate, necessary for hydroxyapatite formation. C1 Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Orthopaed, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Periodont, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Hebrew Univ Jerusalem, Hadassah Fac Dent Med, Dept Periodont, IL-91010 Jerusalem, Israel. RP Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78229 USA. OI Dean, David/0000-0002-4512-9065 FU NIDCR NIH HHS [DE-07263, DE-05932]; NINDS NIH HHS [NSF EEC-9209612] NR 71 TC 10 Z9 10 U1 3 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0171-967X EI 1432-0827 J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD APR PY 1998 VL 62 IS 4 BP 350 EP 358 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZB890 UT WOS:000072518300013 PM 9504961 ER PT J AU Li, FP Stovall, EL AF Li, FP Stovall, EL TI Long-term survivors of cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Natl Coalit Canc Survivorship, Silver Spring, MD 20910 USA. RP Li, FP (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 1998 VL 7 IS 4 BP 269 EP 270 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZG556 UT WOS:000073015500001 PM 9568780 ER PT J AU Duncan, LM Deeds, J Hunter, J Shao, J Holmgren, LM Woolf, EA Tepper, RI Shyjan, AW AF Duncan, LM Deeds, J Hunter, J Shao, J Holmgren, LM Woolf, EA Tepper, RI Shyjan, AW TI Down-regulation of the novel gene melastatin correlates with potential for melanoma metastasis SO CANCER RESEARCH LA English DT Article ID RNA DIFFERENTIAL DISPLAY; MALIGNANT-MELANOMA; MESSENGER-RNA; CUTANEOUS MELANOMA; MURINE MELANOMA; CELL-LINES; IDENTIFICATION; EXPRESSION; SELECTION; SURVIVAL AB We have used differential cDNA display to search for genes whose expression correlates with an aggressive phenotype in variants of the B16 murine melanoma line, B16-F1 and B16-F10, This analysis identified a novel gene, termed melastatin, that is expressed at high levels in poorly metastatic variants of B16 melanoma and at much reduced levels in highly metastatic B16 variants, Melastatin was also found to be differentially expressed in tissue sections of human melanocytic neoplasms, Benign nevi express high levels of melastatin, whereas primary melanomas showed variable melastatin expression, Melastatin transcripts were not detected in melanoma metastases. Within the set of human primary cutaneous melanomas examined, melastatin expression appeared to correlate inversely with tumor thickness, The expression pattern observed suggests that loss of melastatin expression is an indicator of melanoma aggressiveness. C1 Millennium Pharmaceut, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatopathol Unit, Boston, MA 02114 USA. RP Shyjan, AW (reprint author), Millennium Pharmaceut, 640 Mem Dr, Cambridge, MA 02139 USA. NR 29 TC 243 Z9 259 U1 1 U2 9 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 1998 VL 58 IS 7 BP 1515 EP 1520 PG 6 WC Oncology SC Oncology GA ZE314 UT WOS:000072780200036 PM 9537257 ER PT J AU Colston, JT Chandrasekar, B Freeman, GL AF Colston, JT Chandrasekar, B Freeman, GL TI Expression of apoptosis-related proteins in experimental coxsackievirus myocarditis SO CARDIOVASCULAR RESEARCH LA English DT Article DE CD1; C3H.HeJ; mice; coxsackievirus; myocarditis; apoptosis; immunohistochemistry ID TUMOR-NECROSIS-FACTOR; PROGRAMMED CELL-DEATH; NITRIC-OXIDE; INTERLEUKIN-1-BETA-CONVERTING ENZYME; HUMAN MONOCYTES; BCL-2 HOMOLOG; FAS ANTIGEN; GENE; BAX; HEART AB Objective: The extent to which apoptosis contributes to myocyte cell loss during acute carditic viral infection is unknown. To assess whether apoptosis occurs in acute viral myocarditis, and how it is modulated, we studied mice inoculated with coxsackievirus B3 (CVB3). Methods: Five CD1 and C3H.HeJ (C3H) mice/group were sacrificed as saline vehicle-injected controls, and at 1, 2, and 3 weeks post-inoculation (p.i.) with 5 X 10(6) pfu CVB3. Histopathological status and terminal transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assays quantified inflammation, necrosis and apoptosis in myocardium. Apoptosis-related protein immunoreactivity defined presence and location of Bax, Fas, Fas Ligand (FasL), Bcl-2. interleukin-1 beta converting enzyme (ICE), inducible nitric oxide synthase (iNOS) and the proto-oncogene p53. Results: Both strains exhibited significant histopathology at all time points. Saline-injected control animals showed no signs of inflammation and no significant difference in apoptosis-related protein immunoreactivity was observed between strains. Myocardial TUNEL-positive cells were exceedingly rare though apoptosis was present in thymic medulla and spleen follicles. Pro-apoptotic proteins Bax, Fas, and Fast were present in all groups though no clear correlation with histopathology was apparent. By contrast, the anti-apoptotic protein Bcl-2 showed mild immunoreactivity in controls, which increased following infection and correlated well with histopathological scores in both strains. Myocardial iNOS immunoreactivity displayed a similar though weaker staining pattern to Bcl-2 over the 3 week study period in both strains. Neither ICE nor p53 immunoreactivity could be demonstrated in myocardium. Conclusion: Thus, despite marked inflammatory activity, myocyte apoptosis is rare. in acute CVB3 myocarditis in CD1 and C3H.HeJ mice. (C) 1998 Elsevier Science B.V. C1 Univ Texas, Hlth Sci Ctr, Div Cardiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. RP Freeman, GL (reprint author), Univ Texas, Hlth Sci Ctr, Div Cardiol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. EM freeman@uthscsa.edu FU NHLBI NIH HHS [2 T32 HL07350] NR 49 TC 47 Z9 52 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD APR PY 1998 VL 38 IS 1 BP 158 EP 168 DI 10.1016/S0008-6363(97)00323-4 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZT390 UT WOS:000074080500017 PM 9683918 ER PT J AU Medoff, BD Oelberg, DA Kanarek, DJ Systrom, DM AF Medoff, BD Oelberg, DA Kanarek, DJ Systrom, DM TI Breathing reserve at the lactate threshold to differentiate a pulmonary mechanical from cardiovascular limit to exercise SO CHEST LA English DT Article DE COPD; exercise testing; lactate threshold; ventilation ID INTERSTITIAL LUNG-DISEASE; AIR-FLOW OBSTRUCTION; MAXIMAL EXERCISE; VOLUNTARY VENTILATION; ANAEROBIC THRESHOLD; CAPACITY; PREDICTION; ACIDOSIS; PATTERN AB Study objectives: Criteria used to define the respective roles of pulmonary mechanics and cardiovascular disease in limiting exercise performance are usually obtained at peak exercise, but are dependent on maximal patient effort. To differentiate heart from lung disease during a less effort-dependent domain of exercise, the predictive value of the breathing reserve index (BRI=minute ventilation [(V) over dot E]/maximal voluntary ventilation [MVV]) at the lactate threshold (LT) was evaluated. Design: Thirty-two patients with COPD and a pulmonary mechanical limit (PML) to exercise defined by classic criteria at maximum oxygen uptake ((V) over dot o(2)max) were compared with 29 patients with a cardiovascular limit (CVL) and 12 normal control subjects. Expired gases and (V) over dot E were measured breath by breath using a commercially available metabolic cart (Model 2001; MedGraphics Corp; St. Paul, Minn). Arterial blood gases, pH, and lactate were sampled each minute during exercise, and cardiac output ((Q) over dot) was measured by first-pass radionuclide ventriculography (System 77; Baird Corp; Bedford, Mass) at rest and peak exercise. Results: For all patients, the BRI at lactate threshold (BRILT) correlated with the BRI at (V) over dot o(2)max (BRIMAX) (r=0.85, p<0.0001). The BRILT was higher for PML (0.73+/-0.03, mean+/-SEM) vs CVL (0.27+/-0.02, p<0.0001), and vs control subjects (0.24+/-0.03, p<0.0001). A BRILT greater than or equal to 0.42 predicted a PML at maximum exercise, with a sensitivity of 96.9%, a specificity of 95.1%, a positive predictive value of 93.9%, and a negative predictive value of 97.5%. Conclusions: The BRILT, a variable measured during the submaximal realm of exercise, can distinguish a PML from CVL. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Systrom, DM (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, Bulfinch 148,32 Fruit St, Boston, MA 02114 USA. NR 38 TC 20 Z9 20 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 1998 VL 113 IS 4 BP 913 EP 918 DI 10.1378/chest.113.4.913 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA ZG210 UT WOS:000072978200015 PM 9554625 ER PT J AU Yao, JK Moss, HB Kirillova, GP AF Yao, JK Moss, HB Kirillova, GP TI Determination of salivary cortisol by nonisotopic immunoassay SO CLINICAL BIOCHEMISTRY LA English DT Article ID ADOLESCENTS; SERUM C1 VA Pittsburgh Healthcare Syst, Neurochem & Psychopharmacol Lab, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Med Ctr, Western Psychiat Inst & Clin, Ctr Educ & Drug Abuse Res, Pittsburgh, PA USA. RP Yao, JK (reprint author), VA Pittsburgh Healthcare Syst, Neurochem & Psychopharmacol Lab, 7180 Highland Dr, Pittsburgh, PA 15206 USA. FU NIDA NIH HHS [P50-DA 05605] NR 10 TC 14 Z9 14 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0009-9120 J9 CLIN BIOCHEM JI Clin. Biochem. PD APR PY 1998 VL 31 IS 3 BP 187 EP 190 DI 10.1016/S0009-9120(98)00004-6 PG 4 WC Medical Laboratory Technology SC Medical Laboratory Technology GA ZT388 UT WOS:000074080300010 PM 9629493 ER PT J AU Hunter, GJ Hamberg, LM Choi, N Jain, RK McCloud, T Fischman, AJ AF Hunter, GJ Hamberg, LM Choi, N Jain, RK McCloud, T Fischman, AJ TI Dynamic T1-weighted magnetic resonance imaging and positron emission tomography in patients with lung cancer: Correlating vascular physiology with glucose metabolism SO CLINICAL CANCER RESEARCH LA English DT Article ID FDG-PET; CAPILLARY-PERMEABILITY; TUMOR ANGIOGENESIS; X-IRRADIATION; SOLID TUMORS; DELIVERY; CT; METASTASIS; CARCINOMA; ONCOLOGY AB The management of primary lung cancer relies on sophisticated imaging methods to assist in the diagnosis, staging, and evaluation of tumor regression during treatment, The information provided is generally anatomical in nature, except for that provided by positron emission tomography with [F-18]fluorodeoxyglucose, a modality that yields physiological data that have been shown to be useful in identifying neoplasia, based on an elevated glucose metabolic rate, Because the metabolism of malignant tissue depends intimately on neovascularization to provide oxygen and glucose in sufficient quantities to allow tumor growth, the characterization of tumor vascular physiology could be an important tool for assessing and predicting the likely effectiveness of treatment, Our goal was to show the feasibility and practical value of parameters of tumor vascular physiology obtained using dynamic Tl-weighted magnetic resonance imaging (MRI), to correlate them with glucose metabolism and to demonstrate changes in these parameters during and after treatment in patients with lung cancer, Parameters of vascular physiology [permeability-surface area (PS) product and extracellular contrast agent distribution volume] and glucose metabolism were assessed in 14 patients with lung cancer, Glucose metabolism was measured by using [F-18]fluorodeoxyglucose-positron emission tomography. Vascular physiology was assessed by dynamic T1-weighted, contrast-enhanced MRI, The mean PS product in tumor was 0.0015 +/- 0.0002 s(-1) (n = 13) before, 0.0023 +/- 0.0003 s(-1) (n = 3, P = 0.053) midway through, and 0.00075 +/- 0.0002 s(-1) (n = 5, P < 0.03) 2 weeks after treatment, Values for the extracellular contrast distribution space were 0.321 +/- 0.03 before, 0.289 +/- 0.02 midway through, and 0.195 +/- 0.02 (P < 0.01) 2 weeks after therapy, The glucose metabolic rate was significantly correlated with the PS product (P < 0.01) but not with the extracellular contrast distribution space, Our results demonstrate that tumor PS product correlates with glucose metabolism, that chemo-and radiotherapy induce observable and quantifiable changes in these parameters, and that such changes can be measured by irt vivo dynamic MRI. Quantitative dynamic T1-weighted MRI of tumor vascular physiology may have a useful role in the clinical management of lung cancer. C1 Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02129 USA. RP Hunter, GJ (reprint author), Massachusetts Gen Hosp, Dept Radiol, Ctr Imaging & Pharmaceut Res, Bldg 149,13th St,Charlestown Navy Yard, Boston, MA 02129 USA. NR 29 TC 34 Z9 37 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1998 VL 4 IS 4 BP 949 EP 955 PG 7 WC Oncology SC Oncology GA ZG200 UT WOS:000072977200016 PM 9563889 ER PT J AU Baldessarini, RJ Tondo, L AF Baldessarini, RJ Tondo, L TI Recurrence risk in bipolar manic-depressive disorders after discontinuing lithium maintenance treatment: An overview SO CLINICAL DRUG INVESTIGATION LA English DT Review ID PROPHYLACTIC LITHIUM; AFFECTIVE-ILLNESS; RAPID RECURRENCE; FOLLOW-UP; WITHDRAWAL; VALPROATE; TRIAL; LIFE; CARBAMAZEPINE; PREVALENCE AB Lithium remains unequaled in its research support as a standard maintenance treatment for bipolar manic-depressive disorders. It has important beneficial effects on recurring bipolar depression as well as mania, and in both types I and II bipolar syndromes, with powerful antisuicide effects not demonstrated with alternative mood-stabilisers. Data collected from numerous studies indicate that discontinuing lithium maintenance treatment is followed by sharply increased morbidity and possibly mortality, particularly in the first 6 to 12 months. However, we found that gradual discontinuation markedly reduced, and not merely delayed, recurrences of mania or depression after discontinuing lithium, with an even stronger effect in bipolar type II than type I patients. Secondary long-term retreatment with lithium following discontinuation yielded only minor average losses of benefits. Increased early recurrence risk may also arise after stopping long-term treatment with other neuropsychotropic drugs. Such fractions probably reflect physiological adaptations of the brain to pharmacodynamic effects, and their impact may be limited by slow drug discontinuation. The phenomenon of high early post-treatment discontinuation recurrence risk has clinical and scientific implications for the design, management and interpretation of treatment protocols that involve discontinuing long-term treatments in disorders requiring maintenance pharmacotherapy with centrally neuropharmacologically active drugs. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp,McLean Div, Labs Psychiat Res, Belmont, MA USA. Univ Cagliari, Sardinia & Lucio Bini Mood Disorders Ctr, Cagliari, Italy. RP Baldessarini, RJ (reprint author), McLean Hosp, MRC, 115 Mill St, Belmont, MA 02178 USA. EM rjb@mclean.org NR 79 TC 32 Z9 32 U1 2 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-2563 J9 CLIN DRUG INVEST JI Clin. Drug Invest. PD APR PY 1998 VL 15 IS 4 BP 337 EP 351 DI 10.2165/00044011-199815040-00010 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZK162 UT WOS:000073291600010 PM 18370489 ER PT J AU Rubin, RH AF Rubin, RH TI Editorial response: Cytomegalovirus disease and allograft loss after organ transplantation SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID LIVER-TRANSPLANTATION; CHRONIC REJECTION; VIRUS INFECTION; RECIPIENTS; ANTIGENS; RISK C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rubin, RH (reprint author), Massachusetts Gen Hosp, 32 Fruit St, Boston, MA 02114 USA. NR 18 TC 20 Z9 20 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1998 VL 26 IS 4 BP 871 EP 873 DI 10.1086/513948 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZH279 UT WOS:000073091300012 PM 9564466 ER PT J AU Revankar, SG Dib, OP Kirkpatrick, WR McAtee, RK Fothergill, AW Rinaldi, MG Redding, SW Patterson, TF AF Revankar, SG Dib, OP Kirkpatrick, WR McAtee, RK Fothergill, AW Rinaldi, MG Redding, SW Patterson, TF TI Clinical evaluation and microbiology of oropharyngeal infection due to fluconazole-resistant Candida in human immunodeficiency virus-infected patients SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RECURRENT ORAL CANDIDIASIS; POSITIVE PATIENTS; ALBICANS; AIDS; THERAPY AB Signs and symptoms of oropharyngeal candidiasis (OPC) were correlated with microbiology and clinical response to fluconazole in a cohort of patients with advanced human immunodeficiency virus (HIV) infection and recurrent OPC. Sixty-four HIV-infected patients with a median CD4 cell count of <50/mm(3) (range, 3-318/mm(3)) who presented with OPC were enrolled in a longitudinal study. Specimens for cultures were taken weekly until clinical resolution. Therapy with fluconazole was increased weekly as required to a maximum daily dose of 800 mg until resolution of symptoms and oral lesions. Resistant or dose-dependent susceptible yeasts, defined as a minimum inhibitory concentration of greater than or equal to 16 mu g/mL, were detected in 48 (31%) of 155 episodes. Clinical resolution with fluconazole therapy occurred in 107 (100%) of 107 episodes with susceptible yeasts vs. 44 (92%) of 48 episodes with resistant or dose-dependent susceptible strains (P = .008), Patients from whom fluconazole-resistant yeasts were isolated required longer courses of therapy and higher doses of fluconazole for response, but overall, excellent responses to fluconazole were seen in patients with advanced HIV infection. C1 Univ Texas, Hlth Sci Ctr, Dept Med Infect Dis, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Revankar, SG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Infect Dis, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCRR NIH HHS [M01-RR-01346]; NIDCR NIH HHS [1 R01 DE11381-01] NR 19 TC 45 Z9 47 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1998 VL 26 IS 4 BP 960 EP 963 DI 10.1086/513950 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZH279 UT WOS:000073091300029 PM 9564483 ER PT J AU Jorgensen, JH Ferraro, MJ AF Jorgensen, JH Ferraro, MJ TI Antimicrobial susceptibility testing: General principles and contemporary practices SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; RAPID IDENTIFICATION; BROTH MICRODILUTION; AUTOMICROBIC SYSTEM; CLINICAL IMPACT; BACTERIA; ACCURACY; ENTEROCOCCI; PENICILLIN; SELECTION C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Massachusetts Gen Hosp, Microbiol Lab, Boston, MA 02114 USA. RP Jorgensen, JH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 41 TC 55 Z9 58 U1 0 U2 6 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 1998 VL 26 IS 4 BP 973 EP 980 DI 10.1086/513938 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZH279 UT WOS:000073091300032 PM 9564485 ER PT J AU Warner, JJP Navarro, RA AF Warner, JJP Navarro, RA TI Serratus anterior dysfunction - Recognition and treatment SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PARALYSIS; SCAPULA AB Recognition of scapular winging may be difficult, and potential errors in treatment can result. Such treatment errors may cause morbidity for the patient. Tn addition, electrical evidence of long thoracic nerve injury usually is required to confirm the etiology of scapular winging as being caused by serratus anterior dysfunction, Although various conditions may result in scapular winging, primary serratus anterior dysfunction can be treated effectively by transfer of the pectoralis major tendon; however, this surgical approach sometimes may give an unacceptable cosmesis, and there may be local morbidity to the donor site of the iliotibial band graft that is used to augment the tendon transfer, The authors report eight patients with primary chronic scapulothoracic winging refractory to conservative treatment. Five of these patients had an incorrect diagnosis, and this resulted in 17 surgical procedures without resolution of their pain or improvement of function. Of the eight patients who required additional surgery to stabilize the scapula, only five patients had an electromyographic study that showed long thoracic nerve palsy, although all patients had profound scapulothoracic winging. All patients underwent a modified pectoralis major transfer with autogenous semitendinosus and gracilis tendon augmentation using two small incisions. Although one patient had a postoperative infection develop, the remaining seven patients had resolution of their winging, improved function, and satisfactory cosmesis. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, Gray Bldg,6th Floor,55 Fruit St, Boston, MA 02114 USA. NR 28 TC 50 Z9 53 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD APR PY 1998 IS 349 BP 139 EP 148 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA ZK599 UT WOS:000073341300017 PM 9584376 ER PT J AU Breakey, WR Calabrese, L Rosenblatt, A Crum, RM AF Breakey, WR Calabrese, L Rosenblatt, A Crum, RM TI Detecting alcohol use disorders in the severely mentally ill SO COMMUNITY MENTAL HEALTH JOURNAL LA English DT Article ID SCREENING-TEST; CAGE QUESTIONNAIRE; SUBSTANCE ABUSE; DRUG-ABUSE; COMORBIDITY; PREVALENCE; INSTRUMENT AB The frequent co-occurrence of alcoholism with serious mental illnesses ("dual diagnosis") necessitates that clinicians are able to recognize its presence in people with disabling mental illnesses. This study demonstrates that professionals often miss the diagnosis, but that their ability to detect alcoholism can be greatly enhanced by the use of a simple screening tool. Members of an urban psychosocial rehabilitation program who received psychiatric treatment in an affiliated outpatient clinic were interviewed after their clinic therapists and rehabilitation counselors had been asked questions pertaining to their general health and substance use, The members were interviewed with two screening tests, the CAGE and the SMAST, and a clinical DSM-III-R diagnosis of alcohol use disorder was established. Both the SMAST and CAGE had good sensitivity and the addition of a screener enhanced the clinicians' ability to detect alcohol use disorders. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP Breakey, WR (reprint author), Johns Hopkins Hosp, Dept Psychiat, Meyer 4-181, Baltimore, MD 21287 USA. FU NIAAA NIH HHS [K20 AA000168] NR 25 TC 10 Z9 10 U1 1 U2 2 PU HUMAN SCI PRESS INC PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0010-3853 J9 COMMUNITY MENT HLT J JI Community Ment. Health J. PD APR PY 1998 VL 34 IS 2 BP 165 EP 174 DI 10.1023/A:1018793002740 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA ZN651 UT WOS:000073668000006 PM 9620161 ER PT J AU Reed, GL Houng, AK Bianchi, C AF Reed, GL Houng, AK Bianchi, C TI Comparative biochemical and ultrastructural studies of P-selectin in rabbit platelets SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE CD62; monoclonal antibody; platelet; P-selectin; rabbit; thrombin; alpha-granule; activation; ultrastructure; sequence ID GRANULE MEMBRANE-PROTEIN; ACTIVATED PLATELETS; MONOCLONAL-ANTIBODY; SURFACE GLYCOPROTEIN; PLASMA-MEMBRANE; MYELOID CELLS; CLONING; GMP-140; IDENTIFICATION; ADHESION AB The role of platelets in thrombotic vascular disease has been widely studied in rabbits. Yet, in rabbit platelets, there is little known about the alpha-granules, which contain many of the key effector molecules for thrombosis. In this comparative study of rabbit platelets, we have characterized the structure and expression of P-selectin, an alpha-granule membrane protein that mediates leukocyte adhesion and thrombus propagation. The sequences of tryptic peptides of rabbit P-selectin show an overall sequence identity of 74% with human P-selectin, and 69-77% identity with cow, dog, mouse, rat and sheep P-selectins. The mean ( +/- S.D.) apparent molecular mass of reduced rabbit P-selectin is 117 +/- 7 kDa which is similar to 8 kDa larger than the unreduced protein (109 +/- 5 kDa). Rabbit P-selectin appears smaller than human P-selectin, but is comparable to other species P-selectins, that have fewer 'complement regulatory protein' repeat domains. Cell membrane labeling experiments and antibody binding studies indicate that rabbit P-selectin is nearly absent from the surface of resting platelets (290 +/- 30 molecules cell(-1)). However cellular activation with thrombin causes nearly a 30-fold increase in expression to 14200 +/- 1100 molecules cell(-1). P-selectin is also be expressed on the surface of rabbit platelets activated by other agonists like ADP, A23817 and epinephrine. This selective expression is explained by immunoelectronmicroscopic studies, which show that rabbit P-selectin is sequestered in the intracellular granules of resting platelets. After cell activation by thrombin, P-selectin is found decorating the external membranes of platelet pseudopodia and the surface connected canalicular system. In summary, these studies of P-selectin in rabbit platelets indicate that it is similar in structure, cell localization and expression to human and other species P-selectins. This suggests that studies of P-selectin in thrombosis in rabbits are likely to provide useful insights into the role of this molecule in human thrombotic vascular disease and related conditions. (C) 1998 Elsevier Science Inc. All rights reserved. C1 Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Cardiovasc Biol Lab, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Reed, GL (reprint author), Massachusetts Gen Hosp, Boston, MA 02115 USA. EM reed@cvlab.harvard.edu RI bianchi, cesario/H-6238-2012 FU NHLBI NIH HHS [HL-02348] NR 47 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD APR PY 1998 VL 119 IS 4 BP 729 EP 738 DI 10.1016/S0305-0491(98)00049-2 PG 10 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 118FT UT WOS:000075828300014 PM 9787764 ER PT J AU Najavits, LM AF Najavits, LM TI A history of psychiatry: From the era of the asylum to the age of prozac SO CONTEMPORARY PSYCHOLOGY LA English DT Book Review C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Najavits, LM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0010-7549 J9 CONTEMP PSYCHOL JI Comtemp. Psychol. PD APR PY 1998 VL 43 IS 4 BP 281 EP 282 PG 2 WC Psychology, Multidisciplinary SC Psychology GA ZE606 UT WOS:000072811400027 ER PT J AU Posas, F Takekawa, M Saito, H AF Posas, F Takekawa, M Saito, H TI Signal transduction by MAP kinase cascades in budding yeast SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID ACTIVATED PROTEIN-KINASE; GTP-BINDING PROTEIN; PHEROMONE RESPONSE PATHWAY; SACCHAROMYCES-CEREVISIAE; FILAMENTOUS-GROWTH; CANDIDA-ALBICANS; INVASIVE GROWTH; CELL-CYCLE; DOWNSTREAM TARGET; MATING-PHEROMONE AB Budding yeast contain at least four distinct MAPK (mitogen activated protein kinase) cascades that transduce a variety of intracellular signals: mating-pheromone response, pseudohyphal/invasive growth, cell wall integrity, and high osmolarity adaptation. Although each MAPK cascade contains a conserved set of three protein kinases, the upstream activation mechanisms for these cascades are diverse, including a trimeric G protein, monomeric small G proteins, and a prokaryotic-like two-component system. Recently, it became apparent that there is extensive sharing of signaling elements among the MAPK pathways; however, little undesirable cross-talk occurs between various cascades. The formation of multi-protein signaling complexes is probably centrally important for this insulation of individual MAPK cascades. C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Posas, F (reprint author), Harvard Univ, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM haruo_saito@dfci.harvard.edu RI Posas, Francesc/K-1364-2013 OI Posas, Francesc/0000-0002-4164-7076 NR 66 TC 127 Z9 139 U1 1 U2 6 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 1998 VL 1 IS 2 BP 175 EP 182 DI 10.1016/S1369-5274(98)80008-8 PG 8 WC Microbiology SC Microbiology GA 117DJ UT WOS:000075765100006 PM 10066475 ER PT J AU Momtaz, K Fitzpatrick, TB AF Momtaz, K Fitzpatrick, TB TI The benefits and risks of long-term PUVA photochemotherapy SO DERMATOLOGIC CLINICS LA English DT Article ID 8-YEAR FOLLOW-UP; A RADIATION PUVA; PSORIATIC PATIENTS; ULTRAVIOLET-A; MALIGNANT-MELANOMA; SKIN-CANCER; PSORALEN PHOTOCHEMOTHERAPY; CUTANEOUS CARCINOMA; LYMPHOCYTE FUNCTION; ORAL METHOXSALEN AB In 1974 a new photobiologic principle i.e. light + drug, called photochemotherapy was discovered in Boston and immediately confirmed in Vienna. Psoralen + UVA (PUVA) photochemotherapy has now been applied to the treatment of more than 24 heterogeneous groups of diseases, especially psoriasis and mycosis fungoides. After 24 years of experience in thousands of patients with psoriasis and 23 other skin disorders, virtually the only risk is the development of squamous-cell carcinomas. This risk is low with two exceptions: previous history of treatment with ionizing radiation or inorganic trivalent arsenic, and patients with recalcitrant psoriasis who require continuous treatment for many years. In a recent report from a large USA clinical trial, melanoma developed in a few patients with psoriasis treated with PUVA. This prospective clinical trial did not have a control population, and therefore, the conclusion that PUVA can cause melanoma is tentative. C1 Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. RP Momtaz, K (reprint author), Massachusetts Gen Hosp, Profess Off Bldg,275 Cambridge St, Boston, MA 02114 USA. NR 78 TC 31 Z9 31 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD APR PY 1998 VL 16 IS 2 BP 227 EP + PG 9 WC Dermatology SC Dermatology GA ZL075 UT WOS:000073396300003 PM 9589196 ER PT J AU Wysolmerski, JJ Philbrick, WM Dunbar, ME Lanske, B Kronenberg, H Karaplis, A Broadus, AE AF Wysolmerski, JJ Philbrick, WM Dunbar, ME Lanske, B Kronenberg, H Karaplis, A Broadus, AE TI Rescue of the parathyroid hormone-related protein knockout mouse demonstrates that parathyroid hormone-related protein is essential for mammary gland development SO DEVELOPMENT LA English DT Article DE epithelial-mesenchymal interaction; branching morphogenesis; ectodermal dysplasia; generic rescue; keratin 14; organogenesis; PTH/PTHrP receptor; mammary mesenchyme ID INDIAN HEDGEHOG; PEPTIDE; DIFFERENTIATION; MORPHOGENESIS; EXPRESSION; MICE; OVEREXPRESSION; CHONDROCYTES; TISSUE; MESENCHYME AB Parathyroid hormone-related protein (PTHrP) was originally discovered as a tumor product that causes humoral hypercalcemia of malignancy. PTHrP is non known to be widely expressed in normal tissues and growing evidence suggests that it is an important developmental regulatory molecule. We had previously reported that overexpression of PTHrP in the mammary glands of transgenic mice impaired branching morphogenesis during sexual maturity and early pregnancy now demonstrate that PTHrP plays a critical role in the epithelial-mesenchymal communications that guide the initial round of branching morphogenesis that occurs during the embryonic development of the mammary gland. We have rescued the PTHrP-knockout mice from neonatal death by transgenic expression of PTHrP targeted to chondrocytes. These rescued mice are devoid of mammary epithelial ducts, We show that disruption of the PTHrP gene leads to a failure of the initial round of branching growth that is responsible for transforming the mammary bud into the rudimentary mammary duct system, In the absence of PTHrP, the mammary epithelial cells degenerate and disappear. The ability of PTHrP to support embryonic mammary development is a function of amino-terminal PTHrP, acting via the PTH/PTHrP receptor, for ablation of the PTH/PTHrP receptor gene recapitulates the phenotype of PTHrP gene ablation. We have localized PTHrP expression to the embryonic mammary epithelial cells and PTH/PTHrP receptor expression to the mammary mesenchyme using in situ hybridization histochemistry, Finally, we have rescued mammary gland development in PTHrP-null animals by transgenic expression of PTHrP in embryonic mammary epithelial cells. We conclude that PTHrP is a critical epithelial signal received by the mammary mesenchyme and involved in supporting the initiation of branching morphogenesis. C1 Yale Univ, Sch Med, Dept Internal Med, Div Endocrinol & Metab, New Haven, CT 06510 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Endocrine Unit, Boston, MA USA. McGill Univ, Lady Davis Inst Med Res, Dept Internal Med, Div Endocrinol & Metab, Montreal, PQ, Canada. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. RP Wysolmerski, JJ (reprint author), Yale Univ, Sch Med, Dept Internal Med, Div Endocrinol & Metab, New Haven, CT 06510 USA. EM John-Wysolmerski@Yale.edu FU NCI NIH HHS [CA60498]; NIAMS NIH HHS [AR 30102]; NIDDK NIH HHS [DK 31998] NR 36 TC 196 Z9 197 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 1998 VL 125 IS 7 BP 1285 EP 1294 PG 10 WC Developmental Biology SC Developmental Biology GA ZL170 UT WOS:000073405800013 PM 9477327 ER PT J AU Wisotzkey, RG Mehra, A Sutherland, DJ Dobens, LL Liu, XQ Dohrmann, C Attisano, L Raftery, LA AF Wisotzkey, RG Mehra, A Sutherland, DJ Dobens, LL Liu, XQ Dohrmann, C Attisano, L Raftery, LA TI Medea is a Drosophila Smad4 homolog that is differentially required to potentiate DPP responses SO DEVELOPMENT LA English DT Article DE Smad protein; DPP; Medea; midgut patterning; wing patterning; dorsoventral patterning ID DECAPENTAPLEGIC GENE; TRANSCRIPTIONAL ACTIVATOR; REGULATORY ELEMENTS; SIGNALING PATHWAYS; HOMEOTIC GENES; IMAGINAL DISKS; THICK VEINS; I RECEPTORS; PROTEIN; EXPRESSION AB Mothers against dpp (Mad) mediates Decapentaplegic (DPP) signaling throughout Drosophila development. Here we demonstrate that Medea encodes a MAD-related protein that functions in DPP signaling. MEDEA is most similar to mammalian Smad4 and forms heteromeric complexes with MAD. Like dpp, Medea is essential for embryonic dorsal/ventral patterning. However, Mad is essential ire the germline for oogenesis whereas Medea is dispensable. In the wing primordium, loss of Medea most severely affects regions receiving low DPP signal. MEDEA is localized in the cytoplasm, is not regulated by phosphorylation, and requires physical association with MAD for nuclear translocation, Furthermore, inactivating MEDEA mutations prevent nuclear translocation either by preventing interaction with MAD or by trapping MAD/MEDEA complexes in the cytosol, Thus MAD-mediated nuclear translocation is essential for MEDEA function. Together these data show that, while MAD is essential for mediating all DPP signals, heteromeric MAD/MEDEA complexes function to modify or enhance DPP responses. We propose that this provides a general model for Smad4/MEDEA function in signaling by the TGF-beta family. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Toronto, Dept Anat & Cell Biol, Toronto, ON M5G 1A8, Canada. RP Raftery, LA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149 13th St, Charlestown, MA 02129 USA. EM lraftery@cbrc.mgh.harvard.edu RI Raftery, Laurel/H-1406-2012; OI Raftery, Laurel/0000-0003-4797-4163; Liu, Xiao-Qing/0000-0002-4034-5156 NR 73 TC 117 Z9 118 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE, CAMBS, ENGLAND CB4 4DL SN 0950-1991 J9 DEVELOPMENT JI Development PD APR PY 1998 VL 125 IS 8 BP 1433 EP 1445 PG 13 WC Developmental Biology SC Developmental Biology GA ZP631 UT WOS:000073772800008 PM 9502724 ER PT J AU Yelick, PC Abduljabbar, TS Stashenko, P AF Yelick, PC Abduljabbar, TS Stashenko, P TI zALK-8, a novel type I serine/threonine kinase receptor, - Is expressed throughout early zebrafish development SO DEVELOPMENTAL DYNAMICS LA English DT Article DE novel serine/threonine kinase receptor; activin receptor-like-kinases; zebrafish development; transforming growth factor P receptor family members ID SERINE THREONINE KINASE; GROWTH-FACTOR-BETA; ACTIVIN RECEPTOR; CLONING; PROTEIN; FAMILY; SIGNALS; BONE AB Here, we report the isolation and characterization of zebrafish activin receptorlike kinase-8 (zALK-8), a novel type I serine/threonine (ser/thr) kinase receptor of the transforming growth factor beta (TGF-beta) family, zALK-8 is novel, in that it contains an extracellular domain that is quite distinct from that of previously identified ALK receptors 1 through 7, Analysis of the predicted amino acid sequence of the 506 amino acid zALK-8 receptor reveals an ser/thr kinase domain characteristic of type I TGF-beta family member receptors. zALK-8, therefore, is a traditional type I ser/thr kinase receptor of the TGF-beta family, but it may exhibit novel ligand-binding activities, The developmental expression of zALK-8 mRNA was examined by wholemount in situ hybridization analysis using a probe from the 3'-untranslated sequence of zALK-8, which does not cross react with other members of the highly conserved TGF-beta receptor family, zALK-8 mRNA is present as a maternal message that is expressed ubiquitously before the start of zygotic transcription, By 16 hr postfertilization (hpf), zALK-8 mRNA is still expressed fairly evenly throughout the embryo, In 24-hpf embryos, zALK-8 mRNA is expressed predominantly in the developing eye and neural structures, By 48 hpf, zALK-8 mRNA is faintly detectable as a diffuse signal throughout the head, zALK-8 mRNA is not detectable by this method in 72-hpf or 96-hpf embryos, Northern analysis of zALK-8 mRNA in poly(A+) mRNA isolated from 6-9 hpf embryos detects a major transcript of 3.6 kb and a minor transcript of 4.3 kb, zALK-8 mRNA expression correlates well with known functions of TGF-beta family members as early axial patterning and mesoderm-inducing growth factors and as potent growth and differentiation factors in craniofacial development. (C) 1998 Wiley-Liss, Inc. C1 Forsyth Dent Ctr, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Oral Biol, Boston, MA 02115 USA. RP Yelick, PC (reprint author), Forsyth Dent Ctr, Dept Cytokine Biol, 140 The Fenway, Boston, MA 02115 USA. EM pyelick@forsyth.org RI Abduljabbar, Tariq/E-6491-2017 FU NIDCR NIH HHS [DE12024-01, DE12076-01, DEO7378] NR 31 TC 31 Z9 31 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD APR PY 1998 VL 211 IS 4 BP 352 EP 361 DI 10.1002/(SICI)1097-0177(199804)211:4<352::AID-AJA6>3.0.CO;2-G PG 10 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA ZG425 UT WOS:000073000700006 PM 9566954 ER PT J AU Spiegelman, BM AF Spiegelman, BM TI PPAR-gamma: Adipogenic regulator and thiazolidinedione receptor SO DIABETES LA English DT Article ID PROMOTES ADIPOCYTE DIFFERENTIATION; NUCLEAR HORMONE RECEPTORS; NECROSIS-FACTOR-ALPHA; ACID-BINDING PROTEIN; OB GENE-EXPRESSION; FATTY-ACID; INSULIN-RESISTANCE; TRANSCRIPTION FACTOR; ADIPOSE EXPRESSION; GLUCOSE OUTPUT AB The past several years have seen an explosive increase in our understanding of the transcriptional basis of adipose cell differentiation. In particular, a key role has been illustrated for PPAR-gamma, a member of the nuclear hormone receptor superfamily. PPAR-gamma has also been recently identified as the major functional receptor for the thiazolidinedione class of insulin-sensitizing drugs. This review examines the evidence that has implicated this transcription factor in the processes of adipogenesis and systemic insulin action. In addition, several models are discussed that may explain how a single protein can be involved in these related but distinct physiological actions. I also point out several important areas where our knowledge is incomplete and more research is needed. Finally, I discuss how advances in our understanding of nuclear receptor function, particularly the docking of cofactors in a ligand-dependent fashion, should lead to improved drugs that utilize the PPAR-gamma system for the treatment of insulin resistance. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. RP Spiegelman, BM (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu NR 52 TC 1314 Z9 1369 U1 7 U2 88 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1998 VL 47 IS 4 BP 507 EP 514 DI 10.2337/diabetes.47.4.507 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD577 UT WOS:000072700500001 PM 9568680 ER PT J AU Saad, MF Khan, A Sharma, A Michael, R Riad-Gabriel, MG Boyadjian, R Jinagouda, SD Steil, GM Kamdar, V AF Saad, MF Khan, A Sharma, A Michael, R Riad-Gabriel, MG Boyadjian, R Jinagouda, SD Steil, GM Kamdar, V TI Physiological insulinemia acutely modulates plasma leptin SO DIABETES LA English DT Article ID OBESE GENE-EXPRESSION; ADIPOSE-TISSUE; OB GENE; NEUROPEPTIDE-Y; SERUM LEPTIN; SHORT-TERM; BODY-FAT; IN-VITRO; HUMANS; WEIGHT AB Whether insulin acutely regulates plasma leptin in humans is controversial. We examined the dosage-response and time-course characteristics of the effect of insulin on leptin in 10 men (age 42 +/- 2 years [mean +/- SE]; BMI 29.3 +/- 2.0 kg/m(2)). Each individual underwent four 9-h euglycemic clamps (insulin at 20, 40, 80, and 400 mU.m(-2).min(-1)) and a control saline infusion. Although plasma glucose and insulin levels remained constant, leptin diminished from 9.1 +/- 3.0 to 5.9 +/- 2.1 ng/ml (P < 0.001) by the end of the control experiment. Conversely, plasma leptin showed a dosage-dependent increase during the insulin infusions that was evident within 30-60 min. The insulin-induced increase in leptin was proportionately lower in obese insulin-resistant men. Free fatty acids (FFAs) decreased during insulin and did not change during saline infusions. ED50 (the dose producing half-maximal effect) for insulin's effect on leptin and FFA was similar (138 +/- 36 vs. 102 +/- 24 pmol/l, respectively; P = 0.11). To further define the role of physiological insulinemia, we compared the effect of a very low dosage insulin infusion (10 mU.m(-2).min(-1)) with that of a control saline infusion in another group of 10 men (mean age 39 +/- 3 years; BMI 27.1 +/- 1.0 kg/m(2)). Plasma leptin remained stable during that insulin infusion, but fell. by 37 +/- 2% in the control experiment. Thus physiological insulinemia can acutely regulate plasma leptin. Insulin could mediate the effect of caloric intake on leptin and could be a determinant of its plasma concentration. Inadequate insulin-induced leptin production in obese and insulin-resistant subjects may contribute to the development or worsening of obesity. C1 Univ So Calif, Sch Med, Dept Med, Los Angeles, CA 90033 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Saad, MF (reprint author), Univ Calif Los Angeles, Sch Med, Div Endocrinol, 924 Westwood Blvd,Suite 335 Mail Box 15, Los Angeles, CA 90024 USA. FU NCRR NIH HHS [M01 RR-43] NR 48 TC 228 Z9 239 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1998 VL 47 IS 4 BP 544 EP 549 DI 10.2337/diabetes.47.4.544 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD577 UT WOS:000072700500006 PM 9568685 ER PT J AU Higashi, S Clermont, AC Dhir, V Bursell, SE AF Higashi, S Clermont, AC Dhir, V Bursell, SE TI Reversibility of retinal flow abnormalities is disease-duration dependent in diabetic rats SO DIABETES LA English DT Article ID VIDEO FLUORESCEIN ANGIOGRAPHY; MEAN CIRCULATION TIME; BLOOD-FLOW; GLYCEMIC CONTROL; HEMODYNAMIC ABNORMALITIES; INSULIN; RETINOPATHY; MELLITUS; DIACYLGLYCEROL; ENDOTHELIN-1 AB Decreased retinal blood flow has been measured in streptozotocin (STZ)-induced diabetes of 1 week's duration, and primary insulin intervention was effective in maintaining normal retinal blood flow in diabetic rats. Retinal blood-flow abnormalities precede clinical diabetic retinopathy in both diabetic animals and patients. An important characteristic of diabetic retinopathy is the difficulty of reversibility once it has been established. Because altered retinal hemodynamics is a possible marker of early diabetic retinopathy, me investigated in this study whether retinal blood-flow changes in rats can be normalized by secondary insulin intervention following short and chronic periods of untreated STZ-induced diabetes. Subcutaneous insulin pumps were placed into diabetic rats for 1 meek after 1 week of diabetes (a-week group) and after 3 weeks of diabetes (4-week group). Retinal circulatory parameters were determined using image analysis of video fluorescein angiogram recordings. For the a-week group, retinal blood flow was significantly (P < 0.05) reduced in the untreated diabetic rats compared with nondiabetic and insulin-treated diabetic rats (80.6 +/- 29.2, 131.9 +/- 50.1, and 151.3 +/- 54.0 pixels(2)/s respectively). Retinal blood flow was also significantly (P < 0.05) reduced in the 4-week untreated diabetic rats compared with nondiabetic rats (95.7 +/- 22.2 vs. 125.7 +/- 29.5 pixels(2)/s). In contrast to the shorter-duration group, insulin treatment for 1 week after 3 weeks of diabetes did not totally normalize retinal blood flow (117.5 +/- 32.4 pixels(2)/s). These results suggest that vascular abnormalities could become more resistant to normalization following short-term (1 week) insulin treatment after longer periods of untreated diabetes. C1 Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Beetham Eye Inst,Res Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Bursell, SE (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. FU NEI NIH HHS [EY 05110, EY 09602] NR 60 TC 20 Z9 23 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1998 VL 47 IS 4 BP 653 EP 659 DI 10.2337/diabetes.47.4.653 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD577 UT WOS:000072700500021 PM 9568700 ER PT J AU Argyropoulos, G Brown, AM Peterson, R Likes, CE Watson, DK Garvey, WT AF Argyropoulos, G Brown, AM Peterson, R Likes, CE Watson, DK Garvey, WT TI Structure and organization of the human uncoupling protein 2 gene and identification of a common biallelic variant in Caucasian and African-American subjects SO DIABETES LA English DT Article ID UCP C1 Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ctr Mol & Struct Biol, Hollings Canc Ctr, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. RP Garvey, WT (reprint author), Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Dept Med, 171 Ashley Ave, Charleston, SC 29425 USA. FU NCRR NIH HHS [M01-RR1070]; NIDDK NIH HHS [DK-47461] NR 9 TC 25 Z9 28 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 1998 VL 47 IS 4 BP 685 EP 687 DI 10.2337/diabetes.47.4.685 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD577 UT WOS:000072700500025 PM 9568704 ER PT J AU Agrawal, L Emanuele, NV Abraira, C Henderson, WG Levin, SR Sawin, CT Silbert, CK Nuttall, FQ Comstock, JP Colwell, JA AF Agrawal, L Emanuele, NV Abraira, C Henderson, WG Levin, SR Sawin, CT Silbert, CK Nuttall, FQ Comstock, JP Colwell, JA CA VA CSDM Grp TI Ethnic differences in the glycemic response to exogenous insulin treatment in the Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM) SO DIABETES CARE LA English DT Article ID WHITE AMERICANS; FEASIBILITY TRIAL; CIGARETTE-SMOKING; GLUCOSE-TOLERANCE; UNITED-STATES; BLACK; NIDDM; COMPLICATIONS; SECRETION; SENSITIVITY AB OBJECTIVE - The Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus was conducted in NIDDM patients to determine if a significant difference in HbA(1c) could be achieved between groups receiving standard and intensive treatment. We observed differences in the response to exogenous insulin between African-Americans and other intensively treated patients. Therefore, we assessed the variations of response and correlated factors that might explain such differences. RESEARCH DESIGN AND METHODS - One hundred fifty-three men aged 40-69 years with NIDDM for less than or equal to 15 years were randomized to either the standard therapy (n = 78) or the intensive therapy (n = 75) arm. Of the 75 patients in the intensive therapy group, 57 completed the study on insulin therapy alone. Of these, 18 were African-Americans and 39 were non-African-Americans. We conducted an analysis of the data collected to determine differences in baseline characteristics, glycemic response, insulin requirement, body weight, exercise, and basal C-peptide level, factors that may explain a difference in response to insulin therapy. RESULTS - Glycemic control improved in all patients with intensive insulin therapy African-Americans achieved a greater improvement in HbA(1c) compared with non-African-Americans with a similar increment in insulin. This difference could not be explained by differences in body weight, activity, concomitant use of other medicines, or insulin-secretory capacity of the pancreas. CONCLUSIONS - We conclude that ethnic differences may exist in the response to insulin therapy. A knowledge of such differences may aid in achieving good glycemic control, especially since minorities have a greater prevalence of and burden from the microvascular complications of diabetes. C1 Edward Hines Vet Adm Hosp, Endocrinol Diabet Sect 111A, Hines, IL 60141 USA. Edward Hines Vet Adm Hosp, Med Serv, Div Metab, Hines, IL 60141 USA. Edward Hines Vet Adm Hosp, Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. Vet Adm Wadsworth Med Ctr, Special Diagnost & Treatment Ctr, Los Angeles, CA 90073 USA. VA Med Ctr, Endocrine Diabet Sect, Boston, MA USA. VA Med Ctr, Med Serv, Endocrinol Sect, Minneapolis, MN USA. VA Med Ctr, Houston, TX USA. Med Univ S Carolina, Ctr Diabet, Div Endocrinol, Charleston, SC 29425 USA. RP Agrawal, L (reprint author), Edward Hines Vet Adm Hosp, Endocrinol Diabet Sect 111A, Roosevelt Rd & 5th Ave,Box 5000,Bldg 200,Rm 1226, Hines, IL 60141 USA. NR 34 TC 15 Z9 15 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 1998 VL 21 IS 4 BP 510 EP 515 DI 10.2337/diacare.21.4.510 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD293 UT WOS:000072670700008 PM 9571333 ER PT J AU Krolewski, AS Fogarty, DG Warram, JH AF Krolewski, AS Fogarty, DG Warram, JH TI Hypertension and nephropathy in diabetes mellitus: what is inherited and what is acquired? SO DIABETES RESEARCH AND CLINICAL PRACTICE LA English DT Article; Proceedings Paper CT Satellite Symposium on Hypertension and NIDDM - Doubling the Risk, to the 16th Congress of the International-Diabetes-Federation CY JUL 20, 1997 CL HELSINKI, FINLAND SP Int Diabet Federat DE hypertension; nephropathy; genetic ID SODIUM-LITHIUM COUNTERTRANSPORT; CARDIOVASCULAR RISK-FACTORS; CULTURED SKIN FIBROBLASTS; URINARY ALBUMIN EXCRETION; NA+/H+ ANTIPORT ACTIVITY; INSULIN-DEPENDENT DIABETICS; BLOOD-PRESSURE PREDICTS; PIMA-INDIANS; IMMORTALIZED LYMPHOBLASTS; FAMILIAL PREDISPOSITION AB Prolonged duration of diabetes mellitus, poor long term glycemic control and raised blood pressure have all been clearly related to the development of diabetic nephropathy. Evidence exists to suggest that a subset of individuals with diabetes have a genetic predisposition to diabetic nephropathy. Cases of diabetic nephropathy cluster in families and a parental history of hypertension is more common in patients with diabetic nephropathy. Current evidence suggests an important role for hypertension in the genetic susceptibility to diabetic nephropathy but the extent of this is unknown, While cellular and animal studies have generated a plethora of data regarding mechanisms involved in the role of hypertension and diabetic nephropathy, these are not helpful for drawing conclusions in humans. In the following review, we examine the available clinical, epidemiologic and family studies to assess the relationship between the development of hypertension and diabetic nephropathy in IDDM and NIDDM. We will demonstrate the differences in the epidemiology of hypertension in diabetes depending on the type of diabetes and thus, move the emphasis of nephropathy susceptibility away from hypertension per se. We hope to emphasize instead the homogeneity of nephropathy risk in both IDDM and NIDDM and also the idea that a common genetic susceptibility exists for all types of diabetes and is conditional on cumulative exposure to hyperglycemia. Regarding the interaction of hypertension. and nephropathy in diabetes mellitus, any conclusions at this time about what is inherited and what is acquired must be regarded as speculative. However we will discuss some potential mechanisms of hypertension in the evolution of nephropathy and we will allude to the role for novel genetic studies in the search for nephropathy susceptibility gene(s). (C) 1998 Elsevier Science Inland Ltd. All rights reserved. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. EM damian_fogarty@joslin.harvard.edu RI Fogarty, Damian/A-8925-2011 NR 89 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0168-8227 EI 1872-8227 J9 DIABETES RES CLIN PR JI Diabetes Res. Clin. Pract. PD APR PY 1998 VL 39 SU S BP 1 EP 14 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZV241 UT WOS:000074284500001 ER PT J AU Capodieci, P Magi-Galluzzi, C Moreira, G Zeheb, R Loda, M AF Capodieci, P Magi-Galluzzi, C Moreira, G Zeheb, R Loda, M TI Automated in situ hybridization: Diagnostic and research applications SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE in situ hybridization; automation ID EPSTEIN-BARR-VIRUS; POLYMERASE CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; INSITU HYBRIDIZATION; NASOPHARYNGEAL CARCINOMA; INHIBITOR P27; EARLY PHASES; EXPRESSION; GENE; PHOSPHATASE AB Although in situ hybridization has been in use for almost 30 years, its technically demanding nature, the requirements for optimal tissue fixation and preservation, and the turnaround time for the experiments have prevented this technique from becoming widely used in the surgical pathology setting. The use of nonisotopic reporter molecules, the possibility of performing hybridization on archival material, and very recently, automation of the procedure have brought in situ hybridization to the forefront of diagnostic and experimental pathology. We describe our experience with nonradioactive, automated in situ hybridization, compare the technique with traditional manual procedures, and briefly outline its potential applications in diagnostic pathology and in the research setting. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Ventana Med Syst, Tucson, AZ USA. RP Loda, M (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 43 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD APR PY 1998 VL 7 IS 2 BP 69 EP 75 DI 10.1097/00019606-199804000-00002 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 122UF UT WOS:000076089300002 PM 9785004 ER PT J AU Kovacs, TOG Campbell, D Haber, M Rose, P Jennings, DE Richter, J AF Kovacs, TOG Campbell, D Haber, M Rose, P Jennings, DE Richter, J TI Double-blind comparison of lansoprazole 15 mg, lansoprazole 30 mg, and placebo in the maintenance of healed gastric ulcer SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE lansoprazole; gastric ulcer; maintenance therapy; ulcer recurrence ID ACID-SECRETION; COPENHAGEN-COUNTY; DUODENAL-ULCER; DISEASE; RANITIDINE; OMEPRAZOLE; PREVENTION; INHIBITION; ASPIRIN; THERAPY AB Our purpose was to compare the safety and efficacy of lansoprazole 15 mg and 30 mg with placebo in preventing recurrence in 49 patients with a history of gastric ulcer. Within one month, 40% of patients receiving placebo experienced ulcer recurrence compared to 0% and 7% of patients receiving lansoprazole 15 mg and 30 mg, respectively, All placebo patients became symptomatic, experienced ulcer recurrence or withdrew from the study by month 9, As compared to placebo, a significantly (P < 0.001) higher percentage of patients treated with lansoprazole 15 mg (83%) and lansoprazole 30 mg (93%) with healed gastric ulcer disease remained healed at month 12. Of patients asymptomatic at baseline, 100% and 59% of those treated with lansoprazole 15 mg and 30 mg, respectively, remained asymptomatic at month 12. The incidence of adverse events was comparable among the treatment groups. Lansoprazole safely and effectively reduces ulcer recurrence in patients with a history of gastric ulcer disease. C1 W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. Vet Adm Med Ctr, Kansas City, MO 64128 USA. Allegheny Univ Hlth Sci, Dept Pathol, Philadelphia, PA 19102 USA. TAP Holdings, Deerfield, IL 60015 USA. Cleveland Clin Fdn, Dept Gastroenterol, Cleveland, OH 44195 USA. RP Kovacs, TOG (reprint author), W Los Angeles Vet Affairs Med Ctr, Ctr Ulcer Res & Educ, 11301 Wilshire Blvd,Bldg 115,Room 212, Los Angeles, CA 90073 USA. NR 32 TC 11 Z9 11 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD APR PY 1998 VL 43 IS 4 BP 779 EP 785 DI 10.1023/A:1018818115047 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH100 UT WOS:000073072100015 PM 9558034 ER PT J AU Liu, BY Guo, J Lanske, B Divieti, P Kronenberg, HM Bringhurst, FR AF Liu, BY Guo, J Lanske, B Divieti, P Kronenberg, HM Bringhurst, FR TI Conditionally immortalized murine bone marrow stromal cells mediate parathyroid hormone-dependent osteoclastogenesis in vitro SO ENDOCRINOLOGY LA English DT Article ID HEMATOPOIETIC BLAST CELLS; COLONY-STIMULATING FACTOR; OSTEOBLAST-LIKE CELLS; TRANSGENIC MOUSE; PROGENITOR CELLS; PHOSPHOLIPASE-C; PROTEIN-KINASE; DIFFERENTIATION; RECEPTOR; RESORPTION AB PTH recruits and activates osteoclasts to cause bone resorption. These actions of PTH are thought to be mediated indirectly via type 1 PTH/PTH-related peptide receptors (PTH1Rs) expressed by adjacent marrow stromal or osteoblastic cells, although some evidence suggests that PTH may act directly on early hematopoietic osteoclast progenitors. We have established clonal, conditionally immortalized, PTH-responsive, bone marrow stromal cell lines from mice that harbor both a transgene encoding a temperature-sensitive mutant of the simian virus 40 large T antigen and deletion of a single allele of the PTH1R gene. Of 60 stromal cell lines isolated, 45 expressed functional PTH1Rs. During coculture with normal murine spleen cells, 5 of 42 such cell Lines could support formation of tartrate-resistant acid phosphatase-positive, multinucleated cells (TRAP(+) MNCs) in response to 1,25-dihydroxyvitamin D-3, but only 2 of these did so in response to PTH. One of these, MS1 cells, expressed numerous cytokines and proteins characteristic of the osteogenic lineage and showed increased production of interleukin-6 in response to PTH. MS1 cells supported dose-dependent induction by rat (r) PTH-(1-34) (0.1-100 nM) of TRAP(+) MNCs that expressed calcitonin receptors and formed resorption lacunae on dentine slices. This effect of PTH, which required cell to cell contact between MS1 and spleen cells, was mimicked by coadministration of cAMP analog and phorbol ester but only partially by either agent alone. The carboxyl-terminal fragment rPTH-(53-84) also induced osteoclast-like cell formation, but the maximal effect was only 30% as great as that of rPTH-(1-34). Importantly, rPTH-(1-34) induced TRAP(+) MNC formation even when PTH1R(-/-) osteoclast progenitors (from fetal liver of mice homozygous for ablation of the PTH1R gene) were cocultured with MS1 cells. We conclude that activation of PTH1Rs on cells of the osteoclast lineage is not required for PTH-(1-34)-induced osteoclast formation in the presence of appropriate PTH-responsive marrow stromal cells. MS1 cells provide a useful model for further study of PTH regulation of osteoclastogenesis. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bringhurst, FR (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Wellman 5, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK-11794, DK-47038] NR 47 TC 53 Z9 56 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 1998 VL 139 IS 4 BP 1952 EP 1964 DI 10.1210/en.139.4.1952 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZD282 UT WOS:000072669600061 PM 9528982 ER PT J AU Chronos, N Vahanian, A Betriu, A Emanuelsson, H Goldberg, S Gulba, D van Hout, BA AF Chronos, N Vahanian, A Betriu, A Emanuelsson, H Goldberg, S Gulba, D van Hout, BA TI Use of abciximab in interventional cardiology SO EUROPEAN HEART JOURNAL LA English DT Article; Proceedings Paper CT Meeting on Use of GP IIb/IIIa Inhibitors in Coronary Syndromes - State of the Art CY FEB 15-16, 1997 CL DAVOS, SWITZERLAND SP Eli Lilly & Co, Indianapolis ID PERCUTANEOUS CORONARY INTERVENTION; DIRECTIONAL ATHERECTOMY; MYOCARDIAL-INFARCTION; CLINICAL RESTENOSIS; IIB/IIIA INTEGRIN; RANDOMIZED TRIAL; ARTERY LESIONS; ANGIOPLASTY; ANTIBODY; COMPLICATIONS AB The advent of platelet membrane glycoprotein (GP) IIb/IIIa inhibitors has changed the landscape of interventional cardiology. Given the commercial availability of abciximab and expected regulatory approvals for other receptor blockers, defining appropriate use of these agents in the interventional setting is mandated. One key issue is selection of patients who may benefit from GP IIb/IIIa receptor blockade. Focusing specifically on abciximab. data from three large-scale, randomized trials demonstrate that abciximab is appropriate for all patients undergoing percutaneous transluminal coronary angioplasty, regardless of risk stratum. Other important issues to consider when prescribing this therapy include benefits in conjunction with stents and new devices, dosing and timing of administration, and the role of prophylactic versus "bailout" administration. This article reflects a distillation of the views and consensus regarding the use of GP IIb/IIIa inhibitors in patients undergoing coronary intervention expressed by a group of international experts convened in Davos, Switzerland, February 16, 1997. This report attempts to review clinical progress to date, formulate recommendations, and map out potentially fruitful lines of inquiry for future investigation. C1 Emory Univ Hosp, Atlanta, GA 30322 USA. Hop Tenon, F-75970 Paris, France. Univ Barcelona, Barcelona, Spain. Orebro Med Ctr, Orebro, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Franz Volhand Klin, Berlin, Germany. Erasmus Univ, Rotterdam, Netherlands. RP Chronos, N (reprint author), Emory Univ Hosp, 1364 Clifton Rd NE,Suite F606, Atlanta, GA 30322 USA. NR 33 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 1998 VL 19 SU D BP D31 EP D39 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZP242 UT WOS:000073732200005 PM 9597520 ER PT J AU Pagani, O O'Neill, A Castiglione, M Gelber, RD Goldhirsch, A Rudenstam, CM Lindtner, J Collins, J Crivellari, D Coates, A Cavalli, F Thurlimann, B Simoncini, E Fey, M Price, K Senn, HJ AF Pagani, O O'Neill, A Castiglione, M Gelber, RD Goldhirsch, A Rudenstam, CM Lindtner, J Collins, J Crivellari, D Coates, A Cavalli, F Thurlimann, B Simoncini, E Fey, M Price, K Senn, HJ CA Int Breast Cancer Study Grp TI Prognostic impact of amenorrhoea after adjuvant chemotherapy in premenopausal breast cancer patients with axillary node involvement: Results of the International Breast Cancer Study Group (IBCSG) Trial VI SO EUROPEAN JOURNAL OF CANCER LA English DT Article DE breast cancer; adjuvant chemotherapy; amenorrhoea; premenopausal ID OVARIAN-FUNCTION; CLINICAL-TRIALS; CYCLOPHOSPHAMIDE; METHOTREXATE; SURVIVAL; CMF AB Adjuvant chemotherapy-induced amenorrhoea has been shown to be associated with reduced relapses and improved survival for premenopausal breast cancer patients. Amenorrhoea was, therefore, studied to define features of chemotherapy (i.e. duration and timing) and disease-related factors which are associated with its treatment effects. We reviewed data from IBCSG Trial VI, in which accrual was between July 1986 and April 1993. 1196 of the 1475 eligible patients (81%) were evaluable for this analysis. The median follow-up was 60 months. Women who experienced amenorrhoea had a significantly better disease-free survival (DFS) than those who did not (P=0.0004), although the magnitude of the effect was reduced when adjusted for other prognostic factors (P=0.09). The largest treatment effect associated with amenorrhoea was seen in patients assigned to receive only three initial CMF courses (5-yr DFS: 67% versus 49%, no amenorrhoea; hazard ratio, 0.55; 95% confidence interval, 0.38 to 0.81; P=0.002). DFS differences between amenorrhoea categories were larger for patients with ER/PR positive tumours (hazard ratio, 0.65; 95% confidence interval, 0.53 to 0.80; P=0.0001). Furthermore, patients whose menses returned after brief amenorrhoea had a DFS similar to those whose menses ceased and did not recover (hazard ratio, 1.10; 95% confidence interval, 0.75 to 1.62; P=0.63). The effects associated with a permanent or temporary chemotherapy-induced amenorrhoea are especially significant for node-positive breast cancer patients who receive a suboptimal duration of CMF chemotherapy. Cessation of menses, even for a limited time period after diagnosis of breast cancer, might be beneficial and should be prospectively investigated, especially in patients with oestrogen receptor-positive primaries. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Int Breast Canc Study Grp, Bern, Switzerland. W Swedish Breast Canc Study Grp, Gothenburg, Sweden. Inst Oncol, Ljubljana, Slovenia. Anti Canc Council Victoria, Melbourne, Vic, Australia. Ctr Riferimento Oncol, I-33081 Aviano, Italy. Univ Sydney, Sydney, NSW 2006, Australia. Royal Prince Alfred Hosp, Sydney, NSW 2006, Australia. Osped San Giovanni, Swiss Grp Clin Canc Res, SAKK, Bellinzona, Switzerland. Kantonsspital, SAKK, St Gallen, Switzerland. Spedali Civili & Fondaz Beretta, Brescia, Italy. Inselspital, SAKK, Bern, Switzerland. European Inst Oncol, Milan, Italy. RP Goldhirsch, A (reprint author), Osped Civico, Int Breast Canc Study Grp, CH-6900 Lugano, Switzerland. OI Buonadonna, Angela/0000-0002-1930-0308; albertini, alberto/0000-0002-7989-649X NR 24 TC 133 Z9 137 U1 2 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD APR PY 1998 VL 34 IS 5 BP 632 EP 640 DI 10.1016/S0959-8049(97)10036-3 PG 9 WC Oncology SC Oncology GA ZP718 UT WOS:000073781500011 PM 9713266 ER PT J AU Fleming, JC Berger, G Guichard, J Cramer, EM Wagner, DD AF Fleming, JC Berger, G Guichard, J Cramer, EM Wagner, DD TI The transmembrane domain enhances granular targeting of P-selectin SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE regulated secretion; granules; protein trafficking; adhesion receptor ID REGULATED SECRETORY PATHWAY; WEIBEL-PALADE BODIES; MEMBRANE-PROTEIN; ENDOTHELIAL-CELLS; PLASMA-MEMBRANE; CYTOPLASMIC DOMAIN; HELICAL INTERACTIONS; ALPHA; PLATELETS; RECEPTOR AB P-selectin is an integral membrane glycoprotein that is stored in granules of endothelial tells and platelets. The cytoplasmic domain of P-selectin is known to contain at least part of the signal that directs the protein to storage granules. In order to more fully understand how P-selectin is targeted to the regulated secretory pathway; we have expressed chimeric constructs between P-and E-selectin, a protein which is expressed on the cell surface, in a rat insulinoma cell line. Immunofluorescence studies indicated that replating the cytoplasmic domain of E-selectin with that of P-selectin resulted in low-level granular expression. In contrast, when both the transmembrane and cytoplasmic domains of E-selectin were replaced with the analogous domains of P-selectin, the granular localization appeared greatly increased, This was confirmed by immunoelectron microscopy which demonstrated a three-to fourfold improvement in granular targeting, i.e. similar to wild-type P-selectin, The transmembrane domain had to be in the contest of the P-selectin cytoplasmic domain as this membrane-spanning region could not induce granular targeting on its own. These results describe a novel function for the transmembrane domain of P-selectin in enhancing the efficiency of granular targeting and further implicate protein transmembrane domains in intracellular trafficking. C1 Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. Tufts Univ, Sackler Sch Grad Biomed Sci, Program Cell Mol & Dev Biol, Boston, MA 02111 USA. Hop Henri Mondor, INSERM U91, F-94010 Creteil, France. RP Fleming, JC (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, 800 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [R01 HL41002] NR 57 TC 19 Z9 19 U1 0 U2 0 PU GUSTAV FISCHER VERLAG PI JENA PA VILLENGANG 2, D-07745 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD APR PY 1998 VL 75 IS 4 BP 331 EP 343 PG 13 WC Cell Biology SC Cell Biology GA ZN968 UT WOS:000073702100004 PM 9628319 ER PT J AU Cserhalmi-Friedman, PB Baden, H Burgeson, RE Christiano, AM AF Cserhalmi-Friedman, PB Baden, H Burgeson, RE Christiano, AM TI Molecular basis of non-lethal junctional epidermolysis bullosa: identification of a 38 basepair insertion and a splice site mutation in exon 14 of the LAMB3 gene SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE junctional epidermolysis bullosa; splice site mutation; insertion mutation; laminin 5 beta(3) chain gene, genodermatosis ID HOMOZYGOUS NONSENSE MUTATION; BETA-3 CHAIN; MUSCULAR-DYSTROPHY; LAMININ-5 LAMB3; COLLAGEN; DELETION; PATIENT AB Epidermolysis bullosa (EB) is a group of genodermatoses characterized by fragility and easy blistering of the skin. In the junctional forms of EB (JEB), blisters occur at the level of the lamina lucida, and specific mutations have been detected in the genes encoding different components of the hemidesmosomal-anchoring filament complex. In the non-lethal form of JEB (NL-JEB), mutations in genes encoding two of the polypeptide chains of the anchoring filament protein laminin 5 have recently been described. In this study, we searched for mutations in a family using PCR amplification of exon 14 of LAMB3, the laminin 5 beta(3) chain gene, followed by heteroduplex analysis and automated sequencing of the PCR products, We detected a novel combination of mutations in this family, consisting of an out-of frame insertion on one allele, and a splice site mutation on the other allele, representing the first report of a large insertion in LAMB3, together with a splice site mutation inherited in trans, which result in the NL-JEB phenotype. C1 Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Christiano, AM (reprint author), Columbia Univ Coll Phys & Surg, Dept Dermatol, 630 W 168th St,VC-1526, New York, NY 10032 USA. EM amc65@columbia.edu FU NIAMS NIH HHS [AR38923, AR35689, AR43602] NR 22 TC 4 Z9 4 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD APR-JUN PY 1998 VL 7 IS 2-3 BP 105 EP 111 DI 10.1111/j.1600-0625.1998.tb00309.x PG 7 WC Dermatology SC Dermatology GA ZJ236 UT WOS:000073193400010 PM 9583749 ER PT J AU Leverenz, JB Raskind, MA AF Leverenz, JB Raskind, MA TI Early amyloid deposition in the medial temporal lobe of young Down syndrome patients: A regional quantitative analysis SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer's disease; beta-amyloid protein; Down syndrome; hippocampus; plaques ID ALZHEIMERS-DISEASE; DOWNS-SYNDROME; SENILE PLAQUES; NEUROPATHOLOGICAL CHANGES; NEUROFIBRILLARY TANGLES; CEREBRAL-CORTEX; DEMENTIA; PROTEIN; PRECURSOR; AGE AB The presence of the neuropathological alterations of Alzheimer's disease (AD) in essentially all older Down syndrome (DS) patients suggests that the examination of younger DS patients may clarify the early pathological progression of AD. We examined the hippocampus and parahippocampal-inferior temporal gyri of 42 DS patients (ages 4 days to 38 years) for the deposition of amyloid beta protein (A beta) using bath a modified Biel-schowsky stain and immunohistochemistry for A beta protein. The parahippocampal and inferior temporal gyri demonstrated A beta staining in eases as young as 8 years of age. as age and degree of A beta deposition increased, staining included the CA-1/subiculum and dentate molecular layer followed then by the remainder of the CA hippocampal regions. The first neuritic plaques were observed in tale CA-1/subiculum despite this being a later region of A beta deposition. Although A beta staining increased with age, there was substantial variability in the severity of A beta deposition within age groups. These results suggest that within the hippocampal/parahippocampal region there is a progressive stereotypic deposition of A beta. The variable severity of A beta deposition within age groups suggests that, other factors, besides DS, may be contributing to the timing anf severity of A beta deposition. (C) 1998 Academic Press. C1 Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Leverenz, JB (reprint author), Univ Washington, Sch Med, Dept Neurol, Seattle, WA 98195 USA. FU NIA NIH HHS [AG05136, AG00503] NR 34 TC 101 Z9 105 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 1998 VL 150 IS 2 BP 296 EP 304 DI 10.1006/exnr.1997.6777 PG 9 WC Neurosciences SC Neurosciences & Neurology GA ZJ769 UT WOS:000073251100014 PM 9527899 ER PT J AU Brosnan, J AF Brosnan, J TI Parenting the strong willed child: The clinically proven five-week program for parents of two- to six-year-olds SO FAMILY & COMMUNITY HEALTH LA English DT Book Review C1 W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. RP Brosnan, J (reprint author), W Los Angeles Vet Adm Med Ctr, Los Angeles, CA USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU ASPEN PUBL INC PI FREDERICK PA 7201 MCKINNEY CIRCLE, FREDERICK, MD 21704 USA SN 0160-6379 J9 FAM COMMUNITY HEALTH JI Fam. Community Health PD APR PY 1998 VL 21 IS 1 BP 81 EP 82 PG 2 WC Family Studies; Public, Environmental & Occupational Health SC Family Studies; Public, Environmental & Occupational Health GA ZB994 UT WOS:000072529000012 ER PT J AU Prakash, P Leykin, L Chen, ZY Toth, T Sayegh, R Schiff, I Isaacson, K AF Prakash, P Leykin, L Chen, ZY Toth, T Sayegh, R Schiff, I Isaacson, K TI Preparation by differential gradient centrifugation is better than swim-up in selecting sperm with normal morphology (strict criteria) SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 1995 Annual Meeting of the American-Society-of-Andrology CY MAR 31-APR 04, 1995 CL RALEIGH, NORTH CAROLINA SP Amer Soc Androl DE sperm preparation; Percoll; swim-up; morphology ID IN-VITRO FERTILIZATION; INVITRO FERTILIZATION; HUMAN-SPERMATOZOA; PREDICTIVE VALUE; SEMEN; PARAMETERS AB Objective: To evaluate two commonly used methods of sperm preparation with respect to their effects on sperm morphology (strict criteria). Design: Auto-controlled. split sample study performed on the semen of 74 male partners of couples enrolled for IVF. Setting: In vitro fertilization and andrology laboratories at a tertiary care, major teaching hospital. Patient(s): Seventy-four male partners of couples who were scheduled to undergo IVF. Intervention(s): Equal halves of the same semen sample were evaluated for strict criteria sperm morphology before and after preparation by differential gradient centrifugation using Percoll (Pacific Andrology, Montrose, CA) and by the standard swim-up method. Main Outcome Measure(s): The percentage of morphologically normal sperm was assessed using strict criteria before and after the two methods of sperm preparation. Specific parameters studied were individual abnormalities of the head, midpiece, and tail. Result(s): Sperm preparation using differential gradient centrifugation with Percoll produced a significantly greater number of specimens with normal sperm morphology and also showed higher absolute quantitative improvement over the swim-up method. The two methods were comparable in regard to their effects on specific sperm abnormalities !i.e., head, midpiece, and tail defects). Conclusion(s): The differential gradient sperm separation method using Percoll is superior to the swim-up method for selecting sperm with normal morphology as assessed by strict criteria. Because sperm morphology as assessed by strict criteria is a good predictor of oocyte fertilization, this method can be recommended as the method of choice for assisted reproductive technology laboratories. Use of this method may help improve outcome by increasing fertilization rates. (C) 1998 by American Society for Reproductive Medicine.). C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Vincent Androl Labs, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, In Vitro Fertilizat Lab, Boston, MA USA. RP Prakash, P (reprint author), Boston Med Ctr, Dept Obstet & Gynecol, 1 Med Ctr Pl, Boston, MA 02118 USA. NR 18 TC 22 Z9 27 U1 0 U2 1 PU AMER SOC REPRODUCTIVE MEDICINE PI BIRMINGHAM PA 1209 MONTGOMERY HIGHWAY, BIRMINGHAM, AL 35216-2809 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 1998 VL 69 IS 4 BP 722 EP 726 DI 10.1016/S0015-0282(98)00002-8 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA ZF654 UT WOS:000072918700018 PM 9548164 ER PT J AU Wang, TC Goldenring, JR Dangler, C Ito, S Mueller, A Jeon, WK Koh, TJ Fox, JG AF Wang, TC Goldenring, JR Dangler, C Ito, S Mueller, A Jeon, WK Koh, TJ Fox, JG TI Mice lacking secretory phospholipase A(2) show altered apoptosis and differentiation with Helicobacter felis infection SO GASTROENTEROLOGY LA English DT Article ID GROWTH-FACTOR-ALPHA; GROUP-II PHOSPHOLIPASE-A2; INTESTINAL TREFOIL FACTOR; ACTIVE CHRONIC GASTRITIS; TRANSGENIC MICE; SPASMOLYTIC POLYPEPTIDE; EPITHELIAL-CELLS; MOUSE STOMACH; GENE-EXPRESSION; PARIETAL-CELLS AB Background & Aims: Infection with Helicobacter pylori uniformly leads to a chronic superficial gastritis that may progress to atrophic gastritis, a premalignant process, A mouse model of Helicobacter felis infection was used to study possible genetic determinants of the response to infection, Methods: Three inbred mouse strains with known secretory phospholipase A(2) (sPLA(2)) genotypes [BALB/c (+/+), C3H/HeJ (+/+), and C57BL/6 (-/-)] were orally infected with H. felis and examined longitudinally using routine histology, immunocytochemistry, electron microscopy, proliferating cell nuclear antigen, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling, and Northern and Western blot studies. Results: Only the C57BL/6 strain showed increased gastric fundic proliferation and apoptosis in response to infection. In addition, the C57BL/6 mouse showed a marked loss of parietal and chief cells, along with a marked expansion of an aberrant gastric mucous cell lineage that stained positive for spasmolytic polypeptide, In contrast, no significant change in these cell types was observed in BALB/c and C3H/HeJ strains, Increased expression of sPLA(2) was observed in BALB/c and C3H/HeJ after H. felis infection, whereas sPLA(2) expression was absent in C57BL/6 mice. Conclusions: H. felis infection leads to increased apoptosis and altered cellular differentiation in the C57BL/6 mouse, a strain that lacks gastric sPLA(2) expression, Because sPLA(2) has been identified recently as the MOM1 (modifier of MIN) locus that influences polyp formation in the colon, these studies suggest that sPLA(2) may also influence the gastric epithelial response to Helicobacter infection. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Klin Goettingen, Allgemeinchirurg Abt, Goettingen, Germany. RP Wang, TC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 724,32 Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [R01 CA67529] NR 49 TC 161 Z9 167 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1998 VL 114 IS 4 BP 675 EP 689 DI 10.1016/S0016-5085(98)70581-5 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZE219 UT WOS:000072770100012 PM 9516388 ER PT J AU Goke, M Kanai, M Lynch-Devaney, K Podolsky, DK AF Goke, M Kanai, M Lynch-Devaney, K Podolsky, DK TI Rapid mitogen-activated protein kinase activation by transforming growth factor alpha in wounded rat intestinal epithelial cells SO GASTROENTEROLOGY LA English DT Article ID FACTOR-BETA; CARDIAC MYOCYTES; MIGRATION; STRESS; INJURY; PHOSPHORYLATION; EXPRESSION; INVITRO; CASCADE AB Background & Aims: To define signaling events initiating heating after intestinal epithelial injury, activation of mitogen-activated protein kinase (MAPK) pathways was assessed after wounding using an in vitro model. Methods: Proteins isolated from wounded monolayers of nontransformed intestinal epithelial cells (IEC-6) were analyzed for tyrosine phosphorylation and MAPK expression by Western blot. Extracellular signal-regulated kinase (ERK) 1, ERK2, and Raf-1 activities were assessed by immune complex kinase assays. Results: Tyrosine phosphorylation of several proteins including ERK1 was substantially increased 5 minutes after injury. Another MAPK, c-Jun-1-terminal protein kinase (JNK), was also activated after wounding. Conditioned medium from wounded but not intact IEC-6 monolayers resulted in increased activity of ERK1, ERK2, and Raf-1 kinase. Wound-conditioned medium stimulated proliferation of subconfluent IEC-6 cells compared with conditioned medium from intact IEC-6 cultures and contained higher amounts of transforming growth factor (TGF)-alpha than supernatants of confluent IEC-6 cultures. Activation of ERK1 and ERK2 was partially inhibited by neutralizing anti-TGF-alpha. Conclusions: Wounding of intestinal epithelial cells results in activation of Raf-1, ERK1, ERK2, and JNK1 MAPKs and subsequent cell proliferation in vitro. Activation of ERK1 and ERK2 is mediated in part by TGF-alpha. C1 Massachusetts Gen Hosp, Gastroenterol Unit, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Podolsky, DK (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, Dept Med, GRJ-719,55 Fruit St, Boston, MA 02114 USA. EM Podolsky.Daniel@mgh.harvard.edu FU NIDDK NIH HHS [DK 43351, DK 41557] NR 34 TC 78 Z9 82 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1998 VL 114 IS 4 BP 697 EP 705 DI 10.1016/S0016-5085(98)70583-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZE219 UT WOS:000072770100014 PM 9516390 ER PT J AU Fox, JG Dewhirst, FE Shen, ZL Feng, Y Taylor, NS Paster, BJ Ericson, RL Lau, CN Correa, P Araya, JC Roa, I AF Fox, JG Dewhirst, FE Shen, ZL Feng, Y Taylor, NS Paster, BJ Ericson, RL Lau, CN Correa, P Araya, JC Roa, I TI Hepatic Helicobacter species identified in bile and gallbladder tissue from Chileans with chronic cholecystitis SO GASTROENTEROLOGY LA English DT Article ID CAMPYLOBACTER-LIKE ORGANISMS; CHRONIC ACTIVE HEPATITIS; SP-NOV; PYLORI INFECTION; HOMOSEXUAL MEN; MICE; BACTERIUM; CANCER; GASTROENTERITIS; CARCINOMA C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. Louisiana State Univ, Med Ctr, Dept Pathol, New Orleans, LA 70112 USA. Univ La Frontera, Hosp Reg Temuco, Dept Pathol, Temuco, Chile. RP Fox, JG (reprint author), MIT, Div Comparat Med, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM jgfox@mit.edu FU NCI NIH HHS [CA-67529, CA-28842, CA-26731] NR 56 TC 364 Z9 388 U1 0 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 1998 VL 114 IS 4 BP 755 EP 763 DI 10.1016/S0016-5085(98)70589-X PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZE219 UT WOS:000072770100020 PM 9516396 ER PT J AU Jensen, DM Jutabha, R Kovacs, TOG Machicado, GA Gralnek, I Cheng, S Jensen, ME Gornbein, J AF Jensen, DM Jutabha, R Kovacs, TOG Machicado, GA Gralnek, I Cheng, S Jensen, ME Gornbein, J TI Final results of a randomized prospective study of combination banding and sclerotherapy versus sclerotherapy alone for hemostasis of bleeding esophageal varices. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, CURE, Hemostasis Res Grp, Los Angeles, CA USA. 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 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1998 VL 47 IS 4 SU S MA 184 BP AB70 EP AB70 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK314 UT WOS:000073306800184 ER PT J AU Jutabha, R Jensen, DM Kovacs, TOG Machicado, GA Gralnek, IM King, J Jensen, ME AF Jutabha, R Jensen, DM Kovacs, TOG Machicado, GA Gralnek, IM King, J Jensen, ME TI Initial results of a prospective study of combination banding & sclerotherapy compared to sclerotherapy alone for bleeding gastric varices. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, CURE Hemostasis Res Grp, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. 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 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1998 VL 47 IS 4 SU S MA 249 BP AB86 EP AB86 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK314 UT WOS:000073306800248 ER PT J AU Kim, J Officer, T Graham, DY AF Kim, J Officer, T Graham, DY TI Endoscope disinfection may not always be effective: The "Y" connection is an unnecessary Achilles heel of the disinfection process SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 VA Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. 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 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1998 VL 47 IS 4 SU S MA 112 BP AB52 EP AB52 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK314 UT WOS:000073306800113 ER PT J AU Machicado, GA Jensen, DM Kovacs, TG Jutabha, R Randall, G Gornbein, J Jensen, ME Cheng, S Fontana, L AF Machicado, GA Jensen, DM Kovacs, TG Jutabha, R Randall, G Gornbein, J Jensen, ME Cheng, S Fontana, L TI Patients with recurrent GI hemorrhage and colonic angiomas - A randomized study of endoscopic treatment with bipolar or heater probe coagulation SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, CURE, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. 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 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1998 VL 47 IS 4 SU S MA 304 BP AB100 EP AB100 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK314 UT WOS:000073306800302 ER PT J AU Mallery, S Quirk, D Lewandroski, K Centeno, B Warshaw, A Brugge, WR AF Mallery, S Quirk, D Lewandroski, K Centeno, B Warshaw, A Brugge, WR TI EUS-guided FNA with cyst fluid analysis in pancreatic cystic lesions SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 20 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1998 VL 47 IS 4 SU S MA 504 BP AB149 EP AB149 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK314 UT WOS:000073306800500 ER PT J AU Mallery, S Centeno, B Hahn, P Warshaw, A Brugge, WR AF Mallery, S Centeno, B Hahn, P Warshaw, A Brugge, WR TI Comparison of EUS-guided, CT-guided and intraoperative needle biopsy of pancreatic masses. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 20 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1998 VL 47 IS 4 SU S MA 503 BP AB149 EP AB149 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK314 UT WOS:000073306800499 ER PT J AU Mallery, S Zuccaro, G Ciaccia, D Brugge, WR Catalano, M Penman, I Hoffman, B Hawes, R Gress, F Isenberg, G Chak, A Rice, T Van Dam, J AF Mallery, S Zuccaro, G Ciaccia, D Brugge, WR Catalano, M Penman, I Hoffman, B Hawes, R Gress, F Isenberg, G Chak, A Rice, T Van Dam, J TI Clinical outcomes of T1 esophageal carcinoma as staged by EUS: A multicenter evaluation SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH USA. Indiana Univ, Med Ctr, Bloomington, IN 47405 USA. Med Univ S Carolina, Charleston, SC USA. SUNY Stony Brook, Winthrop Univ Hosp, Stony Brook, NY USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 20 Z9 21 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1998 VL 47 IS 4 SU S MA 502 BP AB149 EP AB149 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK314 UT WOS:000073306800498 ER PT J AU Mallery, S Goldberg, SN Brugge, WR AF Mallery, S Goldberg, SN Brugge, WR TI EUS-guided radiofrequency ablation in the pancreas: Preliminary results in a porcine model SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 1998 VL 47 IS 4 SU S MA 37 BP AB34 EP AB34 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZK314 UT WOS:000073306800038 ER PT J AU Hirano, T Fujimoto, J Ueki, T Yamamoto, H Iwasaki, T Morisita, R Sawa, Y Kaneda, Y Takahashi, H Okamoto, E AF Hirano, T Fujimoto, J Ueki, T Yamamoto, H Iwasaki, T Morisita, R Sawa, Y Kaneda, Y Takahashi, H Okamoto, E TI Persistent gene expression in rat liver in vivo by repetitive transfections using HVJ-liposome SO GENE THERAPY LA English DT Article DE cytotoxic T lymphocytes; antibody; in vivo gene transduction ID NUCLEAR-PROTEIN; THERAPY; VIRUS; DNA; HEPATOCYTES; INVIVO; HEPATITIS; DELIVERY; ANTIGEN; CELLS AB Most viral vectors are highly immunogenic and are of limited use for somatic gene therapy that requires repetitive administrations. We have developed a highly efficient gene transduction procedure useful for repetitive transfections using liposome containing hemagglutinating virus of Japan (HVJ-liposome). The Escherichia coli beta-galactosidase (beta-gal) gene was embodied in HVJ-liposome, and introduced directly into the caudal lobe of rat liver that was transiently isolated from a systemic circulation. A 116 kDa beta-gal protein was detected in transfected rat liver tissues by Western blot analysis and it was expressed in more than two-thirds of the liver by histological staining. It was found that the transfection efficiency was not affected by repetitive transfections. In support of these findings, antibody response to HVJ-liposome detected in the rat sera was weak and transient. Furthermore, cytotoxic T lymphocytes were not elicited against autologous rat hepatocytes that were transfected in vivo using HVJ-liposome. Thus, our results demonstrate that the isolation of a target liver from systemic circulation and the direct administration of foreign genes using HVJ-liposomes are useful for high gene transduction and persistent gene expression in the liver. C1 Hyogo Coll Med, Dept Surg 1, Nishinomiya, Hyogo 663, Japan. Hyogo Coll Med, Dept Internal Med 2, Nishinomiya, Hyogo 663, Japan. Osaka Univ, Sch Med, Dept Geriatr Med, Osaka 553, Japan. Osaka Univ, Sch Med, Dept Surg 1, Osaka 553, Japan. Osaka Univ, Sch Med, Inst Cellular & Mol Biol, Osaka 553, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Fujimoto, J (reprint author), Hyogo Coll Med, Dept Surg 1, 1-1 Mukogawacho, Nishinomiya, Hyogo 663, Japan. NR 29 TC 61 Z9 61 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 1998 VL 5 IS 4 BP 459 EP 464 DI 10.1038/sj.gt.3300617 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA ZH127 UT WOS:000073075500005 PM 9614569 ER PT J AU Mulligan, LM Timmer, T Ivanchuk, SM Campling, BG Young, LC Rabbitts, PH Sundaresan, V Hofstra, RMW Eng, C AF Mulligan, LM Timmer, T Ivanchuk, SM Campling, BG Young, LC Rabbitts, PH Sundaresan, V Hofstra, RMW Eng, C TI Investigation of the genes for RET and its ligand complex, GDNF/GFR alpha-1, in small cell lung carcinoma SO GENES CHROMOSOMES & CANCER LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; NEUROTROPHIC FACTOR; TYROSINE KINASE; PROTOONCOGENE PRODUCT; MUTATION-CONSORTIUM; BETA-GLUCURONIDASE; DISEASE PHENOTYPE; C-RET; EXPRESSION; GDNF AB RET is a receptor tyrosine kinase expressed in neuroendocrine cells and in tumors of these cell types. RET activation may be mediated by a ligand complex comprising glial cell line-derived neurotrophic factor (GDNF) and GDNF family receptor alpha-1 (GFR alpha-1). Activating RET mutations are found in the inherited cancer syndrome multiple endocrine neoplasia type 2 and in a subset of the related sporadic tumors, medullary thyroid carcinoma and pheochromocytoma, both being derived from neuroendocrine tissues, In one small study, mutations were identified in another tumor with neuroendocrine features, small cell lung carcinoma (SCLC), To determine whether RET mutations contribute to the pathogenesis of SCLC, we examined a panel of 54 SCLC cell lines. No mutations were identified in RET exons 10, I I, and 13-16, regions previously implicated in SCLC or other neuroendocrine tumors, We further examined the expression pattern of RET and the genes encoding the components of its ligand complex GDNF and GFR alpha-1, in 21 SCLC lines by using RT-PCR. Although we found no consistent pattern of expression for these three genes, RET was expressed in 57% of SCLC lines. Thus, although RET mutations appear unlikely to be an important step in the tumorigenesis of SCLC, the frequent expression of this gene suggests that RET may have a mitogenic role in a subset of SCLC cell lines, (C) 1998 Wiley-Liss, Inc. C1 Queens Univ, Dept Pathol, Kingston, ON K7L 3N6, Canada. Univ Groningen, Dept Med Genet, Groningen, Netherlands. Univ Cambridge, MRC Ctr, Cambridge, England. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol,Human Canc Genet Unit, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Program Populat Sci, Boston, MA USA. RP Mulligan, LM (reprint author), Queens Univ, Dept Paediat, 20 Barrie St, Kingston, ON K7L 3NG, Canada. RI Young, Leah/B-9051-2012; OI Young, Leah/0000-0001-7156-1006; Hofstra, Robert/0000-0001-7498-3829 NR 63 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD APR PY 1998 VL 21 IS 4 BP 326 EP 332 DI 10.1002/(SICI)1098-2264(199804)21:4<326::AID-GCC6>3.0.CO;2-0 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA ZF861 UT WOS:000072940600006 PM 9559344 ER PT J AU Wiederschain, GY Koul, O Aucoin, JM Smith, FI McCluer, RH AF Wiederschain, GY Koul, O Aucoin, JM Smith, FI McCluer, RH TI alpha 1,3 fucosyltransferase, alpha-L-fucosidase, alpha-D-galactosidase, beta-D-galactosidase, and Le(x) glycoconjugates in developing rat brain SO GLYCOCONJUGATE JOURNAL LA English DT Article DE alpha 1,3 fucosyltransferase; SSEA-1; Le(x); alpha-fucosidase; alpha-galactosidase; beta-galactosidase; rat development; forebrain; cerebellum ID FUCOSYL-TRANSFERASE GENE; MOLECULAR-CLONING; GDP-FUCOSE; HUMAN ALPHA-1->3FUCOSYLTRANSFERASES; GLOBOSIDE GALACTOSYLTRANSFERASE; NERVOUS-SYSTEM; UDP-GALACTOSE; LEWIS-X; EXPRESSION; SPECIFICITY AB Fucosyltransferases (FTs) and various glycosidases that are involved in the biosynthesis or degradation of SSEA-1 (Le(x)) antigens and their precursors in the CNS are developmentally regulated. In forebrain and cerebellum with lactosamine (LacNAc) as acceptor the FT activity was maximal at P15-P22, but with the glycolipid substrate paragloboside (nLc(4)) the maximal activity in cerebellum was obtained at P10-P15. The FT activity, with these substrates, was insensitive to N-ethylmaleimide (NEM) and the glycolipid product had an alpha 1,3 linkage (Fuc to GlcNAc) suggesting similarities of the investigated enzyme to the cloned human and rat FT IV. However, the observation of different patterns of FT activity in isoelectrofocused fractions (pH 3.5-10) with different types of acceptors, and the differential expression of Le(x) containing glycolipids and glycoproteins during development strongly suggest the presence of more than one type of FT during development. Data on developmental expression of the hydrolytic enzymes, alpha-L-fucosidase, beta-D-galactosidase and alpha-D-galactosidase, which can potentially hydrolyse SSEA-1 or its precursors, support the notion that SSEA-1 expression is the result of a dynamic balance between the activity of transferases and hydrolases. C1 EK Shriver Ctr, Dept Biomed Sci, Waltham, MA 02254 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, Sch Med, Dept Pediat, Houston, TX 77030 USA. RP Wiederschain, GY (reprint author), EK Shriver Ctr, Dept Biomed Sci, Waltham, MA 02254 USA. EM gwiederschain@Shriver.org FU NICHD NIH HHS [HD05515]; NINDS NIH HHS [NS15037] NR 55 TC 22 Z9 23 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0282-0080 J9 GLYCOCONJUGATE J JI Glycoconjugate J. PD APR PY 1998 VL 15 IS 4 BP 379 EP 388 DI 10.1023/A:1006925918978 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZF914 UT WOS:000072945900008 PM 9613825 ER PT J AU Zheng, WX Luo, MP Welt, C Lambert-Messerlian, G Sung, CJ Zhang, Z Ying, SY Schneyer, AL Lauchlan, SC Felix, JC AF Zheng, WX Luo, MP Welt, C Lambert-Messerlian, G Sung, CJ Zhang, Z Ying, SY Schneyer, AL Lauchlan, SC Felix, JC TI Imbalanced expression of inhibin and activin subunits in primary epithelial ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 01-08, 1997 CL ORLANDO, FLORIDA SP US & Canadian Acad Pathol ID FOLLICLE-STIMULATING-HORMONE; GROWTH-FACTOR-BETA; POSTMENOPAUSAL WOMEN; SURFACE EPITHELIUM; CELL-LINES; DEFICIENT MICE; FOLLISTATIN; CARCINOMA; RECEPTOR; TUMORS AB Objectives. Inhibins and activins are related gonadal peptides with opposing biologic actions on gonadotropin regulation, cell differentiation, and proliferation, The previous study of activin in ovarian cancer cell lines suggests that activin may promote growth of ovarian cancer. Elevated serum inhibin levels were also found in ovarian cancer patients; however, the source of elevated inhibin is unknown. This study is designed to examine the expression of inhibin and activin subunits as well as activin receptor in primary ovarian epithelial tumors to explore their role in the process of ovarian epithelial tumorigenesis. Methods. The protein and mRNA expression of alpha and beta A subunits of inhibin/activin as well as of activin receptor mRNA were examined with immunohistochemistry (IHC) and reverse transcription-polymerase chain reaction (RT-PCR) in 112 ovarian carcinomas, Cases included 59 serous, 23 endometrioid, 16 mucinous, 9 clear cell, and 5 undifferentiated carcinomas. We also tested normal ovary and benign and borderline ovarian tumors for comparison. These included 17 ovarian surface epithelial samples, 6 serous and 5 mucinous cystadenomas, and 9 serous and 7 mucinous tumors of low malignant potential. A total of 139 ovarian tumors were analyzed by IHC and a total of 63 ovarian tumor samples were tested by RT-PCR. Results. Inhibin alpha subunit expression was found in 47% of ovarian surface epithelia and focal alpha immunoreactivity was seen in tumor stroma, but was not found in the epithelial component of ovarian cystadenomas, tumors of low malignant potential (LMP), or carcinomas, Activin beta A subunit was expressed in 93% of surface epithelia, in the epithelial component of all cystadenomas, in 81% of LMP tumors, and in 72% of carcinomas, but not in tumor stroma, Activin expression did not correlate with histologic grades, tumor types, and surgical stages, Activin receptor type I and II mRNA-amplified products were found in virtually all the surface epithelial samples and ovarian tumors. Conclusions. The data suggest that imbalanced expression of inhibin and activin subunits in ovarian surface epithelium may represent an early event which leads to epithelial proliferation. Unopposed beta A and activin receptor expression in epithelial compartment of ovarian tumors suggest that activin may be available as autocrine and/or paracrine factors in ovarian epithelial tumors. But exact roles of inhibin and activin in ovarian epithelial tumors remain to be defined. (C) 1998 Academic Press. C1 Univ So Calif, Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Sch Med, Dept Cell & Neurobiol, Los Angeles, CA 90033 USA. Brown Univ, Women & Infants Hosp, Dept Pathol, Providence, RI USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Zheng, WX (reprint author), Univ So Calif, Los Angeles Cty Med Ctr, Womens & Childrens Hosp, Dept Pathol, 1240 N Mission Rd,1M19, Los Angeles, CA 90033 USA. OI Messerlian, Geralyn/0000-0002-9440-3411; Welt, Corrine/0000-0002-8219-5504 FU NCI NIH HHS [R01 CA51167]; NIDDK NIH HHS [DK-47609] NR 43 TC 65 Z9 68 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD APR PY 1998 VL 69 IS 1 BP 23 EP 31 DI 10.1006/gyno.1998.4958 PG 9 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA ZM278 UT WOS:000073522500006 PM 9570994 ER PT J AU Freire, MBS Ji, LO Onuma, T Orban, T Warram, JH Krolewski, AS AF Freire, MBS Ji, LO Onuma, T Orban, T Warram, JH Krolewski, AS TI Gender-specific association of M235T polymorphism in angiotensinogen gene and diabetic nephropathy in NIDDM SO HYPERTENSION LA English DT Article DE nephropathy; angiotensinogen; polymorphism; diabetes ID IDDM; HYPERTENSION; SUSCEPTIBILITY; DISEASE; VARIANT AB This study examined the association between the development of nephropathy in non-insulin-dependent diabetes mellitus (NIDDM) patients and M235T polymorphism in the angiotensinogen gene. White NIDDM patients with diabetic nephropathy (case subjects, n=117) and patients without any evidence of nephropathy and greater than or equal to 10 years of NIDDM (control subjects, n=125) were selected from among patients of the Joslin Diabetes Center and examined. In addition to a standardized examination, blood was drawn for DNA and determination of M235T genotypes at the angiotensinogen locus. For the angiotensinogen gene, the frequency of the genotype 235T/235T, known to be associated with essential hypertension, was higher among case subjects with nephropathy than in control subjects without this complication. This difference, expressed as the odds ratio for nephropathy among 235T/235T homozygotes in comparison with all other genotypes, was 2.2 (95% confidence interval, 1.1 to 4.4). The difference, however, was confined to men (odds ratio, 4.8; 95% confidence interval, 1.5 to 14.9), with the distribution of genotypes in case and control subjects being equal among women (odds ratio, 1.1). DNA polymorphism M235T in the angiotensinogen gene, which is associated with higher expression of this gene, contributes to the risk of diabetic nephropathy in NIDDM men but not in women. C1 Joslin Diabet Ctr, Sect Epidemiol & Genet, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Epidemiol & Genet, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. NR 24 TC 42 Z9 45 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD APR PY 1998 VL 31 IS 4 BP 896 EP 899 PG 4 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA ZE648 UT WOS:000072815600002 PM 9535411 ER PT J AU Haake, DA Martinich, C Summers, TA Shang, ES Pruetz, JD McCoy, AM Mazel, MK Bolin, CA AF Haake, DA Martinich, C Summers, TA Shang, ES Pruetz, JD McCoy, AM Mazel, MK Bolin, CA TI Characterization of leptospiral outer membrane lipoprotein LipL36: Downregulation associated with late-log-phase growth and mammalian infection SO INFECTION AND IMMUNITY LA English DT Article ID INTERROGANS SEROVAR HARDJO; FRACTURE ELECTRON-MICROSCOPY; LYME-DISEASE SPIROCHETE; BORRELIA-BURGDORFERI; TREPONEMA-PALLIDUM; PATHOGENIC LEPTOSPIRA; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; BOVIS INFECTION; ESCHERICHIA-COLI AB We report the cloning of the gene encoding a 36-kDa leptospiral outer membrane lipoprotein, designated LipL36. We obtained the N-terminal amino acid sequence of a staphylococcal V8 proteolytic-digest fragment in order to design an oligonucleotide probe. A Lambda-Zap II library containing EcoRI fragments of Leptospira kirschneri DNA was screened, and a 2.3-kb DNA fragment which contained the entire structural lipL36 gene was identified. Several lines of evidence indicate that LipL36 is lipid modified in a manner similar to that of LipL41, a leptospiral outer membrane lipoprotein we described in a previous study (E. S. Shang, T. A. Summers, and D. A. Haake, Infect. Immun, 64:2322-2330, 1996). The deduced amino acid sequence of LipL36 would constitute a 364-amino-acid polypeptide,vith a 20-amino-acid signal peptide, followed by an L-X-Y-C lipoprotein signal peptidase cleavage site. LipL36 is solubilized by Triton X-114 extraction of L. kirschneri; phase separation results in partitioning of LipL36 exclusively into the hydrophobic, detergent phase. LipL36 is intrinsically labeled during incubation of L. kirschneri in media containing [H-3]palmitate. Processing of LipL36 is inhibited by globomycin, a selective inhibitor of lipoprotein signal peptidase. After processing, LipL36 is exported to the outer membrane along with LipL41 and lipopolysaccharide. Unlike Lip41, there appears to be differential expression of LipL36. In early-log-phase cultures, LipL36 is one of the most abundant L. kirschneri proteins. However, LipL36 levels drop considerably beginning in mid-log phase. LipL36 expression in vivo was evaluated by examining the humoral immune response to leptospiral antigens in the hamster model of leptospirosis. Hamsters surviving challenge with culture-adapted virulent L. kirschneri generate a strong antibody response to LipL36. In contrast, sera from hamsters surviving challenge with host-adapted L. kirschneri do not recognize LipL36. These findings suggest that LipL36 expression is downregulated during mammalian infection, providing a marker for studying the mechanisms by which pathogenic Leptospira species adapt to the host environment. C1 W Los Angeles Vet Affairs Med Ctr, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Microbiol Mol Genet & Immunol, Los Angeles, CA 90095 USA. USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. RP Haake, DA (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. RI Pruetz, Jill/A-7202-2009 FU NCI NIH HHS [P30 CA016042, CA16042]; NIAID NIH HHS [R01 AI034431, R21 AI034431, R29 AI034431, T32 AI007323, 2-T32-AI07323-06, AI-34431] NR 54 TC 80 Z9 93 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1998 VL 66 IS 4 BP 1579 EP 1587 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZD630 UT WOS:000072706100043 PM 9529084 ER PT J AU Swanson, AF Ezekowitz, RAB Lee, A Kuo, CC AF Swanson, AF Ezekowitz, RAB Lee, A Kuo, CC TI Human mannose-binding protein inhibits infection of HeLa cells by Chlamydia trachomatis SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; BACTERICIDAL ACTIVITY; COMPLEMENT PATHWAY; ANTIGENIC ANALYSIS; CLASSICAL PATHWAY; AMNIOTIC-FLUID; SERUM LECTIN; PNEUMONIAE; FORMS; NEUTRALIZATION AB The role that collectin (mannose binding protein) may play in the host's defense against chlamydial infection was investigated. Recombinant human mannose-binding protein was used in the inhibition of cell culture infection by Chlamydia trachomatis (C/TW-3/OT, E/UW-5/Cx, and L-2/434/Bu), Chlamydia pneumoniae (AR-39), and Chlamydia psittaci (6BC). Mannose-binding protein (MBP) inhibited infection of all chlamydial strains by at least 50% at 0.098 mu g/ml for TW-3 and UW-5, and at 6.25 mu g/ml for 434, AR-39, and 6BC. The ability of MBP to inhibit infection with strain L-2 was not affected by supplementation with complement or addition of an L-2-specific neutralizing monoclonal antibody. Enzyme-linked immunosorbent assay and dot blot analyses showed MEP bound to the surface of the organism to exert inhibition, which appeared to block the attachment of radiolabeled organisms to HeLa cells. Immunoblotting and affinity chromatography indicated that MBP binds to the 40-kDa glycoprotein (the major outer membrane protein) on the outer surface of the chlamydial elementary body, Hapten inhibition assays with monosaccharides and defined oligosaccharides showed that the inhibitory effects of MBP were abrogated by mannose or high-mannose type oligomannose-oligosaccharide. The latter carbohydrate is the ligand of the 40-kDa glycoprotein of C. trachomatis L-2, which is known to mediate attachment, suggesting that the MBP binds to high mannose moieties on the surface of chlamydial organisms. These results suggest that MBP plays a role in first-line host defense against chlamydial infection in humans. C1 Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Pediat Serv, Boston, MA 02114 USA. RP Kuo, CC (reprint author), Univ Washington, Dept Pathobiol, Box 357238, Seattle, WA 98195 USA. EM cckuo@u.washington.edu FU NEI NIH HHS [EY00219] NR 46 TC 43 Z9 45 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1998 VL 66 IS 4 BP 1607 EP 1612 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZD630 UT WOS:000072706100047 PM 9529088 ER PT J AU Cunningham, K Ackerly, H Alt, F Dunnick, W AF Cunningham, K Ackerly, H Alt, F Dunnick, W TI Potential regulatory elements for germline transcription in or near murine S gamma 1 SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE NF-kappa B; STAT6; switch recombination; transgenic mice ID GAMMA-1 SWITCH REGION; DNA-BINDING FACTOR; RESTING B-CELLS; LINE GAMMA-1; GENE-EXPRESSION; PROTEIN-BINDING; IFN-GAMMA; INDUCTION; PROMOTER; IL-4 AB We were interested in identifying cis-acting elements that regulate germline transcription and switch recombination of heavy chain genes. the murine gamma 1 heavy chain gene includes two DNase I hypersensitive sites, which may represent protein:DNA interactions important for germline transcription and switch recombination. One DNase hypersensitive site is at the promoter/l exon boundary (termed 'Site I'); we localized a second pair of DNase hypersensitive sites to just 5' of the S(gamma)1 region (termed 'Site II'). The DNA region of hypersensitive Site II includes a NF-kappa B/Rel binding site and a STAT6 binding site. It is noteworthy that NF-kappa B and STAT6 are induced by the same agents (CD40 ligation and IL-4 respectively) that stimulate germline transcription and switch recombination of the murine gamma 1 gene. Transgenes with the gamma 1 promoter region (DNase hypersensitive Site I), 1(gamma)1 and DNase I hypersensitive Site II expressed germline transcripts with correct regulation, including IL-4 inducibility, However, the level of stable transcripts produced by the transgenes was much lower than that of the endogenous gamma 1 gene, a complete 17 kb gamma 1 transgene or a derivative of the 17 kb gamma 1 transgene that lacked most of C(gamma)1. The promoter/l(gamma)1/Site II transgenes lacked S(gamma)1 and we found that gamma 1 transgenes that lacked only S(gamma)1 also expressed germline transcripts with proper regulation, but at a low level. This suggested that the S(gamma)1 region includes positive elements for regulation of the amount of germline transcripts. C1 Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. Childrens Hosp, HHMI Res Labs, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Dunnick, W (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, 1301 E Catherine, Ann Arbor, MI 48109 USA. FU NCI NIH HHS [CA39068]; NIAID NIH HHS [AI20047, AI31541] NR 47 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD APR PY 1998 VL 10 IS 4 BP 527 EP 536 DI 10.1093/intimm/10.4.527 PG 10 WC Immunology SC Immunology GA ZL129 UT WOS:000073401700018 PM 9620609 ER PT J AU Oslin, D Atkinson, RM Smith, DM Hendrie, H AF Oslin, D Atkinson, RM Smith, DM Hendrie, H TI Alcohol Related Dementia: Proposed clinical criteria SO INTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE alcoholism; dementia; diagnosis ID SOCIAL DRINKING; ALZHEIMERS-DISEASE; COGNITIVE LOSS; CONSUMPTION; BRAIN; DIAGNOSIS; RISK; RELIABILITY; PERFORMANCE; DISORDERS AB Current diagnostic criteria for Alcohol Related Dementia (ARD) are based almost exclusively on clinical judgment. Moreover, there are no guidelines available to assist the clinician or the researcher in distinguishing Alcohol Related Dementia from other causes of dementia such as Alzheimer's Disease (AD). However, this distinction may have implications for the prognosis and treatment of patients. In this article, provisional diagnostic criteria for establishing a diagnosis of Alcohol Related Dementia are proposed for further study. The criteria are based on the available literature on the relationship between alcohol consumption and dementia and were modeled after existing diagnostic criteria for AD and Vascular Dementia. Validity of these criteria for distinguishing AD from ARD will require further study. (C) 1998 John Wiley & Sons, Ltd. C1 Univ Penn, Ralston Penn Ctr, Sect Geriatr Psychiat, Philadelphia, PA 19104 USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Indiana Univ, Sch Med, Bloomington, IN 47405 USA. RP Oslin, D (reprint author), Univ Penn, Ralston Penn Ctr, Sect Geriatr Psychiat, 3614 Chestnut St, Philadelphia, PA 19104 USA. NR 61 TC 85 Z9 86 U1 3 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0885-6230 EI 1099-1166 J9 INT J GERIATR PSYCH JI Int. J. Geriatr. Psychiatr. PD APR PY 1998 VL 13 IS 4 BP 203 EP 212 DI 10.1002/(SICI)1099-1166(199804)13:4<203::AID-GPS734>3.0.CO;2-B PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA ZL443 UT WOS:000073433400004 PM 9646147 ER PT J AU Nielsen, GP Oliva, E Young, RH Rosenberg, AE Prat, J Scully, RE AF Nielsen, GP Oliva, E Young, RH Rosenberg, AE Prat, J Scully, RE TI Primary ovarian rhabdomyosarcoma: A report of 13 cases SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE ovary; neoplasm; sarcoma; rhabdomyosarcoma ID BONE-MARROW METASTASES; SMALL-CELL CARCINOMA; CLINICOPATHOLOGICAL ANALYSIS; ALVEOLAR RHABDOMYOSARCOMA; MESODERMAL TUMOR; DIAGNOSIS; TERATOMA AB Primary ovarian rhabdomyosarcomas were found in 13 patients aged 7 to 79 (mean 37) years who had reported abdominal pain and swelling. Six tumors involved the right ovary, 3 involved the left, 1 involved both, and the laterality was unknown in 3 cases. Four tumors were stage I, 2 were stage II, 4 were stage III, and 2 were stage IV; the stage of 1 tumor is not known. The tumors ranged from 10 to 19.5 (average 16) cm in diameter and had solid sectioned surfaces that varied from yellow to white to pink and from gelatinous to hemorrhagic. Microscopically, 11 tumors were embryonal and 2 were alveolar rhabdomyosarcomas. Follow-up information, available for 11 patients, revealed that 7 died of disease 10 days to 26 months postoperatively; 2 of these patients had stage II disease, 3 had stage III, and 2 had stage IV. Four patients were alive 2 to 9 months postoperatively; 3 had stage I and 1 had stage III disease. These 13 tumors and an additional 10 from the English-language literature are reviewed and the differential diagnosis of ovarian rhabdomyosarcoma is discussed. C1 Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nielsen, GP (reprint author), Massachusetts Gen Hosp, Dept Pathol, James Homer Wright Pathol Labs, Fruit St, Boston, MA 02114 USA. RI Prat, Jaime/G-4679-2011 NR 32 TC 22 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD APR PY 1998 VL 17 IS 2 BP 113 EP 119 DI 10.1097/00004347-199804000-00003 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA ZD626 UT WOS:000072705700003 PM 9553806 ER PT J AU Rivera, JA Werner, J Warshaw, AL Lewandrowski, KB Rattner, DW Fernandez-del Castillo, C AF Rivera, JA Werner, J Warshaw, AL Lewandrowski, KB Rattner, DW Fernandez-del Castillo, C TI Lexipafant fails to improve survival in severe necrotizing pancreatitis in rats SO INTERNATIONAL JOURNAL OF PANCREATOLOGY LA English DT Article DE acute pancreatitis; platelet activating factor; Lexipafant (BB882) ID PLATELET-ACTIVATING-FACTOR; C-REACTIVE PROTEIN; FACTOR ANTAGONIST; MODEL; ALPHA-2-MACROGLOBULIN; AMELIORATION; ELASTASE AB Conclusion. Lexipafant administration fails to improve survival or lessen the disease severity in two experimental models of severe acute pancreatitis. Background. The potent platelet activating factor antagonist Lexipafant has been shown to attenuate the biochemical and histologic changes associated with some animal models of acute pancreatitis, suggesting an important role for this cytokine in its pathogenesis. However, a survival advantage following Lexipafant administration has not been demonstrated. This study evaluates the effect of this platelet activating antagonist on survival in rat models of necrotizing and fulminant hemorrhagic pancreatitis. Methods. Sprague-Dawley rats underwent induction of either acute necrotizing (n = 40) or hemorrhagic pancreatitis (n = 36) with a time-and pressure-controlled bile duct infusion of 10 mM glycodeoxycholic acid (GDOC) or enterokinase 15 U/mL, in combination with supramaximal cerulein stimulation (5 mu g/kg/h). Immediately after pancreatitis induction, rats were randomly divided into three groups and received Lexipafant (1 mg or 10 mg) or saline as a continuous intravenous infusion over 9 h. Twenty-four-hour survival rates were determined and severity of pancreatitis was assessed by pancreatic histology scores. Results. The survival rates for GDOC treated rats were 55% (saline), 50% (1 mg Lexipafant) and 50% (10 mg Lexipafant). As expected, all rats induced with enterokinase and treated with saline died with hemorrhagic pancreatitis within 24 h. The same was true of those treated with high-and low-dose Lexipafant, and there was no difference in survival time. Histology scores did not differ between Lexipafant-treated and control rats in either GDOC or enterokinase rats. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Fernandez-del Castillo, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, WAC 456, Boston, MA 02114 USA. NR 27 TC 19 Z9 20 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0169-4197 J9 INT J PANCREATOL JI Int. J. Pancreatol. PD APR PY 1998 VL 23 IS 2 BP 101 EP 106 DI 10.1385/IJGC:23:2:101 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA ZR972 UT WOS:000074034800002 PM 9629507 ER PT J AU Minsky, BD Coia, L Haller, D Hoffman, J John, M Landry, J Pisansky, TM Willett, C Mahon, I Owen, J Hanks, G AF Minsky, BD Coia, L Haller, D Hoffman, J John, M Landry, J Pisansky, TM Willett, C Mahon, I Owen, J Hanks, G TI Treatment systems guidelines for primary rectal cancer from the 1996 patterns of care study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article ID PREOPERATIVE INFUSIONAL CHEMORADIATION; POSTOPERATIVE RADIATION-THERAPY; ADJUVANT THERAPY; RESECTABLE ADENOCARCINOMA; INTRAOPERATIVE RADIATION; COLORECTAL-CARCINOMA; CURATIVE SURGERY; LOCAL EXCISION; RESECTION; FAILURE AB Purpose: The Patterns of Care Rectal Cancer Committee was formed to develop consensus recommendations for patients with adenocarcinoma of the rectum limited to the pelvis. Methods and Materials: The Committee was composed of a multidisciplinary group of oncologists, and clinical scenarios were chosen to address most of the major treatment controversies in the combined modality treatment of rectal cancer. A literature search was then conducted and the major articles were identified, A modified Delphi technique was used to arrive at consensus. Serial surveys were conducted by distributing questionnaires to the Committee members to consolidate expert opinion. Voting was conducted using a scoring system and opinions were unified to the highest degree possible. Results: Consensus voting was performed for 4 clinical scenarios, Acceptability ratings for treatment were grouped into 3 broad categories: not acceptable, acceptable, and most acceptable. Based on the treatment options, a decision tree was developed that reflects the consensus of the committee. Conclusion: These options may help guide treatment decisions in rectal cancer. (C) 1998 Elsevier Science Inc. C1 Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA. Community Med Ctr, Toms River, NJ USA. Univ Penn, Med Ctr, Dept Med Oncol, Philadelphia, PA 19104 USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Surg Oncol, Philadelphia, PA 19111 USA. St Agnes, Ctr Canc, Fresno, CA USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Amer Coll Radiol, Philadelphia, PA 19103 USA. RP Minsky, BD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, 1275 York Ave, New York, NY 10021 USA. NR 40 TC 21 Z9 28 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 1998 VL 41 IS 1 BP 21 EP 27 DI 10.1016/S0360-3016(98)00027-3 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA ZM005 UT WOS:000073495200005 PM 9588913 ER PT J AU Santoni, R Liebsch, N Finkelstein, DM Hug, E Hanssens, P Goitein, M Smith, AR O'Farrell, D Efird, JT Fullerton, B Munzenrider, JE AF Santoni, R Liebsch, N Finkelstein, DM Hug, E Hanssens, P Goitein, M Smith, AR O'Farrell, D Efird, JT Fullerton, B Munzenrider, JE TI Temporal lobe (TL) damage following surgery and high-dose photon and proton irradiation in 96 patients affected by chordomas and chondrosarcomas of the base of the skull SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE fractionated radiation; skull base tumors; central-nervous-system tolerance; late radiation effects; proton therapy; 3D treatment planning ID RADIATION-THERAPY; WHITE MATTER; MR; FRACTIONATION; RADIOTHERAPY; LESIONS; INJURY; VOLUME AB Purpose: To determine the temporal lobe (TL) damage rate in 96 patients treated with high-dose proton and photon irradiation for chordomas and chondrosarcomas of the base of the skull. Methods and Materials: The records of 96 consecutive patients treated at Massachusetts General Hospital (MGH) and Harvard Cyclotron Laboratory (HCL) between June 1984 and 1993, for chordomas and chondrosarcomas of the base of the skull were reviewed. All the patients had undergone some degree of resection of the tumor prior to radiation therapy. Seventy-five patients were classified as "primary tumors" and 21 as recurrent or regrowing tumors after one or more surgical procedures. All the patients were randomized to receive 66.6 or 72 cobalt Gray equivalent (CGE) on a prospective dose-searching study by proton and photon irradiation (Radiation Therapy Oncology Group #85-26) with conventional fractionation (1.8 CGE/day, 5 fractions/week). All treatments were planned using the three-dimensional (3D) planning system developed at the Massachusetts General Hospital, and the dose was delivered using opposed lateral fields for the photon component and a noncoplanar isocentric technique for the proton component. Clinical symptoms of TL damage were classified into 4 grades. Computerized tomography (CT) and magnetic resonance imaging (MRI) scans were evaluated for white matter changes. Abnormalities associated with persistent or recurrent tumor were distinguished from radiation-induced changes. TLs were delineated on the original scans of the 10 patients with damage and those of a group of 33 patients with no clinical or MRI evidence of injury. Dose distributions were calculated and dose-volume histograms were obtained for these patients. Results: Of the patients, 10 developed TL damage, with bilateral injury in 2 and unilateral injury in 8. The cumulative TL damage incidence at 2 and 5 years was 7.6 and 13.2%, respectively. The MRI areas suggestive of TL damage were always separated from the tumor bed. Symptoms were severe to moderate in 8 patients. Several baseline factors, tumor- or host-related, were analyzed to evaluate their predictivity for TL damage: age, gender, tumor site, histology, type of presentation, type and number of surgical procedures, primary tumor volume, prescribed dose, normal tissue involvement, and volume of TL receiving doses ranging between 10 and 50 CGE or more. Only gender, in a univariate analysis (log rank) was a significant predictor of damage (0.0155), with male patients being at significantly higher risk of TL injury. In a stepwise Cox regression that included gender as a variable, no other baseline variable improved the prediction of damage. Conclusions: The 2- and 5-year cumulative TL damage rates were 7.6 and 13.2%, respectively. Despite the different TL damage rates related to age, tumor volume, number of surgical procedures prior to radiation therapy, and prescribed doses to the tumor, only gender was a significant predictor of damage (p = 0.0155) using a univariate (log rank) test. Chordomas and chondrosarcomas of the base of the skull may represent an interesting model to evaluate the TL damage rates because of their extradural origin, displacing the white matter instead of infiltrating it as gliomas do, because of their longer local recurrence-free survival other than gliomas and other brain tumors and because of the high doses of irradiation delivered to the target volume to obtain local control. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. Dr Daniel Den Hoed Canc Ctr, Rotterdam, Netherlands. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Santoni, R (reprint author), Policlin Careggi, Viale Morgagni 85, I-50134 Florence, Italy. NR 37 TC 61 Z9 62 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 1998 VL 41 IS 1 BP 59 EP 68 DI 10.1016/S0360-3016(98)00031-5 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA ZM005 UT WOS:000073495200010 PM 9588918 ER PT J AU Campbell, EG Louis, KS Blumenthal, D AF Campbell, EG Louis, KS Blumenthal, D TI Looking a gift horse in the mouth - Corporate gifts supporting life sciences research SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INDUSTRY AB Context.-Throughout the last decade a number of studies have been conducted to examine academic-industry research relationships. However, to our knowledge, no studies to date have empirically examined academic scientists' experience with research-related gifts from companies. Objective.-To examine the frequency, importance, and potential implications of research-related gifts from companies to academic life scientists. Design.-A mailed survey conducted in 1994 and 1995 of 3394 faculty who conduct life science research at the 50 universities that received the most research funding from the National Institutes of Health in 1993. Setting.-Research-intensive universities. Participants.-A total of 2167 of the 3394 faculty responded to the survey (response rate, 64%). Main Outcome Measures.-The percentage of faculty who received a research-related gift from a company in the last 3 years, the perceived importance of gifts to respondents' research, and what, if anything, the recipient thought the donor(s) expected in return for the gift. Results.-Forty-three percent of respondents received a research-related gift in the last 3 years independent of a grant or contract. The most frequently received gifts were biomaterials (24%), discretionary funds (15%), research equipment and trips to meetings (11% each), support for students (9%), and other research-related gifts (3%). Of those who received a gift, 66% reported the gift was important to their research, More than half of the recipients reported that donors expected the following in return for the gift: acknowledgment in publications (63%), that the gift not be passed on to a third party (60%), and that the gift be used only for the agreed-on purposes (59%). A total of 32% of recipients reported that the donor wanted prepublication review of any articles or reports stemming from the use of the gift, 30% indicated the company expected testing of their products, and 19% indicated that a donor expected ownership of all patentable results from the research in which a gift was used. However, what recipients thought donors expected differed by the type of gift received. Conclusions.-Research-related gifts are a common and important form of research support for academic life scientists. However, recipients frequently think that donors place restrictions and expect returns that may be problematic for recipients as well as institutions. C1 Massachusetts Gen Hosp, Hlth Policy Res & Dev Unit, Div Gen Internal Med, Boston, MA 02114 USA. Partners Healthcare Syst Inc, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Minnesota, Coll Educ & Human Dev, Minneapolis, MN USA. RP Campbell, EG (reprint author), Med Practices Evaluat Ctr, Hlth Policy Res & Dev Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHGRI NIH HHS [HG00724-01] NR 12 TC 79 Z9 81 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 1 PY 1998 VL 279 IS 13 BP 995 EP 999 DI 10.1001/jama.279.13.995 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA ZD283 UT WOS:000072669700026 PM 9533497 ER PT J AU Wold, C Seage, GR Lenderking, WR Mayer, KH Cai, B Heeren, T Goldstein, R AF Wold, C Seage, GR Lenderking, WR Mayer, KH Cai, B Heeren, T Goldstein, R TI Unsafe sex in men who have sex with both men and women SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE HIV; AIDS; bisexuals; heterosexuals; condoms ID BISEXUAL MEN; IDENTIFIED MEN; SAN-FRANCISCO; UNITED-STATES; CONDOM USE; ALCOHOLISM; BEHAVIOR; AIDS; GAY AB The sexual behaviors of bisexually active men, defined as men having sex with a man and a woman in previous 6 months, were compared with men who had sex with men only. Differential sexual practices associated with HIV risk between the two groups of men, as well as in the bisexual men with their male and female partners, were evaluated. Cross-sectional analyses were performed on baseline data from a prospective cohort of 508 young gay men recruited from bars, college campuses, and a health center in Boston from 1993 to 1994. Odds ratios (OR) and 95% confidence intervals (CI) were calculated on categorical variables, and McNemar's X-2 was used to compare the behaviors of bisexual men with their male versus female sex partners. Six months before the interview, 47 (10%) men had male and female sex partners, and 383 men had only male sex partners during the past year or ever. Fifty-eight percent of the men in the study had a female sexual partner in their lifetime, and 18% during the past year. Bisexual men were more likely to have drinking problems as identified by the Michigan Alcoholism Screening Test (MAST; OR = 3.96, 95% CI = 1.54-10.20), and fewer male partners over their lifetime (mean +/- standard deviation [SD], 24 +/- 42; median, 7; versus mean +/- SD, 69 +/- 516; median, 12), although this difference was not statistically significant. The two groups had similar levels of unprotected anal intercourse (25.5% versus 29.5%); however, bisexual men were half as likely to have anal sex as homosexual men (OR = 0.50; 95% CI = 0.27-0.93). Bisexual men were three times as likely to have unprotected sex with their female partner as their male partner (OR = 3.0; 95% CI = 1.02-8.8). Stratified analysis revealed similar discordant behavior while sober (OR = 4.0), drinking (OR = 7.0), and while drinking with concurrent drug use (OR = 8.0). Among this cohort of men who have sex with men (MSM), a sizable proportion also had vaginal sex with female partners in the previous 6 months. Bisexually active men were more likely to have unprotected sex with their female partners compared with their male partners, potentially increasing the risk for HIV and other sexually transmitted diseases. Behavioral interventions directed toward MSM need to address bisexual behaviors. C1 Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Boston Dept Hlth & Hosp, Inst Urban Hlth Policy & Res, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Massachusetts Gen Hosp, Sch Med, Cambridge, MA 02138 USA. Fenway Community Hlth Ctr, Boston, MA USA. Brown Univ, Sch Med, Providence, RI 02912 USA. RP Seage, GR (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 80 E Concorde St, Boston, MA 02118 USA. FU NIAAA NIH HHS [R01AA9320-02]; PHS HHS [U64-CCU108309-02] NR 19 TC 24 Z9 25 U1 4 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1998 VL 17 IS 4 BP 361 EP 367 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZC552 UT WOS:000072592000011 PM 9525438 ER PT J AU Seage, GR Mayer, KH Wold, C Lenderking, WR Goldstein, R Cai, B Gross, M Heeren, T Hingson, R AF Seage, GR Mayer, KH Wold, C Lenderking, WR Goldstein, R Cai, B Gross, M Heeren, T Hingson, R TI The social context of drinking, drug use, and unsafe sex in the Boston young men study SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES AND HUMAN RETROVIROLOGY LA English DT Article DE alcohol; drug use; unsafe sex; situational setting; homosexual men ID BISEXUAL MEN; UNPROTECTED INTERCOURSE; ALCOHOL-CONSUMPTION; RISK BEHAVIORS; HIV-INFECTION; EXPOSURE; HEALTH; STUDENTS; AIDS AB The objective of this study was to evaluate the relation between drinking, drug use, and unprotected anal intercourse in young men who have sex with men. A cross-sectional analysis of first-visit data from a prospective cohort of 508 young gay men recruited from 1993 through 1994 from bars, college campuses, and the Fenway Community Health Center in Boston was performed. The major outcome measures were any unprotected anal intercourse, after drinking and when sober, stratified by type of sexual partner (steady or nonsteady) during the previous 6 months and during the most recent sexual encounter. The average age of the cohort was 23.3 years; 77.6% were white, and 76.4% were in college. These young men had a median of 10.5 male sexual partners in their lifetimes, and 3 sexual partners in the previous 6 months before enrollment. One hundred and thirty-four (26%) reported unprotected anal intercourse during the previous 6 months. Individuals who had unprotected anal intercourse were more likely to have a drinking problem (odds ratio [OR] = 1.95; 95% confidence interval [CI] = 1.26-3.01) and drank more (20.4 ml/day versus 13.9 ml/day; p less than or equal to 0.01), compared with individuals who did not engage in unprotected anal intercourse. Overall, men were significantly less likely to have unprotected anal intercourse after alcohol or drug use, based on a series of paired analysis (OR = 0.27; 95% CI = 0.15-0.48). However, when we stratified by type of sexual partner, men were signifi cantly more likely to have unprotected anal intercourse with their nonsteady sexual partners after drinking than when sober (OR = 4.33; 95% CI = 1.37-13.7), but were significantly less likely to have unprotected anal intercourse with steady partners (OR = 0.27; 95% CI = 0.15-0.48). The patterns observed as already mentioned for drinking were also found for substance use in general. Men who were more likely to have unprotected anal intercourse after substance use were significantly more likely to have a drinking problem (OR = 7.65; 95% CI = 2.34-24.59). These results suggest that the role of alcohol and unsafe sex in young gay men is complex, with the role of situational factors of paramount importance. Alcohol and substance use interventions designed to reduce HIV risk need to specify the role of substance use in the sexual context to be successful. C1 Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Boston Dept Hlth & Hosp, Inst Urban Hlth Policy & Res, Boston, MA USA. ABT Associates Inc, Cambridge, MA USA. ABT Associates Inc, Bethesda, MD USA. Fenway Community Hlth Ctr, Boston, MA USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA. RP Seage, GR (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, 80 E Concord St, Boston, MA 02118 USA. FU NIAAA NIH HHS [R01AA9320-02]; PHS HHS [U64-CCU108309-02] NR 28 TC 57 Z9 58 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1077-9450 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. PD APR 1 PY 1998 VL 17 IS 4 BP 368 EP 375 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZC552 UT WOS:000072592000012 PM 9525439 ER PT J AU Shinar, AA Harris, WH AF Shinar, AA Harris, WH TI Cemented total hip arthroplasty following previous femoral osteotomy - An average 16-year follow-up study SO JOURNAL OF ARTHROPLASTY LA English DT Article DE femoral osteotomy; total hip arthroplasty; loosening; cemented arthroplasty ID REPLACEMENT; COMPONENT; FIXATION AB The indications for proximal femoral osteotomy would be substantially limited if it significantly compromised the outcome of a subsequent hip arthroplasty. Previous reports have followed only early cementing techniques over intermediate duration. This study comprised 22 primary cemented total hip arthroplasties performed by a single surgeon following failed proximal femoral osteotomies at an average follow-up period of 15.8 years. Three patients who died prior to the 11-year minimum follow-up period are not included, leaving 19 hips for long-term review. All seems were cemented with second-generation techniques. Stem placement and collar-calcar contact, however, were substantially worse compared with historical control subjects. Eight reconstructions required custom miniature or calcar replacement components, and in 6 hips, the stems were inserted only in the diaphysis. Two of 19 femoral components (10.5%) were revised for aseptic loosening and 2 additional femoral components were loose. The average Harris hip score of those not revised was 80.4. Five acetabular components (26.3%) required revision. Four additional cups were loose, yielding a total acetabular loosening rate of 47.4% at 15.5 years. Intertrochanteric osteotomy in general did not affect the expected excellent results of the femoral component using modern cementing techniques. Severe deformity following subtrochanteric osteotomy, however, did adversely affect the outcome. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Harris, WH (reprint author), Massachusetts Gen Hosp, Orthopaed Biomech Lab, GrJ 1126,32 Fruit St, Boston, MA 02114 USA. NR 28 TC 27 Z9 29 U1 1 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD APR PY 1998 VL 13 IS 3 BP 243 EP 253 DI 10.1016/S0883-5403(98)90168-1 PG 11 WC Orthopedics SC Orthopedics GA ZK133 UT WOS:000073288600001 PM 9590634 ER PT J AU Levine, JS Koh, JS Hartwell, D Beller, DI AF Levine, JS Koh, JS Hartwell, D Beller, DI TI Adhesion elicits an intrinsic defect in interleukin-1 expression by macrophages from autoimmune-prone MRL mice SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE adhesion; autoimmunity; interleukin 1; macrophages; systemic lupus erythematosus ID SYSTEMIC LUPUS-ERYTHEMATOSUS; NECROSIS FACTOR-ALPHA; SIGNAL-TRANSDUCTION; TYROSINE PHOSPHORYLATION; GENE INDUCTION; ADHERENCE; INTEGRINS; PATHWAY; MODELS; RNA AB Macrophages (m phi) from prediseased autoimmune-prone MRL/+ and MRL/lpr mice have a marked defect in endotoxin (LPS)-induced expression of several cytokines including interleukin 1 (IL-1). The progressive nature of this defect over time suggests that it may develop in response to specific extracellular stimuli. In this report, we show that adhesion is an essential factor for the development of aberrant IL-1 expression by m phi from autoimmune-prone MRL mice. Thus, when MRL/+ m phi were allowed to adhere before being stimulated with LPS, they demonstrated a striking defect in expression of both IL-1 message and protein in comparison with multiple normal strains. In marked contrast, when MRL/+ m phi were maintained in a non-adherent state by culture on agarose, the IL-1 defect was not evident and IL-1 expression was restored to nearly normal levels. Since an identical defect in IL-1 expression was found when MRL/+ m phi were cultured on a variety of extracellular matrix proteins (including laminin, fibronectin, type I collagen, and type IV collagen), it appears that IL-1 underexpression is dependent on the adhesive state per se rather than on engagement of any one specific adhesion receptor. Moreover, the cytoskeletal inhibitor cytochalasin D had no effect on the magnitude of the defect, indicating that the adhesion-dependent signaling events necessary to elicit IL-1 underexpression are independent of cytoskeletal rearrangement. Taken together, these results indicate that m phi from autoimmune prone MRL/+ mice have an adhesion-dependent signaling abnormality that leads to profound underexpression of the cytokine IL-1. (C) 1998 Academic Press Limited. C1 Boston Med Ctr, Dept Med, Renal Sect, Boston, MA 02118 USA. Boston Med Ctr, Dept Med, Rheumatol Sect, Boston, MA 02118 USA. Boston Med Ctr, Evans Dept Clin Res, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Levine, JS (reprint author), Boston Med Ctr, Dept Med, Renal Sect, Room E428,88 E Newton St, Boston, MA 02118 USA. EM jlevine@bu.edu FU NIAID NIH HHS [AI31418]; NIAMS NIH HHS [AR/AI42732] NR 27 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD APR PY 1998 VL 11 IS 2 BP 141 EP 150 DI 10.1006/jaut.1997.0182 PG 10 WC Immunology SC Immunology GA ZR290 UT WOS:000073959300005 PM 9650093 ER PT J AU Weaver, DR AF Weaver, DR TI The suprachiasmatic nucleus: A 25-year retrospective SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE suprachiasmatic nucleus; circadian rhythms; meeting report; historical article ID CIRCADIAN BEHAVIORAL RHYTHMS; N-ACETYLTRANSFERASE ACTIVITY; CLOCK MUTANTS; RETINOHYPOTHALAMIC PROJECTION; MESOCRICETUS-AURATUS; FUNCTIONAL-ACTIVITY; NEURAL TRANSPLANT; BIOLOGICAL CLOCK; VISUAL PATHWAYS; GOLDEN-HAMSTERS AB The suprachiasmatic nuclei (SCN) of the anterior hypothalamus contain the master circadian pacemaker in mammals. On the occasion of the 25th anniversary of the discovery of the SCN as the circadian clock, Charles A. Czeisler and Steven M. Reppert, organized a meeting to review milestones and recent developments in the study of the SCN, The discovery that the SCN contain tissue necessary for generation of circadian rhythmicity was established by lesion studies published in 1972. The second phase of study demonstrated unequivocally that the SCN contain an autonomous circadian pacemaker. The principal studies in this period showed the presence of metabolic and electrical activity rhythms in the SCN in vivo and progressed to studies showing that the SCN maintain rhythmicity in vitro, demonstrating that the transplanted SCN can restore circadian function following destruction of the host SCN and ultimately showing that single SCN "clock cells" exhibit independent rhythms in firing rate. The third phase of study, aimed at identifying the biochemical and molecular mechanisms responsible for rhythmicity within the SCN, has begun with the identification of circadian mutants (tau mutant hamsters and Clock mutant mice) and the isolation of the Clock gene. This report traces the important steps forward in our understanding of the suprachiasmatic circadian clock by recounting Be information presented at the SCN Silver Anniversary Celebration. C1 Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. RP Weaver, DR (reprint author), Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, GRJ 1226, Boston, MA 02114 USA. NR 78 TC 266 Z9 271 U1 4 U2 15 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD APR PY 1998 VL 13 IS 2 BP 100 EP 112 DI 10.1177/074873098128999952 PG 13 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA ZF023 UT WOS:000072855000002 PM 9554572 ER PT J AU Hopmeyer, J Wilkerson, PW Thorvig, KM Levine, RA Yoganathan, AP AF Hopmeyer, J Wilkerson, PW Thorvig, KM Levine, RA Yoganathan, AP TI Pulsatile flow computational simulations of mitral regurgitation SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID CONVERGENCE REGION; DOPPLER QUANTIFICATION; ORIFICE; VELOCITY; ACCELERATION; ULTRASOUND; CONSTRAINT; INVITRO; IMPACT; SIZE AB The noninvasive quantification of mitral regurgitation remains an important clinical goal. Recently, the flow convergence method was developed to estimate the regurgitant flow rate. This study used three-dimensional pulsatile computational simulations to evaluate the accuracy of the flow convergence method in the presence of complicating factors such as ventricular confinement, noncircular orifice shape, and the presence of aortic outflow. Results showed that in the absence of aortic outflow and ventricular confinement, there was a plateau zone where the calculated flow rate by the hemispheric formula approximated the true flow rate, independent of the orifice shape. In the presence of aortic outflow and in chambers of physiologic dimensions, there was no longer a clear zone where the hemispheric formula was valid. The hemi-elliptic modification of the flow convergence method worked in all cases, independent of the degree of ventricular confinement or the presence of aortic outflow. Therefore, application of the hemi-elliptic formula should be considered in future clinical studies. C1 Georgia Inst Technol, Sch Chem Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. Massachusetts Gen Hosp, Dept Med, Noninvas Cardiol Lab, Cambridge, MA 02000 USA. RP Hopmeyer, J (reprint author), Georgia Inst Technol, Sch Chem Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. FU NHLBI NIH HHS [HL 45485, HL 53702] NR 27 TC 2 Z9 2 U1 0 U2 0 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD APR PY 1998 VL 120 IS 2 BP 245 EP 254 DI 10.1115/1.2798308 PG 10 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA ZM104 UT WOS:000073505100010 PM 10412386 ER PT J AU Ring, D Jupiter, JB AF Ring, D Jupiter, JB TI Fracture-dislocation of the elbow SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID RADIAL HEAD FRACTURES; INTERNAL-FIXATION; REPLACEMENT; JOINT; STABILITY; ARTHROPLASTY; LIGAMENT; EXCISION C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 124 TC 94 Z9 110 U1 0 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 1998 VL 80A IS 4 BP 566 EP 580 PG 15 WC Orthopedics; Surgery SC Orthopedics; Surgery GA ZH688 UT WOS:000073137700014 PM 9563387 ER PT J AU Sharrock, WJ AF Sharrock, WJ TI Bone and the hematopoietic and immune systems: A report of the proceedings of a scientific workshop SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID A-INDUCED OSTEOPENIA; INTERFERON-GAMMA; MARROW CULTURES; STROMAL CELLS; IN-VIVO; MICE; OSTEOPOROSIS; OSTEOCLASTS; RESORPTION; PRECURSORS AB Recent observations underscore the linkage between endochondral bone formation and the establishment of hematopoietic marrow and suggest that interactions among bone, marrow, and the immune system persist in the mature skeleton. A workshop was held at the National Institutes of Health, Bethesda, Maryland, to discuss recent work on these interactions and to identify new areas of research. Marrow stromal cells include the precursors of the osteochondrogenic lineage, exert important influences on osteoclastogenesis and lymphopoiesis, and mediate the effects of some systemic factors on bone turnover. Recent evidence indicates that hematopoietic cells can influence the differentiation of osteogenic cells and suggests that mature lymphocytes can influence osteoclastic and osteoblastic functions. However, interpretation of experiments may be confounded by the potential for stage-specific responses within a cell lineage, the likelihood that divergent pathways compete for limited pools of precursor cells, and the possibility that important cells or factors are still unidentified. Further, in vitro models may be limited by species and anatomical site specificities, the absence of intermediary or accessory cells, and the absence of normal marrow spatial organization and cellular interactions with the extracellular matrix. Nevertheless, current approaches hold the potential for significant advances in our understanding of the relationships between bone and the hematopoietic and immune systems. Refinements of in vitro systems, the use of genetically manipulated mice, and the examination of clinical syndromes promise important insights. Collaborations among bone biologists, hematologists, and immunologists, and between basic scientists and clinical investigators, will be crucial for continued progress. C1 NIAMSD, Musculoskeletal Dis Branch, Extramural Program, NIH, Bethesda, MD 20892 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Yale Univ, New Haven, CT USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Univ Toronto, Toronto, ON, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Helen Hayes Hosp, W Haverstraw, NY USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. St Vincents Inst Med Res, Fitzroy, Vic 3065, Australia. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Washington Univ, St Louis, MO USA. Temple Univ, Sch Med, Philadelphia, PA 19122 USA. Merck Sharp & Dohme Res Labs, W Point, PA USA. Hanson Ctr Canc Res, Adelaide, SA, Australia. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. NCI, Frederick, MD 21701 USA. RP Sharrock, WJ (reprint author), NIAMSD, Musculoskeletal Dis Branch, Extramural Program, NIH, Natcher Bldg,Room 5A2-37A,45 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 30 Z9 32 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD APR PY 1998 VL 13 IS 4 BP 537 EP 543 DI 10.1359/jbmr.1998.13.4.537 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZE554 UT WOS:000072805200001 PM 9556053 ER PT J AU Damon, SE Haugk, KL Birnbaum, RS Quinn, LS AF Damon, SE Haugk, KL Birnbaum, RS Quinn, LS TI Retrovirally mediated overexpression of insulin-like growth factor binding protein 4: Evidence that insulin-like growth factor is required for skeletal muscle differentiation SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID FACTOR IGF BINDING; MYOBLAST DIFFERENTIATION; FACTOR-II; MYOGENIC DIFFERENTIATION; CELL-DIFFERENTIATION; PRIMARY CULTURES; GENE-EXPRESSION; FACTOR-BETA; PROLIFERATION; RECEPTOR AB Recent studies have indicated that the insulin-like growth factors (IGFs) stimulate skeletal myoblast proliferation and differentiation. However, the question of whether IGFs are required for myoblast differentiation has not been resolved. To address this issue directly, we used a retroviral vector (LBP4SN) to develop a subline of mouse C2 myoblasts (C2-BP4) that constitutively overexpress IGF binding protein-4 (IGFBP-4). A control C2 myoblast subline (C2-LNL6) was also developed by using the LNL6 control retroviral vector. C2-BP4 myoblasts expressed sixfold higher levels of IGFBP-4 protein than C2-LNL6 myoblasts. (125)I-IGF-I cross linking indicated that IGFBP-4 overexpression reduced IGF access to the type-1 IGF receptor tenfold. At low plating densities, myoblast proliferation was inhibited, and myoblast differentiation was abolished in C2-BP4 cultures compared with C2-LNL6 cultures. At high plating densities in which nuclear numbers were equal in the two sets of cultures, C2-BP4 myoblast differentiation was inhibited completely. Differentiation was restored in C2-BP4 cells by treatment with high levels of exogenous IGF-I or with des(1-3)IGF-I, an analog of IGF-I with reduced affinity for IGFBPs. These findings confirm the hypothesis that positive differentiation signals from the IGFs are necessary for C2 myoblast differentiation, and they suggest that the present model of myogenic differentiation, which involves only negative external control of differentiation by mitogens, may be incomplete. (C) 1998 Wiley-Liss, Inc. C1 VA Puget Sound Hlth Care Syst, Amer Lake Div, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Amer Lake Div, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. FU NICHD NIH HHS [N01-HD-6-2915] NR 66 TC 36 Z9 37 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 1998 VL 175 IS 1 BP 109 EP 120 DI 10.1002/(SICI)1097-4652(199804)175:1<109::AID-JCP12>3.0.CO;2-6 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA YZ345 UT WOS:000072245100012 PM 9491786 ER PT J AU Palmert, MR Radovick, S Boepple, PA AF Palmert, MR Radovick, S Boepple, PA TI The impact of reversible gonadal sex steroid suppression on serum leptin concentrations in children with central precocious puberty SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; BODY-MASS INDEX; LONG-ACTING ANALOG; NORMAL FEMALE MICE; PLASMA LEPTIN; OBESE GENE; NOCTURNAL RISE; TERM TREATMENT; EARLY-ONSET; GENDER AB Serum leptin concentrations increase during childhood in both sexes. During sexual maturation, levels rise further in girls, but decrease in boys. These data suggest that testosterone either directly suppresses leptin levels or induces changes in body composition that result in lower leptin concentrations. To examine further the relationship between sex steroids and leptin, we performed a longitudinal study in children with central precocious puberty (28 girls and 12 boys) before, during, and after discontinuation of GnRH agonist-induced pituitary-gonadal suppression. Nighttime and daytime leptin levels were measured to determine whether the activity of the pituitary-gonadal axis affects their diurnal variation. In the boys, suppression of testosterone increased leptin levels, whereas resumption of puberty was associated with decreased leptin levels [3.5 +/- 0.8 vs. 9.5 +/- 3.1 ng/dL (P = 0.005) and 12.2 +/- 4.5 us. 7.0 +/- 2.6 ng/dL (P = 0.012), respectively]. Serum leptin levels did not change in the girls with alteration of the pituitary-ovarian axis and consistently exceeded those in boys. Nighttime levels were consistently greater than daytime values by an average of 38.3% in the girls and 29.4% in the boys. These serial observations during reversible pituitary-gonadal suppression suggest that testosterone decreases leptin concentrations, but that estrogen, at least in this childhood model, has no discernible effect. In addition, our data indicate that the presence of the diurnal rhythm in leptin concentrations is independent of the state of the reproductive axis. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Unit, Boston, MA 02114 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Childrens Hosp, Dept Med, Div Endocrinol, Boston, MA 02115 USA. Harvard Univ, Clin Investigator Training Program, Beth Israel Deaconess Med Ctr, MIT Hlth Sci & Technol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pediat Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Boepple, PA (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 5,Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR-02172, RR-01066]; NICHD NIH HHS [HD-18169] NR 52 TC 63 Z9 64 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 1998 VL 83 IS 4 BP 1091 EP 1096 DI 10.1210/jc.83.4.1091 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZG029 UT WOS:000072957800010 PM 9543124 ER PT J AU Patti, ME Brambilla, E Luzi, L Landaker, EJ Kahn, CR AF Patti, ME Brambilla, E Luzi, L Landaker, EJ Kahn, CR TI Bidirectional modulation of insulin action by amino acids SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE insulin resistance; amino acids; ribosomal protein S6 kinase; 1-phosphatidylinositol 3-kinase; phosphoproteins/metabolism ID S6 PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE ACTIVITY; GLUCOSE-TRANSPORT; PHOSPHOENOLPYRUVATE CARBOXYKINASE; 3T3-L1 ADIPOCYTES; RAT HEPATOCYTES; PLASMA-MEMBRANE; MUSCLE CELLS; FATTY-ACIDS; WHOLE-BODY AB Amino acids have been shown to stimulate protein synthesis, inhibit proteolysis, and decrease whole-body and forearm glucose disposal, Using cultured hepatoma and myotube cells, we demonstrate that amino acids act as novel signaling elements in insulin target tissues. Exposure of cells to high physiologic concentrations of amino acids activates intermediates important in the initiation of protein synthesis, including p70 S6 kinase and PHAS-I, in synergy with insulin. This stimulatory effect is largely due to branched chain amino acids, particularly leucine, and can be reproduced by its transamination product, ketoisocaproic acid, Concurrently, amino acids inhibit early steps in insulin action critical for glucose transport and inhibition of gluconeogenesis, including decreased insulin-stimulated tyrosine phosphorylation of IRS-1 and IRS-2, decreased binding of grb 2 and the p85 subunit of phosphatidylinositol 3-kinase to IRS-1 and IRS-2, and a marked inhibition of insulin-stimulated phosphatidylinositol 3-kinase. Taken together, these data support the hypothesis that amino acids act as specific positive signals for maintenance of protein stores, while inhibiting other actions of insulin at multiple levels. This bidirectional modulation of insulin action indicates crosstalk between hormonal and nutritional signals and demonstrates a novel mechanism by which nutritional factors contribute to insulin resistance. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Div Diabet, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM kahnr@joslab.harvard.edu FU NIDDK NIH HHS [DK 33201, P30 DK46200] NR 62 TC 317 Z9 324 U1 7 U2 16 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR 1 PY 1998 VL 101 IS 7 BP 1519 EP 1529 DI 10.1172/JCI1326 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZF791 UT WOS:000072933600026 PM 9525995 ER PT J AU Fridkin, SK Yokoe, DS Whitney, CG Onderdonk, A Hooper, DC AF Fridkin, SK Yokoe, DS Whitney, CG Onderdonk, A Hooper, DC TI Epidemiology of a dominant clonal strain of vancomycin-resistant Enterococcus faecium at separate hospitals in Boston, Massachusetts SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AMPICILLIN-RESISTANT; OUTBREAK; BACTEREMIA; INFECTION; RISK; UNIT AB In 1996, the dominant (43%) strain of vancomycin-resistant enterococci (VRE; type A) at Massachusetts General Hospital was identified at Brigham and Women's Hospital (BWH). To characterize the epidemiology of infection with type A isolates of VRE at BWH, we collected demographic and clinical data for all patients from whom VRE were isolated from a clinical specimen through September 1996. The first clinical isolates from all BWH patients from whom VRE were isolated were typed by pulsed-field gel electrophoresis of SmaI digests of chromosomal DNA. Among patients hospitalized after the first patient at BWH infected with a type A isolate of VRE was identified, exposures were compared between patients who acquired type A isolates of VRE and those who acquired other types of VRE. Isolates from 99 patients identified to have acquired VRE were most commonly from blood (n = 27), urine (n = 19), or wounds (n = 19). Three months after the index patient arrived at BWH and at a time when greater than or equal to 12 types of strains of VRE were present, type A isolates of VRE became dominant; 39 of 75 (52%) of the study cohort had acquired type A isolates of VRE. We found no association between the acquisition of type A isolates of VRE and transfer from another institution or temporal overlap by service, ward, or floor with patients known to have acquired type A isolates of VRE. By multivariate analysis, only residence in the medical intensive care unit (adjusted odds ratio [OR], 3.2; 95% confidence interval [CI], 1.4 to 107) and the receipt of two or more antibiotics per patient-day (adjusted OR, 12.2; 95% CI, 1.2 to 9.0) were associated with the acquisition of strain A. This strain of VRE, dominant at two Boston hospitals, was associated with intensity of antibiotic exposures (i.e., two or more antibiotics per patient-day). We hypothesize that this strain may have unidentified properties providing a mechanism favoring its spread and dominance over other extant isolates, and further studies are needed to define these properties. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Ctr Dis Control & Prevent, Hosp Infect Program, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Atlanta, GA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. NR 21 TC 28 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1998 VL 36 IS 4 BP 965 EP 970 PG 6 WC Microbiology SC Microbiology GA ZC324 UT WOS:000072565800020 PM 9542917 ER PT J AU Caliendo, AM Hewitt, PL Allega, JM Keen, A Ruoff, KL Ferraro, MJ AF Caliendo, AM Hewitt, PL Allega, JM Keen, A Ruoff, KL Ferraro, MJ TI Performance of a PCR assay for detection of Pneumocystis carinii from respiratory specimens SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; INDUCED-SPUTUM; DIAGNOSIS; PNEUMONIA; INFECTION AB This study evaluates the performance of a PCR assay for the detection of Pneumocystis carinii from respiratory specimens that has been designed for use in the clinical microbiology laboratory. The test includes a simple method for nucleic acid extraction and amplification, a colorimetric probe hybridization technique for detection of amplicons, and an internal control to evaluate for the presence of inhibitors of amplification. Two hundred thirty-two clinical specimens (120 induced-sputum [IS] and 112 bronchoalveolar lavage [BAL] specimens) from 168 patients were tested by both immunofluorescent (direct fluorescent-antibody [DFA]) staining and PCR. Of the 112 BAL specimens, 17 were positive for P. carinii by DFA staining and PCR. An additional two specimens were DFA negative and PCR positive. For BAL specimens, the sensitivity and specificity of PCR compared to DFA were 100 and 98%, respectively. Eighteen IS specimens were positive for P. carinii by DFA, and 27 were positive by PCR. One of the 18 DFA-positive IS specimens was negative by PCR; this patient had just completed therapy for P. carinii pneumonia. Of the 10 specimens that were PCR positive and DFA negative, 4 were from patients who had a subsequent BAL specimen that was positive by DFA and PCR. For IS specimens, the sensitivity of DFA and PCR was 82 and 95%, respectively. The specificity of PCR for IS specimens was 94%. Due to the high sensitivity of PCR for the detection of P. carinii from IS specimens, a PCR-based diagnostic test may be a useful screening test and may alleviate the need for bronchoscopy in some patients. C1 Massachusetts Gen Hosp, Clin Microbiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Roche Mol Syst Inc, Branchburg, NJ 08876 USA. RP Caliendo, AM (reprint author), Massachusetts Gen Hosp, Clin Microbiol Lab, Gray B526, Boston, MA 02114 USA. NR 12 TC 38 Z9 42 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1998 VL 36 IS 4 BP 979 EP 982 PG 4 WC Microbiology SC Microbiology GA ZC324 UT WOS:000072565800023 PM 9542920 ER PT J AU Fletcher, JA AF Fletcher, JA TI Ewing's sarcoma oncogene structure: A novel prognostic marker? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID EWS/FLI-1 FUSION GENE; DNA-BINDING; TRANSCRIPTIONAL ACTIVATOR; CHROMOSOME-TRANSLOCATION; CHIMERIC TRANSCRIPTS; EWS GENE; FAMILY; TRANSFORMATION; PROTEIN; TUMORS C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Fletcher, JA (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 26 TC 10 Z9 10 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1241 EP 1243 PG 3 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700001 PM 9552020 ER PT J AU Nichols, CR Catalano, PJ Crawford, ED Vogelzang, NJ Einhorn, LH Loehrer, PJ AF Nichols, CR Catalano, PJ Crawford, ED Vogelzang, NJ Einhorn, LH Loehrer, PJ TI Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced-disseminated germ cell tumors: An eastern cooperative oncology group, southwest oncology group, and cancer and leukemia group B study SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 1995 CL LOS ANGELES, CALIFORNIA SP Amer Soc Clin Oncol ID PROGNOSTIC FACTORS; TESTICULAR CANCER; GROUP PROTOCOL; CHEMOTHERAPY; TRIAL AB Purpose: To compare standard therapy with bleomycin, etoposide, and cisplatin (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as primary treatment of men with advanced, disseminated germ cell tumors, Patients and Methods: A total of 304 men with advanced disseminated germ cell rumors were randomly allocated to receive four courses of BEP or VIP, Two hundred ninety-nine patients were assessable for toxicity and 286 were assessable for response, Complete response rates, favorable response (complete remission, surgical free of disease, continuous partial remission for 2+ years), time to treatment failure, and overall survival were assessed, Results: Overall complete remission rate (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%) were not significantly different between the two treatments, Grade 3 or worse toxicity, particularly hematologic and genitourinary toxicity, was significantly more common in patients who received VIP, Conclusion: BEP and VIP produce comparable favorable response rare and survival in patients with poor-risk germ cell tumors, The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity, Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors. (C) 1998 by American Society of Clinical Oncology. C1 Indiana Univ, Sch Med, Div Hematol Oncol, Med Ctr, Indianapolis, IN 46202 USA. Indianapolis Vet Adm Hosp, Indianapolis, IN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado, Denver, CO 80202 USA. Univ Chicago, Chicago, IL 60637 USA. RP Nichols, CR (reprint author), Indiana Univ, Sch Med, Div Hematol Oncol, Med Ctr, Room 473,535 Barnhill Dr, Indianapolis, IN 46202 USA. EM craig_nichols@iucc.iupui.edu FU NCI NIH HHS [CA49883, CA23318, CA42777] NR 15 TC 161 Z9 163 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1287 EP 1293 PG 7 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700008 PM 9552027 ER PT J AU Colevas, AD Busse, PM Norris, CM Fried, M Tishler, RB Poulin, M Fabian, RL Fitzgerald, TJ Dreyfuss, A Peters, ES Adak, S Costello, R Barton, JJ Posner, MR AF Colevas, AD Busse, PM Norris, CM Fried, M Tishler, RB Poulin, M Fabian, RL Fitzgerald, TJ Dreyfuss, A Peters, ES Adak, S Costello, R Barton, JJ Posner, MR TI Induction chemotherapy with docetaxel, cisplatin, fluorouracil, and leucovorin for squamous cell carcinoma of the head and neck: A phase I/II trial SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LOCALLY ADVANCED HEAD; RANDOMIZED TRIAL; ALTERNATING CHEMOTHERAPY; LARYNX PRESERVATION; CONTINUOUS-INFUSION; III TRIAL; STAGE-III; CANCER; RADIOTHERAPY; RADIATION AB Purpose: A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-FU), and leucovorin (TPFL5) induction chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Twenty-three previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status less than or equal to 2 were treated with TPFL5. Postchemotherapy home support included intravenous fluids, prophytactic antibiotics, and granulocyte colony-stimulating factor (G-CSF). Docetaxel dose was escalated to determine the maximum-tolerated dose (MTD). Fifteen patients were treated with three cycles of TPFLS at MTD. patients who achieved either a partial response (PR) or complete response (CR) to three cycles of TPFL5 then received definitive twice-daily radiation therapy. Toxicity and clinical and pathologic response to TPFL5 were assessed. Results: Twenty-three patients received a total of 69 cycles of TPFL5. The MTD was determined to be docetaxel 60 mg/m(2). Dose-limiting toxicity (DLT) was neutropenia. Additional significant toxicities at MTD were nausea, mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The overall response rate to TPFL5 was 100%, which included 14 of 23 (61%) clinical CRs and nine of 23 (39%) clinical PRs. primary-site clinical and pathologic CR rates were 19 of 22 (86%) CRs and 20 of 22 (91%) CRs, respectively. Fight patients had less than a CR in the neck to chemotherapy and, therefore, had postradiation neck dissections, four of which were positive for residual tumor. Conclusion: TPFL5 is a tolerable induction regimen in patients with good performance status. The DLT is neutropenia with significant mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The high response rates to TPFL5 justify further evaluation of this combination of agents in the context of formal clinical trials. (C) 1998 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Oral Med & Dent, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy & Otolaryngol, Boston, MA USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. RP Colevas, AD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St, Boston, MA 02115 USA. EM alexander_colevas@dfci.harvard.edu OI /0000-0003-4928-6532 NR 39 TC 87 Z9 89 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1331 EP 1339 PG 9 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700015 PM 9552034 ER PT J AU Goldhirsch, A Coates, AS Colleoni, M Castiglione-Gertsch, M Gelber, RD AF Goldhirsch, A Coates, AS Colleoni, M Castiglione-Gertsch, M Gelber, RD CA Int Breast Canc Study Grp TI Adjuvant chemoendocrine therapy in postmenopausal breast cancer: Cyclophosphamide, methotrexate, and fluorouracil dose and schedule may make a difference SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTRAVENOUS CMF; FOLLOW-UP; CHEMOTHERAPY; TAMOXIFEN; TRIAL AB Purpose: Adjuvant cytotoxics prolong disease-free survival (DFS) and overall survival (OS) in patients with operable breast cancer. The first reported effective adjuvant combination regimen consisted of oral cyclophosphamide on days 1 to 14 with intravenous methotrexate and fluorouracil on days 1 and 8, repeated every 28 days (classical CMF). These drugs have since been extensively used with or without endocrine therapies and/or other cytotoxic agents. Although doses and schedules have varied widely, the combination of these three drugs is generically referred to as CMF. Results: Reducing the dose and/or altering the schedule of CMF have compromised its efficacy in metastatic breast cancer. Reduction below standard dose of a similar regimen also gave inferior results in the adjuvant setting. Conclusion: Details of dose and schedule may therefore explain part of the heterogeneity of results observed with CMF. Particular controversy surrounds the contribution of CMF in postmenopausal women who are also receiving tamoxifen (TAM). However, the trials that demonstrated a significant benefit for the addition of CMF to TAM, even in postmenopausal women with estrogen receptor-positive tumors, used classical CMF. Therefore, adherence to the classical dose and schedule is recommended when CMF is used in adjuvant therapy. (C) 1998 by American Society of Clinical Oncology. C1 European Inst Oncol, Dept Med & Radiat Oncol, Int Breast Canc Study Grp, Dept Med & Radiat Oncol, I-20141 Milan, Italy. Int Breast Canc Study Grp Coordinat Ctr, Bern, Switzerland. Univ Sydney, Royal Prince Alfred Hosp, Dept Med, Australian New Zealand Breast Canc Trials Grp, Sydney, NSW 2006, Australia. Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn, Boston, MA USA. RP Goldhirsch, A (reprint author), European Inst Oncol, Dept Med & Radiat Oncol, Int Breast Canc Study Grp, Dept Med & Radiat Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM agoldhirsch@sakk.ch FU NCI NIH HHS [CA-75362] NR 24 TC 50 Z9 51 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1358 EP 1362 PG 5 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700018 PM 9552037 ER PT J AU Nixon, AJ Manola, J Gelman, R Bornstein, B Abner, A Hetelekidis, S Recht, A Harris, JR AF Nixon, AJ Manola, J Gelman, R Bornstein, B Abner, A Hetelekidis, S Recht, A Harris, JR TI No long-term increase in cardiac-related mortality after breast-conserving surgery and radiation therapy using modern techniques SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 26-30, 1996 CL LOS ANGELES, CALIFORNIA SP Amer Soc Therapeut Radiol & Oncol ID POSTOPERATIVE RADIOTHERAPY; CANCER PATIENTS; TRIAL AB Purpose: To determine whether left-breast irradiation using modern techniques after breast-conserving surgery leads to an increased risk of cardiac-related mortality. Methods: Between 1968 and 1986, 1,624 patients were treated for unilateral stage I or II breast cancer at the Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA, with conservative surgery and breast irradiation. Seven hundred forty-five patients with a potential follow-up of at least 12 years were analyzed. Clinical, pathologic, and treatment characteristics were compared between the 365 patients (49%) who received left-sided irradiation and the 380 patients (51%) who received right-sided irradiation. The relationship between left-sided breast irradiation and the risk of nonbreast cancer-and cardiac-related mortality was examined. Results: There was no significant difference in the distribution of clinical, pathologic, or treatment characteristics between the two groups, with the exception of a small difference in pathologic tumor size (medians, left, 2.0 cm, right, 1.5 cm; P = .007). At 12 years, a majority of patients still were alive. Slightly more patients with left-sided tumors had died of breast cancer (31% v 27%; P = NS). Equivalent proportions from each group died of nonbreast cancer causes (11%), including nine patients (2%) from each group who died from cardiac causes. The risk of cardiac mortality did not increase as time after treatment increased for patients who received left-sided irradiation compared with right-sided irradiation, A model that controlled for clinical, pathologic, and treatment differences showed no significant increase in any category of cause of death (breast, cardiac, or other) for patients who received left-sided irradiation. Conclusion: These results suggest that modern breast radiotherapy is not associated with an increased risk of cardiac-related mortality within at least the first 12 years after treatment. (C) 1998 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Med, Dept Radiat Oncol, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Biostat, Boston, MA 02215 USA. RP Nixon, AJ (reprint author), Harvard Univ, Sch Med, Dept Radiat Oncol, Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. EM anixon@bidmc.harvard.edu NR 17 TC 121 Z9 123 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1374 EP 1379 PG 6 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700021 PM 9552040 ER PT J AU Lindley, C Vasa, S Sawyer, WT Winer, EP AF Lindley, C Vasa, S Sawyer, WT Winer, EP TI Quality of life and preferences for treatment following systemic adjuvant therapy for early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID AXILLARY DISSECTION; OF-LIFE; CHEMOTHERAPY; MASTECTOMY; IMPACT; CARCINOMA; WOMEN AB Purpose: To evaluate the quality of life (QOL) of breast cancer patients who survived 2 to 5 years following initiation of adjuvant cytotoxic and/or hormonal therapy and to characterize relationships between QOL and patient physical symptoms, sexual function, and preferences regarding adjuvant treatment. Patients and Methods: Eighty-six patients who had completed systemic adjuvant therapy for early-stage breast cancer between 1988 and 1991 were surveyed by written questionnaire and telephone interview. Sociodemographic information was obtained for each patient, and patients were asked to complete the Functional Living Index-Cancer (FLIC), the Symptom Distress Scale (SDS), the Medical Outcomes Study (MOS) Short Form 36 (SF-36), a series of questions regarding sexual function, and a survey about preferences for adjuvant therapy in relation to possible benefit. Results: The mean FLIC score among all patients was 138.3 (+/- 12.2), which suggests a high level of QOL. The reported frequency of moderate to severe symptoms was generally low (ie, < 15%), with fatigue (31.4%), insomnia (23.3%), and local numbness at the site of surgery (22.1%) occurring with greatest frequency patients reported a wide range of sexual difficulties. Preference assessment showed that more than 65% of patients were willing to undergo 6 months of chemotherapy for a 5% increase in likelihood of cancer cure. Conclusion: Self-rated QOL in breast cancer patients 2 to 5 years following adjuvant therapy was generally favorable. Less than one third of patients reported moderate to severe symptoms. Selected aspects of sexual function appeared to be compromised, The majority of patients indicated a willingness to accept 6 months of chemotherapy for small to modest potential benefit. (C) 1998 by American Society of Clinical Oncology. C1 Univ N Carolina, Sch Pharm & Med, Chapel Hill, NC 27599 USA. Dana Farber Canc Inst, Breast Oncol Ctr, Boston, MA 02115 USA. RP Lindley, C (reprint author), Univ N Carolina, Sch Pharm, Beard Hall,CB 7360, Chapel Hill, NC 27599 USA. EM CLindley.Pharmn@mhs.unc.edu NR 31 TC 173 Z9 175 U1 2 U2 10 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1380 EP 1387 PG 8 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700022 PM 9552041 ER PT J AU Glantz, MJ Cole, BF Recht, L Akerley, W Mills, P Saris, S Hochberg, F Calabresi, P Egorin, MJ AF Glantz, MJ Cole, BF Recht, L Akerley, W Mills, P Saris, S Hochberg, F Calabresi, P Egorin, MJ TI High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: Is intrathecal chemotherapy necessary? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NERVOUS-SYSTEM PHARMACOLOGY; CEREBROSPINAL-FLUID; MENINGEAL CARCINOMATOSIS; PROGNOSTIC FACTORS; INTRAVENTRICULAR METHOTREXATE; NEOPLASTIC MENINGITIS; CYTOSINE-ARABINOSIDE; CONSECUTIVE PATIENTS; OMMAYA RESERVOIRS; BREAST-CANCER AB Purpose: Standard treatments for neoplastic meningitis are only modestly effective and are associated with significant morbidity, Isolated reports suggest that concurrent systemic and intrathecal (IT) therapy may be more effective than IT therapy alone. We present our experience, which includes CSF and serum pharmacokinetic data, on the use of high-dose (HD) intravenous (IV) methotrexate (MTX) as the sole treatment for neoplastic meningitis. Patients and Methods: Sixteen patients with solid-tumor neoplastic meningitis received one to four courses (mean, 2.3 courses) of HD (8 g/m(2) over 4 hours) IV MTX and leucovorin rescue. Serum and CSF MTX concentrations were measured daily. Toxicity, response, and survival were retrospectively compared with a reference group of 15 patients treated with standard IT MTX during the same time interval. Results: Peak methotrexate concentrations ranged from 3.7 to 55 mu mol/L (mean, 17.1 mu mol/L) in CSF and 178 to 1,700 mu mol/L (mean, 779 mu mol/L) in serum, Cytotoxic CSF and serum MTX concentrations were maintained much longer than with IT dosing. Toxicity was minimal, Cytologic clearing was seen in 81% of patients compared with 60% of patients treated intrathecally (P = .3). Median survival in the HD IV MTX group was 13.8 months versus 2.3 months in the IT MTX group (P = .003). Conclusion: HD IV MTX is easily administered and well tolerated. This regimen achieves prolonged cytotoxic serum MTX concentrations and CSF concentrations at least comparable to those achieved with standard IT therapy. Cytologic clearing and survival may be superior in patients treated with HD IV MTX. Prospective studies and a reconsideration of the use of IT chemotherapy for patients with neoplastic meningitis are warranted. (C) 1998 by American Society of Clinical Oncology. C1 Brown Univ, Sch Med, Dept Med, Providence, RI 02912 USA. Brown Univ, Sch Med, Dept Community Hlth, Providence, RI 02912 USA. Brown Univ, Sch Med, Dept Neurosurg, Providence, RI 02912 USA. Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Univ Maryland, Ctr Canc, Div Dev Therapeut, Baltimore, MD 21201 USA. RP Glantz, MJ (reprint author), Mem Hosp, Dept Med, 111 Brewster St, Pawtucket, RI 02860 USA. EM mjg@brownvm.brown.edu NR 61 TC 138 Z9 142 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 1998 VL 16 IS 4 BP 1561 EP 1567 PG 7 WC Oncology SC Oncology GA ZF220 UT WOS:000072875700048 PM 9552066 ER PT J AU Sorkin, BC Niederman, R AF Sorkin, BC Niederman, R TI Short chain carboxylic acids decrease human gingival keratinocyte proliferation and increase apoptosis and necrosis SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE growth regulation; epithelium; keratinocytes; short chain carboxylic acids ID PERIODONTAL-DISEASE; EPITHELIAL-CELLS; CREVICULAR FLUID; BUTYRATE; ACTIVATION; INHIBITION; PROPIONATE; DIAGNOSIS; P53 AB Epithelia are key barriers to infections. In periodontal disease, the gingival sulcular epithelium becomes ulcerated. In this report, we test the hypothesis that short-chain carboxylic acids (SCCA) inhibit keratinocyte proliferation, increase necrosis and apoptosis, and may thus promote ulceration. SCCA produced by bacteria are present at millimolar concentrations in the periodontal pockets of subjects with periodontal disease. SCCA concentrations are higher in subjects with severe disease than in those with mild disease, and are not detectable in healthy subjects. Cell proliferation is critical for maintenance of epithelial barrier function. All SCCA tested, when neutralized, decreased epithelial cell proliferation (as measured by H-3-thymidine incorporation) in a dose-dependent manner. We found that epithelial cell viability decreased with increasing SCCA concentrations, accounting at least partly for the decreased H-3-thymidine incorporation. For all conditions we tested, SCCA-induced apoptosis preceded and exceeded necrosis. While the molecular mechanism(s) for these effects remain to be determined, the results indicate that SCCA derived from caries- or periodontal disease-associated bacteria could alter gingival barrier function. C1 Forsyth Dent Ctr, Dept Cytokine Biol, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Periodontol, Boston, MA 02115 USA. RP Sorkin, BC (reprint author), Forsyth Dent Ctr, Dept Cytokine Biol, 140 Fenway, Boston, MA 02115 USA. OI Sorkin, Barbara/0000-0001-8198-6921 FU NIDCR NIH HHS [DE11098, DE08415] NR 28 TC 17 Z9 18 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD APR PY 1998 VL 25 IS 4 BP 311 EP 315 DI 10.1111/j.1600-051X.1998.tb02446.x PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA ZE004 UT WOS:000072747300007 PM 9565282 ER PT J AU Conigliaro, J Lofgren, RP Hanusa, BH AF Conigliaro, J Lofgren, RP Hanusa, BH TI Screening for problem drinking - Impact on physician behavior and patient drinking habits SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE alcohol abuse; problem drinking; screening; brief interventions ID IDENTIFICATION TEST AUDIT; PRIMARY-CARE PATIENTS; ALCOHOL-USE; BRIEF INTERVENTIONS; CAGE QUESTIONNAIRE; PROBLEM DRINKERS; SUBSTANCE ABUSE; UNITED-STATES; PREVALENCE; DISORDERS AB OBJECTIVE: To assess the effect of a screen for problem drinking on medical residents and their patients. DESIGN: Descriptive cohort study. SETTING: Veterans Affairs Medical Clinic. PATIENTS: Patients were screened 2 weeks before a scheduled visit (n = 714). Physicians were informed if their patients scored positive. MEASUREMENTS AND MAIN RESULTS: Physician discussion of alcohol use was documented through patient interview and chart review. Self-reported alcohol consumption was recorded. Of 236 current drinkers, 28% were positive for problem drinking by the Alcohol Use Disorders Identification Test (AUDIT). Of 58 positive patients contacted at 1 month, 78% recalled a discussion about alcohol use, 58% were advised to decrease drinking, and 9% were referred for treatment. In 57 positive patient charts, alcohol use was noted in 33 (58%), and a recommendation in 14 (25%). Newly identified patients had fewer notations than patients with prior alcohol problems. Overall, 6-month alcohol consumption decreased in both AUDIT-positive and AUDIT-negative patients. The proportion of positive patients who consumed more than 16 drinks per week (problem drinking) decreased from 58% to 49%. Problem drinking at 6 months was independent of physician discussion or chart notation. CONCLUSIONS: Resident physicians discussed alcohol use in a majority of patients who screened positive for alcohol problems but less often offered specific advice or treatment. Furthermore, residents were less likely to note concerns about alcohol use in charts of patients newly identified. Finally, a screen for alcohol abuse may influence patient consumption. C1 VA Pittsburgh Hlth Care Syst, Gen Internal Med Sect, Pittsburgh, PA USA. RP Conigliaro, J (reprint author), VA Pittsburgh Hlth Care Syst 11A, Sect Gen Med, Univ Dr C, Pittsburgh, PA 15240 USA. NR 33 TC 27 Z9 28 U1 3 U2 3 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 1998 VL 13 IS 4 BP 251 EP 256 DI 10.1046/j.1525-1497.1998.00075.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA ZF826 UT WOS:000072937100005 PM 9565388 ER PT J AU Conde, MV Williams, JW Mulrow, CD AF Conde, MV Williams, JW Mulrow, CD TI Targeting depression interviewing - An exercise in diagnostic reasoning SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article ID NATIONAL-COMORBIDITY-SURVEY; MAJOR DEPRESSION; UNITED-STATES; PREVALENCE; DISORDERS C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. RP Conde, MV (reprint author), Audie L Murphy Mem Vet Hosp, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. RI Williams, Jr., John/A-3696-2008 OI Williams, Jr., John/0000-0002-5267-5558 NR 10 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 1998 VL 13 IS 4 BP 262 EP 265 DI 10.1046/j.1525-1497.1998.00077.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA ZF826 UT WOS:000072937100007 PM 9565390 ER PT J AU Webb, IJ Beach, M Daley, JF Schott, DM Anderson, KC AF Webb, IJ Beach, M Daley, JF Schott, DM Anderson, KC TI Sequential CD34+ and CD4+ cell selection from leukapheresis components SO JOURNAL OF HEMATOTHERAPY LA English DT Article ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST DISEASE; BLOOD STEM-CELLS; ALLOGENEIC MARROW; LYMPHOCYTES-T; DEPLETION; LEUKEMIA; PREVENTION AB We tested the feasibility of sequential selection of CD34+ and CD4+ cell-enriched fractions from aliquots of five autologous leukapheresis components. CD34+ cells were seleced from a median 8.0 x 10(8) mononuclear cells using the CellPro CEPRATE LC cell separation system, All cells in the CD34-depleted fraction (median 4.8 x 10(8), range 0.6-10.0 x 10(8)) were then incubated with the appropriate antibodies for CD4+ cell selection and passed through a second LC column, Median target cell purities of the CD34+ cell-enriched fraction and CD4+ cell-enriched fraction were 90.5% and 86.0%, respectively, This study demonstrates that high purity CD34+ and CD4+ cell-enriched fractions can be isolated sequentially from leukapheresis components. In addition, CD8+ lymphocytes, implicated in graft-versus-host disease, were depleted in the course of both positive selection procedures, This approach could decrease the number of donor procedures by providing separate CD34+-enriched and CD4+-enriched populations for allogeneic peripheral blood progenitor cell transplantation and subsequent donor lymphocyte infusion from the same leukapheresis component. C1 Dana Farber Canc Inst, Cell Manipulat Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Gene Transfer Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Cryopreservat Lab, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Webb, IJ (reprint author), Dana Farber Canc Inst, Cell Manipulat Lab, 44 Binney St,Dana 530, Boston, MA 02115 USA. NR 14 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1061-6128 J9 J HEMATOTHER JI J. Hematother. PD APR PY 1998 VL 7 IS 2 BP 169 EP 174 DI 10.1089/scd.1.1998.7.169 PG 6 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA ZL514 UT WOS:000073441200009 PM 9597574 ER PT J AU Stack, AM Malley, R Thompson, CM Kobzik, L Siber, GR Saladino, RA AF Stack, AM Malley, R Thompson, CM Kobzik, L Siber, GR Saladino, RA TI Minimum protective serum concentrations of pneumococcal anti-capsular antibodies in infant rats SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the Society-for-Pediatric-Research CY MAY 02-06, 1997 CL WASHINGTON, D.C. SP Soc Pediat Res ID MEMBRANE PROTEIN COMPLEX; CONJUGATE VACCINE; POLYSACCHARIDE VACCINE; DISEASE; IMMUNOGENICITY; EPIDEMIOLOGY; EFFICACY; CHILDREN; TRIAL AB Infant rats were passively immunized to determine the protective capacity of pneumococcal anticapsular antibodies. Animal-passaged strains of Streptococcus pneumoniae serotypes 1, 4, 5, 6b, 7f, 9v, 14, 18c, 19f, and 23f were used as challenge inocula (1-1500 cfu) in a model of pulmonary infection that resulted in bacteremia, meningitis, and death. From untreated control animals, histologic sections of lung demonstrated infiltrative pneumonia and lung homogenate cultures grew S. pneumoniae at concentrations of 10(3)-10(8) cfu per gram of lung tissue. A type-specific anti-capsular antibody serum concentration of 0.1-1.15 mu g/mL resulted in a statistically significant reduction in mortality compared with the reduction in untreated controls, except for serotype 14, which required 2.32 mu ug/mL for a significant reduction in mortality. The serum antibody level that provided 50% reduction in mortality ranged from 0.1-3.5 mu ug/mL for all serotypes. C1 Childrens Hosp, Div Emergency Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Infect Dis Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Saladino, RA (reprint author), Childrens Hosp, Div Emergency Med, Dept Med, 300 Longwood Ave, Boston, MA 02115 USA. NR 20 TC 27 Z9 28 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1998 VL 177 IS 4 BP 986 EP 990 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZD747 UT WOS:000072719400020 PM 9534972 ER PT J AU Kjelsberg, MA Seifert, P Edelman, ER Rogers, C AF Kjelsberg, MA Seifert, P Edelman, ER Rogers, C TI Design-dependent variations in coronary stent stenosis measured as precisely by angiography as by histology SO JOURNAL OF INVASIVE CARDIOLOGY LA English DT Article DE in-stent stenosis; stent recoil; acute luminal gain ID MUSCLE CELL-PROLIFERATION; BALLOON ANGIOPLASTY; PREVENT RESTENOSIS; FEMORAL ARTERIES; CONTROLLED TRIAL; HEPARIN; MODEL; IMPLANTATION; ATHERECTOMY; VALIDATION AB Background. Coronary stent restenosis is a growing clinical concern which, because restenosis may vary with stent design, requires a validated, accurate, and sensitive method of evaluation as new stents are developed. Histologic analysis of arterial cross sections, a highly accurate tool in animal models, has limited applicability in humans. Quantitative coronary angiography, while commonly used in the clinical evaluation of coronary interventions, has a controversial role as an adequate measure of restenosis, and few studies have validated quantitative angiography in diseased arteries. We tested the hypothesis that in-stent stenosis could be assessed as accurately by pre-mortem angiography as by post-mortem histology, allowing angiographic discrimination of variable late luminal loss provoked by stents of different designs. Methods and Results. Stent stenosis in porcine coronary arteries was assessed by quantitative coronary angiography and histology at 3, 28 and 56 days. Four stainless steel stent designs were studied: a slotted tube configuration with or without a polymer wrap and a corrugated ring configuration with or without a polymer coating. Although acute luminal gain (mean stent:artery ratio 1.07 +/- 0.01) and stent recoil (mean stent diameter at follow-up 2.65 +/- 0.02 mm) were similar for all designs and time points, significant differences in late luminal loss were observed and were detected as accurately by angiography as by histology. At 28 days, the polymer wrapped slotted tube design resulted in a nearly two-fold greater late loss than its bare metal counterpart (1.40 +/- 0.09 mm vs. 0.80 +/- 0.12 mm, p < .001 by angiography; 1.33 +/- 0.10 mm vs. 0.67 +/- 0.06 mm, p < .0001 by histology), while there was no significant difference in 28 day late loss between the polymer coated and bare metal corrugated ring designs (p = NS by angiography or histology). Time point differences were also observed both angiographically and histologically, with marked progression of lumen loss between 3 and 28 days and slower but persistent progression between 28 and 56 days. Overall comparison of individual lumen diameter measurements for all stented arteries independent of design or duration of follow-up demonstrated a precise correlation between angiography and histology Cy = 0.96x +0.25, p < .0001, r(2) = 0.82). Conclusions. Coronary stents of varied designs provoke markedly different degrees of late luminal loss, and these differences can be measured as accurately by quantitative angiography as by histologic analysis of arterial cross sections. This may be due to optimization of angiographic measurements by the concentric nature of intimal thickening in stented arteries, and to structural rigidity imparted by the stent, preserving arterial lumen size for histologic analysis. Quantitative angiography, therefore, may represent an adequate endpoint in clinical trials comparing stent designs. C1 Harvard Univ, Div Cardiovasc, Sch Med,Brigham & Womens Hosp, Dept Med,Cardiac Catheterizat Lab, Boston, MA 02115 USA. RP Kjelsberg, MA (reprint author), Harvard Univ, Div Cardiovasc, Sch Med,Brigham & Womens Hosp, Dept Med,Cardiac Catheterizat Lab, 75 Francis St, Boston, MA 02115 USA. EM mkjelsberg@bics.bwh.harvard.edu NR 41 TC 4 Z9 4 U1 0 U2 1 PU HEALTH MANAGEMENT PUBLICATIONSINC PI WAYNE PA 950 WEST VALLEY RD, STE 2800, WAYNE, PA 19087 USA SN 1042-3931 J9 J INVASIVE CARDIOL JI J. Invasive Cardiol. PD APR PY 1998 VL 10 IS 3 BP 142 EP 150 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZJ185 UT WOS:000073188000003 ER PT J AU Calautti, E Cabodi, S Kedersha, N Dotto, GP AF Calautti, E Cabodi, S Kedersha, N Dotto, GP TI Tyrosine phosphorylation and Src family kinases control keratinocyte cell-cell adhesion SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 481 EP 481 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200080 ER PT J AU Maytin, EV Lin, JC Habener, JF AF Maytin, EV Lin, JC Habener, JF TI The transcription factor C/EBP beta directs the expression of the keratin K10 gene in differentiating murine keratinocytes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 493 EP 493 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200157 ER PT J AU Prowse, D Lee, D Magro, C Baden, H Brissette, J AF Prowse, D Lee, D Magro, C Baden, H Brissette, J TI Ectopic Whn expression in transgenic mice causes developmental defects and epidermal hyperplasia. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 495 EP 495 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200166 ER PT J AU Kishimoto, J Ehama, R Jiang, N Burgeson, R AF Kishimoto, J Ehama, R Jiang, N Burgeson, R TI Human versican promoter-driven lacZ activity in transgenic mouse skin and hair dermal papilla. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 497 EP 497 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200178 ER PT J AU Kobayashi, T Kishimoto, J Ehama, R Hudson, D Burgeson, RE AF Kobayashi, T Kishimoto, J Ehama, R Hudson, D Burgeson, RE TI Expressions of matrix metalloproteinase (MMP)-9 and involucrin from keratinocytes are simultaneously induced by keratinocyte differentiating factor (KDF)-1 after the stimulation of high calcium concentration. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 497 EP 497 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200179 ER PT J AU Champliaud, MF Olson, PF Burgeson, RE Baden, HP AF Champliaud, MF Olson, PF Burgeson, RE Baden, HP TI Characterization of the protein structure of sciellin, a unique precursor of the cornified envelope of keratinizing tissues. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 505 EP 505 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200226 ER PT J AU Rheinwald, J Palanisamy, A Benwood, J Feldman, R Sauter, E AF Rheinwald, J Palanisamy, A Benwood, J Feldman, R Sauter, E TI Premalignant human keratinocytes exhibiting extended replicative lifespans and EGF-independence cultured from dysplastic oral epithelial lesions. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Div Dermatol, Sch Med, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 522 EP 522 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200330 ER PT J AU Nghiem, P Schreiber, SL AF Nghiem, P Schreiber, SL TI PIK-related kinases in the response to DNA damage by UV. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 524 EP 524 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200339 ER PT J AU Di Cunto, F Topley, G Calautti, E Hsiao, J Ong, L Seth, PK Dotto, GP AF Di Cunto, F Topley, G Calautti, E Hsiao, J Ong, L Seth, PK Dotto, GP TI Dual pattern of p21 regulation and function in primary keratinocyte differentiation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 538 EP 538 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200426 ER PT J AU Amano, S Nishiyama, T Kobayashi, T Burgeson, RE Nakayama, Y AF Amano, S Nishiyama, T Kobayashi, T Burgeson, RE Nakayama, Y TI Possible relationship between MMP-9 induction and increased release of laminin 5 in human keratinocytes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Shiseido Res Ctr, Yokohama, Kanagawa, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. RI Nishiyama, Toshio/C-5434-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 551 EP 551 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200502 ER PT J AU Lee, PK Sugerman, PB Qureshi, AA Kochevar, IE Lerner, EA AF Lee, PK Sugerman, PB Qureshi, AA Kochevar, IE Lerner, EA TI Ultraviolet B stimulates nitric oxide production in human keratinocytes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs,Dept Dermatol, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 553 EP 553 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200516 ER PT J AU Lee, PK Sugerman, PB Oureshi, AA Lerner, LH Lerner, EA AF Lee, PK Sugerman, PB Oureshi, AA Lerner, LH Lerner, EA TI Nitric oxide production and differential cellular localization of nitric oxide synthases in human keratinocytes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 554 EP 554 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200523 ER PT J AU Lerner, LH Qureshi, AA Lee, PK Lerner, EA AF Lerner, LH Qureshi, AA Lee, PK Lerner, EA TI Nitric oxide synthases in normal human skin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Cutaneous Biol Res Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 557 EP 557 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200538 ER PT J AU Gonzalez, S Rajadhyaksha, M Rubinstein, G White, WM Gonzalez, E Anderson, RR AF Gonzalez, S Rajadhyaksha, M Rubinstein, G White, WM Gonzalez, E Anderson, RR TI Non-invasive histologic characterization of skin diseases using in vivo confocal scanning laser microscopy. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dermatol Clin,Dept Dermatol, Boston, MA USA. Lucid Technol Inc, Henrietta, NY USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 580 EP 580 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200679 ER PT J AU Gonzalez, S Rubinstein, G White, WM Rajadhyaksha, M Anderson, RR AF Gonzalez, S Rubinstein, G White, WM Rajadhyaksha, M Anderson, RR TI Reactive confocal imaging of psoriasis in vivo. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Lucid Technol Inc, Henrietta, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 582 EP 582 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200686 ER PT J AU Gonzalez, S White, WM Rubinstein, G Rajadhyaksha, M Zavislan, J Fewkes, JL Anderson, RR AF Gonzalez, S White, WM Rubinstein, G Rajadhyaksha, M Zavislan, J Fewkes, JL Anderson, RR TI In vivo real-time confocal imaging of non-pigmented cutaneous neoplasms. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. Lucid Technol Inc, Henrietta, NY USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 583 EP 583 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200694 ER PT J AU White, WM Rajadhyaksha, M Gonzalez, S Fabian, RL Anderson, RR AF White, WM Rajadhyaksha, M Gonzalez, S Fabian, RL Anderson, RR TI Clinical, real-time confocal imaging of human oral mucosa in vivo. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Otolaringol Head & Neck Surg Serv, Boston, MA USA. Lucid Technol Inc, Henrietta, NY USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 588 EP 588 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200723 ER PT J AU Echtermeyer, F Baciu, PC Saoncella, S Goetinck, PF AF Echtermeyer, F Baciu, PC Saoncella, S Goetinck, PF TI The core protein, and not the glycosaminoglycan chains, of syndecan-4 determines the formation of actin stress fibers and focal adhesions in CHO cells. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 593 EP 593 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200757 ER PT J AU Gerecke, DR Champliaud, MF Kobayashi, T Burgeson, RE AF Gerecke, DR Champliaud, MF Kobayashi, T Burgeson, RE TI A novel 205-kDA antigen in the extracellular matrix of skin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 600 EP 600 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200796 ER PT J AU Wong, WR Kossodo, S Moran, M Kochevar, IE AF Wong, WR Kossodo, S Moran, M Kochevar, IE TI Cytokines differentially modulate matrix-metalloproteinase expression in three-dimensional collagen matrices. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 600 EP 600 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200798 ER PT J AU Tian, WD Gillies, R Kollias, N AF Tian, WD Gillies, R Kollias, N TI Endogenous fluorescence of collagen cross links is a marker for aging and a dosimeter for UV a radiation. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 601 EP 601 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200805 ER PT J AU Kishimoto, J Ehama, R Jiang, N Ge, Y Kobayashi, T Burgeson, R AF Kishimoto, J Ehama, R Jiang, N Ge, Y Kobayashi, T Burgeson, R TI Human vascular endothelial growth factor (VEGF) promoter-driven green fluorescent protein expression in transgenic mouse skin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 606 EP 606 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200830 ER PT J AU Romero, RA Gonzalez, S Maytin, EV AF Romero, RA Gonzalez, S Maytin, EV TI Transcription factor C/EBP beta in rhino mouse epidermis is upregulated by retinol but not retinoic acid. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med Endocrinol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 607 EP 607 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200840 ER PT J AU Kaya, G Rodriguez, I Jorcano, JL Vassalli, P Stamenkovic, I AF Kaya, G Rodriguez, I Jorcano, JL Vassalli, P Stamenkovic, I TI Cutaneous delayed-type hypersensitivity response is inhibited in transgenic mice with keratinocyte-specific CD44 expression defect. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Univ Hosp Geneva, Dept Dermatol, Geneva, Switzerland. Univ Hosp Geneva, DHURDV, Geneva, Switzerland. Univ Geneva, Med Ctr, Dept Pathol, CH-1211 Geneva, Switzerland. CIEMAT, Dept Cell & Mol Biol, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 608 EP 608 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200842 ER PT J AU Foitzik, K Paus, R Handjiski, B Doetschman, T Dotto, GP AF Foitzik, K Paus, R Handjiski, B Doetschman, T Dotto, GP TI Characterization of newborn skin and adult skin grafts from TGF-beta 2 knock-out mice. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Humboldt Univ, Dept Dermatol, Berlin, Germany. Univ Cincinnati, Dept Mol Genet, Cincinnati, OH USA. Univ Cincinnati, Dept Biochem, Cincinnati, OH USA. Univ Cincinnati, Dept Microbiol, Cincinnati, OH USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 626 EP 626 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200950 ER PT J AU Bhol, KC Rojas, AI Khan, IU Ahmed, AR AF Bhol, KC Rojas, AI Khan, IU Ahmed, AR TI Presence of IL 10 in the serum and blister fluid of patients with pemphigus vulgaris: Correlation of disease activity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Med Sch, Ctr Blood Res, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 662 EP 662 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738201170 ER PT J AU Kollias, N DaSilva, D Canfield, D AF Kollias, N DaSilva, D Canfield, D TI Fluorescence imaging excited in the visible is a powerful tool in the evaluation of non inflammatory acne. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA USA. Canfield Sci Inc, Fairfield, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 687 EP 687 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738201317 ER PT J AU Kossodo, S Wong, WR Moran, M Kocheyar, IE AF Kossodo, S Wong, WR Moran, M Kocheyar, IE TI Divergent basal and ultraviolet-induced expression of matrix-metalloproteinases in monolayers and collagen gels. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 692 EP 692 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738201351 ER PT J AU Gillies, R Kollias, N AF Gillies, R Kollias, N TI Evaluation of sunscreen-induced UVA photoprotection measured noninvasively in vivo on human skin. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 697 EP 697 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738201377 ER PT J AU Gonzalez, S Vibhaghool, B Sherwood, M Flotte, T Kollias, N AF Gonzalez, S Vibhaghool, B Sherwood, M Flotte, T Kollias, N TI The phototoxicity of photodynamic therapy may be selectively suppresses or enhanced by modulation of the cutaneous vasculature. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 697 EP 697 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738201379 ER PT J AU Doolittle, MH Ben-Zeev, O Briquet-Laugier, V AF Doolittle, MH Ben-Zeev, O Briquet-Laugier, V TI Enhanced detection of lipoprotein lipase by combining immunoprecipitation with Western blot analysis SO JOURNAL OF LIPID RESEARCH LA English DT Article DE affinity purified chicken anti-LPL antibody; chicken IgG Fab production; immunomatrix ID DROSOPHILA-MELANOGASTER CELLS; TRANSLOCATION; GLYCOSYLATION; PURIFICATION; EXPRESSION; DEFICIENT; PROMOTER; ENZYME AB This manuscript describes the problems inherent in combining immunoprecipitation of lipoprotein lipase (LPL) with its detection by Western blot, and how these problems can be circumvented by the preparation of suitable immunoreagents. These reagents used during the immunoprecipitation step, include Fab fragments of the primary antibody (chicken anti-bovine LPL), and a covalently linked immunomatrix of the secondary antibody (rabbit anti-chicken Igc). The use of these reagents in conjunction with Western blot detection virtually eliminates the problem of non-relevant protein detection when analyzing LPL from complex biological samples. Moreover, this approach can be adapted to detect any protein with the same inherent problems as LPL, such as hepatic lipase. C1 W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Doolittle, MH (reprint author), W Los Angeles Vet Affairs Med Ctr, Lipid Res Lab, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NHLBI NIH HHS [HL28481] NR 20 TC 10 Z9 10 U1 1 U2 1 PU LIPID RESEARCH INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 1998 VL 39 IS 4 BP 934 EP 942 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZF025 UT WOS:000072855200020 PM 9555956 ER PT J AU Knowlton, AA Kapadia, S Torre-Amione, G Durand, JB Bies, R Young, J Mann, DL AF Knowlton, AA Kapadia, S Torre-Amione, G Durand, JB Bies, R Young, J Mann, DL TI Differential expression of heat shock proteins in normal and failing human hearts SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE heat shock proteins; hsp27; hsp60; hsp70; hsp72; hsp90; cardiomyopathy; heart failure ID TUMOR-NECROSIS-FACTOR; INDUCED CELL-DEATH; DILATED CARDIOMYOPATHY; FACTOR RECEPTORS; STRESS PROTEIN; MESSENGER-RNA; APOPTOSIS; RABBIT; HSP70; GENE AB Background: heat shock proteins (hsp) constitute an endogenous stress response that protects cells from injury. Most work on these important proteins has focused on the immediate response to acute stress in cell culture systems and mammalian models of heart disease. Little is known about the expression of the hsps in human hearts. We were interested in whether there was increased expression of the hsps in heart failure, a setting of chronic, sustained stress. Five different hsps were examined: hsp27, hsp60, hsp72, hsc70 and hsp90. Methods and results: three groups of explanted hearts were studied: dilated cardiomyopathy (DCM), ischemic cardiomyopathy (IHD), and normal controls. Western-blotting with a standard curve of purified protein on each blot was used to quantify the expression of the hsps. Hsp27 was increased almost two-fold in DCM compared to normal hearts, and was significantly greater than in IHD hearts. Levels of hsp60 were doubled in both DCM and MD hearts (P<0.05). Hsp72, hsc70 and hsp90 were not significantly changed. Conclusions: this study shows for the first time that differential changes in hsp levels occur in end-stage heart failure. Since hsps can render cells resistant to apoptosis, and are associated with the mitochondria and the cytoskeleton, which are known to be abnormal in heart failure, these studies may lead to new insights into the pathogenesis of cardiac decompensation. (C) 1998 Academic Press Limited. C1 VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Cleveland Clin, Cleveland, OH 44106 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. RP Knowlton, AA (reprint author), VA Med Ctr, 151C,2002 Holcombe, Houston, TX 77030 USA. OI Mann, Douglas /0000-0002-2516-0145 FU NHLBI NIH HHS [HL92510] NR 45 TC 116 Z9 122 U1 1 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD APR PY 1998 VL 30 IS 4 BP 811 EP 818 DI 10.1006/jmcc.1998.0646 PG 8 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA ZK958 UT WOS:000073384700010 PM 9602430 ER PT J AU Sayers, ST Khan, N Ahmed, Y Shahid, R Khan, T AF Sayers, ST Khan, N Ahmed, Y Shahid, R Khan, T TI Preparation of brain-derived neurotrophic factor- and neurotrophin-3-secreting Schwann cells by infection with a retroviral vector SO JOURNAL OF MOLECULAR NEUROSCIENCE LA English DT Article DE gene therapy; brain-derived neurotrophic factor (BDNF); neurotrophin-3 (NT-3); retroviral vector; Schwann cells; spinal cord injury ID NERVE GROWTH-FACTOR; RAT SPINAL-CORD; FACTOR MESSENGER-RNA; HUMAN-GENE-THERAPY; MOLECULAR-CLONING; FACTOR FAMILY; AXONAL GROWTH; MOTOR NEURONS; EXPRESSION; BDNF AB One reason that the central, nervous system of adult mammals does not regenerate after injury is that neurotrophic factors are present only in low concentrations in these tissues. Recent studies have shown that the application of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) acts to encourage the regrowth of motor and sensory fibers after spinal cord injury. Other studies have reported that the regrowth of axons after injury was enhanced by the implantation of Schwann cells, which normally secrete BDNF and NTT-3. The purpose of the present study was to genetically modify Schwann cells to secrete increased amounts of BDNF or NT-3 by infection with a retroviral vector. Retroviral vectors were constructed by the Ligation of BDNF or NT-3 cDNA to the LXSN vector. Viruses were generated from the plasmid forms of the vectors by transient transfection of PA317 amphotrophic retroviral packaging cells. Viruses were harvested and used to infect the human Schwann cell line designated NF-1T. Northern blot analysis of poly (At) RNA prepared from Schwann cells that were infected with BDNF- or NT3-containing virus showed the presence of BDNF or NTT-3 mRNA. An enzyme-linked immunosorbent assay (ELISA) for BDNF and NT-3 was performed on media the cells were grown in, and on cellular extracts prepared from the BDNF- and NT3-infected Schwann cells. The ELISA results demonstrated that the Schwann cells were secreting increased levels of immunologically active BDNF or NT-3. Immunocytochemical staining of these cells revealed the presence of these two neurotrophic factors located in perinuclear granules. These neurotrophic factor-secreting Schwann cells are currently being evaluated for their efficacy in the treatment of spinal cord injury. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Rehabil Res & Dev Ctr, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Dept Neurol, Maywood, IL 60153 USA. RP Sayers, ST (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Rehabil Res & Dev Ctr, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. NR 58 TC 21 Z9 26 U1 0 U2 1 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0895-8696 J9 J MOL NEUROSCI JI J. Mol. Neurosci. PD APR PY 1998 VL 10 IS 2 BP 143 EP 160 DI 10.1007/BF02737125 PG 18 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 104BZ UT WOS:000074993500007 PM 9699155 ER PT J AU Coffey, BJ Miguel, EC Biederman, J Baer, L Rauch, SL O'Sullivan, RL Savage, CR Phillips, K Borgman, A Green-Leibovitz, MI Moore, E Park, KS Jenike, MA AF Coffey, BJ Miguel, EC Biederman, J Baer, L Rauch, SL O'Sullivan, RL Savage, CR Phillips, K Borgman, A Green-Leibovitz, MI Moore, E Park, KS Jenike, MA TI Tourette's disorder with and without obsessive-compulsive disorder in adults: Are they different? SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article ID ATTENTION-DEFICIT DISORDER; PSYCHIATRIC STATUS; BIPOLAR DISORDER; HYPERACTIVE BOYS; GENETIC-FACTORS; ADHD PROBANDS; COMORBIDITY; RELATIVES; BEHAVIOR; PSYCHOPATHOLOGY AB Clinical research has documented a bidirectional overlap between Tourette's disorder (TD) and obsessive-compulsive disorder (OCD) from familial-genetic, phenomenological, comorbidity, and natural history perspectives. Patients with Tourette's disorder plus obsessive-compulsive disorder (TD+OCD), a putative subtype, share features of both. The purpose of this exploratory study was to evaluate correlates of patients with TD, OCD, and TD+OCD to determine whether TD+OCD is a subtype of TD, OCD, or an additive form of both. Sixty-one subjects with TD, OCD, or TD+OCD were evaluated with the Structured Clinical Interview for DSM-III-R supplemented with additional modules. The three groups differed in the rates of bipolar disorder (p < .04), social phobia (p < .02), body dysmorphic disorder (p < .002), attention deficit hyperactivity disorder (p < .03), and substance use disorders (p < .04). These findings were accounted for by the elevated rates of the disorders in the TD+OCD group compared with the TD and OCD groups. These finding are most consistent with the hypothesis that TD+OCD is a more severe disorder than TD and OCD and may be more etiologically linked to TD than to OCD. These findings highlight the importance of assessment of the full spectrum of psychiatric comorbidity in patients with TD and OCD. C1 Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, Belmont, MA 02138 USA. Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02138 USA. Massachusetts Gen Hosp E, OCD Clin, Charlestown, MA 02129 USA. Massachusetts Gen Hosp E, Res Unit, Charlestown, MA 02129 USA. RP Coffey, BJ (reprint author), Massachusetts Gen Hosp, Joint Program Pediat Psychopharmacol, 115 Mill St,Recrat Bldg, Belmont, MA 02138 USA. RI Miguel, Euripedes/B-2871-2008 NR 48 TC 65 Z9 68 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 1998 VL 186 IS 4 BP 201 EP 206 DI 10.1097/00005053-199804000-00001 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZG798 UT WOS:000073040800001 PM 9569887 ER PT J AU Wei, ML Andreadis, A AF Wei, ML Andreadis, A TI Splicing of a regulated exon reveals additional complexity in the axonal microtubule-associated protein tau SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE microtubule-associated protein tau; expression pattern of regulated isoforms; cryptic sites; alternative splicing regulation ID PERIPHERAL NERVOUS-SYSTEM; NEUROBLASTOMA-CELLS; RNA; SEQUENCE; GENE; LOCALIZATION; SITE; HETEROGENEITY; DOMAINS; RECOGNITION AB Tau is a microtubule-associated protein whose transcript undergoes complex regulated splicing in the mammalian nervous system, Exon 6 of the gene is an alternatively spliced cassette whose expression pattern and splicing regulation had not been previously analyzed in the human. The expression profile of exon 6 is completely different from that of the better-analyzed exons 2, 3, 4A, and 10, implying the utilization of distinct regulatory factors. The default splicing behavior of the exon had demonstrated the existence of what were initially considered cryptic splice sites. However, analysis of the expression pattern of exon 6 suggests that these splice sites are utilized in certain human tissues and, if translated, would result in a radically altered tau protein. Lastly, expression of exon 6 minigene constructs in cells indicates that its flanking exons are involved in its inclusion and in the modulation of the ratio of its variants. C1 EK Shriver Ctr Mental Retardat, Dept Biomed Sci, Waltham, MA 02154 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Andreadis, A (reprint author), EK Shriver Ctr Mental Retardat, Dept Biomed Sci, 200 Trapelo Rd, Waltham, MA 02154 USA. FU NICHD NIH HHS [P01 HD05515] NR 67 TC 43 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1998 VL 70 IS 4 BP 1346 EP 1356 PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZC308 UT WOS:000072564100002 PM 9523550 ER PT J AU Hyman, BT Gomez-Isla, T Irizarry, MC AF Hyman, BT Gomez-Isla, T Irizarry, MC TI Stereology: A practical primer for neuropathology SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; NEURONS; NUMBER C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp, Dept Neurol, 149 13th,CNY 6405, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG00793, AG08487] NR 16 TC 68 Z9 69 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD APR PY 1998 VL 57 IS 4 BP 305 EP 310 DI 10.1097/00005072-199804000-00001 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZG528 UT WOS:000073012700001 PM 9600222 ER PT J AU Alonzo, NC Hyman, BT Rebeck, GW Greenberg, SM AF Alonzo, NC Hyman, BT Rebeck, GW Greenberg, SM TI Progression of cerebral amyloid angiopathy: Accumulation of amyloid-beta 40 in affected vessels SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE aging; amyloid; apolipoprotein E; Hemorrhage; stroke ID PROTEIN A-BETA; SPORADIC ALZHEIMERS-DISEASE; APOLIPOPROTEIN-E EPSILON-4; DOWN-SYNDROME; E GENOTYPE; DEPOSITION; PLAQUES; HEMORRHAGE; BRAIN; A-BETA-42(43) AB Cerebrovascular deposits of amyloid (cerebral amyloid angiopathy, or CAA) are generally asymptomatic, but in advanced cases, they can lead to vessel rupture and hemorrhage. The process of progression in CAA was studied by comparison of postmortem brains with asymptomatic ("mild") CAA to brains with the form of the disease associated with hemorrhage ("severe CAA"). Cortical and meningeal vessels were immunostained for beta-amyloid and examined by confocal microscopy and by systematic quantitative sampling. We focused on 2 quantitative parameters: the proportion of vessels affected by amyloid (a measure of amyloid seeding of vessels) and the amount of amyloid per affected vessel (a measure of growth of existing lesions). Surprisingly, there was no difference between the proportion of affected cortical vessels in mild and severe CAA (0.29 vs 0.32, p = 0.65), but rather an increase in the area of the 40 amino acid form of beta-amyloid per affected cortical vessel (198.5 +/- 38.7 vs 455.8 +/- 100.9 mu m(2)/vessel, p < 0.007). Increasing doses (from 0 to 1 to 2 copies) of the apolipoprotein E epsilon 4 allele were also associated with greater amyloid per vessel without change in the proportion of affected vessels within each class of CAA severity. These findings suggest that progression from asymptomatic to advanced CAA reflects progressive accumulation of amyloid in vessels previously seeded with amyloid, and that this process is selectively enhanced by apolipoprotein E epsilon 4. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Wang ACC 836, Boston, MA 02114 USA. FU NIA NIH HHS [AG00725, AG12406, AG14473] NR 46 TC 127 Z9 131 U1 0 U2 1 PU AMER ASSN NEUROPATHOLOGISTS INC PI LAWRENCE PA 1041 NEW HAMPSHIRE ST, LAWRENCE, KS 66044 USA SN 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD APR PY 1998 VL 57 IS 4 BP 353 EP 359 DI 10.1097/00005072-199804000-00008 PG 7 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA ZG528 UT WOS:000073012700008 PM 9600229 ER PT J AU Spear, MA Herrlinger, U Rainov, N Pechan, P Weissleder, R Breakefield, XO AF Spear, MA Herrlinger, U Rainov, N Pechan, P Weissleder, R Breakefield, XO TI Targeting gene therapy vectors to CNS malignancies SO JOURNAL OF NEUROVIROLOGY LA English DT Review DE CNS malignancies; brain tumor; vector; targeting; gene therapy; glioma; glioblastoma ID TUMOR-INFILTRATING LYMPHOCYTES; CENTRAL-NERVOUS-SYSTEM; BLOOD-BRAIN-BARRIER; ACTIVATED KILLER CELLS; NECROSIS-FACTOR-ALPHA; ESTABLISHED PULMONARY METASTASES; ENDOTHELIAL GROWTH-FACTOR; POLYLYSINE DNA COMPLEXES; MURINE LEUKEMIA-VIRUS; THYMIDINE KINASE GENE AB Gene therapy offers significant advantages to the field of oncology with the addition of specifically and uniquely engineered mechanisms of halting malignant proliferation through cytotoxicity or reproductive arrest. To confer a true benefit to the therapeutic ratio (the relative toxicity to tumor compared to normal tissue) a vector or the transgene it carries must selectively affect or access tumor cells. Beyond the selective toxicities of many transgene products, which frequently parallel that of contemporary chemotherapeutic agents, lies the potential utility of targeting the vector. This review presents an overview of current and potential methods for designing vectors targeted to CNS malignancies through selective delivery, cell entry, transport or transcriptional regulation. The topic of delivery encompasses physical and pharmaceutic means of increasing the relative exposure of tumors to vector, Cell entry based methodologies are founded on increasing relative uptake of vector through the chemical or recombinant addition of ligand and antibody domains which selectively bind receptors expressed on target cells. Targeted transport involves the potential for using cells to selectively carry vectors or transgenes into tumors. Finally, promoter and enhancer systems are discussed which have potential for selectivity activating transcription to produce targeted transgene expression or vector propagation. C1 Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Diagnost Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Spear, MA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 179 TC 18 Z9 18 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 1998 VL 4 IS 2 BP 133 EP 147 PG 15 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA ZG503 UT WOS:000073010200001 PM 9584951 ER PT J AU Parr, MJ Wen, PY Schaub, M Khoury, SJ Sayegh, MH Fine, HA AF Parr, MJ Wen, PY Schaub, M Khoury, SJ Sayegh, MH Fine, HA TI Immune parameters affecting adenoviral vector gene therapy in the brain SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE adenovirus; gene therapy; beta-galactosidase; neuroimmunology; brain; inflammation ID CENTRAL-NERVOUS-SYSTEM; RECOMBINANT ADENOVIRUS; IN-VIVO; EXPRESSION; RESPONSES; INFLAMMATION; PROTEIN; TYPE-5; CELLS; MODEL AB Gene therapy utilizing replication deficient adenoviral vectors represents a potentially promising approach to the treatment of brain tumors. Limited duration of systemic transgene expression and inefficient transduction following repeat systemic vector administration secondary to an effective anti-vector immune response limits the potential application of first generation adenoviral vectors. Whether host immune responses will significantly limit the use of these vectors within the immunopriviledged environment of the central nervous system remains to be elucidated. Following a single intravenous injection of a beta-galactosidase expressing adenoviral vector (Ad.CMV-beta gal), we found maximal beta gal transgene expression in systemic sites (i.e. liver) at day 4, with almost complete disappearance by day 7. In contrast, significant beta-galactosidase activity was seen for greater than 28 days following a single intracerebral inoculum of virus. Rechallenge experiments demonstrated complete protection against repeat systemic vector administration, whereas intracerebral transgene expression was not affected by prior systemic or intracerebral exposure to adenoviruses. These data suggest that systemic anti-adenoviral vector immune responses are attenuated within the central nervous system and may not pose as significant a problem for the treatment of brain tumors as for other systemic indications. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. RP Fine, HA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Neurooncol, 44 Binney St, Boston, MA 02115 USA. OI khoury, samia/0000-0003-3198-6063 NR 39 TC 26 Z9 26 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 1998 VL 4 IS 2 BP 194 EP 203 PG 10 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA ZG503 UT WOS:000073010200006 PM 9584956 ER PT J AU Wei, MX Li, FQ Ono, Y Gauldie, J Chiocca, EA AF Wei, MX Li, FQ Ono, Y Gauldie, J Chiocca, EA TI Effects on brain tumor cell proliferation by an adenovirus vector that bears the Interleukin-4 gene SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE brain tumors; gene therapy; interleukin-4; recombinant adenovirus vectors ID HERPES-SIMPLEX VIRUS; IN-VIVO; THERAPY; REGRESSION; SYSTEM; MODEL; BROMODEOXYURIDINE; FRACTION; GLIOMA; MICE AB A recombinant adenovirus vector bearing the IL-4 gene (AD-IL-4) was used to infect rat glioma C6 cells in culture at multiplicity of infections (MOI) from 50 to 1800. C6 cell proliferation was not altered significantly by adenoviral infection. However, IL-4 production increased in a dose-dependent manner. To ascertain effects on in vivo cell proliferation, a subcutaneous tumor model was used. Rat C6 glioma cells alone or C6 mixed with the control virus bearing the LacZ gene (Ad-LacZ) produced tumors that measured an average of approximately 3000 mm(3) 35 days after implantation. In contrast, C6 cells mixed with Ad-IL-4 produced significant inhibition of tumor growth (P=0.035 compared to C6 tumor; P=0.023 compared to C6+Ad-LacZ tumor. Student's t test). IL-4 levels in mice serum were measured by ELISA and reached a peak of approximately 700 pg/ml at 14 days. These preliminary results showed that adenovirus-mediated delivery of the IL-4 gene may result in a significant inhibition of rat C6 cell tumor growth. Further studies will be necessary to refine this anti-tumor effect for as a potential therapy for cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab,Neurosurg Serv, Boston, MA 02114 USA. McMaster Univ, Dept Pathol, Hamilton, ON, Canada. RP Chiocca, EA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mol Neurooncol Lab,Neurosurg Serv, Boston, MA 02114 USA. FU NINDS NIH HHS [NS24279-08] NR 24 TC 13 Z9 14 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD APR PY 1998 VL 4 IS 2 BP 237 EP 241 PG 5 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA ZG503 UT WOS:000073010200010 PM 9584960 ER PT J AU Ocone, R Netti, P AF Ocone, R Netti, P TI Gianni Astarita: An appreciation SO JOURNAL OF NON-NEWTONIAN FLUID MECHANICS LA English DT Biographical-Item C1 Univ Nottingham, Dept Chem Engn, Nottingham NG9 2RD, England. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Ocone, R (reprint author), Univ Nottingham, Dept Chem Engn, Nottingham NG9 2RD, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0377-0257 J9 J NON-NEWTON FLUID JI J. Non-Newton. Fluid Mech. PD APR PY 1998 VL 76 IS 1-3 BP 3 EP 3 PG 1 WC Mechanics SC Mechanics GA ZK144 UT WOS:000073289800002 ER PT J AU Siegner, SW Giovanoni, RL Erickson, KA Netland, PA AF Siegner, SW Giovanoni, RL Erickson, KA Netland, PA TI Distribution of verapamil and norverapamil in the eye and systemic circulation after topical administration of verapamil in rabbits SO JOURNAL OF OCULAR PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID CALCIUM-CHANNEL BLOCKERS; NORMAL-TENSION GLAUCOMA; OPEN-ANGLE GLAUCOMA; BLOCKING-AGENTS; OCULAR-TISSUES; PHARMACOKINETICS; LOCALIZATION; PENETRATION; NIMODIPINE; ANTAGONIST AB Our purpose was to determine the pharmacokinetics of verapamil and its active metabolite norverapamil after topical administration of verapamil in rabbits. New Zealand white albino rabbits were given 50 mu l of verapamil ophthalmic formulation topically in each eye. Samples obtained at various time points were analyzed with high performance liquid chromatography and tandem mass spectrometry. The elimination half-life of verapamil after treatment with 0.5% verapamil was 0.76 hour for aqueous, 4.34 hours for vitreous, and 1.82 hours for serum. The peak concentrations for aqueous, vitreous, and serum were 2.34 x 10(-6) M by 0.5 hour, 1.57 x 10(-7) M at 2 hours, and 3.39 x 10(-8) M by 0.5 hour following instillation of one drop of 0.5% verapamil; and 1.41 x 10(-6) M by 0.5 hour, 5.48 x 10(-8) M at 4 hours, and 1.20 x 10(-8) M by 0.5 hour following 0.25% verapamil, respectively. The metabolite norverapamil was found at peak concentrations of 8.65 x 10(-8) M by 0.5 hour in aqueous, 1.65 x 10(-8) M at 2 hours in vitreous, and 1.30 x 10(-9) M by 0.5 hr in serum following administration of 0.5% verapamil. The elimination half-life of norverapamil for aqueous, vitreous, and serum following treatment with 0.5% verapamil was 0.91 hour, 1.43 hours, and 3.60 hours, respectively. We conclude that topical verapamil, administered to the rabbit eye, is rapidly absorbed in the aqueous, vitreous, and blood. Norverapamil, which is an active metabolite of verapamil, can be detected in the aqueous and vitreous of the rabbit eye after topical administration, suggesting enzymatic degradation of verapamil within the eye. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. RP Netland, PA (reprint author), Univ Tennessee, Dept Ophthalmol, 956 Court Ave, Memphis, TN 38163 USA. NR 38 TC 5 Z9 5 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1080-7683 J9 J OCUL PHARMACOL TH JI J. Ocular Pharmacol. Ther. PD APR PY 1998 VL 14 IS 2 BP 159 EP 168 DI 10.1089/jop.1998.14.159 PG 10 WC Ophthalmology; Pharmacology & Pharmacy SC Ophthalmology; Pharmacology & Pharmacy GA ZH290 UT WOS:000073092500008 PM 9572542 ER PT J AU Blais, MA Hilsenroth, MJ Fowler, JC AF Blais, MA Hilsenroth, MJ Fowler, JC TI Rorschach correlates of the DSM-IV histrionic personality disorder SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID BORDERLINE; ADOLESCENTS; ATTACHMENT; ANXIETY; SCALES AB Rorschach assessment data have long been rationally linked to the psychiatric condition of hysteria. This study represents the first empirical attempt to explore the associations among select Rorschach variables, the Diagnostic and Statistical Manual of Mental Disorders (4th ed. [DSM-IV]; American Psychiatric Association, 1994) Histrionic Personality Disorder (HPD) criteria, and two self-report measures of hysteria. We correlated four Rorschach variables with total symptom scores for DSM-IV Cluster B Personality Disorders (Borderline, Antisocial, Narcissistic, and Histrionic). We found two Rorschach variables, FC+CF+C and T (Exner, 1993), to be significantly and meaningfully correlated with both the DSM-IV HPD total score (number of criteria) and the individual HPD criteria. Although not significantly associated with the HPD total score, Denial (DEN; Lerner & Lerner, 1980) was associated with one individual HPD criterion. Furthermore, DEN was significantly correlated with the MMPI-2 Hysteria (Ny) scale. The results are reviewed in terms of their clinical utility and the insights they offer into the psychological characteristics of the DSM-IV HPD. C1 Massachusetts Gen Hosp, Inpatient Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Univ Arkansas, Dept Psychol, Fayetteville, AR 72701 USA. RP Blais, MA (reprint author), Massachusetts Gen Hosp, Inpatient Psychiat Serv, Blake 11,55 Fruit St, Boston, MA 02114 USA. NR 34 TC 9 Z9 10 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD APR PY 1998 VL 70 IS 2 BP 355 EP 364 DI 10.1207/s15327752jpa7002_12 PG 10 WC Psychology, Clinical; Psychology, Social SC Psychology GA 102EE UT WOS:000074910700012 PM 9697335 ER PT J AU Baba, H Kohno, T Okamoto, M Goldstein, PA Shimoji, K Yoshimura, M AF Baba, H Kohno, T Okamoto, M Goldstein, PA Shimoji, K Yoshimura, M TI Muscarinic facilitation of GABA release in substantia gelatinosa of the rat spinal dorsal horn SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CHOLINERGIC RECEPTORS; AUTORADIOGRAPHIC LOCALIZATION; INTRATHECAL NEOSTIGMINE; HIPPOCAMPAL SLICE; SYNAPTIC CURRENTS; NEURONS INVITRO; BINDING-SITES; GUINEA-PIG; BRAIN-STEM; CORD AB 1. Blind patch clamp recordings were made from substantia gelatinosa (SG) neurones in the adult rat spinal cord slice to study the mechanisms of cholinergic modulation of GABAergic inhibition. 2. In the majority of SG neurones tested, carbachol (10 mu M) increased the frequency (677 % of control) of spontaneous GABAergic inhibitory postsynaptic currents (IPSCs). A portion of these events appeared to result from the generation of spikes by GABAergic interneurones, since large amplitude IPSCs were eliminated by tetrodotoxin (1 mu M). 3. The effect of carbachol on spontaneous IPSCs was mimicked by neostigmine, suggesting that GABAergic interneurones are under tonic regulation by cholinergic systems. 4. The frequency of GABAergic miniature IPSCs in the presence of tetrodotoxin (1 mu M) was also increased by carbachol without affecting amplitude distribution, indicating that acetylcholine facilitates quantal release of GABA through presynaptic mechanisms 5. Neither the M-1 receptor agonist McN-A-343 (10-300 mu M) nor the M-2 receptor agonist, arecaidine (10-100 mu M), mimicked the effects of carbachol. All effects of carbachol and neostigmine were antagonized by atropine (1 mu M), while pirenzepine (100 nM), methoctramine (1 mu M) and hexahydrosiladifenidol hydrochloride, p-fluoro-analog (100 nM) had no effect. 6. Focal stimulation of deep dorsal horn, but not dorsolateral funiculus, evoked a similar increase in IPSC frequency to that evoked by carbachol, and neostigmine. The stimulation induced facilitation of GABAergic transmission lasted for 2-3 min post stimulation, and the effect was antagonized by atropine (100 nM). 7. Our observations suggest that GABAergic interneurones possess muscarinic receptors on both axon terminals and somatodendritic sites, that the activation of these receptors increases the excitability of inhibitory interneurones and enhances GABA release in SG and that the GABAergic inhibitory system is further controlled by cholinergic neurones located in the deep dorsal horn. Those effects may be responsible for the antinociceptive action produced by the intrathecal administration of muscarinic agonists and acetylcholinesterase inhibitors. C1 Niigata Univ, Sch Med, Dept Anaesthesiol, Niigata 951, Japan. Columbia Univ Coll Phys & Surg, Dept Anaesthesiol, New York, NY 10032 USA. Saga Med Sch, Dept Physiol, Saga 849, Japan. RP Baba, H (reprint author), Massachusetts Gen Hosp, Dept Anaesthesia, MGH E 4th Floor,149 13th St, Charlestown, MA 02129 USA. NR 37 TC 80 Z9 81 U1 0 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 1 PY 1998 VL 508 IS 1 BP 83 EP 93 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA ZH998 UT WOS:000073169400008 PM 9490821 ER PT J AU Eisenberg, LS Dirks, DD Takayanagi, S Martinez, AS AF Eisenberg, LS Dirks, DD Takayanagi, S Martinez, AS TI Subjective judgments of clarity and intelligibility for filtered stimuli with equivalent speech intelligibility index predictions SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE subjective judgments; category rating; clarity; intelligibility ID PAIRED-COMPARISON JUDGMENTS; SOUND QUALITY JUDGMENTS; HEARING-AID SELECTION; MAGNITUDE ESTIMATION; CONTINUOUS DISCOURSE; FREQUENCY RESPONSES; ARTICULATION INDEX; LISTENERS; RELIABILITY; SENSITIVITY AB The purpose of this investigation was to determine whether subjective judgments of clarity or intelligibility would be rated equally among conditions in which speech was equated for predicted intelligibility (using the Speech Intelligibility Index, SII) but varied in bandwidth. Twenty listeners with normal hearing rated clarity and intelligibility for sentence material (Hearing In Noise Test) in speech-shaped noise at six paired low- and high-pass Filtered conditions in which SII was equated for each pair. For three paired conditions, predicted intelligibility increased as SII increased monotonically (0.3, 0.4, 0.5). In the remaining paired conditions, SII continued to increase monotonically (0.6, 0.7, 0.8) but predicted intelligibility was held at a maximal level (greater than or equal to 95%). Predicted intelligibility was estimated from the transfer function relating SII to speech recognition scores determined in preliminary experiments. Differences in ratings between paired low-and high-pass filtered sentences did not reach statistical significance for either clarity or intelligibility, indicating that the spectral differences at equivalent Sits did not influence the judgments for either of the two dimensions. For conditions in which predicted intelligibility increased, both clarity and intelligibility ratings increased in a similar manner. For conditions in which predicted intelligibility was maximized, intelligibility ratings remained the same statistically across conditions while clarity ratings changed modestly. Although high correlations were observed between clarity and intelligibility ratings, intelligibility ratings were consistently higher than clarify ratings For comparable conditions. The results indicated that listeners with normal hearing produced clarity and intelligibility ratings for the same speech material and experimental conditions that were highly related but differed in magnitude. Caution is required when substituting clarity For intelligibility. C1 Univ Calif Los Angeles, Sch Med, Div Head & Neck Surg, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Linguist, Los Angeles, CA 90024 USA. W Los Angeles Vet Adm Med Ctr, Los Alamos, NM USA. RP Eisenberg, LS (reprint author), House Ear Inst, 2100 W 3rd St,5th Floor, Los Angeles, CA 90057 USA. EM leisenberg@hei.org FU NIDCD NIH HHS [T32 DC00029-07, 5 K08 DC 00083-05] NR 45 TC 32 Z9 32 U1 3 U2 5 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD APR PY 1998 VL 41 IS 2 BP 327 EP 339 PG 13 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA ZH627 UT WOS:000073130500009 PM 9570586 ER PT J AU Kumra, S Jacobsen, LK Lenane, M Karp, BI Frazier, JA Smith, AK Bedwell, J Lee, P Malanga, CJ Hamburger, S Rapoport, JI AF Kumra, S Jacobsen, LK Lenane, M Karp, BI Frazier, JA Smith, AK Bedwell, J Lee, P Malanga, CJ Hamburger, S Rapoport, JI TI Childhood-onset schizophrenia: An open-label study of olanzapine in adolescents SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE olanzapine; clozapine; childhood-onset schizophrenia ID OPEN TRIAL; CLOZAPINE; HALOPERIDOL; CHILDREN; DISORDER; PROGRESS AB Objective: Olanzapine, a potent 5-HT2a/2c, dopamine D1D2D4 antagonist with anticholinergic activity, has a profile of known receptor affinity similar to that of clozapine. This pilot study examined the efficacy of olanzapine for treatment-refractory childhood-onset schizophrenia in eight patients who had received 8-week open-label trials. For comparison, data are included from 15 patients who had received g-week open-label clozapine trials using identical rating instruments (largely by the same raters) in the same treatment setting. Method: Twenty-three children and adolescents with an onset of DSM-III-R schizophrenia by age 12 for whom at least two different typical neuroleptics had been ineffective participated in the two separate studies. Some of the patients were intolerant of clozapine, although it had been effective (n = 4). Patients receiving olanzapine were evaluated over 8 weeks with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Positive Symptoms, the Scale for the Assessment of Negative Symptoms, and the Clinical Global Impressions Scale for Improvement. Results: For the eight patients who received olanzapine trials, at week 8 there was a 17% improvement in the BPRS total score, a 27% improvement in the Scale for the Assessment of Negative Symptoms, and a 1% improvement in the Scale for the Assessment of Positive Symptoms, relative to "ideal" admission status on typical neuroleptics. In contrast, the magnitude of the effect sizes for each of the clinical ratings was larger at week 6 of the previous clozapine trial than for an 8-week olanzapine trial, relative to admission status on typical neuroleptics. For the four children who had received both clozapine and olanzapine, BPRS total scores were significantly lower at week 6 of clozapine treatment compared with week 6 of olanzapine treatment (p = .03). Conclusion: These data provide preliminary evidence for the efficacy of olanzapine for some children and adolescents with treatment-refractory schizophrenia, but they also suggest the need for a more rigorous double-blind comparison of these two atypical antipsychotics. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Kumra, S (reprint author), NIMH, Child Psychiat Branch, Bldg 10,10 Ctr Dr MSC1600,Room 6N240, Bethesda, MD 20892 USA. OI Malanga, C.J./0000-0003-4808-3995 NR 45 TC 108 Z9 109 U1 7 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1998 VL 37 IS 4 BP 377 EP 385 DI 10.1097/00004583-199804000-00015 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZD162 UT WOS:000072657600015 PM 9549958 ER PT J AU Geller, D Biederman, J Jones, J Park, K Schwartz, S Shapiro, S Coffey, B AF Geller, D Biederman, J Jones, J Park, K Schwartz, S Shapiro, S Coffey, B TI Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Review DE obsessive-compulsive disorder; juveniles; review ID PROSPECTIVE FOLLOW-UP; CEREBROSPINAL-FLUID NEUROCHEMISTRY; DOUBLE-BLIND; CLOMIPRAMINE TREATMENT; PSYCHIATRIC-DISORDERS; TOURETTES-SYNDROME; COMMUNITY SAMPLE; ADOLESCENTS; CHILDREN; CHILDHOOD AB Objective: To examine the clinical correlates of obsessive-compulsive disorder (OCD) in children and adolescents. Method: A systematic review of the extant literature an juvenile OCD was conducted examining age at onset, gender distribution, symptom phenomenology, psychiatric comorbidity, neurological and perinatal history, family psychiatric history, cognitive and neuropsychological profiles, and treatment and outcome in juvenile OCD subjects. Results: Juvenile OCD was associated with a unique peak of age at onset indicating a bimodal incidence of the disorder, male preponderance, a distinct pattern of comorbidity with attention-deficit/hyperactivity disorder and other developmental disorders as well as frequent associated neuropsychological deficits, an increased familial loading for OCD, and frequent absence of insight. Conclusion: These findings show that juvenile OCD is associated with a unique set of correlates that appear to differ from findings reported in studies of adult OCD subjects. Although in need of confirmation, these findings suggest that juvenile OCD may be a developmental subtype of the disorder. Since juvenile OCD is likely to continue into adulthood, these findings stress the importance of considering age at onset in clinical and research studies of adults with OCD. C1 McLean Hosp, Belmont, MA 02178 USA. Massachusetts Gen Hosp, Joint Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Geller, D (reprint author), McLean Hosp, 115 Mill St, Belmont, MA 02178 USA. NR 66 TC 174 Z9 179 U1 7 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 1998 VL 37 IS 4 BP 420 EP 427 DI 10.1097/00004583-199804000-00020 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA ZD162 UT WOS:000072657600020 PM 9549963 ER PT J AU Rabeneck, L Palmer, A Knowles, JB Seidehamel, RJ Harris, CL Merkel, KL Risser, JMH Akrabawi, SS AF Rabeneck, L Palmer, A Knowles, JB Seidehamel, RJ Harris, CL Merkel, KL Risser, JMH Akrabawi, SS TI A randomized controlled trial evaluating nutrition counseling with or without oral supplementation in malnourished HIV-infected patients SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; PARENTERAL-NUTRITION; MEGESTROL-ACETATE; BODY-COMPOSITION; VIRUS INFECTION; AIDS; CACHEXIA; ENERGY; MASS AB Objective To evaluate the effects of nutrition counseling with or without oral supplementation in malnourished patients infected with the human immunodeficiency virus (HIV). Design Randomized controlled trial. Subjects HIV-infected men (n=118) who were less than 90% of usual weight for height or who had lost more than 10% of body weight. Intervention Nutrition counseling alone (control group) vs nutrition counseling plus enteral supplementation (supplement group) for 6 weeks. AU patients were instructed to consume a diet that exceeded estimated total energy expenditure by 960 kcal/day. Main outcome measures Weight, skinfold thickness, fat-free mass, grip strength, quality of life, and cognitive function (Buschke test). Statistical analyses Differences in baseline variables and outcomes were evaluated using analysis of variance or the Wilcoxon rank sum test. Results Ninety-nine men completed at least 4 weeks of treatment, 49 in the supplement group and 50 in the control group. Half the patients in each treatment group achieved at least 80% of their energy target. No differences in weight, skinfold thickness measurements, or quality of life were observed. Compared with the control group, the supplement group had larger increases in fat-free mass and grip strength, although the differences did not reach statistical significance. Applications In the short term, nutrition counseling with or without oral supplementation can achieve a substantial increase in energy intake in about 50% of malnourished HIV-infected patients. Although further study is needed to evaluate long-term effects, these findings suggest that nutrition counseling has an important role in the management of malnourished HIV-infected patients. C1 Dept Vet Affairs Med Ctr, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Mead Johnson Nutr Grp, Evansville, IN USA. RP Rabeneck, L (reprint author), Vet Adm Med Ctr, 111D,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 18 TC 44 Z9 45 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD APR PY 1998 VL 98 IS 4 BP 434 EP 438 DI 10.1016/S0002-8223(98)00099-6 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZG012 UT WOS:000072955900016 PM 9550167 ER PT J AU Perkowski, LC Stroup-Benham, CA Markides, KS Lichtenstein, MJ Angel, RJ Guralnik, JM Goodwin, JS AF Perkowski, LC Stroup-Benham, CA Markides, KS Lichtenstein, MJ Angel, RJ Guralnik, JM Goodwin, JS TI Lower-extremity functioning in older Mexican Americans and its association with medical problems SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID PERFORMANCE-BASED MEASURES; NON-HISPANIC WHITES; PHYSICAL PERFORMANCE; DIABETIC-RETINOPATHY; ELDERLY PEOPLE; RISK-FACTORS; DISABILITY; HEALTH; DISEASE; PREDICTORS AB OBJECTIVE: To describe lower-extremity functioning in community-dwelling older Mexican Americans and to examine its relationship with medical problems. DESIGN: Cross-sectional analyses of survey and performance-based data obtained in a population-based study employing area probability sampling. SETTING: Households within selected census tracts of five Southwestern states: Arizona, California, Colorado, New Mexico, and Texas. PARTICIPANTS: A total of 2873 Mexican Americans aged 65 years and older. MEASUREMENTS: A multidimensional questionnaire assessing demographic, sociocultural, and health variables. Standardized tests of lower-extremity physical functioning included measures of standing balance, repeated chair stands, walking, and an overall summary measure. RESULTS: Regression analyses revealed that being more than age 75 and female, having arthritis diabetes, visual impairments, or being obese or underweight were all significantly associated with performance on both individual and summary tests of lower-extremity functioning. In separate regression analyses, the total number of medical conditions was also associated with performance. CONCLUSIONS: The likelihood of predicting performance or inability to complete tests of lower-extremity functioning was greatest for those aged 80 and older, those with arthritis or diabetes, and those with three or more medical conditions. Because of the high prevalence of diabetes in Mexican Americans, documentation of the association of diabetes with performance-based tests of lower-extremity functioning may help guide early interventions targeted to prevent progression to more severe limitations or disability. C1 Univ So Calif, Sch Med, Div Med Educ, Los Angeles, CA 90033 USA. Univ Texas, Med Branch, Dept Prevent Med & Community Hlth, Galveston, TX 77550 USA. Univ Texas, Med Branch, Ctr Aging, Galveston, TX 77550 USA. Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Univ Texas, Dept Sociol, Austin, TX 78712 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. RP Perkowski, LC (reprint author), Univ So Calif, Sch Med, Div Med Educ, 1975 Zonal Ave, KAM 211A, Los Angeles, CA 90033 USA. FU NIA NIH HHS [R01-AG10939] NR 62 TC 34 Z9 35 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 1998 VL 46 IS 4 BP 411 EP 418 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZG164 UT WOS:000072973100002 PM 9560061 ER PT J AU Coleman, EA Wagner, EH Grothaus, LC Hecht, J Savarino, J Buchner, DM AF Coleman, EA Wagner, EH Grothaus, LC Hecht, J Savarino, J Buchner, DM TI Predicting hospitalization and functional decline in older health plan enrollees: Are administrative data as accurate as self-report? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article; Proceedings Paper CT AGS Annual Meeting CY MAY, 1997 CL ATLANTA, GEORGIA ID COMPREHENSIVE GERIATRIC ASSESSMENT; RANDOMIZED TRIAL; ADMISSION; RISK; ADULTS; OUTCOMES; QUESTIONNAIRE; MANAGEMENT; CRITERIA; VALIDITY AB OBJECTIVE: To compare the predictive accuracy of two validated indices, one that uses self-reported variables and a second that uses variables derived from administrative data sources, to predict future hospitalization. To compare the predictive accuracy of these same two indices for predicting future functional decline. DESIGN: A longitudinal cohort study with 4 years of follow-up. SETTING: A large staff model HMO in western Washington State. PARTICIPANTS: HMO Enrollees 65 years and older (n = 2174) selected at random to participate in a health promotion trial and who completed a baseline questionnaire. MEASUREMENT: Predicted probabilities from the two indices were determined for study participants for each of two outcomes: hospitalization two or more times in 4 years and functional decline in 4 years, measured by Restricted Activity Days. The two indices included similar demographic charac teristics, diagnoses, and utilization predictors. The probabilities from each index were entered into a Receiver Operating Characteristic (ROC) curve program to obtain the Area Under the Curve (AUG) for comparison of predictive accuracy. RESULTS: For hospitalization, the AUC of the self-report and administrative indices were .696 and .694, respectively (difference between curves, P = .828). For functional decline, the AUC of the two indices were .714 and .691, respectively (difference between curves, P = .144). CONCLUSIONS: Compared with a self-report index, the administrative index affords wider population coverage, freedom from nonresponse bias, lower cost, and similar predictive accuracy. A screening strategy utilizing administrative data sources may thus prove more valuable for identifying high risk older health plan enrollees for population-based interventions designed to improve their health status. C1 Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatr Med, Robert Wood Johnson Clin Scholars Program, Seattle, WA 98104 USA. Univ Washington, Dept Med, Seattle, WA 98104 USA. VA Puget Sound Hlth Care Syst, NW HSR&D Field Program, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Hlth Serv, Seattle, WA 98195 USA. RP Coleman, EA (reprint author), Univ Washington, Harborview Med Ctr, Div Gerontol & Geriatr Med, Robert Wood Johnson Clin Scholars Program, Box 359755,325 9th Ave,HH565, Seattle, WA 98104 USA. NR 39 TC 55 Z9 56 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 1998 VL 46 IS 4 BP 419 EP 425 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZG164 UT WOS:000072973100003 PM 9560062 ER PT J AU Liu, YJ Stagni, G Walden, JG Shepherd, AMM Lichtenstein, MJ AF Liu, YJ Stagni, G Walden, JG Shepherd, AMM Lichtenstein, MJ TI Thioridazine dose-related effects on biomechanical force platform measures of sway in young and old men SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID NURSING-HOME RESIDENTS; ANTIPSYCHOTIC DRUG-USE; RISK-FACTORS; AGED WOMEN; BALANCE; FALLS; TRIAZOLAM; MOBILITY; SCALE; TRIAL AB OBJECTIVE: Thioridazine (TDZ) is associated with an increased risk of falls. The purpose of this study was to determine whether (1) thioridazine increases Biomechanics Force Platform (BFP) measures of sway in a dose-related manner, (2) there is a difference in sway between young and old men, (3) there is a correlation between sway and orthostatic changes in BP and HR. DESIGN: Seven younger (aged 20-42) and five older (aged 70-76) healthy male volunteers received, in a randomized order double-blind design, a single oral dose of 0, 25, and 50 mg of TDZ on three separate days at least 7 days apart and 75 mg on the fourth day of the study. Sway and blood pressure were measured for 24 hours. SETTING: A general clinical research center. MEASUREMENTS: Biomechanics force platform measures of postural sway were measured as the movement of the center of pressure. The elliptical area (EA) and average velocity (AV) were calculated with eyes open and eyes closed. Blood pressure and heart rate were measured for 5 minutes supine and 5 minutes standing. RESULTS: Thioridazine increases BFP sway in a dose-dependent manner. EA increased from 0.56 (SD =.51) cm(2) for placebo to 0.88 (SD = 1.09) cm(2) for 75 mg TDZ. AV increased from 1.07 (SD =.27) cm/sec, placebo, to 1.43 (SD =.55) cm/sec, 75 mg TDZ. Older men swayed more than younger men. Changes followed the expected time course for TDZ. EA and AV were associated with HR and BP, e.g., SEP versus In(EA) and In(AV) (r = -0.21 and r = -0.22, respectively; P<.0001). CONCLUSIONS: Thioridazine increases validated measures of fall risk dose dependently in young and old men. This may explain the effects of neuroleptic drugs on fall risk in older people. C1 Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Div Clin Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Clin Pharmacol, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Spinal Cord Injury Ctr, Dept Surg, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, Geriatr Res Educ & Clin Ctr 182, San Antonio, TX USA. RP Shepherd, AMM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pharmacol, Div Clin Pharmacol, 7703 Floyd Curl Dr,5-4 MCD, San Antonio, TX 78284 USA. FU NCRR NIH HHS [MO1-RR-01346] NR 40 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 1998 VL 46 IS 4 BP 431 EP 437 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZG164 UT WOS:000072973100005 PM 9560064 ER PT J AU Knight, EL Kiely, DK Fish, LC Marcantonio, ER Minaker, KL AF Knight, EL Kiely, DK Fish, LC Marcantonio, ER Minaker, KL TI Atrial natriuretic peptide level contributes to a model of future mortality in the oldest old SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID CONGESTIVE-HEART-FAILURE; NURSING-HOME PATIENTS; SERUM-ALBUMIN LEVEL; RISK; POLYPEPTIDE; DISABILITY; MORBIDITY; PREDICTOR; VENTRICLE; DEMENTIA AB OBJECTIVES: To determine if atrial natriuretic peptide (ANP) level is associated with mortality in the oldest old and to develop a comprehensive model of mortality in the oldest old using clinical and laboratory parameters. DESIGN: Prospective cohort study with 7 years of follow-up. SETTING: A 725-bed life care facility. PARTICIPANTS: 282 frail older individuals (mean age 88, range 70-102). MEASUREMENTS: Variables measured included age, gender, Charlson Comorbidity Index, functional measurements, weight, blood pressure, and multiple laboratory variables, including ANP. Main outcome measurement was death. RESULTS: Eighty-four percent (237/282) of subjects died during the 7-year follow-up period. On univariate analysis, the risk ratio (RR) for ANP tertile was 1.28. On bivariate analysis, adjusting for the development of congestive heart failure, the RR was 1.22. On multivariate analysis, the following variables were associated with mortality: ANP tertile (RR 1.24), age (RR 1.04), female gender (RR 0.43), Charlson Comorbidity Index score (RR 1.13), mentation score (RR 1.27), BUN/Cr ratio (RR 1.04), albumin level (RR 0.63), and hemoglobin level (RR 0.84). CONCLUSIONS: ANP level and other variables are independent risk factors for mortality in frail individuals. ANP level may indicate homeostatic failure to adapt to fluid volume changes or may reflect subclinical heart disease. ANP level contributes to a multivariate model of mortality in frail older individuals. C1 Massachusetts Gen Hosp, Geriatr Med Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Knight, EL (reprint author), Massachusetts Gen Hosp, Geriatr Med Unit, 100 Charles River Plaza,5th Fl, Boston, MA 02114 USA. FU NIA NIH HHS [5 K08 AG-00455, AG-04390, AG-00599] NR 27 TC 11 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 1998 VL 46 IS 4 BP 453 EP 457 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZG164 UT WOS:000072973100008 PM 9560067 ER PT J AU Lichtenstein, MJ Hazuda, HP AF Lichtenstein, MJ Hazuda, HP TI Cross-cultural adaptation of the hearing handicap inventory for the elderly-screening version (HHIE-S) for use with Spanish-speaking Mexican Americans SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article ID TEST-RETEST RELIABILITY; OLDER ADULTS; IMPAIRMENT; VALIDATION AB OBJECTIVE: To cross-culturally adapt the Hearing Handicap Inventory for the Elderly-Screening Version (HHIE-S) for use with older Spanish-speaking Mexican Americans. SUBJECTS AND SETTING: Two different samples were used. First, a convenience sample of 100 older community-dwelling Mexican American men and women in San Antonio, Texas, was used to test technical equivalence of the Spanish and English language versions of the HHIE-S. Second, a neighborhood-based sample of older Mexican Americans was used to establish conceptual (n = 433) and criterion equivalence (n = 381) of the two HHIE-S language versions. METHODS: Independent forward and back translations were done to create a Spanish language version of the HHIE-S. In the convenience sample, subjects were administered the English and Spanish HHIE-S in random order on separate days. In the neighborhood sample, the HHIE-S was given on one occasion in the language of the subject's preference. Depressive symptoms were assessed using the Geriatric Depression scale to see if the two language versions of the HHIE-S were similarly associated with depression (conceptual equivalence). Hearing impairment was assessed using the Welch-Allyn Audioscope(TM) to see if the two language versions were similarly associated with an audiometric measure for hearing loss (criterion equivalence). RESULTS: In the convenience sample, the overall mean (SD) Spanish and English HHIE-S scores were 6.2 (8.7) and 6.2 (9.3), respectively (P = 1.00). Total scores of the English and Spanish versions were highly correlated (r =.89), and regression analysis indicated that the two language versions gave nearly identical results. In the neighborhood-based sample, men had higher HHIE-S scores than women (OR 2.0, 95% CI = 1.3-3.5). Having depressive symptoms (OR 3.2, 95% CI = 1.9-5.5) or hearing impairment (OR 6.1, 95% CI = 3.5-10.5) was associated with higher HHIE-S scores. After adjustment for gender, depressive symptoms, and/or hearing impairment, the language of interview was not associated with HHIE-S score. CONCLUSION: We have developed and tested a Spanish translation of the HHIE-S that yields equivalent results to those obtained with the English version in bilingual Mexican Americans. The Spanish HHIE-S presented here is suitable for clinical use and research studies involving older Mexican Americans. C1 Audie L Murphy Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Div Geriatr & Gerontol, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Div Clin Epidemiol, San Antonio, TX USA. RP Lichtenstein, MJ (reprint author), Audie L Murphy Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU AHRQ HHS [HS-07397]; NCRR NIH HHS [MO1-RR-01346]; NIA NIH HHS [R01-AG10444] NR 25 TC 18 Z9 21 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 1998 VL 46 IS 4 BP 492 EP 498 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZG164 UT WOS:000072973100016 PM 9560075 ER PT J AU Hopmeyer, J He, SQ Thorvig, KM McNeil, E Wilkerson, PW Levine, RA Yoganathan, AP AF Hopmeyer, J He, SQ Thorvig, KM McNeil, E Wilkerson, PW Levine, RA Yoganathan, AP TI Estimation of mitral regurgitation with a hemielliptic curve-fitting algorithm: In vitro experiments with native mitral valves SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID COLOR-FLOW DOPPLER; CONVERGENCE REGION; BLOOD VELOCITY; ORIFICE; QUANTIFICATION; INVITRO AB To date, studies on the mitral flow convergence method have used rigid, circular, or slit orifices to represent the regurgitant orifice. In this study, explanted porcine mitral valves, with the entire mitral apparatus preserved, were mounted in an in vitro model to reproduce the three-dimensional regurgitant orifice geometry while permitting close control and measurement of the experimental conditions. This experimental setup permitted the evaluation of the hemispheric and hemielliptic formulas under realistic physiologic conditions. In this study, a heart rate of 70 beats/min was used with cardiac outputs between 1.5 and 6 L/min. Peak regurgitant flow rates ranged from 7 to 16 L/min (regurgitant jet velocities ranged from 2 to 5.5 m/sec); peak aortic flow rates ranged from 9 to 30 L/min. Four native mitral valves were used for these studies for a total of 28 stages. Although the hemielliptic modification has previously shown success in vitro and computationally, it has not been used clinically because of difficulty imaging the flow convergence region in three orthogonal planes. A curve-fitting algorithm was developed to extract the hemielliptic dimensions from two standard ultrasound views by rotating the transducer 90 degrees. Improved agreement was obtained between true and calculated flow rates by the hemielliptic formula (y = 1.02 x + 0.29; r = 0.91) compared with the hemispheric formula (y = 1.18 x-2.2; r = 0.66). This method provides accurate results with a realistic three-dimensional regurgitant orifice geometry and has the capability of being incorporated as a function key on an ultrasound machine for clinical application. C1 Georgia Inst Technol, Sch Chem Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. Georgia Inst Technol, Sch Mech Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. Georgia Inst Technol, Inst Bioengn & Biosci, Atlanta, GA 30332 USA. Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,Noninvas Cardiol Lab, Boston, MA USA. RP Yoganathan, AP (reprint author), Georgia Inst Technol, Sch Chem Engn, Cardiovasc Fluid Mech Lab, Atlanta, GA 30332 USA. FU NHLBI NIH HHS [HL 45485, HL 53702, HL 52009] NR 25 TC 12 Z9 12 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 1998 VL 11 IS 4 BP 322 EP 331 DI 10.1016/S0894-7317(98)70099-9 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZH646 UT WOS:000073132800004 PM 9571581 ER PT J AU Grandaliano, G Choudhury, GG Poptic, E Woodruff, K Barnes, JL Abboud, HE AF Grandaliano, G Choudhury, GG Poptic, E Woodruff, K Barnes, JL Abboud, HE TI Thrombin regulates PDGF expression in bovine glomerular endothelial cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID GROWTH-FACTOR; MESANGIAL CELLS; PROSTACYCLIN PRODUCTION; FIBRIN DEPOSITION; INVITRO; RELEASE; GLOMERULONEPHRITIS; ISOFORMS; GENE AB The proteolytic enzyme thrombin is produced during activation of the coagulation pathway. Intraglomerular fibrin deposition and thrombosis are common pathologic features of several glomerular diseases, including transplant rejection. The effect of thrombin on platelet-derived growth factor (PDGF) production and DNA synthesis in well characterized bovine glomerular endothelial cells (G/endo) was studied. DNA synthesis was measured as the amount of [H-3]thymidine incorporated into acid-insoluble material. PDGF released in the supernatant was measured by Western blotting and by a radioreceptor assay. PDGF mRNA expression was analyzed by solution hybridization, using human genomic PDGF B-chain (c-sis) and A-chain cDNA probes. G/endo constitutively secrete PDGF activity in serum-free medium. Thrombin stimulates PDGF production and increases the expression of mRNA that hybridizes with labeled B-chain but not A-chain probe, whereas epidermal growth factor and transforming growth factor-ct stimulate the expression of PDGF A-chain mRNA. In addition, thrombin stimulates DNA synthesis with a peak effect at 24 h, Unlike endothelial cells from other microvascular beds, G/endo did not respond to any of the three PDGF isoforms BE, AB, or AA. These data demonstrate that bovine G/endo produce PDGF and that thrombin stimulates de novo synthesis of PDGF from these cells. Because mesangial, but not bovine, G/endo express PDGF receptors, PDGF released by G/endo is Likely to modulate mesangial cell functions such as proliferation and matrix production by means of a paracrine mechanism. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, San Antonio, TX 78284 USA. RP Abboud, HE (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. RI Grandaliano, Giuseppe/G-2963-2012 FU NIDDK NIH HHS [DK 43988, DK 33665, DK 50190] NR 42 TC 17 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 1998 VL 9 IS 4 BP 583 EP 589 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA ZE284 UT WOS:000072776600007 PM 9555660 ER PT J AU Gallagher, JG Riggs, DS Byrne, CA Weathers, FW AF Gallagher, JG Riggs, DS Byrne, CA Weathers, FW TI Female partners' estimations of male veterans' combat-related PTSD severity SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE PTSD; couples; assessment; concordance; veterans ID ATTENTION; EMOTION AB This study investigated concordance between male Vietnam veterans' and their female partners' reports of veterans' posttraumatic stress disorder (PTSD) symptoms. Fifty male Vietnam combat veterans and their partners rated the severity of their own PTSD symptoms. Also, partners rated the severity of veterans' symptoms. Results indicated modest levels of agreement in reports of symptom presence/absence. Partner ratings of veterans' PTSD severity were positively correlated with veteran reports and partners' own self-reported PTSD symptoms. After controlling for veterans' self-reported symptoms, partners' symptoms significantly predicted their estimates of veterans' avoidance symptoms, but not veterans' reexperiencing or hyperarousal symptoms. Theoretical and practical implications of these findings are discussed. C1 Vet Adm Med Ctr, Natl Ctr PTSD 116B2, Boston, MA 02130 USA. Tufts Univ, Sch Med, Medford, MA 02155 USA. RP Riggs, DS (reprint author), Vet Adm Med Ctr, Natl Ctr PTSD 116B2, 150 S Huntington Ave, Boston, MA 02130 USA. NR 8 TC 23 Z9 23 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 1998 VL 11 IS 2 BP 367 EP 374 DI 10.1023/A:1024411422586 PG 8 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZG878 UT WOS:000073049100011 PM 9565921 ER PT J AU Unger, WS Gould, RA Babich, M AF Unger, WS Gould, RA Babich, M TI The development of a scale to assess war-time atrocities: The War Events Scale SO JOURNAL OF TRAUMATIC STRESS LA English DT Article DE atrocity; combat-related PTSD ID POSTTRAUMATIC-STRESS-DISORDER; VIETNAM; RELIABILITY; EXPERIENCE; VALIDITY; TRAUMA AB The War Events Scale (WES) was developed to assist clinicians with the assessment of war zone veterans' exposure to, and participation in war-time atrocities distinct from combat, and their current distress from these events. Data concerning content validity, test-retest reliability, infernal consistency, as well as correlational data with the Combat Exposure Scale and the Mississippi Scale are presented. Results indicate that the WES does have adequate internal consistency and test-retest reliability, and correlates moderately with the Combat Exposure and Mississippi Scales. Initial results suggest that the WES may be helpful in collecting extremely sensitive information concerning the exposure of war zone veterans to atrocities. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anxiety Disorders Program, Boston, MA 02114 USA. Vet Adm Med Ctr, Providence, RI 02908 USA. Cape Cod Hosp, Hyannis, MA USA. RP Gould, RA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anxiety Disorders Program, WACC 815,15 Parkman St, Boston, MA 02114 USA. NR 19 TC 7 Z9 7 U1 0 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD APR PY 1998 VL 11 IS 2 BP 375 EP 383 DI 10.1023/A:1024463406656 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA ZG878 UT WOS:000073049100012 PM 9565922 ER PT J AU Collins, MM Stafford, RS O'Leary, MP Barry, MJ AF Collins, MM Stafford, RS O'Leary, MP Barry, MJ TI How common is prostatitis? A national survey of physician visits SO JOURNAL OF UROLOGY LA English DT Article; Proceedings Paper CT 92nd Annual Meeting of the American-Urological-Association CY APR 12-17, 1997 CL NEW ORLEANS, LOUISIANA SP Amer Urol Assoc DE prostate; prostatitis; epidemiology; antibiotics; ambulatory care AB Purpose: We used a national data base to explore the epidemiology of physician visits for genitourinary symptoms or a diagnosis of prostatitis. Materials and Methods: We analyzed 58,955 visits by men 18 years old or older to office based physicians of all specialties, as included in the National Ambulatory Medical Care Surveys from 1990 to 1994. Physicians selected by random sampling completed visit forms that included information on patient reasons for visits and physician diagnoses. Results: From 1990 to 1994, 5% of all ambulatory visits by men 18 years old or older included genitourinary symptoms as a reason for the visit. In almost 2 million visits annually prostatitis was listed as a diagnosis, including 0.7 million by men 18 to 50 years old and 0.9 million by those older than 50 years. Of the prostatitis visits 46 and 47% were to urologists and primary care physicians, respectively. A prostatitis diagnosis was assigned at 8 and 1% of all urologist and primary care physician visits, respectively. The odds of a prostatitis diagnosis were 13-fold greater at visits to urologists compared with visits to primary care physicians, and approximately 2-fold greater in the south than in the northeast. Surprisingly, compared with men 66 years old or older, prostatitis was more commonly diagnosed in men 36 to 65 than men 18 to 35 years old. When a prostatitis diagnosis was given, antimicrobial use was likely to be reported 45% of the time for men with and 27% for those without genitourinary symptoms. Visits to primary care physicians were more often associated with antimicrobial use than visits to urologists. Conclusions: Genitourinary symptoms are a frequent. reason for office visits by younger and older men, and prostatitis is a common diagnosis. Despite a report that less than 10% of prostatitis cases are bacterial, a much higher proportion of men in whom prostatitis is diagnosed receive antimicrobials. C1 Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. RP Collins, MM (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Boston, MA 02114 USA. FU AHRQ HHS [HS 08397, HS 07892]; NHLBI NIH HHS [K08HL03548] NR 26 TC 236 Z9 291 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 1998 VL 159 IS 4 BP 1224 EP 1228 DI 10.1016/S0022-5347(01)63564-X PG 5 WC Urology & Nephrology SC Urology & Nephrology GA ZB163 UT WOS:000072442700036 PM 9507840 ER PT J AU Rudnick, DM Dretler, SP AF Rudnick, DM Dretler, SP TI Intrarenal pseudoaneurysm following ureterorenoscopy and electrohydraulic lithotripsy SO JOURNAL OF UROLOGY LA English DT Article DE pseudoaneurysm; electrohydraulic lithotripsy C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rudnick, DM (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 1998 VL 159 IS 4 BP 1290 EP 1291 DI 10.1016/S0022-5347(01)63583-3 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA ZB163 UT WOS:000072442700055 PM 9507855 ER PT J AU Asakura, H Selengut, JD Orme-Johnson, WH Dretler, SP AF Asakura, H Selengut, JD Orme-Johnson, WH Dretler, SP TI The effect of calprotectin on the nucleation and growth of struvite crystals as assayed by light microscopy in real-time SO JOURNAL OF UROLOGY LA English DT Article DE urinary calculi; urease; urinary tract infections; urine ID UREASE-INDUCED CRYSTALLIZATION; PROTEIN; URINE; IDENTIFICATION; QUANTITATION; INVITRO; MATRIX; ZINC AB Purpose: To use light microscopy to observe the urease-induced growth of struvite crystals in real-time, and to compare the effects of various proteins on that growth. Materials and Methods: Artificial urine, with and without citrate, and a minimal urine solution containing only urea and the components of struvite and apatite were incubated with urease and test proteins in the depressions of culture slides. The number and size of rectangular and X-shaped struvite crystals were recorded using a low-power phase contrast microscope. Results: The formation of crystalline struvite appears to occur after the formation of an amorphous calcium-and magnesium-containing phase. The extent of this amorphous phase is dependent on the presence of calcium and citrate, both of which strongly promote its formation over the crystalline phase. alpha-globulin, gamma-globulin and chymotrypsin inhibitor all result in the same amount of crystalline struvite as bovine serum albumin which is used as a control. Calprotectin, on the other hand, causes consistent and significant reductions in the number and size of struvite crystals under a wide range of conditions. No changes in the morphology of the struvite crystals were observed. Conclusions: Calprotectin, the dominant protein of infection stone matrix, has distinctive properties which affect the formation and growth of struvite crystals. The presence of citrate in synthetic urine dramatically reduces the number of struvite crystals observed. The present method for observing the effects of putative infection stone inhibitors appears to have merit. C1 Harvard Univ, Dept Urol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. RP Dretler, SP (reprint author), Harvard Univ, Dept Urol, Massachusetts Gen Hosp, Sch Med, WACC 4,486,15 Parkman St, Boston, MA 02114 USA. NR 20 TC 9 Z9 10 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 1998 VL 159 IS 4 BP 1384 EP 1389 DI 10.1016/S0022-5347(01)63621-8 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA ZB163 UT WOS:000072442700093 PM 9507889 ER PT J AU Cambria, RP Davison, JK Giglia, JS Gertler, JP AF Cambria, RP Davison, JK Giglia, JS Gertler, JP TI Mesenteric shunting decreases visceral ischemia during thoracoabdominal aneurysm repair SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID AORTIC-ANEURYSM; NEUROLOGIC COMPLICATIONS; BYPASS; OPERATIONS AB Purpose: A technique to decrease visceral ischemic time during thoracoabdominal aneurysm (TAA) repair is reported. Methods: A 10 mm Dacron side-arm graft is attached to the aortic prosthesis and positioned immediately distal to the planned proximal thoracic aortic anastomosis. On completion of the anastomosis, a 16 to 22 Fr perfusion catheter is attached to the side-arm graft and inserted into the orifice of the celiac axis or superior mesenteric artery. The cross-clamp is then placed on the aortic graft distal to the mesenteric side-arm graft. Pulsatile arterial perfusion is thus established to the visceral circulation while intercostal anastomoses or reconstruction of celiac, superior mesenteric, and right renal arteries is performed. Visceral ischemic time and the rise in end-tidal Pco(2) after reconstruction of the visceral vessels in patients with mesenteric shunting was compared with a control group matched for aneurysm extent and treated immediately before use of the mesenteric shunt technique. Results: Between July and Oct, 1996, the technique was applied in 15 patients undergoing type I, II, or III TAA repair with a clamp and sew technique. The mean decrease in systolic arterial pressure was 12.5 +/- 8.5 mm Hg, with a concomitant rise in end-tidal Pco(2) (mean, 6.9 +/- 5.8 mm Hg), after perfusion was established through the mesenteric shunt. Mean time to establishment of visceral perfusion through the shunt was 25.5 +/- 4.4 minutes; the resultant decrement in visceral ischemic time averaged 31.3 minutes (i.e., until celiac, superior mesenteric, and right rend arteries were reconstructed). Compared with controls, patients with shunts had a significantly decreased (6.9 +/- 5.8 versus 21.6 +/- 8.4 mm Hg; p = 0.0003) rise in end-tidal CO2 on completion of visceral vessel reconstruction. Conclusions: In-line mesenteric shunting is a simple method to decrease visceral ischemia during TAA repair, and it is adaptable to clamp and sew or partial bypass and distal perfusion operative techniques. C1 Massachusetts Gen Hosp, Surg Serv, Div Vasc Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Div Anesthesia, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Cambria, RP (reprint author), Massachusetts Gen Hosp, Surg Serv, Div Vasc Surg, 15 Parkman St WAC 458, Boston, MA 02114 USA. NR 17 TC 36 Z9 36 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 1998 VL 27 IS 4 BP 745 EP 749 DI 10.1016/S0741-5214(98)70242-3 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA ZK806 UT WOS:000073365600021 PM 9576090 ER PT J AU Li, A Katinger, H Posner, MR Cavacini, L Zolla-Pazner, S Gorny, MK Sodroski, J Chou, TC Baba, TW Ruprecht, RM AF Li, A Katinger, H Posner, MR Cavacini, L Zolla-Pazner, S Gorny, MK Sodroski, J Chou, TC Baba, TW Ruprecht, RM TI Synergistic neutralization of simian-human immunodeficiency virus SHIV-vpu(+) by triple and quadruple combinations of human monoclonal antibodies and high-titer anti-human immunodeficiency virus type 1 immunoglobulins SO JOURNAL OF VIROLOGY LA English DT Article ID CD4 BINDING-SITE; PASSIVE-IMMUNIZATION; ENVELOPE GLYCOPROTEIN; CD4-BINDING SITE; SIV INFECTION; CONFORMATIONAL EPITOPE; CYNOMOLGUS MACAQUES; RHESUS-MONKEYS; HIV-1 GP120; V3 DOMAIN AB We have tested triple and quadruple combinations of human monoclonal antibodies (MAbs), which are directed against various epitopes on human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins, and a high-titer anti-HIV-1 human immunoglobulin (HIVIG) preparation for their abilities to neutralize a chimeric simian-human immunodeficiency virus (SHIV-vpu(+)). This virus encodes the HIV-1 strain IIIB env, tat, rev, and vpu genes. The quantitative nature of the Chou-Talalay method (Adv. Enzyme Regul. 22:27-55, 1984) allows ranking of various combinations under identical experimental conditions. Of all triple combinations tested, the most potent neutralization was seen with MAbs 694/98D plus 2F5 plus 2G12 (directed against domains on V3, gp41, and gp120, respectively) as measured by the total MAb concentration required to reach 90% neutralization (90% effective concentration [EC90], 2.0 mu g/ml). All triple combinations involving MAbs and/or HIVIG that were tested yielded synergy with combination index values of <1; the dose reduction indices (DRIs) ranged from 3.1 to 26.2 at 90% neutralization. When four MAbs (the previous three plus MAb F105, directed against the CD4 binding site) were combined, higher neutralization potency (EC90, 1.8 mu g/ml) and a higher degree of synergy compared to any triple combination were seen. The mean DRIs of the quadruple combination were approximately twice that of the most synergistic triple combination. We conclude that human MAbs targeting different HIV-1 envelope glycoprotein epitopes exhibit strong synergy when used in combination, a fact that could be exploited clinically for passive immunoprophylaxis against HIV-1. C1 Dana Farber Canc Inst, Lab Viral Pathogenesis, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Human Retrovirol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Agr Univ Vienna, Inst Appl Microbiol, A-1190 Vienna, Austria. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Hematol, Boston, MA 02215 USA. Vet Affairs Med Ctr, Res Ctr AIDS & HIV Infect, New York, NY 10010 USA. Mem Sloan Kettering Canc Ctr, Lab Preclin Pharmacol, New York, NY 10021 USA. Tufts Univ, Sch Med, Dept Pediat, Div Newborn Med, Boston, MA 02111 USA. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, Lab Viral Pathogenesis, 44 Binney St, Boston, MA 02115 USA. RI Chou, Ting-Chao/B-4111-2009 OI Chou, Ting-Chao/0000-0002-3340-1594 FU NIAID NIH HHS [R01 AI026926, R01 AI034266, R01 AI036085, R01-AI26926, R01-AI34266, R01-AI36085] NR 51 TC 62 Z9 63 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 3235 EP 3240 PG 6 WC Virology SC Virology GA ZC506 UT WOS:000072586900079 PM 9525650 ER PT J AU Ghorpade, A Xia, MQ Hyman, BT Persidsky, Y Nukuna, A Bock, P Che, MH Limoges, J Gendelman, HE Mackay, CR AF Ghorpade, A Xia, MQ Hyman, BT Persidsky, Y Nukuna, A Bock, P Che, MH Limoges, J Gendelman, HE Mackay, CR TI Role of the beta-chemokine receptors CCR3 and CCR5 in human immunodeficiency virus type 1 infection of monocytes and microglia SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-DEFICIENCY-SYNDROME; HIV-1 INFECTION; LYMPHOCYTES; INDIVIDUALS; REPLICATION; RESISTANCE; ENTRY; CELL; STEP; IDENTIFICATION AB Human immunodeficiency virus type 1 (HIV-1) infection in mononuclear phagocyte lineage cells (monocytes, macrophages, and microglia) is a critical component in the pathogenesis of viral infection. Viral replication in macrophages sen;es as a reservoir, a site of dissemination, and an instigator for neurological sequelae during HIV-1 disease. Recent studies demonstrated that chemokine receptors are necessary coreceptors for HIV-1 entry which determine viral tropism for different cell types. To investigate the relative contribution of the beta-chemokine receptors CCR3 and CCR5 to viral infection of mononuclear phagocytes we utilized a panel of macrophage-tropic HIV-1 strains (from blood and brain tissue) to infect highly purified populations of monocytes and microglia. Antibodies to CD4 (OKT4A) abrogated HIV-1 infection. The beta chemokines and antibodies to CCR3 failed to affect viral infection of both macrophage cell types. Antibodies to CCR5 (3A9) prevented monocyte infection but only slowed HIV replication in microglia. Thus, CCR5, not CCR3, is an essential receptor for HIV-1 infection of monocytes. Microglia express both CCR5 and CCR3, but antibodies to them fail to inhibit viral entry, suggesting the presence of other chemokine receptors for infection of these cells. These studies demonstrate the importance of mononuclear phagocyte heterogeneity in establishing HIV-1 infection and persistence. C1 Univ Nebraska, Med Ctr, Ctr Neurovirol & Neurodegenerat Disorders, Omaha, NE 68198 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Alzheimers Res Ctr, Boston, MA 02114 USA. LeukoSite Inc, Cambridge, MA 02142 USA. RP Gendelman, HE (reprint author), Univ Nebraska, Med Ctr, Ctr Neurovirol & Neurodegenerat Disorders, Box 985215,600 S 42nd St, Omaha, NE 68198 USA. EM hegendel@mail.unme.edu RI Mackay, Charles/A-9673-2008 OI Mackay, Charles/0000-0002-6338-7340 FU NINDS NIH HHS [P01 NS031492, P01 NS31492-05, R01 NS034239, R01 NS036126, R01 NS34239-04, 1 R01 NS36126-01] NR 44 TC 125 Z9 127 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 3351 EP 3361 PG 11 WC Virology SC Virology GA ZC506 UT WOS:000072586900091 PM 9525662 ER PT J AU Montefiori, DC Reimann, KA Wyand, MS Manson, K Lewis, MG Collman, RG Sodroski, JG Bolognesi, DP Letvin, NL AF Montefiori, DC Reimann, KA Wyand, MS Manson, K Lewis, MG Collman, RG Sodroski, JG Bolognesi, DP Letvin, NL TI Neutralizing antibodies in sera from macaques infected with chimeric simian-human immunodeficiency virus containing the envelope glycoproteins of either a laboratory-adapted variant or a primary isolate of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; PERSISTENT INFECTION; RHESUS-MONKEYS; HIV-1; VACCINE; GP120; AIDS; OLIGOMER; FUSION; SEROTYPES AB The magnitude and breadth of neutralizing antibodies raised in response to infection with chimeric simian-human immunodeficiency virus (SHIV) in rhesus macaques were evaluated. Infection with either SHIV-HXB2, SHIV-89.6, or SHIV-89.6PD raised high-titer neutralizing antibodies to the homologous SHIV (SHIV-89.6P in the ease of SHIV-89.6PD-infected animals) and significant titers of neutralizing antibodies to human immunodeficiency virus type 1 (HIV-1) strains MN and SF-2. With few exceptions, however, titers of neutralizing antibodies to heterologous SHIV were low or undetectable. The antibodies occasionally neutralized heterologous primary isolates of HIV-1; these antibodies required >40 weeks of infection to reach detectable levels. Notable was the potent neutralization of the HIV-1 89.6 primary isolate by serum samples from SHIV-89.6infected macaques. These results demonstrate that SHIV-HXB2, SHIV-89.6, and SHIV-89.6P possess highly divergent, strain-specific neutralization epitopes. The results also provide insights into the requirements for raising neutralizing antibodies to primary isolates of HIV-1. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. GTC Mason Labs, Worcester, MA USA. Henry M Jackson Fdn, Rockville, MD USA. Univ Penn, Sch Med, Div Pulm & Crit Care, Philadelphia, PA 19104 USA. RP Montefiori, DC (reprint author), Duke Univ, Med Ctr, Dept Surg, Box 2926, Durham, NC 27710 USA. EM monte005@mc.duke.edu FU NCI NIH HHS [R01 CA050139]; NCRR NIH HHS [K01 RR000163, K26 RR000168, P51 RR000163, P51 RR000168, T32 RR007000]; NIAID NIH HHS [R37 AI020729, AI-15114, AI-35166, P30 AI028691, R01 AI020729, R01 AI033832, R01 AI035502]; PHS HHS [6S-1649] NR 46 TC 67 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 3427 EP 3431 PG 5 WC Virology SC Virology GA ZC506 UT WOS:000072586900104 PM 9525675 ER PT J AU Kraut, JA Hiura, J Shin, JM Smolka, A Sachs, G Scott, D AF Kraut, JA Hiura, J Shin, JM Smolka, A Sachs, G Scott, D TI The Na+-K+-ATPase beta 1 subunit is associated with the HK alpha 2 protein in the rat kidney SO KIDNEY INTERNATIONAL LA English DT Article DE renal H+-K+-ATPase; H+-K+-ATPase beta subunit; Na+-K+-ATPase beta(1) subunit ID FUNCTIONAL EXPRESSION; GASTRIC H,K-ATPASE; DISTAL COLON; ALPHA-SUBUNIT; H+; H+,K+-ATPASE; TRANSPORT; OUABAIN; TUBULE; CELLS AB The Na-K-ATPase beta 1 subunit. acts as the beta subunit for the HK alpha(2) protein in the rat kidney. The colonic H+-K+-ATPase is a member of the P-type ATPases, and has been shown to contribute to potassium transport by the mammalian kidney; and colon. The P-type ATPases often consist of an alpha subunit that contains the catalytic site and a beta subunit that participates In regulation of enzyme activity; and targeting of the enzyme to the plasma membrane. The cDNA of the alpha subunit (HK alpha(2)) has been cloned and the HK alpha(2) protein has been isolated from the rat kidney and colon. However, a unique beta subunit for the colonic H+-K+-ATPase has not been described. To determine if one of the known beta subunits present in the kidney might act as the beta subunit for the colonic H+-K+-ATPase, microsomes enriched in the colonic H+-K+-ATPase were isolated using an HK alpha(2)-specific antibody (AS 31.7) and the Minimac magnetic separation system. Immunoblots of rat kidney microsomal protein isolated with antibody AS 31.7 were probed with antibodies directed against the gastric HK beta subunit. Na+-K+-ATPase alpha 1, and Na+-K+-ATPase beta 1 subunits. A band of the appropriate size was detected with Na+-K+-ATPase beta(1)-specific antibodies, but not those directed against HK beta(1). These data suggest that Na+-K+-ATPase beta(1) could be the beta subunit for the colonic H+-K+-ATPase in the kidney. C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Div Nephrol 691 111L, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med,W Los Angeles Vet Affairs Med Ctr, Membrane Biol Lab, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Med Univ S Carolina, Div Med, Columbia, SC USA. RP Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Div Nephrol 691 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK43138] NR 32 TC 35 Z9 35 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 EI 1523-1755 J9 KIDNEY INT JI Kidney Int. PD APR PY 1998 VL 53 IS 4 BP 958 EP 962 DI 10.1046/j.1523-1755.1998.00841.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA ZD423 UT WOS:000072683700018 PM 9551404 ER PT J AU Hricik, DE Harrington, JT Madias, NE King, AJ Perrone, RD Singh, A Levey, AS Williams, ME AF Hricik, DE Harrington, JT Madias, NE King, AJ Perrone, RD Singh, A Levey, AS Williams, ME TI Combined kidney-pancreas transplantation SO KIDNEY INTERNATIONAL LA English DT Editorial Material DE transplantation; euglycemia; pancreatic transplant; endocrine system; diabetes; end-stage renal disease ID I DIABETIC RECIPIENTS; QUALITY-OF-LIFE; TERM GLUCOSE CONTROL; ALLOGRAFT-REJECTION; RENAL-FUNCTION; MULTIVARIATE-ANALYSIS; GLOMERULAR STRUCTURE; EXOCRINE SECRETIONS; ALONE TRANSPLANTS; ENTERIC DRAINAGE C1 Univ Hosp Cleveland, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Med, Div Nephrol, Cleveland, OH 44106 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr W, Boston, MA 02215 USA. RP Hricik, DE (reprint author), Univ Hosp Cleveland, Dept Med, 11100 Euclid Ave, Cleveland, OH 44106 USA. NR 103 TC 7 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 1998 VL 53 IS 4 BP 1091 EP 1102 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA ZD423 UT WOS:000072683700038 PM 9551424 ER PT J AU Kobayashi, T Taniguchi, S Ye, Y Niekrasz, M Nour, B Cooper, DKC AF Kobayashi, T Taniguchi, S Ye, Y Niekrasz, M Nour, B Cooper, DKC TI Comparison of bile chemistry between humans, baboons, and pigs: Implications for clinical and experimental liver xenotransplantation SO LABORATORY ANIMAL SCIENCE LA English DT Article ID HEPATIC-FAILURE; TRANSPLANTATION; PRIMATE C1 Baptist Med Ctr, Oklahoma Transplantat Inst, Oklahoma City, OK 73112 USA. Univ Oklahoma, Hlth Sci Ctr, Div Anim Resources, Oklahoma City, OK USA. RP Cooper, DKC (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. OI Nour, Bakr/0000-0003-1684-1907 NR 22 TC 13 Z9 14 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD APR PY 1998 VL 48 IS 2 BP 197 EP 200 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 109KF UT WOS:000075321000013 PM 10090014 ER PT J AU de la Monte, SM Sohn, YK Ganju, N Wands, JR AF de la Monte, SM Sohn, YK Ganju, N Wands, JR TI p53- and CD95-associated apoptosis in neurodegenerative diseases SO LABORATORY INVESTIGATION LA English DT Article ID PROGRAMMED CELL-DEATH; ALZHEIMERS-DISEASE; DNA FRAGMENTATION; FAS; DIFFERENTIATION; EXPRESSION; INVOLVEMENT; LINEAGE; SYSTEM; MICE AB Apoptosis is likely to be an important mechanism of cell loss in neurodegenerative diseases, but the signaling cascades activated before DNA fragmentation have nut yet been determined. p53 or CD95 gene up-regulation precedes apoptosis in many cell types, and a potential role for these molecules in apoptosis of neurons and glial cells has already been demonstrated in Alzheimer's disease (AD). To determine whether apoptosis in other neurodegenerative diseases is mediated by similar mechanisms, p53 and CD95 expression were examined in postmortem central nervous system tissues from patients with diffuse Lewy body disease (DLBD), Pick's disease (PkD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and Down's syndrome plus Alzheimer's disease (DN+AD). Quantitative immunoblot analysis demonstrated higher temporal lobe levels of p53 and CD95 proteins in DLBD, PkD, and DN+AD, and higher temporal lobe levels of CD95 only in MSA and PSP relative to PD and aged controls (for all, p < 0.01). In histologic sections, increased p53 immunoreactivity was localized in neuronal and glial cell nuclei, neuronal perikarya, and dystrophic neuritic and glial cell processes in the frontal (Area 11) and temporal (Area 21) robes in DLBD, PkD, and DN+AD, the motor cortex and spinal ventral horns in ALS, and the striatum and midbrain in DLBD, MSA, PD, and PSP. Increased CD95 expression and nuclear DNA fragmentation were present in the same cell types and structures that manifested increased nuclear p53 immunoreactivity. The results suggest that p53- or CD95-associated apoptosis may be a common mechanism of cell loss in several important neurodegenerative diseases. In addition, the presence of abundant p53-immunoreactive neurites and glial cell processes appears to be a novel feature of neurodegeneration shared by these distinct diseases. C1 Massachusetts Gen Hosp, Ctr Canc, Div Neuropathol, Boston, MA USA. Massachusetts Gen Hosp, Ctr Canc, Alzheimers Dis Res Ctr, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA USA. RP de la Monte, SM (reprint author), Massachusetts Gen Hosp E, Ctr Canc, Room 7308,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA-35711]; NIAAA NIH HHS [AA-11431] NR 37 TC 151 Z9 153 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 1998 VL 78 IS 4 BP 401 EP 411 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA ZH996 UT WOS:000073169200004 PM 9564885 ER PT J AU de Mora, F Williams, CMM Frenette, PS Wagner, DD Hynes, RO Galli, SJ AF de Mora, F Williams, CMM Frenette, PS Wagner, DD Hynes, RO Galli, SJ TI P- and E-selectins are required for the leukocyte recruitment, but not the tissue swelling, associated with IgE- and mast cell-dependent inflammation in mouse skin SO LABORATORY INVESTIGATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; ALLERGIC AIRWAY INFLAMMATION; DEFICIENT MICE; ADHESION MOLECULE-1; IN-VIVO; CONTACT HYPERSENSITIVITY; ENDOTHELIAL SELECTINS; INFILTRATION; INHIBITION; SUSCEPTIBILITY AB Many studies, in both experimental animal and human systems, have indicated that P- and/or E-selectins may contribute importantly to the leukocyte recruitment that occurs in association with mast cell-dependent inflammatory responses. We used mice that genetically lack P-selectin (P -/-), E-selectin (E -/-), or both selectins (P/E -/-) to investigate the possible roles of these selectins in the IgE- and mast cell-dependent recruitment of neutrophils to the skin of mice. We found that a lack of either or both selectins had little or no effect on the extent of mast cell degranulation or the tissue swelling associated with these reactions. Moreover, a lack of either P-or E-selectin alone did not reduce the neutrophil infiltration at the reaction sites. However, mice lacking both P-and E-selectins exhibited an almost complete ablation of IgE- and mast cell-dependent neutrophil recruitment. These findings show that P-and E-selectins can express overlapping functions in leukocyte recruitment associated with IgE- and mast cell-dependent cutaneous tale-phase reactions in mouse skin, and that a lack of both selectins results in a virtual elimination of IgE-dependent leukocyte recruitment. C1 Beth Israel Deaconess Med Ctr, Div Expt Pathol, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Ctr Blood Res, Dept Pathol, Boston, MA 02115 USA. MIT, Howard Hughes Med Inst, Cambridge, MA USA. MIT, Ctr Canc Res, Dept Biol, Cambridge, MA USA. RP Galli, SJ (reprint author), Beth Israel Deaconess Med Ctr, Div Expt Pathol, Dept Pathol, POB 15707, Boston, MA 02215 USA. RI Frenette, Paul/J-8272-2012; de Mora, Fernando/O-4636-2014 OI de Mora, Fernando/0000-0002-3002-6004 FU NCI NIH HHS [CA/AI-72074]; NHLBI NIH HHS [HL-53756]; NIAID NIH HHS [AI/GM-23990] NR 42 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 1998 VL 78 IS 4 BP 497 EP 505 PG 9 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA ZH996 UT WOS:000073169200013 PM 9564894 ER PT J AU Gliklich, RE Rounds, MF Cheney, ML Varvares, MA AF Gliklich, RE Rounds, MF Cheney, ML Varvares, MA TI Combining free flap reconstruction and craniofacial prosthetic technique for orbit, scalp, and temporal defects SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 31-FEB 02, 1997 CL BOSTON, MASSACHUSETTS SP Amer Laryngol Rhinol & Otol Soc, E Sect ID MAXILLARY DEFECTS; BONE AB Objectives: To identify factors leading to successful application of prosthetic techniques following free flap reconstruction of the orbit, scalp, and temporal region. Study Design: Retrospective review. Methods: Twenty-eight patients who underwent free flap reconstruction for defects of these regions between 1989 and 1996 were reviewed for clinical parameters, flap loss, patient survival, and implant loss rate. Prosthetic usage rates were compared before and after introduction of a site-specific reconstructive algorithm, Results: Free Bap success rate was 93%, whereas osseointegrated implant loss rate mas 11%, In addition to implants, a reconstructive strategy that provided thin, vascular tissue between bone and shin, a flat platform in the temporal region, and preservation of orbital cavity depth led to increased prosthetic usage. Conclusions: Craniofacial prosthetic techniques can significantly augment the results of free flap surgery for the orbit, scalp, and temporary region, Successful combination of these techniques requires a site-specific surgical approach. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Gliklich, RE (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Facial Plast & Reconstruct Surg, 243 Charles St, Boston, MA 02114 USA. NR 17 TC 12 Z9 12 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 1998 VL 108 IS 4 BP 482 EP 487 DI 10.1097/00005537-199804000-00004 PN 1 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA ZF846 UT WOS:000072939100004 PM 9546256 ER PT J AU Fried, MP Hsu, LG Jolesz, FA AF Fried, MP Hsu, LG Jolesz, FA TI Inter-active magnetic resonance imaging-guided biopsy in the head and neck: Initial patient experience SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Laryngological-Rhinological-and-Otological-Society CY MAY 11-14, 1997 CL SCOTTSDALE, ARIZONA SP Amer Laryngol Rhinol & Otol Soc Inc ID FINE-NEEDLE ASPIRATION; CYTOLOGY; DIAGNOSIS; LESIONS; SYSTEM AB Because of its excellent soft tissue resolution, magnetic resonance imaging (MRP) can optimize image guidance for interventional and surgical procedures, Notably, needle biopsy of head and neck lesions has been used for years, deeper lesions often requiring some form of image guidance, The closed space of diagnostic MRI scanners proves cumbersome for interventional . The authors report on the first head and neck image-guided biopsies performed in a new, investigational "open configuration" intraoperative MRI scanner, Vertical space between the scanner's upright coils gives access to the patient while imaging; image acquisition is as fast as 2 sec/image, Biopsies were performed can seven patients (parotid, parapharyngeal space, second cervical. vertebra; five specimens were diagnostic, Both general anesthesia and intravenous sedation were used,The procedures were without complications, Imaging provided definition of anatomy to direct needle placement. Access to the patient allowed for both percuetaneous and transoral approaches, The environment of the open map net is well suited for biopsy of the head and neck, and near real-time intraoperative MRI has promise for guiding more complex head and neck procedures, Further study should optimize the quality of the images and the interactibility of localization and targeting and fully utilize MRI's three-dimensional imaging capabilities. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Joint Ctr Otolaryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Joint Ctr Otolaryngol, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Fried, MP (reprint author), Harvard Univ, Sch Med, Dept Otol & Laryngol, Joint Ctr Otolaryngol, 333 Longwood Ave, Boston, MA 02115 USA. NR 15 TC 15 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 1998 VL 108 IS 4 BP 488 EP 493 DI 10.1097/00005537-199804000-00005 PN 1 PG 6 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA ZF846 UT WOS:000072939100005 PM 9546257 ER PT J AU Gacek, MR Gacek, RR Gantz, B McKenna, M Goodman, M AF Gacek, MR Gacek, RR Gantz, B McKenna, M Goodman, M TI Pseudoepitheliomatous hyperplasia versus squamous cell carcinoma of the external auditory canal SO LARYNGOSCOPE LA English DT Article AB Four case reports are presented to demonstrate the clinical and histopathologic similarity of pseudoepitheliomatous hyperplasia (PII) to squamous cell carcinoma (SCC) in the external auditory canal (EAC). in all four cases the original report of SCC on a biopsy specimen of an EAC lesion was corrected on review to PH, In one patient conservative management resulted in resolution of the EAC lesion, A. second patient underwent radiation therapy and partial temporal bone resection with no SCC found in the surgical specimen, A third patient's ear canal had healed with conservative treatment and repeated biopsy revealed no malignancy, After a 6-year symptom-free interval, she developed invasive SCC with bone involvement that required surgery and radiation treatment, A fourth patient underwent, a sleeve resect-ion of the skin of the EAC that proved to be PR, and no evidence of SCC was found, A thoughtful clinical history, careful physical examination, response to conservative treatment, and close communication with the pathologist should be exercised in the evaluation of EAC lesions. C1 Univ Iowa, Dept Otolaryngol, Iowa City, IA USA. SUNY Hlth Sci Ctr, Dept Otolaryngol, Syracuse, NY 13210 USA. Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Gacek, RR (reprint author), 750 E Adams St, Syracuse, NY 13210 USA. NR 8 TC 17 Z9 18 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 1998 VL 108 IS 4 BP 620 EP 623 DI 10.1097/00005537-199804000-00029 PN 1 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA ZF846 UT WOS:000072939100029 PM 9546281 ER PT J AU Mandeville, JB Marota, JJA Kosofsky, BE Keltner, JR Weissleder, R Rosen, BR Weisskoff, RM AF Mandeville, JB Marota, JJA Kosofsky, BE Keltner, JR Weissleder, R Rosen, BR Weisskoff, RM TI Dynamic functional imaging of relative cerebral blood volume during rat forepaw stimulation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE fMRI; CBV; rat; contrast agent ID HUMAN VISUAL-CORTEX; CONTRAST AGENTS; IRON-OXIDE; BRAIN; OXYGENATION; ACTIVATION; FLOW; NMR; MRI; WATER AB Dynamic measurements of regional changes in cerebral blood volume (CBV) were performed in rat models of hypercarbia and focal neuronal activation using T-2-weighted imaging after injection of an intravascular contrast agent with a very long blood half-life. Calculated percent CBV change during hypercarbia was consistent with literature results from other noninvasive modalities. Equivalent percent CBV increases were found using spin-and gradient-echo images, suggesting proportional changes in blood volume for capillaries and small veins. During electrical stimulation of rat forepaw, focal CBV response to stimulation (24 +/- 4%) was significantly delayed relative to blood oxygen level dependent (BOLD) signal after both onset and cessation of stimulation. Poststimulus CBV decay was temporally consistent with the BOLD poststimulus undershoot. The use of exogenous agent increased the functional contrast-to-noise ratio relative to BOLD imaging by 5.7 +/- 1.3 at a magnetic field strength of 2 Tesla and 1.5 +/- 0.2 at 4.7 Tesla. C1 Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesiol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Mandeville, JB (reprint author), Massachusetts Gen Hosp, NMR Ctr, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01CA48729]; NHLBI NIH HHS [R01HL39810]; NIDA NIH HHS [DA09467] NR 44 TC 398 Z9 404 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn.Reson.Med. PD APR PY 1998 VL 39 IS 4 BP 615 EP 624 DI 10.1002/mrm.1910390415 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZD581 UT WOS:000072700900014 PM 9543424 ER PT J AU McHorney, CA AF McHorney, CA TI Methodological inquiries in health status assessment SO MEDICAL CARE LA English DT Editorial Material ID QUALITY-OF-LIFE; MENTAL-HEALTH; DOUBLE-BLIND; DEPRESSION; OUTCOMES C1 Univ Wisconsin, Sch Med, Madison, WI 53706 USA. William S Middleton Mem Vet Hosp, Hlth Serv Res & Dev Program, Madison, WI USA. RP McHorney, CA (reprint author), Univ Wisconsin, Sch Med, Madison, WI 53706 USA. NR 28 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 1998 VL 36 IS 4 BP 445 EP 448 DI 10.1097/00005650-199804000-00001 PG 4 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA ZF245 UT WOS:000072878200001 PM 9544585 ER PT J AU Ubel, PA Spranca, MD DeKay, ML Hershey, JC Asch, DA AF Ubel, PA Spranca, MD DeKay, ML Hershey, JC Asch, DA TI Public preferences for prevention versus cure: What if an ounce of prevention is worth only an ounce of cure? SO MEDICAL DECISION MAKING LA English DT Article DE rationing; allocation; person tradeoff; public survey; ethics ID HEALTH-CARE; TRADE-OFF AB Background. The belief that small preventive efforts bring large benefits may explain why many people say they value prevention above all other types of health care. However, it often takes a great deal of preventive medicine to prevent a bad outcome. This study explores whether people value prevention or cure more when each brings the same magnitude of benefit and examines whether preferences for prevention or cure vary according to the severity of the disability of the patients who can receive the preventive or curative intervention. Methods. 289 prospective jurors were presented with a policy dilemma involving how best to allocate funds to benefit people with varying levels of disability. Each project was said to influence the functional ability of 100 nursing home residents, either by improving their level of function or by preventing their level of function from declining. Results. When given a choice between preventive and curative interventions, more subjects preferred the preventive intervention (37% vs 21%, p = 0.002). However, when the strength of people's preferences was taken into account, the preference for preventive interventions was not statistically significant (p = 0.135). With both preventive and curative interventions, the subjects preferred helping patients with more severe disabilities (p < 0.005 for both comparisons). This preference for helping more severely disabled patients did not differ for prevention and cure (p = 0.663). Conclusion. When the magnitude of benefit was held constant, the subjects slightly preferred prevention over cure. In addition, they preferred directing limited resources toward those with greater disabilities, regardless of whether those resources were targeted toward prevention or cure. These findings suggest that previously stated preferences for prevention over cure may result from a belief that small efforts at prevention will be repaid by large reductions in the later need for cure. C1 Univ Penn, Sch Med, Ctr Bioeth, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Rand Corp, Santa Monica, CA USA. Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. Univ Penn, Wharton Sch, Pittsburgh, PA USA. RP Ubel, PA (reprint author), Univ Penn, Sch Med, Ctr Bioeth, Div Gen Internal Med, 3401 Market St,Suite 320, Philadelphia, PA 19104 USA. NR 10 TC 32 Z9 32 U1 0 U2 2 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD APR-JUN PY 1998 VL 18 IS 2 BP 141 EP 148 PG 8 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA ZG626 UT WOS:000073022700002 PM 9566447 ER PT J AU Asch, DA Hershey, JC DeKay, ML Pauly, MV Patton, JP Jedrziewski, MK Frei, F Giardine, R Kant, JA Mennuti, MT AF Asch, DA Hershey, JC DeKay, ML Pauly, MV Patton, JP Jedrziewski, MK Frei, F Giardine, R Kant, JA Mennuti, MT TI Carrier screening for cystic fibrosis: Costs and clinical outcomes SO MEDICAL DECISION MAKING LA English DT Article DE cost-effectiveness; cystic fibrosis; decision making; economics; ethics; genetics; health policy; health screening; methodology; modeling ID PRENATAL-DIAGNOSIS; SPONTANEOUS-ABORTION; PREGNANCIES; ULTRASOUND; WILLINGNESS; ATTITUDES; BENEFITS; ENZYMES; GENE; PAY AB Objectives. To evaluate the costs and clinical effects of 16 alternative strategies for cystic fibrosis (CF) carrier screening in the reproductive setting; and to test the sensitivity of the results to assumptions about cost and detection rate, stakeholder perspective, DNA test specificity, chance of nonpaternity, and couples' reproductive plans. Method. Cost-effectiveness analysis. Results. A sequential screening strategy had the lowest cost per CF birth avoided. In this strategy, the first partner was screened with a standard test that identifies 85% of carriers. The second partner was screened with an expanded test if the first partner's screen was positive. This strategy identified 75% of anticipated CF births at a cost of $367,000 each. This figure does not include the lifetime medical costs of caring for a patient with CF, and it assumes that couples who identify a pregnancy at risk will choose to have prenatal diagnosis and termination of affected pregnancies. The cost per CF birth identified is approximately half this figure when couples plan two children. Conclusions. The cost-effectiveness of CF carrier screening depends greatly on couples' reproductive plans. CF carrier screening is most cost-effective when it is performed sequentially, when the information is used for more than one pregnancy, and when the intention of the couple is to identify and terminate affected pregnancies. These conclusions are important for policy considerations regarding population-based screening for CF, and may also have important implications for screening for less common diseases. C1 Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Ctr Bioeth, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Dept Hlth Care Syst, Philadelphia, PA 19104 USA. Univ Rochester, Simon Sch Business, Rochester, NY 14627 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Asch, DA (reprint author), Univ Penn, Sch Med, Div Gen Internal Med, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM asch@wharton.upenn.edu FU NHGRI NIH HHS [R01-1HG00616, R01-1HG00621] NR 36 TC 17 Z9 18 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD APR-JUN PY 1998 VL 18 IS 2 BP 202 EP 212 PG 11 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA ZG626 UT WOS:000073022700008 PM 9566453 ER PT J AU McGibbon, CA Palmer, WE Krebs, DE AF McGibbon, CA Palmer, WE Krebs, DE TI A general computing method for spatial cartilage thickness from co-planar MRI SO MEDICAL ENGINEERING & PHYSICS LA English DT Article DE MRI; acetabulum; cartilage thickness; spatial thickness distribution ID ARTICULAR-CARTILAGE; HYALINE CARTILAGE; ULTRASONIC MEASUREMENT; KNEE; QUANTIFICATION; JOINT; OPTIMIZATION; CCM; HIP AB Techniques for assessing cartilage thickness from planar magnetic resonance (MR) images have traditionally accounted for surface curvature only in the image plane. Many joints, such as the knee and hip, have significant curvature normal (transverse) to the image plane which results in overestimation of in-plane cartilage thickness measurements. We developed a generalized computing method for calculating spatial thickness distribution of joint cartilage from co-planar MR images which accounts for transverse surface curvature. We applied the technique using fat-suppressed SPGR (spoiled gradient recalled in the steady-state) MR images of two human acetabulae and compared the results with a previously validated spherical model of the acetabulum which also accounts for transverse curvature of the cartilage surface. The agreement between the generalized model and validated spherical model was very good for both acetabular specimens (correlation: r = 0.998, p < 0.001; differences: p > 0.63). We conclude that the generalized method is acceptable for computing spatial cartilage thickness distribution of joints with complex geometries, such as the knee. (C) 1998 IPEM. published by Elsevier Science Ltd. C1 Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP McGibbon, CA (reprint author), Massachusetts Gen Hosp, Dept Orthopaed, Biomot Lab, RSH 010,40 Parkman St, Boston, MA 02114 USA. FU NICHD NIH HHS [R01-HD30063] NR 21 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1350-4533 J9 MED ENG PHYS JI Med. Eng. Phys. PD APR PY 1998 VL 20 IS 3 BP 169 EP 176 DI 10.1016/S1350-4533(98)00016-2 PG 8 WC Engineering, Biomedical SC Engineering GA ZZ884 UT WOS:000074778200002 PM 9690486 ER PT J AU Holt, JC Hatcher, VB Caulfield, JB Norton, P Umeda, PK Melendez, JA Martino, L Mudzinsky, SP Blumenstock, F Slayter, HS Margossian, SS AF Holt, JC Hatcher, VB Caulfield, JB Norton, P Umeda, PK Melendez, JA Martino, L Mudzinsky, SP Blumenstock, F Slayter, HS Margossian, SS TI Cloning of the cDNA and nucleotide sequence of a skeletal muscle protease from myopathic hamsters SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE cardiomyopathy; serine proteases; myosin light chain 2; cDNA cloning; mast cells; mekratin ID MAST-CELL PROTEASE; CARDIAC MYOSIN; HUMAN HEART; LIGHT CHAIN-2; IMMUNOLOGICAL CHARACTERIZATION; DILATED CARDIOMYOPATHY; MOLECULAR-CLONING; SUBUNIT FUNCTION; IDENTIFICATION; CHYMASE AB A neutral protease with an estimated M-r of about 26 kD and responsible for cleavage of myosin LC2 was isolated from hamster skeletal muscle. Complementary DNAs were generated by RT-PCR using total hamster muscle RNA and degenerate oligonucleotide primers based on the sequences of two internal peptides. The nucleotide sequences of the resultant cDNAs were subsequently determined and the complete amino acid sequence of the protease deduced. Although the hamster protein shared 63-85% identity in nucleotide and amino acid sequences with rat and mouse mast cell proteases, it had a higher degree of specificity for myosin LC2 than mast cell proteases which also digested myosin LC1 and myosin heavy chains. As a result, the hamster protease was designated mekratin because of its unique enzymatic specificities to distinguish it from other mast cell proteases. A polyclonal antibody was raised specific to the hamster muscle and human cardiac muscle mekratins without apparent cross-reaction with rat mast cell proteases. We have earlier demonstrated the presence in excess of a neutral protease that specifically cleaves LC2 in human hearts obtained at end stage idiopathic dilated cardiomyopathy (IDC). Western analyses revealed that heart tissue from patients with IDC contained 5-10 fold more mekratin than control samples. Furthermore, the level of the protease in human IDC tissues was similar to that seen in myopathic hamster skeletal muscle. No bands were recognized by the antibody when IDC myofibrils were probed due to the removal of soluble proteins during sample preparation. Thus, these results strongly suggest that the anti-mekratin antibody will provide positive identification of IDC in many cases and diagnosis by exclusion may be replaced. C1 Rhone Poulenc Rorer Cent Res, King Of Prussia, PA 19406 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Albany Med Coll, Dept Biochem & Mol Biol, Albany, NY 12208 USA. Albany Med Coll, Dept Med, Albany, NY 12208 USA. Albany Med Coll, Dept Pathol & Lab Med, Albany, NY 12208 USA. Albany Med Coll, Dept Physiol & Cell Biol, Albany, NY 12208 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Margossian, SS (reprint author), Ferrahian Armenian Sch, 5300 White Oak Ave, Encino, CA 91316 USA. EM smargossian@worldnet.att.net FU NHLBI NIH HHS [HL44094, HL49597] NR 43 TC 7 Z9 10 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 1998 VL 181 IS 1-2 BP 125 EP 135 DI 10.1023/A:1006842332340 PG 11 WC Cell Biology SC Cell Biology GA ZD328 UT WOS:000072674200014 PM 9562249 ER PT J AU Aramburu, J Garcia-Cozar, F Raghavan, A Okamura, H Rao, A Hogan, PG AF Aramburu, J Garcia-Cozar, F Raghavan, A Okamura, H Rao, A Hogan, PG TI Selective inhibition of NFAT activation by a peptide spanning the calcineurin targeting site of NFAT SO MOLECULAR CELL LA English DT Article ID TRANSCRIPTION FACTOR NFAT1; CYCLOSPORINE-A; T-CELLS; NUCLEAR FACTOR; PROTEIN PHOSPHATASE-1; SIGNAL-TRANSDUCTION; CYTOKINE GENES; SMOOTH-MUSCLE; LYMPHOCYTES-T; TAU-PROTEIN AB NFAT transcription factors play a key role in the immune response. The activation of NFAT proteins is controlled by calcineurin, the calmodulin-dependent phosphatase that is inhibited by the immunosuppressive drugs cyclosporin A and FK506. Here, we identify a short conserved sequence in NFAT proteins that targets calcineurin to NFAT. Mutation of a single residue in this sequence impairs the calcineurin-mediated dephosphorylation and nuclear translocation of NFAT1. Peptides spanning the region inhibit the ability of calcineurin to bind to and dephosphorylate NFAT proteins, without affecting the phosphatase activity of calcineurin against other substrates. When expressed intracellularly, a corresponding peptide inhibits NFAT dephosphorylation, nuclear translocation, and NFAT-mediated gene expression in response to stimulation. Thus, disruption of the enzyme-substrate docking interaction that directs calcineurin to NFAT can effectively block NFAT-dependent functions. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Garcia-Cozar, Francisco/A-6212-2013; Aramburu, J/G-8991-2014 OI Garcia-Cozar, Francisco/0000-0003-3720-259X; Aramburu, J/0000-0001-9279-9523 FU PHS HHS [AL 40127] NR 55 TC 202 Z9 208 U1 0 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD APR PY 1998 VL 1 IS 5 BP 627 EP 637 DI 10.1016/S1097-2765(00)80063-5 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZK610 UT WOS:000073342400001 PM 9660947 ER PT J AU Coughlin, EM Christensen, E Kunz, PL Krishnamoorthy, KS Walker, V Dennis, NR Chalmers, RA Elpeleg, ON Whelan, D Pollitt, RJ Ramesh, V Mandell, R Shih, VE AF Coughlin, EM Christensen, E Kunz, PL Krishnamoorthy, KS Walker, V Dennis, NR Chalmers, RA Elpeleg, ON Whelan, D Pollitt, RJ Ramesh, V Mandell, R Shih, VE TI Molecular analysis and prenatal diagnosis of human fumarase deficiency SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE fumarase deficiency; fumaric aciduria; inborn error of metabolism; gene mutation; prenatal diagnosis; chorionic villi; single-strand conformation polymorphism ID NUCLEOTIDE-SEQUENCE; ESCHERICHIA-COLI; 2 SIBLINGS; GENE; MITOCHONDRIAL; LIVER AB Fumarase deficiency is a rare autosomal recessive disorder of the citric acid cycle causing severe neurological impairment. The cDNA for both the rat and human enzymes has been cloned previously and shown to encode a coding region of 1.46kb, To scan for mutations in fumarase-deficient patients we amplified the coding region of fumarase from fibroblast/lymphoblast cDNA employing the oligonucleotide primers designed from the published human and rat cDNA sequence. We then directly sequenced the polymerase chain reaction product. Zn seven unrelated patients, we detected four missense mutations (A265T, D383V, F269C, K187R), a nonsense mutation (W458X), a 3-bp AAA insertion that introduces an additional lysine residue at codon 435, and a spontaneous new mutation resulting in a 74-bp deletion (66del74), Seven at-risk pregnancies were monitored with one prenatal diagnosis of fumarase deficiency by molecular analysis and favorable outcome of the other pregnancies as predicted by enzyme assay of cultured fetal cells or molecular analysis. (C) 1998 Academic Press. C1 Massachusetts Gen Hosp, Amino Acid Disorder Lab, Boston, MA 02129 USA. Univ Copenhagen, Dept Clin Genet, DK-1168 Copenhagen, Denmark. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02129 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Southampton Gen Hosp, Southampton SO9 4XY, Hants, England. Southampton Univ Hosp, Southampton, Hants, England. Univ London, St Georges Hosp, Sch Med, London, England. Shaare Zedek Med Ctr, Metab Unit, IL-91031 Jerusalem, Israel. Hamilton Hlth Sci Corp, Genet Serv, McMaster Div, Hamilton, ON, Canada. Childrens Hosp Western Bank, Sheffield, S Yorkshire, England. Massachusetts Gen Hosp, Mol Neurogenet Unit, Boston, MA 02129 USA. RP Shih, VE (reprint author), Massachusetts Gen Hosp, Amino Acid Disorder Lab, Bldg 149,13th St, Boston, MA 02129 USA. FU NINDS NIH HHS [NS05096] NR 25 TC 42 Z9 43 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 1998 VL 63 IS 4 BP 254 EP 262 DI 10.1006/mgme.1998.2684 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA ZV078 UT WOS:000074266300002 PM 9635293 ER PT J AU Clausen, BE Bridges, SL Lavelle, JC Fowler, PG Gay, S Koopman, WJ Schroeder, HW AF Clausen, BE Bridges, SL Lavelle, JC Fowler, PG Gay, S Koopman, WJ Schroeder, HW TI Clonally-related immunoglobulin V-H domains and nonrandom use of D-H gene segments in rheumatoid arthritis synovium SO MOLECULAR MEDICINE LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; VARIABLE REGION GENES; HUMAN-ANTIBODY REPERTOIRE; HIGH ENDOTHELIAL VENULES; HEAVY-CHAIN DIVERSITY; PERIPHERAL B-CELLS; GERM-LINE GENES; SOMATIC MUTATION; NUCLEOTIDE-SEQUENCES; PREFERENTIAL UTILIZATION AB Background: Synovia of patients with long-standing rheumatoid arthritis (RA) are typically infiltrated with B lymphocytes and plasma cells that secrete large amounts of immunoglobulin. The CDR3 of an immunoglobulin heavy chain is composed of the V-H-D-H-J(H) join, with interposed N region addition, and thus defines clonal relatedness. Furthermore, the CDR3 lies at the center of the antigen binding site, so its length and composition influence antigen binding. We sought definitive evidence of an antigen-driven B cell response (i.e., clones derived from the same V-H, D-H, and J(H) gene segments with shared somatic mutations) in RA synovial mRNA transcripts, and to characterize CDR3 intervals at the target of inflammation in this autoimmune disease. Materials and Methods: We screened a cDNA library generated from unselected cells from the knee joint of a 62-year-old white female with long-standing RA. This technique does not have the potential bias of selecting for antibodies that express a particular reactivity such as rheumatoid factor. C gamma recombinants were sequenced and progenitor V-H, D-H, and J(H) gene segments were assigned and somatic mutations determined by comparison to germline sequences. Analyses of D-H reading frame utilization and hydropathy characteristics of CDR3s were performed. Results: Two of 67 recombinants were derived from the same V-H (V3-11) and J(H) gene segments, demonstrated shared mutations, and contained nearly identical V-H- D-H-J(H) joins, including N region addition. Three other recombinants contained identical sequence throughout the variable domain. We also found preferential utilization of a limited number of V-H and D-H gene segments and marked preference for a D-H reading frame encoding predominantly hydrophilic residues. Conclusions: Analysis of expressed heavy chain variable domains strongly supports the hypothesis that the B cell response in RA synovium is at least in part antigen driven and oligoclonal. C1 Univ Alabama, Div Dev & Clin Immunol, Wallace Tumor Inst 378, Birmingham, AL 35294 USA. Univ Alabama, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP Schroeder, HW (reprint author), Univ Alabama, Div Dev & Clin Immunol, Wallace Tumor Inst 378, Birmingham, AL 35294 USA. EM harry.schroeder@ccc.uab.edu RI CLAUSEN, Bjorn/A-8229-2010 OI CLAUSEN, Bjorn/0000-0002-2484-7842 FU NIAID NIH HHS [AI18958]; NIAMS NIH HHS [AR01867, AR03555] NR 81 TC 14 Z9 15 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1076-1551 J9 MOL MED JI Mol. Med. PD APR PY 1998 VL 4 IS 4 BP 240 EP 257 PG 18 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZP317 UT WOS:000073740200005 PM 9606177 ER PT J AU Knapik, EW Goodman, A Ekker, M Chevrette, M Delgado, J Neuhauss, S Shimoda, N Driever, W Fishman, MC Jacob, HJ AF Knapik, EW Goodman, A Ekker, M Chevrette, M Delgado, J Neuhauss, S Shimoda, N Driever, W Fishman, MC Jacob, HJ TI A microsatellite genetic linkage map for zebrafish (Danio rerio) SO NATURE GENETICS LA English DT Article ID HUMAN GENOME; MOUSE; EMBRYOS AB We have constructed a zebrafish genetic linkage map consisting of 705 simple sequence-length polymorphism markers (SSLPs). The map covers 2350 centimorgans (cM) of the zebrafish genome with an average resolution of 3.3 cM. It is a complete map in genetic mapping terms (there is one linkage group for each of the 25 chromosomes), and it has been confirmed by somatic-cell hybrids and centromere-mapping using half-tetrad analysis. The markers are highly polymorphic in the zebrafish strains used for genetic crosses and provide a means to compare genetic segregation of developmental mutations between laboratories. These markers will provide an initial infrastructure for the positional cloning of the nearly 600 zebrafish genes identified as crucial to vertebrate development,and will become the anchor for the physical map of the zebrafish genome. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Univ Ottawa, Ottawa Civic Hosp, Loeb Inst Med Res, Ottawa, ON K1Y 4E9, Canada. McGill Univ, Dept Surg, Montreal, PQ H3G 1A4, Canada. Montreal Gen Hosp, Res Inst, Montreal, PQ H3G 1A4, Canada. RP Knapik, EW (reprint author), Med Coll Wisconsin, Dept Physiol, 8701 Watertown Plank Rd, D-85758 Neuherberg, Germany. EM fishman@cvrc-taco.mgh.harvard.edu RI Knapik, Ela/J-6172-2014 FU NCRR NIH HHS [RR08888] NR 33 TC 255 Z9 268 U1 0 U2 13 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1998 VL 18 IS 4 BP 338 EP 343 DI 10.1038/ng0498-338 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZE078 UT WOS:000072755500015 PM 9537415 ER PT J AU Postlethwait, JH Yan, YL Gates, MA Horne, S Amores, A Brownlie, A Donovan, A Egan, ES Force, A Gong, ZY Goutel, C Fritz, A Kelsh, R Knapik, E Liao, E Paw, B Ransom, D Singer, A Thomson, M Abduljabbar, TS Yelick, P Beier, D Joly, JS Larhammar, D Rosa, F Westerfield, M Zon, LI Johnson, SL Talbot, WS AF Postlethwait, JH Yan, YL Gates, MA Horne, S Amores, A Brownlie, A Donovan, A Egan, ES Force, A Gong, ZY Goutel, C Fritz, A Kelsh, R Knapik, E Liao, E Paw, B Ransom, D Singer, A Thomson, M Abduljabbar, TS Yelick, P Beier, D Joly, JS Larhammar, D Rosa, F Westerfield, M Zon, LI Johnson, SL Talbot, WS TI Vertebrate genome evolution and the zebrafish gene map SO NATURE GENETICS LA English DT Article ID NEURAL CREST; EXPRESSION; MUTATIONS AB In chordate phylogeny, changes in the nervous system. jaws. and appendages transformed meek filter feeders into fearsome predators(1). Gene duplication is thought to promote such innovation(2). Vertebrate ancestors probably had single copies of genes now found in multiple copies in vertebrates(3) and gene maps suggest that this occurred by polyploidization(2-7). It has been suggested that one genome duplication event occurred before, and one after the divergence of ray-finned and lobe-finned fishes(5). Holland et at, however. have argued that because various vertebrates have several HOX clusters. two rounds of duplication occurred before the origin of jawed fishes(3). Such gene-number data. however. do not distinguish between tandem duplications and polyploidization events, nor whether independent duplications occurred in different lineages. To investigate these matters. we mapped 144 zebrafish genes and compared the resulting map with mammalian maps. Comparison revealed large conserved chromosome segments. Because duplicated chromosome segments in zebrafish often correspond with specific chromosome segments in mammals. it is likely that two polyploidization events occurred prior to the divergence of fish and mammal lineages. This zebrafish gene map will facilitate molecular identification of mutated zebrafish genes, which can suggest functions for human genes known only by sequence. C1 Univ Oregon, Inst Neurosci, Eugene, OR 97403 USA. NYU, Med Ctr, Skirball Inst, Dev Genet Program, New York, NY 10016 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Natl Univ Singapore, Dept Zool, Singapore 117548, Singapore. Ecole Normale Super, F-75231 Paris, France. Univ Bath, Sch Biol & Biochem, Dev Biol Programme, Bath BA2 7AY, Avon, England. Massachusetts Gen Hosp, Charlestown, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Lab Genet Poissons, Jouy En Josas, France. Uppsala Univ, Dept Med Pharmacol, Uppsala, Sweden. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Forsyth Dent Ctr, Dept Cytokine Biol, Boston, MA 02115 USA. RP Postlethwait, JH (reprint author), Univ Oregon, Inst Neurosci, 1254, Eugene, OR 97403 USA. EM jpostle@oregon.uoregon.edu RI Kelsh, Robert/B-6445-2008; Gong, Zhiyuan/H-8794-2012; Knapik, Ela/J-6172-2014; Abduljabbar, Tariq/E-6491-2017 OI Kelsh, Robert/0000-0002-9381-0066; Gong, Zhiyuan/0000-0002-9660-5260; FU NCRR NIH HHS [R01RR10715, R01RR12349]; NICHD NIH HHS [P01HD22486] NR 30 TC 578 Z9 596 U1 3 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1998 VL 18 IS 4 BP 345 EP 349 DI 10.1038/ng0498-345 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA ZE078 UT WOS:000072755500016 PM 9537416 ER PT J AU Yamasaki, L Bronson, R Williams, BO Dyson, NJ Harlow, E Jacks, T AF Yamasaki, L Bronson, R Williams, BO Dyson, NJ Harlow, E Jacks, T TI Loss of E2F-1 reduces tumorigenesis and extends the lifespan of Rb1(+/-) mice SO NATURE GENETICS LA English DT Article ID S-PHASE ENTRY; FIBROBLASTS LEADS; CHIMERIC MICE; APOPTOSIS; GENE; RB; EXPRESSION; MOUSE; OVEREXPRESSION; INDUCTION AB Mutation of the retinoblastoma tumour-suppressor gene (RB) leads to the deregulation of many proteins and transcription factors that interact with the retinoblastoma gene product (pRB), including members of the E2F transcription factor family(1,2). As pRB is known to repress E2F transcriptional activity and overexpression of E2F is sufficient for cell cycle progression, it is thought that pRB suppresses growth in part by repressing E2F-mediated transcription(3). Previously, we reported that loss of E2f1 in mice results in tissue-specific tumour induction and tissue atrophy(4), demonstrating that E2F-1 normally controls growth both positively and negatively in a tissue-specific fashion(4,5). To determine whether E2F-1 deregulation-as a result of loss of pRB-promotes proliferation in vivo, we have tested whether loss of E2f1 interferes with the pituitary and thyroid tumorigenesis that occurs in Rb1(+/-) mice(6-9). We have found that loss of E2f1 reduces the frequency of pituitary and thyroid tumours, and greatly lengthens the lifespan of Rb1(+/-); E2f1(-/-) animals, demonstrating that E2F-1 is an important downstream target of pRB during tumorigenesis. Furthermore. loss of E2f1 reduces a previously reported strain-dependent difference in Rb1(+/-) lifespan(9,10), suggesting that E2f1 or an E2F-1-regulated gene acts as a genetic modifier between the 129/Sv and C57BL/6 strains. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Tufts Univ, Sch Vet Med, Dept Pathol, USDA,Human Nutr Res Ctr Aging, Boston, MA 02111 USA. MIT, Ctr Canc Res, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Yamasaki, L (reprint author), Columbia Univ, Dept Biol Sci, 1102 Fairchild Bldg,1212 Amsterdam Ave, New York, NY 10027 USA. RI Williams, Bart/A-3539-2013 OI Williams, Bart/0000-0002-5261-5301 NR 28 TC 223 Z9 225 U1 0 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 1998 VL 18 IS 4 BP 360 EP 364 DI 10.1038/ng0498-360 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA ZE078 UT WOS:000072755500019 PM 9537419 ER PT J AU Schwartz, MW AF Schwartz, MW TI Orexins and appetite: The big picture of energy homeostasis gets a little bigger SO NATURE MEDICINE LA English DT Editorial Material ID NEUROPEPTIDE-Y; HYPERPHAGIA; OBESITY C1 Univ Washington, Dept Med, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Schwartz, MW (reprint author), Univ Washington, Dept Med, Seattle, WA 98108 USA. RI Schwartz, Michael/H-9950-2012 NR 14 TC 14 Z9 14 U1 1 U2 2 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1998 VL 4 IS 4 BP 385 EP 386 DI 10.1038/nm0498-385 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZF531 UT WOS:000072906800024 PM 9546775 ER PT J AU Scadden, DT AF Scadden, DT TI Mother knows best SO NATURE MEDICINE LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Partners CancerCare, Boston, MA 02129 USA. RP Scadden, DT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dana Farber Partners CancerCare, Boston, MA 02129 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1998 VL 4 IS 4 BP 390 EP 391 DI 10.1038/nm0498-390 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZF531 UT WOS:000072906800027 PM 9546778 ER PT J AU Buckner, RL Koutstaal, W Schacter, DL Wagner, AD Rosen, BR AF Buckner, RL Koutstaal, W Schacter, DL Wagner, AD Rosen, BR TI Functional-anatomic study of episodic retrieval using fMRI I. Retrieval effort versus retrieval success SO NEUROIMAGE LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; PREFRONTAL CORTEX; MEMORY RETRIEVAL; FRONTAL-CORTEX; HUMAN BRAIN; VERBAL INFORMATION; RECOGNITION MEMORY; SHORT-TERM; ACTIVATION; DISSOCIATION AB A number of recent functional imaging studies have identified brain areas activated during tasks involving episodic memory retrieval. The identification of such areas provides a foundation for targeted hypotheses regarding the more specific contributions that these areas make to episodic retrieval. As a beginning effort toward such an endeavor, whole-brain functional magnetic resonance imaging (fMRI) was used to examine 14 subjects during episodic word recognition in a block-designed fMRI experiment. Study conditions were manipulated by presenting either shallow or deep encoding tasks. This manipulation yielded two recognition conditions that differed with regard to retrieval effort and retrieval success: shallow encoding yielded low levels of recognition success with high levels of retrieval effort, and deep encoding yielded high levels of recognition success with low levels of effort. Many brain areas were activated in common by these two recognition conditions compared to a low level fixation condition, including left and right prefrontal regions often detected during PET episodic retrieval paradigms (e.g., R. L. Buckner ct at., 1996, J. Neurosci. 16, 6219-6235) thereby generalizing these findings to fMRI. Characterization of the activated regions in relation to the separate recognition conditions showed (1) bilateral anterior insular regions and a left dorsal prefrontal region were more active after shallow encoding, when retrieval demanded greatest effort, and (2) right anterior prefrontal cortex, which has been implicated in episodic retrieval, was most active during successful retrieval after deep encoding. We discuss these findings in relation to component processes involved in episodic retrieval and in the context of a companion study using event-related fMRI. (C) 1998 Academic Press. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr,Dept Radiol, Boston, MA USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. Stanford Univ, Dept Psychol, Stanford, CA 94305 USA. RP Buckner, RL (reprint author), Washington Univ, Dept Psychol, St Louis, MO 63130 USA. OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441]; NIDCD NIH HHS [DC03245] NR 45 TC 225 Z9 226 U1 3 U2 13 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR PY 1998 VL 7 IS 3 BP 151 EP 162 DI 10.1006/nimg.1998.0327 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZM920 UT WOS:000073589600001 PM 9597657 ER PT J AU Buckner, RL Koutstaal, W Schacter, DL Dale, AM Rotte, M Rosen, BR AF Buckner, RL Koutstaal, W Schacter, DL Dale, AM Rotte, M Rosen, BR TI Functional-anatomic study of episodic retrieval II. Selective averaging of event-related fMRI trials to test the retrieval success hypothesis SO NEUROIMAGE LA English DT Article ID MEMORY AB In a companion paper (R. L. Buckner et al., 1998, NeuroImage 7, 151-162) we used fMRI to identify brain areas activated by episodic memory retrieval. Prefrontal areas were shown to differentiate component processes related to retrieval success and retrieval effort in block-designed paradigms. Importantly, a right anterior prefrontal area was most active during task blocks involving greatest retrieval success, consistent with an earlier PET study by M. D. Rugg ef al. (1996, Brain 119, 2073-2083). However, manipulation of these variables within the context of blocked trials confounds differences related to varying levels of retrieval success with potential shifts in subjects' strategies due to changes in the probability of target events across blocks, To test more rigorously the hypothesis that certain areas are directly related to retrieval success, we adopted recently developed procedures for event-related fMRI. Fourteen subjects studied words under deep encoding and were then tested in a mixed trial paradigm where old and new words were randomly presented. This recognition testing procedure activated similar areas to the blocked trial paradigm, with all areas showing similar levels of activation across old and new items. Of critical importance, significant activation was detected in right anterior prefrontal cortex for new items when subjects correctly indicated they were new (correct rejections). These findings go against the retrieval success hypothesis as formally proposed and provide an important constraint for interpretation of this region's role in episodic retrieval. Furthermore, anterior prefrontal activation was found to occur late, relative to other brain areas, suggesting that it may be involved in retrieval verification or monitoring processes or perhaps even in anticipation of subsequent trial events (although an alternative possibility, that the late onset is mediated by a late vascular response, cannot be ruled out). These findings and their relation to the results obtained in the companion blocked-trial paradigm are discussed, a 1998 Academic Press. C1 Washington Univ, Dept Psychol, St Louis, MO 63130 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Nucl Magnet Resonance Ctr,Dept Radiol, Boston, MA USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. Otto Von Guericke Univ, Dept Neurophysiol, Magdeburg, Germany. RP Buckner, RL (reprint author), Washington Univ, Dept Psychol, St Louis, MO 63130 USA. RI Dale, Anders/A-5180-2010; OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [AG08441]; NIDCD NIH HHS [DC03245] NR 31 TC 214 Z9 215 U1 0 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR PY 1998 VL 7 IS 3 BP 163 EP 175 DI 10.1006/nimg.1998.0328 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA ZM920 UT WOS:000073589600002 PM 9597658 ER PT J AU Fisher, CM AF Fisher, CM TI Lacunes: Small, deep cerebral infarcts SO NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Fisher, CM (reprint author), Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. NR 0 TC 20 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1998 VL 50 IS 4 BP 841 EP 841 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ178 UT WOS:000073187300001 PM 9566356 ER PT J AU Greenberg, SM Vonsattel, JPG Segal, AZ Chiu, RI Clatworthy, AE Liao, A Hyman, BT Rebeck, GW AF Greenberg, SM Vonsattel, JPG Segal, AZ Chiu, RI Clatworthy, AE Liao, A Hyman, BT Rebeck, GW TI Association of apolipoprotein E epsilon 2 and vasculopathy in cerebral amyloid angiopathy SO NEUROLOGY LA English DT Article ID ONSET ALZHEIMER-DISEASE; BETA-PROTEIN; A-BETA; ALLELE; DEPOSITION; A-BETA-42(43); HEMORRHAGE; PATHOLOGY; PLAQUES; BRAIN AB Objective: Hemorrhage related to cerebral amyloid angiopathy (CAA) appears to occur through a multistep pathway that includes deposition of beta-amyloid in cerebral vessels and specific vasculopathic changes in the amyloid-laden vessels, such as cracking of the vessel wall. Recent reports suggest a positive association between CAA-related hemorrhage and both the apolipoprotein E (APOE) epsilon 4 allele and, unexpectedly, the APOE epsilon 2 allele. Unlike APOE epsilon 4, APOE epsilon 2 does not appear to act through increased beta-amyloid deposition. We therefore sought to determine whether it might specifically accelerate the second step in this pathway, that is, development of the vasculopathic changes that lead to hemorrhage. Methods: To determine the role of APOE in development of vasculopathic changes, we compared APOE genotypes in two groups of postmortem brains: 52 brains with complete amyloid replacement of vessel walls but without vasculopathic changes, and 23 brains with complete amyloid replacement of vessels with the accompanying changes of cracking of the vessel wall and paravascular leaking of blood. Results: Frequency of APOE epsilon 2 was significantly greater in the group with vasculopathy (0.09) than the group without (0.01, p = 0.03), The groups did not differ in mean age or extent of neuritic plaques. Analysis of a clinical series of patients with CAA-related hemorrhage confirmed an overrepresentation of APOE epsilon 2 as well as an association between this allele and earlier age of first hemorrhage. Conclusions: These data suggest that APOE epsilon 2 and epsilon 4 might promote CAA-related hemorrhage through separate mechanisms: epsilon 4 by enhancing amyloid deposition and epsilon 2 by causing amyloid-laden vessels to undergo the vasculopathic changes that lead to rupture. C1 Harvard Univ, Wang Ambulatory Care Ctr 836, Massachusetts Gen Hosp, Dept Neurol,Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Boston, MA 02114 USA. RP Greenberg, SM (reprint author), Harvard Univ, Wang Ambulatory Care Ctr 836, Massachusetts Gen Hosp, Dept Neurol,Sch Med, Boston, MA 02114 USA. FU NIA NIH HHS [AG14473, AG12406, AG00725] NR 34 TC 148 Z9 153 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1998 VL 50 IS 4 BP 961 EP 965 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ178 UT WOS:000073187300025 PM 9566379 ER PT J AU Guttmann, CRG Jolesz, FA Kikinis, R Killiany, RJ Moss, MB Sandor, T Albert, MS AF Guttmann, CRG Jolesz, FA Kikinis, R Killiany, RJ Moss, MB Sandor, T Albert, MS TI White matter changes with normal aging SO NEUROLOGY LA English DT Article ID AGE-RELATED-CHANGES; MAGNETIC-RESONANCE; CEREBROSPINAL-FLUID; CEREBRAL-CORTEX; RHESUS-MONKEY; NORMAL ADULTS; HUMAN BRAIN; VOLUMES; SEGMENTATION; IMAGES AB We evaluated brain tissue compartments in 72 healthy volunteers between the ages of 18 and 81 years with quantitative MRI. The intracranial fraction of white matter was significantly lower in the age categories above 59 years. The CSF fraction increased significantly with age, consistent with previous reports. The intracranial percentage of gray matter decreased somewhat with age, but there was no significant difference between the youngest subjects and the subjects above 59. A covariance adjustment for the volume of hyperintensities did not alter the foregoing results. The intracranial percentage of white matter volume was strongly correlated with the percentage volume of CSF. The finding of a highly significant decrease with age in white matter, in the absence of a substantial decrease in gray matter, is consistent with recent neuropathologic reports in humans and nonhuman primates. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Albert, MS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Psychiat Gerontol 149-9124,Bldg 149,13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01-CA67165]; NIA NIH HHS [P01-AG04953]; NINDS NIH HHS [N01-NS-0-2397] NR 44 TC 283 Z9 288 U1 2 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1998 VL 50 IS 4 BP 972 EP 978 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ178 UT WOS:000073187300027 PM 9566381 ER PT J AU Kelly, PJ McDonald, CT Neill, GO Thomas, C Niles, J Rordorf, G AF Kelly, PJ McDonald, CT Neill, GO Thomas, C Niles, J Rordorf, G TI Middle cerebral artery main stem thrombosis in two siblings with familial thrombotic thrombocytopenic purpura SO NEUROLOGY LA English DT Article ID STROKE AB Idiopathic thrombotic thrombocytopenic purpura (TTP) is frequently complicated by microinfarcts in cerebral cortex and subcortical white matter. We describe two sisters who suffered massive hemispheric infarction due to thrombosis of the middle cerebral artery main stem during exacerbations of TTP. Acute TTP may be associated with intraluminal thrombosis of large-diameter arteries in addition to arterioles and capillaries. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Lahey Hitchcock Clin, Dept Pathol, Burlington, MA USA. RP Kelly, PJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, Wang ACC 835,Fruit St, Boston, MA 02114 USA. NR 10 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1998 VL 50 IS 4 BP 1157 EP 1160 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ178 UT WOS:000073187300062 PM 9566416 ER PT J AU Biousse, V Newman, NJ Lessell, S AF Biousse, V Newman, NJ Lessell, S TI Audible pulsatile tinnitus in idiopathic intracranial hypertension SO NEUROLOGY LA English DT Article ID DIAGNOSIS C1 Emory Univ, Ctr Eye, Sch Med, Dept Ophthalmol,Neuroophthalmol Unit, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02115 USA. RP Newman, NJ (reprint author), Emory Univ, Ctr Eye, Sch Med, Dept Ophthalmol,Neuroophthalmol Unit, 1365-B Clifton Rd NE, Atlanta, GA 30322 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD APR PY 1998 VL 50 IS 4 BP 1185 EP 1186 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA ZJ178 UT WOS:000073187300073 PM 9566427 ER PT J AU Niethammer, M Valtschanoff, JG Kapoor, TM Allison, DW Weinberg, RJ Craig, AM Sheng, M AF Niethammer, M Valtschanoff, JG Kapoor, TM Allison, DW Weinberg, RJ Craig, AM Sheng, M TI CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90 SO NEURON LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; CLUSTERING ACTIVITY; POTASSIUM CHANNEL; GUANYLATE KINASES; HUMAN HOMOLOG; DROSOPHILA; IDENTIFICATION; TUBULIN; SUBUNIT; FAMILY AB The synaptic protein PSD-95/SAP90 binds to and clusters a variety of membrane proteins via its two N-terminal PDZ domains. We report a novel protein, CRIPT, which is highly conserved from mammals to plants and binds selectively to the third PDZ domain (PDZ3) of PSD-95 via its C terminus. While conforming to the consensus PDZ-binding C-terminal sequence (X-S/TX-V-COOH), residues at the -1 position and upstream of the last four amino acids of CRIPT determine its specificity for PDZ3. In heterologous cells, CRIPT causes a redistribution of PSD-95 to microtubules. In brain, CRIPT colocalizes with PSD-95 in the postsynaptic density and can be coimmunoprecipitated with PSD-95 and tubulin. These findings suggest that CRIPT may regulate PSD-95 interaction with a tubulin-based cytoskeleton in excitatory synapses. C1 Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ N Carolina, Dept Cell Biol & Anat, Chapel Hill, NC 27599 USA. Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Univ Illinois, Dept Cell & Struct Biol, Urbana, IL 61801 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. RI Craig, Ann Marie/M-2054-2014 FU NINDS NIH HHS [NS29879, NS33184, NS35050] NR 65 TC 227 Z9 231 U1 1 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 1998 VL 20 IS 4 BP 693 EP 707 DI 10.1016/S0896-6273(00)81009-0 PG 15 WC Neurosciences SC Neurosciences & Neurology GA ZK649 UT WOS:000073346500009 PM 9581762 ER PT J AU Sauman, I Reppert, SM AF Sauman, I Reppert, SM TI Brain control of embryonic circadian rhythms in the silkmoth Antheraea pernyi SO NEURON LA English DT Article ID ECLOSION HORMONE; PERIOD PROTEIN; CLOCK; TIMELESS; MECHANISM; INSECTS; LIGHT AB The clock protein PER is necessary for circadian control of egg-hatching behavior in the silkmoth Antheraea pernyi. Since the brain and midgut of the silkmoth embryo contain PER-positive cells, we examined the circadian clock potential of these embryonic tissues. Transplantation experiments indicate that the circadian clock controlling egg-hatching behavior resides in brain, and that a humoral factor mediates this circadian regulation. We also used ligation experiments on first instar larvae to show that the circadian control of PER movement into the nuclei of midgut epithelial cells is dependent on an intact (connected) brain. These results implicate a novel brain factor in the circadian regulation of egg-hatching behavior and provide further evidence for differing mechanisms of PER control among species. C1 Acad Sci Czech Republ, Inst Entomol, CR-37005 Ceske Budejovice, Czech Republic. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Dev Chronobiol, Serv Pediat, Boston, MA 02114 USA. RP Sauman, I (reprint author), Acad Sci Czech Republ, Inst Entomol, Branisovska 31, CR-37005 Ceske Budejovice, Czech Republic. RI Sauman, Ivo/H-2071-2014 NR 23 TC 22 Z9 22 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 1998 VL 20 IS 4 BP 741 EP 748 DI 10.1016/S0896-6273(00)81012-0 PG 8 WC Neurosciences SC Neurosciences & Neurology GA ZK649 UT WOS:000073346500012 PM 9581765 ER PT J AU Mendez, MF Cherrier, MM AF Mendez, MF Cherrier, MM TI The evolution of alexia and simultanagnosia in posterior cortical atrophy SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article DE alexia; simultanagnosia; posterior cortical atrophy; dementia ID ALZHEIMERS-DISEASE; BALINTS-SYNDROME; VISUAL AGNOSIA; PURE ALEXIA; WORD-FORM; DEMENTIA; DYSLEXIA; PATIENT; DEFECT AB Early alexia and higher visual impairments characterize Posterior cortical atrophy (PCA), a progressive dementing syndrome most often caused by Alzheimer disease. Posterior cortical atrophy is rare, and the nature of the visual impairments in PCA are unclear. The authors observed two patients who had an insidiously progressive reading difficulty characterized by letter-by-letter reading and otherwise intact cognitive functions. Over time, these patients developed "ventral simultanannosia" with preserved detection of multiple stimuli but inability to interpret whole scenes. Subsequently, they progressed to Balint syndrome with "dorsal simultanagnosia," optic ataxia, and oculomotor apraxia. Structural imaging was normal, but functional imaging revealed posterior cortical dysfunction. On a letter reading task, both patients had a word superiority effect, and on a whole word reading task, they could not read most words with missing or crosshatched letters. An inability to assess whole scenes progressed to an inability to detect more than one stimulus in an array. These findings suggest an evolution of PCA with progressive difficulty in visual integration beginning with letters, progressing to whole scenes, and culminating in Balint syndrome. These changes may reflect an extension of the pathophysiology of PCA from the extrastriate visual cortex to its occipitotemporal and occipitoparietal connections. C1 W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit 116AF, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Mendez, MF (reprint author), W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 35 TC 31 Z9 32 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD APR PY 1998 VL 11 IS 2 BP 76 EP 82 PG 7 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 173JB UT WOS:000078976400004 PM 9652488 ER PT J AU Barker, FG Chang, SM Gutin, PH Malec, MK McDermott, MW Prados, MD Wilson, CB AF Barker, FG Chang, SM Gutin, PH Malec, MK McDermott, MW Prados, MD Wilson, CB TI Survival and functional status after resection of recurrent glioblastoma multiforme SO NEUROSURGERY LA English DT Article; Proceedings Paper CT 7th Canadian Neuro-Oncology Meeting CY MAY, 1996 CL MONTREAL, CANADA DE glioblastoma multiforme; Karnofsky performance score; prognostic factors; reoperation ID CANCER CLINICAL-TRIALS; MALIGNANT BRAIN-TUMORS; QUALITY-OF-LIFE; PROPENSITY SCORE; SELECTION BIAS; STEREOTAXIC RADIOSURGERY; ANAPLASTIC GLIOMA; REOPERATION; ASTROCYTOMA; THERAPY AB OBJECTIVE: To determine the selection factors for and results of second resections performed to treat recurrent glioblastoma multiforme (CM), we studied 301 patients with GM who were treated from the time of diagnosis using two prospective clinical protocols. METHODS: The patients were prospectively followed from the time of diagnosis, using clinical and radiographic criteria after maximal surgical resection and external beam radiotherapy with or without adjuvant chemotherapy. Resection of recurrent CM was performed at the recommendation of the treating clinicians. The results of the second resections were retrospectively reviewed and analyzed using multivariate logistic regression, Kaplan-Meier-Turnbull survival analysis, Cox regression, and propensity score stratification. RESULTS: Forty-six patients underwent second resections during the study period. The actuarial rate of the second resections was 15% of the patients 1 year after diagnosis and 31% 2 years after diagnosis, Younger age (P = 0.01) and more extensive initial resection (P = 0.02), but not Karnofsky Performance Scale (KPS) score at the time of diagnosis or recurrence, predicted a higher chance of selection for reoperation after initial tumor recurrence. Twenty-eight percent of the patients had improved KPS scores after undergoing reoperation, 49% were stable, and 23% had declines in KPS scores of 10 to 30 points. There was no operative mortality. After reoperation, 85% of the patients received chemotherapy, 11% received brachytherapy-or underwent stereotactic radiosurgery, and 17% underwent third resections. The median survival period after reoperation was 36 weeks. Higher preoperative KPS scores predicted longer survival periods after reoperation (P = 0.03). Age and interval since diagnosis were not significant prognostic factors. The median high-quality survival period (KPS score, greater than or equal to 70) was 18 weeks. The median survival period after first tumor progression was 23 weeks for 130 patients treated using the same protocols who did not undergo reoperations. Patients who did undergo reoperations experienced clinically and statistically significantly longer survival periods. However, this was determined to be partially because of selection bias. CONCLUSION: Survival after resection of recurrent GM remains poor despite advances in imaging, operative technique, and adjuvant therapies. High-quality survival after resection of recurrence to treat CM seems to have increased significantly since an earlier report from our institution. C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Neurol Surg, Neurooncol Serv, San Francisco, CA 94143 USA. RP Barker, FG (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Neurosurg Serv, Cox 315,Fruit St, Boston, MA 02114 USA. FU NCI NIH HHS [CA09291, CA 13525] NR 66 TC 170 Z9 176 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 1998 VL 42 IS 4 BP 709 EP 720 DI 10.1097/00006123-199804000-00013 PG 12 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZK415 UT WOS:000073318600012 PM 9574634 ER PT J AU Lyubimov, AV Babin, VV Kartashov, AI AF Lyubimov, AV Babin, VV Kartashov, AI TI Developmental neurotoxicity and immunotoxicity of 2,4,6-tribromophenol in Wistar rats SO NEUROTOXICOLOGY LA English DT Article DE 2,4,6-tribromophenol; inhalation; developmental neurotoxicity; embryotoxicity; fetotoxicity ID PRENATAL EXPOSURE; TOXICITY; ALUMINUM; BEHAVIOR AB Pregnant Wistar rats were exposed to 2,4,6-Tribromophenol (TBP) by whole body inhalation (0, 0.03, 0.1, 0.3, 1.0 mg/m3,24hr/day,7days/week,from day 1 to 21 of gestation). Significant decreases in orientation reactions were noted at concentrations of 1.0 mg/m(3) (p<0.05) in the open field test. Nonsignificant trends (p>0.05) toward decreased horizontal movement and emotionality in the open field and increased electrical impulse skin pain threshold (SPT) were observed. No significant exposure-related differences in the nonspecific immunological status (phagocytosis and blood anti-microbe activity) of pregnant rats were seen after the exposure. Preimplantation and postimplantation embryo losses were significantly increased in a dose-dependent manner and were seen in all treated groups except the lowest concentration (0.03 mg/m(3)) group. Signs of retarded fetal skeletal development and increased frequencies of visceral abnormalities were found at concentrations of 0.1 and 1.0 mg/m(3). Significant effects were found for lower incisor eruption and ear unfolding at a concentration of 0.3 mg/m(3). The grooming behavior of 30-day old male progeny was significantly less than control in all experimental groups: Grooming behavior in female subjects exposed to a concentration of 0.3 mg/m(3) and emotionality in subjects exposed to a concentration of 1 mg/m(3) were decreased significantly. At 60 days of age emotional reactions were significantly decreased in female subjects from the 0.03, 0.3 and 1.0 mg/m(3) groups. SPT was significantly increased in the 1 mg/m(3) group for both male and female pups. Thus, evidence of CNS depression influence of TBP both in maternal and offspring groups was found. The NOEL (No Observed Effect Level) for developmental neurotoxicity is thus <0.03 mg/m(3), and the NOEL for maternal neurotoxicity is 0.3 mg/m(3). These results suggest that exposure to TBP for 24hr/day throughout gestation may cause developmental neurotoxicity, embryotoxicity and fetotoxicity, but not immunotoxicity. (C) 1998 Intox Press, Inc. C1 Ctr Ecol & Biotesting, Perm 61400, Russia. Beth Israel Deaconnes Med Ctr, Boston, MA 02215 USA. RP Lyubimov, AV (reprint author), Univ Minnesota Hosp & Clin, Environm Med & Pathol Lab, Stone Lab 1, 1st Floor,421 29th Ave SE, Minneapolis, MN 55414 USA. NR 23 TC 19 Z9 19 U1 2 U2 9 PU INTOX PRESS INC PI LITTLE ROCK PA PO BOX 24865, LITTLE ROCK, AR 72221 USA SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD APR PY 1998 VL 19 IS 2 BP 303 EP 312 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA ZE075 UT WOS:000072755200014 PM 9553967 ER PT J AU Damek, D Hochberg, F AF Damek, D Hochberg, F TI Chemotherapy for brain tumors - The Pech/Peterson/Cairncross article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID METHOTREXATE C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Damek, D (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI HUNTINGTON PA 17 PROSPECT ST, HUNTINGTON, NY 11743 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 1998 VL 12 IS 4 BP 547 EP 548 PG 2 WC Oncology SC Oncology GA ZK407 UT WOS:000073317800013 ER PT J AU Fong, DS Frederick, AR Blumenkranz, MS Walton, DS AF Fong, DS Frederick, AR Blumenkranz, MS Walton, DS TI Exudative retinal detachment in X-linked retinoschisis SO OPHTHALMIC SURGERY AND LASERS LA English DT Article ID JUVENILE RETINOSCHISIS; DIAGNOSIS AB X-linked retinoschisis is a vitreoretinal dystrophy characterized by foveal and peripheral retinoschisis in the nerve fiber layer. Although many associated peripheral retinal findings have been reported, few reports have described massive exudative retinal detachments in patients with X-linked retinoschisis. The authors report the unusual occurrence of Coats'-like exudative retinopathy in two patients with X-linked retinoschisis. Both patients had peripheral massive exudative retinal detachments. C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Jules Stein Eye Inst, King Drew Med Ctr, Los Angeles, CA 90024 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Stanford Univ, Sch Med, Dept Ophthalmol, Stanford, CA 94305 USA. RP Fong, DS (reprint author), Kaiser Permanente Med Ctr, Dept Ophthalmol, 1011 Baldwin Pk Ave, Baldwin Pk, CA 91706 USA. NR 17 TC 8 Z9 9 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0022-023X J9 OPHTHALMIC SURG LAS JI Ophthalmic Surg. Lasers PD APR PY 1998 VL 29 IS 4 BP 332 EP 335 PG 4 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA ZG664 UT WOS:000073026800012 PM 9571668 ER PT J AU Hartstein, ME Grove, AS Woog, JJ Shore, JW Joseph, MP AF Hartstein, ME Grove, AS Woog, JJ Shore, JW Joseph, MP TI The multidisciplinary management of psammomatoid ossifying fibroma of the orbit SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Annual Symposium of the American-Society-of-Ophthalmic-Plastic-and-Reconstructive-Surgery CY OCT 28, 1995 CL ATLANTA, GEORGIA SP Amer Soc Ophthalm Plast & Reconstruct Surg ID SINUSES; FOSSA AB Objective: To discuss the multidisciplinary management of psammomatoid ossifying fibroma (POF) of the orbit and to clarify the clinicopathologic terminology. Design: The authors present a cohort of cases of POF involving the frontal and ethmoid sinuses and the orbit and discuss the nomenclature and literature. Participants: Three patients with POF and their treatment are discussed. Intervention: Patients were worked up and treated by a multidisciplinary team using imaging studies and histopathologic analysis. Reconstruction, if necessary, was carried out at the time of excision or in a second-stage procedure. Main Outcome Measures: In each case, the lesion was completely excised and has not recurred. Results: The diagnosis of POF was made in each case, and the patient underwent successful resection of the tumor. Conclusion: The authors' experience suggests that a multidisciplinary approach, including a radiologist, pathologist, neurosurgeon, otolaryngologist, craniofacial surgeon, and orbital specialist, may be useful in the evaluation and management of these lesions. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Otolaryngol, Boston, MA USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Hartstein, ME (reprint author), 8729 Delmar Apt 2W, St Louis, MO 63124 USA. NR 13 TC 13 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1998 VL 105 IS 4 BP 591 EP 595 DI 10.1016/S0161-6420(98)94009-X PG 5 WC Ophthalmology SC Ophthalmology GA ZF080 UT WOS:000072860600010 PM 9544629 ER PT J AU Davis, EA Azar, DT Jakobs, FM Stark, WJ AF Davis, EA Azar, DT Jakobs, FM Stark, WJ TI Refractive and keratometric results after the triple procedure - Experience with early and late suture removal SO OPHTHALMOLOGY LA English DT Article ID EXPOSED MONOFILAMENT SUTURES; PENETRATING KERATOPLASTY; POSTKERATOPLASTY ASTIGMATISM; CORNEAL TRANSPLANTATION; VISUAL-ACUITY; COMPLICATIONS; BACTERIAL; KERATITIS AB Objective: The objective of this study was to determine the outcome of early and late suture removal after the triple procedure (i.e., penetrating keratoplasty, cataract extraction, lens implant). Design and Participants: The refractive and keratometric results of 106 eyes undergoing the triple procedure were reviewed. The target postoperative refractive error was -1 diopter (D). Results: Average length of follow-up was 40.3 months, Twenty eyes had sutures removed early (<18 months after surgery), 39 had sutures removed late (greater than or equal to 18 months after surgery), and 47 had sutures still intact al last followup. A best spectacle-corrected visual acuity of 20/40 or better was achieved in 90% of eyes with sutures removed early, 82.1% with sutures removed late, and 70.2% with sutures in place. For all eyes, the mean spherical equivalent at last follow-up was -2.50 D, with 75% of eyes falling between -4 and +2 D. The mean final refractive error was -3.40 +/- 3.53 D for eyes with sutures removed early and -1.79 +/- 3.99 D for eyes with sutures removed late. Eyes with sutures remaining had a mean final refractive error of -0.33 +/- 2.25 D. There was an overall decrease in refractive and keratometric astigmatism after both early and late suture removal with no significant difference between groups. However, there was a wide range of change with some eyes experiencing a decrease and others an increase in astigmatism. Mean postoperative K readings increased significantly for both groups after suture removal (final mean K, 47.00 D) but remained stable for eyes with sutures in. Conclusion: The authors data suggest that ?he final refractive error and net change in refractive and keratometric astigmatism after the triple procedure are not dependent on the timing of suture removal. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Corneal & Refract Surg Serv, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Wilmer Eye Inst, Baltimore, MD USA. RP Davis, EA (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Corneal & Refract Surg Serv, 8th Floor,243 Charles St, Boston, MA 02114 USA. NR 23 TC 80 Z9 81 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1998 VL 105 IS 4 BP 624 EP 630 DI 10.1016/S0161-6420(98)94015-5 PG 7 WC Ophthalmology SC Ophthalmology GA ZF080 UT WOS:000072860600016 PM 9544635 ER PT J AU Power, WJ Tugal-Tutkun, I Foster, CS AF Power, WJ Tugal-Tutkun, I Foster, CS TI Long-term follow-up of patients with atopic keratoconjunctivitis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT Centennial Meeting of the American-Academy-of-Ophthalmology CY OCT 27-31, 1996 CL CHICAGO, ILLINOIS SP Amer Acad Ophthalmol ID OCULAR COMPLICATIONS; DERMATITIS; CYCLOSPORINE; ECZEMA AB Objective: This study aimed to review the presenting features, treatment administered to, histopathologic findings, and complications encountered in a cohort of patients with atopic keratoconjunctivitis. Design: The study design was a retrospective cohort series. Participants: The medical records of 20 patients with atopic keratoconjunctivitis and a minimum follow-up of 3 years were reviewed. Main Outcome Measures: Conjunctival and corneal complications, visual acuity before and after surgery, and histopathologic features on conjunctival biopsy were measured. Results: Significant keratopathy developed in 70% of patients, corneal neovascularization in 60%, fornix foreshortening in 25%, and symblepharon in 20% during the course of their disease, Eleven patients (12 eyes) required penetrating keratoplasty (3 for tectonic purposes and 8 for visual rehabilitation). Vision improved by four or more lines of Snellen acuity in four eyes, improved by two lines in two eyes, remained the same in five eyes, and worsened by two lines in one eye after keratoplasty. Cataract surgery was performed in seven patients (nine eyes) with vision improving by four or more lines in six patients (eight eyes). Conclusion: Atopic keratoconjunctivitis is a potentially blinding disease that may result in a poor visual outcome as a result of corneal complications, Elective surgical intervention may be of benefit and can be considered in those patients whose inflammation is well controlled. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Immunol, Boston, MA USA. Istanbul Univ, Dept Ophthalmol, Istanbul, Turkey. RP Power, WJ (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Cornea Serv, 243 Charles St, Boston, MA 02114 USA. NR 24 TC 37 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1998 VL 105 IS 4 BP 637 EP 642 DI 10.1016/S0161-6420(98)94017-9 PG 6 WC Ophthalmology SC Ophthalmology GA ZF080 UT WOS:000072860600018 PM 9544637 ER PT J AU Netland, PA Terada, H Dohlman, CH AF Netland, PA Terada, H Dohlman, CH TI Glaucoma associated with keratoprosthesis SO OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 100th Annual Meeting of the American-Academy-of-Ophthalmology CY OCT 27-NOV 01, 1996 CL CHICAGO, ILLINOIS SP Amer Acad Ophthalmol ID CLINICAL-EXPERIENCE; IMPLANT AB Objective: This study aimed to review the authors clinical experience with glaucoma associated with keratoprosthesis in patients with severe corneal disease. Design: The study design was a retrospective review of case series. Participants: The authors studied 55 eyes in 52 patients with keratoprostheses with follow-up of 21 +/- 16 months (range, 3-77 months). Intervention: Glaucoma drainage devices were implanted in 36 eyes (35 Ahmed valves, 1 Krupin valve) with 21 +/- 15 months' follow-up (range, 3-64 months). Main Outcome Measures: Clinical outcome assessment included vision, intraocular pressure (IOP), visual fields, optic disc appearance, and identification of complications. Results: Glaucoma was found in the majority (64%) of eyes treated with keratoprostheses, identified in 20 eyes (36%) before surgery and an additional 15 eyes (28%) after surgery. Of the 36 eyes treated with glaucoma drainage devices, IOP was controlled in 29 eyes (81%), with 9 eyes (25%) requiring additional medications. Continued progression of glaucoma occurred in 5 (14%) of 36 eyes with keratoprostheses and glaucoma drainage implants (4 of these eyes had advanced glaucomatous optic nerve damage before surgery). There were nine nonvision-threatening complications due to drainage implants. Compared with the preoperative visual acuity, vision was markedly improved in 63%, unchanged in 17%, and worse in 20% of eyes after keratoprosthesis surgery. Conclusion: Elevation of IOP is common in patients with keratoprosthesis, and prevention or treatment with glaucoma drainage implants is effective. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA USA. RP Netland, PA (reprint author), Univ Tennessee, Dept Ophthalmol, 956 Court Ave, Memphis, TN 38163 USA. NR 19 TC 83 Z9 90 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 1998 VL 105 IS 4 BP 751 EP 757 DI 10.1016/S0161-6420(98)94034-9 PG 7 WC Ophthalmology SC Ophthalmology GA ZF080 UT WOS:000072860600035 PM 9544652 ER PT J AU Smith, DJ King, WF Gilbert, JV Taubman, MA AF Smith, DJ King, WF Gilbert, JV Taubman, MA TI Structural integrity of infant salivary immunoglobulin A (IgA) in IgA1 protease-rich environments SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE IgA1 protease; secretory IgA; Streptococcus mitis ID STREPTOCOCCUS-SANGUIS; VIRIDANS STREPTOCOCCI; HEMOPHILUS-INFLUENZAE; ORAL STREPTOCOCCI; DENTAL PLAQUE; SECRETORY IGA; A PROTEASE; GENE; COLONIZATION; SUBCLASSES AB IgA1 protease-secreting Streptococcus mitis often dominate the oral flora of the neonate and young infant at a time when salivary IgA concentrations are low and usually enriched in the secretory IgA1 subclass. To study the possible influence of these degradative enzymes on emerging host immunity, the presence of IgA1 protease-secreting streptococci was related to the structural integrity of salivary IgA in 24 infants who were between 3 and 18 weeks of age. At least one IgA1 protease-secreting strain could be isolated from the oral mucosa of 79% of the infants and comprised a mean of 38% of the total streptococcal flora of these infants. Chromatographic analyses of resting whole saliva from 16 infants revealed, however, that 95% of the secretory IgA (range 88-100%) remained intact, indicating that minimal immediate IgA proteolysis occurred in the bulk salivary phase. Proteolysis of infant salivary IgA, presumably by indigenous IgA1 protease, could be observed after extended (more than 7 h) in situ incubation of whole saliva at 37 degrees C. Salivary IgA antibody activities to S. mitis components were demonstrated by Western blot in infants colonized with an IgA1 protease-secreting flora. Preliminary evidence suggested that salivary antibody activity in some infants may be directed to IgA1 protease. Thus, the infant's antibody defenses not only appear very early in life but are substantively intact in the bulk salivary phase, even when the oral cavity is colonized with IgA1 protease-secreting streptococcal flora. C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr Hosp, Sch Med, Dept Med,Gastroenterol Div, Boston, MA 02111 USA. RP Smith, DJ (reprint author), Forsyth Dent Ctr, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-06153, DE-09677]; NIDDK NIH HHS [DK-34928] NR 35 TC 7 Z9 7 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD APR PY 1998 VL 13 IS 2 BP 89 EP 96 DI 10.1111/j.1399-302X.1998.tb00718.x PG 8 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA ZA690 UT WOS:000072391300004 PM 9573799 ER PT J AU Jasty, M AF Jasty, M TI Jumbo cups and morselized graft SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article AB Revision of failed acetabular components presents a formidable problem due to associated loss of bone and sclerosis of the remaining bone. Uncemented acetabular components with porous surfaces have revolutionized acetabular revision surgery. They can be stabilized into the existing host bone with supplemental screws even in the face of major bone loss. Nonstructural particulate bone grafts can then be used to supplement the bone stock. With large defects, jumbo acetabular components ranging in sizes from 70 to 80 millimeter outer diameters can be stabilized on the acetabular rim while the defects can be grafted with morsalized bone. Nineteen of such revisions performed for major bone loss without pelvic discontinuity between February 1986 and December 1988 were evaluated at a mean follow-up period of ten years (range eight to eleven years). One component had been revised for sepsis. None of the others had been revised. Definite radiographic failure of fixation of the acetabular component was not seen on any of the other hips. These results strongly support the use of jumbo uncemented acetabular components with morsalized bone grafts even in the face of major acetabular bone loss. C1 Massachusetts Gen Hosp, Hip & Implant Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Jasty, M (reprint author), Massachusetts Gen Hosp, Hip & Implant Unit, 55 Fruit St, Boston, MA 02114 USA. NR 14 TC 48 Z9 51 U1 2 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD APR PY 1998 VL 29 IS 2 BP 249 EP + DI 10.1016/S0030-5898(05)70323-0 PG 7 WC Orthopedics SC Orthopedics GA ZD598 UT WOS:000072702600009 PM 9553570 ER PT J AU Fried, MP Morrison, PR AF Fried, MP Morrison, PR TI Computer-augmented endoscopic sinus surgery SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article AB Review of current literature on computer-augmented endoscopic sinus surgery reflects a sustained interest in developing a role for available frameless stereotactic technologies to provide image guidance for the surgeon. The interest is motivated by the prospect of increased intraoperative patient safety in that image guidance assists the surgeon in navigating through diseased or surgically revised complex anatomy. The authors feel that in time the technique will enable a new level of efficiency in endoscopic sinus surgery. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Otol & Laryngol, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Harvard Med Laser Ctr, Boston, MA USA. Brigham & Womens Hosp, Div Otolaryngol, Boston, MA 02115 USA. Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. RP Fried, MP (reprint author), Joint Ctr Otolaryngol, 333 Longwood Ave, Boston, MA 02115 USA. NR 17 TC 12 Z9 12 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 1998 VL 31 IS 2 BP 331 EP + DI 10.1016/S0030-6665(05)70052-9 PG 11 WC Otorhinolaryngology SC Otorhinolaryngology GA ZL998 UT WOS:000073494600009 PM 9518441 ER PT J AU Ung, F Li, KK Keith, DA McKenna, MJ AF Ung, F Li, KK Keith, DA McKenna, MJ TI Giant cell reparative granuloma of the temporal bone: Case report and review of the literature SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Review ID MIDDLE CRANIAL FOSSA; MANDIBULAR CONDYLE; SKULL BASE; TUMOR; LESIONS; DISLOCATION; MAXILLA C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Ung, F (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 23 TC 21 Z9 24 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD APR PY 1998 VL 118 IS 4 BP 525 EP 529 DI 10.1177/019459989811800415 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA ZG007 UT WOS:000072955300017 PM 9560106 ER PT J AU Ansley, JF Cunningham, MJ AF Ansley, JF Cunningham, MJ TI Treatment of aural foreign bodies in children SO PEDIATRICS LA English DT Article DE foreign body; ear; children ID EAR; NOSE AB Objective. To determine the proper treatment of children and adolescents with foreign bodies of the external auditory canal (EAC). Design. Retrospective case series. Setting. Specialty care referral hospital. Patients. All patients younger than 18 years of age who presented in the emergency ward or office setting with a foreign body of the EAC during a 5-year period. Results. One hundred ninety-one patients with aural foreign bodies were identified. Age at presentation ranged from 10 months to 17 years with 141 patients (74%) younger than 8 years old. Twenty-seven different objects were encountered with pebbles, beads, insects, and plastic toys the most common. Fifty-seven (30%) of the patients required surgical removal of the aural foreign body under general anesthesia. Conclusion. Adequate immobilization and proper instrumentation allow the uncomplicated removal of many EAC foreign bodies in the pediatric population. The use of general anesthesia is preferred in very young children and in children of any age with aural foreign bodies whose contour, composition, or location predispose to traumatic removal in the ambulatory setting. Criteria for otolaryngologic referral and consideration of operative microscopic removal are outlined. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Cunningham, MJ (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. NR 12 TC 32 Z9 32 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 1998 VL 101 IS 4 BP 638 EP 641 DI 10.1542/peds.101.4.638 PG 4 WC Pediatrics SC Pediatrics GA ZE903 UT WOS:000072843200013 PM 9521948 ER PT J AU Baker, RR Lichtenberg, PA Moye, J AF Baker, RR Lichtenberg, PA Moye, J TI A practice guideline for assessment of competency and capacity of the older adult SO PROFESSIONAL PSYCHOLOGY-RESEARCH AND PRACTICE LA English DT Article AB This article identifies the need for a conceptual and practical model for conducting psychological assessments for competency and capacity in the older adult as part of a legal determination of competency. The role of practice guidelines in responding to this need is discussed, and a practice guideline is described to assist practitioners in responding to requests for such assessments. C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Rehabil Inst Michigan, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Phys Med & Rehabil, Detroit, MI 48202 USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Baker, RR (reprint author), S Texas Vet Hlth Care Syst, San Antonio, TX USA. RI Moye, Jennifer/F-2240-2017 OI Moye, Jennifer/0000-0002-3434-347X NR 21 TC 10 Z9 10 U1 0 U2 2 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7028 J9 PROF PSYCHOL-RES PR JI Prof. Psychol.-Res. Pract. PD APR PY 1998 VL 29 IS 2 BP 149 EP 154 DI 10.1037//0735-7028.29.2.149 PG 6 WC Psychology, Multidisciplinary SC Psychology GA ZD922 UT WOS:000072739000010 ER PT J AU Rasmussen, DD AF Rasmussen, DD TI Effects of chronic nicotine treatment and withdrawal on hypothalamic proopiomelanocortin gene expression and neuroendocrine regulation SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE nicotine; proopiomelanocortin; endorphins; hypothalamus; mRNA; withdrawal ID MESSENGER-RNA LEVELS; BETA-ENDORPHIN; CIGARETTE-SMOKING; ARCUATE NUCLEUS; ABSTINENCE SYNDROME; CONDITIONED TOLERANCE; INSITU HYBRIDIZATION; DOPAMINE RELEASE; MEDIAN-EMINENCE; RAT AB Considerable evidence suggest that some responses to smoking and nicotine are mediated by forebrain beta-endorphinergic opioid mechanisms. It has also been demonstrated that nicotine stimulates rat tuberoinfundibular dopaminergic activity. Since we have proposed that interactions between mediobasohypothalamic (MBH) dopaminergic and beta-endorphinergic mechanisms have a key role in neuroendocrine integration, we investigated the effects of chronic nicotine treatment and withdrawal on: (1) MBH concentrations of proopiomelanocortin (POMC, precursor for beta-endorphin biosynthesis) mRNA; (2) MBH concentrations of tyrosine hydroxylase (TH, rate limiting enzyme in catecholamine biosynthesis) mRNA; (3) corresponding, serum prolactin, corticosterone, luteinizing hormone (LH), and testosterone concentrations. POMC and TH mRNA levels were measured by RNase protection/solution hybridization assay; serum hormone levels were measured by radioimmunoassay. Adult male rats received subcutaneous injections of either nicotine or saline during the dark period of each day on an increasing frequency (1-3 injections/day) and dosage (0.4-0.5 mg nicotine/kg body weight) schedule over 4 weeks. The rats were sacrificed after 4 weeks treatment and at 1. 3, 7, 14 and 21 days withdrawal. Chronic daily nicotine administration induced significant changes in serum corticosterone, serum prolactin, MBH TH mRNA, and MBH POMC mRNA concentrations that tended to persist through day 3 of withdrawal; serum prolactin and MBH POMC mRNA concentrations were suppressed whereas serum corticosterone and MBH TH mRNA concentrations were stimulated. None of the parameters were significantly different from control levels following 7 or more days of withdrawal from nicotine, except for a significant decrease of MBH POMC mRNA concentrations on day 21. Chronic daily nicotine or withdrawal did not significantly alter serum LH or testosterone concentrations. These results suggest that chronic nicotine inhibited POMC gene expression and thus, probably, biosynthesis of beta-endorphin and other opiomelanocortins. We hypothesize that suppression of forebrain beta-endorphin synthesis in response to long-term nicotine exposure produces a chronically opioid deficient condition which may play an important role in maintaining nicotine self-administration and in mediating some changes during the nicotine withdrawal syndrome. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Mental Hlth Serv, Seattle, WA 98195 USA. RP Rasmussen, DD (reprint author), VA Med Ctr, Res Serv 151, Amer Lake, Tacoma, WA 98493 USA. EM drasmuss@u.washington.edu NR 67 TC 34 Z9 36 U1 2 U2 5 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 1998 VL 23 IS 3 BP 245 EP 259 PG 15 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 100KA UT WOS:000074814300003 PM 9695129 ER PT J AU Curtin, HD Ishwaran, H Mancuso, AA Dalley, RW Caudry, DJ McNeil, BJ AF Curtin, HD Ishwaran, H Mancuso, AA Dalley, RW Caudry, DJ McNeil, BJ TI Comparison of CT and MR imaging in staging of neck metastases SO RADIOLOGY LA English DT Article DE computed tomography (CT), comparative studies; head and neck neoplasms, CT; head and neck neoplasms, MR; lymphatic system, neoplasms; magnetic resonance (MR), comparative studies ID CERVICAL LYMPH-NODES; SQUAMOUS-CELL CARCINOMA; CLINICALLY NEGATIVE NECK; CONVENTIONAL SPIN-ECHO; COMPUTED-TOMOGRAPHY; ELECTIVE IRRADIATION; ORAL-CANCER; DISSECTION; DISEASE; HEAD AB PURPOSE: To compare the abilities of magnetic resonance (MR) imaging and computed tomography (CT) in detection of lymph node metastasis from head and neck squamous cell carcinoma. MATERIALS AND METHODS: MR imaging and CT were performed with standard protocols in patients with known carcinoma of the oral cavity, oropharynx, hypopharynx, or larynx. Histopathologic examination was performed to validate imaging findings. Between 1991 and 1994, 213 patients undergoing 311 neck dissections were accrued at three institutions. RESULTS: For the upper jugular and spinal accessory regions, the areas under the receiver operating characteristic curve for combined information on size and internal abnormality were 0.80 for CT and 0.75 for MR imaging. Sensitivities, specificities, negative predictive values (NPVs), and positive predictive values (PPVs) were calculated for various size criteria with and without internal abnormality information. With use of a 1-cm size or an internal abnormality to indicate a positive node, CT had an NPV of 84% and a PPV of 50%, and MR imaging had an NPV of 79% and a PPV of 52%. CT achieved an NPV of 90%, correlating with a PPV of 44%, with use of 5-mm size as an indicator of a positive node. CONCLUSIONS: CT performed slightly better than MR imaging for all interpretative criteria. However, a high NPV was achieved only when a low size criterion was used and was therefore associated with a relatively low PPV. C1 Massachusetts Eye & Ear Infirm, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Ottawa, Dept Math & Stat, Ottawa, ON K1N 6N5, Canada. Univ Florida, Coll Med, Gainesville, FL USA. Univ Florida, Shands Hosp, Dept Radiol, Gainesville, FL USA. Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Curtin, HD (reprint author), Massachusetts Eye & Ear Infirm, Dept Radiol, 243 Charles St, Boston, MA 02114 USA. FU NCI NIH HHS [UO1CA54019] NR 49 TC 196 Z9 209 U1 0 U2 3 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 1998 VL 207 IS 1 BP 123 EP 130 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZD211 UT WOS:000072662500019 PM 9530307 ER PT J AU Kaufman, KR Gerner, R AF Kaufman, KR Gerner, R TI Lamotrigine toxicity secondary to sertraline SO SEIZURE-EUROPEAN JOURNAL OF EPILEPSY LA English DT Article DE lamotrigine; sertraline; toxicity; metabolism; glucuronidation; epilepsy ID EPIDERMAL NECROLYSIS; ANTICONVULSANT; METABOLISM; VALPROATE AB Blood level monitoring helps to determine the therapeutic and toxic ranges for anticonvulsants and antidepressants. We investigated initial drug-drug interactions between lamotrigine and sertraline. We report on case histories of two epileptic patients who were initially on lamotrigine and to whom sertraline was added to control psychiatric features. In case 1, a total daily dose of 25 mg sertraline, with nondetectable sertraline and desmethylsertraline blood levels, resulted in a doubling of the lamotrigine blood level with symptoms of toxicity. In case 2, a 25 mg reduction in the total daily dose of sertraline resulted in halving of the lamotrigine blood level even though the lamotrigine dosage was increased by 33%. This shows that sertraline has potent interactions with lamotrigine metabolism. The authors hypothesize that inhibition of glucuronidation is responsible. Clinicians are advised to observe for symptoms of toxicity and to do serial blood levels to monitor this interaction. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, New Brunswick, NJ 08901 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Neurol, New Brunswick, NJ 08901 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat & Behav Sci, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90024 USA. RP Kaufman, KR (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Psychiat, 125 Paterson St,Clin Acad Bldg,Suite 2200, New Brunswick, NJ 08901 USA. NR 12 TC 63 Z9 63 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1059-1311 J9 SEIZURE-EUR J EPILEP JI Seizure PD APR PY 1998 VL 7 IS 2 BP 163 EP 165 DI 10.1016/S1059-1311(98)80074-5 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZN974 UT WOS:000073702700014 PM 9627209 ER PT J AU Hansen, KE Arnason, J Bridges, AJ AF Hansen, KE Arnason, J Bridges, AJ TI Autoantibodies and common viral illnesses SO SEMINARS IN ARTHRITIS AND RHEUMATISM LA English DT Review DE autoantibodies; viral infection; parvovirus; hepatitis A, B, C; human immunodeficiency virus ID ACQUIRED IMMUNODEFICIENCY SYNDROME; PARVOVIRUS B19 INFECTION; A VIRUS-INFECTION; ANTICARDIOLIPIN ANTIBODIES; LUPUS ANTICOAGULANT; RHEUMATOID-FACTOR; HEPATITIS-C; MONONUCLEOSIS; CRYOGLOBULINEMIA; AUTOIMMUNITY AB Objectives: To review the literature about common autoantibodies produced in association with viral infection. Methods: Medline review of the medical literature published in English. Results: Common viral infections are often associated with low-titer, polyspecific autoantibodies. However, high-titer antinuclear antibodies, double-stranded DNA antibodies, anticardiolipin antibodies, and other subtype antibodies may be found. Hepatitis C and B virus, human immunodeficiency virus, and parvovirus B19 appear to be associated with autoantibodies more commonly than other viruses. Conclusions: Transient autoantibodies resulting from viral infections are not uncommon. Clinical and laboratory follow-up over time will help distinguish between connective tissue disease and self-limited illness. Copyright (C) 1998 by W.B. Saunders Company. C1 Univ Wisconsin Hosp & Clin, Ctr Clin Sci H6 367, Madison, WI 53792 USA. William S Middleton Mem Vet Hosp, Madison, WI 53705 USA. RP Bridges, AJ (reprint author), Univ Wisconsin Hosp & Clin, Ctr Clin Sci H6 367, 600 Highland Ave, Madison, WI 53792 USA. NR 39 TC 46 Z9 49 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0049-0172 J9 SEMIN ARTHRITIS RHEU JI Semin. Arthritis Rheum. PD APR PY 1998 VL 27 IS 5 BP 263 EP 271 DI 10.1016/S0049-0172(98)80047-4 PG 9 WC Rheumatology SC Rheumatology GA ZJ120 UT WOS:000073181500001 PM 9572708 ER PT J AU Georgopoulos, K AF Georgopoulos, K TI Transcription factors in hemopoiesis - Introduction SO SEMINARS IN IMMUNOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD APR PY 1998 VL 10 IS 2 BP 101 EP 102 DI 10.1006/smim.1998.0110 PG 2 WC Immunology SC Immunology GA 131NF UT WOS:000076581600001 ER PT J AU Nichogiannopoulou, A Trevisan, M Friedrich, C Georgopoulos, K AF Nichogiannopoulou, A Trevisan, M Friedrich, C Georgopoulos, K TI Ikaros in hemopoietic lineage determination and homeostasis SO SEMINARS IN IMMUNOLOGY LA English DT Review DE hemopoiesis; Ikaros; lymphocyte development ID HEMATOPOIETIC STEM-CELLS; DNA-BINDING PROTEINS; TRANSCRIPTION FACTOR; COMPETITIVE REPOPULATION; DENDRITIC CELLS; GENE ENCODES; BONE-MARROW; T-CELLS; MOUSE; PROGENITORS AB Studies on the molecular mechanisms that control hemopoietic differentiation have focused on signaling cas cedes and nuclear effecters that drive this complex develop mental system in a regulated fashion. Here we review the role of Ikaros, the founding member of a unique family of zinc finger transcription factors in this developmental process. Studies on an Ikaros null mutation have revealed an essential role for this factor in lymphoid cell fate determination and at subsequent branch points of the T cell differentiation pathway. Differences in the phenotypes of a null and a dominant negative (DN) Ikaros mutation provide insight into a regulatory network through which Ikaros proteins exert their effects in development. In addition a comparative a analysis of the hemopoietic stern cell and precursor compartment resulting from the two Ikaros mutations reveals a profound yet not absolute requirement for Ikaros in the production and differentiation of these populations. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Grp, Charlestown, MA 02129 USA. RP Nichogiannopoulou, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Grp, Charlestown, MA 02129 USA. NR 31 TC 31 Z9 31 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD APR PY 1998 VL 10 IS 2 BP 119 EP 125 DI 10.1006/smim.1998.0113 PG 7 WC Immunology SC Immunology GA 131NF UT WOS:000076581600004 PM 9618757 ER PT J AU Thrall, JH Boland, G AF Thrall, JH Boland, G TI Telemedicine in practice SO SEMINARS IN NUCLEAR MEDICINE LA English DT Review ID TELERADIOLOGY WORKSTATION; DIGITIZED RADIOGRAPHS; DIAGNOSTIC-ACCURACY; VIRTUAL REALITY; COMPRESSION; IMAGES AB Telemedicine is defined as the "delivery of health care and sharing of medical knowledge over a distance using telecommunication systems." The concept of telemedicine is not new. Beyond the use of the telephone, there were numerous attempts to develop telemedicine programs in the 1960s mostly based on interactive television. The early experience was conceptionally encouraging but suffered inadequate technology. With a few notable exceptions such as the telemetry of medical data in the space program, there was very little advancement of telemedicine in the 1970s and 1980s. Interest in telemedicine has exploded in the 1990s with the development of medical devices suited to capturing images and other data in digital electronic form and the development and installation of high speed, high bandwith telecommunication systems around the world. Clinical applications of telemedicine are now found in virtually every specialty. Teleradiology is the most common application followed by cardiology, dermatology, psychiatry, emergency medicine, home health care, pathology, and oncology. The technological basis and the practical issues are highly variable from one clinical application to another. Teleradiology, including telenuclear medicine, is one of the more well-defined telemedicine services. Techniques have been developed for the acquisition and digitization of images, image compression, image transmission, and image interpretation. The American College of Radiology has promulgated standards for teleradiology, including the requirement for the use of high resolution 2000 x 2000 pixel workstations for the interpretation of plain films. Other elements of the standard address image annotation, patient confidentiality, workstation functionality, cathode ray tube brightness, and image compression. Teleradiology systems are now widely deployed in clinical practice. Applications include providing service from larger to smaller institutions, coverage of outpatient clinics, imaging centers, and nursing homes. Teleradiology is also being used in international applications. Unresolved issues in telemedicine include licensure, the development of standards, reimbursement for services, patient confidentiality, and telecommunications infrastructure and cost. A number of states and medical boards have instituted policies and regulations to prevent physicians who are not licensed in the respective state to provide telemedicine services. This is a major impediment to the delivery of telemedicine between states. Telemedicine, including teleradiology, is here to stay and is changing the practice of medicine dramatically. National and international communications networks are being created that enable the sharing of information and knowledge at a distance. Technological barriers are being overcome leaving organizational, legal, financial, and special interest issues as the major impediments to the further development of telemedicine and realization of its benefits. Copyright (C) 1998 by W.B. Saunders Company. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 49 TC 38 Z9 38 U1 2 U2 13 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0001-2998 J9 SEMIN NUCL MED JI Semin. Nucl. Med. PD APR PY 1998 VL 28 IS 2 BP 145 EP 157 DI 10.1016/S0001-2998(98)80004-4 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZH561 UT WOS:000073123700004 PM 9579416 ER PT J AU Deutsch, JC AF Deutsch, JC TI Normal digestive physiology and the evaluation of digestive function SO SEMINARS IN ONCOLOGY LA English DT Review ID EXOCRINE PANCREATIC FUNCTION; BILE-ACID MALABSORPTION; FEEDBACK-REGULATION; BREATH TEST; SECRETION; CHOLECYSTOKININ; ABSORPTION; FAT; RELEASE C1 Univ Colorado, Hlth Sci Ctr, Div Gastroenterol, Denver, CO 80262 USA. Denver Vet Affairs Hosp, Denver, CO USA. RP Deutsch, JC (reprint author), Univ Colorado, Hlth Sci Ctr, Div Gastroenterol, 4200 E 9th Ave,Box B-158, Denver, CO 80262 USA. NR 31 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1998 VL 25 IS 2 SU 6 BP 4 EP 11 PG 8 WC Oncology SC Oncology GA ZT176 UT WOS:000074056800002 PM 9625377 ER PT J AU Elias, AD AF Elias, AD TI High-dose therapy for adult soft tissue sarcoma: Dose response and survival SO SEMINARS IN ONCOLOGY LA English DT Review ID COMBINATION CHEMOTHERAPY; IFOSFAMIDE; DOXORUBICIN; BONE; CYCLOPHOSPHAMIDE; MESNA; TRIAL; BLOOD C1 Dana Farber Canc Inst, Dept Internal Med, Div Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Elias, AD (reprint author), Dana Farber Canc Inst, Dept Internal Med, Div Med Oncol, 44 Binney St, Boston, MA 02115 USA. NR 30 TC 13 Z9 13 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1998 VL 25 IS 2 SU 4 BP 19 EP 23 PG 5 WC Oncology SC Oncology GA ZK911 UT WOS:000073376800004 PM 9578058 ER PT J AU Bessesen, DH Faggioni, R AF Bessesen, DH Faggioni, R TI Recently identified peptides involved in the regulation of body weight SO SEMINARS IN ONCOLOGY LA English DT Review ID OB/OB MICE; LEPTIN; OBESE; GENE; MUTATION; HUMANS; TUBBY C1 Denver Hlth Med Ctr, Denver, CO 80204 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. RP Bessesen, DH (reprint author), Denver Hlth Med Ctr, Mail Code 4000,777 Bancock St, Denver, CO 80204 USA. FU NIDDK NIH HHS [DK40990, DK49448, DK47311] NR 27 TC 13 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 1998 VL 25 IS 2 SU 6 BP 28 EP 32 PG 5 WC Oncology SC Oncology GA ZT176 UT WOS:000074056800005 PM 9625380 ER PT J AU Zietman, AL AF Zietman, AL TI Radiation therapy or prostatectomy: An old conflict revisited in the PSA era. A radiation oncologist's viewpoint SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID RADICAL PROSTATECTOMY; FOLLOW-UP; SURGICAL MARGINS; ANTIGEN; CANCER; ADENOCARCINOMA; RADIOTHERAPY; CARCINOMA; BIOPSY; RECURRENCE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. RP Zietman, AL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 30 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD APR PY 1998 VL 8 IS 2 BP 81 EP 86 DI 10.1016/S1053-4296(98)80003-9 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA ZF906 UT WOS:000072945100003 PM 9516588 ER PT J AU Hunt, LM Valenzuela, MA Pugh, JA AF Hunt, LM Valenzuela, MA Pugh, JA TI Porque me toco a mi? Mexican American diabetes patients' causal stories and their relationship to treatment behaviors SO SOCIAL SCIENCE & MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Applied-Anthropology CY MAR 29-APR 02, 1995 CL ALBUQUERQUE, NEW MEXICO SP Soc Appl Anthropol DE diabetes; Locus of Control; causal model; behavioral factors; patient perspective; Mexican Americans ID CHRONIC ILLNESS; HEALTH BELIEFS; EDUCATION; MELLITUS; LOCUS; MANAGEMENT; IDEOLOGY; SCALES; ADULTS; FOCUS AB This paper reports findings from an ethnographic study of self-care behaviors and illness concepts among Mexican-American non-insulin dependent diabetes mellitus (NIDDM) patients. Open-ended interviews were conducted with 49 NIDDM patients from two public hospital outpatient clinics in South Texas. They are self-identified Mexican-Americans who have had NIDDM for at least 1 yr, and have no major impairment due to NIDDM. Interviews focused on their concepts and experiences in managing their illness and their self-care behaviors. Clinical assessment of their glucose control was also extracted from their medical records. The texts of patient interviews were content analyzed through building and refining thematic matrixes focusing on their causal explanations and treatment behaviors. We found patients' causal explanations of their illness often are driven by an effort to connect the illness in a direct and specific way to their personal history and their past experience with treatments. While most cite biomedically accepted causes such as heredity and diet, they elaborate these concepts into personally relevant constructs by citing Provoking Factors, such as behaviors or events. Their causal models are thus both specific to their personal history and consistent with their experiences with treatment success or failure. Based on these findings, we raise a critique of the Locus of Control Model of treatment behavior prevalent in the diabetes education literature. Our analysis suggests that a sense that one's own behavior is important to the disease onset may reflect patients' evaluation of their experience with treatment outcomes, rather than determining their level of activity in treatment. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX 78284 USA. Univ Texas, Dept Social Sci, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Hunt, LM (reprint author), Univ Texas, Hlth Sci Ctr, Sch Nursing, San Antonio, TX 78284 USA. OI Pugh, Jacqueline/0000-0003-4933-141X FU AHRQ HHS [1-UO1-HSO7397] NR 61 TC 91 Z9 94 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD APR PY 1998 VL 46 IS 8 BP 959 EP 969 DI 10.1016/S0277-9536(97)10014-4 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA ZD022 UT WOS:000072643000003 PM 9579748 ER PT J AU Tomford, WW AF Tomford, WW TI Principles of preservation of soft tissue allografts SO SPORTS MEDICINE AND ARTHROSCOPY REVIEW LA English DT Article DE allografts; cryopreservation; freezing; preservation; transplantation ID ANTERIOR CRUCIATE LIGAMENT; BONE ALLOGRAFTS; RECONSTRUCTION; SURVIVAL AB Preserved soft tissues serve as allograft replacements for damaged ligaments and menisci in orthopedic surgery. Currently, the most popular method for preserving or storing soft tissue allografts is freezing. During freezing, cryopreservation is used to preserve cell viability in the grafts, with the goal of transplantation of living native cells in a transplanted allograft. Cell cryopreservation efforts have met with mixed success. Cellular viability in cryopreserved soft tissues has not been high in terms of the percentage of cells originally in the grafts and studies suggest, through comparison of donor and recipient (host) DNA, that all donor cells in the transplanted graft are replaced by host cells within a few months. Nonetheless, based on several clinical studies, cryopreserved soft tissues seem to function reasonably well in many circumstances as replacements for ligaments and menisci. Further research is necessary to achieve the goal of cellular transplantation within the grafts, but the current method of storing and preserving soft tissue allografts seems to provide satisfactory replacement tissues in many cases. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Tomford, WW (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 15 Parkman St,WACC 508, Boston, MA 02114 USA. NR 38 TC 0 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-8592 J9 SPORTS MED ARTHROSC JI Sports Med. Arthrosc. Rev. PD APR-JUN PY 1998 VL 6 IS 2 BP 124 EP 130 PG 7 WC Sport Sciences SC Sport Sciences GA 259MT UT WOS:000083898200008 ER PT J AU Goldstein, IB Bartzokis, G Hance, DB Shapiro, D AF Goldstein, IB Bartzokis, G Hance, DB Shapiro, D TI Relationship between blood pressure and subcortical lesions in healthy elderly people SO STROKE LA English DT Article DE blood pressure; elderly; heart rate; magnetic resonance imaging ID WHITE-MATTER LESIONS; RISK-FACTORS; HYPERTENSIVE PATIENTS; STROKE; VOLUME AB Background and Purpose-The relationship between blood pressure (BP) and heart rate (HR) and MRI assessments of subcortical T2 hyperintensities was evaluated in healthy elderly men and women. Methods-Casual and 24-hour ambulatory BPs and HR measurements were taken of 144 elderly individuals, aged 55 to 79 years. Subjects had no evidence of previous health disorders. MRT scans of white matter, subcortical gray matter, and insular subcortex were coded for severity of hyperintensities. Results-Mean casual BP for the group was 120/72 mm Hg. With age and sex accounted for, individuals with the highest severity rating of white matter hyperintensities had higher casual, awake, and sleep systolic BPs; higher awake diastolic BPs; greater awake systolic BP variability; and a smaller nocturnal fall in systolic and diastolic BPs than individuals with less severe ratings, Higher severity ratings for subcortical gray matter hyperintensities were associated with elevations in casual, awake, and asleep systolic BPs and a smaller HR drop during sleep. Subjects with higher ratings for the insular subcortex had higher systolic and diastolic BPs (casual, awake, and asleep), greater HR variability during sleep, and a smaller nocturnal fall in HR, Conclusions-Casual and 24-hour ambulatory BPs and some ambulatory HR measures are associated with subcortical lesions of the brain. Longitudinal studies are needed to further explore the relationship between white matter lesions and cardiovascular measures, as well as the significance of these lesions for cerebrovascular disease in healthy elderly subjects. C1 Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Biobehav Sci, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Radiol, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA USA. RP Goldstein, IB (reprint author), Univ Calif Los Angeles, Dept Psychiat, 760 Westwood Plaza, Los Angeles, CA 90024 USA. EM irisg@ucla.edu RI Bartzokis, George/K-2409-2013 FU NIA NIH HHS [AG-11595] NR 30 TC 76 Z9 78 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 1998 VL 29 IS 4 BP 765 EP 772 PG 8 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZF529 UT WOS:000072906600005 PM 9550509 ER PT J AU Lo, EH Bosque-Hamilton, P Meng, W AF Lo, EH Bosque-Hamilton, P Meng, W TI Inhibition of poly(ADP-ribose) polymerase - Reduction of ischemic injury and attenuation of N-methyl-D-aspartate-induced neurotransmitter dysregulation SO STROKE LA English DT Article DE DNA repair; excitotoxicity; glutamates; nitric oxide; stroke, ischemic; rats ID CENTRAL NERVOUS-SYSTEM; CEREBRAL-ARTERY OCCLUSION; NITRIC-OXIDE; DNA-DAMAGE; TAURINE; DEATH; RAT; PHOSPHATIDYLETHANOLAMINE; MICRODIALYSIS; ACTIVATION AB Background and Purpose-The nuclear enzyme poly(ADP-ribose) polymerase (PARP) may play a role in DNA repair. However, in cerebral ischemia, excessive PARP activation may lead to energy depletion and exacerbation of neuronal damage, We examined the effect of inhibiting PARP on (1) the degree of cerebral injury in a rat model of transient focal ischemia and (2) the degree of neurotransmitter dysregulation induced by local cortical perfusion of N-methyl-D-aspartate (NMDA). Methods-In experiment 1, rats were subjected to transient ischemia for 90 minutes by occlusion of the middle cerebral artery. After 22.5 hours of reperfusion, lesions were quantified by tetrazolium staining. Untreated rats were compared with those treated with the PARP inhibitor 3-aminobenzamide (10 mg/kg), In experiment 2, rats were implanted with microdialysis probes in the cortex, and 1 mmol/L NMDA was perfused for 2 hours. Extracellular concentrations of neurotransmitter and neuromodulator amino acids were measured. Untreated rats were compared with those given 10 mg/kg 3-aminobenzamide. Results-In experiment 1, PARP inhibition significantly reduced lesion volumes: 204+/-43 mm(3) (untreated) 90 +/- 24 mm(3) (treated), Neuroprotection was primarily manifested in the cortex. In experiment 1, NMDA perfusion resulted in large elevations of glutamate, taurine, and the lipid component phosphoethanolamine. Levels of the NMDA site modulator D-serine were reduced, and glycine levels appeared unchanged. 3-Aminobenzamide significantly attenuated the elevations in glutamate and phosphoethanolamine but had no effects on D-serine and glycine. Conclusions-Inhibition of PARP reduced injury after transient focal ischemia in rats and attenuated NMDA-induced glutamate efflux and overall neurotransmitter dysregulation. The deleterious effects of excessive PARP activation may be related in part to amplification of excitotoxicity, possibly by cellular energy depletion and additional transmitter release and/or reduced reuptake. C1 Massachusetts Gen Hosp, Harvard Med Sch, Neuroprotect Res Lab, Dept Neurol, Charlestown, MA USA. Massachusetts Gen Hosp, Harvard Med Sch, Neuroprotect Res Lab, Dept Radiol, Charlestown, MA USA. RP Lo, EH (reprint author), Harvard Med Sch, Neuroprotect Res Lab, MGH E Bldg 149,Room 2322, Charlestown, MA 02129 USA. EM eng@cipr.mgh.harvard.edu FU NINDS NIH HHS [NS32806] NR 51 TC 106 Z9 106 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0039-2499 J9 STROKE JI Stroke PD APR PY 1998 VL 29 IS 4 BP 830 EP 836 PG 7 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA ZF529 UT WOS:000072906600017 PM 9550519 ER PT J AU Goodkin, R Laska, LL AF Goodkin, R Laska, LL TI Vascular and visceral injuries associated with lumbar disc surgery: Medicolegal implications SO SURGICAL NEUROLOGY LA English DT Review DE lumbar disc surgery; ventral perforation; vascular/visceral injury; medicolegal implications ID ARTERIOVENOUS-FISTULA; INTERVERTEBRAL-DISK; URETERAL INJURY; OUTCOME ANALYSIS; COMPLICATIONS; DISCECTOMY; SECONDARY; LAMINECTOMY; ANATOMY AB Symptomatic perforation of the anterior annulus fibrosus/anterior longitudinal ligament during surgery for herniated lumbar disc disease is one of the more solemn and sobering complications experienced by neurosurgeons or orthopedic surgeons. This complication frequently results in the death of the patient. Its occurrence is probably more common than the medical community would expect. The authors report 21 cases since 1985 in which an injury to an intra-abdominal vessel or viscera occurred. In all cases litigation resulted and a settlement or verdict was rendered. A review of the literature is presented and the medicolegal implications of symptomatic ventral perforations of the annulus fibrosus/anterior longitudinal ligament are discussed. (C) 1998 by Elsevier Science Inc. C1 Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Tennessee State Univ, Coll Business, Nashville, TN 37203 USA. RP Goodkin, R (reprint author), Univ Washington, Sch Med, Dept Neurol Surg, Box 356470, Seattle, WA 98195 USA. NR 124 TC 58 Z9 62 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-3019 J9 SURG NEUROL JI Surg. Neurol. PD APR PY 1998 VL 49 IS 4 BP 358 EP 370 DI 10.1016/S0090-3019(97)00372-8 PG 13 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA ZE443 UT WOS:000072793100001 PM 9537654 ER PT J AU Hsu, JH Brent, GA AF Hsu, JH Brent, GA TI Thyroid hormone receptor gene knockouts SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID EMBRYONIC STEM-CELLS; C-ERBA-ALPHA; V-ERBA; MESSENGER-RNAS; DIFFERENTIAL EXPRESSION; GENERALIZED RESISTANCE; RESPONSE ELEMENT; GENOMIC LOCUS; BETA-GENE; STRUCTURAL-ANALYSIS AB The thyroid hormone receptor genes, TR alpha and TR beta, differ in developmental expression and tissue distribution. TR beta knockout mice have goiter, elevated thyroid hormone and TSH levels, and a functional auditory defect. In contrast, mice with TR alpha 1/alpha 2 inactivation have thyroid hypoplasia, low serum thyroid hormone levels, growth arrest and delayed small intensive maturation. Mice with selective TR alpha 1 inactivation have apparent normal growth and development, but have bradycardia and reduced body temperature. The dramatic differences between these mice with TR beta and TR alpha gene inactivations indicate the differential functional of these genes. The influence of these gene inactivations on thyroid-stimulating hormone regulation is central to the resulting phenotypes. C1 Univ Calif Los Angeles, Sch Med, Dept Med, Mol Endocrinol Lab,W Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Physiol, Mol Endocrinol Lab,W Los Angeles VA Med Ctr, Los Angeles, CA 90073 USA. RP Hsu, JH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Mol Endocrinol Lab,W Los Angeles VA Med Ctr, Bldg 114,Room 230,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 96 TC 41 Z9 42 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 1998 VL 9 IS 3 BP 103 EP 112 DI 10.1016/S1043-2760(98)00026-5 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA ZU314 UT WOS:000074184300003 PM 18406250 ER PT J AU Mandelboim, O Kent, S Davis, DM Wilson, SB Okazaki, T Jackson, R Hafler, D Strominger, JL AF Mandelboim, O Kent, S Davis, DM Wilson, SB Okazaki, T Jackson, R Hafler, D Strominger, JL TI Natural killer activating receptors trigger interferon gamma secretion from T cells and natural killer cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE-PHOSPHATASE 1C; INHIBITORY RECEPTOR; HLA-C; NK CELLS; MOLECULES; P58; LYMPHOCYTES; SPECIFICITY; EXPRESSION; CLONING AB Proliferation of human CD4+ alpha beta T cells expressing a natural killer cell activating receptor (NKAR) has been shown to be enhanced, particularly in response to low doses of antigen, if the target cells present appropriate human class I major histocompatibility complex (MHC) molecules. Here, we show that NKAR also enhance proliferation and killing of target cells by subsets of CD8+ alpha beta and CD8+ gamma delta T cells, as well as by NK cells. Strikingly, interferon gamma secretion from all of these types of lymphocytes was markedly increased by interaction of the NKAR with their MHC class I ligands, independently of enhancement of proliferation. Thus, the recognition of class I MHC molecules by NKAR on both T cells and NK cells may provide a regulatory mechanism that affects immune responses through the secretion of interferon gamma and possibly other cytokines. It represents a signal for cytokine secretion alternative and/or augmentative to that through the T cell receptor. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 01238 USA. Joslin Diabet Ctr, Immunol Sect, Boston, MA 02215 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Mandelboim, O (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 7 Divin Ave, Cambridge, MA 01238 USA. FU NCI NIH HHS [CA-47554]; NIDDK NIH HHS [K11DK0235] NR 32 TC 54 Z9 54 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 31 PY 1998 VL 95 IS 7 BP 3798 EP 3803 DI 10.1073/pnas.95.7.3798 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE957 UT WOS:000072848500087 PM 9520447 ER PT J AU Shuster, E AF Shuster, E TI The Nuremberg Code: Hippocratic ethics and human rights SO LANCET LA English DT Article C1 Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Shuster, E (reprint author), Vet Affairs Med Ctr, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM Shuster.Evelyne@Forum.va.gov NR 28 TC 29 Z9 32 U1 3 U2 9 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 28 PY 1998 VL 351 IS 9107 BP 974 EP 977 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA ZE227 UT WOS:000072770900046 PM 9734958 ER PT J AU Sachdev, D Chirgwin, JM AF Sachdev, D Chirgwin, JM TI Order of fusions between bacterial and mammalian proteins can determine solubility in Escherichia coli SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID PORCINE PEPSINOGEN; PROCATHEPSIN-D; EXPRESSION; RHODANESE; MITOCHONDRIAL; STABILIZATION; MUTAGENESIS; MUTATIONS AB We made fusions between Escherichia coli maltose-binding protein (MBP) and the mammalian aspartic proteinases pepsinogen or procathepsin D. When MBP was at the N-terminus, the fusions were soluble in E. coli. When the order was reversed, the chimeric proteins formed inclusion bodies. The data suggest that the solubility of fusion proteins is controlled by whether the protein domains emerging first from the ribosome normally fold into soluble or insoluble states. The soluble MBP-aspartic proteinase fusions were stable but proteolytically inactive. MBP-pepsinogen, however, was efficiently renatured from 8 M urea in vitro, suggesting that the E. coli cytoplasm does not support folding of the mammalian partner protein to the native state. Thus, inclusion body formation may be the consequence, rather than the cause, of non-native folding in vivo, and in E. coli soluble proteins may fold into states different from those reached in vitro. (C) 1998 Academic Press. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA. Audie L Murphy Mem Vet Adm Med Ctr, Res Serv, San Antonio, TX 78284 USA. RP Chirgwin, JM (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Endocrinol & Metab, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. FU NCI NIH HHS [P01 CA 40035] NR 32 TC 42 Z9 45 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 27 PY 1998 VL 244 IS 3 BP 933 EP 937 DI 10.1006/bbrc.1998.8365 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZF658 UT WOS:000072919100059 PM 9535771 ER PT J AU Lecine, P Blank, V Shivdasani, R AF Lecine, P Blank, V Shivdasani, R TI Characterization of the hematopoietic transcription factor NF-E2 in primary murine megakaryocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUCINE ZIPPER PROTEIN; GLOBIN GENE-EXPRESSION; LOCUS-CONTROL REGION; SMALL MAF PROTEINS; CDNA CLONING; MICE LACKING; MPL LIGAND; C-MPL; BINDING; FAMILY AB Biochemical analysis of megakaryocytes, the precursors of blood platelets, is limited by their rarity in vivo, and studies on lineage-specific gene expression have been conducted exclusively in cell lines with limited megakaryocytic potential. Mice lacking the transcription factor NF-E2 display arrested megakaryocyte differentiation and profound thrombocytopenia. To study the heterodimeric NF-E2 protein in primary cells, we cultured mouse fetal livers with the c-Mpl ligand, obtained highly enriched megakaryocyte populations, and readily detected NF-E2 activity in nuclear extracts. As in erythroid cells, p45 NF-E2 is the only large subunit in primary megakaryocytes that dimerizes with distinct small Maf proteins to constitute a heterogeneous NF-E2 complex. Whereas p18/MafK is the predominant small Maf protein in erythroid cells, the related polypeptides MafG and/or MafF predominate in megakaryocytes. Although this represents the first example of differential small Maf protein expression among closely related blood lineages, the DNA-binding specificity of NF-E2 is similar in both cell types. Although the megakaryocyte protein preferentially binds an asymmetric AP-1-related motif, it also recognizes cAMP-responsive element related sequences, albeit with lower affinity, and nucleotides outside the core sequence influence the DNA-protein interaction. These results demonstrate the feasibility of biochemical studies on primary murine megakaryocytes and provide a basis to dissect the critical functions of NF-E2 in megakaryocyte differentiation. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Shivdasani, R (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Lecine, Patrick/H-9338-2016 FU NHLBI NIH HHS [HL03290] NR 40 TC 48 Z9 50 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 27 PY 1998 VL 273 IS 13 BP 7572 EP 7578 DI 10.1074/jbc.273.13.7572 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZD917 UT WOS:000072738500056 PM 9516460 ER PT J AU Hollander, GA Zuklys, S Morel, C Mizoguchi, E Mobisson, K Simpson, S Terhorst, C Wishart, W Golan, DE Bhan, AK Burakoff, SJ AF Hollander, GA Zuklys, S Morel, C Mizoguchi, E Mobisson, K Simpson, S Terhorst, C Wishart, W Golan, DE Bhan, AK Burakoff, SJ TI Monoallelic expression of the interleukin-2 locus SO SCIENCE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; VERSUS-HOST DISEASE; CELL GROWTH-FACTOR; T-CELLS; CD28 RECEPTOR; RECOMBINANT INTERLEUKIN-2; SIGNAL-TRANSDUCTION; AUTOIMMUNE-DISEASE; PROTEIN-TYROSINE; ANTIGEN RECEPTOR AB The lymphokine interleukin-2 (IL-2) is responsible for autocrine cell cycle progression and regulation of immune responses. Uncontrolled secretion of IL-2 results in adverse reactions ranging from anergy, to aberrant T cell activation, to autoimmunity. With the use of fluorescent in situ hybridization and single-cell polymerase chain reaction in cells with different IL-2 alleles; IL-2 expression in mature thymocytes and T cells was found to be tightly controlled by monoallelic expression. Because IL-2 is encoded at a nonimprinted autosomal locus, this result represents an unusual regulatory mode for controlling the precise expression of a single gene. C1 Univ Basel, Sch Med, Dept Res, CH-4031 Basel, Switzerland. Univ Basel, Sch Med, Childrens Hosp, CH-4031 Basel, Switzerland. Harvard Univ, Sch Med, Dept Pediat, Dana Farber Canc Inst,Div Pediat Oncol, Boston, MA 02115 USA. Novartis Pharma, Preclin Res, CH-4002 Basel, Switzerland. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Burakoff, SJ (reprint author), Univ Basel, Sch Med, Dept Res, CH-4031 Basel, Switzerland. FU NCI NIH HHS [P01 CA39542-09]; NIAID NIH HHS [R01 AI17258-18]; NIDDK NIH HHS [R01 DK47677] NR 55 TC 188 Z9 190 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 27 PY 1998 VL 279 IS 5359 BP 2118 EP 2121 DI 10.1126/science.279.5359.2118 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZE274 UT WOS:000072775600051 PM 9516115 ER PT J AU Teng, MK Smolyar, A Tse, AGD Liu, JH Liu, J Hussey, RE Nathenson, SG Chang, HC Reinherz, EL Wang, JH AF Teng, MK Smolyar, A Tse, AGD Liu, JH Liu, J Hussey, RE Nathenson, SG Chang, HC Reinherz, EL Wang, JH TI Identification of a common docking topology with substantial variation among different TCR-peptide-MHC complexes SO CURRENT BIOLOGY LA English DT Article ID T-CELL RECEPTOR; CLASS-I H-2K(B); VIRAL PEPTIDE; MOLECULE; ORIENTATION; BINDING AB Whether T-cell receptors (TCRs) recognize antigenic peptides bound to major histocompatability complex (MHC) molecules through common or distinct docking modes is currently uncertain. We report the crystal structure of a complex between the murine N15 TCR [1-4] and its peptide-MHC ligand, an octapeptide fragment representing amino acids 52-59 of the vesicular stomatitis virus nuclear capsid protein (VSV8) bound to the murine H-2K(b) class I MHC molecule, Comparison of the structure of the N15 TCR-VSV8-H-2K(b) complex with the murine 2C TCR-dEV8-H-2K(b) [5] and the human A6 TCR-Tax-HLA-A2 [6] complexes revealed a common docking mode, regardless of TCR specificity or species origin, in which the TCR variable Va domain overlies the MHC alpha 2 helix and the V beta domain overlies the MHC alpha 1 helix, As a consequence, the complementary determining regions CDR1 and CDR3 of the TCR V alpha and V beta domains make the major contacts with the peptide, while the CDR2 loops interact primarily with the MHC, Nonetheless, in terms of the details of the relative orientation and disposition of binding, there is substantial variation in TCR parameters, which we term twist, tilt and shift, and which define the variation of the V module of the TCR relative to the MHC antigen-binding groove. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Immunobiol Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP Wang, JH (reprint author), Univ Sci & Technol China, Dept Biol, Hefei 230026, Peoples R China. EM jwang@red.dfci.harvard.edu NR 19 TC 96 Z9 96 U1 1 U2 4 PU CURRENT BIOLOGY LTD PI LONDON PA 34-42 CLEVELAND STREET, LONDON W1P 6LB, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 26 PY 1998 VL 8 IS 7 BP 409 EP 412 DI 10.1016/S0960-9822(98)70160-5 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZE608 UT WOS:000072811600020 PM 9545202 ER PT J AU Vlahakes, GJ Drucker, EA Mark, EJ Hanna, GJ AF Vlahakes, GJ Drucker, EA Mark, EJ Hanna, GJ TI A 46-year-old man with chest pain and coronary ostial stenosis - Syphilitic aortitis with coronary ostial stenosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CARDIOVASCULAR SYPHILIS; TAKAYASUS AORTITIS; ARTERY DISEASE C1 Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Vlahakes, GJ (reprint author), Massachusetts Gen Hosp, Cardiac Surg Unit, Boston, MA 02114 USA. NR 54 TC 6 Z9 6 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 26 PY 1998 VL 338 IS 13 BP 897 EP 903 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZD284 UT WOS:000072669800008 ER PT J AU Hiyama, H Iavarone, A Reeves, SA AF Hiyama, H Iavarone, A Reeves, SA TI Regulation of the cdk inhibitor p21 gene during cell cycle progression is under the control of the transcription factor E2F SO ONCOGENE LA English DT Article DE E2F; p21; cell cycle; transcription ID PROTEIN FAMILY MEMBERS; RETINOBLASTOMA PROTEIN; IN-VIVO; C-MYC; P53-INDEPENDENT EXPRESSION; FUNCTIONAL INTERACTION; PROMOTER; BINDING; ARREST; GROWTH AB The control of cell cycle progression is orchestrated by an extraordinary diverse and dynamic in function group of proteins. Critical in the progression are the actions of the E2F family of transcription factors which regulate the expression of genes necessary for the G(1)/S transition and the WAF/CIP/KIP family of cdk inhibitors which can inhibit cell cycle progression. In this report, we have identified E2F binding sites in both the human and mouse p21 promoters that bind E2F protein complexes from nuclear extracts in a cell cycle-dependent manner. In ectopic expression experiments we determined that E2F1, but not E2F4, can strongly transactivate the human p21 gene through these E2F binding sites which are located in the -215/+1 region of the p21 gene. The transactivation of the p21 gene through regulatory elements within the -215/+1 region of the promoter was correlated with increased levels of endogenous E2F1 and p21 proteins at the G(1)/S boundary. The significance of transactivation of the p21 gene by E2F is that p21 function is important in cell cycle progression as well as for cell cycle arrest. Indeed, E2F- induced levels of p21 protein during the G(1)/S transition is consistent with the recent findings demonstrating that p21 acts as an assembly factor for kinase active cyclin/cdk/p21 complexes. C1 Massachusetts Gen Hosp, Ctr Neurosci, Neurosurg Serv, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Mem Sloan Kettering Canc Ctr, Cell Biol & Genet Program, New York, NY 10021 USA. RP Reeves, SA (reprint author), Massachusetts Gen Hosp, Ctr Neurosci, Neurosurg Serv, Boston, MA 02129 USA. NR 59 TC 102 Z9 102 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 26 PY 1998 VL 16 IS 12 BP 1513 EP 1523 DI 10.1038/sj.onc.1201667 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA ZD962 UT WOS:000072743200001 PM 9569018 ER PT J AU Buswell, L Beyea, SC AF Buswell, L Beyea, SC TI Flushing protocols for tunneled central venous catheters: An integrative review of the literature SO ONLINE JOURNAL OF KNOWLEDGE SYNTHESIS FOR NURSING LA English DT Review DE catheters; heparin; thrombosis; catheter care; central venous catheters ID ATRIAL CATHETER AB (1) The flushing regimes for and associated practices related to tunneled central venous catheters (Hickman and Broviac) vary widely. Recommendations for flushing tunneled central venous catheters are abundant in the literature, but few are research-based. This manuscript describes the clinical problem and summarizes six research-based studies that appear in the literature. Practice recommendations based on this review include using 5 mL of 10 unit/ mL of heparin once or twice weekly. It is clear that additional prospective randomized studies are needed to elucidate the optimal flushing regime for patients with tunneled central venous catheters. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Perioperat Nursing Res Assoc Operating Room Nurse, Denver, CO USA. RP Buswell, L (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 19 TC 1 Z9 1 U1 1 U2 1 PU SIGMA THETA TAU INT PI INDIANAPOLIS PA 550 W NORTH STREET, INDIANAPOLIS, IN 46202 USA SN 1072-7639 J9 ONLINE J KNOWL SYN N JI Online J. Knowl. Synth. Nurs. PD MAR 24 PY 1998 VL 5 IS 3 BP art. no. EP 3 PG 9 WC Nursing SC Nursing GA 171DY UT WOS:000078848300001 PM 12874713 ER PT J AU Mathey-Prevot, B Perrimon, N AF Mathey-Prevot, B Perrimon, N TI Mammalian and Drosophila blood: JAK of all trades? SO CELL LA English DT Review ID SYSTEM C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Dept Genet, Boston, MA 02115 USA. RP Mathey-Prevot, B (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 21 TC 39 Z9 40 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 20 PY 1998 VL 92 IS 6 BP 697 EP 700 DI 10.1016/S0092-8674(00)81396-3 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZD198 UT WOS:000072661200001 PM 9529244 ER PT J AU Puigserver, P Wu, ZD Park, CW Graves, R Wright, M Spiegelman, BM AF Puigserver, P Wu, ZD Park, CW Graves, R Wright, M Spiegelman, BM TI A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis SO CELL LA English DT Article ID BROWN ADIPOSE-TISSUE; MITOCHONDRIAL UNCOUPLING PROTEIN; THYROID-HORMONE RECEPTOR; ADIPOCYTE DIFFERENTIATION; TRANSCRIPTIONAL ACTIVATION; ENERGY-BALANCE; MESSENGER-RNA; IN-VITRO; EXPRESSION; GENE AB Adaptive thermogenesis is an important component of energy homeostasis and a metabolic defense against obesity. We have cloned a novel transcriptional coactivator of nuclear receptors, termed PGC-1, from a brown fat cDNA library. PGC-I mRNA expression is dramatically elevated upon cola exposure of mice in both brown fat and skeletal muscle, key thermogenic tissues. PGC-1 greatly increases the transcriptional activity of PPAR gamma and the thyroid hormone receptor on the uncoupling protein (UCP-1) promoter. Ectopic expression of PGC-1 in white adipose cells activates expression of UCP-1 and key mitochondrial enzymes of the respiratory chain, and increases the cellular content of mitochondrial DNA. These results indicate that PGC-1 plays a key role in linking nuclear receptors to the transcriptional program of adaptive thermogenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Chicago, Dept Med, Div Gastroenterol, Chicago, IL 60637 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIDDK NIH HHS [R37DK31405] NR 57 TC 2046 Z9 2132 U1 21 U2 125 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 20 PY 1998 VL 92 IS 6 BP 829 EP 839 DI 10.1016/S0092-8674(00)81410-5 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZD198 UT WOS:000072661200015 PM 9529258 ER PT J AU Boileau, T Ferruzzi, M Sartor, O Schwartz, S Erdman, J Clinton, S AF Boileau, T Ferruzzi, M Sartor, O Schwartz, S Erdman, J Clinton, S TI Lycopene isomers and carotenoid profiles in African American (AA) and Caucasian (C) men SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Louisiana State Univ, Shreveport, LA 71105 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Illinois, Urbana, IL 61801 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4957 BP A856 EP A856 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501339 ER PT J AU Chang, JF Phillips, J Kufe, D Greenburg, G AF Chang, JF Phillips, J Kufe, D Greenburg, G TI MUC1 can function as a potent negative regulator of T cell activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. Cell Genesys Inc, Foster City, CA 94404 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5381 BP A929 EP A929 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501762 ER PT J AU Craft, N Garnett, K Hedley-Whyte, ET Fitch, K Haitema, T Dorey, CK AF Craft, N Garnett, K Hedley-Whyte, ET Fitch, K Haitema, T Dorey, CK TI Carotenoids, tocopherols, and vitamin A in human brain SO FASEB JOURNAL LA English DT Meeting Abstract C1 Craft Technol Inc, Wilson, NC 27893 USA. Appl Food Biotechnol, OFallon, MO 63366 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5601 BP A967 EP A967 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501983 ER PT J AU Cunningham, K Ackerly, H Claflin, L Collins, J Wu, PQ Ford, C Dunnick, W Lansford, R Alt, F AF Cunningham, K Ackerly, H Claflin, L Collins, J Wu, PQ Ford, C Dunnick, W Lansford, R Alt, F TI Germline transcription and switch recombination of a murine VDJ mu delta gamma 1 transgene SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp, HHMI Res Labs, Boston, MA 02115 USA. RI Lansford, Rusty/C-6956-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6119 BP A1058 EP A1058 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502501 ER PT J AU Fahy, LM Taylor, JA AF Fahy, LM Taylor, JA TI Direct application of B-mode carotid ultrasonography to arterial baroreflex gain determination in humans. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Beth Isreal Deaconess Med Ctr, Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3990 BP A688 EP A688 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500373 ER PT J AU Fitzgibbon, WR Ploth, DW AF Fitzgibbon, WR Ploth, DW TI Bradykinin acts via luminal B-2 receptors to decrease distal nephron Na absorption in rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3972 BP A685 EP A685 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500358 ER PT J AU Freidman, T Sachs, DH Iacomini, J AF Freidman, T Sachs, DH Iacomini, J TI Purified CD4(+) T lymphocytes reject porcine skin grafts in an immunodeficient mouse model SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5212 BP A900 EP A900 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501596 ER PT J AU Hales, CA Quinn, DA Volokhov, A Du, HK AF Hales, CA Quinn, DA Volokhov, A Du, HK TI Possible role for HgCl2 sensitive aquaporins in ventilator induced pulmonary edema SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4502 BP A777 EP A777 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500885 ER PT J AU Lantz, CS Boesiger, J Song, CH Kimura, K Mach, N Kobavashi, T Mulligan, RC Nawa, Y Dranoff, G Galli, SJ AF Lantz, CS Boesiger, J Song, CH Kimura, K Mach, N Kobavashi, T Mulligan, RC Nawa, Y Dranoff, G Galli, SJ TI Role for interleukin-3 (IL-3) in mast cell and basophil development and parasite immunity revealed by IL-3-deficient mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Beth Israel Deaconness Med Ctr, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5178 BP A894 EP A894 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501559 ER PT J AU Li, TK Bierer, BE AF Li, TK Bierer, BE TI FK506- and calmodulin-independent binding of the immunophilin FKBP51 to calcineurin SO FASEB JOURNAL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5438 BP A939 EP A939 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501820 ER PT J AU Mukherjee, P Zhou, J Sotnikov, A Mangian, H Blackburn, G Visek, W Clinton, S AF Mukherjee, P Zhou, J Sotnikov, A Mangian, H Blackburn, G Visek, W Clinton, S TI Energy intake stimulates prostate tumor growth by enhancing VEGF expression and tumor angiogenesis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Univ Illinois, Coll Med, Div Nutr Sci, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3821 BP A658 EP A658 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500205 ER PT J AU Murtaza, A Freeman, GJ Kuchroo, VK AF Murtaza, A Freeman, GJ Kuchroo, VK TI Strength of costimulatory signal dictates functional responses by T cell clones SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6285 BP A1086 EP A1086 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502667 ER PT J AU Murua, J Mazariegos, M Valdez, C Solomons, NW Smith, RJ AF Murua, J Mazariegos, M Valdez, C Solomons, NW Smith, RJ TI Body composition and growth hormone secretion in the Guatemala's oldest-old survivors. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Ctr Studies Sensory Impairment Aging & Metab, Guatemala City 01011, Guatemala. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5589 BP A965 EP A965 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501974 ER PT J AU Quinn, DA Hales, CA Joseph, PM Bonventre, JV Force, T AF Quinn, DA Hales, CA Joseph, PM Bonventre, JV Force, T TI Stretch induces activation of stress activated protein kinases (SAPK) in type II alveolar cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Pulm Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4504 BP A777 EP A777 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500886 ER PT J AU Senpuku, H Fujisawa, T Shikata, K Hattori, M AF Senpuku, H Fujisawa, T Shikata, K Hattori, M TI MHC IA-restricted T cell response to GAD peptide is insufficient for development of diabetes in intra-MHC recombinant NOD mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6347 BP A1097 EP A1097 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502730 ER PT J AU Tsukaguchi, H Shayakul, C Mackenzie, B Berger, UV van Hoek, AN Hediger, MA AF Tsukaguchi, H Shayakul, C Mackenzie, B Berger, UV van Hoek, AN Hediger, MA TI Expression cloning and characterization of an osmotic solute channel from rat liver SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6033 BP A1043 EP A1043 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502418 ER PT J AU Ufret-Vincenty, R Pak, SH Quigley, L Wucherfennig, K Brocke, S AF Ufret-Vincenty, R Pak, SH Quigley, L Wucherfennig, K Brocke, S TI Induction of experimental autoimmune encephalomyelitis by pathogen derived peptides. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, NIB, Neurol Dis Sect, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6310 BP A1090 EP A1090 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502692 ER PT J AU Williams, AW Clinton, SK Lee, CM Erdman, JW AF Williams, AW Clinton, SK Lee, CM Erdman, JW TI A comparison of dietary supplementation with tomato extract, tomato powder, or lycopene on the tissue distribution of lycopene and LNCaP prostate tumor growth in mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5594 BP A966 EP A966 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501979 ER PT J AU Woods, LL Ingelfinger, JR AF Woods, LL Ingelfinger, JR TI Maternal Na+ intake modulates renal renin mRNA in the newborn rat. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3949 BP A681 EP A681 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500333 ER PT J AU Xu, YC Bunegin, M Jin, DC Abboud, HE AF Xu, YC Bunegin, M Jin, DC Abboud, HE TI Apoptosis of glomerular cells is an early manifestation of immunecomplex-mediated glomerulonephritis in the rat SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4615 BP A796 EP A796 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500997 ER PT J AU Yang, XF Weber, GF Cantor, H AF Yang, XF Weber, GF Cantor, H TI Newly-identified Bcl-x gamma regulates apoptosis in T-cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5368 BP A927 EP A927 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501752 ER PT J AU Zhou, JR Mukherjee, P Clinton, SK Blackburn, GL AF Zhou, JR Mukherjee, P Clinton, SK Blackburn, GL TI Soybean components inhibit the growth of human prostate cancer cell line LNCaP in SCID mice via alteration in cell apoptosis, angiogenesis, and proliferation. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Nutr Metab Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3822 BP A658 EP A658 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500208 ER PT J AU Khaw, BA Narula, J Vural, I Torchilin, VP AF Khaw, BA Narula, J Vural, I Torchilin, VP TI Cytoskeleton-specific immunoliposomes: sealing of hypoxic cells and intracellular delivery of DNA SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE immunoliposomes; cytoskeletal antigens; cardiocytes; hypoxia; cell salvage; DNA delivery ID MYOSIN-SPECIFIC ANTIBODY; MYOCARDIAL-INFARCTION; LOCALIZATION; REPERFUSION AB Various pathological conditions, including hypoxia and inflammation, provoke cell membrane lesions. These lesions represent microscopic holes in the sarcolemma through which the components of the cytoskeleton become exposed to the surroundings. Labeled antibodies against intracellular cytoskeletal antigens, such as antimyosin antibody, may be used to reveal cell membrane lesions. Being coupled to liposomes, such antibodies can deliver phospholipid vesicles to the affected cell surface and 'plug' them directly into the holes. The in vitro antimyosin antibody-mediated liposome transport to cytoskeletal antigen of hypoxic cardiomyocytes was used in order: (1) to prevent cell deaths by sealing membrane lesions; and (2) to achieve intracellular DNA delivery. A hypoxic model of injury in H9C2 rat embryonic cardiocytes was used in these experiments. Under hypoxic culture conditions, cells were incubated with 150-200 nm antimyosin-immunoliposomes (IL), plain liposomes (PL), and non-specific IgG-liposomes (IgL). After hypoxia (which lasted in different experiments from 1 to 5 days), cell viability was assessed following [H-3]thymidine incorporation, Trypan Blue exclusion test and by fluorescent microscopy. All tests demonstrated highly improved survival of hypoxic cells in the presence of IL (up to 95% survival after 24 h of hypoxia), whereas, cell survival in the presence of control PL and IgL never exceeded 40%. The presence of IL maintained the survival of hypoxic cells for approximately 5 days, while all control cultures never survived for more than 24-36 h. In addition, salvaged cells maintained normal proliferation after hypoxia in the presence of IL. Electron microscopy experiments with silver grains containing IL demonstrated that after incubation, silver grains can be identified in the cytoplasm, which we see as evidence of possible fusion of 'plugging' liposomes with cell membrane. Based on this phenomenon, it is hypothesized that if target cells are under artificial stress, cytoskeleton-specific IL can deliver their contents into the cytoplasm, which provides a good opportunity for the intracellular delivery of drugs and DNA. This hypothesis was confirmed by successful delivery of a plasmid pEScFv 2G42D7 (antimyosin antibody) vector in hypoxic H9C2 cardiocytes by IL. (C) 1998 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. Northeastern Univ, Ctr Cardiovasc Trageting, Boston, MA 02115 USA. RP Torchilin, VP (reprint author), Massachusetts Gen Hosp, Ctr Imaging & Pharmaceut Res, Charlestown, MA 02129 USA. NR 12 TC 2 Z9 2 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD MAR 20 PY 1998 VL 162 IS 1-2 BP 71 EP 76 DI 10.1016/S0378-5173(97)00414-6 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZF682 UT WOS:000072921500010 ER PT J AU Bazzoni, G Ma, L Blue, ML Hemler, ME AF Bazzoni, G Ma, L Blue, ML Hemler, ME TI Divalent cations and ligands induce conformational changes that are highly divergent among beta(1) integrins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-ADHESION MOLECULE-1; MONOCLONAL-ANTIBODY; ALPHA(5)BETA(1) INTEGRINS; FIBRONECTIN RECEPTOR; SIGNAL-TRANSDUCTION; CYTOPLASMIC DOMAINS; DEPENDENT EPITOPE; REGULATORY REGION; COLLAGEN RECEPTOR; BINDING FUNCTION AB Here we show striking differences in conformational regulation among beta(1) integrins. Upon manganese stimulation, a beta(1) epitope defined by monoclonal antibody (mAb) 9EG7 was induced strongly (on alpha(4) beta(1)), moderately (on alpha(5) beta(1)), weakly (on alpha(2) beta(1)), or was scarcely detectable (on alpha(6) beta(1) and alpha(3) beta(1)). Comparable results were seen for the beta(1) epitope defined by mAb 15/7. Likewise, soluble ligands caused strong (alpha(4) beta(1)), moderate (alpha(5) beta(1)), weak (alpha(2) beta(1), alpha(6) beta(1)), Or minimal (alpha(3) beta(1)) induction of the 9EG7 epitope. Exchange or deletion of alpha chain cytoplasmic tails did not alter Mn2+-induced 9EG7 epitope levels. Upon removal of calcium by EGTA or EDTA, the hierarchy of 9EG7 epitope induction was similar (alpha(5) beta(1) > alpha(2) beta(1) > alpha(6) beta(1) > alpha(3) beta(1)), except that EGTA reduced rather than induced 9EG7 expression on alpha(4) beta(1). Thus in contrast to other beta(1) integrins, calcium uniquely supports constitutive expression of the 9EG7 epitope on alpha(4) beta(1). Likewise, calcium supported vascular cell adhesion molecule-stimulated 9EG7 appearance on alpha(4) beta(1), whereas calcium inhibited ligand-induced 9EG7 epitope on other integrins. Constitutive expression of 9EG7 on alpha(4) beta(1) was eliminated by a D698E mutation in alpha(4), suggesting that Asp-698 may play a key role in maintaining atypical alpha(4) beta(1) response to calcium. In conclusion, our results (i) demonstrate that mAb such as 9EG7 and 15/7 have limited diagnostic utility as reporters of ligand or Mn2+ occupancy for beta(1) integrins, (ii) indicate pronounced differences in conformational flexibilities (alpha(4) beta(1) > alpha(5) beta(1) > alpha(2) beta(1) > alpha(6) beta(1) > alpha(3) beta(1)), (iii) allow us to hypothesize that beta(1) integrins may differ markedly in conformation-dependent inside-out signaling, and (iv) have uncovered an atypical alpha(4) beta(1) response to calcium that requires alpha(4) Asp-698. C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Bayer Res Ctr, W Haven, CT 06516 USA. RP Hemler, ME (reprint author), Harvard Univ, Dana Farber Canc Inst, Sch Med, Rm M-413,44 Binney St, Boston, MA 02115 USA. EM Martin_Hemler@DFCI.HARVARD.EDU RI Ma, Lan/B-9295-2009 OI Ma, Lan/0000-0001-9034-5472 FU NCI NIH HHS [CA42368] NR 73 TC 79 Z9 81 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 20 PY 1998 VL 273 IS 12 BP 6670 EP 6678 DI 10.1074/jbc.273.12.6670 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE277 UT WOS:000072775900014 PM 9506964 ER PT J AU Singh, BN AF Singh, BN TI Antiarrhythmic drugs: A reorientation in light of recent developments in the control of disorders of rhythm SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Can Antiarrhythmic Drugs Survive Survival Trials CY AUG 26, 1997 CL STOCKHOLM, SWEDEN ID VENTRICULAR INTRACELLULAR POTENTIALS; CARDIAC-ARRHYTHMIAS; INTRAVENOUS AMIODARONE; MYOCARDIAL-INFARCTION; SUDDEN-DEATH; DOUBLE-BLIND; ATRIAL; MUSCLE; TACHYARRHYTHMIAS; REPOLARIZATION AB Numerous developments in our knowledge of arrhythmias during the past decade or so have had a major influence on antiarrhythmic drug therapy. It has become increasingly evident that arrhythmias merit treatment not only for the relief of symptoms, with improvement in quality of life, but also for the prolongation of survival by decreasing arrhythmic deaths. No longer can mere suppression of arrhythmias, symptomatic or asymptomatic, be equated with prolonged survival. We now know that antiarrhythmic drugs that act by blocking sodium channels can increase mortality and that the most important determinants of arrhythmia mortality are the degree and nature of ventricular dysfunction. To these considerations must be added the advances in nonpharmacologic approaches to controlling cardiac arrhythmias. There has been a shift to the use of implantable devices and of drugs with alternative modes of action, such as beta blockers and class III drugs (e.g., sotalol, amiodarone). However, the side-effect profiles of these 2 classes of compounds have led to the synthesis and characterization of agents that act simply by blocking greater than or equal to 1 membrane ion channels, The isolated block of the rapid component of the delayed rectifier potassium current (I-Kr) has been associated with patent antifibrillatory activity in the atria, with a neutral (e.g., with dofetilide) or deleterious (with d-sotalol) effect on mortality in postinfarct survivors. Therefore, the focus now is on compounds that can block > 1 ion channel (e.g., tedisamil and azimilide). Azimilide is the first of the class III agents that blocks both components of the delayed rectifier potassium current. The drug's overall action is associated with a spectrum of electrophysiologic properties that hold promise in the control of atrial and ventricular arrhythmias, with potential for improving survival in patients at risk for cardiac arrest. (C) 1998 by Excerpta Medica, Inc. C1 W Los Angeles Vet Affairs Med Ctr, Div Cardiol 111E, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. RP Singh, BN (reprint author), W Los Angeles Vet Affairs Med Ctr, Div Cardiol 111E, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 75 TC 40 Z9 40 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 EI 1879-1913 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 19 PY 1998 VL 81 IS 6A SI SI BP 3D EP 13D DI 10.1016/S0002-9149(98)00147-7 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZE882 UT WOS:000072841100002 PM 9537217 ER PT J AU Thomas, MK Lloyd-Jones, DM Thadhani, RI Shaw, AC Deraska, DJ Kitch, BT VAmvakas, EC Dick, IM Prince, RL Finkelstein, JS AF Thomas, MK Lloyd-Jones, DM Thadhani, RI Shaw, AC Deraska, DJ Kitch, BT VAmvakas, EC Dick, IM Prince, RL Finkelstein, JS TI Hypovitaminosis D in medical inpatients SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID VITAMIN-D DEFICIENCY; POSTMENOPAUSAL WOMEN; D SUPPLEMENTATION; HIP-FRACTURES; ELDERLY PERSONS; BONE LOSS; POPULATION; EXPOSURE; SUNLIGHT; CALCIUM AB Background: Vitamin D deficiency is a major risk factor for bone loss and fracture. Although hypovitaminosis D has been detected frequently in elderly and housebound people, the prevalence of vitamin D deficiency among patients hospitalized on a general medical service is unknown. Methods We assessed vitamin D intake, ultraviolet-light exposure, and risk factors for hypovitaminosis D and measured serum 25-hydroxyvitamin D, parathyroid hormone, and ionized calcium in 290 consecutive patients on a general medical ward. Results A total of 164 patients (57 percent)were considered vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, less than or equal to 15 ng per milliliter), of whom 65 (22 percent) were considered severely vitamin D-deficient (serum concentration of 25-hydroxyvitamin D, <8 ng.per milliliter). Serum 25-hydroxyvitamin D concentrations were related inversely to parathyroid hormone concentrations. Lower vitamin D intake, less exposure to ultraviolet light, anticonvulsant-drug therapy, renal dialysis, nephrotic syndrome, hypertension, diabetes mellitus, winter season, higher serum concentrations of parathyroid hormone and alkaline phosphatase, and lower serum concentrations of ionized calcium and albumin were significant univariate predictors of hypovitaminosis D. Sixty-six percent of the patients who consumed less than the recommended daily amount of vitamin D and 37 percent of the patients with intakes above the recommended daily amount were vitamin D-deficient. inadequate vitamin D intake, winter season, and housebound status were independent predictors of hypovitaminosis D in a multivariate model. In a subgroup of 77 patients less than 65 years of age without known risk factors for hypovitaminosis D, the prevalence of vitamin D deficiency was 42 percent. Conclusions Hypovitaminosis D is common in general medical inpatients, including those with vitamin D intakes exceeding the recommended daily amount and those without apparent risk factors for vitamin D deficiency. (C) 1998, Massachusetts Medical Society. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Western Australia, Dept Med, Perth, WA 6009, Australia. Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia. RP Finkelstein, JS (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 55 Fruit St,Bulfinch 327, Boston, MA 02114 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NCRR NIH HHS [RR-1066]; NIDDK NIH HHS [DK07028, R29-DK43341] NR 35 TC 887 Z9 912 U1 1 U2 22 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 19 PY 1998 VL 338 IS 12 BP 777 EP 783 DI 10.1056/NEJM199803193381201 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA ZC163 UT WOS:000072546800001 PM 9504937 ER PT J AU Greene, MF Roberts, DJ Mark, EJ Blatman, RN Roberts, DJ Cohen, M Colvin, RB AF Greene, MF Roberts, DJ Mark, EJ Blatman, RN Roberts, DJ Cohen, M Colvin, RB TI Cardiovascular collapse after vaginal delivery in a patient with a history of cesarean section - Amniotic fluid embolism. Uterine rupture. Placenta accreta with focal placenta increta. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID MATERNAL PULMONARY CIRCULATION; TRIAL; LABOR; DIAGNOSIS; PREGNANCY; PREVIA; CELLS C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Greene, MF (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 34 TC 7 Z9 7 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 19 PY 1998 VL 338 IS 12 BP 821 EP 826 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA ZC163 UT WOS:000072546800008 ER PT J AU Simon, SL Domier, C Rawson, R Ling, W AF Simon, SL Domier, C Rawson, R Ling, W TI Cognitive consequences of methamphetamine abuse on tests of frontal lobe function. SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Medicat Dev Unit, Los Angeles, CA 90073 USA. Matrix Inst Addict, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR 18 PY 1998 VL 10 SU S BP 64 EP 64 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZJ263 UT WOS:000073196500183 ER PT J AU Beversdorf, DQ Anderson, JM Nadeau, S Heilman, KM Manning, S Nordgren, R Felopulos, G Bauman, M AF Beversdorf, DQ Anderson, JM Nadeau, S Heilman, KM Manning, S Nordgren, R Felopulos, G Bauman, M TI Verbal recall in autism: Effects of context & emotion SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Meeting Abstract C1 Univ Florida, Dept Neurol, Gainesville, FL USA. Dartmouth Med Sch, Dept Neurol, Hanover, NH USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RI Beversdorf, David/M-2786-2016 OI Beversdorf, David/0000-0002-0298-0634 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MIT PRESS PI CAMBRIDGE PA 55 HAYWARD STREET, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD MAR 18 PY 1998 VL 10 SU S BP 112 EP 112 PG 1 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA ZJ263 UT WOS:000073196500325 ER PT J AU Bullock, BP Habener, JF AF Bullock, BP Habener, JF TI Phosphorylation of the cAMP response element binding protein CREB by cAMP-dependent protein kinase A and glycogen synthase kinase-3 alters DNA-binding affinity, conformation, and increases net charge SO BIOCHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR CREB; NUCLEAR FACTOR CREB; POLYACRYLAMIDE-GEL ELECTROPHORESIS; SOMATOSTATIN GENE-TRANSCRIPTION; CYCLIC-AMP; COMPLEX-FORMATION; RNA-POLYMERASE; ACTIVATOR; EXPRESSION; REPRESSOR AB The cAMP response element binding protein CREB activates the transcription of genes in response to phosphorylation by cAMP-dependent protein kinase A (PKA) and other protein kinases, Phosphorylated CREB activates transcription by recruiting transcriptional co-activators such as the CREB binding protein. Here, we describe experiments that analyze the effects of phosphorylation on the DNA binding affinity of CREB and the structural characteristics of the CREB/DNA complex in solution, Analysis of deletion mutants of CREB indicate that amino acid sequences within the transactivation domain promote high-affinity binding of CREB to fluorescently labeled oligonucleotides containing cAMP response elements. In vitro experiments indicate that phosphorylation is processive between PKA as the initial kinase and glycogen synthase kinase-3 (GSK-3) but not casein kinase II as the secondary kinase. Fluorescent electrophoretic mobility shift assays show that phosphorylation by PKA results in a 3-5-fold increase in the binding affinity of CREB to both the symmetrical somatostatin CRE (SMS-CRE) and the asymmetric somatostatin upstream element (SMS-UE). Processive phosphorylation of CREB by GSK-3 attenuates the enhanced DNA binding in response to PKA thus acts as an inhibitor of PKA-induced binding. Ferguson plot analyses demonstrate that phosphorylation of CREB by PKA and GSK-3 result in an increase in the spherical size and the net positive surface charge of the CREB/DNA complex. Moreover, these analyses uncovered the unexpected finding that CREB associates as a tetramer both in the presence and absence of DNA, These findings suggest a model by which phosphorylation of CREB alters the secondary structure and charge characteristics of the CREB/DNA complex resulting in an alteration in binding affinity. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Massachusetts Gen Hosp, Mol Endocrinol Lab, WEL320,50 Blossom St, Boston, MA 02114 USA. EM habenerj@a1.mgh.harvard.edu FU NIDDK NIH HHS [DK25532, DK30457] NR 77 TC 116 Z9 118 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 17 PY 1998 VL 37 IS 11 BP 3795 EP 3809 DI 10.1021/bi970982t PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZE116 UT WOS:000072759300025 PM 9521699 ER PT J AU Alper, C Clement, G Gabuzda, D Reinherz, E Crawford, K AF Alper, C Clement, G Gabuzda, D Reinherz, E Crawford, K TI CD2 distinguishes human blood dendritic cell precursors from monocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1602 BP A275 EP A275 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401598 ER PT J AU Arbuckle, MR Harley, JB James, JA AF Arbuckle, MR Harley, JB James, JA TI Anti-Sm B/B ' antibodies in SLE patient sera initially target PPPGMRPP SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Oklahoma, Oklahoma Med Res Fdn, Oklahoma City, OK USA. US Dept Vet Affairs, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3531 BP A608 EP A608 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403525 ER PT J AU Bersohn, MM Carmack, C AF Bersohn, MM Carmack, C TI Sodium-calcium exchange activity in atria and ventricles of rabbit and rat hearts SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Los Angeles, W Los Angeles VA Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 593 BP A102 EP A102 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400595 ER PT J AU Chang, YS Munn, LL Jain, RK Tarbell, JM AF Chang, YS Munn, LL Jain, RK Tarbell, JM TI Effect of vascular endothelial growth factor on transport properties of human umbilical vein endothelial cell monolayers. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Penn State Univ, Dept Physiol, University Pk, PA 16802 USA. Penn State Univ, Dept Chem Engn, University Pk, PA 16802 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 131 BP A23 EP A23 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400131 ER PT J AU Copeland, T Blackburn, G Grosvenor, M Winters, B Wynder, E Marsoobian, V AF Copeland, T Blackburn, G Grosvenor, M Winters, B Wynder, E Marsoobian, V TI Increased reported energy intake using enhanced telephone recall data collection: From the women's intervention nutrition study (WINS) SO FASEB JOURNAL LA English DT Meeting Abstract C1 Beth Israel Deac Med Ctr, Boston, MA 02215 USA. Amer Hlth Fdn, New York, NY 10017 USA. Univ Calif Los Angeles, Los Angeles Cty Harbor Med Ctr, Torrance, CA 90502 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3060 BP A527 EP A527 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403055 ER PT J AU Crawford, K Wang, C Kitchens, B Gabuzda, D Reinherz, E Alper, C AF Crawford, K Wang, C Kitchens, B Gabuzda, D Reinherz, E Alper, C TI CD2-induced activation of human blood dendritic cell precursors SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Ctr Blood Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1746 BP A300 EP A300 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401741 ER PT J AU Das, M Dempsey, EC Stenmark, KR AF Das, M Dempsey, EC Stenmark, KR TI Selective subpopulations of pulmonary artery adventitial fibroblasts exhibit unique proliferative and apoptotic capabilities. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, CVP Lab, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dev Biol Lab, Denver, CO 80262 USA. Denver VAMC, Denver, CO 80262 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1971 BP A339 EP A339 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401967 ER PT J AU Dubey, DP Husain, Z Belalcazar, V Levitan, E Mirza, NM Yunis, D Younes, S Yunis, EJ AF Dubey, DP Husain, Z Belalcazar, V Levitan, E Mirza, NM Yunis, D Younes, S Yunis, EJ TI Short lifespan of H-2 congenic B10.AKM mice is associated with a defect in immune function: A murine model for accelerated immune senescence. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3601 BP A620 EP A620 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403596 ER PT J AU Durant, W Liao, L Peyton, KJ Schafer, AI AF Durant, W Liao, L Peyton, KJ Schafer, AI TI Thrombin stimulates vascular smooth muscle cell polyamine synthesis by inducing cationic amino acid transporter and ornithine decarboxylase gene expression. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 612 BP A105 EP A105 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400613 ER PT J AU Esch, TR Taubman, MA AF Esch, TR Taubman, MA TI IgG passively transfers salivary hypofunction in the NOD mouse of Sjogren's syndrome. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Forsyth Dent Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3536 BP A609 EP A609 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403533 ER PT J AU Gazdag, AC Dumke, CL Kahn, CR Cartee, GD AF Gazdag, AC Dumke, CL Kahn, CR Cartee, GD TI Decreased insulin-stimulated glucose transport in skeletal muscle of adult, but not young, IRS-1 (+/-) mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Wisconsin, Biodynam Lab, Madison, WI 53706 USA. Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1501 BP A257 EP A257 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401494 ER PT J AU Hill, GR Cooke, KR Crawford, JM Brinson, Y Ferrara, JLM AF Hill, GR Cooke, KR Crawford, JM Brinson, Y Ferrara, JLM TI IL-11 promotes Th2 polarization and reduces GVHD following allogeneic BMT. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, New Haven, CT 06510 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3388 BP A584 EP A584 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403383 ER PT J AU Janech, MG Fitzgibbon, WR Miller, DH Lacy, ER Ploth, DW AF Janech, MG Fitzgibbon, WR Miller, DH Lacy, ER Ploth, DW TI Effect of dilution on renal excretory function of the Atlantic stingray, Dasyatis sabina. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Univ Charleston, Charleston, SC 29424 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2458 BP A423 EP A423 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402452 ER PT J AU Jones, R Jacobson, M Gabbiani, G AF Jones, R Jacobson, M Gabbiani, G TI Differentiation of microvascular precursor cells to smooth muscle cells in hyperoxic pulmonary hypertension (PK): Expression of the cytoskeletal protein desmin. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Ctr Med Univ Geneva, Geneva, Switzerland. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1972 BP A339 EP A339 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401965 ER PT J AU Kang, JX Li, Y Leaf, A AF Kang, JX Li, Y Leaf, A TI Mannose-6-phosphate/insulin-like growth factor-II receptor is a novel receptor for retinoic acid SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2513 BP A433 EP A433 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402508 ER PT J AU Kline, DD Yang, T Huang, PL Prabhakar, NR AF Kline, DD Yang, T Huang, PL Prabhakar, NR TI Evidence for augmented peripheral chemoreceptor sensitivity to hypoxia in mutant mice deficient in neuronal nitric oxide synthase. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 973 BP A167 EP A167 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400972 ER PT J AU Koike, G Fuks, A Jacob, HJ Lander, ES Lernmark, A Luthman, H Matsumoto, K AF Koike, G Fuks, A Jacob, HJ Lander, ES Lernmark, A Luthman, H Matsumoto, K TI Comprehensive total genome scans to map genes responsible for diabetes mellitus in the rat. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Med Coll Wisconsin, Milwaukee, WI 53226 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. McGill Univ, Montreal, PQ, Canada. MIT, Whitehead Inst, Cambridge, MA 02142 USA. Univ Washington, Seattle, WA 98195 USA. Karolinska Hosp, S-10401 Stockholm, Sweden. Univ Tokushima, Tokushima 770, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2083 BP A358 EP A358 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402076 ER PT J AU Kroning, R Lichtenstein, AK Nagami, GT AF Kroning, R Lichtenstein, AK Nagami, GT TI Inhibition of cisplatin toxicity and uptake in renal tubule epithelial cells by L-cysteine. SO FASEB JOURNAL LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 669 BP A115 EP A115 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400670 ER PT J AU Larsen, C Mirza, N Yunis, D Levitan, E Wang, Z Lara, M Dubey, DP Yunis, EJ Alper, CA AF Larsen, C Mirza, N Yunis, D Levitan, E Wang, Z Lara, M Dubey, DP Yunis, EJ Alper, CA TI Anergy or tolerance in non-responders to hepatitis B vaccine is due to a defect in Th cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3604 BP A620 EP A620 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403600 ER PT J AU Levitan, E Husain, Z Mirza, N Gill, S Younes, S Alper, CA Yunis, EJ Dubey, DP AF Levitan, E Husain, Z Mirza, N Gill, S Younes, S Alper, CA Yunis, EJ Dubey, DP TI Natural killer inhibitory receptor (NKIR) and CD16 are downregulated in HLA class I homozygotes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3511 BP A604 EP A604 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403506 ER PT J AU Linnemeyer, PA Seaman, WE AF Linnemeyer, PA Seaman, WE TI Expression of functional NK-complex receptors on mouse uterine decidual NK cells during pregnancy. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco VAMC, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3491 BP A601 EP A601 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403487 ER PT J AU M'Rini, C Lowe, JB von Andrian, UH AF M'Rini, C Lowe, JB von Andrian, UH TI Role of fucosyltransferases IV and VII in leukocyte rolling in venules of peripheral lymph nodes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3375 BP A581 EP A581 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403370 ER PT J AU Mack, K Wei, R Shiramizu, B Herndier, B Abbey, N Gascon, R Elbaggari, A Hurt, M Earnst, T McGrath, M AF Mack, K Wei, R Shiramizu, B Herndier, B Abbey, N Gascon, R Elbaggari, A Hurt, M Earnst, T McGrath, M TI HIV cis-activation of the c-fes protooncogene in lymphoma associated clonal macrophages SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif San Francisco, Sequential Med Sci Inc, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1727 BP A296 EP A296 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401722 ER PT J AU Manilay, JO Sykes, M AF Manilay, JO Sykes, M TI NK cell reactivity to host and donor antigens in mixed allogeneic bone marrow chimeras SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3498 BP A602 EP A602 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403491 ER PT J AU Melder, RJ Schopf, U Marecos, EM Friedrich, S Weissleder, R Jain, RK AF Melder, RJ Schopf, U Marecos, EM Friedrich, S Weissleder, R Jain, RK TI Systemic distribution and tumor delivery of injected lymphocytes in mice. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1631 BP A280 EP A280 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401625 ER PT J AU Munn, LL Gerszten, RE Lee, KH Rosenzweig, A Jain, RK AF Munn, LL Gerszten, RE Lee, KH Rosenzweig, A Jain, RK TI Localized gene transduction of microvascular endothelial cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Munn, Lance/L-3950-2016 OI Munn, Lance/0000-0003-0698-7232 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 221 BP A38 EP A38 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400221 ER PT J AU Nakamura, MC Linnemeyer, PA Seaman, WE AF Nakamura, MC Linnemeyer, PA Seaman, WE TI Expression and function of chimeric NKR-P1/Ly-49 receptors on RNK-16 natural killer cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94121 USA. San Francisco VAMC, San Francisco, CA 94121 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3499 BP A602 EP A602 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403494 ER PT J AU Narra, V Islam, S Kinane, TB Donahoe, PK Schnitzer, JJ AF Narra, V Islam, S Kinane, TB Donahoe, PK Schnitzer, JJ TI Decreased mitogen-activated protein kinase activity in prenatal rat lungs with congenital diaphragmatic hernias. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1830 BP A314 EP A314 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401825 ER PT J AU Pan, L Bungard, D Brinson, Y Teshima, T Ferrara, JLM AF Pan, L Bungard, D Brinson, Y Teshima, T Ferrara, JLM TI G-CSF mobilized donor cells for allogeneic BMT improves immune reconstitution and maintains the GVL effect. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RI teshima, takanori/G-1671-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3395 BP A585 EP A585 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403392 ER PT J AU Ruff, LJ Dempsey, EC AF Ruff, LJ Dempsey, EC TI Bryostatin-1 attenuates hypoxic growth of bovine pulmonary artery smooth muscle cells in vitro. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, CVP Res Lab, Denver, CO 80262 USA. Denver VA Med Ctr, Denver, CO 80262 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 1970 BP A339 EP A339 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401964 ER PT J AU Stein, J Cheng, GY Stockton, B von Andrian, UH AF Stein, J Cheng, GY Stockton, B von Andrian, UH TI Selectin-mediated leukocyte adhesion in vivo: Ectodomain distribution determines tethering efficiency, but not rolling velocity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 224 BP A38 EP A38 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400225 ER PT J AU Tottempudi, P Reyland, ME Das, M Hoagland, KD Dempsey, EC AF Tottempudi, P Reyland, ME Das, M Hoagland, KD Dempsey, EC TI Regulation of protein kinase C-alpha gene expression in bovine pulmonary artery smooth muscle cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Denver VAMC, Denver, CO 80262 USA. Univ Colorado, CVP Res Lab, Hlth Sci Ctr, Denver, CO 80262 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2753 BP A474 EP A474 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402748 ER PT J AU Yauch, RL Berditchevski, F Hemler, ME AF Yauch, RL Berditchevski, F Hemler, ME TI The epithelial-associated integrin, alpha 3 beta 1, specifically complexes with CD151 and phosphatidylinositol 4-kinase SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Birmingham, CRC Inst Canc Studies, Birmingham B15 2TA, W Midlands, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 2157 BP A371 EP A371 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006402153 ER PT J AU Morimura, H Fishman, GA Grover, SA Fulton, AB Berson, EL Dryja, TP AF Morimura, H Fishman, GA Grover, SA Fulton, AB Berson, EL Dryja, TP TI Mutations in the RPE65 gene in patients with autosomal recessive retinitis pigmentosa or Leber congenital amaurosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID MICROSOMAL PROTEIN; EPITHELIUM AB RPE65 is a protein of unknown function expressed specifically by the retinal pigment epithelium. We examined all 14 exons of this gene in 147 unrelated patients with autosomal recessive retinitis pigmentosa (RP), in 15 patients with isolate RP, and in 45 patients with Leber congenital amaurosis (LCA). Sequence anomalies that were likely to be pathogenic were found in two patients with recessive RP, in one patient with isolate RP recategorized as recessive, and in seven patients with LCA. Cosegregation analysis in each available family showed that all affected individuals were either homozygotes or compound heterozygotes and that all unaffected individuals were either heterozygote carriers or homozygous wild type, In one family, there was one instance of a new mutation not present in either parent of the affected individual, In another family, affected members with recessive RP in three branches (i.e., three distinct pairs of parents) were compound heterozygotes for the same two mutations or homozygous for one of them, Based on our results, mutations in the RPE65 gene appear to account for approximate to 2% of cases of recessive RP and approximate to 1.6% of cases of LCA. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. Illinois Eye & Ear Infirm, UIC Eye Ctr, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. RP Dryja, TP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. OI Grover, Sandeep/0000-0002-3771-7510 FU NEI NIH HHS [R01 EY000169, EY00169, EY08683, R01 EY008683, R37 EY000169] NR 12 TC 272 Z9 282 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 17 PY 1998 VL 95 IS 6 BP 3088 EP 3093 DI 10.1073/pnas.95.6.3088 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA ZC589 UT WOS:000072596200069 PM 9501220 ER PT J AU Watnick, PI Butterton, JR Calderwood, SB AF Watnick, PI Butterton, JR Calderwood, SB TI The interaction of the Vibrio cholerae transcription factors, Fur and IrgB, with the overlapping promoters of two virulence genes, irgA and irgB SO GENE LA English DT Article DE Vibrio cholerae; irgB; irgA; DNA-protein interactions; LysR; virulence factors ID ESCHERICHIA-COLI; RNA-POLYMERASE; EXPRESSION; IRON; TOXIN; MUTAGENESIS; SIDEROPHORE; REPRESSOR; STRAINS; VECTOR AB irgA, a virulence gene in Vibrio cholerae, encodes a 77 kDa outer membrane protein. irgA expression is activated by irgB, which encodes a LysR-type transcription factor and is divergently transcribed from a promoter overlapping that of irgA. Expression of irgA and irgB is repressed by iron and Fur. A 200 bp DNA fragment containing the irgA-irgB intergenic region was inserted between the Escherichia coli phoA and lacZ genes, respectively, to generate operon fusions to the two promoters, and this construct was crossed into the chromosomal lacZ gene of V. choler ae. This DNA fragment was sufficient to produce regulation of irgA-phoA and irgB-lacZ transcription by iron, Fur and IrgB. Purified V. cholerae Fur and IrgB overexpressed in E. coli bound simultaneously to this DNA fragment in gel shift experiments, and footprints of both proteins on the irgA-irgB intergenic region were observed using DNaseI footprinting. The Fur footprint overlapped a Fm box, previously identified by homology with the E. coli Fur box. The position of the IrgB footprint was consistent with activation of irgA transcription and repression of irgB transcription by IrgB. We present a model for the interaction of Fur and IrgB in transcriptional regulation of irgA. (C) 1998 Elsevier Science B.V. C1 Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. FU NIAID NIH HHS [AI34968, K08 AI001588] NR 22 TC 24 Z9 25 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 16 PY 1998 VL 209 IS 1-2 BP 65 EP 70 DI 10.1016/S0378-1119(98)00018-3 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA ZF866 UT WOS:000072941100009 PM 9524224 ER PT J AU Mader, SL Alley, PA AF Mader, SL Alley, PA TI Age-related changes in adenylyl cyclase activity in rat aorta membranes SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE aging; adenylyl cyclase; vascular; beta-adrenergic receptors ID VASCULAR SMOOTH-MUSCLE; BETA-ADRENERGIC RESPONSIVENESS; CYCLIC-AMP METABOLISM; PROTEIN; RELAXATION; RECEPTOR; BINDING; ADRENOCEPTOR; SYSTEM; CELLS AB Blood vessels from aged animals and humans have impaired relaxation and cAMP production to beta-adrenergic stimulation. Direct activators of adenylyl cyclase (AC) such as forskolin are not affected. We hypothesized that analogous findings would occur in membrane preparations. Aortic media membrane preparations from Fischer 344 rats of four age groups (6 weeks to 24 months) were studied. Basal AC activity increased significantly with age. Forskolin-stimulated activity compared to basal tended to be greater in the 6-week and 6-month preparations compared to the 12- and 24-month preparations. AC activity was assessed in the presence of the G protein activators (GTP, GppNHp, NaF). There was no age-related decrease in responsiveness. The receptor agonists isoproterenol (beta-adrenergic), and PGE-1 (prostaglandin), were studied. There was no significant age-related change in responsiveness over basal activity to either of these agonists. There was a slight, but significant increase in the isoproterenol responsiveness over GTP responsiveness in the 6-week-old animals which also approached significance in the 6-month-old animals, but was not seen in the 12- and 24-month-old animals. These data suggest that using a membrane system to assess age-related changes in beta-adrenergic responsiveness in vascular smooth muscle does not retain the robust differences seen in whole vessels. (C) 1998 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97207 USA. RP Mader, SL (reprint author), Oregon Hlth Sci Univ, Portland VA Med Ctr, POB 1035 11V, Portland, OR 97207 USA. EM mader@portland.va.gov NR 22 TC 10 Z9 10 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing. Dev. PD MAR 16 PY 1998 VL 101 IS 1-2 BP 111 EP 118 DI 10.1016/S0047-6374(97)00168-1 PG 8 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA ZF487 UT WOS:000072902400009 PM 9593317 ER PT J AU Peters, DM Gies, EK Gelb, CR Peterfreund, RA AF Peters, DM Gies, EK Gelb, CR Peterfreund, RA TI Agonist-induced desensitization of A(2B) adenosine receptors SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE adenosine A(2B) receptors; desensitization; FLAG epitope tag; cAMP production; northern blot; western blot ID MOLECULAR-CLONING; MESSENGER-RNA; PC12 CELLS; GUINEA-PIG; RAT-BRAIN; ANALOGS; A(2A); PHOSPHORYLATION; EXPRESSION; SUBTYPES AB Agonist-induced desensitization has been described for the A(1), A(2A), and A(3) adenosine receptor subtypes of the G protein-coupled receptor superfamily. Desensitization of the fourth adenosine receptor subtype, the A(2B) adenosine receptor (A(2B)R), has not been studied extensively. We sought to determine whether the A(2B)R is subject to agonist-induced desensitization. COS 7 cells, which exhibit endogenous expression of the A(2B)R, and transfected CHO cells, which stably express a modified rat A(2B)R bearing a 5' FLAG epitope tag, were studied. Cyclic AMP (cAMP) responsiveness to an acute challenge was measured after pretreating (desensitizing) cells with the adenosine receptor agonist 5'-N-ethylcarboxamidoadenosine (NECA). Incubation with NECA resulted in hyporesponsiveness to acute agonist challenge in both COS 7 and transfected CHO cells. Desensitized cells exhibited restoration of cAMP responses after recovery for 24 hr in growth medium. Choleratoxin-induced cAMP responses were preserved in desensitized cells, and high concentrations of NECA were unable to overcome the desensitization. Membrane levels of the epitope-tagged A(2B)R were assessed by western blot in transiently transfected COS 7 cells. The expression of epitope-tagged A(2B)Rs was not different between control and desensitized cells. In northern blot analysis, levels of endogenous A(2B)R mRNA were similar in control and desensitized COS 7 cells. We conclude that the A,,R is subject to agonist-induced desensitization with preserved expression of A(2B)R mRNA and protein. Uncoupling of the A(2B) adenosine receptor from the G protein complex may contribute to the mechanism of desensitization. BIOCHEM PHARMACOL 55;6:813-882, 1998. (C) 1998 Elsevier Science Inc. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Peterfreund, RA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. NR 38 TC 23 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 15 PY 1998 VL 55 IS 6 BP 873 EP 882 DI 10.1016/S0006-2952(97)00560-1 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZC895 UT WOS:000072629800019 PM 9586960 ER PT J AU Moffitt, TE Brammer, GL Caspi, A Fawcett, JP Raleigh, M Yuwiler, A Silva, P AF Moffitt, TE Brammer, GL Caspi, A Fawcett, JP Raleigh, M Yuwiler, A Silva, P TI Whole blood serotonin relates to violence in an epidemiological study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE serotonin; violence; aggression; platelet ID FLUID 5-HYDROXYINDOLEACETIC ACID; DISRUPTIVE BEHAVIOR DISORDERS; HUMAN PLATELET SEROTONIN; IMPULSIVE FIRE SETTERS; CEREBROSPINAL-FLUID; AGGRESSIVE-BEHAVIOR; MONOAMINE METABOLITES; PERSONALITY-DISORDERS; HEALTHY-VOLUNTEERS; AUTISTIC DISORDER AB Background: Clinical and animal studies suggest that brain serotonergic systems may regulate aggressive behavior; however, the serotonin/violence hypothesis has not been assessed at the epidemiological level. For study of an epidemiological sample we examined blood serotonin, because certain physiological and behavioral findings suggested that it might serve as an analog marker for serotonergic function. Methods: Whole blood serotonin was measured in a representative birth cohort of 781 21-year-old women (47%) and men (53%). Violence was measured using cumulative court conviction records and participants' self-reports. Potential intervening factors addressed were: gender, age, diurnal variation, diet, psychiatric medications, illicit drug history, season of phlebotomy, plasma tryptophan, platelet count, body mass, suicide attempts, psychiatric diagnoses, alcohol, tobacco, socioeconomic status, IQ, and overall criminal offending. Results: Whole blood serotonin related to violence among men but not women. Violent men's mean blood serotonin level was 0.48 SD above the male population norm and 0.56 SD above the mean of nonviolent men. The finding was specific to violence, as opposed to general crime, and it was robust across two different methods of measuring violence. Together, the intervening variables accounted for 25% of the relation between blood serotonin and violence. Conclusions: To our knowledge, this is the first demonstration that an index of serotonergic function is related to violence in the general population. (C) 1998 Society of Biological Psychiatry. C1 Inst Psychiat, London SE5 8AF, England. Univ Wisconsin, Madison, WI USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Otago, Sch Pharm, Dunedin, New Zealand. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Otago, Sch Med, Dunedin, New Zealand. RP Moffitt, TE (reprint author), Inst Psychiat, 111 Denmark Hill, London SE5 8AF, England. RI caspi, avshalom/D-5294-2011; Moffitt, Terrie/D-5295-2011 OI Moffitt, Terrie/0000-0002-8589-6760 FU NIMH NIH HHS [MH-45070, MH-49414] NR 91 TC 79 Z9 84 U1 3 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 1998 VL 43 IS 6 BP 446 EP 457 DI 10.1016/S0006-3223(97)00340-5 PG 12 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA ZB552 UT WOS:000072484000009 PM 9532350 ER PT J AU Peled, A Gonzalo, JA Lloyd, C Gutierrez-Ramos, JC AF Peled, A Gonzalo, JA Lloyd, C Gutierrez-Ramos, JC TI The chemotactic cytokine eotaxin acts as a granulocyte-macrophage colony-stimulating factor during lung inflammation SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; GROWTH-FACTOR-BETA; IL-8 RECEPTOR HOMOLOG; PROGENITOR CELLS; C-KIT; ALLERGIC INFLAMMATION; INDUCED PROLIFERATION; MOLECULAR-CLONING; MICE LACKING; TNF-ALPHA AB During inflammatory processes, inflamed tissues signal the bone marrow (BM) to produce more mature leukocytes in ways that are not yet understood. We report here that, during the development of lung allergic inflammation, the administration of neutralizing antibodies to the chemotactic cytokine, Eotaxin, prevented the increase in the number of myeloid progenitors produced in the BM, therefore reducing the output of mature myeloid cells from BM. Conversely, the in vivo administration of Eotaxin increased the number of myeloid progenitors present in the BM. Furthermore, we found that, in vitro, Eotaxin is a colony-stimulating factor for granulocytes and macrophages. Eotaxin activity synergized with stem cell factor but not with interleukin-3 or granulocyte-macrophage colony-stimulating factor and was inhibited by pertussis toxin. We report also that CCR-3, the receptor for Eotaxin, was expressed by hematopoietic progenitors (HP). Thus, during inflammation, Eotaxin acts in a paracrine way to shift the differentiation of BM HP towards the myeloid lineage. (C) 1998 by The American Society of Hematology. C1 Millennium Pharmaceut Inc, Cambridge, MA 02139 USA. Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Gutierrez-Ramos, JC (reprint author), Millennium Pharmaceut Inc, 640 Mem Dr, Cambridge, MA 02139 USA. FU NCPDCID CDC HHS [CICYT PB93-0317]; NHLBI NIH HHS [HL 148675-02, HL94-10-B]; Wellcome Trust [087618] NR 36 TC 40 Z9 43 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1998 VL 91 IS 6 BP 1909 EP 1916 PG 8 WC Hematology SC Hematology GA ZB156 UT WOS:000072442000010 PM 9490673 ER PT J AU Huang, M Stolina, M Sharma, S Mao, JT Zhu, L Miller, PW Wollman, J Herschman, H Dubinett, SM AF Huang, M Stolina, M Sharma, S Mao, JT Zhu, L Miller, PW Wollman, J Herschman, H Dubinett, SM TI Non-small cell lung cancer cyclooxygenase-2-dependent regulation of cytokine balance in lymphocytes and macrophages: Up-regulation of interleukin 10 and down-regulation of interleukin 12 production SO CANCER RESEARCH LA English DT Article ID BRONCHOALVEOLAR LAVAGE FLUID; SYNTHASE MESSENGER-RNA; CLASS-I EXPRESSION; SWISS 3T3 CELLS; PROSTAGLANDIN E(2); T-CELLS; COLORECTAL-CANCER; BRONCHOGENIC-CARCINOMA; ANTITUMOR IMMUNITY; EPITHELIAL-CELLS AB Tumor-derived prostaglandin E-2 (PGE(2)) modifies cytokine balance and inhibits host immunity, We hypothesized that a high level of PGE(2) production by lung tumor cells is dependent on tumor cyclooxygenase (COX)-2 expression, We found that PGE(2) production by A549 non-small cell lung cancer (NSCLC) cells was elevated up to 50-fold in response to interleukin (IL)-1 beta, Reversal of IL-1 beta-induced PGE(2) production in A549 cells was achieved by specific pharmacological or antisense oligonucleotide inhibition of COX-2 activity or expression, In contrast, specific COX-1 inhibition was not effective, Consistent with these findings, IL-1 beta induced COX-2 mRNA expression and protein production in A549 cells, Specific inhibition of COX-2 abrogated the capacity of IL-1 beta-stimulated A549 cells to induce IL-10 in lymphocytes and macrophages, Furthermore, specific inhibition of A549 COX-2 reversed the tumor-derived PGE(2)-dependent inhibition of macrophage IL-12 production when whole blood was cultured in tumor supernatants, Our results indicate that lung tumor-derived PGE(2) plays a pivotal role in promoting lymphocyte and macrophage IL-10 induction while simultaneously inhibiting macrophage IL-12 production, Immunohistochemistry of human NSCLC tissues obtained from lung cancer resection specimens revealed cytoplasmic staining for COX-2 within tumor cells, This is the first description of functional COX-2 expression by NSCLC cells and the definition of a pathway whereby tumor COX-2 expression and a high level of PGE(2) production mediate profound alteration in cytokine balance in the lung cancer microenvironment. C1 Univ Calif Los Angeles, Sch Med,W Los Angeles Vet Affairs Med Ctr, Dept Med,Div Pulm & Crit Care Med, Pulm Immunol Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Biol Chem & Mol & Med Pharmacol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Pathol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90073 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med,W Los Angeles Vet Affairs Med Ctr, Dept Med,Div Pulm & Crit Care Med, Pulm Immunol Lab, 111Q,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NCI NIH HHS [CA09120, CA71818]; NIGMS NIH HHS [GM24797] NR 84 TC 374 Z9 394 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 1998 VL 58 IS 6 BP 1208 EP 1216 PG 9 WC Oncology SC Oncology GA ZB892 UT WOS:000072518500025 PM 9515807 ER PT J AU Goldmann, WH Galneder, R Ludwig, M Xu, WM Adamson, ED Wang, N Ezzell, RM AF Goldmann, WH Galneder, R Ludwig, M Xu, WM Adamson, ED Wang, N Ezzell, RM TI Differences in elasticity of vinculin-deficient F9 cells measured by magnetometry and atomic force microscopy SO EXPERIMENTAL CELL RESEARCH LA English DT Article; Proceedings Paper CT Annual ASCB Meeting CY 1996 CL SAN FRANCISCO, CALIFORNIA SP ASCB DE vinculin-regulated cellular elasticity ID CYTOSKELETAL PROTEIN VINCULIN; EXTRACELLULAR-MATRIX; ALPHA-ACTININ; CARCINOMA-CELLS; BINDING-SITE; INTRAMOLECULAR ASSOCIATION; FOCAL ADHESIONS; HUMAN PLATELETS; TALIN-BINDING; TAIL DOMAINS AB We have investigated a mouse F9 embryonic carcinoma cell line, in which both vinculin genes were inactivated by homologous recombination, that exhibits defective adhesion and spreading [Cell ct al. (1995) Proc. Natl. Acad. Sci. USA 92, 9161-9165]. Using a magnetometer and RGD-coated magnetic microbeads, we measured the local effect of loss and replacement of vinculin on mechanical force transfer across integrins. Vinculin-deficient F9Vin(-/-) cells showed a 21% difference in relative stiffness compared to wildtype cells. This was restored to near wild-type levels after transfection and constitutive expression of increasing amounts of vinculin into F9Vin(-/-) cells. In contrast, the transfection of vinculin constructs deficient in amino acids 1-288 (containing the talin-and alpha-actinin-binding site) or substituting tyrosine for phenylalanine (phosphorylation site, amino acid 822) in F9Vin(-/-) cells resulted in partial restoration of stiffness. Using atomic force microscopy to map the relative elasticity of entire F9 cells by 128 x 128 (n = 16,384) force scans, we observed a correlation with magnetometer measurements. These findings suggest that vinculin may promote cell adhesion and spreading by stabilizing focal adhesions and transferring mechanical stresses that drive cytoskeletal remodeling, thereby affecting the elastic properties of the cell. (C) 1998 Academic Press. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Surg Res Unit, Charlestown, MA 02129 USA. Univ Munich, Lehrstuhl Angew Phys, D-80799 Munich, Germany. Burnham Inst, La Jolla, CA 92037 USA. Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Bldt 149,13th St, Charlestown, MA 02129 USA. EM goldman@helix.mgh.harvard.edu RI Wang, Ning/B-6966-2008; Goldmann, Wolfgang/H-5572-2013 FU NHLBI NIH HHS [HL-33009] NR 48 TC 83 Z9 87 U1 2 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR 15 PY 1998 VL 239 IS 2 BP 235 EP 242 DI 10.1006/excr.1997.3915 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA ZD716 UT WOS:000072716300005 PM 9521841 ER PT J AU Gu, ZY Nomura, M Simpson, BB Lei, H Feijen, A van den Eijnden-van Raaij, J Donahoe, PK Li, E AF Gu, ZY Nomura, M Simpson, BB Lei, H Feijen, A van den Eijnden-van Raaij, J Donahoe, PK Li, E TI The type I activin receptor ActRIB is required for egg cylinder organization and gastrulation in the mouse SO GENES & DEVELOPMENT LA English DT Article DE activin; serine/threonine kinase receptor; gene targeting; mesoderm induction; gastrulation ID BONE MORPHOGENETIC PROTEIN-4; EMBRYONIC STEM-CELLS; GROWTH-FACTOR-BETA; THREONINE KINASE RECEPTORS; INDUCE AXIAL MESODERM; TGF-BETA; VENTRALIZING FACTOR; TRUNCATED ACTIVIN; TARGETED MUTATION; PRIMITIVE STREAK AB ActRIB is a type I transmembrane serine/threonine kinase receptor that has been shown to form heteromeric complexes with the type II activin receptors to mediate activin signal. To investigate the function of ActRIB in mammalian development, we generated ActRIB-deficient ES cell lines and mice by gene targeting. Analysis of the ActRIB(-/-) embryos showed that the epiblast and the extraembryonic ectoderm were disorganized, resulting in disruption and developmental arrest of the egg cylinder before gastrulation. To assess the function of ActRIB in mesoderm formation and gastrulation, chimera analysis was conducted. We found that ActRIB(-/-) ES cells injected into wild-type blastocysts were able to contribute to the mesoderm in chimeric embryos, suggesting that ActRIB is not required for mesoderm formation. Primitive streak formation, however, was impaired in chimeras when ActRIB(-/-) cells contributed highly to the epiblast. Further, chimeras generated by injection of wild-type ES cells into ActRIB(-/-) blastocysts formed relatively normal extraembryonic tissues, but the embryo proper developed poorly probably resulting from severe gastrulation defect. These results provide genetic evidence that ActRIB functions in both epiblast and extraembryonic cells to mediate signals that are required for egg cylinder organization and gastrulation. C1 Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp E,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Surg, Massachusetts Gen Hosp,Pediat Surg Res Lab, Boston, MA 02114 USA. Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. RP Li, E (reprint author), Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp E,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. NR 59 TC 159 Z9 163 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS PI PLAINVIEW PA 1 BUNGTOWN RD, PLAINVIEW, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 15 PY 1998 VL 12 IS 6 BP 844 EP 857 DI 10.1101/gad.12.6.844 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA ZE221 UT WOS:000072770300009 PM 9512518 ER PT J AU Scott, HS Antonarakis, SE Lalioti, MD Rossier, C Silver, PA Henry, MF AF Scott, HS Antonarakis, SE Lalioti, MD Rossier, C Silver, PA Henry, MF TI Identification and characterization of two putative human arginine methyltransferases (HRMT1L1 and HRMT1L2) SO GENOMICS LA English DT Article ID RNA-BINDING PROTEINS; SACCHAROMYCES-CEREVISIAE; N-METHYLTRANSFERASE; CHROMOSOME 21Q22.3; NUCLEAR-PROTEIN; GENE; YEAST; LOCUS; EXPRESSION; LOCALIZATION AB RNA-binding proteins such as heterogeneous nuclear ribonucleoproteins (hnRNPs), which contain the bulk of methylated arginine residues in eukaryotic cells, play many essential roles in the metabolism of nuclear pre-mRNA. Arginine methyltransferase activity has also been implicated in signal transduction events with components of the cellular growth and viral response pathways, We recently characterized a single yeast hnRNP methyltransferase (HMT1). We now present the identification and characterization of two putative human arginine methyltransferases termed HRMT1L1 and HRMT1L2, In addition to methyltransferase similarities, the N-terminal region of the HRMT1L1 protein contains an Src homology 3 domain, HRMT1L1 maps to a YAC containing the telomere of chromosome 21q, Three alternatively spliced HRMT1L2 transcripts with variable 5'-ends were observed, encoding proteins of 343, 347, and 361 amino acids, respectively. HRMT1L2 maps to human chromosome 19q, Recombinant HRMT1L2 protein encoded by the most common 5'-variant exhibited methyltransferase activity in vitro. Furthermore, in vivo activity was demonstrated by complementation of a yeast HMT1 mutant strain, The identification of highly conserved Hmt1p human homologues that function in yeast indicates that analyses of this class of enzymes in yeast may be directly applicable to higher eukaryotes. The possible roles of HRMT1L1 and HRMT1L2 in human disease are currently unknown. (C) 1998 Academic Press. C1 Univ Geneva, Sch Med, Dept Genet & Microbiol, Lab Human Mol Genet, CH-1211 Geneva 4, Switzerland. Hop Cantonal Geneva, Div Med Genet, CH-1211 Geneva, Switzerland. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Cellular & Mol Biol, Boston, MA 02115 USA. RP Antonarakis, SE (reprint author), Univ Geneva, Sch Med, Dept Genet & Microbiol, Lab Human Mol Genet, 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. RI Scott, Hamish/B-2122-2009; Antonarakis, Stylianos/N-8866-2014 OI Scott, Hamish/0000-0002-5813-631X; Antonarakis, Stylianos/0000-0001-8907-5823 NR 37 TC 118 Z9 120 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR 15 PY 1998 VL 48 IS 3 BP 330 EP 340 DI 10.1006/geno.1997.5190 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA ZF473 UT WOS:000072901000007 PM 9545638 ER PT J AU Lu, M Kuroki, M Amano, S Tolentino, M Keough, K Kim, I Bucala, R Adamis, AP AF Lu, M Kuroki, M Amano, S Tolentino, M Keough, K Kim, I Bucala, R Adamis, AP TI Advanced glycation end products increase retinal vascular endothelial growth factor expression SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article; Proceedings Paper CT 67th Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY APR 21-26, 1996 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol DE advanced glycation end products; diabetic retinopathy; vascular endothelial growth factor; gene expression; retina ID PROLIFERATIVE DIABETIC-RETINOPATHY; MESSENGER-RNA; FACTOR VEGF; RECEPTOR; PROTEINS; PRIMATE; NEOVASCULARIZATION; ANGIOGENESIS; DYSFUNCTION; INHIBITION AB Advanced glycation end products (AGEs) are linked with the development of diabetic retinopathy; however, the pathogenic mechanisms are poorly defined. Vascular endothelial growth factor (VEGF) levels are increased in ischemic and nonischemic diabetic retina, and VEGF is required for the development of retinal and iris neovascularization. Moreover, VEGF alone can induce much of the concomitant pathology of diabetic retinopathy. In this study, we found that AGEs increased VEGF mRNA levels in the ganglion, inner nuclear, and retinal pigment epithelial (RPE) cell layers of the rat retina. In vitro, AGEs increased VEGF mRNA and secreted protein in human RPE and bovine vascular smooth muscle cells, The AGE-induced increases in VEGF expression were dose-and time-dependent, inhibited by antioxidants, and additive with hypoxia, Use of an anti-VEGF antibody blocked the capillary endothelial cell proliferation induced by the conditioned media of AGE-treated cells. AGEs may participate in the pathogenesis of diabetic retinopathy through their ability to increase retinal VEGF gene expression. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Surg Res Lab, Boston, MA 02115 USA. Picower Inst Med Res, Manhasset, NY 11030 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM adamis@al.tch.harvard.edu FU PHS HHS [325] NR 34 TC 290 Z9 300 U1 0 U2 11 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 15 PY 1998 VL 101 IS 6 BP 1219 EP 1224 DI 10.1172/JCI1277 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZE072 UT WOS:000072754900004 PM 9502762 ER PT J AU Teoh, G Urashima, M Greenfield, EA Nguyen, KA Lee, JF Chauhan, D Ogata, A Treon, SP Anderson, KC AF Teoh, G Urashima, M Greenfield, EA Nguyen, KA Lee, JF Chauhan, D Ogata, A Treon, SP Anderson, KC TI The 86-kD subunit of Ku autoantigen mediates homotypic and heterotypic adhesion of multiple myeloma cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE CD40; ligands; DNA-dependent protein kinase; cell membrane; IL-6 ID DEPENDENT PROTEIN-KINASE; STRAND BREAK REPAIR; DNA-BINDING; V(D)J RECOMBINATION; IN-VITRO; B-CELLS; INTERLEUKIN-6 SECRETION; KU80-DEFICIENT CELLS; AUTO-ANTIGEN; EXPRESSION AB Previous studies have shown that triggering multiple myeloma (MM) cells via CD40 induces IL-6-mediated autocrine growth as well as increased expression of cell surface adhesion molecules including CD11a, CD11b, CD11c, and CD18. In this study,we generated the 5E2 mAb which targets an antigen that is induced upon CD40 ligand (CD40L) activation of MM cells. Immunofluorescence, immunoprecipitation, and protein sequencing studies identified the target antigen of 5E2 mAb as the 86-kD subunit of the Ku autoantigen, We demonstrate that increased cell surface expression of Ku on CD40L-treated cells is due to migration of Ku from the cytoplasm to the cell surface membrane, Moreover, cell surface Ku on CD40L-treated MM cells mediates homotypic adhesion of tumor cells, as well as heterotypic adhesion of tumor cells to bone marrow stromal cells and to human fibronectin; and 5E2 mAb abrogates IL-6 secretion triggered by tumor cell adherence to bone marrow stromal cells. These data suggest that CD40L treatment induces a shift of Ku from the cytoplasm to the cell surface, and are the first to show that Ku functions as an adhesion molecule. They further suggest that cell surface Ku may play a role in both autocrine and paracrine IL-6-mediated MM cell growth and survival. C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Singapore Gen Hosp, Dept Haematol, Singapore 0316, Singapore. Dana Farber Canc Inst, Mol Biol Core Facil, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu FU NCI NIH HHS [CA 50947] NR 62 TC 53 Z9 55 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAR 15 PY 1998 VL 101 IS 6 BP 1379 EP 1388 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA ZE072 UT WOS:000072754900022 PM 9502780 ER PT J AU Shen, J Andrews, DM Pandolfi, F Boyle, LA Kersten, CM Blatman, RN Kurnick, JT AF Shen, J Andrews, DM Pandolfi, F Boyle, LA Kersten, CM Blatman, RN Kurnick, JT TI Oligoclonality of V delta 1 and V delta 2 cells in human peripheral blood mononuclear cells: TCR selection is not altered by stimulation with gram-negative bacteria SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DELTA-T-CELLS; PSEUDOMONAS-AERUGINOSA; JUNCTIONAL DIVERSITY; RECEPTOR REPERTOIRE; SCLEROSIS PATIENTS; ESCHERICHIA-COLI; LYMPHOCYTES; EXPANSION; ANTIGENS; CLONES AB Despite the enormous potential repertoire of gamma delta T cells, there are several observations which suggest that the expressed gamma delta repertoire in the periphery of normal individuals is often quite restricted, To assess selective expansions among gamma delta T cells from both adult and newborn blood samples, PBMC from 12 normal adults and cord blood from 15 normal newborns were analyzed for TCRDV1 and TCRDV2 junctional diversity by CDR3 size spectratyping and single-strand conformational polymorphism, Although TCRBV usage showed extensive heterogeneity in adults and newborns, both populations often showed CDR3 region restriction for TCRDV1 and TCRDV2. Analysis of the CDR3 spectratype patterns of newborn twins suggested that clonal selection for TCRDV is independent of genetic background, The possible role of Gram-negative bacteria In driving selective responsiveness of gamma delta T cells in PBMCs from adults was examined by in vitro stimulation with Escherichia coli and Pseudomonas aeruginosa, Donors whose TCRDV repertoire was highly clonal in the unstimulated blood cells showed the same predominant clones among the bacteria-stimulated cultures, In individuals whose gamma delta T cells were less restricted, in vitro stimulation did not select for clonality; rather, the TCRDV repertoires were similar before and after bacterial stimulation, Together, these data indicate that gamma delta T cells are often clonally restricted in adults as well as in newborns and suggest that the prominent stimulatory activity of Gram-negative bacteria does not by itself account for the restriction or diversity of the gamma delta T cell repertoire. C1 Massachusetts Gen Hosp, Pathol Res Lab, Charlestown, MA 02129 USA. Catholic Univ Rome, Chair Semeiot Med, Rome, Italy. Massachusetts Gen Hosp, Vincent Mem Obstet Serv, Boston, MA 02114 USA. RP Kurnick, JT (reprint author), Massachusetts Gen Hosp, Pathol Res Lab, 7th Floor,149 13th St, Charlestown, MA 02129 USA. NR 37 TC 12 Z9 17 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 3048 EP 3055 PG 8 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900061 PM 9510210 ER PT J AU Lin, JW Wyszynski, M Madhavan, R Sealock, R Kim, JU Sheng, M AF Lin, JW Wyszynski, M Madhavan, R Sealock, R Kim, JU Sheng, M TI Yotiao, a novel protein of neuromuscular junction and brain that interacts with specific splice variants of NMDA receptor subunit NR1 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE yotiao; NMDA receptor neuromuscular junction; neuronal synapse; postsynaptic density; cytoskeleton; coiled coil protein; yeast two-hybrid ID POSTSYNAPTIC DENSITY; GUANYLATE KINASES; PSD-95 FAMILY; K+ CHANNELS; RAT-BRAIN; LOCALIZATION; HIPPOCAMPUS; DYSTROPHIN; MEMBRANES; REGIONS AB The molecular machinery underlying neurotransmitter receptor immobilization at postsynaptic sites is poorly understood. The NMDA receptor subunit NR1 can form clusters in heterologous cells via a mechanism dependent on the alternatively spliced C1 exon cassette in its intracellular C-terminal tail, suggesting a functional interaction between NR1 and the cytoskeleton. The yeast two-hybrid screen was used here to identify yotiao, a novel coiled coil protein that interacts with NR1 in a C1 exon-dependent manner. Yotiao mRNA (11 kb) is present modestly in brain and abundantly in skeletal muscle and pancreas. On Western blots, yotiao appears as an similar to 230 kDa band that is present in cerebral cortex, hippocampus, and cerebellum. Biochemical studies reveal that yotiao fractionates with cytoskeleton-associated proteins and with the postsynaptic density. With regard to immunohistochemistry, two anti-yotiao antibodies display a somatodendritic staining pattern similar to each other and to the staining pattern of NR1. Yotiao was colocalized by double-label immunocytochemistry with NR1 in rat brain and could be coimmunoprecipitated with NR1 from heterologous cells. Thus yotiao is an NR1-binding protein potentially involved in cytoskeletal attachment of NMDA receptors. Consistent with a general involvement in postsynaptic structure, yotiao was also found to be specifically concentrated at the neuromuscular junction in skeletal muscle. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurobiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ N Carolina, Dept Physiol, Chapel Hill, NC 27599 USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 423,50 Blossom St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS33145, NS35050] NR 52 TC 229 Z9 234 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 1998 VL 18 IS 6 BP 2017 EP 2027 PG 11 WC Neurosciences SC Neurosciences & Neurology GA ZA482 UT WOS:000072367700012 PM 9482789 ER PT J AU Hobert, O D'Alberti, T Liu, YX Ruvkun, G AF Hobert, O D'Alberti, T Liu, YX Ruvkun, G TI Control of neural development and function in a thermoregulatory network by the LIM homeobox gene lin-11 SO JOURNAL OF NEUROSCIENCE LA English DT Article DE LIM homeobox gene; neurogenesis; thermotaxis; neural function; axon pathfinding; axon fasciculation ID NEMATODE CAENORHABDITIS-ELEGANS; C-ELEGANS; MOTOR-NEURONS; CELL LINEAGE; CHEMOSENSORY NEURONS; HOMEODOMAIN PROTEIN; NERVOUS-SYSTEM; SYNAPTIC INPUT; EXPRESSION; DIFFERENTIATION AB We show here that the lin-11 LIM homeobox gene is expressed in nine classes of head, ventral cord, and tail neurons and functions at a late step in the development of a subset of these neurons, In a lin-11 null mutant, all lin-11-expressing neurons are generated. Several of these neurons, however, exhibit neuroanatomical as well as functional defects, In the lateral head ganglion, lin-11 functions in a neural network that regulates thermosensory behavior. It is expressed in the AIZ interneuron that processes high temperature input and is required for the function of AIZ in the thermoregulatory neural network. Another LIM homeobox gene, ttx-3, functions in the antagonistic thermoregulatory interneuron AIY (Hobert et al., 1997), Thus, distinct LIM genes specify the functions of functionally related antagonistic interneurons within a neural network dedicated for thermoregulatory processes, Both ttx-3 and lin-11 expression are maintained throughout adulthood, suggesting that these LIM homeobox genes play a role in the functional maintenance of this neural circuit, We propose that particular LIM homeobox genes specify the distinct features of functionally related neurons that generate patterned behaviors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Ruvkun, G (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Mol Biol,Dept Genet, Wellman 8, Boston, MA 02114 USA. OI Hobert, Oliver/0000-0002-7634-2854 NR 60 TC 89 Z9 95 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 15 PY 1998 VL 18 IS 6 BP 2084 EP 2096 PG 13 WC Neurosciences SC Neurosciences & Neurology GA ZA482 UT WOS:000072367700018 PM 9482795 ER PT J AU Bernhard, J Gelber, RD Hurny, C AF Bernhard, J Gelber, RD Hurny, C TI Workshop on missing data in quality of life research in cancer clinical trials: Practical and methodological issues - Preface SO STATISTICS IN MEDICINE LA English DT Editorial Material C1 Swiss Grp Clin Canc Res, Coordinating Ctr, CH-3008 Bern, Switzerland. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Harvard Univ, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Int Breast Canc Study Grp, Bern, Switzerland. RP Bernhard, J (reprint author), Swiss Grp Clin Canc Res, Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. NR 0 TC 11 Z9 11 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 1998 VL 17 IS 5-7 BP 511 EP 512 DI 10.1002/(SICI)1097-0258(19980315/15)17:5/7<511::AID-SIM798>3.0.CO;2-C PG 2 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA ZB211 UT WOS:000072447800001 ER PT J AU Bernhard, J Peterson, HF Coates, AS Gusset, H Isley, M Hinkle, R Gelber, RD Castiglione-Gertsch, M Hurny, C AF Bernhard, J Peterson, HF Coates, AS Gusset, H Isley, M Hinkle, R Gelber, RD Castiglione-Gertsch, M Hurny, C CA Int Breast Canc Study Grp TI Quality of life assessment in International Breast Cancer Study Group (IBCSG) trials: Practical issues and factors associated with missing data SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Missing Data in Quality of Life Research in Cancer Clinical Trials - Practical and Methodological Issues CY JUL 01-03, 1997 CL BAD HORN, SWITZERLAND SP Swiss Group Clin Canc Res ID OF-LIFE; ADJUVANT THERAPY; CHEMOTHERAPY AB We report on our experience of quality of life (QL) assessment in adjuvant clinical trials of the International Breast Cancer Study Group (IBCSG), with special emphasis on cultural and logistical aspects of international organization that are unique to this group. Data are presented regarding submission rates of assessments before and after treatment failure, and timing of assessments relative to chemotherapy administration. To identify areas where rates might be improved, we investigated the association between missing data and sociodemographic and biomedical factors, treatment assignment, institution, chemotherapy compliance and toxicity in a trial of adjuvant chemoendocrine therapy for post-menopausal patients with breast cancer (IBCSG VII). The factors most highly associated with missing data were institution and chemotherapy compliance. (C) 1998 John Wiley & Sons, Ltd. C1 Int Breast Canc Study Grp, Coordinating Ctr, CH-3008 Bern, Switzerland. Dana Farber Canc Inst, Dept Biostat Sci, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Univ Sydney, Australian New Zealand Breast Canc Trials Grp, Sydney, NSW 2006, Australia. Univ Sydney, Dept Canc Med, Sydney, NSW 2006, Australia. Frontier Sci & Technol Res Fdn, Int Breast Canc Study Grp, Data Management Ctr, Amherst, NY 14226 USA. Inselspital Bern, Med Div Lory, CH-3010 Bern, Switzerland. RP Bernhard, J (reprint author), Int Breast Canc Study Grp, Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. NR 16 TC 19 Z9 21 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 1998 VL 17 IS 5-7 BP 587 EP 601 DI 10.1002/(SICI)1097-0258(19980315/15)17:5/7<587::AID-SIM806>3.0.CO;2-# PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA ZB211 UT WOS:000072447800009 PM 9549808 ER PT J AU Fairclough, DL Peterson, HF Chang, V AF Fairclough, DL Peterson, HF Chang, V TI Why are missing quality of life data a problem in clinical trials of cancer therapy? SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Missing Data in Quality of Life Research in Cancer Clinical Trials - Practical and Methodological Issues CY JUL 01-03, 1997 CL BAD HORN, SWITZERLAND SP Swiss Group Clin Canc Res ID OPERABLE BREAST-CANCER; MODELS AB Assessment of health related quality of life has become an important endpoint in many cancer clinical trials. Because the participants of these trials often experience disease and treatment related morbidity and mortality, non-random missing assessments are inevitable. Examples are presented from several such trials that illustrate the impact of missing data on the analysis of QOL in these trials, The sensitivity of different analyses depends on the proportion of assessments that are missing and the strength of the association of the underlying reasons for missing data with disease and treatment related morbidity and mortality. In the setting of clinical trials of cancer therapy, the assumption that the data are missing completely at random (MCAR) and analyses of complete cases is usually unjustified. Further, the assumption of missing at random (MAR) may also be violated in many trials and models appropriate for non-ignorable missing data should be explored. Recommendations are presented to minimize missing data, to obtain useful documentation concerning the reasons for missing data and to perform sensitivity analyses. (C) 1998 John Wiley & Sons, Ltd. C1 AMC Canc Res Ctr, Ctr Methodol Res & Biometry, Denver, CO 80214 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. NJ Vet Affairs Care Syst, Med Serv, Hematol Oncol Sect, E Orange, NJ 07018 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Med, Newark, NJ 07103 USA. RP Fairclough, DL (reprint author), AMC Canc Res Ctr, Ctr Methodol Res & Biometry, 1600 Pierce St, Denver, CO 80214 USA. FU NCI NIH HHS [CA-23318] NR 16 TC 83 Z9 85 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 1998 VL 17 IS 5-7 BP 667 EP 677 DI 10.1002/(SICI)1097-0258(19980315/15)17:5/7<667::AID-SIM813>3.3.CO;2-Y PG 11 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA ZB211 UT WOS:000072447800016 PM 9549815 ER PT J AU Fairclough, DL Peterson, HF Cella, D Bonomi, P AF Fairclough, DL Peterson, HF Cella, D Bonomi, P TI Comparison of several model-based methods for analysing incomplete quality of life data in cancer clinical trials SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Workshop on Missing Data in Quality of Life Research in Cancer Clinical Trials - Practical and Methodological Issues CY JUL 01-03, 1997 CL BAD HORN, SWITZERLAND SP Swiss Group Clin Canc Res ID OPERABLE BREAST-CANCER; LONGITUDINAL DATA; OF-LIFE; THERAPY AB This paper considers five methods of analysis of longitudinal assessment of health related quality of life (QOL) in two clinical trials of cancer therapy. The primary difference in the two trials is the proportion of participants who experience disease progression or death during the period of QOL assessments. The sensitivity of estimation of parameters and hypothesis tests to the potential bias as a consequence of the assumptions of missing completely at random (MCAR), missing at random (MAR) and non-ignorable mechanisms are examined. The methods include complete case analysis (MCAR), mixed-effects models (MAR), a joint mixed-effects and survival model and a pattern-mixture model. Complete case analysis overestimated QOL in both trials. In the adjuvant breast cancer trial, with 15 per cent disease progression, estimates were consistent across the remaining four methods. In the advanced non-small-cell lung cancer trial, with 35 per cent mortality, estimates were sensitive to the missing data assumptions and methods of analysis. (C) 1998 John Wiley & Sons, Ltd. C1 AMC Canc Res Ctr, Ctr Res Methodol & Biometry, Denver, CO 80214 USA. Dana Farber Canc Inst, Div Biometr, Boston, MA 02115 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. RP Fairclough, DL (reprint author), AMC Canc Res Ctr, Ctr Res Methodol & Biometry, 1600 Pierce St, Denver, CO 80214 USA. FU NCI NIH HHS [CA-23318] NR 16 TC 77 Z9 79 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 1998 VL 17 IS 5-7 BP 781 EP 796 DI 10.1002/(SICI)1097-0258(19980315/15)17:5/7<781::AID-SIM821>3.0.CO;2-O PG 16 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA ZB211 UT WOS:000072447800024 PM 9549823 ER PT J AU Delmonico, FL Snydman, DR AF Delmonico, FL Snydman, DR TI Organ donor screening for infectious diseases - Review of practice and implications for transplantation SO TRANSPLANTATION LA English DT Article ID HEPATITIS-C VIRUS; LINKED IMMUNOSORBENT-ASSAY; CYTOMEGALO-VIRUS; PANCREATIC TRANSPLANTATION; KIDNEY-TRANSPLANTATION; RENAL-TRANSPLANTATION; IMMUNOGLOBULIN-M; LIVER-DISEASE; TRANSMISSION; RECIPIENTS C1 Tufts Univ, Sch Med, Dept Med, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA USA. RP Delmonico, FL (reprint author), New England Organ Bank, 1 Gateway Ctr, Newton, MA 02158 USA. RI Snydman, David/O-3889-2014 OI Snydman, David/0000-0003-0119-3978 NR 73 TC 53 Z9 54 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 1998 VL 65 IS 5 BP 603 EP 610 DI 10.1097/00007890-199803150-00001 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZC396 UT WOS:000072573800001 PM 9521191 ER PT J AU Mourad, GJ Preffer, FI Wee, SL Powelson, JA Kawai, T Delmonico, FL Knowles, RW Cosimi, AB Colvin, RB AF Mourad, GJ Preffer, FI Wee, SL Powelson, JA Kawai, T Delmonico, FL Knowles, RW Cosimi, AB Colvin, RB TI Humanized IgG1 and IgG4 anti-CD4 monoclonal antibodies - Effects on lymphocytes in the blood, lymph nodes, and renal allografts in cynomolgus monkeys SO TRANSPLANTATION LA English DT Article ID T-CELL ACTIVATION; TRANSPLANTATION TOLERANCE; NEGATIVE SIGNAL; RECIPIENTS; OKT4A; REJECTION; RECEPTOR; SURVIVAL; INDUCTION; ANTIGEN AB Background. Optimizing therapeutic monoclonal antibody (mAb) depends on the incorporation of the necessary effector functions and the development of hypoantigenic "humanized" antibodies by genetic engineering, which then need to be tested in appropriate preclinical trials, Methods. Constructs of humanized OKT4A containing the complementarity-determining region (CDR) of murine OKT4A and the framework and constant regions of human light (kappa) and heavy chains (IgG1 and IgG4) were prepared and tested in cynomolgus monkeys who received a renal allograft, A prophylactic course of CDR-OKT4A/human (h) IgG1 or CDR-OKT4A/hIgG4, either as high-dose single bolus (10 mg/kg) or as low-dose multiple infusion (1 mg/kg for 12 days) was given, and the effects on graft survival, immunohistology, circulating cells, and lymph node cells were assessed, Results, The IgG1 isotype induced coating of T cells, modulation of surface CD4 molecules, and profound depletion of CD4(+) lymphocytes in peripheral blood, which persisted as long as the animals were followed (up to 7 weeks). The IgG4 isotype induced only cell coating without cell clearance or modulation. Iq lymph nodes, coating of lymphocytes (approximately 60%) was seen with both isotypes in the earliest sample (6 hr), After 2 days, significant depletion of lymph node CD4 cells was evident, with a decrease in the CD4 to CD8 ratio in the IgG1-treated group; no depletion occurred in the IgG4 group, The emigration of CD4(+) cells into the allograft was significantly delayed in the CDR-OKT4A/hIgG1-treated animals when compared with the CDR-OKT4A/hIgG4 group as judged by immunocytochemistry (23.8+/-13.2 days vs, 7.4+/-1.5 days, P<0.001) or interleukin-2-promoted T-cell outgrowth from allograft biopsies (22.2+/-11.0 days vs. 6.3+/-0.5 days, P<0.01). Conclusions, This study demonstrates that the in vivo effects of CDR-grafted OKT4A are dependent on its isotype, The depleting mAb CDR-OKT4A/hIgG1 significantly delays the entry of CD4(+) cells into the graft, inhibiting the early phase of rejection, However, graft rejection occurs when CD4(+) cells eventually infiltrate the graft, even in the presence of depressed levels of circulating CD4(+) cells. Both isotypes demonstrated therapeutic efficacy: graft survival was prolonged over controls. In the case of CDR-OKT4A/hIgG4, neither lymphocyte depletion, antigenic modulation, nor prevention of infiltration is necessary for a beneficial effect, which indicates that this mAb blocks CD4 function or renders the CD4(+) cell less responsive, The lack of depletion is a feature of potential clinical advantage in minimizing the risk of excessive immunosuppression. C1 Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Transplant Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RW Johnson Pharmaceut Res Inst, Raritan, NJ 08869 USA. RP Colvin, RB (reprint author), Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. FU NHLBI NIH HHS [P01-HL-18646] NR 32 TC 29 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 1998 VL 65 IS 5 BP 632 EP 641 DI 10.1097/00007890-199803150-00006 PG 10 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZC396 UT WOS:000072573800006 PM 9521196 ER PT J AU Coito, AJ Korom, S Graser, E Volk, HD Van de Water, L Kupiec-Weglinski, JW AF Coito, AJ Korom, S Graser, E Volk, HD Van de Water, L Kupiec-Weglinski, JW TI Blockade of very late antigen-4 integrin binding to fibronectin in allograft recipients - I. Treatment with connecting segment-1 peptides prevents acute rejection by suppressing intragraft mononuclear cell accumulation, endothelial activation, and cytokine expression SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the American-Society-of-Transplant-Physicians CY MAY 10-14, 1997 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Physicians ID MURINE CARDIAC GRAFTS; NATURAL-KILLER-CELLS; CD4+ T-CELLS; EXTRACELLULAR-MATRIX; LYMPHOCYTE MIGRATION; ADHESION MOLECULE-1; MONOCLONAL-ANTIBODY; LEUKOCYTE ADHESION; VCAM-1 EXPRESSION; ALPHA SECRETION AB Background. Allograft rejection is associated with infiltration of inflammatory cells and local deposition of fibronectin (FN). This study was carried out to examine the hypothesis that peptides known to specifically block adhesive interactions between the connecting segment-1 (CS1)-binding domain of FN and (alpha 4 beta 1 integrin on circulating cells may interfere with the immune cascade, which would lead to acute rejection in transplant recipients. Methods and Results. Cardiac allografts from Lewis x Brown Norway F-1 hybrids were rejected in 7+/-1 days in Lewis rats, Treatment with bioactive CS1 peptides (4 mg/kg/day i.v. for 7 days) abrogated acute rejection and prolonged cardiac allograft survival to 13+/-1 days (P<0.001). This effect correlated with decreased expression of total fibronectin and cell adhesion molecules, such as alpha 4 beta 1, vascular cell adhesion molecule-1, intercellular adhesion molecule-1, as well as reduced infiltration by CD4(+) and CD8(+) T cells at the graft site. Treatment with CS1 peptides decreased alloantigen activation, as evidenced by decreased intragraft infiltration by CD25(+) cells, and diminished expression of mRNA coding for Th1 (interleukin [IL]-2, interferon-gamma)-and Th2 (IL-4, IL-5, IL-6)-type cytokines. CS1-mediated immunosuppressive effects could be reversed and acute rejection recreated after adjunctive treatment of rats with recombinant IL-2. Conclusion. Our data are consistent with the model in which in vivo interaction between the alpha 4 beta 1 integrin receptor and the cell-associated CS1 motif of FN is critical for rejection cascade. The novel therapeutic approach of selectively blocking the alpha 4 beta 1-FN activation pathway with CS1 peptides prevents acute allograft rejection by inhibiting expansion of antigen-specific T cells and inducing a transient state of cytokine-responsive anergy in the residual T-cell population. C1 Univ Calif Los Angeles, Dumont Transplant Ctr, Div Liver & Pancreas Transplantat, Sch Med, Los Angeles, CA 90095 USA. Humboldt Univ, Inst Med Immunol, D-10098 Berlin, Germany. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Burns Inst, Dept Surg, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Surg,Surg Res Lab, Boston, MA 02115 USA. RP Kupiec-Weglinski, JW (reprint author), Univ Calif Los Angeles, Dumont Transplant Ctr, Div Liver & Pancreas Transplantat, Sch Med, 77-120 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. FU NIAID NIH HHS [AI23847]; NIGMS NIH HHS [GM36812] NR 56 TC 21 Z9 22 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD MAR 15 PY 1998 VL 65 IS 5 BP 699 EP 706 DI 10.1097/00007890-199803150-00017 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA ZC396 UT WOS:000072573800017 PM 9521206 ER PT J AU Addona, GH Sandermann, H Kloczewiak, MA Husain, SS Miller, KW AF Addona, GH Sandermann, H Kloczewiak, MA Husain, SS Miller, KW TI Where does cholesterol act during activation of the nicotinic acetylcholine receptor? SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE acetylcholine receptor; reconstitution; gating; cholesterol ID LIPID-PROTEIN INTERACTIONS; MARMORATA ELECTRIC ORGAN; TORPEDO-CALIFORNICA; POSTSYNAPTIC MEMBRANES; BINDING-SITES; MODULATION; ANESTHETICS; CLEAVAGE; FLUIDITY; MOVEMENT AB Why agonist-induced activation of the nicotinic acetylcholine receptor (nAcChoR) fails completely in the absence of cholesterol is unknown. Affinity-purified nAcChoRs from Torpedo reconstituted into 1,2-dioleoyl-sn-glycero-3-phosphatidycholine/ 1,2-dioleoyl-sn-glycero-3-phosphate/steroid bilayers ar mole ratios of 58:12:30 were used to distinguish between three regions of the membrane where cholesterol might act: the Lipid bilayer, the lipid-protein interface, or sites within the protein itself. In the bilayer, the role of fluidity has been ruled out and certain neutral lipids can substitute for cholesterol [C. Sunshine, M.G. McNamee, Biochim. Biophys. Acta 1191 (1994) 59-64], therefore, we first tested the hypothesis that flip-flop of cholesterol across the membrane is important; a plausible mechanism might be the relief of mechanical bending strain induced by a conformation change that expands the two leaflets of the bilayer asymmetrically. Cholesterol analogs prevented from flipping by charged groups attached to the 3-position's hydroxyl supported channel opening, contrary to this hypothesis. The second hypothesis :is that interstitial cholesterol binding sites exist deep within the nAcChoR that must be occupied for channel opening to occur. When cholesterol hemisuccinate was covalently 'tethered' to the glycerol backbone of phosphatidylcholine, channel opening was still supported, Thus, if there are functionally important cholesterol sites, they must be very close to the lipid-protein interface and might be termed periannular. (C) 1998 Elsevier Science B.V. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. GSF Forschungszentrum Umwelt & Gesundheit, Inst Biochem Pflanzenpathol, D-85764 Oberschleissheim, Germany. RP Miller, KW (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM k_miller@helix.mgh.harvard.edu FU NIAAA NIH HHS [AA-07040]; NIGMS NIH HHS [GM15904] NR 50 TC 48 Z9 48 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 1998 VL 1370 IS 2 BP 299 EP 309 DI 10.1016/S0005-2736(97)00280-0 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZG870 UT WOS:000073048300013 PM 9545586 ER PT J AU Goldmann, WH Galneder, R Ludwig, M Kromm, A Ezzell, RM AF Goldmann, WH Galneder, R Ludwig, M Kromm, A Ezzell, RM TI Differences in F9 and 5.51 cell elasticity determined by cell poking and atomic force microscopy SO FEBS LETTERS LA English DT Article; Proceedings Paper CT ASCB Meeting CY DEC 13-17, 1997 CL WASHINGTON, D.C. SP Amer Soc Cell Biol DE vinculin-regulated cellular elasticity ID INTERFERENCE CONTRAST MICROSCOPY; EMBRYONAL CARCINOMA-CELLS; WILD-TYPE; VINCULIN; ADHESION; DISRUPTION; LOCOMOTION AB We studied the elasticity of both a wild type (F9) mouse embryonic carcinoma and a vinculin-deficient (5.51) cell line, which was produced by chemical mutagenesis. Using cell poking, we measured the effects of loss of vinculin on the elastic properties of these cells, F9 cells were about 20% more resistant to indentation by the cell poker (a glass stylus) than were 5.51 cells, Using the atomic force microscope to map the elasticity of wild type and vinculin-deficient cells by 128 x 128 force scans, we observed a correlation of elasticity with cell poking elastometric measurements. These findings, as well as previous atomic force, theologic, and magnetometric measurements [Goldmann and Ezzell, Exp, Cell Res. 226 (1996) 234-237; Ezzell et al., Exp. Cell Res, 231 (1997) 14-26], indicate that vinculin is an integral part of the cytoskeletal network. (C) 1998 Federation of European Biochemical Societies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Surg Res Unit, Charlestown, MA 02129 USA. Univ Munich, Lehrstuhl Angew Phys, D-80799 Munich, Germany. RP Goldmann, WH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Surg Res Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 15 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD MAR 13 PY 1998 VL 424 IS 3 BP 139 EP 142 DI 10.1016/S0014-5793(98)00155-0 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZE640 UT WOS:000072814800005 PM 9539137 ER PT J AU Arnould, T Kim, E Tsiokas, L Jochimsen, F Gruning, W Chang, JD Walz, G AF Arnould, T Kim, E Tsiokas, L Jochimsen, F Gruning, W Chang, JD Walz, G TI The polycystic kidney disease 1 gene product mediates protein kinase C alpha-dependent and c-Jun N-terminal kinase-dependent activation of the transcription factor AP-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID JNK/SAPK SIGNALING PATHWAY; SYSTEM EFFECTOR FUNCTION; RECEPTOR ZETA-CHAIN; T-CELL; DIFFERENTIAL ACTIVATION; EPITHELIAL-CELLS; DOMAINS; EXPRESSION; PROLIFERATION; TRANSDUCTION AB Autosomal dominant polycystic kidney disease (ADPKD) is a common hereditary disorder that accounts far 8-10% of end stage renal disease, PKD1, one of two recently isolated ADPKD gene products, has been implicated in cell-cell and cell-matrix interactions, However, the signaling pathway of PKD1 remains undefined, We found that the C-terminal 226 amino acids of PKD1 transactivate an AP-1. promoter construct in human embryonic kidney cells (293T). PKD1-induced transcription is specific for AP-1; promoter constructs containing cAMP response element-binding protein, c-Fos, c-Myc, or NF kappa B-binding sites are unaffected by PKD1. In vitro kinase assays revealed that PKD1 triggers the activation of c-Jun N-terminal kinase (JNK), but not of mitogen-activated protein kinases p38 or p44, Dominant-negative Rac-1 and Cdc42 mutations abrogated PKD1-mediated JNK and AP-1 activation, suggesting a critical role for small GTP-binding proteins in PKD1-mediated signaling. Several protein kinase C (PRC) inhibitors decreased PKD1-mediated AP-1 activation, Conversely, expression of the C-terminal domain of PKD1 increased PRC activity in 293T cells, A dominant-negative PKC alpha, but not a dominant-negative PKC beta or delta, abrogated PKD1-mediated AP-1 activation, These findings indicate that small GTP-binding proteins and PKC alpha mediate PKD1-induced JNK/AP-1 activation, together comprising a signaling cascade that may regulate renal tubulogenesis. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Renal Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Cardiol Div, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Mol & Dev Neurosci, Boston, MA 02114 USA. RP Walz, G (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med,Renal Div, 330 Brookline Ave, Boston, MA 02215 USA. EM gwalz@bidmc.harvard.edu FU NIMH NIH HHS [MH-01147] NR 65 TC 130 Z9 133 U1 2 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6013 EP 6018 DI 10.1074/jbc.273.11.6013 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500007 PM 9497315 ER PT J AU Servidei, T Aoki, Y Lewis, SE Symes, A Fink, JS Reeves, SA AF Servidei, T Aoki, Y Lewis, SE Symes, A Fink, JS Reeves, SA TI Coordinate regulation of STAT signaling and c-fos expression by the tyrosine phosphatase SHP-2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CILIARY NEUROTROPHIC FACTOR; LEUKEMIA INHIBITORY FACTOR; CULTURED SYMPATHETIC NEURONS; NEUROBLASTOMA CELL-LINE; GENE-EXPRESSION; PROTEIN-KINASE; GROWTH-FACTORS; CYCLIC-AMP; JAK-STAT; ACTIVATION AB The src homology 2 (SH2) domain-containing protein-tyrosine phosphatase SHP-2 has been implicated as an important positive regulator of several mitogenic signaling pathways. SHP-2 has more recently been shown to be tyrosine phosphorylated and recruited to the gp130 component of the ciliary neurotrophic factor (CNTF) receptor complex upon stimulation with CNTF. CNTF does not, however, have a proliferative effect on responsive cells, but rather enhances the survival and differentiation of sympathetic, motor, and sensory neurons, In this study, expression of an interfering mutant of SHP-2 in the neuroblastoma cell line NBFL increased CNTF induction of a vasoactive intestinal peptide (VIP) reporter gene, and in cultures of sympathetic neurons, it resulted in an up-regulation of endogenous VIP and substance P (SP) gene expression. Members of the CNTF family of cytokines transmit their signal by activating signaling pathways involving both STAT and Fos-Jun transcription factors. In CNTF-stimulated NBFL cells that constitutively express the SHP-2 interfering mutant, there was increased and prolonged formation of STAT/DNA complexes, but decreased AP-1 binding activity, that mirrored a down-regulation of c-fos expression both at the mRNA and protein level. Taken together, these data indicate that SHP-2 has dual and opposing roles in a signaling cascade triggered by the same ligand, as illustrated by its ability to differentially regulate the levels of activity of both STAT and AP-1 transcription factors. C1 Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02129 USA. Massachusetts Gen Hosp, Program Neurosci, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA. RP Reeves, SA (reprint author), Massachusetts Gen Hosp, Neurosurg Serv, 149 13th St, Boston, MA 02129 USA. EM reeves@helix.mgh.harvard.edu RI Symes, Aviva/S-7471-2016 OI Symes, Aviva/0000-0003-2557-9939 FU NINDS NIH HHS [R01 NS27514-08] NR 72 TC 46 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6233 EP 6241 DI 10.1074/jbc.273.11.6233 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500040 PM 9497348 ER PT J AU Meriin, AB Gabai, VL Yaglom, J Shifrin, VI Sherman, MY AF Meriin, AB Gabai, VL Yaglom, J Shifrin, VI Sherman, MY TI Proteasome inhibitors activate stress kinases and induce Hsp72 - Diverse effects on apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMALL NUCLEAR RIBONUCLEOPROTEIN; TUMOR-NECROSIS-FACTOR; HEAT-SHOCK PROTEINS; CELL-DEATH; JNK ACTIVATION; U937 CELLS; PHOSPHORYLATION; RESISTANCE; SIGNAL AB Inhibition of the major cytosolic protease, proteasome, has been reported to induce programmed cell death in several cell lines, while with other lines, similar inhibition blocked apoptosis triggered by a variety of harmful treatments. To elucidate the mechanism of pro- and antiapoptotic action of proteasome inhibitors, their effects on U937 lymphoid and 293 kidney human tumor cells were tested, Treatment with peptidyl aldehyde MG132 and other proteasome inhibitors led to a steady increase in activity of c-Jun N-terminal kinase, JNK1, which is known to initiate the apoptotic program in response to certain stresses. Dose dependence of MG132-induced JNK activation was parallel with that of apoptosis. Furthermore, inhibition of the JNK signaling pathway strongly suppressed MG132-induced apoptosis. These data indicate that JNK is critical for the cell death caused by proteasome inhibitors. An antiapoptotic action of proteasome inhibitors could be revealed by a short incubation of cells with MG132 followed by its withdrawal. Under these conditions, the major heat shock protein Hsp72 accumulated in cells and caused suppression of JNK activation in response to certain stresses. Accordingly, pretreatment with MG132 reduced JNK-dependent apoptosis caused by heat shock or ethanol, but it was unable to block JNK-independent apoptosis induced by TNF alpha. Therefore, proteasome inhibitors activate JNK, which initiates an apoptotic program, and simultaneously they induce Hsp72, which suppresses JNK-dependent apoptosis. A balance between these two effects might define the fate of cells exposed to the inhibitors. C1 Boston Biomed Res Inst, Boston, MA 02114 USA. Inst Influenza, St Petersburg 197022, Russia. Med Radiol Res Ctr, Obninsk 249020, Russia. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sherman, MY (reprint author), Boston Biomed Res Inst, Boston, MA 02114 USA. EM sherman@bbri.harvard.edu RI Gabai, Vladimir/I-1650-2013 NR 37 TC 226 Z9 229 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6373 EP 6379 DI 10.1074/jbc.273.11.6373 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500059 PM 9497367 ER PT J AU Ohashi, Y Tachibana, K Kamiguchi, K Fujita, H Morimoto, C AF Ohashi, Y Tachibana, K Kamiguchi, K Fujita, H Morimoto, C TI T cell receptor-mediated tyrosine phosphorylation of Cas-L, a 105-kDa Crk-associated substrate-related protein, and its association of Crk and C3G SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FOCAL ADHESION KINASE; SH3 DOMAIN; SRC; COMPLEXES; BINDING; GROWTH; IDENTIFICATION; COSTIMULATION; LYMPHOCYTES; ACTIVATION AB Cas-L (pp105), a Crk-associated substrate (p130(Cas))-related protein, was first identified as a 105-kDa protein that is tyrosine-phosphorylated following beta 1 integrin cross-linking in T cells. Cas-L contains possible multiple binding sites for the Src homology (SH) 2 domains of various signaling molecules, and appears to be involved in signal transduction through phosphorylated tyrosine-mediated protein-protein interaction, Since Cas-L is preferentially expressed in lymphocytes, it is conceivable that Cas-L plays an important role in lymphocyte-specific signals. Here, we show the involvement of Cas-L in the T cell receptor (TCR)/CD3 signaling pathway, Cas-L is transiently phosphorylated following CD3 cross-linking, and tyrosine-phosphorylated Cas-L binds to Crk and C3G. Furthermore, a Cas-L mutant that lacks the SH3 domain, the binding site for focal adhesion kinase (FAK), is also tyrosine-phosphorylated upon CD3 cross-linking, but not upon beta 1 integrin crosslinking, suggesting that FAK is not involved in CD3-dependent Cas-L phosphorylation. Taken together, the present study indicates a novel signaling pathway mediated by tyrosine-phosphorylated Cas-L upon the TCR/CD3 stimulation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Clin Immunol, Minato Ku, Tokyo, Japan. Univ Tokyo, Inst Med Sci, Ctr AIDS Res, Minato Ku, Tokyo, Japan. RP Tachibana, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Tumor Immunol, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI29530]; NIAMS NIH HHS [AR33713] NR 33 TC 50 Z9 51 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 13 PY 1998 VL 273 IS 11 BP 6446 EP 6451 DI 10.1074/jbc.273.11.6446 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZB597 UT WOS:000072488500069 PM 9497377 ER PT J AU Singer, DE AF Singer, DE TI Anticoagulation to prevent stroke in atrial fibrillation and its implications for managed care SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Treatment of Atrial Fibrillation in the Era of Managed Care CY AUG 17, 1996 CL NEW YORK, NEW YORK SP 3M Pharm ID COST-EFFECTIVENESS; RISK-FACTORS; WARFARIN; COMPLICATIONS; FRAMINGHAM; THERAPY; ASPIRIN; TRIALS AB Nonrheumatic atrial fibrillation (AFib) is the most potent common risk factor for stroke, raising the risk of stroke 5-fold. Six randomized trials of anticoagulation in AFib consistently demonstrated a reduction in the risk of stroke by about two-thirds, In these trials, anticoagulation in AFib was quite safe, In contrast, randomized trials indicate that aspirin confers only a small reduction in risk of stroke, at best, Pooled data from the first set of randomized trials indicate that prior stroke, hypertension, diabetes, and increasing age are independent risk factors for future stroke with AFib, individuals <65 years old with none of the other risk factors might safely avoid anticoagulation; for all others, anticoagulation seems indicated. Studies of hemorrhagic risk highlight the importance of keeping the international normalized ratio (INR) <4.0, Recent analyses also reveal that risk of ischemic stroke in AFib increases greatly at INR levels <2.0. Efficacy and safety of anticoagulation in AFib depend on maintaining the INR between 2.0-3.0. Cost-effectiveness studies indicate that anticoagulation for AFib is among the most efficient preventive interventions in adults. Importantly, the benefits of anticoagulation in AFib accrue immediately The implications for managed care organizations are that anticoagulation for AFib should be encouraged in their covered populations, and that dedicated anticoagulation services should be developed to promote system-wide control of anticoagulation intensity, Quality measures would include the proportion of patients with AFib who are anticoagulated, and the percentage of time patients' INR levels are between 2.0-3.0. Managed care organizations can benefit from recent research on anticoagulation for AFib; they have a responsibility to support future research and development efforts, (C) 1998 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Med Serv, S50-9, Boston, MA 02114 USA. NR 30 TC 8 Z9 8 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 12 PY 1998 VL 81 IS 5A SI SI BP 35C EP 40C DI 10.1016/S0002-9149(98)00185-4 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZD656 UT WOS:000072709200006 PM 9525571 ER PT J AU Keane, D Zou, L Ruskin, J AF Keane, D Zou, L Ruskin, J TI Nonpharmacologic therapies for atrial fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Treatment of Atrial Fibrillation in the Era of Managed Care CY AUG 17, 1996 CL NEW YORK, NEW YORK SP 3M Pharm ID VENTRICULAR CYCLE LENGTH; INTERNAL CARDIOVERSION; SINUS RHYTHM; WAVE-FORMS; P-WAVE; DEFIBRILLATION; ARRHYTHMIAS; PREVENTION; HUMANS; SHEEP AB The limited efficacy and proarrhythmic risks of antiarrhythmic drug therapies for atrial fibrillation have led to the exploration of a wide spectrum of alternative therapeutic approaches. The diversity of the approaches is warranted by the current absence of a single procedure that can safety and effectively cure atrial fibrillation. The interventional therapies that are currently under most active development include implantable atrial defibrillator therapy, prophylactic atrial pacing in combination with drug therapy, multisite regional pace-entrainment of atrial fibrillation by rapid pacing, atrial surgery, and catheter ablation for atrial fibrillation. The current limitations of these procedures include: (1) for the implantable atrial defibrillator-patient tolerance of low energy shocks and early recurrence of atrial fibrillation; (2) for prophylactic pacing-limited efficacy in a small proportion of the total atrial fibrillation population; (3) for multisite regional pace-entrainment-lack of proved efficacy and difficulty in the expansion and merging of the entrained regions; (4) for atrial surgery-highly invasive as a stand-alone procedure; and (5) for catheter ablation-lack of proved long-term efficacy, shortcomings of currently available technology, and risk of thromboembolic stroke. It is evident that more basic and clinical research as well as technologic innovation are needed. However, it is likely that some of these new therapies, possibly in combination with antiarrhythmic drug therapy, will offer considerable clinical benefit to selected patients with symptomatic atrial fibrillation. (C) 1998 by Excerpta Medica, Inc. C1 Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Keane, D (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. NR 51 TC 9 Z9 9 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 12 PY 1998 VL 81 IS 5A SI SI BP 41C EP 45C DI 10.1016/S0002-9149(98)00186-6 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZD656 UT WOS:000072709200007 PM 9525572 ER PT J AU Rosowsky, A Papoulis, AT Queener, SF AF Rosowsky, A Papoulis, AT Queener, SF TI 2,4-diamino-6,7-dihydro-5H-cyclopenta[d]pyrimidine analogues of trimethoprim as inhibitors of Pneumocystis carinii and Toxoplasma gondii dihydrofolate reductase SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACQUIRED IMMUNODEFICIENCY SYNDROME; NERVOUS-SYSTEM TOXOPLASMOSIS; ANTITUMOR-ACTIVITY; OPPORTUNISTIC INFECTIONS; ANTIFOLATE ACTIVITY; TRIMETREXATE; PIRITREXIM; PNEUMONIA; POTENT; ANTIPNEUMOCYSTIS AB Three previously unreported (R,S)-2,4-diamino-5-[(3,4,5-trimethoxyphenyl)alkyl]-6,7-dihydro- 5H-cyclopenta[d]pyrimidines 15a-c were synthesized as analogues of trimethoprim (TMP) and were tested as inhibitors of Pneumocystis carinii, Toxoplasma gondii, and rat liver dihydrofolate reductase (DHFR). The length of the alkyl bridge between the cyclopenta[d]pyrimidine and trimethoxyphenyl moiety ranged from one in 15a to three carbons in 15c. The products were tested as competitive inhibitors of the reduction of dihydrofolate by Pneumocystis carinii, Toxoplasma gondii, and rat liver DHFR. Compounds 15a-c had IC50 values of >32, 1.8 and 1.3 mu M, respectively, against P. carinii DHFR, as compared to 12 mu M for TMP. Against the T. gondii enzyme, 15a-c had IC50 values of 21, 0.14 and 0.14 mu M, respectively as compared to 2.7 mu M for TMP. Inhibitors 15b and 15c with two-and three-carbon bridges were significantly more potent than 15a against all three enzymes. Unlike TMP, 15b and 15c were better inhibitors of the rat liver enzyme than of the microbial enzymes. The potency of 15b and 15c against rat liver DHFR was less than has been reported for the corresponding 6,7-dihydro-5H-cyclopenta[d]pyrimidines with a classical p-aminobenzoyl-L-glutamate side chain as inhibitors of bovine, murine, and human DHFR. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Indiana Univ, Sch Med, Dept Pharmacol & Toxicol, Indianapolis, IN 46202 USA. RP Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [N01-AI35171, R01-AI29904] NR 36 TC 24 Z9 24 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 12 PY 1998 VL 41 IS 6 BP 913 EP 918 DI 10.1021/jm970614n PG 6 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA ZC178 UT WOS:000072548600013 PM 9526565 ER EF