FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Boussiotis, VA Freeman, GJ Berezovskaya, A Grass, J Nadler, LM AF Boussiotis, VA Freeman, GJ Berezovskaya, A Grass, J Nadler, LM TI p27(kip1) is a central regulator of clonal expansion and IL-2 transcription in helper T cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1647 BP 370A EP 370A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301696 ER PT J AU Andre, P Denis, C Subbarao, S Economopoulos, M Hynes, RO Wagner, DD AF Andre, P Denis, C Subbarao, S Economopoulos, M Hynes, RO Wagner, DD TI Platelets adhere and translocate on von Willebrand factor (vWF) in stimulated veins in vivo. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. HHMI, Cambridge, MA USA. MIT, Ctr Canc Res, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1656 BP 372A EP 372A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301705 ER PT J AU Italiano, JE Lecine, PL Shivdasani, RA Hartwig, JH AF Italiano, JE Lecine, PL Shivdasani, RA Hartwig, JH TI Platelets mature only at the ends of proplatelet extensions. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RI Lecine, Patrick/H-9338-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1657 BP 372A EP 372A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301706 ER PT J AU Weisberg, EL Griffin, JD AF Weisberg, EL Griffin, JD TI Amplification of the BCR/ABL gene in transformed hematopoietic cell lines resistant to the ABL tyrosine kinase inhibitor STI571. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1719 BP 387A EP 387A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301768 ER PT J AU Wu, CJ Alyea, EP Soiffer, RJ Dranoff, G Ritz, J AF Wu, CJ Alyea, EP Soiffer, RJ Dranoff, G Ritz, J TI Serologic identification of antigens associated with response to donor lymphocyte infusion (DLI) for relapsed CML, after allogeneic BMT. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1723 BP 388A EP 388A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301772 ER PT J AU Hill, GR Teshima, T Krijanovski, OI Rebel, V Cooke, KR Brinson, YS Ferrara, JLM AF Hill, GR Teshima, T Krijanovski, OI Rebel, V Cooke, KR Brinson, YS Ferrara, JLM TI The p55 TNF alpha receptor on donor T cells plays a critical role in acute graft-versus-host disease. SO BLOOD LA English DT Meeting Abstract C1 Mater Med Res Inst, S Brisbane, Australia. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat Oncol, Boston, MA USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. Univ Michigan, Sch Med, Dept Pediat, Ann Arbor, MI USA. RI teshima, takanori/G-1671-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1740 BP 392A EP 392A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301789 ER PT J AU Porter, DL Confer, D King, R Bate-Boyle, B Antin, JH AF Porter, DL Confer, D King, R Bate-Boyle, B Antin, JH TI Leukapheresis of volunteer unrelated donors: Collection of donor leukocytes for treatment of relapsed leukemia or EBV-lymphoproliferative disorders. SO BLOOD LA English DT Meeting Abstract C1 Univ Penn, Philadelphia, PA 19104 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 4989 BP 393B EP 393B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701833 ER PT J AU Klein, C Robert, C Cheng, G Kupper, TS von Andrian, UH Mulligan, RC AF Klein, C Robert, C Cheng, G Kupper, TS von Andrian, UH Mulligan, RC TI Genetically engineered dendritic cells mediate increased anti-tumor immunity and can be targeted to lymph nodes. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1761 BP 398A EP 398A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301810 ER PT J AU Gabrilove, JL Einhorn, LH Cleeland, CS Livingston, RB Winer, E AF Gabrilove, JL Einhorn, LH Cleeland, CS Livingston, RB Winer, E TI Once-weekly dosing of epoetin alfa increases hemoglobin (Hb) and improves quality of life (QOL) in patients with hematologic malignancies. SO BLOOD LA English DT Meeting Abstract C1 Mt Sinai Med Ctr, New York, NY 10029 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Washington, Seattle, WA 98195 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1771 BP 400A EP 400A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301820 ER PT J AU Heinrich, M Silvey, K Zigler, A Griffith, D Montalto, M Chai, L Zhi, Y Hoatlin, M AF Heinrich, M Silvey, K Zigler, A Griffith, D Montalto, M Chai, L Zhi, Y Hoatlin, M TI Post-transcriptional regulation of human FANCC expression during cell cycle progression is dependent upon activity of the proteasome. SO BLOOD LA English DT Meeting Abstract C1 Portland VA Med Ctr, Div Hematol, Portland, OR USA. Oregon Hlth Sci Univ, Div Hematol, Portland, OR 97201 USA. RI zigler, arie/C-2667-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1812 BP 409A EP 409A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301861 ER PT J AU Yamashita, T Garcia-Higuera, I Tetteh, N Futaki, H Yagasaki, H Nakahata, T Andrea, ADD Asano, A AF Yamashita, T Garcia-Higuera, I Tetteh, N Futaki, H Yagasaki, H Nakahata, T Andrea, ADD Asano, A TI A cytoplasmic serine protein kinase binds, phosphorylates, and regulates the function of the Fanconi anemia protein, FANCA. SO BLOOD LA English DT Meeting Abstract C1 Univ Tokyo, Inst Med Sci, Tokyo, Japan. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1810 BP 409A EP 409A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301859 ER PT J AU Lee, JS Denham, J Chung, M Nisbet-Brown, E Sieff, C D'Andrea, AD Mulligan, R AF Lee, JS Denham, J Chung, M Nisbet-Brown, E Sieff, C D'Andrea, AD Mulligan, R TI Preclinical studies of gene transfer ln fanconi anemia: Efficient gene transfer and lack of toxicity of a high titered VSV-G pseudotyped retrovirus vector. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 5075 BP 413B EP 413B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701919 ER PT J AU Garcia-Higuera, I Kuang, Y Hagan, R Moriguchi, L D'Andrea, AD AF Garcia-Higuera, I Kuang, Y Hagan, R Moriguchi, L D'Andrea, AD TI Overexpression of the Fanconi anemia protein, FANCA, functionally complements a Fanconi anemia group H cell line. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1837 BP 414A EP 415A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790301886 ER PT J AU Earle, C Menzin, J Lang, K Mallick, R Berger, M AF Earle, C Menzin, J Lang, K Mallick, R Berger, M TI Short-term outcomes of treatment for relapsed acute myeloid leukemia (AML): Findings from a clinical study and a comparative chart review. SO BLOOD LA English DT Meeting Abstract C1 Boston Hlth Econ, Billerica, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Wyeth Ayerst Res, Radnor, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 5120 BP 423B EP 423B PN 2 PG 1 WC Hematology SC Hematology GA 257PM UT WOS:000083790701964 ER PT J AU Olszak, IT Poznansky, MC Evans, RH Brown, EM Scadden, DT AF Olszak, IT Poznansky, MC Evans, RH Brown, EM Scadden, DT TI Extracellular calcium is an ionic chemokine for human immune cells. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, AIDS Res Ctr, Charlestown, MA USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA. Brigham & Womens Hosp, Div Endocrine, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1884 BP 425A EP 425A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301933 ER PT J AU Gaetaniello, L Pozzi, N Baiestrieri, B Matrecano, E Ritz, J Pignata, C AF Gaetaniello, L Pozzi, N Baiestrieri, B Matrecano, E Ritz, J Pignata, C TI Altered expression of IL-12 receptor in children with very high serum IgE levels. SO BLOOD LA English DT Meeting Abstract C1 Univ Naples Federico II, Immunol Unit, Dept Pediat, Naples, Italy. Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RI Pignata, Claudio/O-2466-2013 OI Pignata, Claudio/0000-0003-1568-9843 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1929 BP 434A EP 434A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301978 ER PT J AU Gilleece, MH Boussiotis, VA Tangye, S Haber, DA Nadler, LM Nichols, KE AF Gilleece, MH Boussiotis, VA Tangye, S Haber, DA Nadler, LM Nichols, KE TI Perturbed CD28 costimulation and activation-induced death in X-linked lymphoproliferative syndrome. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. DNAX Res Inst, Palo Alto, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1931 BP 435A EP 435A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301980 ER PT J AU Maecker, B Sherr, DH Shen, C Vonderheide, RH von Bergwelt-Baildon, MS Bedor, MM Schnipper, DR Nadler, LM Schultze, JL AF Maecker, B Sherr, DH Shen, C Vonderheide, RH von Bergwelt-Baildon, MS Bedor, MM Schnipper, DR Nadler, LM Schultze, JL TI Targeting universal tumor antigens with cytotoxic T cells: Potential of CYP1B1 for broadly applicable antigen-specific immunotherapy. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 2 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1945 BP 438A EP 438A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301994 ER PT J AU Witzens, M Trojan, A Harig, S Gribben, JG AF Witzens, M Trojan, A Harig, S Gribben, JG TI Cytotoxic T cells generated against HLA-A2 binding peptides kill peptide pulsed targets and tumor cells expressing c-myc, but not bcl-1 or bcl-2. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1947 BP 438A EP 438A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301996 ER PT J AU Witzens, M Trojan, A Harig, S Gribben, JG AF Witzens, M Trojan, A Harig, S Gribben, JG TI Generation of cytotoxic T cells against immunogenic peptides from heat shock proteins: Implications for immunotherapy of cancer. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1946 BP 438A EP 438A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790301995 ER PT J AU Christodoulides, NJ Feng, SJ Resendiz, J Kroll, MH AF Christodoulides, NJ Feng, SJ Resendiz, J Kroll, MH TI Pathological shear stress directly causes serine phosphorylation of platelet filamin A (actin binding protein-280) that associates with GPIb alpha. SO BLOOD LA English DT Meeting Abstract C1 Rice Univ, Houston, TX 77251 USA. Baylor Coll Med, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1969 BP 443A EP 443A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302018 ER PT J AU Methia, N Andre, P Denis, C Economopoulos, M Subbarao, S Wagner, DD AF Methia, N Andre, P Denis, C Economopoulos, M Subbarao, S Wagner, DD TI Delayed fatty streak formation in von Willebrand factor-deficient mice. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 1999 BP 450A EP 450A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302048 ER PT J AU Wu, LA Woodson, RD Churchill, WH Goodnough, LT Kao, KJ McGurk, S Olson, JD Surgenor, DM Wallace, EL AF Wu, LA Woodson, RD Churchill, WH Goodnough, LT Kao, KJ McGurk, S Olson, JD Surgenor, DM Wallace, EL TI Institutional bias determines autologous blood predeposit and blood transfusion outcomes in radical prostatectomy. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Univ Wisconsin, Madison, WI 53706 USA. Harvard Univ, Sch Med, Boston, MA USA. Washington Univ, St Louis, MO 63130 USA. Univ Florida, Gainesville, FL 32611 USA. Univ Iowa, Iowa City, IA 52242 USA. Ctr Management Syst, Snowmass Village, CO USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2053 BP 461A EP 461A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302102 ER PT J AU Yang, XF Ye, Q Han, RZ On, M Bassing, CH Sleckman, BP Alt, FW Cantor, H AF Yang, XF Ye, Q Han, RZ On, M Bassing, CH Sleckman, BP Alt, FW Cantor, H TI Genomic organization of the Bcl-x gamma gene and complex regulation of its 3'untranslated region. SO BLOOD 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 AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2090 BP 469A EP 469A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302139 ER PT J AU Wang, ZY Bonelli, A Carlesso, N Scadden, DT AF Wang, ZY Bonelli, A Carlesso, N Scadden, DT TI Ectopic expression of Eph B4 (HTK) promotes 32D cell growth and reduces IL-3 dependence. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Expt Hematol & AIDS Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2103 BP 472A EP 472A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302152 ER PT J AU Baek, KH Mondoux, M Jaster, R D'Andrea, AD AF Baek, KH Mondoux, M Jaster, R D'Andrea, AD TI DUB-2A, a new member of the due subfamily of hematopoietic deubiquitinating enzymes. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Rostock, Inst Med Biochem, Rostock, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2111 BP 473A EP 473A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302160 ER PT J AU Brasher, BB Van Etten, RA AF Brasher, BB Van Etten, RA TI Characterization of c-Abl tyrosine kinase activity: High basal activity and stimulation by autophosphorylation. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2175 BP 486A EP 486A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302224 ER PT J AU Moller, MB Kania, PW Ino, Y Gerdes, AM Nielsen, O Louis, DN Skjodt, K Pedersen, NT Borregaard, N AF Moller, MB Kania, PW Ino, Y Gerdes, AM Nielsen, O Louis, DN Skjodt, K Pedersen, NT Borregaard, N TI E2f-1: A marker of treatment failure and poor prognosis in diffuse large B-cell lymphoma SO BLOOD LA English DT Meeting Abstract C1 Univ So Denmark Odense Univ, Dept Pathol, Odense, Denmark. Univ So Denmark Odense Univ, Dept Clin Genet, Odense, Denmark. Univ So Denmark Odense Univ, Dept Immunol & Microbiol, Odense, Denmark. Massachusetts Gen Hosp, Dept Pathol Neuropathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Moller, Michael/G-8340-2016 OI Moller, Michael/0000-0003-2041-3630 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2285 BP 510A EP 510A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302334 ER PT J AU Ye, CC Swinnen, LJ Fan, HX Grogan, TM Gulley, ML AF Ye, CC Swinnen, LJ Fan, HX Grogan, TM Gulley, ML TI Bc16 is not overexpressed in post-transplant lymphoproliferative disorder (PTLD). SO BLOOD LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78285 USA. Loyola Univ, Dept Med, Chicago, IL 60611 USA. Univ Arizona, Dept Pathol, Tucson, AZ USA. Audie L Murphy Mem Vet Hosp, Lab Serv, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2322 BP 519A EP 519A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302371 ER PT J AU de Leval, L Shipp, M Neuberg, D Ferry, J Harris, N AF de Leval, L Shipp, M Neuberg, D Ferry, J Harris, N TI Nodal diffuse large B-cell lymphomas (DLB-CLs) are more likely to be derived from germinal center B-cells than extranodal DLB-CLs. SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2331 BP 521A EP 521A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302380 ER PT J AU Greipp, PR Leong, T Van Ness, BG Kay, NE Kyle, RA Oken, MM Oken, M AF Greipp, PR Leong, T Van Ness, BG Kay, NE Kyle, RA Oken, MM Oken, M TI Post treatment survival is predicted by the plasma cell labeling index measured at completion of therapy and by the pretreatment B2M in ECOG protocol E9486. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. Eastern Cooperat Oncol Grp, Dept Stat, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Inst Human Genet, Minneapolis, MN 55455 USA. Abbott NW Hosp, Virginia Piper Canc Inst, Minneapolis, MN 55407 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2392 BP 535A EP 535A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302441 ER PT J AU Greipp, PR Leong, T Van Ness, BG Kay, NE Kyle, RA Oken, MM AF Greipp, PR Leong, T Van Ness, BG Kay, NE Kyle, RA Oken, MM TI Bone marrow plasma cell labeling index and C-reactive protein measured at relapse are independent prognostic factors for post-relapse survival in ECOG protocol E9486. SO BLOOD LA English DT Meeting Abstract C1 Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Dept Stat, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN USA. Abbott NW Hosp, Virginia Piper Canc Inst, Minneapolis, MN 55407 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2399 BP 536A EP 536A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302448 ER PT J AU Shinn, CA Byrd, JC Neuberg, DS Flinn, IW Grever, MR AF Shinn, CA Byrd, JC Neuberg, DS Flinn, IW Grever, MR TI Overexpression of MDM2 in leukemic cells in previously treated patients with chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2422 BP 542A EP 542A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302471 ER PT J AU Hideshima, T Chauhan, D Raje, N Treon, SP Shima, Y Tai, YT Davis, F Anderson, KC AF Hideshima, T Chauhan, D Raje, N Treon, SP Shima, Y Tai, YT Davis, F Anderson, KC TI Characterization of signaling cascades triggered by human IL-6 versus kaposi's sarcoma-associated herpes virus encode viral IL-6. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2455 BP 549A EP 549A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302504 ER PT J AU Cooke, KR Gerbitz, A Hill, GR Crawford, JM Teshima, T Rossignol, D Ferrara, JLM AF Cooke, KR Gerbitz, A Hill, GR Crawford, JM Teshima, T Rossignol, D Ferrara, JLM TI Inhibition of endotoxin induced cellular activation reduces acute graft versus host disease by attenuating intestinal toxicity mediated by TNF alpha. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Div Pediat Oncol, Boston, MA 02115 USA. Univ Florida, Dept Pathol, Gainesville, FL 32611 USA. Eisai Res Inst, Andover, MA USA. Univ Michigan, Ctr Canc, Blood & Bone Marrow Stem Cell Tranplantat Program, Ann Arbor, MI 48109 USA. RI teshima, takanori/G-1671-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2458 BP 550A EP 550A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302507 ER PT J AU van den Brink, MRM Moore, E Horndasch, KJ Crawford, JM Hoffman, J Murphy, GF Burakoff, SJ AF van den Brink, MRM Moore, E Horndasch, KJ Crawford, JM Hoffman, J Murphy, GF Burakoff, SJ TI Fas-deficient B6.LPR and fas ligand-defective B6.GLD mice are more susceptible to graft-versus-host disease. SO BLOOD LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Florida, Coll Med, Gainesville, FL USA. Thomas Jefferson Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2459 BP 550A EP 550A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302508 ER PT J AU Soiffer, R Weller, E Alyea, E Fisher, D Freedman, A Gribben, J Schlossman, R Antin, J Ritz, J AF Soiffer, R Weller, E Alyea, E Fisher, D Freedman, A Gribben, J Schlossman, R Antin, J Ritz, J TI Comparative rates of engraftment, GVHD, and disease relapse following CD6+T cell depleted BMT from HLA matched related and unrelated donors. SO BLOOD LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2515 BP 563A EP 563A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302564 ER PT J AU Tallman, MS Neuberg, D Bennett, JM Francois, C Paietta, E DeWald, G Cassileth, P Oken, M Wiernik, P Rowe, JM AF Tallman, MS Neuberg, D Bennett, JM Francois, C Paietta, E DeWald, G Cassileth, P Oken, M Wiernik, P Rowe, JM TI Acute megakaryocytic leukemia: The Eastern cooperative oncology group (ECOG) experience. SO BLOOD LA English DT Meeting Abstract C1 Northwestern Univ, Sch Med, Chicago, IL USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rochester, Ctr Canc, Rochester, NY USA. New York Med Coll, OLM Canc Ctr, Bronx, NY USA. Mayo Clin, Rochester, MN USA. Univ Miami, Sch Med, Miami, FL USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Eastern Cooperat Oncol Grp, Brookline, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2656 BP 596A EP 596A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302705 ER PT J AU Li, S Gillessen, S Dranoff, G Van Etten, RA AF Li, S Gillessen, S Dranoff, G Van Etten, RA TI Interleukin-3 and granulocyte-macrophage colony-stimulating factor are not required for induction of chronic myeloid leukemia-like disease in mice by the p210 BCR/ABL oncogene. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2672 BP 600A EP 600A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302721 ER PT J AU Million, RP Van Etten, RA AF Million, RP Van Etten, RA TI The Grb2 binding site is required for induction of chronic myeloid leukemia-like disease in mice by the Bcr/Abl tyrosine kinase. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2673 BP 600A EP 601A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790302722 ER PT J AU Krackhardt, A Trojan, A Gribben, JG AF Krackhardt, A Trojan, A Gribben, JG TI Generation of autologous T cell responses against CLL cells: Implications for immunotherapy. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2676 BP 601A EP 601A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302725 ER PT J AU Boussiotis, VA Murphy, W Zeller, J Berezovskaya, A Roncarolo, M Chen, ZM Nadler, LM Blazar, BR AF Boussiotis, VA Murphy, W Zeller, J Berezovskaya, A Roncarolo, M Chen, ZM Nadler, LM Blazar, BR TI Molecular basis of GVHD control induced by IL-10 and TGF-beta. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. TIGET, Milan, Italy. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2690 BP 604A EP 605A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790302739 ER PT J AU Ho, V Weller, E Lee, S Antin, J Soiffer, R AF Ho, V Weller, E Lee, S Antin, J Soiffer, R TI FeV1 and T-cell depletion are significant prognostic factors for severe pulmonary complications after hematopoietic stem cell transplantation. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Adult Oncol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Biostat, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2702 BP 607A EP 607A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302751 ER PT J AU Alyea, EP Schlossman, RL Canning, CM Weller, EA Webb, IJ Anderson, KC Ritz, J AF Alyea, EP Schlossman, RL Canning, CM Weller, EA Webb, IJ Anderson, KC Ritz, J TI CD6 T cell depleted allogeneic bone marrow transplant followed by CD4+donor lymphocyte infusion for patients with multiple myeloma. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2708 BP 609A EP 609A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302757 ER PT J AU Kuang, Y Garcia-Higuera, I D'Andrea, AD AF Kuang, Y Garcia-Higuera, I D'Andrea, AD TI The Fanconi Anemia protein, FANCG, binds directly to the nuclear localization signal (NLS) of FANCA and regulates nuclear accumulation of the FA protein complex. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2725 BP 613A EP 613A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302774 ER PT J AU Donovan, JW Poor, C Bowers, D Waters, S Zou, GY Neuberg, D Moghrabi, A Sallan, S Gribben, JG AF Donovan, JW Poor, C Bowers, D Waters, S Zou, GY Neuberg, D Moghrabi, A Sallan, S Gribben, JG TI Concordance of MRD results in matched bone marrow and peripheral blood samples indicate that peripheral blood could be a sole sample source for MRD detection in pediatric acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. St Justine Hosp, Montreal, PQ, Canada. RI Zou, Guangyong/K-6408-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2781 BP 626A EP 626A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302830 ER PT J AU Veiga, JP Keenan, TD Barata, JT Sallan, SE Nadler, LM Cardoso, AA AF Veiga, JP Keenan, TD Barata, JT Sallan, SE Nadler, LM Cardoso, AA TI Peroxisome proliferator-activated receptor-gamma (PPAR gamma) expression by bone marrow endothelium reveals a potential target for therapeutic intervention in acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2785 BP 627A EP 627A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302834 ER PT J AU Trojan, A Schultze, JL Witzens, M Vonderheide, RH Ladetto, M Donovan, JW Gribben, JG AF Trojan, A Schultze, JL Witzens, M Vonderheide, RH Ladetto, M Donovan, JW Gribben, JG TI Shared immunoglobulin framework-derived peptides function as cytotoxic T cell epitopes expressed commonly in B cell malignancies. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2796 BP 629A EP 629A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302845 ER PT J AU Howard, O Gribben, J Neuberg, D Grossbard, M Poor, C Janicek, M Shipp, M AF Howard, O Gribben, J Neuberg, D Grossbard, M Poor, C Janicek, M Shipp, M TI Rituxan/CHOP induction therapy in newly diagnosed patients with mantle cell lymphoma. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2804 BP 631A EP 631A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302853 ER PT J AU Gesbert, F Sillaber, C Griffin, JD AF Gesbert, F Sillaber, C Griffin, JD TI Role of STAT5 in BCR/ABL mediated survival and growth factor independence. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2809 BP 632A EP 632A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302858 ER PT J AU Sillaber, C Gesbert, F Frank, DA Sattler, M Griffin, JD AF Sillaber, C Gesbert, F Frank, DA Sattler, M Griffin, JD TI STAT5 activation contributes to growth and viability in BCR/ABL transformed cells. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2808 BP 632A EP 632A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302857 ER PT J AU Schultze, JL Maecker, B von Bergwelt-Baildon, M Gribben, JG Nadler, LM AF Schultze, JL Maecker, B von Bergwelt-Baildon, M Gribben, JG Nadler, LM TI Cytokine profile of CD40-activated B-CLL: Opportunities to refine cellular vaccines in B cell malignancies. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2816 BP 634A EP 634A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302865 ER PT J AU Mapara, MY Swenson, K Zhao, GL Pearson, D Pelot, MR Sykes, M AF Mapara, MY Swenson, K Zhao, GL Pearson, D Pelot, MR Sykes, M TI A novel cyclophosphamide (CTX) based non-myeloablative conditioning regimen: Induction of tolerance and effects of delayed donor lymphocyte infusions (DLI). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RI mapara, markus/A-2134-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2820 BP 635A EP 635A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302869 ER PT J AU Teshima, T Mach, N Hill, GR Dranoff, G Ferrara, JLM AF Teshima, T Mach, N Hill, GR Dranoff, G Ferrara, JLM TI Vaccine induced graft-versus-tumor effects are separable from graft-versus-host disease. SO BLOOD LA English DT Meeting Abstract C1 Univ Michigan, Ctr Canc, Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. RI teshima, takanori/G-1671-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2821 BP 635A EP 635A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302870 ER PT J AU Yang, YG Qi, J Sykes, M AF Yang, YG Qi, J Sykes, M TI IFN-gamma downmodulates graft-versus-host disease while mediating graft-versus-leukemic effects. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect,Surg Serv, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2822 BP 635A EP 635A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302871 ER PT J AU Freedman, A Gribben, J Kuhlman, C Jallow, H Houde, H Jarpe, M Letizia, C Monroy, R Schmittling, R Zonno, A Ogier, W Atkinson, K AF Freedman, A Gribben, J Kuhlman, C Jallow, H Houde, H Jarpe, M Letizia, C Monroy, R Schmittling, R Zonno, A Ogier, W Atkinson, K TI Effective purging of autologus hematopoietic stem cell (HSC) transplants for non-hodgkin's lymphoma (NHL) using high density microparticles coated with anti-CD19 and anti-CD20 monoclonal antibodies: Elimination of B cells, high CD34(+) cell yield and rapid engraftment. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Eligix Inc, Medford, MA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2835 BP 638A EP 638A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302884 ER PT J AU Hochberg, EP Chillemi, AC Wu, CJ Neuberg, D Canning, C Hartman, K Soiffer, RJ Kalams, SA Ritz, J AF Hochberg, EP Chillemi, AC Wu, CJ Neuberg, D Canning, C Hartman, K Soiffer, RJ Kalams, SA Ritz, J TI Quantitation of T cell receptor differentiation in vivo after adult allogeneic bone marrow transplantation by measurement of T cell receptor rearrangement excision circles (TREC). SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2838 BP 639A EP 639A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302887 ER PT J AU Shirihai, OS Gregory, T Orkin, SH Weiss, MJ AF Shirihai, OS Gregory, T Orkin, SH Weiss, MJ TI ABC-me: A novel GATA-1-induced mitochondrial erythroid transporter involved in heme biosynthesis. SO BLOOD LA English DT Meeting Abstract C1 Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Howard Hughes Med Inst, Coconut Grove, FL 33133 USA. Ontogeny Inc, Boston, MA USA. RI Weiss, Mitchell/A-1245-2013 NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2855 BP 643A EP 643A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302904 ER PT J AU Turecek, PL Lenting, PJ van Mourik, JA Binder, B Mihaly, J Denis, C Wagner, D Dorner, F Schwarz, HP AF Turecek, PL Lenting, PJ van Mourik, JA Binder, B Mihaly, J Denis, C Wagner, D Dorner, F Schwarz, HP TI Low density lipoprotein receptor-related protein (LRP) mediates the clearance of factor VIII in vWF-deficient mice. SO BLOOD LA English DT Meeting Abstract C1 Baxter Hyland Immuno, Vienna, Austria. CLB, Amsterdam, Netherlands. Univ Vienna, Dept Vasc Biol, Vienna, Austria. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA USA. RI Lenting, Peter/F-8269-2013 OI Lenting, Peter/0000-0002-7937-3429 NR 0 TC 7 Z9 7 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2874 BP 647A EP 647A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302923 ER PT J AU Herley, MT D'Andrea, AD Ney, PA AF Herley, MT D'Andrea, AD Ney, PA TI Physical and functional interactions between the erythropoietin receptor and a truncated form of the Stk/RON receptor tyrosine kinase. SO BLOOD LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Dept Biochem, Memphis, TN 38105 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2898 BP 652A EP 652A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302947 ER PT J AU Golub, TR Slonim, D Tamayo, P Huard, C Gaasenbeek, M Mesirov, J Coller, H Loh, M Downing, JR Caligiuri, MA Bloomfield, CD Lander, ES AF Golub, TR Slonim, D Tamayo, P Huard, C Gaasenbeek, M Mesirov, J Coller, H Loh, M Downing, JR Caligiuri, MA Bloomfield, CD Lander, ES TI Gene expression pattern recognition for cancer classification. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead Inst, Cambridge, MA 02142 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Ohio State Univ, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2916 BP 656A EP 657A PN 1 PG 2 WC Hematology SC Hematology GA 257PH UT WOS:000083790302965 ER PT J AU Putti, MC Cardoso, AA Stripecke, R Grier, H Nadler, LM AF Putti, MC Cardoso, AA Stripecke, R Grier, H Nadler, LM TI Induction of a dendritic cell phenopyte is the most efficient strategy to improve the immunogenicity of childhood acute myeloid leukemia. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. Clin Pediat Hematol Oncol, Padua, Italy. Univ So Calif, Inst Genet Med, Los Angeles, CA 90089 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2922 BP 658A EP 658A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302971 ER PT J AU Veiga, JP Sallan, SE Nadler, LM Cardoso, AA AF Veiga, JP Sallan, SE Nadler, LM Cardoso, AA TI De novo angiogenesis confers a selective advantage to leukemic cells through contact-dependent maintenance of anti-apoptotic gene expression. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2924 BP 658A EP 658A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302973 ER PT J AU Tai, YT Teoh, G Urashima, M Chauhan, D Treon, SP Raje, N Hideshima, T Shima, Y Davies, FE Anderson, KC AF Tai, YT Teoh, G Urashima, M Chauhan, D Treon, SP Raje, N Hideshima, T Shima, Y Davies, FE Anderson, KC TI Ku86 variants (Ku86v) with decreased DNA end binding (DEB) activity are expressed in patient multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2942 BP 663A EP 663A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790302991 ER PT J AU Gazda, H Lipton, JM Niemeyer, CM Willig, TN Tchernia, G Narla, M Ploszynska, A Vlachos, A Glader, BE Rokicka-Milewska, R Ohara, A Baker, D Webber, A Viskochil, DH Nathan, DG Beggs, AH Sieff, CA AF Gazda, H Lipton, JM Niemeyer, CM Willig, TN Tchernia, G Narla, M Ploszynska, A Vlachos, A Glader, BE Rokicka-Milewska, R Ohara, A Baker, D Webber, A Viskochil, DH Nathan, DG Beggs, AH Sieff, CA TI Evidence for linkage of familial Diamond-Blackfan Anemia to chromosome 8p23.2-23.1 and for non-19q non-8p disease. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. CUNY Mt Sinai Sch Med, Div Pediat Hematol Oncol, New York, NY 10029 USA. Univ Freiburg, Childrens Hosp, D-7800 Freiburg, Germany. Hop Bicetre, Dept Hematol, Kremlin Bicetre, France. LBNL, Berkeley, CA USA. Univ Gdansk, Dept Pediat Hematol Oncol, PL-80952 Gdansk, Poland. Stanford Univ, Div Pediat Hematol Oncol, Sch Med, Stanford, CA 94305 USA. Warsaw Sch Med, Dept Pediat Hematol Oncol, Warsaw, Poland. Toho Univ, Sch Med, Dept Pediat, Tokyo, Japan. Princess Margaret Hosp Children, Dept Pediat Haematol Oncol, Perth, WA, Australia. Univ Utah, Sch Med, Div Med Genet, Salt Lake City, UT 84112 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2983 BP 673A EP 673A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303032 ER PT J AU Hirano, N Schultze, JL Butler, MO Guinan, EC Nadler, LM AF Hirano, N Schultze, JL Butler, MO Guinan, EC Nadler, LM TI Identification of kinectin as a target antigen in immune-mediated aplastic anemia. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2985 BP 673A EP 673A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303034 ER PT J AU Vonderheide, RH Schultze, JL Hahn, WC Anderson, KS Kuroda, MJ Letvin, NL Nadler, LM AF Vonderheide, RH Schultze, JL Hahn, WC Anderson, KS Kuroda, MJ Letvin, NL Nadler, LM TI Generation of telomerase-specific HLA-A3-restricted cytotoxic T lymphocytes from patient blood: Implications for widely applicable anti-cancer immunotherapy. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RI Schultze, Joachim/D-7794-2011 OI Schultze, Joachim/0000-0003-2812-9853 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 2999 BP 677A EP 677A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303048 ER PT J AU Avigan, DE Gong, JLG Wu, ZK Chen, DS Kashiwaba, M Koido, S Kufe, D AF Avigan, DE Gong, JLG Wu, ZK Chen, DS Kashiwaba, M Koido, S Kufe, D TI Activation of antitumor cytotoxic T lymphocytes by fusions of human dendritic cells and breast carcinoma cells. SO BLOOD LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3006 BP 679A EP 679A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303055 ER PT J AU Song, WJ Sullivan, MG Legare, RD Loh, M Roy, DC Busque, L Willman, C Gewirtz, AM Speck, NA Bushweller, JH Li, FP Poncz, M Maris, JM Gilliland, DG AF Song, WJ Sullivan, MG Legare, RD Loh, M Roy, DC Busque, L Willman, C Gewirtz, AM Speck, NA Bushweller, JH Li, FP Poncz, M Maris, JM Gilliland, DG TI Haploinsufficiency of CBFA2 (AML1) causes familial thrombocytopenia with propensity to develop acute myelogenous leukemia (FPD/AML). SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Brown Univ, Program Womens Oncol, Providence, RI 02912 USA. Univ Montreal, Hematol Res Ctr, Montreal, PQ H3C 3J7, Canada. Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA. Univ Penn, Philadelphia, PA 19104 USA. Dartmouth Coll, Dartmouth Med Sch, Hanover, NH 03756 USA. Univ Virginia, Charlottesville, VA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3007 BP 679A EP 679A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303056 ER PT J AU Zhang, P Zhang, X Iwama, A Yu, C Smith, KA Torbett, B Orkin, SH Tenen, DG AF Zhang, P Zhang, X Iwama, A Yu, C Smith, KA Torbett, B Orkin, SH Tenen, DG TI PU.1 inhibits GATA-1 function by blocking GATA-1 DNA binding: Potential role in normal hematopoiesis and leukemogenesis. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Childrens Hosp, Sch Med, Hematol Oncol Div,Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Scripps Res Inst, Dept Immunol & Mol Expt Med, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3023 BP 683A EP 683A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303072 ER PT J AU Sattler, M Verma, S Uemura, N Byrne, CH Salgia, R Griffin, JD AF Sattler, M Verma, S Uemura, N Byrne, CH Salgia, R Griffin, JD TI The polyinositol 5-phosphatase SHIP regulates migration in hematopoietic cells and is involved in a new signaling pathway containing SHIP, DOK, and CRKL. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3032 BP 685A EP 685A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303081 ER PT J AU Inoue, A Morimoto, A Hitzler, JK Pestina, TI Jackson, CW Tanaka, R Bronson, RT Chong, M McKinnon, PJ Inukai, T Ashmun, RA Grosveld, GC Look, AT AF Inoue, A Morimoto, A Hitzler, JK Pestina, TI Jackson, CW Tanaka, R Bronson, RT Chong, M McKinnon, PJ Inukai, T Ashmun, RA Grosveld, GC Look, AT TI Targeted inactivation of Slug, an anti-apoptotic zinc-finger transcription factor, renders mice hypersensitive to ionizing radiation. SO BLOOD LA English DT Meeting Abstract C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Tufts Univ, Sch Med & Vet Med, Boston, MA 02111 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3040 BP 687A EP 687A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303089 ER PT J AU Arico, M Valsecchi, MG Camitta, B Schrappe, M Chessells, J Baruchel, A Gaynon, P Silvermann, L Janka-Schaub, G Kamps, W Pui, CH Masera, G AF Arico, M Valsecchi, MG Camitta, B Schrappe, M Chessells, J Baruchel, A Gaynon, P Silvermann, L Janka-Schaub, G Kamps, W Pui, CH Masera, G TI Heterogeneity of treatment outcome in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: A collaborative study of 326 patients. SO BLOOD LA English DT Meeting Abstract C1 Policlin San Matteo, IRCCS, I-27100 Pavia, Italy. Univ Verona, Dept Publ Hlth, I-37100 Verona, Italy. Midwest Children Canc Ctr, Dept Pediat, Milwaukee, WI USA. Med Hochschule, Dept Pediat Hematol Oncol, Hannover, Germany. Inst Child Hlth, Dept Hematol Oncol, London, England. Hop St Louis, Dept Pediat Hematol, Paris, France. Childrens Hosp, Dept Hematol Oncol, Los Angeles, CA 90027 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Hamburg, Dept Pediat Hematol Oncol, Hamburg, Germany. Beatrix Children Hosp, Dept Pediat Oncol, Groningen, Netherlands. St Jude Childrens Res Hosp, Dept Hematol Oncol, Memphis, TN 38105 USA. RI Schrappe, Martin/A-8109-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3072 BP 695A EP 695A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303121 ER PT J AU Putti, MC Veiga, JP Sallan, SE Nadler, LM Cardoso, AA AF Putti, MC Veiga, JP Sallan, SE Nadler, LM Cardoso, AA TI Differential sensitivity of bone marrow endothelium to chemotherapeutic drugs: Implications for the treatment of childhood acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Clin Pediat Hematol Oncol, Padua, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3081 BP 697A EP 697A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303130 ER PT J AU Soignet, S Frankel, S Tallman, M Douer, D Kantarjian, H Stone, R Sievers, E Kalaycio, M Coutre, S Ellison, R Warrell, RP AF Soignet, S Frankel, S Tallman, M Douer, D Kantarjian, H Stone, R Sievers, E Kalaycio, M Coutre, S Ellison, R Warrell, RP TI US multicenter trial of arsenic trioxide (AT) in acute promyelocytic leukemia (APL). SO BLOOD LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Georgetown Univ, Washington, DC USA. Northwestern Univ, Houston, TX USA. Univ So Calif, Los Angeles, CA USA. MD Anderson Canc Ctr, Houston, TX USA. Dana Farber Canc Ctr, Boston, MA USA. Univ Washington, Seattle, WA 98195 USA. Cleveland Clin, Cleveland, OH 44106 USA. Stanford Univ, Palo Alto, CA 94304 USA. PolaRx Biopharmaceut Inc, New York, NY USA. NR 0 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3084 BP 698A EP 698A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303133 ER PT J AU Aguiar, RCT Yakushijin, Y Kharbanda, S Fletcher, J Salgia, R Shipp, MA AF Aguiar, RCT Yakushijin, Y Kharbanda, S Fletcher, J Salgia, R Shipp, MA TI The risk related BAL gene increases the migration of aggressive B-cell lymphomas. SO BLOOD LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3091 BP 699A EP 699A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303140 ER PT J AU Chauhan, D Pandey, P Avraham, S Hideshima, T Treon, SP Raje, N Davis, FE Tai, YT Shima, Y Kharbanda, S Anderson, KC AF Chauhan, D Pandey, P Avraham, S Hideshima, T Treon, SP Raje, N Davis, FE Tai, YT Shima, Y Kharbanda, S Anderson, KC TI Interleukin-6 (IL-6) -induced SHP2 activation mediates resistance to dexamethasone (Dex) - Induced RAFTK activation and apoptosis in multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Cambridge, MA 02138 USA. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3103 BP 702A EP 702A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303152 ER PT J AU Spitzer, TR McAfee, S Sackstein, R Multani, P Colby, C Weymouth, D Saidman, S Sachs, DH Sykes, M AF Spitzer, TR McAfee, S Sackstein, R Multani, P Colby, C Weymouth, D Saidman, S Sachs, DH Sykes, M TI Mixed lymphohematopoietic chimerism following non-myeloablative conditioning and HLA-matched allogeneic bone marrow transplantation (BMT): The effects on chimerism and anti-tumor response of prophylactic donor leukocyte infusion (DLI). SO BLOOD LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3134 BP 709A EP 709A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303183 ER PT J AU Stewart, AK Schiller, G Vescio, R Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Sahebi, F Tarantolo, S Stiff, P Schlossman, R Brown, RA Tully, H Sing, A Jacobs, C White, M Dipersio, JF Anderson, KC Berenson, J AF Stewart, AK Schiller, G Vescio, R Ballester, O Noga, S Rugo, H Freytes, C Stadtmauer, E Sahebi, F Tarantolo, S Stiff, P Schlossman, R Brown, RA Tully, H Sing, A Jacobs, C White, M Dipersio, JF Anderson, KC Berenson, J TI CD34 selection does not prolong disease free or overall survival in myeloma patients undergoing autologous stem cell transplant: Results of a prase III study. SO BLOOD LA English DT Meeting Abstract C1 Toronto Hosp, Toronto, ON M5T 2S8, Canada. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ S Florida, Tampa, FL 33620 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, Austin, TX 78712 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Nebraska, Lincoln, NE 68583 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Loyola Univ, New Orleans, LA 70118 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Washington Univ, St Louis, MO 63130 USA. CellPro, Bothell, WA USA. NR 0 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 SU 1 MA 3151 BP 714A EP 714A PN 1 PG 1 WC Hematology SC Hematology GA 257PH UT WOS:000083790303200 ER PT J AU Gordon, LI Young, M Weller, E Habermann, TM Winter, JN Glick, J Ghosh, C Flynn, P Cassileth, PA AF Gordon, LI Young, M Weller, E Habermann, TM Winter, JN Glick, J Ghosh, C Flynn, P Cassileth, PA TI A phase II trial of 200% ProMACE-CytaBOM-in patients with previously untreated aggressive lymphomas: Analysis of response, toxicity, and dose intensity SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; LARGE-CELL LYMPHOMA; BONE-MARROW TRANSPLANTATION; STANDARD REGIMEN CHOP; PROGNOSTIC-SIGNIFICANCE; INTERMEDIATE-GRADE; PROLIFERATIVE ACTIVITY; PROTEIN EXPRESSION; BCL-2 EXPRESSION; ONCOLOGY-GROUP AB We showed in a phase I trial that the maximum tolerated dose of the ProMACE-CytaBOM regimen in patients with aggressive lymphoma was 200% (Gordon et al, J Clin Oncol 14:1275, 1996). Based on these observations, we initiated a phase II trial designed to determine response, toxicity, and dose intensity using this regimen. We analyzed 74 patients with advanced-stage (III or IV) or bulky stage II aggressive lymphoma. The overall complete response rate was 69% (72% in evaluable patients). With a median follow-up of 4.5 years, the median survival has not yet been reached. The 4-year survival rate is 73% (95% confidence interval [CI] 62, 83%) and no difference was observed among International Prognostic Index (IPI) groups. The 4-year disease-free survival was 71% (95% CI 58, 84%) with no statistical difference between patients with IPI 0 to 1 versus 2 to 4. The toxicity was acceptable, though the grade 4 hematologic toxicity rate for this regimen was 100%. Grade 4 nonhematologic toxicity was 36%. Three cases of either myelodysplastic syndrome or acute leukemia occurred at 7 months, 3.4 years, and 4.2 years after registration. Cytogenic analysis was available in two cases, showing inv(16) without French American British classification (FAB) M4 Po histology in one patient and a Bq-syndrome in the other. These data suggest that 200% ProMACE-CytaBOM with either granulocyte-macrophage colony-stimulating factor (GM-CSF) or G-CSF results in a high complete remission rate and a disease-free survival comparable to any prior risk-based analysis in aggressive lymphoma. Before using this regimen in general practice, phase III clinical trials should be conducted. (C) 1999 by The American Society of Hematology. C1 Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Cedar Rapids Oncol Project, Cedar Rapids, IA USA. Metro Minnesota CCOP, St Louis Pk, MN USA. Univ Miami, Sylvester Canc Ctr, Miami, FL USA. RP Gordon, LI (reprint author), Northwestern Univ, Sch Med, Dept Med, 303 E Chicago Ave, Chicago, IL 60611 USA. OI Gordon, Leo/0000-0003-1666-7064 FU NCI NIH HHS [CA 13650, CA 17145, CA 23318] NR 39 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 BP 3307 EP 3314 PG 8 WC Hematology SC Hematology GA 254NG UT WOS:000083618600004 PM 10552939 ER PT J AU Freedman, AS Neuberg, D Mauch, P Soiffer, RJ Anderson, KC Fisher, DC Schlossman, R Alyea, EP Takvorian, T Jallow, H Kuhlman, C Ritz, J Nader, LM Gribben, JG AF Freedman, AS Neuberg, D Mauch, P Soiffer, RJ Anderson, KC Fisher, DC Schlossman, R Alyea, EP Takvorian, T Jallow, H Kuhlman, C Ritz, J Nader, LM Gribben, JG TI Long-term follow-up of autologous bone marrow transplantation in patients with relapsed follicular lymphoma SO BLOOD LA English DT Article ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; POLYMERASE CHAIN-REACTION; HIGH-DOSE THERAPY; MYELODYSPLASTIC SYNDROME; MALIGNANT-LYMPHOMAS; ANTI-CD20 ANTIBODY; SECONDARY MALIGNANCIES; MONOCLONAL-ANTIBODIES; BCL-2 TRANSLOCATION AB We report the results of high-dose chemoradiotherapy and anti-B-cell monoclonal antibody-purged autologous bone marrow transplantation (ABMT) in patients with relapsed indolent follicular lymphoma. Between March 1985 and May 1995, 153 patients underwent ABMT using a uniform ablative regimen with cyclophosphamide and total body irradiation and bone marrow (BM) purging. All patients received multiple chemotherapy regimens before ABMT. At BM harvest, only 30% of patients were in complete remission, and overt BM infiltration was present in 47%. The disease-free survival (DFS) and overall survival (OS) are estimated to be 42% and 66% at 8 years, respectively. Patients whose BM was negative by polymerase chain reaction (PCR) for bc12/IgH rearrangement after purging experienced longer freedom from recurrence than those whose BM remained PCR positive (P < .0001). Continued PCR negativity in follow-up BM samples was also strongly predictive of continued complete remission (CR). The 12-year survival from diagnosis for these 153 patients is 69%. Considering that the median survival from diagnosis and first recurrence of patients with advanced follicular lymphoma are 8 and 5 years, respectively, our results provide evidence that myeloablative therapy and ABMT may prolong overall survival. (C) 1999 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Adult Oncol & Biostat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Therapy, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA USA. RP Freedman, AS (reprint author), Dana Farber Canc Inst, Dept Hematol Malignancies, Boston, MA 02115 USA. RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA 66996] NR 60 TC 263 Z9 267 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 BP 3325 EP 3333 PG 9 WC Hematology SC Hematology GA 254NG UT WOS:000083618600006 PM 10552941 ER PT J AU Cardoso, AA Veiga, JP Ghia, P Afonso, HM Haining, WN Sallan, SE Nadler, LM AF Cardoso, AA Veiga, JP Ghia, P Afonso, HM Haining, WN Sallan, SE Nadler, LM TI Adoptive T-cell therapy for B-cell acute lymphoblastic leukemia: preclinical studies SO BLOOD LA English DT Article ID ACTIVATED KILLER-CELLS; BONE-MARROW; ENDOTHELIAL-CELLS; PERIPHERAL-BLOOD; INTERLEUKIN-2 INDUCTION; LAK GENERATION; CD40 LIGAND; IN-VITRO; LYMPHOCYTES; MIGRATION AB We have previously shown that leukemia-specific cytotoxic T cells (CTL) can he generated from the bone marrow of most patients with B-cell precursor acute leukemias. If these antileukemia CTL are to be used for adoptive immunotherapy, they must have the capability to circulate, migrate through endothelium, home to the bone marrow, and, most importantly, lyse the leukemic cells in a leukemia-permissive bone marrow microenvironment. We demonstrate here that such antileukemia T-cell lines are overwhelmingly CD8(+) and exhibit an activated phenotype. Using a transendothelial chemotaxis assay with human endothelial cells, we observed that these T cells can be recruited and transmigrate through vascular and bone marrow endothelium and that these transmigrated cells preserve their capacity to lyse leukemic cells, Additionally, these antileukemia T-cell lines are capable of adhering to autologous stromal cell layers. Finally, autologous antileukemia CTL specifically lyse leukemic cells even in the presence of autologous marrow stroma. Importantly, these antileukemia T-cell lines do not lyse autologous stromal cells. Thus, the capacity to generate anti-leukemia-specific T-cell lines coupled with the present findings that such cells can migrate, adhere, and function in the presence of the marrow microenvironment enable the development of clinical studies of adoptive transfer of antileukemia CTL for the treatment of ALL. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Porto, Abel Salazar Inst Biomed Sci, Oporto, Portugal. RP Cardoso, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, D-538,44 Binney St, Boston, MA 02115 USA. EM cardoso@mbcrr.harvard.edu RI Ghia, Paolo/K-7138-2016 OI Ghia, Paolo/0000-0003-3750-7342 FU NCI NIH HHS [P01-CA66996-01, P01-CA68484-02] NR 59 TC 26 Z9 27 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 1999 VL 94 IS 10 BP 3531 EP 3540 PG 10 WC Hematology SC Hematology GA 254NG UT WOS:000083618600029 PM 10552964 ER PT J AU Sgroi, DC Teng, S Robinson, G LeVangie, R Hudson, JR Elkahloun, AG AF Sgroi, DC Teng, S Robinson, G LeVangie, R Hudson, JR Elkahloun, AG TI In vivo gene expression profile analysis of human breast cancer progression SO CANCER RESEARCH LA English DT Article ID LASER CAPTURE MICRODISSECTION; TISSUE-FACTOR; ANNEXIN-I; MICROARRAY; CELLS; CHEMOKINES; GENOME AB The development and use of molecular-based therapy for breast cancer and other human malignancies will require a detailed molecular genetic analysis of patient tissues. The recent development of laser capture microdissection and high density cDNA arrays now pro,ides a unique opportunity to generate gene expression profiles of cells from various stages of tumor progression as it occurs in the actual neoplastic tissue milieu. We report the combined use of laser capture microdissection and high-throughput cDNA microarrays to monitor in vivo gene expression levels in purified normal, invasive, and metastatic breast cell populations from a single patient. These in vivo gene expression profiles were verified by real-time quantitative PCR and immunohistochemistry. The combined use of Laser capture microdissection and cDNA microarray analysis provides a powerful new approach to elucidate the in vivo molecular events surrounding the development and progression of breast cancer and is generally applicable to the study of malignancy. C1 Res Genet Inc, Microarray Dept, Huntsville, AL 35801 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Boston, MA 02129 USA. Childrens Hosp, Boston, MA 02115 USA. RP Elkahloun, AG (reprint author), Res Genet Inc, Microarrays Dept, 2700 Mem Pkwy, Huntsville, AL 35801 USA. NR 25 TC 321 Z9 339 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1999 VL 59 IS 22 BP 5656 EP 5661 PG 6 WC Oncology SC Oncology GA 258RQ UT WOS:000083853300004 PM 10582678 ER PT J AU Weng, LP Smith, WM Dahia, PLM Ziebold, U Gil, E Lees, JA Eng, C AF Weng, LP Smith, WM Dahia, PLM Ziebold, U Gil, E Lees, JA Eng, C TI PTEN suppresses breast cancer cell growth by phosphatase activity-dependent G(1) arrest followed by cell death SO CANCER RESEARCH LA English DT Article ID BANNAYAN-ZONANA-SYNDROME; TUMOR-SUPPRESSOR; PHOSPHATIDYLINOSITOL 3-KINASE; PROTEIN-KINASE; COWDEN-DISEASE; GLIOMA-CELLS; GERMLINE MUTATIONS; GENE-EXPRESSION; MAMMALIAN-CELLS; FACTOR-I AB PTEN/MMAC1/TEP1, a tumor suppressor gene, is frequently mutated in a variety of human cancers. Germ-line mutations of phosphatase and tensin homolog, deleted on chromosome ten (PTEN) are found in two inherited hamartoma tumor syndromes: Cowden syndrome, which has a high risk of breast, thyroid, and other cancers; and Bannayan-Zonana syndrome, a related disorder. PTEN encodes a phosphatase that recognizes both protein substrates and phosphatidylinositol-3,4,5-triphosphate. The Lipid phosphatase activity of PTEN seems to be important for growth suppression through inhibition of the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. We established clones with stable PTEN expression controlled by a tetracycline-inducible system to examine the consequences of increased levels of mild-type and mutant PTEN expression in a well-characterized breast cancer line, MCF-7. When we overexpressed PTEN in MCF-7, growth suppression was observed, but only if PTEN phosphatase activity is preserved. The initial growth suppression was attributable to G(1) cell cycle arrest, whereas subsequent growth suppression was attributable to a combination of G(1) arrest and cell death. Of note, the decrease in Akt phosphorylation preceded the onset of suppression of cell growth. Treatment of MCF-7 cells with wortmannin, a PI3K inhibitor, caused cell growth inhibition in a way similar to the effects of overexpression of PTEN in this cell. In general, the inverse correlation between PTEN protein level and Akt phosphorylation was found in a panel of breast cancer cell lines. Therefore, PTEN appears to suppress breast cancer growth through down-regulating PI3K signaling, which Leads to the blockage of cell cycle progression and the induction of cell death, in a sequential manner. C1 Ohio State Univ, Human Canc Genet Program, Ctr Comprehens Canc, Columbus, OH 43210 USA. Ohio State Univ, Clin Canc Genet Program, Ctr Comprehens Canc, Columbus, OH 43210 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. MIT, Ctr Canc Res, Dept Biol, Cambridge, MA 02139 USA. Univ Cambridge, CRC, Human Canc Genet Res Grp, Cambridge CB2 2QQ, England. RP Eng, C (reprint author), Ohio State Univ, Human Canc Genet Program, Ctr Comprehens Canc, 420 W 12th Ave,Room 690C MRF, Columbus, OH 43210 USA. RI Ziebold, Ulrike/N-4487-2013 FU NCI NIH HHS [P30 CA16058] NR 51 TC 183 Z9 196 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1999 VL 59 IS 22 BP 5808 EP 5814 PG 7 WC Oncology SC Oncology GA 258RQ UT WOS:000083853300029 PM 10582703 ER PT J AU Halpern, HJ Chandramouli, GVR Barth, ED Yu, C Peric, M Grdina, DJ Teicher, BA AF Halpern, HJ Chandramouli, GVR Barth, ED Yu, C Peric, M Grdina, DJ Teicher, BA TI Diminished aqueous microviscosity of tumors in murine models measured with in vivo radiofrequency electron paramagnetic resonance SO CANCER RESEARCH LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; NMR RELAXATION-TIMES; HIGH-RESOLUTION; CARCINOGENESIS MODEL; INTRACELLULAR WATER; CERVICAL-CARCINOMA; CELL-CYCLE; SPIN LABEL; HA-RAS; VISCOSITY AB Using very low frequency in vivo electron paramagnetic resonance (EPR), we have compared, for the first time, the average microviscosity of the total aqueous compartment of murine fibrosarcomas and that of normal leg tissue in a living animal, EPR spectra from dissolved nitroxide spin probes report the solvent microviscosity, The tumor aqueous microviscosity, 1.8 +/- 0.1 centipoise, was significantly lower than that of the corresponding normal tissue, 2.9 +/- 0.3 centipoise, a difference of 38 +/- 7%, These results confirm the commonly observed increase in the water proton transverse relaxation times (T-2) in magnetic resonance imaging of hyperproliferative states, for example, malignancy. The specificity of the localization of the EPR signal indicates a substantial portion of the T-2 increase seen in magnetic resonance imaging derives from decreased bulk-water viscosity. The effect of this microviscosity differences may be the basis of several physiological differences between tumors and normal tissues which could confer a growth rate advantage to tumor tissue. C1 Univ Chicago, Ctr Med, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Halpern, HJ (reprint author), Univ Chicago, Ctr Med, Dept Radiat & Cellular Oncol, 5841 S Maryland Ave,MC 1105, Chicago, IL 60637 USA. FU NCI NIH HHS [CA-50679, CA-37435, CA69538] NR 66 TC 34 Z9 34 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 1999 VL 59 IS 22 BP 5836 EP 5841 PG 6 WC Oncology SC Oncology GA 258RQ UT WOS:000083853300033 PM 10582707 ER PT J AU Zhang, M Magit, D Botteri, F Shi, HY He, KW Li, ML Furth, P Sager, R AF Zhang, M Magit, D Botteri, F Shi, HY He, KW Li, ML Furth, P Sager, R TI Maspin plays an important role in mammary gland development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE maspin; serpin; lobular-alveolar structure; mammary development; whey acidic protein ID PLASMINOGEN-ACTIVATOR INHIBITOR-1; TRANSGENIC MICE; EPITHELIAL-CELLS; GENE-EXPRESSION; APOPTOSIS; MATRIX; SERPIN; PROTEINASES; INVOLUTION; CANCER AB Maspin is a unique member of the serpin family, which functions as a class II tumor suppressor gene. Despite its known activity against tumor invasion and motility, little is known about maspin's functions in normal mammary gland development. In this paper, we show that maspin does not act as a tPA inhibitor in the mammary gland. However, targeted expression of maspin by the whey acidic protein gene promoter inhibits the development of lobular-alveolar structures during pregnancy and disrupts mammary gland differentiation. Apoptosis was increased in alveolar cells from transgenic mammary glands at midpregnancy. However, the rate of proliferation was increased in early lactating glands to compensate for the retarded development during pregnancy. These findings demonstrate that maspin plays an important role in mammary development and that its effect is stage dependent. (C) 1999 Academic Press. C1 Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Maryland, Baltimore, MD 21201 USA. Friedrich Miescher Inst, CH-4002 Basel, Switzerland. RP Zhang, M (reprint author), Baylor Coll Med, Dept Cell Biol, 1 Baylor Plaza, Houston, TX 77030 USA. NR 38 TC 52 Z9 54 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 1999 VL 215 IS 2 BP 278 EP 287 DI 10.1006/dbio.1999.9442 PG 10 WC Developmental Biology SC Developmental Biology GA 256LK UT WOS:000083726600012 PM 10545237 ER PT J AU Miyabayashi, T Palfreyman, MT Sluder, AE Slack, F Sengupta, P AF Miyabayashi, T Palfreyman, MT Sluder, AE Slack, F Sengupta, P TI Expression and function of members of a divergent nuclear receptor family in Caenorhabditis elegans SO DEVELOPMENTAL BIOLOGY LA English DT Article DE nuclear receptors; C-elegans; expression pattern; overexpression; hypodermal seam cells ID GREEN FLUORESCENT PROTEIN; GLR-1 GLUTAMATE-RECEPTOR; THYROID-HORMONE RECEPTOR; MUSCLE-CELL ATTACHMENT; C-ELEGANS; GLUCOCORTICOID RECEPTOR; GENE-EXPRESSION; AMINO-ACIDS; TRANSCRIPTIONAL CONTROL; ESTROGEN-RECEPTOR AB Nuclear receptors (NRs) are a large class of ligand-regulated transcriptional modulators that have been shown to play roles in many developmental processes. The Caenorhabditis elegans genome is predicted to encode a large and divergent family of NR proteins. The functions of most of these genes are unknown. As a first step toward defining their roles, we have initiated an expression and functional survey of a subset of these genes. In this study, we demonstrate expression of 21 of 28 NR genes examined, indicating that a large fraction of the predicted genes likely encode functional gene products. We show that five genes are expressed predominantly in neuronal cells, while others are expressed in multiple cell types. Interestingly, we find that eight genes are expressed exclusively in the lateral hypodermal (seam) cells. These eight genes share a high degree of overall homology and cluster in a neighbor-joining tree derived from sequence analysis of the NRs, suggesting that they arose by gene duplication from a common ancestor. We show that overexpression of each of three members of this subfamily results in similar developmental defects, consistent with a redundant role for these genes in the function of the lateral hypodermal cells. (C) 1999 Academic Press. C1 Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. Brandeis Univ, Volen Ctr Complex Syst, Waltham, MA 02454 USA. Asahi Chem Ind Co Ltd, Fuji, Shizuoka 416, Japan. Univ Georgia, Dept Cellular Biol, Athens, GA 30602 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Sengupta, P (reprint author), Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. OI Slack, Frank/0000-0001-8263-0409 FU NIGMS NIH HHS [GM-18663, GM56223] NR 97 TC 78 Z9 90 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD NOV 15 PY 1999 VL 215 IS 2 BP 314 EP 331 DI 10.1006/dbio.1999.9470 PG 18 WC Developmental Biology SC Developmental Biology GA 256LK UT WOS:000083726600015 PM 10545240 ER PT J AU Tekki-Kessaris, N Bonventre, JV Boulter, CA AF Tekki-Kessaris, N Bonventre, JV Boulter, CA TI Characterization of the mouse Kid1 gene and identification of a highly related gene, Kid2 SO GENE LA English DT Article DE kidney; KRAB; transcription factor; zinc finger ID ZINC-FINGER PROTEINS; TRANSCRIPTION FACTOR; REPRESSOR DOMAIN; EXPRESSION; RESOLUTION; SUBFAMILY; TIF1-BETA; KIDNEY AB Kid1 encodes a zinc finger protein that has been implicated in renal cell differentiation. Levels of Kid1 mRNA correlate with maturation of kidney tubule epithelia in rat post-natal kidney development and during kidney regeneration following injury. KID1 is a putative transcriptional repressor, containing a KRAB domain at its amino terminus that mediates transcriptional repression in transient cell transfection assays when fused to a heterologous DNA-binding domain. In this paper, we describe the isolation and characterization of the mouse homologue of Kid1 and the identification of a novel highly related mouse gene, Kid2, Kid1 and Kid2 are tightly linked on mouse chromosome 11 and show conservation across mammals. Both genes are expressed predominantly in the mouse adult kidney and brain, but transcripts are also detected in embryonic brain, kidney, gut and lung, suggesting an additional role for these genes during mouse development. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Cambridge, MA 02129 USA. RP Boulter, CA (reprint author), Univ Cambridge, Dept Genet, Downing St, Cambridge CB2 3EH, England. RI Boulter, Catherine/A-6607-2010; OI Kessaris, Nicoletta/0000-0003-1191-6009 FU NIDDK NIH HHS [DK 39773] NR 25 TC 6 Z9 8 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 NOV 15 PY 1999 VL 240 IS 1 BP 13 EP 22 DI 10.1016/S0378-1119(99)00440-0 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 258RR UT WOS:000083853400002 PM 10564808 ER PT J AU Chadwick, BP Gill, S Leyne, M Mull, J Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Slaugenhaupt, SA AF Chadwick, BP Gill, S Leyne, M Mull, J Liebert, CB Robbins, CM Pinkett, HW Makalowska, I Maayan, C Blumenfeld, A Axelrod, FB Brownstein, M Slaugenhaupt, SA TI Cloning, genomic organization and expression of a putative human transmembrane protein related to the Caenorhabditis elegans M01F1.4 gene SO GENE LA English DT Article DE 9q31; Ashkenazi Jewish; neuropathy; peripheral nervous system; recessive ID FAMILIAL DYSAUTONOMIA; EXON AMPLIFICATION; CHROMOSOME; STRATEGY AB A novel human transcript CG-2 (C9ORF5), was isolated from the familial dysautonomia candidate region on 9q31 using a combination of cDNA selection and exon trapping. CG-2 was detected as a relatively abundant 8 kb transcript in all adult and fetal tissues with the exception of adult thymus, Genomic analysis of CG-2 identified 18 exons that span more than 110 kb, The gene encodes a 911-amino-acid protein with a predicted molecular weight of 101 kDa and a hypothetical pI of 9.03. Sequence analysis of CG-2 indicates that it is likely to encode a transmembrane protein. Here, we assess CG-2 as a candidate for familial dysautonomia, (C) 1999 Published by Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Inst Human Genet, Boston, MA USA. Natl Human Genome Res Inst, Canc Genet Branch, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, Genome Technol Branch, NIH, Bethesda, MD USA. Hadassah Univ Hosp, Dept Pediat, IL-91120 Jerusalem, Israel. Hadassah Univ Hosp, Unit Dev Mol Biol & Genet Engn, IL-91120 Jerusalem, Israel. NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA. RP Slaugenhaupt, SA (reprint author), HIM Bldg Room 422,77 Ave Louis Pasteur, Boston, MA 02115 USA. RI Brownstein, Michael/B-8609-2009; Pinkett, Heather/M-9235-2014 FU NINDS NIH HHS [NS36326] NR 17 TC 5 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD NOV 15 PY 1999 VL 240 IS 1 BP 67 EP 73 DI 10.1016/S0378-1119(99)00432-1 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 258RR UT WOS:000083853400007 PM 10564813 ER PT J AU Rebel, VI Hartnett, S Hill, GR Lazo-Kallanian, SB Ferrara, JLM Sieff, CA AF Rebel, VI Hartnett, S Hill, GR Lazo-Kallanian, SB Ferrara, JLM Sieff, CA TI Essential role for the p55 tumor necrosis factor receptor in regulating hematopoiesis at a stem cell level SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE hematopoietic stem cell; cell differentiation; cytokine receptors ID COLONY-STIMULATING FACTOR; GROWTH-FACTOR-BETA; BONE-MARROW CULTURES; P75 TNF RECEPTORS; FACTOR-ALPHA; IN-VIVO; PROGENITOR CELLS; FETAL LIVER; PATCH ORGANOGENESIS; ENDOTHELIAL-CELLS AB Hematopoietic stem cell (HSC) self-renewal is a complicated process, and its regulatory mechanisms are poorly understood. Previous studies have identified tumor necrosis factor (TNF)-alpha as a pleiotropic cytokine, which, among other actions, prevents various hematopoietic progenitor cells from proliferating and differentiating in vitro. However, its role in regulating longterm repopulating HSCs in vivo has not been investigated. In this study, mice deficient for the p55 or the p75 subunit of the TNF receptor were analyzed in a variety of hematopoietic progenitor and stem cell assays. In older p55(-/-) mice (>6 mo), we identified significant differences in their hematopoietic system compared with age-matched p75(-/-) or wild-type counterparts. Increased marrow cellularity and increased numbers of myeloid and erythroid colony-forming progenitor cells (CFCs), paralleled by elevated peripheral blood cell counts, were found in p55-deficient mice. In contrast to the increased myeloid compartment, pre-B CFCs were deficient in older p55(-/-) mice. In addition, a fourfold decrease in the number of HSCs could be demonstrated in a competitive repopulating assay. Secondary transplantations of marrow cells from primary recipients of p55(-/-) marrow revealed impaired self-renewal ability of p55-deficient HSCs. These data show that, in vivo, signaling through the p55 subunit of the TNF receptor is essential for regulating hematopoiesis at the stem cell level. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Rebel, VI (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Rm M613,44 Binney St, Boston, MA 02115 USA. RI Hill, Geoffrey/O-2630-2016 OI Hill, Geoffrey/0000-0003-2994-0429 FU NCI NIH HHS [P01 CA039542, P01 CA39542]; NHLBI NIH HHS [R01 HL55709] NR 70 TC 54 Z9 55 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 15 PY 1999 VL 190 IS 10 BP 1493 EP 1503 DI 10.1084/jem.190.10.1493 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 256GY UT WOS:000083718600013 PM 10562323 ER PT J AU Zeng, DF Gazit, G Dejbakhsh-Jones, S Balk, SP Snapper, S Taniguchi, M Strober, S AF Zeng, DF Gazit, G Dejbakhsh-Jones, S Balk, SP Snapper, S Taniguchi, M Strober, S TI Heterogeneity of NK1.1(+) T cells in the bone marrow: Divergence from the thymus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TCR ALPHA-CHAIN; ANTIGEN RECEPTOR; RECEPTOR-ALPHA/BETA(+) CELLS; EXTRATHYMIC DEVELOPMENT; INTESTINAL EPITHELIUM; SELECTIVE REDUCTION; PRODUCE IL-4; NUDE LOCUS; MOUSE CD1; NKT CELLS AB NK1.1(+) T cells in the mouse thymus and bone marrow were compared because some marrow NK1.1(+) T cells have been reported to be extrathymically derived. Almost all NK1.1(+) T cells in the thymus were depleted in the CD1(-/-), beta(2)m(-/-), and J(alpha)281(-/-) mice as compared with wild-type mice. CD8(+)NK1/1(+). T cells were not clearly detected, even in the wild-type mice. In bone marrow from the wild-type mice, CD8(+)NK1.1(+) T cells were easily detected, about twice as numerous as CD4(+)NK1.1(+) T cells, and were similar in number to CD4(-)CD8(-)NK1.1(+) T cells. All three marrow NK1.1(+) T cell subsets were reduced about 4-fold in CD1(-/-) mice. No reduction was observed in CD8(+)NK1.1(+) T cells in the bone marrow of J(alpha)281(-/-) mice, but marrow CD8(+)NK1.1(+) T cells were markedly depleted in beta(2)m(-/-) mice. All NK1.1(+) T cell subsets in the marrow of wild-type mice produced high levels of IFN-gamma, IL-4, and IL-10. Although the numbers of marrow CD4(-)CD8(-)NK1.1(+) T cells in beta(2)m(-/-) and J(alpha)281(-/-) mice were similar to those in wild-type mice, these cells had a Th1-like pattern (high IFN-gamma and low IL-4 and IL-10). In conclusion, the large majority of NK1.1(+) T cells in the bone marrow are CD1 dependent. Marrow NK1.1(+) T cells include CD8(+), V(alpha)14-J(alpha)281-, and beta(2)m-independent subsets that are not clearly detected in the thymus. C1 Stanford Univ, Sch Med, Div Rheumatol & Immunol, Dept Med, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Dept Hematol & Oncol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02215 USA. Chiba Univ, Grad Sch Med, CREST, Chiba, Japan. Chiba Univ, Grad Sch Med, Dept Mol Immunol, Chiba, Japan. RP Strober, S (reprint author), Stanford Univ, Sch Med, Div Rheumatol & Immunol, Dept Med, 300 Pasteur Dr,Room S105B, Stanford, CA 94305 USA. RI Taniguchi, Masaru/N-7932-2015 OI Taniguchi, Masaru/0000-0001-7821-7179 FU NHLBI NIH HHS [HL57443, HL58250]; NIAID NIH HHS [AI40093] NR 46 TC 58 Z9 59 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 NOV 15 PY 1999 VL 163 IS 10 BP 5338 EP 5345 PG 8 WC Immunology SC Immunology GA 254XB UT WOS:000083638400022 PM 10553057 ER PT J AU Thomis, DC Aramburu, J Berg, LJ AF Thomis, DC Aramburu, J Berg, LJ TI The Jak family tyrosine kinase Jak3 is required for IL-2 synthesis by naive/resting CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR-GAMMA CHAIN; MICE LACKING JAK3; INTERLEUKIN-2-DEFICIENT MICE; LYMPHOID DEVELOPMENT; EXPRESSION; ACTIVATION; INDUCTION; PROLIFERATION; HOMEOSTASIS; CYTOKINES AB The Jak family tyrosine kinase, Jak3, is involved in signaling through cytokine receptors using the common gamma-chain. Mice deficient in Jak3 have mature T cells, all of which have an activated/memory cell phenotype but are unresponsive to in vitro stimulation Due to this activated phenotype, it has been impossible to determine whether Jak3 plays a role in the responsiveness of naive/resting T cells. To circumvent this difficulty, we generated naive/resting Jak3-negative T cells by two genetic approaches. After stimulation, these cells failed to produce significant amounts of IL-2, Although no signaling defect could be detected, we did find that naive/resting Jak3-negative T cells have substantially reduced levels of the transcription factor NF-AT1 and moderately reduced levels of c-Jun and c-Fos, On the basis of these data, we propose that Jak3-dependent cytokine signals may be required to maintain the normal levels of basal transcription factors required for immediate responsiveness to Ag activation. C1 Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01655 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Berg, LJ (reprint author), Univ Massachusetts, Med Ctr, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. RI Aramburu, J/G-8991-2014 OI Aramburu, J/0000-0001-9279-9523 NR 30 TC 16 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 NOV 15 PY 1999 VL 163 IS 10 BP 5411 EP 5417 PG 7 WC Immunology SC Immunology GA 254XB UT WOS:000083638400031 PM 10553066 ER PT J AU Sato, N Kuziel, WA Melby, PC Reddick, RL Kostecki, V Zhao, WG Maeda, N Ahuja, SK Ahuja, SS AF Sato, N Kuziel, WA Melby, PC Reddick, RL Kostecki, V Zhao, WG Maeda, N Ahuja, SK Ahuja, SS TI Defects in the generation of IFN-gamma are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, or CCR2-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL VISCERAL LEISHMANIASIS; FUNCTIONAL EXPRESSION; MOLECULAR-CLONING; IMMUNE-RESPONSE; HOST-DEFENSE; HIV-1 CORECEPTOR; CUTTING EDGE; MIP-1-ALPHA; TH1; CELLS AB We investigated the immune responses in mice lacking CCR2, CCR5, or macrophage inflammatory protein-la (MIP-1 alpha), a ligand for CCR5, in two situations: following T cell stimulation or after challenge with Leishmania donovani, an intracellular microbe whose control is dependent on a Th1 immune response. Mice deficient in CCR5, MIP-1 alpha, or CCR2 had reduced IFN-gamma responses following ligation of the TCR, Reduced IFN-gamma responses following PMA and ionomycin were also observed in CD8(+) T cells of CCR5(-/-) and CCR2(-/-) mice. During the early phases of infection, all three knockout mice had low Ag-specific IFN-gamma responses. However, this reduced IFN-gamma response was overcome during a state of persistent Ag stimulation (chronic infection), and was not associated with an adverse parasitologic outcome in any of the gene-targeted mouse strains, To the contrary, during the late phase of infection, an exaggerated Ag-specific IFN-gamma response was evident in CCR5(-/-) and MIP-1 alpha(-/-) mice, and this correlated,vith an enhanced control of parasite replication. Although granuloma formation was abnormal in each of the knockout mice, there was no correlation between the number or architecture of the granulomas and parasite burden. Collectively, these findings indicate an important role for CCR5, MIP-1 alpha, and CCR2 in granulomatous inflammation, and that CCR5 and MIP-1 alpha, possibly acting through CCR5, might play a deleterious role in the outcome of chronic L, donovani infection, Our data also suggest that there might be cross-talk between TCR and chemokine receptor signaling pathways. C1 Univ Texas, Hlth Sci Ctr, Dept Med,Audie L Murphy Div, S TExas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol,Audie L Murphy Div, S TExas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Inst Cell & Mol Biol, Austin, TX 78712 USA. Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. RP Ahuja, SS (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med,Audie L Murphy Div, S TExas Vet Hlth Care Syst, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIAID NIH HHS [AI43279] NR 42 TC 116 Z9 121 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1999 VL 163 IS 10 BP 5519 EP 5525 PG 7 WC Immunology SC Immunology GA 254XB UT WOS:000083638400044 PM 10553079 ER PT J AU Stevenson, MA Zhao, MJ Asea, A Coleman, CN Calderwood, SK AF Stevenson, MA Zhao, MJ Asea, A Coleman, CN Calderwood, SK TI Salicylic acid and aspirin inhibit the activity of RSK2 kinase and repress RSK2-dependent transcription of cyclic AMP response element binding protein- and NF-kappa B-responsive genes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; HEAT-SHOCK FACTOR-1; RIBOSOMAL S6 KINASE; SODIUM-SALICYLATE; RHEUMATOID-ARTHRITIS; IN-VITRO; ACTIVATION; DOMAIN; CELLS; ALPHA AB Sodium salicylate (NaSal) and other nonsteroidal anti-inflammatory drugs (NSAIDs) coordinately inhibit the activity of NF-kappa B, activate heat shock transcription factor 1 and suppress cytokine gene expression in activated monocytes and macrophages, Because our preliminary studies indicated that these effects could be mimicked by inhibitors of signal transduction, we have studied the effects of NSAIDs on signaling molecules potentially downstream of LPS receptors in activated macrophages. Our findings indicate that ribosomal S6 kinase 2 (RSK2), a 90-kDa ribosomal S6 kinase with a critical role as an effector of the RAS-mitogen-activated protein kinase pathway and a regulator of immediate early gene transcription is a target for inhibition by the NSAIDs. NSAIDs inhibited the activity of purified RSK2 kinase in vitro and of RSK2 in mammalian cells and suppressed the phosphorylation of RSK2 substrates cAMP response element binding protein (CREB) and I-kappa B alpha in vivo. Additionally, NaSal inhibited the phosphorylation by RSK2 of CREB and I-kappa B alpha on residues crucial for their transcriptional activity in vivo and thus repressed CREB and NF-kappa B-dependent transcription. These experiments suggest that RSK2 is a target for NSAIDs in the inhibition of monocyte-specific gene expression and indicate the importance of RSK2 and related kinases in cell regulation, indicating a new area for anti-inflammatory drug discovery. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St,D810, Boston, MA 02115 USA. RI Asea, Alexzander/I-4112-2013 OI Asea, Alexzander/0000-0003-3592-3481 FU NCI NIH HHS [CA50642, CA47407, CA31303] NR 40 TC 57 Z9 60 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 1999 VL 163 IS 10 BP 5608 EP 5616 PG 9 WC Immunology SC Immunology GA 254XB UT WOS:000083638400055 PM 10553090 ER PT J AU Wetzel, RK Arystarkhova, E Sweadner, KJ AF Wetzel, RK Arystarkhova, E Sweadner, KJ TI Cellular and subcellular specification of Na,K-ATPase alpha and beta isoforms in the postnatal development of mouse retina SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Na,K-ATPase; retina; photoreceptor; development; isoforms; immunofluorescence ID 2 DIFFERENT NA,K-ATPASES; RAT RETINA; ADHESION MOLECULE; MONOCLONAL-ANTIBODIES; ENZYMATIC-PROPERTIES; PIGMENT EPITHELIUM; ADENOSINE-TRIPHOSPHATASE; PHOTORECEPTOR CELLS; MURINE NA,K-ATPASE; SUBUNIT ISOFORMS AB The Na,K-ATPase is a dominant factor in retinal energy metabolism, and unique combinations of isoforms of its alpha and beta subunits are expressed in different cell types and determine its functional properties. We used isoform-specific antibodies and fluorescence confocal microscopy to determine the expression of Na,K-ATPase alpha and beta subunits in the mouse and rat retina. In the adult retina, alpha 1 was found in Muller and horizontal cells, alpha 2 in some Muller glia, and alpha 3 in photoreceptors and all retinal neurons. beta 1 was largely restricted to horizontal, amacrine, and ganglion cells; beta 2 was largely restricted to photoreceptors, bipolar cells, and Muller glia; and beta 3 was largely restricted to photoreceptors. Photoreceptor inner segments have the highest concentration of Na,K-ATPase in adult retinas. Isoform distribution exhibited marked changes during postnatal development. alpha 3 and beta 2 were in undifferentiated photoreceptor somas at birth but only later were targeted to inner segments and synaptic terminals. beta 3, in contrast, was expressed late in photoreceptor differentiation and was immediately targeted to inner segments. A high level of beta 1 expression in horizontal cells preceded migration, whereas increases in beta 2 expression in bipolar cells occurred very late, coinciding with synaptogenesis in the inner plexiform layer. Most of the spatial specification of Na,K-ATPase isoform expression was completed before eye opening and the onset of electroretinographic responses on postnatal day 13 (P13), but quantitative increase continued until P22 in parallel with synaptogenesis. C1 Massachusetts Gen Hosp, Ctr Neurosci, Lab Membrane Biol, Charlestown, MA 02129 USA. RP Sweadner, KJ (reprint author), 149 6118 Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS27653] NR 54 TC 60 Z9 60 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1999 VL 19 IS 22 BP 9878 EP 9889 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 254JG UT WOS:000083607700025 PM 10559397 ER PT J AU Yoshida, N Kristiansen, A Liberman, MC AF Yoshida, N Kristiansen, A Liberman, MC TI Heat stress and protection from permanent acoustic injury in mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE sound conditioning; acoustic trauma; cochlea; hearing; heat shock; quantitative PCR ID GUINEA-PIG COCHLEA; ULTRASTRUCTURAL-CHANGES; DISTORTION PRODUCTS; SHOCK PROTEIN-27; NOISE EXPOSURE; RAT COCHLEA; STEREOCILIA; TRAUMA; HYPERTHERMIA; STIMULUS AB The inner ear can be permanently damaged by overexposure to high-level noise; however, damage can be decreased by previous exposure to moderate level, nontraumatic noise (Canlon et al., 1988). The mechanism of this "protective" effect is unclear, but a role for heat shock proteins has been suggested. The aim of the present study was to directly test protective effects of heat stress in the ear. For physiological experiments, CBA/CaJ mice were exposed to an intense octave band of noise (8-16 kHz) at 100 dB SPL for 2 hr, either with or without previous whole-body heat stress (rectal temperature to 41.5 degrees C for 15 min). The interval between heat stress and sound exposure varied in different groups from 6 to 96 hr. One week later, inner ear function was assessed in each animal via comparison of compound action potential thresholds to mean values from unexposed controls. Permanent threshold shifts (PTSs) were similar to 40 dB in the group sound-exposed without previous heat stress. Heat-stressed animals were protected from acoustic injury: mean PTS in the group with 6 hr heat-stress-trauma interval was reduced to similar to 10 dB. This heat stress protection disappeared when the treatment-trauma interval surpassed 24 hr. A parallel set of quantitative PCR experiments measured heat-shock protein mRNA in the cochlea and showed 100- to 200-fold increase over control 30 min after heat treatment, with levels returning to baseline at 6 hr after treatment. Results are consistent with the idea that upregulation of heat shock proteins protects the ear from acoustic injury. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Tohoku Univ, Grad Sch Med, Dept Otolaryngol, Sendai, Miyagi 9808574, Japan. RP Liberman, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC-0188] NR 44 TC 104 Z9 108 U1 0 U2 4 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 15 PY 1999 VL 19 IS 22 BP 10116 EP 10124 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 254JG UT WOS:000083607700047 PM 10559419 ER PT J AU Kelly, K AF Kelly, K TI Overcoming paralysis: Into the water and out of the wheelchair. 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 NOV 15 PY 1999 VL 124 IS 19 BP 90 EP 90 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 256ZG UT WOS:000083755900225 ER PT J AU Wekerle, T Sayegh, MH Ito, H Hill, J Chandraker, A Pearson, DA Swenson, KG Zhao, GL Sykes, M AF Wekerle, T Sayegh, MH Ito, H Hill, J Chandraker, A Pearson, DA Swenson, KG Zhao, GL Sykes, M TI Anti-CD154 or CTLA4lg obviates the need for thymic irradiation in a non-myeloablative conditioning regimen for the induction of mixed hematopoietic chimerism and tolerance. SO TRANSPLANTATION LA English DT Article ID BONE-MARROW TRANSPLANTATION; ANTIBODY MAB INJECTIONS; WHOLE-BODY IRRADIATION; LONG-TERM ACCEPTANCE; VERSUS-HOST DISEASE; T-CELL TOLERANCE; ALLOGENEIC CHIMERISM; CYNOMOLGUS MONKEYS; CARDIAC ALLOGRAFTS; NEGATIVE SELECTION AB Background. Thymic irradiation (TI) or repeated administration of T cell-depleting monoclonal antibodies (TCD mAbs) is required in a previously described non-myeloablative regimen allowing allogeneic marrow engraftment with stable mixed chimerism and tolerance, As both treatments might be associated with toxicity in the clinical setting, we evaluated whether T-cell costimulatory blockade could be used to replace them. Methods. C57BL/6 mice received depleting anti-CD4 and anti-CD8 mAbs on day -5, 3 Gy whole body irradiation (day 0), and 15x10(6) fully MHC-mismatched, B10.A bone marrow cells. In addition, hosts were injected with an anti-CD154 mAb (day 0) and/or CTLA4Ig (day +2), Chimerism in peripheral blood was followed by flow cytometric (FACS) analysis, and tolerance was assessed by skin grafting, and also by mixed lymphocyte reaction (MLR) and cell-mediated lympholysis (CML) assays. The frequency of certain V beta families was determined by FACS to assess deletion of donor-reactive T cells. Results, Chimerism was transient and tolerance was not present in animals receiving TCD mAbs on day -5 without costimulatory blockade. The addition of anti-CD154 and CTLA4Ig, alone or in combination, reliably permitted induction of high levels of stable (>6 months) multi-lineage chimerism, with specific tolerance to skin grafts and donor antigens by MLR and CML assays. Long-term chimeras showed deletion of donor-reactive CD4(+) peripheral blood lymphocytes, splenocytes, and mature thymocytes, Administration of TCD mAbs only 1 day before bone marrow transplantation plus anti-CD154 also allowed induction of permanent chimerism and tolerance, Conclusions. One injection of anti-CD154 or CTLA4Ig overcomes the need for TI or prolonged host TCD in a preclinical model for the induction of mixed chimerism and deletional tolerance and thus further decreases the toxicity of this protocol. Achievement of tolerance with conditioning given over 24 hr suggests applicability to cadaveric organ transplantation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, Boston, MA 02129 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Lab Immunogenet & Transplantat, Boston, MA 02115 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Transplantat Biol Res Ctr, Bone Marrow Transplantat Sect, MGH E,13th St,Bldg 149-5102, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 FU NHLBI NIH HHS [R01 HL49915] NR 51 TC 91 Z9 96 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 1999 VL 68 IS 9 BP 1348 EP 1355 DI 10.1097/00007890-199911150-00022 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 256TT UT WOS:000083743000022 PM 10573075 ER PT J AU Zhang, K Weiss, NT Tarazi, FI Kula, NS Baldessarini, RJ AF Zhang, K Weiss, NT Tarazi, FI Kula, NS Baldessarini, RJ TI Effects of alkylating agents on dopamine D-3 receptors in rat brain: selective protection by dopamine SO BRAIN RESEARCH LA English DT Article DE alkylation; autoradiography; D-3 and D-2 dopamine receptor; EEDQ; NIPS ID IRREVERSIBLE BLOCKADE; BINDING-SITES; N-ETHOXYCARBONYL-2-ETHOXY-1,2-DIHYDROQUINOLINE; INVIVO; LOCALIZATION; D-2-LIKE; INVITRO; NEUROBIOLOGY; VOLTAMMETRY; RECOVERY AB Dopamine D-3 receptors are structurally highly homologous to other D-2-like dopamine receptors, but differ from them pharmacologically. D-3 receptors are notably resistant to alkylation by 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), which readily alkylates D-2 receptors. We compared EEDQ with N-(p-isothiocyanatophenethyl)spiperone (NIPS), a selective D-2-like receptor alkylating agent, for effects on D-3 and D-2 receptors in rat brain using autoradiographic analysis. Neither agent occluded D-3 receptors in vivo at doses that produced substantial blockade of D-2 receptors, even after catecholamine-depleting pretreatments. In vitro, however, D-3 receptors were readily alkylated by both NIPS (IC50 = 40 nM) and EEDQ (IC50 = 12 mu M). These effects on D-3 sites were blocked by nM concentrations of dopamine, whereas mu M concentrations were required to protect D-2 receptors from the alkylating agents. The findings are consistent with the view that alkylation of D-3 receptors in vivo is prevented by its high affinity for even minor concentrations of endogenous dopamine. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. RP Zhang, K (reprint author), McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-19907, MH-34006, MH-437370] NR 35 TC 14 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD NOV 13 PY 1999 VL 847 IS 1 BP 32 EP 37 DI 10.1016/S0006-8993(99)02024-7 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 256UU UT WOS:000083745500005 PM 10564733 ER PT J AU Brambilla, D Reichelderfer, PS Bremer, JW Shapiro, DE Hershow, RC Katzenstein, DA Hammer, SM Jackson, B Collier, AC Sperling, RS Fowler, MG Coombs, RW AF Brambilla, D Reichelderfer, PS Bremer, JW Shapiro, DE Hershow, RC Katzenstein, DA Hammer, SM Jackson, B Collier, AC Sperling, RS Fowler, MG Coombs, RW CA Adult & Pediat AIDS Clinical Trial Women Infant Transmission Study C Virology Quality Assurance Program TI The contribution of assay variation and biological variation to the total variability of plasma HIV-1 RNA measurements SO AIDS LA English DT Article; Proceedings Paper CT 12th International Conference on AIDS CY JUN-JUL -, 1998 CL GENEVA, SWITZERLAND DE clinical trials; HIV diagnostic tests; viral load ID IMMUNODEFICIENCY-VIRUS TYPE-1; CD4 CELL COUNTS; VIRAL LOAD; ZIDOVUDINE TREATMENT; CUBIC MILLIMETER; INFECTED ADULTS; TRANSMISSION; THERAPY; QUANTIFICATION; MARKERS AB Objectives: To assess the specific contributions of assay variation and biological variation to the total variation of plasma HIV-1 RNA measured by the Roche Monitor assay and the extent to which batch assays reduced both assay variability and total variability compared with real-time determinations. Design: A retrospective analysis of data obtained from three trials conducted by the Adult and Pediatric AIDS Clinical Trials Groups (ATCG), the Women and Infants Transmission Study (WITS) and the NIAID-sponsored Virology Quality Assurance Program. Methods: Within-subject variation was assessed from stored, serially collected plasma samples from 663 subjects enrolled in the ACTG and WITS studies. Interassay and intra-assay variation were estimated from two of the clinical trials and 22 laboratories that participated in a quality assurance program and were used to estimate the effect of real-time testing on total variation. Results: The total variation (standard deviation) from a random effects model was 0.26 log(10) RNA copies/ml. The estimated interassay variation was 0.08 log(10) and intra-assay variation was 0.12 log(10) RNA copies/ml. Biological variation accounted for 56-80% of total variation. The effect of real-time testing compared with batch testing was minimal. Conclusion: Our estimates of total within-subject HIV-1 RNA variation support the current recommendation to obtain at least two specimens, preferably obtained less than 2 weeks apart, for viral RNA measurement before starting therapy. The major contribution of biological variation to the total variation supports the use of real-time HIV-1 RNA assays, provided that consistent specimen collection procedures are followed and acceptable assay proficiency is maintained. (C) 1999 Lippincott Williams & Wilkins. C1 New England Res Inst, Watertown, MA 02472 USA. NICHHD, Bethesda, MD 20892 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Illinois, Sch Publ Hlth, Chicago, IL USA. Univ Illinois, Coll Med, Chicago, IL USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Deaconess Med Ctr, Boston, MA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. Mt Sinai Sch Med, New York, NY USA. NIAID, Bethesda, MD 20892 USA. RP Brambilla, D (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. FU NIAID NIH HHS [AI-27664, N0-AI-35172, UO1-AI-4110] NR 29 TC 62 Z9 63 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 12 PY 1999 VL 13 IS 16 BP 2269 EP 2279 DI 10.1097/00002030-199911120-00009 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 252PF UT WOS:000083510700009 PM 10563712 ER PT J AU Shirasu, K Lahaye, T Tan, MW Zhou, FS Azevedo, C Schulze-Lefert, P AF Shirasu, K Lahaye, T Tan, MW Zhou, FS Azevedo, C Schulze-Lefert, P TI A novel class of eukaryotic zinc-binding proteins is required for disease resistance signaling in barley and development in C-elegans SO CELL LA English DT Article ID POWDERY MILDEW INTERACTION; PROGRAMMED CELL-DEATH; OXIDATIVE BURST; GENE ML-A12; PLANTS; ARABIDOPSIS; PATHOGEN; FINGER; LOCUS; RESPONSES AB Barley Rar1 is a convergence point in the signaling of resistance to powdery mildew, triggered by multiple race-specific resistance (R) genes. Rar1 is shown to function upstream of H2O2 accumulation in attacked host cells, which precedes localized host cell death. We isolated Rar1 by map-based cloning. The sequence of the deduced 25.5 kDa protein reveals two copies of a 60-amino acid domain, CHORD, conserved in tandem organization in protozoa, plants, and metazoa. CHORD defines a novel eukaryotic Zn2+-binding domain. Silencing of the C. elegans CHORD-containing gene, chp, results in semisterility and embryo lethality, suggesting an essential function of the wild-type gene in nematode development. Our findings indicate that plant R genes have recruited a fundamental cellular control element for signaling of disease resistance and cell death. C1 John Innes Ctr Plant Sci Res, Sainsbury Lab, Norwich NR4 7UH, Norfolk, England. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Schulze-Lefert, P (reprint author), John Innes Ctr Plant Sci Res, Sainsbury Lab, Colney Lane, Norwich NR4 7UH, Norfolk, England. RI Schulze-Lefert, Paul/A-7746-2008; Shirasu, Ken/A-4455-2010; Schulze-Lefert, Paul/B-6707-2011 OI Shirasu, Ken/0000-0002-0349-3870; NR 42 TC 241 Z9 266 U1 2 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 12 PY 1999 VL 99 IS 4 BP 355 EP 366 DI 10.1016/S0092-8674(00)81522-6 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 256CX UT WOS:000083709300003 PM 10571178 ER PT J AU Wang, YX Neamati, N Jacob, J Palmer, I Stahl, SJ Kaufman, JD Huang, PL Huang, PL Winslow, HE Pommier, Y Wingfield, PT Lee-Huang, S Bax, A Torchia, DA AF Wang, YX Neamati, N Jacob, J Palmer, I Stahl, SJ Kaufman, JD Huang, PL Huang, PL Winslow, HE Pommier, Y Wingfield, PT Lee-Huang, S Bax, A Torchia, DA TI Solution structure of anti-HIV-1 and anti-tumor protein MAP30: Structural insights into its multiple functions SO CELL LA English DT Article ID RIBOSOME-INACTIVATING PROTEINS; POKEWEED ANTIVIRAL PROTEIN; ADENOSINE GLYCOSIDASE ACTIVITY; RICIN A-CHAIN; CRYSTAL-STRUCTURE; STAPHYLOCOCCAL NUCLEASE; BACKBONE DYNAMICS; STRANDED-DNA; J-COUPLINGS; NMR AB We present the solution structure of MAP30, a plant protein with anti-HIV and anti-tumor activities. Structural analysis and subsequent biochemical assays lead to several novel discoveries. First, MAP30 acts like a DNA glycosylase/apurinic (ap) lyase, an additional activity distinct from its known RNA N-glycosidase activity toward the 28S rRNA. Glycosylase/ap lyase activity explains MAP30's apparent inhibition of the HIV-1 integrase, MAP30's ability to irreversibly relax supercoiled DNA, and may be an alternative cytotoxic pathway that contributes to MAP30's anti-HIV/anti-tumor activities. Second, two distinct, but contiguous, subsites are responsible for MAP30's glycosylase/ap lyase activity. Third, Mn2+ and Zn2+ interact with negatively charged surfaces next to the catalytic sites, facilitating DNA substrate binding instead of directly participating in catalysis. C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Mol Struct Biol Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Prot Express Lab, NIH, Bethesda, MD 20892 USA. Amer BioSci, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Lee-Huang, S (reprint author), NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. FU NIAID NIH HHS [R01 AI-31343] NR 63 TC 56 Z9 68 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 12 PY 1999 VL 99 IS 4 BP 433 EP 442 DI 10.1016/S0092-8674(00)81529-9 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 256CX UT WOS:000083709300010 PM 10571185 ER PT J AU Puigserver, P Adelmant, C Wu, ZD Fan, M Xu, JM O'Malley, B Spiegelman, BM AF Puigserver, P Adelmant, C Wu, ZD Fan, M Xu, JM O'Malley, B Spiegelman, BM TI Activation of PPAR gamma coactivator-1 through transcription factor docking SO SCIENCE LA English DT Article ID STEROID-RECEPTOR COACTIVATOR-1; HISTONE ACETYLTRANSFERASE; ONCOPROTEIN; BINDING; SRC-1; E1A AB Transcriptional coactivators have been viewed as constitutively active components, using transcription factors mainly to Localize their functions. Here, it is shown that PPAR gamma coactivator-1 (PGC-1) promotes transcription through the assembly of a complex that includes the histone acetyltransferases steroid receptor coactivator-1 (SRC-1) and CREB binding protein (CBP)/p300. PGC-1 has a Low inherent transcriptional activity when it is not bound to a transcription factor. The docking of PGC-1 to peroxisome proliferator-activated receptor gamma (PPAR gamma) stimulates an apparent conformational change in PGC-1 that permits binding of SRC-1 and CBP/p300, resulting in a Large increase in transcriptional activity. Thus, transcription factor docking switches on the activity of a coactivator protein. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77040 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 [DK54477] NR 21 TC 374 Z9 391 U1 1 U2 15 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 NOV 12 PY 1999 VL 286 IS 5443 BP 1368 EP 1371 DI 10.1126/science.286.5443.1368 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255NF UT WOS:000083675500045 PM 10558993 ER PT J AU Chung, CY Iida-Klein, A Wyatt, LE Rudkin, GH Ishida, K Yamaguchi, DT Miller, TA AF Chung, CY Iida-Klein, A Wyatt, LE Rudkin, GH Ishida, K Yamaguchi, DT Miller, TA TI Serial passage of MC3T3-E1 cells alters osteoblastic function and responsiveness to transforming growth factor-beta 1 and bone morphogenetic protein-2 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID AGED RATS; GENE-EXPRESSION; INVITRO; PHENOTYPE; DIFFERENTIATION; PROLIFERATION; LINE; SENESCENCE; FIBROBLAST; OSTEOGENIN AB The murine-derived clonal MC3T3-E1 cell is a well-studied osteoblast-like cell line. To understand the effects of serial passages on its cellular function, we examined changes in cell morphology, gap junctional intercellular communication (GJIC), proliferation, and osteoblastic function between early passage (<20) and late passage (>65) cells. MC3T3-E1 cells developed an elongated, spindle shape after multiple passages. Intercellular communication decreased significantly (33%) in late vs. early passage cells. Transforming growth factor-beta 1 (TGF-beta 1) stimulated cell proliferation in early passage cells and induced c-fos expression, while it inhibited proliferation in late passage cells. Using alkaline phosphatase (ALP) activity and osteocalcin (OC) secretion as markers for osteoblastic function and differentiation, we demonstrated that both markers were significantly reduced after multiple cell passages. Bone morphogenetic protein-2 (BMP-2) significantly enhanced ALP activity and OC secretion in early passage cells while TGF-beta 1 exerted an opposite effect. Both BMP-8 and TGF-beta 1 had minimal effects on late passage cells. We conclude that serial passage alters MC3T3-E1 cell morphology, and significantly diminishes GJIC, osteoblastic function, TGF-beta 1-mediated cell proliferation, and responsiveness to TGF-beta 1 and BMP-2. Cell passage numbers should be clearly defined in functional studies involving MC3T3-E1 cells. (C) 1999 Academic Press.. C1 W Los Angeles Vet Affairs Med Ctr, Plast Surg Res Lab, Plast Surg Sect, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, GRECC, Los Angeles, CA 90073 USA. W Los Angeles Vet Affairs Med Ctr, Res Serv, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA 90095 USA. RP Miller, TA (reprint author), W Los Angeles Vet Affairs Med Ctr, Plast Surg Res Lab, Plast Surg Sect, Bldg 114,Room 221,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIA NIH HHS [F32AG05708-01] NR 36 TC 51 Z9 51 U1 0 U2 4 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 NOV 11 PY 1999 VL 265 IS 1 BP 246 EP 251 DI 10.1006/bbrc.1999.1639 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 256JB UT WOS:000083721200041 PM 10548521 ER PT J AU Ghaffari, S Wu, H Gerlach, M Han, Y Lodish, HF Daley, GQ AF Ghaffari, S Wu, H Gerlach, M Han, Y Lodish, HF Daley, GQ TI BCR-ABL and v-SRC tyrosine kinase oncoproteins support normal erythroid development in erythropoietin receptor-deficient progenitor cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; FACTOR-DEPENDENT CELLS; DNA-BINDING ACTIVITY; SH2 DOMAIN; CONSTITUTIVE ACTIVATION; PHILADELPHIA-CHROMOSOME; PROLACTIN RECEPTOR; BONE-MARROW; IN-VIVO; C-ABL AB Erythropoietin (Epo)-independent differentiation of erythroid progenitors is a major characteristic of myeloproliferative disorders, including chronic myeloid leukemia. Epo receptor (EpoR) signaling is crucial for normal erythroid development, as evidenced by the properties of Epo(-/-) and EpoR(-/-) mice, which contain a normal number of fetal liver erythroid progenitors but die in utero from a severe anemia attributable to the absence of red cell maturation. Here we show that two constitutively active cytoplasmic protein tyrosine kinases, p210(BCR-ABL) v-SRC, can functionally replace the EpoR and support full proliferation, differentiation, and maturation of fetal liver erythroid progenitors from EpoR(-/-) mice. These protein tyrosine kinases can also partially complement the myeloid growth factors IL-3, IL-6, and Steel factor, which are normally required in addition to Epo for erythroid development. Additionally, BCR-ABL mutants that lack residues necessary for transformation of fibroblasts or bone marrow cells can fully support: normal erythroid development. These results demonstrate that activated tyrosine kinase oncoproteins implicated in tumorigenesis and human leukemia can functionally complement for cytokine receptor signaling pathways to support normal erythropoiesis in EpoR-deficient cells. Moreover, terminal differentiation of erythroid cells requires generic signals provided by activated protein tyrosine kinases and does not require a specific signal unique to a cytokine receptor. C1 Whitehead Inst Biomed Res, Nine Cambridge Ctr, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Daley, GQ (reprint author), Whitehead Inst Biomed Res, Nine Cambridge Ctr, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM daley@wi.mit.edu FU NCI NIH HHS [CA76418-01]; NHLBI NIH HHS [HL 32262, P01 HL032262] NR 52 TC 36 Z9 38 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 9 PY 1999 VL 96 IS 23 BP 13186 EP 13190 DI 10.1073/pnas.96.23.13186 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255BJ UT WOS:000083649400040 PM 10557295 ER PT J AU Li, CJ Li, YZ Pinto, AV Pardee, AB AF Li, CJ Li, YZ Pinto, AV Pardee, AB TI Potent inhibition of tumor survival in vivo by beta-lapachone plus taxol: Combining drugs imposes different artificial checkpoints SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CELL-CYCLE; CANCER CELLS; APOPTOSIS; P53; INDUCTION; ARREST; LYMPHOCYTES; DIVISION; TAT AB Ablation of tumor colonies was seen in a wide spectrum of human carcinoma cells in culture after treatment with the combination of beta-lapachone and taxol, two low molecular mass compounds. They synergistically induced death of cultured ovarian, breast, prostate, melanoma, lung, colon, and pancreatic cancer cells. This synergism is schedule dependent; namely, taxol must be added either simultaneously or after beta-lapachone, This combination therapy has unusually potent antitumor activity against human ovarian and prostate tumor prexenografted in mice. There is little host toxicity. Cells can commit to apoptosis at cell-cycle checkpoints, a mechanism that eliminates defective cells to ensure the integrity of the genome. We hypothesize that when cells are treated simultaneously with drugs activating more than one different cell-cycle checkpoint, the production of conflicting regulatory signaling molecules induces apoptosis in cancer cells. beta-lapachone causes cell-cycle delays in late G(1) and S phase, and taxol arrests cells at G(2)/M. Cells treated with both drugs were delayed at multiple checkpoints before committing to apoptosis. Our findings suggest an avenue for developing anticancer therapy by exploiting apoptosis-prone "collisions" at cell-cycle checkpoints. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Ctr Ciencias Desaude, BR-21941590 Rio De Janeiro, Brazil. RP Li, CJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Cell Growth & Regulat, 44 Binney St, Boston, MA 02115 USA. EM cjli@mbcrr.harvard.edu FU NCI NIH HHS [R01CA61253] NR 26 TC 145 Z9 149 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 9 PY 1999 VL 96 IS 23 BP 13369 EP 13374 DI 10.1073/pnas.96.23.13369 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255BJ UT WOS:000083649400072 PM 10557327 ER PT J AU Behar, O Mizuno, K Badminton, M Woolf, CJ AF Behar, O Mizuno, K Badminton, M Woolf, CJ TI Semaphorin 3A growth cone collapse requires a sequence homologous to tarantula hanatoxin SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PERIPHERAL-NERVE PROJECTION; SCORPION TOXIN; DEPENDENT BINDING; SPINAL-CORD; RECEPTOR; GUIDANCE; CALCIUM; ACTIVATION; NEUROPILIN; IONOPHORE AB Axonal guidance is key to the formation of neuronal circuitry. Semaphorin 3A (Sema 3A; previously known as semaphorin ill, semaphorin D, and collapsin-1), a secreted subtype of the semaphorin family, is an important axonal guidance molecule in vitro and in vivo. The molecular mechanisms of the repellent activity of semaphorins are, however, poorly understood. We have now found that the secreted semaphorins contain a short sequence of high homology to hanatoxin, a tarantula K+ and Ca2+ ion channel blocker. Point mutations in the hanatoxin-like sequence of Sema 3A reduce its capacity to repel embryonic dorsal root ganglion axons. Sema 3A growth cone collapse activity is inhibited by hanatoxin, general Ca2+ channel blockers, a reduction in extracellular or intracellular Ca2+, and a calmodulin inhibitor, but not by K+ channel blockers. Our data support an important role for Ca2+ in mediating the Sema 3A response and suggest that Sema 3A may produce its effects by causing the opening of Ca2+ channels. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Plast Res Grp,Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Childrens Hosp, Div Cardiovasc, Charlestown, MA 02129 USA. Univ London Univ Coll, Dept Anat & Dev Biol, London WC1E 6BT, England. RP Behar, O (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Plast Res Grp,Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. EM behar@helix.mgh.harvard.edu FU NINDS NIH HHS [NS38253-01, R01 NS038253] NR 36 TC 37 Z9 37 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 NOV 9 PY 1999 VL 96 IS 23 BP 13501 EP 13505 DI 10.1073/pnas.96.23.13501 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255BJ UT WOS:000083649400095 PM 10557350 ER PT J AU Jirage, D Tootle, TL Reuber, TL Frost, LN Feys, BJ Parker, JE Ausubel, FM Glazebrook, J AF Jirage, D Tootle, TL Reuber, TL Frost, LN Feys, BJ Parker, JE Ausubel, FM Glazebrook, J TI Arabidopsis thaliana PAD4 encodes a lipase-like gene that is important for salicylic acid signaling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SYSTEMIC ACQUIRED-RESISTANCE; ENHANCED DISEASE SUSCEPTIBILITY; PROTEIN KINASE-C; PERONOSPORA-PARASITICA; DEFENSE RESPONSES; MUTANTS; EXPRESSION; ACTIVATION; EDS1; NPR1 AB The Arabidopsis PADI gene previously was found to be required for expression of multiple defense responses including camalexin synthesis and PR-I gene expression in response to infection by the bacterial pathogen Pseudomonas syringae pv, maculicola. This report describes the isolation of PAD4, The predicted PAD4 protein sequence displays similarity to triacyl glycerol lipases and other esterases, The PAD4 transcript was found to accumulate after P. syringae infection or treatment with salicylic acid (SA). PAD4 transcript levels were very low in infected pad4 mutants. Treatment with SA induced expression of PAD4 mRNA in pad4-1, pad4-3, and pad4-4 plants but not in pad4-2 plants. Induction of PAD4 expression by P, syringae was independent of the regulatory factor NPR1 but induction by SA was NPR1-dependent. Taken together with the previous observation that pad4 mutants have a defect in accumulation of SA upon pathogen infection, these results suggest that PAD4 participates in a positive regulatory loop that increases SA levels, thereby activating SA-dependent defense responses. C1 Univ Maryland, Mol & Cell Biol Grad Program, College Pk, MD 20742 USA. Univ Maryland, Ctr Agr Biotechnol, Maryland Biotechnol Inst, College Pk, MD 20742 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Sainsbury Lab, Norwich NR4 7UH, Norfolk, England. RP Glazebrook, J (reprint author), Novartis Agr Discovery Inst Inc, 3115 Merryfield Row,Suite 100, San Diego, CA 92121 USA. EM jane.glazebrook@nadii.novartis.com OI Glazebrook, Jane/0000-0001-5167-736X FU NIGMS NIH HHS [GM 48707, R01 GM048707, R37 GM048707] NR 33 TC 335 Z9 350 U1 1 U2 31 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 NOV 9 PY 1999 VL 96 IS 23 BP 13583 EP 13588 DI 10.1073/pnas.96.23.13583 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 255BJ UT WOS:000083649400109 PM 10557364 ER PT J AU Viel, A AF Viel, A TI alpha-actinin and spectrin structures: an unfolding family story SO FEBS LETTERS LA English DT Article DE spectrin; alpha-actinin; structure; electrostatic interaction ID INTERCHAIN BINDING; TAIL-END AB In red blood cells, the integrity of the spectrin network is essential for normal cell shape and elasticity. To understand the molecular basis for spectrin's mechanical properties, one must determine how spectrin subunits interact with each other. The newly described crystallographic structures of two consecutive homologous repeats of human alpha-actinin, a member of the spectrin superfamily, shed new light on alpha-actinin interchain binding properties, Here I present evidence that interchain binding at the tail end of the spectrin molecule is likely to occur via a mechanism similar to that observed for alpha-actinin, (C) 1999 Federation of European Biochemical Societies. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Viel, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 10 TC 22 Z9 24 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 5 PY 1999 VL 460 IS 3 BP 391 EP 394 DI 10.1016/S0014-5793(99)01372-1 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 255HM UT WOS:000083663500001 PM 10556504 ER PT J AU Widlund, HR Kuduvalli, PN Bengtsson, M Cao, H Tullius, TD Kubista, M AF Widlund, HR Kuduvalli, PN Bengtsson, M Cao, H Tullius, TD Kubista, M TI Nucleosome structural features and intrinsic properties of the TATAAACGCC repeat sequence SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MYOTONIC-DYSTROPHY GENE; POSITIONING SEQUENCES; CRYSTAL-STRUCTURE; TRIPLET REPEATS; DNA FLEXIBILITY; HELICAL REPEAT; BASE-PAIRS; CHROMATIN; MOBILITY; COMPLEX AB Nucleosomes, the fundamental building blocks of chromatin, play an architectural role in ensuring the integrity of the genome and act as a regulator of transcription. Intrinsic properties of the underlying DNA sequence, such as flexibility and intrinsic bending, direct the formation of nucleosomes, We have earlier identified genomic nucleosome-positioning sequences with increased in vitro ability for nucleosome formation. One group of sequences bearing a 10-base pair consensus repeat sequence of TATAAACGCC had the highest reported nucleosome affinity from genomic material. Here, we report the intrinsic physical properties of this sequence and the structural details of the nucleosome it forms, as analyzed by footprinting techniques, The minor groove is buried toward the histone octamer at the AA steps and facing outwards at the CC steps. By cyclization kinetics, the overall helical repeat of the free DNA sequence was found to be 10.5 base pairs/turn. Our experiments also showed that this sequence is highly flexible, having a J-factor 25-fold higher than that of random sequence DNA, In addition, the data suggest that twist flexibility is an important determinant for translational nucleosome positioning, particularly over the dyad region. C1 Chalmers Univ Technol, Lundberg Inst, Dept Biochem & Biophys, SE-41390 Gothenburg, Sweden. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA. Boston Univ, Dept Chem, Boston, MA 02215 USA. RP Kubista, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Dana 630,44 Binney St, Boston, MA 02115 USA. RI Tullius, Thomas/A-9685-2008; Kubista, Mikael/A-5689-2008 OI Tullius, Thomas/0000-0003-4425-796X; Kubista, Mikael/0000-0002-2940-352X FU NIGMS NIH HHS [GM41930, R01 GM041930, R01 GM041930-10] NR 33 TC 62 Z9 69 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 NOV 5 PY 1999 VL 274 IS 45 BP 31847 EP 31852 DI 10.1074/jbc.274.45.31847 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100017 PM 10542209 ER PT J AU Carter, PH Shimizu, M Luck, MD Gardella, TJ AF Carter, PH Shimizu, M Luck, MD Gardella, TJ TI The hydrophobic residues phenylalanine 184 and leucine 187 in the type-1 parathyroid hormone (PTH) receptor functionally interact with the amino-terminal portion of PTH-(1-34) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; PROTEIN-LINKED RECEPTOR; (PTH)/PTH-RELATED PEPTIDE; TRANSMEMBRANE RESIDUES; EXTRACELLULAR LOOP; BINDING-AFFINITY; CROSS-LINKING; DOMAIN; SITE; MUTAGENESIS AB Recent mutagenesis and cross-linking studies suggest that three regions of the PTH-1 receptor play important roles in ligand interaction: (i) the extreme NH2-terminal region, (ii) the juxtamembrane base of the amino-terminal extracellular domain, and (iii) the third extracellular loop. In this report, Re analyzed the second of these segments in the rat PTH-I receptor (residues 182-190) and its role in functional interaction with short PTH fragment analogs. Twenty-eight singly substituted PTH-I receptors were transiently transfected into COS-7 cells and shown to be fully expressed by surface antibody binding analysis, Alanine scanning analysis identified phe(184), Arg(186), Leu(187), and Ile(190) as important determinants of maximum binding of I-125-Iabeled bovine PTH-(1-34) and I-125-labeled bovine PTH-(3-34) and determinants of responsiveness to the NH2-terminal analog, PTH (1-14) in cAMP stimulation assays. Alanine mutations at these four sites augmented the ability of the COOH-terminal peptide [Glu(22),Trp(23)]PTHrP-(15-36) to inhibit the cAMP response induced by PTH-(1-34). At Phe(184) and Leu(187), hydrophobic substitutions (e.g. Ile, Met, or Leu) preserved PTH-(1-34)-mediated cAMP signaling potency, whereas hydrophilic substitutions (e.g. Asp, Glu, Lys, or Arg) weakened this response by 20-fold or more, as compared with the unsubstituted receptor's response. The results suggest that hydrophobicity at positions occupied by phe(184) and Leu(187) in the PTH-1 receptor plays an important role in determining functional interaction with the 3-14 portion of PTH. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK11794] NR 32 TC 33 Z9 34 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 NOV 5 PY 1999 VL 274 IS 45 BP 31955 EP 31960 DI 10.1074/jbc.274.45.31955 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100032 PM 10542224 ER PT J AU Altiok, S Batt, D Altiok, N Papautsky, A Downward, J Roberts, TM Avraham, H AF Altiok, S Batt, D Altiok, N Papautsky, A Downward, J Roberts, TM Avraham, H TI Heregulin induces phosphorylation of BRCA1 through phosphatidylinositol 3-kinase/AKT in breast cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-KINASE-B; DNA-DAMAGE; CYCLE; GENE; AKT; EXPRESSION; DIFFERENTIATION; REQUIREMENT; INVOLVEMENT; INHIBITION AB The breast cancer susceptibility gene BRCA1 encodes a nuclear phosphoprotein that acts as a tumor suppressor, Phosphorylation of BRCA1 has been implicated in altering its function, however, the pathway(s) that leads to the phosphorylation of BRCA1 has not been described, Here, a signaling pathway by which heregulin induces cell cycle-independent phosphorylation of BRCA1 was delineated. We showed that heregulin stimulation induced the phosphorylation of BRCA1 and concomitant activation of the serine/threonine kinase AKT in T47D human breast cancer cells. Heregulin-induced phosphorylation of BRCA1 was abrogated by phosphatidylinositol 3-kinase (PI3K) inhibitors and by a dominant-negative AKT, In the absence of heregulin, the ectopic expression of the constitutively active p110 subunit of PI3K: was sufficient to induce BRCA1 phosphorylation. Furthermore, the purified glutathione S-transferase/AKT kinase phosphorylated BRCA1 in vitro. We have also shown that the phosphorylation of BRCA1 by ABT occurs on the residue Thr-509, which is located in the nuclear localization signal. These results reveal a novel signaling pathway that links extracellular signals to the phosphorylation of BRCA1 in breast cancer cells. C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Childrens Hosp, Div Neurosci, Boston, MA 02115 USA. Imperial Canc Res Fund, Signal Transduct Lab, London WC2A 3PX, England. RP Avraham, H (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, 3rd Fl,4 Blackfan Circle, Boston, MA 02115 USA. FU NCI NIH HHS [CA76226]; NHLBI NIH HHS [HL51456, HL55445] NR 29 TC 89 Z9 89 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 NOV 5 PY 1999 VL 274 IS 45 BP 32274 EP 32278 DI 10.1074/jbc.274.45.32274 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100074 PM 10542266 ER PT J AU Li, SL Schlegel, W Valente, AJ Clark, RA AF Li, SL Schlegel, W Valente, AJ Clark, RA TI Critical flanking sequences of PU.1 binding sites in myeloid-specific promoters SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; TRANSCRIPTION FACTOR PU.1; HEMATOLOGICALLY IMPORTANT MUTATIONS; STIMULATING FACTOR-RECEPTOR; GENE-EXPRESSION; B-LYMPHOCYTES; ETS FAMILY; REQUIRES; MACROPHAGE; C/EBP AB The myeloid-specific transcription factor PU.1 is essential for expression of p47(phox), a component of the superoxide-forming phagocyte NADPH oxidase. The consensus PU.1 binding sequence (GAGGAA) is located on the non-coding strand from position -40 to -45 relative to the transcriptional start site of the p47phox promoter. A promoter construct extending to -46 was sufficient to drive tissue-specific expression of the luciferase reporter gene, but extension of the promoter from -46 to -48 resulted in a significant increase in reporter expression. Mutations of the nucleotides G at -46 and/or T at -47 reduced both reporter expression and PU.1 binding, whereas mutations at -48 had no effect, The PU.1 binding avidity of these sequences correlated closely with their capacity to dictate reporter gene transcription. In parallel studies on the functional PU.1 site in the promoter of CD18, mutations of nucleotides G and T at positions -76 and -77 (corresponding to -46 and -47, respectively, of the p47phox promoter) reduced PU.1 binding and nearly abolished the contribution of this element to promoter activity. We conclude that the immediate flanking nucleotides of the PU.1 consensus motif have significant effects on PU.1 binding avidity and activity and that this region is the dominant cis element regulating p47phox expression. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78229 USA. Univ Geneva, Fdn Rech Med, CH-1211 Geneva, Switzerland. RP Clark, RA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NIAID NIH HHS [AI20866, R01 AI020866, R37 AI020866] NR 36 TC 34 Z9 34 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 NOV 5 PY 1999 VL 274 IS 45 BP 32453 EP 32460 DI 10.1074/jbc.274.45.32453 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252ZL UT WOS:000083532100098 PM 10542290 ER PT J AU Singh, BN AF Singh, BN TI Overview of trends in the control of cardiac arrhythmia: Past and future SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material ID VENTRICULAR TACHYARRHYTHMIAS; IMPLANTABLE DEFIBRILLATOR; SUDDEN-DEATH; AMIODARONE; EFFICACY; AGENT; DRUG; REPOLARIZATION; TACHYCARDIA; MORTALITY C1 W Los Angeles Vet Affairs Med Ctr, Div Cardiol 111E, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 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 53 TC 7 Z9 7 U1 0 U2 2 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 NOV 4 PY 1999 VL 84 IS 9A SI SI BP 3R EP 10R PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 253EV UT WOS:000083544400002 PM 10568654 ER PT J AU Nattel, S Singh, BN AF Nattel, S Singh, BN TI Evolution, mechanisms, and classification of antiarrhythmic drugs: Focus on class III actions SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 71st Scientific Session of the American-Heart-Association Meeting CY NOV 08-12, 1998 CL DALLAS, TEXAS SP Amer Heart Assoc ID RECTIFIER K+-CURRENT; EXPERIMENTAL ATRIAL-FIBRILLATION; ACUTE MYOCARDIAL-INFARCTION; VENTRICULAR INTRACELLULAR POTENTIALS; CARDIAC PURKINJE-FIBERS; REVERSE USE DEPENDENCE; TORSADE-DE-POINTES; POTASSIUM CHANNEL; CONTROLLED TRIALS; CLINICAL-TRIALS AB Since the use of cinchona bark to treat heart palpitations in the 1700s, antiarrhythmic drug therapy has developed with the discovery of new compounds and the identification of ionic, cellular, and tissue mechanisms of action. Classifications have been developed that organize the large amount of information available about antiarrhythmic drugs around groups of compounds with common mechanisms of action. Despite important and well-recognized limitations, antiarrhythmic drug classification is still widely used. In particularly broad use is the system developed by Singh and Vaughan Williams in the early 1970s and subsequently modified by Singh and Hauswirth and by Harrison. This classification divides drug actions into class I for sodium-channel blockade (with subclasses IA, IS and IC), class II for adrenergic antagonism, class III for action-potential prolongation, and class IV for calcium-channel blockade. The development of class I drugs was curtailed when studies showed that potent sodium-channel blockers (particularly IC agents) can increase mortality in patients with active coronary artery disease. The emphasis in drug development shifted to class III agents, but their use has been limited by the risk of ventricular tachyarrhythmia induction associated with QT prolongation. Current research focuses on the development of new class III drugs that may have improved safety by virtue of greater selectivity of action at faster rates (like those of arrhythmia) or for atrial tissue. Alternative approaches include the modification of existing molecules (like amiodarone) to maintain positive properties while removing undesirable ones, and treatments that target development of the arrhythmia substrate instead of the final electrical product. (C)1999 by Excerpta Medica, Inc. C1 Montreal Heart Inst, Dept Med, Res Ctr, Montreal, PQ H1T 1C8, Canada. Univ Montreal, Dept Med, Montreal, PQ H1T 1C8, Canada. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. RP Nattel, S (reprint author), Montreal Heart Inst, Dept Med, Res Ctr, 5000 Belanger St E, Montreal, PQ H1T 1C8, Canada. NR 78 TC 51 Z9 54 U1 0 U2 3 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 NOV 4 PY 1999 VL 84 IS 9A SI SI BP 11R EP 19R PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 253EV UT WOS:000083544400003 PM 10568655 ER PT J AU Ogunyankin, KO Singh, BN AF Ogunyankin, KO Singh, BN TI Mortality reduction by antiadrenergic modulation of arrhythmogenic substrate: Significance of combining beta blockers and amiodarone SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 71st Scientific Session of the American-Heart-Association Meeting CY NOV 08-12, 1998 CL DALLAS, TEXAS SP Amer Heart Assoc ID ACUTE MYOCARDIAL-INFARCTION; LEFT-VENTRICULAR DYSFUNCTION; SUDDEN CARDIAC DEATH; HEART-FAILURE; NERVOUS-SYSTEM; BLOCKADE; DRUG; EXPERIENCE; THERAPY; TRIAL AB Over the last 3 decades, there have been numerous experimental and clinical studies that utilized beta blockers for acute as well as chronic myocardial syndromes, especially in the setting of myocardial infarction in which the focus has been on mortality reduction. The results of these studies demonstrated the benefits of these agents at all stages of coronary artery disease. Although these data have always indicated that beta blockade per se is an antiarrhythmic as well as an antifibrillatory mechanism, the recognition of this phenomenon has been slow in finding universal appreciation. More recent studies have evaluated the additive role of beta blockers to newer therapies, A number of investigations have now established that this class of drugs does exert antifibrillatory action in preventing the occurrence of ventricular tachycardia (VT) and ventricular fibrillation (VF), thereby reducing sudden arrhythmic death and prolonging survival. it is of interest that 2 of the leading antiarrhythmic dregs, amiodarone and sotalol, also have antiadrenergic properties. This article reviews the expanding role of beta-blocking drugs in the control and prevention of life-threatening ventricular tachyarrhythmias with a particular focus on the evidence for synergistic benefits when they are combined with other interventions, especially amiodarone. (C)1999 by Excerpta Medica, Inc. C1 Bassett Healthcare, Div Cardiol, Cooperstown, NY 13326 USA. Univ Calif Los Angeles, W Los Angeles Vet Adm Med Ctr, Sch Med, Div Cardiol, Los Angeles, CA USA. RP Ogunyankin, KO (reprint author), Bassett Healthcare, Div Cardiol, 1 Atwell Rd, Cooperstown, NY 13326 USA. NR 55 TC 7 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 NOV 4 PY 1999 VL 84 IS 9A SI SI BP 76R EP 82R PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 253EV UT WOS:000083544400012 PM 10568664 ER PT J AU Singh, BN Mody, FV Lopez, B Sarma, JSM AF Singh, BN Mody, FV Lopez, B Sarma, JSM TI Antiarrhythmic agents for atrial fibrillation: Focus on prolonging atrial repolarization SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 71st Scientific Session of the American-Heart-Association Meeting CY NOV 08-12, 1998 CL DALLAS, TEXAS SP Amer Heart Assoc ID LOW-DOSE AMIODARONE; LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; TORSADE-DE-POINTES; CLASS-III AGENTS; SINUS RHYTHM; ELECTRICAL CARDIOVERSION; CARDIAC-ARRHYTHMIAS; SUPRAVENTRICULAR TACHYARRHYTHMIAS; AZIMILIDE DIHYDROCHLORIDE AB Atrial fibrillation (AF) has been the subject of considerable attention and intensive clinical research in recent years. Current opinion among physicians on the management of AF favors the restoration and maintenance of normal sinus rhythm. This has several potential benefits, including the alleviation of arrhythmia-associated symptoms, hemodynamic improvements, and possibly a reduced risk of thromboembolic events. After normal sinus rhythm has been restored, antiarrhythmic therapy is necessary to reduce the frequency of AF recurrence, in the selection of an antiarrhythmic agent, both efficacy and safety should be taken into consideration. Many antiarrhythmic agents have the capacity to provoke proarrhythmia, which may result in an increase in mortality. This is of particular concern with sodium-channel blockers in the context of patients with structural heart disease. Flecainide and propafenone are well tolerated and effective in maintaining sinus rhythm in patients without significant cardiac disease but with AF. Recent interest has focused on the use of class III antiarrhythmic agents, such as amiodarone, sotalol, dofetilide (recently of AF and atrial flutter), and azimilide (still to be approved) in patients with AF and structural heart disease. To date, amiodarone and sotalol still hold the greatest interest, and although controlled clinical trials with these agents have been few,a number are in progress and some have been recently completed. These agents are effective in maintaining normal sinus rhythm in patients with paroxysmal and persistent AF and are associated with a low incidence of proarrhythmia when used appropriately. Because of the relative paucity of placebo-controlled trials of antiarrhythmic agents in patients with AF, experience until recently has tended to dictate treatment decisions. Increasingly, selection of drug therapy is being based on a careful and individualized benefit-risk evaluation by means of controlled clinical trials, an approach that is likely to dominate the overall approach to the control of atrial fibrillation in the largest numbers of cases of the arrhythmia. Pharmacologic therapy is likely to be dominated by compounds that exert their predominant effect by prolonging atrial repolarization, (C)1999 by Excerpta Medica, Inc. C1 W Los Angeles Vet Affairs Med Ctr, Dept Med, Cardiol Sect, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Singh, BN (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Med, Cardiol Sect, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 77 TC 11 Z9 14 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 NOV 4 PY 1999 VL 84 IS 9A SI SI BP 161R EP 173R PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 253EV UT WOS:000083544400025 PM 10568677 ER PT J AU D'Aquila, R Walker, B AF D'Aquila, R Walker, B TI Exploring the benefits and limits of highly active antiretroviral therapy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; PLASMA VIREMIA; CELL RESPONSES; IN-VIVO; HIV-1; INFECTION RP D'Aquila, R (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Charlestown, MA 02129 USA. NR 27 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 3 PY 1999 VL 282 IS 17 BP 1668 EP 1669 DI 10.1001/jama.282.17.1668 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 250BD UT WOS:000083368400034 PM 10553795 ER PT J AU Barach, P AF Barach, P TI Teaching hospitals in trouble: Finding solutions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Barach, P (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 3 PY 1999 VL 282 IS 17 BP 1686 EP 1686 DI 10.1001/jama.282.17.1686 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 250BD UT WOS:000083368400041 ER PT J AU Aveline, BM Redmond, RW AF Aveline, BM Redmond, RW TI Selective photoexcitation of the thione and thiol forms of N-hydroxypyridine-4(1H)thione: A tautomeric heteroaromatic system SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID LASER FLASH-PHOTOLYSIS; SUBSTITUTED BENZENETHIYL RADICALS; PYRIDINE N-OXIDE; THIYL RADICALS; ADDITION RATES; VINYL MONOMERS; HYDROGEN-ATOM; PHOTOPHYSICAL PROPERTIES; EXTINCTION COEFFICIENTS; HYDROXYL RADICALS AB The strong solvent-dependence of the tautomeric equilibrium exhibited by N-hydroxypyridine-4(1H)thione (4-NHPT) and the distinct absorption properties of the thione and thiol tautomers offer the rare opportunity to investigate the photochemistry of each form independently. Laser flash photolysis studies have revealed that triplet state formation was the main photoprocess undergone by the thione tautomer of 4-NHPT in protic solvents (Phi(T) = 0.90, lambda(exc) = 355 nm), whereas pulsed excitation (lambda(exc) = 308 nm) of the thiol form in apolar media resulted in a less efficient intersystem crossing (Phi(T) = 0.19) accompanied by homolytic S-H bond cleavage (Phi(S-H) = 0.24). The latter process leads to the production of the N-oxy-4-pyridinethiyl radical (4-PyNOS .). In most organic solvents, however, the thione and thiol tautomers of 4-NHPT coexist. Under these conditions, the form absorbing the excitation light was observed to undergo the expected primary photochemistry followed by secondary processes involving reaction with the ground state of the nonexcited tautomer (i.e., electron transfer from the thione triplet state to the thiol form and addition of 4-PyNOS to the carbon-sulfur double bond of the tautomeric thione). Contrary to the closely related N-hydroxypyridine-2(1H)-thione, 4-NHPT was not found to be a primary photochemical precursor of hydroxyl radicals ( OH) in organic solvents. The results obtained in this work are discussed in terms of structure/photoreactivity and with regard to the reported photobiological effects of N-hydroxypyridinethiones. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. RP Aveline, BM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. NR 67 TC 8 Z9 8 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 3 PY 1999 VL 121 IS 43 BP 9977 EP 9985 DI 10.1021/ja991951j PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 254YH UT WOS:000083641500011 ER PT J AU Thorndike, AN Ferris, TG Stafford, RS Rigotti, NA AF Thorndike, AN Ferris, TG Stafford, RS Rigotti, NA TI Rates of US physicians counseling adolescents about smoking SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HEALTH PROMOTION; PRACTITIONERS; INTERNISTS; ADVICE AB Background: The health care system provides an important opportunity for addressing tobacco use among youths, but there is little information about how frequently physicians discuss smoking with their adolescent patients. We analyzed data from the National Ambulatory Medical Care Surveys to assess the prevalence and the predictors of physicians' identification of smoking status and counseling about smoking at office visits by adolescents. Methods: From 1991 through 1996, 5087 physicians recorded data on 16648 visits by adolescents aged 11-21 years. We determined the proportion of office visits at which physicians identified an adolescent's smoking status and counseled about smoking and then identified predictors of these outcomes with logistic regression. Statistical tests were two-sided. Results: In 1991, physicians identified an adolescent's smoking status at 72.4% of visits but provided smoking counseling at only 1.6% of all adolescent visits and 16.9% of visits by adolescents identified as smokers. These proportions did not increase from 1991 through 1996. Compared with specialists, primary care physicians were more likely to identify smoking status (odds ratio [OR] = 1.70; 95% confidence interval [CI] = 1.53-1.89) and to counsel about smoking (OR = 3.43; 95% CI = 2.18-5.38), Patients with diagnoses of conditions potentially complicated by smoking were more likely to have their smoking status identified and to be counseled about smoking. Younger and nonwhite adolescents were less likely to be counseled about smoking than older and white teens. Conclusions: We found that physicians frequently identified adolescents' smoking status but rarely counseled them about smoking. Physicians' practices did not improve in the first half of the 1990s, despite a clear consensus about the importance of this activity and the publication of physician guidelines targeting this population. Physicians treating adolescents are missing opportunities to discourage tobacco use among teens. C1 Massachusetts Gen Hosp, Gen Med Unit, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Tobacco Res & Treatment Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Thorndike, AN (reprint author), Massachusetts Gen Hosp, Gen Med Unit, Div Gen Med, S50-9, Boston, MA 02114 USA. FU BHP HRSA HHS [PE11001]; NHLBI NIH HHS [HL03548]; NICHD NIH HHS [HD00850] NR 37 TC 59 Z9 59 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 3 PY 1999 VL 91 IS 21 BP 1857 EP 1862 DI 10.1093/jnci/91.21.1857 PG 6 WC Oncology SC Oncology GA 252FK UT WOS:000083491300016 PM 10547392 ER PT J AU Gorin, MB Breitner, JCS De Jong, PTVM Hageman, GS Klaver, CCW Kuehn, MH Seddon, JM AF Gorin, MB Breitner, JCS De Jong, PTVM Hageman, GS Klaver, CCW Kuehn, MH Seddon, JM TI The genetics of age-related macular degeneration SO MOLECULAR VISION LA English DT Article ID ONSET ALZHEIMER-DISEASE; BEAVER DAM EYE; RETINITIS-PIGMENTOSA; APOLIPOPROTEIN-E; RETINAL DEGENERATION; SERIAL ANALYSIS; OLIGONUCLEOTIDE ARRAYS; FUNDUS-FLAVIMACULATUS; STARGARDTS-DISEASE; CLINICAL-FEATURES AB Age-related macular degeneration (AMD) is increasingly recognized as a complex genetic disorder in which one or more genes contribute to an individual's susceptibility for developing the condition. Twin and family studies as well as population-based genetic epidemiologic methods have convincingly demonstrated the importance of genetics in AMD, though the extent of heritability, the number of genes involved, and the phenotypic and genetic heterogeneity of the condition remain unresolved. The extent to which other hereditary macular dystrophies such as Stargardts disease, familial radial drusen (malattia leventinese), Best's disease, and peripherin/RDS-related dystrophy are related to AMD remains unclear. Alzheimer's disease, another late onset, heterogeneous degenerative disorder of the central nervous system, offers a valuable model for identifying the issues that confront AMD genetics. C1 Univ Pittsburgh, Sch Med, Dept Ophthalmol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA 15213 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Mental Hyg, Baltimore, MD USA. Netherlands Ophthalm Res Inst, NL-1100 AC Amsterdam, Netherlands. Erasmus Univ, Sch Med, Dept Biostat & Epidemiol, Rotterdam, Netherlands. Erasmus Univ, Sch Med, Dept Ophthalmol, Rotterdam, Netherlands. Univ Iowa Hosp & Clin, Dept Ophthalmol & Visual Sci, Ctr Macular Degenerat, Iowa City, IA 52242 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Gorin, MB (reprint author), Univ Pittsburgh, Sch Med, Dept Ophthalmol, Eye & Ear Inst Bldg,203 Lothrop St, Pittsburgh, PA 15213 USA. NR 64 TC 0 Z9 0 U1 0 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 3 PY 1999 VL 5 IS 24-35 BP U31 EP U36 PG 6 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 260ER UT WOS:000083937000006 ER PT J AU Hunink, MGM Kuntz, KM Fleischmann, KE Brady, TJ AF Hunink, MGM Kuntz, KM Fleischmann, KE Brady, TJ TI Noninvasive imaging for the diagnosis of coronary artery disease: Focusing the development of new diagnostic technology SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID ELECTRON-BEAM CT; COMPUTED-TOMOGRAPHY; ANGIOGRAPHY; METAANALYSIS; STENOSES; RECONSTRUCTIONS; CALCIFICATION; PERFORMANCE; CALCIUM AB Background: New tests, such as magnetic resonance imaging (MRI) and electron-beam computed tomography (CT), are being developed for the diagnosis of coronary artery disease. Objective: To determine the conditions that a new test must meet to be a cost-effective alternative to established imaging tests. Design: Decision model and cost-effectiveness analysis. Data Sources: Literature review and meta-analysis. Target Population: 55-year-old men and 65-year-old women presenting with chest pain. Time Horizon: Lifetime of the patient. Perspective: Health care policy. Interventions: MRI, electron-beam CT, exercise echocardiography, exercise single-photon emission CT, and coronary angiography. Outcome Measures: Target sensitivity and specificity values for a new noninvasive test. Results of Base-Case Analysis: Assuming that society is willing to pay $75 000 per quality-adjusted life-year (QALY) gained, a new test that costs $1000 would need a sensitivity of 94% and a specificity of 90% to be cost-effective. Results of Sensitivity Analysis: Assuming that society is willing to pay $50 000 per QALY gained, a new test that costs $1000 or more would never be cost-effective. For a test that costs $500, the sensitivity and specificity must each be 95%. Conclusions: New imaging techniques, such as MRI and electron-beam CT, must be relatively inexpensive and have excellent sensitivity and specificity to be cost-effective compared with other techniques for the diagnosis of coronary artery disease. Similar analyses in other areas of health care may help to focus the development of new diagnostic technology. C1 Erasmus Med Ctr, Dept Epidemiol & Biostat, NL-3000 DR Rotterdam, Netherlands. Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Boston, MA 02114 USA. Univ Calif San Francisco, Sch Med, Div Cardiol, San Francisco, CA USA. Erasmus Med Ctr, Dept Radiol, NL-3000 DR Rotterdam, Netherlands. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ctr Innovat Minimally Invas Therapy, Partners Healthcare Syst, Boston, MA 02114 USA. RP Hunink, MGM (reprint author), Erasmus Med Ctr, Dept Epidemiol & Biostat, Room EE21-40A,Box 1738, NL-3000 DR Rotterdam, Netherlands. FU NHLBI NIH HHS [1K08HL02964-01] NR 31 TC 32 Z9 32 U1 1 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 NOV 2 PY 1999 VL 131 IS 9 BP 673 EP 680 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 251LB UT WOS:000083446200006 PM 10577330 ER PT J AU Forman, SA AF Forman, SA TI A hydrophobic photolabel inhibits nicotinic acetylcholine receptors via open-channel block following a slow step SO BIOCHEMISTRY LA English DT Article ID NONCOMPETITIVE ANTAGONIST; PROTEIN; REGIONS; STATE AB 3-(Trifluoromethyl)-3-(m-iodophenyl)diazirine (TID) is a hydrophobic inhibitor of nicotinic acetylcholine receptors (nAChRs) and a photolabel that incorporates both at the lipid-protein interface and within the gated pore. On the basis of Torpedo vesicle studies, TID is thought to selectively inhibit the closed nAChR state, The nAChR site(s) mediating TID inhibition is unknown. We investigated the state dependence and kinetics of TID inhibition electrophysiologically using rapidly superfused membrane patches expressing mouse muscle nAChRs. Currents from patches simultaneously exposed to ACh and TID show no inhibition of peak currents relative to acetylcholine (ACh) alone but demonstrate slow (10 s(-1)) TID inhibition, Patch preexposure to TID before ACh results in a burst of current followed by rapid [TID]-dependent inhibition at a bimolecular rate of 1.8 x 10(8) M-1 s(-1), indicating that TID selectively inhibits open channels. We also determined sensitivity to TLD in two nAChRs containing mutations in their pore-forming M2 domains. The alpha L251T mutation eliminates sensitivity to TID inhibition, while the alpha S252I mutation enhances this sensitivity 4-fold compared to wild type. These results indicate that TID inhibition of nAChRs follows two distinct kinetic steps. The rate-limiting step, which shows features suggesting a diffusion barrier, precedes rapid open-state-dependent TID binding to an inhibition site near the putative nAChR gate. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Forman, SA (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, CLN-3, Boston, MA 02114 USA. FU NIGMS NIH HHS [P01-GM58448] NR 19 TC 25 Z9 25 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 2 PY 1999 VL 38 IS 44 BP 14559 EP 14564 DI 10.1021/bi9914457 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 255JF UT WOS:000083665200014 PM 10545178 ER PT J AU Mendes, LA Picard, MH Jacobs, AK Thompson, CR Sleeper, LA Hochman, JS Davidoff, R AF Mendes, LA Picard, MH Jacobs, AK Thompson, CR Sleeper, LA Hochman, JS Davidoff, R TI Cardiogenic shack: Predictors of outcome based on right and left ventricular size and function at presentation SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. New England Res Inst, Watertown, MA 02172 USA. St Lukes Roosevelt Hosp Ctr, New York, NY 10025 USA. RI Thompson, Christopher/F-3967-2010 OI Thompson, Christopher/0000-0001-9206-376X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 98 BP 19 EP 20 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100099 ER PT J AU Picard, MH Davidoff, R Mendes, LA Thompson, CR Dzavik, V Goldberger, M Abboud, R Sleeper, LA White, HD LeJemtel, TH Hochman, JS AF Picard, MH Davidoff, R Mendes, LA Thompson, CR Dzavik, V Goldberger, M Abboud, R Sleeper, LA White, HD LeJemtel, TH Hochman, JS TI Determinants of mortality from cardiogenic shack: Observations from the SHOCK trial SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Univ Alberta Hosp, Edmonton, AB T6G 2B7, Canada. Montefiore Hosp & Med Ctr, Bronx, NY 10461 USA. New England Res Inst, Watertown, MA 02172 USA. Green Lane Hosp, Auckland 3, New Zealand. Albert Einstein Coll Med, Bronx, NY 10467 USA. St Lukes Roosevelt Hosp Ctr, New York, NY 10025 USA. RI Thompson, Christopher/F-3967-2010 OI Thompson, Christopher/0000-0001-9206-376X NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 94 BP 19 EP 19 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100095 ER PT J AU McNamara, DM Starling, RC Dec, GW Torre-Amione, G Gass, A Janosko, KM Tokarczyk, T Holubkov, R Feldman, AM AF McNamara, DM Starling, RC Dec, GW Torre-Amione, G Gass, A Janosko, KM Tokarczyk, T Holubkov, R Feldman, AM TI Intervention in myocarditis and acute cardiomyopathy with immune globulin: Results from the randomized placebo controlled IMAC trial SO CIRCULATION LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. NR 0 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 104 BP 21 EP 21 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100105 ER PT J AU Laham, RJ Pearlman, J Datta, R Gao, L Baim, DS AF Laham, RJ Pearlman, J Datta, R Gao, L Baim, DS TI Biosense-guided laser myocardial revascularization improves 30-day and 6-month regional wall motion, perfusion, and collateralization of the treated zone(s) SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 111 BP 22 EP 22 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100112 ER PT J AU Chandar, JS Rao, PS Lloyd, TR Palacios, IF Zamora, R Sideris, EB AF Chandar, JS Rao, PS Lloyd, TR Palacios, IF Zamora, R Sideris, EB TI Atrial septal defect closure with 4th generation Buttoned device: Results on US multicenter FDA phase II clinical trial SO CIRCULATION LA English DT Meeting Abstract C1 St Louis Univ, St Louis, MO 63103 USA. Univ Miami, Miami, FL 33152 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Arizona, Tucson, AZ USA. Pediat Cardiol & Custom Med Devices, Amarillo, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 150 BP 30 EP 30 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100151 ER PT J AU Shioi, T Hampton, TG Douglas, PS Izumo, S AF Shioi, T Hampton, TG Douglas, PS Izumo, S TI Dominant negative P21(ras) causes a progressive dilated cardiomyopathy in transgenic mice SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 265 BP 52 EP 52 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100266 ER PT J AU Shioi, TS Douglas, PS Izumo, S AF Shioi, TS Douglas, PS Izumo, S TI Cardiac specific overexpression of focal adhesion kinase induces cardiac hypertrophy SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 264 BP 52 EP 52 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100265 ER PT J AU Buck, T Mucci, RA Holmvang, G Handschumacher, MD Levine, RA AF Buck, T Mucci, RA Holmvang, G Handschumacher, MD Levine, RA TI Direct quantification of regurgitation by the power-velocity integral: Can it be applied to eccentric jets? SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 370 BP 72 EP 72 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100371 ER PT J AU Hung, J Handschumacher, MD Rudski, L Chow, CM Guerrero, JL Levine, RA AF Hung, J Handschumacher, MD Rudski, L Chow, CM Guerrero, JL Levine, RA TI Persistence of ischemic mitral regurgitation despite annular ring reduction: Mechanistic insights from 3D echocardiography SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 11 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 374 BP 73 EP 73 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100375 ER PT J AU Raizner, AE Oesterle, SN Waksman, R Chiu, JKH Tate, D White, LR Levy, GV Kaluza, GL Ali, NM AF Raizner, AE Oesterle, SN Waksman, R Chiu, JKH Tate, D White, LR Levy, GV Kaluza, GL Ali, NM TI Inhibition of restenosis with beta-emitting radiation (P-32): The final report of the PREVENT trial SO CIRCULATION LA English DT Meeting Abstract C1 Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Hosp Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Baylor Coll Med, VAMC, Houston, TX 77030 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 386 BP 75 EP 75 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100387 ER PT J AU Cohen, DJ Taira, DA Berezin, RA Jones, N Cox, DA Brodie, BR Morice, MC Stone, GW Grines, CL AF Cohen, DJ Taira, DA Berezin, RA Jones, N Cox, DA Brodie, BR Morice, MC Stone, GW Grines, CL TI The cost-effectiveness of coronary stenting in acute myocardial infarction: Results from the Stent-PAMI trial SO CIRCULATION LA English DT Meeting Abstract C1 Beth Israel Deacones Med Ctr, Boston, MA USA. LeBauer CV Res Fdn, Greensboro, NC USA. Inst Cardiovasc Paris Sud, Antony, France. Washington Hosp Ctr, Washington, DC 20010 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 447 BP 87 EP 88 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100448 ER PT J AU Kuhlencordt, PJ Dombkowski, D Atkinson, WJ Preffer, F Huang, PL AF Kuhlencordt, PJ Dombkowski, D Atkinson, WJ Preffer, F Huang, PL TI Effects of targeted deletion of endothelial nitric oxide synthase on activation of cultured murine microvascular endothelial cells. SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 570 BP 110 EP 111 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100570 ER PT J AU Gyurko, R Fishman, MC Huang, PL AF Gyurko, R Fishman, MC Huang, PL TI Modulation of cardiac relaxation by nitric oxide and atrial natriuretic peptide SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 572 BP 111 EP 111 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100572 ER PT J AU Gu, XL Caldwell, RB El Shabrawey, M Tsai, N Bartoli, M Huang, PL Brooks, SE AF Gu, XL Caldwell, RB El Shabrawey, M Tsai, N Bartoli, M Huang, PL Brooks, SE TI Knockout of endothelial nitric oxide synthase decreases peroxynitrite formation and reduces cepillary dropout in oxygen induced retinopathy SO CIRCULATION LA English DT Meeting Abstract C1 Med Coll Georgia, Augusta, GA 30912 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 582 BP 113 EP 113 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417100582 ER PT J AU Shioi, T Kang, PM Douglas, PS Yballe, CM Cantley, LC Lawitts, JA Izumo, S AF Shioi, T Kang, PM Douglas, PS Yballe, CM Cantley, LC Lawitts, JA Izumo, S TI Phosphoinositide 3-kinase selectively regulates cell size and specific gene expression in the adult mouse heart SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1032 BP 200 EP 200 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101031 ER PT J AU Malave, HA Taylor, AA Lee-Jackson, D Mann, DL AF Malave, HA Taylor, AA Lee-Jackson, D Mann, DL TI Elevated circulating levels of tumor necrosis factor correlate with depressed heart rate variability in patients with heart failure SO CIRCULATION LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1063 BP 206 EP 206 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101062 ER PT J AU Sodian, R Hoerstrup, SP Sperling, JS Daebritz, S Martin, DP Moran, AM Schoen, FJ Vacanti, JP Mayer, JE AF Sodian, R Hoerstrup, SP Sperling, JS Daebritz, S Martin, DP Moran, AM Schoen, FJ Vacanti, JP Mayer, JE TI Early in vivo experience with autologous tissue engineered trileaflet heart valves SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Metabolix Inc, Cambridge, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Acad Hosp, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1090 BP 211 EP 211 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101089 ER PT J AU Lansky, AJ Danchenko, A Oesterle, SN Desal, KJ Modl, N Proctor, B Hall, L Conway, T Raizner, AE AF Lansky, AJ Danchenko, A Oesterle, SN Desal, KJ Modl, N Proctor, B Hall, L Conway, T Raizner, AE TI Patterns of intimal hyperplasia after P-32 brachytherapy: Results from the PREVENT randomized clinical trial SO CIRCULATION LA English DT Meeting Abstract C1 Washington Hosp Ctr, Washington, DC 20010 USA. Bethesda Naval Med Ctr, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Methodist Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1153 BP 222 EP 223 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101152 ER PT J AU Tanabe, H Omoto, T LaRaia, PJ Viahakes, GJ AF Tanabe, H Omoto, T LaRaia, PJ Viahakes, GJ TI High oxygen concentration and L-arginine exacerbate myocardial reperfusion injury in cardiac surgery under cardiopulmonary bypass SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1182 BP 228 EP 228 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101181 ER PT J AU De Lee, X Gold, H Ghanti, R Pitris, C Guerrera, JL Jesser, C Fujimoto, JG Brezinski, ME AF De Lee, X Gold, H Ghanti, R Pitris, C Guerrera, JL Jesser, C Fujimoto, JG Brezinski, ME TI High resolution imaging of stents and atherosclerotic plaques with optical coherence tomography SO CIRCULATION LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1186 BP 229 EP 229 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101185 ER PT J AU Rodriguez, A Palacios, IF Navia, MAJ Baldi, J Grinfeld, L Martinez, J Perez-Bali-o, N Vogel, D Garrido, M Grinfeld, R Oliveri, R O'Neill, WW AF Rodriguez, A Palacios, IF Navia, MAJ Baldi, J Grinfeld, L Martinez, J Perez-Bali-o, N Vogel, D Garrido, M Grinfeld, R Oliveri, R O'Neill, WW TI Argentine randomized study: Coronary angioplasty with stenting vs. coronary artery bypass surgery in patients with multiple vessel disease (ERACI II): 30 day and long-term follow-up results. SO CIRCULATION LA English DT Meeting Abstract C1 Otamendi Hosp, Buenos Aires, DF, Argentina. Massachusetts Gen Hosp, Boston, MA 02114 USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1212 BP 234 EP 234 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101211 ER PT J AU Lepore, JJ Pereira, N Maroo, A Ginns, L Bigatello, LM Dec, GW Rubin, R Zapol, WM Bloch, KD Semigran, MJ AF Lepore, JJ Pereira, N Maroo, A Ginns, L Bigatello, LM Dec, GW Rubin, R Zapol, WM Bloch, KD Semigran, MJ TI Sildenafil is a pulmonary vasodilator which augments and prolongs vasodilatation by inhaled nitric oxide in patients with pulmonary hypertension SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1247 BP 240 EP 240 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101246 ER PT J AU Chao, W Matsui, T Li, L Rosenzweig, A AF Chao, W Matsui, T Li, L Rosenzweig, A TI Adenoviral expression of IGF-I or CrmA blocks cardiomyocyte apoptosis in vitro SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1471 BP 281 EP 281 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101470 ER PT J AU Matsui, T Tao, JZ Lee, KH Li, L Franke, TF Hajjar, RJ Rosenzweig, A AF Matsui, T Tao, JZ Lee, KH Li, L Franke, TF Hajjar, RJ Rosenzweig, A TI Adenoviral gene transfer of myr-Akt prevents cardiomyocyte injury in vitro and in vivo SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Samsung Med Ctr, Seoul, South Korea. Columbia Univ, New York, NY 10027 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1470 BP 281 EP 281 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101469 ER PT J AU Haider, N Kharbanda, S Chandrashekhar, Y Srinivasula, SM Fitzpatrick, JM Anand, I Alnemri, ES Narula, J AF Haider, N Kharbanda, S Chandrashekhar, Y Srinivasula, SM Fitzpatrick, JM Anand, I Alnemri, ES Narula, J TI Caspase-3 mediated cleavage of troponin-C at evolutionarily-conserved calcium-binding site: Relevance of apoptosis in heart failure SO CIRCULATION LA English DT Meeting Abstract C1 MCP Hahnemann Univ, Philadelphia, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 0 TC 10 Z9 10 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1479 BP 283 EP 283 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101478 ER PT J AU Oesterle, SN Ali, NM Sanborn, TA Dean, LS Resar, JR Schaer, GL Heuser, RR Schofield, PM Ramee, SR Knopf, WD Yeung, AC AF Oesterle, SN Ali, NM Sanborn, TA Dean, LS Resar, JR Schaer, GL Heuser, RR Schofield, PM Ramee, SR Knopf, WD Yeung, AC TI Percutaneous transmyocardial laser revascularization (PMR): Final results from the PACIFIC trial SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Baylor Coll Med, Vet Adm Med Ctr, Houston, TX 77030 USA. Cornell Univ, Med Ctr, New York Hosp, New York, NY 10021 USA. Univ Alabama, Birmingham, AL USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Phoenix Heart Ctr, Phoenix, AZ USA. Mayo Clin, Rochester, MN USA. Papworth Hosp, Cambridge CB3 8RE, England. Ochsner Hosp, New Orleans, LA USA. St Josephs Hosp, Atlanta, GA USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1592 BP 304 EP 305 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101591 ER PT J AU Heidenreich, PA Parsons, L Every, NR AF Heidenreich, PA Parsons, L Every, NR TI Long-term outcomes and resource utilization after admission for unstable angina SO CIRCULATION LA English DT Meeting Abstract C1 Palo Alto VA Hlth Care Syst, Palo Alto, CA USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1667 BP 318 EP 318 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101665 ER PT J AU Corvera-Tindel, TE Dracup, KA Doering, LV AF Corvera-Tindel, TE Dracup, KA Doering, LV TI Specific activity scale is a predictor of peak oxygen consumption in heart failure SO CIRCULATION LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. Greater Los Angeles VA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1696 BP 324 EP 324 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101694 ER PT J AU Gerszten, RE Meiler, S Li, L Rosenzweig, A AF Gerszten, RE Meiler, S Li, L Rosenzweig, A TI ICAM-1 supports adhesion of MCP-1-activated monocytes under physiological flew conditions in vitro SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1749 BP 334 EP 334 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101747 ER PT J AU Laufs, U Endres, M Stagliano, N Amin-Hanjani, S Yang, SX Huang, PL Moskowitz, MA Liao, JK AF Laufs, U Endres, M Stagliano, N Amin-Hanjani, S Yang, SX Huang, PL Moskowitz, MA Liao, JK TI Inhibitors of rho GTPase and the actin cytoskeleton decreases cerebral infarct size by upregulating endothelial nitric oxide synthase SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1778 BP 339 EP 339 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101776 ER PT J AU O'Donnell, MJ White, LT Alpert, NM Lewandowski, ED AF O'Donnell, MJ White, LT Alpert, NM Lewandowski, ED TI Long chain fatty acid transport and oxidation rates in mitochondria of intact hearts from dynamic mode 13C NMR SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1809 BP 345 EP 345 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101807 ER PT J AU Rubenstein, MH Sheynberg, BV Harrell, LC Schunkert, H Bazari, H Palacios, IF AF Rubenstein, MH Sheynberg, BV Harrell, LC Schunkert, H Bazari, H Palacios, IF TI Percutaneous coronary revascularization in patients with mild vs. severe renal failure SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 1920 BP 366 EP 366 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417101918 ER PT J AU Sanchez, LS Bloch, KD AF Sanchez, LS Bloch, KD TI Nitric oxide regulates cGMP and cAMP phosphodiesterase enzyme activity and gene expression in rat pulmonary artery smooth muscle SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2018 BP 384 EP 384 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102016 ER PT J AU Quinn, DA Volokhov, A Cindhuchao, N Hales, CA AF Quinn, DA Volokhov, A Cindhuchao, N Hales, CA TI Inflammatory lung cells and macrophage inflammatory protein in ventilator-induced lung injury SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2027 BP 386 EP 386 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102025 ER PT J AU Januzzi, JL Movsowitz, HD Choi, J Abernethy, WB Isselbacher, EM AF Januzzi, JL Movsowitz, HD Choi, J Abernethy, WB Isselbacher, EM TI Recurrent pain goes not predict adverse outcome in acute type B aortic dissection SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2039 BP 388 EP 388 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102037 ER PT J AU Every, NR Neil, N Cohen, DJ Spertus, JA Ramsey, S Weaver, WD Taira, DA AF Every, NR Neil, N Cohen, DJ Spertus, JA Ramsey, S Weaver, WD Taira, DA TI Resource utilization and health status impact of primary stent vs optimal PTCA: The OPUS trial SO CIRCULATION LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Henry Ford Hlth Care Syst, Detroit, MI USA. RI Neil, Nancy/I-4913-2012 OI Neil, Nancy/0000-0002-1442-028X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2058 BP 392 EP 392 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102056 ER PT J AU Go, AS Hylek, EM Phillips, KA Henault, LE Selby, JV Singer, DE AF Go, AS Hylek, EM Phillips, KA Henault, LE Selby, JV Singer, DE TI Prevalence of atrial fibrillation: National implications for management and stroke prevention: The AnTicoagulation and risk factors in atrial fibrillation (ATRIA) study SO CIRCULATION LA English DT Meeting Abstract C1 Kaiser Permanente Med Care Program, Oakland, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2082 BP 397 EP 397 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102080 ER PT J AU Olin, KL Kunjathor, VV DeBeer, F Wright, TN Chait, A LeBoeuf, RC O'Brien, KD AF Olin, KL Kunjathor, VV DeBeer, F Wright, TN Chait, A LeBoeuf, RC O'Brien, KD TI Co-localization of serum amyloid A with apolipoprotein A-I and perlecan in lesions of atherosclerosis-prone mice SO CIRCULATION LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Kentucky, Lexington, KY USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2103 BP 400 EP 401 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102101 ER PT J AU Meiler, SE Gerszten, RE Matsui, T Li, L Rosenzweig, A AF Meiler, SE Gerszten, RE Matsui, T Li, L Rosenzweig, A TI Adenoviral expression of a dominant-negative IKK beta blocks monocyte adhesion to TNF-stimulated vascular endothelium under laminar flow conditions SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Clin Physiol, Pisa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2141 BP 407 EP 407 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102139 ER PT J AU del Monte, F Harding, SE Gwathmey, JK Rosenzweig, A Hajjar, RJ AF del Monte, F Harding, SE Gwathmey, JK Rosenzweig, A Hajjar, RJ TI Overexpression of SERCA2a by gene transfer restores contractile function in isolated failing human ventricular cardiac myocytes SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Univ London Imperial Coll Sci Technol & Med, London, England. Boston Univ, Sch Med, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2201 BP 418 EP 418 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102199 ER PT J AU Nanda, NC Hack, TC Wistran, DC Carr, MA Hall, JJ Ryan, T Mohler, ER Foley, DA Labovitz, AJ DeMaria, AN Picard, MH AF Nanda, NC Hack, TC Wistran, DC Carr, MA Hall, JJ Ryan, T Mohler, ER Foley, DA Labovitz, AJ DeMaria, AN Picard, MH TI Multicenter evaluation of Sonovue (TM) for improved endocardial border delineation: Comparison with Albunex (R) SO CIRCULATION LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Deaconess Nashoba Hosp, Ayer, MA USA. Cardiol Phys Inc, Salem, MA USA. Louisiana CV Res Ctr, New Orleans, LA USA. Winona Hosp, Med Res Consortium, Indianapolis, IN USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Penn, Hlth Syst, Philadelphia, PA 19104 USA. Mayo Clin, Rochester, MI USA. St Louis Univ, Med Ctr, St Louis, MO USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2347 BP 446 EP 446 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102344 ER PT J AU Meta, T Orlov, MV McGovern, BA Garan, H Ruskin, JN Galvin, JM AF Meta, T Orlov, MV McGovern, BA Garan, H Ruskin, JN Galvin, JM TI Infections associated with implantable cardioverter defibrillators: A problem of the past? SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2445 BP 464 EP 464 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102442 ER PT J AU Ratcliffe, MB Wallace, AW Teerlink, JR Hong, J Salahieh, A Sung, SH AF Ratcliffe, MB Wallace, AW Teerlink, JR Hong, J Salahieh, A Sung, SH TI Radiofrequency heating of chronic ovine myocardial infarction leads to sustained reductions in infarct sire and left ventricular volume SO CIRCULATION LA English DT Meeting Abstract C1 UCSF, San Francisco VA Med Ctr, San Francisco, CA USA. RI Teerlink, John/D-2986-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2710 BP 514 EP 514 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102706 ER PT J AU Hoerstrup, SP Sodian, R Sperling, JS Martin, DP Schoen, FJ Vacanti, JP Mayer, JE AF Hoerstrup, SP Sodian, R Sperling, JS Martin, DP Schoen, FJ Vacanti, JP Mayer, JE TI A trileaflet heart valve crown in vitro SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Metabolix Inc, Cambridge, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2779 BP 527 EP 528 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102775 ER PT J AU Philbin, EF DiSalvo, TG Dec, GW AF Philbin, EF DiSalvo, TG Dec, GW TI Lower socioeconomic status is an independent risk factor for hospital readmission for heart failure SO CIRCULATION LA English DT Meeting Abstract C1 Henry Ford Hosp, Detroit, MI 48202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2783 BP 528 EP 528 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102779 ER PT J AU Lipshultz, SE Lipsitz, SR Sallan, SE Dalton, V Mone, SM Gelber, RD Colan, SD AF Lipshultz, SE Lipsitz, SR Sallan, SE Dalton, V Mone, SM Gelber, RD Colan, SD TI Chronic progressive LV systolic dysfunction and afterload excess years after doxorubicin therapy for childhood acute lymphoblastic leukemia SO CIRCULATION LA English DT Meeting Abstract C1 Univ Rochester, Rochester, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2792 BP 530 EP 530 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102788 ER PT J AU Goukassian, D de Mora, JF Urena, J Andres, V AF Goukassian, D de Mora, JF Urena, J Andres, V TI PCA-4230, a potent inhibitor of Erk-2 activity and Rb hyperphosphorylation that represses vascular smooth muscle cell growth and attenuates neointimal hyperplasia SO CIRCULATION LA English DT Meeting Abstract C1 St Elizabeths Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2880 BP 546 EP 547 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102876 ER PT J AU Bloch, DK Filippov, G Fogel, M Hassoun, P AF Bloch, DK Filippov, G Fogel, M Hassoun, P TI Exposure of rat pulmonary artery smooth muscle cells to low oxygen concentrations decreases expression of soluble guanylate cyclase, a nitric oxide receptor SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. New England Med Ctr, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 2903 BP 551 EP 551 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417102899 ER PT J AU Vancon, AC Buck, T Levine, RA AF Vancon, AC Buck, T Levine, RA TI The two-chamber papillary muscle view: 3D echo characterization of a new view to study the mitral apparatus SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3024 BP 573 EP 574 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103020 ER PT J AU Gerszten, RE Matsui, T Yoshida, M Force, T Rosenzweig, A AF Gerszten, RE Matsui, T Yoshida, M Force, T Rosenzweig, A TI PI 3-kinase is necessary far MCP-1-induced adhesion of the monacytic THP-1 cell line under laminar flow conditions in vitro SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. Tokyo Med & Dent Univ, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3243 BP 615 EP 615 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103239 ER PT J AU Mach, FA Marx, N Sauty, A Luster, AD Plutzky, J AF Mach, FA Marx, N Sauty, A Luster, AD Plutzky, J TI PPAR gamma activators selectively inhibit the IFN gamma-inducible CXC chemokines IP-10, mig, and I-TAC in endothelial cells SO CIRCULATION LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3241 BP 615 EP 615 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103237 ER PT J AU Schoenberger, J Levy, H Gruenig, E Ronald, E Sangwatanaroj, S Fatkin, D Staeckler, H Halpin, C Philbin, EF Katus, HA Seidman, JG Seidman, CE AF Schoenberger, J Levy, H Gruenig, E Ronald, E Sangwatanaroj, S Fatkin, D Staeckler, H Halpin, C Philbin, EF Katus, HA Seidman, JG Seidman, CE TI Dilated cardiomyopathy and sensorineurinal hearing loss: A heritable syndrome, that maps to 6q23-24 SO CIRCULATION LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Howard Hughes Med Inst, Boston, MA USA. Univ Heidelberg, Heidelberg, Germany. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Lubeck, D-2400 Lubeck, Germany. RI Katus, Hugo/P-1712-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3261 BP 618 EP 619 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103257 ER PT J AU Buck, T Mucci, RA Guerrero, JL Holmvang, G Handschumacher, MD Levine, RA AF Buck, T Mucci, RA Guerrero, JL Holmvang, G Handschumacher, MD Levine, RA TI The power-velocity integral at the vena contracta as a new approach for direct quantification of mitral regurgitation: Calibration using mitral inflow to promote practical application SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3450 BP 654 EP 655 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103446 ER PT J AU Buck, T Holmvang, G Mucci, RA Handschumacher, MD Levine, RA AF Buck, T Holmvang, G Mucci, RA Handschumacher, MD Levine, RA TI The integral of power times velocity at the vena contracta: A new method for direct quantification of aortic regurgitant flow SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3451 BP 655 EP 655 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103447 ER PT J AU Gewirtz, H Skopicki, HA Abraham, SA Fischman, AJ AF Gewirtz, H Skopicki, HA Abraham, SA Fischman, AJ TI Relationship between myocardial flow reserve and metabolic viability in myocardial segments with reduced resting blood flow SO CIRCULATION LA English DT Meeting Abstract C1 Columbia Univ, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3484 BP 661 EP 661 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103480 ER PT J AU Yoshida, M Gerszten, RE Rosenzweig, A Gimbrone, MA Yasukochi, Y Numano, F AF Yoshida, M Gerszten, RE Rosenzweig, A Gimbrone, MA Yasukochi, Y Numano, F TI HMG-CoA reductase inhibitor-induced reduction of monocyte adhesion to vascular endothelium involves small GTP binding protein Rho dependent mechanism SO CIRCULATION LA English DT Meeting Abstract C1 Tokyo Med & Dent Univ, Tokyo, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3657 BP 693 EP 693 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103651 ER PT J AU Feener, EP Bouchie, JL Chen, HC Wilden, PA Bagot, C AF Feener, EP Bouchie, JL Chen, HC Wilden, PA Bagot, C TI Purinergic regulation of plasminogen activator inhibitor-1 (PAI-1) expression in vascular smooth muscle cells SO CIRCULATION LA English DT Meeting Abstract C1 Univ Missouri, Columbia, MO USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 3944 BP 747 EP 747 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103936 ER PT J AU Boecker, W Grazette, L Haq, S Matsui, T Meller, SE Semigran, MJ Force, T Hajjar, RJ AF Boecker, W Grazette, L Haq, S Matsui, T Meller, SE Semigran, MJ Force, T Hajjar, RJ TI Effect of anti-erbB-2 antibody alone and in combination with doxorubicin an cardiac myocyte apoptosis SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4004 BP 758 EP 759 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417103996 ER PT J AU Lemos, PA Martinez, EE Harrell, LC Ramires, JAF Gama, MN Horta, PE Kajita, LJ Esteves, A Perin, MA Soares, PR Zalc, S Palacios, IF AF Lemos, PA Martinez, EE Harrell, LC Ramires, JAF Gama, MN Horta, PE Kajita, LJ Esteves, A Perin, MA Soares, PR Zalc, S Palacios, IF TI Stenting versus balloon angioplasty with provisonal stenting for the treatment of small reference diameter vessels SO CIRCULATION LA English DT Meeting Abstract C1 Univ Sao Paulo, INCOR, Sao Paulo, Brazil. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Perin, Marco/O-2309-2014; Lemos, Pedro/G-5758-2013 OI Lemos, Pedro/0000-0002-6782-750X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4174 BP 790 EP 790 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104166 ER PT J AU Boecker, W Hajjar, RJ AF Boecker, W Hajjar, RJ TI Adenoviral mediated cardiac tissue-specific expression by the myosin light chain 2v (MLC 2v) promoter in vitro and in vivo SO CIRCULATION LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4299 BP 814 EP 815 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104290 ER PT J AU Aurigemma, GP Williams, D Reda, DJ Gottdiener, JS AF Aurigemma, GP Williams, D Reda, DJ Gottdiener, JS TI Ventricular and myocardial function following LV mass reduction in hypertensives: Results from the department of veterans affairs cooperative study of single drug therapy in hypertension SO CIRCULATION LA English DT Meeting Abstract C1 Univ Massachusetts, Worcester, MA 01605 USA. US Dept Vet Affairs, Hines, IL 60141 USA. St Francis Hosp, Roslyn, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 2 PY 1999 VL 100 IS 18 SU S MA 4556 BP 863 EP 863 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 250YD UT WOS:000083417104546 ER PT J AU Simon, SR Shaneyfelt, TM Collins, MM Cook, EF Fletcher, RH AF Simon, SR Shaneyfelt, TM Collins, MM Cook, EF Fletcher, RH TI Faculty training in general internal medicine: A survey of graduates from a research-intensive fellowship program SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT Annual American-College-of-Physicians Meeting CY APR 01-03, 1998 CL SAN DIEGO, CALIFORNIA SP Amer Coll Physicians AB Purpose. To determine the fellowship experiences and career activities of the graduates of a research-intensive general internal medicine fellowship program. Method. In 1975 the authors surveyed all graduates of the Harvard General Internal Medicine Fellowship Program, a research-intensive fellowship begun in 1979. Results. Of 105 surveys delivered to graduates, 103 (98%) were returned. During the fellowship, 82 graduates (80%) presented research findings at regional or national meetings, 89 (86%) published peer-reviewed articles based on their fellowship work, 75 (73%) precepted residents or medical students in the ambulatory setting, and 67 (65%) taught medical students in the preclinical years. At the time of the survey, 100 graduates (97%) held academic appointments: 48 as clinician- investigators, 23 as clinician- administrators, 15 as clinician - educators, and 15 as clinicians. Conclusion. Graduates of this research-intensive fellowship pursued academic careers with research, teaching, administration, and clinical activities. Directors of similar fellowship programs should prepare their graduates for all these activities. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Teaching Ctr, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Gen Internal Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Div Gen Med & Primary Care, Clin Epidemiol Sect, Boston, MA 02115 USA. RP Simon, SR (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Teaching Ctr, 126 Brookline Ave,Suite 200, Boston, MA 02215 USA. FU BHP HRSA HHS [T32 PE11001-09] NR 10 TC 14 Z9 14 U1 0 U2 0 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD NOV PY 1999 VL 74 IS 11 BP 1253 EP 1255 DI 10.1097/00001888-199911000-00022 PG 3 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 256UE UT WOS:000083744100027 PM 10587691 ER PT J AU Maisto, SA Conigliaro, J McNeil, M Kraemer, K O'Connor, M Kelley, ME AF Maisto, SA Conigliaro, J McNeil, M Kraemer, K O'Connor, M Kelley, ME TI Factor structure of the SOCRATES in a sample of primary care patients SO ADDICTIVE BEHAVIORS LA English DT Article DE brief interventions; alcohol problems; primary care; SOCRATES; factor structure ID RANDOMIZED CONTROLLED TRIAL; BRIEF INTERVENTIONS; DRINKERS; ALCOHOL; READINESS; VALIDITY; DRINKING AB Motivation or readiness to change has been studied intensively in recent years in research on the use of brief interventions to change alcohol problems in the primary care setting. The purpose of this study was to investigate the factor structure and concurrent and predictive evidence for validity of the short Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES), a 19-item self-report instrument developed to measure readiness to change alcohol problems in individuals presenting for specialized alcohol treatment. The participants were 210 men and 91 women who were identified as "at-risk" drinkers in 13 community primary care clinics. These individuals completed the SOCRATES and a number of other assessments as part of a preintervention evaluation. A principal components analysis of the SOCRATES data revealed a two-factor structure; a confirmatory factor analysis showed that this structure was a better fit to the data than the three-factor structure that Miller and Tonigan (1996) identified for the SOCRATES. The two factors (9 and 6 items, respectively), seemed to measure perceived degree of severity of an existing alcohol problem (caned "Amrec" because it consisted of Miller and Tonigan's ambivalence and recognition items) and taking action to change or to maintain changes in one that exists (called "Taking Steps"). Predictions of significant and nonsignificant correlations between the two derived factors and other baseline variables (alcohol consumption, related problems and symptoms; and demographic factors) generally were confirmed. In addition, baseline Amrec scores were related in predicted directions to 6-month alcohol consumption and related problems data, but the magnitude of these relationships were reduced when other variables that correlated with Amrec or when the 6-month data were taken into account. In general, Taking Steps showed little or no relationship to the 6-month data. The results are compared to previous work with the SOCRATES and suggestions for future research are discussed. (C) 1999 Elsevier Science Ltd. C1 Syracuse Univ, Dept Psychol, Syracuse, NY 13244 USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Vet Affairs Pittsburgh Hlth Care Syst, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Ctr Res Hlth Care, Pittsburgh, PA 15260 USA. RP Maisto, SA (reprint author), Syracuse Univ, Dept Psychol, 430 Huntington Hall, Syracuse, NY 13244 USA. FU NIAAA NIH HHS [AA1029, 5K08-AA00235] NR 29 TC 40 Z9 41 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4603 J9 ADDICT BEHAV JI Addict. Behav. PD NOV-DEC PY 1999 VL 24 IS 6 BP 879 EP 892 DI 10.1016/S0306-4603(99)00047-7 PG 14 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 258KX UT WOS:000083839300013 PM 10628520 ER PT J AU Wilkemeyer, MF Pajerski, M Charness, ME AF Wilkemeyer, MF Pajerski, M Charness, ME TI Alcohol inhibition of cell adhesion in BMP-treated NG108-15 cells SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; ethyl; cell adhesion; neuronal; fetal alcohol syndrome ID PROTEIN-KINASE-C; MOLECULE L1; NEURAL CELLS; OSTEOGENIC PROTEIN-1; GENE-EXPRESSION; NERVOUS-SYSTEM; ETHANOL; RECEPTORS; INCREASES; TOLERANCE AB Background: The ii cell adhesion molecule is expressed as alternatively spliced neuronal and nonneuronal isoforms. We have reported that in transfected fibroblasts, ethanol variably inhibits cell-cell adhesion mediated by the nonneuronal isoform of human ii. In contrast, ethanol consistently inhibits morphogenetic changes and cell-cell adhesion in NG108-15 cells treated with OP-l (BMP-7), a powerful inducer of L1 and N-CAM gene expression. Methods: All studies were performed by using NG108-15 cells cultured:in serum-free medium. Cell morphology was assessed by a quantitative assay of cell clustering. Cell adhesion was measured by a short-term re-aggregation assay, and isoforms of ii were characterized by RT-PCR and sequencing. Results:We show that ethanol inhibits the morphogenetic effects of BMP-2, BMP-4, BMP-5, and BMP-6, each of which increases the expression of ii and N-CAM. Pretreatment of NG108-15 cells with 25-100 mM ethanol did not induce tolerance to ethanol's inhibition of OP-1 morphogenesis or cell-cell adhesion. Ethanol or anti-ii Fab fragments partially inhibited cell-cell adhesion in OP-1-treated NG108-15 cells. The combination of ethanol and Fab fragments did not inhibit cell-cell adhesion more than Fab fragments alone. As in L1-transfected fibroblasts, a series of n-alcohols displayed a cutoff between butanol and pentanol for inhibition of cell-cell adhesion in OP-1-treated NG108-15 cells. RT-PCR and direct sequencing revealed that the neuronal isoform was the sole or predominant ii isoform in OP-lr treated NG108-15 cells. Conclusions: These data suggest that ethanol inhibits cell-cell adhesion in OP-1-treated NG108-15 cells by interacting directly or indirectly with the neuronal isoform of L1. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol 127,Neurol Serv, W Roxbury, MA 02132 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. RP Charness, ME (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Dept Neurol 127,Neurol Serv, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. FU NIAAA NIH HHS [AA11297, AA09669] NR 40 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 1999 VL 23 IS 11 BP 1711 EP 1720 DI 10.1097/00000374-199911000-00002 PG 10 WC Substance Abuse SC Substance Abuse GA 259LU UT WOS:000083896000002 PM 10591586 ER PT J AU de la Monte, SM Ghanbari, H Ghanbari, K Averback, P Wands, JR AF de la Monte, SM Ghanbari, H Ghanbari, K Averback, P Wands, JR TI AD7c-NTP biomarker for Alzheimer's disease SO ALZHEIMERS REPORTS LA English DT Review DE AD7c-NTP; Alzheimer's disease; cerebrospinal fluid; diagnostic assays; neuronal thread protein; urine ID THREAD PROTEIN EXPRESSION; CEREBROSPINAL-FLUID; ENZYME-IMMUNOASSAY; GENE-EXPRESSION; DOWN-SYNDROME; BRAIN; PATTERNS; MODULATION; PATHOLOGY; APOPTOSIS AB This article reviews the discovery and probable function of the AD7c-NTP gene and describes the sensitivity and specificity of assays used to detect elevated levels of the similar to 41 kD AD7c-NTP protein in cerebrospinal fluid and urine. In addition, we present solid evidence that both the cerebrospinal fluid and urine assays for AD7c-NTP can be used as surrogate markers and diagnostic aids to detect possible or probable Alzheimer's disease. Importantly, the AD7c-NTP assays have demonstrated value for ruling-out the diagnosis of Alzheimer's disease and alerting caretakers to pursue other potential causes of dementia or cognitive impairment. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Brown Univ, Rhode Isl Hosp, Sch Med, Providence, RI 02903 USA. NYMOX Corp, Montreal, PQ, Canada. NYMOX Corp, Rockville, MD USA. RP de la Monte, SM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 28 TC 4 Z9 4 U1 2 U2 3 PU MEDICAL SCIENCE JOURNALS PI CAMBRIDGE PA UNIV CAMBRIDGE, DEPT MEDICINE, PO BOX 157, LEVEL 5, ADDENBROOKES HOSPITAL, HILLS R, CAMBRIDGE CB2 2QQ, ENGLAND SN 1461-6130 J9 ALZHEIMERS REP JI Alzheimers Rep. PD NOV PY 1999 VL 2 IS 6 BP 327 EP 332 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 273NR UT WOS:000084714200002 ER PT J AU Sherman, SE D'Agostino, RB Silbershatz, H Kannel, WB AF Sherman, SE D'Agostino, RB Silbershatz, H Kannel, WB TI Comparison of past versus recent physical activity in the prevention of premature death and coronary artery disease SO AMERICAN HEART JOURNAL LA English DT Article ID EXERCISE; MORTALITY; HEALTH; WOMEN; MEN; DEPRESSION; STROKE AB Background People who are physically active live longer, but it is unclear whether this is because of physical activity in the distant or more recent post. Methods We assessed activity levels in 5209 men and women in the Framingham Heart Study from 1956 to 1958 and again from 1969 to 1973. We included individuals who were alive and without cardiovascular disease in the period 1969 to 1973. The primary outcome was death from all causes during the 16 years after the 1969 to 1973 assessment. Secondary outcomes were incidence and mortality rate of: cardiovascular disease. We used Cox proportional hazards regression to calculate the relative risk of being sedentary, both unadjusted and controlling for smoking, weight, systolic blood pressure, cholesterol, glucose intolerance, left ventricular hypertrophy, chronic obstructive pulmonary disease, and cancer. Results The overall 16-year mortality rate was 37% for men and 27% For women. When both distant and recent activity levels were included along with major cardiovascular disease risk Factors, for recent activity the most active tertile had lower overall mortality rate than the least active tertile for men (risk ratio 0.58, 95% confidence interval, 0.43-0.79) and women (risk ratio 0.61, 95% confidence interval, 0.45-0.82). For distant activity there was no difference in overall mortality rate between the most and least active tertiles either for men or for women. Adjusting for major cardiovascular disease risk factors had little effect on the results. Conclusions The reduction in overall mortality rates is more associated with recent activity than distant activity. These results suggest that for sedentary patients, it may never be tao late to begin exercising. C1 Sepulveda Ambulatory Care & Nursing Ctr, VA Greater Los Angeles Healthcare Syst, Primary Ambulatory Care & Educ Ctr, Sepulveda, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. RP Sherman, SE (reprint author), Vet Adm Med Ctr, PACE Ctr 00PG, 16111 Plummer St, Sepulveda, CA 91343 USA. FU NIA NIH HHS [AG 10415-01] NR 24 TC 36 Z9 39 U1 1 U2 5 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 NOV PY 1999 VL 138 IS 5 BP 900 EP 907 DI 10.1016/S0002-8703(99)70015-3 PN 1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251WD UT WOS:000083468600015 PM 10539821 ER PT J AU Mukamal, KJ Muller, JE Maclure, M Sherwood, JB Mittleman, MA AF Mukamal, KJ Muller, JE Maclure, M Sherwood, JB Mittleman, MA TI Lack of effect of recent alcohol consumption on the course of acute myocardial infarction SO AMERICAN HEART JOURNAL LA English DT Article ID HEART-DISEASE; BLOOD-FLOW; ISCHEMIC-HEART; ETHANOL; RISK; POPULATION; REPERFUSION; ANGINA; SIZE AB Background and Objective Alcohol has marked effects on hemodynamic and hemostatic variables that might alter the presentation of acute myocardial infarction that Follows its use. We sought to determine whether recent alcohol consumption alters the course or complications of acute myocardial infarction. Methods in the Determinants of Myocardial Infarction Onset Study, we performed chart reviews and face-to-face inter views with 2.161 patients who did not receive thrombolytic therapy. We assessed alcohol use before infarction, peak creatine kinase levels (1043 patients), electrocardiographic interpretations (1408 patients), and the presence of ventricular arrhythmias or congestive heart failure (all patients). Results Among the 2161 patients, 399 (18.5%) drank alcohol within 24 hours before myocardial infarction. We found no significant difference in mean peak creatine kinase level between those who had recently used alcohol and those who had not in an adjusted comparison (-6.1% difference; 95% confidence interval [Cl] -20.3%-10.7%; P = .46). We also found no differences in adjusted risk for Q-wave infarction, congestive heart failure, or ventricular arrhythmias (odds ratios 1.03 [95% CI, 0.73-1.45; P = .88], 1.01 [95% CI, 0.57-1.54; P = .95], and 1.04 [95% CI, 0.66-1.65; P = .86]). Categorization of the duration since last alcohol use into 6-hour intervals revealed no trends between time since last use of alcohol and any of these outcomes, Conclusions Recent alcohol use is not associated with changes in infarct size or risk for Q-wove infarction, congestive heart failure, or ventricular arrhythmia among this population. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. RP Mukamal, KJ (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, E Campus,330 Brookline Ave,LY-303, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL41016]; NIAAA NIH HHS [1-F32AA05534] NR 30 TC 11 Z9 11 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 NOV PY 1999 VL 138 IS 5 BP 926 EP 933 DI 10.1016/S0002-8703(99)70019-0 PN 1 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251WD UT WOS:000083468600019 PM 10539825 ER PT J AU Ardehali, A Kessler, D Foroushani, F Laks, H AF Ardehali, A Kessler, D Foroushani, F Laks, H TI Multivessel coronary artery bypass surgery without cardiopulmonary bypass SO AMERICAN HEART JOURNAL LA English DT Article ID BEATING HEART; OCTOPUS; FLOW AB Background There is limited experience with complete myocardial revascularization on a beating heart. Using a mechanical stabilization system, we sought to determine if complete coronary revascularization is feasible without cardiopulmonary bypass and what the short-term clinical outcome would be. Methods From February through September 1998, 26 patients underwent complete myocardial revascularization with Medtronics Octopus Tissue Stabilization System. Mean age for the group was 62 +/- 7 years (range 48 to 78 years); 11% had prior interventions. Mean preoperative ejection fraction was 49% +/- 14% (range 20% to 66%); 38% of operations were performed urgently. The mean number of vessels grafted was 3.0 +/- 0.9 (range 1 to 5 grafts/patient). In 96% of patients, at least one arterial graft was used. Fifteen percent of patients had 2 or more arterial grafts. In 58% of patients, a branch of circumflex coronary artery was bypassed. Results The median time to extubation was 2 hours (range 0 to 37 hours). None of the patients had perioperative myocardial infarction, cerebrovascular accident, or renal failure requiring dialysis. The 30-day survival rate was 100%. Angiographic follow-up was not available. At a mean follow-up period of 3.8 +/- 2.9 months, all patients remained free of angina and none has required cardiac reintervention. Conclusions Complete myocardial revascularization on a beating heart can be achieved with the currently available stabilization systems and is associated with low perioperative complications and satisfactory short-term clinical outcomes. The long-term outcomes and graft patency remain to be determined. C1 Univ Calif Los Angeles, Med Ctr, Div Cardiothorac Surg, Sch Med,Dept Surg, Los Angeles, CA 90095 USA. W Los Angeles Vet Adm Hosp, Dept Surg, Los Angeles, CA USA. RP Ardehali, A (reprint author), Univ Calif Los Angeles, Med Ctr, Div Cardiothorac Surg, Sch Med,Dept Surg, 62-232 CHS,10833 Le Conte Ave, Los Angeles, CA 90095 USA. NR 16 TC 5 Z9 5 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 1999 VL 138 IS 5 BP 983 EP 986 DI 10.1016/S0002-8703(99)70027-X PN 1 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251WD UT WOS:000083468600027 PM 10539833 ER PT J AU Lloyd-Jones, DM Camargo, CA Giugliano, RP Walsh, CR O'Donnell, CJ AF Lloyd-Jones, DM Camargo, CA Giugliano, RP Walsh, CR O'Donnell, CJ TI Characteristics and prognosis of patients with suspected acute myocardial infarction and elevated MB relative index but normal total creatine kinase SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CORONARY-ARTERY DISEASE; SERUM TROPONIN-T; UNSTABLE ANGINA; CK-MB; RISK; ISOENZYME; INJURY; DEATH; EVOLUTION; DIAGNOSIS AB "MB Leak" patients who develop an elevated MB rela tive index with a normal total creatine kinase (CK) level are not as well characterized as those who have diagnostic enzyme elevations in the setting of ST elevation (up arrow) or non-ST up arrow acute myocardial infarction (AMI). During a 1-year period, we studied all patients hospitalized in an urban academic hospital with suspected AMI who developed an elevated MB relative index within 24 hours of presentation. OF 595 patients, 44% had MB Leak, 34% had non-ST up arrow AMI and 22% had ST up arrow AMI. patients with MB Leak and non-ST up arrow AMI were significantly older than those with ST up arrow AMI (mean ages 69, 71, and 63 years, respectively; p <0.001), and were more likely to have previous AMI (55%, 46%, 12%; p, <0.001) or past coronary revascularization (40%, 19%, 12%; p <0.001). The in-hospital death rate of patients with MB Leak was half that of patients with non-ST up arrow AMI or ST up arrow AMI (6%, 12%, 12%; p = 0.03). By 1 year after presentation, the death rate of patients with MB Leak (17%) was intermediate between that of non-ST up arrow AMI (24%) and ST up arrow AMI (14%). Within the MB Leak group, those with elevated absolute CK-MB levels were at highest risk. In a multivariable model using MB Leak as the referent, the relative risks for 1 year death were 1.4 (95% confidence interval, 0.9 to 2.2) for patients with non-ST up arrow AM and 1.7(0.8 to 3.4) for patients with ST up arrow AMI. patients with MB Leak are at high risk for cardiovascular events in the hospital and for death by 1 year. Therefore, they may benefit from early aggressive therapy and risk stratification. These results suggest that CK-MB should be measured in all patients with suspected AMI, regardless of their total CK level. (C) 1999 by Excerpta Medica, Inc. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. RP Lloyd-Jones, DM (reprint author), NHLBI, Framingham Heart Study, 5 Thurber St, Framingham, MA 01702 USA. RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [HL-03533, HL-07575] NR 26 TC 11 Z9 12 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 NOV 1 PY 1999 VL 84 IS 9 BP 957 EP 962 DI 10.1016/S0002-9149(99)00480-4 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 252BB UT WOS:000083479900001 PM 10569646 ER PT J AU Nagurney, JT Brown, DFM Novelline, RA Kim, J Fischer, RH AF Nagurney, JT Brown, DFM Novelline, RA Kim, J Fischer, RH TI Plain abdominal radiographs and abdominal CT scans for nontraumatic abdominal pain - Added value? SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE CT scan; abdominal pain; abdominal radiographs; acute abdomen ID ACUTE ABDOMEN; DIAGNOSIS; IMPACT; MANAGEMENT; EMERGENCY AB We conducted a retrospective descriptive study to determine the value of plain abdominal radiographs in emergency department (ED) patients also receiving abdominal computed tomography scans (CT) for the evaluation of nontraumatic abdominal, back and flank pain (NTAP). Cases were identified through radiology log books. Medical records and radiology reports were reviewed to determine whether the CT confirmed the findings of the plain abdominal radiographs, and whether the clinical course confirmed the results of either, Test characteristics for the plain abdominal radiograph and for the CT, using the clinical course Including subsequent invasive procedures as the gold standard, were calculated. Of 177 patients who received CTs, 97 (55%) also received plain abdominal radiographs. Among the 74 patients who were admitted to the hospital and had complete data, the sensitivity and specificity for the plain abdominal radiographs were .43 and .75 respectively, compared to .91 and .94 for the CT scan (P-sens. <.05, P-spec. <.05). In 4 patients (5%), both studies failed to identify pathology shown in a subsequent procedure. In ED patients with NTAP, the plain abdominal radiograph may have some value as a screening tool; however, in patients in wham a CT is likely to be ordered anyway, a plain abdominal radiograph is unhelpful and often misleading. (Am J Emerg Med 1999;17:668-671. Copyright (C) 1999 by W.B. Saunders Company). C1 Massachusetts Gen Hosp, Dept Emergency Med, Clin 117, Boston, MA 02114 USA. RP Nagurney, JT (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Clin 117, 55 Fruit St, Boston, MA 02114 USA. NR 16 TC 10 Z9 10 U1 2 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 1999 VL 17 IS 7 BP 668 EP 671 DI 10.1016/S0735-6757(99)90155-9 PG 4 WC Emergency Medicine SC Emergency Medicine GA 261KZ UT WOS:000084009500010 PM 10597085 ER PT J AU Weinrauch, LA Kennedy, FJ Burger, A Gleason, RE Keough, J D'Elia, JA AF Weinrauch, LA Kennedy, FJ Burger, A Gleason, RE Keough, J D'Elia, JA TI Prospective evaluation of autonomic dysfunction in aggressive management of diabetic microangiopathy SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE autonomic dysfunction; diabetes mellitus; insulin; proteinuria ID HEART-RATE-VARIABILITY; PANCREAS TRANSPLANTATION; GLYCOSYLATED HEMOGLOBIN; KIDNEY-TRANSPLANTATION; MELLITUS; NEUROPATHY; TERM; RISK; NEPHROPATHY; MORTALITY AB Twenty-six type I diabetic nephropathy patients in a rigorous schedule for glucose control to preserve kidney function were studied to determine autonomic functional changes during 18 months. Intercurrent and nonrelated acute illness, withdrawal from the study for personal reasons, or failure to undergo testing on schedule resulted in complete data at 1 year for 26 of the original 41 patients enrolled, 24 patients completing a further 6 months. Glycohemoglobin Ale dropped for the total group from 9.0 to 7.9 at 6 months, 8.0 at 12 months, and 8.1 at 18 months (P < .01). Autonomic function tests revealed baseline results that were below the anticipated normals for age in 38% to 56% of patients. Timed ventilatory heart rate variations measured for the total group were 1.11, 1.13, 1.10, and 1.09 (normal greater than or equal to 1.20). Valsalva heart rate variations for the total group were 1.27, 1.30, 1.255, and 1.35 (normal greater than or equal to 1.50). Assumption of upright posture-related heart rate variations for the total group were 1.10, 1.07, 1.07, and 1.06 (normal greater than or equal to 1.20). Mean arterial :pressure day/night ratios for the total group were 1.04, 1.05, 1.05, and 1.08 (normal greater than or equal to 1.10). Group analysis based on differences in insulin treatment programs, levels of blood pressure, and levels of renal function revealed no significant differences from the total group or companion groups during 18 months. Patients with a glycohemoglobin Ale of <8.0% were more likely to normalize mean arterial pressure day/night ratios than those with glycohemoglobin Ale greater than or equal to 8.0%. We conclude that aggressive glucose control in diabetic patients with proteinuria for a period of 18 months resulted in a reproducible pattern of autonomic function tests during that period of time with neither worsening nor improvement. The restoration of day/night mean arterial pressure variation in a minority of patients should be studied with a larger cohort. (C) 1999 American Journal of Hypertension, Ltd. C1 Mt Auburn Hosp, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA USA. Harvard Med Sch, Dept Med, Joslin Renal Unit, Joslin Diabet Ctr, Boston, MA USA. Mayo Clin & Mayo Fdn, Mayo Med Sch, Div Endocrine, Dept Med, Rochester, MN 55905 USA. RP D'Elia, JA (reprint author), 1 Joslin Pl, Boston, MA 02215 USA. OI Weinrauch, Larry/0000-0003-1357-9528 NR 31 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD NOV PY 1999 VL 12 IS 11 BP 1135 EP 1139 DI 10.1016/S0895-7061(99)00098-9 PN 1 PG 5 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 258VL UT WOS:000083859900013 PM 10604492 ER PT J AU Burstin, HR Conn, A Setnik, G Rucker, DW Cleary, PD O'Neil, AC Orav, EJ Sox, CM Brennan, TA AF Burstin, HR Conn, A Setnik, G Rucker, DW Cleary, PD O'Neil, AC Orav, EJ Sox, CM Brennan, TA CA Harvard Emergency Dept Quality S TI Benchmarking and quality improvement: The Harvard Emergency Department Quality Study SO AMERICAN JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT 19th Annual National Meeting of the Society-of-General-Internal-Medicine CY MAY 02-04, 1996 CL WASHINGTON, D.C. SP Soc Gen Internal Med ID PUBLIC HOSPITAL EMERGENCY; HEALTH SYSTEM REFORM; PATIENT SATISFACTION; PRACTICE GUIDELINES; CARE; PHYSICIAN; MANAGEMENT; MEDICINE; LEADERS; MALPRACTICE AB PURPOSE: To determine whether feedback of comparative information was associated with improvement in medical record and patient-based measures of quality in emergency departments. SUBJECTS AND METHODS: During 1-month study periods in 1993 and 1995, all medical records for patients who presented to five Harvard teaching hospital emergency departments with one of six selected chief complaints (abdominal pain, shortness of breath, chest pain, hand laceration, head trauma, or vaginal bleeding) were reviewed for the percent compliance with process-of-care guidelines. Patient-reported problems and patient ratings of satisfaction with emergency department care were collected from eligible patients using patient questionnaires. After reviewing benchmark information, emergency department directors designed quality improvement interventions to improve compliance with the process-of-care guidelines and improve patient-reported quality measures. RESULTS: In the preintervention period, 4,876 medical records were reviewed (99% of those eligible), 2,327 patients completed on-site questionnaires (84% of those eligible), and 1,386 patients completed 10-day follow-up questionnaires (80% of a random sample of eligible participants). In the postintervention period, 6,005 medical records were reviewed (99% of those eligible), 2,899 patients completed on-site questionnaires (84% of those eligible), and 2,326 patients completed 10-day follow-up questionnaires (80% of all baseline participants). In multivariate analyses, adjusting for age, urgency, chief complaint, and site, compliance with process-of-care guidelines increased from 55.9% (preintervention) to 60.4% (postintervention, P = 0.0001). We also found a 4% decrease (from 24% to 20%) in the rate of patient-reported problems with emergency department care (P = 0.0001). There were no significant improvements in patient ratings of satisfaction. CONCLUSION: Feedback of benchmark information and subsequent duality improvement efforts led to small, although significant, improvement in compliance with process-of-care guidelines and patient-reported measures of quality. The measures that relied on patient reports of problems with care, rather than patient ratings of satisfaction with care, seemed to be more responsive to change. These results support the value of bench-marking and collaboration. Am J Med. 1999;107:437-449. (C) 1999 by Excerpta Medica, Inc. C1 Brigham & Womens Hosp, Dept Med, Div Gen Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Mt Auburn Hosp, Dept Emergency Med, Cambridge, MA USA. Beth Israel Hosp, Dept Emergency Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Brennan, TA (reprint author), Brigham & Womens Hosp, Dept Qual Management Serv, 75 Francis St, Boston, MA 02115 USA. FU AHRQ HHS [HS00062-02] NR 59 TC 57 Z9 57 U1 0 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 1999 VL 107 IS 5 BP 437 EP 449 DI 10.1016/S0002-9343(99)00269-7 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 253YC UT WOS:000083583900005 PM 10569298 ER PT J AU Azar, DT Wiley, WF AF Azar, DT Wiley, WF TI Double-knot transscleral suture fixation technique for displaced intraocular lenses SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CILIARY SULCUS; MANAGEMENT AB PURPOSE: To describe a simplified new technique for repositioning and attaching a suture to the haptic of a displaced posterior chamber intraocular lens (IOL), METHODS: We describe a double-knot technique for repositioning and transscleral suture fixation of a subluxed posterior chamber IOL after penetrating keratoplasty. Two 10-0 Prolene transscleral sutures on straight needles are passed around the IOL haptic, tied extraocularly, and used to secure the repositioned haptic of the TOL. A second knot ties the transscleral suture in the scleral bed, stabilizing the haptic in the ciliary sulcus. RESULTS: In the case described, the IOL was stable and well positioned 2 months after surgery. CONCLUSION: The double-knot technique for intraocular repositioning and transscleral suture fixation of displaced posterior chamber IOLs reduces the extensive intraocular manipulation and scleral incisions required for IOL exchange and may reduce chronic irritation associated with iris fixation. (C) 1999 by Elsevier Science Inc. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Med Coll Ohio, Toledo, OH 43699 USA. RP Azar, DT (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. NR 5 TC 23 Z9 25 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 1999 VL 128 IS 5 BP 644 EP 646 DI 10.1016/S0002-9394(99)00244-5 PG 3 WC Ophthalmology SC Ophthalmology GA 252PP UT WOS:000083511500020 PM 10577540 ER PT J AU Levine, RA AF Levine, RA TI Somatic (Craniocervical) tinnitus and the dorsal cochlear nucleus hypothesis SO AMERICAN JOURNAL OF OTOLARYNGOLOGY LA English DT Article ID BRAIN-STEM; SUPPRESSION; PROJECTIONS; HEARING; NEURONS; STIMULATION; PATHWAY; SOUND; NOISE; CATS AB Purpose: Of all nonauditory sensory systems, only the somatosensory system seems to be related to tinnitus (eg, temporomandibular joint syndrome and whiplash). The purpose of this study is to describe the distinguishing characteristics of tinnitus associated with somatic events and to use these characteristics to develop a neurological model of somatic tinnitus. Materials and Methods: Case series. Results: Some patients with tinnitus, but no other hearing complaints, share several clinical features including (1) an associated somatic disorder of the head or upper neck, (2) localization of the tinnitus to the ear ipsilateral to the somatic disorder, (3) no vestibular complaints, and (4) no abnormalities on neurological examination. Pure tone and speech audiometry of the 2 ears is always symmetric and usually within normal limits. Based on these clinical features, it is proposed that somatic (craniocervical) tinnitus, like otic tinnitus, is caused by disinhibition of the ipsilateral dorsal cochlear nucleus. Nerve fibers whose cell bodies lie in the ipsilateral medullary somatosensory nuclei mediate this effect. These neurons receive inputs from nearby spinal trigeminal tract, fasciculus cuneatus, and facial, vagal, and glossopharyngeal nerve fibers innervating the middle and external ear. Conclusions: Somatic (craniocervical) modulation of the dorsal cochlear nucleus may account for many previously poorly understood aspects of tinnitus and suggests novel tinnitus treatments. Copyright a 1999 by W.B. Saunders Company. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, Boston, MA 02114 USA. RP Levine, RA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [P01 DC00119, R21 DC03255] NR 68 TC 136 Z9 146 U1 2 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0196-0709 J9 AM J OTOLARYNG JI Am. J. Otolaryngol. PD NOV-DEC PY 1999 VL 20 IS 6 BP 351 EP 362 DI 10.1016/S0196-0709(99)90074-1 PG 12 WC Otorhinolaryngology SC Otorhinolaryngology GA 257GX UT WOS:000083775100001 PM 10609479 ER PT J AU Staecker, H Chow, H Nadol, JB AF Staecker, H Chow, H Nadol, JB TI Osteomyelitis, lateral sinus thrombosis, and temporal lobe infarction caused by infection of a percutaneous cochlear implant SO AMERICAN JOURNAL OF OTOLOGY LA English DT Article DE complications; cochlear implants; lateral sinus thrombosis; percutaneous ID SURGICAL COMPLICATIONS; PROSTHESES; TISSUE AB Objective: Cochlear implantation has become a routine operation in the last 10 years. The most common soft tissue complications with transcutaneous cochlear implants include infection or necrosis of the flap and extrusion of the implant and device failure. The most common complication reported with percutaneous devices include minor skin irritations at the pedestal site, retraction of skin from the pedestal site, and loosening of screws that retain the pedestal. We describe one case of lateral sinus thrombosis and secondary temporal lobe infarction caused by infection of a screw anchoring the percutaneous pedestal of an Ineraid implant. Study Design: Case report. Setting: Tertiary referral center. Conclusions: Intracranial complications of a percutaneous bone-anchored pedestal may occur with little prodrome. Computed tomography (CT) scan of the pedestal and bone anchoring screws may be indicated if local evidence of infection persists. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Staecker, H (reprint author), Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, 243 Charles St, Boston, MA 02114 USA. OI Staecker, Hinrich/0000-0002-0348-3015 NR 15 TC 12 Z9 12 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-9763 J9 AM J OTOL JI Am. J. Otol. PD NOV PY 1999 VL 20 IS 6 BP 726 EP 728 PG 3 WC Otorhinolaryngology SC Otorhinolaryngology GA 392UT UT WOS:000166431500005 PM 10565715 ER PT J AU Walsh, S Murphy, M Silverman, M Odze, R Antonioli, D Goldman, H Loda, M AF Walsh, S Murphy, M Silverman, M Odze, R Antonioli, D Goldman, H Loda, M TI p27 expression in inflammatory bower disease-associated neoplasia - Further evidence of a unique molecular pathogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol ID ULCERATIVE-COLITIS; CELL-CYCLE; COLORECTAL TUMORIGENESIS; INHIBITOR P27(KIP1); MUTATIONS OCCUR; GENE-MUTATIONS; MICE LACKING; CANCER; DIFFERENTIATION; DYSPLASIA AB The cyclin-dependent kinase inhibitor p27 is a negative regulator of the transition from G1 to S phase of the cell cycle, protects against inflammatory injury and promotes epithelial differentiation. Because p27 protein has been shown to be abnormally expressed both in dysplasia associated with Barrett's esophagus and in sporadic colorectal adenomas, we used immunohistochemistry to evaluate p27 expression in inflammatory bowel disease (IBD)-associated dysplasia and carcinomas. Normal, inflamed, and transitional mucose, sporadic adenomas, and sporadic colonic carcinomas were studied as controls. In normal colonic epithelium p27 expression was restricted to the superficial, terminally differentiated cells. In colitic and inflamed diverticular mucosa p27 was expressed in the base of the crypts in 86 and 70% of cases, respectively. Similarly, in transitional mucosa adjacent to sporadic carcinomas p27 was expressed in the base of the crypts in all cases. Strong p27 expression extended more frequently from the base of the crypts to superficial cells in IBD-associated dysplasia than in sporadic adenomas (P < 0.007). Twenty of 20 (100%) IBD-associated carcinomas showed low p27 expression (<50% nuclei positive) compared to 6 of 20 (30%) stage-matched sporadic colorectal carcinomas (P < 0.001). We conclude (i) aberrant p27 protein expression in inflamed and IBD-associated nondysplastic mucosa is indistinguishable from that found in transitional mucosa adjacent to sporadic carcinomas; (ii) p27 is overexpressed in dysplastic lesions, perhaps as an attempt to counterbalance proliferative stimuli; and (iii) IBD-associated colorectal carcinomas have significantly lower p27 expression, commonly associated with poor prognosis, than stage-matched sporadic colorectal carcinomas. These findings further substantiate the existence of divergent molecular pathogenetic pathways between these types of carcinomas and suggest an intrinsically more aggressive behavior of IBD-associated colon carcinomas compared to sporadic ones. C1 Harvard Univ, Dept Adult Oncol, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Lahey Hitchcock Med Ctr, Dept Pathol, Burlington, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Loda, M (reprint author), Harvard Univ, Dept Adult Oncol, Dana Farber Canc Inst, Sch Med, Dana 740B,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA5PO1CA44704-10] NR 53 TC 29 Z9 30 U1 0 U2 2 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 NOV PY 1999 VL 155 IS 5 BP 1511 EP 1518 DI 10.1016/S0002-9440(10)65466-1 PG 8 WC Pathology SC Pathology GA 253ZT UT WOS:000083587600016 PM 10550307 ER PT J AU Yuan, PQ Yang, H AF Yuan, PQ Yang, H TI Hypothyroidism induces Fos-like immunoreactivity in ventral medullary neurons that synthesize TRH SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE thyroid hormones; thyroxine; raphe pallidus; raphe obscurus; parapyramidal regions ID THYROTROPIN-RELEASING-HORMONE; DORSAL VAGAL COMPLEX; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; GASTRIC-ACID SECRETION; THYROID-HORMONE; GENE-EXPRESSION; C-FOS; NERVOUS-SYSTEM; RAT HYPOTHALAMUS; RAPHE PALLIDUS AB Altered thyroid statuses are associated with autonomic disorders. Thyrotropin-releasing hormone (TRH) in medullary nuclei regulates vagal efferent activity. Induction of Fos-like immunoreactivity (IR) in medullary TRH-synthesizing neurons was investigated in 24-h fasted rats with different thyroid statuses. Hypo- and hyperthyroidism were induced by 6-N-propyl-2-thiouracil (PTU) in drinking water and a daily intraperitoneal injection of thyroxine (T-4; 10 mu g.100 g(-1).day(-1)), respectively, for 1-4 mk. The numbers of Fos-like IR positive neurons in the raphe pallidus, raphe obscurus, and parapyramidal regions, which were low in euthyroid rats (0-2/section), increased remarkably as the hypothyroidism progressed and were negatively correlated with serum T-4 levels. At the 4th wk, Fos-like IR positive neurons were 10- to 70-fold higher compared with euthyroid controls. Simultaneous T-4 replacement (2 mu g.100 g(-1).day(-1)) prevented the increases of Fos-like IR in PTU-treated rats. Hyperthyroidism did not change the number of Fos-like IR neurons in the raphe nuclei but reduced it in the parapyramidal regions. Double immunostaining revealed that most of the Fos-like IR induced by hypothyroidism was located in the prepro-TRH IR positive neurons. The selective and sustained induction of Fos-like IR in TRH-synthesizing neurons in ventral medullary nuclei by hypothyroidism indicates that these neurons play a role in the autonomic disorders observed in altered thyroid statuses. C1 W Los Angeles Vet Affairs Med Ctr, CURE, DDRC, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. RP Yang, H (reprint author), W Los Angeles Vet Affairs Med Ctr, CURE, DDRC, 11301 Wilshire Blvd,Bldg 115,Rm 203, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK-41301, DK-50255] NR 63 TC 10 Z9 10 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 NOV PY 1999 VL 277 IS 5 BP E927 EP E936 PG 10 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 254EJ UT WOS:000083598700021 PM 10567022 ER PT J AU Hartwig, W Werner, J Jimenez, RE Z'Graggen, K Weimann, J Lewandrowski, KB Warshaw, AL Fernandez-Del Castillo, C AF Hartwig, W Werner, J Jimenez, RE Z'Graggen, K Weimann, J Lewandrowski, KB Warshaw, AL Fernandez-Del Castillo, C TI Trypsin and activation of circulating trypsinogen contribute to pancreatitis-associated lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article; Proceedings Paper CT 1998 Meeting of the American-Pancreatic-Association CY NOV 05-06, 1998 CL CHICAGO, ILLINOIS SP Amer Pancreat Assoc DE acute pancreatitis; proteases; leukocytes ID RESPIRATORY-DISTRESS SYNDROME; NECROTIZING PANCREATITIS; VASCULAR-PERMEABILITY; NEUTROPHILS; PATHOGENESIS; COMPLEMENT; SERUM; PREDICTION; ZYMOGENS; ASSAY AB Pancreatic proteases are secreted in acute pancreatitis, but their contribution to associated lung injury is unclear. Applying models of mild edematous (intravenous caerulein) and severe necrotizing (intraductal glycodeoxycholic acid) pancreatitis in rats, we showed that both trypsinogen and trypsin concentrations in peripheral blood, as well as lung injury, correlate with the severity of the disease. To isolate the potential contribution of proteases to lung injury, trypsin or trypsinogen was injected into healthy rats or trypsinogen secreted in caerulein pancreatitis was activated by intravenous enterokinase. Pulmonary injury induced by protease infusions was dose dependent and was ameliorated by neutrophil depletion. Trypsinogen activation worsened lung injury in mild pancreatitis. In vitro incubation of leukocytes with trypsinogen showed that stimulated leukocytes can convert trypsinogen to trypsin. In conclusion, this study demonstrates that the occurrence and severity of pancreatitis-associated lung injury (PALI) corresponds to the levels of circulating trypsinogen and its activation to trypsin. Neutrophils are involved in both protease activation and development of pulmonary injury. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Fernandez-Del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, WACC 336,15 Parkman St, Boston, MA 02114 USA. NR 41 TC 52 Z9 53 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1999 VL 277 IS 5 BP G1008 EP G1016 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 257YN UT WOS:000083810500013 PM 10564107 ER PT J AU Quaroni, A Tian, JQ Goke, M Podolsky, DK AF Quaroni, A Tian, JQ Goke, M Podolsky, DK TI Glucocorticoids have pleiotropic effects on small intestinal crypt cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE cell proliferation; steroid receptors; cyclin-dependent kinase inhibitors; p21(WAF/Cip1); p27(Kip1) ID GROWTH-FACTOR-BETA; RAT SMALL-INTESTINE; SUCRASE-ISOMALTASE GENE; EPITHELIAL-CELLS; TRANSCRIPTIONAL ELEMENTS; MONOCLONAL-ANTIBODIES; POSTNATAL-DEVELOPMENT; MEMBRANE-PROTEIN; HEPATOMA-CELLS; FACTOR-ALPHA AB Glucocorticoids have long been known to accelerate maturation of the intestinal tract, but the molecular mechanisms that account for their physiological function in the epithelium remain poorly characterized. Using rat intestinal epithelial cell lines (IEC-B, IEC-17, and IEC-18) as models, we have characterized glucocorticoid receptors in crypt cells and documented striking morphological, ultrastructural, and functional alterations induced by these hormones in intestinal cells. They include arrest of growth, formation of tight junctions, appearance of long, slender microvilli, reorganization of the endoplasmic reticulum and trans-Golgi network, and downregulation of the cell cycle regulatory proteins cyclin-dependent kinase 6 and p27(Kip1). These effects are consistent with the activation or modulation of multiple genes important in the physiological function of absorptive villous cells but are probably not directly involved in the induction of cell differentiation. C1 Cornell Univ, Physiol Sect, Ithaca, NY 14853 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Quaroni, A (reprint author), Cornell Univ, Physiol Sect, T8 008A VRT, Ithaca, NY 14853 USA. FU NIDDK NIH HHS [DK-48331] NR 71 TC 48 Z9 48 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 1999 VL 277 IS 5 BP G1027 EP G1040 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 257YN UT WOS:000083810500015 PM 10564109 ER PT J AU Mannstadt, M Juppner, H Gardella, TJ AF Mannstadt, M Juppner, H Gardella, TJ TI Receptors for PTH and PTHrP: their biological importance and functional properties SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE parathyroid hormone; peptide hormone family; class II G protein-coupled receptor; receptor binding; signal transduction; structure-activity relationship; receptor mutagenesis; photochemical cross-linking; constitutively active receptor; receptor mutations in human disease; parathyroid hormone-related peptide ID HORMONE-RELATED PEPTIDE; PSEUDOHYPOPARATHYROIDISM TYPE-IB; MESSENGER-RIBONUCLEIC-ACID; PROTEIN-COUPLED RECEPTORS; VASOACTIVE INTESTINAL POLYPEPTIDE; OSTEOCLAST DIFFERENTIATION FACTOR; ENDOCHONDRAL BONE-FORMATION; CARBOXYL-TERMINAL REGION; HUMAN PTH/PTHRP RECEPTOR; C ACTIVATION DOMAIN AB Receptors for PTH and PTHrP: their biological importance and functional properties. The type 1 receptor (PTH1R) for parathyroid hormone (PTH)and parathyroid hormone-related peptide (PTHrP) is a G protein-coupled receptor that is highly expressed in bone and kidney and mediates in these tissues the PTH-dependent regulation of mineral ion homeostasis. The PTH1R also mediates the paracrine actions of PTHrP, which play a particularly vital role in the process of endochondral bone formation. These important functions, the likely involvement of the PTH1R in certain genetic diseases affecting skeletal development and calcium homeostasis, and the potential utility of PTH in treating osteoporosis have been the driving force behind intense investigations of both the receptor and its peptide ligands. Recent lines of work have led to the identification of constitutively active PTH1Rs in patients with Jansen's metaphyseal chondrodysplasia, the demonstration of inverse agonism by certain ligand analogs, and the discovery of the PTH-2 receptor subtype that responds to PTH but not PTHrP. As reviewed herein, a detailed exploration of the receptor-ligand interaction process is currently being pursued through the use of site-directed mutagenesis and photoaffinity cross-linking methods; ultimately, such work could enable the development of novel PTH receptor ligands that have therapeutic value in treating diseases such as osteoporosis and certain forms of hypercalcemia. C1 Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pediat, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Dept Med & Pediat, Endocrine Unit, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu NR 123 TC 109 Z9 110 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 1999 VL 277 IS 5 BP F665 EP F675 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 258BN UT WOS:000083818300001 PM 10564229 ER PT J AU Rigotti, NA Arnsten, JH McKool, KM Wood-Reid, KM Singer, DE Pasternak, RC AF Rigotti, NA Arnsten, JH McKool, KM Wood-Reid, KM Singer, DE Pasternak, RC TI The use of nicotine-replacement therapy by hospitalized smokers SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE smoking cessation; nicotine; tobacco use disorder; hospitalization ID SMOKING-CESSATION; TRIAL AB Background: No-smoking policies are mandatory in U.S. hospitals. Consequently, smokers who are hospitalized must temporarily stop smoking. Nicotine-replacement therapy (NRT) could help hospitalized smokers relieve nicotine withdrawal symptoms, comply with no-smoking policies, and sustain tobacco abstinence after discharge. The extent of NRT use in the hospital setting is unknown. We describe the prevalence and patterns of NRT use in hospitalized smokers. Design: Prospective observational study within a randomized smoking-intervention trial. Setting/Participants: Six hundred fifty adult smokers admitted to the medical and surgical services of a large urban teaching hospital that prohibits smoking in all indoor areas. Follow-up was at 6 months. Main Outcome Measure: Inpatient pharmacy records of nicotine patch or gum use. Results: Only 34 of 650 smokers (5.2%) received NRT during their hospital stay, including only 9.6% of smokers who reported difficulty refraining from smoking while hospitalized and 9.0% of hospitalized smokers with nicotine withdrawal. NRT was more likely to be prescribed to patients with nicotine withdrawal (OR 2.23; 95% CI: 1.01, 4.90), a higher daily cigarette consumption (OR 1.04; 95% CI: 1.01, 1.06), and a longer hospitalization (OR 1.05; 95% CI: 1.00, 1.10). NRT use was independent of a patient's intention to quit smoking after discharge and was not associated with smoking cessation 1 and 6 months after discharge. Conclusions: NRT was rarely used in this hospital, even among those who could have benefited from it to treat nicotine-withdrawal symptoms. When NRT was used, relief of nicotine withdrawal, rather than assistance with smoking cessation, appeared to be the primary goal. Greater use of NRT could benefit the estimated 6.5 million smokers who are hospitalized annually by reducing nicotine withdrawal, encouraging smoking cessation, and ensuring compliance with hospital no-smoking policies. C1 Massachusetts Gen Hosp, Gen Internal Med Unit, Tobacco Res & Treatment Program, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Rigotti, NA (reprint author), Massachusetts Gen Hosp, Gen Internal Med Unit, Tobacco Res & Treatment Program, Dept Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NCI NIH HHS [CA01673] NR 22 TC 27 Z9 28 U1 1 U2 2 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 NOV PY 1999 VL 17 IS 4 BP 255 EP 259 DI 10.1016/S0749-3797(99)00095-1 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 252HL UT WOS:000083496000001 PM 10606193 ER PT J AU Goisman, RM Warshaw, MG Keller, MB AF Goisman, RM Warshaw, MG Keller, MB TI Psychosocial treatment prescriptions for generalized anxiety disorder, panic disorder, and social phobia, 1991-1996 SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Pharmacologic prescriptions for anxiety disorders have changed significantly in the last decade. This article investigates whether psychosocial treatments, as reported by 362 subjects in the Harvard/Brown Anxiety Disorders Research Program from 1991 to 1996, changed as well. Method: Subjects were interviewed in 1991 and 1995-1996 to determine which psychosocial treatments (behavioral, cognitive, dynamic, or relaxation or meditation) they had received. Results: The percentage of subjects who received each type of psychosocial treatment either declined or remained the same from 1991 to 1995-1996. Dynamic psychotherapy remained the most frequently used method of these four. The percentage of subjects receiving any such method declined. Conclusions: Behavioral and cognitive treatment, two empirically validated forms of psychotherapy, were less frequently used than dynamic psychotherapy, which lacks such validation. All use of verbal treatment methods declined from 1991 to 1995-1996. C1 Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Boston, MA USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Butler Hosp, Providence, RI 02906 USA. RP Goisman, RM (reprint author), Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. FU NIMH NIH HHS [R01 MH051415, MH-51415] NR 9 TC 115 Z9 117 U1 2 U2 7 PU AMER PSYCHIATRIC PRESS, INC PI WASHINGTON PA 1400 K ST, N W, STE 1101, WASHINGTON, DC 20005 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 1999 VL 156 IS 11 BP 1819 EP 1821 PG 3 WC Psychiatry SC Psychiatry GA 251LA UT WOS:000083446100026 PM 10553751 ER PT J AU Kirmse, M Fujino, Y Hromi, J Mang, H Hess, D Kacmarek, RM AF Kirmse, M Fujino, Y Hromi, J Mang, H Hess, D Kacmarek, RM TI Pressure-release tracheal gas insufflation reduces airway pressures in lung-injured sheep maintaining eucapnia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; CONTROL VENTILATION; PERMISSIVE HYPERCAPNIA; MECHANICAL VENTILATION; TIDAL VOLUME; CATHETER; MODEL; DOGS; FLOW; COMBINATION AB Although tracheal gas insufflation (TCI) has proved to be a useful adjunct to mechanical ventilation, end-inspiratory as well as end-expiratory pressures may increase. We investigated the ability of continuous-flow TCI to maintain eucapnia while reducing airway pressure (Paw) and tidal volume (VT). Seven sheep (36 +/- 2 kg) were ventilated using the Drager Evita 4 in the pressure control plus mode where flow is released via the expiratory valve to maintain constant inspiratory pressure. To avoid TCI-generated positive end-expiratory pressure (PEEP), a prototype reverse flow TCI tube was used. Two TCI flows (5 and 10 L/min) were investigated pre- and postsaline lavage-induced lung injury. inspiratory pressures and VT were significantly reduced as TGI flow increased. At 10 L/min TCI flow the carinal pressures (Pcar) and VT were reduced pre- and postinjury by 15% and 20%, and by 28% and 34%, respectively. Tidal volume to dead space ratio (V-D/V-T) decreased preinjury from 0.49 +/- 0.1 to 0.18 +/- 0.2 and postinjury from 0.62 +/- 0.1 to 0.33 +/- 0.1 at a TGI flow of 10 L/min. The combination of the reverse flow TCI tube and a ventilator with an inspiratory pressure relief mechanism kept set end-inspiratory and end-expiratory pressures constant. This TCI system effectively reduced set Paw and Vr while maintaining eucapnia. C1 Massachusetts Gen Hosp, Resp Care Dept Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Kacmarek, RM (reprint author), Massachusetts Gen Hosp, Resp Care Dept Lab, Boston, MA 02114 USA. NR 24 TC 10 Z9 10 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 NOV PY 1999 VL 160 IS 5 BP 1462 EP 1467 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 258KQ UT WOS:000083838700005 PM 10556106 ER PT J AU Reiner, B Siegel, E Protopapas, Z Hooper, F Ghebrekidan, H Scanlon, M AF Reiner, B Siegel, E Protopapas, Z Hooper, F Ghebrekidan, H Scanlon, M TI Impact of filmless radiology on frequency of clinician consultations with radiologists SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 96th Annual Meeting of the American-Roentgen-Ray-Society CY MAY 05-10, 1996 CL SAN DIEGO, CALIFORNIA SP Amer Roentgen Ray Soc ID SERVICE AB OBJECTIVE. The purpose of the study was to determine the impact of filmless operation on the relative frequency of in-person consultations in the radiology department between radiologists and clinicians. CONCLUSION. The transition to filmless operation at the Baltimore Veterans Affairs Medical Center was associated with an 82% reduction in the in-person consultation rate for general radiography and a 44% reduction for cross-sectional imaging despite an increase in the volume of studies. The major reason for this decrease was the convenient access to current and prior images provided by the PACS (picture archiving and communication system). Radiology departments contemplating a transition to filmless operation should prepare for communication with clinicians to shift from being mostly in person to being conducted more and more through electronic forms of communication. C1 Vet Affairs Maryland Hlth Care Syst, Dept Radiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Radiol, Baltimore, MD 21201 USA. Amer Radiol Serv, Baltimore, MD 21208 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Philadelphia Vet Affairs Med Ctr, Dept Radiol, Philadelphia, PA 19104 USA. RP Siegel, E (reprint author), Vet Affairs Maryland Hlth Care Syst, Dept Radiol, 10 N Greene St, Baltimore, MD 21201 USA. NR 21 TC 62 Z9 63 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 NOV PY 1999 VL 173 IS 5 BP 1169 EP 1172 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 249BM UT WOS:000083312300004 PM 10541082 ER PT J AU Lev, MH Schaefer, PW AF Lev, MH Schaefer, PW TI Subarachnoid gadolinium enhancement mimicking subarachnoid hemorrhage on FLAIR MR images SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 5 TC 10 Z9 10 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 NOV PY 1999 VL 173 IS 5 BP 1414 EP 1415 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 249BM UT WOS:000083312300058 PM 10541135 ER PT J AU Cuadra-Garcia, I Proulx, GM Wu, CL Wang, CC Pilch, BZ Harris, NL Ferry, JA AF Cuadra-Garcia, I Proulx, GM Wu, CL Wang, CC Pilch, BZ Harris, NL Ferry, JA TI Sinonasal lymphoma - A clinicopathologic analysis of 58 cases from the Massachusetts General Hospital SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Lymphoma; Nasal; Paranasal sinus; T cell; B cell; natural killer cell; Epstein-Barr virus; HIV ID NON-HODGKINS-LYMPHOMA; EPSTEIN-BARR-VIRUS; T-CELL LYMPHOMA; PARA-NASAL SINUSES; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN-IMMUNODEFICIENCY-VIRUS; LETHAL MIDLINE GRANULOMA; PARANASAL SINUSES; POLYMORPHIC-RETICULOSIS; IMMUNOPHENOTYPIC ANALYSIS AB Few large series compare lymphomas of the nasal cavity with those of the paranasal sinuses. We studied the cases of 58 patients, 34 males and 24 females, aged 7 to 92 years (mean, 57 years), who had lymphoma involving the nasal cavity or paranasal sinuses. Thirty-three patients had diffuse large B-cell lymphoma (DLBCL). Twenty-three were male and 10 were female, with an age range of 7 to 91 years (mean, 63 years); two were HIV-positive. Only 2 of 11 cases tested tone in an HIV-positive patient and one of lymphomatoid granulomatosis type) were Epstein-Barr virus (EBV)-positive. Thirty (91%) involved paranasal sinuses, 10 with nasal involvement, whereas three cases had nasal, but not sinus, involvement. At last follow-up, 16 (67%) were free of disease 7 to 169 months later (mean, 65 months), and 8 (33%) had died of disease 2 to 166 months later (mean, 45 months). Seventeen patients had nasal-type natural killer (NK)/T-cell lymphoma. There were 10 women and 7 men, aged 27 to 78 years (mean, 48 years). Thirteen of 14 were EBV-positive. Sixteen patients had nasal involvement, eight with sinus involvement. Eleven (73%) of 15 were alive and well 6 to 321 months later(mean, 139 months), three (20%) died of lymphoma 1, 11, and 12 months later, and one (7%) is alive with disease. There was one case each of marginal zone B-cell lymphoma, Burkitt's lymphoma, Burkitt-like lymphoma, peripheral T-cell lymphoma of unspecified type, and adult T-cell lymphoma/leukemia. In an additional three cases, the lymphomas were composed predominantly of large cells, but no immunophenotyping could be performed for subclassification. In 19 cases (17 DLBCLs, 1 Burkitt-like lymphoma, and 1 lymphoma of uncertain Lineage), presenting symptoms included complaints related to the eyes. In 16 cases (13 DLBCLs, 1 Burkitt-like lymphoma, 1 nasal NK/T-cell lymphoma, and 1 lymphoma of uncertain lineage), the orbit was invaded by lymphoma. In our series, the most common lymphoma to arise in the sinonasal area is DLBCL, followed by nasal NK/T-cell lymphoma. Comparison of these two types of lymphoma showed that lymphomas involving sinuses without nasal involvement were predominantly DLBCLs (20 of 21), whereas nasal cavity lymphomas without sinus involvement were usually NK/T-cell type (8 of 11) (p = 0.000125). Compared with patients with DLBCL, patients with nasal NK/T-cell lymphoma were overall younger, with a lower male-to-female ratio. Lymphomas of B-cell lineage were more likely to be associated with symptoms related to the eyes (p < 0.0005) and to have extension to the orbit (p < 0.01) than were lymphomas of T- or NK-cell lineage. In contrast to results of Asian studies in which nasal NK/T-cell lymphoma has a very poor prognosis, our nasal NK/T-cell lymphomas had an outcome similar to that of DLBCL. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Roswell Pk Canc Inst, Dept Radiat Med, Buffalo, NY 14263 USA. Inst Mexicano Segura Social, Ctr Med Nacl Siglo XXI, Hosp Oncol, Dept Patol, Mexico City, DF, Mexico. RP Ferry, JA (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 56 TC 86 Z9 96 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1999 VL 23 IS 11 BP 1356 EP 1369 DI 10.1097/00000478-199911000-00006 PG 14 WC Pathology; Surgery SC Pathology; Surgery GA 251VW UT WOS:000083467900006 PM 10555004 ER PT J AU Rosenberg, AE Nielsen, GP Keel, SB Renard, LG Fitzek, MM Munzenrider, JE Liebsch, NJ AF Rosenberg, AE Nielsen, GP Keel, SB Renard, LG Fitzek, MM Munzenrider, JE Liebsch, NJ TI Chondrosarcoma of the base of the skull - A clinicopathologic study of 200 cases with emphasis on its distinction from chordoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE chondrosarcoma; chordoma; skull base; immunohistochemistry; radiation therapy; prognosis ID CRANIAL BASE; MYXOID CHONDROSARCOMA; CARTILAGINOUS TUMORS; CHONDROID CHORDOMA AB Conventional chondrosarcoma (CSA) of the skull base is an uncommon neoplasm that can resemble chordoma, and indeed it is misdiagnosed frequently as such. This has important clinical implications, because when heated with similar aggressive treatment strategies, CSA has a much better prognosis than chordoma. In an effort to identify those morphologic nd immunohistochemical features that help to identify conventional skull base CSA correctly and to understand its prognosis better, particularly compared with chordoma, when treated with sugery and proton beam irradiation, the authors performed a clinicopathologic analysis of 200 CSAs. The patients ranged in age from 10 to 79 years (mean, 39 years), 87 patients were male and 113 patients were female, and most presented with symptoms related to the central nervous system. Approximately 6% of the tumors arose in the sphenoethmoid complex, 28% originated in the clivus, and 66% developed in the tempero-occipital junction. Histologically, 15 tumors (7.5%) were classified as hyaline CSA, 59 (29.5%) as myxoid CSA, and 126 (63%) as mixed hyaline and myxoid CSA. A total of 101 (50.5%) tumors were grade 1, 57 (28.5%) had areas of grades 1 and 2, and 42 (21%) were pure grade 2 neoplasms. The vast majority of patients originated from referring hospitals,and the diagnosis was changed prospectively at our institution to CSA from chordoma in 74 patients (37%). Of the tumors studied immunohistochemically, 96 of 97 (98.9%) stained for S-100 protein, 0 of 97 (0%) stained for keratin, and faint staining for epithelial membrane antigen was seen in 7 of 88 tumors (7.95%). All patients underwent high-dose postoperative fractionated precision conformal radiation therapy with a dose that ranged from 64.2 to 79.6 Cobalt-Gray-equivalents (median, 72.1 Cobalt-Gray-equivalents, given in 38 fractions. The 200 patients had a median follow-up of 63 months (range, 2.1 mos-18.5 yrs). Tumor control was defined as lack of progression by clinical and radiographic assessment. Based on this definition, there were three local recurrences, and two of these patients died of tumor-related complications. The 5- and 10-year local control rates were 99% and 98% respectively, and the 5- and 10-year disease-specific survival rates were both 99%. In contrast to CSA, the 5- and 10-year survival rates of chordoma have been reported to be approximately 51% and 35% respectively, and in our institution intensive treatment has resulted in 5- and 10-year progression-free survival rates of 70% and 45% respectively. CSA of the skull base can be distinguished reliably from chordoma, and this distinction is important because skull base CSA has an excellent prognosis when treated with surgery and proton beam irradiation, whereas chordomas have a substantially poorer clinical course despite similar aggressive management. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Rosenberg, AE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, 32 Fruit St, Boston, MA 02114 USA. NR 26 TC 140 Z9 152 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 1999 VL 23 IS 11 BP 1370 EP 1378 DI 10.1097/00000478-199911000-00007 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 251VW UT WOS:000083467900007 PM 10555005 ER PT J AU Yusin, JS Crawford, WW Klaustermeyer, WB AF Yusin, JS Crawford, WW Klaustermeyer, WB TI Facial edema, oral ulcers, and a cutaneous eruption following a dental procedure utilizing diflunisal and mepivacaine SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID ALLERGIC REACTION; HYPERSENSITIVITY C1 VA Greater Los Angeles VA Hlth Care Syst, Med Serv, Allergy & Immunol Div, Los Angeles, CA 90073 USA. VA Greater Los Angeles VA Hlth Care Syst, Res Serv, Allergy & Immunol Div, Los Angeles, CA 90073 USA. W Los Angeles VA Med Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Klaustermeyer, WB (reprint author), VA Greater Los Angeles VA Hlth Care Syst, Med Serv, Allergy & Immunol Div, 111R,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. NR 20 TC 2 Z9 2 U1 0 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD NOV PY 1999 VL 83 IS 5 BP 353 EP 355 DI 10.1016/S1081-1206(10)62830-X PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 259KA UT WOS:000083892000003 PM 10582713 ER PT J AU Augood, SJ Martin, DM Ozelius, LJ Breakefield, XO Penney, JB Standaert, DG AF Augood, SJ Martin, DM Ozelius, LJ Breakefield, XO Penney, JB Standaert, DG TI Distribution of the mRNAs encoding torsinA and torsinB in the normal adult human brain SO ANNALS OF NEUROLOGY LA English DT Article ID DOPA-RESPONSIVE DYSTONIA; MESSENGER-RNA; GENE DYT1; PARKINSONISM; EXPRESSION; NEURONS; BINDING; FAMILY; DRUGS; CELLS AB To gain insight into the neural pathways involved in the pathogenesis of DYT1 dystonia, we have mapped the cellular expression of the mRNA encoding torsinA and the closely related family member, torsinB, in normal adult human brain. Here, we report an intense expression of torsinA mRNA in the substantia nigra pars compacta dopamine neurons, the locus ceruleus, the cerebellar dentate nucleus, Purkinje cells, the basis pontis, numerous thalamic nuclei, the pedunculopontine nucleus, the oculomotor nucleus, the hippocampal formation, and the frontal cortex. Within the caudate-putamen, the cellular expression of torsinA mRNA was heterogeneous; a moderate signal was found overlying large cholinergic neurons, and most striatal neurons exhibited only a very weak signal. A moderate signal was detected in numerous midbrain and hindbrain nuclei. A weak cellular signal was detected in neurons of the globus pallidus and subthalamic nucleus. In marked contrast to torsinA, no specific mRNA signal was detected for torsinB. That torsinA mRNA is enriched in several basal ganglia nuclei, including the dopamine neurons in the substantia nigra, is intriguing since it suggests that DYT1 dystonia may be associated with a dysfunction in dopamine transmission. C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Augood, SJ (reprint author), Massachusetts Gen Hosp, Neurol Serv, WRN 408,32 Fruit St, Boston, MA 02114 USA. OI Standaert, David/0000-0003-2921-8348 FU NINDS NIH HHS [NS28384, NS31579, NS31862] NR 37 TC 91 Z9 96 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1999 VL 46 IS 5 BP 761 EP 769 DI 10.1002/1531-8249(199911)46:5<761::AID-ANA12>3.0.CO;2-Z PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 252JH UT WOS:000083498000012 PM 10553994 ER PT J AU Nygaard, TG Raymond, D Chen, CP Nishino, I Greene, PE Jennings, D Heiman, GA Klein, C Saunders-Pullman, RJ Kramer, P Ozelius, LJ Bressman, SB AF Nygaard, TG Raymond, D Chen, CP Nishino, I Greene, PE Jennings, D Heiman, GA Klein, C Saunders-Pullman, RJ Kramer, P Ozelius, LJ Bressman, SB TI Localization of a gene for myoclonus-dystonia to chromosome 7q21-q31 SO ANNALS OF NEUROLOGY LA English DT Article ID DOMINANT INHERITANCE; LINKAGE ANALYSIS; MUTATIONS; ALCOHOL; EPILEPSY; FAMILY AB Essential myoclonus-dystonia is a neurological condition characterized by myoclonic and dystonic muscle contractions and the absence of other neurological signs or laboratory abnormalities; it is often responsive to alcohol. The disorder may be familial with apparent autosomal dominant inheritance. We report a large kindred with essential familial myoclonus-dystonia and map a locus for the disorder to a 28-cM region of chromosome 7q21-q31. C1 Vet Adm Med Ctr, Dept Neurol, E Orange, NJ 07019 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurosci, Newark, NJ 07103 USA. Beth Israel Med Ctr, Dept Neurol, New York, NY 10003 USA. Columbia Univ, Dept Neurol, New York, NY USA. Columbia Univ, Dept Psychiat, New York, NY USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Charlestown, MA USA. Albert Einstein Coll Med, Dept Neurol, Bronx, NY 10467 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA. RP Bressman, SB (reprint author), Beth Israel Med Ctr, Phillips Ambulatory Care Ctr, Dept Neurol, 10 Union Sq E,Suite 2R, New York, NY 10003 USA. OI Nishino, Ichizo/0000-0001-9452-112X FU NINDS NIH HHS [R01 NS26656] NR 20 TC 70 Z9 71 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 1999 VL 46 IS 5 BP 794 EP 798 DI 10.1002/1531-8249(199911)46:5<794::AID-ANA19>3.0.CO;2-2 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 252JH UT WOS:000083498000019 PM 10554001 ER PT J AU Fields-Jones, S Koletsky, A Wilding, G O'Rourke, M O'Rourke, T Eckardt, J Yates, B McGuirt, C Burris, HA AF Fields-Jones, S Koletsky, A Wilding, G O'Rourke, M O'Rourke, T Eckardt, J Yates, B McGuirt, C Burris, HA TI Improvements in clinical benefit with vinorelbine in the treatment of hormone-refractory prostate cancer: A phase II trial SO ANNALS OF ONCOLOGY LA English DT Article DE clinical benefit; prostate cancer; vinorelbine ID PALLIATIVE END-POINTS; RANDOMIZED TRIAL; ORAL ETOPOSIDE; ESTRAMUSTINE; MITOXANTRONE; PREDNISONE; ANTIGEN AB Background: Clinical activity is difficult to assess by traditional response endpoints in patients with advanced prostate cancer. We used clinical benefit response to assess the activity of vinorelbine (Navelbine(R)) in patients with hormone-refractory prostate cancer. Patients and methods: Forty-nine men with hormone-refractory prostate cancer received vinorelbine weekly for eight weeks followed by every-other-week dosing. Clinical benefit response was defined by improvement in 1 of the following categories for at least 12 weeks and stable response or better in the other 2: pain index (analgesic consumption and pain intensity), Karnofsky performance status, and tumor status. Results: Of 37 evaluable patients, 14 (39%) achieved clinical benefit for a median duration of 6 months (range 3-24 months). Toxicities consisted primarily of brief neutropenia and mild nausea. Conclusion: These findings indicate that vinorelbine is well tolerated in men with hormone-refractory prostate cancer and produces durable clinical benefit as defined by improvement in pain index and performance status. C1 Brooke Army Med Ctr, Canc Therapy & Res Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX USA. JFK Comprehens Canc Ctr, Lake Worth, FL USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Hematol & Oncol Associates PA, Greenville, SC USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Burris, HA (reprint author), Sarah Cannon Canc Ctr, 250 25th Ave N,Suite 412, Nashville, TN 37203 USA. NR 11 TC 50 Z9 50 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 1999 VL 10 IS 11 BP 1307 EP 1310 DI 10.1023/A:1008315106697 PG 4 WC Oncology SC Oncology GA 278FZ UT WOS:000084979300011 PM 10631457 ER PT J AU Kass, ES Salman, S AF Kass, ES Salman, S TI Imaging case study of the month - Developmental changes in the antrum of child with chronic maxillary atelectasis SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article ID SINUS HYPOPLASIA C1 NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Kass, ES (reprint author), NIH, Bldg 10,Room 8B07,10 Ctr Dr MSC 1750, Bethesda, MD 20892 USA. NR 9 TC 3 Z9 3 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 NOV PY 1999 VL 108 IS 11 BP 1091 EP 1094 PN 1 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 256LB UT WOS:000083725800012 PM 10579238 ER PT J AU Gray, SL Mahoney, JE Blough, DK AF Gray, SL Mahoney, JE Blough, DK TI Adverse drug events in elderly patients receiving home health services following hospital discharge SO ANNALS OF PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT 18th Annual Meeting of the American-College-of-Clinical-Pharmacy CY NOV 04-12, 1997 CL PHOENIX, ARIZONA SP Amer Coll Clin Pharm DE adverse drug events; hospital discharge ID OLDER OUTPATIENTS; RISK; ADMISSION; FALLS AB OBJECTIVE: TO assess incidence, healthcare consequences, and identify risk factors for adverse drug events (ADEs) in elderly patients receiving home health services during the month following hospital discharge. METHODS: This was a prospective cohort study of three home health agencies in Madison, Wisconsin, and its surrounding area. The sample consisted of 256 participants aged greater than or equal to 65 years who were hospitalized for medical illness, received home nursing after discharge, and completed the one-month interview. The main outcome measure was self-reported ADEs (possible, probable, or definite) during the month following hospital discharge. RESULTS: Incidence of ADEs was 20%, Fifty-two participants (20.3%) reported 64 ADEs: 23 possible, 37 probable, and four definite. The most common ADEs involved the gastrointestinal tract (31.3%) and the central nervous system (31.3%). Of 53 ADEs reported to providers, 59% of the drugs were discontinued or altered. One ADE resulted in hospitalization. In logistic regression, female gender (OR = 2.26; 95% CI 1.06 to 4.77) and the interaction between number of new medications and cognition were significantly associated with ADEs. The risk of an event increased with the number of new medications at discharge; however, risk was elevated primarily for participants with lower cognition. CONCLUSIONS: ADEs were common during the month following hospital discharge, were more frequent in women, and often resulted in medication changes. Individuals at particular risk were those with lower cognition who were discharged with several new medications. C1 Univ Washington, Sch Pharm, Seattle, WA 98195 USA. Univ Wisconsin, Dept Med, Madison, WI USA. William S Middleton Mem Vet Hosp, Ctr Geriatr Res Educ & Clin, Madison, WI USA. RP Gray, SL (reprint author), Univ Washington, Sch Pharm, Box 357630, Seattle, WA 98195 USA. FU NIA NIH HHS [K08AG00623, K08AG00808-01] NR 30 TC 58 Z9 59 U1 0 U2 2 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 1999 VL 33 IS 11 BP 1147 EP 1153 DI 10.1345/aph.19036 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 256HG UT WOS:000083719400001 PM 10573310 ER PT J AU Aghassi, D Carpo, B Eng, K Grevelink, JM AF Aghassi, D Carpo, B Eng, K Grevelink, JM TI Complications of aesthetic laser surgery SO ANNALS OF PLASTIC SURGERY LA English DT Review ID CARBON-DIOXIDE LASER; PULSED-DYE-LASER; PORT-WINE STAINS; Q-SWITCHED RUBY; ERBIUM-YAG LASER; PHOTOAGED FACIAL SKIN; HAIR REMOVAL; TATTOO REMOVAL; DOSE-RESPONSE; SHORT-TERM AB Aesthetic laser surgery is not risk free. It behooves the laser surgeon to become intimately familiar with the potential adverse effects of laser use to guard against and to minimize their occurrence. Moreover, patients must be thoroughly, clearly, and honestly educated about the procedure and its risks so that their expectations are realistic and so that any complications that do occur can be recognized early and treated appropriately. This review summarizes basic laser safety and discusses the nature of complications that may occur during continuous-wave, pulsed dye, pigment-specific, hair removal, and resurfacing laser procedures. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Grevelink, JM (reprint author), 50 Staniford St,8th Floor, Boston, MA 02114 USA. NR 74 TC 5 Z9 5 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-7043 J9 ANN PLAS SURG JI Ann. Plast. Surg. PD NOV PY 1999 VL 43 IS 5 BP 560 EP 569 DI 10.1097/00000637-199911000-00018 PG 10 WC Surgery SC Surgery GA 253LD UT WOS:000083557300020 PM 10560877 ER PT J AU Holman, WL Peterson, ED Athanasuleas, CL Allman, RM Sansom, M Kiefe, C Sherrill, RG AF Holman, WL Peterson, ED Athanasuleas, CL Allman, RM Sansom, M Kiefe, C Sherrill, RG CA Alabama CABG Cooperative Project S TI Alabama Coronary Artery Bypass Grafting Cooperative Project: Baseline data SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 24-29, 1999 CL SAN ANTONIO, TEXAS SP Soc Thorac Surgeons ID NEW-YORK-STATE; SURGERY; MORTALITY; QUALITY; VOLUME AB Background. The Alabama Cooperative CABG Project is a statewide process-oriented analysis of coronary artery bypass grafting (CABG). The purpose of this report is to present the first information generated by this analysis, which will serve as a baseline for subsequent quality improvement projects. Methods. Medical records of Medicare beneficiaries from Alabama, a comparison state, and a national random sample who had isolated CABG between July 1, 1995, and June 30, 1996, were examined. Fifty-six demographic, procedural, and outcome variables were abstracted. Quality indicators identified by the Alabama Quality Assurance Foundation Study Group included: internal mammary artery use, prescription of aspirin at discharge, duration of postoperative intubation, use of intraaortic balloon pump, readmission to intensive care unit, hospital readmission within 30 days, return to the operating room for bleeding, and in-patient mortality. Benchmark performance rates for quality indicators reflecting care processes were calculated. Results. Alabama, the comparison state, and the national sample consisted of 4,092, 2,290, and 1,119 patients, respectively. The processes of care and outcome, including risk-adjusted mortality, for CABG across the state of Alabama are generally similar to other states and nationwide samples. However, there was considerable variation at the local hospital level in Alabama for each quality indicator. Conclusions. The data provide a "snapshot" of practice patterns for CABG in Alabama. A specific quality indicator (duration of intubation) was identified as a focus for statewide improvement. Hospital-specific variations in quality indicators suggested opportunities for improvement in other indicators at a number of hospitals. (C) 1999 by The Society of Thoracic Surgeons. C1 Univ Alabama, Dept Surg, Birmingham Vet Affairs Med Ctr, Alabama Qual Assurance Fdn, Birmingham, AL 35294 USA. Duke Univ, Med Ctr, Durham, NC USA. RP Holman, WL (reprint author), Univ Alabama, Dept Surg, Birmingham Vet Affairs Med Ctr, Alabama Qual Assurance Fdn, Birmingham, AL 35294 USA. RI Allman, Richard/D-5964-2011 FU PHS HHS [500-96-P605] NR 17 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 1999 VL 68 IS 5 BP 1592 EP 1598 DI 10.1016/S0003-4975(99)01000-0 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 259HF UT WOS:000083887900005 PM 10585026 ER PT J AU D'Ambra, MN AF D'Ambra, MN TI Autologous blood donation with recombinant human erythropoietin in anemic patients - Invited commentary SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP D'Ambra, MN (reprint author), Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 1999 VL 68 IS 5 BP 1656 EP 1656 DI 10.1016/S0003-4975(99)00840-1 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 259HF UT WOS:000083887900019 ER PT J AU Todd, R Wong, DTW AF Todd, R Wong, DTW TI Oncogenes SO ANTICANCER RESEARCH LA English DT Review DE oncogene; carcinogenesis; amplification; translocation; mitogenic signal transduction pathway; cell cycle; apoptosis ID GROWTH-FACTOR RECEPTOR; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE-ACTIVITY; TUMOR-SUPPRESSOR GENES; BLADDER-CARCINOMA ONCOGENE; AVIAN-SARCOMA VIRUSES; C-ABL PROTEIN; SIGNAL-TRANSDUCTION; FACTOR-ALPHA; EGF-RECEPTOR AB Oncogenes are gain-of-function mutations of normal normal regulatory genes or photo-oncogenes. Originally discovered in retroviruses initiating a variety of animal and avian cancers, oncogenes nle believed to be important contributors to human carcinogenesis. Photo-oncogenes are altered by point mutation, amplification or. rearrangement. Structural alteration of proto-oncogenes leads to a quantitative ol qualitative expression change of the corresponding protein product. Oncoproteins subvert signal transduction pathways at the cell surface, in the cytosol and/or in the nucleus. Together with other oncoproteins or in the absence of tumor suppressor gene products, oncogenes contribute to human cancer formation by supporting accelerated proliferation, de-regulating cell cycle control or blocking apoptosis. C1 Harvard Univ, Sch Dent Med, Dept Oral Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, Boston, MA 02115 USA. RP Todd, R (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Dent Med, 188 Longwood Ave, Boston, MA 02115 USA. EM randy-todd@hms.harvard.edu NR 175 TC 34 Z9 35 U1 3 U2 8 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 1999 VL 19 IS 6A BP 4729 EP 4746 PG 18 WC Oncology SC Oncology GA 284EE UT WOS:000085317100009 PM 10697588 ER PT J AU Michaelson, J AF Michaelson, J TI The role of molecular discreteness in normal and cancerous growth SO ANTICANCER RESEARCH LA English DT Review DE cancerous growth; carcinogenesis ID HUMAN-BREAST-CANCER; NATURAL-HISTORY; CELLS; DIFFERENTIATION; EXPRESSION; RECEPTOR; ORGANIZATION; INACTIVATION; COMMITMENT; MODEL AB The physicochemical events that underlie biological processes are inevitably either/or events. Either a growth factor molecule binds to a cell, or it doesn't. Either a site on a cyclin molecule is phosphorylated, ol it isn't. Either a regulatory molecule binds to a DNA sequence, ol it doesn't. These molecular either/or events lead to cellular either/or events. Either a cell divides, or it doesn't. Either a cell dies, ol it doesn't. Either a cell turns on a particular gene, ol it doesn't. Either a tumor cell stays where it is, ol it forms a distant metastasis. By considering biological processes as the macroscopic aggregate results of these many individual microscopic either/or events, we can gain considerable insight into both normal and cancerous growth. In fact, as will be outlined here, such discrete modeling may allow us to see how the normal cellular populations of the body can grow to predictable sizes, at predictable times, and to predictable shapes. Such modeling can also allow us to gain insight into how normal cellular populations may become cancerous cellular populations. Indeed, such an approach allows us do a sufficiently good job of imitating the growth and spread of tumors as to be able to make estimates the most effective ways to both detect and a eat cancer. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Canc Ctr, Boston, MA 02129 USA. RP Michaelson, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Canc Ctr, Bldg 149,13th St, Boston, MA 02129 USA. NR 47 TC 10 Z9 10 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 1999 VL 19 IS 6A BP 4853 EP 4867 PG 15 WC Oncology SC Oncology GA 284EE UT WOS:000085317100020 PM 10697599 ER PT J AU Zonios, G Perelman, LT Backman, VM Manoharan, R Fitzmaurice, M Van Dam, J Feld, MS AF Zonios, G Perelman, LT Backman, VM Manoharan, R Fitzmaurice, M Van Dam, J Feld, MS TI Diffuse reflectance spectroscopy of human adenomatous colon polyps in vivo SO APPLIED OPTICS LA English DT Article ID OPTICAL-PROPERTIES; LIGHT-SCATTERING; NONINVASIVE DETERMINATION; TISSUE FLUORESCENCE; BIOLOGICAL TISSUE; REFRACTIVE-INDEX; OXYGENATION; INVIVO; DYSPLASIA; DIAGNOSIS AB Diffuse reflectance spectra were collected from adenomatous colon polyps (cancer precursors) and normal colonic mucosa of patients undergoing colonoscopy. We analyzed the data by using an analytical light diffusion model, which was tested and validated on a physical tissue model composed of polystyrene beads and hemoglobin. Four parameters were obtained: hemoglobin concentration, hemoglobin oxygen saturation, effective scatterer density, and effective scatterer size. Normal and adenomatous tissue sites exhibited differences in hemoglobin concentration and, on average, in effective scatterer size;which were in general agreement with other studies that employ standard methods. These results suggest that diffuse reflectance can be used to obtain tissue information about tissue structure and composition in vivo. (C) 1999 Optical Society of America. C1 Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. MIT, George R Harrison Spect Lab, Cambridge, MA 02139 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. RP Zonios, G (reprint author), Massachusetts Gen Hosp, Wellman Labs Photomed, GHX 630, Boston, MA 02114 USA. EM zonios@helix.mgh.harvard.edu NR 46 TC 346 Z9 347 U1 4 U2 22 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD NOV 1 PY 1999 VL 38 IS 31 BP 6628 EP 6637 DI 10.1364/AO.38.006628 PG 10 WC Optics SC Optics GA 253LF UT WOS:000083557500022 PM 18324198 ER PT J AU Kistler, JP Furie, KL AF Kistler, JP Furie, KL TI Strategic location of large-vessel atherothrombotic cerebral vascular disease SO ARCHIVES OF NEUROLOGY LA English DT Editorial Material ID THERAPY; STROKE C1 Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Kistler, JP (reprint author), Massachusetts Gen Hosp, Neurol Serv, VBK 802,32 Fruit St, Boston, MA 02114 USA. NR 13 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 1999 VL 56 IS 11 BP 1329 EP 1330 DI 10.1001/archneur.56.11.1329 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 253KG UT WOS:000083555300003 PM 10555650 ER PT J AU Field, AE Camargo, CA Taylor, CB Berkey, CS Colditz, GA AF Field, AE Camargo, CA Taylor, CB Berkey, CS Colditz, GA TI Relation of peer and media influences to the development of purging behaviors among preadolescent and adolescent girls SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID EATING DISORDERS; BODILY ATTRACTIVENESS; BULIMIA-NERVOSA; THIN STANDARD; WEIGHT CONCERNS; RISK-FACTORS; SELF-ESTEEM; BODY-IMAGE; WOMEN; PREVENTION AB Objective: To assess prospectively the relation of peer and media influences on the risk of development of purging behaviors. Design: Prospective cohort study. Setting: One year follow-up of 6982 girls aged 9 to 14 years in 1996 who completed questionnaires in 1996 and 1997 and reported in 1996 that they did not use vomiting or laxatives to control weight. Main Outcome Measure: Self-report of using vomiting or laxatives at least monthly to control weight. Results: During 1 year of follow-up, 74 girls began using vomiting or laxatives at least monthly to control weight. Tanner stage of pubic hair development was predictive of beginning to purge (odds ratio [OR] = 1.8; 95% confidence interval [CI], 1.3-2.4). Independent of age and Tanner stage of pubic hair development, importance of thinness to peers (OR = 2.3; 95% CT, 1.8-3.0) and trying to look like females on television, in movies, or in magazines (OR = 1.9; 95% CI, 1.6-2.3) were predictive of beginning to purge at least monthly. Regardless of the covariates included in the logistic regression model, the risk of beginning to purge increased approximately 30% to 40% per 1-category increase in frequency of trying to look like females on television, in movies, or in magazines. Conclusions: Both peers and popular culture, independent of each other, exert influence on girls' weight control beliefs and behaviors. Therefore, to make eating disorder prevention programs more effective, efforts should be made to persuade the television, movie, and magazine industries to employ more models and actresses whose weight could be described as healthy, not underweight. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Stanford Med Sch, Dept Psychiat & Behav Sci, Stanford, CA USA. Harvard Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA USA. Harvard Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Field, AE (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NHLBI NIH HHS [HL-03533]; NIDDK NIH HHS [DK-46834, DK 46200] NR 48 TC 143 Z9 147 U1 6 U2 35 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 NOV PY 1999 VL 153 IS 11 BP 1184 EP 1189 PG 6 WC Pediatrics SC Pediatrics GA 252HN UT WOS:000083496200013 PM 10555723 ER PT J AU Kaihara, S Vacanti, JP AF Kaihara, S Vacanti, JP TI Tissue engineering - Toward new solutions for transplantation and reconstructive surgery SO ARCHIVES OF SURGERY LA English DT Article ID ACUTE LIVER-FAILURE; ENHANCE HEPATOCELLULAR SURVIVAL; SHORT BOWEL SYNDROME; HEPATOCYTE TRANSPLANTATION; PARENTERAL-NUTRITION; MICROENCAPSULATED HEPATOCYTES; CELL TRANSPLANTATION; PANCREATIC-ISLETS; POLYMER DEVICES; GENE-THERAPY AB Great advances in the field of transplantation have been made in the last half of this century. However, the severe scarcity of donor organs, especially in the pediatric population, has become a major limitation A new field, tissue engineering, applies the principles of biology and engineering toward the development of biological substitutes that restore, maintain, or improve tissue function. This article discusses the groundwork and challenges of this interdisciplinary field and its attempts to provide solutions to create new tissue for transplantation and other fields of reconstructive surgery. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Kyoto Univ, Fac Med, Dept Transplantat Immunol, Kyoto, Japan. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Warren 11,55 Fruit St, Boston, MA 02114 USA. NR 71 TC 22 Z9 25 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 NOV PY 1999 VL 134 IS 11 BP 1184 EP 1188 DI 10.1001/archsurg.134.11.1184 PG 5 WC Surgery SC Surgery GA 252UF UT WOS:000083520100003 PM 10555631 ER PT J AU Huang, Y Mironova, M Lopes-Virella, MF AF Huang, Y Mironova, M Lopes-Virella, MF TI Oxidized LDL stimulates matrix metalloproteinase-1 expression in human vascular endothelial cells SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE oxidized LDL; metalloproteinases; endothelium; collagen ID LOW-DENSITY-LIPOPROTEIN; HUMAN ATHEROSCLEROTIC PLAQUE; ACUTE CORONARY SYNDROMES; SMOOTH-MUSCLE CELLS; INTERSTITIAL COLLAGENASE; OXIDATIVE MODIFICATION; GENE-EXPRESSION; INVITRO; ANGIOGENESIS; PROTEINASES AB It has been well documented that acute myocardial infarction is triggered by disruption of atherosclerotic plaques. Immunocytochemistry studies have shown that matrix metalloproteinase-1 (MMP-1) is specifically expressed by cells present in atherosclerotic plaques, including luminal and neovascular endothelial cells. Since MMP-1 degrades type I collagen, a major type of collagen in atherosclerotic lesions, it is likely that MMP-1 is involved in promoting destabilization of plaques. To date, however, the stimulatory factors that induce MMP-1 expression in endothelial cells have not been well defined. In the present study, we found that oxidized low density lipoprotein (LDL) stimulated MMP-1 release from both human umbilical vein and aortic endothelial cells. We also found that oxidized LDL markedly stimulated MMP-1 expression in these cells and that the degree of LDL oxidation was positively correlated with the level of MMP-1 mRNA expression. Furthermore, our data showed that stimulated MMP-1 secretion was inhibited by actinomycin D and that the nascent MMP-1 mRNA synthesis was stimulated by oxidized LDL, indicating that oxidized LDL activated transcription of the MMP-1 gene. Finally, both zymography and activity assays demonstrated that collagenase activity in conditioned medium was stimulated by oxidized LDL. Taken together, these results have shown for the first time that oxidized LDL stimulates MMP-1 transcription and secretion by vascular endothelial cells, suggesting that oxidized LDL may be a potent stimulator for MMP-1 expression in atherosclerotic plaques, thus promoting plaque rupture. C1 Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. RP Lopes-Virella, MF (reprint author), Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, 114 Doughty St, Charleston, SC 29403 USA. FU NHLBI NIH HHS [HL-55782] NR 30 TC 78 Z9 83 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 1999 VL 19 IS 11 BP 2640 EP 2647 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 256LA UT WOS:000083725700009 PM 10559006 ER PT J AU Durante, W Peyton, KJ Schafer, AI AF Durante, W Peyton, KJ Schafer, AI TI Platelet-derived growth factor stimulates heme oxygenase-1 gene expression and carbon monoxide production in vascular smooth muscle SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE platelet-derived growth factor; carbon monoxide; heme oxygenase ID HUMAN-SKIN FIBROBLASTS; CORONARY-ARTERY DISEASE; NITRIC-OXIDE SYNTHESIS; OXIDATIVE STRESS; TRANSCRIPTIONAL ACTIVATION; SODIUM ARSENITE; CELLS; INDUCTION; BILIRUBIN; PROTEIN AB Recent studies indicate that vascular smooth muscle cells (VSMCs) generate CO from the degradation of heme by the enzyme heme oxygenase-l (HO-1). Because platelet-derived growth factor (PDGF) modulates various responses of VSMCs, we examined whether this peptide regulates the expression of HO-1 and the production of CO by rat aortic SMCs. Treatment of SMCs with PDGF resulted in a time- and concentration-dependent increase in the levels of HO-1 mRNA and protein. Both actinomycin D and cycloheximide blocked PDGF-stimulated HO-1 mRNA and protein. In addition, PDGF stimulated the production of reactive oxygen species by SMCs. Both the PDGF-mediated generation of reactive oxygen species and the induction of HO-1 protein was inhibited by the antioxidant N-acetyl-L-cysteine. Incubation of platelets with PDGF-treated SMCs resulted in a significant increase in platelet cGMP concentration that was reversed by treatment of SMCs with the HO-1 inhibitor tin protoporphyrin-IX or by addition of the CO scavenger hemoglobin to platelets. In contrast, the nitric oxide inhibitor methyl-L-arginine did not block the stimulatory effect of PDGF-treated SMCs on platelet cGMP. Finally, incubation of SMCs with the releasate from collagen-activated platelets induced HO-1 protein expression that was blocked by a neutralizing antibody to PDGF. These results demonstrate that either administered exogenously or released by platelets, PDGF stimulates HO-1 gene expression and CO synthesis in vascular smooth muscle. The ability of PDGF to induce HO-1-catalyzed CO release by VSMCs may represent a novel mechanism by which this growth factor regulates vascular cell and platelet function. C1 Houston VA Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pharmacol, Houston, TX 77030 USA. RP Durante, W (reprint author), Houston VA Med Ctr, Bldg 109,Room 130,2002 Holcombe Blvd, Houston, TX 77030 USA. FU NHLBI NIH HHS [HL-36045, HL-59976] NR 57 TC 51 Z9 55 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD NOV PY 1999 VL 19 IS 11 BP 2666 EP 2672 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 256LA UT WOS:000083725700012 PM 10559009 ER PT J AU Fried, L AF Fried, L TI Mortality in peritoneal dialysis patients SO ASAIO JOURNAL LA English DT Review ID STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; PREDICTIVE VALUE; CAPD PATIENTS; TECHNIQUE SURVIVAL; SERUM-ALBUMIN; DEATH RISK; FAILURE; EXPERIENCE; MORBIDITY AB The incidence of end-stage renal disease is growing. Mortality remains high, despite improvements in care. Much of this can be explained by the presence of cardiovascular disease and other co-morbid conditions that are present at the start of dialysis. However, the dialysis treatment itself may exacerbate these conditions, and dialysis related factors such as adequacy, cytokine production, and dialysis-related infections are important factors in survival. Early studies reported similar or better survival on peritoneal dialysis (compared with hemodialysis), although more recent studies have questioned this finding. This review summarizes the information on mortality in peritoneal dialysis patients. C1 Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care Syst, Renal Sect, Pittsburgh, PA USA. RP Fried, L (reprint author), Univ Pittsburgh, Sch Med, Renal Electrolyte Div, 938 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15213 USA. NR 73 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD NOV-DEC PY 1999 VL 45 IS 6 BP 526 EP 530 DI 10.1097/00002480-199911000-00004 PG 5 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 259MD UT WOS:000083896900003 PM 10593681 ER PT J AU Kaelin, WG AF Kaelin, WG TI Functions of the retinoblastoma protein SO BIOESSAYS LA English DT Review ID CYCLIN-DEPENDENT KINASES; TRANSCRIPTION FACTOR E2F-1; ZINC-FINGER PROTEIN; LARGE T-ANTIGEN; S-PHASE ENTRY; GENE-PRODUCT; CELL-CYCLE; HISTONE DEACETYLASE; REPRESS TRANSCRIPTION; GROWTH SUPPRESSION AB The retinoblastoma protein (pRB) can both positively and negatively regulate transcription. The former correlates with its ability to promote differentiation and the latter with its ability to regulate entry into S-phase. pRB negatively regulates transcription by forming complexes with members of the E2F transcription factor family. These complexes, when bound to E2F sites within certain target genes, actively repress transcription through a variety of mechanisms including physical interaction with adjacent transcriptional activation domains and recruitment of proteins that directly, or indirectly, lead to histone deacetylation. pRB function is. in turn, modulated by phosphorylation mediated by cyclin-dependent kinases. Emerging data suggest that combinatorial control of pRB function may be achieved through the use of different phosphoacceptor sites, different cyclin/cdk docking sites, and different cyclin/cdk complexes. The untimely activation of E2F responsive genes can induce apoptosis. This comes about at least partly through the induction of ARF, which leads to the stabilization and activation of p53. BioEssays 1999;21:950-958. (C) 1999 John Wiley & Sons, Inc. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Kaelin, WG (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NR 83 TC 160 Z9 168 U1 2 U2 6 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0265-9247 J9 BIOESSAYS JI Bioessays PD NOV PY 1999 VL 21 IS 11 BP 950 EP 958 DI 10.1002/(SICI)1521-1878(199911)21:11<950::AID-BIES7>3.3.CO;2-4 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 251BL UT WOS:000083424700007 PM 10517868 ER PT J AU Biederman, J Spencer, T AF Biederman, J Spencer, T TI Attention-deficit/hyperactivity disorder (ADHD) as a noradrenergic disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Norepinephrine - New Vistas for and Old Neurotransmitter CY MAR, 1999 CL KEY WEST, FLORIDA SP Soc Biol Psychiat DE ADHD; noradrenergic; psychiatry ID DEFICIT HYPERACTIVITY DISORDER; DOPAMINE D4 RECEPTOR; DOUBLE-BLIND; TOURETTES-SYNDROME; NOVELTY SEEKING; COGNITIVE FUNCTION; DRD4 GENE; CHILDREN; DESIPRAMINE; METHYLPHENIDATE AB This review revisits the thesis that a dysregulation of the central noradrenergic networks may underlie the pathophysiology of ADHD. We review the pertinent neurobiological and pharmacological literature on ADHD. The noradrenergic system has been intimately associated with the modulation of higher cortical functions including attention, alertness, vigilance and executive function, Noradrenergic activation is known to profoundly affect the performance of attention, especially the maintenance of arousal, a cognitive function known to be deficient in ADHD. Data from family, adoption, twin, and segregation analysis strongly support a genetic hypothesis for this disorder. Although molecular genetic studies of ADHD are relatively new and far from definitive, several replicated reports have found associations between ADHD with DAT and D4 receptor genes. Brain imaging studies fit well with the idea that dysfunction in fronto-subcortical pathways occurs in ADHD with ifs underlying dysregulation of noradrenergic function. A wealth of pharmacological data (within and without the stimulant literature) provides strong evidence for selective clinical activity in ADHD for drugs with noradrenergic and dopaminergic pharmacological profiles, Available research provides compelling theoretic, basic biologic and clinical support for the notion that ADHD is a brain disorder of likely genetic etiology with etiologic and pathophysiologic heterogeneity, NL Neurobiological and pharmacological data provide compelling support for a noradrenergic hypothesis of ADHD and suggest that drugs with noradrenergic activity may play an important role in the therapeutics of this disorder. (C) 1999 Society of Biological Psychiatry. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, WACC 725,15 Parkman St, Boston, MA 02114 USA. FU NIMH NIH HHS [R01MH41314, R29MH57511] NR 90 TC 281 Z9 293 U1 8 U2 27 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 NOV 1 PY 1999 VL 46 IS 9 BP 1234 EP 1242 DI 10.1016/S0006-3223(99)00192-4 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 252AH UT WOS:000083478200011 PM 10560028 ER PT J AU Levin, J Peng, JP Baker, GR Villeval, JL Lecine, P Burstein, SA Shivdasani, RA AF Levin, J Peng, JP Baker, GR Villeval, JL Lecine, P Burstein, SA Shivdasani, RA TI Pathophysiology of thrombocytopenia and anemia in mice lacking transcription factor NF-E2 SO BLOOD LA English DT Article ID MURINE MEGAKARYOCYTES; PLATELET FORMATION; BONE-MARROW; IN-VIVO; THROMBOPOIETIN; ERYTHROPOIESIS; EXPRESSION; LINEAGES; LEUKEMIA; ABSENCE AB Expression of the p45 subunit of transcription factor NF-E2 is restricted to selected blood cell lineages, including megakaryocytes and developing erythrocytes. Mice lacking p45 NF-EP show profound thrombocytopenia, resulting from a late arrest in megakaryocyte differentiation, and a number of red blood cell defects, including anisocytosis and hypochromia, Here we report results of studies aimed to explore the pathophysiology of these abnormalities. Mice lacking NF-EP produce very few platelet-like particles that display highly disorganized ultrastructure and respond poorly to platelet agonists, features consistent with the usually lethal hemorrhage in these animals. Thrombocytopenia was evident during fetal life and was not corrected by splenectomy in adults. Surprisingly, fetal NF-E2-deficient megakaryocyte progenitors showed reduced proliferation potential in vitro. Thus, NF-ES is required for regulated megakaryocyte growth as well as for differentiation into platelets. All the erythroid abnormalities were reproduced in lethally irradiated wildtype recipients of hematopoietic cells derived from NF-E2-null fetuses. Whole blood from mice lacking p45 NF-E2 showed numerous small red blood cell fragments; however, survival of intact erythrocytes in vivo was indistinguishable from control mice. Considered together, these observations indicate a requirement for NF-E2 in generating normal erythrocytes, Despite impressive splenomegaly at baseline, mice lacking p45 NF-ES survived splenectomy, which resulted in increased reticulocyte numbers. This reveals considerable erythroid reserve within extra-splenic sites of hematopoiesis and suggests a role for the spleen in clearing abnormal erythrocytes, Our findings address distinct aspects of the requirements for NF-E2 in blood cell homeostasis and establish its roles in proper differentiation of megakaryocytes and erythrocytes. (C) 1999 by The American Society of Hematology. C1 Univ Calif San Francisco, Sch Med, Dept Lab Med, San Francisco, CA 94143 USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ Oklahoma, Hlth Sci Ctr, WK Warren Med Res Inst, Oklahoma City, OK USA. Brigham & Womens Hosp, Dept Adult Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Lecine, Patrick/H-9338-2016 NR 28 TC 67 Z9 70 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1999 VL 94 IS 9 BP 3037 EP 3047 PG 11 WC Hematology SC Hematology GA 249UG UT WOS:000083351200013 PM 10556187 ER PT J AU Shankar, P Xu, Z Lieberman, J AF Shankar, P Xu, Z Lieberman, J TI Viral-specific cytotoxic T lymphocytes lyse human immunodeficiency virus-infected primary T lymphocytes by the granule exocytosis pathway SO BLOOD LA English DT Article ID CELL-MEDIATED CYTOTOXICITY; HEPATITIS-C VIRUS; CD38 ANTIGEN EXPRESSION; TUMOR-NECROSIS-FACTOR; FAS LIGAND; HIV-INFECTION; CTL CLONES; LYMPHOPROLIFERATIVE SYNDROME; HIV-1-INFECTED PATIENTS; NONCYTOPATHIC VIRUSES AB Cytotoxic T lymphocytes (CTL) lyse antigen-bearing target cells by two distinct pathways. Whereas granule exocytosis targets any antigen-bearing cell, fas-mediated cytotoxicity kills only fas-expressing cells and does not require antigen expression. Fas pathway activation can potentially lead to lysis of uninfected bystander cells. We examined the relative usage of the two pathways by CTL clones and cell lines directed against four different human immunodeficiency virus (HIV) proteins in lysing primary HIV-infected targets. Although fas was expressed on HIV-infected primary CD4(+) T cells, their lysis by antigen-specific CD8(+) CTL was only by the granule pathway. Fas ligand (fasL) was not detectable on antigen-specific CD8 clones, T-cell lines, or circulating HIV-specific CD8 T cells from HIV-infected donors, stained with a tetrameric HLA-AZ-HIV-peptide complex. Fast expression by HIV-specific CTL clones was not activated by exposure to HIV-presenting cells, but was after unphysiological stimulation with phorbol myristate acetate (PMA). CTL clones did not lyse bystander Jurkat cells, but HIV-infected primary CD4(+) T cells lysed uninfected bystander cells by the fas-mediated pathway. These results suggest that HIV-specific CD8(+) CTL do not cause HIV immunopathology by lysing bystander cells. On the contrary, fas-mediated lysis of uninfected cells by HIV-infected cells may contribute to CD4 decline. (C) 1999 by The American Society of Hematology. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RP Lieberman, J (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Lieberman, Judy/A-2717-2015 FU NIAID NIH HHS [AI-36611, AI-38819, AI-45406] NR 73 TC 55 Z9 55 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1200 19TH ST, NW, STE 300, WASHINGTON, DC 20036-2422 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 1999 VL 94 IS 9 BP 3084 EP 3093 PG 10 WC Hematology SC Hematology GA 249UG UT WOS:000083351200019 PM 10556193 ER PT J AU Frei, E Richardson, P Avigan, D Bunnell, C Wheeler, C Elias, A AF Frei, E Richardson, P Avigan, D Bunnell, C Wheeler, C Elias, A TI The interval between courses of high-dose chemotherapy with stem cell rescue: therapeutic hypotheses SO BONE MARROW TRANSPLANTATION LA English DT Article DE high-dose chemotherapy; stem cell rescue; resistance; hypotheses ID METASTATIC BREAST-CANCER; BONE-MARROW TRANSPLANTATION; ALKYLATING-AGENTS; COMBINATION CHEMOTHERAPY; MULTIDRUG-RESISTANCE; SOLID TUMORS; SUPPORT; APOPTOSIS; INVITRO; TRIAL AB The interval between courses of chemotherapy have classically been kept to a minimum in order to maximize dose intensity. Certain clinical observations suggest that longer intervals, particularly in the high-dose setting, may be more effective. This is based in part on the evidence that resistance is reversible over time and that the interval should be sufficient to allow for such a reversal. Clinical evidence for such reversibility include the following. In metastatic breast cancer, double or double high-dose stem cell rescue (HD-SCR) studies involving a minimal interval, have not, at least as yet, been shown to be superior to single HD-SCR, In Hodgkin's disease, response after relapse correlates directly with duration of time to relapse. Tn a comparative study of metastatic breast cancer, early HD-SCR preceded by daunorubicin induction was inferior to delayed HD-SCR, The latter was not preceded by induction chemotherapy, In a comparative study of childhood ALL, patients randomized to delayed (4 month interval) intensification had a significantly; superior survival as compared to patients randomized to immediate (1 month interval) intensification. Taken together, these clinical observations indicate that resistance is reversible and that optimization of the interval must take this into account. Cytokinetic modeling of those clinical studies also found that delayed HD-SCR could result in a superior effect. Cytokinetic models of minimal residual tumor which were also examined included the Skipper exponential model, the Norton-Simon model which emphasizes the Gompertzian effect, the clonal evolution model, and the Retsky-Demisheli model which derives from a bimodal relapse pattern above, Biological and clinical data have resulted in a clinical protocol in the CALGB wherein patients with metastatic breast cancer are randomly allocated to (1) a single HD-SCR arm; (2) a double HD-SCR with a 5-week interval; and (3) a double HD-SCR arm with a 16 week interval. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Frei, E (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 48 TC 5 Z9 5 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 NOV PY 1999 VL 24 IS 9 BP 939 EP 945 DI 10.1038/sj.bmt.1702012 PG 7 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 255HJ UT WOS:000083663200001 PM 10556951 ER PT J AU Mao, JR AF Mao, JR TI NMDA and opioid receptors: their interactions in antinociception, tolerance and neuroplasticity SO BRAIN RESEARCH REVIEWS LA English DT Review DE NMDA; opioid receptor; interaction ID PROTEIN-KINASE-C; EXCITATORY AMINO-ACID; NITRIC-OXIDE SYNTHASE; RAT SPINAL-CORD; CENTRAL-NERVOUS-SYSTEM; IN-SITU HYBRIDIZATION; MESSENGER-RNA DISTRIBUTION; D-ASPARTATE RECEPTORS; MORPHINE-TOLERANCE; IMMUNOHISTOCHEMICAL LOCALIZATION AB Over the last several years, significant progress has been made in our understanding of interactions between the N-methyl-D-aspartate (NMDA) and opioid receptors. Such interactions have been demonstrated at. two distinct sites: (1) modulation of NMDA receptor-mediated electrophysiological events by opioids; and (2) intracellular events involving interactions between NMDA and opioid receptors. Furthermore, a considerable number of studies have shown the involvement of such interactions in neural mechanisms of nociceptive transmission, antinociception in acute and chronic pain states, opioid tolerance/dependence, and neuroplasticity. Importantly, emerging evidence indicates that activation of NMDA receptors may differentially modulate functions mediated by distinct opioid receptor subtypes, namely mu, delta, and kappa receptors. These studies have greatly enriched our knowledge regarding both NMDA and opioid receptor systems and have shed light on neurobiology of both acute and chronic pain. The advancement of such knowledge also promotes new strategies for better clinical management of pain patients. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr, 15 Parkman St,Suite WAC-324, Boston, MA 02114 USA. FU NIDA NIH HHS [DA08835] NR 139 TC 180 Z9 193 U1 0 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD NOV PY 1999 VL 30 IS 3 BP 289 EP 304 DI 10.1016/S0165-0173(99)00020-X PG 16 WC Neurosciences SC Neurosciences & Neurology GA 260PC UT WOS:000083958200005 PM 10567729 ER PT J AU Huang, PL AF Huang, PL TI Neuronal and endothelial nitric oxide synthase gene knockout mice SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article; Proceedings Paper CT Meeting on NO Brazil, Basic and Clinical Aspects ofNitric Oxide CY MAR 10-13, 1999 CL FOZ DO IGUACU, BRAZIL DE nitric oxide; targeted disruption; gene knockout; endothelium; stroke; atherosclerosis ID LONG-TERM POTENTIATION; NEUROTRANSMITTER RELEASE; CEREBRAL-ISCHEMIA; MUTANT MICE; PEROXYNITRITE; MESSENGER; LACKING; ROLES AB Targeted disruption of the neuronal nitric oxide synthase (nNOS) and endothelial nitric oxide synthase (eNOS) genes has led to knockout mice that lack these isoforms, These animal models have been useful to study the roles of nitric oxide (NO) in physiologic processes. nNOS knockout mice have enlarged stomachs and defects in the inhibitory junction potential involved in gastrointestinal motility. eNOS knockout mice are hypertensive and lack endothelium-derived relaxing factor activity. When these animals are subjected to models of focal ischemia, the nNOS mutant mice develop smaller infarcts, consistent with a role for nNOS in neurotoxicity following cerebral ischemia. In contrast, eNOS mutant mice develop larger infarcts, and show a more pronounced hemodynamic effect of vascular occlusion. The knockout mice also show that nNOS and eNOS isoforms differentially modulate the release of neurotransmitters in various regions of the brain. eNOS knockout mice respond to vessel injury with greater neointimal proliferation, confirming that reduced NO levels seen in endothelial dysfunction change the vessel response to injury. Furthermore, eNOS mutant mice still show a protective effect of female gender, indicating that the mechanism of this protection cannot be Limited to upregulation of eNOS expression. The eNOS mutant mice also prove that eNOS modulates the cardiac contractile response to beta-adrenergic agonists and baseline diastolic relaxation. Atrial natriuretic peptide, upregulated in the hearts of eNOS mutant mice, normalizes cGMP levels and restores normal diastolic relaxation. C1 Harvard Univ, Sch Med, Dept Med, Cardiovasc Res Ctr, Boston, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Huang, PL (reprint author), Massachusetts Gen Hosp East, Cardiovasc Res Ctr, 149 E 13th St, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL52818]; NINDS NIH HHS [NS33335] NR 28 TC 38 Z9 42 U1 0 U2 1 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD NOV PY 1999 VL 32 IS 11 BP 1353 EP 1359 DI 10.1590/S0100-879X1999001100005 PG 7 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 261KB UT WOS:000084007400005 PM 10559836 ER PT J AU Swartz, MA Kristensen, CA Melder, RJ Roberge, S Calautti, E Fukumura, D Jain, RK AF Swartz, MA Kristensen, CA Melder, RJ Roberge, S Calautti, E Fukumura, D Jain, RK TI Cells shed from tumours show reduced clonogenicity, resistance to apoptosis, and in vivo tumorigenicity SO BRITISH JOURNAL OF CANCER LA English DT Article DE tumour cell shedding; clonogenicity; tumour perfusion; experimental metastasis; tumorigenicity; metastatic potential ID CANCER METASTASIS; GROWTH; ADENOCARCINOMA; ANGIOGENESIS; MICE AB The goal of this study was to compare growth characteristics of cells shed from a tumour with the native tumour cells. The human colon adenocarcinoma LS174T and its highly metastatic subline LS UM 6 were grown as tissue-isolated tumours in nude mice and perfused to collect shed cells. The tumours were then excised and prepared into single-cell suspensions. Clonogenicity in 0.3-0.9% agarose, apoptotic fraction, and in vivo tumorigenicity were determined for each population. In both tumour lines, shed cells were less cionogenic, more apoptotic and less tumorigenic than cells isolated directly from their native tissue. These findings suggest that shed cells have a low metastatic potential compared to native tumour cells, most likely because they represent an apoptotic population. (C) 1999 Cancer Research Campaign. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RI Swartz, Melody/B-7633-2009; Swartz, Melody/F-9563-2011; OI CALAUTTI, Vincenzo/0000-0002-4439-9709 FU NCI NIH HHS [R35-CA-56591] NR 20 TC 42 Z9 42 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD NOV PY 1999 VL 81 IS 5 BP 756 EP 759 DI 10.1038/sj.bjc.6690760 PG 4 WC Oncology SC Oncology GA 250LH UT WOS:000083389500002 PM 10555742 ER PT J AU D'Amico, AV Vogelzang, NJ AF D'Amico, AV Vogelzang, NJ TI Prostate brachytherapy - Increasing demand for the procedure despite the lack of standardized quality assurance and long term outcome data SO CANCER LA English DT Editorial Material ID RADICAL PROSTATECTOMY; CANCER; IMPLANTATION; THERAPY C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Hematol Oncol Sect, Chicago, IL 60637 USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,Dept Radiat Oncol, 75 Francis St,L-2 Level, Boston, MA 02115 USA. NR 20 TC 11 Z9 11 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1999 VL 86 IS 9 BP 1632 EP 1634 DI 10.1002/(SICI)1097-0142(19991101)86:9<1632::AID-CNCR2>3.0.CO;2-5 PG 3 WC Oncology SC Oncology GA 251EB UT WOS:000083430700002 PM 10547533 ER PT J AU Mankin, HJ AF Mankin, HJ TI Chondrosarcomas of digits - Are they really malignant? SO CANCER LA English DT Editorial Material ID BONE C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Orthopaed Oncol Serv, Boston, MA USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Serv, Gray 604, Boston, MA 02114 USA. NR 10 TC 15 Z9 15 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 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 1999 VL 86 IS 9 BP 1635 EP 1637 DI 10.1002/(SICI)1097-0142(19991101)86:9<1635::AID-CNCR3>3.0.CO;2-# PG 3 WC Oncology SC Oncology GA 251EB UT WOS:000083430700003 PM 10547534 ER PT J AU Dohadwala, M Luo, J Lin, Y Sharma, S Stolina, M Zhu, L Dubinett, S AF Dohadwala, M Luo, J Lin, Y Sharma, S Stolina, M Zhu, L Dubinett, S TI Antisense inhibition of cyclooxygenase-2 blocks invasion and promotes apoptosis in non-small cell lung cancer (NSCLC) SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Immunol Pulm Lab, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Hlthcare Ctr, Los Angeles, CA 90073 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1999 VL 6 IS 6 SU S MA O11 BP S3 EP S3 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 265JR UT WOS:000084240100012 ER PT J AU Huang, M Kogai, T Lin, Y Batra, RK Hershman, JM Brent, GA Dubinett, SM AF Huang, M Kogai, T Lin, Y Batra, RK Hershman, JM Brent, GA Dubinett, SM TI Increased radioisotope uptake in non-small cell lung cancer following transfection with the sodium/iodide symporter gene SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Canc Gene Med Res Enhancement Award Program, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1999 VL 6 IS 6 SU S MA O80 BP S21 EP S21 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 265JR UT WOS:000084240100079 ER PT J AU Spear, MA Ladner, R Beltzer, J Breakefield, XO AF Spear, MA Ladner, R Beltzer, J Breakefield, XO TI Phage display epitopes selected against malignant glioma cells using a viable fluid phase method SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Univ Calif San Diego, Ctr Canc, Translat Canc Res Program, Gene Therapy Program, La Jolla, CA 92093 USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Dyax Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1999 VL 6 IS 6 SU S MA P58 BP S15 EP S15 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 265JR UT WOS:000084240100057 ER PT J AU Sun, F Spear, MA AF Sun, F Spear, MA TI Novel HSV-1 amplicon vector targeting system allows generation of amplicon producer cell lines SO CANCER GENE THERAPY LA English DT Meeting Abstract C1 Univ Calif San Diego, Ctr Canc, Translat Canc Res Program, Gene Therapy Program, La Jolla, CA USA. Massachusetts Gen Hosp, Mol Neurogenet Unit, Dept Neurol, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Dyax Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STOCKTON PRESS PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD NOV-DEC PY 1999 VL 6 IS 6 SU S MA P57 BP S15 EP S15 PG 1 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 265JR UT WOS:000084240100056 ER PT J AU Suit, HD AF Suit, HD TI Importance of hypoxic cells to radiation treatment: Further considerations SO CANCER JOURNAL FROM SCIENTIFIC AMERICAN LA English DT Editorial Material ID HYPERBARIC-OXYGEN; NECK-CANCER; RADIOTHERAPY; CARBOGEN/NICOTINAMIDE; NICOTINAMIDE; CARBOGEN; ARCON; HEAD C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Suit, HD (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU SCI AMERICAN INC PI NEW YORK PA 415 MADISON AVE, NEW YORK, NY 10017 USA SN 1081-4442 J9 CANCER J SCI AM JI Cancer J. Sci. Am. PD NOV-DEC PY 1999 VL 5 IS 6 BP 334 EP 335 PG 2 WC Oncology SC Oncology GA 263UU UT WOS:000084144300004 PM 10606472 ER PT J AU Van Cleave, J Devine, P Odom-Ball, P AF Van Cleave, J Devine, P Odom-Ball, P TI Multidisciplinary cave of hepatocellular carcinoma SO CANCER PRACTICE LA English DT Article DE hepatocellular carcinoma; multidisciplinary care; neoplasm, liver; supportive care ID CANCER AB OBJECTIVES: Multidisciplinary care of cancer patients in varied settings is well described in the literature, but there is little specifically describing the multidisciplinary care of the patient with hepatocellular carcinoma (T-ICC). The purpose of this article is to describe HCC and the multidisciplinary approach at the Philadelphia Veterans Affairs Medical Center (PVAMC), MATERIALS AND METHODS: HCC is one of the most common solid tumors in the world. but it is rare in North America. It is associated with environmental carcinogens identified in animal studies, hepatitis B and C, cirrhosis of any etiology, and various metabolic diseases. No reliable therapy has been established for HCC. Surgical resection is the best treatment, but it is possible only in the patient with adequate hepatic reserve and limited-stage cancer. From January 1995 to May 1995, 22 patients at PVAMC received a diagnosis of primary HCC. One patient was a candidate for surgery hva patients received radiation therapy, and one patient underwent chemoembolization. Eighteen patients presented with an advanced-stage disease and comorbidities. RESULTS: Therapy goals in these 18 patients sere limited to supportive care and enhancement of quality of life. A multidisciplinary team provided care to this challenging patient population. The multidisciplinary team treating HCC at PVAMG consisted of physicians, nurses, pharmacists, social workers, and a chaplain. Most care occurred in the outpatient setting. Supportive therapy included the controlling of ascites and abdominal discomfort, hepatic encephalopathy, and pruritus. Opioids relieved abdominal pain Psychiatric support;and counseling helped patients and families cope with the poor prognosis. CONCLUSIONS: A multidisciplinary team approach helped provide care for this challenging population. Through anecdotal reports. patients and family expressed satisfaction with their care. Research is needed to systematically test interventions designed to enhance quality of life in patients with HCC. C1 Philadelphia Vet Affairs Med Ctr, Hematol Oncol Serv, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Radiat Oncol Serv, Philadelphia, PA 19104 USA. RP Van Cleave, J (reprint author), Philadelphia Vet Affairs Med Ctr, Hematol Oncol Serv, 38th & Woodland, Philadelphia, PA 19104 USA. RI Van Cleave, Janet/E-1524-2014 OI Van Cleave, Janet/0000-0001-7011-4298 NR 23 TC 8 Z9 8 U1 3 U2 8 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1065-4704 J9 CANCER PRACT JI Cancer Pract. PD NOV-DEC PY 1999 VL 7 IS 6 BP 302 EP 308 DI 10.1046/j.1523-5394.1999.76007.x PG 7 WC Oncology; Health Care Sciences & Services; Nursing SC Oncology; Health Care Sciences & Services; Nursing GA 252FP UT WOS:000083491700011 PM 10732528 ER PT J AU Lal, A Lash, AE Altschul, SF Velculescu, V Zhang, L McLendon, RE Marra, MA Prange, C Morin, PJ Polyak, K Papadopoulos, N Vogelstein, B Kinzler, KW Strausberg, RL Riggins, GJ AF Lal, A Lash, AE Altschul, SF Velculescu, V Zhang, L McLendon, RE Marra, MA Prange, C Morin, PJ Polyak, K Papadopoulos, N Vogelstein, B Kinzler, KW Strausberg, RL Riggins, GJ TI A public database for gene expression in human cancers SO CANCER RESEARCH LA English DT Article ID P53-INDUCED APOPTOSIS; SERIAL ANALYSIS; GLIOBLASTOMA; PROGRESSION; PROFILES; CELLS; TUMOR AB A public database, SAGEmap, was created as a component of the Cancer Genome Anatomy Project to provide a central location for depositing, retrieving, and analyzing human gene expression data. This database uses serial analysis of gene expression to quantify transcript levels in both malignant and normal human tissues. By accessing SAGEmap (http://www.ncbi.nlm.nih.gov/SAGE) the user can compare transcript populations between any of the posted libraries. As an initial demonstration of the database's utility, gene expression in human glioblastomas was compared with that of normal brain white matter. Of the 47,174 unique transcripts expressed in these two tissues, 471 (1.0%) were differentially expressed by more than 5-fold (P < 0.001). Classification of these genes revealed functions consistent with the biological properties of glioblastomas, in particular: angiogenesis, transcription, and cell cycle related genes. C1 Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. Washington Univ, Genome Sequencing Ctr, St Louis, MO 63108 USA. Univ Calif Lawrence Livermore Natl Lab, IMAGE Consortium, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. NIA, Gerontol Res Ctr, Biol Chem Lab, Baltimore, MD 21224 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Columbia Univ, Dept Pathol, New York, NY 10032 USA. NCI, Off Director, Canc Genome Anat Project, Bethesda, MD 20892 USA. RP Riggins, GJ (reprint author), Duke Univ, Med Ctr, Dept Pathol, Box 3156, Durham, NC 27710 USA. RI Papadopoulos, Nickolas/K-7272-2012; Marra, Marco/B-5987-2008; OI Lash, Alex/0000-0003-3787-1590 NR 20 TC 322 Z9 338 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 1 PY 1999 VL 59 IS 21 BP 5403 EP 5407 PG 5 WC Oncology SC Oncology GA 252KG UT WOS:000083500200002 PM 10554005 ER PT J AU Harrell, L Schunkert, H Palacios, IF AF Harrell, L Schunkert, H Palacios, IF TI Risk predictors in patients scheduled for percutaneous coronary revascularization SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE PTCA; percutaneous coronary interventions; clinical outcomes; stents; atherectomy ID BALLOON ANGIOPLASTY; ARTERY DISEASE; DIRECTIONAL ATHERECTOMY; DETERMINANTS; COMPLICATIONS; MORPHOLOGY; EXPERIENCE; PLACEMENT; CLOSURE; QCA AB Traditionally, procedural risks associated with conventional balloon coronary angioplasty have been largely attributed to unfavorable lesion morphology. However, factors predicting adverse events in the current practice of percutaneous coronary revascularization are unclear. The present study was undertaken to determine factors predicting major adverse events (death or Q-wave myocardial infarction or emergency bypass surgery) in 3,335 consecutive patients undergoing percutaneous coronary revascularization in the current practice of percutaneous coronary revascularization. During the period of observation, the rate of lesions treated successfully increased from 91% to 95% (P < 0.0001), whereas the rate of major adverse events (MACE) decreased from 3.6% to 1.6% (odds ratio [OR], 0.70 per year). Using multiple stepwise logistic regression analysis, cardiogenic shock (OR, 8.59; confidence interval [CI], 4.27-17.27), renal disease (OR, 3.33; CI, 1.95-5.69), evolving myocardial infarction (OR, 2.80; CI, 1.47-5.31), congestive heart failure (OR, 2.18; CI, 1.23-3.86), total number of lesions treated (OR, 1.28; CI, 1.03-1.591, age (OR, 1.03; CI, 1.01-1.06), and history of prior coronary intervention (OR, 0.51; CI 0.26-0.99) were identified as independent predictors of MACE. In addition, vascular disease (OR, 2.48; CI 1.37-4.50) and unstable angina pectoris (OR, 0.44; CI 0.25-0.79) were related to adverse events when patients in cardiogenic shock were excluded from the model. With the exception of most unfavorable lesion morphology (AHA/ACC lesion type C; OR, 2.05; CI, 1.19-3.52), anatomic parameters added no further information. In the present era of device technology, success rates of percutaneous coronary revascularization procedures have increased and remain to be determined by lesion morphology. In contrast, the rate of MACE is declining and best predicted by easily identified patient characteristics. Cathet. Cardiovasc. Intervent. 48:253-264 1999. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Cardiac Catheterizat Lab, Boston, MA 02114 USA. Univ Regensburg, Med Klin & Poliklin Innere Med 2, D-8400 Regensburg, Germany. RP Palacios, IF (reprint author), Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Cardiac Catheterizat Lab, Bulfinch 105,Fruit St, Boston, MA 02114 USA. NR 25 TC 19 Z9 21 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 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD NOV PY 1999 VL 48 IS 3 BP 253 EP 260 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 251DZ UT WOS:000083430500003 PM 10525222 ER PT J AU Blackstone, C Sheng, M AF Blackstone, C Sheng, M TI Protein targeting and calcium signaling microdomains in neuronal cells SO CELL CALCIUM LA English DT Review ID LONG-TERM POTENTIATION; METABOTROPIC GLUTAMATE RECEPTORS; D-ASPARTATE RECEPTOR; HIPPOCAMPAL PYRAMIDAL NEURONS; NITRIC-OXIDE SYNTHASE; NMDA RECEPTOR; POSTSYNAPTIC DENSITY; DENDRITIC SPINES; IN-VIVO; NEUROTRANSMITTER RELEASE AB Over the last several years, a number of optical imaging, physiological, and molecular studies have clarified the mechanisms underlying differential calcium signaling in the postsynaptic neuron. These studies have revealed the existence of membrane-associated calcium microdomains, which are often specifically coupled to distinct protein signaling pathways. In this review, we discuss how these signaling microdomains are organized and regulated, emphasizing the structural and molecular features of synaptic protein complexes containing the metabotropic and N-methyl-D-aspartate (NMDA) glutamate receptors and the L-type voltage-dependent calcium channels (VDCCs). We conclude with a discussion of how these different signaling complexes may interact with one another, relationships which may be important in orchestrating the complex calcium signaling underlying developmental and activity-dependent changes in synaptic function. (C) Harcourt Publishers Ltd. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Neurobiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sheng, M (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Dept Neurobiol, 50 Blossom St,Wellman 423, Boston, MA 02114 USA. NR 97 TC 31 Z9 32 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD NOV PY 1999 VL 26 IS 5 BP 181 EP 192 DI 10.1054/ceca.1999.0071 PG 12 WC Cell Biology SC Cell Biology GA 264DE UT WOS:000084164400005 PM 10643556 ER PT J AU Kennedy, JS Raab, M Rudd, CE AF Kennedy, JS Raab, M Rudd, CE TI Signaling scaffolds in immune cells SO CELL CALCIUM LA English DT Review ID PROTEIN-TYROSINE KINASE; WISKOTT-ALDRICH SYNDROME; RECEPTOR-ZETA-CHAIN; TANDEM SH2 DOMAINS; T-CELLS; ADAPTER PROTEIN; MOLECULAR-CLONING; CYTOSKELETAL REORGANIZATION; INTERLEUKIN-2 PRODUCTION; THYMOCYTE DEVELOPMENT AB Of the past several years progress in understanding TCR signal transduction has led to the discovery of new kinases, adapter molecules and multiple signaling pathways. The study of molecules such as LAT, SLP-76, FYB, SKAP-55 and VAV have revealed multiple mechanisms with which to control the activation of downstream signaling pathways through RAS, PLCgamma-1 and ERK/MAPK. Signaling through SLP-76 can play a role in TCR-induced cytoskeleton changes through activation of effector molecules in the RAC/RHO-family of GTPases. In addition, SLP-76 through its association with FYB/FYN-T appears to play a role in IL-2 gene transcription following TCR activation. Finally, these newly identified adaptor molecules, such as LAT, may be crucial in T-cell activation by enhancing the recruitment of critical kinases to glycolipid-enriched microdomains of the activated T-cell receptor complex. (C) Harcourt Publishers Ltd. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Rudd, CE (reprint author), 44 Binney St, Boston, MA 02115 USA. NR 69 TC 21 Z9 21 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4160 J9 CELL CALCIUM JI Cell Calcium PD NOV PY 1999 VL 26 IS 5 BP 227 EP 235 DI 10.1054/ceca.1999.0069 PG 9 WC Cell Biology SC Cell Biology GA 264DE UT WOS:000084164400010 PM 10643561 ER PT J AU Yoon, KH Quickel, RR Tatarkiewicz, K Ulrich, TR Hollister-Lock, J Trivedi, N Bonner-Weir, S Weir, GC AF Yoon, KH Quickel, RR Tatarkiewicz, K Ulrich, TR Hollister-Lock, J Trivedi, N Bonner-Weir, S Weir, GC TI Differentiation and expansion of beta cell mass in porcine neonatal pancreatic cell clusters transplanted into nude mice SO CELL TRANSPLANTATION LA English DT Article DE islet transplantation; xenotransplantation; neonatal pancreatic cell clusters; porcine islets; beta cell expansion; islet differentiation ID LARGE-SCALE ISOLATION; ISLET CELLS; PIG PANCREAS; XENOGRAFTS; CULTURE; GLUCOSE; XENOTRANSPLANTATION; LANGERHANS; REVERSAL; SURVIVAL AB Neonatal porcine pancreas has considerable capacity for growth and differentiation, making it an attractive potential sourer of islet tissue for xenotransplantation. Pancreases from 1-3-day-old newborn pigs were digested with collagenase and cultured for 8 days. The resulting cellular aggregates are called porcine neonatal pancreatic cell clusters (NPCCs). The mean yield of NPCCs from a newborn pig was 28,200 +/- 1700 islet equivalents. Cytokeratin 7 (CK7) was used as a marker for the immunostaining of pancreatic duct cells. In neonatal pancreas, 18% of the insulin-positive cells co-stained for CK7, thus bring protodifferentiated, NPCCs also contained protodifferentiated cells; insulin/PP and insulin/somatostatin co-stained cells were more common than insulin/glucagon cells. Between 1 and 8 days of culture, the DNA content of the NPCCs fell to 16% and the insulin content to 33% of the starting value, mainly due to the preferential loss of exocrine cells. Transplantation of 2000 or 4000 NPCCs into diabetic nude mice typically normalized glucose values in 10-20 weeks. Mice with successful grafts had lower fasting blood glucose levels than normal mice and accelerated glucose clearance after an IP glucose load. The starting NPCCs consisted of 17% insulin-staining cells, but the grafts of mice with reversed diabetes consisted of 94% beta cells, with some co-stained for CK7, indicating that the grafts still contained immature cells. The mass of insulin-producing cells rose from 0.22 +/- 0.08 mg 1 week after transplantation to 4.34 +/- 0.27 mg in mice sacrificed at 27-35 weeks. In summary, NPCCs contain mostly islet precursor cells, which when transplanted into nude mice undergo striking differentiation and beta cell expansion. C1 Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Weir, GC (reprint author), Joslin Diabet Ctr, Div Res, Sect Islet Transplantat & Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-50657, DK-35449, DK-36836] NR 33 TC 58 Z9 60 U1 1 U2 3 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PD NOV-DEC PY 1999 VL 8 IS 6 BP 673 EP 689 PG 17 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 285DH UT WOS:000085374000013 PM 10701496 ER PT J AU Tilly, JL Kolesnick, RN AF Tilly, JL Kolesnick, RN TI Sphingolipid signaling in gonadal development and function SO CHEMISTRY AND PHYSICS OF LIPIDS LA English DT Article DE ceramide; sphingomyelinase; apoptosis; germ cell; oocyte; sperm; ovary; testis ID GERM-CELL APOPTOSIS; DAUNORUBICIN-INDUCED APOPTOSIS; RADIATION-INDUCED APOPTOSIS; CERAMIDE-INDUCED APOPTOSIS; CULTURED GRANULOSA-CELLS; FAS-INDUCED APOPTOSIS; N-TERMINAL KINASE; EPIDIDYMAL MATURATION; NEUTRAL SPHINGOMYELINASE; DEATH AB Sphingolipid second messengers, such as ceramide and sphingosine-1-phosphate, signal proliferation, differentiation and death in mammalian cells. The object of this article is to highlight the potential impact of this new information on the study of female and male gonadal development and function. Since the generation of competent gametes by both sexes is precisely regulated by maturational (meiotic) and apoptotic (quality-control) checkpoints, it is proposed that lipid signaling molecules serve as important contributors to the regulation of gametogenesis. The function of sphingolipid molecules in mediating stress- or damage-induced apoptosis in the germ line, an event most-likely associated with impaired gonadal function and infertility, is also discussed. Collectively, these areas represent exciting research directions that may ultimately lead to the development of new therapeutics to coordinate and control fertility in males and females. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Lab Signal Transduct, New York, NY 10021 USA. RP Tilly, JL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol,Vincent Ctr Reprod Biol, VBK137E-GYN,55 Fruit St, Boston, MA 02114 USA. NR 46 TC 12 Z9 12 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-3084 J9 CHEM PHYS LIPIDS JI Chem. Phys. Lipids PD NOV PY 1999 VL 102 IS 1-2 BP 149 EP 155 DI 10.1016/S0009-3084(99)00083-3 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 245YZ UT WOS:000083137300015 PM 11001569 ER PT J AU Levine, SM Angel, L Anzueto, A Susanto, I Peters, JI Sako, EY Bryan, CL AF Levine, SM Angel, L Anzueto, A Susanto, I Peters, JI Sako, EY Bryan, CL TI A low incidence of posttransplant lymphoproliferative disorder in 109 lung transplant recipients SO CHEST LA English DT Article DE Epstein-Barr virus; lung transplantation; posttransplant lymphoproliferative disorder ID EPSTEIN-BARR-VIRUS; ORGAN-TRANSPLANTATION; ACYCLOVIR THERAPY; SINGLE-CENTER; RISK FACTOR; IMMUNOSUPPRESSION; HEART; ALLOGRAFT; LYMPHOMAS; INFECTION AB Study objectives: The incidence of posttransplant lymphoproliferative disorder (PTLD) has been reported to range from 6.4 to 20% in lung transplant (LT) recipients. Postulated contributing factors include Epstein-Barr virus (EBV) infection and the use of immunosuppression, particularly muromonab-CD3 (OKT3)(Orthoclone OKT-3; Ortho Biotech; Raritan, NJ). We sought to examine these PTLD risk factors in 109 LT recipients at our institution who survived >1 month. Design: Retrospective review of EBV serology of all LT recipients at our institution. Our standard transplant protocol includes OKT3 for induction and refractory rejection, as well as lifelong acyclovir for herpes prophylaxis, We do not perform EBV donor-recipient matching. Setting: A university-based LT center. Results: We found that 5 of 109 patients were serologically negative for EBV prior to lung transplantation, and all of these patients converted following lung transplantation, The mean time to conversion was 151 days (range, 11 to 365 days). One fatal case of PTLD was documented in an EBV seroconverter (one of five patients) 12 weeks status posttransplantation for lymphangioleiomyomatosis. One nonfatal extrathoracic PTLD was documented in a seropositive patient (1 of 104 patients) 33 months posttransplantation. Conclusions: We conclude the following: (1) PTLD in LT recipients may have a lower incidence (2 of 109 patients; 1.8%) than previously reported, despite an aggressive immunosuppressive regimen; and (2) the incidence of PTLD is higher in patients with primary EBV infection (20% vs 1%). C1 S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, Pulm Sect 111E, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Pulm Dis Crit Care Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, Div Cardiothorac Surg & Transplant, San Antonio, TX 78284 USA. RP Levine, SM (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Mem Vet Hosp Div, Pulm Sect 111E, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. NR 25 TC 41 Z9 42 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 1999 VL 116 IS 5 BP 1273 EP 1277 DI 10.1378/chest.116.5.1273 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 256KF UT WOS:000083723900025 PM 10559086 ER PT J AU McCully, K Mancini, D Levine, S AF McCully, K Mancini, D Levine, S TI Nuclear magnetic resonance spectroscopy - Its role in providing valuable insight into diverse clinical problems SO CHEST LA English DT Article DE humans; magnetic resonance spectroscopy; metabolism; muscle; respiratory disease ID OBSTRUCTIVE PULMONARY-DISEASE; PERIPHERAL MUSCLE WEAKNESS; SKELETAL-MUSCLE; HEART-FAILURE; EXERCISE; RECOVERY; METABOLISM; KINETICS; P-31-MRS; FATIGUE AB Skeletal muscle plays an important role in respiratory and cardiovascular physiology. The ability to measure metabolic changes in skeletal muscle has been enhanced with the advent of magnetic resonance spectroscopy (MRS). MRS measurements have been used to understand the metabolic control of respiration and to evaluate metabolic changes in the muscle in patients with respiratory and cardiac diseases. The key to the respiratory control measurements is the ability to measure intracellular pH with MRS. Muscle oxidative metabolism has been measured in two ways: during steady-state exercise and using recovery kinetics. The similarities in the metabolic findings for pulmonary and coronary disease suggest the potential for some interesting common pathways. C1 Univ Georgia, Ramsey Student Ctr, Dept Exercise Sci, Athens, GA 30602 USA. Columbia Univ, Dept Cardiol, New York, NY USA. Vet Affairs Med Ctr, Div Pulm Med, Philadelphia, PA USA. RP McCully, K (reprint author), Univ Georgia, Ramsey Student Ctr, Dept Exercise Sci, Athens, GA 30602 USA. NR 41 TC 20 Z9 21 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 1999 VL 116 IS 5 BP 1434 EP 1441 DI 10.1378/chest.116.5.1434 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 256KF UT WOS:000083723900048 PM 10559109 ER PT J AU Lin, AL Shi, QH Johnson, DA Paterson, TF Rinaldi, MG Yeh, CK AF Lin, AL Shi, QH Johnson, DA Paterson, TF Rinaldi, MG Yeh, CK TI Further characterization of human salivary anticandidal activities in a human immunodeficiency virus-positive cohort by use of microassays SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID CANDIDA-ALBICANS; DEFENSE-MECHANISMS; ORAL CANDIDIASIS; HIV-1 INFECTION; HEALTHY-ADULTS; PAROTID-SALIVA; AIDS; HISTATINS; PROTEINS; GROWTH AB Salivary anticandidal activities play an important role in oral candidal infection. R. P. Santarpia et al, (Oral Microbiol, Immunol, 7:38-43, 1992) developed in vitro anticandidal assays to measure the ability of saliva to inhibit the viability of Candida albicans blastoconidia and the formation of germ tubes by C. albicans, In this report, we describe modifications of these assays for use with small volumes of saliva (50 to 100 mu l). For healthy subjects, there is strong inhibition of blastoconidial viability in stimulated parotid (75%), submandibular-sublingual (74%), and whole (97%) saliva, as well as strong inhibition of germ tube formation (>80%) for all three saliva types. The susceptibility of several Candida isolates to inhibition of viability by saliva collected from healthy subjects is independent of body source of Candida isolation (blood, oral cavity, or vagina) or the susceptibility of the isolate to the antifungal drug fluconazole. Salivary anticandidal activities in human immunodeficiency virus (HIV)-infected patients were significantly lower than those in healthy controls for inhibition of blastoconidial viability (P < 0.05) and germ tube formation (P < 0.001), Stimulated whole-saliva flow rates were also significantly lower (P < 0.05) for HIV-infected patients. These results show that saliva of healthy individuals has anticandidal activity and that this activity is reduced in the saliva of HIV-infected patients. These findings may help explain the greater incidence of oral candidal infections for individuals with AIDS. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin 182, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Community Dent, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. RP Yeh, CK (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, Ctr Geriatr Res Educ & Clin 182, San Antonio, TX 78284 USA. FU NIDCR NIH HHS [R01 DE011381, DE-11381, DE-12188] NR 27 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD NOV PY 1999 VL 6 IS 6 BP 851 EP 855 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 254RF UT WOS:000083625400014 PM 10548575 ER PT J AU Duan, ZF Feller, AJ Penson, RT Chabner, BA Seiden, MV AF Duan, ZF Feller, AJ Penson, RT Chabner, BA Seiden, MV TI Discovery of differentially expressed genes associated with paclitaxel resistance using cDNA array technology: Analysis of interleukin (IL) 6, IL-8, and monocyte chemotactic protein 1 in the paclitaxel-resistant phenotype SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN OVARIAN-CANCER; AUTOCRINE GROWTH-FACTOR; CELL CARCINOMA; NUDE-MICE; TAXOL; APOPTOSIS; DISPLAY; ANGIOGENESIS; CHEMOKINES; ETOPOSIDE AB In an attempt to define the molecular changes associated with the paclitaxel-resistant phenotype in human cancer, a paclitaxel-resistant ovarian cancer cell Line, SKOV-3(TR), was established through stepwise selection in increasing paclitaxel concentrations. SROV-3(TR) was cross- resistant to doxorubicin and vincristine and overexpressed multidrug resistance gene 1 but not multidrug resistance associated protein. SKOV-3(TR) and the paclitaxel-sensitive SKOV-3 parent line were characterized using human cDNA array technology that examined expression of a wide variety of genes involved in cell growth, signal transduction, cell death, and immune function. cDNA probes from reverse transcribed mRNAs of both paclitaxel-resistant and parent cells were compared to identify genes differentially expressed in the paclitaxel-resistant cells. Of 588 different human cDNA transcripts compared, 6 genes were found to be markedly decreased, and 12 genes increased in the resistant subline. Northern analysis and/or reverse transcription-PCR confirmed that 12 of these 18 genes were over- or underexpressed in SKOV-3(TR), In addition, at Least eight of the genes were found differentially expressed in several other paclitaxel- and/or doxorubicin-resistant cell lines, both those with increased multidrug resistance expression and those without. Included in the set of overexpressed genes were the cytokines/chemokines interleukin 6, interleukin 8, and monocyte chemotactic protein 1, ELISA assays confirm that mRNA overexpression of these cytokine/chemokines was associated with the increased secretion of these molecules in the tissue culture supernatant. Evaluation of supernatants from an expanded collection of paclitaxel- and Adriamycin-resistant cell lines demonstrated that all of the resistant lines had significant overexpression of at least one cytokine/chemokine as compared with their drug-sensitive parent line. The overexpression of these cytokines seemed to be stable and associated with a drug-resistant phenotype with only a modest induction of cytokine expression in the parent line with short-term paclitaxel exposure. These findings suggest that the development of paclitaxel resistance is accompanied by multiple changes in gene expression including stable alterations in selective chemokine and cytokine expression. The role these associated genetic changes have in the drug-resistant phenotype is discussed. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. NR 50 TC 122 Z9 137 U1 0 U2 5 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 NOV PY 1999 VL 5 IS 11 BP 3445 EP 3453 PG 9 WC Oncology SC Oncology GA 258RP UT WOS:000083853200017 PM 10589757 ER PT J AU Masiakos, PT MacLaughlin, DT Maheswaran, S Teixeira, J Fuller, AF Shah, PC Kehas, DJ Kenneally, MK Dombkowski, DM Ha, TU Preffer, FI Donahoe, PK AF Masiakos, PT MacLaughlin, DT Maheswaran, S Teixeira, J Fuller, AF Shah, PC Kehas, DJ Kenneally, MK Dombkowski, DM Ha, TU Preffer, FI Donahoe, PK TI Human ovarian cancer, cell lines, and primary ascites cells express the human mullerian inhibiting substance (MIS) type II receptor, bind, and are responsive to MIS SO CLINICAL CANCER RESEARCH LA English DT Article ID SERINE THREONINE KINASE; GROWTH-FACTOR-BETA; TGF-BETA; DEVELOPMENTAL EXPRESSION; SEXUAL DEVELOPMENT; DUCT REGRESSION; OOCYTE MEIOSIS; TUMOR-GROWTH; RAT OVARY; HORMONE AB Six human ovarian cancer cell lines and samples of ascites cells isolated from 27 patients with stage In or IV ovarian papillary serous cystadenocarcinoma were studied individually to test whether recombinant human Mullerian inhibiting substance (rhMIS) acts via its receptor, To do these experiments, we scaled up production of rhMIS and labeled it successfully with biotin for binding studies, cloned the human MIS type II receptor for mRNA detection, and raised antibodies to an extracellular domain peptide for protein detection. These probes were first tested on the human ovarian cancer cell lines and then applied to primary ovarian ascites cells. rhMIS inhibited colony growth of five of six cell lines that expressed the human MIS type II receptor mRNA by Northern analysis while not inhibiting receptor-negative COS cells, Flow cytometry performed on MIS-sensitive ovarian cancer cell lines demonstrated specific and saturable binding of rhMIS (K-d = 10.2 nM). Ascites cells from 15 of 27 or 56% of patients tested bound biotinylated MIS (MIS-biotin) and, of the 11 that grew in soft agarose, 9 of 11 or 82% showed statistically significant inhibition of colony formation. Of the 15 patients who bound biotinylated MIS, mRNA was available for analysis from 9, and 8 of 9 expressed MIS type II. receptor mRNA by reverse transcription-PCR, showing a statistically significant correlation, compared,with binding, by chi(2) analysis (P = 0.025), Solid ovarian cancers,were positive for the MIS type LI receptor protein by immunohistochemical staining, which colocalized with staining for antibody to CA-125 (OC-125), Thus, the detection of the MIS type II receptor by flow cytometry may be a useful predictor of therapeutic response to MIS and mag be a modality to rapidly choose patients with late-stage ovarian cancer for treatment with MIS. C1 Massachusetts Gen Hosp, Pediat Surg Res Labs, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pediat Surg Serv, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Flow Cytometry Lab, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Pediat Surg Res Labs, 55 Fruit St,WRN 11, Boston, MA 02114 USA. EM donahoe.patricia@mgh.harvard.edu FU NCI NIH HHS [R01 CA17393]; NICHD NIH HHS [P30 HD28138, R01 HD32113] NR 48 TC 73 Z9 81 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV PY 1999 VL 5 IS 11 BP 3488 EP 3499 PG 12 WC Oncology SC Oncology GA 258RP UT WOS:000083853200023 PM 10589763 ER PT J AU Patnaik, A Rowinsky, E Hammond, L Thurman, A Hidalgo, M Siu, L Williams, J Holroyd, K Nelson, K Von Hoff, DD Eckhardt, GS AF Patnaik, A Rowinsky, E Hammond, L Thurman, A Hidalgo, M Siu, L Williams, J Holroyd, K Nelson, K Von Hoff, DD Eckhardt, GS TI A phase I and pharmacokinetic (PK) study of the unique angiogenesis inhibitor squalamine lactate (MSI-1256F). SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Canc Therapy & Res Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. Magainin Phrmaceut Inc, Plymouth Meeting, PA USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 5 SU S MA 15 BP 3732S EP 3732S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700016 ER PT J AU Chakravarti, A Zehr, EM Zietman, AL Shipley, WU Goggins, WB Finkelstein, DM Young, RH Wu, CL AF Chakravarti, A Zehr, EM Zietman, AL Shipley, WU Goggins, WB Finkelstein, DM Young, RH Wu, CL TI Thymosin beta 16 predicts for distant failure in patients with clinically localized prostate cancer. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol & Urol, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 5 SU S MA 68 BP 3743S EP 3743S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700069 ER PT J AU Hansen-Algenstaedt, N Algenstaedt, P Achilles, EG Stoll, BR Padera, TP Fukumura, D Kothe, R Ruther, W Jain, RK AF Hansen-Algenstaedt, N Algenstaedt, P Achilles, EG Stoll, BR Padera, TP Fukumura, D Kothe, R Ruther, W Jain, RK TI Tumor oxygenation during hormone ablation and chemotherapie. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Hosp Hamburg, Dept Orthopaed Surg, D-20246 Hamburg, Germany. Univ Hosp Hamburg, Dept Hepatobiliary Surg, D-20246 Hamburg, Germany. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 5 SU S MA 196 BP 3769S EP 3769S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700195 ER PT J AU Damia, G Silvestri, S Filiberti, L Broggini, M D'Incalci, M AF Damia, G Silvestri, S Filiberti, L Broggini, M D'Incalci, M TI Importance of DNA repair mechanisms for the sensitivity of tumor cells to ET-743. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. PharmaMar Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 5 SU S MA 303 BP 3790S EP 3790S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700302 ER PT J AU Hornicke, FJ Weissbach, L Nielsen, GP Fondren, G Harmon, D Jimeno, J Chabner, BA Faircloth, GT AF Hornicke, FJ Weissbach, L Nielsen, GP Fondren, G Harmon, D Jimeno, J Chabner, BA Faircloth, GT TI In vitro effect of the tetrahydroisoquinoline alkaloid Ecteinascidin-743 (ET-743) on chondrosarcoma (CHSA) cells. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. PharmaMar Inc, Cambridge, MA USA. NR 0 TC 2 Z9 2 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 NOV PY 1999 VL 5 SU S MA 304 BP 3790S EP 3790S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700303 ER PT J AU Supko, JG Lu, H Jimeno, JM Grant, W Faircloth, GT AF Supko, JG Lu, H Jimeno, JM Grant, W Faircloth, GT TI Preclinical pharmacology studies with the marine natural product Kahalalide F SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 PharmaMar USA Inc, Cambridge, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. PharmaMar SA, Madrid, Spain. NR 0 TC 9 Z9 9 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 NOV PY 1999 VL 5 SU S MA 315 BP 3792S EP 3792S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700314 ER PT J AU Aboody, KS Bower, KA Shivji, S Brown, A McDonough, CB Rainov, NG Black, PM Breakefield, XO Snyder, EY AF Aboody, KS Bower, KA Shivji, S Brown, A McDonough, CB Rainov, NG Black, PM Breakefield, XO Snyder, EY TI A novel strategy for gene therapy delivery to brain tumors: Genetically modified neural stem cells (NSCs) display tropism for intracranial gliomas. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 HMS, Childrens Hosp, Dept Neurol, Boston, MA USA. HMS, Childrens Hosp, Dept Pediat, Boston, MA USA. HMS, Childrens Hosp, Dept Neurosurg, Boston, MA USA. HMS, Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Boston, MA USA. HMS, Brigham & Womens Hosp, Dept Neurosurg, Brain tumor Serv, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 5 SU S MA 460 BP 3822S EP 3822S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700458 ER PT J AU Seiden, M Swenerton, K Matulonis, U Rose, P Batist, G Verma, S Oza, A Popadiuk, C Bessette, P Angers, E Ette, E Harding, MW Charpentier, D AF Seiden, M Swenerton, K Matulonis, U Rose, P Batist, G Verma, S Oza, A Popadiuk, C Bessette, P Angers, E Ette, E Harding, MW Charpentier, D TI A Phase II study of IncelTM (biricodar, VX-710) plus paclitaxel in women with advanced ovarian cancer refractory to paclitaxel therapy. SO CLINICAL CANCER RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. BCCA, Vancouver, BC, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. Macdonald Womens Hosp, Cleveland, OH USA. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. ORCC, Ottawa, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. H Bliss Murphy Canc Ctr, St Johns, NF, Canada. CUSE, Fleurimont, PQ, Canada. BioChem Pharma, Laval, PQ, Canada. Vertex Pharmaceut Inc, Cambridge, MA USA. CHUM, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 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 NOV PY 1999 VL 5 SU S MA 530 BP 3836S EP 3836S PG 1 WC Oncology SC Oncology GA 260JL UT WOS:000083945700527 ER PT J AU Perlmutter, GS AF Perlmutter, GS TI Axillary nerve injury SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID INFERIOR CAPSULAR SHIFT; MULTIDIRECTIONAL INSTABILITY; CONTACT SPORTS; SHOULDER AB Axillary nerve injury remains the most common peripheral nerve injury to affect the shoulder, It most often is seen after glenohumeral joint dislocation, proximal humerus fracture, or a direct blow to the deltoid muscle. Compression neuropathy has been reported to occur in the quadrilateral space syndrome, although the true pathophysiology of this disorder remains unclear. The axillary nerve is vulnerable during any operative procedure involving the inferior aspect of the shoulder and iatrogenic injury remains a serious complication of shoulder surgery. During the acute phase of injury, the shoulder should be rested, and when clinically indicated, a patient should undergo an extensive rehabilitation program emphasizing range of motion and strengthening of the shoulder girdle muscles. If no axillary nerve recovery is observed by 3 to 6 months after injury, surgical exploration may be indicated, especially if the mechanism of injury is consistent with nerve rupture. Patients who sustain injury to the axillary nerve have a variable prognosis for nerve recovery although return of function of the involved shoulder typically is good to excellent, depending on associated ligamentous or bony injury. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Perlmutter, GS (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg, 275 Cambridge St,Suite 403, Boston, MA 02114 USA. NR 32 TC 62 Z9 62 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 1999 IS 368 BP 28 EP 36 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 254XT UT WOS:000083640100005 PM 10613150 ER PT J AU Leffert, RD Perlmutter, GS AF Leffert, RD Perlmutter, GS TI Thoracic outlet syndrome - Results of 282 transaxillary first rib resections SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID CONDUCTION; DIAGNOSIS AB Thoracic outlet syndrome may follow trauma but also may be seen as a result of postural abnormalities of the shoulder girdle, Cervical ribs and other anatomic variations are not prerequisites for the diagnosis, although they may be more common in patients with thoracic outlet syndrome, The diagnosis is made by history and physical examination, There is no reliable laboratory diagnostic test to confirm or exclude the diagnosis. Proper selection of candidates for surgery can produce excellent and good results in a high percentage of cases, The transaxillary approach to first rib resection is tolerated well, and serious complications should be unusual when the procedure is performed by an experienced surgeon, Postoperative attention to shoulder girdle mechanics is important in the prevention of recurrence of symptoms and treating them should they occur. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Leffert, RD (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, White 1003,55 Fruit St, Boston, MA 02114 USA. NR 23 TC 27 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 1999 IS 368 BP 66 EP 79 PG 14 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 254XT UT WOS:000083640100009 PM 10613154 ER PT J AU Sangwan, VS Akpek, EK Voo, I Zhao, TZ Pinar, V Yang, J Christen, W Baltatzis, S Wild, R Foster, CS AF Sangwan, VS Akpek, EK Voo, I Zhao, TZ Pinar, V Yang, J Christen, W Baltatzis, S Wild, R Foster, CS TI Krill protease effects on wound healing after corneal alkali burn SO CORNEA LA English DT Article DE corneal alkali burn; corneal ulceration; krill protease; metalloproteinase ID EPIDERMAL GROWTH-FACTOR; CONJUNCTIVAL TRANSPLANTATION; RABBIT CORNEA; ULCERATION; COLLAGENASE; METALLOPROTEINASE; DEGRADATION; PREVENTION; CITRATE; PERFORATION AB Purpose. To study the effect of a novel protease in the development and progression of corneal ulceration secondary to alkali burning. Methods. By using a 4N alkali burn model of corneal ulceration in rabbits, the effects and efficacy of topical application of a novel protease (PHM-101) capable of degrading metalloproteinases was studied for 28 days of treatment and 7 days off treatment for its effect on corneal ulceration and recurrent erosion. Results. At day 28, both the protease- and placebo-treated groups had different numbers of eyes showing reepithelialization [nine (45%) of 20 and six (33%) of 18, respectively]. By day 35 the protease-treated group had significantly fewer recurrent epithelial defects [two (13%) of 15 vs. eight (61%) of 13; p = 0.02]. Similarly, at day 35 the protease treated group showed significantly less corneal ulceration [two (13%) of 15 vs, six (46%) of 13; p = 0.02], and those ulcers were of a lesser severity (three units vs. 17.76 units). No difference was found in the degree of stromal edema or neovascularization, nor was there any difference in histopathologic characteristics of inflammatory cell infiltration and corneal scarring. Conclusion. We conclude that this novel protease is efficient in reducing recurrent corneal epithelial defects and stromal ulceration after alkali burning. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Ocular Immunol & Uveitis Serv, Dept Ophthalmol,Hilles Immunol Lab, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med,Ocular Immunol & Uveitis Serv, Dept Ophthalmol,Hilles Immunol Lab, 243 Charles St, Boston, MA 02114 USA. OI Sangwan, Virender/0000-0002-8229-4158 NR 40 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD NOV PY 1999 VL 18 IS 6 BP 707 EP 711 DI 10.1097/00003226-199911000-00014 PG 5 WC Ophthalmology SC Ophthalmology GA 253XB UT WOS:000083581300015 PM 10571303 ER PT J AU Bartlett, JD Simmer, JP AF Bartlett, JD Simmer, JP TI Proteinases in developing dental enamel SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE amelogenesis; matrix metalloproteinases; mineralization; serine proteinases ID LINKED AMELOGENESIS IMPERFECTA; DEVELOPING BOVINE ENAMEL; HUMAN MATRIX METALLOPROTEINASE; PORCINE IMMATURE ENAMEL; MOLECULAR-CLONING; SHEATH PROTEINS; CYSTEINE PROTEINASES; TISSUE DISTRIBUTION; PROTEOLYTIC-ENZYME; FUNCTIONAL-ASPECTS AB For almost three decades, proteinases have been known to reside within developing dental enamel. However, identification and characterization of these proteinases have been slow and difficult, because they are present in very small quantities and they are difficult to purify directly from the mineralizing enamel. Enamel matrix proteins such as amelogenin, ameloblastin, and enamelin are cleaved by proteinases soon after they are secreted, and their cleavage products accumulate in the deeper, more mature enamel layers, while the full-length proteins are observed only at the surface. These results suggest that proteinases are necessary for "activating" enamel proteins so the parent proteins and their cleavage products may perform different functions. A novel matrix metalloproteinase named enamelysin (MMP-20) was recently cloned from tooth tissues and was later shown to localize primarily within the most recently formed enamel. Furthermore, recombinant porcine enamelysin was demonstrated to cleave recombinant porcine amelogenin at virtually all of the sites that have previously been described in vivo. Therefore, enamelysin is at least one enzyme that may be important during early enamel development. As enamel development progresses to the later stages, a profound decrease in the enamel protein content is observed. Proteinases have traditionally been assumed to degrade the organic matrix prior to its removal from the enamel. Recently, a novel serine proteinase named enamel matrix serine proteinase-1 (EMSPI) was cloned from enamel organ epithelia. EMSPI localizes primarily to the early maturation stage enamel and may, therefore, be involved in the degradation of proteins prior to their removal from the maturing enamel. Other, as yet unidentified, proteinases and proteinase inhibitors are almost certainly present within the forming enamel and await discovery. C1 Forsyth Inst, Dept Biomineralizat, Boston, MA 02115 USA. Forsyth Inst, Harvard Foryth Dept Oral Biol, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Sch Dent, Dept Pediat Dent, San Antonio, TX 78284 USA. RP Forsyth Inst, Dept Biomineralizat, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE 12098, DE-10721, R29 DE012098] NR 109 TC 174 Z9 178 U1 2 U2 12 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PD NOV PY 1999 VL 10 IS 4 BP 425 EP 441 PG 17 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 291MW UT WOS:000085741500001 PM 10634581 ER PT J AU Baldeon, ME Walker, WA AF Baldeon, ME Walker, WA TI Luminal regulators of intestinal immune responses SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mucosal Immunol Lab,Combined Program Pediat Gastr, Charlestown, MA 02129 USA. RP Walker, WA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mucosal Immunol Lab,Combined Program Pediat Gastr, 149 13th St,Room 3401, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 1999 VL 15 IS 6 BP 521 EP 522 DI 10.1097/00001574-199911000-00011 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 247GD UT WOS:000083212000011 ER PT J AU Abramson, S Niles, JL AF Abramson, S Niles, JL TI Anticoagulation in continuous renal replacement therapy SO CURRENT OPINION IN NEPHROLOGY AND HYPERTENSION LA English DT Review ID MOLECULAR-WEIGHT HEPARIN; CONTINUOUS ARTERIOVENOUS HEMOFILTRATION; CONTINUOUS VENOVENOUS HEMOFILTRATION; REGIONAL CITRATE ANTICOAGULATION; CONTINUOUS HEMODIAFILTRATION; STANDARD HEPARIN; HEPATIC-FAILURE; HEMODIALYSIS; PROSTACYCLIN; HEMORRHAGE AB Continuous renal replacement therapies (CRRTs) allow for gradual solute and fluid removal, In very sick patients with acute renal failure, they may be better tolerated than hemodialysis. The major drawback to CRRTs is the need for anticoagulation to maintain filter patency, The patients who are likely to benefit from CRRTs are also at higher risk for bleeding from systemic anticoagulation. The most commonly used form of anticoagulation for CRRTs, low-dose heparin, causes bleeding in 10-50% of patients, Regional anticoagulation using protamine may reduce the risk of bleeding, but it is difficult to use. Low molecular weight heparin and prostacyclin both may partially reduce bleeding, but are difficult to dose. Regional anticoagulation with citrate is easy to use and has been shown to prolong filter life without systemic anticoagulation, It is the anticoagulant of choice for most patients on CRRT, Curr Opin Nephrol Hypertens 8:701-707. (C) 1999 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Renal 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. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. RP Niles, JL (reprint author), Massachusetts Gen Hosp, Dialysis Unit, Bigelow 1052,55 Fruit St, Boston, MA 02114 USA. NR 42 TC 39 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1062-4821 J9 CURR OPIN NEPHROL HY JI Curr. Opin. Nephrol. Hypertens. PD NOV PY 1999 VL 8 IS 6 BP 701 EP 707 DI 10.1097/00041552-199911000-00009 PG 7 WC Urology & Nephrology; Peripheral Vascular Disease SC Urology & Nephrology; Cardiovascular System & Cardiology GA 269QM UT WOS:000084489100009 PM 10630816 ER PT J AU Mendez, MF Ottowitz, W Brown, CV Cummings, JL Perryman, KM Mandelkern, MA AF Mendez, MF Ottowitz, W Brown, CV Cummings, JL Perryman, KM Mandelkern, MA TI Dementia with leukoaraiosis: Clinical differentiation by temporoparietal hypometabolism on (18)FDG-PET imaging SO DEMENTIA AND GERIATRIC COGNITIVE DISORDERS LA English DT Article DE dementia; leukoaraiosis; vascular dementia; Alzheimer's disease; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; PROBABLE ALZHEIMERS-DISEASE; HEALTHY ELDERLY SUBJECTS; CEREBRAL WHITE-MATTER; VASCULAR DEMENTIA; MAGNETIC-RESONANCE; LEUKO-ARAIOSIS; FDG PET; OXYGEN-METABOLISM; SENILE DEMENTIA AB Patients with dementia and leukoaraiosis may have either Alzheimer's disease (AD) with cerebrovascular changes or a form of vascular dementia (VaD). The presence or absence of the characteristic AD pattern of bilateral temporoparietal hypometabolism on (18)FDG-PET was used to differentiate 30 patients with progressive dementia and severe leukoaraiosis. Compared to 18 patients with the typical AD pattern (group I), the remaining 12 (group II) had better recognition memory, and greater difficulty with sustained attention and serial reversals. Better recognition memory, confluent periventricular leukoaraiosis, and poorer sustained attention distinguished all group II patients from group I. Dementia patients with severe leukoaraiosis and bilateral temporoparietal hypometabolism may have predominant AD; those who lack this pattern and have confluent leukoaraiosis may have a greater contribution from VaD. Copyright (C) 1999 S. Karger AG, Basel. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Neurol & Psychiat, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Biobehav Sci, Los Angeles, CA 90024 USA. UC Irvine, Dept Phys, Los Angeles, CA USA. RP Mendez, MF (reprint author), W Los Angeles Vet Affairs Med Ctr, Neurobehav Unit 691 116AF, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIA NIH HHS [AG10123] NR 60 TC 11 Z9 11 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-8008 J9 DEMENT GERIATR COGN JI Dement. Geriatr. Cogn. Disord. PD NOV-DEC PY 1999 VL 10 IS 6 BP 518 EP 525 DI 10.1159/000017199 PG 8 WC Geriatrics & Gerontology; Clinical Neurology; Psychiatry SC Geriatrics & Gerontology; Neurosciences & Neurology; Psychiatry GA 254WK UT WOS:000083635000015 PM 10559569 ER PT J AU Ross, EV Yashar, SS Naseef, GS Barnette, DJ Skrobal, M Grevelink, J Anderson, RR AF Ross, EV Yashar, SS Naseef, GS Barnette, DJ Skrobal, M Grevelink, J Anderson, RR TI A pilot study of in vivo immediate tissue contraction with CO2 skin laser resurfacing in a live farm pig SO DERMATOLOGIC SURGERY LA English DT Article ID HIGH-ENERGY; IN-VITRO; CO2-LASER; SHRINKAGE; RHYTIDES; COLLAGEN AB BACKGROUND. It has been suggested that tissue ablation, collagen shrinkage, and new collagen deposition contribute to the clinical outcome of laser skin resurfacing. OBJECTIVE. TO Study the effects of fluence and pass number on thermal damage and tissue shrinkage, eve performed experiments in an in vivo farm pig model. METHODS. A CO2 laser was used to treat the flank skin of a farm pig. There were nine treatment sites based on number of passes and fluence per pass. Wound surface areas were measured pretreatment and immediately posttreatment. Biopsies were performed immediately after irradiation. RESULTS. Surface area measurements showed that immediate contraction tended to increase with increasing fluence and pass number up to a maximum of approximately 38% shrinkage, after which the percent contraction remained constant. Thermal damage increased with pass number for low and moderate fluence groups; however, in high fluence groups the thermal damage remained constant with an increasing number of passes. CONCLUSIONS. Our results suggest that CO2 laser resurfacing produces immediate tissue contraction and residual thermal damage that is saturable for multiple passes and high fluences. For small fluences, however, there is an almost linear increase in thermal damage and shrinkage with an increasing number of passes. C1 Massachusetts Gen Hosp, Dept Dermatol, Wellman Labs Photomed, Boston, MA 02114 USA. Naval Med Ctr San Diego, Dept Dermatol, San Diego, CA USA. RP Ross, EV (reprint author), USN Hosp, Box 324,34800 Bob Wilson Dr, San Diego, CA 92134 USA. NR 20 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1076-0512 J9 DERMATOL SURG JI Dermatol. Surg. PD NOV PY 1999 VL 25 IS 11 BP 851 EP 856 DI 10.1046/j.1524-4725.1999.99091.x PG 6 WC Dermatology; Surgery SC Dermatology; Surgery GA 253FA UT WOS:000083544900007 PM 10594596 ER PT J AU Valverde, AM Kahn, CR Benito, M AF Valverde, AM Kahn, CR Benito, M TI Insulin signaling in insulin receptor substrate (IRS)-1-deficient brown adipocytes requirement of IRS-1 for lipid synthesis SO DIABETES LA English DT Article ID GROWTH-FACTOR-I; PHOSPHATIDYLINOSITOL 3-KINASE; PRIMARY CULTURES; HORMONAL-REGULATION; GENE-EXPRESSION; IGF-I; KINASE; DIFFERENTIATION; MICE; STIMULATION AB Immortalized fetal brown adipocyte cell lines have been generated from homozygous (-/-) and heterozygous (+/-) insulin receptor substrate (IRS)-1-deficient mice, as well as from wild-type mice (+/+). Under growing conditions, these cell lines maintained the expression of the adipogenic marker fatty acid synthase and uncoupling protein-1, a tissue-specific thermogenic marker. The IRS-1 (-/-) brown adipocytes lacked IRS-1 protein expression and had a significant increase in IRS-2 protein expression. Insulin-induced tyrosine phosphorylation of IRS-1 was reduced by 50% in heterozygous IRS-1-deficient cells and was totally absent in homozygous cells, while tyrosine phosphorylation of IRS-2 showed a gradual increase. Insulin receptor alpha-subunit protein content and beta-subunit tyrosine kinase activity remained unchanged upon insulin stimulation, regardless of the lack of IRS-1. Brown adipocytes from homozygous IRS-1-deficient mice showed no IRS-1-associated p85 alpha subunit of phosphatidylinositol 3-kinase (PI 3-kinase) or IRS-1-associated PI 3-kinase activity in response to insulin, but exhibited enhanced IRS-2-associated p85 alpha subunit; and IRS-2-associated PI 3-kinase activity. Overall insulin-induced PI 3-kinase activity associated to antiphosphotyrosine immune complexes was decreased by 30% in the homozygous IRS-1-deficient brown adipocytes. Downstream PI 3-kinase, activated Akt (protein kinase B) was decreased by 92% in an insulin-stimulated homozygous IRS-1-deficient brown adipocyte cell line, whereas the expression of Akt was similar in the three cell lines. However, activated p70 S6 kinase (p70(s6k)) remained unchanged. Although brown adipocyte cell lines showed similar cytosolic lipid content in the presence of 10% fetal calf serum, cytosolic lipid content; was reduced in both serum-deprived heterozygous and homozygous IRS-1-deficient cells, Insulin treatment for 24 h doubled the cytosolic lipid content in wild-type and heterozygous IRS-1-deficient brown adipocyte cell lines but failed to increase the cytosolic lipid content in homozygous IRS-1-deficient cells. Our results strongly suggest increase the cytosolic lipid content in homozygous that IRS-1/PI 3-kinase/Akt activation is an essential requirement for insulin stimulation of lipid synthesis in brown adipocytes. C1 Univ Complutense Madrid, Fac Farm, Dept Bioquim & Biol Mol, E-28040 Madrid, Spain. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. RP Benito, M (reprint author), Univ Complutense Madrid, Fac Farm, Dept Bioquim & Biol Mol, Ciudad Univ, E-28040 Madrid, Spain. NR 33 TC 40 Z9 45 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 NOV PY 1999 VL 48 IS 11 BP 2122 EP 2131 DI 10.2337/diabetes.48.11.2122 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 248GR UT WOS:000083267200002 PM 10535444 ER PT J AU Bektas, A Suprenant, ME Wogan, LT Plengvidhya, N Rich, SS Warram, JH Krolewski, AS Doria, A AF Bektas, A Suprenant, ME Wogan, LT Plengvidhya, N Rich, SS Warram, JH Krolewski, AS Doria, A TI Evidence of a novel type 2 diabetes locus 50 cM centromeric to NIDDM2 on chromosome 12q SO DIABETES LA English DT Article; Proceedings Paper CT 1999 Annual Meeting of the American-Diabetes-Association CY 1999 CL SAN DIEGO, CALIFORNIA SP Amer Diabet Assoc ID NUCLEAR FACTOR-1-ALPHA GENE; LINKAGE ANALYSIS; YOUNG; MUTATIONS; MAPS AB To replicate the recent finding of a type 2 diabetes locus (NIDDM2) on 12q, families segregating early-onset autosomal-dominant type 2 diabetes were screened for linkage. Included were 26 Caucasian and 6 non-Caucasian pedigrees with an average age at diabetes diagnosis of 37 +/- 18 years. Affected (n = 233) and nonaffected (n = 152) family members were genotyped for 17 markers covering 90 cM on chromosome 12q. While no evidence for linkage was detected at the NIDDM2 locus, a Linkage peak was observed 50 cM centromeric to NIDDM2 at markers D12S375 and D12S1052. In a nonparametric analysis, the Z(all) score was 2.9 (P = 0.015) at D12S375, and increased to 3.8 (P = 0.007) among Caucasian families. Further increase in significance was observed in pedigrees with poor insulin response, with a maximum Z(all) of 6.2 (P = 0.002) at D12S375. Suggestive evidence of linkage was also detected by the parametric analysis, with the heterogeneity logarithm of odds score peaking at 2.5 (alpha = 0.15) between D12S375 and D12S1052. In summary our data indicate that the NIDDM2 locus does not play a major role in early-onset autosomal-dominant type 2 diabetes. Rather, they strongly suggest that a previously undetected type 2 diabetes locus exists 50 cM from NIDDM2 on 12q. C1 Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Doria, A (reprint author), Joslin Diabet Ctr, Div Res, Sect Genet & Epidemiol, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK36836, DK47475, DK55523] NR 20 TC 36 Z9 39 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 1999 VL 48 IS 11 BP 2246 EP 2251 DI 10.2337/diabetes.48.11.2246 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 248GR UT WOS:000083267200019 PM 10535461 ER PT J AU Cagliero, E Levina, EV Nathan, DM AF Cagliero, E Levina, EV Nathan, DM TI Immediate feedback of HbA(1c) levels improves glycemic control in type I and insulin-treated type 2 diabetic patients SO DIABETES CARE LA English DT Article ID IMMUNOLOGICAL METHOD; GLYCATED HEMOGLOBIN; PERFORMANCE; MELLITUS; SYSTEM; HBA1C AB OBJECTIVE - Accurate and reliable HbA(1c) results can be obtained at the time of the office visit by using benchtop analyzers. We tested the hypothesis that immediately available HbA(1c) result; could improve glycemic control by changing physician or patient behavior or both. RESEARCH DESIGN AND METHODS- A randomized controlled trial was conducted in 201 type 1 and insulin-treated type 2 diabetic patients attending an academic diabetes center. HbA(1c) levels, changes in insulin therapy, and use of health care resources were assessed during a 12-month follow-up period. RESULTS - HbA(1c) levels decreased significantly at 6 and 12 months in the immediate assay group (-0,57 +/- 1.44 and -0.40 +/- 1.65%, respectively; P < 0.01) but did not change in the control group (-0.11 +/- 0.79 and -0.19 +/- 1.16%, respectively; NS). The changes were similar for both type 1 and type 2 diabetic patients. There were no differences in the rates of hypoglycemic events or use of health care resources. CONCLUSIONS - In the setting of a controlled randomized trial, the immediate feedback of HbA(1c) results at the time of patient encounters resulted in a significant improvement of glycemic control at 6-month follow-up and persisted for the 12-month study . The introduction of this assay was positively received by both patients and physicians. C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. RP Cagliero, E (reprint author), Massachusetts Gen Hosp, Ctr Diabet, 50 Staniford St, Boston, MA 02114 USA. NR 18 TC 110 Z9 116 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1999 VL 22 IS 11 BP 1785 EP 1789 DI 10.2337/diacare.22.11.1785 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247FB UT WOS:000083209500005 PM 10546008 ER PT J AU Lim, SC Caballero, AE Smakowshi, P LoGerfo, FW Horton, ES Veves, A AF Lim, SC Caballero, AE Smakowshi, P LoGerfo, FW Horton, ES Veves, A TI Soluble intercellular adhesion molecule, vascular cell adhesion molecule, and impaired microvascular reactivity are early markers of vasculopathy in type 2 diabetic individuals without microalbuminuria SO DIABETES CARE LA English DT Article ID ENDOTHELIAL DYSFUNCTION; INSULIN-RESISTANCE; MELLITUS; DISEASE; COMPLICATIONS; NIDDM; RISK; IDDM AB OBJECTIVE - Using von Willebrand Factor (VWF) as a marker of endothelial function, previous studies have shown that the development of microalbuminuria is associated with the onset of endothelial dysfunction in individuals with type 2 diabetes. We tested the hypothesis that endothelial dysfunction is already evident in normoalbuminuric individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS - We used laser Doppler imaging scanning to measure vasodilation in the forearm skin in response to iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). Multiple indicators of endothelial function-soluble intercellular adhesion molecule (sVCAM), soluble vascular cell adhesion molecule (sVCAM), vWF, and microvascular reactivity-were measured in 20 healthy control subjects, 45 normoalbuminuric (urinary albumin/creatinine ratio <30 mu g/mg) individuals with type 2 diabetes, and 14 microalbuminuric (urinary albumin/creatinine ratio between 30 and 300 mu g/mg) individuals with type 2 diabetes. RESULTS - Serum sICAM and sVCAM levels were elevated in the normalbuminuric (305 +/- 120, 851 +/- 284 ng/ml) and microalbuminuric (300 +/- 89, 845 +/- 252 ng/ml) individuals with diabetes when compared with the healthy control subjects (213 +/- 58, 661 +/- 176 ng/ml) (P < 0.01), Furthermore, the microvascular endothelium-dependent and -independent vasodilation was reduced in the normoalbuminuric (76 +/- 44, 70 +/- 33) (percent increase in perfusion over baseline) and microalbuminuric (74 +/- 41, 73 +/- 28) individuals with diabetes compared with healthy control subjects (126 +/- 67, 120 +/- 47) (P < 0.05). In contrast, plasma VWF was elevated only in the microalbuminuric individuals with diabetes (129 +/- 35%) compared with the normoalbuminuric individuals with diabetes (110 +/- 34) and healthy control subjects (111.3 +/- 39) (P < 0.05). On stepwise multivariate analysis, fasting blood glucose was the most important contributing factor to the variation in microvascular reactivity and sVCAM, whereas insulin resistance (by homeostasis model assessment) was the most important contributing factor to the variation in sICAM. Addition of all clinical and biochemical measures explained only 15-22% of the variation in sICAM, sVCAM, and microvascular reactivity. CONCLUSIONS- Multiple markers of endothelial dysfunction were evident in normoalbuminuric individuals with type 2 diabetes. The pathogenic process of vasculopathy in type 2 diabetes occurs early and may be operative before the development of microalbuminuria. C1 Harvard Univ, Microcirculat Lab, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Joslin Diabet Ctr, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Dept Med, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. Harvard Univ, Div Vasc Surg, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Microcirculat Lab, Beth Israel Deaconess Med Ctr, Sch Med, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. FU NIDDK NIH HHS [2P30-DK-36836] NR 26 TC 93 Z9 95 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 1999 VL 22 IS 11 BP 1865 EP 1870 DI 10.2337/diacare.22.11.1865 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247FB UT WOS:000083209500018 PM 10546021 ER PT J AU Laffel, L AF Laffel, L TI Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes SO DIABETES-METABOLISM RESEARCH AND REVIEWS LA English DT Review DE acetoacetate; beta-hydroxybutyrate; diabetes; diabetic ketoacidosis; ketone bodies ID ORTHOTOPIC LIVER-TRANSPLANTATION; FATTY-ACID OXIDATION; BETA-HYDROXYBUTYRATE; BODY RATIO; ALCOHOLIC KETOACIDOSIS; BLOOD-GLUCOSE; SALICYLATE INTOXICATION; SPURIOUS KETONURIA; KINETIC METHOD; ISLET FUNCTION AB Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available. The two main ketone bodies are acetoacetate (AcAc) and 3-beta-hydroxybutyrate (3HB), while acetone is the third, and least abundant, ketone body. Ketones are always present in the blood and their levels increase during fasting and prolonged exercise. They are also found in the blood of neonates and pregnant women. Diabetes is the most common pathological cause of elevated blood ketones. In diabetic ketoacidosis (DKA), high levels of ketones are produced in response to low insulin levels and high levels of counterregulatory hormones. In acute DKA, the ketone body ratio (3HB : AcAc) rises from normal (1 : 1) to as high as 10 : 1. In response to insulin therapy, 3HB levels commonly decrease long before AcAc levels. The frequently employed nitroprusside test only detects AcAc in blood and urine. This test is inconvenient, does not assess the best indicator of ketone body levels (3HB), provides only a semiquantitative assessment of ketone levels and is associated with false-positive results. Recently, inexpensive quantitative tests of 3HB levels have become available for use with small blood samples (5-25 mu l). These tests offer new options for monitoring and treating diabetes and other states characterized by the abnormal metabolism of ketone bodies. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Med, Joslin Clin, Boston, MA 02215 USA. RP Laffel, L (reprint author), Harvard Univ, Sch Med, Joslin Clin, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu NR 144 TC 376 Z9 384 U1 22 U2 87 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1520-7560 J9 DIABETES-METAB RES JI Diabetes-Metab. Res. Rev. PD NOV-DEC PY 1999 VL 15 IS 6 BP 412 EP 426 DI 10.1002/(SICI)1520-7560(199911/12)15:6<412::AID-DMRR72>3.0.CO;2-8 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 279BE UT WOS:000085022800006 PM 10634967 ER PT J AU Centeno, BA Stockwell, JW Lewandrowski, KB AF Centeno, BA Stockwell, JW Lewandrowski, KB TI Cyst fluid cytology and chemical features in a case of lymphoepithelial cyst of the pancreas: A rare and difficult preoperative diagnosis SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE pancreas; lymphoepithelial cyst; cyst fluid analysis ID NEEDLE ASPIRATION BIOPSY; DIFFERENTIAL-DIAGNOSIS; LESIONS; CT AB Most pancreatic cysts (90%) are inflammatory pseudocysts. Approximately 10% of pancreatic cysts are neoplasms, including serous cystadenomas, and mucinous tumors, some of which are malignant. Analysis of pancreatic cyst fluid obtained by percutaneous or endoscopic fine-needle aspiration is increasingly being used for the preoperative diagnosis of pancreatic or peripancreatic cysts. However, cyst fluid chemical and cytologic features in less common types of pancreatic cysts have not been reported. Lymphoepithelial cyst of the pancreas is exceedingly rare, and only occasional individual reports have described cyst fluid findings. We report on a case of lymphoepithelial cyst of the pancreas developing in a middle-aged man. Cyst fluid aspirated under radiological guidance showed elevated levels of carcinoembryonic antigen (CEA), CA19-9, CA 125, and amylase, and a viscosity greater than that of serum. A cell block preparation of a fine-needle aspiration showed tissue fragments with a keratinized squamous lining and a lymphocytic infiltrate in the wall, and abundant background keratinous debris. The cytologic and biochemical findings in this case exhibit similarities to the findings reported in other reports, and may represent a recognizable pattern on cyst fluid analysis. Diagn. Cytopathol. 1999;21:328-330. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lewandrowski, KB (reprint author), Massachusetts Gen Hosp, Dept Clin Chem, Gray 5,Fruit St, Boston, MA 02114 USA. NR 25 TC 26 Z9 26 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD NOV PY 1999 VL 21 IS 5 BP 328 EP 330 DI 10.1002/(SICI)1097-0339(199911)21:5<328::AID-DC6>3.0.CO;2-J PG 3 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 246UJ UT WOS:000083182700006 PM 10527479 ER PT J AU Sadeghi, S Pitman, MB Weir, MM AF Sadeghi, S Pitman, MB Weir, MM TI Cytologic features of metastatic sebaceous carcinoma: Report of two cases with comparison to three cases of basal cell carcinoma SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE sebaceous carcinoma; basal cell carcinoma; fine needle aspiration biopsy ID FINE-NEEDLE ASPIRATION; PILOMATRIXOMA CALCIFYING EPITHELIOMA; DIAGNOSIS; SKIN; MALHERBE; MELANOMA; TUMOR; NECK AB The cytologic findings of two cases of metastatic sebaceous carcinoma are described and compared to three cases of locally recurrent basal cell carcinoma. Morphological findings for sebaceous carcinoma in fine-needle aspiration biopsy (FNAB) smears included cellular, loosely cohesive cell clusters with central necrosis, squamous pearl formation, and adjacent keratin debris. The tumor cells had moderate amounts of vacuolated cytoplasm, round to oval vesicular nuclei with clumped chromatin, nucleoli, some nuclear overlap, and numerous mitotic figures. An interesting finding was the presence of numerous multinucleated giant cells, probably responding to extravasated lipid or keratin material. In contrast, the FNAB smears of basal cell carcinoma typically were less cellular, with more tightly cohesive and small clusters of uniform hyperchromatic basaloid cells with high nuclear to cytoplasmic ratios, and a narrow rim of cytoplasm without vacuolization. The morphologic features of sebaceous carcinoma in FNAB smears appear to be distinct from those of basal cell carcinoma. FNAB can be a useful preoperative diagnostic technique to distinguish these two cutaneous malignancies. Diagn. Cytopathol. 1999;21:340-345. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Pitman, MB (reprint author), Massachusetts Gen Hosp, Dept Pathol, 14 Fruit St,Warren 2, Boston, MA 02114 USA. NR 29 TC 7 Z9 8 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 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD NOV PY 1999 VL 21 IS 5 BP 340 EP 345 PG 6 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 246UJ UT WOS:000083182700009 PM 10527482 ER PT J AU Garcia-Olmo, D Ontanon, J Garcia-Olmo, DC Vallejo, M Cifuentes, J AF Garcia-Olmo, D Ontanon, J Garcia-Olmo, DC Vallejo, M Cifuentes, J TI Experimental evidence does not support use of the "no-touch" isolation technique in colorectal cancer SO DISEASES OF THE COLON & RECTUM LA English DT Article; Proceedings Paper CT XXII Congreso Nacional de Cirugia CY NOV 09-13, 1998 CL MADRID, SPAIN DE colorectal cancer; no-touch isolation technique; tumor cell circulation; reverse transcriptase-polymerase chain reaction ID POLYMERASE CHAIN-REACTION; TUMOR-CELLS; METASTASIS; CARCINOMA; BLOOD AB PURPOSE: The benefits of the "no-touch" isolation technique usually performed to prevent the circulation of tumor cells are not evident. The aim of this study was to determine whether conventional surgical procedures for treatment of colon cancer could provoke the circulation of tumor cells detected by a genetic technology. METHODS: Sixteen patients undergoing resection for colorectal cancer and two patients with irresectable tumors were studied. No patient showed liver or lung metastasis. With specific primers for carcinoembryonic antigen, we used reverse transcriptase-polymerase chain reaction to analyze tumor biopsy specimens and blood samples obtained from the antecubital vein before and after surgery and from the main drainage vein of the tumor when the tumor had been extracted. Peritoneal fluid was also collected in irrecsectable cases. RESULTS: Amplification of cDNA with carcinoembryonic antigen-specific primers was achieved with all tumor biopsies and samples of peritoneal fluid. In two patients carcinoembryonic antigen reverse transcriptase-polymerase chain reaction products were detected in antecubital vein blood before surgery and in one of them also after surgery. Only in one patient (Dukes C) were carcinoembryonic antigen reverse transcriptase-polymerase chain reaction products detected from the main drainage vein of the tumor. In serial dilution experiments we determined that the limit of detection of this method was ten tumor cells in 2 mi of blood. CONCLUSION: Our data suggest that the use of no-touch isolation techniques in colorectal cancer is not justified, based on lack of evidence indicating the detachment of cells from the tumor at surgery. C1 Hosp Gen Albacete, Serv Cirurgia Gen, Albacete 02006, Spain. Hosp Gen Albacete, Expt Res Unit, Albacete 02006, Spain. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Reprod Endocrine Unit, Boston, MA USA. RP Garcia-Olmo, D (reprint author), Hosp Gen Albacete, Serv Cirurgia Gen, Hnos Falco S-N, Albacete 02006, Spain. RI Garcia-Olmo, Dolores C./L-5733-2014 NR 12 TC 13 Z9 15 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0012-3706 J9 DIS COLON RECTUM JI Dis. Colon Rectum PD NOV PY 1999 VL 42 IS 11 BP 1449 EP 1454 DI 10.1007/BF02235045 PG 6 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 254RX UT WOS:000083626900018 PM 10566533 ER PT J AU Roy, P Tretyakov, O Wright, J Waxman, DJ AF Roy, P Tretyakov, O Wright, J Waxman, DJ TI Stereoselective metabolism of ifosfamide by human P-450S 3A4 and 2B6. Favorable metabolic properties of R-enantiomer SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN LIVER-MICROSOMES; N-DECHLOROETHYLATION; CYTOCHROMES P450; DRUG-METABOLISM; CYCLOPHOSPHAMIDE; ACTIVATION; PHARMACOKINETICS; RAT; IDENTIFICATION; CHLOROACETALDEHYDE AB The anticancer prodrug ifosfamide (IFA) contains a chiral phosphorous atom and is administered clinically as a racemic mixture of R and S enantiomers. Animal model studies and clinical data indicate enantioselective differences in cytochrome P-450 (CYP) metabolism, pharmacokinetics, and therapeutic efficacy between the two enantiomers; however, the metabolism of individual IFA enantiomers has not been fully characterized. The role of CYP enzymes in the stereoselective metabolism of R-IFA and S-IFA was investigated by monitoring the formation of both 4-hydroxy (activated) and N-dechloroethyl (DCl) (inactive, neurotoxic) metabolites. In the 4-hydroxylation reaction, cDNA-expressed CYPs 3A4 and 3A5 preferentially metabolized R-IFA, whereas CYP2B6 was more active toward S-IFA. Enantioselective IFA 4-hydroxylation (R > S) was observed with six of eight human liver samples. In the N-dechloroethylation reaction, CYPs 3A4 and 2B6 both catalyzed a significantly higher intrinsic metabolic clearance (V-max/K-m) of S-IFA compared with R-IFA. Striking P-450 form specificity in the formation of individual DCl metabolites was evident. CYPs 3A4 and 3A5 preferentially produced (R)N2-DCl-IFA and (R)N3-DCl-IFA (derived from R-IFA and S-IFA, respectively), whereas CYP2B6 correspondingly formed (S)N3-DCl-IFA and (S)N2-DCl-IFA. In human liver microsomes, the CYP3A-specific inhibitor troleandomycin suppressed (R)N2- and (R)N3-DCl-IFA formation by >80%, whereas (S) N2- and (S)N3-DCl-IFA formation were selectively inhibited (>85%) by a CYP2B6-specific monoclonal antibody. The overall extent of IFA N-dechloroethylation varied with the CYP3A4 and CYP2B6 content of each liver, but was significantly lower for R-IFA (32 +/- 13%) than for S-IFA (62 +/- 17%, n = 8; p < .001) in all livers examined. R-IFA thus has more favorable liver metabolic properties than S-IFA with respect to less extensive N-dechloroethylation and more rapid 4-hydroxylation, indicating that R-IFA may have a distinct clinical advantage over racemic IFA. C1 Boston Univ, Dept Biol, Div Cell & Mol Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Waxman, DJ (reprint author), Boston Univ, Dept Biol, Div Cell & Mol Biol, 5 Cummington St, Boston, MA 02215 USA. FU NCI NIH HHS [CA49248] NR 52 TC 59 Z9 61 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD NOV PY 1999 VL 27 IS 11 BP 1309 EP 1318 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 248MK UT WOS:000083278900013 PM 10534317 ER PT J AU Ayas, NT Malhotra, A Epstein, LJ AF Ayas, NT Malhotra, A Epstein, LJ TI Alternative therapies for sleep apnea SO DRUGS OF TODAY LA English DT Review ID POSITIVE AIRWAY PRESSURE; SEROTONERGIC EXCITATORY DRIVE; EXCESSIVE DAYTIME SLEEPINESS; GENIOGLOSSAL MUSCLE-ACTIVITY; CPAP THERAPY; MEDROXYPROGESTERONE ACETATE; HYPOGLOSSAL MOTONEURONS; ORAL APPLIANCES; OBESE PATIENTS; DOUBLE-BLIND AB Obstructive sleep apnea is characterized by the repetitive collapse of the upper airway during sleep. A variety of nonsurgical treatments for obstructive sleep apnea have been developed, including behavioral therapies, continuous positive airway pressure (CPAP) devices, oral appliances and medications. Presently, CPAP is considered the first-line treatment for moderate to severe sleep apnea and one of the first-line treatments for mild disease. However, the effectiveness of CPAP is compromised because a large proportion of patients cannot tolerate the devices. Oral appliances are one of the first-line therapies for mild sleep apnea and a treatment for more severe disease if CPAP cannot be tolerated. Medications have thus far been unsuccessful as a treatment option for sleep apnea. Ail patients should be counseled to avoid sleep deprivation and sedatives (including alcohol) and to lose weight if obese. (C) 1999 Prous Science. Ail rights reserved. C1 Brockton W Roxbury Vet Adm Med Ctr, Pulm & Crit Care Med Sect, W Roxbury, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Epstein, LJ (reprint author), Brockton W Roxbury Vet Affairs Med Ctr, Pulm Sect, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 90 TC 0 Z9 0 U1 0 U2 1 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0025-7656 J9 DRUGS TODAY JI Drugs Today PD NOV PY 1999 VL 35 IS 11 BP 811 EP 821 DI 10.1358/dot.1999.35.11.562555 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 284FW UT WOS:000085321100001 PM 12973373 ER PT J AU Copeland, PM AF Copeland, PM TI The incidentally discovered adrenal mass: An update SO ENDOCRINOLOGIST LA English DT Article ID DEXAMETHASONE SUPPRESSION TEST; CONTRAST-ENHANCED CT; CUSHINGS-SYNDROME; DIFFERENTIAL-DIAGNOSIS; COMPUTED-TOMOGRAPHY; ADENOMAS; TUMORS; DISTINCTION; NONADENOMAS; BENIGN AB Incidentally discovered adrenal masses are commonly found on imaging studies of the adrenal glands performed for other reasons. The evaluation of these "adrenal incidentalomas" requires a synthesis of clinical, biochemical, and imaging data. The most common adrenal incidentaloma is a benign adenoma without detectable biochemical hyperfunction. Recent advances in categorization by the percent washout of intravenous contrast over several minutes on computed tomography scans enable one to distinguish most adenomas from nonadenomas, History, physical examination, laboratory screening, and computed tomography characteristics direct the need for further testing and/or follow-up. Additional valuable techniques include chemical shift magnetic resonance imaging, adrenal cortical scintigraphy, and fine needle aspiration biopsy. Surgical resection is indicated for only a minority of adrenal masses. C1 N Shore Med Ctr, Dept Med, Salem, MA 01970 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Copeland, PM (reprint author), N Shore Med Ctr, Dept Med, 55 Highland Ave, Salem, MA 01970 USA. NR 45 TC 9 Z9 9 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-2144 J9 ENDOCRINOLOGIST JI Endocrinologist PD NOV-DEC PY 1999 VL 9 IS 6 BP 415 EP 423 DI 10.1097/00019616-199911000-00003 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 259CJ UT WOS:000083876100003 ER PT J AU Carter, PH Juppner, H Gardella, TJ AF Carter, PH Juppner, H Gardella, TJ TI Studies of the N-terminal region of a parathyroid hormone-related peptide(1-36) analog: Receptor subtype-selective agonists, antagonists, and photochemical cross-linking agents SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-LINKED RECEPTOR; PTH-RELATED PEPTIDE; COMMON RECEPTOR; BINDING DOMAINS; AMINO-TERMINUS; CELLS; RAT; ACTIVATION; CALCITONIN; EXPRESSION AB The N-terminal regions of PTH and PTH-related peptide (PTHrP) are involved in receptor-mediated signaling and subtype selectivity. To better understand the molecular basis for these processes, we first prepared a series of [(I,W23)-W-5,Y-36]-PTHrP(1-36)NH2 analogs having stepwise deletions of residues 1-4 and characterized them with the human (h)PTH-1 and hPTH-2 receptor subtypes stably transfected in LLC-PK1 cells. Deletions beyond residue 2 caused progressive and severe losses in cAMP-signaling efficacy without dramatically diminishing receptor-binding affinity; consistent with this, [I-5,W-23]PTHrP(5-36) was a potent antagonist for both PTH receptor subtypes. We then prepared and characterized photolabile analogs of [I-5,W-23,Y-36]-PTHrP(1-36)NH2 that were singly modified with para-benzoyl-L-phenylalanine (Bpa) along the first six residues. These full-length analogs exhibited receptor subtype-selective agonism, antagonism, and photochemical cross-linking profiles. In particular, the [Bpa(2)]- and [Bpa(4)]-substituted analogs selectively antagonized and preferentially cross-linked to the PTH-1 receptor and PTH-S receptor, respectively. These results demonstrate that the 1-5 region of [I-5,W-23] -PTHrP(1-36) is critical for activating the PTH-1 and PTH-2 receptors and suggest that the individual residues in this region play distinct roles in modulating the activation states of the two receptors. The cross-linking of both agonist and antagonist ligands to these PTH receptors lays the groundwork for identifying critical signaling determinants in the ligand binding pocket of the receptor. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Gardella, TJ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. EM gardella@helix.mgh.harvard.edu NR 39 TC 39 Z9 39 U1 0 U2 1 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 NOV PY 1999 VL 140 IS 11 BP 4972 EP 4981 DI 10.1210/en.140.11.4972 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600008 PM 10537121 ER PT J AU Amling, M Priemel, M Holzmann, T Chapin, K Rueger, JM Baron, R Demay, MB AF Amling, M Priemel, M Holzmann, T Chapin, K Rueger, JM Baron, R Demay, MB TI Rescue of the skeletal phenotype of vitamin D receptor-ablated mice in the setting of normal mineral ion homeostasis: Formal histomorphometric and biomechanical analyses SO ENDOCRINOLOGY LA English DT Article ID D-DEFICIENT RATS; PARATHYROID-HORMONE; BONE HISTOMORPHOMETRY; RICKETS; CALCIUM; DIFFERENTIATION; PHOSPHORUS; ALOPECIA; GROWTH AB 1,25-Dihydroxyvitamin D-3 has been shown to play an important role in vitro in regulating osteoblast gene transcription and promoting osteoclast differentiation. To address the role of the vitamin D receptor (VDR) in skeletal homeostasis, formal histomorphometric analyses were performed in VDR null mice in the setting of impaired mineral ion homeostasis as well as in VDR null mice in whom normal mineral ion homeostasis had been preserved. In hypocalcemic VDR null mice, there was an increase in bone volume as a result of a dramatic increase in osteoid. There was also an increase in the number of osteoblasts without a significant change in the number of osteoclasts. Examination of the growth plate revealed marked disorganization, with an increase in vascularity and matrix. Biomechanical parameters demonstrated increased bone fragility in the hypocalcemic VDR null mice. In the VDR ablated mice in whom normal mineral ion homeosfasis had been preserved, none of these measurements was significantly different from those in wild-type littermates raised under identical conditions. Notably, the morphology and width of the growth plate were indistinguishable from those in wild-type controls, demonstrating that a calcium/phosphorus/lactose-enriched diet started at 16 days of age in the VDR null mice permits the development of both normal morphology in the growth cartilage and adjacent metaphysis and normal biomechanical competence of cortical bone. Thus, the principle action of the VDR in skeletal growth, maturation, and remodeling is its role in intestinal calcium absorption. The skeletal consequences of VDR ablation are a result df impaired intestinal calcium absorption and/or the resultant secondary hyperparathyroidism and hypophosphatemia. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. Univ Hamburg, Sch Med, Dept Trauma Surg, D-2000 Hamburg, Germany. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA. RP Demay, MB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Wellman 501, Boston, MA 02114 USA. EM demay@helix.mgh.harvard.edu NR 23 TC 306 Z9 311 U1 0 U2 2 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 NOV PY 1999 VL 140 IS 11 BP 4982 EP 4987 DI 10.1210/en.140.11.4982 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600009 PM 10537122 ER PT J AU Zhang, SL Chen, X Filep, JG Tang, SS Ingelfinger, JR Chan, JSD AF Zhang, SL Chen, X Filep, JG Tang, SS Ingelfinger, JR Chan, JSD TI Insulin inhibits angiotensinogen gene expression via the mitogen-activated protein kinase pathway in rat kidney proximal tubular cells SO ENDOCRINOLOGY LA English DT Article ID DEPENDENT DIABETES-MELLITUS; ELEMENT-BINDING PROTEIN; II-INDUCED HYPERTROPHY; CELLULAR HYPERTROPHY; RESPONSE ELEMENT; MESSENGER-RNA; GROWTH-FACTOR; TGF-BETA; GLUCOSE; RENIN AB The present study aimed to investigate the molecular mechanism(s) of insulin action on angiotensinogen (ANG) secretion and gene expression in kidney proximal tubular cells exposed to high levels of glucose. Immortalized rat proximal tubular cells (IRPTC) were cultured in monolayer. The levels of rat ANG and ANG messenger RNA in the IRPTC were quantified by a specific RIA for rat ANG (RIA-rANG) and by an RT-PCR assay. Insulin inhibited the stimulatory effect of a high level of glucose (25 mM) and phorbol la-myristate 13-acetate, an activator of protein kinase C) on the secretion of ANG and the expression of the ANG messenger RNA in IRPTC. This inhibitory action of insulin on the ANG secretion and gene expression was blocked by PD98059 tan inhibitor of mitogen-activated protein kinase kinase) but not by Wortmannin tan inhibitor of phosphatidylinositol-3-kinase). PD98059 was effective in inhibiting the phosphorylation of MEK 1/2 and p44/42 MAP kinase in IRPTC stimulated by insulin. These studies demonstrate that insulin prevents the stimulatory effect of high levels of glucose on the expression of the renal ANG gene in IRPTC, at least in part, via the MAPK kinase signal transduction pathway, subsequently inhibiting the activation of the local renal renin-angiotensin system. C1 Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, Montreal, PQ H1T 2M4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. RP Zhang, SL (reprint author), Univ Montreal, Maisonneuve Rosemont Hosp, Res Ctr, 5415 Blvd Assompt, Montreal, PQ H1T 2M4, Canada. NR 45 TC 21 Z9 21 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 NOV PY 1999 VL 140 IS 11 BP 5285 EP 5292 DI 10.1210/en.140.11.5285 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600046 PM 10537159 ER PT J AU Stoffers, DA Heller, RS Miller, CP Habener, JF AF Stoffers, DA Heller, RS Miller, CP Habener, JF TI Developmental expression of the homeodomain protein IDX-1 in mice transgenic for an IDX-1 promoter/lacZ transcriptional reporter SO ENDOCRINOLOGY LA English DT Article ID HOMEOBOX FACTOR STF-1; ENDOCRINE PANCREAS; INSULIN GENE; BETA-CELLS; RAT; DIFFERENTIATION; MORPHOGENESIS; REGENERATION; POLYPEPTIDE; EXOCRINE AB Expression of the homeodomain transcription factor IDX-1 (also known as IPF-1, STF-1, and PDX-1) is required for pancreas development, because disruption of the gene in mice and humans results in pancreatic agenesis. During embryonic development the idx-1 gene is first expressed in a localized region of foregut endoderm from which the duodenum and pancreas later develop. To more fully understand the role of IDX-1 in pancreas development, transgenic mice expressing the Escherichia coli lacZ gene under control of the 5'-proximal 4.6 kb of the idx-1 promoter were created as a reporter for the developmental expression of IDX-1. Here we show that the determinants for the developmental and tissue-specific expression of the endogenous idx-1 gene are faithfully reproduced by the 4.6-kb region of the idx-1 promoter. Expression of lacZ is detected in the development of the exocrine and endocrine pancreas in pancreatic ducts, common bile and cystic ducts, pyloric glands of the distal stomach, Brunner's glands, the intestinal epithelium of the duodenum, and the spleen. The observed spatial and temporal pattern of lacZ expression directed by the IDX-1 promoter further supports an important role of IDX-1 in specifying the development of several endodermal structures within the midsegment of the body. An unexpected finding is that IDX-1 promoter-driven (transcriptional) lacZ activity does not always coincide with the localization of IDX-1 messenger RNA by in situ, hybridization and IDX-1 protein by immunocytochemistry in adult rat duodenum, suggesting the existence of regulation of IDX-1 expression at the posttranscriptional level of expression of the idx-1 gene. C1 Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, Boston, MA 02114 USA. RP Habener, JF (reprint author), Harvard Univ, Mol Endocrinol Lab, Massachusetts Gen Hosp, Sch Med,Howard Hughes Med Inst, 55 Fruit St,WEL320, Boston, MA 02114 USA. EM habenerj@a1.mgh.harvard.edu RI Heller, R.Scott/A-7279-2008; Stoffers, Doris/H-6157-2012 NR 36 TC 89 Z9 93 U1 0 U2 1 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 1999 VL 140 IS 11 BP 5374 EP 5381 DI 10.1210/en.140.11.5374 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 247BK UT WOS:000083200600056 PM 10537169 ER PT J AU Chasan-Taber, L Willett, WC Seddon, JM Stampfer, MJ Rosner, B Colditz, GA Hankinson, SE AF Chasan-Taber, L Willett, WC Seddon, JM Stampfer, MJ Rosner, B Colditz, GA Hankinson, SE TI A prospective study of vitamin supplement intake and cataract extraction among US women SO EPIDEMIOLOGY LA English DT Article DE cataract; cataract extraction; diet; female; prospective studies; vitamins ID LENS OPACITIES; ANTIOXIDANT VITAMINS; RISK-FACTORS; QUESTIONNAIRE; CAROTENOIDS AB We prospectively examined the association between vitamin supplement intake and the incidence of cataract extraction during 12 years of follow-up in a cohort of 47,152 female nurses. Women were 45 years or older and free of diagnosed cancer in 1980; others were added as they reached 45 years of age, for a total of 73,956 women. During 720,082 years of follow-up, 1,377 senile cataracts were diagnosed and extracted. Those who used multivitamins or separate supplements of vitamin C, E, or A did not have decreased risks of cataract as compared with nonusers even for use of 10 or more years. After adjusting for cataract risk factors, including cigarette smoking, body mass index, and diabetes mellitus, users of vitamin C supplements for 10 or more years had a relative risk (RR) of 0.95 [95% confidence interval (CI) = 0.76-1.20]. Associations were stronger among long-term vitamin C supplement users who were never smokers (RR = 0.71; 95% CI = 0.47-1.08) and less than 60 years of age (RR = 0.72; 95% CI = 0.49-1.04). These findings suggest that there is little overall benefit of longterm use of vitamin supplements for risk of cataracts requiring extraction. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Channing Labs, Nurses Hlth Study, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356]; NEI NIH HHS [EYE-09611] NR 24 TC 44 Z9 45 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1044-3983 EI 1531-5487 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1999 VL 10 IS 6 BP 679 EP 684 DI 10.1097/00001648-199911000-00006 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 248TB UT WOS:000083290500006 PM 10535780 ER PT J AU Tomeo, CA Rich-Edwards, JW Michels, KB Berkey, CS Hunter, DJ Frazier, AL Willett, WC Buka, SL AF Tomeo, CA Rich-Edwards, JW Michels, KB Berkey, CS Hunter, DJ Frazier, AL Willett, WC Buka, SL TI Reproducibility and validity of maternal recall of pregnancy-related events SO EPIDEMIOLOGY LA English DT Article DE recall; pregnancy; delivery; reproducibility; validity ID BIRTH-WEIGHT; BREAST-CANCER; MEDICAL RECORDS; FETAL GROWTH; ADULT HYPERTENSION; DIABETES-MELLITUS; GLUCOSE-TOLERANCE; THRIFTY PHENOTYPE; PERINATAL FACTORS; RISK-FACTORS AB We assessed the reproducibility and validity of a questionnaire that asks mothers to recall pregnancy-related events from thirty or more years ago. Among 146 women who completed the questionnaire twice, responses were highly reproducible for pre-pregnancy height and weight (r = 0.95), pregnancy complications (r = 0.74), substance use (r = 0.80), preterm delivery (r = 0.82), birthweight (r = 0.94), and breastfeeding (r = 0.89). Among 154 women whose questionnaire responses were compared to data collected during their pregnancies, recall was highly accurate for height (r = 0.90), pre-pregnancy weight (r = 0.86), birthweight (r = 0.91), and smoking (sensitivity = 0.86, specificity = 0.94). These findings suggest that long-term maternal recall is both reproducible and accurate for many factors related to pregnancy and delivery. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Maternal & Child Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. RP Tomeo, CA (reprint author), Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Buka, Stephen/H-7335-2014 OI Buka, Stephen/0000-0002-8578-9308 FU NCI NIH HHS [CA40356, CA50385]; NIDDK NIH HHS [DK46200] NR 28 TC 233 Z9 235 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 1999 VL 10 IS 6 BP 774 EP 777 DI 10.1097/00001648-199911000-00022 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 248TB UT WOS:000083290500021 PM 10535796 ER PT J AU Morita, R Miyazaki, E Shah, PU Castroviejo, IP Delgado-Escueta, AV Yamakawa, K AF Morita, R Miyazaki, E Shah, PU Castroviejo, IP Delgado-Escueta, AV Yamakawa, K TI Exclusion of the JRK/JH8 gene as a candidate for human childhood absence epilepsy mapped on 8q24 SO EPILEPSY RESEARCH LA English DT Article DE JRK/JH8 gene; epilepsy; absence; jerky; childhood absence epilepsy; ECA1; 8q24 ID SEIZURES; CONVULSIONS; JERKY; MICE AB Childhood absence epilepsy (CAE), one of the most common epilepsies in children, is genetically and phenotypically heterogeneous. One of the genes responsible for human CAE associated with tonic-clonic seizures has been mapped to chromosome band 8q24 by genetic linkage analysis and is termed ECA1. Recently, we isolated and mapped the JRK/JH8 gene, a human homologue of the mouse epilepsy gene, jerky, on 8q24. The epilepsy phenotype of the mice with inactivated jerky gene as well as its chromosomal localization proposed JRK/JH8 as a prominent candidate for the CAE gene. To confirm whether the JRK/JH8 gene is responsible for ECA1, we performed mutational analyses in the coding region of JRK/JH8 in two CAE families mapped on 8q24, using heteroduplex and direct sequencing methods. We identified seven nucleotide changes, two of which lead to amino acid substitutions. However, these changes did not co-segregate with the disease phenotype. In addition, we redefined the location of JRK/JH8 to be more than 4 Mb distant from D8S502 and ECA1. Thus, negative results of mutation analyses and detailed physical mapping exclude JRK/JH8 as the ECA1 gene. (C) 1999 Elsevier Science B.V. All rights reserved. C1 RIKEN, Inst Phys & Chem Res, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. Univ Calif Los Angeles, Sch Med, Comprehens Epilepsy Program, Epilepsy Genom Labs, Los Angeles, CA 90073 USA. W Los Angeles DVA Med Ctr, Los Angeles, CA 90073 USA. KEM Hosp, Bombay, Maharashtra, India. Seth GS Med Coll, Bombay, Maharashtra, India. Pediat Neurol Univ Hosp La Paz, Madrid, Spain. RP Yamakawa, K (reprint author), RIKEN, Inst Phys & Chem Res, Brain Sci Inst, Neurogenet Lab, 2-1 Hirosawa, Wako, Saitama 3510198, Japan. RI Yamakawa, Kazuhiro/N-5050-2015 FU NINDS NIH HHS [5PO1-NS21908] NR 15 TC 16 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD NOV PY 1999 VL 37 IS 2 BP 151 EP 158 DI 10.1016/S0920-1211(99)00061-3 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 239WE UT WOS:000082792200006 PM 10510981 ER PT J AU Klupa, T Malecki, M Hanna, L Sieradzka, J Frey, J Warram, JH Sieradzki, J Krolewski, AS AF Klupa, T Malecki, M Hanna, L Sieradzka, J Frey, J Warram, JH Sieradzki, J Krolewski, AS TI Amino acid variants of the vitamin D-binding protein and risk of diabetes in white Americans of European origin SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID GLUCOSE-TOLERANCE; INSULIN-SECRETION; PIMA-INDIANS; ASIANS; GENE AB Background: Genetic variants of vitamin D-binding protein (DBP) have been reported to be associated, not only with diabetes, but also with prediabetic traits, in several populations. There are two known polymorphisms in exon 11 of the DBP gene that result in amino acid variants: at codons 416 GAT --> GAG (Asp-->Glu) and 420 ACG-->AAG (Thr-->Lys). Objective: To examine the association of these polymorphisms with diabetes In white Americans of European origin. Methods: We studied unrelated individuals: 181 with type 1 diabetes, 215 with type 2 diabetes, and 163 healthy controls. Exon 11 was amplified using polymerase chain reaction and the two alleles were determined by digestion with specific endonucleases: HaeIII and StyI, respectively, Results: At codon 416, Asp/Glu allele frequencies were 45%/55% in patients with type I diabetes, 43%/57% in patients with type 2 diabetes, and 46%/54% in controls (chi(2) = 0.69, 2 d.f., P<0.71). At codon 420, corresponding Lys/Thr frequencies were 27%/73%, 30%/70%, and 30%/70% (chi(2) =1.25, 2 d.f, P=0.53). Distributions of genotypes at both loci, and the haplotypes defined by the two loci, were also very similar in all groups. Conclusion: DNA polymorphisms in the DBP gene are not associated with diabetes in white Americans of European origin. C1 Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Jagiellonian Univ, Sch Med, Dept Metab Dis, Krakow, Poland. RP Krolewski, AS (reprint author), Joslin Diabet Ctr, Sect Genet & Epidemiol, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK-36836, DK-47475] NR 19 TC 29 Z9 31 U1 0 U2 2 PU SCANDINAVIAN UNIVERSITY PRESS PI OSLO PA PO BOX 2959 TOYEN, JOURNAL DIVISION CUSTOMER SERVICE, N-0608 OSLO, NORWAY SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD NOV PY 1999 VL 141 IS 5 BP 490 EP 493 DI 10.1530/eje.0.1410490 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 257PU UT WOS:000083791300007 PM 10576765 ER PT J AU Lu, B Humbles, A Bota, D Gerard, C Moser, B Soler, D Luster, AD Gerard, NP AF Lu, B Humbles, A Bota, D Gerard, C Moser, B Soler, D Luster, AD Gerard, NP TI Structure and function of the murine chemokine receptor CXCR3 SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE chemokine; chemokine receptor; IP10; CXCR3; mouse ID HUMAN T-LYMPHOCYTES; SUBSTANCE-P; CHEMOTACTIC CYTOKINES; MOLECULAR-CLONING; INTERLEUKIN-8; EXPRESSION; BINDING; ANAPHYLATOXIN; INFLAMMATION; NEUTROPHILS AB The gene encoding the murine homologue of human CXCR3 exists in a single copy consisting of two exons with an intron interrupting the coding sequence between nucleotides 10 and 11. The deduced amino acid sequence is 86% identical to the predicted human sequence. Murine CXCR3 mRNA is detectable in bone marrow cells cultured in the presence of IL-2 but not unstimulated cells. It is also detectable at low abundance in normal mouse spleen, lymph node, mammary gland, and thymus. Transfection of murine CXCR3 in murine pre-B lymphocyte line (CXCR3/L1.2) conferred binding of the ligands IP10, ITAC and Mig with K-D's of 1.35 +/- 0.56, 1.41 +/- 0.20, and 11.65 +/- 0.90 nM, respectively. Lower affinity binding was observed for several beta or CC chemokines (eotaxin, MCP-3, MIP3 alpha and SLC/6Ckine/Exodus 2). ITAC, IP10 and Mig induced chemotaxis with an order of potency ITAC > IP10 = Mig. The chemokines also increased intracellular calcium concentration and were variably desensitized to repeated agonist stimulation. The hierarchy for cross-desensitization was ITAC > Mig > IP10. Thus, while Mig, ITAC and IP10 all act on the same receptor for binding and agonist stimulation, they may interact with different receptor conformational isoforms to produce divergent responses. C1 Harvard Univ, Childrens Hosp, Sch Med, Ina Sue Perlmutter Lab Enders 144, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Blood Res,Dept Med, Boston, MA 02115 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Ctr Blood Res,Dept Pediat, Boston, MA 02115 USA. Univ Bern, Theodor Kocher Inst, Bern, Switzerland. Leukosite Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Gerard, NP (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Ina Sue Perlmutter Lab Enders 144, 300 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [AI/HL39579] NR 36 TC 60 Z9 61 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 1999 VL 29 IS 11 BP 3804 EP 3812 DI 10.1002/(SICI)1521-4141(199911)29:11<3804::AID-IMMU3804>3.0.CO;2-9 PG 9 WC Immunology SC Immunology GA 255UT UT WOS:000083689100042 PM 10556837 ER PT J AU Van Landeghem, GF Tabatabaie, P Beckman, G Beckman, L Andersen, PM AF Van Landeghem, GF Tabatabaie, P Beckman, G Beckman, L Andersen, PM TI Manganese-containing superoxide dismutase signal sequence polymorphism associated with sporadic motor neuron disease SO EUROPEAN JOURNAL OF NEUROLOGY LA English DT Article DE manganese-containing superoxide dismutase; mitochondria; signal sequence; motor neuron disease; amyotrophic lateral sclerosis; oxidative stress ID AMYOTROPHIC-LATERAL-SCLEROSIS; APOLIPOPROTEIN-E EPSILON-4; ANTERIOR HORN NEURONS; OXIDATIVE DAMAGE; ENERGY-METABOLISM; SPINAL-CORDS; ALS; MITOCHONDRIA; PROTEIN; MUTANT AB An alanin-9valin (Ala-9Val) polymorphism in the mitochondrial targeting sequence of manganese-containing superoxide dismutase (Mn-SOD) has recently been described. We studied this polymorphism in 72 Swedish patients with sporadic motor neuron diseases (MND) and controls using an oligonucleotide ligation assay. There were significant differences in genotype between MND patients and controls (P=0.025), and between male and female MND patients (P=0.009). Individuals homozygous for the Ala allele had a higher risk for MM) [odds ratio, 2.9; 95% confidence interval (CI), 1.3-6.6], which was increased when including only females in the analysis (odds ratio, 5.0; 95% CI, 1.8-14.0). In classical amyotrophic lateral sclerosis, the odds ratio was 3.8 (95% CI, 1.3-10.0), and 5.5 (95% CI, 1.5-19.9) when including only females. The results suggest that mutations influencing the cellular allocation of Mn-SOD may be a risk factor in MND, especially in females, and that MND may be a disease of misdistribution of the superoxide dismutase enzymes. fur J Neurol 6:639-644 (C) 1999 Lippincott Williams & Wilkins. C1 Massachusetts Gen Hosp, Dept Neurol, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. Umea Univ, Dept Med Genet, S-90187 Umea, Sweden. Umea Univ, Dept Clin Neurosci, S-90187 Umea, Sweden. Gotland Univ Coll, S-90187 Umea, Sweden. RP Andersen, PM (reprint author), Massachusetts Gen Hosp, Dept Neurol, Day Neuromuscular Res Lab, Charlestown, MA 02129 USA. NR 46 TC 48 Z9 48 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1351-5101 J9 EUR J NEUROL JI Eur. J. Neurol. PD NOV PY 1999 VL 6 IS 6 BP 639 EP 644 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 260LT UT WOS:000083952700002 PM 10529750 ER PT J AU van Eps, RGS Mark, LL Schiereck, J LaMuraglia, GM AF van Eps, RGS Mark, LL Schiereck, J LaMuraglia, GM TI Photodynamic therapy inhibits the injury-induced fibrotic response of vascular smooth muscle cells SO EUROPEAN JOURNAL OF VASCULAR AND ENDOVASCULAR SURGERY LA English DT Article DE PDT; smooth-muscle cells; matrix; injury; collagen ID RAT CAROTID ARTERIES; EXTRACELLULAR-MATRIX; INTIMAL HYPERPLASIA; GROWTH-FACTOR; ENDOTHELIAL-CELLS; RESTENOSIS; LESIONS; PROLIFERATION; PREVENTION AB Objectives: excessive deposition of extracellular matrix (ECM) proteins plays a key role in the intervention-related vascular fibroproliferative response, resulting in intimal hyperplasia (IH). Cytokines, such as Platelet-derived growth factor (PDGF), released after vascular injury and deposited in the ECM, are known to stimulate production of matrix proteins. Photodynamic therapy (PDT), the combination of light and a photosensitive dye to produce free radicals, is a novel approach to inhibit experimental IH by the local eradication of smooth-muscle cells (SMC) and alteration of ECM. This in vitro study examined whether PDT can inhibit the fibrotic response of vascular SMC. Materials and methods: the Effect of PDT on important pro-fibrotic factors was determined by performing PDT of isolated ECM, injured SMC and pure PDGF. SMC production of collagen was monitored by cellular [H-3]-proline incorporation. Results: untreated SMC seeded on ECM demonstrated an increase of 50% in collagen production (p<0.0001) as compared to SMC on an empty plate. This increase was also seen when SMC tons incubated with the conditioned media of mechanically injured SMC, or pure PDGF. However, after PDT of ECM, injured SMC or PDGF, there was an inhibition of 40% (p<0.05) in SMC-collagen production. Conclusions: these findings indicate that PDT can interfere with factors that lead to the vascular fibrotic response. In this way, PDT, with its cytotoxic and extracellular effects, can promote healing of the vessel wall without the stimulus of fibrosis that can lend to restenosis. C1 Harvard Univ, Div Vasc Surg, Gen Surg Serv, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. RP LaMuraglia, GM (reprint author), Harvard Univ, Div Vasc Surg, Gen Surg Serv, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. NR 23 TC 12 Z9 12 U1 0 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1078-5884 J9 EUR J VASC ENDOVASC JI Eur. J. Vasc. Endovasc. Surg. PD NOV PY 1999 VL 18 IS 5 BP 417 EP 423 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 261EQ UT WOS:000083996400009 ER PT J AU Celedon, JC Speizer, FE Drazen, JM Weiss, ST Campbell, EJ Carey, VJ Reilly, JJ Ginns, L Silverman, EK AF Celedon, JC Speizer, FE Drazen, JM Weiss, ST Campbell, EJ Carey, VJ Reilly, JJ Ginns, L Silverman, EK TI Bronchodilator responsiveness and serum total IgE levels in families of probands with severe early-onset COPD SO EUROPEAN RESPIRATORY JOURNAL LA English DT Article DE bronchodilator response; chronic obstructive pulmonary disease; familial aggregation; genetic epidemiology; genetics; immunoglobulin E ID OBSTRUCTIVE PULMONARY-DISEASE; FORCED EXPIRATORY VOLUME; AIR-FLOW OBSTRUCTION; CHRONIC-BRONCHITIS; ENVIRONMENTAL DETERMINANTS; VENTILATORY FUNCTION; IDENTICAL-TWINS; ONE 2ND; SMOKERS; DECLINE AB Bronchodilator responsiveness has been associated with a subsequent accelerated decline in forced expiratory volume in one second (FEV1), Therefore, bronchodilator responsiveness and total serum immunoglobulin E(IgE) levels were assessed in 184 adult first-degree relatives of probands with severe early-onset chronic obstructive pulmonary disease (COPD) and a control group. Greater bronchodilator responsiveness was found among current smokers or exsmokers who were first-degree relatives of early-onset COPD probands than in currently or exsmoking controls, expressed as increase in FEV1 as a percentage of baseline (5.8+/-8.1 versus 2.9+/-5.1%, p<0.01), absolute increase in FEV1 from baseline (120+/-130 versus 60+/-110 mL, p<0.05), and increase in FEV1 as a percentage of the predicted value (3.6+/-4.1 versus 2.2+/-3.9%, p<0.05). However, elevated total serum IgE Levels were not found in first-degree relatives of early-onset COPD probands compared with control subjects. The increased bronchodilator responsiveness among currently smoking/exsmoking first-degree relatives of early-onset COPD probands suggests that these individuals may have enhanced susceptibility to the detrimental effects of cigarette smoking. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Gen Med Serv, Pulm & Crit Care Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Utah, Hlth Serv Ctr, Dept Internal Med, Salt Lake City, UT USA. RP Silverman, EK (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Drazen, Jeffrey/E-5841-2012 FU NCRR NIH HHS [MO1 RR02635]; NHLBI NIH HHS [HL07427, HL46440] NR 31 TC 19 Z9 19 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD NOV PY 1999 VL 14 IS 5 BP 1009 EP 1014 DI 10.1183/09031936.99.14510099 PG 6 WC Respiratory System SC Respiratory System GA 261TE UT WOS:000084024500004 PM 10596682 ER PT J AU Bhatia, SN Balis, UJ Yarmush, ML Toner, M AF Bhatia, SN Balis, UJ Yarmush, ML Toner, M TI Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells SO FASEB JOURNAL LA English DT Review DE liver; coculture; bioartificial liver; hepatocyte morphology ID ADULT-RAT HEPATOCYTES; LONG-TERM CULTURES; LIVER PARENCHYMAL-CELLS; JUNCTIONAL INTERCELLULAR COMMUNICATION; CO-CULTIVATION SYSTEM; IN-VITRO; EPITHELIAL-CELLS; GROWTH-FACTOR; GENE-EXPRESSION; TRIGLYCERIDE ACCUMULATION AB Heterotypic cell interaction between parenchymal cells and nonparenchymal neighbors has been reported to modulate cell growth, migration, and/or differentiation. in both the developing and adult liver, cell-cell interactions are imperative for coordinated organ function. In vivo, cocultivation of hepatocytes and nonparenchymal cells has been used to preserve and modulate the hepatocyte phenotype, We summarize previous studies in this area as well as recent advances in microfabrication that have allowed for more precise control over cell-cell interactions through 'cellular patterning' or 'micropatterning', Although the precise mechanisms by which nonparenchymal cells modulate the hepatocyte phenotype remain unelucidated, some new insights on the modes of cell signaling, the extent of cell-cell interaction, and the ratio of cell populations are noted, Proposed clinical applications of hepatocyte cocultures, typically extracorporeal bioartificial liver support systems, are reviewed in the context of these new findings, Continued advances in microfabrication and cell culture will allow further study of the role of cell communication in physiological and pathophysiological processes as well as in the development of functional tissue constructs for medical applications.-Bhatia, S. N., Balis, U. J., Yarmush, M. L., Toner, M. Effect of cell-cell interactions in preservation of cellular phenotype: cocultivation of hepatocytes and nonparenchymal cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Crippled Children, Boston, MA 02114 USA. RP Toner, M (reprint author), Massachusetts Gen Hosp, Ctr Engn Med, Bigelow 1401,55 Fruit St, Boston, MA 02114 USA. FU NCRR NIH HHS [RR 13322]; NIDDK NIH HHS [DK 3371] NR 120 TC 575 Z9 601 U1 7 U2 67 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 NOV PY 1999 VL 13 IS 14 BP 1883 EP 1900 PG 18 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 255GG UT WOS:000083660700001 PM 10544172 ER PT J AU Sternini, C Wong, H Pham, T de Giorgio, R Miller, LJ Kuntz, SM Reeve, JR Walsh, JH Raybould, HE AF Sternini, C Wong, H Pham, T de Giorgio, R Miller, LJ Kuntz, SM Reeve, JR Walsh, JH Raybould, HE TI Expression of cholecystokinin A receptors in neurons innervating the rat stomach and intestine SO GASTROENTEROLOGY LA English DT Article ID SUBTYPE-SPECIFIC ANTIBODIES; MESSENGER-RNA EXPRESSION; GASTRIC-ACID SECRETION; GASTROINTESTINAL-TRACT; PEPTIDE IMMUNOREACTIVITY; FUNCTIONAL EXPRESSION; VAGAL INNERVATION; AFFERENT NEURONS; DIGESTIVE-SYSTEM; SUBSTANCE-P AB Background & Aims: Two distinct receptors, cholecystokinin (CCK)-A and CCK-B, mediate CCK effects in the digestive system. The aim of this study was to elucidate the cellular sites of expression of CCK-A receptor in the rat stomach and small intestine. Methods: We developed and characterized an antibody to the N-terminal region (LDQPQPSKEWQSA) of rat CCK-A receptor and used it for localization studies with immunohistochemistry. Results: Specificity of the antiserum was demonstrated by (1) detection of a broad band at 85-95 kilodaltons in Western blots of membranes from CCK-A receptor CHO-transfected cells; (2) cell surface staining of CCK-A receptor-transfected cells, (3) translocation of CCK-A receptor immunostaining in CCK-A receptor-transfected cells after exposure to CCK; and (4) abolition of tissue immunostaining by preadsorbtion of the antibody with the peptide used for immunization. CCK-A receptor immunoreactivity was localized to myenteric neurons and to fibers in the muscle and mucosa. In the stomach, myenteric neurons and mucosal fibers were abundant. Many CCK-A receptor myenteric neurons contained the inhibitory transmitter vasoactive intestinal polypeptide, and some were immunoreactive for the excitatory transmitter substance P. Subdiaphragmatic vagotomy reduced the density of CCK-A receptor fibers in the gastric mucosa by approximately 50%, whereas celiac/superior mesenteric ganglionectomy had no detectable effect on fiber density. Conclusions: CCK-A receptor is expressed in functionally distinct neurons of the gastrointestinal tract. CCK-A receptor may mediate reflexes stimulated by CCK through the release of other transmitters from neurons bearing the receptor. C1 W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurobiol, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Physiol, Div Digest Dis, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90024 USA. Univ Bologna, Dept Internal Med & Gastroenterol, I-40126 Bologna, Italy. Mayo Clin & Mayo Fdn, Ctr Basic Res & Digest Dis, Rochester, MN 55905 USA. RP W Los Angeles Vet Affairs Med Ctr, CURE Digest Dis Res Ctr, 11301 Wilshire Blvd,Bldg 115,Room 2245, Los Angeles, CA 90073 USA. EM csternin@ucla.edu OI De Giorgio, Roberto/0000-0003-0867-5873 FU NIDDK NIH HHS [DK 54155] NR 49 TC 69 Z9 69 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 1999 VL 117 IS 5 BP 1136 EP 1146 DI 10.1016/S0016-5085(99)70399-9 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 250NH UT WOS:000083394100017 PM 10535877 ER PT J AU Stoler, JM McGuirk, CK Lieberman, E Ryan, L Holmes, LB AF Stoler, JM McGuirk, CK Lieberman, E Ryan, L Holmes, LB TI Malformations reported in chorionic villus sampling exposed children: A review and analytic synthesis of the literature SO GENETICS IN MEDICINE LA English DT Article DE chorionic villus sampling; vascular disruption; gastroschisis; intestinal atresia ID LIMB-REDUCTION DEFECTS; COMPLETED FOLLOW-UP; VASCULAR PATHOGENESIS; PRENATAL-DIAGNOSIS; SINGLE OPERATOR; WEEKS GESTATION; FIRST-TRIMESTER; AMNIOCENTESIS; EXPERIENCE; DISRUPTION AB Purpose: To determine whether the frequency of vascular disruption defects, other than limb defects, is increased in reports of chorionic villus sampling (CVS) exposed children compared with an unexposed population. Methods: Only studies that reported the total number of CVS-exposed pregnancies and details of pregnancy outcome, including all the malformations, were included. Twenty-five articles met these criteria. Results: The frequencies of gastroschisis, intestinal atresias, and clubfoot were significantly increased among the CVS-exposed infants as compared with the baseline unexposed population. The frequencies of other vascular disruption defects, including Poland sequence, amniotic band sequence, and cleft lip/cleft palate, were not increased. Conclusion: CVS-exposed children have an increased frequency of intestinal atresia, gastroschisis, and clubfoot compared with the nonexposed population. The fact that an increased frequency of other defects attributed to vascular disruption was not found may be due to under-ascertainment, misclassification, or "lumping" of the defects identified in previous studies. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Stoler, JM (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, 55 Fruit St,Warren 801, Boston, MA 02114 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 45 TC 16 Z9 18 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD NOV-DEC PY 1999 VL 1 IS 7 BP 315 EP 322 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 271JL UT WOS:000084590400001 PM 11263542 ER PT J AU Walhout, AJM Vidal, M AF Walhout, AJM Vidal, M TI A genetic strategy to eliminate self-activator baits prior to high-throughput yeast two-hybrid screens SO GENOME RESEARCH LA English DT Article ID PROTEIN-PROTEIN; SACCHAROMYCES-CEREVISIAE; FUNCTIONAL-ANALYSIS; REVERSE 2-HYBRID; GENOME SEQUENCE; SYSTEM; DROSOPHILA; REGULATORS; MAP AB Large-scale sequencing projects have predicted high numbers of gene products for which no functional information is yet available. Hence, large-scale projects, such as gene knockouts, gene expression profiles, and protein-interaction mapping, are currently under way to initiate the understanding of the Function of these gene products. The high-throughput strategies that are currently being developed to generate protein-interaction maps include automated versions of the yeast two-hybrid system. These strategies rely oil the large-scale construction of DNA-binding domain/protein-of-interest hybrid constructs [DB-X baits]. An inherent problem of large-scale two-hybrid systems is that a high percentage of cloned sequences encode polypeptides that, when fused to DB, can activate transcription in the absence of any two-hybrid-interacting partner protein. Here, we describe and validate a genetic strategy that efficiently eliminates such self-activator baits prior to screening procedures. The strategy is based on a negative-growth selection and is compatible with high-throughput settings. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM Vidal@helix.mgh.harvard.edu OI Walhout, Marian/0000-0001-5587-3608 FU NHGRI NIH HHS [R01 HG001715, 1 RO1 HG01715 A1] NR 34 TC 35 Z9 35 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 EI 1549-5469 J9 GENOME RES JI Genome Res. PD NOV PY 1999 VL 9 IS 11 BP 1128 EP 1134 DI 10.1101/gr.9.11.1128 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 258EL UT WOS:000083825100012 PM 10568752 ER PT J AU Leung, MK Jones, T Michels, CL Livingston, DM Bhattacharya, S AF Leung, MK Jones, T Michels, CL Livingston, DM Bhattacharya, S TI Molecular cloning and chromosomal localization of the human CITED2 gene encoding p35srj/Mrg1 SO GENOMICS LA English DT Article ID MELANOCYTE-SPECIFIC GENE; TRANSCRIPTION FACTORS; CPG ISLANDS; COACTIVATOR; P300/CBP; BINDING; MSG1; PURIFICATION; EXPRESSION; CBP/P300 AB P35srj is a ubiquitously expressed nuclear protein that binds the transcriptional coactivators p300 and CREB-binding protein (CBP), It is an alternatively spliced isoform of Mrg1, a cytokine-inducible factor that has transformation activity, P35srj interferes with the recruitment of p300/CBP by the transcription factor HIF-1 alpha, a process that is essential for the transcriptional response to hypoxia. Here we report the cloning of the human gene CITED2, which encodes p35srj and Mrg1, The CITED2 gene is composed of three exons and two introns, An unusually large (3 kb) CpG island covers both the promoter and the transcribed portions of the gene. The 5'-flanking region of the gene is active as a promoter in transient transfection assays and contains multiple STAT-binding sites, in keeping with its responsiveness to different cytokines, Fluorescence in situ hybridization, and identity to a known human sequence-tagged site (D6S2114), was used to map the CITED2 gene to chromosome 6q23.3, (C) 1999 Academic Press. C1 Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Imperial Canc Res Fund, London WC2A 3PX, England. RP Bhattacharya, S (reprint author), Univ Oxford, Dept Cardiovasc Med, Wellcome Trust Ctr Human Genet, Roosevelt Dr, Oxford OX3 7BN, England. RI Jones, Tania/C-8912-2011; Bhattacharya, Shoumo/F-4127-2010; Corbett-Jones, Tania/E-4891-2013 OI Jones, Tania/0000-0002-0067-3382; Corbett-Jones, Tania/0000-0002-0067-3382 FU Wellcome Trust NR 28 TC 37 Z9 42 U1 1 U2 5 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 NOV 1 PY 1999 VL 61 IS 3 BP 307 EP 313 DI 10.1006/geno.1999.5970 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 258ED UT WOS:000083824400009 PM 10552932 ER PT J AU Tuncer, ZS Bernstein, MR Wang, J Goldstein, DP Berkowitz, RS AF Tuncer, ZS Bernstein, MR Wang, J Goldstein, DP Berkowitz, RS TI Repetitive hydatidiform mole with different male partners SO GYNECOLOGIC ONCOLOGY LA English DT Article DE repetitive hydatidiform mole ID GESTATIONAL TROPHOBLASTIC DISEASE; IN-VITRO FERTILIZATION AB Objective. The aim of this study was to determine the role of parental factors that may relate to the pathogenesis of molar pregnancy. Methods. A retrospective review of six patients who had a molar pregnancy with at least two different partners at New England Trophoblastic Disease Center between 1965 and March 1999 was performed. Results. A total of 34 pregnancies with 20 different partners were observed in 6 patients. These pregnancies resulted in 15 (44.1%) hydatidiform moles, 8 (23.5%) term live births, 7 (20.6%) therapeutic abortions, 3 (8.8%) spontaneous abortions, and 1 pre-term delivery, While 5 patients had a molar pregnancy with 2 different partners, 1 patient had a molar pregnancy with 3 different partners. Two patients developed persistent postmolar gestational trophoblastic tumor in 3 (20.0%) of the 15 episodes of molar pregnancy. Three of the male partners reported a total of 7 healthy children from prior relationships. Conclusion. The experience in these six patients suggests that a primary oocyte problem may contribute to the development of molar pregnancy. (C) 1999 Academic Press. C1 Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol,Gillette Ctr Womens Canc, New England Trophoblast Dis Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Tuncer, ZS (reprint author), Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Div Gynecol Oncol,Gillette Ctr Womens Canc, New England Trophoblast Dis Ctr, 75 Francis St, Boston, MA 02115 USA. NR 17 TC 15 Z9 17 U1 0 U2 0 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 NOV PY 1999 VL 75 IS 2 BP 224 EP 226 DI 10.1006/gyno.1999.5562 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 255FX UT WOS:000083659800007 PM 10525376 ER PT J AU Vegh, GL Tuncer, ZS Fulop, V Genest, DR Mok, SC Berkowitz, RS AF Vegh, GL Tuncer, ZS Fulop, V Genest, DR Mok, SC Berkowitz, RS TI Matrix metalloproteinases and their inhibitors in gestational trophoblastic diseases and normal placenta SO GYNECOLOGIC ONCOLOGY LA English DT Article DE MMP; TIMP; trophoblastic disease; placenta ID 72-KD METALLOPROTEINASE; IV COLLAGENASE; POOR-PROGNOSIS; CANCER; EXPRESSION; INVASION; METASTASIS; CHORIOCARCINOMA; ADENOCARCINOMA; MARIMASTAT AB Objective. Our purpose was to investigate the expression of matrix metalloproteinases (MMPs) in gestational trophoblastic diseases and normal first-trimester placenta. Methods. Paraffin sections of 16 partial moles, 25 complete moles, 10 gestational choriocarcinomas, and 11 normal first-trimester placentas were studied immunohistochemically for expression of MMP-1, MMP-2, MMP-3, MMP-9, MMP-13, and tissue inhibitor of metalloproteinase-1 (TIMP-1). Results. Nine (90.0%) of the choriocarcinoma cases showed strong intensity of staining for MMP-1. Choriocarcinoma exhibited significantly stronger staining for MMP-1 than syncytiotrophoblast in normal placenta (P < 0.01), partial mole (P < 0.01), and complete mole (P < 0.01). Choriocarcinoma also shouted significantly stronger staining for MMP-1 than the extravillous trophoblast in placenta (P < 0.05). MMP-2 was expressed only in syncytio- and extravillous trophoblasts in normal placenta, partial mole, and complete mole. Choriocarcinoma and the extravillous trophoblast in partial mole and complete mole had significantly stronger staining for MMP-2 than the extravillous trophoblast in placenta (P < 0.05, P < 0.01, P < 0.01, respectively). Choriocarcinoma also exhibited significantly stronger staining for MMP-2 than syncytiotrophobIasts in placenta (P < 0.01), partial mole (P = 0.05), and complete mole (P < 0.01). The expression of MMP-3, MMP-9, and MMP-13 was similar in all four tissues with the predominance of syncytiotrophoblast for MMP-3 and MMP-13 and cytotrophoblast for MMP-9. While 8 (73.0%) placentas, 14 (87.5%) partial moles, and 19 (76.0%) complete moles showed strong immunoreactivity for TIMP-1 in syncytiotrophoblasts, no strong staining was found in choriocarcinomas (P < 0.01, P < 0.01, P < 0.01, respectively). Conclusion. The extravillous trophoblast of first-trimester placenta has significantly less expression of MMP-1 than choriocarcinoma and significantly less expression of MMP-1 than choriocarcinoma and extravillous trophoblast of partial and complete mole. The expression of TIMP-1 was significantly less in choriocarcinoma than the syncytiotrophoblast of normal placenta, partial mole, and complete mole. MMPs and their inhibitors may play a role in the pathogenesis of gestational trophoblastic diseases. (C) 1999 Academic Press. C1 Harvard Univ, Brigham & Womens Hosp,Div Gynecol Oncol, Dana Farber Canc Inst,Lab Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol,Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp,Gillette Ctr Womens Canc, Dana Farber Canc Inst,Div Womens & Perinatal Path, New England Trophoblast Dis Ctr,Dept Pathol,Sch M, Boston, MA 02115 USA. Haynal Imre Univ Hlth Sci, Dept Obstet & Gynecol, Budapest, Hungary. RP Vegh, GL (reprint author), Harvard Univ, Brigham & Womens Hosp,Div Gynecol Oncol, Dana Farber Canc Inst,Lab Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol,Sch Med, Boston, MA 02115 USA. NR 29 TC 38 Z9 48 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 NOV PY 1999 VL 75 IS 2 BP 248 EP 253 DI 10.1006/gyno.1999.5564 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 255FX UT WOS:000083659800012 PM 10525381 ER PT J AU Tsuang, MT Stone, WS Faraone, SV AF Tsuang, MT Stone, WS Faraone, SV TI Schizophrenia: A review of genetic studies SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review ID SCHIZOTYPAL PERSONALITY-DISORDER; EYE TRACKING DYSFUNCTIONS; FINNISH ADOPTIVE FAMILY; AFFECTED SIBLING PAIRS; SINGLE DOMINANT GENE; GENOME-WIDE SEARCH; LINKAGE ANALYSIS; SUSCEPTIBILITY LOCUS; POTENTIAL LINKAGE; CHROMOSOME 6P AB Despite the complexities of schizophrenia, notable progress has been achieved in its diagnosis and treatment over the last 25 years. In this article we review the genetic research that provides the foundation far continued advances. One of the bases of our current understanding involves the observation that schizophrenia often runs in families. The development and utilization of stringent, reliable diagnostic criteria, together with the advent of modern family, twin, and adoption paradigms, demonstrate the importance of genetic factors in understanding the familial basis of the! disorder. Refinements in diagnostic criteria have also enabled advances in understanding the likely mode-or modes-of genetic transmission of both schizophrenia and related disorders. After reviewing representative studies in these areas, we examine genetic linkage studies and our progress toward identifying the genes that cause schizophrenia. Although consistent results have been difficult to obtain and much work remains to be done, evidence for areas of vulnerability has been converging at particular chromosomal sites (e.g., 6p, 8p, and 22q), allowing for cautious optimism. Finally, we discuss challenges and prospects for the new millennium, including the clinical and ethical implications of genetic investigations. C1 Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Brockton W Roxbury Vet Affairs Med Ctr, Brockton, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Psychiat Serv, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. RP Tsuang, MT (reprint author), Massachusetts Mental Hlth Ctr, 74 Fenwood Rd, Boston, MA 02115 USA. OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [1 R01MH41879-01, 1 R37MH43518-01, 5 UO1 MH46318-02] NR 207 TC 79 Z9 82 U1 6 U2 11 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 1999 VL 7 IS 4 BP 185 EP 207 DI 10.1093/hrp/7.4.185 PG 23 WC Psychiatry SC Psychiatry GA 256MX UT WOS:000083730100001 PM 10579099 ER PT J AU Kent, SC Hafler, DA Stromingr, JL Wilson, SB AF Kent, SC Hafler, DA Stromingr, JL Wilson, SB TI Noncanonical V alpha 24J alpha Q T cells with conservative alpha chain CDR3 region amino acid substitutions are restricted by CD1d SO HUMAN IMMUNOLOGY LA English DT Article DE human; noncanonical; T-cell receptor; alpha chain; CD1d ID IMMUNOGLOBULIN-E PRODUCTION; I-LIKE MOLECULE; MOUSE CD1; TCR-ALPHA; SELECTIVE REDUCTION; ANTIGEN RECEPTOR; MICE; RECOGNITION; EXPRESSION; IL-4 AB Human NKRP-1A (CD161)+ T cells include members of a family of CD4+ or CD4-/CD8-lymphocytes that utilize an invariant a chain in the T-cell receptor (TCR). The alpha chain consists of the V alpha 24 segment joined to J alpha 18 (J alpha Q) (TCRAV24/AJ18). These families of T cells rapidly produce both interleukin-4 and interferon-gamma upon TCR cross-linking, and are restricted by CD1d. To determine the spectrum of allowable V/J rearrangements in the V alpha 24+ CD4-/CD8- family, TCR V alpha 24 chain transcripts derived from the total CD4-/CD8-population in peripheral blood mononuclear cells were sequenced. A second invariant rearrangement, V alpha 24J alpha 45, was Found in two donors. In addition. a subset of 15 clones with single amino acid substitutions in the CDR3 were identified and used to define CD1d restriction All 15 variant clones were indistinguishable from invariant clones on the basis Of surface phenotype and response to CD3 cross-linking. Movever, CD1d was the restriction element only for those clones with the conservative substitution of threonine or asparagine for serine at the V/J junction. Thus, the family of human CD161 + T cells can be extended to include a subset of V alpha 24-J alpha Q rearrangements with a single amino acid substitution that defines a V alpha 24 CDR3 residue critical for CD1d restriction. (C)American Society for Histocompatibility and Immunogenetics, 1999. Published by Elsevier Science Inc. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Wilson, SB (reprint author), Dana Farber Canc Inst, Dana 1414,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R35 CA 47554]; NIAID NIH HHS [N01 AI45198]; NIDDK NIH HHS [DK02345] NR 42 TC 19 Z9 19 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD NOV PY 1999 VL 60 IS 11 BP 1080 EP 1089 DI 10.1016/S0198-8859(99)00109-3 PG 10 WC Immunology SC Immunology GA 261WE UT WOS:000084032600010 PM 10600006 ER PT J AU Sahoo, T Johnson, EW Thomas, JW Kuehl, PM Jones, TL Dokken, CG Touchman, JW Gallione, CJ Lee-Lin, SQ Kosofsky, B Kurth, JH Louis, DN Mettler, G Morrison, L Gil-Nagel, A Rich, SS Zabramski, JM Boguski, MS Green, ED Marchuk, DA AF Sahoo, T Johnson, EW Thomas, JW Kuehl, PM Jones, TL Dokken, CG Touchman, JW Gallione, CJ Lee-Lin, SQ Kosofsky, B Kurth, JH Louis, DN Mettler, G Morrison, L Gil-Nagel, A Rich, SS Zabramski, JM Boguski, MS Green, ED Marchuk, DA TI Mutations in the gene encoding KRIT1, a Krev-1/rap1a binding protein, cause cerebral cavernous malformations (CCM1) SO HUMAN MOLECULAR GENETICS LA English DT Article ID CHROMOSOME 7Q; TUBEROUS SCLEROSIS; NATURAL-HISTORY; YAC CONTIG; HUMAN DNA; RAS; IDENTIFICATION; PRODUCT; LINKAGE; FAMILIES AB Cerebral cavernous malformations (CCM) are congenital vascular anomalies of the brain that can cause significant neurological disabilities, including intractable seizures and hemorrhagic stroke. One locus for autosomal dominant CCM (CCM1) maps to chromosome 7q21-q22. Recombination events in linked family members define a critical region of similar to 2 Mb and a shared disease haplotype associated with a presumed founder effect in families of Mexican-American descent points to a potentially smaller region of interest. Using a genomic sequence-based positional cloning strategy, we have identified KRIT1, encoding a protein that interacts with the Krev-1/rap1a tumor suppressor, as the CCM1 gene. Seven different KRIT1 mutations have been identified in 23 distinct CCM1 families. The identical mutation is present in 16 of 21 Mexican-American families analyzed, substantiating a founder effect in this population. Other Mexican-American and non-Hispanic Caucasian CCM1 kindreds harbor other KRIT1 mutations. Identification of a common Mexican-American mutation has potential clinical significance for presymptomatic diagnosis of CCM in this population. In addition, these data point to a key role for the Krev-1/rap1a signaling pathway in angiogenesis and cerebrovascular disease. C1 Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. St Joseph Hosp, Barrow Neurol Inst, Dept Neurogenet, Phoenix, AZ 85013 USA. St Joseph Hosp, Barrow Neurol Inst, Dept Neurosurg, Phoenix, AZ 85013 USA. Natl Human Genome Res Inst, NIH, Genome Technol Branch, Bethesda, MD 20892 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Marshfield Clin, Ctr Med Genet, Marshfield, WI 54449 USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Charlestown, MA 02129 USA. Childrens Hosp Eastern Ontario, Div Genet, Ottawa, ON K1H 8L1, Canada. Univ New Mexico, Sch Med, Dept Neurol, Albuquerque, NM 87131 USA. Hosp Ruber Int, Madrid 28034, Spain. Bowman Gray Sch Med, Dept Publ Hlth Sci & Neurol, Winston Salem, NC 27157 USA. RP Marchuk, DA (reprint author), Duke Univ, Med Ctr, Dept Genet, Durham, NC 27710 USA. OI Morrison, Leslie/0000-0002-0092-193X NR 55 TC 203 Z9 208 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 1999 VL 8 IS 12 BP 2325 EP 2333 DI 10.1093/hmg/8.12.2325 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 255FL UT WOS:000083658800023 PM 10545614 ER PT J AU Murphy, M Signoretti, S Nasser, I Sherburne, B Loda, M AF Murphy, M Signoretti, S Nasser, I Sherburne, B Loda, M TI Detection of concurrent/recurrent non-Hodgkin's lymphoma in effusions by PCR SO HUMAN PATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE non-Hodgkin's lymphoma; lymphocytic effusions; polymerase chain reaction; IgH/TCR gene rearrangements ID POLYMERASE CHAIN-REACTION; B-CELL LYMPHOMAS; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IMMUNOGLOBULIN GENE REARRANGEMENT; CHRONIC LYMPHOCYTIC-LEUKEMIA; PLEURAL EFFUSION; CYTOLOGIC SPECIMENS; CEREBROSPINAL-FLUID; MONOCLONALITY; INVOLVEMENT AB A subset of patients with non-Hodgkin's lymphoma (NHL), present with or subsequently develop lymphonytic effusions. Differential diagnosis between reactive lymphocytosis and recurrent low-grade NHL is difficult by cytology alone. We studied the use of polymerase chain reaction (PCR)-based techniques to detect concurrent/recurrent NHL. Both primary tumors and atypical lymphocytic effusions of 12 low-grade B-NHL patients and 4 T-NHL patients were studied. Six pleural effusions (reactive/carcinomatous), in patients; with no history of NHL, were included. Samples were amplified by PCR, using Fr3, Fr2, LJH, and VLJH primers specific for the immunoglobulin heavy chain (IgH) gene and V gamma-8, V gamma 9, V gamma 10, V gamma 11 and J gamma 1/J gamma 2 consensus primers specific for the T-cell receptor gamma (TCR-gamma) gene. IgH gene PCR products were analyzed by polyacrylamide gel electrophoresis (PAGE). TCR-gamma gene PCR products were analyzed using a novel nonradioactive single-strand conformational polymorphism (SSCP) procedure. IgH gene rearrangement analysis demonstrated monoclonality in 11/12 primary low-grade B-NHLs. Identical monoclonal bands were found in both primary tumor and effusion in 9 patients. TCR-gamma gene rearrangement analysis demonstrated monoclonality in 4 of 4 primary T-NHLs. Identical monoclonal banded patterns were found in both primary tumor and effusion in 3 patients. Our results strongly support the diagnosis of concurrent/recurrent NHL in 13 of 16 (81%) cases of atypical lymphocytic effusions. IgH/PAGE and TCR-gamma/SSCP analyses are useful tools in the diagnoses of lymphocytic effusions in patients with NHL. Copyright (C) 1999 by W.B. Saunders Company. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Loda, M (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 36 TC 7 Z9 7 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD NOV PY 1999 VL 30 IS 11 BP 1361 EP 1366 DI 10.1016/S0046-8177(99)90069-2 PG 6 WC Pathology SC Pathology GA 254DP UT WOS:000083596900015 PM 10571518 ER PT J AU Fauser, BCJM Devroey, P Yen, SSC Gosden, R Crowley, WF Baird, DT Bouchard, P AF Fauser, BCJM Devroey, P Yen, SSC Gosden, R Crowley, WF Baird, DT Bouchard, P TI Minimal ovarian stimulation for IVF: appraisal of potential benefits and drawbacks SO HUMAN REPRODUCTION LA English DT Editorial Material ID IN-VITRO FERTILIZATION; NORMAL MENSTRUAL-CYCLE; HORMONE ANTAGONIST CETRORELIX; IMMATURE HUMAN OOCYTES; INVITRO FERTILIZATION; FOLLICULAR DEVELOPMENT; ASSISTED-REPRODUCTION; LUTEINIZING-HORMONE; MULTIPLE-GESTATION; POLYCYSTIC OVARIES C1 Erasmus Univ, Ctr Med, Div Reprod Med, Dept Obstet & Gynecol, Rotterdam, Netherlands. Univ Libre Brussels, Dept Reprod Med, Brussels, Belgium. Univ Calif San Diego, Dept Reprod Med, Div Reprod Med, La Jolla, CA 92093 USA. Univ Leeds, Ctr Reprod Growth & Dev, Leeds, W Yorkshire, England. Harvard Univ, Sch Med, Reprod Endocrine Sci Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Edinburgh, Ctr Reprod Biol, Dept Obstet & Gynaecol, Edinburgh EH3 9EW, Midlothian, Scotland. Hop St Antoine, Serv Endocrinol, F-75571 Paris, France. RP Fauser, BCJM (reprint author), Erasmus Univ, Ctr Med, Div Reprod Med, Dept Obstet & Gynecol, Rotterdam, Netherlands. FU NICHD NIH HHS [P30 HD028138] NR 77 TC 131 Z9 134 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 EI 1460-2350 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 1999 VL 14 IS 11 BP 2681 EP 2686 DI 10.1093/humrep/14.11.2681 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 254FA UT WOS:000083600200001 PM 10548600 ER PT J AU Konadu, E Donohue-Rolfe, A Calderwood, SB Pozsgay, V Shiloach, J Robbins, JB Szu, SSC AF Konadu, E Donohue-Rolfe, A Calderwood, SB Pozsgay, V Shiloach, J Robbins, JB Szu, SSC TI Syntheses and immunologic properties of Escherichia coli O157O-specific polysaccharide and Shiga toxin 1 B subunit conjugates in mice SO INFECTION AND IMMUNITY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; VIBRIO-CHOLERAE; O157-H7; PURIFICATION; VACCINE; LIPOPOLYSACCHARIDE; LOCALIZATION; PERSPECTIVE; INFECTION; IMMUNITY AB Escherichia coli O157 is the major cause of diarrhea-associated hemolytic uremic syndrome (HUS). Strains causing HUS contain either Shiga toxin 1 (Stx1) or Stx2, or both. In adult volunteers, conjugate vaccines of detoxified lipopolysaccharide (LPS) elicited bactericidal antibodies to E. coli O157. Here, the detoxified LPS was conjugated with improved schemes to the nontoxic B subunit of Stx1. Mice injected with these bivalent conjugates elicited both bactericidal antibodies to E. coli O157 and neutralization antibodies to Stx1. C1 NICHHD, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Vet Med, Medford, MA 01536 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Szu, SSC (reprint author), NICHHD, NIH, Room 424,Bldg 6, Bethesda, MD 20892 USA. NR 28 TC 21 Z9 29 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD NOV PY 1999 VL 67 IS 11 BP 6191 EP 6193 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249QD UT WOS:000083343000091 PM 10531288 ER PT J AU Rhew, DC Goetz, MB AF Rhew, DC Goetz, MB TI Pneumonia in the elderly patient SO INFECTIOUS DISEASES IN CLINICAL PRACTICE LA English DT Review ID COMMUNITY-ACQUIRED PNEUMONIA; GRAM-NEGATIVE BACILLI; NURSING-HOME PATIENTS; LOW-RISK PATIENTS; PNEUMOCOCCAL VACCINE; OROPHARYNGEAL COLONIZATION; REQUIRING HOSPITALIZATION; STREPTOCOCCUS-PNEUMONIAE; CHLAMYDIA-PNEUMONIAE; CARE AB SIR WILLIAM OSLER once stated that pneumonia is a friend of the elderly. Whether it be friend or foe, pneumonia in the elderly patient certainly is a common, and when untreated, rapidly fatal condition. Overall, pneumonia is the most common cause of death due to infection in persons aged 60 years or older, and it is the fourth most common cause of death overall for persons aged 80 years or older. The rate of pneumonia in elderly persons is nearly four times that of the general population [1]. C1 Univ Calif Los Angeles, Sch Med, Div Infect Dis, W Los Angeles VA Med Ctr,Dept Med, Los Angeles, CA 90073 USA. RP Goetz, MB (reprint author), Univ Calif Los Angeles, Sch Med, Div Infect Dis, W Los Angeles VA Med Ctr,Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. OI Goetz, Matthew/0000-0003-4542-992X NR 50 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1056-9103 J9 INFECT DIS CLIN PRAC JI Infect. Dis. Clin. Pract. PD NOV PY 1999 VL 8 IS 8 BP 361 EP 367 DI 10.1097/00019048-199911000-00005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 249YL UT WOS:000083360900005 ER PT J AU Goldsmith, CAW Hamada, K Ning, YY Qin, GZ Catalano, P Murthy, GGK Lawrence, J Kobzik, L AF Goldsmith, CAW Hamada, K Ning, YY Qin, GZ Catalano, P Murthy, GGK Lawrence, J Kobzik, L TI Effects of environmental aerosols on airway hyperresponsiveness in a murine model of asthma SO INHALATION TOXICOLOGY LA English DT Article ID RESPIRATORY HEALTH; PM10 POLLUTION; INFLAMMATION; INHALATION; CHILDREN; PARTICULATE; EXPOSURE; PARTICLE; SYMPTOMS; METAL AB Increased morbidity in persons suffering from inflammatory lung diseases, such as asthma and bronchitis, has been associated with air pollution particles. One hypothesis is that particles can cause an amplification of the pulmonary inflammation associated with these diseases, thus worsening affected individuals' symptoms. This hypothesis was tested in a murine model of asthma by inhalation exposure to (1) concentrated air particles (CAPs), (2) the leachate of residual oil fly ash (ROFA-S), and (3) lipopolysaccharide (LPS). Allergen-sensitized mice (ip ovalbumin, OVA) were 21 days old when challenged with an aerosol of 3% OVA in phosphate-buffered saline (PBS) for 10 min (controls were challenged with PBS only) for 3 days. On the same days, mice were further exposed to 1 of 3 additional agents: CAPs (or filtered air) for 6 h/day; LPS (5 mu g/ml, or PBS) for 10 min/day; or ROFA-S (leachate of 50 mg/ml, or PBS) for 30 min on day 2 only. At 24 h later, mice challenged with OVA aerosol showed airway inflammation and airway hyperresponsiveness (AHR) to methacholine (Mch), features absent in mice challenged with PBS alone. Both OVA- and PBS-challenged mice subsequently exposed to ROFA-S showed increased AHR to Mch when compared to their respective controls (OVA only or PBS only). In contrast, when OVA-challenged mice were further exposed to CAPs or LPS, no changes in AHR were seen in comparison to mice challenged with OVA only. Bronchoalveolar lavage (BAL) analysis and histopathology 48 h postexposure showed OVA-induced allergic inflammation. No significant additional effects were caused by CAPs or ROFA-S. LPS, in contrast, caused significant increases in total cell, macrophage, and polymorphonuclear cell numbers. The data highlight discordance between airway inflammation and hyperresponsiveness. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Physiol Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Kobzik, L (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Physiol Program, Bldg II-221,665 Huntington Ave, Boston, MA 02115 USA. FU NHLBI NIH HHS [T32 HL07118]; NIEHS NIH HHS [ES08129, ES00002] NR 28 TC 30 Z9 30 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0895-8378 J9 INHAL TOXICOL JI Inhal. Toxicol. PD NOV PY 1999 VL 11 IS 11 BP 981 EP 998 PG 18 WC Toxicology SC Toxicology GA 259PJ UT WOS:000083902000001 PM 10562693 ER PT J AU Asawanonda, P Taylor, CR AF Asawanonda, P Taylor, CR TI Wood's light in dermatology SO INTERNATIONAL JOURNAL OF DERMATOLOGY LA English DT Review ID PHOTODYNAMIC DIAGNOSIS; TUBEROUS SCLEROSIS; SKIN; FLUORESCENCE; LAMP; EFFICACY; THERAPY; MELASMA C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. RP Taylor, CR (reprint author), Massachusetts Gen Hosp, Dept Dermatol, 55 Fruit St,BAR 410, Boston, MA 02114 USA. NR 44 TC 54 Z9 55 U1 4 U2 9 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0011-9059 J9 INT J DERMATOL JI Int. J. Dermatol. PD NOV PY 1999 VL 38 IS 11 BP 801 EP 807 DI 10.1046/j.1365-4362.1999.00794.x PG 7 WC Dermatology SC Dermatology GA 274YH UT WOS:000084792300001 PM 10583611 ER PT J AU Mallouk, Y Vayssier-Taussat, M Bonventre, JV Polla, BS AF Mallouk, Y Vayssier-Taussat, M Bonventre, JV Polla, BS TI Heat shock protein 70 and ATP as partners in cell homeostasis (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Review DE heat shock protein; adenosine triphosphate; homeostasis ID CHAIN BINDING-PROTEIN; ISCHEMIA-REPERFUSION INJURY; GLUCOSE-REGULATED PROTEINS; STRESS PROTEIN; TRANSCRIPTION FACTOR; PEPTIDE-BINDING; GENE-EXPRESSION; MESSENGER-RNA; DNA-BINDING; IN-VIVO AB Heat shock proteins (HSP) are molecular chaperones, involved in many cellular functions such as protein folding, transport, maturation and degradation. Since they control the quality of newly synthesized proteins, HSP take part in cellular homeostasis. The Hsp70 family in particular exerts these 'house-keeping' functions in an adenosine triphosphate (ATP)-dependent manner. ATP is the main energy source used by cells to assume fundamental functions (respiration, proliferation, differentiation, apoptosis). Therefore, ATP levels have to be adapted to the requirements of the cells and ATP generation must constantly compensate ATP consumption. Nevertheless, under particular stress conditions, ATP levels decrease, threatening cell homeostasis and integrity. Cells have developed adaptive and protective mechanisms, among which Hsp70 synthesis and overexpression. In this review, we focus on the mechanisms which regulate Hsp70 expression under ATP depletion, using ischaemia as a paradigmatic model for ATP depletion in vivo, and analyze the molecular targets for Hsp70-mediated protection against ATP depletion. We also consider how these Hsp70-mediated protective effects could be applied in the therapeutical approaches of human diseases associated with cellular ATP depletion. C1 Grp Hosp & Univ Cochin Port Royal, Physiol Resp Lab, Univ Paris 05, F-75014 Paris, France. Massachusetts Gen Hosp, Charlestown, MA 02115 USA. Harvard Univ, Sch Med, Charlestown, MA 02115 USA. RP Polla, BS (reprint author), Grp Hosp & Univ Cochin Port Royal, Physiol Resp Lab, Univ Paris 05, 24 Rue Faubourg St Jacques, F-75014 Paris, France. NR 121 TC 55 Z9 59 U1 1 U2 5 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD NOV PY 1999 VL 4 IS 5 BP 463 EP 474 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251EG UT WOS:000083431200001 PM 10534567 ER PT J AU D'Amico, AV Renshaw, AA Arsenault, L Schultz, D Richie, JP AF D'Amico, AV Renshaw, AA Arsenault, L Schultz, D Richie, JP TI Clinical predictors of upgrading to gleason grade 4 or 5 disease at radical prostatectomy: Potential implications for patient selection for radiation and androgen suppression therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; Gleason grade; prostate-specific antigen; patient selection ID PATHOLOGICAL FEATURES; GLAND VOLUME; CANCER; ANTIGEN; MEN; PROGNOSIS; TRIAL AB Purpose: A survival benefit has been suggested by the Radiation Therapy Oncology Group (RTOG) for the addition of androgen suppression to external beam radiation therapy for patients with locally advanced and high-grade disease. This study was performed to identify clinical factors that predicted high-grade disease at prostatectomy (i.e., Gleason grade 4 or 5) in patients with clinically localized and low-grade disease (i.e., Gleason grades 1-3) at biopsy. These pretreatment factors may allow for the identification of patients likely to derive a survival benefit from the addition of androgen suppression to external beam radiaton therapy while awaiting the results of the prospective randomized trials. Methods and Materials: Concordance testing of both the primary and secondary biopsy and prostatectomy Gleason grades was performed in 693 patients with clinical Stage T-1c,T- 2 prostate cancer managed with a radical prostatectomy (RP). For the subset of 420 patients with low-grade disease (i.e., Gleason grade less than or equal to 3) a logistic regression multivariable analysis was performed to evaluate the ability of the preoperative prostate-specific antigen (PSA), clinical stage, and ultrasound determined prostate gland volume to predict for upgrading to high-grade disease (i.e., Gleason grade 4 or 5). Results: Forty percent of men with low-grade disease at biopsy were found to have high-grade disease at RP. Men who have at least a 50% chance of being upgraded from biopsy Gleason grade less than or equal to 3 to prostatectomy Gleason grade greater than or equal to 4 disease included those with prostate gland volumes less than or equal to 75 cm(3) and a PSA > 20 ng/ml or a PSA > 10 and less than or equal to 20 and clinical Stage T-2b,T- 2c. For men with prostate gland volumes > 75 cm(3), only those with both PSA > 20 ng/ml and clinical Stage T-2b,T- 2c were at a significant risk of upgrading. Conclusion: Until the randomized data become available, clinical factors may be useful in identifying patients with clinically localized prostate cancer who are likely to benefit from combined androgen suppression and external beam radiation therapy. (C) 1999 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Brigham & Womens Hosp, Dept Urol, Boston, MA USA. Millersville Univ, Dept Math, Millersville, PA USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave,5th Floor, Boston, MA 02215 USA. NR 20 TC 58 Z9 60 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1999 VL 45 IS 4 BP 841 EP 846 DI 10.1016/S0360-3016(99)00260-6 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 254QQ UT WOS:000083624000002 PM 10571187 ER PT J AU D'Amico, AV Renshaw, AA Schultz, D Rocha, S Richie, JP AF D'Amico, AV Renshaw, AA Schultz, D Rocha, S Richie, JP TI The impact of the biopsy gleason score on PSA outcome for prostate cancer patients with PSA <= 10 ng/ml and T1C,2A: Implications for patient selection for prostate-only therapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; biopsy Gleason score; prostatectomy Gleason score; prostate-specific antigen; outcome ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; ANTIGEN AB Purpose: This study was performed to determine the ability of the biopsy Gleason score, prostate-specific antigen (PSA) level, and the 1992 American Joint Commission on Cancer (AJCC) clinical T-stage for predicting time to postoperative PSA failure for patients with a PSA less than or equal to 10 ng/ml and T1c or T2a disease. Specific attention is given to the patient subgroup with biopsy Gleason 3 + 4 vs. 4 + 3. Methods and Materials: A concordance map of the biopsy and prostatectomy Gleason grades and a clinical-pathologic correlation of the PSA, biopsy Gleason score, and 1992 AJCC T-stage and pathologic stage were performed. A Cox regression multivariable analysis was used to evaluate the ability of the biopsy Gleason score, PSA, and 1992 AJCC T-stage to predict time to PSA failure for 457 men managed with a radical prostatectomy (RP). Results: The absence of prostatectomy Gleason grade 4 or 5 disease was noted in 71%, 50%, and 11% of patients with biopsy Gleason score 2-6, 3 + 4, and greater than or equal to 4 + 3 disease respectively while pathologic evidence of seminal vesicle invasion was noted in 2%, 4%, and 17% of these patients respectively. Estimates of 5-year PSA failure-free survival rates were not statistically different for patients with biopsy Gleason score 2-6 vs. 3 + 4 (79% vs. 81%; p = 0.93), but were significantly different for patients having biopsy Gleason score 2-6 vs. 4 + 3 (79% vs. 62%; p = 0.04) or 26 vs. 8-10 (79% vs. 18%; p = 0.0001) prostate cancer. Conclusion: Based on the pathologic stage and PSA. control data following RP, patients,vith biopsy Gleason 3 + 4 disease and PSA less than or equal to 10 ng/ml and 1992 AJCC T1c or T2a disease may be suitable candidates for radiation therapy directed at the prostate only. (C) 1999 Elsevier Science Inc. C1 Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. Brigham & Womens Hosp, Dept Urol, Boston, MA USA. Millersville Univ, Dept Math, Millersville, PA USA. RP D'Amico, AV (reprint author), Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, 330 Brookline Ave,5th Floor, Boston, MA 02215 USA. NR 14 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1999 VL 45 IS 4 BP 847 EP 851 DI 10.1016/S0360-3016(99)00290-4 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 254QQ UT WOS:000083624000003 PM 10571188 ER PT J AU Dubey, A Recht, A Come, SE Gelman, RS Silver, B Harris, JR Shulman, LN AF Dubey, A Recht, A Come, SE Gelman, RS Silver, B Harris, JR Shulman, LN TI Concurrent CMF and radiation therapy for early stage breast cancer: Results of a pilot study SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE breast neoplasms; radiotherapy; chemotherapy; breast-conserving surgery ID SURGICAL ADJUVANT BREAST; POSITIVE AXILLARY NODES; CONSERVATIVE SURGERY; PREMENOPAUSAL WOMEN; LOCAL-CONTROL; CHEMOTHERAPY; RADIOTHERAPY; CYCLOPHOSPHAMIDE; METHOTREXATE; FLUOROURACIL AB Purpose: The optimal sequencing of chemotherapy (CT) and radiotherapy (RT) for patients with early-stage breast cancer treated with breast-conserving therapy is unresolved, Given the concerns arising from delaying either CT or RT, we conducted a pilot study of a concurrent CT-RT regimen in the hope that this would reduce side effects without decreasing efficacy. Methods and Materials: From 1992-1994, 112 patients with 0-3 positive nodes received 6 monthly cycles of classic oral chemotherapy with cyclophosphamide, methotrexate, and fi-fluorouracil (5-FU) (CMP). On day 15 of cycle 1, patients started tangential field RT (39.6 Gy in 22 fractions), followed by a 16 Gy boost in 8 fractions, Median follow-up time for surviving patients was 53 months. Results: Moist desquamation developed during or shortly after RT in 50% of patients, but only 5 patients required treatment breaks. Grade 4 neutropenia during RT occurred in 16 patients, but only 1 required hospitalization, One patient developed Grade 2 radiation pneumonitis. Ninety-three percent of patients received at least 85% of prescribed drug doses. Cosmetic scores of 51 evaluable patients approximately 2 years after the end of chemotherapy were 47% excellent, 43% good, and 10% fair. We have observed 4 local failures and 20 distant failures. Conclusions: This concurrent CT-RT scheme had acceptable toxicity and outcome, Further comparison of this approach allowing prompt initiation of both CT and RT to alternative sequences is warranted. (C) 1999 Elsevier Science Inc. C1 Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Joint Ctr Radiat Therapy, Boston, MA USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Recht, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, E Campus,Finard Bldg B25,330 Brookline Ave, Boston, MA 02215 USA. NR 51 TC 29 Z9 31 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 1 PY 1999 VL 45 IS 4 BP 877 EP 884 DI 10.1016/S0360-3016(99)00295-3 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 254QQ UT WOS:000083624000008 PM 10571193 ER PT J AU Hagstrom, SA Duyao, M North, MA Li, TS AF Hagstrom, SA Duyao, M North, MA Li, TS TI Retinal degeneration in tulp1(-/-) mice: Vesicular accumulation in the interphotoreceptor matrix SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID RDS MUTANT MICE; RECESSIVE RETINITIS-PIGMENTOSA; PHOSPHODIESTERASE BETA-SUBUNIT; DISK MEMBRANE MORPHOGENESIS; ROD OUTER SEGMENT; TUBBY GENE FAMILY; TRANSGENIC MICE; IMMUNOCYTOCHEMICAL LOCALIZATION; MOLECULAR CHARACTERIZATION; PLASMA-MEMBRANE AB PURPOSE. The Tulp1 gene is a member of the tubby gene family with unknown function. Mutations in the human TULP1 gene cause autosomal recessive retinitis pigmentosa. To understand the pathogenic mechanism associated with TULP1 mutations and to explore the physiologic function of this protein, we examined tissue distribution of the Tulp1 protein in normal mice and the photoreceptor disease phenotype in Tulp1-ablated mice. METHODS. Tissue distribution of the Tulp1 protein in normal mice was examined by immunoblotting and immunocytochemistry. The disease phenotype in tulp1(-/-) mice was studied by light and electron microscopy, electroretinography (ERG), and immunocytochemistry. These results were compared with another mouse model of retinal degeneration carrying a rhodopsin mutation. RESULTS. Tulp1 is found exclusively in photoreceptors, localizing predominantly in the inner segments. It is a soluble protein with an apparent molecular weight of approximately 70 kDa. Photoreceptor degeneration developed in tulp1(-/-) mice, with early involvement of both rods and cones. At the early stage of degeneration, rod and cone opsins, but not peripherin/RDS, exhibited prominent ectopic localization. Electron microscopy revealed massive accumulation of extracellular vesicles surrounding the distal inner segments. CONCLUSIONS. The function of Tulp1 is required to maintain viability of rod and cone photoreceptors. Extracellular vesicular accumulation is not a common phenomenon associated with photoreceptor degeneration but appears to be a distinct ultrastructural feature shared by a small group of retinal disease models. The defect in tulp1(-/-) mice may be consistent with a loss of polarized transport of nascent opsin to the outer segments. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Mol Genet Inst, Boston, MA 02114 USA. AxyS Pharmaceut, La Jolla, CA USA. RP Li, TS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY06915, EY10309] NR 41 TC 78 Z9 78 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 1999 VL 40 IS 12 BP 2795 EP 2802 PG 8 WC Ophthalmology SC Ophthalmology GA 250UN UT WOS:000083406700008 PM 10549638 ER PT J AU Reilly-Harrington, NA Alloy, LB Fresco, DM Whitehouse, WG AF Reilly-Harrington, NA Alloy, LB Fresco, DM Whitehouse, WG TI Cognitive styles and life events interact to predict bipolar and unipolar symptomatology SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Article ID BECK DEPRESSION INVENTORY; UNIVERSITY POPULATION; LEARNED HELPLESSNESS; CLINICAL DEPRESSION; SOCIOTROPY AUTONOMY; ATTRIBUTIONAL STYLE; AFFECTIVE-DISORDER; SELF-SCHEMA; STRESS; SPECIFICITY AB This study examined the interaction of cognitive style (as assessed self-report and information-processing battery) and stressful life events in predicting the clinician-rated depressive and manic symptomatology of participants with Research Diagnostic Criteria lifetime diagnoses of bipolar disorder (n = 49), unipolar depression (n = 97), or no lifetime diagnosis (n = 23). Bipolar and unipolar participants' attributional styles, dysfunctional attitudes, and negative self-referent information processing as assessed at Time 1 interacted significantly with the number of negative life events that occurred between Times 1 and 2 to predict increases in depressive symptoms from Time 1 to Time 2. Within the bipolar group, participants' Time 1 attributional styles and dysfunctional attitudes interacted significantly, and their self-referent information processings interacted marginally, with intervening life events to predict increases in manic symptoms from Time 1 to Time 2. These findings provide support for the applicability of cognitive vulnerability-stress theories of depression to bipolar spectrum disorders. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. RP Reilly-Harrington, NA (reprint author), Harvard Univ, Bipolar Res Program, 50 Staniford St,Suite 580, Boston, MA 02114 USA. RI Fresco, David/F-6522-2013; OI Fresco, David/0000-0001-6736-3912 FU PHS HHS [48216, 52617] NR 60 TC 123 Z9 124 U1 4 U2 12 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 1999 VL 108 IS 4 BP 567 EP 578 DI 10.1037//0021-843X.108.4.567 PG 12 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 263KE UT WOS:000084123200003 PM 10609421 ER PT J AU Boppart, MD Aronson, D Gibson, L Roubenoff, R Abad, LW Bean, J Goodyear, LJ Fielding, RA AF Boppart, MD Aronson, D Gibson, L Roubenoff, R Abad, LW Bean, J Goodyear, LJ Fielding, RA TI Eccentric exercise markedly increases c-Jun NH2-terminal kinase activity in human skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE mitogen-activated protein kinase kinase 4; injury; interleukin-6 ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAY; N-TERMINAL KINASE; GENE-EXPRESSION; SMOOTH-MUSCLE; STRESS; PHOSPHORYLATION; INTERLEUKIN-6; CYTOKINES; RECEPTOR AB Eccentric contractions require the lengthening of skeletal muscle during force production and result in acute and prolonged muscle injury. Because a variety of stressors, including physical exercise and injury, can result in the activation of the c-Jun NH2-terminal kinase (JNK) intracellular signaling cascade in skeletal muscle, we investigated the effects of eccentric exercise on the activation of this stress-activated protein kinase in human skeletal muscle. Twelve healthy subjects (7 men, 5 women) completed maximal concentric or eccentric knee extensions on a KinCom isokinetic dynamometer (10 sets, 10 repetitions). Percutaneous needle biopsies were obtained from the vastus lateralis muscle 24 h before exercise (basal), immediately postexercise, and 6 h postexercise. Whereas both forms of exercise increased JNK activity immediately postexercise, eccentric contractions resulted in a much higher activation (15.4 +/- 4.5 vs. 3.5 +/- 1.4-fold increase above basal, eccentric vs. concentric). By 6 h after exercise, JNK activity decreased back to baseline values. In contrast to the greater activation of JNK with eccentric exercise, the mitogen-activated protein kinase kinase 4, the immediate upstream regulator of JNK, was similarly activated by concentric and eccentric exercise. Because the activation of JNK promotes the phosphorylation of a variety of transcription factors, including c-Jun, the results from this study suggest that JNK may be involved in the molecular and cellular adaptations that occur in response to injury-producing exercise in human skeletal muscle. C1 Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Hlth Sci, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Dept Phys Med & Rehabil, Boston, MA 02111 USA. RP Fielding, RA (reprint author), Boston Univ, Sargent Coll Hlth & Rehabil Sci, Dept Hlth Sci, 635 Commonwealth Ave, Boston, MA 02215 USA. RI Aronson, Doron/F-3390-2010; Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 FU NIAMS NIH HHS [AR-42238] NR 43 TC 68 Z9 72 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1999 VL 87 IS 5 BP 1668 EP 1673 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 255NA UT WOS:000083675000015 PM 10562607 ER PT J AU Aljuri, N Freitag, L Venegas, JG AF Aljuri, N Freitag, L Venegas, JG TI Modeling expiratory flow from excised tracheal tube laws SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE flow limitation; tracheal cross-sectional area and collapse; wave speed ID AIRWAY AB Flow limitation during forced exhalation and gas trapping during high-frequency ventilation are affected by upstream viscous losses and by the relationship between transmural pressure (Ptm) and cross-sectional area (A(tr)) of the airways, i.e., tube law (TL). Our objective was to test the validity of a simple lumped-parameter model of expiratory flow limitation, including the measured TL, static pressure recovery, and upstream viscous losses. To accomplish this objective, we assessed the TLs of various excised animal tracheae in controlled conditions of quasi-static (no flow) and steady forced expiratory flaw. At, was measured from digitized images of inner tracheal walls delineated by transillumination at an axial location defining the minimal area during forced expiratory flow. Tracheal TLs followed closely the exponential form proposed by Shapiro (A. H. Shapiro. J. Biomech. Eng. 99: 126-147, 1977) for elastic tubes: Ptm = K-p [(A(tr)/A(tr0))(-n) - 1], where A(tr0) is A(tr) at Ptm = 0 and K-p is a parametric factor related to the stiffness of the tube wall. Using these TLs, we found that the simple model of expiratory flow limitation described well the experimental data. Independent of upstream resistance, all tracheae with an exponent n < 2 experienced flow limitation, whereas a trachea with n > 2 did not. Upstream viscous losses, as expected, reduced maximal expiratory flow. The TL measured under steady-flow conditions was stiffer than that measured under expiratory no-flow conditions, only if a significant static pressure recovery from the choke point to atmosphere was assumed in the measurement. C1 Harvard Univ, Dept Anesthesia BioEngn, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Ruhrlandklin Essen, Essen, Germany. RP Venegas, JG (reprint author), Harvard Univ, Dept Anesthesia BioEngn, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38267] NR 12 TC 7 Z9 7 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 1999 VL 87 IS 5 BP 1973 EP 1980 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 255NA UT WOS:000083675000051 PM 10562643 ER PT J AU Chakravarti, A Spiro, IJ Hug, EB Mankin, HJ Efird, JT Suit, HD AF Chakravarti, A Spiro, IJ Hug, EB Mankin, HJ Efird, JT Suit, HD TI Megavoltage radiation therapy for axial and inoperable giant-cell tumor of bone SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article AB Background Treatment of giant-cell tumor of bone generally involves aide en bloc resection of the lesion and the surrounding bone or curettage with or without bone-grafting or the use of cement. Radiation therapy has been used for patients who cannot be operated on for medical reasons or who have a tumor that is technically difficult to resect or that cannot be resected because of its location. We performed the present study to evaluate the efficacy of megavoltage radiation in terms of lack of tumor progression and treatment-related morbidity: Methods: Twenty patients who had giant-tell tumor of bone were managed with a single course of megavoltage radiation (forty to seventy gray administered at 1.8 to 2.0 gray per fraction with an average total duration of treatment of five to seven weeks) between March 1973 and March 1992, We used megavoltage photons, 160-megaelectron-volt proton beams, or a combination of the two. Results: After a median duration of follow-up of 9.3 Sears, the tumor had not progressed in seventeen of the twenty patients. Thus, the actuarial ten-year rate for lack of progression was 85 percent. Local regrowth was evident in one patient who had received radiation alone and in two of the thirteen patients who had been managed with partial resection and radiation. Operative treatment was successful in the three patients in whom the radiation treatment had failed. No radiation-induced tumors were observed in our series. Conclusions We concluded that giant-cell tumor of bone was effectively treated with megavoltage radiation in our series of twenty patients in whom operative resection would have been difficult or tvas not feasible, The rate of tumors that did not progress with this regimen of radiation is similar to that reported by investigators from several other centers. Furthermore, these results closely rival those obtained with modern curettage procedures. Malignant sarcomatous transformation was not observed in our series. A longer duration of follow-up of a larger group of patients is necessary to provide a better estimate of the risk of malignant transformation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Chakravarti, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02114 USA. NR 15 TC 52 Z9 57 U1 1 U2 1 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 NOV PY 1999 VL 81A IS 11 BP 1566 EP 1573 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 253XW UT WOS:000083583200008 PM 10565648 ER PT J AU Mithofer, K Grabowski, EF Rosenberg, AE Ryan, DP Mankin, HJ AF Mithofer, K Grabowski, EF Rosenberg, AE Ryan, DP Mankin, HJ TI Symptomatic ganglioneuroma of bone - A case report SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID NEURO-BLASTOMA; NEUROBLASTIC TUMORS; MATURATION; DIAGNOSIS; FEATURES C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Mithofer, K (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. NR 32 TC 7 Z9 7 U1 0 U2 0 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 NOV PY 1999 VL 81A IS 11 BP 1589 EP 1595 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 253XW UT WOS:000083583200011 PM 10565651 ER PT J AU Estepa, JC Aguilera-Tejero, E Lopez, I Almaden, Y Rodriguez, M Felsenfeld, AJ AF Estepa, JC Aguilera-Tejero, E Lopez, I Almaden, Y Rodriguez, M Felsenfeld, AJ TI Effect of phosphate on parathyroid hormone secretion in vivo SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article ID RENAL-FAILURE; IN-VITRO; SECONDARY HYPERPARATHYROIDISM; CALCEMIC RESPONSE; HIGH PHOSPHORUS; CELL-PROLIFERATION; GENE-EXPRESSION; PTH SECRETION; MESSENGER-RNA; CITRATE CLAMP AB Alterations in phosphate homeostasis play an important role in the development of secondary hyperparathyroidism in renal failure. Until recently, it was accepted that phosphate retention only increased parathyroid hormone (PTH) secretion through indirect mechanisms affecting calcium regulation and calcitriol synthesis. However, recent in vitro studies have suggested that phosphate may directly affect PTH secretion. Our goal was to determine whether in vivo an intravenous phosphate infusion stimulated PTH secretion in the absence of changes in serum calcium. Three different doses of phosphate were infused intravenously during 120 minutes to increase the serum phosphate concentration in dogs. Sulfate was also infused intravenously as a separate experimental control. A simultaneous calcium clamp was performed to maintain a normal ionized calcium concentration throughout all studies. At the lowest dose of infused phosphate (1.2 mmol/kg), serum phosphate values increased to similar to 3 mM, but PTH values did not increase. At higher doses of infused phosphate (1.6 mmol/kg and 2.4 mmol/kg), the increase in serum phosphate to values of similar to 4 mM and 5 mM, respectively, was associated with increases in PTH, even though the ionized calcium concentration did not change. Increases in PTH were not observed until 30-60 minutes into the study. These increases were not sustained, since by 120 minutes PTH values were not different from baseline or controls despite the maintenance of marked hyperphosphatemia. During the sulfate infusion, serum sulfate values increased by similar to 3-fold, but no change in PTH values were observed. In conclusion, an acute elevation in serum phosphate stimulated PTH secretion in the intact animal, but the magnitude of hyperphosphatemia exceeded the physiologic range. Future studies are needed to determine whether PTH stimulation is more sensitive to phosphate loading in states of chronic phosphate retention, Moreover, the mechanisms responsible for the delay in PTH stimulation and the failure to sustain the increased PTH secretion need further evaluation. C1 Hosp Univ Reina Sofia, Unidad Invest, Cordoba 14004, Spain. Univ Cordoba, Fac Vet, Dept Med & Cirugia Anim, Cordoba, Spain. Hosp Univ Reina Sofia, Serv Nefrol, Cordoba 14004, Spain. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Rodriguez, M (reprint author), Hosp Univ Reina Sofia, Unidad Invest, Avda Menedez Pidal S-N, Cordoba 14004, Spain. RI Rodriguez, teresa/H-5452-2011 NR 55 TC 47 Z9 47 U1 0 U2 1 PU AMER SOC BONE & MINERAL RES PI DURHAM PA PO BOX 2759, DURHAM, NC 27715-2759 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 1999 VL 14 IS 11 BP 1848 EP 1854 DI 10.1359/jbmr.1999.14.11.1848 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 250BF UT WOS:000083368600006 PM 10571684 ER PT J AU Yasuhara, S Kanakubo, E Perez, ME Kaneki, M Fujita, T Okamoto, T Martyn, JAJ AF Yasuhara, S Kanakubo, E Perez, ME Kaneki, M Fujita, T Okamoto, T Martyn, JAJ TI The 1999 Moyer Award - Burn injury induces skeletal muscle apoptosis and the activation of caspase pathways in rats SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID DNA-FRAGMENTATION; SACCHAROMYCES-CEREVISIAE; CERAMIDE; STRESS; SPHINGOLIPIDS; INFARCTION; INHIBITOR; PROTEINS; DEATH; CELLS AB Burn injury induces many metabolic disorders, including altered protein kinetics with muscle weakness. The skeletal muscle weakness that occurs as a result of the loss of muscle mass causes hypoventilation and dependence on respirators, a condition that increases morbidity and mortality. The presence or absence of apoptosis in muscle, which can be a cause of the loss of muscle mass, was studied in rats after they had received scald burns to 40% of their body surface areas. The potential pro-apoptotic pathways that were activated were also examined. The burn injury produced did trot directly destroy the muscle beneath; muscles just beneath the burned surface showed dramatic apoptotic changes according to assessments with the cell death enzyme-linked immunosorbent assay and in situ TdT-mediated dUTP-X nick-end labeling staining. The extent of apoptosis reached a peak on postburn days 3 and 7. Of note is that apoptosis was also confirmed in muscles at sites distant from the burn injury (eg, tibialis anterior) on both postburn days 3 and 7, a condition that is suggestive of the systemic effects of pro-apoptotic factors. To show that heat itself causes the initiation of the pro-apoptotic signaling, muscle-derived C2C12 cells were subjected to heat treatment at 55 degrees C. Ceramide, a key apoptotic second messenger, was observed to increase in the caveolae fraction but not in non-caveolae fraction of these muscle cells. In muscle tissue from burned rats, stress-activated protein kinase (a downstream-signaling kinase of ceramide) was activated soon after burn injury; this finding is consistent with the hypothesis that ceramide plays a role in burn-induced apoptosis. Caspase-1, -3, and -9, important final apoptotic enzymes involved with the downstream signaling of stress-activated protein kinase, were also activated after barn injury in muscle tissue from burned rats. These findings confirm the hypothesis that apoptosis occurs in skeletal muscle and that major apoptotic pathways are activated after a burn injury. Further characterization of these apoptotic signaling cascades may provide new therapeutic targets for the prevention of burn-induced muscle wasting. C1 Harvard Univ, Massachusetts Gen Hosp, Shriners Burns Inst, Dept Anesthesiol, Boston, MA 02114 USA. Univ Tokyo, Dept Internal Med 4, Tokyo, Japan. Cleveland Clin Fdn, Dept Neurosci, Cleveland, OH 44106 USA. RP Martyn, JAJ (reprint author), Shriners Hosp Crippled Children, Dept Anesthesiol, 51 Blossom St, Boston, MA 02114 USA. NR 30 TC 41 Z9 43 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD NOV-DEC PY 1999 VL 20 IS 6 BP 462 EP 470 DI 10.1097/00004630-199920060-00007 PG 9 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 265WJ UT WOS:000084268800006 PM 10613683 ER PT J AU Sheridan, RL Weber, JM Schulz, JT Ryan, CM Low, HM Tompkins, RG AF Sheridan, RL Weber, JM Schulz, JT Ryan, CM Low, HM Tompkins, RG TI Management of severe toxic epidermal necrolysis in children SO JOURNAL OF BURN CARE & REHABILITATION LA English DT Article ID STEVENS-JOHNSON SYNDROME; CATHETERS AB Toxic epidermal necrolysis (TEN) is a severe form of erythema multiforme that results in extensive epidermal sloughing; the condition is associated with a mortality of up to 70%. From 1991 to 1998, 10 children with severe toxic epidermal necrolysis were referred to a regional pediatric burn facility. Wounds were managed with strategy involving prevention of wound desiccation and superinfection, including the frequent use of biologic wound coverings. Children unable to guard their airway because of extensive oropharyngeal involvement were prophylactically intubated. Enteral nutrition was stressed. Steroids were not used and antibiotics were administered to managed specific foci of infection only. The 2 boys and 8 girls had an average age of 7.2 +/- 1.8 years (range 6 months to 15 years) and sloughed surface area of 76 +/- 6% of the body surface (range 50 to 95%). Antibiotics (3 children), anticonvulsants (3 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were felt to have triggered the syndrome. Six children (60%) required intubation for an average of 9.7 +/- 1.8 days (range 2 to 14 days). Buccal mucosal involvement occurred in 9 (90%) and ocular involvement in 9 (90%). Although infectious complications were common (2 pneumonias, 2 urinary infections, 1 bacteremia, 2 central line infections, and 2 candidemias), all children survived after lengths of stay in the burn unit averaging: 19 +/- 3 (range 6 to ) days. The most common long-term morbidity was keratitis sicca (2 children 20%), finger nail deformities (3 children, 30%), and variegated skin pigment changes (5 children, 50%). Although having both a cutaneous and visceral wound that predispose them to infectious complications, most children with TEN will survive if managed with a strategy emphasizing biologic wound closure, intensive nutritional support, and early detection and treatment of septic foci. Burn units have the resource set required to manage severe TEN and early referral of such children may have a favorable impact on survival. C1 Shriners Burns Hosp, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Sheridan, RL (reprint author), Shriners Burns Hosp, 51 Blossom St, Boston, MA 02114 USA. NR 23 TC 37 Z9 37 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0273-8481 J9 J BURN CARE REHABIL JI J. Burn Care Rehabil. PD NOV-DEC PY 1999 VL 20 IS 6 BP 497 EP 500 DI 10.1097/00004630-199920060-00012 PG 4 WC Emergency Medicine; Rehabilitation; Surgery SC Emergency Medicine; Rehabilitation; Surgery GA 265WJ UT WOS:000084268800011 PM 10613688 ER PT J AU Hess, D AF Hess, D TI Filters and anesthesia breathing circuits: Can we cut costs without harm? SO JOURNAL OF CLINICAL ANESTHESIA LA English DT Editorial Material ID MECHANICAL VENTILATION; NOSOCOMIAL PNEUMONIA; BACTERIAL FILTERS; COLONIZATION; HUMIDIFIERS; INFECTION; STRATEGY; PATIENT; REDUCE; RATES C1 Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. RP Hess, D (reprint author), Massachusetts Gen Hosp, Dept Resp Care, Ellison 401,55 Fruit St, Boston, MA 02114 USA. NR 18 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0952-8180 J9 J CLIN ANESTH JI J. Clin. Anesth. PD NOV PY 1999 VL 11 IS 7 BP 531 EP 533 DI 10.1016/S0952-8180(99)00094-X PG 3 WC Anesthesiology SC Anesthesiology GA 267XB UT WOS:000084383600001 PM 10624633 ER PT J AU Haugen, BR Pacini, F Reiners, C Schlumberger, M Ladenson, PW Sherman, SI Cooper, DS Graham, KE Braverman, LE Skarulis, MC Davies, TF DeGroot, LJ Mazzaferri, EL Daniels, GH Ross, DS Luster, M Samuels, MH Becker, DV Maxon, HR Cavalieri, RR Spencer, CA McEllin, K Weintraub, BD Ridgway, EC AF Haugen, BR Pacini, F Reiners, C Schlumberger, M Ladenson, PW Sherman, SI Cooper, DS Graham, KE Braverman, LE Skarulis, MC Davies, TF DeGroot, LJ Mazzaferri, EL Daniels, GH Ross, DS Luster, M Samuels, MH Becker, DV Maxon, HR Cavalieri, RR Spencer, CA McEllin, K Weintraub, BD Ridgway, EC TI A comparison of recombinant human thyrotropin and thyroid hormone withdrawal for the detection of thyroid remnant or cancer SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HAMSTER OVARY CELLS; THYROGLOBULIN MEASUREMENT; STIMULATING HORMONE; CARCINOMA; PAPILLARY; THERAPY; I-131; BIOACTIVITY; METASTASES AB Recombinant human TSH has been developed to facilitate monitoring for thyroid carcinoma recurrence or persistence without the attendant morbidity of hypothyroidism seen after thyroid hormone withdrawal. The objectives of this study were to compare the effect of administered recombinant human TSH with thyroid hormone withdrawal on the results of radioiodine whole body scanning (WBS) and serum thyroglobulin (Tg) levels. Two hundred and twenty-nine adult patients with differentiated thyroid cancer requiring radioiodine WBS were studied. Radioiodine WBS and serum Tg measurements were performed after administration of recombinant human TSH and again after thyroid hormone withdrawal in each patient. Radioiodine whole body scans were concordant between the recombinant TSH-stimulated and thyroid hormone withdrawal phases in 195 of 220 (89%) patients. Of the discordant scans, 8 (4%) had superior scans after recombinant human TSH administration, and 17 (8%) had superior scans after thyroid hormone withdrawal (P = 0.108). Based on a serum Tg level of 2 ng/mL or more, thyroid tissue or cancer was detected during thyroid hormone therapy in 22%, after recombinant human TSH stimulation in 52%, and after thyroid hormone withdrawal in 56% of patients with disease or tissue limited to the thyroid bed and in 80%, 100%, and 100% of patients, respectively, with metastatic disease. A combination of radioiodine WBS and serum Tg after recombinant human TSH stimulation detected thyroid tissue or cancer in 93% of patients with disease or tissue limited to the thyroid bed and 100% of patients with metastatic disease. In conclusion, recombinant human TSH administration is a safe and effective means of stimulating radioiodine uptake and serum Tg levels in patients undergoing evaluation for thyroid cancer persistence and recurrence. C1 Univ Colorado, Hlth Sci Ctr, Div Endocrinol, Denver, CO 80262 USA. Univ Pisa, Div Endocrinol, I-56124 Pisa, Italy. Univ Wurzburg, Nukl Med Klin & Poliklin, D-97070 Wurzburg, Germany. Inst Gustave Roussy, Nucl Med Serv, F-94805 Villejuif, France. Johns Hopkins Univ, Sch Med, Div Endocrinol & Metab, Baltimore, MD 21287 USA. Univ Texas, MD Anderson Canc Ctr, Dept Med Specialties, Houston, TX 77030 USA. Sinai Hosp, Div Endocrinol, Baltimore, MD 21215 USA. Oregon Hlth & Sci Univ, Div Endocrinol, Portland, OR 97201 USA. Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. CUNY Mt Sinai Sch Med, Div Endocrinol, New York, NY 10029 USA. Univ Chicago, Med Ctr, Dept Med, Chicago, IL 60637 USA. Ohio State Univ, Ctr Hlth Sci, Dept Internal Med, Columbus, OH 43210 USA. Massachusetts Gen Hosp, Thyroid Unit, Boston, MA 02114 USA. Cornell Univ, Med Ctr, New York Hosp, Div Nucl Med, New York, NY 10021 USA. Univ Cincinnati, Med Ctr, Cincinnati, OH 45267 USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Univ So Calif, Dept Med, Los Angeles, CA 90033 USA. Genzyme Transgen Corp, Boston, MA 02139 USA. Univ Maryland, Sch Med, Mol Endocrinol Lab, Baltimore, MD 21201 USA. RP Haugen, BR (reprint author), Univ Colorado, Hlth Sci Ctr, Div Endocrinol, B151,4200 E 9th Ave, Denver, CO 80262 USA. RI Ain, Kenneth/A-5179-2012; OI Ain, Kenneth/0000-0002-2668-934X; Sherman, Steven/0000-0002-3079-5153 FU NCRR NIH HHS [M01-RR-43] NR 23 TC 381 Z9 401 U1 1 U2 5 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 NOV PY 1999 VL 84 IS 11 BP 3877 EP 3885 DI 10.1210/jc.84.11.3877 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KM UT WOS:000083555800004 PM 10566623 ER PT J AU Lim, SC Caballero, AE Arora, S Smakowski, P Bashoff, EM Brown, FM Logerfo, FW Horton, ES Veves, A AF Lim, SC Caballero, AE Arora, S Smakowski, P Bashoff, EM Brown, FM Logerfo, FW Horton, ES Veves, A TI The effect of hormonal replacement therapy on the vascular reactivity and endothelial function of healthy individuals and individuals with type 2 diabetes SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FLOW-MEDIATED VASODILATION; CORONARY HEART-DISEASE; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; ESTROGEN; DYSFUNCTION; MELLITUS; RISK; ATHEROSCLEROSIS; LIPOPROTEINS AB Estrogens protect healthy women from cardiovascular disease. However, epidemiological data suggest that women with diabetes are denied the cardioprotection associated with estrogens. Whether or not hormonal replacement therapy(HRT) confers cardiovascular benefits in postmenopausal women with diabetes is not known. The aim of this study was to examine the effects of HRT on the microvascular reactivity and endothelial function of individuals with and without diabetes. We studied the following groups of individuals: premenopausal healthy women [n = 28, age 41 +/- 8 yr (mean =/- SD)], premenopausal women with type 2 diabetes (n = 16, age 43 +/- 6 yr); postmenopausal healthy women (n = 12, age 57 +/- 4 yr), postmenopausal women with diabetes (n = 17, age 62 +/- 5 yr); postmenopausal healthy women on HRT (n = 13, age 51 +/- 5 yr), postmenopausal women with diabetes on HRT (n = 11, age 57 +/- 7 yr). We used laser Doppler flowmetry to measure forearm cutaneous vasodilatation in response to iontophoresis of 1% acetylcholine (endothelium dependent) and 1% sodium nitroprusside (endothelium independent). the endothelium-dependent vasodilation was significantly higher in premenopausal healthy women (180 +/-: 67%; increase over baseline) compared to premenopausal diabetic women (87 +/-: 41%; P < 0.001). endothelium-dependent vasodilation was also higher in postmenopausal healthy women on HRT (143 +/- 52) compared with postmenopausal diabetic women on HRT (86 +/- 61), postmenopausal healthy women without HRT (104 +/- 43), and postmenopausal diabetic women without HRT (74 +/- 28; P < 0.001). A similar pattern of responses was observed in the endothelium-independent vasodilation (premenopausal healthy women, 126 +/- 56; premenopausal diabetic women, 88 +/- 26; postmenopausal healthy women on HRT, 121 +/- 37; postmenopausal diabetic women on HRT, 88 +/- 41; postmenopausal healthy women without HRT, 84 +/- 36; and postmenopausal diabetic women without HRT, 73 +/- 36; P < 0.001). Soluble intercellular adhesion molecule (sICAM) was also measured among all the women with diabetes. Premenopausal women with diabetes (248.9 +/- 56 ng/ml) and post menopausal women with diabetes on HRT (257.7 +/- 49 ng/ml) had lower sICAM levels compared with the postmenopausal diabetic women without HRT (346.4 +/- 149 ng/ml; P < 0.05). We conclude that menopausal status and type 2 diabetes are associated with impaired microvascular reactivity. HRT substantially improves microvascular reactivity in postmenopausal healthy women. In contrast, the effect of HRT on the microvascular reactivity of postmenopausal diabetic women is less apparent. However, the use of HRT among women with diabetes is associated with lower sICAM levels, suggesting an attenuation in endothelial activation. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Vasc Surg, Boston, MA 02215 USA. RP Veves, A (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Microcirculat Lab, Palmer 317,W Campus,1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@caregroup.harvard.edu NR 31 TC 47 Z9 47 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 NOV PY 1999 VL 84 IS 11 BP 4159 EP 4164 DI 10.1210/jc.84.11.4159 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KM UT WOS:000083555800047 PM 10566666 ER PT J AU John, MR Goodman, WG Gao, P Cantor, TL Salusky, IB Juppner, H AF John, MR Goodman, WG Gao, P Cantor, TL Salusky, IB Juppner, H TI A novel immunoradiometric assay detects full-length human PTH but not amino-terminally truncated fragments: Implications for PTH measurements in renal failure SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INTERMITTENT CALCITRIOL THERAPY; PARATHYROID-HORMONE RELEASE; SECONDARY HYPERPARATHYROIDISM; PERIPHERAL METABOLISM; CALCIUM-CONCENTRATION; OSTEODYSTROPHY; GROWTH; INVIVO; BONE; CCPD AB In 8 adolescents with end-stage renal disease (ESRD), basal PTH concentrations measured with a novel immunoradiometric assay (IRMA) (Scantibodies Laboratory, Inc.; S-IRMA) were invariably lower than those estimated with an established assay (Nichols Institute; N-IRMA) (263 +/- 228 versus 645 +/- 442 pg/ml, respectively; p<0.00001). During in vivo dynamic testing, set points for calcium-regulated PTB release were indistinguishable for both IRMAs (1.21 +/- 0.05 versus 1.22 +/- 0.06). However, maximal PTH concentrations were significantly lower when measured by S-IRMA then by N-IRMA (557 +/- 448 and 1114 +/- 606 pg/ml, respectively); minimum PTH concentrations were 41 +/- 65 pg/ml (5.0 +/- 4.2% of maximum) and 189 +/- 137 pg/ml (13.6 +/- 7.2% of maximum), respectively. Correlation between PTH and blood ionized calcium indicated that PTH measured by S-IRMA decreased more readily than the concentrations determined by N-IRMA. The N-IRMA showed indistinguishable cross-reactivity with hPTH(1-84) and hPTH(7-84), while the S-IRMA detected only the full-length peptide. Furthermore, the radiolabeled detection antibody of the N-IRMA interacted equivalently with hPTH(1-34) and hPTH(2-34), while the S-IRMA showed crossreactivity only with hPTH(1-34). These differences in assay specificity could explain the observed differences in ESRD, and suggest that PTH concentrations estimated by the S-IRMA reflect more accurately the amount of biologically active PTH in the circulation. Since low concentrations of PTH are frequently associated with adynamic bone disease, our findings may have significant implications for the treatment of renal osteodystrophy with calcium and/or biologically active vitamin D analogs. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Scantibodies Lab, Santee, CA 92071 USA. Univ Calif Los Angeles, Sch Med, Dept Pediat, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. RP Juppner, H (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,WEL 501, Boston, MA 02114 USA. EM jueppner@helix.mgh.harvard.edu FU NCRR NIH HHS [RR-00865]; NIDDK NIH HHS [DK-35423] NR 21 TC 193 Z9 202 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 1999 VL 84 IS 11 BP 4287 EP 4290 DI 10.1210/jc.84.11.4287 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 253KM UT WOS:000083555800070 PM 10566687 ER PT J AU Tanzi, RE AF Tanzi, RE TI A genetic dichotomy model for the inheritance of Alzheimer's disease and common age-related disorders SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID POLYMORPHISM; ONSET; RISK C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Charlestown, MA 02129 USA. RP Tanzi, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Genet & Aging Res Unit, Bldg 149,13th St, Charlestown, MA 02129 USA. NR 21 TC 92 Z9 105 U1 2 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1999 VL 104 IS 9 BP 1175 EP 1179 DI 10.1172/JCI8593 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WL UT WOS:000083469300006 PM 10545516 ER PT J AU Wojtaszewski, JFP Higaki, Y Hirshman, MF Michael, MD Dufresne, SD Kahn, CR Goodyear, LJ AF Wojtaszewski, JFP Higaki, Y Hirshman, MF Michael, MD Dufresne, SD Kahn, CR Goodyear, LJ TI Exercise modulates postreceptor insulin signaling and glucose transport in muscle-specific insulin receptor knockout mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID RAT SKELETAL-MUSCLE; GLYCOGEN-SYNTHASE KINASE-3; 3T3-L1 ADIPOCYTES; PROTEIN; CONTRACTIONS; 3-KINASE; INVOLVEMENT; STIMULATION; METABOLISM; NETWORK AB Physical exercise promotes glucose uptake into skeletal muscle and makes the working muscles more sensitive to insulin. To understand the role of insulin receptor (IR) signaling in these responses, we studied the effects of exercise and insulin on skeletal muscle glucose metabolism and insulin signaling in mice lacking insulin receptors specifically in muscle. Muscle-specific insulin receptor knockout (MIRKO) mice had normal resting 2-deoxy-glucose (2DG) uptake in soleus muscles but had no significant response to insulin. Despite this, MIRKO mice displayed normal exercise-stimulated 2DG uptake and a normal synergistic activation of muscle 2DG uptake with the combination of exercise plus insulin. Glycogen content and glycogen synthase activity in resting muscle were normal in MIRKO mice, and exercise, but not insulin, increased glycogen synthase activity. Insulin, exercise, and the combination of exercise plus insulin did not increase IR tyrosine phosphorylation or phosphatidylinositol 3-kinase activity in MIRKO muscle. In contrast, insulin alone produced a small activation of Akt and glycogen synthase kinase-3 in MIRKO mice, and prior exercise markedly enhanced this insulin effect. In conclusion, normal expression of muscle insulin receptors is not needed for the exercise-mediated increase in glucose uptake and glycogen synthase activity in vivo. The synergistic activation of glucose transport with exercise plus insulin is retained in MIRKO mice, suggesting a phenomenon mediated by nonmuscle cells or by downstream signaling events. C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Wojtaszewski, Jorgen /P-6583-2014 OI Wojtaszewski, Jorgen /0000-0001-9785-6830 FU NIAMS NIH HHS [AR42238, AR45670, R01 AR042238, R01 AR045670]; NIDDK NIH HHS [DK31036, F32 DK009817, R01 DK031036, R37 DK031036] NR 38 TC 128 Z9 133 U1 1 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1999 VL 104 IS 9 BP 1257 EP 1264 DI 10.1172/JCI7961 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WL UT WOS:000083469300014 PM 10545524 ER PT J AU Zeng, NX Athmann, C Kang, T Lyu, RM Walsh, JH Ohning, GV Sachs, G Pisegna, JR AF Zeng, NX Athmann, C Kang, T Lyu, RM Walsh, JH Ohning, GV Sachs, G Pisegna, JR TI PACAP type I receptor activation regulates ECL cells and gastric acid secretion SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VASOACTIVE-INTESTINAL-PEPTIDE; ENTEROCHROMAFFIN-LIKE CELLS; ADENYLATE-CYCLASE; FUNCTIONAL EXPRESSION; SIGNAL-TRANSDUCTION; SPLICE VARIANTS; POLYPEPTIDE; HISTAMINE; RAT; CLONING AB Pituitary adenylate cyclase activating polypeptide (PACAP) is present in gastric nerves, and PACAP receptors (PAC1) are found on gastric enterochromaffin-like (ECL) cells. Expression of PAC1 splice variants in purified ECL cells was determined by RT-PCR. PACAP effects on ECL cells were analyzed by video imaging of [Ca2+](i) and histamine release; its effects on gastric glands were examined by confocal microscopy of [Ca2+](i) in ECL and parietal cells. PACAP action on D cells was measured by [Ca2+](i) and radioimmunoassay. PACAP effects on acid secretion were determined in fistula rats with or without neutralizing anti-somatostatin antibodies. All splice variants of PAC1 were found, but vasoactive intestinal polypeptide (VIP) receptor (VPAC) products were absent. PACAP-27 and -38 dose-dependently raise [Ca2+](i) in ECL cells and stimulate histamine release. VIP had a much lower affinity, which demonstrates the presence of PAC1 but not VPAC. PACAP elevated [Ca2+](i) in ECL and parietal cells of superfused gastric glands, but only the parietal cell signal was inhibited by ranitidine, showing the absence of PAC1 on parietal cells and demonstrating functional coupling between the cell types. PACAP and VIP stimulated calcium signaling and somatostatin release from D cells with almost equal efficacy. Acid secretion was stimulated after intravenous injection of PACAP into rats treated with somatostatin antibody. PACAP is a candidate as a mediator of neural regulation of acid secretion. C1 Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlth Care Syst W, Vet Adm,Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90073 USA. RP Sachs, G (reprint author), Univ Calif Los Angeles, Vet Affairs Greater Los Angeles Hlth Care Syst W, Vet Adm,Digest Dis Res Ctr, Ctr Ulcer Res & Educ, Bldg 113,Room 326, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [DK17294, DK40615, DK41301, P30 DK041301] NR 27 TC 66 Z9 67 U1 0 U2 0 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1999 VL 104 IS 10 BP 1383 EP 1391 DI 10.1172/JCI7537 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 256RF UT WOS:000083738700011 PM 10562300 ER PT J AU Ullrich, R Bloch, KD Ichinose, F Steudel, W Zapol, WM AF Ullrich, R Bloch, KD Ichinose, F Steudel, W Zapol, WM TI Hypoxic pulmonary blood flow redistribution and arterial oxygenation in endotoxin-challenged NOS2-deficient mice SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; ACUTE LUNG INJURY; RELAXING FACTOR; VASOCONSTRICTION; INHIBITION; RESPONSES; SHEEP; RATS; DOG AB Sepsis and endotoxemia impair hypoxic pulmonary vasoconstriction (HPV), thereby reducing arterial oxygenation and enhancing hypoxemia. Endotoxin induces nitric oxide (NO) production by NO synthase 2 (NOS2). To assess the role of NO and NOS2 in the impairment of HPV during endotoxemia, we measured in vivo the distribution of total pulmonary blood flow (QPA) between the right (QRPA) and left (QLPA) pulmonary arteries before and after left mainstem bronchus occlusion (LMBO) in mice with and without a congenital deficiency of NOS2. LMBO reduced QLPA/QPA equally in saline-treated wild-type and NOS2-deficient mice. However, prior challenge with Escherichia coli endotoxin markedly impaired the ability of LMBO to reduce QLPA/QPA in wild-type, but not in NOS2-deficient, mice. After endotoxin challenge and LMBO, systemic oxygenation was impaired to a greater extent in wild-type than in NOS2-deficient mice. When administered shortly after endotoxin treatment, the selective NOS2 inhibitor L-NIL preserved HPV in wild-type mice. High concentrations of inhaled NO attenuated HPV in NOS2-deficient mice challenged with endotoxin. These findings demonstrate that increased pulmonary NO levels (produced by NOS2 or inhaled at high levels from exogenous sources) are necessary during the septic process to impair HPV, ventilation/perfusion matching and arterial oxygenation in a murine sepsis model. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL42397, HL55377, R01 HL042397] NR 31 TC 56 Z9 57 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1999 VL 104 IS 10 BP 1421 EP 1429 DI 10.1172/JCI6590 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 256RF UT WOS:000083738700015 PM 10562304 ER PT J AU Hani, EH Stoffers, DA Chevre, JC Durand, E Stanojevic, V Dina, C Habener, JF Froguel, P AF Hani, EH Stoffers, DA Chevre, JC Durand, E Stanojevic, V Dina, C Habener, JF Froguel, P TI Defective mutations in the insulin promoter factor-1 (IPF-1) gene in late-onset type 2 diabetes mellitus SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PANCREAS DEVELOPMENT; HOMEODOMAIN PROTEIN; TRANSACTIVATION; YOUNG; PATHOGENESIS; MICE; SCAN AB Type 2 diabetes mellitus is a common disabling disease with onset in middle-aged individuals, caused by an imbalance between insulin production and action. Genetic studies point to major genetic components, but, with the exception of maturity-onset diabetes of the young (MODY), specific diabetes susceptibility genes remain to be identified. Recent studies showed that a dominant negative mutation in the insulin promoter factor-1 (IPF-1), a pancreatic beta-cell specific transcription factor, causes pancreatic agenesis and MODY. Thus, we investigated 192 French, non-MODY type 2 diabetic families for mutations in IPF-1. We identified 3 novel IPF-1 mutations, including 2 substitutions (Q59L and D76N) and an in-frame proline insertion (InsCCG243). Functional transactivation assays of these IPF-1 mutant isoforms in a beta-pancreatic tumor cell line transfected with a transcriptional reporter and IPF-1 expression plasmids demonstrate a significant inhibition of basal insulin promoter activity (stronger with the InsCCG243 mutant). We find that the InsCCG243 mutation is linked, in 2 families, to an autosomal dominant-like late-onset form of type 2 diabetes, in which insulin secretion becomes progressively impaired. The lower penetrance D76N and Q59L mutations were more prevalent and were associated with a relative risk of 12.6 for diabetes and with decreased glucose-stimulated insulin-secretion in nondiabetic subjects. We propose that IPF-1 mutations can cause MODY or apparently monogenic late-onset diabetes and that they represent a significant risk factor for type 2 diabetes in humans. C1 Inst Pasteur, CNRS, UPRES A8090, Inst Biol, F-59000 Lille, France. Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp,Lab Mol Endocrinol, Boston, MA 02114 USA. RP Froguel, P (reprint author), Inst Pasteur, CNRS, UPRES A8090, 1 Rue Professeur Calmette, F-59019 Lille, France. RI Stoffers, Doris/H-6157-2012; Chevre, Jean-Claude/C-3943-2015; Dina, Christian/D-3535-2015 OI Chevre, Jean-Claude/0000-0002-5329-5231; Dina, Christian/0000-0002-7722-7348 FU NIDDK NIH HHS [P01 DK002456, DK 30457, DK 02456] NR 25 TC 167 Z9 176 U1 0 U2 6 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA ROOM 4570 KRESGE I, 200 ZINA PITCHER PLACE, ANN ARBOR, MI 48109-0560 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 1999 VL 104 IS 9 BP R41 EP R48 DI 10.1172/JCI7469 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 251WL UT WOS:000083469300021 PM 10545531 ER PT J AU Haber, DA AF Haber, DA TI Breast cancer in carriers of BRCA1 and BRCA2 mutations: Tackling a molecular and clinical conundrum SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID EMBRYONIC LETHALITY; YOUNG-WOMEN; GENE BRCA1; DNA-DAMAGE; TAMOXIFEN; PREVENTION; TRIAL; RAD51; RISK C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Haber, DA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. NR 35 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 NOV PY 1999 VL 17 IS 11 BP 3367 EP 3370 PG 4 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700001 PM 10550129 ER PT J AU Bubley, GJ Carducci, M Dahut, W Dawson, N Daliani, D Eisenberger, M Figg, WD Freidlin, B Halabi, S Hudes, G Hussain, M Kaplan, R Myers, C Oh, W Petrylak, DP Reed, E Roth, B Sartor, O Scher, H Simons, J Sinibaldi, V Small, EJ Smith, MR Trump, DL Vollmer, R Wilding, G AF Bubley, GJ Carducci, M Dahut, W Dawson, N Daliani, D Eisenberger, M Figg, WD Freidlin, B Halabi, S Hudes, G Hussain, M Kaplan, R Myers, C Oh, W Petrylak, DP Reed, E Roth, B Sartor, O Scher, H Simons, J Sinibaldi, V Small, EJ Smith, MR Trump, DL Vollmer, R Wilding, G TI Eligibility and response guidelines for phase II clinical trials in androgen-independent prostate cancer: Recommendations from the prostate-specific antigen working group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THERAPY; MARKER; CARCINOMA AB Purpose: Prostate-specific antigen (PSA) is a glycoprotein that is found almost exclusively in normal and neoplastic prostate cells. For patients with metastatic disease, changes in PSA will often antedate changes in bone scan. Furthermore, many but not all investigators have observed an association between a decline in PSA levels of 50% or greater and survival. Since the majority of phase II clinical trials for patients with androgen-independent prostate cancer (AIPC) have used PSA as a marker, we believed it wets important for investigators to agree on definitions and values for a minimum set of parameters for eligibility and PSA declines and to develop a common approach to outcome analysis and reporting. We held a consensus conference with 26 leading investigators in the field of AIPC to define these parameters. Result: We defined four patient groups: (1) progressive measurable disease, (2) progressive bone metastasis, (3) stable metastases and a rising PSA, and (4) rising PSA and no other evidence of metastatic disease. The purpose of determining the number of patients whose PSA level drops in a phase II trial of AIPC is to guide the selection of agents for further testing and phase III trials. We propose that investigators report at a minimum a PSA decline of at least 50% and this must be confirmed by a second PSA value 4 or more weeks later. patients may not demonstrate clinical or radiographic evidence of disease progression during this time period. Some investigators may want to report additional measures of PSA changes (ie, 75% decline, 90% decline). Response duration and the time to PSA progression may also be important clinical end point. Conclusion: Through this consensus conference, we believe we have developed practical guidelines for using PSA as ct measurement of outcome. Furthermore, the use of common standards is important as we determine which agents should progress to randomized trials which will use survival as an end point. (C) 1999 by American Society of Clinical Oncology. C1 NCI, Med Branch, Bethesda, MD 20892 USA. Dana Farber Canc Ctr, Beth Israel Deaconess Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Duke Univ, Durham, NC USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Wayne State Univ, Detroit, MI USA. Univ Virginia, Charlottesville, VA USA. Columbia Univ, New York, NY USA. Vanderbilt Univ, Louisiana State Med Ctr, New Orleans, LA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Wisconsin, Madison, WI USA. RP Figg, WD (reprint author), NCI, Med Branch, Bldg 10,Room 5A01,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Oh, William/B-9163-2012; Figg Sr, William/M-2411-2016 OI Oh, William/0000-0001-5113-8147; NR 25 TC 733 Z9 755 U1 0 U2 7 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 NOV PY 1999 VL 17 IS 11 BP 3461 EP 3467 PG 7 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700015 PM 10550143 ER PT J AU Pappo, AS Anderson, JR Crist, WM Wharam, MD Breitfeld, PP Hawkins, D Raney, RB Womer, RB Parham, DM Qualman, SJ Grier, HE AF Pappo, AS Anderson, JR Crist, WM Wharam, MD Breitfeld, PP Hawkins, D Raney, RB Womer, RB Parham, DM Qualman, SJ Grier, HE TI Survival after relapse in children and adolescents with rhabdomyosarcoma: A report from the intergroup rhabdomyosarcoma study group SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID OF-PEDIATRIC-ONCOLOGY; SOFT-TISSUE SARCOMA; PHASE-II; TUMORS; IFOSFAMIDE; PROGNOSIS; CHILDHOOD; TRIAL AB Background: Despite advances in therapy, nearly 30% of children with rhabdomyasarcoma experience progressive or relapsed disease, which is often fatal. Patients and Methods: To facilitate the development of a retrieval therapy protocol, we studied potential risk factors that were predictive of survival after first relapse in 605 children who were enrolled onto three consecutive Intergroup Rhabdomyosarcoma Study Group protocols, Results: The median survival time from first recurrence was 0.8 years; the estimated percentage of patients who survived 5 years from first recurrence was 17% +/- 2% (mean +/- SE). Univariate analysis showed that tumor histology was an important predictor of 5-year survival (P <.001): the 5-year survival rate was 64% for patients with botryoid tumors (n = 19), 26% for patients with embryonal tumors (n = 313), and 5% for patients with alveolar or undifferentiated sarcoma (n = 273). Further analysis identified prognostic factors within histologic subtypes (P <.001). For patients with embryonal tumors, the estimated 5-year survival rate was 52% for patients who initially presented with stage 1 or group I disease, 20% for those with stage 2/3 or group II/III disease, and 12% for those with group IV disease. For patients with stage 1/group I disease, estimated 5-year survival rates were higher for patients with local (72%) or regional (50%) recurrence than for those with distant (30%) recurrence. Among patients with alveolar or undifferentiated sarcoma, only the disease group predicted outcome: the 5-year survival estimate was 40% for group I versus 3% for groups II through IV. We identified a "favorable risk" group (approximately 20% of patients) whose 5-year estimated survival rate was near 50%; for all other patients, the estimated survival was near 10%. Conclusion: This analysis demonstrates that the probability of 5-year survival after relapse for rhabdomyosarcoma is dependent on several factors at the time of initial diagnosis, including histologic subtype, disease group, and stage. These findings will form the basis of a multi-institutional risk-adapted relapse protocol for childhood rhabdomyosarcoma. (C) 1999 by American Society of Clinical Oncology. C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Mayo Clin, Rochester, MN USA. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Childrens Hosp & Med Ctr, Seattle, WA 98105 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Childrens Hosp, Columbus, OH 43205 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Pappo, AS (reprint author), Intergrp Rhabdomyosarcoma Study Grp Operat Off, Mayo 9-30E,200 1st St SW, Rochester, MN 55905 USA. FU NCI NIH HHS [CA24507, CA72989] NR 20 TC 104 Z9 108 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 NOV PY 1999 VL 17 IS 11 BP 3487 EP 3493 PG 7 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700018 PM 10550146 ER PT J AU Colevas, AD Norris, CM Tishler, RB Fried, MP Gomolin, HI Amrein, P Nixon, A Lamb, C Costello, R Barton, J Read, R Adak, S Posner, MR AF Colevas, AD Norris, CM Tishler, RB Fried, MP Gomolin, HI Amrein, P Nixon, A Lamb, C Costello, R Barton, J Read, R Adak, S Posner, MR TI Phase II trial of docetaxel, cisplatin, fluorouracil, and leucovorin as induction for squamous cell carcinoma of the head and neck SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LOCALLY ADVANCED HEAD; HIGH-DOSE LEUCOVORIN; RANDOMIZED TRIAL; STAGE-III; CANCER; CHEMOTHERAPY; 5-FLUOROURACIL; RADIOTHERAPY; INFUSION; CHEMORADIOTHERAPY AB Purpose: To evaluate the toxicity and efficacy of a 4-day regimen of docetaxel, cisplatin, fluorouracil, and leucovorin (TPFL4) in patients with locoregionally advanced squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods: Thirty previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status of 2 or less were treated with TPFL4. Postchemotherapy support included prophylactic growth factors and antibiotics. Patients who achieved a complete response (CR) or partial response (PR) to three cycles of TPFL4 received definitive twice-daily radiation therapy. The primary end points were toxicity and response to TPFL4, Results: Eighty-five cycles were administered to 30 patients, The major acute toxicities to TPFL4 were mucositis and nausea. One patient died of neutropenic sepsis during therapy. Additional major toxicities were neutropenia, anorexia, nephropathy, neuropathy, and diarrhea. Fourteen percent of all cycles were associated with hospitalization for toxicity. The overall clinical response rate to TPFL4 was 93%, with 63% CRs and 30% PRs. Primary tumor site clinical and pathologic response rates were 93% and 68%, respectively. Conclusion: TPFL4 has an acceptable toxicity profile in good-performance-status patients. Modification of the 5-day TPFL regimen (TPFL5: shorter chemotherapy infusion time, earlier intervention with growth factors and antibiotics) led to fewer episodes of febrile neutropenia and hospitalization. Response rates to TPFL justify further evaluation of combinations of these agents in the context of formal clinical trials. (C) 1999 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Head & Neck Oncol Program, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Joint Ctr Otolaryngol, Joint Ctr Radiat Therapy,Dept Internal Med, Boston, MA 02115 USA. Harvard Univ, Vanguard Med Assoc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Colevas, AD (reprint author), Dana Farber Canc Inst, Head & Neck Oncol Program, 44 Binney St, Boston, MA 02115 USA. NR 33 TC 96 Z9 101 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 NOV PY 1999 VL 17 IS 11 BP 3503 EP 3511 PG 9 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700020 PM 10550148 ER PT J AU Ng, AK Weeks, JC Mauch, PM Kuntz, KM AF Ng, AK Weeks, JC Mauch, PM Kuntz, KM TI Decision analysis on alternative treatment strategies for favorable-prognosis, early-stage Hodgkin's disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BONE-MARROW TRANSPLANTATION; EXTENDED-FIELD RADIOTHERAPY; RADIATION-THERAPY SALVAGE; SOUTHWEST-ONCOLOGY-GROUP; HIGH-DOSE CHEMOTHERAPY; RANDOMIZED TRIAL; CLINICAL-TRIALS; BREAST-CANCER; FOLLOW-UP; COMBINATION CHEMOTHERAPY AB Purpose: To compare the therapeutic outcomes of various treatment strategies in early-stage, favorable-prognosis Hodgkin's disease (HD) using methods of decision analysis, Methods: We constructed a decision-analytic model to determine the life expectancy and quality-adjusted life expectancy for a hypothetical cohort of clinically or pathologically staged 25-year-old patients with early-stage, favorable-prognosis HD treated with varying degrees of initial therapy, Markov models were used to simulate the lifetime clinical course of patients, and baseline probability estimates were derived from published study results, Results: Among patients with pathologic stage (PS)I to II, mantle and para-aortic (MPA) radiotherapy was favored over combined-modality therapy (CMT), mantle radiotherapy, and chemotherapy by 1.18, 1.33, and 1.55 years, respectively. For patients with clinical stage (CS) I to II, the treatment options of MPA-splenic radiotherapy, CMT, and chemotherapy yielded similar survival outcomes, Sensitivity analysis showed that the decision between CMT and MPA-splenic radiotherapy was highly influenced by the precise values of the estimates of treatment efficacy and long-term morbidity, the quality-of-life value assigned to the postsplenic irradiation state, and the time discount value used in the model, probabilistic sensitivity analysis demonstrated that even it future studies doubled the precision of the estimates of the treatment-related variables, it would be impossible to demonstrate the superiority of one treatment over the other, Conclusion: Our model predicted that on average, MPA radiotherapy was clearly the preferred treatment for PS I to II patients. For CS I to It patients the treatment decision is a toss-up between MPA-splenic radiotherapy and CMT, emphasizing the importance of patient preference exploration and shared decision making between patient and physician when choosing between treatments. (C) 1999 by American Society of Clinical Oncology. C1 Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. RP Kuntz, KM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Risk Anal, Dept Hlth Policy & Management, 718 Huntington Ave, Boston, MA 02115 USA. NR 65 TC 14 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 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV PY 1999 VL 17 IS 11 BP 3577 EP 3585 PG 9 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700029 PM 10550157 ER PT J AU Oh, WK Kantoff, PW AF Oh, WK Kantoff, PW TI Treatment of locally advanced prostate cancer: Is chemotherapy the next step? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID NEOADJUVANT HORMONAL-THERAPY; STAGE-C ADENOCARCINOMA; TERM FOLLOW-UP; EXTERNAL-BEAM RADIATION; RADICAL PROSTATECTOMY; ANDROGEN DEPRIVATION; PREMENOPAUSAL WOMEN; ADJUVANT TREATMENT; LOCALIZED DISEASE; ONCOLOGY GROUP AB Purpose: Management of locally advanced prostate cancer remains controversial. Various single and combination modality approaches have been advocated, but an accepted standard of care remains undefined. The purpose of this review is to define the current knowledge in managing locally advanced prostate cancer and to propose new treatment approaches based an current knowledge. Materials and Methods: A MEDLINE search to detect all relevant articles on the management of locally advanced prostate cancer was performed. A review of the staging, natural history, and prognosis of this disease was also performed. Results: The lack of a clearly defined treatment approach to patients with locally advanced prostate cancer stems from multiple factors, including ambiguities in clinical staging, inadequate knowledge of the natural history of the cancer, and a dearth of comparative randomized trials evaluating efficacy of different therapies. Single modality treatment, including radical prostatectomy (RP) or external-beam radiotherapy alone, is associated with high rates of failure, The use of adjuvant hormonal ablation therapy in combination with external-beam radiotherapy has shown improvement in progression-free and overall survival, although similar improvements have not been clearly demonstrated for surgical patients treated with hormonal therapy. New advances in chemotherapy for hormone-refractory prostate cancer suggest that response rates may be as high as 50% or more, and current trials are evaluating the addition of chemotherapy to hormonal ablation in either surgery or radiation therapy in locally advanced prostate cancer. Conclusion: Optimal management of locally advanced prostate cancer remains undefined, Standard treatment options include RP, external beam radiotherapy, or hormonal ablation therapy, alone or in combination. New approacher being tested include improved methods for delivering radiation or combining hormonal ablation with surgery or radiation. It is possible that other forms of systemic therapy including chemotherapy, may become important components of multimodality treatment, Clinical trials designed to test this hypothesis are ongoing. (C) 1999 by American Society of Clinical Oncology. C1 Dana Farber Canc Inst, Dept Adult Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Oh, WK (reprint author), 44 Binney St, Boston, MA 02115 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 72 TC 25 Z9 25 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 NOV PY 1999 VL 17 IS 11 BP 3664 EP 3675 PG 12 WC Oncology SC Oncology GA 251YJ UT WOS:000083473700037 PM 10550165 ER PT J AU Sharma, R Saini, S AF Sharma, R Saini, S TI Role and limitations of magnetic resonance imaging in the diagnostic work-up of patients with liver cancer SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article; Proceedings Paper CT Workshop on Multiple Perspectives in Magnetic Resonance Imaging Contrast CY NOV 06-08, 1998 CL MILAN, ITALY SP Bracco SpA DE liver; cancer; contrast media ID FOCAL NODULAR HYPERPLASIA; ENHANCED MR; ARTERIAL PORTOGRAPHY; HEPATIC METASTASES; HEPATOCELLULAR-CARCINOMA; HELICAL CT; PATHOLOGICAL CORRELATION; TUMORS; HEMANGIOMAS; LESIONS AB The main objectives of liver imaging are detection and characterization of focal liver lesions. There is a wide range of imaging modalities available for the work-up of patients with liver cancer. In the current environment of cost containment, the most appropriate modality should be chosen to answer the clinical question. Contrast-enhanced computed tomography is currently the modality of choice for liver imaging for routine applications. Until recently magnetic resonance imaging was used only as a problem solving technique for lesions that were equivocal after contrast-enhanced computed tomography. However magnetic resonance with the use of tissue specific contrast agents, has already challenged the role of computed tomography portography in preoperative staging of liver cancer, and may soon completely replace this technique. It is also the primary modality for screening patients with cirrhosis for hepatocellular carcinoma. This review describes the role of magnetic resonance imaging, in the evaluation of patients with liver cancer, and outlines a rational approach for the diagnostic work-up of these patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging, Boston, MA 02115 USA. RP Saini, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiol,Div Abdominal Imaging, Ellison 234,55 Fruit St, Boston, MA 02115 USA. NR 28 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV PY 1999 VL 23 SU 1 BP S39 EP S44 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 268AM UT WOS:000084391500006 PM 10608396 ER PT J AU Gonzalez, S Rubinstein, G Mordovtseva, V Rajadhyaksha, M Anderson, RR AF Gonzalez, S Rubinstein, G Mordovtseva, V Rajadhyaksha, M Anderson, RR TI In vivo abnormal keratinization in Darier-White's disease as viewed by real-time confocal imaging SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Article ID MICROSCOPY AB Darier-White's disease is a rare autosomal-dominant disorder of keratinization. The underlying pathology for the clinical presentation is acantholysis, and various types of dyskeratosis and acanthosis. In this study, we utilized a non-invasive optical imaging modality, confocal reflectance microscopy, to identify specific histologic features of DarierWhite's disease in vivo. Micrographic findings in the confocal images were corps ronds, suprabasal clefts, acantholytic suprabasal keratinocytes, and villi. Real-time confocal images are illustrative and can be well correlated with known light microscopic phenomena, particularly in the case of keratinization abnormalities in Darier-White's disease. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Lucid Inc, Henrietta, NY USA. RP Gonzalez, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, BHX-630,55 Blossom St, Boston, MA 02114 USA. OI Mordovtseva, V.V./0000-0002-6396-2720 NR 14 TC 30 Z9 31 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD NOV PY 1999 VL 26 IS 10 BP 504 EP 508 DI 10.1111/j.1600-0560.1999.tb01797.x PG 5 WC Dermatology; Pathology SC Dermatology; Pathology GA 260ZM UT WOS:000083983400005 PM 10599941 ER PT J AU Finkel, MA Nadel, ES Brown, DFM Reisner, A Zirkin, W Chung, W Macnow, L Cranmer, H Lewiss, R Griffey, R Davis, M AF Finkel, MA Nadel, ES Brown, DFM Reisner, A Zirkin, W Chung, W Macnow, L Cranmer, H Lewiss, R Griffey, R Davis, M TI Respiratory distress and hypertension in pregnancy - Discussion SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material ID MAGNESIUM-SULFATE; HYDRALAZINE; ECLAMPSIA; LABETALOL C1 Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Emergency Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Nadel, ES (reprint author), Brigham & Womens Hosp, Dept Emergency Med, 75 Francis St, Boston, MA 02115 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD NOV-DEC PY 1999 VL 17 IS 6 BP 1039 EP 1043 DI 10.1016/S0736-4679(99)00140-7 PG 5 WC Emergency Medicine SC Emergency Medicine GA 257GB UT WOS:000083773200020 PM 10595893 ER PT J AU Gilad, JZ Teles, R Goodson, M White, RR Stashenko, P AF Gilad, JZ Teles, R Goodson, M White, RR Stashenko, P TI Development of a clindamycin-impregnated fiber as an intracanal medication in endodontic therapy SO JOURNAL OF ENDODONTICS LA English DT Article ID INFECTED ROOT CANALS; BLACK-PIGMENTED BACTEROIDES; APICAL PERIODONTITIS; CLINICAL SYMPTOMS; TEETH; BACTERIA AB The effectiveness of traditional endodontic intracanal medications in reducing bacterial numbers and preventing acute flare-ups and pain continues to be questioned, In the present study, a new local delivery device was developed that releases a substantive dose of clindamycin into root canals. Clindamycin-impregnated ethylene vinyl acetate (EVA) fibers were produced, and the sensitivity of common endodontic microbes to the fibers were established. An in vitro model was developed to persistently infect 32 extracted human teeth with endodontic pathogens to test the efficacy of the clindamycin/EVA fibers in reducing the number of colony-forming units, The clindamycin/EVA fibers were shown to be effective in reducing growth of common endodontic microbes on blood agar plates, and in significantly reducing growth of Prevotella intermedia, Fusobacterium nucleatum, and Streptococcus intermedius in extracted human teeth, thus indicating merit in further exploring the potential of these fibers as intracanal medications. C1 Harvard Univ, Sch Dent Med, Dept Endodont, Boston, MA 02115 USA. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Gilad, JZ (reprint author), Harvard Univ, Sch Dent Med, Dept Endodont, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-09018, DE-11664] NR 19 TC 8 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD NOV PY 1999 VL 25 IS 11 BP 722 EP 727 DI 10.1016/S0099-2399(99)80117-4 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 252VV UT WOS:000083523700006 PM 10726537 ER PT J AU Curhan, GC AF Curhan, GC TI Epidemiologic evidence for the role of oxalate in idiopathic nephrolithiasis SO JOURNAL OF ENDOUROLOGY LA English DT Article ID KIDNEY-STONES; DIETARY CALCIUM; BEVERAGE USE; BODY-SIZE; VITAMIN-C; RISK; NUTRIENTS; WOMEN AB The importance of dietary and urinary oxalate in the formation of calcium oxalate kidney stones is widely accepted. Although the epidemiologic evidence for the role of oxalate remains largely indirect, recent prospective observations suggest its importance. The inverse association between dietary calcium intake and the risk of stone formation may be attributable to decreased gastrointestinal absorption of dietary oxalate and, thus, lower urinary oxalate concentrations, Further, the decreased risk of stone formation in women who consume large doses of vitamin Bg may be secondary to decreased oxalate production. The increased risk of nephrolithiasis observed with increasing body size may also be secondary to increased endogenous oxalate production. However, the frequency of hyperoxaluria is not substantially different in cases and controls for either sex. Notably, men have both higher stone incidence rates and higher mean urinary oxalate concentrations than women. Additional studies are needed to determine more precisely the role of dietary oxalate, More valid and comprehensive information on the oxalate content of food are desperately needed, Because the data on dietary oxalate are inconclusive, the routine restriction of dietary oxalate needs to be reexamined. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Curhan, GC (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK45362] NR 15 TC 16 Z9 16 U1 0 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD NOV PY 1999 VL 13 IS 9 BP 629 EP 631 DI 10.1089/end.1999.13.629 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 264MQ UT WOS:000084186400006 PM 10608513 ER PT J AU Nichogiannopoulou, A Trevisan, M Neben, S Friedrich, C Georgopoulos, K AF Nichogiannopoulou, A Trevisan, M Neben, S Friedrich, C Georgopoulos, K TI Defects in hemopoietic stem cell activity in Ikaros mutant mice SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE transcription factors; hemopoiesis; flk2; c-kit regulation ID HEMATOPOIETIC STEM; COMPETITIVE REPOPULATION; DEFINITIVE HEMATOPOIESIS; TRANSCRIPTION FACTOR; MOLECULAR CONTROL; MOUSE EMBRYO; GENE LEADS; PROGENITORS; DIFFERENTIATION; SYSTEM AB Here we provide evidence that the Ikaros family of DNA binding factors is critical for the activity of hemopoietic stem cells (HSCs) in the mouse. Mice homozygous for an Ikaros null mutation display a >30-fold reduction in long-term repopulation units, whereas mice homozygous for an Ikaros dominant negative mutation have no measurable activity. The defect in HSC activity is also illustrated by the ability of wild-type marrow to repopulate unconditioned Ikaros mutants. A progressive reduction in multipotent CFU-S,, (colony-forming unit-spleen) progenitors and the earliest erythroid-restricted precursors (BFU-E [burst-forming unit-erythroid]) is also detected in the Ikaros mutant strains consistent with the reduction in HSCs. Nonetheless, the more mature clonogenic erythroid and myeloid precursors are less affected, indicating either the action of a compensatory mechanism to provide more progeny or a negative role of Ikaros at later stages of erythromyeloid differentiation. In Ikaros mutant mice, a decrease in expression of the tyrosine kinase receptors fk-2 and c-kit is observed in the lineage-depleted c-kit(+)Sca-1(+) population that is normally enriched for HSCs and may in part contribute to the early hemopoietic phenotypes manifested in the absence of Ikaros. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Bayer Corp, Div Biotechnol, Berkeley, CA 94710 USA. RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI033062, R01 AI33062] NR 34 TC 140 Z9 141 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1999 VL 190 IS 9 BP 1201 EP 1213 DI 10.1084/jem.190.9.1201 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253JF UT WOS:000083552800002 PM 10544193 ER PT J AU Sonoda, KH Exley, M Snapper, S Balk, SP Stein-Streilein, J AF Sonoda, KH Exley, M Snapper, S Balk, SP Stein-Streilein, J TI CD1-reactive natural killer T cells are required for development of systemic tolerance through an immune-privileged site SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE innate immunity; immune deviation; anterior chamber-associated immune deviation autoimmunity; i.v. tolerance ID IMMUNOGLOBULIN-E PRODUCTION; ANTIGEN-PRESENTING CELLS; SPLENIC B-CELLS; TCR ALPHA-CHAIN; ANTERIOR-CHAMBER; DEVIATION ACAID; IMMUNOSUPPRESSIVE ACTIVITY; SELECTIVE REDUCTION; SOLUBLE-ANTIGEN; IL-4 PRODUCTION AB Systemic tolerance can be elicited by introducing antigen into an immune-privileged site, such as the eye, or directly into the blood. Both routes of immunization result in a selective deficiency of systemic delayed type hypersensitivity. Although the experimental animal model of anterior chamber-associated immune deviation (ACAID) occurs in most mouse strains, ACAID cannot be induced in several mutant mouse strains that are coincidentally deficient in natural killer T (NKT) cells. Therefore, this model for immune-privileged site-mediated tolerance provided us with an excellent format for studying the role of NKT cells in the development of tolerance. The following data show that CD1-reactive NKT cells are required for the development of systemic tolerance induced via the eye as follows: (a) CD1 knockout mice were unable to develop ACAID unless they were reconstituted with NKT cells together with CD1(+) antigen-presenting cells; (b) specific antibody depletion of NKT cells in vivo abrogated the development of ACAID; and (c) anti-CD1 monoclonal antibody treatment of wild-type mice prevented ACAID development. Significantly, CD1-reactive NKT cells were not required for intravenously induced systemic tolerance, thereby establishing that different mechanisms mediate development of tolerance to antigens inoculated by these routes. A critical role for NKT cells in the development of systemic tolerance associated with an immune-privileged site suggests a mechanism involving NKT cells in sell-tolerance and their defects in autoimmunity. C1 Harvard Univ, Sch Med, Canc Biol Program,Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Dept Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Pulm & Crit Care,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA 02114 USA. RP Stein-Streilein, J (reprint author), Harvard Univ, Sch Med, Schepens Eye Res Inst, 20 Staniford St, Boston, MA 02114 USA. FU NEI NIH HHS [R01 EY11989-01]; NIAID NIH HHS [R01 AI33911, R01 AI42955] NR 56 TC 268 Z9 280 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 1 PY 1999 VL 190 IS 9 BP 1215 EP 1225 DI 10.1084/jem.190.9.1215 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 253JF UT WOS:000083552800003 PM 10544194 ER PT J AU Rulon, JJ Cho, CG Guerra, LL Bux, RC Gulley, ML AF Rulon, JJ Cho, CG Guerra, LL Bux, RC Gulley, ML TI Activated protein C resistance is uncommon in sudden death due to pulmonary embolism SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; forensic pathology; activated protein C resistance; sudden death; pulmonary embolism; deep venous thrombosis ID FACTOR-V-LEIDEN; POOR ANTICOAGULANT RESPONSE; VENOUS THROMBOEMBOLISM; THROMBOPHILIA; THROMBOSIS; MUTATION AB Activated protein C resistance (APC-R)is the most common inherited defect of the coagulation system known to date, affecting 3-5% of Americans. It is an autosomal dominant disorder associated with an increased risk of venous thrombosis and is reportedly found in 21% of individuals with deep venous thrombosis. Medical examiners are in a unique position to make the diagnosis since a fatal pulmonary embolism may be the first manifestation of the disorder. This study examines the prevalence of APC-R in individuals who die suddenly of pulmonary embolism to help medical examiners decide if routine testing is indicated. We examined 66 cases of sudden death due to pulmonary embolism seen at the Bexar County Forensic Science Center in San Antonio, Texas, from 1993-1997. The median age was 46 years with a range of 14 to 93 years. Fifty-three percent were Caucasian, 24% were African-American, and 23% were Hispanic. Twenty-seven percent had no known risk factors for pulmonary embolism. Whole blood was tested for the factor V codon 506Q mutation responsible for APC-R using polymerase chain reaction. The prevalence of APC-R was 4.5%, which is similar to the prevalence of APC-R in the general American population. These data imply that individuals with APC-R are not at increased risk for sudden death due to pulmonary embolism, or, conversely, that most fatal pulmonary emboli seen in the medical examiner setting are not induced by APC-R. Routine postmortem testing for the factor V 506Q mutation does not appear indicated at this time, given the low prevalence and high cost of testing. C1 Delta Pathol Associates, Stockton, CA 95355 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78284 USA. Bexar Cty Forens Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. RP Rulon, JJ (reprint author), Delta Pathol Associates, 2291 W March Lane,Suite 179E, Stockton, CA 95355 USA. NR 14 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 1999 VL 44 IS 6 BP 1111 EP 1113 PG 3 WC Medicine, Legal SC Legal Medicine GA 293BA UT WOS:000085830600001 PM 10582351 ER PT J AU Getchell, WS Larsen, GC Morris, CD McAnulty, JH AF Getchell, WS Larsen, GC Morris, CD McAnulty, JH TI Epidemiology of syncope in hospitalized patients SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE syncope; prognosis; mortality ID UNEXPLAINED SYNCOPE; DIAGNOSING SYNCOPE; UNKNOWN ORIGIN; FOLLOW-UP; IMPACT; PREDICTORS AB OBJECTIVE: To describe the etiologies of syncope in hospitalized patients and determine the factors that influence survival after discharge. DESIGN: Observational retrospective cohort, SETTING: Department of Veterans Affairs hospital, group-model HMO, and Medicare population in Oregon. PATIENTS: Hospitalized individuals (n = 1,516: mean age +/- SD, 73.0 +/- 13.4 years) with an admission or discharge diagnosis of syncope (ICD-9-CM 780.2) during 1992, 1993, or 1994, MEASUREMENTS AND MAIN RESULTS: During a median hospital stay of 3 days, most individuals received an electrocardiogram (97%) and prolonged electrocardiographic monitoring (90%), but few underwent electrophysiology testing (2%) or tilt-table testing (0.7%). The treating clinicians identified cardiovascular causes of syncope in 19% of individuals and noncardiovascular causes in 40%. The remaining 42% of individuals were discharged with unexplained syncope. Complete heart block (2.4%) and ventricular tachycardia (2.3%) were rarely identified as the cause of syncope. Pacemakers were implanted in 28% of the patients with cardiovascular syncope and 0.4% of the others. No patient received an implantable defibrillator. Ah-cause mortality +/- SE was 1.1% +/- 0.3% during the admission, 13% +/- 1% at 1 year, and 41% +/- 2% at 4 years. The adjusted relative risk (RR) of dying for individuals with cardiovascular syncope (RR 1.18; 95% confidence interval [CI] 0.92, 1.50) did not differ from that for unexplained syncope (RR 1.0) and noncardiovascular syncope (RR 0.94; 95% CI 0.77, 1.16), CONCLUSIONS: Among these elderly patients hospitalized with syncope, noncardiovascular causes were twice as common as cardiovascular causes. Because survival was not related to the cause of syncope, clinicians cannot be reassured that hospitalized elderly patients with noncardiovascular and unexplained syncope will have excellent outcomes. C1 Oregon Hlth Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97201 USA. RP Getchell, WS (reprint author), Portland VA Med Ctr, Cardiol Sect, 3710 SW US Vet Hosp Dr, Portland, OR 97207 USA. FU AHRQ HHS [T32 HS000069, T32 HS00069] NR 27 TC 56 Z9 57 U1 0 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 NOV PY 1999 VL 14 IS 11 BP 677 EP 687 DI 10.1046/j.1525-1497.1999.03199.x PG 11 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 257CF UT WOS:000083764000005 PM 10571716 ER PT J AU Chin, KR Jupiter, JB AF Chin, KR Jupiter, JB TI Treatment of triplane fractures of the head of the proximal phalanx SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE fracture; phalanx; interphalangeal; condylar; articular AB We report the morphology and treatment of 2 cases of a triplane intra-articular bicondylar fracture of the head of the proximal phalanx. Fracture lines in the coronal, sagittal, and transverse planes characterize this fracture, making it highly unstable. Open reduction and internal fixation using two 1.5-mm interfragmentary screws oriented in a dorsal to volar direction resulted in anatomic restoration of the articular surfaces and satisfactory functional results. In 1 case, autogenous cancellous bone graft was harvested from the ipsilateral radial styloid to support the articular fragments. (1 Hand Surg 1999;24A:1263-1268. Copyright (C) 1999 by the American Society for Surgery of the Hand.). C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Hand Serv, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Orthopaed Surg,Orthopaed Hand Serv, WACC 527, Boston, MA 02114 USA. NR 9 TC 10 Z9 10 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 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD NOV PY 1999 VL 24A IS 6 BP 1263 EP 1268 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 256QZ UT WOS:000083738000020 PM 10584951 ER PT J AU Jansson, M Backstrom, E Bjorndal, A Holmberg, V Rossi, P Fenyo, EM Popovic, M Albert, J Wigzell, H AF Jansson, M Backstrom, E Bjorndal, A Holmberg, V Rossi, P Fenyo, EM Popovic, M Albert, J Wigzell, H TI Coreceptor usage and RANTES sensitivity of non-syncytium-inducing HIV-1 isolates obtained from patients with AIDS SO JOURNAL OF HUMAN VIROLOGY LA English DT Article DE phenotype; AIDS; coreceptor usage; chemokine sensitivity ID HUMAN-IMMUNODEFICIENCY-VIRUS; MACROPHAGE-TROPIC HIV-1; DISEASE PROGRESSION; REVERSE-TRANSCRIPTASE; REPLICATIVE CAPACITY; BIOLOGICAL PHENOTYPE; FUSION COFACTOR; TYPE-1 VARIANTS; CELL TROPISM; V3 LOOP AB Objectives: The biologic phenotype of HTV-1 primary isolates obtained from -50% of patients who progress to AIDS switches from non-syncytium-inducing (NSI) to syncytium-inducing (SI). We evaluated possible associations between virus coreceptor usage, sensitivity to inhibition by beta-chemokines, and disease progression of patients who continue to yield NSI isolates after developing AIDS. Study Design/Methods: Sequential virus isolates were analyzed for biologic phenotype using the MT-2 cell assay, for sensitivity to beta-chemokines using RANTES inhibition, and for coreceptor usage using U87.CD4 and GHOST.CD4 cells expressing different chemokine/orphan receptors or donor peripheral blood mononuclear cells (PBMC) defective in CCR5 expression. In addition, the env V3 region was sequenced and the length of the V2 region determined. Results: All NSI isolates, regardless of patient status at time of isolation, were dependent on CCR5 expression for cell entry. Furthermore, there was no indication of broadened coreceptor usage of NSI isolates obtained from persons with late-stage AIDS. A majority of NSI isolates remained RANTES sensitive; however, virus variants with reduced sensitivity were observed. The V2 lengths and the V3 sequences exhibited no or minor changes at analysis of sequential NSI isolates. Conclusions: Our data suggest that NSI isolates obtained from AIDS patients remain CCR5 dependent (ie, R5) and, in many cases, also remain sensitive to RANTES inhibition. However, virus variants with decreased sensitivity to RANTES inhibition may evolve during disease progression, not only as a result of a switch from NSI to SI but also in patients who develop AIDS while continuing to maintain R5 isolates. GenBank Accession Numbers: AF199032-AF199043. C1 Karolinska Inst, Microbiol & Tumorbiol Ctr, Stockholm, Sweden. Tor Vergata Univ, Childrens Hosp Bambino Gesu, Ctr Pediat Immunol, Rome, Italy. South Hosp, Venhalsan, Stockholm, Sweden. Univ Maryland, Ctr Med Biotechnol, Inst Human Virol, Baltimore, MD 21201 USA. Karolinska Inst, Swedish Inst Infect Dis Control, Stockholm, Sweden. RP Jansson, M (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,Smith 706, Boston, MA 02115 USA. RI rossi, paolo/D-6504-2012; OI ROSSI, PAOLO/0000-0003-2620-7918 NR 60 TC 44 Z9 44 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1090-9508 J9 J HUMAN VIROL JI J. Human Virol. PD NOV-DEC PY 1999 VL 2 IS 6 BP 325 EP 338 PG 14 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 288BR UT WOS:000085542400002 PM 10774549 ER PT J AU Sharma, S Stolina, M Lin, Y Gardner, B Miller, PW Kronenberg, M Dubinett, SM AF Sharma, S Stolina, M Lin, Y Gardner, B Miller, PW Kronenberg, M Dubinett, SM TI T cell-derived IL-10 promotes lung cancer growth by suppressing both T cell and APC function SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-I EXPRESSION; COLONY-STIMULATING FACTOR; PULSED DENDRITIC CELLS; INTERFERON-GAMMA; INTERLEUKIN-12 PRODUCTION; IMPAIRED INTERLEUKIN-12; CYTOKINE PRODUCTION; COLORECTAL-CANCER; IMMUNE-RESPONSE; DOWN-REGULATION AB We have found previously that human lung cancers potently induce T lymphocyte IL-10 production in vitro. To assess the impact of enhanced T cell-derived IL-10 on antitumor immunity in vivo, we utilized transgenic mice expressing IL-10 under the control of the IL-2 promoter. We have shown previously that Lewis lung carcinoma cells (3LL) have more aggressive growth potential in IL-10 transgenic mice compared with control littermates. In this study, we show that transfer of T cells from IL-10 transgenic mice to control littermates transferred the IL-10 immunosuppressive effect and led to enhanced 3LL tumor growth. In addition to changes in T cell-mediated immunity, professional APC from IL-10 transgenic mice were found to have significantly suppressed capacity to induce MHC alloreactivity, CTL responses, and IL-12 production. Tumor Ag-pulsed dendritic cells from IL-10 transgenic mice also failed to generate antitumor reactivity. These results suggest that increased levels of T cell-derived IL-10 severely impair antitumor immunity in vivo, due to defects in both T cell and APC function. C1 Univ Calif Los Angeles, Sch Med, Wadsworth Pulm Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Sch Med, Ctr Hlth Sci 37 131, Div Pulm & Crit Care Med, 10833 LeConte Ave, Los Angeles, CA 90095 USA. FU NCI NIH HHS [R01 CA71818] NR 63 TC 154 Z9 163 U1 1 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 1999 VL 163 IS 9 BP 5020 EP 5028 PG 9 WC Immunology SC Immunology GA 248BT UT WOS:000083256000051 PM 10528207 ER PT J AU Dallalio, G North, M McKenzie, SW Means, RT AF Dallalio, G North, M McKenzie, SW Means, RT TI Cytokine and cytokine receptor concentrations in bone marrow supernatant from patients with HIV: Correlation with hematologic parameters SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Article DE human immunodeficiency virus; cytokines; tumor necrosis factor; macrophage inflammatory protein; RANTES ID TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; PERIPHERAL-BLOOD MONOCYTES; FACTOR-ALPHA; HEMATOPOIETIC PROGENITORS; MESSENGER-RNA; STROMAL CELLS; ANEMIA; INTERLEUKIN-1; INTERFERON AB Background: To determine the concentrations of tumor necrosis factor (TNF)alpha, soluble TNF receptors (sTNFR), interleukin (IL)-1 beta, gamma-interferon (IFN), macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and RANTES to which hematopoietic progenitors are exposed in vivo in HIV patients and the correlation of these concentrations with hematologic parameters, cytokine and cytokine receptor concentrations were measured by ELISA in bone marrow aspirate supernatants from 19 HIV patients undergoing diagnostic evaluation and 14 healthy paid volunteer controls, IL-1 beta and gamma-IFN were rarely detectable. All cytokines/receptors detectable in marrow supernatant, except RANTES, showed mean concentrations 1.6- to 6.2-fold higher in patients with HIV compared to healthy controls. Methods: Elevated TNF-alpha and MIP-1 beta were associated with marrow involvement by lymphoma, Hodgkin disease, or mycobacterial infection, Concentrations of all cytokines/receptors measured correlated with the severity of anemia. CD8+ lymphocytes were inversely correlated with concentrations of all cytokines measured other than MIP-1 alpha, To identify differences specific to HIV infection, marrow supernatant cytokine concentrations were also evaluated in 9 non-HIV patients undergoing diagnostic marrow examination. Significant differences were observed in TNF alpha, MIP1 alpha, and IL-1 beta concentrations. Results: These studies demonstrate that concentrations of these cytokines and receptors are elevated in bone marrow supernatant of HIV-infected patients with hematologic abnormalities, and that these concentrations correlate with clinical parameters in these patients. Conclusions: Evaluation of local concentrations of cytokines may be relevant to understanding tissue-specific pathology in HIV-infected individuals, C1 Ralph H Johnson Dept Vet Affairs Med Ctr, Med Serv 111, Hematol Oncol Sect, Div Hematol Oncol, Charleston, SC 29401 USA. Ralph H Johnson Dept Vet Affairs Med Ctr, Div Infect Dis, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. RP Means, RT (reprint author), Ralph H Johnson Dept Vet Affairs Med Ctr, Med Serv 111, Hematol Oncol Sect, Div Hematol Oncol, 109 Bee St, Charleston, SC 29401 USA. RI Means, Robert/A-4454-2008 FU NHLBI NIH HHS [HL57303] NR 40 TC 4 Z9 4 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD NOV PY 1999 VL 47 IS 9 BP 477 EP 483 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 253HP UT WOS:000083551200005 PM 10572378 ER PT J AU Forsch, RA Rosowsky, A AF Forsch, RA Rosowsky, A TI Synthesis of gamma-[N-15]-L-glutamyl derivatives of 5,10-dideazatetrahydrofolate SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE 5,10-dideazatetrahydrofolic acid; gamma-oligo[N-15]glutamic acid derivatives ID NUCLEAR-MAGNETIC-RESONANCE; COLI DIHYDROFOLATE-REDUCTASE; 5,10-DIDEAZA-5,6,7,8-TETRAHYDROFOLIC ACID DDATHF; ANTIFOLATE LOMETREXOL DDATHF; DENOVO PURINE SYNTHESIS; PHASE-I; (6R)-5,10-DIDEAZA-5,6,7,8-TETRAHYDROFOLIC ACID; FOLATE ANTIMETABOLITE; NMR CHARACTERIZATION; CARBONIC-ANHYDRASE AB A synthesis of the mono-, di-, and tri[N-15]glutamate forms of the potent de novo purine synthesis inhibitor and anticancer agent (6R,6S)-5,10-dideaza-5,6,7,8-tetrahydrofolate (6R,6S-DDATHF) from (6R,6S)-5, 10-dideaza-5,6,7,8-tetrahydropteroic acid is described. These isotopically labelled compounds are potentially useful as N-15 nmr probes of the interaction of DDATHF and its polyglutamates with three key enzymes of one-carbon metabolism, glycinamide ribonucleotide formyltransferase, (GARFT), aminoim idazolecarboxamide formyltransferase (AICARFT), and folylpolyglutamate synthetase (FPGS). 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. RP Forsch, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 38 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 1999 VL 42 IS 11 BP 1103 EP 1117 DI 10.1002/(SICI)1099-1344(199911)42:11<1103::AID-JLCR269>3.0.CO;2-E PG 15 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 251GG UT WOS:000083435800010 ER PT J AU Briquet-Laugier, V Ben-Zeev, O White, A Doolittle, MH AF Briquet-Laugier, V Ben-Zeev, O White, A Doolittle, MH TI cld and lec23 are disparate mutations that affect maturation of lipoprotein lipase in the endoplasmic reticulum SO JOURNAL OF LIPID RESEARCH LA English DT Article DE lipoprotein lipase; density gradient centrifugation; heparin affinity; glycan processing; endoplasmic reticulum; lipase folding; calnexin; endoplasmic reticulum chaperones ID THIOL-DEPENDENT REDUCTASE; N-LINKED OLIGOSACCHARIDES; PROTEIN DISULFIDE-ISOMERASE; CULTURED BROWN ADIPOCYTES; ALPHA-D-MANNOSIDASE; RAT-LIVER GOLGI; HEPATIC LIPASE; SECRETORY PATHWAY; QUALITY-CONTROL; MOLECULAR CHAPERONE AB The mutations cld (combined Lipase deficiency) and lec23 disrupt in a similar manner the expression of lipoprotein lipase (LPL), Whereas cld affects an unknown gene, lec23 abolishes the activity of alpha-glucosidase I, an enzyme essential for proper folding and assembly of nascent glycoproteins, The hypothesis that cld,like lec23, affects the folding/assembly of nascent LPL was confirmed by showing that in cell lines homozygous for these mutations (Cld and Lec23, respectively), the majority of LPL was inactive, displayed heterogeneous aggregation, and had a decreased affinity for heparin. While inactive LPL was retained in the ER, a small amount of LPL that had attained a native conformation was transported through the Golgi and secreted. Thus, Cld and Lec23 cells recognized and retained the majority of LPL as misfolded, maintaining the standard of quality control. Examination of candidate factors affecting protein maturation, such as glucose addition and trimming, proteins involved in lectin chaperone cycling, and other abundant ER chaperones, revealed that calnexin levels were dramatically reduced in livers from cld/cld mice; this finding was also confirmed in Cld cells.We conclude that cld may affect components in the ER, such as calnexin, that play a role in protein maturation. Whether the reduced calnexin levels per se contribute to the LPL deficiency awaits confirmation.-Briquet-Laugier, V., O. Ben-Zeev, A. White, and M. H. Doolittle. cld and lec23 are disparate mutations that affect maturation of Lipoprotein Lipase in the endoplasmic reticulum. 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. Univ Texas, SW Med Ctr, Ctr Human Nutr, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75235 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 87 TC 24 Z9 24 U1 0 U2 0 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 NOV PY 1999 VL 40 IS 11 BP 2044 EP 2058 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 252UU UT WOS:000083521300012 PM 10553008 ER PT J AU Leaf, A Kang, JX Xiao, YF Billman, GE Voskuyl, RA AF Leaf, A Kang, JX Xiao, YF Billman, GE Voskuyl, RA TI The antiarrhythmic and anticonvulsant effects of dietary n-3 fatty acids SO JOURNAL OF MEMBRANE BIOLOGY LA English DT Review DE omega-3; n-3; omega-6; n-6; eicosapentaenoic acid; docosahexaenoic acid; arrhythmias; seizures ID RAT CARDIAC MYOCYTES; VENTRICULAR-FIBRILLATION; FISH-OIL; LONG-CHAIN; MYOCARDIAL-INFARCTION; PURKINJE-FIBERS; NA+ CHANNELS; ISCHEMIA; ARRHYTHMIAS; PREVENTION AB It has been shown in animals and probably in humans, that n-3 polyunsaturated fatty acids (PUFAs) are antiarrhythmic. We report recent studies on the antiarrhythmic actions of PUFAs. The PUFAs stabilize the electrical activity of isolated cardiac myocytes by modulating sarcolemmal ion channels, so that a stronger electrical stimulus is required to elicit an action potential and the refractory period is markedly prolonged. Inhibition of voltage-dependent sodium currents, which initiate action potentials in excitable tissues, and of the L-type calcium currents, which initiate release of sarcoplasmic calcium stores that increase cytosolic free calcium concentrations and activate the contractile proteins in myocytes, appear at present to be the probable major antiarrhythmic mechanism of the PUFAs. C1 Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Ohio State Univ, Dept Physiol, Columbus, OH 45210 USA. Leiden Univ, Med Ctr, Dept Physiol, NL-2100 AA Heemstede, Netherlands. Stichting Epilepsie Instellingen Nederland, NL-2100 AA Heemstede, Netherlands. RP Leaf, A (reprint author), Massachusetts Gen Hosp, Dept Med, Bldg 149,13th St, Charlestown, MA 02129 USA. RI Billman, George/E-2758-2011 FU NIDDK NIH HHS [DK38165] NR 55 TC 54 Z9 56 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0022-2631 J9 J MEMBRANE BIOL JI J. Membr. Biol. PD NOV 1 PY 1999 VL 172 IS 1 BP 1 EP 11 DI 10.1007/s002329900578 PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Physiology SC Biochemistry & Molecular Biology; Cell Biology; Physiology GA 253AQ UT WOS:000083534800001 PM 10552009 ER PT J AU Miller, MA Kolb, PE Leverenz, JB Peskind, ER Raskind, MA AF Miller, MA Kolb, PE Leverenz, JB Peskind, ER Raskind, MA TI Preservation of noradrenergic neurons in the locus ceruleus that coexpress galanin mRNA in Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE galanin; locus ceruleus; Alzheimer's disease; noradrenergic system ID RAT VENTRAL HIPPOCAMPUS; MESSENGER-RNA LEVELS; TYROSINE-HYDROXYLASE; GENE-EXPRESSION; COERULEUS NEURONS; BASAL FOREBRAIN; SENILE DEMENTIA; CEREBRAL-CORTEX; PHOSPHOINOSITIDE TURNOVER; CHOLINERGIC DYSFUNCTION AB Galanin (GAL) innervation is hypertrophied in the basal forebrain and cortex of patients with Alzheimer's disease (AD). Increased GAL could exacerbate the cognitive and behavioral deficits of AD because GAL acts as an inhibitory modulator of cholinergic and noradrenergic neurotransmission. The locus ceruleus (LC) may be a source of increased GAL in AD because (a) GAL is coexpressed in a subset of LC neurons, (b) GAL expression is up-regulated with neuronal injury, and (c) the LC undergoes extensive degeneration in AD. Therefore, we have used in situ hybridization histochemistry to measure GAL gene expression in the LC of AD patients and sex- and age-matched nondemented controls. Despite the extensive loss of norepinephrine neurons with AD, GAL mRNA-expressing neurons in the LC did not differ between groups. This resulted in a significant increase in the percentage of neuromelanin-pigmented cells that coexpressed GAL in AD patients compared with controls. These findings wise the possibility that the increased incidence of GAL expression among remaining LC neurons contributes to the hyperinnervation of GAL fibers in AD. Furthermore, GAL may be neuroprotective in the LC. C1 Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Mental Illness Ctr, Seattle, WA USA. RP Miller, MA (reprint author), LifeSpan BioSci, 700 Blanchard St, Seattle, WA 98121 USA. FU NIA NIH HHS [AG10917, AG05136]; NINDS NIH HHS [NS33606] NR 74 TC 31 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 1999 VL 73 IS 5 BP 2028 EP 2036 PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 247AV UT WOS:000083199200028 PM 10537062 ER PT J AU Newell, KL Hyman, BT Growdon, JH Hedley-Whyte, ET AF Newell, KL Hyman, BT Growdon, JH Hedley-Whyte, ET TI Application of the National Institute on Aging (NIA)-Reagan Institute criteria for the neuropathological diagnosis of Alzheimer disease SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer disease; diagnostic criteria; neuritic plaques; neurofibrillary tangles; topographic staging methods ID PROGRESSIVE SUPRANUCLEAR PALSY; LEWY BODIES; DEMENTIA; CONSORTIUM; BRAINS AB The Khachaturian criteria and the Consortium to Establish a Registry for Alzheimer Disease (CERAD) criteria for the neuropathological assessment of Alzheimer disease (AD) emphasize sl:nile or neuritic plaques, age, and clinical history. A new scheme stressing topographic staging of neurofibrillary changes in addition to neuritic plaques has been proposed by the National Institute on Aging (NIA)-Reagan Institute Consensus Conference. This scheme assigns cases to high, intermediate, or low likelihood categories that the dementia is due to AD. We applied this method to 84 brains from subjects with clinical and neuropathological diagnoses of AD (n = 33), non-AD dementing illnesses (n = 34), including dementia with Lewy bodies (DLB) and progressive supranuclear palsy (PSP), and no neurological disease (n = 17). We also used Khachaturian and CERAD criteria. Neurofibrillary tangle and neuropil thread densities were assessed on 6-micrometer-thick modified Bielschowsky-stained paraffin sections from entorhinal-perirhinal cortex, CA1 of hippocampus, and neocortex including inferior temporal, visual association, and primary visual cortices. Each case was assigned a Braak and Braak stage. Using the NIA-Reagan criteria, we found excellent agreement between clinical history of AD dementia and brains assigned to the high likelihood category that dementia was due to AD. Among brains diagnosed neuropathologically with other degenerative diseases, MA-Reagan criteria were more conservative than previous criteria, and these cases were Likely to be categorized as intermediate or low likelihood that dementia was due to AD. All brains front nondemented subjects were assigned to the low (81%) or intermediate (19%) categories. In summary, we found good correlation between the NIA-Reagan criteria and clinical dementia, and there was generally good agreement between these criteria and existing neuropathological methods, Khachaturian and CERAD. in diagnosing AD. In studying several other neurodegenerative diseases, such as DLB, which shows neuropathological and clinical overlap with AD, the staging of neurofibrillary changes offered potential diagnostic refinement. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charles S Kubik Neuropathol Lab, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp E, Alzheimer Dis Res Unit, 149 13th St,Room 6405, Charlestown, MA 02129 USA. FU NIA NIH HHS [AG05134] NR 23 TC 139 Z9 141 U1 0 U2 0 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 NOV PY 1999 VL 58 IS 11 BP 1147 EP 1155 DI 10.1097/00005072-199911000-00004 PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 255ZL UT WOS:000083700000004 PM 10560657 ER PT J AU Ahlfors, SP Simpson, GV Dale, AM Belliveau, JW Liu, AK Korvenoja, A Virtanen, J Huotilainen, M Tootell, RBH Aronen, HJ Ilmoniemi, RJ AF Ahlfors, SP Simpson, GV Dale, AM Belliveau, JW Liu, AK Korvenoja, A Virtanen, J Huotilainen, M Tootell, RBH Aronen, HJ Ilmoniemi, RJ TI Spatiotemporal activity of a cortical network for processing visual motion revealed by MEG and fMRI SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; SUPERIOR TEMPORAL SULCUS; FRONTAL EYE-FIELD; HUMAN CEREBRAL-CORTEX; EVENT-RELATED FMRI; HUMAN AREA V5; HUMAN BRAIN; PARIETAL CORTEX; FUNCTIONAL-ANALYSIS; SELECTIVE ATTENTION AB Spatiotemporal activity of a cortical network for processing visual motion revealed by MEG and fMRI. J. Neurophysiol. 82: 2545-2555, 1999. A sudden change in the direction of motion is a particularly salient and relevant feature of visual information. Extensive research has identified cortical areas responsive to visual motion and characterized their sensitivity to different features of motion, such as directional specificity. However, relatively little is known about responses to sudden changes in direction. Electrophysiological data from animals and functional imaging data from humans suggest a number of brain areas responsive to motion, presumably working as a network. Temporal patterns of activity allow the same network to process information in different ways. The present study in humans sought to determine which motion-sensitive areas are involved in processing changes in the direction of motion and to characterize the temporal patterns of processing within this network of brain regions. To accomplish this, we used both magnetoencephalography (MEG) and functional magnetic resonance imaging ( fMRI). The fMRI data were used as supplementary information in the localization of MEG sources. The change in the direction of visual motion was found to activate a number of areas, each displaying a different temporal behavior. The fMRI revealed motion-related activity in areas MT+ (the human homologue of monkey middle temporal area and possibly also other motion sensitive areas next to MT), a region near the posterior end of the superior temporal sulcus (pSTS), V3A, and V1/V2. The MEG data suggested additional frontal sources. An equivalent dipole model for the generators of MEG signals indicated activity in MT+. starting at 130 ms and peaking at 170 ms after the reversal of the direction of motion, and then again at similar to 260 ms. Frontal activity began 0-20 ms later than in MT+, and peaked similar to 180 ms. Both pSTS and FEF+ showed long-duration activity continuing over the latency range of 200-400 ms. MEG responses in the region of V3A and V1/V2 were relatively small, and peaked at longer latencies than the initial peak in MT+. These data revealed characteristic patterns of activity in this cortical network for processing sudden changes in the direction of visual motion. C1 Albert Einstein Coll Med, Rose F Kennedy Ctr, Dept Neurol, Dynam Brain Imaging Lab, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Univ Helsinki, Cent Hosp, Dept Radiol, Helsinki, Finland. Univ Helsinki, Cent Hosp, Med Engn Ctr, BioMag Lab, Helsinki, Finland. Univ Helsinki, Cognit Brain Res Unit, Helsinki, Finland. RP Ahlfors, SP (reprint author), Albert Einstein Coll Med, Rose F Kennedy Ctr, Dept Neurol, Dynam Brain Imaging Lab, Room 915,1300 Morris Pk Ave, Bronx, NY 10461 USA. RI Korvenoja, Antti/C-2292-2009; Dale, Anders/A-5180-2010; Ilmoniemi, Risto/E-9704-2012; Ahlfors, Seppo/P-3644-2016; OI Ilmoniemi, Risto/0000-0002-3340-2618; Huotilainen, Minna/0000-0002-7251-6984 FU NIMH NIH HHS [MH-DA52176]; NINDS NIH HHS [NS37462, NS27900] NR 92 TC 169 Z9 172 U1 3 U2 9 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 1999 VL 82 IS 5 BP 2545 EP 2555 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 259CE UT WOS:000083875700045 PM 10561425 ER PT J AU White, AR Multhaup, G Maher, F Bellingham, S Camakaris, J Zheng, H Bush, AI Beyreuther, K Masters, CL Cappai, R AF White, AR Multhaup, G Maher, F Bellingham, S Camakaris, J Zheng, H Bush, AI Beyreuther, K Masters, CL Cappai, R TI The Alzheimer's disease amyloid precursor protein modulates copper-induced toxicity and oxidative stress in primary neuronal cultures SO JOURNAL OF NEUROSCIENCE LA English DT Article DE Alzheimer's; copper; free radicals; culture; knockout; lipid peroxidation; neurons ID AMYOTROPHIC-LATERAL-SCLEROSIS; CU,ZN-SUPEROXIDE DISMUTASE MUTANT; RAT HIPPOCAMPAL-NEURONS; PRION PROTEIN; BETA-PROTEIN; HYDROGEN-PEROXIDE; SUPEROXIDE-DISMUTASE; NEURITE OUTGROWTH; RADICAL FORMATION; CORTICAL-NEURONS AB The amyloid precursor protein (APP) of Alzheimer's disease can reduce copper (II) to copper (I) in a cell-free system potentially leading to increased oxidative stress in neurons. We used neuronal cultures derived from APP knock-out (APP(-/-)) and wild-type (WT) mice to examine the role of APP in copper neurotoxicity. WT cortical, cerebellar, and hippocampal neurons were significantly more susceptible than their respective APP(-/-) neurons to toxicity induced by physiological concentrations of copper but not by zinc or iron. There was no difference in copper toxicity between APLP2(-/-) and WT neurons, demonstrating specificity for APP-associated copper toxicity. Copper uptake was the same in WT and APP(-/-) neurons, suggesting APP may interact with copper to induce a localized increase in oxidative stress through copper (I) production. This was supported by significantly higher levels of copper-induced lipid peroxidation in WT neurons. Treatment of neuronal cultures with a peptide corresponding to the human APP copper-binding domain (APP142-166) potentiated copper but not iron or zinc toxicity. Incubation of APP142-166 with low-density lipoprotein (LDL) and copper resulted in significantly increased lipid peroxidation compared to copper and LDL alone. Substitution of the copper coordinating histidine residues with asparagines (APP142-166(H147N, H149N, H151N)) abrogated the toxic effects. A peptide corresponding to the zinc-binding domain (APP181-208) failed to induce copper or zinc toxicity in neuronal cultures. These data support a role for the APP copper-binding domain in APP-mediated copper (I) generation and toxicity in primary neurons, a process that has important implications for Alzheimer's disease and other neurodegenerative disorders. C1 Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. Mental Hlth Res Inst, Parkville, Vic 3052, Australia. Univ Heidelberg, Ctr Biol Mol, D-69120 Heidelberg, Germany. Univ Melbourne, Dept Genet, Parkville, Vic 3052, Australia. Merck Res Labs, Dept Genet & Mol Biol, Rahway, NJ 07065 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Genet & Aging Unit, Charlestown, MA 02129 USA. RP Cappai, R (reprint author), Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia. RI Bellingham, Shayne/E-5665-2012; Cappai, Roberto/B-3347-2010; Bush, Ashley/A-1186-2007; White, Anthony/P-5596-2016 OI Cappai, Roberto/0000-0002-9505-8496; Bush, Ashley/0000-0001-8259-9069; White, Anthony/0000-0003-1802-9891 NR 60 TC 153 Z9 158 U1 0 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1999 VL 19 IS 21 BP 9170 EP 9179 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 246RG UT WOS:000083177900005 PM 10531420 ER PT J AU Chen, JF Huang, ZH Ma, JY Zhu, JM Moratalla, R Standaert, D Moskowitz, MA Fink, JS Schwarzschild, MA AF Chen, JF Huang, ZH Ma, JY Zhu, JM Moratalla, R Standaert, D Moskowitz, MA Fink, JS Schwarzschild, MA TI A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE A(2A) adenosine receptor; ischemia; stroke; purine receptor; knock-out; neuroprotection ID AMINO-ACID RELEASE; RAT CEREBRAL-CORTEX; NERVOUS-SYSTEM; IN-VIVO; STRIATUM; GENE; ANTAGONISTS; EXPRESSION; AGONISTS; PHARMACOLOGY AB Extracellular adenosine critically modulates ischemic brain injury, at least in part through activation of the A(1) adenosine receptor. However, the role played by the A(2A) receptor has been obscured by intrinsic limitations of A(2A) adenosinergic agents. To overcome these pharmacological limitations, we explored the consequences of deleting the A(2A) adenosine receptor on brain damage after transient focal ischemia. Cerebral morphology, as well as vascular and physiological measures (before, during, and after ischemia) did not differ between A(2A) receptor knock-out and wild-type littermates. The volume of cerebral infarction, as well as the associated neurological deficit induced by transient filament occlusion of the middle cerebral artery, were significantly attenuated in A(2A) receptor knock-out mice. This neuroprotective phenotype of A(2A) receptor-deficient mice was observed in different genetic backgrounds, confirming A(2A) receptor disruption as its cause. Together with complimentary pharmacological studies, these data suggest that A(2A) receptors play a prominent role in the development of ischemic injury within brain and demonstrate the potential for anatomical and functional neuroprotection against stroke by A(2A) receptor antagonists. C1 Massachusetts Gen Hosp, Dept Neurol & Neurosci, Mol Neurobiol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol & Neurosci, Stroke & Neurovasc Regulat Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol & Neurosurg, Neurol Res Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Chen, JF (reprint author), Massachusetts Gen Hosp E, Mol Neurobiol Lab, 13th St, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Moratalla, Rosario/H-9280-2015; OI Moratalla, Rosario/0000-0002-7623-8010; Standaert, David/0000-0003-2921-8348 FU NIDA NIH HHS [DA07496]; NINDS NIH HHS [5P50 NS10828, NS01729] NR 53 TC 292 Z9 303 U1 0 U2 6 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 NOV 1 PY 1999 VL 19 IS 21 BP 9192 EP 9200 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 246RG UT WOS:000083177900007 PM 10531422 ER PT J AU Libby, RT Lavallee, CR Balkema, GW Brunken, WJ Hunter, DD AF Libby, RT Lavallee, CR Balkema, GW Brunken, WJ Hunter, DD TI Disruption of laminin beta 2 chain production causes alterations in morphology and function in the CNS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE synapse development; laminin; photoreceptor; ERG; apoptosis; extracellular matrix ID MOUSE RETINA; CELL-DEATH; PHOTORECEPTOR DIFFERENTIATION; MUSCULAR-DYSTROPHY; SYNAPTIC CLEFT; RABBIT RETINA; RAT RETINA; EXPRESSION; LOCALIZATION; ADULT AB From the elegant studies of Ramon y Cajal (1909) to the current advances in molecular cloning (e.g., Farber and Danciger, 1997), the retina has served as an ideal model for the entire CNS. We have taken advantage of the well described anatomy, physiology, and molecular biology of the retina to begin to examine the role of the laminins, one component of the extracellular matrix, on the processes of neuronal differentiation and synapse formation in the CNS. We have examined the effect of the deletion of one laminin chain, the beta 2 chain, on retinal development. The gross development of retinas from laminin beta 2 chain-deficient animals appears normal, and photoreceptors are formed. However, these retinas exhibit several pathologies: laminin beta 2 chain-deficient mice display abnormal outer segment elongation, abnormal electroretinograms, and abnormal rod photoreceptor synapses. Morphologically, the outer segments are reduced by 50% in length; the outer plexiform layer of mutant animals is disrupted specifically, because only 7% of observed rod invaginating synapses appear normal, whereas the inner plexiform layer is undisturbed; finally, the rate of apoptosis in the mutant photoreceptor layer is twice that of control mice. Physiologically, the electroretinogram is altered; the amplitude of the b-wave and the slope of the b-wave intensity-response function are both decreased, consistent with synaptic disruption in the outer retina. Together, these results emphasize the prominence of the extracellular matrix and, in particular, the laminins in the development and maintenance of synaptic function and morphogenesis in the CNS. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Biol, Charlestown, MA 02129 USA. Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. Tufts Univ, Sch Med, Dept Neurosci, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Anat & Cell Biol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Dept Ophthalmol, Boston, MA 02111 USA. RP Brunken, WJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Biol, Bldg 149,13th St, Charlestown, MA 02129 USA. OI Libby, Richard/0000-0003-2844-7632 NR 56 TC 96 Z9 98 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 1 PY 1999 VL 19 IS 21 BP 9399 EP 9411 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 246RG UT WOS:000083177900029 PM 10531444 ER PT J AU Lee, EJ Ayoub, IA Harris, FB Hassan, M Ogilvy, CS Maynard, KI AF Lee, EJ Ayoub, IA Harris, FB Hassan, M Ogilvy, CS Maynard, KI TI Mexiletine and magnesium independently, but not combined, protect against permanent focal cerebral ischemia in Wistar rats SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE metabolic inhibition; sodium channel blocker; calcium channel blocker; neuroprotection; stroke ID SODIUM-CHANNEL BLOCKER; ARTERY OCCLUSION; CNS ISCHEMIA; NEURONS; STROKE; MODEL; MECHANISMS; REDUCTION; THERAPY; AGENTS AB The neuroprotective effect of mexiletine (Mex), a potent Na+ channel blocker which decreases neuronal energy demands and prevents energy depletion during ischemia, was evaluated in Wistar rats subjected to permanent middle cerebral artery (MCA) occlusion. Postmortem infarct volumes were determined by quantitative image analysis of triphenyltetrazolium (TTC)-stained brain sections. Pretreatment with Mex resulted in a significant infarct volume reduction when administered intraperitoneally, either at the dosage of 50 or 60 mg/kg, 1 hr before MCA occlusion (P < 0.05). Delayed treatment with Mex (50 mg/kg) also had neuroprotective effects when given at 0.5 hr (< 0.05), but not 2-4 hr, after MCA occlusion, Intraarterial administration of MgSO4 (90 mg/kg), in combination with Mex at 60 mg/kg, showed no additive neuroprotective effect, although each agent independently reduced the MCA occlusion-induced infarction volume (P < 0.05). Our results indicate that a single, acute administration of Mex is neuroprotective against permanent focal cerebral ischemia, but perhaps chronic administration is needed to establish a more effective therapeutic window beyond 0.5 hr, Moreover, the present in vivo data do not favor a combined use of Mg2+ With Mex for limiting ischemic injury in the brain, since these agents caused cardiopulmonary suppression, which may have led to the loss of the neuroprotective effect of each agent independently, J, Neurosci, Res. 58:442-448, 1999, (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Neurophysiol Lab, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Natl Cheng Kung Univ, Med Ctr, Dept Surg, Div Neurosurg, Tainan, Taiwan. Ohio State Univ, Coll Med, Columbus, OH 43210 USA. RP Maynard, KI (reprint author), Massachusetts Gen Hosp, Neurophysiol Lab, Neurol Serv, Edwards 414,55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS01732] NR 35 TC 30 Z9 31 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 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 1999 VL 58 IS 3 BP 442 EP 448 DI 10.1002/(SICI)1097-4547(19991101)58:3<442::AID-JNR10>3.0.CO;2-4 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 249AC UT WOS:000083308700010 PM 10518118 ER PT J AU Hashimoto, A Palmer, EL Scott, JA Abraham, SA Fischman, AJ Force, TL Newell, JB Rabito, CA Zervos, GD Yasuda, T AF Hashimoto, A Palmer, EL Scott, JA Abraham, SA Fischman, AJ Force, TL Newell, JB Rabito, CA Zervos, GD Yasuda, T TI Complications of exercise and pharmacologic stress tests: Differences in younger and elderly patients SO JOURNAL OF NUCLEAR CARDIOLOGY LA English DT Article DE exercise stress test; adenosine dipyridamole; adverse effect complication of stress test ID CORONARY-ARTERY DISEASE; MYOCARDIAL-ISCHEMIA; TL-201 SCINTIGRAPHY; ADENOSINE; DIPYRIDAMOLE; SAFETY; LEVEL; ACCURACY; INFUSION; PROFILE AB Background. Age characteristics of patients undergoing various types of stress tests are important because of differences in clinical background and exercise performance between the young and elderly. Adverse effects of pharmacologic agents are known to be more common in the elderly, who are less able to perform vigorous exercise stress testing. We investigated the clinical background, performance characteristics, and complication rate of various stress tests in younger (less than or equal to 75 years old) and elderly (>75 years old) patient populations. Methods. A total of 3412 patients (2796 younger, 616 elderly) underwent 5 types of stress tests with (1) technetium-99m sestamibi (MIBI) single photon emission computed tomography: symptom-limited exercise (Ex, 1598 younger, 173 elderly), (2) dipyridamole infusion (0.14 mg/kg/min, 4 minutes) without exercise (D, 260 younger, 114 elderly), (3) with exercise (DEx, 339 younger, 112 elderly), (4) adenosine infusion (0.14 mg/kg/min, 5 minutes) without exercise (A, 253 younger, 101 elderly), and (5) with exercise (AEx, 346 younger, 116 elderly). Results. Sixty-seven percent of patients in the younger population were able to achieve 85% of the maximum predicted heart rate, whereas 54% of the elderly reached this level of exercise. No patient had life-threatening complications. In both the younger and elderly groups, chest discomfort, feelings of impending syncope, flushing, and fall in blood pressure occurred less frequently in DEx than D and in AEx than A. Sinus bradycardia occurred less frequently in AEx than A in the younger (1.2% vs 4.3%, P < .05) and elderly groups (0.9% vs 6.9%, P < .05). Atrioventricular block was less frequent in AEx than A in the younger group (3.2% vs 7.9%, P < .05) but not so in the elderly group (13.0% vs 17.8%, not significant). The frequency of ischemic electrocardiographic changes in DEx and AEx was very similar to that of Ex in both the younger and elderly groups, although ischemic electrocardiographic changes in D and A are known to be less frequent. Conclusion. Of the elderly group who were judged to be fit to exercise to 85% of maximum predicted heart rate, nearly half failed to reach this level. In contrast, the younger patients were able to achieve this level in 67% of tests. Supplementation with modest exercise reduced most of the pharmacologically related adverse effects. The elderly group was not protected from atrioventricular block as effectively as the younger group by additional exercise in the adenosine stress test. Ischemic electrocardiographic changes in the pharmacologic stress test were as frequent as in the exercise stress test when modest supplementary exercise was added to the pharmacologic protocol. There mere no deaths, myocardial infarction, or other major complications. These observations suggest that exercise and pharmacologic stress tests are safe in the elderly, including those patients more than 75 pears old. C1 Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Yasuda, T (reprint author), Massachusetts Gen Hosp, Div Nucl Med, 32 Fruit St, Boston, MA 02114 USA. OI Force, Thomas/0000-0002-0450-8659 NR 25 TC 25 Z9 25 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1071-3581 J9 J NUCL CARDIOL JI J. Nucl. Cardiol. PD NOV-DEC PY 1999 VL 6 IS 6 BP 612 EP 619 DI 10.1016/S1071-3581(99)90098-3 PG 8 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 264YY UT WOS:000084212400009 PM 10608588 ER PT J AU Mariani, G Villa, G Rossettin, PF Spallarossa, P Bezante, GP Brunelli, C Pak, KY Khaw, BA Strauss, HW AF Mariani, G Villa, G Rossettin, PF Spallarossa, P Bezante, GP Brunelli, C Pak, KY Khaw, BA Strauss, HW TI Detection of acute myocardial infarction by Tc-99m-labeled D-glucaric acid imaging in patients with acute chest pain SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE acute myocardial infarction; scintigraphic imaging; Tc-99m labeling; D-glucaric acid; perfusion imaging ID ACUTE CARDIAC ISCHEMIA; TECHNETIUM-99M PYROPHOSPHATE; THROMBOLYTIC THERAPY; EMERGENCY ROOM; ANTIMYOSIN FAB; SCINTIGRAPHY; DIAGNOSIS; NECROSIS; ANTIBODY; TRIAGE AB Definitive diagnosis of acute myocardial infarction early in the process is often difficult. An imaging agent that localized quickly and specifically in areas of acute necrosis could provide this critical diagnostic information. To determine whether imaging with Tc-99m-labeled D-glucaric acid (GLA) could provide this information, we imaged a group of patients presenting with symptoms suggestive of acute infarction. Methods: Twenty-eight patients presenting to the emergency department with symptoms highly suggestive of acute infarction were injected with Tc-99m-GLA and imaged about 3 h later. Results: The sensitivity of lesion detection was remarkably time dependent. Fourteen patients with acute infarction injected within 9 h of onset of chest pain had positive scans, even in the presence of persistent occlusion. The remaining 14 patients had negative scans. Nine patients with negative scans had acute infarction but were injected more than 9 h after onset of chest pain. The final diagnosis in the remaining 5 patients was unstable angina (3 injected <9 h and 2 injected >9 h after onset of chest pain). Six patients were reinjected with Tc-99m-GLA 4-6 wk after their initial study to determine whether persistent positive scans occurred with this agent. All 6 had negative scans. Conclusion: This study suggests that Tc-99m-GLA localizes in zones of acute myocardial necrosis when injected within 9 h of onset of infarction. C1 Univ Genoa, Sch Med, Nucl Med Serv, DIMI, I-16132 Genoa, Italy. Univ Genoa, Sch Med, Dept Internal Med, Cardiol Unit, Genoa, Italy. Northeastern Univ, Ctr Drug Targeting & Anal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mol Targeting Technol Inc, Malvern, PA USA. Stanford Univ, Sch Med, Dept Radiol, Div Nucl Med, Stanford, CA 94305 USA. RP Mariani, G (reprint author), Univ Genoa, Sch Med, Nucl Med Serv, DIMI, Viale Benedetto XV,N 6, I-16132 Genoa, Italy. NR 38 TC 28 Z9 29 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 1999 VL 40 IS 11 BP 1832 EP 1839 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 253BH UT WOS:000083536400013 PM 10565778 ER PT J AU Woodin, MA Liu, YC Hauser, R Smith, TJ Christiani, DC AF Woodin, MA Liu, YC Hauser, R Smith, TJ Christiani, DC TI Pulmonary function in workers exposed to low levels of fuel-oil ash SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID FLOW AB Previously, we reported significant lung function changes after exposure to fuel-oil ash during a boiler overhaul in which median PM10 and vanadium concentrations mere 2.9 mg/m(3) and 11.9 mu g/m(3), respectively. lit this study, we examined prospectively 18 boilermakers involved in the short-term, partial overhaul of a large, oil-fired boiler where occupational exposures to PM10 and metals were relatively low. Vanadium and PM10 exposure levels were measured before and during boiler work. For PM10, median exposure before and during boiler work was 0.5 and 0.6 mg/m(3), respectively. For vanadium, median exposure before and during boiler work was 1.0 and 12.7 mu g/m(3), respectively, comparable with the results of our previous study. Spirometric (PFT) testing was done three times first day on the job (PFT1), end of overhaul (PFT2), and 2 weeks post-overhaul (PFT3). Spirometry results were analyzed using repeated measures analysis of variance. No significant differences were found. Boilermakers working on a short-term overhaul of an oil-fired boiler exhibited no significant change in any lung function parameter comparing pre-, during, and 2 weeks post-exposure. The comparatively low levels of exposure to PM10, and vanadium observed during boiler work, the short duration of the overhaul, and the healthy worker effect are possible explanations for these results. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm & Crit Care Unit,Dept Med, Boston, MA USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. FU NIEHS NIH HHS [ES07069, ES00002, ES05947] NR 19 TC 10 Z9 10 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1076-2752 J9 J OCCUP ENVIRON MED JI J. Occup. Environ. Med. PD NOV PY 1999 VL 41 IS 11 BP 973 EP 980 DI 10.1097/00043764-199911000-00009 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 254YR UT WOS:000083642300009 PM 10570503 ER PT J AU August, M Faquin, WC Ferraro, NF Kaban, LB AF August, M Faquin, WC Ferraro, NF Kaban, LB TI Fine-needle aspiration biopsy of intraosseous jaw lesions SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the American-Association-of-Oral-and-Maxillofacial-Surgeons CY SEP 16-20, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Oral & Maxillofacial Surgeons ID GIANT-CELL TUMOR; BONE-LESIONS; ORAL CAVITY; DIAGNOSIS; CYTOLOGY; MARKERS; CYSTS AB Purpose: This study assessed diagnostic accuracy, determined reasons for error, and evaluated modifications to improve the reliability of fine-needle aspiration biopsy (FNAB) of primary jaw lesions. Patients and Methods: This was a retrospective review of 32 FNABs of intraosseous jaw lesions performed at the Massachusetts General and Children's Hospital between 1933 and 1998. A consistent, standardized technique was used, and each case was evaluated for 1) adequacy of cells to allow diagnosis, 2) presence of malignant cells, and 3) correlation between FNAB diagnosis and the final histopathology. Results: Material obtained by FNAB was adequate for evaluation in 30 of 32 cases. No complications were reported. Malignant cells were found in 5 of 30 cases. FNAB diagnosis was confirmed by histopathology in all 5 of these specimens (100% accuracy). The FNAB diagnosis of benign lesions was confirmed in 17 of 25 cases (68%). The most common benign lesions were odontogenic cysts, ameloblastomas, and fibro-osseous and giant cell lesions. Incorrect diagnosis was related to lack of architectural context of the FNAB material, sampling of a nonrepresentative part of a large lesion, and inadequate quantity or quality of the aspirate. Conclusions: FNAB is a useful technique to distinguish between malignant and benign intraosseous jaw lesions. Its simplicity, suitability as an outpatient procedure, rapidity of interpretation, and minimal. morbidity potentially make it the diagnostic tool of choice in the hospital setting. C1 Massachusetts Gen Hosp, Harvard Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA USA. Childrens Hosp, Ctr Med, Boston, MA USA. RP August, M (reprint author), Massachusetts Gen Hosp, Harvard Sch Dent Med, Dept Oral & Maxillofacial Surg, 55 Fruit St,WRN 1201, Boston, MA 02114 USA. NR 21 TC 21 Z9 24 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 1999 VL 57 IS 11 BP 1282 EP 1286 DI 10.1016/S0278-2391(99)90859-5 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 250ZJ UT WOS:000083419900002 PM 10555791 ER PT J AU Troulis, MJ AF Troulis, MJ TI Mandibular lengthening using preprogrammed intraoral tooth-borne distraction devices - Discussion SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Troulis, MJ (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 6 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 1999 VL 57 IS 11 BP 1322 EP 1323 DI 10.1016/S0278-2391(99)90870-4 PG 2 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 250ZJ UT WOS:000083419900013 ER PT J AU Jupiter, JB AF Jupiter, JB TI Plate fixation of fractures of the distal aspect of the radius: Relative indications SO JOURNAL OF ORTHOPAEDIC TRAUMA LA English DT Article ID FOREARM; WRIST C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Hand Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Orthopaed Surg, Cambridge, MA 02138 USA. RP Jupiter, JB (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Orthopaed Hand Serv, ACC 527,15 Parkman St, Boston, MA 02114 USA. NR 50 TC 14 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-5339 J9 J ORTHOP TRAUMA JI J. Orthop. Trauma PD NOV PY 1999 VL 13 IS 8 BP 559 EP 569 DI 10.1097/00005131-199911000-00009 PG 11 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 252RW UT WOS:000083516900009 PM 10714783 ER PT J AU Rudolph, CD Winter, HS AF Rudolph, CD Winter, HS CA NASPGN Executive Council NASPGN Training Educ Comm TI NASPGN guidelines for training in pediatric gastroenterology SO JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION LA English DT Article C1 Childrens Hosp, Med Ctr, Div Pediat Gastroenterol & Nutr, Cincinnati, OH 45229 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. RP Rudolph, CD (reprint author), Childrens Hosp, Med Ctr, Div Pediat Gastroenterol & Nutr, 3333 Burnet Ave, Cincinnati, OH 45229 USA. NR 5 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-2116 J9 J PEDIATR GASTR NUTR JI J. Pediatr. Gastroenterol. Nutr. PD NOV PY 1999 VL 29 SU 1 BP S1 EP S26 DI 10.1097/00005176-199911001-00001 PG 26 WC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics SC Gastroenterology & Hepatology; Nutrition & Dietetics; Pediatrics GA 314AV UT WOS:000087032700001 PM 10554139 ER PT J AU McLean, TW Hertel, C Young, ML Marcus, K Schizer, MA Gebhardt, M Weinstein, HJ Perez-Atayde, A Grier, HE AF McLean, TW Hertel, C Young, ML Marcus, K Schizer, MA Gebhardt, M Weinstein, HJ Perez-Atayde, A Grier, HE TI Late events in pediatric patients with Ewing sarcoma/primitive neuroectodermal tumor of bone: The Dana-Farber Cancer Institute/Children's Hospital experience SO JOURNAL OF PEDIATRIC HEMATOLOGY ONCOLOGY LA English DT Article DE Ewing sarcoma; primitive neuroectodermal tumor; bone tumor; late events; second malignant neoplasms; long-term follow-up ID 2ND MALIGNANT NEOPLASMS; TERM FOLLOW-UP; COMBINED-MODALITY THERAPY; MULTIMODAL THERAPY; CHILDHOOD-CANCER; PROGNOSTIC FACTOR; SARCOMA FAMILY; CELL TUMORS; CHILDREN; LEUKEMIA AB The outcome for 82 pediatric patients with Ewing sat-coma (ES) and primitive neuroectodermal tumor (PNET) of bone is reported; the patients were treated at the Dana-Farber Cancer Institute (DFCI) and Children's Hospital (CH) in Boston, MA (USA) from 1971-1988. The charts of all patients with ES/PNET of bone treated during this period were reviewed for disease status, therapy, sites of relapse, information on second malignancies, and survival status. Eighty-two patients with ES/PNET of bone treated at DFCI/CH were identified. The 10-year event-free survival (EFS) rates were 12% (95% confidence interval [CI] 0, 27%) and 38% (95% CI 26, 51%) for patients with and without metastases, respectively (P = 0.002), the overall survival(OS) rates were 17% (95% CI 1, 33%) and 48% (95% CI 35, 61%) for patients with and without metastases (P = 0.001). Median follow-up for surviving patients is 10.2 years. Primary site in the pelvis also was associated with a poor outcome for patients with no metastatic disease (P = 0.006 OS, P = 0.03 EFS). Thirty-one patients survived in first remission at least 5 years from diagnosis, and of these, five experienced relapse of original disease, and five experienced secondary malignancies. Pediatric patients treated for ES/PNET of bone remain at risk for life-threatening events into the second decade of follow-up. After 5 years, the risk of second malignant neoplasm is at least as high as the risk of late relapse. Prolonged follow-up of patients with ES and PNET of bone is indicated. C1 Wake Forest Univ, Sch Med, Dept Pediat, Winston Salem, NC 27157 USA. Wayne State Univ, Basic Med Sci Dept, Detroit, MI USA. Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. Childrens Hosp, Joint Ctr Radiat Therapy, Dept Radiat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Pulm, Boston, MA 02115 USA. Childrens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Pediat, Div Hematol Oncol, Boston, MA 02114 USA. RP McLean, TW (reprint author), Wake Forest Univ, Sch Med, Dept Pediat, Med Ctr Blvd, Winston Salem, NC 27157 USA. NR 53 TC 27 Z9 29 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1077-4114 J9 J PEDIAT HEMATOL ONC JI J. Pediatr. Hematol. Oncol. PD NOV-DEC PY 1999 VL 21 IS 6 BP 486 EP 493 DI 10.1097/00043426-199911000-00009 PG 8 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 261YY UT WOS:000084040000008 PM 10598659 ER PT J AU Sarment, DP Korostoff, J D'Angelo, M Polson, AM Feldman, RS Billings, PC AF Sarment, DP Korostoff, J D'Angelo, M Polson, AM Feldman, RS Billings, PC TI In situ localization and characterization of active proteases in chronically inflamed and healthy human gingival tissues SO JOURNAL OF PERIODONTOLOGY LA English DT Article DE gingiva/enzymology; inflammation; periodontal diseases/diagnosis; proteases/analysis; spectroscopy; fluorescence; matrix metalloproteases; serine proteases ID CREVICULAR FLUID; MATRIX METALLOPROTEINASES; ADULT PERIODONTITIS; JUVENILE PERIODONTITIS; EXTRACELLULAR-MATRIX; HUMAN NEUTROPHIL; MESSENGER-RNA; CATHEPSIN-G; IN-SITU; COLLAGENASE AB Background: Studies have indicated an important role for host-derived proteases in the pathogenesis of periodontal disease. The objectives of this study were: 1) to develop an assay measuring protease activity in situ and 2) to localize and characterize the enzymatic activity in intact inflamed and healthy gingiva. Methods: Gingival specimens were prepared and overlaid with a quenched fluorescent substrate. Protease activity was visualized by fluorescence microscopy and correlated with histologic features. Results: In inflamed tissues, enzymatic activity was detected mainly in the connective tissue (predominantly matrix metalloproteases) and, to some extent, in the epithelium (predominantly serine proteases). In contrast, clinically healthy tissues failed to exhibit significant amounts of protease activity. Quantitative and qualitative characteristics of protease activity in intact tissues were found to be pH dependent. Conclusions: The method described here enabled assessment of active proteases in intact tissues where cell-cell and cell-matrix interactions had been maintained. Our results indicate that there are substantial differences in the distribution of specific proteases between clinically healthy and inflamed periodontal tissues. C1 Univ Penn, Sch Dent Med, Dept Periodont, Philadelphia, PA USA. Univ Penn, Sch Dent Med, Dept Anat & Histol, Philadelphia, PA 19104 USA. Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Sarment, DP (reprint author), Univ Michigan, Sch Dent, Dept Periodont Prevent Geriatr, 1011 N Univ Ave, Ann Arbor, MI 48109 USA. NR 50 TC 10 Z9 10 U1 0 U2 1 PU AMER ACAD PERIODONTOLOGY PI CHICAGO PA 737 NORTH MICHIGAN AVENUE, SUITE 800, CHICAGO, IL 60611-2690 USA SN 0022-3492 J9 J PERIODONTOL JI J. Periodont. PD NOV PY 1999 VL 70 IS 11 BP 1303 EP 1312 DI 10.1902/jop.1999.70.11.1303 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 259JB UT WOS:000083889800006 PM 10588493 ER PT J AU Kim, SS Kaihara, S Benvenuto, MS Choi, RS Kim, BS Mooney, DJ Vacanti, JP AF Kim, SS Kaihara, S Benvenuto, MS Choi, RS Kim, BS Mooney, DJ Vacanti, JP TI Effects of anastomosis of tissue-engineered neointestine to native small bowel SO JOURNAL OF SURGICAL RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Academic-Surgery CY NOV 18-22, 1998 CL SEATTLE, WASHINGTON SP Assoc Acad Surg DE intestinal cell transplantation; tissue engineering; regeneration ID PANCREATIC SECRETIONS; TRANSPLANTATION; RAT; GROWTH; TUBES; BILE AB Background. Our laboratory is investigating the tissue engineering of small intestine using intestinal epithelial organoid units seeded onto highly porous biodegradable polymer matrices. This study investigated the effects of anastomosis of tissue-engineered intestine to native small bowel alone or combined with small bowel resection on neointestinal regeneration. Methods. Intestinal epithelial organoid units harvested from neonatal Lewis rats were seeded onto biodegradable polymer tubes and implanted into the omentum of adult Lewis rats as follows: (1) implantation alone (n = 9); (2) implantation followed by anastomosis to native small bowel at 3 weeks (n = 11); and (3) implantation after small bowel resection and anastomosis to native small bowel at 3 weeks (n = 8). All constructs were harvested at 10 weeks and examined by histology. Morphometric analysis of the neomucosa was obtained using a computer image analysis program. Results. Cyst development was noted in all animals. All anastomoses were patent at 10 weeks. Histology revealed the development of a vascularized tissue with a neomucosa lining the lumen of the cyst with invaginations resembling crypt-villus structures. Morphometric analysis demonstrated significantly greater villus number, villus height, crypt number, crypt area, and mucosal surface length in groups 2 and 3 compared with group 1, and significantly greater villus number, villus height, crypt area, and mucosal surface length in group 3 compared with group 2 (P < 0.05, ANOVA, Tukey test). Conclusion. Intestinal epithelial organoid units transplanted on biodegradable polymer tubes can regenerate into complex tissue resembling small intestine. Anastomosis to native small bowel combined with small bowel resection and anastomosis alone contribute significant regenerative stimuli for the morphogenesis and differentiation of tissue-engineered neointestine. (C) 1999 Academic Press. C1 Harvard Univ, Sch Med, Dept Surg, Lab Transplantat & Tissue Engn, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Univ Chicago Hosp, Dept Surg, Chicago, IL 60637 USA. Univ Michigan, Dept Chem Engn, Ann Arbor, MI 48109 USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, 50 Fruit St, Boston, MA 02114 USA. RI Kim, Byung-Soo/O-2352-2013 NR 23 TC 30 Z9 31 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD NOV PY 1999 VL 87 IS 1 BP 6 EP 13 DI 10.1006/jsre.1999.5743 PG 8 WC Surgery SC Surgery GA 254ZR UT WOS:000083644800002 PM 10527698 ER PT J AU Kitzis, V Engrav, LH Quinn, LS AF Kitzis, V Engrav, LH Quinn, LS TI Transient exposure to tumor necrosis factor-alpha inhibits collagen accumulation by cultured hypertrophic scar fibroblasts SO JOURNAL OF SURGICAL RESEARCH LA English DT Article DE hypertrophic scar; cell culture; tumor necrosis factor-alpha; collagen; insulin-like growth factor-binding proteins ID GROWTH-FACTOR-BETA; DERMAL FIBROBLASTS; MESSENGER-RNA; FACTOR-I; TRANSFORMING GROWTH-FACTOR-BETA-1; INTERFERON-GAMMA; IGF-I; EXPRESSION; BINDING; PROTEIN AB Background. Hypertrophic scars (HS) are frequent consequences of deep dermal injury, such as deep partial-thickness burns and abrasions, and are characterized by overproduction of collagen. In vitro studies have shown that cultured HS fibroblasts produce elevated levels of collagen and insulin-like growth factor-binding protein 3 (IGFBP-3). Additionally, histological studies have indicated HS contain fewer tumor necrosis factor alpha (TNF-alpha)-positive infiltrating cells and express lower levels of TNF-alpha mRNA, suggesting TNF-alpha, which can inhibit collagen expression in some systems, may function to deactivate the wound healing process in scars. HS also exhibit increased levels of transforming growth factor beta (TGF-beta), a facts that stimulates collagen and extracellular matrix deposition by fibroblasts and also stimulates IGFBP-3 expression. In some systems, IGFBP-3 mediates the effects of TGF-beta. The present study sought to determine the effects of continuous and transient TNF-alpha exposure on collagen and IGFBP-3 expression by cultured;Hg fibroblasts and to investigate the role of IGFBP-3 in collagen accretion by HS fibroblasts. Materials and Methods. Superficial and deep dermal HS fibroblasts from four patients were cultured. Fibroblasts were cultured in serum-free medium and exposed to 0-2 ng/ml TNF-alpha for 0, 1, 4, or 72 h. After 72 h of culture, medium samples were processed for Western blot analysis of type I collagen accumulation or for ligand blot analysis of IGFBP-3 accumulation. The effects of an anti-IGFBP-3 neutralizing antibody on collagen accumulation were also assessed. Results. Treatment of superficial and deep HS fibroblasts with TNF-alpha resulted in dose-dependent decreases in accumulation of both type I collagen and IGFBP-3 in the culture medium (P < 0.01). However, using the anti-IGFBP-3 neutralizing antibody, a causal relationship between decreased IGFBP-3 and decreased collagen accumulation could not be demonstrated. Transient exposure of cultured HS fibroblasts to TNF-alpha for as little as 1 h was as effective as continuous exposure to TNF-alpha for 72 h in inhibiting collagen accumulation. Conclusions. These results support the hypothesis that TNF-alpha functions as a wound healing deactivation signal that is deficient in HS. Although TNF-alpha inhibited accretion of both collagen and IGFBP-3, the role of IGFBP-3 in HS remains unresolved. This study suggests that transient TNF-alpha exposure may be used to inhibit collagen overaccumulation in HS and that the timing of TNF-alpha exposure following dermal injury may not be critical for this inhibition. (C) 1999 Academic Press. C1 VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Tacoma, WA 98493 USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Surg, Div Plast & Reconstruct Surg, Seattle, WA 98195 USA. RP Quinn, LS (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 151 Amer Lake, Tacoma, WA 98493 USA. NR 39 TC 18 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-4804 J9 J SURG RES JI J. Surg. Res. PD NOV PY 1999 VL 87 IS 1 BP 134 EP 141 DI 10.1006/jsre.1999.5747 PG 8 WC Surgery SC Surgery GA 254ZR UT WOS:000083644800019 PM 10527715 ER PT J AU McKinney, MF Delgutte, B AF McKinney, MF Delgutte, B TI A possible neurophysiological basis of the octave enlargement effect SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AUDITORY-NERVE FIBERS; COMPLEX TONES; MELODIC OCTAVE; LOW-FREQUENCY; PITCH; MECHANISMS; DEPENDENCE; RESPONSES; ALGORITHM; ORIGIN AB Although the physical octave is defined as. a simple ratio of 2:1, listeners prefer slightly greater octave ratios. Ohgushi [J. Acoust. Sec. Am. 73, 1693-1700 (1983)] suggested that a temporal model for octave matching would predict this octave enlargement effect because, in response to pure tones, auditory-nerve interspike intervals are slightly larger than the stimulus period. In an effort to test Ohgushi's hypothesis, auditory-nerve single-unit responses to pure-tone stimuli were collected from Dial-anesthetized cats. It was found that although interspike interval distributions show clear phase-locking to the stimulus, intervals systematically deviate from integer multiples of the Stimulus period. Due to refractory effects, intervals smaller than 5 msec are slightly larger than the stimulus period and deviate most for small intervals. On the other hand, first-order intervals are smaller than the stimulus period for stimulus frequencies less than 500 Hz, It is shown that this deviation is the combined effect of phase-locking and multiple spikes within one stimulus period. A model;for octave matching was implemented which compares frequency estimates of two tones based on their interspike interval distributions. The model: quantitatively predicts the octave enlargement effect. These results are consistent with the idea that musical pitch is derived from auditory-nerve interspike interval distributions. (C) 1999 Acoustical Society of America. [S0001-4966(99)05111-5]. C1 Harvard Univ, MIT, Dept Speech & Hearing Sci, Div Hlth Sci & Technol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Harvard Univ, MIT, Speech & Hearing Sci Program, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. RP McKinney, MF (reprint author), Harvard Univ, MIT, Dept Speech & Hearing Sci, Div Hlth Sci & Technol, 243 Charles St, Boston, MA 02114 USA. OI , /0000-0003-1349-9608 FU NIDCD NIH HHS [R01 DC002258, R01 DC002258-05, R01 DC02258, T32 DC000038, T32 DC00038] NR 49 TC 14 Z9 14 U1 0 U2 3 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 1999 VL 106 IS 5 BP 2679 EP 2692 DI 10.1121/1.428098 PG 14 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 257MN UT WOS:000083785800037 PM 10573885 ER PT J AU Pagnoni, A Kligman, AM Kollias, N Goldberg, S Stoudemayer, T AF Pagnoni, A Kligman, AM Kollias, N Goldberg, S Stoudemayer, T TI Digital fluorescence photography can assess the suppressive effect of benzoyl peroxide on Propionibacterium acnes SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article AB Background: Porphyrins produced by Propionibacterium acnes exhibit an orange-red fluorescence under UVA light. The amount of fluorescence can be estimated by digital fluorescence photography. Objective: We thought that digital fluorescence photography would be a quicker and simpler method than bacteriologic culture to demonstrate depopulation of P acnes in sebaceous follicles. We used benzoyl peroxide to bring about rapid suppression of P acnes. Methods: Benzoyl peroxide 10% was applied twice daily for 7 days to the faces of 9 subjects. Five subjects were untreated controls. Digital fluorescence photographs of cheek and nose, and scrub samples for quantitative recovery of P acnes from the cheek were taken at baseline, day 3, day 7 (end of treatment), and day 16 (regression phase). Results: The effect of benzoyl peroxide against P acnes was clearly demonstrated both by culture and by fluorescence photography after only 3 days. Image analysis of porphyrin fluorescence correlated well with the decrease in P acnes density from scrub cultures. No further decrease was observed at day 7 (end of therapy). Ten days later there a as a return to baseline values, although in some subjects these remained lower. Conclusion: Digital fluorescence photography is a reliable, fast, and easy screening technique to demonstrate the suppressive effect of topical antibacterial agents on P acnes. C1 SKIN Inc, Conshohocken, PA 19428 USA. Univ Penn, Dept Dermatol, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Dermatol,Wellman Labs, Boston, MA 02115 USA. RP Pagnoni, A (reprint author), SKIN Inc, 151 E 10th Ave, Conshohocken, PA 19428 USA. NR 16 TC 28 Z9 30 U1 1 U2 2 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD NOV PY 1999 VL 41 IS 5 BP 710 EP 716 DI 10.1016/S0190-9622(99)70005-8 PN 1 PG 7 WC Dermatology SC Dermatology GA 249VH UT WOS:000083353600006 PM 10534632 ER PT J AU Barker, LH Bigler, ED Johnson, SC Anderson, CV Russo, AA Boineau, B Blatter, DD AF Barker, LH Bigler, ED Johnson, SC Anderson, CV Russo, AA Boineau, B Blatter, DD TI Polysubstance abuse and traumatic brain injury: Quantitative magnetic resonance imaging and neuropsychological outcome in older adolescents and young adults SO JOURNAL OF THE INTERNATIONAL NEUROPSYCHOLOGICAL SOCIETY LA English DT Review DE substance abuse; traumatic brain injury; quantitative neuroimaging ID CEREBRAL BLOOD-FLOW; CHRONIC COCAINE ABUSERS; CENTRAL-NERVOUS-SYSTEM; HEAD-INJURY; ALCOHOL-ABUSE; SUBSTANCE-ABUSE; KORSAKOFFS-SYNDROME; LONG-TERM; VOCATIONAL-REHABILITATION; PSYCHIATRIC DISEASE AB Few studies have examined the consequences of alcohol and drug abuse on TBI though they commonly co-occur. Both TBI and substance abuse independently result in neuropathological changes in the brain such as ventricular enlargement and cortical atrophy, thus it is reasonable to hypothesize that the combination of the two would result in more significant cerebral damage. In this study, 3 groups of patients-traumatically brain injured (TBI) with substance abuse (N = 19), TBI without substance abuse (N = 19), and substance abuse with no TBI (N = 16)-were compared with normal controls (N = 20) on several quantitative MRI (QMRI) measures. Since TBI most frequently occurs in older adolescents and young men, we examined only male participants between 16 and 30 years of age. Comparing young substance abusers to controls resulted in no QMRI differences. When controlling for head injury severity, the effects of substance abuse in combination with TBI resulted in greater atrophic changes than seen in any other group, TBI and substance abuse patients' neuropsychological test performances also were examined, and no differences were found among patient groups on any measures. These findings have implications for the deleterious interaction of substance abuse combining with TBI to result in greater neuropathological changes that can be detected by QMRI techniques. C1 Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. Dartmouth Coll, Hanover, NH 03755 USA. Brigham Young Univ, Provo, UT 84602 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Heritage Residential Treatment Ctr, Provo, UT USA. LDS Hosp, Salt Lake City, UT USA. RP Bigler, ED (reprint author), Brigham Young Univ, Dept Psychol, POB 25543, Provo, UT 84602 USA. EM erin_bigler@byu.edu NR 149 TC 21 Z9 21 U1 3 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 1355-6177 J9 J INT NEUROPSYCH SOC JI J. Int. Neuropsychol. Soc. PD NOV PY 1999 VL 5 IS 7 BP 593 EP 608 PG 16 WC Clinical Neurology; Neurosciences; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 265WF UT WOS:000084268500002 PM 10645702 ER PT J AU Wilkinson, RA Fishman, JA AF Wilkinson, RA Fishman, JA TI Effect of thermal injury with Pseudomonas aeruginosa infection on pulmonary and systemic bacterial clearance SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Article DE bacteremia; bacterial clearance; bacterial translocation; burn; pneumonia; Pseudomonas aeruginosa; sepsis; thermal injury ID RESPIRATORY-DISTRESS SYNDROME; TUMOR-NECROSIS-FACTOR; PLASMA CYTOKINES; LUNG; PERMEABILITY; CELLS AB Background: Despite improvements in burn mound care, infections, particularly pneumonia, remain a major hurdle to recovery from thermal injury. After burns, a variety of systemic immune and inflammatory changes contribute to the risk of infection. Clinically, infection coupled with burn injury seems to adversely affect susceptibility to subsequent infection. Methods: Using a mouse model of 10% total body surface area, full-thickness, third-degree burns with quantitative bacterial cultures of multiple tissues, the effect of graded intratracheal and intraperitoneal infections with Pseudomonas aeruginosa on the development of infection was assessed. Results: P. aeruginosa infection of blood and lung were demonstrated in burned mice 4 hours after they received 1 to 7.2 x 10(5) P. aeruginosa intratracheally but not in unburned control mice. Disseminated infection from endogenous bacterial species (Proteus, Enteroeoccus, Streptococcus) involving the lungs, liver, blood, and subeschar space mas observed in mice that received both burns and infection with P. aeruginosa (intraperitoneally and intratracheally) but not with infection or burn alone (p < 0.01). After burns, pulmonary bacterial clearance was delayed in association with both pulmonary infection (7.2 x 10(5) P. aeruginosa intratracheally) and intraperitoneal infection (10(7) P. aeruginosa intraperitoneally). Histologically, diffuse pneumonitis was observed in mice that received burns and infection but not in mice with either infection or burns alone. Conclusion: Small thermal injuries coupled with transient infection of the lungs or peritoneum delay the clearance of bacteria from the lungs and contribute to infection of the lungs, liver, burn site, and blood by endogenous organisms. These studies support the synergy of relatively small thermal injuries with infectious exposures in the pathogenesis of pneumonia and systemic infections after burns. C1 Massachusetts Gen Hosp, Div Infect Dis, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA USA. Shriners Hosp Crippled Children, Boston Unit, Boston, MA USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 149 13th St,Room 5238, Charlestown, MA 02129 USA. NR 26 TC 11 Z9 11 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5282 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD NOV PY 1999 VL 47 IS 5 BP 912 EP 917 DI 10.1097/00005373-199911000-00016 PG 6 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 254QM UT WOS:000083623700018 PM 10568721 ER PT J AU Ray, CE Shenoy, SS McCarthy, PL Broderick, KA Kaufman, JA AF Ray, CE Shenoy, SS McCarthy, PL Broderick, KA Kaufman, JA TI Weekly prophylactic urokinase instillation in tunneled central venous access devices SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article; Proceedings Paper CT 1999 SCVIR Annual Meeting CY 1999 CL ORLANDO, FLORIDA DE catheters and catheterization, central venous access; central venous access; urokinase ID RADIOLOGIC PLACEMENT; RESTORING FUNCTION; CATHETERS; MALIGNANCIES; THROMBOSIS; WARFARIN; INFUSION; PORTS AB PURPOSE: To determine the safety and efficacy of weekly prophylactic urokinase therapy in tunneled central venous access devices (VADs). MATERIALS END METHODS: A prospective, randomized study was performed in 105; patients who underwent tunneled VAD placement between March 1997 and April 1998, The patients were randomized to receive either twice-daily heparin flushes (14 heparin flushes per week; group A, n = 52) or twice-daily heparin flushes with once-weekly urokinase (UK) instillation (13 heparin flushes, one UK flush per week; group B, n = 53), Patients were followed up by examination and/or interview at 1, 3, and 6 months for signs and symptoms of delayed catheter-related complications. RESULTS: The total number of indwelling catheter-days was similar between groups (5,450 in group A, 5,276 in group B), The total number of infectious complications and fibrin sheaths formed was greater for group A (n = 11; 21.1%) than group B (n = 3; 5.7%) (P = .02), There were no side effects noted from the prophylactic UK administrations. CONCLUSION: Prophylactic UR is advantageous in preventing delayed catheter-related complications. C1 Roswell Pk Canc Inst, Dept Intervent Radiol, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Hematol Oncol, Buffalo, NY 14263 USA. Massachusetts Gen Hosp, Dept Vasc Radiol, Boston, MA 02114 USA. RP Ray, CE (reprint author), Denver Hlth Med Ctr, 777 Bannock St,Mail Code 0024, Denver, CO 80204 USA. NR 18 TC 26 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD NOV-DEC PY 1999 VL 10 IS 10 BP 1330 EP 1334 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 259EL UT WOS:000083881500005 PM 10584647 ER PT J AU Brown, HEV Chen, HM Engelman, A AF Brown, HEV Chen, HM Engelman, A TI Structure-based mutagenesis of the human immunodeficiency virus type 1 DNA attachment site: Effects on integration and cDNA synthesis SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; REVERSE TRANSCRIPTION; RETROVIRAL DNA; HIV-1; INITIATION; MUTATIONS; INVITRO; LOOP; RNA; CONSTRUCTION AB Sequences at the ends of linear retroviral cDNA important for integration define the viral DNA attachment (aft) site. Whereas determinants of human immunodeficiency virus type 1 (HIV-1) integrase important for replication in T lymphocytes have been extensively characterized, regions of the att site important for viral spread have not been thoroughly examined. Previous transposon-mediated footprinting of preintegration complexes isolated from infected cells revealed enhanced regions of bacteriophage Mu insertion near the ends of HIV-1 cDNA, in the regions of the att sites, Here, we identified the subterminal cDNA sequences cleaved during in vitro footprinting and used this structure-based information together with results of previous work to construct and characterize 24 att site mutant viruses. We found that although subterminal cDNA sequences contributed to HIV-1 replication, the identities of these bases were not critical for integration. In contrast, the phylogenetically conserved CA dinucleotides located at the ends of HIV-1 contributed significantly to virus replication and integration. Mutants containing one intact CA end displayed delays in peak virus growth compared to the wild type. In contrast, double mutant viruses lacking both CAs were replication defective, The A of the CA appeared to be the most critical determinant of integration, because two different U5 mutant viruses containing the substitution of TG for CA partially reverted by changing the G back to A. We also identified a U5 deletion mutant in which the CA played a crucial role in reverse transcription. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Engelman, A (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. FU NIAID NIH HHS [AI39394, R01 AI039394, R37 AI039394] NR 38 TC 64 Z9 64 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 NOV PY 1999 VL 73 IS 11 BP 9011 EP 9020 PG 10 WC Virology SC Virology GA 244VJ UT WOS:000083071200012 PM 10516007 ER PT J AU Rodriguez, A Armstrong, M Dwyer, D Flemington, E AF Rodriguez, A Armstrong, M Dwyer, D Flemington, E TI Genetic dissection of cell growth arrest functions mediated by the Epstein-Barr virus lytic gene product, Zta SO JOURNAL OF VIROLOGY LA English DT Article ID DNA-BINDING SPECIFICITY; ORAL HAIRY LEUKOPLAKIA; EPITHELIAL-CELLS; LEUCINE-ZIPPER; TRANSCRIPTIONAL ACTIVATION; HUMAN CYTOMEGALOVIRUS; DIMERIZATION DOMAIN; TRANSACTIVATOR ZTA; DEPENDENT KINASES; MAMMALIAN-CELLS AB Expression of the Epstein-Barr virus (EBV) latency-associated genes activates cell cycle progression and drives immortalization of the infected cell. In contrast, progression of the EBV replication program occurs most efficiently in growth-arrested cells. Previous studies showed that the EBV-encoded immediate-early transcription factor, Zta, can induce expression of the cyclin-dependent kinase inhibitors, p21 and p27, the tumor suppressor, p53, and cell growth arrest. Moreover, Zta-mediated induction of growth arrest occurs independently of its transcriptional transactivation function. Here we show that substitution of Zta's basic DNA binding domain with the analogous region of the Zta homologue, c-Fos, abrogates Zta's ability to induce growth arrest and to induce p21, p27, or p53 expression, suggesting that protein-protein interactions between this region of Zta and key cell cycle control proteins are involved in signaling cell cycle arrest. We also show that despite the crucial role for Zta's basic domain in eliciting cell growth arrest, its amino terminus is required for efficient induction of p27 and it modulates the level of p53 induction. Last, we provide evidence that Zta-mediated inductions of p21, p27, and p53 occur, at least in part, through distinct pathways. Therefore, Zta interacts with multiple growth arrest pathways, a property which may have evolved partly as a means to ensure that lytic replication occurs in a growth-arrested setting in multiple different tissues in various states of differentiation. C1 Dana Farber Canc Inst, Dept CIA, Boston, MA 02446 USA. Harvard Univ, Boston, MA 02115 USA. RP Flemington, E (reprint author), Dana Farber Canc Inst, Dept CIA, Rm D1420b, Boston, MA 02446 USA. RI Rodriguez, Antonio/L-2422-2013 OI Rodriguez, Antonio/0000-0003-2455-6583 FU NIGMS NIH HHS [R01 GM048045, R01 GM48045] NR 68 TC 44 Z9 46 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 NOV PY 1999 VL 73 IS 11 BP 9029 EP 9038 PG 10 WC Virology SC Virology GA 244VJ UT WOS:000083071200014 PM 10516009 ER PT J AU Meisler, JG Rasgon, N Nonacs, R AF Meisler, JG Rasgon, N Nonacs, R TI Toward optimal health: The experts respond to depression SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Editorial Material C1 Univ Calif Los Angeles, Menopause Related Mood Disorders Program, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Perinatal Psychiat Clin Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD NOV PY 1999 VL 8 IS 9 BP 1141 EP 1146 DI 10.1089/jwh.1.1999.8.1141 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 259VW UT WOS:000083915500004 ER PT J AU Bailey, JW Cohen, LS AF Bailey, JW Cohen, LS TI Prevalence of mood and anxiety disorders in women who seek treatment for premenstrual syndrome SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID PRIMARY-CARE; CHEST PAIN; FOLLOW-UP; UNDERTREATMENT; ASSOCIATION; DEPRESSION; SYMPTOMS; DISTRESS AB Many women experience symptoms of premenstrual irritability, reactivity of mood, anxiety, and change in appetite and sleep. Whereas some women experience these symptoms exclusively during the premenstrual phase of the menstrual cycle, others may have premenstrual complaints but actually suffer from mood and anxiety symptoms across the entire menstrual cycle. We sought to determine the extent to which women who seek treatment for premenstrual syndrome (PMS) actually suffer from symptoms of sufficient severity and duration to meet formal criteria for mood or anxiety disorders. Two hundred six women who responded to advertisements for a treatment study of premenstrual dysphoric disorder (PMDD) and who were screened by telephone for study eligibility were included in the current investigation. A telephone questionnaire keyed to the Structured Clinical Interview for Diagnosis (SCID-I/P) was used to screen for the presence of current mood and anxiety disorders. Approximately 39% (n = 80) of respondents met criteria for mood or anxiety disorders or both. Mood disorders were noted almost twice as commonly as anxiety disorders. The high prevalence of mood disorders in the sample underscores the need for clinicians to be aware of the overlap between reported PMS symptoms and underlying depressive disorder. Given that early identification and treatment of mood disorder can increase the likelihood of recovery and lower risk for recurrent illness, clinicians should have a low threshold for ruling out mood and anxiety disorders in women with complaints of premenstrual symptoms. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, Boston, MA 02114 USA. RP Cohen, LS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Perinatal & Reprod Psychiat Clin Res Program, 15 Parkman St,WACC 812, Boston, MA 02114 USA. NR 14 TC 27 Z9 28 U1 0 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD NOV PY 1999 VL 8 IS 9 BP 1181 EP 1184 DI 10.1089/jwh.1.1999.8.1181 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 259VW UT WOS:000083915500009 PM 10595331 ER PT J AU Chaloupka, JC Mangla, S Huddle, DC Roth, TC Mitra, S Ross, DA Sasaki, CT AF Chaloupka, JC Mangla, S Huddle, DC Roth, TC Mitra, S Ross, DA Sasaki, CT TI Evolving experience with direct puncture therapeutic embolization for adjunctive and palliative management of head and neck hypervascular neoplasms SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 29-31, 1999 CL PROVIDENCE, RHODE ISLAND SP Amer Laryngol Rhinol & Otol Soc, Eastern Sect DE head neoplasms; neck neoplasms; therapeutic embolization; interventional neuroradiology; experimental ID ETHANOL; TUMOR AB Objectives: The use of percutaneous, direct puncture therapeutic embolization (DPTE) of hypervascular head and neck neoplasms is a relatively new modality that may be used to supplement or supplant conventional endovascular transarterial embolization. Although the preliminary clinical experience reported by a single group has been favorable, extensive case series experience is lacking. This prompted us to review our recent clinical experience with these techniques to determine safety, efficacy, and emerging role in the overall neurointerventional therapeutic armamentarium. Study Design: A retrospective analysis of the previous 34 consecutive cases of hypervascular tumors undergoing DPTE referred to our service for therapeutic devascularization was performed, Methods: Complete case record review was undertaken. Twenty-six of 34 cases involved DPTE of head and neck neoplasms. Conventional diagnostic angiography was performed for therapeutic planning and to assist in precise localization. When performed, standard microcatheter transarterial embolization techniques were used either before or after attempted DPTE, Cyanoacrylate embolic mixtures (n-butyl cyanoacrylate [NBCA], lipiodol, powdered tungsten) were used in 21 of 24 cases, and absolute ethanol in 3 of 24, Direct puncture angiography of the targeted tumor neovasculature was always performed before DPTE. Results: Twenty-four of 26 cases had technically successful DPTE, Combined transarterial embolization with DPTE was used in 16 of 24 cases, although for the last 12 cases, 9 were treated predominantly or exclusively by DPTE. There were no major or minor clinical complications, and there was one asymptomatic technical complication. Total or near-total devascularization was achieved in all cases, All preoperative cases had excellent hemostasis within the resected tumor bed. Conclusions: Our results lend further support to the safety and efficacy of DPTE in the management of hypervascular neoplasms of the head and neck. With our increasing experience, this technique is evolving into a primary therapeutic modality for optimal tumor devascularization. C1 Univ Iowa Hosp & Clin, Dept Radiol, Sect Intervent Neuroradiol, Iowa City, IA 52242 USA. Yale Univ, Sch Med, Dept Radiol, Neuroradiol Sect, New Haven, CT USA. Yale Univ, Sch Med, Dept Surg, Otolaryngol Sect, New Haven, CT USA. Massachusetts Gen Hosp, Dept Radiol, Sect Intervent Neuroradiol, Boston, MA 02114 USA. Cent Illinois Neurosci Fdn, Bloomington, IL USA. RP Chaloupka, JC (reprint author), Univ Iowa Hosp & Clin, Dept Radiol, Sect Intervent Neuroradiol, JPP 3891,200 Hawkins Dr, Iowa City, IA 52242 USA. NR 14 TC 47 Z9 48 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD NOV PY 1999 VL 109 IS 11 BP 1864 EP 1872 DI 10.1097/00005537-199911000-00028 PG 9 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 253LA UT WOS:000083557000028 PM 10569424 ER PT J AU Ritchie, KA Aprikyan, AAG Bowen-Pope, DF Norby-Slycord, CJ Conyers, S Sitnicka, E Bartelmez, SH Hickstein, DD AF Ritchie, KA Aprikyan, AAG Bowen-Pope, DF Norby-Slycord, CJ Conyers, S Sitnicka, E Bartelmez, SH Hickstein, DD TI The Tel-PDGFR beta fusion gene produces a chronic myeloproliferative syndrome in transgenic mice SO LEUKEMIA LA English DT Article DE Tel-PDGFR beta; myeloproliferative syndrome; transgenic mice ID CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; GROWTH-FACTOR RECEPTOR; DUCHENNE MUSCULAR-DYSTROPHY; SIGNALING PATHWAYS; PLATELET; EXPRESSION; TRANSLOCATION; FAMILY; MODEL AB Chronic myelomonocytic leukemia (CMML) is a pre-leukemic syndrome that displays both myelodysplastic and myeloproliferative features. The t(5;12) chromosomal translocation, present in a subset of CMML patients with myeloproliferation fuses the amino terminal portion of the ets family member, Tel, with the transmembrane and tyrosine kinase domains of platelet-derived growth factor receptor beta (PDGFR beta) gene. To investigate the role of this fusion protein in the pathogenesis of CMML, we expressed the Tel-PDGFR beta fusion cDNA in hematopoietic cells of transgenic mice under the control of the human CD11a promoter. Transgenic founders and their offspring express the transgene specifically in hematopoietic tissues and develop a myeloproliferative syndrome characterized by: overproduction of mature neutrophils and megakaryocytes in the bone marrow; splenomegaly with effacement of splenic architecture by extramedullary hematopoiesis; an abnormal population of leukocytes cc-expressing lymphoid and myeloid markers; and increased numbers of colonies in in vitro bone marrow CFU assays. All mice expressing the transgene exhibited at least one of these features of dysregulated myelopoiesis, and 20% progressed to a myeloid or lymphoid malignancy. This murine model of CMML parallels a myeloproliferative syndrome in humans and implicates the Tel-PDGFR beta fusion protein in its pathogenesis. C1 VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv 113, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98195 USA. Seattle Biomed Res Inst, Seattle, WA 98109 USA. Univ Washington, Sch Publ Hlth, Dept Pathobiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Ritchie, KA (reprint author), VA Puget Sound Hlth Care Syst, Pathol & Lab Med Serv 113, 1660 S Columbian Way, Seattle, WA 98195 USA. FU NHLBI NIH HHS [K08HL02959]; NIDDK NIH HHS [DK48708-02] NR 56 TC 37 Z9 39 U1 0 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD NOV PY 1999 VL 13 IS 11 BP 1790 EP 1803 DI 10.1038/sj.leu.2401494 PG 14 WC Oncology; Hematology SC Oncology; Hematology GA 255HT UT WOS:000083664000018 PM 10557054 ER PT J AU Stone, M AF Stone, M TI Webster's new explorer medical dictionary. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, M (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 NOV 1 PY 1999 VL 124 IS 18 BP 75 EP 75 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 250MY UT WOS:000083393200038 ER PT J AU Hoge, RD Atkinson, J Gill, B Crelier, GR Marrett, S Pike, GB AF Hoge, RD Atkinson, J Gill, B Crelier, GR Marrett, S Pike, GB TI Investigation of BOLD signal dependence on cerebral blood flow and oxygen consumption: The deoxyhemoglobin dilution model SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE BOLD contrast; aerobic metabolism; perfusion; hypercapnia ID MACAQUE STRIATE CORTEX; BRAIN ACTIVATION; FUNCTIONAL MRI; STIMULATION; HUMANS; FMRI; DYNAMICS; ANATOMY AB The relationship between blood oxygenation level-dependent (BOLD) MRI signals, cerebral blood flow (CBF), and oxygen consumption (CMRO2) in the physiological steady state was investigated. A quantitative model, based on flow-dependent dilution of metabolically generated deoxyhemoglobin, was validated by measuring BOLD signals and relative CBF simultaneously in the primary visual cortex (V1) of human subjects (N = 12) during graded hypercapnia at different levels of visual stimulation. BOLD and CBF responses to specific conditions were averaged across subjects and plotted as points in the BOLD-CBF plane, tracing out lines of constant CMRO2. The quantitative deoxyhemoglobin dilution model could be fit to these measured iso-CMRO2 contours without significant (P less than or equal to 0.05) residual error and yielded MRI-based CMRO2 measurements that were in agreement with PET results for equivalent stimuli. BOLD and CBF data acquired during graded visual stimulation were then substituted into the model with constant parameters varied over plausible ranges. Relative changes in CBF and CMRO2 appeared to be coupled in an approximate ratio of similar to 2:1 for all realistic parameter settings. Magn Reson Med 42:849-863, 1999, (C) 1999 Wiley-Liss, Inc. C1 McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA USA. RP Hoge, RD (reprint author), McGill Univ, Montreal Neurol Inst, McConnell Brain Imaging Ctr, 3801 Univ St,Room WB325, Montreal, PQ H3A 2B4, Canada. RI Pike, Bruce/K-5562-2014; OI Pike, Bruce/0000-0001-8924-683X; Marrett, Sean/0000-0001-8179-6511 NR 40 TC 337 Z9 340 U1 5 U2 14 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD NOV PY 1999 VL 42 IS 5 BP 849 EP 863 DI 10.1002/(SICI)1522-2594(199911)42:5<849::AID-MRM4>3.0.CO;2-Z PG 15 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 251LV UT WOS:000083447900004 PM 10542343 ER PT J AU Mandeville, JB Marota, JJA Ayata, C Moskowitz, MA Weisskoff, RM Rosen, BR AF Mandeville, JB Marota, JJA Ayata, C Moskowitz, MA Weisskoff, RM Rosen, BR TI MRI measurement of the temporal evolution of relative CMRO(2) during rat forepaw stimulation SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE CMRO(2); BOLD; undershoot; temporal mismatch; rat ID CEREBRAL BLOOD-VOLUME; FOCAL BRAIN ACTIVATION; MAGNETIC-RESONANCE; OXIDATIVE-METABOLISM; SOMATOSENSORY CORTEX; SENSORY STIMULATION; SIGNAL CHANGES; GLUCOSE-UPTAKE; VISUAL-CORTEX; FLOW AB This study reports the first measurement of the relative cerebral metabolic rate of oxygen utilization (rCMRO(2)) during functional brain activation with sufficient temporal resolution to address the dynamics of blood oxygen level-dependent (BOLD) MRI signal. During rat forepaw stimulation, rCMRO(2) was determined in somatosensory cortex at 3-sec intervals, using a model of BOLD signal and measurements of the change in BOLD transverse relaxation rate, the resting state BOLD transverse relaxation rate, relative cerebral blood flow (rCBF), and relative cerebral blood volume (rCBV), Average percentage changes from 10 to 30 sec after onset of forepaw stimulation for rCBF, rCBV, rCMRO(2), and BOLD relaxation rate were 62 +/- 16, 17 +/- 2, 19 +/- 17, and -26 +/- 12, respectively. A poststimulus undershoot in BOLD signal was quantitatively attributed to the temporal mismatch between changes in blood flow and volume, and not to the role of oxygen metabolism. Magn Reson Med 42:944-951, 1999. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, MGH NMR Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Mandeville, JB (reprint author), Massachusetts Gen Hosp, MGH NMR Ctr, Bldg 149,Room 2301,13th St, Charlestown, MA 02129 USA. EM jbm@nmr.mgh.harvard.edu RI Moskowitz, Michael/D-9916-2011 FU NHLBI NIH HHS [2R01HL39810]; NIDA NIH HHS [DA00384, DA09467] NR 49 TC 167 Z9 170 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 1999 VL 42 IS 5 BP 944 EP 951 DI 10.1002/(SICI)1522-2594(199911)42:5<944::AID-MRM15>3.0.CO;2-W PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 251LV UT WOS:000083447900015 PM 10542354 ER PT J AU Barkhof, J Schut, G Flanz, JB Goitein, M Schippers, JM AF Barkhof, J Schut, G Flanz, JB Goitein, M Schippers, JM TI Verification of the alignment of a therapeutic radiation beam relative to its patient positioner SO MEDICAL PHYSICS LA English DT Article DE quality asurance; alignment; radiation therapy; proton beam therapy ID PROTON AB An easily-used system has been developed for routine measurements of the alignment of beams used for radiation therapy. The position of a beam of circular cross section is measured with respect to a steel sphere fixed to the patient positioning table and which should coincide with the isocenter. Since measurements can be done at all gantry angles (if one is available) and with all possible orientations of the patient table, the system is particularly suited for rapid and accurate measurements of gantry and/or couch isocentricity. Because it directly measures beam-to-positioner offset, the system provides an inclusive alignment verification of the total treatment system. The system has been developed for use with proton beams, but it could equally be used for alignment checks of an x-ray beam from a linear accelerator or other source. The measuring instrument consists of a scintillation screen viewed by a CCD camera, mounted on the gantry downstream of the sphere, The steel sphere is not large enough to stop protons of all energies of interest; however, it will always modify the energy and direction of protons which intersect it, creating a region of lower intensity (a "shadow'') in the light spot created by the proton beam hitting the screen. The position of the shadow with respect to the light spot is a measure of the alignment of the system. An image-analysis algorithm has been developed for an automatic determination of the position of the shadow with respect to the light spot. The specifications and theoretical analysis of the system have been derived from Monte Carlo simulations, which are validated by measurements. We have demonstrated that the device detects beam misalignments with an accuracy (1 s.d.) of 0.05 mm, which is in agreement with the expected performance. This accuracy is more than sufficient to detect the maximum allowed misalignment of +/- 0.5 mm. (C) 1999 American Association of Physicists in Medicine. [S0094-2405(99)00611-2]. C1 Kernfys Versneller Inst, NL-9747 AA Groningen, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NE Proton Therapy Ctr, Boston, MA 02114 USA. RP Schippers, JM (reprint author), Kernfys Versneller Inst, Zernikelaan 25, NL-9747 AA Groningen, Netherlands. EM schippers@kvi.nl FU NCI NIH HHS [CA21239, CA 59267] NR 11 TC 10 Z9 10 U1 0 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 1999 VL 26 IS 11 BP 2429 EP 2437 DI 10.1118/1.598761 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 257HE UT WOS:000083775800031 PM 10587228 ER PT J AU Iannoli, P Miller, JH Wang, HT Bode, B Souba, WW Avissar, NE Sax, HC AF Iannoli, P Miller, JH Wang, HT Bode, B Souba, WW Avissar, NE Sax, HC TI Characterization of l-leucine transport systemin brush border membranes from human and rabbit small intestine SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID AMINO-ACID-TRANSPORT; VESICLES AB The branched-chain amino acids (BCAAs) leucine, isoleucine, and valine are beneficial to catabolic patients by improving hepatic protein synthesis and nitrogen economy, yet;their transport from the intestinal lumen is not well-defined. The leucine transport system in human and rabbit small intestine was characterized using a brush border membrane vesicle (BBMV) model. Sodium and pH dependence and transport activity along the longitudinal axis of the small bowel were determined. Transport kinetics and inhibition profiles were defined. Although previous studies in other tissues show leucine transport to be mostly a Nac-independent process, our studies show that leucine transport is a predominantly Na+-dependent process occurring mainly via a single saturable pH-independent transporter resembling system B-0 in the intestine. This system B-0 transporter demonstrates stereoisomeric specificity. There is also a minor Nai-independent transport component (<6% in rabbits). Leucine uptake in both rabbits and humans is significantly greater than the uptake of other clinically relevant nutrients such as glutamine. In the rabbit, ileal leucine transport is significantly greater than jejunal uptake. While the affinities of the human and rabbit transporters are similar, the rabbit transporter has greater carrier capacity (maximal transport velocity [V-max]). These findings suggest that the transport of leucine in the gut mucosa is significantly different from the transport in other tissues. Copyright (C) 1999 by W.B. Saunders Company. C1 Univ Rochester, Med Ctr, Dept Surg, 601 Elmwood Ave, Rochester, NY 14642 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Univ Rochester, Med Ctr, Dept Surg, 601 Elmwood Ave, Rochester, NY 14642 USA. FU NIDDK NIH HHS [R29-DK47989-02] NR 13 TC 9 Z9 11 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 EI 1532-8600 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 1999 VL 48 IS 11 BP 1432 EP 1436 DI 10.1016/S0026-0495(99)90155-5 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 256VM UT WOS:000083747200017 PM 10582553 ER PT J AU Sattler, M Verma, S Byrne, CH Shrikhande, G Winkler, T Algate, PA Rohrschneider, LR Griffin, JD AF Sattler, M Verma, S Byrne, CH Shrikhande, G Winkler, T Algate, PA Rohrschneider, LR Griffin, JD TI BCR/ABL directly inhibits expression of SHIP, an SH2-containing polyinositol-5-phosphatase involved in the regulation of hematopoiesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; POLYPHOSPHATE 5-PHOSPHATASE SHIP; INOSITOL PHOSPHATASE SHIP; COLONY-STIMULATING FACTOR; DNA-BINDING ACTIVITY; BCR-ABL; PHILADELPHIA-CHROMOSOME; TRANSFORMING ACTIVITY AB The BCR/ABL oncogene causes chronic myelogenous leukemia (CML), a myeloproliferative disorder characterized by clonal expansion of hematopoietic progenitor cells and granulocyte lineage cells. The SH2-containing inositol-5-phosphatase SHIP is a 145-kDa protein which has been shown to regulate hematopoiesis in mice. Targeted disruption of the murine SHIP gene results in a myeloproliferative syndrome characterized by a dramatic increase in numbers of granulocyte-macrophage progenitor cells in the marrow and spleen. Also, hematopoietic progenitor cells from SHIP-/- mice are hyperresponsive to certain hematopoietic growth factors, a phenotype very similar to the effects of BCR/ABL in murine cells. In a series of ECR/ABL-transformed hematopoietic cell lines, Philadelphia chromosome (Ph)-positive cell lines, and primary cells from patients with CML, the expression of SHIP was found to be absent or substantially reduced compared to untransformed cell lines or leukemia cells lacking BCR/ABL. Ba/F3 cells in which expression of BCR/ABL was under the control of a tetracycline-inducible promoter showed rapid loss of p145 SHIP, coincident with induction of BCR/ABL expression. Also, an ABL-specific tyrosine kinase inhibitor, CGP57148B (STI571), rapidly caused reexpression of SHIP, indicating that BCR/ABL directly, but reversibly, regulates the expression of SHIP protein. The estimated half-life of SHIP protein was reduced from 18 h to less than 3 h. However, SHIP mRNA also decreased in response to BCR/ABL, suggesting that SHIP protein levels could be affected by more than one mechanism. Reexpression of SHIP in BCR/ABL-transformed Ba/F3 cells altered the biological behavior of cells in culture. The reduction of SHIP due to BCR/ABL is likely to directly contribute to the pathogenesis of CML. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Dept Basic Sci, Seattle, WA 98109 USA. RP Sattler, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK50654, P01 DK050654] NR 66 TC 82 Z9 84 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1999 VL 19 IS 11 BP 7473 EP 7480 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 247CM UT WOS:000083203100018 PM 10523635 ER PT J AU Turkson, J Bowman, T Adnane, J Zhang, Y Djeu, JY Sekharam, M Frank, DA Holzman, LB Wu, J Sebti, S Jove, R AF Turkson, J Bowman, T Adnane, J Zhang, Y Djeu, JY Sekharam, M Frank, DA Holzman, LB Wu, J Sebti, S Jove, R TI Requirement for Ras/Rac1-mediated p38 and c-Jun N-terminal kinase signaling in Stat3 transcriptional activity induced by the Src oncoprotein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; EPIDERMAL GROWTH-FACTOR; RHO-FAMILY GTPASES; NIH 3T3 CELLS; V-SRC; CONSTITUTIVE ACTIVATION; PHOSPHATIDYLINOSITOL 3-KINASE; DIFFERENTIAL ACTIVATION; SERINE PHOSPHORYLATION; SELECTIVE ACTIVATION AB Signal transducers and activators of transcription (STATs) are transcription factors that mediate normal biologic responses to cytokines and growth factors. However, abnormal activation of certain STAT family members, including Stat3, is increasingly associated with oncogenesis. In fibroblasts expressing the Src oncoprotein, activation of Stat3 induces specific gene expression and is required for cell transformation. Although the Src tyrosine kinase induces constitutive Stat3 phosphorylation on tyrosine, activation of Stat3-mediated gene regulation requires both tyrosine and serine phosphorylation of Stat3. We investigated the signaling pathways underlying the constitutive Stat3 activation in Src oncogenesis. Expression of Ras or Rac1 dominant negative protein blocks Stat3-mediated gene regulation induced by Src in a manner consistent with dependence on p38 and c-Jun N-terminal kinase (JNK). Both of these serine/threonine kinases and Stat3 serine phosphorylation are constitutively induced in Src-transformed fibroblasts. Furthermore, inhibition of p38 and JNK activities suppresses constitutive Stat3 serine phosphorylation and Stat3-mediated gene regulation. In vitro kinase assays with purified full-length Stat3 as the substrate show that both JNK and p38 can phosphorylate Stat3 on serine. Moreover, inhibition of p38 activity and thus of Stat3 serine phosphorylation results in suppression of transformation by v-Src but not v-Ras, consistent with a requirement for Stat3 serine phosphorylation in Src transformation. Our results demonstrate that Ras- and Rac1-mediated p38 and JNK signals are required for Stat3 transcriptional activity induced by the Src oncoprotein. These findings delineate a network of tyrosine and serine/threonine kinase signaling pathways that converge on Stat3 in the context of oncogenesis. C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Mol Oncol Program, Tampa, FL 33612 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Program Immunol, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Immunol & Med Microbiol, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Dept Biochem & Mol Biol, Tampa, FL 33612 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. RP Jove, R (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Mol Oncol Program, 12902 Magnolia Dr, Tampa, FL 33612 USA. FU NCI NIH HHS [CA76661, CA55652, R01 CA055652] NR 78 TC 185 Z9 186 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1999 VL 19 IS 11 BP 7519 EP 7528 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 247CM UT WOS:000083203100023 PM 10523640 ER PT J AU Ubeda, M Vallejo, M Habener, JF AF Ubeda, M Vallejo, M Habener, JF TI CHOP enhancement of gene transcription by interactions with Jun/Fos AP-1 complex proteins SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GLUCOSE-REGULATED PROTEINS; ELEMENT-BINDING PROTEIN; PROGRAMMED CELL-DEATH; RESPONSE ELEMENT; DNA-BINDING; ENDOPLASMIC-RETICULUM; LEUCINE-ZIPPER; MESSENGER-RNA; C-FOS; DIFFERENTIAL REGULATION AB The transcription factor CHOP (C/EBP homologous protein 10) is a bZIP protein induced by a variety of stimuli that evoke cellular stress responses and has been shown to arrest cell growth and to promote programmed cell death. CHOP cannot form homodimers but forms stable heterodimers with the C/EBP family of activating transcription factors. Although initially characterized as a dominant negative inhibitor of C/EBPs in the activation of gene transcription, CHOP-C/EBP can activate certain target genes. Here we show that CHOP interacts with members of the immediate-early response, growth-promoting AP-1 transcription factor family, JunD, c-Jun, and c-Fos, to activate promoter elements in the somatostatin, JunD, and collagenase genes. The leucine zipper dimerization domain is required for interactions with AP-1 proteins and transactivation of transcription. Analyses by electrophoretic mobility shift assays and by an in vivo mammalian two-hybrid system for protein-protein interactions indicate that CHOP interacts with AP-1 proteins inside cells and suggest that it is recruited to the AP-1 complex by a tethering mechanism rather than by direct binding of DNA. Thus, CHOP not only is a negative or a positive regulator of C/EBP target genes but also, when tethered to AP-1 factors, can activate AP-1 target genes. These findings establish the existence of a new mechanism by which CHOP regulates gene expression when cells are exposed to cellular stress. C1 Massachusetts Gen Hosp, Mol Endocrinol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrinol Unit, 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, 55 Fruit St,WEL320, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK30457] NR 54 TC 101 Z9 104 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1999 VL 19 IS 11 BP 7589 EP 7599 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 247CM UT WOS:000083203100030 PM 10523647 ER PT J AU Lee, KY Ladha, MH McMahon, C Ewen, ME AF Lee, KY Ladha, MH McMahon, C Ewen, ME TI The retinoblastoma protein is linked to the activation of Ras SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SKELETAL-MUSCLE CELLS; LARGE TUMOR-ANTIGEN; LARGE-T-ANTIGEN; GLUCOCORTICOID RECEPTOR; GENE-EXPRESSION; MAMMALIAN-CELLS; LOW-PENETRANCE; CYCLE CONTROL; RB-1 GENE; DIFFERENTIATION AB The inner membrane-bound protein Ras integrates various extracellular signals that are subsequently communicated from the cytoplasm to the nucleus via the Raf/MEK/MAPK cascade. Here we show that the retinoblastoma protein pRb, previously reported to be a nuclear target of this pathway, can in turn influence the activation state of Ras. Rb-deficient fibroblasts display elevated levels (up to 30-fold) of activated Ras during G(1). Expression of wild-type pRb or a number of pRb mutants defective in E2F regulation reverses this effect. We provide evidence that the mid-G(1) activation of Ras in Rb-deficient cells, which occurs at the level of guanine nucleotide binding, differs from that of epidermal growth factor-induced stimulation of pas, being dependent on protein synthesis. The aberrant levels of Ras activity associated with loss of pRb may be responsible fur the differentiation defects in Rb-deficient cells, because suppression of Ras activity in Rb-/- fibroblasts restores the transactivation function of MyoD and the expression of a late marker of skeletal muscle differentiation. These data suggest that nuclear-cytoplasmic communication between pRb and Ras is bidirectional. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ewen, ME (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [R01 CA065842, CA65842] NR 64 TC 53 Z9 53 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 1999 VL 19 IS 11 BP 7724 EP 7732 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 247CM UT WOS:000083203100044 PM 10523661 ER PT J AU Venti, AM Moir, R Bridges, KR Tanzi, RE Bush, A Van Nostrand, WE Rogers, JT AF Venti, AM Moir, R Bridges, KR Tanzi, RE Bush, A Van Nostrand, WE Rogers, JT TI The amino terminus of secreted amyloid precursor protein exhibits ferroxidase activity SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Dartmouth Coll, Hanover, NH 03755 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. SUNY, Dept Psychiat & Behav Sci, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 349 BP 60A EP 60A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500348 ER PT J AU Sorkin, BC Jonsson, MV Poveromo, JD Mohamed, NAS Shaulov, A Esch, TR AF Sorkin, BC Jonsson, MV Poveromo, JD Mohamed, NAS Shaulov, A Esch, TR TI E-cadherin expression on leukocytes in a mouse model for Sjogren's syndrome SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Cairo Univ, Cairo, Egypt. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 404 BP 70A EP 70A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500404 ER PT J AU Trettel, F Persichetti, F Rigamonti, D Cattaneo, E MacDonald, ME AF Trettel, F Persichetti, F Rigamonti, D Cattaneo, E MacDonald, ME TI Nuclear and cytoplasmic location of huntingtin in embryonic neurons suggests multiple functions SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Univ Milan, Inst Pharmacol Sci, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 577 BP 100A EP 100A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500580 ER PT J AU Kyriakis, JM Makkinje, A Force, T Bonventre, JV AF Kyriakis, JM Makkinje, A Force, T Bonventre, JV TI Gene 33, an immediate-early gene induced in response to Pro-II gamma pertrophic stresses, encodes an adapter protein that binds Cdc42Hs and activates SAPK/JNK SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Diabet Res Lab, MGH E, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 682 BP 118A EP 118A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500682 ER PT J AU Chen, LF Wang, F Meng, HP Corey, DP Sellers, JR AF Chen, LF Wang, F Meng, HP Corey, DP Sellers, JR TI Baculovirus-mediated expression of myosin X. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 NHLBI, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 952 BP 164A EP 164A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673500951 ER PT J AU Huang, JN Park, I Ellingson, EM Littlepage, L Pellman, DS AF Huang, JN Park, I Ellingson, EM Littlepage, L Pellman, DS TI In vivo analysis or the timing of APC activity. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Texas Childrens Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1127 BP 194A EP 194A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501128 ER PT J AU Hilditch-Maguire, PA Calzonetti, T Joyner, AL MacDonald, ME AF Hilditch-Maguire, PA Calzonetti, T Joyner, AL MacDonald, ME TI Huntingtin is required during embryogenesis. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1198 BP 207A EP 207A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501199 ER PT J AU Aballay, A Damiani, MT Ren, MD Adesnik, M Mayorga, LS Sabatini, DD Stahl, PD Colombo, MI AF Aballay, A Damiani, MT Ren, MD Adesnik, M Mayorga, LS Sabatini, DD Stahl, PD Colombo, MI TI Rab11 stimulates fluid phase and mannose receptor-mediated endocytosis by regulating endosome fusion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Nacl Cuyo, RA-5500 Mendoza, Argentina. NYU, New York, NY USA. Washington Univ, St Louis, MO 63130 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1284 BP 221A EP 221A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501283 ER PT J AU Wiederhold, T James, M Stemmer-Rachamimov, A Pinney-Michalowski, D Levenson, R Gonzalez-Agosti, C Gusella, J Louis, D Ramesh, V AF Wiederhold, T James, M Stemmer-Rachamimov, A Pinney-Michalowski, D Levenson, R Gonzalez-Agosti, C Gusella, J Louis, D Ramesh, V TI The MERM interactor NHE-RF is up-regulated and displays a response through estrogen in breast cancer SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1401 BP 242A EP 242A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501401 ER PT J AU Geiser, JR Kahana, JA Silver, P Hoyt, MA AF Geiser, JR Kahana, JA Silver, P Hoyt, MA TI Establishing the role of S-cerevisiae Bik1p and Pac1p within the cytoplasmic dynein complex. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Western Michigan Univ, Kalamazoo, MI 49008 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1436 BP 248A EP 248A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501438 ER PT J AU Italiano, JE Lecine, P Shivdasani, RA Hartwig, JH AF Italiano, JE Lecine, P Shivdasani, RA Hartwig, JH TI Ultrastructure and dynamics of platelet formation by megakaryocytes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Lecine, Patrick/H-9338-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1487 BP 257A EP 257A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501487 ER PT J AU Clarke, MSF Vanderburg, CR Carpenter, J Howerte, C Abbasi, T Feeback, DL AF Clarke, MSF Vanderburg, CR Carpenter, J Howerte, C Abbasi, T Feeback, DL TI Macromolecular loading and transfection of adherent cells utilizing a navel hypergravity-assisted impact-mediated loading device. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Space Res Assoc, Houston, TX 77058 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1566 BP 270A EP 270A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501567 ER PT J AU Ross, AJ Mahar, P Waymire, K Knudson, M Korsmeyer, S MacGregor, G AF Ross, AJ Mahar, P Waymire, K Knudson, M Korsmeyer, S MacGregor, G TI Bclw and Bax regulate survival of Sertoli cells in the testis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Emory Univ, Atlanta, GA 30322 USA. Univ Iowa, Coll Med, Iowa City, IA 52242 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1613 BP 279A EP 279A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501614 ER PT J AU Kedersha, NL Gupta, M Miller, IJ Streuli, M Anderson, P AF Kedersha, NL Gupta, M Miller, IJ Streuli, M Anderson, P TI Phosphorylation of eIF-2 alpha promotes the recruitment of untranslated mRNAs to TIA-1/R+ stress granules SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1699 BP 293A EP 293A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501700 ER PT J AU Altschuler, Y Casanova, JE Apodaca, G Liu, SH Brodsky, FM Mostov, KE AF Altschuler, Y Casanova, JE Apodaca, G Liu, SH Brodsky, FM Mostov, KE TI ARF6 and ARNO regulate a dynamin and clathrin dependent endocytosis pathway at the apical surface of MDCK cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Calif San Francisco, Sch Med, San Francisco, CA 94132 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, GW Hooper Fdn, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1779 BP 307A EP 307A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501780 ER PT J AU Huang, R Lian, JP Crossley, L Robinson, D Toker, A Badwey, JA AF Huang, R Lian, JP Crossley, L Robinson, D Toker, A Badwey, JA TI Antagonists of calcium fluxes and calmodulin (CaM) block activation of the p21-activated protein kinases (Paks) in neutrophils. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Biomed Res Inst, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1841 BP 318A EP 318A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501840 ER PT J AU Sharma, PC Goldmann, WH Arnaout, AM AF Sharma, PC Goldmann, WH Arnaout, AM TI Regulation of focal adhesion kinase (pp125FAK) by p56lck and protein kinase c (PKC). SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RI Goldmann, Wolfgang/H-5572-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 1945 BP 336A EP 336A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673501947 ER PT J AU Maravei, DV Morita, Y Kuida, K Tilly, JL AF Maravei, DV Morita, Y Kuida, K Tilly, JL TI Pre- and postnatal ovarian apoptosis defects in caspase-9-deficient mice. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Vertex Pharmaceut Inc, Cambridge, MA 02139 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2037 BP 352A EP 352A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502036 ER PT J AU Meyer, GE Kim, B Shelden, E Feldman, EL AF Meyer, GE Kim, B Shelden, E Feldman, EL TI Phosphoinositol-3 kinase is required for insulin-like growth Factor-I-Mediated motility in neuroblastoma cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2197 BP 380A EP 380A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502196 ER PT J AU Wang, X Kumar, R Goldenring, JR Cassanova, JE AF Wang, X Kumar, R Goldenring, JR Cassanova, JE TI Rab11a and Rab25 regulate distinct aspects of apical recycling endosome function. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Med Coll Georgia, Augusta, GA 30912 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2292 BP 396A EP 396A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502291 ER PT J AU Aballay, A Drenkard, E Plotnikova, J Ausubel, FM AF Aballay, A Drenkard, E Plotnikova, J Ausubel, FM TI The intracellular survival of Pseudomonas aeruginosa is reduced by mutations in virulence-related genes. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2297 BP 397A EP 397A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502299 ER PT J AU Guenette, SY Hyman, BT Tanzi, RE Rebeck, GW AF Guenette, SY Hyman, BT Tanzi, RE Rebeck, GW TI The hFE65L adapter protein binds APP and LRP. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2323 BP 401A EP 401A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502324 ER PT J AU McCarthy, KM Francis, SA McCormack, JM Rogers, RA Lynch, RD Schneeberger, EE AF McCarthy, KM Francis, SA McCormack, JM Rogers, RA Lynch, RD Schneeberger, EE TI Distribution of claudin-1-myc, but not occludin-vsvg, is altered when over-expressed in MDCK cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Massachusetts, Lowell, MA 01854 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2363 BP 408A EP 408A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502362 ER PT J AU Jost-Paquin, K Thompson, CM Francis, S Schneeberger, EE Lynch, RD AF Jost-Paquin, K Thompson, CM Francis, S Schneeberger, EE Lynch, RD TI Methyl-beta-cyclodextrin induced changer in phospholipase D (PLD) activity are coincident with alterations in transepithelial electrical resistance (TER) of MDCK cell monolayers SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Massachusetts, Lowell, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2366 BP 409A EP 409A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502369 ER PT J AU Troxell, ML Gopalakrishnan, S Poteat, BA Nelson, WJ Schneeberger, EE Marrs, JA AF Troxell, ML Gopalakrishnan, S Poteat, BA Nelson, WJ Schneeberger, EE Marrs, JA TI Cadherin functions revealed by mutant E-cadherin phenotype in MDCK cells. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Stanford Univ, Sch Med, Stanford, CA 94305 USA. Indiana Univ, Bloomington, IN 47405 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2367 BP 409A EP 409A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502367 ER PT J AU Roth, J Zuber, C Spiro, MJ Spiro, RG Guhl, B Roth, J AF Roth, J Zuber, C Spiro, MJ Spiro, RG Guhl, B Roth, J TI Immunolocalization of endomannosidase in the intermediate compartment and Golgi apparatus suggests post-endoplasmic reticulum glucose trimming and protein quality control. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Univ Zurich, Div Cell & Mol Pathol, CH-8091 Zurich, Switzerland. Harvard Univ, Sch Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2397 BP 414A EP 414A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502396 ER PT J AU Frank, SR Altschuler, Y Mostov, KE Casanova, JE AF Frank, SR Altschuler, Y Mostov, KE Casanova, JE TI ARNO and ARF6 coordinately regulate cell spreading and migration SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. UCSF, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2409 BP 416A EP 416A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502410 ER PT J AU Santy, LC Frank, SR Hatfield, J Casanova, JE AF Santy, LC Frank, SR Hatfield, J Casanova, JE TI Regulation of ARNO nucleotide exchange by a PH domain electrostatic switch SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2408 BP 416A EP 416A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502407 ER PT J AU Jonasch, E Mosterman, B Mier, JW Janssen, RAJ AF Jonasch, E Mosterman, B Mier, JW Janssen, RAJ TI Radicicol and KSR restore the expression of the tumor suppressor tropomyosin in transformed cells. Role of uncoupling Elk activity from ERK activation. SO MOLECULAR BIOLOGY OF THE CELL LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CELL BIOLOGY PI BETHESDA PA PUBL OFFICE, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 1999 VL 10 SU S MA 2435 BP 421A EP 421A PG 1 WC Cell Biology SC Cell Biology GA 255MW UT WOS:000083673502435 ER PT J AU Huang, LL Pardee, AB AF Huang, LL Pardee, AB TI beta-lapachone induces cell cycle arrest and apoptosis in human colon cancer cells SO MOLECULAR MEDICINE LA English DT Article ID DNA TOPOISOMERASE-I; HUMAN-FIBROBLASTS; P53; INDUCTION; INHIBITOR; CAMPTOTHECIN; REPAIR; DEATH; POLYMERASE; EXPRESSION AB Background: Human colon cancers have a high frequency of p53 mutations, and cancer cells expressing mutant p53 tend to be resistant to current chemo- and radiation therapy. It is thus important to find therapeutic agents that can inhibit colon cancer cells with altered p53 status. beta-Lapachone, a novel topoisomerase inhibitor, has been shown to induce cell death in human promyelocytic leukemia and prostate cancer cells through a p53-independent pathway. Here we examined the effects of beta-lapachone on human colon cancer cells. Materials and Methods: Several human colon cancer cell Lines, SW480, SW620, and DLD1, with mutant or defective p53, were used. The antiproliferative effects of beta-lapachone were assessed by colony formation assays, cell cycle analysis, and apoptosis analysis, including annexin V staining and DNA laddering analysis. The effects on cell cycle and apoptosis regulatory proteins were examined by immunoblotting. Results: All three cell lines, SW480, SW620, and DLD1, were sensitive to beta-lapachone, with an IC50 of 2 to 3 mu M in colony formation assays, a finding similar to that previously reported for prostate cancer cells. However, these cells were arrested in different stages of S phase. At 24 hr post-treatment, beta-lapachone induced S-, late S/G2-, and early S-phase arrest in SW480, SW620, and DLD1 cells, respectively. The cell cycle alterations induced by beta-lapachone were congruous with changes in cell cycle regulatory proteins such as cyclin A, cyclin B1, cdc2, and cyclin D1. Moreover, beta-lapachone induced apoptosis, as demonstrated by annexin V staining, now cytometric analysis of DNA content, and DNA laddering analysis. Furthermore, down-regulation of mutant p53 and induction of p27 in SW480 cells, and induction of pro-apoptotic protein Bar in DLD1 cells may be pertinent to the anti-proliferative and apoptotic effects of beta-lapachone on these cells. Conclusions: beta-Lapachone induced cell cycle arrest and apoptosis in human colon cancer cells through a p53-independent pathway. For human colon cancers, which often contain p53 mutations, beta-lapachone may prove to be a promising anticancer agent that can target cancer cells, especially those with mutant p53. C1 Dana Farber Canc Inst, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. RP Huang, LL (reprint author), Dana Farber Canc Inst, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [2-T32-CA09361, R01CA61253] NR 42 TC 52 Z9 56 U1 0 U2 1 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 NOV PY 1999 VL 5 IS 11 BP 711 EP 720 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 280BA UT WOS:000085081100001 PM 10656873 ER PT J AU Imai, M Takigami, K Guckelberger, O Enjyoji, K Smith, RN Lin, Y Csizmadia, E Sevigny, J Rosenberg, RD Bach, FH Robson, SC AF Imai, M Takigami, K Guckelberger, O Enjyoji, K Smith, RN Lin, Y Csizmadia, E Sevigny, J Rosenberg, RD Bach, FH Robson, SC TI Modulation of nucleotide triphosphate diphosphohydrolase-1 (NTPDase-1)/cd39 in xenograft rejection SO MOLECULAR MEDICINE LA English DT Article ID ENDOTHELIAL-CELL ACTIVATION; VASCULAR ATP-DIPHOSPHOHYDROLASE; ADENINE-NUCLEOTIDES; CARDIAC XENOGRAFTS; EXTRACELLULAR ATP; PLATELET-FUNCTION; ECTO-ATPASES; INHIBITION; THROMBOREGULATION; CD39 AB Background: There is increasing evidence showing that extracellular nucleotides may be important mediators of vascular inflammation. Nucleotide triphosphate diphos-phohydrolase-1 (NTPDase-1, identical to CD39), the major vascular endothelial ectonucleotidase, is responsible for the hydrolysis of both extracellular ATP and ADP in the blood plasma to AMP. Studies were therefore conducted to evaluate the role of vascular NTPDase-1/cd39 in modulating platelet activation and vascular injury in cardiac xenografts. Materials and Methods: Cardiac xenografts from both wild-type and cd39 knockout mice (C57BL/6 x 129 Svj) were transplanted into Lewis rats. Alterations in cd39 mRNA transcripts and NTPDase activity expression were evaluated in wild-type grafts in untreated rats and then following complement depletion and immunosuppression. Rejection responses were studied with both mutant and wildtype grafts in the following models: presensitization with or without complement depletion, complement depletion alone, and with chronic immunosuppression to induce long-term graft survival. Results: NTPDase biochemical activity in wild-type xenografts rapidly decreased after transplantation but soon rebounded with graft survival. Elevated levels of cd39 mRNA with associated increases in NTPDase activity were observed in all long-term surviving wild-type grafts. Hyperacute xenograft rejection times were comparable in wild-type and mutant grafts but cd39-deficient grafts were subject to more rapid rejection and exhibited pronounced vascular injury in complement-depleted presensitized rats. The cd39-deficient grafts in immunosuppressed recipients were subject to increased intravascular platelet sequestration and fibrin deposition; this resulted in focal myocardial infarction in long-term surviving mutant xenografts. Conclusions: Augmentation of NTPDase-1 activity may be an important adaptive response for graft survival. Our results suggest that NTPDase-1/cd39 influences pathways of vascular injury in cardiac xenografts. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Asahikawa Med Coll, Dept Surg 2, Asahikawa, Hokkaido, Japan. MIT, Dept Biol, Cambridge, MA USA. Natl Cardiovasc Ctr, Clin Pathol Lab, Osaka, Japan. Massachusetts Gen Hosp, Dept Pathol, Immunopathol Unit, Boston, MA 02114 USA. RP Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Surg, 99 Brookline Ave, Boston, MA 02215 USA. EM srobson@caregroup.harvard.edu RI Lin, Yijun/B-5711-2009; Sevigny, Jean/E-8039-2012 OI Sevigny, Jean/0000-0003-2922-1600 FU NHLBI NIH HHS [HL 57307]; PHS HHS [P01-41484] NR 41 TC 36 Z9 36 U1 0 U2 1 PU FEINSTEIN INST MED RES PI MANHASSET PA 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1076-1551 EI 1528-3658 J9 MOL MED JI Mol. Med. PD NOV PY 1999 VL 5 IS 11 BP 743 EP 752 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 280BA UT WOS:000085081100004 PM 10656876 ER PT J AU Watnick, PI Kolter, R AF Watnick, PI Kolter, R TI Steps in the development of a Vibrio cholerae El Tor biofilm SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; PSEUDOMONAS-AERUGINOSA; TWITCHING MOTILITY; MICROBIAL BIOFILMS; GENETIC-ANALYSIS; RESISTANCE; FLAGELLAR; EXOPOLYSACCHARIDE; COLONIZATION; EXPRESSION AB We report that, in a simple, static culture system, wildtype Vibrio cholerae EI Tor forms a three-dimensional biofilm with characteristic water channels and pillars of bacteria. Furthermore, we have isolated and characterized transposon insertion mutants of V. cholerae that are defective in biofilm development. The transposons were localized to genes involved in (i) the biosynthesis and secretion of the mannose-sensitive haemagglutinin type IV pilus (MSHA); (ii) the synthesis of exopolysaccharide; and (iii) flagellar motility. The phenotypes of these three groups suggest that the type IV pilus and flagellum accelerate attachment to the abiotic surface, the flagellum mediates spread along the abiotic surface, and exopolysaccharide is involved in the formation of three-dimensional biofilm architecture. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Kolter, R (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, 200 Longwood Ave, Boston, MA 02115 USA. FU NIAID NIH HHS [K08 AI001588, K08 AI001588-01, K08AI01588]; NIGMS NIH HHS [GM58213, R01 GM058213] NR 39 TC 374 Z9 397 U1 4 U2 30 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 1999 VL 34 IS 3 BP 586 EP 595 DI 10.1046/j.1365-2958.1999.01624.x PG 10 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 255QG UT WOS:000083680500017 PM 10564499 ER PT J AU Tarazi, FI Baldessarini, RJ AF Tarazi, FI Baldessarini, RJ TI Dopamine D-4 receptors: significance for molecular psychiatry at the millennium SO MOLECULAR PSYCHIATRY LA English DT Review DE antipsychotics; attention deficit hyperactivity disorder; D-4; dopamine; mRNA; Parkinson's disease; psychotic disorders; receptors; schizophrenia ID DEFICIT HYPERACTIVITY DISORDER; ATYPICAL ANTIPSYCHOTIC-DRUGS; NUCLEUS-ACCUMBENS-SEPTI; D4 RECEPTOR; RAT-BRAIN; MESSENGER-RNA; CEREBRAL-CORTEX; HIGH-AFFINITY; IN-VIVO; PHARMACOLOGICAL CHARACTERIZATION AB Extraordinary progress has been made in the molecular, genetic, anatomical, and pharmacological characterization of dopamine D-4, receptors in animal and human brain. Clarification of the neurochemical and physiological roles of these cerebral receptors is emerging, Postmortem neuropathological studies have inconsistently linked D-4, receptors to psychotic disorders, and genetic studies have failed to sustain conclusive associations between D-4, receptors and schizophrenia. However, associations are emerging between D-4, receptors and other neuropsychiatric disorders, including attention deficit hyperactivity disorder, mood disorders, and Parkinson's disease, as well as specific personality traits such as novelty-seeking. Selective D-4, agonists and antagonists have been developed as useful experimental probes, D-4, antagonists, so far, have proved ineffective in treatment of schizophrenia, but testing in a broader range of disorders may yield clinically useful drugs, D-4, receptors appear to have broad implications for the pathophysiology of neuropsychiatric illnesses and their improved treatment. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Tarazi, FI (reprint author), Harvard Univ, Sch Med, McLean Hosp, Mailman Res Ctr, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-34006, MH-19905, MH-47370] NR 115 TC 60 Z9 61 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 1999 VL 4 IS 6 BP 529 EP 538 DI 10.1038/sj.mp.4000674 PG 10 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 258KN UT WOS:000083838500005 PM 10578234 ER PT J AU Sieberer, MG Vieregge, P Klein, C Ozelius, LJ Wandinger, KP AF Sieberer, MG Vieregge, P Klein, C Ozelius, LJ Wandinger, KP TI Concordant late onset of craniocervical dystonia in a pair of monozygotic twins SO MOVEMENT DISORDERS LA English DT Article ID IDIOPATHIC TORSION DYSTONIA; ADULT-ONSET; CERVICAL DYSTONIA; FOCAL DYSTONIA; CHROMOSOME 18P; FAMILY; GENE C1 Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. Med Univ Lubeck, Inst Immunol, D-23538 Lubeck, Germany. Massachusetts Gen Hosp, Mol Neurogenet Lab, Boston, MA USA. RP Vieregge, P (reprint author), Med Univ Lubeck, Dept Neurol, Ratzeburger Allee 160, D-23538 Lubeck, Germany. FU NINDS NIH HHS [NS38142-01] NR 28 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD NOV PY 1999 VL 14 IS 6 BP 1040 EP 1043 DI 10.1002/1531-8257(199911)14:6<1040::AID-MDS1025>3.0.CO;2-9 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 255QM UT WOS:000083681100025 PM 10584687 ER PT J AU Adebanjo, OA Anandatheerthavarada, HK Koval, AP Moonga, BS Biswas, G Sun, L Sodam, BR Bevis, PJR Huang, CLH Epstein, S Lai, FA Avadhani, NG Zaidi, M AF Adebanjo, OA Anandatheerthavarada, HK Koval, AP Moonga, BS Biswas, G Sun, L Sodam, BR Bevis, PJR Huang, CLH Epstein, S Lai, FA Avadhani, NG Zaidi, M TI A new function for CD38/ADP-ribosyl cyclase in nuclear Ca2+ homeostasis SO NATURE CELL BIOLOGY LA English DT Article ID RAT-LIVER NUCLEI; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR; EXTRACELLULAR CA2+; PHOSPHOLIPASE-C; CALCIUM; RELEASE; PROTEIN; KINASE AB Nucleoplasmic calcium ions (Ca2+) influence nuclear functions as critical as gene transcription, apoptosis, DNA repair, topoisomerase activation and polymerase unfolding. Although both inositol trisphosphate receptors and ryanodine receptors, types of Ca2+ channel, are present in the nuclear membrane, their role in the homeostasis of nuclear Ca2+ remains unclear. Here we report the existence in the inner nuclear membrane of a functionally active CD38/ADP-ribosyl cyclase that has its catalytic site within the nucleoplasm. We propose that the enzyme catalyses the intranuclear cyclization of nicotinamide adenine dinucleotide to cyclic adenosine diphosphate ribose. The latter activates ryanodine receptors of the inner nuclear membrane to trigger nucleoplasmic Ca2+ release. C1 CUNY Mt Sinai Sch Med, Div Endocrinol, New York, NY 10029 USA. Med Coll Penn & Hahnemann Univ, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Dept Anim Biol, Philadelphia, PA 19104 USA. Univ Cambridge, Physiol Lab, Cardiff CB2 3EG, S Glam, Wales. Univ Wales, Coll Med, Cardiff CF14 4XN, S Glam, Wales. RP Zaidi, M (reprint author), CUNY Mt Sinai Sch Med, Div Endocrinol, Mailbox 1055,1 Gustave Levy Pl, New York, NY 10029 USA. RI Huang, Christopher/A-6248-2008 FU NCI NIH HHS [R37-CA22762]; NIA NIH HHS [R01-AG14917] NR 27 TC 116 Z9 118 U1 0 U2 2 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 1999 VL 1 IS 7 BP 409 EP 414 PG 6 WC Cell Biology SC Cell Biology GA 252ZX UT WOS:000083533100013 PM 10559984 ER PT J AU Malecki, MT Jhala, US Antonellis, A Fields, L Doria, A Orban, T Saad, M Warram, JH Montminy, M Krolewski, AS AF Malecki, MT Jhala, US Antonellis, A Fields, L Doria, A Orban, T Saad, M Warram, JH Montminy, M Krolewski, AS TI Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitus SO NATURE GENETICS LA English DT Article ID MOLECULAR-CLONING; CRYSTAL-STRUCTURE; GENE; YOUNG; P300; DIFFERENTIATION; RECOGNITION; BINDING; REGION; DIMER C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Univ Calif Los Angeles, Sch Med, Div Endocrinol, Los Angeles, CA USA. RP Krolewski, AS (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. FU NIDDK NIH HHS [DK-36836, DK-47475] NR 25 TC 341 Z9 367 U1 0 U2 12 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 NOV PY 1999 VL 23 IS 3 BP 323 EP 328 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 257QC UT WOS:000083792200022 PM 10545951 ER PT J AU Madsen, LS Andersson, EC Jansson, L Krogsgaard, M Andersen, CB Engberg, J Strominger, JL Svejgaard, A Hjorth, JP Holmdahl, R Wucherpfennig, KW Fugger, L AF Madsen, LS Andersson, EC Jansson, L Krogsgaard, M Andersen, CB Engberg, J Strominger, JL Svejgaard, A Hjorth, JP Holmdahl, R Wucherpfennig, KW Fugger, L TI A humanized model for multiple sclerosis using HLA-DR2 and a human T-cell receptor SO NATURE GENETICS LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; BASIC-PROTEIN PEPTIDE; TRANSGENIC MICE; MYELIN; SUSCEPTIBILITY; EXPRESSION; COMPLEX; SCREEN; LOCI; CD4 C1 Aarhus Univ Hosp, Skejby Sygehus, Dept Clin Immunol, DK-8000 Aarhus, Denmark. Rigshosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark. Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark. Royal Danish Sch Pharm, Dept Pharmacol, DK-2100 Copenhagen, Denmark. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Aarhus Univ, Inst Mol & Struct Biol, Aarhus, Denmark. Univ Lund, Sect Med Inflammat Res, Lund, Sweden. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Fugger, L (reprint author), Aarhus Univ Hosp, Skejby Sygehus, Dept Clin Immunol, DK-8000 Aarhus, Denmark. NR 30 TC 221 Z9 224 U1 1 U2 6 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 NOV PY 1999 VL 23 IS 3 BP 343 EP 347 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 257QC UT WOS:000083792200026 PM 10610182 ER PT J AU Goulder, PJR Walker, BD AF Goulder, PJR Walker, BD TI The great escape - AIDS viruses and immune control SO NATURE MEDICINE LA English DT Editorial Material ID CYTOTOXIC T-LYMPHOCYTES; PRIMARY INFECTION; SELECTION; PROGRESSION; VARIANTS C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02120 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Goulder, PJR (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 13th St,Bldg 149,Rm 5218, Charlestown, MA 02120 USA. NR 16 TC 48 Z9 49 U1 1 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 1999 VL 5 IS 11 BP 1233 EP 1235 DI 10.1038/15184 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 305PZ UT WOS:000086550600022 PM 10545982 ER PT J AU Li, P Kerchner, GA Sala, C Wei, F Huettner, JE Sheng, M Zhuo, M AF Li, P Kerchner, GA Sala, C Wei, F Huettner, JE Sheng, M Zhuo, M TI AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses SO NATURE NEUROSCIENCE LA English DT Article ID PROTEIN-KINASE-C; SPINOTHALAMIC TRACT NEURONS; LONG-TERM POTENTIATION; DORSAL HORN; SILENT SYNAPSES; GLUTAMATE RECEPTORS; RAT; CORD; TRANSMISSION; DOMAIN AB Silent synapses form between some primary sensory afferents and dorsal horn neurons in the spinal cord. Molecular mechanisms for activation or conversion of silent synapses to conducting synapses are unknown. Serotonin can trigger activation of silent synapses in dorsal horn neurons by recruiting AMPA receptors. AMPA-receptor subunits GluR2 and GluR3 interact via their cytoplasmic C termini with PDZ-domain-containing proteins such as GRIP (glutamate receptor interacting protein), but the functional significance of these interactions is unclear. Here we demonstrate that protein interactions involving the GluR2/3 C terminus are important for serotonin-induced activation of silent synapses in the spinal cord. Furthermore, PKC is a necessary and sufficient trigger for this activation. These results implicate AMPA receptor-PDZ interactions in mechanisms underlying sensory synaptic potentiation and provide insights into the pathogenesis of chronic pain. C1 Washington Univ, Sch Med, Dept Anesthesiol Anat & Neurobiol, St Louis, MO 63110 USA. 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. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Zhuo, M (reprint author), Washington Univ, Sch Med, Dept Anesthesiol Anat & Neurobiol, Campus Box 8054,660 S Euclid Ave, St Louis, MO 63110 USA. RI Zhuo, Min/A-2072-2008; Huettner, James/C-5219-2012; Sala, Carlo/A-2493-2009 OI Zhuo, Min/0000-0001-9062-3241; Sala, Carlo/0000-0003-0662-9523 FU NINDS NIH HHS [R01 NS030888] NR 46 TC 142 Z9 146 U1 1 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 1999 VL 2 IS 11 BP 972 EP 977 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 259FF UT WOS:000083883300013 PM 10526335 ER PT J AU Salat, DH Stangl, PA Kaye, JA Janowsky, JS AF Salat, DH Stangl, PA Kaye, JA Janowsky, JS TI Sex differences in prefrontal volume with aging and Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE frontal lobe; prefrontal; sex characteristics; aging; aged; Alzheimer's disease; magnetic resonance imaging; gray matter; human ID HEALTHY OLDEST-OLD; GENDER DIFFERENCES; GRAY-MATTER; IN-VIVO; CEREBRAL-CORTEX; BRAIN ATROPHY; DEMENTIA; MR; EPIDEMIOLOGY; HIPPOCAMPUS AB We used volumetric magnetic resonance imaging to examine sex differences in prefrontal tissue volumes of healthy aged and patients with Alzheimer's disease (AD). Healthy subjects had greater total prefrontal volume than AD, and men had greater total prefrontal volume than women (ps less than or equal to 0.02). This was true for both gray and white matter volumes. There were no interactions between group and sex for total prefrontal volume. An exploratory analysis of each group suggested that sex differences in both gray and white matter in healthy aging are not sustained in AD. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland Vet Affairs Med Ctr, Portland, OR 97201 USA. RP Salat, DH (reprint author), Oregon Hlth Sci Univ, Dept Behav Neurosci, 3181 SW Sam Jackson Pk Rd, Portland, OR 97201 USA. OI Kaye, Jeffrey/0000-0002-9971-3478 FU NIA NIH HHS [AG0817, AG12611]; NIMH NIH HHS [MH11855] NR 25 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 1999 VL 20 IS 6 BP 591 EP 596 DI 10.1016/S0197-4580(99)00067-6 PG 6 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 281FW UT WOS:000085148100003 PM 10674424 ER PT J AU Friston, KJ Zarahn, E Josephs, O Henson, RNA Dale, AM AF Friston, KJ Zarahn, E Josephs, O Henson, RNA Dale, AM TI Stochastic designs in event-related fMRI SO NEUROIMAGE LA English DT Article DE functional neuroimaging; fMRI; stochastic; event-related; experimental design ID FUNCTIONAL MRI; RESPONSES; TRIALS AB This article considers the efficiency of event-related fMRI designs in terms of the optimum temporal pattern of stimulus or trial presentations. The distinction between "stochastic" and "deterministic" is used to distinguish between designs that are specified in terms of the probability that an event will occur at a series of time points (stochastic) and those in which events always occur at prespecified time (deterministic). Stochastic designs may be "stationary," in which the probability is constant, or nonstationary, in which the probabilities change with time. All these designs can be parameterized in terms of a vector of occurrence probabilities and a prototypic design matrix that embodies constraints (such as the minimum stimulus onset asynchrony) and the model of hemodynamic responses. A simple function of these parameters is presented and used to compare the relative efficiency of different designs. Designs with slow modulation of occurrence probabilities are generally more efficient than stationary designs. Interestingly the most efficient design is a conventional block design. A critical point, made in this article, is that the most efficient design for one effect may not be the most efficient for another. This is particularly important when considering evoked responses and the differences among responses. The most efficient designs for evoked responses, as opposed to differential responses, require trial-free periods during which baseline levels can be attained. In the context of stochastic, rapid-presentation designs this is equivalent to the inclusion of "null events." (C) 1999 Academic Press. C1 Inst Neurol, Wellcome Dept Cognit Neurol, London WC1N 3BG, England. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, NMR Ctr, Charlestown, MA 02129 USA. RP Friston, KJ (reprint author), Inst Neurol, Wellcome Dept Cognit Neurol, Queen Sq, London WC1N 3BG, England. RI Friston, Karl/D-9230-2011; Dale, Anders/A-5180-2010 OI Friston, Karl/0000-0001-7984-8909; FU NCRR NIH HHS [RR13609]; Wellcome Trust NR 18 TC 378 Z9 384 U1 2 U2 11 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 NOV PY 1999 VL 10 IS 5 BP 607 EP 619 DI 10.1006/nimg.1999.0498 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 257JN UT WOS:000083778900012 PM 10547338 ER PT J AU Brooks, BR AF Brooks, BR TI Defining optimal management in ALS: from first symptoms to announcement - Introduction SO NEUROLOGY LA English DT Editorial Material AB The advances in treatment for amyotrophic lateral sclerosis (ALS) have demonstrated the need to diagnose this disease precisely and directly. Two international initiatives, at El Escorial in 1990 and at Airlie House in 1998, have grappled with the clinical and laboratory elements that may accelerate the diagnostic process. Shortly after the Airlie House meeting in 1998, an international group of clinical neurologists met to discuss optimal management strategies in ALS. The goals were to examine current diagnosis and treatment pathways and to attempt to devise an algorithm that would foster early diagnosis, thus enhancing the possibility of optimal treatment. C1 Univ Wisconsin, ALS Clin Res Ctr, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Brooks, BR (reprint author), Univ Wisconsin Hosp & Clin, ALS Clin Res Ctr, Ctr Clin Sci, H6-563, Madison, WI 53792 USA. NR 3 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1999 VL 53 IS 8 SU 5 BP S1 EP S3 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 254HJ UT WOS:000083605600001 PM 10560629 ER PT J AU Brooks, BR AF Brooks, BR TI What are the implications of early diagnosis? Maintaining optimal health as long as possible SO NEUROLOGY LA English DT Article AB As yet, there is no staging system for amyotrophic lateral sclerosis (ALS). One early attempt to define disease stages; consisted of post-hoc analysis of the international, placebo-controlled, clinical trials of riluzole. In this analysis, live health states were defined for ALS (mild, moderate, severe, terminal, death) to determine whether therapeutic intervention with riluzole could favorably influence the time spent in the different stages. The time spent in the mild and:moderate disease states (taken together) was considerably longer in patients treated with riluzole than in those treated:with placebo (317 days compared with 242 days). Riluzole did not influence the median time in the mild, severe, or terminal ALS: stages but did slightly shorten the time in the moderate ALS stage compared with placebo. In all the ALS stages, the 75th percentile of time in that state appeared to be extended.: Survival analysis indicated that the relative risk was less than 1.0 with riluzole treatment in the moderate, severe, and terminal health states but not in the mild health state, when it remained at 1.0. The time to failure was longer in patients in the moderate, severe, and terminal ALS stages but was significantly longer only in the moderate ALS stage. These findings indicate that future studies of therapeutic intervention should examine rigorously defined stages of disease Ito examine end points other than death. The development of a staging system, analogous to the ones used in oncology, has implications for the concept of early diagnosis. C1 Univ Wisconsin, ALS Clin Sci Ctr, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Brooks, BR (reprint author), Univ Wisconsin Hosp & Clin, ALS Clin Res Ctr, Ctr Clin Sci, H6-563, Madison, WI 53792 USA. NR 1 TC 7 Z9 7 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1999 VL 53 IS 8 SU 5 BP S43 EP S45 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 254HJ UT WOS:000083605600012 PM 10560637 ER PT J AU Brooks, BR AF Brooks, BR TI Earlier is better: the benefits of early diagnosis SO NEUROLOGY LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS AB The concept of earlier diagnosis of amyotrophic lateral sclerosis (ALS) requires in-depth investigation of its benefits and consequences. First, how good must a treatment be before ALS is determined to be a treatable condition? Analogy with cancer therapy suggests that a good quality of life after treatment is an essential feature of a "good" therapy. Survival in some diseases may be prolonged without a significant improvement in the patient's quality of life. Neurologists need to be clear about what they are trying to achieve in prolonging survival and maintaining a good quality of life for their patients with ALS. Second, can early diagnosis extend apparent survival in the absence of a therapeutic intervention that significantly affects the disease process? Earlier diagnosis on the basis of confirmed clinical signs and, earlier institution of therapy may lead to a perception of improved survival, which is greater in young ALS patients. Third, can early diagnosis provide a benefit through prolongation of the time the patient remains able to work? Any therapeutic intervention to slow the early stages of the disease would benefit patients who wanted to maintain their self-esteem by continuing to work. Finally, earlier diagnosis of ALS requires decisions to be made concerning the acceptable rate of misdiagnosis, which at present reaches 10% false-positive and up to 44% false-negative. C1 Univ Wisconsin, ALS Clin Res Ctr, Madison, WI 53706 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. RP Brooks, BR (reprint author), Univ Wisconsin Hosp & Clin, Ctr Clin Sci, ALS Clin Res Ctr, H6-563, Madison, WI 53792 USA. NR 6 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV PY 1999 VL 53 IS 8 SU 5 BP S53 EP S54 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 254HJ UT WOS:000083605600015 PM 10560640 ER PT J AU Shipp, TD Zelop, CM Repke, JT Cohen, A Caughey, AB Lieberman, E AF Shipp, TD Zelop, CM Repke, JT Cohen, A Caughey, AB Lieberman, E TI Intrapartum uterine rupture and dehiscence in patients with prior lower uterine segment vertical and transverse incisions SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID PREVIOUS CESAREAN DELIVERY; VAGINAL BIRTH; TRIAL; LABOR; SECTION; SAFE AB Objective: To determine whether gravidas with prior low vertical uterine incision(s) are at a higher risk for uterine rupture during a trial of labor after cesarean delivery than women with prior low transverse uterine incision(s). Methods: The medical records of women undergoing a trial of labor after prior cesarean delivery over a 12-year period (July 1984-June 1996) at a tertiary-care hospital were reviewed. Maternal and perinatal outcomes for women with prior low transverse and low vertical incision were compared. Women whose low vertical incision was noted to extend into the corpus of the uterus were excluded. All uterine scar disruptions, which included both symptomatic ruptures and detected asymptomatic dehiscences, were analyzed together, and ruptures were examined separately. Results: The outcomes of 2912 patients undergoing trial of labor for the low transverse group and 377 patients undergoing trial of labor for the low vertical group were compared. Overall, there were 38 (1.3%) scar disruptions in the low transverse group and six (1.6%) in the low vertical group, P = .6. There were 28 (1.0%) symptomatic ruptures in the low transverse group and 3 (0.8%) in the low vertical group, P > .999. The study had a power of 89% to detect an increase in the low vertical rupture rate from 1% (as noted for low transverse incisions) to 3%. Conclusion: Gravidas with a prior low vertical uterine incision are not at increased risk for uterine rupture during a trial of labor compared with women with a prior low transverse uterine incision. (C) 1999 by The American College of Obstetricians and Gynecologists. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. Univ Chicago, Chicago Lying In Hosp, Chicago, IL USA. RP Shipp, TD (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Founders 430, Boston, MA 02114 USA. NR 18 TC 44 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 1999 VL 94 IS 5 BP 735 EP 740 DI 10.1016/S0029-7844(99)00398-1 PN 1 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 249CW UT WOS:000083316100018 PM 10546720 ER PT J AU Ferrigno, P Silver, PA AF Ferrigno, P Silver, PA TI Regulated nuclear localization of stress-responsive factors: how the nuclear trafficking of protein kinases and transcription factors contributes to cell survival SO ONCOGENE LA English DT Review DE nuclear transport; protein phosphorylation; p53; Akt/PKB; NF-AT; STATs ID NF-KAPPA-B; NUCLEOCYTOPLASMIC TRANSPORT; MAP KINASE; MOLECULAR-CLONING; TUMOR-SUPPRESSOR; EXPORT RECEPTOR; TRANSFER-RNA; INTRAMOLECULAR MASKING; IMPORT RECEPTOR; PORE COMPLEX AB The details of nuclear transport mechanisms are emerging rapidly, Largely through work with model organisms. Here, we briefly describe these advances, with an emphasis on the remaining challenges. We then address the nuclear transport of some high profile cellular regulators, including p53 and the proto-oncogene PKB/Akt, We discuss the mechanisms that contribute to the differential subcellular localization of these proteins. Finally, me analyse the provocative patterns that emerge from our overview. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Silver, PA (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. NR 101 TC 35 Z9 35 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV 1 PY 1999 VL 18 IS 45 SI SI BP 6129 EP 6134 DI 10.1038/sj.onc.1203132 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 251LL UT WOS:000083447100007 PM 10557104 ER PT J AU Newton, HB Fine, HA AF Newton, HB Fine, HA TI NCCN clinical practice guidelines for nonimmunosuppressed primary CNS lymphoma SO ONCOLOGY-NEW YORK LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; HIGH-DOSE METHOTREXATE; RADIATION-THERAPY; CHEMOTHERAPY; SURVIVAL; BRAIN C1 Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Newton, HB (reprint author), Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. NR 13 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 1999 VL 13 IS 11A SU S BP 153 EP 160 PG 8 WC Oncology SC Oncology GA 371KR UT WOS:000165178600012 ER PT J AU Shipley, WU AF Shipley, WU TI The Krieg/Hoffman article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Shipley, WU (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 1999 VL 13 IS 11 BP 1523 EP 1523 PG 1 WC Oncology SC Oncology GA 392WG UT WOS:000166435100012 ER PT J AU Rubin, PAD Fay, AM Remulla, HD Maus, M AF Rubin, PAD Fay, AM Remulla, HD Maus, M TI Ophthalmic plastic applications of acellular dermal allografts SO OPHTHALMOLOGY LA English DT Article ID EYELID RETRACTION; GRAFTS; SCLERA AB Purpose: Clinical problems of contracted conjunctival fornices, superior sulcus defects, and soft tissue contour defects in the periorbital region have not shown good, sustained results with a range of autologous and alloplastic implants. AlloDerm (Lifecell Corp., Woodlands, TX) is an acellular dermal graft processed from human donor tissue. The authors sought to assess the efficacy of AlloDerm as a soft tissue replacement in a variety of oculoplastic applications. Design: Retrospective, noncomparative case series, Participants: Twenty-three patients. Methods: Applications were broadly classified as barrier/scaffolding (i.e., primary and secondary implant coverage, lid spacer graft) and volume augmentation (i.e., superior sulcus and other periorbital soft tissue contour defects). Barrier grafts were applied as single sheets. Stacked sheets or rolled grafts were used for augmentation. Collectively, this material was used in 29 cases with 3 to 16 months' follow-up. Main Outcome Measures: Clinical evaluation of outcome and complications. Results: As a soft tissue scaffolding and barrier implant, AlloDerm persisted sufficiently to permit repopulation with native tissue. Rolled/stacked implants demonstrated unpredictable resorption. Upper eyelid grafts seemed to have higher resorption rates than lower eyelid grafts. One case of anophthalmic superior sulcus augmentation required two revision surgeries to provide sufficient volume augmentation. The grafts were well tolerated, with no cases of infection or explanation. Conclusion: Acellular human dermis is an excellent barrier and reconstructive grafting material that provides an alternative to autologous grafts and other alloplastic material, avoids harvesting autologous tissue, possesses excellent handling properties, and is associated with minimal inflammation. Long-term follow-up is required to evaluate persistence. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Thomas Jefferson Univ, Wills Eye Hosp, Oculoplast Serv, Philadelphia, PA 19107 USA. RP Rubin, PAD (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 18 TC 56 Z9 88 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1999 VL 106 IS 11 BP 2091 EP 2097 DI 10.1016/S0161-6420(99)90488-8 PG 7 WC Ophthalmology SC Ophthalmology GA 251KZ UT WOS:000083446000017 PM 10571342 ER PT J AU Foster, CS Ahmed, AR AF Foster, CS Ahmed, AR TI Intravenous immunoglobulin therapy for ocular cicatricial pemphigoid - A preliminary study SO OPHTHALMOLOGY LA English DT Article ID IMMUNOSUPPRESSIVE THERAPY; IMMUNE GLOBULIN AB Objective: To report the effects of intravenous immunoglobulin treatment of ten patients with progressive ocular cicatricial pemphigoid who did not respond to conventional immunomodulatory regimens. Design: Noncomparative, interventional case series. Participants: Ten patients with biopsy-proven progressive cicatricial pemphigoid affecting the eyes who did not respond adequately to other local and systemic immunosuppressive treatment regimens. Intervention: Intravenous infusions of pooled human immunoglobulin, 2 to 3 g/kg body weight/cycle, divided over 3 days, and repeated every 2 to 6 weeks. Main Outcome Measures: Reduction in conjunctival inflammation, prevention of progression of subepithelial conjunctival fibrosis, improvement in ocular symptoms (discomfort, photophobia), improved visual acuity, reduction in extraocular mucosal lesions. Results: Clinical deterioration was arrested and resolution of chronic conjunctivitis was documented in all ten patients. Maximum therapeutic effect was observed and maintained after a minimum of 4 cycles of therapy; three patients required 12 cycles before disease control. The duration of therapy in these ten patients has been 16 to 23 months (mean, 19.3 months) with no treatment-induced side effects. Extraocular mucosal lesion resolution has occurred in all but one patient. Visual acuity has stabilized or improved in all ten patients, and subjective complaints of discomfort and photophobia have decreased in all patients. Conclusions: Intravenous immunoglobulin immunomodulatory therapy can be a safe and effective therapy for otherwise treatment-resistant ocular cicatricial pemphigoid. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis & Immunol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral Med, Boston, MA 02115 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Uveitis & Immunol Serv, 243 Charles St, Boston, MA 02114 USA. NR 28 TC 104 Z9 108 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1999 VL 106 IS 11 BP 2136 EP 2143 DI 10.1016/S0161-6420(99)90496-7 PG 8 WC Ophthalmology SC Ophthalmology GA 251KZ UT WOS:000083446000025 PM 10571350 ER PT J AU Da Mata, A Burk, SE Netland, PA Baltatzis, S Christen, W Foster, CS AF Da Mata, A Burk, SE Netland, PA Baltatzis, S Christen, W Foster, CS TI Management of uveitic glaucoma with Ahmed glaucoma valve implantation SO OPHTHALMOLOGY LA English DT Article ID TRABECULECTOMY; 5-FLUOROURACIL AB Objective: To evaluate the safety and efficacy of Ahmed glaucoma valve implantation for the management of glaucoma associated with chronic uveitis. Design: Retrospective, noncomparative case series. Participants: Nineteen patients (21 eyes) with chronic uveitis underwent Ahmed glaucoma valve implantation for uncontrolled glaucoma between 1995 and 1998. Intervention: All patients had their uveitis controlled before surgery via immunomodulatory therapy. Ahmed glaucoma valve implantation was performed, Immunosuppression was continued in the early postoperative period for strict control of inflammation. Main Outcome Measures: Control of intraocular pressure (IOP). A secondary outcome measure was the number of antiglaucoma medications required to achieve the desired IOP. Visual acuity and complications associated with the surgery were monitored. Results: The postoperative follow-up averaged 24.5 months. At the most recent visit, all 21 eyes had IOPs between 5 and 18 mmHg. The average pressure reduction after Ahmed glaucoma valve implantation was 23.7 mmHg, The average number of antiglaucoma medicines required to achieve the desired IOP was reduced from 3.5 before surgery to 0.6 after surgery. No eye lost even a single line of Snellen acuity at the most recent postoperative visit. Two eyes developed hypotony in the course of follow-up. One resolved without specific intervention, and the other eye required two autologous blood injections and tube ligature to correct the hypotony. One eye underwent Ahmed glaucoma valve replacement for abrupt valve failure, Two eyes underwent penetrating keratoplasty for reasons believed to be unrelated to the glaucoma surgery, Kaplan-Meier life-table analysis showed a cumulative probability of success after Ahmed glaucoma valve implantation of 94% at 1 year. Conclusions: Ahmed glaucoma valve implantation can be an effective and safe method in the management of uveitic glaucoma. The authors hypothesize that control of the patients' uveitis, through preoperative and long-term postoperative immunomodulatory therapy, may have contributed to the success rate reported herein. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. Univ Tennessee, Sch Med, Dept Ophthalmol, Memphis, TN USA. Univ Athens, Dept Ophthalmol, Athens, Greece. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Prevent Med, Boston, MA 02114 USA. RP Foster, CS (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Ocular Immunol & Uveitis Serv, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 53 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD NOV PY 1999 VL 106 IS 11 BP 2168 EP 2172 DI 10.1016/S0161-6420(99)90500-6 PG 5 WC Ophthalmology SC Ophthalmology GA 251KZ UT WOS:000083446000030 PM 10571354 ER PT J AU Kemker, BJ Corey, JP Branca , J Gliklich, RE AF Kemker, BJ Corey, JP Branca , J Gliklich, RE TI Development of the Allergy Outcome Survey for allergic rhinitis SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT Meeting of the American-Academy-of-Otolaryngic-Allergy-Foundation CY MAY 06-10, 1998 CL PALM BEACH, FLORIDA SP Amer Acad Otolaryng Allergy Fdn ID HEALTH SURVEY SF-36; CHRONIC SINUSITIS AB The Allergy Outcome Survey (AOS) is a reliable measure used to monitor patients with allergic rhinitis, It was developed for and included in the Outcomes Measures of Immunotherapy in Allergic Rhinitis (OMIAR-1) project, designed to study the benefits of immunotherapy in the treatment of allergic rhinitis, Preliminary results indicate that AOS is specific, brief, reliable, and easy to use. Also, it is useful for evaluating change with therapy and can be used alone as a performance metric or in combination with other measures as part of a more complete outcomes monitoring system. As the OMIAR-1 study progresses, more information will be available on the advantages and limitations of the AOS. C1 Univ Chicago, Sect Otolaryngol Head & Neck Surg, Dept Otolaryngol Head & Neck Surg, Chicago, IL 60637 USA. Massachusetts Eye & Ear Infirm, Clin Outcomes Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Cambridge, MA 02138 USA. RP Corey, JP (reprint author), Univ Chicago, Sect Otolaryngol Head & Neck Surg, Dept Otolaryngol Head & Neck Surg, 5841 S Maryland Ave,MC 1035, Chicago, IL 60637 USA. NR 7 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 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 1999 VL 121 IS 5 BP 603 EP 605 DI 10.1016/S0194-5998(99)70065-3 PG 3 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 252JG UT WOS:000083497900019 PM 10547479 ER PT J AU Lee, S Kollias, N McAuliffe, DJ Flotte, TJ Doukas, AG AF Lee, S Kollias, N McAuliffe, DJ Flotte, TJ Doukas, AG TI Topical drug delivery in humans with a single photomechanical wave SO PHARMACEUTICAL RESEARCH LA English DT Article DE 5-aminolevulinic acid; ruby laser; photoacoustics; shock waves; stress waves; transdermal drug delivery ID 5-AMINOLEVULINIC ACID; IN-VITRO; PERCUTANEOUS ABSORPTION; PROTOPORPHYRIN-IX; STRATUM-CORNEUM; STRESS WAVES; PHONOPHORESIS; ULTRASOUND; MEMBRANE; SKIN AB Purpose. Assess the feasibility of in vivo topical drug delivery in humans with a single photomechanical wave. Methods. Photomechanical waves were generated with a 23 nsec Q-switched ruby laser. In vive fluorescence spectroscopy was used as an elegant non-invasive assay of transport of 5-aminolevulinic acid into the skin following the application of a single photomechanical wave. Results. The barrier function of the human stratum corneum in vive may be modulated by a single (110 nsec) photomechanical compression wave without adversely affecting the viability and structure of the epidermis and dermis. Furthermore, the stratum corneum barrier always recovers within minutes following a photomechanical wave. The application of the photomechanical wave did not cause any pain. The dose delivered across the stratum corneum depends on the peak pressure and has a threshold at similar to 350 bar. A 30% increase in peak pressure, produced a 680% increase in the amount delivered. Conclusions. Photomechanical waves may have important implications for transcutaneous drug delivery. C1 Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Labs Photomed, Boston, MA 02114 USA. RP Lee, S (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Massachusetts Gen Hosp,Wellman Labs Photomed, Boston, MA 02114 USA. NR 30 TC 50 Z9 53 U1 0 U2 5 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD NOV PY 1999 VL 16 IS 11 BP 1717 EP 1721 DI 10.1023/A:1018954015441 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 254BE UT WOS:000083591000008 PM 10571277 ER PT J AU Andreassen, OA Weber, C Jorgensen, HA AF Andreassen, OA Weber, C Jorgensen, HA TI Coenzyme Q10 does not prevent oral dyskinesias induced by long-term haloperidol treatment of rats SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE neuroleptics; antioxidants; oxidative stress; vacuous chewing movements; tardive dyskinesia; HPLC ID VACUOUS CHEWING MOVEMENTS; LOW-DENSITY-LIPOPROTEIN; TARDIVE-DYSKINESIA; MITOCHONDRIAL ENCEPHALOMYOPATHY; STRIATAL LESIONS; 3-NITROPROPIONIC ACID; INDUCED DEGENERATION; HUNTINGTONS-DISEASE; CEREBROSPINAL-FLUID; LIPID-PEROXIDATION AB Tardive dyskinesia (TD) is a debilitating side effect of long-term treatment with neuroleptics with an unclear pathophysiologic basis. It has been proposed that TD may be a result of neuroleptic-induced oxidative stress. To investigate this hypothesis, we studied if neuroleptic-induced oral dyskinesias in rats, a putative analogue to human TD, could be prevented by the antioxidant coenzyme Q10 (CoQ10). Rats received 16 weeks of treatment with haloperidol decanoate (HAL) IM alone or together with orally administered CoQ10, and the behavior was recorded during and after treatment. HAL significantly increased the level of oral dyskinesias, and the increase persisted for 12 weeks after drug withdrawal. Cotreatment with CoQ10 did not attenuate the development of HAL-induced oral dyskinesia. Despite adequate absorption of orally administered CoQ10, shown by the increased serum levels of CoQ10, no increase of either CoQ10 or coenzyme Q9 was detected in the brain. These results suggest that cotreatment with CoQ10 does not inhibit the development of HAL-induced oral dyskinesias in rats, and that further studies seem to be needed in order to clarify the pharmakokinetics of CoQ10 in rats. (C) 1999 Elsevier Science Inc. C1 Univ Bergen, Dept Physiol, Bergen, Norway. Tech Univ Denmark, Dept Biochem & Nutr, Copenhagen, Denmark. Univ Bergen, Sect Sandviken Hosp, Dept Psychiat, Bergen, Norway. RP Andreassen, OA (reprint author), Massachusetts Gen Hosp, Dept Neurol, Warren 411,Fruit St, Boston, MA 02114 USA. NR 64 TC 7 Z9 7 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 1999 VL 64 IS 3 BP 637 EP 642 DI 10.1016/S0091-3057(99)00118-5 PG 6 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 249VY UT WOS:000083355000027 PM 10548281 ER PT J AU Lee, WPA Constantinescu, MA Butler, PEM AF Lee, WPA Constantinescu, MA Butler, PEM TI Effect of early mobilization on healing of nerve repair: Histologic observations in a canine model SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Association-of-Plastic-Surgeons CY MAY 17-20, 1998 CL MONTREAL, CANADA SP Amer Assoc Plastic Surgeons AB The effect of early mobilization on the healing of nerve repair was studied in a canine model. Median and ulnar nerves in the left wrist of 16 adult mongrel dogs were transected and immediately repaired. No motion of the repaired forelimb was allowed in the immobilized group (n = 10),while controlled passive motion between 30 and 90 degrees of wrist flexion was begun on the first postoperative day for 10 minutes twice daily in the mobilized group (n = 6). The pattern of revascularization and collagen formation at neurorrhaphy was examined by transillumination of India ink-injected specimen and by conventional histologic sections. Re Revascularization of nerve repair was found to occur by in growth of capillaries from proximal and distal nerve ends, which typically crossed the neurorrhaphy by 3 weeks in the immobilized group. Following early mobilization, there was a persistent "hypovascular zone" at the nerve repair site for up to 6 weeks. In addition, more scar tissue was generated by early motion according to gross observation and quantitative collagen analysis. Early mobilization, therefore, seems to impede nerve regeneration by delaying revascularization and enhancing scar formation. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Plast Surg Res Lab, Cambridge, MA 02138 USA. RP Lee, WPA (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr 453, Boston, MA 02114 USA. NR 17 TC 14 Z9 14 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD NOV PY 1999 VL 104 IS 6 BP 1718 EP 1725 PG 8 WC Surgery SC Surgery GA 249NW UT WOS:000083340000016 PM 10541174 ER PT J AU Siegel, M Biener, L Rigotti, NA AF Siegel, M Biener, L Rigotti, NA TI The effect of local tobacco sales laws on adolescent smoking initiation SO PREVENTIVE MEDICINE LA English DT Article DE adolescent behavior; adolescents; smoking; tobacco; youth ID CIGARETTE SALES; YOUTH ACCESS; UNITED-STATES; MINORS; ENFORCEMENT; COMMUNITIES; POLICIES; PROGRAM AB Background. More than 700 communities have enacted laws prohibiting the sale of tobacco to miners, but little is known about the impact of such laws on youth smoking behavior. The objective of this study was to determine whether local tobacco sales laws decrease the rate of progression to established smoking among adolescents. Methods. We conducted a prospective cohort study of 592 Massachusetts youths who did not smoke and were ages 12-15 years at the time of a baseline, random-digit-dial, telephone survey in 1993 and who were reinterviewed in 1997. Results. Youths living in towns with a local tobacco sales ordinance at baseline were significantly less likely to progress to established smoking (defined as having smoked at least 100 cigarettes in one's life) than youths living in a town without an ordinance (odds ratio = 0.60; 95% confidence interval 0.37, 0.97). The magnitude of this effect was unchanged after controlling for potential confounding variables. However, there was no relationship between living in a town with an ordinance and youths' perceived access to tobacco. Conclusions. Local tobacco sales laws are associated with reduced rates of adolescent smoking initiation, but in this setting, this effect did not appear to be mediated through reduced access to cigarettes. (C) 1999 American Health Foundation and Academic Press. C1 Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02118 USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Tobacco Res & Treatment Program,Gen Med Div, Boston, MA 02114 USA. RP Siegel, M (reprint author), Boston Univ, Sch Publ Hlth, Dept Social & Behav Sci, 715 Albany St,TW2, Boston, MA 02118 USA. OI Biener, Lois/0000-0002-4130-8138 NR 41 TC 40 Z9 40 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV PY 1999 VL 29 IS 5 BP 334 EP 342 DI 10.1006/pmed.1999.0551 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 254EA UT WOS:000083597900004 PM 10564624 ER PT J AU Oates, JC Christensen, EF Reilly, CM Self, SE Gilkeson, GS AF Oates, JC Christensen, EF Reilly, CM Self, SE Gilkeson, GS TI Prospective measure of serum 3-nitrotyrosine levels in systemic lupus erythematosus: Correlation with disease activity SO PROCEEDINGS OF THE ASSOCIATION OF AMERICAN PHYSICIANS LA English DT Article DE lupus nephritis; nitric oxide; peroxynitrite; severity-of illness index; superoxide ID NITRIC-OXIDE SYNTHASE; MRL-LPR/LPR MICE; 3 ETHNIC-GROUPS; TYROSINE NITRATION; SUPEROXIDE-DISMUTASE; PEROXYNITRITE; NEPHRITIS; EXPRESSION; PROGNOSIS; MESSENGER AB Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease. Overproduction of nitric oxide (NO) has been implicated in its pathogenesis. Several retrospective studies have indicated a correlation between serum nitrate and nitrite (NOX) and disease activity. This measure of NO production can be falsely elevated by exogenous dietary and medication sources of NOX and Variably reduced by serum thiols. These variables can make NOX a less reliable tool for studying the role of NO in SLE. Peroxynitrite, a by-product of NO and superoxide, nitrates tyrosine moieties. The resulting 3-nitrotyrosine (3NT) serves as a long-term indicator of NO-mediated protein modifications that is not affected by exogenous sources of NOX or serum thiols. We hypothesized that for these reasons serum 3NT levels would correlate with lupus disease activity more significantly than serum NOX. To address this hypothesis, we prospectively evaluated lupus disease activity, serum protein 3NT levels, and NOX levels in a cohort of lupus patients at 3-month intervals, Serum 3NT correlated with disease activity among African-Americans, while NOX correlated with disease activity among Caucasians. Subjects with active lupus nephritis had higher levels of serum 3NT than those without renal disease. Immunohistochemical analysis of renal biopsies from subjects with active proliferative lupus nephritis revealed renal expression of inducible NO synthase. The results of this study suggest that overproduction of NO may play a pathogenic role in SLE and lupus nephritis. Serum 3NT may be a useful, new tool for studying the contributions of NO to the pathogenesis of SLE. C1 Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Res Serv, Charleston, SC USA. RP Oates, JC (reprint author), Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, 96 Jonathan Lucas St,Suite 912,POB 250623, Charleston, SC 29425 USA. FU NCRR NIH HHS [5MO1RR01070] NR 40 TC 56 Z9 57 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1081-650X J9 P ASSOC AM PHYSICIAN JI Proc. Assoc. Am. Phys. PD NOV-DEC PY 1999 VL 111 IS 6 BP 611 EP 621 DI 10.1046/j.1525-1381.1999.99110.x PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 254QY UT WOS:000083624700013 PM 10591091 ER PT J AU Nishizawa, M Nishizawa, K AF Nishizawa, M Nishizawa, K TI Local-scale repetitiveness in amino acid use in eukaryote protein sequences: A genomic factor in protein evolution SO PROTEINS-STRUCTURE FUNCTION AND GENETICS LA English DT Article DE yeast; gene duplication; point mutation; correlation; zinc finger motif; gene rearrangement; arbitrariness; constraints ID CODING SEQUENCES; DNA-SEQUENCES; GENES; ALIGNMENT; DATABASE; FAMILIES; REPEATS AB We showed previously that the use of arginine versus lysine residues in eukaryote proteins is correlated positively with local GC content of the genome within approximate to 50 residues. Cumulative analyses show that the tendency for self-clustering (or repetitive use) generally is the case for all types of amino acids except for certain hydrophobic types. The degree to which each of the amino acids is used recurrently is weak for ancient proteins (or protein domains), those that are conserved through both eukaryotes and prokaryotes, but strong for modern proteins, which are unique to organisms of particular phyla, These findings support the idea that repetitiveness occurs due to a propensity of genomic DNA to cause tandem genomic duplication. A protein sequence with high repetitiveness tends to be unique in the homology search, which may indicate the weaker constraints and, hence, more arbitrary use of amino acids. Simulation analyses suggest that tandem gene duplications on a very small scale (1 or 2 codons) is an important causal factor in maintaining repetitiveness in the presence of concomittant occurrence of substitutive point mutation. For yeast proteins, approximate to 1.3 duplication events per 1,000 residues on average are likely to occur, whereas 10 events of substitution mutation occur. It also is suggested that duplication enhances the probability of occurrence of some peptide motifs, such as those found in zinc lingers and segments with extreme physicochemical characteristics, and, thus, that local repetitiveness is a genomic factor influencing the evolution of eukaryote proteins, Proteins 1999;37:284-292, (C) 1999 Wiley-Liss, Inc. C1 Teikyo Univ, Sch Med, Dept Biochem, Tokyo 173, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Nishizawa, K (reprint author), Teikyo Univ, Sch Med, Dept Biochem, Tokyo 173, Japan. NR 30 TC 11 Z9 12 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 1 PY 1999 VL 37 IS 2 BP 284 EP 292 DI 10.1002/(SICI)1097-0134(19991101)37:2<284::AID-PROT13>3.3.CO;2-W PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 250GD UT WOS:000083379900013 PM 10584073 ER PT J AU Goff, DC Bagnell, AL Perlis, RH AF Goff, DC Bagnell, AL Perlis, RH TI Glutamatergic augmentation strategies for cognitive impairment in schizophrenia SO PSYCHIATRIC ANNALS LA English DT Article ID NEUROLEPTIC-FREE SCHIZOPHRENICS; PHENCYCLIDINE-INDUCED DEFICITS; NMDA RECEPTOR SUBUNITS; D-CYCLOSERINE; PREFRONTAL CORTEX; NEGATIVE SYMPTOMS; MESSENGER-RNAS; EXPRESSION; KETAMINE; GLYCINE C1 Massachusetts Gen Hosp, Psychot Disorders Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA 02114 USA. RP Goff, DC (reprint author), Freedom Trial Clin, 25 Staniford St, Boston, MA 02114 USA. NR 48 TC 2 Z9 2 U1 1 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 1999 VL 29 IS 11 BP 649 EP 654 PG 6 WC Psychiatry SC Psychiatry GA 254RC UT WOS:000083625100011 ER PT J AU Winkelman, JW Herzog, DB Fava, M AF Winkelman, JW Herzog, DB Fava, M TI The prevalence of sleep-related eating disorder in psychiatric and non-psychiatric populations SO PSYCHOLOGICAL MEDICINE LA English DT Article; Proceedings Paper CT 147th Annual Meeting of the American-Psychiatric-Association CY MAY 21-26, 1994 CL PHILADELPHIA, PENNSYLVANIA SP Amer Psychiat Assoc, NIMH, Dept Vet Affairs, Cooperat Studies Program, Med Res Serv ID BULIMIA AB Background. Sleep-related eating disorder is a little-described syndrome combining features of sleep disorders and eating disorders. The behaviour consists of partial arousals from sleep followed by rapid ingestion of food, commonly with at least partial amnesia for the episode the following day. The aim of this study was to provide an estimate of the prevalence of sleep-related eating disorder. Methods. The Inventory of Nocturnal Eating, a self-report questionnaire addressing nocturnal eating and sleep disturbance, was administered to out-patients (N = 126) and in-patients (N = 24) with eating disorders, obese subjects (N = 126) in a trial of an anorexic agent, depressed subjects (N = 207) in an antidepressant trial, and an unselected group (N = 217) of college students. Sleep-related eating disorder was operationally defined as nocturnal eating with a self-reported reduced level of awareness, occurring at least once per week. Results. Almost 5.0% (33/700) of the sample described symptoms consistent with sleep-related eating disorder. The in-patient eating disorders group had nearly twice the prevalence (16.7 %) of the out-patient eating disorder sample (8.7 %), which had nearly twice the prevalence of the next highest group, the student sample (4.6 %). Subjects with sleep-related eating disorder endorsed more symptoms consistent with sleep disorders and had higher levels of depression and dissociation than those without nocturnal eating. Conclusions. Sleep-related eating disorder is more common than is generally recognized, especially in those with a daytime eating disorder. Sleep disorder symptoms are often associated with sleep-related eating disorder, as are depression and dissociation. Evaluation of individuals with eating disorders should include assessment for sleep-related eating. C1 Brigham & Womens Hosp, Sleep Disorders Ctr, Sleep Disorders Serv, Div Endocrinol & Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Psychiat, Sleep Disorders Serv, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. RP Winkelman, JW (reprint author), Brigham & Womens Hosp, Sleep Disorders Ctr, Sleep Disorders Serv, Div Endocrinol & Hypertens, 75 Francis St,Tower 5D, Boston, MA 02115 USA. NR 20 TC 54 Z9 56 U1 0 U2 1 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH STREET, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 1999 VL 29 IS 6 BP 1461 EP 1466 DI 10.1017/S0033291799008272 PG 6 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 266KQ UT WOS:000084299500021 PM 10616953 ER PT J AU Taylor, E AF Taylor, E TI William James and Sigmund Freud: "The future of psychology belongs to your work" SO PSYCHOLOGICAL SCIENCE LA English DT Biographical-Item AB Although James and Freud are generally not considered scientific by experimental psychologists, both wrote about their view of what a scientific psychology should look like. Their radically different philosophical epistemologies and historical origins are reviewed to provide an understanding of their respective visions for psychology James took his stand on a new metaphysical foundation for the way experiments should be conducted with his formulation of radical empiricism. Freud attempted a neurological explanation of the unconscious in his "Project for a Scientific Psychology" Remarkably, their definitions of psychology as a science had a similar ring. Likely, this is because both took a phenomenological position with regard to how they defined science, which is also probably the primary reason their ideas on the subject have always been rejected by experimentalists. The humanistic implications of the neuroscience revolution, however, have caused a reassessment of their respective positions, as philosophical questions about the nature of consciousness have brought both Freud and James back into vogue, but in new and unexpected ways. C1 Harvard Univ, Cambridge, MA 02138 USA. RP Taylor, E (reprint author), Massachusetts Gen Hosp, Psychol Testing Ctr, 5 Emerson Pl, Boston, MA 02114 USA. NR 0 TC 8 Z9 9 U1 1 U2 9 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD NOV PY 1999 VL 10 IS 6 BP 465 EP 469 DI 10.1111/1467-9280.00190 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 273UJ UT WOS:000084725700002 ER PT J AU Stilley, CS Miller, DJ Manzetti, JD Marino, IR Keenan, RJ AF Stilley, CS Miller, DJ Manzetti, JD Marino, IR Keenan, RJ TI Optimism and coping styles: A comparison of candidates for liver transplantation with candidates for lung transplantation SO PSYCHOTHERAPY AND PSYCHOSOMATICS LA English DT Article DE optimism; coping; liver transplantation; lung transplantation ID QUALITY-OF-LIFE; HEART-TRANSPLANTATION; SOCIAL SUPPORT; DISTRESS; PREDICTORS AB Background: Dispositional optimism and adaptive coping styles have been shown to correlate with each other and with physical and psychological well-being in a number of studies with medical patients. Few studies in the transplant literature evaluate psychological characteristics of patients across medical diagnoses. A comparison of optimism and coping styles among candidates for liver and lung transplantation is presented. Method: Subjects were 73 candidates for lung transplantation at the University of Pittsburgh Medical Center and 76 candidates for liver transplantation at the Pittsburgh VA Healthcare System. All candidates were classified according to medical diagnosis and history of substance abuse (alcohol/drugs or smoking). There were no significant between- or within-group differences on optimism. Results: There was a significant difference within both groups, according to history of substance abuse on the coping style 'acceptance'. There were also significant between-group differences on a number of coping styles. Conclusions: This preliminary study is intended to suggest direction for future research; studying psychological variables known to impact on health apart from medical diagnosis may provide data pertinent to selection criteria and the design of interventions to more effectively maximize the benefit of transplantation for all concerned. Copyright (C) 1999 S. Karger AG, Basel. C1 Univ Pittsburgh, Sch Educ, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Dept Surg, Div Cardiothorac Surg, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Thomas E Starzl Transplantat Ctr, Pittsburgh, PA USA. Dept Vet Affairs, Natl Liver Transplant Ctr, Pittsburgh, PA USA. RP Stilley, CS (reprint author), Univ Pittsburgh, Sch Nursing, 3500 Victoria St,Room 460, Pittsburgh, PA 15261 USA. NR 16 TC 13 Z9 13 U1 2 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0033-3190 J9 PSYCHOTHER PSYCHOSOM JI Psychother. Psychosom. PD NOV-DEC PY 1999 VL 68 IS 6 BP 299 EP 303 DI 10.1159/000012347 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 254VY UT WOS:000083633900003 PM 10559709 ER PT J AU Staab, EV Brady, TJ AF Staab, EV Brady, TJ TI Revitalizing the radiology research enterprise SO RADIOGRAPHICS LA English DT Article DE radiological society of North America; radiology and radiologists C1 NCI, Rockville, MD 20852 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Staab, EV (reprint author), NCI, 6130 Execut Blvd,Rm 800, Rockville, MD 20852 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 1999 VL 19 IS 6 BP 1405 EP 1405 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 252YL UT WOS:000083529800001 ER PT J AU McLoud, TC AF McLoud, TC TI Coronary artery calcification as an indicator of preclinical coronary artery disease - Invited commentary SO RADIOGRAPHICS LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP McLoud, TC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV-DEC PY 1999 VL 19 IS 6 BP 1419 EP 1419 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 252YL UT WOS:000083529800004 ER PT J AU Staab, EV Brady, TJ AF Staab, EV Brady, TJ TI Revitalizing the radiology research enterprise SO RADIOLOGY LA English DT Editorial Material DE Radiological Society of North America; radiology and radiologists C1 NCI, Rockville, MD 20852 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Staab, EV (reprint author), NCI, 6130 Execut Blvd,Rm 800, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1999 VL 213 IS 2 BP 316 EP 316 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 249AE UT WOS:000083308900002 ER PT J AU Novelline, RA Rhea, JT Rao, PM Stuk, JL AF Novelline, RA Rhea, JT Rao, PM Stuk, JL TI Helical CT in emergency radiology SO RADIOLOGY LA English DT Article DE computed tomography (CT), helical; emergency medical service system; state-of-art reviews; trauma ID BLUNT ABDOMINAL-TRAUMA; COMPUTED TOMOGRAPHIC ANGIOGRAPHY; CONTRAST-ENHANCED CT; SPIRAL CT; PULMONARY-EMBOLISM; SUSPECTED APPENDICITIS; AORTIC DISSECTION; URETERAL CALCULI; THORACIC AORTA; DIAGNOSIS AB Today, a wide range of traumatic and nontraumatic emergency conditions are quickly and accurately diagnosed with helical computed tomography (CT). Many traditional emergency imaging procedures have been replaced with newer helical, CT techniques that can be performed in less time and with greater accuracy, less patient discomfort, and decreased cost. The speed of helical technology permits CT examination of seriously ill patients in the emergency department, as well as patients who might not have been taken to CT previously because of the length of the examinations of the past. Also, helical technology permits multiple, sequential CT scans to be quickly obtained in the same patient, a great advance for the multiple-trauma patient. Higher quality CT examinations result from decreased respiratory misregistration, enhanced intravenous contrast material opacification of vascular structures and parenchymal organs, greater flexibility in image reconstruction, and improved multiplanar and three-dimensional reformations. This report summarizes the role and recommended protocols for the helical CT diagnosis of thoracic aortic trauma; aortic dissection; pulmonary embolism; acute conditions of the neck soft tissues; abdominal trauma; urinary tract stones; appendicitis; diverticulitis; abdominal aortic aneurysm; fractures of the face, spine, and extremities; and acute stroke. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Novelline, RA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Blossom St,POB 9657,FND 210, Boston, MA 02114 USA. NR 59 TC 146 Z9 153 U1 4 U2 8 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1999 VL 213 IS 2 BP 321 EP 339 PG 19 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 249AE UT WOS:000083308900004 PM 10551209 ER PT J AU Goldberg, SN Walovitch, RC Straub, JA Shore, MT Gazelle, GS AF Goldberg, SN Walovitch, RC Straub, JA Shore, MT Gazelle, GS TI Radio-frequency-induced coagulation necrosis in rabbits: Immediate detection at US with a synthetic microsphere contrast agent SO RADIOLOGY LA English DT Article DE animals; liver neoplasms, US; radiofrequency (RF) ablation; ultrasound (US), contrast media; ultrasound (US), Doppler studies ID RADIOFREQUENCY TISSUE ABLATION; HEPATOCELLULAR-CARCINOMA; ULTRASOUND; METASTASES; TUMORS; ENHANCEMENT; TEMPERATURE; MASSES; SIZE AB PURPOSE: To determine whether a synthetic ultrasonographic (US) contrast agent can be used to differentiate coagulation necrosis from untreated tumor immediately after radio-frequency ablative therapy. MATERIALS AND METHODS: VX2 (adenocarcinoma) tumors (0.8-1.5-cm diameter) were implanted into 12 rabbits. Gray-scale and color Doppler US were performed with or without intravenous injection of a US contrast agent composed of poly-lactide-co-glycolic acid polymeric (PLGA) microspheres (2-mu m diameter) filled with perfluorocarbon gas, Radio frequency was applied to each nodule for 6 minutes at 127 mA +/- 33 (mean +/- SD) (tip temperature, 92 degrees C +/- 2). Repeat US with a second dose of the contrast agent was performed immediately after ablation. In four animals, a third dose was administered 30-120 minutes after ablation. Radiologic-histopathologic correlation was performed and included in vivo staining and studies of mitochondrial function. RESULTS: Intense contrast agent enhancement was seen throughout the tumor prior to ablation. At gray-scale US, ablation produced hyperechoic foci, which were within 1 mm of the foci identified at histopathologic examination in seven of 12 animals (58%). After the administration of contrast material, foci devoid of previously visualized enhancement, which measured 7.3-15.0 mm, were identified. these were within 1 mm of the size of the foci identified at histopathologic examination in 11 of 12 animals (92%, P < .01). In two animals, enhancement depicted viable tumor, which appeared hyperechoic, on nonenhanced images. On delayed images, hyperechoic areas decreased in size, whereas the nonenhanced region remained unchanged. CONCLUSION: A PLGA microspherical US contrast agent enabled the immediate detection of coagulation necrosis as a region devoid of contrast enhancement after radio-frequency ablation in rabbit hepatic tumors. Therefore, this agent could provide real-time guidance during complex ablative procedures and may provide an efficient technique for postprocedural assessment. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Acusphere, Dept Res & Dev, Cambridge, MA USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. NR 25 TC 62 Z9 65 U1 0 U2 6 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 1999 VL 213 IS 2 BP 438 EP 444 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 249AE UT WOS:000083308900020 PM 10551224 ER PT J AU Arbuckle, MR Reichlin, M Harley, JB James, JA AF Arbuckle, MR Reichlin, M Harley, JB James, JA TI Shared early autoantibody recognition events in the development of anti-Sm B/B ' in human lupus SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; GLUTAMIC-ACID DECARBOXYLASE; RO SS-A; T-CELL; PEPTIDE IMMUNIZATION; IMMUNE-RESPONSE; ANTIBODIES; EPITOPE; ERYTHEMATOSUS; DISEASE AB Many aspects of the immune maturation are uncharted. For ordinary human autoimmune systems there are no complete descriptions of the progression from an initial antigenic epitope to a maximally complex immune response. In this study we have exploited a large serial collection of human sera to investigate the development of the anti-Sm autoimmune response in systemic lupus ertythematosus (SLE). The results suggest a similar, if not virtually identical, stepwise progression in the early humoral immune maturation of anti-Sm. The amino acid sequence PPPGMRPP comprises the first epitope in the anti-Sm B/B' response and its close relative, PPPGMRGP, the second. Epitopes are subsequently enlarged by the incorporation of neighbouring amino acids. The third and fourth epitopes are also recognised by an antibody in a nearly identical sequence in different lupus patients. A column absorption with PPPGMRPP demonstrates that the epitope spreading among the first four early epitopes appears to occur by the sequential generation of crossreactive antibodies. Unexpectedly, epitope spreading in this system occurs in a predictable fashion by involving essentially the same sequence of antigenic structures from person to person. In addition, these data support the lupus anti-Sm antibodies originating against a single antigenic structure and, hence, strongly support a unifying mechanism in the generation of these autoantibodies. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. US Dept Vet Affairs, Oklahoma City, OK USA. RP James, JA (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [AI31584]; NIAMS NIH HHS [AR081981, AR42474] NR 39 TC 62 Z9 62 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0300-9475 J9 SCAND J IMMUNOL JI Scand. J. Immunol. PD NOV PY 1999 VL 50 IS 5 BP 447 EP 455 PG 9 WC Immunology SC Immunology GA 252ZW UT WOS:000083533000001 PM 10564545 ER PT J AU Ubel, PA AF Ubel, PA TI Dose response - Intelligent rationing by physicians is the first step to a health-care system that society can afford SO SCIENCES-NEW YORK LA English DT Article C1 Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. RP Ubel, PA (reprint author), Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 E 63RD ST, NEW YORK, NY 10021 USA SN 0036-861X J9 SCIENCES JI Sci.-New York PD NOV-DEC PY 1999 VL 39 IS 6 BP 18 EP 23 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 251RG UT WOS:000083458200011 PM 15584152 ER PT J AU Freytes, CO AF Freytes, CO TI Vascular access investigation comes of age SO SUPPORTIVE CARE IN CANCER LA English DT Editorial Material C1 Univ Texas, Hlth Sci Ctr, Adult Bone Marrow Transplant Program, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Dept Med, Div Hematol, San Antonio, TX 78284 USA. RP Freytes, CO (reprint author), Univ Texas, Hlth Sci Ctr, Adult Bone Marrow Transplant Program, 7703 Floyd Curl Dr, San Antonio, TX 78284 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD NOV PY 1999 VL 7 IS 6 BP 373 EP 374 DI 10.1007/s005200050293 PG 2 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 249FQ UT WOS:000083322700002 PM 10541975 ER PT J AU Sheridan, RL Zapol, WM Ritz, RH Tompkins, RG AF Sheridan, RL Zapol, WM Ritz, RH Tompkins, RG TI Low-dose inhaled nitric oxide in acutely burned children with profound respiratory failure SO SURGERY LA English DT Article ID SELECTIVE PULMONARY VASODILATOR; RIGHT VENTRICULAR-FUNCTION; END-EXPIRATORY PRESSURE; DISTRESS-SYNDROME; PERMISSIVE HYPERCAPNIA; INHALATION INJURY; MECHANICAL VENTILATION; TIDAL VOLUME; GAS-EXCHANGE; OVINE MODEL AB Background, Inhaled nitric oxide (NO) is a rapidly acting selective pulmonary vasodilator that partial ly reverses the pathophysiology of acute respiratory distress syndrome (ARDS). Methods. After human studies approval, we studied II burned children with severe ARDS in a trial of inhaled NO therapy, assessing ifs effect on intrapulmonary shunt as measured by the PaO2/FiO2 ratio (PFR). There were 12 episodes of administration; 1 child runs treated twice. Results. The children had an average age of 8.3 +/- 4.8 years (mean +/- SEM, range II months to 14 years) and average burn size of 64% +/- 22%. Al the time of enrollment, the PFR averaged 95 +/- 50 and Murray lung score 3.1 +/- 0.5. Inhaled NO was begun an average of 6.3 +/- 9.5 days after injury and was administered for an average of 7.8 +/- 7.2 days at an average dose of 6.7 +/- 2.4 parts per million. PFR improved an average of 162% +/- 214%. Eight of the II children (73%) survived. The 3 nonsurvivors had similar admission PFR values (100 +/- 75 versus 93 +/- 44, P = .089) bud a significantly less favorable initial response to inhaled NO, with a percentage of improvement in PFR at I hour? after enrollment of 7.3% +/- 6.4% versus 213% +/- 226% (P = .026). There were no complications,related to NO administration. Conclusions. Inhaled NO can be safely administered to treat ARDS in children with acute burns and appears to improve their ventilatory management. An immediate improvement in PFR with inhaled NO may correlate with survival. C1 Massachusetts Gen Hosp, Shriners Burns Hosp, Dept Surg, Div Burns & Trauma, Boston, MA 02114 USA. Harvard Univ, Shriners Burns Hosp, Dept Surg, Div Burns & Trauma,Med Sch, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Dept Anesthesia & Crit Care, Sch Med, Boston, MA 02114 USA. RP Sheridan, RL (reprint author), Massachusetts Gen Hosp, Shriners Burns Hosp, Dept Surg, Div Burns & Trauma, 51 Blossom St, Boston, MA 02114 USA. FU PHS HHS [H142397] NR 62 TC 22 Z9 23 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 1999 VL 126 IS 5 BP 856 EP 862 DI 10.1067/msy.2099.100382 PG 7 WC Surgery SC Surgery GA 252XU UT WOS:000083528200008 PM 10568185 ER PT J AU Lin, AE Genest, DR Brown, DL AF Lin, AE Genest, DR Brown, DL TI Circumferential abdominal skin defect possibly due to umbilical cord encirclement SO TERATOLOGY LA English DT Article AB We report on a newborn black male twin with a distinctive circumferential abdominal skin defect who was identified through the Active Malformation Surveillance Program at the Brigham and Women's Hospital. There were no other malformations, and amniotic disruption was not present. Although it cannot be proven, we believe that this skin defect may have been caused by in utero encirclement of the abdomen by an umbilical cord. (C) 1999 Wiley-Liss,Inc. C1 Brigham & Womens Hosp, Dept Newborn Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Serv Pediat, Genet & Teratol Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Lin, AE (reprint author), Brigham & Womens Hosp, Teratol Program, Old PBBH B5-501,75 Francis St, Boston, MA 02115 USA. NR 6 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD NOV PY 1999 VL 60 IS 5 BP 258 EP 259 PG 2 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 250ZW UT WOS:000083421000005 PM 10525202 ER PT J AU Matthews, N Liu, ZL Geesaman, BJ Qian, N AF Matthews, N Liu, ZL Geesaman, BJ Qian, N TI Perceptual learning on orientation and direction discrimination SO VISION RESEARCH LA English DT Article DE motion; training; generalization; transfer; specificity; learning rate ID MOTION DISCRIMINATION; SPECIFICITY; IMPROVEMENT; HYPERACUITY; VISION AB Two experiments were conducted to determine the extent to which perceptual learning transfers between orientation and direction discrimination. Naive observers were trained to discriminate orientation differences between two single-line stimuli, and direction differences between two single-moving-dot stimuli. In the first experiment, observers practiced the orientation and direction tasks along orthogonal axes in the fronto-parallel plane. In the second experiment, a different group of observers practiced both tasks along a single axis. Perceptual learning was observed on both tasks in both experiments. Under the same-axis condition, the observers' orientation sensitivity was found to be significantly elevated after the direction training, indicating a transfer of learning from direction to orientation. There was no evidence of transfer in any other cases tested. In addition, the rate of learning on the orientation task was much higher than the rate on the direction task. The implications of these findings on the neural mechanisms subserving orientation and direction discrimination are discussed. (C) 1999 Elsevier Science Ltd. All rights reserved. C1 Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02139 USA. RP Qian, N (reprint author), Columbia Univ, Ctr Neurobiol & Behav, 722 W 168th St, New York, NY 10032 USA. FU NIMH NIH HHS [MH54125] NR 30 TC 45 Z9 48 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD NOV PY 1999 VL 39 IS 22 BP 3692 EP 3701 DI 10.1016/S0042-6989(99)00069-3 PG 10 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 229BR UT WOS:000082174100005 PM 10746139 ER PT J AU Auchincloss, H AF Auchincloss, H TI Literature update 1999, part 2 SO XENOTRANSPLANTATION LA English DT Article C1 Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, Boston, MA 02114 USA. RP Auchincloss, H (reprint author), Massachusetts Gen Hosp, Surg Serv, Transplantat Unit, GRB 504, Boston, MA 02114 USA. NR 78 TC 1 Z9 1 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV PY 1999 VL 6 IS 4 BP 281 EP 286 DI 10.1034/j.1399-3089.1999.00036.x PG 6 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 284RP UT WOS:000085346500006 PM 10704071 ER PT J AU Giesler, M Bajtay, D Levine, RA Stein, E Grossmann, G Kochs, M Hoher, M Hombach, V AF Giesler, M Bajtay, D Levine, RA Stein, E Grossmann, G Kochs, M Hoher, M Hombach, V TI Aortic regurgitant flow by color Doppler measurement of the local velocity 7 mm above the leak orifice - Part 2: comparison with cardiac catheterization SO ZEITSCHRIFT FUR KARDIOLOGIE LA English DT Review DE aortic regurgitation; color Doppler; flow convergence ID CONVERGENCE REGION; VALVULAR REGURGITATION; MITRAL REGURGITATION; IN-VITRO; AREA; ECHOCARDIOGRAPHY; QUANTIFICATION; ACCELERATION; INSUFFICIENCY; INVITRO AB Aims: An in vitro study of the flow convergence region in aortic regurgitation has shown that regurgitant flow rate, can be derived from the local velocity v((7 mm)) at 7 mm distance above the leak orifice. This clinical study was performed to test this method inpatients. Methods and results: In 67 patients with aortic regurgitation, the flow convergence region was imaged by color Doppler. By analogy with the afore mentioned in vitro study, velocity profiles of the acceleration across the now convergence region were read from the color maps. The profiles were fitted by using a multiplicative regression model. The v((7) (mm)) was read from the regression curve, and instantaneous regurgitant flow Q was derived from the v((7 mm)) with the equation developed in vitro (Q = v((7 mm)) . cm(2)/0.28). Q showed a close association with the angiographic grade. Q-derived regurgitant stroke volume correlated significantly with invasive measurements by the angio-Fick method (r = 0.897, SEE = 19.9 ml, y = 0.88x + 5.9 ml). Conclusions: Within the color Doppler flow convergence region of aortic regurgitation, the local velocity at 7 mm distance to the leak reflects regurgitant flow rate. C1 Univ Ulm, Med Klin & Poliklin, Innere Med Abt 2, D-89081 Ulm, Germany. Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. RP Giesler, M (reprint author), Univ Ulm, Med Klin & Poliklin, Innere Med Abt 2, Robert Koch Str 8, D-89081 Ulm, Germany. RI Hoeher, Martin/M-6880-2014 OI Hoeher, Martin/0000-0001-7814-3202 NR 30 TC 1 Z9 1 U1 0 U2 0 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PLATZ DER DEUTSCHEN EINHEIT 25, D-64293 DARMSTADT, GERMANY SN 0300-5860 J9 Z KARDIOL JI Z. Kardiol. PD NOV PY 1999 VL 88 IS 11 BP 896 EP 905 DI 10.1007/s003920050367 PG 14 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 266NE UT WOS:000084305400002 PM 10643057 ER PT J AU Goggins, WB Finkelstein, DM Zaslavsky, AM AF Goggins, WB Finkelstein, DM Zaslavsky, AM TI Applying the cox proportional hazards model for analysis of latency data with interval censoring SO STATISTICS IN MEDICINE LA English DT Article ID INCUBATION PERIOD; HOMOSEXUAL MEN; SURVIVAL-DATA; EM ALGORITHM; AIDS AB The latency time of an infectious disease is defined as the time from infection to disease onset. This paper applies the proportional hazards model to estimate the effect of covariates on latency when the time of disease onset is exact or right-censored but the time of infection is interval-censored. We use a Monte Carlo EM algorithm to estimate parameters of the joint distribution of infection times and latency times. At each EM iteration, exact infection times are multiply imputed from the density determined by the parameters of the infection and latency time distributions. The methodology is tested using a simulation study and is applied to data from a cohort of haemophiliacs with HIV disease. Copyright (C) 1999 John Wiley & Sons, Ltd. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. RP Finkelstein, DM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 677 Huntington Ave, Boston, MA 02115 USA. FU NCI NIH HHS [CA74302]; NIAID NIH HHS [N0-AI95030] NR 18 TC 13 Z9 13 U1 0 U2 2 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 OCT 30 PY 1999 VL 18 IS 20 BP 2737 EP 2747 DI 10.1002/(SICI)1097-0258(19991030)18:20<2737::AID-SIM199>3.0.CO;2-7 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 246WH UT WOS:000083187500006 PM 10521863 ER PT J AU Sodroski, JG AF Sodroski, JG TI HIV-1 entry inhibitors in the side pocket SO CELL LA English DT Review ID ENVELOPE GLYCOPROTEIN; PEPTIDE INHIBITOR; ATOMIC-STRUCTURE; GP41; REPLICATION; FUSION C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Sodroski, JG (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 18 TC 84 Z9 85 U1 2 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 29 PY 1999 VL 99 IS 3 BP 243 EP 246 DI 10.1016/S0092-8674(00)81655-4 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 251HX UT WOS:000083440600002 PM 10555140 ER PT J AU Okano, M Bell, DW Haber, DA Li, E AF Okano, M Bell, DW Haber, DA Li, E TI DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development SO CELL LA English DT Article ID EMBRYONIC STEM-CELLS; ICF SYNDROME; MOUSE CELLS; GERM-LINE; CYTOSINE-5 METHYLTRANSFERASES; DENOVO METHYLATION; RETROVIRAL GENOMES; DE-NOVO; GENE; EXPRESSION AB The establishment of DNA methylation patterns requires de novo methylation that occurs predominantly during early development and gametogenesis in mice. Here we demonstrate that two recently identified DNA methyltransferases, Dnmt3a and Dnmt3b, are essential for de novo methylation and for mouse development. inactivation of both genes by gene targeting blocks de novo methylation in ES cells and early embryos, but it has no effect on maintenance of imprinted methylation patterns. Dnmt3a and Dnmt3b also exhibit nonoverlapping functions in development, with Dnmt3b specifically required for methylation of centromeric minor satellite repeats. Mutations of human DNMT3B are found in ICF syndrome, a developmental defect characterized by hypomethylation of pericentromeric repeats. Our results indicate that both Dnmt3a and Dnmt3b function as de novo methyltransferases that play important roles in normal development and disease. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Canc Ctr, Charlestown, MA 02129 USA. RP Li, E (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Cardiovasc Res Ctr, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA82389]; NIGMS NIH HHS [GM52106] NR 47 TC 2775 Z9 2901 U1 20 U2 234 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 29 PY 1999 VL 99 IS 3 BP 247 EP 257 DI 10.1016/S0092-8674(00)81656-6 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 251HX UT WOS:000083440600003 PM 10555141 ER PT J AU Zhang, KH Tarazi, FI Kula, NS Baldessarini, RJ Neumeyer, JL AF Zhang, KH Tarazi, FI Kula, NS Baldessarini, RJ Neumeyer, JL TI Selective alkylatation of dopamine D-2 and D-4 receptors in rat brain by N-(p-isothiocyanatophenethyl)spiperone SO NEUROSCIENCE LETTERS LA English DT Article DE alkylation; autoradiography; dopamine receptors; 1-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline; N-(p-isothiocyanatophenethyl)spiperone ID DIFFERENTIAL REGULATION; ANTIPSYCHOTIC-DRUGS; N-ETHOXYCARBONYL-2-ETHOXY-1,2-DIHYDROQUINOLINE; SUBTYPES; SITES AB Effects of the D-2-like receptor alkylating agent NIPS (N-[p-isothiocyanatophenethyl]spiperone) on dopamine receptors in rat brain were characterized by radioreceptor assays and quantitative autoradiography. NIPS alkylated D-2 and D-4 receptors concentration-dependently in brain sections and transfected cells. NIPS also alkylated both receptors dose-dependently in vivo, with no effect on dopamine D-1-like or serotonin 5-HT2 receptors at a dose that occluded 75% of D-2 and D-4 receptors. Pretreatment with D-2-like receptor selective antagonist haloperidol completely blocked the effects of NIPS. The findings demonstrate that NIPS selectively alkylates D-2 and D-4 receptors, indicating its potential utility for studies of these receptors. (C) 1999 Elsevier Science Ireland Ltd. Atl rights reserved. C1 Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Neuropharmacol Lab, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA 02115 USA. RP Zhang, KH (reprint author), Massachusetts Gen Hosp, McLean Div, Mailman Res Ctr, Neuropharmacol Lab, 115 Mill St, Belmont, MA 02478 USA. FU NIMH NIH HHS [MH-47370, MH-19905, MH-34006] NR 20 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 29 PY 1999 VL 274 IS 3 BP 155 EP 158 DI 10.1016/S0304-3940(99)00700-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 250MN UT WOS:000083392300004 PM 10548413 ER PT J AU Armstrong, K Schwartz, JS Asch, DA AF Armstrong, K Schwartz, JS Asch, DA TI Direct sale of sildenafil (Viagra) to consumers over the Internet SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID MEDICAL INFORMATION; QUALITY C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Armstrong, K (reprint author), Univ Penn, Sch Med, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA73619] NR 22 TC 66 Z9 68 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 28 PY 1999 VL 341 IS 18 BP 1389 EP 1392 DI 10.1056/NEJM199910283411810 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 249XE UT WOS:000083357800010 PM 10536133 ER PT J AU Alexander, JW Light, JA Donaldson, LA Delmonico, FL Diethelm, AG Wilkinson, A Rosenthal, JT Thistlethwaite, JR Hunsicker, LG Matas, AJ First, MR Reinsmoen, NL Rose, SM AF Alexander, JW Light, JA Donaldson, LA Delmonico, FL Diethelm, AG Wilkinson, A Rosenthal, JT Thistlethwaite, JR Hunsicker, LG Matas, AJ First, MR Reinsmoen, NL Rose, SM CA Cooperative Clin Trials Transplant TI Evaluation of pre- and posttransplant donor-specific transfusion/cyclosporine A in non-HLA identical living donor kidney transplant recipients SO TRANSPLANTATION LA English DT Article ID ANTIGEN-SPECIFIC HYPOREACTIVITY; BLOOD-TRANSFUSION; ALLOGENEIC MICROCHIMERISM; RENAL-TRANSPLANTATION; ALLOGRAFT SURVIVAL; GRAFT-SURVIVAL; CYCLOSPORINE; LUNG; DST; INDUCTION AB Background. The beneficial effects of donor specific transfusion (DST) have become controversial in the cyclosporine era, This study was performed to evaluate the potential benefits of a new protocol for administering DSTs in the perioperative period. Methods. Non-HLA identical living donor kidney transplant recipients were randomized prospectively to control or to receive a DST 24 hr before transplant and 7-10 days posttransplant, All patients received similar immunosuppression according to protocol. Results. The protocol had 212 evaluable patients (115 transfused and 97 control). There were no differences in 1- and a-year graft and patient survival, causes of graft failure, incidence and types of infection, repeat hospitalization, or the ability to withdraw steroids. Immunological hyporesponsiveness (by mixed lymphocyte culture) occurred more frequently in transfused patients (18%) than controls (3%) (P=0.04), Blood stored for greater than or equal to 3 days was associated with fewer early rejections than blood stored less than or equal to 2 days. Overall, class II antigen mismatches were associated with more rejection episodes than class I antigen mismatches. However, transfused patients, but not control patients, with more class I antigen mismatches were more likely to have rejections. Conclusions. Administration of DSTs by the method described had no practical influence on patient or graft survival for up to 2 years. However, donor-specific hyporesponsiveness was more common in transfused patients (18 vs. 3%). Longer follow-up will be needed to determine whether DST will be associated with long-term benefit. C1 Univ Cincinnati, Med Ctr, Coll Med, Dept Surg, Cincinnati, OH 45267 USA. Washington Hosp Ctr, Dept Transplantat, Washington, DC 20010 USA. EMMES Corp, Potomac, MD 20854 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Univ Alabama, Sch Med, Birmingham, AL 35294 USA. Univ Calif Los Angeles, Med Ctr, Dept Urol, Los Angeles, CA 90095 USA. Univ Chicago, Dept Surg, Chicago, IL 60637 USA. Univ Iowa, Div Nephrol, Iowa City, IA 52242 USA. Univ Minnesota, Dept Surg, Minneapolis, MN 55455 USA. NIAID, Genet & Transplantat Branch, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA. RP Alexander, JW (reprint author), Univ Cincinnati, Med Ctr, Coll Med, Dept Surg, 231 Bethesda Ave, Cincinnati, OH 45267 USA. NR 26 TC 15 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 1999 VL 68 IS 8 BP 1117 EP 1124 DI 10.1097/00007890-199910270-00010 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 252HT UT WOS:000083496600010 PM 10551639 ER PT J AU Somasundaran, P Simpson, S Ivanov, I Jain, RK Sarkar, D AF Somasundaran, P Simpson, S Ivanov, I Jain, RK Sarkar, D TI Thinning and rupture of aqueous surfactant films on silica SO LANGMUIR LA English DT Article AB The thinning and rupture of aqueous surfactant films on silica is investigated using the interferometric technique and free bubbles, which approximate flotation more realistically than the captive bubble method. Different rupture mechanisms are observed at different pH values for aqueous films of dodecylamine on silica? explaining the pH dependence of quartz flotation using amine. While at low pH rupture is accompanied by the breaking off of a large drop in the center and subsequent formation of large irregular drops, at high pH ruptured spots grow to large circular drops. C1 Columbia Univ, NSF, IUCR,Ctr Adv Surfactants, Langmuir Ctr Colloids & Interfaces, New York, NY 10027 USA. Rogers Corp, Rogers, CT 06263 USA. Univ Sofia, Fac Chem, Lab Thermodynam, BU-1126 Sofia, Bulgaria. Massachusetts Gen Hosp, Steele Lab Tumor Biol, Boston, MA 02114 USA. RP Somasundaran, P (reprint author), Columbia Univ, NSF, IUCR,Ctr Adv Surfactants, Langmuir Ctr Colloids & Interfaces, 911 Mudd Bldg, New York, NY 10027 USA. NR 33 TC 5 Z9 5 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD OCT 26 PY 1999 VL 15 IS 22 BP 7658 EP 7661 DI 10.1021/la9814485 PG 4 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 252KQ UT WOS:000083501000038 ER PT J AU Morehouse, H Buratowski, RM Silver, PA Buratowski, S AF Morehouse, H Buratowski, RM Silver, PA Buratowski, S TI The importin/karyopherin Kap114 mediates the nuclear import of TATA-binding protein SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID EUKARYOTIC INITIATION FACTOR-5A; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTION FACTOR; RABBIT RETICULOCYTES; FACTOR 5A; YEAST; REV; EXPORT; RNA; TRANSPORT AB Two high copy suppressors of temperature-sensitive TATA-binding protein (TBP) mutants were isolated. One suppressor was TIF51A, which encodes eukaryotic translation initiation factor 5A. The other high copy suppressor. YGL241W, also known as KAP114, is one of 14 importin/karyopherin proteins in yeast. These proteins mediate the transport of specific macromolecules into and out of the nucleus. Cells lacking Kap114 partially mislocalize TBP to the cytoplasm. Kap114 binds TBP in vitro, and binding is disrupted in the presence of GTP gamma S. Therefore, Kap114 is an importer of TBP into the nucleus, but alternative impart pathways must also exist. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Buratowski, S (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NR 39 TC 26 Z9 27 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 OCT 26 PY 1999 VL 96 IS 22 BP 12542 EP 12547 DI 10.1073/pnas.96.22.12542 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000063 PM 10535958 ER PT J AU Da Costa, XJ Brockman, MA Alicot, E Ma, MH Fischer, MB Zhou, XN Knipe, DM Carroll, MC AF Da Costa, XJ Brockman, MA Alicot, E Ma, MH Fischer, MB Zhou, XN Knipe, DM Carroll, MC TI Humoral response to herpes simplex virus is complement-dependent SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID VESICULAR STOMATITIS-VIRUS; B-CELL RESPONSE; IMMUNE-RESPONSE; ANTIBODY-RESPONSE; LYMPHOCYTES-B; ANTIGEN PRESENTATION; ACQUIRED-IMMUNITY; GERMINAL-CENTERS; GUINEA-PIGS; IN-VIVO AB The complement system represents a cascade of serum proteins, which provide a major effector function in innate immunity. Recent studies have revealed that complement links innate and adaptive immunity via complement receptors CD21/CD35 in that it enhances the B cell memory response to noninfectious protein antigens introduced i.v. To examine the importance of complement for immune responses to virus infection in a peripheral tissue, we compared the B cell memory response of mice deficient in complement C3, C4, or CD21/CD35 with wild-type controls. We found that the deficient mice failed to generate a normal memory response, which is characterized by a reduction in IgG antibody and germinal centers. Thus, complement is important not only in the effector function of innate immunity but also in the stimulation of memory B cell responses to viral-infected cell antigens in both blood and peripheral tissues. C1 Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Microbiol & Mol Genet, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Pediat, Sch Med, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Dept Pathol, Sch Med, Longwood Ave, Boston, MA 02115 USA. OI Brockman, Mark/0000-0001-6432-1426 FU NIAID NIH HHS [P01 AI042257, P01-AI-42257] NR 52 TC 87 Z9 90 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 OCT 26 PY 1999 VL 96 IS 22 BP 12708 EP 12712 DI 10.1073/pnas.96.22.12708 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000092 PM 10535987 ER PT J AU Monroe, RJ Chen, F Ferrini, R Davidson, L Alt, FW AF Monroe, RJ Chen, F Ferrini, R Davidson, L Alt, FW TI RAG2 is regulated differentially in B and T cells by elements 5 ' of the promoter SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID V(D)J RECOMBINATION; GENE-EXPRESSION; DEVELOPING THYMOCYTES; CD8 EXPRESSION; IMMUNE-SYSTEM; IG-KAPPA; REARRANGEMENT; LYMPHOCYTES; TRANSPOSITION; TRANSCRIPTION AB To study RAG2 gene regulation in vivo, we developed a blastocyst complementation method in which RAG2-deficient embryonic stem cells were transfected with genomic crones containing RAG2 and then assessed for their ability to generate lymphocytes, A RAG2 genomic clone that contained only the RAG2 promoter sequences rescued V(D)J recombination in RAG2-deficient pro-B cell lines, but did not rescue development of RAG2-deficient lymphocytes in vivo. However. inclusion of varying lengths of sequences 5' of the RAG2 promoter generated constructs capable of rescuing only in vivo B cell development, as well as other constructs that rescued both B and T cell development. In particular, the 2-kb 5' region starting just upstream of the RAG2 promoter, as well as the region from 2-7 kb 5', could independently drive B cell development, but not efficient T cell development. Deletion of the 2-kb 5' region from the murine germ line demonstrated that this region was not required for RAG expression sufficient to generate normal B or T cell numbers, implying redundancy among 5' elements. We conclude that RAG2 expression in vivo requires elements beyond the core promoter, that such elements contribute to differential regulation in the B vs. T lineages, and that sequences sufficient to direct B cell expression are located in the promoter-proximal 5' region. C1 Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Ctr Blood Res, Boston, MA 02115 USA. FU NIAID NIH HHS [AI20047, AI35714, P01 AI035714, R01 AI020047, R37 AI020047] NR 41 TC 34 Z9 35 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 OCT 26 PY 1999 VL 96 IS 22 BP 12713 EP 12718 DI 10.1073/pnas.96.22.12713 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000093 PM 10535988 ER PT J AU Alessandrini, A Namura, S Moskowitz, MA Bonventre, JV AF Alessandrini, A Namura, S Moskowitz, MA Bonventre, JV TI MEK1 protein kinase inhibition protects against damage resulting from focal cerebral ischemia SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TYROSINE PHOSPHORYLATION; MAP KINASE; SYNAPSIN-I; ACTIVATION; EXPRESSION; NEURONS; INJURY; CORTEX; CELLS; RATS AB The MEK1 (MAP kinase/ERK kinase)/ERK (extracellular-signal-responsive kinase) pathway has been implicated in cell growth and differentiation [Seger, R. & Krebs, E. G. (1995) FASEB J. 9, 726-735]. Here we show that the MEK/ERK pathway is activated during focal cerebral ischemia and may play a role in inducing damage. Treatment of mice 30 min before ischemia with the MEK1-specific inhibitor PD98059 [Alessi, D. R., Cuenda, A., Cohen, P., Dudley, D. T. & Saltiel, A. R. (1995) J. Biol. Chem. 270, 27489-27494] reduces focal infarct Volume at 22 hr after ischemia by 55% after transient occlusion of the middle cerebral artery. This is accompanied by a reduction in phospho-ERK1/2 immunohistochemical staining. MEK1 inhibition also results in reduced brain damage 72 hr after ischemia, with focal infarct Volume reduced by 36%. This study indicates that the MEK1/ERK pathway contributes to brain injury during focal cerebral ischemia and that PD98059, a MEK1-specific antagonist is a potent neuroprotective agent. C1 Massachusetts Gen Hosp, Med Serv, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02115 USA. Natl Cardiovasc Ctr, Res Inst, Suita, Osaka 5658565, Japan. RP Alessandrini, A (reprint author), Massachusetts Gen Hosp E, 149 13th St,Suite 4002, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011 FU NIDDK NIH HHS [R37-DK39773]; NINDS NIH HHS [2P50NS10828, P50 NS010828] NR 23 TC 367 Z9 396 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 1999 VL 96 IS 22 BP 12866 EP 12869 DI 10.1073/pnas.96.22.12866 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 250DD UT WOS:000083373000119 PM 10536014 ER PT J AU Tambouret, R Szyfelbein, WM Pitman, MB AF Tambouret, R Szyfelbein, WM Pitman, MB TI Ultrasound-guided fine-needle aspiration biopsy of the thyroid SO CANCER CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 28-MAR 06, 1998 CL BOSTON, MASSACHUSETTS SP US & Canadian Acad Pathol DE thyroid; parathyroid; cytology; ultrasound-guided fine-needle aspiration biopsy ID PARATHYROID LESIONS; NODULES; MANAGEMENT; ULTRASONOGRAPHY; CYTOLOGY; INCIDENTALOMAS; DILEMMA; DISEASE; GLAND AB BACKGROUND. We reviewed the Massachusetts General Hospital experience with ultrasound-guided fine-needle aspiration biopsies (FNABs) of the thyroid to determine the indications, rate of unsatisfactory smears, correlation with excisional biopsy results, and verification of efficient use of personnel time. METHODS. All radiologically guided FNABs of the thyroid from January 1993 through lune 1997 were reviewed. As a measure of efficient use of technologist time, a sample of times spent by the technologist during the procedure for 20 cases in 1993 and 1997 was compared with that of an equal number of random nonthyroid image guided FNABs. RESULTS. Two hundred-ninety FNABs were identified in 251 patients, representing 12% of all thyroid FNABs and 11% of all radiologically guided FNABs. Indications in the 251 patients included multiple nodules (78), solitary nodules (61), complex nodules (39), prior failed FNAB (39), thyroid bed abnormalities post-thyroidectomy (21), difficult access (7), and investigation of recurrent tumor in residual thyroid lobe (6). Available records indicated 118 lesions were palpable and 45 were nonpalpable; the physical examination characteristics of the remainder (88) were not stated. Diagnoses included 44 unsatisfactory cases (15%), 103 macrofollicular lesions, 20 microfollicular lesions, 26 mixed macro/ microfollicular lesions, 5 oxyphilic lesions, 1 trabecular pattern, 15 nonspecific follicular cell pattern, 9 follicular cell atypia, 30 cysts, 11 thyroiditis, 23 malignant tumors, and 3 other (1 parathyroid, 2 lymph node). Eighty-nine FNABs from 76 patients had subsequent surgical biopsy. Excisional biopsies in 14 unsatisfactory FNABs were benign. In the remaining 75 FNABs from 67 patients, 18 malignancies on FNAB were correctly diagnosed, but 3 other papillary carcinomas were only qualified as atypical follicular cells on cytology. No false-positive cases occurred. Of 15 macrofollicular lesions on cytology, 10 were adenomas on excision, only 2 of which were microfollicular adenomas, and 4 were adenomatous nodules. An aspirate of a parathyroid adenoma was misinterpreted as a macrofollicular lesion of the thyroid. Three microfollicular lesions on FNAB proved to be nodular hyperplasia on excision, and the other 11 were adenomas, 5 of them microfollicular. Average technologist time was significantly longer for thyroid FNABs than nonthyroid FNABs in 1993, but in the 1997 sample no significant difference was identified. CONCLUSIONS. Radiologically guided FNAB of the thyroid is a clinically useful procedure with a high correlation between benign lesions not needing excision (macrofollicular), and lesions that need excision (microfollicular/oxyphilic cell or malignant). Technologist time needed for immediate evaluation tends to decrease with increasing operator experience. Cancer (Cancer Cytopathol) 1999;87:299-305. (C) 1999 American Cancer Society. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Tambouret, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 28 TC 25 Z9 29 U1 0 U2 0 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 1999 VL 87 IS 5 BP 299 EP 305 DI 10.1002/(SICI)1097-0142(19991025)87:5<299::AID-CNCR10>3.0.CO;2-M PG 7 WC Oncology; Pathology SC Oncology; Pathology GA 248GZ UT WOS:000083267900010 PM 10536356 ER PT J AU Foley, J Wysolmerski, JJ Missero, C King, CS Philbrick, WM AF Foley, J Wysolmerski, JJ Missero, C King, CS Philbrick, WM TI Regulation of parathyroid hormone-related protein gene expression in murine keratinocytes by E1A isoforms: a role for basal promoter and Ets-1 site SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE PTHrP; E1A; repression; keratinocyte; coactivator ID PEPTIDE GENE; HUMORAL HYPERCALCEMIA; IN-VITRO; TRANSFORMING GROWTH-FACTOR-BETA-1; TRANSCRIPTIONAL REPRESSION; BINDING-PROTEIN; RAS ONCOGENE; CELL-LINES; TRANSACTIVATION; IDENTIFICATION AB PTHrP gene expression was evaluated in a murine keratinocyte line, Pam 212K, transformed with EIA and ras. We found that the 12S-E1A oncogene, with or without ras transformation, markedly reduced PTHrP mRNA expression. Using transient transfection assays, we found that the 12S isoform repressed activity from a 5'PTHrP-driven reporter gene. E1A-induced repression of PTHrP reporter constructs appears to be mediated by sequences within minimal promoter region. The 13S-E1A isoform did not repress PTHrP reporter gene activity, and a 13S-deletion mutant that lacked the repressor domains activated a subset of reporter constructs. Mutation of an Ets-1 binding site upstream of the basal promoter substantially decreased activation of reporter constructs by this 13S-deletion mutant. These findings suggest that the E1A oncoprotein may serve as a model for both activation and repression of PTHrP gene expression. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved. C1 Yale Univ, Sch Med, Dept Med, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Indiana Univ, Med Sci Program, Bloomington, IN 47405 USA. RP Foley, J (reprint author), Yale Univ, Sch Med, Dept Med, 333 Cedar St, New Haven, CT 06520 USA. FU NCI NIH HHS [CA63765, CA60498] NR 60 TC 13 Z9 13 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD OCT 25 PY 1999 VL 156 IS 1-2 BP 13 EP 23 DI 10.1016/S0303-7207(99)00151-3 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 250VU UT WOS:000083410600003 PM 10612419 ER PT J AU Neuwirth, ZE AF Neuwirth, ZE TI Lifeline SO LANCET LA English DT Editorial Material C1 Bronx Vet Affairs Med Ctr, Bronx, NY USA. RP Neuwirth, ZE (reprint author), Lenox Hill Hosp, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 23 PY 1999 VL 354 IS 9188 BP 1484 EP 1484 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 248LY UT WOS:000083277400065 ER PT J AU Marino, M Friedlander, JA McCluskey, RT Andrews, D AF Marino, M Friedlander, JA McCluskey, RT Andrews, D TI Identification of a heparin-binding region of rat thyroglobulin involved in megalin binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-RELATED PROTEIN; LDL RECEPTOR; LOW-DENSITY; SULFATE PROTEOGLYCANS; LIPOPROTEIN-LIPASE; POLYACRYLAMIDE GELS; MASS-SPECTROMETRY; HEYMANN NEPHRITIS; AFFINITY-BINDING; APOLIPOPROTEIN-E AB We recently showed that thyroglobulin (Tg) is a heparin-binding protein and that heparin inhibits binding of Tg to its endocytic receptor megalin (gp330), Here we have identified a heparin-binding region in the carboxyl-terminal portion of rat Tg and have studied its involvement in megalin binding. Rat thyroid extracts, obtained by ammonium sulfate precipitation, were separated by column fractionation into four Tg polypeptides, with apparent masses of 660, 330, 210, and 50 kDa. As assessed by enzyme-linked immunoadsorbent assays and ligand blot binding assays, megalin bound to intact Tg (660 and 330 kDa) and, to a even greater extent, to the 210-kDa Tg polypeptide, Furthermore, the 210-kDa Tg polypeptide inhibited megalin binding to intact Tg by similar to 70%, Solid phase assays showed binding of biotin-labeled heparin to intact Tg and to the 210-kDa Tg polypeptide, We characterized the 810-kDa Tg polypeptide by matrix-assisted laser desorption/ionization mass spectrometry analysis and found that it corresponds to the carboxyl-terminal portion of rat Tg, We developed a synthetic peptide corresponding to a 15-amino acid sequence in the carboxyl-terminal portion of rat Tg (Arg(689)-Lys(703)), containing a heparin-binding consensus sequence (SRRLKRP) and demonstrated heparin binding to this peptide. A rabbit antibody raised against the peptide recognized intact Tg in its native conformation and under denaturing conditions. This antibody markedly reduced heparin-binding to intact Tg, indicating that the region of native Tg corresponding to the peptide is involved in heparin binding. Furthermore, the anti-Tg peptide antibody almost completely inhibited binding of megalin to Tg, suggesting that the Tg region containing the peptide sequence is required for megalin binding. Physiologically, Tg binding to megalin on thyroid cells may be facilitated by Tg interaction with heparin-libe molecules (heparan sulfate proteoglycans) via adjacent binding sites. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Res Lab, Charlestown, MA 02129 USA. Univ Pisa, Dept Endocrinol, I-56100 Pisa, Italy. RP Marino, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pathol Res Lab, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK 46301] NR 52 TC 34 Z9 34 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 22 PY 1999 VL 274 IS 43 BP 30377 EP 30386 DI 10.1074/jbc.274.43.30377 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248LT UT WOS:000083276700010 PM 10521414 ER PT J AU Kumar, S Avraham, S Bharti, A Goyal, J Pandey, P Kharbanda, S AF Kumar, S Avraham, S Bharti, A Goyal, J Pandey, P Kharbanda, S TI Negative regulation of PYK2/related adhesion focal tyrosine kinase signal transduction by hematopoietic tyrosine phosphatase SHPTP1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASES; MYELOID-LEUKEMIA CELLS; GRB2-MEDIATED ASSOCIATION; DIFFERENTIAL REGULATION; C-ABL; PYK2; DNA; PP125(FAK); SRC; EXPRESSION AB Related adhesion focal tyrosine kinase (RAFTK) (also known as PYK2) is a cytoplasmic tyrosine kinase related to the focal adhesion kinase (FAK) p125(FAK). RAFTK is rapidly phosphorylated on tyrosine residues in response to various stimuli, such as tumor necrosis factor-alpha, changes in osmolarity, elevation in intracellular calcium concentration, lysophosphatidic acid, and bradykinin. Overexpression of RAFTK induces activation of c-Jun amino-terminal kinase (also known as stress-activated protein kinase), mitogen-activated protein kinase (MAPK), and p38 MAPK. The present studies demonstrate that RAFTK binds constitutively to the protein tyrosine phosphatase SHPTP1. In contrast to PTP1B, overexpression of wild-type SHPTP1 blocks tyrosine phosphorylation of RAFTK. The results further demonstrate that RAFTK is a direct substrate of SHPTP1 in vitro. Moreover, treatment of PC12 cells with bradykinin is associated with inhibition in tyrosine phosphorylation of RAFTK in the presence of SHPTP1. Furthermore, in contrast to the phosphatase-dead SHPTP1 C4535 mutant, overexpression of wild-type SHPTP1 blocks interaction of RAFTK with the SH2-domain of c-Src and inhibits RAFTK-mediated MAPK activation. Significantly, cotransfection of RAFTK with SHPTP1 did not inhibit RAFTK-mediated c-Jun amino-terminal kinase activation. Taken together, these findings suggest that SHPTP1 plays a negative role in PYK2/RAFTK signaling by dephosphorylating RAFTK. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Inst Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Inst Med, Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02115 USA. New England Med Ctr, Dept Radiat Oncol, Boston, MA 02111 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA75216]; NHLBI NIH HHS [HL55445] NR 36 TC 17 Z9 17 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 OCT 22 PY 1999 VL 274 IS 43 BP 30657 EP 30663 DI 10.1074/jbc.274.43.30657 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248LT UT WOS:000083276700048 PM 10521452 ER PT J AU Brinkman, BMN Telliez, JB Schievella, AR Lin, LL Goldfeld, AE AF Brinkman, BMN Telliez, JB Schievella, AR Lin, LL Goldfeld, AE TI Engagement of tumor necrosis factor (TNF) receptor 1 leads to ATF-2-and p38 mitogen-activated protein kinase-dependent TNF-alpha gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID KAPPA-B ACTIVATION; SIGNAL-TRANSDUCTION; 55-KDA RECEPTOR; MICE DEFICIENT; CELL-DEATH; INFECTION; MONOCYTOGENES; ANTIBODIES; RESISTANT; PATHWAYS AB Engagement of the tumor necrosis factor-alpha (TNF-alpha) receptors by the TNF-alpha ligand results in the rapid induction of TNF-alpha gene expression. The study presented here shows that autoregulation of TNF-alpha gene transcription by selective signaling through tumor necrosis factor receptor 1 (TNFR1) requires p38 mitogen-activated protein (MAP) kinase activity and the binding of the transcription factors ATF-2 and Jun to the TNF-alpha cAMP-response element (CRE) promoter element. Consistent with these findings, TNFR1 engagement results in increased p38 MAP kinase activity and p38-dependent phosphorylation of ATF-2. Furthermore, overexpression of MADD ((M) under bar AP kinase-(a) under bar ctivating (d) under bar eath (d) under bar omain protein), an adapter protein that binds to the death domain of TNFR1 and activates MAP kinase cascades, results in CRE-dependent induction of TNF-alpha gene expression. Thus, the TNF-alpha CRE site is the target of TNFR1 stimulation and mediates the autoregulation of TNF-alpha gene transcription. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Genet Inst, Small Molecule Drug Discovery Grp, Cambridge, MA 02139 USA. RP Goldfeld, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. RI Brinkman, Brigitta/C-1100-2009 FU NCI NIH HHS [CA58735] NR 33 TC 77 Z9 79 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 OCT 22 PY 1999 VL 274 IS 43 BP 30882 EP 30886 DI 10.1074/jbc.274.43.30882 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248LT UT WOS:000083276700077 PM 10521481 ER PT J AU Alberta, JA Auger, KR Batt, D Iannarelli, P Hwang, G Elliott, HL Duke, R Roberts, TM Stiles, CD AF Alberta, JA Auger, KR Batt, D Iannarelli, P Hwang, G Elliott, HL Duke, R Roberts, TM Stiles, CD TI Platelet-derived growth factor stimulation of monocyte chemoattractant protein-1 gene expression is mediated by transient activation of the phosphoinositide 3-kinase signal transduction pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C-FOS PROMOTER; MULTIPLE SEQUENCE ELEMENTS; SERUM RESPONSE ELEMENTS; KINASE IN-VITRO; NF-KAPPA-B; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSCRIPTION FACTOR; FACTOR INDUCTION; BINDING SITE; 3T3 CELLS AB Platelet-derived growth factor (PDGF) stimulates transcription of an immediate-early gene set in Balb/c 3T3 cells. One cohort of these genes, typified by c-fos, is induced within minutes following activation of PDGF receptors. A second cohort responds to PDGF only after a significant time delay, although induction is still a primary response to receptor activation as shown by "superindnction" in the presence of the protein synthesis inhibitor cycloheximide. PDGF-receptor activated signaling pathways for the "slow" immediate-early genes are poorly resolved. Using gain-of-function mutations together with small molecule inhibitors of kinase activity, we show that activation of PI 3-kinase is both necessary and sufficient for the induction of the prototype slow immediate-early gene, monocyte chemoattractant-1 (MCP-1), Following activation of PDGF receptors, MCP-1 mRNA does not begin to accumulate for at least 90 min. However, only a brief (10 min) interval of PI 3-kinase activity is required to trigger this delayed response. The serine/threonine protein kinase, Akt/PKB, likely functions as a downstream affector of PI 3-kinase for this induction. C1 Dana Farber Canc Inst, Dept Microbiol & Mol Genet, Div Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Stiles, CD (reprint author), Dana Farber Canc Inst, Dept Microbiol & Mol Genet, Div Canc Biol, 44 Binney St, Boston, MA 02115 USA. FU NICHD NIH HHS [P01 HD24826] NR 62 TC 20 Z9 20 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 OCT 22 PY 1999 VL 274 IS 43 BP 31062 EP 31067 DI 10.1074/jbc.274.43.31062 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 248LT UT WOS:000083276700102 PM 10521506 ER PT J AU Sestan, N Artavanis-Tsakonas, S Rakic, P AF Sestan, N Artavanis-Tsakonas, S Rakic, P TI Contact-dependent inhibition of cortical neurite growth mediated by notch signaling SO SCIENCE LA English DT Article ID MAMMALIAN NUMB; IN-VITRO; NEUROGENESIS; DIFFERENTIATION; SYNAPTOGENESIS; TRANSCRIPTION; LOCALIZATION; ACTIVATION; DISEASE; PATHWAY AB The exuberant growth of neurites during development becomes markedly reduced as cortical neurons mature. In vitro studies of neurons from mouse cerebral cortex revealed that contact-mediated Notch signaling regulates the capacity of neurons to extend and elaborate neurites, Up-regulation of Notch activity was concomitant with an increase in the number of interneuronal contacts and cessation of neurite growth. In neurons with low Notch activity, which readily extend neurites, up-regulation of Notch activity either inhibited extension or caused retraction of neurites. Conversely, in more mature neurons that had ceased their growth after establishing numerous connections and displayed high Notch activity,inhibition of Notch signaling promoted neurite extension. Thus, the formation of neuronal contacts results in activation of Notch receptors, Leading to restriction of neuronal growth and a subsequent arrest in maturity. C1 Yale Univ, Sch Med, Neurobiol Sect, New Haven, CT 06510 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Rakic, P (reprint author), Yale Univ, Sch Med, Neurobiol Sect, 333 Cedar St, New Haven, CT 06510 USA. FU NINDS NIH HHS [NS14841, NS26084] NR 50 TC 413 Z9 429 U1 0 U2 4 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 OCT 22 PY 1999 VL 286 IS 5440 BP 741 EP 746 DI 10.1126/science.286.5440.741 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 248XZ UT WOS:000083303200045 PM 10531053 ER PT J AU Mao, ZX Bonni, A Xia, F Nadal-Vicens, M Greenberg, ME AF Mao, ZX Bonni, A Xia, F Nadal-Vicens, M Greenberg, ME TI Neuronal activity-dependent cell survival mediated by transcription factor MEF2 SO SCIENCE LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; CREB PHOSPHORYLATION; ACTIVATION; NUCLEUS; CALCIUM; DEATH; DROSOPHILA; MYOGENESIS; APOPTOSIS AB During mammalian development, electrical activity promotes the calcium-dependent survival of neurons that have made appropriate synaptic connections. However, the mechanisms by which calcium mediates neuronal survival during development are not well characterized. A transcription-dependent mechanism was identified by which calcium influx into neurons promoted cell survival. The transcription factor MEF2 was selectively expressed in newly generated postmitotic neurons and was required for the survival of these neurons. Calcium influx into cerebellar granule neurons Led to activation of p38 mitogen-activated protein kinase-dependent phosphorylation and activation of MEF2. Once activated, MEF2 regulated neuronal survival by stimulating MEF2-dependent gene transcription. These findings demonstrate that MEF2 is a calcium-regulated transcription factor and define a function for MEF2 during nervous system development that is distinct from previously Well-characterized functions of MEF2 during muscle differentiation. C1 Childrens Hosp, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. RP Greenberg, ME (reprint author), Childrens Hosp, Dept Neurol, Div Neurosci, Boston, MA 02115 USA. RI Xia, Fen/G-3708-2013 FU NICHD NIH HHS [P30-HD18655]; NINDS NIH HHS [5T32NS07112, NS28829] NR 32 TC 362 Z9 373 U1 0 U2 9 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 22 PY 1999 VL 286 IS 5440 BP 785 EP 790 DI 10.1126/science.286.5440.785 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 248XZ UT WOS:000083303200058 PM 10531066 ER PT J AU Santy, LC Frank, SR Hatfield, JC Casanova, JE AF Santy, LC Frank, SR Hatfield, JC Casanova, JE TI Regulation of ARNO nucleotide exchange by a PH domain electrostatic switch SO CURRENT BIOLOGY LA English DT Article ID PROTEIN-KINASE-C; ADP-RIBOSYLATION FACTOR; PLASMA-MEMBRANE; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; HOMOLOGY DOMAINS; SUBSTRATE MARCKS; ACTIVATION; CYTOHESIN-1; PLECKSTRIN; PHOSPHORYLATION AB ARNO is a member of a family of guanine nucleotide exchange factors that activate small GTPases called ADP-ribosylation factors (ARFs) [1-3], which regulate vesicular trafficking and, in one case (ARF6), also regulate cortical actin structure [4], ARNO is located at the plasma membrane, and in the presence of activated protein kinase C (PKC) can induce cortical actin rearrangements reminiscent of those produced by active ARF6 [5-8]. High-affinity binding of ARNO to membranes, which is required for exchange activity, is mediated cooperatively by a pleckstrin homology (PH) domain and an adjacent carboxy-terminal polybasic domain [3,9]. ARNO is phosphorylated in vivo by PKC on a single serine residue, S392, located within the carboxy-terminal polybasic domain, Mutation of S392 to alanine does not prevent ARNO-mediated actin rearrangements, suggesting that phosphorylation does not lead to ARNO activation [6], Here, we report that phosphorylation negatively regulates ARNO exchange activity through a 'PH domain electrostatic switch'. Introduction of a negatively charged phosphate into the polybasic domain reduced interaction of ARNO with membranes both in vitro and in vivo, and inhibited exchange in vitro. This regulated membrane association is similar to the myristoyl electrostatic switch that controls membrane binding of the myristoylated alanine-rich C kinase substrate (MARCKS) [10], but to our knowledge is the first demonstration of an electrostatic switch regulating the membrane interaction of a protein containing a PH domain. This mechanism allows regulation of ARNO lipid binding and exchange activity at two levels, phosphoinositide-dependent recruitment and PKC dependent displacement from the membrane. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Immunol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Biol & Biomed Sci, Charlestown, MA 02129 USA. Massachusetts Gen Hosp E, Combined Program Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. RP Casanova, JE (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Cell Biol, Box 439, Charlottesville, VA 22908 USA. FU NIAID NIH HHS [AI-32991]; NIDDK NIH HHS [F32-DK-09924] NR 22 TC 50 Z9 50 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 21 PY 1999 VL 9 IS 20 BP 1173 EP 1176 DI 10.1016/S0960-9822(00)80019-6 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 248RM UT WOS:000083289200018 PM 10531036 ER PT J AU Cenciarelli, C Chiaur, DS Guardavaccaro, D Parks, W Vidal, M Pagano, M AF Cenciarelli, C Chiaur, DS Guardavaccaro, D Parks, W Vidal, M Pagano, M TI Identification of a family of human F-box proteins SO CURRENT BIOLOGY LA English DT Article ID MOTIF; PATHWAY AB F-box proteins are an expanding family of eukaryotic proteins characterized by an approximately 40 amino-acid motif, the F box (so named because cyclin F was one of the first proteins in which this motif was identified) [1], Some F-box proteins have been shown to be critical for the controlled degradation of cellular regulatory proteins [2,3]. In fact, F-box proteins are one of the four subunits of ubiquitin protein ligases called SCFs. The other three subunits are the Skp1 protein; one of the cullin proteins (Cul1 in metazoans and Cdc53 or Cul A in the yeast Saccharomyces cerevisiae); and the recently identified Rod protein (also called Rbx1 or Hrt1), SCF ligases bring ubiquitin conjugating enzymes (either Ubc3 or Ubc4) to substrates that are specifically recruited by the different F-box proteins. The need for high substrate specificity and the large number of known F box proteins in yeast and worms [2,4] suggest the existence of a large family of mammalian F-box proteins, Using Skp1 as a bait in a yeast two-hybrid screen and by searching DNA databases, we identified a family of 26 human F-box proteins, 25 of which were novel. Some of these proteins contained WD-40 domains or leucine-rich repeats; others contained either different protein-protein interaction modules or no recognizable motifs. We have named the F-box proteins that contain WD-40 domains Fbws, those containing leucine-rich repeats Fbls, and the remaining ones Fbxs, We have further characterized representative members of these three classes of F-box proteins. C1 NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Dept Pediat, New York, NY 10016 USA. NYU, Sch Med, Kaplan Comprehens Canc Ctr, New York, NY 10016 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. RP Pagano, M (reprint author), NYU, Sch Med, Dept Pathol, MSB 548,550 1st Ave, New York, NY 10016 USA. FU NCI NIH HHS [R01 CA76584]; NIGMS NIH HHS [R01 GM57587] NR 14 TC 256 Z9 287 U1 0 U2 15 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 21 PY 1999 VL 9 IS 20 BP 1177 EP 1179 DI 10.1016/S0960-9822(00)80020-2 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 248RM UT WOS:000083289200019 PM 10531035 ER PT J AU Dienstag, JL Schiff, ER Wright, TL Perrillo, RP Hann, HWL Goodman, Z Crowther, L Condreay, LD Woessner, M Rubin, M Brown, NA AF Dienstag, JL Schiff, ER Wright, TL Perrillo, RP Hann, HWL Goodman, Z Crowther, L Condreay, LD Woessner, M Rubin, M Brown, NA CA US Lamivudine Invest Grp TI Lamivudine as initial treatment for chronic hepatitis B in the United States SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Gastroenterological-Association / Digestive Disease Week CY MAY 16-22, 1998 CL NEW ORLEANS, LOUISIANA SP Amer Gastroenterol Assoc ID TERM FOLLOW-UP; VIRUS-INFECTION; INTERFERON-ALFA; THERAPY; TRIAL; POLYMERASE; REPLICATION; RESISTANCE; MUTATIONS AB Background Although the nucleoside analogue lamivudine has shown promise in patients with chronic hepatitis B, long-term data on patients from the United States are lacking. Methods We randomly assigned previously untreated patients with chronic hepatitis B to receive either 100 mg of oral lamivudine or placebo daily for 52 weeks. We then followed them for an additional 16 weeks to evaluate post-treatment safety and the durability of responses. The primary end point with respect to efficacy was a reduction of at least 2 points in the score on the Histologic Activity Index. On this scale, scores can range from 0 (normal) to 22 (most severe abnormalities). Results Of the 143 randomized patients, 137 were included in the efficacy analysis: 66 in the lamivudine group and 71 in the placebo group. The other six patients were excluded at the base-line visit because of the absence of a documented history of hepatitis B surface antigen for at least six months. After 52 weeks of treatment, lamivudine recipients were more likely than placebo recipients to have a histologic response (52 percent vs. 23 percent, P<0.001), loss of hepatitis B e antigen (HBeAg) in serum (32 percent vs. 11 percent, P=0.003), sustained suppression of serum hepatitis B virus (HBV) DNA to undetectable levels (44 percent vs. 16 percent, P<0.001), and sustained normalization of serum alanine aminotransferase levels (41 percent vs. 7 percent, P<0.001), and they were less likely to have increased hepatic fibrosis (5 percent vs. 20 percent, P=0.01). Lamivudine recipients were also more likely to undergo HBeAg seroconversion, defined as the loss of HBeAg, undetectable levels of serum HBV DNA, and the appearance of antibodies against HBeAg (17 percent vs. 6 percent, P=0.04). HBeAg responses persisted in most patients for 16 weeks after the discontinuation of treatment. Lamivudine was well tolerated. Self-limited post-treatment elevations in serum alanine aminotransferase were more common in lamivudine recipients: 25 percent had serum alanine aminotransferase levels that were at least three times base-line levels, as compared with 8 percent of placebo recipients (P=0.01). The clinical condition of all patients remained stable during the study. Conclusions In U.S. patients with previously untreated chronic hepatitis B, one year of lamivudine therapy had favorable effects on histologic, virologic, and biochemical features of the disease and was well tolerated. HBeAg responses were usually sustained after treatment. (N Engl J Med 1999;341:1256-63.) (C)1999, Massachusetts Medical Society. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Liver Biliary Pancreas Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Miami, Med Ctr, Ctr Liver Dis, Miami, FL 33152 USA. Vet Affairs Med Ctr, Miami, FL 33125 USA. Vet Affairs Med Ctr, Div Gastroenterol, San Francisco, CA 94121 USA. Alton Ochsner Med Fdn & Ochsner Clin, Div Gastroenterol, New Orleans, LA 70121 USA. Thomas Jefferson Univ, Jefferson Med Coll, Div Gastroenterol & Hepatol, Philadelphia, PA 19107 USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. Glaxo Wellcome Inc, Res Triangle Pk, NC 27709 USA. RP Dienstag, JL (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. FU NCRR NIH HHS [M01RR01066] NR 35 TC 1005 Z9 1069 U1 2 U2 19 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 21 PY 1999 VL 341 IS 17 BP 1256 EP 1263 DI 10.1056/NEJM199910213411702 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 247NF UT WOS:000083226300002 PM 10528035 ER PT J AU Miguel-Hidalgo, JJ Robinson, CP AF Miguel-Hidalgo, JJ Robinson, CP TI Histone H1 degrees expression in the developing cat retina SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE histone; retina cell type; terminal differentiation ID CELL-PROLIFERATION; GENE-EXPRESSION; GLIAL-CELLS; IN-VIVO; DIFFERENTIATION; ACCUMULATION; MOUSE; NEURONS; H10 AB Histone H1 degrees is a subtype of the non-core H1 histones located in the linker region of DNA between nucleosome cores and postulated to be involved in the regulation of gene expression. Studies in both the mouse retina and rat brain have correlated the terminal differentiation of cell types in these tissues to the expression of H1 degrees. The expression of H1 degrees in mouse retina occurs after light exposure suggesting that light may trigger the expression of H1 degrees. The aims of the present research were to: (1) describe the relationship of the appearance of H1 protein immunoreactivity to the formation of cell types and layers in the cat retina; and (2) determine whether H1" may be dependent on exposure to light or on other postnatal developmental events. We find the nuclei of ganglion, amacrine, and prospective bipolar cells contain H1 degrees immunoreactivity before birth, prior to the terminal differentiation of these cells. In the cat retina, expression of H1 degrees occurs prior to Light exposure. These results show that the expression of H1 degrees protein is not required for the terminal differentiation of retinal cell types in the car. Additionally, we find no requirement for Light exposure prior to H1 degrees expression, These findings are at variance with the findings in the mouse retina and are inconsistent with any cross species requirement for the expression of this histone in the terminal differentiation of cell types in the retina. (C) 1999 Elsevier Science B.V. All rights reserved. C1 Univ Calif Davis, Dept Psychol, Davis, CA 95616 USA. Greater Los Angeles Vet Adm Healthcare Syst, Los Angeles, CA USA. RP Robinson, CP (reprint author), Univ So Calif, Dept Neurol, 1975 Zonal Ave,KAM 410, Los Angeles, CA 90033 USA. OI Miguel-Hidalgo, Jose Javier/0000-0002-4094-1249 NR 25 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD OCT 20 PY 1999 VL 117 IS 1 BP 39 EP 45 DI 10.1016/S0165-3806(99)00095-4 PG 7 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 253PL UT WOS:000083564900005 ER PT J AU Rowitch, DH Kispert, A McMahon, AP AF Rowitch, DH Kispert, A McMahon, AP TI Pax-2 regulatory sequences that direct transgene expression in the developing neural plate and external granule cell layer of the cerebellum SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE transgenic mouse; gene regulation; neural plate; rhombomere; Pax-2; transcription factor; midbrain-hindbrain junction; Sonic hedgehog ID MOUSE OTX2; INT-1 PROTOONCOGENE; PRIMITIVE ENDODERM; MIDBRAIN; HINDBRAIN; BRAIN; GENES; WNT-1; GASTRULATION; FOREBRAIN AB Expression of Pax-2 in the mouse gastrula is the first marker of the midbrain-hindbrain region, To address roles played by transcription factors in the process of neural plate pattern formation and to facilitate gain-of-function approaches in the study of midbrain-hindbrain and cerebellar development, we characterized regulatory sequences at the Pax-2 locus using an in vivo transgenic mouse reporter assay. An 8.5 kb fragment of genomic DNA located upstream of Pax-2 directed lacZ expression prior to neurulation (7.5 days post-coitum, dpc) in a region fated to become midbrain and hindbrain, and subsequently in developing neuroepithelium. While similar to the pattern of Pax-2 expression, reporter gene activity extended beyond the boundaries of Pax-2 expression, most probably reflecting purdurance of beta-galactosidase activity and an absence of DNA sequences that restrict Pax-2 expression to rhombomere 1 by 9.5 dpc, In the fetal and neonatal brain, Pax-2-lacZ activity was confined largely to Purkinje cells and the external granule cell layer (EGL) of the cerebellum. A 4 kb regulatory element, in contrast, initiated neural expression at 8.25 dpc in the anterior hindbrain, but recapitulated all later aspects of Pax-2-lacZ activity observed with the larger transgene. These results indicate the presence of regulatory sequences upstream of the Pax-2 locus capable of directing gene expression in the developing midbrain, first rhombomere of the hindbrain, and its principal derivative, the cerebellum. Successful misexpression of Sonic hedgehog demonstrates that Pax-2 regulatory sequences should prove generally useful for transgenic gain-of-function approaches in mice. (C) 1999 Elsevier Science B.V, All rights reserved. C1 Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pediat, Div Newborn Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Rowitch, DH (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Dana 640D, Boston, MA 02115 USA. NR 42 TC 21 Z9 21 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD OCT 20 PY 1999 VL 117 IS 1 BP 99 EP 108 DI 10.1016/S0165-3806(99)00104-2 PG 10 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 253PL UT WOS:000083564900012 ER PT J AU Zhang, SM Hunter, DJ Rosner, BA Colditz, GA Fuchs, CS Speizer, FE Willett, WC AF Zhang, SM Hunter, DJ Rosner, BA Colditz, GA Fuchs, CS Speizer, FE Willett, WC TI Dietary fat and protein in relation to risk of non-Hodgkin's lymphoma among women SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HETEROCYCLIC AMINE CONTENT; HUMAN IMMUNE STATUS; ACID COMPOSITION; CANCER INCIDENCE; VARYING DEGREES; UNITED-STATES; FOOD; QUESTIONNAIRE; CONSUMPTION; DONENESS AB Background: Non-Hodgkin's lymphoma occurs more frequently in individuals with suppressed immune status, and some types of dietary fat and protein have been associated with decreased immune responses. In this study, we examined the intake of specific types of dietary fat and protein in relation to the risk of non-Hodgkin's lymphoma. Methods: We documented 199 incident cases of non-Hodgkin's lymphoma in a cohort of 88410 women, who were enrolled in the Nurses' Health Study and were aged 34-60 years in 1980, during 14 years of follow-up. Relative risks of the disease and 95% confidence intervals (95% CIs) were calculated. All P values are two-sided and were considered to be statistically significant for P<.05. Results: Intake of saturated fat was associated with an increase in risk that was not statistically significant; the multivariate relative risk for the highest versus the lowest quintiles of intake was 1.4 (95% CI = 0.7-3.0; P for trend =.42). Intake of beef, pork, or lamb as a main dish was associated with a statistically significantly increased risk of non-Hodgkin's lymphoma; the multivariate relative risk for consumption of these meats at least once per day as compared with less than once per week was 2.2 (95% CI = 1.1-4.4; P for trend =.002), Higher intake of trans unsaturated fat was also statistically significantly associated with an increased risk of the disease; the multivariate relative risk for the highest versus the lowest quintiles was 2.4 (95% CI = 1.3-4.6; P for trend =.01). Higher intake of red meat cooked by broiling or barbecuing-but not by roasting, pan-frying, or boiling or stewing-was associated with an increase in risk that was not statistically significant. Conclusions: Greater dietary intake of certain meats and fats was associated with a higher risk of non-Hodgkin's lymphoma. These relationships and their potential mechanisms deserve further examination. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Harvard Ctr Canc Prevent, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Zhang, SM (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 665 Huntington Ave, Boston, MA 02115 USA. EM Shumin.Zhang@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA40356] NR 36 TC 92 Z9 92 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-. Natl. Cancer Inst. PD OCT 20 PY 1999 VL 91 IS 20 BP 1751 EP 1758 DI 10.1093/jnci/91.20.1751 PG 8 WC Oncology SC Oncology GA 247XP UT WOS:000083246500014 PM 10528026 ER PT J AU Potosky, AL Harlan, LC Stanford, JL Gilliland, FD Hamilton, AS Albertsen, PC Eley, JW Liff, JM Deapen, D Stephenson, RA Legler, J Ferrans, CE Talcott, JA Litwin, MS AF Potosky, AL Harlan, LC Stanford, JL Gilliland, FD Hamilton, AS Albertsen, PC Eley, JW Liff, JM Deapen, D Stephenson, RA Legler, J Ferrans, CE Talcott, JA Litwin, MS TI Prostate cancer practice patterns and quality of life: The prostate cancer outcomes study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LONG-TERM SURVIVAL; RADICAL PROSTATECTOMY; OF-LIFE; PATIENT; POPULATION; SURVEILLANCE; EPIDEMIOLOGY; DECISION; THERAPY; MEN C1 NCI, Appl Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. New Mexico Tumor Registry, Albuquerque, NM USA. Univ So Calif, Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ Connecticut, Ctr Hlth, Div Urol, Farmington, CT USA. Emory Univ, Rollins Sch Publ Hlth, Georgia Ctr Canc Stat, Atlanta, GA 30322 USA. Univ Utah, Dept Med, Div Urol, Salt Lake City, UT 84112 USA. Univ Illinois, Coll Nursing, Chicago, IL USA. Massachusetts Gen Hosp, Dept Gen Internal Med, Boston, MA 02114 USA. Univ Calif Los Angeles, Sch Med, Dept Urol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Hlth Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA USA. RP Potosky, AL (reprint author), NIH, EPN, Rm 313,6130 Execut Blvd MSC 7344, Bethesda, MD 20892 USA. NR 43 TC 158 Z9 159 U1 1 U2 2 PU NATL CANCER INSTITUTE PI BETHESDA PA 9030 OLD GEORGETOWN RD, BETHESDA, MD 20814 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 20 PY 1999 VL 91 IS 20 BP 1719 EP 1724 DI 10.1093/jnci/91.20.1719 PG 6 WC Oncology SC Oncology GA 247XP UT WOS:000083246500009 PM 10528021 ER PT J AU Lorenz, K AF Lorenz, K TI The sharer SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material C1 W Los Angeles Vet Affairs Med Ctr, Dept Internal Med, Los Angeles, CA 90073 USA. RP Lorenz, K (reprint author), W Los Angeles Vet Affairs Med Ctr, Dept Internal Med, 11303 Wilshire Blvd,Code 111G, Los Angeles, CA 90073 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 19 PY 1999 VL 131 IS 8 BP 625 EP 626 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 246ZR UT WOS:000083196600012 PM 10523226 ER PT J AU Martinez, V Barrachina, MD Wang, LX Tache, Y AF Martinez, V Barrachina, MD Wang, LX Tache, Y TI Intracerebroventricular leptin inhibits gastric emptying of a solid nutrient meal in rats SO NEUROREPORT LA English DT Article DE brain-gut; food intake; gastric emptying; leptin; Long Evans; OB-protein ID FOOD-INTAKE; RECEPTOR; BRAIN AB THE effects of leptin injected intracerebroventricularly (i.c.v.) or i.p. on food intake and gastric emptying of a solid nutrient meal mere studied in fasted Long-Evan rats. Leptin (3 mu g, i.c.v.) reduced the 5 h cumulative food intake by 39% and gastric transit by 50% while i.p. leptin (300 mu g) resulted in a 35% decrease in food intake and no change in gastric transit after 5 h. Lower i.p. doses of leptin (30 or 3 mu g) did not alter food intake. These results show that central, unlike peripheral, injection of leptin inhibits gastric transit of an ingested meal; such a central action of leptin may contribute to the greater potency of i.c.v. than i.p. leptin to suppress food intake. (C) 1999 Lippincott Williams & Wilkins. C1 CURE, Vet Adm Greater Los Angeles, Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Div Digest Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Inst Brain Res, Los Angeles, CA 90073 USA. RP Tache, Y (reprint author), CURE, Vet Adm Greater Los Angeles, Digest Dis Res Ctr, Bldg 115,Rm 203,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. RI Martinez, Vicente/N-1189-2014 FU NIDDK NIH HHS [DK-33061, DK-41301] NR 22 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD OCT 19 PY 1999 VL 10 IS 15 BP 3217 EP 3221 DI 10.1097/00001756-199910190-00017 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 247YY UT WOS:000083249600018 PM 10574563 ER PT J AU Macneil, MA Heussy, JK Dacheux, RF Raviola, E Masland, RH AF Macneil, MA Heussy, JK Dacheux, RF Raviola, E Masland, RH TI The shapes and numbers of amacrine cells: Matching of photofilled with Golgi-stained cells in the rabbit retina and comparison with other mammalian species SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE fluorescence; morphology; classification; dendrites ID INNER PLEXIFORM LAYER; INDOLEAMINE-ACCUMULATING NEURONS; MACAQUE MONKEY RETINA; CAT RETINA; GANGLION-CELLS; BIPOLAR CELLS; SYNAPTIC CONNECTIONS; CHOLINERGIC NEURONS; GROUND-SQUIRREL; PRIMATE RETINA AB Amacrine cells of the rabbit retina were studied by "photofilling," a photochemical method in which a fluorescent product is created within an individual cell by focal irradiation of the nucleus; and by Golgi impregnation. The photofilling method is quantitative, allowing an estimate of the frequency of the cells. The Golgi method shows their morphology in better detail. The photofilled sample consisted of 261 cells that were imaged digitally in through-focus series from a previous study (MacNeil and Masland [1998] Neuron 20:971-982). The Golgi material consisted of 49 retinas that were stained as wholemounts. Eleven of these subsequently were cut in vertical section. Of the many hundreds of cells stained, digital through-focus series were recorded for 208 of the Golgi-impregnated cells. The two methods were found to confirm one another: Most cells revealed by photofilling were recognized easily by Golgi staining, and vice versa. The greater resolution of the Golgi method allowed a more precise description of the cells and several types of amacrine cell were redefined. Two new types were identified. The two methods, taken together, provide an essentially complete accounting of the populations of amacrine cells present in the rabbit retina. Many of them correspond to amacrine cells that have been described in other mammalian species, and these homologies are reviewed. (C) 1999 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Univ Alabama, Eye Fdn Hosp, Dept Ophthalmol, Birmingham, AL 35233 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 429, Boston, MA 02114 USA. FU NEI NIH HHS [EY-01344, EY-03011] NR 78 TC 175 Z9 177 U1 0 U2 6 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 OCT 18 PY 1999 VL 413 IS 2 BP 305 EP 326 PG 22 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 238GU UT WOS:000082703200010 PM 10524341 ER PT J AU Janusonis, S Fite, KV Foote, W AF Janusonis, S Fite, KV Foote, W TI Topographic organization of serotonergic dorsal raphe neurons projecting to the superior colliculus in the Mongolian gerbil (Meriones unguiculatus) SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE dorsal raphe nucleus; serotonin (5-HT); visual system; dorsal tegmental nucleus; laterodorsal tegmental nucleus; topography ID GABAERGIC SYNAPTIC INNERVATION; CENTRAL-NERVOUS-SYSTEM; CAT BRAIN-STEM; IMMUNOREACTIVE NEURONS; SUPRACHIASMATIC NUCLEUS; SEROTONINERGIC PROJECTIONS; INTERGENICULATE LEAFLET; CHOLERA-TOXIN; CELL-BODIES; RAT AB Recent evidence suggests that the dorsal raphe nucleus (DRN) of the brainstem is a collection of neuronal clusters having different neurochemical characteristics and efferent projection patterns. To gain further insight into the neuroanatomic organization of the DRN, neuronal populations projecting to the superior colliculus (SC) were mapped in a highly visual rodent, the Mongolian gerbil (Meriones unguiculatus). Retrograde tracers Fluoro-Cold (FG) or cholera toxin subunit-B (CTB) were injected into the superficial layers of the SC, and serotonin (5-hydroxytryptamine, 5-HT) -positive cells were identified by using immunocytochemistry in the FG-injected animals. Based on its projections to the SC, the DRN was divided into five rostrocaudal levels. In the rostral and middle levels of the DRN, virtually all FG-fined cells occurred in the lateral DRN, and 36-55% of 5-HT-immunoreactive (Ei-HT-ir) cells were also double-labeled with FG. Caudally, FG-filled cells occurred in the lateral, ventromedial, and interfascicular DRN; and 44, 12, and 31% of 5-HT-ir cells, respectively, were also FG-filled. The dorsomedial DRN contained only a small proportion of FG-filled cells at its most caudal level and was completely devoid of FG-filled cells more rostrally. The CTB-injected animals showed a similar distribution of retrogradely labeled cells in the DRN. Topographically, the dorsal tegmental nucleus and the laterodorsal tegmental nucleus appeared to be closely associated with B-HT-ir cells in the caudal DRN. These results suggest that the lateral DRN and the ventromedial/interfascicular DRN may be anatomically, morphologically, and neurochemically unique subdivisions of the gerbil DRN. (C) 1999 Wiley-Liss, Inc. C1 Univ Massachusetts, Neurosci & Behav Program, Amherst, MA 01003 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Janusonis, S (reprint author), Univ Massachusetts, Neurosci & Behav Program, Tobin Hall, Amherst, MA 01003 USA. NR 73 TC 31 Z9 32 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 OCT 18 PY 1999 VL 413 IS 2 BP 342 EP 355 DI 10.1002/(SICI)1096-9861(19991018)413:2<342::AID-CNE12>3.0.CO;2-# PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 238GU UT WOS:000082703200012 PM 10524343 ER PT J AU Winandy, S Wu, L Wang, JH Georgopoulos, K AF Winandy, S Wu, L Wang, JH Georgopoulos, K TI Pre-T cell receptor (TCR) and TCR-controlled checkpoints in T cell differentiation are set by Ikaros SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE thymocyte; selection; signaling; homeostasis; malignancy ID GENE REARRANGEMENT; NEGATIVE SELECTION; BETA-CHAIN; MICE; EXPRESSION; LYMPHOCYTES; THYMOCYTES; MUTATION; THYMUS AB T cell differentiation relies on pre-T cell receptor (TCR) and TCR signaling events that take place at successive steps of the pathway. Here, we show that two of these T cell differentiation checkpoints are regulated by Ikaros. In the absence of Ikaros, double negative thymocytes can differentiate to the double positive stage without expression of a pre-TCR complex. Subsequent events in T cell development mediated by TCR involving transition from the double positive to the single positive stage are also regulated by Ikaros. Nonetheless, ill Ikaros-deficient thymocytes, the requirement of pre-TCR expression for expansion of immature thymocytes as they progress to the double positive stage is still maintained, and the T cell malignancies that invariably arise in the thymus of Ikaros-deficient mice are dependent on either pre-TCR or TCR signaling. We conclude that Ikaros regulates T cell differentiation, selection, and homeostasis by providing signaling thresholds for pre-TCR and TCR. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3050, Australia. RP Georgopoulos, K (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Bldg 149,13th St, Charlestown, MA 02129 USA. FU NIAID NIH HHS [R01 AI038342, R01 AI38342-03] NR 26 TC 104 Z9 104 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 18 PY 1999 VL 190 IS 8 BP 1039 EP 1048 DI 10.1084/jem.190.8.1039 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 248LV UT WOS:000083277000001 PM 10523602 ER EF