FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kim, DR Oettinger, MA AF Kim, DR Oettinger, MA TI Regulation of V(D)J recombination by interaction beta;een phosphorylated RAG2 and 14-3-3 SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Ulsan, Immunomodulat Res Ctr, Ulsan 680749, South Korea. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1042 EP A1042 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100768 ER PT J AU Li, X Martin, F Kearney, JF Carte, RH AF Li, X Martin, F Kearney, JF Carte, RH TI Differences in BCR signaling in mature splenic B cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Alabama, Birmingham, AL USA. Birmingham VAMC, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A970 EP A970 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100345 ER PT J AU Liblau, RS Cornet, A Savidge, T Cabarocca, J Desreumaux, P Lassmann, H AF Liblau, RS Cornet, A Savidge, T Cabarocca, J Desreumaux, P Lassmann, H TI A transgenic model of jejuno-ileo colitis by autoimmune targeting of enteric glia. SO FASEB JOURNAL LA English DT Meeting Abstract C1 INSERM, CJF 9711, F-75654 Paris 13, France. Hop La Pitie Salpetriere, Immunol Lab, Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dept Gastroenterol, Lille, France. Klin Inst Neurol, Vienna, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A977 EP A977 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100382 ER PT J AU McAdam, A Chang, T Lumelsky, A Ling, V Collins, M Chernova, T Sharpe, AH Freeman, GJ AF McAdam, A Chang, T Lumelsky, A Ling, V Collins, M Chernova, T Sharpe, AH Freeman, GJ TI Mouse inducible costimulatory (ICOS) molecule expression is increased by CD28 costimulation and regulates development of Th2 cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Genet, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1169 EP A1169 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101513 ER PT J AU Melby, PC Chandrasekar, B Zhao, W AF Melby, PC Chandrasekar, B Zhao, W TI Susceptibility of hamsters to an intracellular pathogen is associated with a defect in IFN-gamma-mediated macrophage activation SO FASEB JOURNAL LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1031 EP A1031 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100702 ER PT J AU Newman, M Livingston, B Sette, A Chesnut, R Kalams, S AF Newman, M Livingston, B Sette, A Chesnut, R Kalams, S TI Identification and immunological evaluation of conserved HIV-1 supertype epitopes restricted by HLA-A2. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Epimmune Inc, San Diego, CA 92121 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A942 EP A942 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100175 ER PT J AU Quinones, M Melby, PC Ahuja, SK Ahuja, SS AF Quinones, M Melby, PC Ahuja, SK Ahuja, SS TI Microbe-induced mobilization of preformed, membrane-associated IL-12 from dendritic cells is a determinant for the rapid induction of TH1 responses SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1180 EP A1180 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101581 ER PT J AU Rotzschke, O Falk, K Santambrogio, L Dorf, ME Brosnan, C Strominger, JL AF Rotzschke, O Falk, K Santambrogio, L Dorf, ME Brosnan, C Strominger, JL TI Induction and suppression of EAE with oligomerized T cell epitopes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Cambridge, MA 02138 USA. Max Delbruck Ctr Mol Med, Berlin, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1117 EP A1117 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101209 ER PT J AU Santambrogio, L Sato, AK Fischer, FR Stern, LJ Strominger, JL AF Santambrogio, L Sato, AK Fischer, FR Stern, LJ Strominger, JL TI Empty class II MHC protein and the chaperone H2-DM expressed on the surface of immature dendritic cell SO FASEB JOURNAL LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1161 EP A1161 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101465 ER PT J AU Shi, HN Liu, HY Nagler-Anderson, C AF Shi, HN Liu, HY Nagler-Anderson, C TI Adjuvant effect of intestinal helminth infection on the response to a model food antigen SO FASEB JOURNAL LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mucosal Immunol Lab, Charlestown, MA 02129 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1198 EP A1198 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101683 ER PT J AU Stern, LJ Sato, AK Fischer, FR Strominger, JL Santambrogio, L AF Stern, LJ Sato, AK Fischer, FR Strominger, JL Santambrogio, L TI Empty class II MHC molecules: allele and cell-type specificity and developmental regulation SO FASEB JOURNAL LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A944 EP A944 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100191 ER PT J AU Suri-Payer, E Cantor, H AF Suri-Payer, E Cantor, H TI Requirements for the development and prevention of murine autoimmune gastritis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Gothenburg Univ, Dept Rheumatol, S-41346 Gothenburg, Sweden. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A993 EP A993 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643100480 ER PT J AU Weisbart, RH Baldwin, R Huh, B Zack, DJ Nishimura, R AF Weisbart, RH Baldwin, R Huh, B Zack, DJ Nishimura, R TI Novel protein transfection of primary rat cortical neurons utilizing an antibody that penetrates living cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Vet Affairs Greater Los Angeles Healthcare Syst, Dept Med, Div Rheumatol, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 20 PY 2000 VL 14 IS 6 SU S BP A1135 EP A1135 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 307FQ UT WOS:000086643101314 ER PT J AU Rosowsky, A Wright, JE Vaidya, CM Forsch, RA Bader, H AF Rosowsky, A Wright, JE Vaidya, CM Forsch, RA Bader, H TI Analogues of the potent nonpolyglutamatable antifolate N-alpha-(4-amino-4-deoxypteroyl)-N-delta-hemiphthaloyl-L-ornithine (PT523) with modifications in the side chain, p-aminobenzoyl moiety, or 9,10-bridge: Synthesis and in vitro antitumor activity SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID HUMAN DIHYDROFOLATE-REDUCTASE; METHOTREXATE ANALOGS; BIOLOGICAL-ACTIVITY; FOLYLPOLYGLUTAMATE SYNTHETASE; CONVENIENT SYNTHESIS; AMINOPTERIN ANALOGS; FOLATE ANALOGS; INHIBITORS; ACID; PTERIDINES AB Seven N-alpha-(4-amino-4-deoxypteroyl)-N-sigma-hemiphtha (2, PT523) analogues were synthesized by modifications of the literature synthesis of the corresponding AMT (1) analogues and were tested as inhibitors of tumor cell growth. in growth assays against cultured CCRF-CEM human leukemic cells exposed to drug for 72 h, the IC50 values of analogues in which N-10 was replaced by CH2 and CHMe were found to be 0.55 +/- 0.07 and 0.63 +/- 0.08 nM, and thus these analogues are more potent than 1 (IC50 = 4.4 +/- 1.0 nM) or 2 (IC50 = 1.5 +/-: 0.39 nM). The 10-ethyl-10-deaza analogue of 2 (IC50 = 1.2 +/- 0.25 nM) was not statistically different from 2 but was more potent than edatrexate, the 10-ethyl-10-deaza analogue of 1, which had an IC50 of 3.3 +/- 0.36 nM. In contrast, the analogue of 2 with both an ethyl and a CO2Me group at the 10-position had an IC50 of 54 +/- 4.9 nM, showing this modification to be unfavorable. The 4-amino-1-naphthoic acid analogue of 2 had an IC50 Of 1.2 +/- 0.22 nM, indicating that replacement of the p-aminobenzoic acid (pABA) moiety does not diminish cytotoxicity. The analogues in which the (CH2)(3) Side chain was replaced by slightly longer CH2SCH2 and (CH2)(2)-SCH2 groups gave IC50 values of 4.4 +/- 1.1 and 5.0 +/- 0.56 nM and thus were somewhat less potent than the parent molecule. However the analogues in which the aromatic COOH group was at the meta and para positions of the phthaloyl ring had IC50 values of 7.5 +/- 0.47 and 55 +/- 0.07 nM, confirming the low potency we had previously observed with these compounds against other cell lines. Overall, the results in this study support the conclusion that, while the position of the phthaloyl COOH group and the length of the amino acid side chain in 2 are important determinants of cytotoxic potency, changes in the pABA region and 9,10-bridge are well-tolerated and can even increase potency. 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 Rosowsky, A (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA25394, CA70349] NR 41 TC 16 Z9 17 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD APR 20 PY 2000 VL 43 IS 8 BP 1620 EP 1634 DI 10.1021/jm990630f PG 15 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 308DL UT WOS:000086695200021 PM 10780919 ER PT J AU Gao, YJ Ferguson, DO Xie, W Manis, JP Sekiguchi, J Frank, KM Chaudhuri, J Horner, J DePinho, RA Alt, FW AF Gao, YJ Ferguson, DO Xie, W Manis, JP Sekiguchi, J Frank, KM Chaudhuri, J Horner, J DePinho, RA Alt, FW TI Interplay of p53 and DNA-repair protein XRCC4 in tumorigenesis, genomic stability and development SO NATURE LA English DT Article ID STRAND BREAK REPAIR; V(D)J RECOMBINATION; TRANSLOCATIONS; TRANSPOSITION; CELLS; RAG1; MICE AB XRCC4 is a non-homologous end-joining protein employed in DNA double strand break repair and in V(D)J recombination(1,2). In mice, XRCC4-deficiency causes a pleiotropic phenotype, which includes embryonic lethality and massive neuronal apoptosis 2. When DNA damage is not repaired, activation of the cell cycle checkpoint protein p53 can lead to apoptosis(3). Here we show that p53-deficiency rescues several aspects of the XRCC4-deficient phenotype, including embryonic lethality, neuronal apoptosis, and impaired cellular proliferation. However, there was no significant rescue of impaired V(D)J recombination or lymphocyte development. Although p53-deficiency allowed postnatal survival of XRCC4-deficient mice, they routinely succumbed to pro-B-cell lymphomas which had chromosomal translocations linking amplified c-myc oncogene and IgH locus sequences. Moreover, even XRCC4-deficient embryonic fibroblasts exhibited marked genomic instability including chromosomal translocations. Our findings support a crucial role for the non-homologous end-joining pathway as a caretaker of the mammalian genome, a role required both for normal development and for suppression of tumours. C1 Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. OI Sekiguchi, JoAnn/0000-0002-7178-4258 NR 25 TC 397 Z9 403 U1 0 U2 5 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 20 PY 2000 VL 404 IS 6780 BP 897 EP 900 DI 10.1038/35009138 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 306XY UT WOS:000086625000051 PM 10786799 ER PT J AU Trainer, PJ Drake, WM Katznelson, L Freda, PU Herman-Bonert, V van der Lely, AJ Dimaraki, EV Stewart, PM Friend, KE Vance, ML Besser, GM Scarlett, JA Thorner, MO Parkinson, C Klibanski, A Powell, JS Barkan, AL Sheppard, MC Maldonado, M Rose, DR Clemmons, DR Johannson, G Bengtsson, BA Stavrou, S Kleinberg, DL Cook, DM Phillips, LS Bidlingmaier, M Strasburger, CJ Hackett, S Zib, K Bennett, WF Davis, RJ AF Trainer, PJ Drake, WM Katznelson, L Freda, PU Herman-Bonert, V van der Lely, AJ Dimaraki, EV Stewart, PM Friend, KE Vance, ML Besser, GM Scarlett, JA Thorner, MO Parkinson, C Klibanski, A Powell, JS Barkan, AL Sheppard, MC Maldonado, M Rose, DR Clemmons, DR Johannson, G Bengtsson, BA Stavrou, S Kleinberg, DL Cook, DM Phillips, LS Bidlingmaier, M Strasburger, CJ Hackett, S Zib, K Bennett, WF Davis, RJ TI Treatment of acromegaly with the growth hormone-receptor antagonist pegvisomant SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID LONG-TERM TREATMENT; TRANSSPHENOIDAL SURGERY; FOLLOW-UP; OCTREOTIDE; THERAPY; CABERGOLINE AB Background: Patients with acromegaly are treated with surgery, radiation therapy, and drugs to reduce hypersecretion of growth hormone, but the treatments may be ineffective and have adverse effects. Pegvisomant is a genetically engineered growth hormone-receptor antagonist that blocks the action of growth hormone. Methods: We conducted a 12-week, randomized, double-blind study of three different daily doses of pegvisomant (10 mg, 15 mg, and 20 mg) and placebo, given subcutaneously, in 112 patients with acromegaly. Results: The mean (+/-SD) serum concentration of insulin-like growth factor I (IGF-I) decreased from base line by 4.0+/-16.8 percent in the placebo group, 26.7+/-27.9 percent in the group that received 10 mg of pegvisomant per day, 50.1+/-26.7 percent in the group that received 15 mg of pegvisomant per day, and 62.5+/-21.3 percent in the group that received 20 mg of pegvisomant per day (P<0.001 for the comparison of each pegvisomant group with placebo), and the concentrations became normal in 10 percent, 54 percent, 81 percent, and 89 percent of patients, respectively (P<0.001 for each comparison with placebo). Among patients treated with 15 mg or 20 mg of pegvisomant per day, there were significant decreases in ring size, soft-tissue swelling, the degree of excessive perspiration, and fatigue. The score for total symptoms and signs of acromegaly decreased significantly in all groups receiving pegvisomant (P less/equal 0.05). The incidence of adverse effects was similar in all groups. Conclusions: On the basis of these preliminary results, treatment of patients who have acromegaly with a growth hormone-receptor antagonist results in a reduction in serum IGF-I concentrations and in clinical improvement. (N Engl J Med 2000;342:1171-7.) (C) 2000, Massachusetts Medical Society. C1 Christie Univ Hosp, Manchester, Lancs, England. Univ S Manchester Hosp, Manchester M20 8LR, Lancs, England. St Bartholomews Hosp, London, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Acad Hosp Dijkzigt, NL-3000 DR Rotterdam, Netherlands. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Univ Birmingham, Birmingham, W Midlands, England. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Sensus Drug Dev, Austin, TX 78701 USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. NYU, Med Ctr, New York, NY 10016 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Munich, Klinikum Innenstadt, D-8000 Munich, Germany. Statworks, Chapel Hill, NC USA. RP Scarlett, JA (reprint author), Sensus Drug Dev, 98 San Jacinto Blvd,Suite 430, Austin, TX 78701 USA. OI Trainer, Peter/0000-0003-0146-3835 NR 27 TC 451 Z9 461 U1 2 U2 21 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 APR 20 PY 2000 VL 342 IS 16 BP 1171 EP 1177 DI 10.1056/NEJM200004203421604 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 305DG UT WOS:000086523700004 PM 10770982 ER PT J AU Hayes, FJ Eichhorn, JH Pena, CS Mark, EJ Katznelson, L Perakis, CR AF Hayes, FJ Eichhorn, JH Pena, CS Mark, EJ Katznelson, L Perakis, CR TI A 60-year-old man with persistent gynecomastia after excision of a pituitary adenoma - Leydig-cell tumor of the testis, estrogenic, with gynecomastia. Pituitary macroadenoma, gonadotroph type, nonfunctioning. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PROGNOSTIC FACTORS; HORMONAL PROFILE; NORMAL MEN; HYPOGONADISM; FEMINIZATION; INHIBITION; SECRETION; ESTRADIOL; FEATURES; THERAPY C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA USA. RP Hayes, FJ (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. NR 39 TC 4 Z9 4 U1 0 U2 0 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 APR 20 PY 2000 VL 342 IS 16 BP 1196 EP 1204 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 305DG UT WOS:000086523700008 ER PT J AU Erickson, LC Torchiana, DF Schneider, EC Newburger, JW Hannan, EL AF Erickson, LC Torchiana, DF Schneider, EC Newburger, JW Hannan, EL TI The relationship between managed care insurance and use of lower-mortality hospitals for CABG surgery SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID SOCIAL-CLASS; DISTANCE; RACE; TIME AB Context Explicit information about the quality of coronary artery bypass graft (CABG) surgery has been available for nearly a decade in New York State; however, the extent to which managed care insurance plans direct enrollees to the lowest-mortality CABG surgery hospitals remains unknown. Objective To compare the proportion of patients with managed care insurance and fee-for-service (FFS) insurance who undergo CABG surgery at lower-mortality hospitals. Design A retrospective cohort study of CABG surgery discharges from 1993 to 1996, using New York Department of Health databases and multivariate analysis to estimate the use of lower-mortality hospitals by patients with different types of health Insurance. Setting Cardiac surgical centers in New York, of which 14 were classified as lower-mortality hospitals (mean rate, 2.1%) and 17 were classified as higher-mortality hospitals (mean rate, 3.2%). Patients A total of 58 902 adults older than 17 years who were hospitalized for CABG surgery. Patients were excluded if their CABG surgery was combined with any valve procedure or left ventricular aneurysm resection or if they were younger than 65 years and enrolled in Medicare FFS or Medicare managed care. Main Outcome Measure Probability of a patient receiving CABG surgery at a lower-mortality hospital. Results Compared with patients with private FFS insurance (n = 18 905), patients with private managed care insurance (n = 7169) and Medicare managed care insurance (n = 880) were less likely to receive CABG surgery at a lower-mortality hospital (relative risk [RR] of surgery at a lower-mortality hospital compared with patients with private FFS insurance, 0.77; 95% confidence interval [CI], 0.74-0.81; P<.001; and RR, 0.61;95% CI, 0.54-0.70; P<.001,respectively, after controlling for multiple potential confounding factors). Patients with Medicare FFS insurance used lower-mortality hospitals at rates more similar to those with private FFS insurance (n = 31 948; RR, 0.95; 95% CI, 0.91-0.98; P = .004), Conclusions Patients in New York State with private managed care and Medicare managed care insurance were significantly less likely to use lower-mortality hospitals for CABG surgery compared with patients with private FFS insurance. C1 Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Div Cardiovasc Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg,Div Cardiovasc Surg, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. SUNY Albany, Dept Hlth Policy Management & Behav, Albany, NY 12222 USA. RP Erickson, LC (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. OI Schneider, Eric/0000-0002-1132-5084 NR 34 TC 45 Z9 45 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 19 PY 2000 VL 283 IS 15 BP 1976 EP 1982 DI 10.1001/jama.283.15.1976 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 303RC UT WOS:000086436600032 PM 10789665 ER PT J AU Wiedemann, HP Komara, J Welsh, C Fulkerson, WJ MacIntyre, N Mallatratt, L Sebastian, M Thompson, D Govert, JA Brower, RG Morris, AH Clemmer, T Davis, R Orme, J Young, M Gooder, V Jesberger, S Gottlieb, J Elmer, M Matthay, MA Daniel, B Kallet, R Luce, JM Abraham, E Glodowski, J Lockrem, J McIntyre, R Parsons, P Reid, K Stevens, C Silverman, HJ Corral, W Toews, GB Arnoldi, D Bartlett, RH Dechert, R Watts, C Lanken, PN Anderson, H Finkel, B Hanson, CW Barton, R Mone, M Hudson, LD Davis, D Maier, RV Steinberg, KP Wheeler, AP Bernard, G Stroud, M Swindell, B Thompson, BT Anckiewicz, M Hayden, D Molay, F Bernard, GR Gail, DB Bosken, CH Randall, P Waclawiw, M Steinberg, KP Maier, RV Schoenfeld, D Thompson, BT AF Wiedemann, HP Komara, J Welsh, C Fulkerson, WJ MacIntyre, N Mallatratt, L Sebastian, M Thompson, D Govert, JA Brower, RG Morris, AH Clemmer, T Davis, R Orme, J Young, M Gooder, V Jesberger, S Gottlieb, J Elmer, M Matthay, MA Daniel, B Kallet, R Luce, JM Abraham, E Glodowski, J Lockrem, J McIntyre, R Parsons, P Reid, K Stevens, C Silverman, HJ Corral, W Toews, GB Arnoldi, D Bartlett, RH Dechert, R Watts, C Lanken, PN Anderson, H Finkel, B Hanson, CW Barton, R Mone, M Hudson, LD Davis, D Maier, RV Steinberg, KP Wheeler, AP Bernard, G Stroud, M Swindell, B Thompson, BT Anckiewicz, M Hayden, D Molay, F Bernard, GR Gail, DB Bosken, CH Randall, P Waclawiw, M Steinberg, KP Maier, RV Schoenfeld, D Thompson, BT CA ARDS Network TI Ketoconazole for early treatment of acute lung injury and acute respiratory distress syndrome - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PHARMACOKINETICS; INHIBITION; ENDOTOXIN; ARDS AB Context Three clinical studies have suggested that ketoconazole, a synthetic imidazole with anti-inflammatory activity, may prevent the development of acute respiratory distress syndrome (ARDS) in critically ill patients. However, the use of ketoconazole as treatment for acute lung injury (ALI) and ARDS has not been previously studied. Objective To test the efficacy of ketoconazole in reducing mortality and morbidity in patients with ALI or ARDS. Design Randomized, double-blind, placebo-controlled trial conducted from March 1996 to January 1997. Setting Twenty-four hospitals associated with 10 network centers in the United States, constituting the ARDS Network. Patients A total of 234 patients with ALI or ARDS. Intervention Patients were randomly assigned to receive ketoconazole, 400 mg/d (n=117),or placebo (n=117), initiated within 36 hours of fulfilling study entry criteria and given enterally for up to 21 days. Main Outcome Measures Primary outcome measures were the proportion of patients alive with unassisted breathing at hospital discharge and the number of days of unassisted breathing (ventilator-free days) during 28 days of follow-up. Secondary outcome measures included the proportion of patients achieving unassisted breathing for 48 hours or more, the number of organ failure-free days, and changes in plasma interleukin 6 (IL-6) and urinary thromboxane A(2) metabolites (thromboxane B-2 [TXB2] and 11-dehydro-TXB2). Results In-hospital mortality (SE) was 34.1 % (4.3 %) for the placebo group and 35.2 % (4.3 %) for the ketoconazole group (P=.85). The median number of ventilator-free days within 28 days of randomization was 9 in the placebo group and 10 in the ketoconazole group (P=.89). There were no statistically significant differences in the n umber of organ failure-free days, pulmonary physiology, or adverse events between treatment groups. The median serum ketoconazole level was 1.25 mu g/mL and serum levels greater than 0.5 mu g/mL were detected in 96% of patients assayed. Plasma IL-6, urinary TXB2, and 11-dehydro-TXB2 levels were unaffected by ketoconazole. Conclusions In these patients with ALI or ARDS, ketoconazole was safe and bioavailable but did not reduce mortality or duration of mechanical ventilation or improve lung function. These data do not support the use of ketoconazole,for the early treatment of ALI or ARDS. C1 Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Thompson, BT (reprint author), Massachusetts Gen Hosp, Pulm & Crit Care Unit, 55 Fruit St, Boston, MA 02114 USA. EM tthompson1@partners.org NR 31 TC 147 Z9 152 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 19 PY 2000 VL 283 IS 15 BP 1995 EP 2002 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 303RC UT WOS:000086436600035 ER PT J AU Schonberger, J Levy, H Grunig, E Sangwatanaroj, S Fatkin, D MacRae, C Stacker, H Halpin, C Eavey, R Philbin, EF Katus, H Seidman, JG Seidman, CE AF Schonberger, J Levy, H Grunig, E Sangwatanaroj, S Fatkin, D MacRae, C Stacker, H Halpin, C Eavey, R Philbin, EF Katus, H Seidman, JG Seidman, CE TI Dilated cardiomyopathy and sensorineural hearing loss - A heritable syndrome that maps to 6q23-24 SO CIRCULATION LA English DT Article DE cardiomyopathy; hearing loss, sensorineural; genetics ID LANGE-NIELSEN-SYNDROME; HYPERTROPHIC CARDIOMYOPATHY; ALSTROM-SYNDROME; GENE; MUTATION; LOCUS; EPIDEMIOLOGY; MESENCHYME; FREQUENCY; CAPSULIN AB Background-Dilated cardiomyopathy (DCM) and sensorineural hearing loss (SNHL) are prevalent disorders that occur alone or as components of complex multisystem syndromes. Multiple genetic loci have been identified that, when mutated, cause DCM or SNHL. However, the isolated coinheritance of these phenotypes has not been previously recognized. Methods and Results-Clinical evaluations of 2 kindreds demonstrated autosomal-dominant transmission and age-related penetrance of both SNHL and DCM in the absence of other disorders. Moderate-to-severe hearing loss was evident by late adolescence, whereas ventricular dysfunction produced progressive congestive heart failure after the fourth decade. DNA samples from the larger kindred (29 individuals) were used to perform a genome-wide linkage study. polymorphic loci on chromosome 6q23 to 24 were coinherited with the disease (maximum logarithm of odds score, 4.88 at locus D6S2411). The disease locus must lie within a 2.8 cM interval between loci D6S975 and D6S292. a location that overlaps an SNHL disease locus (DFNA10). However, DFNA10 does not cause cardiomyopathy. The epicardin gene, which encodes a transcription factor expressed in the myocardium and cochlea, was assessed as a candidate gene by nucleotide sequence analysis; no mutations were identified. Conclusions-A syndrome of juvenile-onset SNHL and adult-onset DCM is caused by a mutation at 6q23 to 24 (locus designated CMD1J). Recognition of this cardioauditory disorder allows for the identification of young adults at risk for serious heart disease, thereby enabling early intervention. Definition of the molecular cause of this syndrome may provide new information about important cell physiology common to both the ear and heart. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Childrens Hosp, Dept Pulm Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Brigham & Womens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Univ Heidelberg, Dept Med 3, Heidelberg, Germany. Univ Lubeck, Dept Med 2, Lubeck, Germany. Henry Ford Hosp, Sect Heart Failure & Cardiac Transplantat, Detroit, MI 48202 USA. RP Seidman, CE (reprint author), Harvard Univ, Sch Med, Dept Genet, Alpert Room 533,200 Longwood Ave, Boston, MA 02115 USA. RI Katus, Hugo/P-1712-2016 FU NICHD NIH HHS [K-12-HD 00850] NR 37 TC 53 Z9 56 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 APR 18 PY 2000 VL 101 IS 15 BP 1812 EP 1818 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 310EE UT WOS:000086812900011 PM 10769282 ER PT J AU Kuppenbender, KD Standaert, DG Feuerstein, TJ Penney, JB Young, AB Landwehrmeyer, GB AF Kuppenbender, KD Standaert, DG Feuerstein, TJ Penney, JB Young, AB Landwehrmeyer, GB TI Expression of NMDA receptor subunit mRNAs in neurochemically identified projection and interneurons in the human striatum SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE basal ganglia; in situ hybridization; cholinergic neurons; Huntington's disease; glutamate receptors ID D-ASPARTATE RECEPTOR; MESSENGER-RNA EXPRESSION; IN-SITU HYBRIDIZATION; HUMAN BASAL GANGLIA; GLUTAMIC-ACID DECARBOXYLASE; GAMMA-AMINOBUTYRIC-ACID; EXCITATORY AMINO-ACIDS; EARLY GENE-EXPRESSION; HUMAN-BRAIN; HUNTINGTONS-DISEASE AB N-methyl-D-aspartate (NMDA) receptors are composed of subunits from two families: NR1 and NR2. We used a dual-label in situ hybridization technique to assess the levels of NR1 and NR2A-D messenger ribonucleic acid (mRNA) expressed in projection neurons and interneurons of the human striatum. The neuronal populations were identified with digoxigenin-tagged complementary RNA probes for preproenkephalin (ENK) and substance P (SP) targeted to striatal projection neurons, and somatostatin (SOM), glutamic acid decarboxylase 67 kD (GAD(67)), and choline acetyltransferase (ChAT) targeted to striatal interneurons. Intense NR1 signals were found over all striatal neurons. NR2A signals were high over GAD(67)-positive neurons and intermediate over SP-positive neurons. ENK-positive neurons displayed low NR2A signals, whereas ChAT- and SOM-positive neurons were unlabeled. NR2B signals were intense over all neuronal populations in striatum. Signals for NR2C and NR2D were weak. Only ChAT-positive neurons displayed moderate signals, whereas all other interneurons and projection neurons were unlabeled. Moderate amounts of NR2D signal were detected over SOM- and ChAT-positive neurons; GAD(67)- and SP-positive striatal neurons displayed low and ENK-positive neurons displayed no NR2D hybridization signal. These data suggest that all human striatal neurons have NMDA receptors, but different populations have different subunit compositions that may affect function as well as selective vulnerability. J. Comp. Neurol. 419:407-421, 2000. (C) 2000 Wiley-Liss, Inc. C1 Univ Freiburg, Dept Neurol, D-79106 Freiburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. RP Landwehrmeyer, GB (reprint author), Poliklin Neurol, Steinhovelstr 9, D-89075 Ulm, Germany. OI Standaert, David/0000-0003-2921-8348 FU NIMH NIH HHS [MH/NS31862]; NINDS NIH HHS [NS31579, NS34361] NR 88 TC 66 Z9 67 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD APR 17 PY 2000 VL 419 IS 4 BP 407 EP 421 DI 10.1002/(SICI)1096-9861(20000417)419:4<407::AID-CNE1>3.0.CO;2-I PG 15 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 299PQ UT WOS:000086207400001 PM 10742712 ER PT J AU Krogsgaard, M Wucherpfennig, KW Canella, B Hansen, BE Svejgaard, A Pyrdol, J Ditzel, H Raine, C Engberg, J Fugger, L AF Krogsgaard, M Wucherpfennig, KW Canella, B Hansen, BE Svejgaard, A Pyrdol, J Ditzel, H Raine, C Engberg, J Fugger, L TI Visualization of myelin basic protein (MBP) T cell epitopes in multiple sclerosis lesions using a monoclonal antibody specific for the human histocompatibility leukocyte antigen (HLA)-DR2-MBP 85-99 complex SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE multiple sclerosis; antigen presentation; myelin basic protein; autoimmunity; microglia ID CLASS-II COMPLEXES; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MHC CLASS-II; CENTRAL-NERVOUS-SYSTEM; RECOMBINANT ANTIBODY; CLONAL EXPANSION; DENDRITIC CELLS; ALPHA-CHAIN; PEPTIDE; MOLECULES AB Susceptibility to multiple sclerosis (MS) is associated with the human histocompatibility leukocyte antigen (HLA)-DR2 haplotype, suggesting that major histocompatibility complex class II-restricted presentation of central nervous system-derived antigens is important in the disease process. Antibodies specific for defined HLA-DR2-peptide complexes may therefore be valuable tools for studying antigen presentation in MS. We have used phage display technology to select HLA-DR2-peptide-specific antibodies from HLA-DR2-transgenic mice immunized with HLA-DR2 molecules complexed with an immunodominant myelin basic protein (MBP) peptide (residues 85-99). Detailed characterization of one clone (MK16) demonstrated that both DR2 and the MBP peptide were required for recognition. Furthermore, MK16 labeled intra- and extracellular HLA-DR2-MBP peptide complexes when antigen-presenting cells (APCs) were pulsed with recombinant MBP. In addition, MK16 inhibited interleukin 2 secretion by two transfectants that expressed human MBP-specific T cell receptors. Analysis of the structural requirement for MK16 binding demonstrated that the two major HLA-DR2 anchor residues of MBP 85-99 and the COOH-terminal part of the peptide, in particular residues Val-96, Pro-EX, and Arg-99, were important for binding. Based on these results, the antibody was used to determine if the HLA-DR2-MBP peptide complex is presented in MS lesions. The antibody stained APCs in MS lesions, in particular microglia/macrophages but also in some cases hypertrophic astrocytes. Staining of APCs was only observed in MS cases with the HLA-DR2 haplotype but not in cases that carried other haplotypes. These results demonstrate that HLA-DR2 molecules in MS lesions present a myelin-derived self-peptide and suggest that microglia/macrophages rather than astrocytes are the predominant APCs in these lesions. C1 Royal Danish Sch Pharm, Dept Pharmacol, DK-2100 Copenhagen, Denmark. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Pathol Neuropathol, Bronx, NY 10461 USA. Univ Copenhagen Hosp, Dept Clin Immunol, DK-2100 Copenhagen, Denmark. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. Aarhus Univ Hosp, Skejby Sygehus, Dept Clin Immunol, DK-8200 Aarhus N, Denmark. RP Fugger, L (reprint author), Aarhus Univ Hosp, Skejby Sygehus, Dept Clin Immunol, DK-8200 Aarhus N, Denmark. OI Ditzel, Henrik J./0000-0003-3927-5135 NR 66 TC 139 Z9 143 U1 1 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 17 PY 2000 VL 191 IS 8 BP 1395 EP 1412 DI 10.1084/jem.191.8.1395 PG 18 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 307JU UT WOS:000086650800013 PM 10770805 ER PT J AU Frenette, PS Denis, CV Weiss, L Jurk, K Subbarao, S Kehrel, B Hartwig, JH Vestweber, D Wagner, DD AF Frenette, PS Denis, CV Weiss, L Jurk, K Subbarao, S Kehrel, B Hartwig, JH Vestweber, D Wagner, DD TI P-selectin glycoprotein ligand 1 (PSGL-1) is expressed on platelets and can mediate platelet-endothelial interactions in vivo SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE P-selectin; endothelium; hemostasis; inflammation; adhesion ID VON-WILLEBRAND-FACTOR; IN-VIVO; LEUKOCYTE TRAFFICKING; MOUSE PERITONEUM; AMINO-TERMINUS; CELLS; NEUTROPHILS; RECEPTOR; RECOGNITION; MIGRATION AB The platelet plays a pivotal role in maintaining vascular integrity. In a manner similar to leukocytes, platelets interact with selectins expressed on activated endothelium. P-selectin glycoprotein ligand 1 (PSGL-1) is the main P-selectin ligand expressed on leukocytes. Searching for platelet ligand(s), we used a P-selectin-immunoglobulin G (IgG) chimera to affinity purify sur face-biotinylated proteins from platelet lysates. P-selectin-bound ligands were eluted with ethylenediaminetetraacetic acid. An similar to 210-kD biotinylated protein was isolated from both human neutrophil and platelet preparations. A band of the same size was also immunopurified from human platelets using a monoclonal anti-human PSGL-1 antibody and could be blotted with P-selectin-IgG. Under reducing conditions, both the predicted PSGL-1 similar to 210-kD dimer and the similar to 120-kD monomer were isolated from platelets. Comparative immunoelectron microscopy and Western blotting experiments suggested that platelet PSGL-1 expression is 25-100-fold lower than that of leukocytes. However, patients with chronic idiopathic thrombocytopenic purpura who harbor predominantly young platelets displayed greater expression, indicating that PSGL-1 expression may be decreased during platelet aging. By flow cytometry, thrombin-activated platelets from normal individuals exhibited greater expression than those unstimulated. An inhibitory anti-PSGL-1 antibody significantly reduced platelet rolling in mesenteric venules, as observed by intravital microscopy. Our results indicate that functional PSGL-1 is expressed on platelets, and suggest an additional mechanism by which selectins and their ligands participate in inflammatory and/or hemostatic responses. C1 CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol,Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Munster, Zentrum Mol Biol Entzundung, Inst Cell Biol, D-48149 Munster, Germany. Univ Munster, Dept Anaesthesiol & Intens Care Med, D-48149 Munster, Germany. RP Frenette, PS (reprint author), CUNY Mt Sinai Sch Med, Dept Med, 1 Gustave L Levy Pl,Box 1079, New York, NY 10029 USA. RI Frenette, Paul/J-8272-2012; Weiss, Linnea/K-8062-2014; Denis , Cecile/A-7649-2011; OI Denis , Cecile/0000-0001-5152-9156; Vestweber, Dietmar/0000-0002-3517-732X FU NHLBI NIH HHS [P01 HL056949, P01HL56949, P60HL28381, R01 HL041002, R01HL41002] NR 39 TC 240 Z9 253 U1 0 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 17 PY 2000 VL 191 IS 8 BP 1413 EP 1422 DI 10.1084/jem.191.8.1413 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 307JU UT WOS:000086650800014 PM 10770806 ER PT J AU Savage, CR Deckersbach, T Heckers, S Wilhelm, S Wagner, AD Schacter, DL Baer, L Jenike, MA Rauch, SL AF Savage, CR Deckersbach, T Heckers, S Wilhelm, S Wagner, AD Schacter, DL Baer, L Jenike, MA Rauch, SL TI The contribution of orbitofrontal cortex to episodic memory impairment in OCD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Dept Psychol, Cambridge, MA USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 0 TC 1 Z9 1 U1 0 U2 5 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 APR 15 PY 2000 VL 47 IS 8 SU S MA 42 BP 13S EP 13S DI 10.1016/S0006-3223(00)00304-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200040 ER PT J AU Seidman, LJ Faraone, SV Goldstein, JM Cirillo, M Makris, N Kennedy, D Kremen, WS Toomey, R Caviness, VS Tsuang, MT AF Seidman, LJ Faraone, SV Goldstein, JM Cirillo, M Makris, N Kennedy, D Kremen, WS Toomey, R Caviness, VS Tsuang, MT TI Medial temporal lope memory system dysfunction in relatives of patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 48 BP 15S EP 15S DI 10.1016/S0006-3223(00)00310-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200046 ER PT J AU Eliaz, Y Johnson, J Westwood, Z Schuff, N Deicken, RF AF Eliaz, Y Johnson, J Westwood, Z Schuff, N Deicken, RF TI Abnormal cortico-thalamic-cerebellar circuitry in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 San Francisco Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, Magnet Resonance Unit, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 70 BP 21S EP 21S DI 10.1016/S0006-3223(00)00332-2 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200068 ER PT J AU Cirillo, MA Seidman, LJ Makris, N Goldstein, JM Kennedy, D Caviness, VS Faraone, SV Tsuang, MT AF Cirillo, MA Seidman, LJ Makris, N Goldstein, JM Kennedy, D Caviness, VS Faraone, SV Tsuang, MT TI Fornix and mammillary body volumes in individuals with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 15 PY 2000 VL 47 IS 8 SU S MA 78 BP 24S EP 24S DI 10.1016/S0006-3223(00)00340-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200076 ER PT J AU Seidman, LJ Goldstein, JM Makris, N Kennedy, D Kremen, WS Toomey, R Caviness, VS Faraone, SV Tsuang, MT AF Seidman, LJ Goldstein, JM Makris, N Kennedy, D Kremen, WS Toomey, R Caviness, VS Faraone, SV Tsuang, MT TI Subcortical brain abnormalities in patients with schizophrenia: An MRI morphometric study SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Davis, Sacramento, CA 95817 USA. RI Kennedy, David/H-3627-2012 NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 79 BP 24S EP 24S DI 10.1016/S0006-3223(00)00341-3 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200077 ER PT J AU Elman, I Goldstein, DS Adler, CM Breier, A AF Elman, I Goldstein, DS Adler, CM Breier, A TI Mechanism of peripheral noradrenergic stimulation by risperidone SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Psychiat, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 179 BP 54S EP 54S DI 10.1016/S0006-3223(00)00441-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200177 ER PT J AU Grunhaus, L Lisanby, SH George, MS Maeda, F AF Grunhaus, L Lisanby, SH George, MS Maeda, F TI Magnetic stimulation of the brain: Correlates of antidepressant response SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Chaim Sheba Med Ctr, Div Psychiat, IL-52621 Tel Hashomer, Israel. Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Biol Psychiat, New York, NY 10032 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 185 BP 56S EP 56S DI 10.1016/S0006-3223(00)00448-0 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200183 ER PT J AU Yao, JK Reddy, RD Pettegrew, JW van Kammen, DP Horrobin, DF Mahadik, SP AF Yao, JK Reddy, RD Pettegrew, JW van Kammen, DP Horrobin, DF Mahadik, SP TI Membrane deficits in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Med Coll Georgia, Augusta, GA 30912 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 190 BP 58S EP 58S DI 10.1016/S0006-3223(00)00453-4 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200188 ER PT J AU Lorberbaum, JP Emmanuel, NP Mintzer, O Kapp, R Crawford, M Morton, A Johnson, MR Book, SW Hamner, MB Nahas, Z Arana, GW Ballenger, JC Lydiard, RB George, MS AF Lorberbaum, JP Emmanuel, NP Mintzer, O Kapp, R Crawford, M Morton, A Johnson, MR Book, SW Hamner, MB Nahas, Z Arana, GW Ballenger, JC Lydiard, RB George, MS TI Chances in anxiety after prefrontal rTMS in patients with GAD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 269 BP 81S EP 82S DI 10.1016/S0006-3223(00)00533-3 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200266 ER PT J AU Lorberbaum, JP Newman, JD Horwitz, AR Dubno, JR Hamner, MB Bohning, DE Shastri, A Ballenger, JC Lydiard, RB George, MS AF Lorberbaum, JP Newman, JD Horwitz, AR Dubno, JR Hamner, MB Bohning, DE Shastri, A Ballenger, JC Lydiard, RB George, MS TI Activating brain regions involved in social attachment SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Charleston, SC 29425 USA. Ralph H Johnson VA Med Ctr, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 324 BP 97S EP 98S DI 10.1016/S0006-3223(00)00588-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200320 ER PT J AU Dougherty, DD Bonab, AA Alpert, NM Rauch, SL Fava, M Ottowitz, W Livni, E Fischman, AJ AF Dougherty, DD Bonab, AA Alpert, NM Rauch, SL Fava, M Ottowitz, W Livni, E Fischman, AJ TI Pet receptor studies of major depression with anger attacks SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Butler Hosp, Providence, RI 02906 USA. Brown Med Sch, Providence, RI 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 356 BP 107S EP 108S DI 10.1016/S0006-3223(00)00620-X PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200352 ER PT J AU Pegues, M Eliaz, Y Chosiad, L Schuff, N Amend, D Deicken, RF AF Pegues, M Eliaz, Y Chosiad, L Schuff, N Amend, D Deicken, RF TI Tissue volume corrected hippocampal NAA is reduced in schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 San Francisco Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Magnet Resonance Unit, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 354 BP 107S EP 107S DI 10.1016/S0006-3223(00)00618-1 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200350 ER PT J AU Arciniegas, DB Topkoff, JL Rojas, DC Sheeder, JL Teale, PD Reite, ML Adler, LE AF Arciniegas, DB Topkoff, JL Rojas, DC Sheeder, JL Teale, PD Reite, ML Adler, LE TI Reduced hippocampal volume in association with P50 nonsuppression following traumatic brain injury SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. RI Arciniegas, David/A-3792-2009; Rojas, Don/F-4296-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 359 BP 108S EP 109S DI 10.1016/S0006-3223(00)00623-5 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200355 ER PT J AU Tsuang, MT Seidman, LJ Makris, N Kennedy, D Caviness, VS Kremen, WS Toomey, R Goldstein, JM Faraone, SV AF Tsuang, MT Seidman, LJ Makris, N Kennedy, D Caviness, VS Kremen, WS Toomey, R Goldstein, JM Faraone, SV TI Verbal memory and hippocampal volumes in relatives of patients with schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Harvard Univ, Inst Psychiat Epidemiol & Genet, Boston, MA USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Calif Davis, Sacramento, CA 95817 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 APR 15 PY 2000 VL 47 IS 8 SU S MA 396 BP 121S EP 121S DI 10.1016/S0006-3223(00)00664-8 PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200392 ER PT J AU Deicken, RF Eliaz, Y Chosiad, L Johnson, C Schuff, N AF Deicken, RF Eliaz, Y Chosiad, L Johnson, C Schuff, N TI Altered prefrontal-thalamic neuronal integrity in bipolar I disorder SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 San Francisco Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, Magnet Resonance Unit, San Francisco, CA USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 407 BP 124S EP 125S DI 10.1016/S0006-3223(00)00677-6 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200403 ER PT J AU Nahas, Z Oliver, NC Johnson, MR Molloy, M Hughes, PL Ballenger, JC Risch, SC George, MS AF Nahas, Z Oliver, NC Johnson, MR Molloy, M Hughes, PL Ballenger, JC Risch, SC George, MS TI Feasibility and efficacy of left prefrontal rTMS as a maintenance antidepressant SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Radiol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Charleston, SC USA. NR 0 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 515 BP 156S EP 157S DI 10.1016/S0006-3223(00)00785-X PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200511 ER PT J AU Hamner, MB Ulmer, HG Faldowski, RA Frueh, BC Twomey, TJ Tyson, C Lorberbaum, JP Teneback, CC Huber, MG Arana, GW AF Hamner, MB Ulmer, HG Faldowski, RA Frueh, BC Twomey, TJ Tyson, C Lorberbaum, JP Teneback, CC Huber, MG Arana, GW TI A randomized, controlled trial of risperidone for psychotic features in PTSD SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Ralph H Johnson Vet Adm Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2000 VL 47 IS 8 SU S MA 521 BP 158S EP 159S DI 10.1016/S0006-3223(00)00791-5 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304ZW UT WOS:000086515200517 ER PT J AU Schiffer, CA Miller, K Larson, RA Amrein, PC Antin, JH Zani, VJ Stone, RM AF Schiffer, CA Miller, K Larson, RA Amrein, PC Antin, JH Zani, VJ Stone, RM TI A double-blind, placebo-controlled trial of pegylated recombinant human megakaryocyte growth and development factor as an adjunct to induction and consolidation therapy for patients with acute myeloid leukemia SO BLOOD LA English DT Article ID PROPHYLACTIC PLATELET TRANSFUSIONS; HUMAN THROMBOPOIETIN; MPL LIGAND; IN-VIVO; THROMBOCYTOPENIA; CHEMOTHERAPY; ADULTS; FILGRASTIM; THRESHOLD; CANCER AB Newly diagnosed patients with acute myeloid leukemia (AML) were randomized to receive either 2.5 or 5 mu g/kg/day of pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) or a placebo administered subcutaneously after completion of chemotherapy. The study evaluated the toxicity of PEG-rHuMGDF and any effect on the duration of thrombocytopenia, Each of 35 patients under 60 years of age received the following therapy: 45 mg/m(2) daunorubicin on days 1-3, 100 mg/m(2) cytarabine (ARA-C) for 7 days, and 2 gm/m(2) high-dose ARA-C (HIDAC) for 6 doses on days 8-10, The 22 patients 60 years or older received standard daunorubicin and ARA-C without HIDAC, PEG-rHuMGDF was well tolerated, and no specific toxicities could be attributed to its use, There was no difference in the time to achieve a platelet count of at least 20 x 10(9)/L, among the 3 groups (median 28-30 days for patients less than 60 years old and 21-23 days for patients 60 years or older). Patients receiving PEG-rHuMGDF achieved higher platelet counts after remission. However there was no significant difference in the number of days on which platelet transfusions were administered among the 3 groups. The complete remission rate was 71% for patients less than 60 years and 64% for those 60 years or older, with no significant difference among the 3 groups. Postremission consolidation chemotherapy with either placebo or PEG-rHuMGDF was given to 28 patients beginning the day after completion of chemotherapy. There was no apparent difference In the time that was necessary to reach a platelet count of at least 20 or 50 x 10(9)/L or more platelets: or in the number of platelet transfusions received. In summary, PEG-rHuMGDF was well tolerated by patients receiving induction and consolidation therapy for AML; however, there was no effect on the duration of severe thrombocytopenia or the platelet transfusion requirement, (Blood, 2000;95:2530-2535) (C) 2000 by The American Society of Hematology. C1 Wayne State Univ, Sch Med, Barbara Ann Karmanos Canc Inst, Detroit, MI USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Tufts Univ, Sch Med, New England Med Ctr, Boston, MA 02111 USA. Univ Chicago, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Massachuetts Gen Hosp, Cambridge, MA 02138 USA. RP Schiffer, CA (reprint author), Harper Hosp, Div Hematol Oncol, 505 Hudson,3990 John Rd, Detroit, MI 48201 USA. OI Larson, Richard/0000-0001-9168-3203 NR 30 TC 76 Z9 83 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 APR 15 PY 2000 VL 95 IS 8 BP 2530 EP 2535 PG 6 WC Hematology SC Hematology GA 303KH UT WOS:000086420700012 PM 10753831 ER PT J AU Donovan, JW Ladetto, M Zou, GY Neuberg, D Poor, C Bowers, D Gribben, JG AF Donovan, JW Ladetto, M Zou, GY Neuberg, D Poor, C Bowers, D Gribben, JG TI Immunoglobulin heavy-chain consensus probes for real-time PCR quantification of residual disease in acute lymphoblastic leukemia SO BLOOD LA English DT Article ID QUANTITATIVE PCR; FOLLICULAR LYMPHOMA; FLUOROGENIC PROBES; ANTIGEN SELECTION; T-CELL; POLYMERASE; CHILDHOOD; REMISSION; ASSAY; DNA AB Tumor-related immunoglobulin heavy-chain (IgH) rearrangements are markers for polymerase chain reaction (PCR) detection of minimal residual disease (MRD) in B-cell malignancies. Nested PCR with patient IgH allele-specific oligonucleotide primers can detect 1 tumor cell in 10(4) to 10(6) normal cells. In childhood acute lymphoblastic leukemia (ALL), persistence of PCR-detectable disease is associated with increased risk of relapse. The clinical significance of qualitative PCR data can be limited, however, because patients can harbor detectable MRD for prolonged periods without relapse. Recent studies indicate that a quantitative rise in tumor burden identifies patients who are at high risk for relapse, Therefore, an efficient and reliable PCR method for MRD quantification is needed for ALL patients. We have developed a real-time PCR method to quantify MRD with IgH V-H gene family consensus fluorogenically labeled probes. With this method, a small number of probes can be used to quantify MRD in a large number of different patients. The assay was found to be both accurate and reproducible over a wide range and capable of detecting approximately 1 tumor cell in 5 x 10(4) normal cells. We demonstrate that this methodology can discriminate between patients with persistence of MRD who relapse and those who do not. This technique is generally applicable to B-cell malignancies and is currently being used to quantify MRD in a number of prospective clinical studies at our institution. (Blood. 2000;95:2651-2658) (C) 2000 by The American Society of Hematology. C1 Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Adult Oncol, Boston, MA USA. RP Donovan, JW (reprint author), Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. RI Zou, Guangyong/K-6408-2013; OI LADETTO, Marco/0000-0002-8283-2681 FU NCI NIH HHS [P01 CA68484] NR 36 TC 99 Z9 102 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 APR 15 PY 2000 VL 95 IS 8 BP 2651 EP 2658 PG 8 WC Hematology SC Hematology GA 303KH UT WOS:000086420700028 PM 10753847 ER PT J AU Hurwitz, CA Silverman, LB Schorin, MA Clavell, LA Dalton, VK Glick, KM Gelber, RD Sallan, SE AF Hurwitz, CA Silverman, LB Schorin, MA Clavell, LA Dalton, VK Glick, KM Gelber, RD Sallan, SE TI Substituting dexamethasone for prednisone complicates remission induction in children with acute lymphoblastic leukemia SO CANCER LA English DT Article DE dexamethasone; remission induction; acute lymphoblastic leukemia; pediatrics ID ACUTE LYMPHOCYTIC-LEUKEMIA; LONG-TERM SURVIVORS; MENINGEAL LEUKEMIA; CHILDHOOD LEUKEMIA; GLUCOCORTICOIDS; METHOTREXATE; APOPTOSIS; DEATH AB BACKGROUND, The authors report the occurrence of fatal or near-fatal sepsis in 16 of 38 children with newly diagnosed acute lymphoblastic leukemia (ALL] treated with a new induction regimen that differed from its predecessor by the substitution of dexamethasone for prednisone. METHODS. The frequency of septic deaths among 38 children who received multiagent remission induction therapy, including dexamethasone (6 mg/m(2)) daily for 28 days (pilot protocol 91-01P), was compared with the frequency of septic deaths among children previously treated (protocol 87-01) and subsequently treated (protocol 91-01) in consecutive Dana-Farber Cancer Institute (DFCI) ALL trials with induction therapy that included 21 and 28 days of prednisone (40 mg/m(2)), respectively. Except for dexamethasone in protocol 91-01P, the remission induction agents used were identical in substance to those used in protocol 87-01. Protocol 91-01, the successor 91-01P, was also similar, with the exception of the deletion of a single dose of L-asparaginase. RESULTS. Sixteen of the 38 children (42%) treated on the DFCI 91-01P had documented gram positive or gram negative sepsis (17 episodes] during remission induction, including 4 toxic deaths (11%). in contrast, there were 4 induction deaths among 369 children (1%) treated on protocol 87-01 (P = 0.0035) and 1 induction death among 377 children (<1%) treated on protocol 91-01 (P = 0.0003). CONCLUSIONS, Substitution of dexamethasone for prednisone or methylprednisolone in an otherwise intensive conventional induction regimen for previously untreated children with ALL resulted in an alarmingly high incidence of septic episodes and toxic deaths. Awareness of this complication, considering that the substitution has no apparent benefit in the efficacy of remission induction, argues against its routine use in intensive induction regimens for children with ALL., Cancer 2000;88:1964-9, (C) 2000 American Cancer Society. C1 Maine Med Ctr, Barbara Bush Childrens Hosp, Maine Childrens Canc Program, Scarborough, ME 04074 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Ochsner Med Inst, Dept Pediat Hematol Oncol, New Orleans, LA USA. San Jorge Childrens Hosp, Dept Pediat Hematol Oncol, Santurce, PR USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Hurwitz, CA (reprint author), Maine Med Ctr, Barbara Bush Childrens Hosp, Maine Childrens Canc Program, 100 US Route 1,Unit 107, Scarborough, ME 04074 USA. FU NCI NIH HHS [CA68484] NR 29 TC 77 Z9 80 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD APR 15 PY 2000 VL 88 IS 8 BP 1964 EP 1969 PG 6 WC Oncology SC Oncology GA 303RM UT WOS:000086437800027 PM 10760775 ER PT J AU Hartford, AC Gohongi, T Fukumura, D Jain, RK AF Hartford, AC Gohongi, T Fukumura, D Jain, RK TI Irradiation of a primary tumor, unlike surgical removal, enhances angiogenesis suppression at a distal site: Potential role of host-tumor interaction SO CANCER RESEARCH LA English DT Article ID PROSTATE-SPECIFIC ANTIGEN; LEWIS-LUNG-CARCINOMA; VASCULAR-PERMEABILITY; IONIZING-RADIATION; ANGIOSTATIN; INHIBITOR; GROWTH; CANCER; MICROENVIRONMENT; MICROCIRCULATION AB Changes in distal angiogenesis in response to irradiation of primary tumors are not known. To this end, PC-3, a human prostate carcinoma, and FSA-II, a murine fibrosarcoma, were grown in the gastrocnemius muscles of male nude mice. Distal angiogenesis was measured in gel containing human recombinant basic fibroblast growth factor placed in the cranial windows of these mice. PC-3-bearing mice showed inhibition of distal angiogenesis, as compared with non-tumor-bearing controls. Surgical removal of tumors tended to accelerate distal angiogenesis; in comparison, after irradiation of the PC-3 primary tumor, rates of angiogenesis in the cranial window were retarded. Irradiation of the non-tumor-bearing leg or of non-tumor-bearing animals showed no measurable effect on rate of growth of vessels in the cranial window. Similar results were found with the FSA-II tumors, with slowed distal angiogenesis in tumor-bearing animals and further suppression in animals with irradiated tumors. These results demonstrate that the effect of irradiation of a primary tumor on angiogenesis at a distal site may differ from the effect of surgical removal of the primary tumor. Unlike surgery, irradiation of a tumor may enhance angiogenic suppression at a distal site, and this difference may involve host-tumor interaction. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Cox 7, Boston, MA 02114 USA. FU NCI NIH HHS [R35-CA56591, R37-CA13311] NR 24 TC 51 Z9 52 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2000 VL 60 IS 8 BP 2128 EP 2131 PG 4 WC Oncology SC Oncology GA 308EA UT WOS:000086696500014 PM 10786673 ER PT J AU Martin, K Kritzman, DM Price, LM Koh, B Kwan, CP Zhang, XH Mackay, A O'Hare, MJ Kaelin, DM Mutter, GL Pardee, AB Sager, R AF Martin, K Kritzman, DM Price, LM Koh, B Kwan, CP Zhang, XH Mackay, A O'Hare, MJ Kaelin, DM Mutter, GL Pardee, AB Sager, R TI Linking gene expression patterns to therapeutic groups in breast cancer SO CANCER RESEARCH LA English DT Article ID MAMMARY EPITHELIAL-CELLS; DIFFERENTIAL DISPLAY; CDNA MICROARRAYS; MYOEPITHELIAL CELLS; TUMOR PROGRESSION; ESTROGEN-RECEPTOR; PROTEINS; LINES; DNA; CLASSIFICATION AB A major objective of current cancer research is to develop a detailed molecular characterization of tumor cells and tissues that is linked to clinical information. Toward this end, we have identified approximately one-quarter of all genes that were aberrantly expressed in a breast cancer cell line using differential display. The cancer cells lost the expression of many genes involved in cell adhesion, communication, and maintenance of cell shape, while they gained the expression of many synthetic and metabolic enzymes important for cell proliferation, High-density, membrane-based hybridization arrays were used to study mRNA expression patterns of these genes in cultured cells and archived tumor tissue. Cluster analysis was then used to identify groups of genes, the expression patterns of which correlated with clinical information. Two clusters of genes, represented by p53 and maspin, had expression patterns that strongly associated with estrogen receptor status. A third cluster that included HSP-90 tended to be associated with clinical tumor stage, whereas a forth cluster that included keratin 14 tended to be associated with tumor size. Expression levels of these clinically relevant gene clusters allowed breast tumors to be grouped into distinct categories. Gene expression fingerprints that include these four gene clusters have the potential to improve prognostic accuracy and therapeutic outcomes for breast cancer patients. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. UCL, Sch Med, Breast Canc Lab, Ludwig Inst Canc Res, London W1P 6DB, England. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Martin, K (reprint author), Dana Farber Canc Inst, Dept Canc Biol, D610B,44 Binney St, Boston, MA 02115 USA. RI Mutter, George/C-5819-2009 NR 48 TC 99 Z9 112 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2000 VL 60 IS 8 BP 2232 EP 2238 PG 7 WC Oncology SC Oncology GA 308EA UT WOS:000086696500030 PM 10786689 ER PT J AU Nagy, H Goda, K Szakacs, G Arceci, R Varadi, A Sarkadi, B Mechetner, E Szabo, G AF Nagy, H Goda, K Szakacs, G Arceci, R Varadi, A Sarkadi, B Mechetner, E Szabo, G TI Fluorescence resonance energy transfer studies of function-related changes in the oligomerization and conformational state of Pgp SO CYTOMETRY LA English DT Meeting Abstract C1 Univ Debrecen, Dept Biophys & Cell Biol, Debrecen, Hungary. Natl Inst Hematol & Immunol, Budapest, Hungary. Dana Farber Canc Inst, Boston, MA 02115 USA. Hungarian Acad Sci, Inst Enzymol, Budapest, Hungary. Oncotech Inc, Irvine, CA 92614 USA. RI Szakacs, Gergely/A-2580-2009; Sarkadi, Balazs/I-5024-2013 OI Szakacs, Gergely/0000-0002-9311-7827; NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PD APR 15 PY 2000 VL 42 IS 2 BP 151 EP 152 PG 2 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 312DV UT WOS:000086928700067 ER PT J AU Marten, NW Stohlman, SA Atkinson, RD Hinton, DR Fleming, JO Bergmann, CC AF Marten, NW Stohlman, SA Atkinson, RD Hinton, DR Fleming, JO Bergmann, CC TI Contributions of CD8(+) T cells and viral spread to demyelinating disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MOUSE HEPATITIS-VIRUS; CENTRAL-NERVOUS-SYSTEM; MURINE CORONAVIRUS JHM; MONOCLONAL-ANTIBODIES; NUCLEOCAPSID PROTEIN; MULTIPLE-SCLEROSIS; STRAIN MHV-4; IN-VIVO; MICE; INFECTION AB Acute and chronic demyelination are hallmarks of CNS infection by the neurotropic JHM strain of mouse hepatitis virus. Although infectious virus is cleared by CD8(+) T cells, both viral RNA and activated CD8(+) T cells remain in the CNS during persistence potentially contributing to pathology, To dissociate immune from virus-mediated determinants initiating and maintaining demyelinating disease, mice were infected with two attenuated viral variants differing in a hypervariable region of the spike protein. Despite similar viral replication and tropism, one infection was marked by extensive demyelination and paralysis, whereas the other resulted in no clinical symptoms and minimal neuropathology, Mononuclear cells from either infected brain exhibited virus specific ex vivo cytolytic activity, which was rapidly lost during viral clearance. As revealed by class I tetramer technology the paralytic variant was superior in inducing specific CD8(+) T cells during the acute disease. However, after infectious virus was cleared, twice as many virus-specific IFN-gamma-secreting CD8(+) T cells were recovered from the brains of asymptomatic mice compared with mice undergoing demyelination, suggesting that IFN-gamma ameliorates rather than perpetuates JHM strain of mouse hepatitis virus-induced demyelination. The present data thus indicate that in immunocompetent mice, effector CD8(+) T cells control infection without mediating either clinical disease or demyelination. In contrast, demyelination correlated with early and sustained infection of the spinal cord. Rapid viral spread, attributed to determinants within the spike protein and possibly perpetuated by suboptimal CD8(+) T cell effector function, thus ultimately leads to the process of immune-mediated demyelination. C1 Univ So Calif, Dept Neurol, Keck Sch Med, Los Angeles, CA 90033 USA. Univ So Calif, Dept Mol Microbiol & Immunol, Keck Sch Med, Los Angeles, CA 90033 USA. Univ So Calif, Dept Pathol, Keck Sch Med, Los Angeles, CA 90033 USA. Univ Wisconsin, Madison, WI 53792 USA. William S Middleton Mem Vet Hosp, Madison, WI 53792 USA. RP Bergmann, CC (reprint author), 1333 San Pablo St,MCH 142, Los Angeles, CA 90033 USA. FU NIAID NIH HHS [AI33314]; NINDS NIH HHS [NS07149, NS18146] NR 63 TC 37 Z9 40 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 APR 15 PY 2000 VL 164 IS 8 BP 4080 EP 4088 PG 9 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300020 PM 10754301 ER PT J AU Morimoto, S Kanno, Y Tanaka, Y Tokano, Y Hashimoto, H Jacquot, S Morimoto, C Schlossman, SF Yagita, H Okumura, K Kobata, T AF Morimoto, S Kanno, Y Tanaka, Y Tokano, Y Hashimoto, H Jacquot, S Morimoto, C Schlossman, SF Yagita, H Okumura, K Kobata, T TI CD134L engagement enhances human B cell Ig production: CD154/CD40, CD70/CD27, and CD134/CD134L interactions coordinately regulate T cell-dependent B cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD40 LIGAND; OX40 LIGAND; HYPER-IGM; ACTIVATION MOLECULE; SOLUBLE FORM; IN-VIVO; DIFFERENTIATION; EXPRESSION; ANTIGEN; IDENTIFICATION AB CD134 is a member of the TNFR family expressed on activated T cells, whose ligand, CD134L, is found preferentially on activated B cells. We have previously reported that the CD70/CD27 interaction may be more important in the induction of plasma cell differentiation after the expansion phase induced by the CD154/CD40 interaction has occurred, When CD134-transfected cells were added to PBMCs stimulated with pokeweed mitogen, IgG production was enhanced in a dose-dependent fashion. Addition of CD134-transfected cells to B cells stimulated with Staphylococcus aureus Cowan I strain/IL-2 resulted in little if any enhancement of B cell IgG production and proliferation. We found that while CD134-transfected cells induced no IgG production by themselves, it greatly enhanced IgG production in the presence of CD40 stimulation or T cell, cytokines such as IL-4 and IL-10. The addition of CD134-transfected cells showed only a slight increase in the number of plasma cells compared with that in the culture without them, indicating that an increased Ig production rate per cell is responsible for the observed enhancing effect of CD134L engagement rather than increase in plasma cell generation. These results strongly suggest different and sequential roles of the TNF/TNFR family molecules in human T cell-dependent B cell responses through cell-cell contacts and the cytokine network. C1 Dokkyo Univ, Sch Med, Inst Med Sci, Div Immunol, Mibu, Tochigi 3210293, Japan. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. Juntendo Univ, Sch Med, Dept Rheumatol, Tokyo 113, Japan. Univ Ryukyus, Fac Med, Okinawa Asia Res Ctr Med Sci, Okinawa, Japan. Japan Sci & Technol Corp, Core Res Evolut Sci & Technol, Tokyo, Japan. Dana Farber Canc Inst, Div Tumor Immunol, Boston, MA 02115 USA. RP Kobata, T (reprint author), Dokkyo Univ, Sch Med, Inst Med Sci, Div Immunol, 880 Kitakobayashi, Mibu, Tochigi 3210293, Japan. NR 36 TC 60 Z9 63 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2000 VL 164 IS 8 BP 4097 EP 4104 PG 8 WC Immunology SC Immunology GA 303GZ UT WOS:000086415300022 PM 10754303 ER PT J AU Stone, ME AF Stone, ME TI Human diseases and conditions, vol 3. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD APR 15 PY 2000 VL 125 IS 7 BP 72 EP 72 PG 1 WC Information Science & Library Science SC Information Science & Library Science GA 302QR UT WOS:000086377200021 ER PT J AU O'Rourke, RW Kang, SM Lower, JA Feng, S Ascher, NL Baekkeskov, S Stock, PG AF O'Rourke, RW Kang, SM Lower, JA Feng, S Ascher, NL Baekkeskov, S Stock, PG TI A dendritic cell line genetically modified to express CTLA4-IG as a means to prolong islet allograft survival SO TRANSPLANTATION LA English DT Article; Proceedings Paper CT 24th Annual Scientific Meeting of the American-Society-of-Transplant-Surgeons CY MAY 15-22, 1998 CL CHICAGO, ILLINOIS SP Amer Soc Transplant Surgeons ID DONOR-SPECIFIC TRANSFUSION; LONG-TERM ACCEPTANCE; IN-VIVO; CARDIAC ALLOGRAFTS; TOLERANCE; UNRESPONSIVENESS; MACROPHAGE; MICE AB Background. Dendritic cells are potent antigen-presenting cells that bind allogeneic T cells. They are thus candidates for targeting immunoregulatory molecules to the alloreactive T cell compartment and suppressing the alloimmune response. Method. A dendritic cell line derived from the BALB/c mouse (H2(d)) was genetically modified to express the immunoregulatory molecule CTLA4-Ig. The ability of these dendritic cell transfectants to downregulate the alloimmune response was tested in an islet transplant model. Allogeneic C57B1/6 (H2(b)) mice were rendered diabetic with streptozocin, and they received BALB/c islet (H2(d)) transplants. Mice were administered 25 million untransfected or CTLA4-Ig-transfected D2SC/1 cells i.v. on the day of islet transplantation and 6 days later[fnc]. Result. Mice treated with CTLA4-Ig-transfected D2SC/1 cells demonstrated prolonged allograft survival (mean=20 days, median=17 days, SD=9.39) compared with mice treated with untransfected D2SC/1 cells (mean=12 days, median=11 days, SD=2.74) or untreated control mice (mean=11 days, median=11 days SD=1.41). Third party allograft survival was not prolonged in mice receiving similar treatment. Conclusions. These results demonstrate that a genetically modified dendritic cell line can suppress the alloimmune response and prolong islet allograft survival in an allospecific manner. The findings also suggest that genetically modified dendritic cells may be useful in targeting alloreactive T cells and prolonging allograft survival. C1 Univ Calif San Francisco, Dept Transplant Surg, Transplantat Lab, San Francisco, CA 94143 USA. Univ Calif San Francisco, Hormone Res Inst, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Transplantat, Boston, MA 02114 USA. RP Stock, PG (reprint author), Univ Calif San Francisco, Dept Transplant Surg, Transplantat Lab, 505 Parnassus Ave, San Francisco, CA 94143 USA. FU NIDDK NIH HHS [DKR0147043] NR 23 TC 41 Z9 44 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 APR 15 PY 2000 VL 69 IS 7 BP 1440 EP 1446 DI 10.1097/00007890-200004150-00039 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 307YM UT WOS:000086681800040 PM 10798768 ER PT J AU Zhao, Y Rodriguez-Barbosa, JI Swenson, K Barth, RN Shimizu, A Arn, JS Sachs, DH Sykes, M AF Zhao, Y Rodriguez-Barbosa, JI Swenson, K Barth, RN Shimizu, A Arn, JS Sachs, DH Sykes, M TI The induction of specific pig skin graft tolerance by grafting with neonatal pig thymus in thymectomized mice SO TRANSPLANTATION LA English DT Article ID XENOGENEIC BARRIER; CELLS; TRANSPLANTATION; CHIMERAS; DONOR AB Background. Xenogeneic donor-specific tolerance can be induced by transplanting fetal pig thymus and liver tissue (FP THY/LIV) to thymectomized (ATX), T/NK cell-depleted mice. By using neonatal pig tissue, we hoped to overcome two obstacles that arise with the use of fetal pig tissue: (1) the inability to keep fetal pigs alive after harvesting their thymic tissue, resulting in unavailability of their skin or other organs for grafting; and (2) the limited fetal thymic tissue yield, making application to large animals and humans more difficult. Methods. Neonatal pig thymus tissue (NP THY) was grafted into ATX, T/NK cell-depleted, 3Gy whole body-irradiated, originally immunocompetent B6 mice to evaluate the ability of NP THY to reconstitute mouse CD4(+) T cells and to induce xenogeneic tolerance to donor pig skin grafts. Results. Repopulation of mouse CD4(+) T cells in the peripheral tissues was observed in T/NK cell-depleted, ATX B6 mice that received NP THY with or without neonatal pig spleen (NP SPL), but not in those receiving NP SPL alone, indicating that pig thymus grafting was necessary and sufficient for mouse T cell recovery. Seven of nine NP THY/SPL-grafted ATX mice and two of six NP THY-grafted ATX mice that reconstituted >5% CD4(+) cells in PBL accepted donor pig skin long-term without lymphocyte infiltration, whereas they rejected allogeneic BALB/c skin and third party pig skin grafts as rapidly as euthymic mice. Conclusions. NP THY can support the development of mouse CD4(+) T cells that are functional and specifically tolerant to donor pig antigens in ATX, T\NK cell-depleted, 3 Gy whole body-irradiated, originally immunocompetent B6 mice. Additional grafting of NP SPL with NP THY improves the efficiency of tolerance induction in this model. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02129 USA. RP Sykes, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Bone Marrow Transplantat Sect, Transplantat Biol Res Ctr,Surg Serv, MGH E,Bldg 149,13th St, Boston, MA 02129 USA. RI RODRIGUEZ-BARBOSA, JOSE IGNACIO/C-7808-2011; Barth, Rolf/B-2542-2014 FU NHLBI NIH HHS [P01-HL186461]; NIAID NIH HHS [P01-AI39755] NR 15 TC 17 Z9 18 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD APR 15 PY 2000 VL 69 IS 7 BP 1447 EP 1451 DI 10.1097/00007890-200004150-00040 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 307YM UT WOS:000086681800041 PM 10798769 ER PT J AU Kumar, V Sabatini, D Pandey, P Gingras, AC Majumder, PK Kumar, M Yuan, ZM Carmichael, G Weichselbaum, R Sonenberg, N Kufe, D Kharbanda, S AF Kumar, V Sabatini, D Pandey, P Gingras, AC Majumder, PK Kumar, M Yuan, ZM Carmichael, G Weichselbaum, R Sonenberg, N Kufe, D Kharbanda, S TI Regulation of the rapamycin and FKBP-target 1/mammalian target of rapamycin and cap-dependent initiation of translation by the c-Abl protein-tyrosine kinase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MESSENGER-RNA TRANSLATION; CELL-CYCLE ARREST; GROWTH-FACTOR-II; P70 S6 KINASE; DNA-DAMAGE; PHAS-I; PHOSPHATIDYLINOSITOL 3-KINASE; ATAXIA-TELANGIECTASIA; IONIZING-RADIATION; STRESS-RESPONSE AB The c-Abl protein-tyrosine kinase is activated by ionizing radiation and certain other DNA-damaging agents. The rapamycin and FKBP-target 1 (RAFT1), also known as FKBP12-rapamycin-associated protein (FRAP, mTOR), regulates the p70S6 kinase (p70(S6k)) and the eukaryotic initiation factor 4E (eIF4E)-binding protein 1 (4E-BP1), The present results demonstrate that c-Abl binds directly to RAFT1 and phosphorylates RAFT1 in vitro and in vivo. c-Abl inhibits autophosphorylation of RAFT1 and RAFT1-mediated phosphorylation p70S6k. The functional significance of the c-Abl-RAFT1 interaction is further supported by the finding that eIF4E-dependent translation in mouse embryo fibroblasts from Abl(-/-) mice is significantly higher than that compared in wildtype cells. The results also demonstrate that exposure of cells to ionizing radiation is associated with c-Abl-mediated binding of 4E-BP1 to eIF4E and inhibition of translation. These findings with the c-Abl tyrosine kinase represent the first demonstration of a negative physiologic regulator of RAFT1-mediated 5' cap-dependent translation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. McGill Univ, Dept Biochem, McGill Canc Ctr, Montreal, PQ H3G 1Y6, Canada. Univ Connecticut, Ctr Hlth, Dept Microbiol, Farmington, CT 06030 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. RI Gingras, Anne-Claude/E-9982-2010 OI Gingras, Anne-Claude/0000-0002-6090-4437 FU NCI NIH HHS [CA75216] NR 76 TC 40 Z9 41 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 APR 14 PY 2000 VL 275 IS 15 BP 10779 EP 10787 DI 10.1074/jbc.275.15.10779 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304DB UT WOS:000086466600012 PM 10753870 ER PT J AU van Royen, M Carbo, N Busquets, S Alvarez, B Quinn, LS Lopez-Soriano, FJ Argiles, JM AF van Royen, M Carbo, N Busquets, S Alvarez, B Quinn, LS Lopez-Soriano, FJ Argiles, JM TI DNA fragmentation occurs in skeletal muscle during tumor growth: A link with cancer cachexia? SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE DNA fragmentation; skeletal muscle; cancer cachexia ID NECROSIS-FACTOR-ALPHA; UBIQUITIN GENE-EXPRESSION; TISSUE PROTEIN-TURNOVER; NF-KAPPA-B; CELL-DEATH; INDUCED APOPTOSIS; TNF RECEPTOR-1; BEARING RATS; MALNUTRITION; THERAPY AB In two different experimental models of cancer cachexia, the rat Yoshida AH-130 ascites hepatoma and the mouse Lewis lung carcinoma, the implantation of the tumor caused a loss of body weight which was associated with a reduction in the weight of different skeletal muscles, as well as with their protein content. The decrease in protein content was accompanied by a reduction in DNA content. Interestingly, the protein/DNA ratio was unchanged in the skeletal muscle of the tumor-bearing animals as compared with the nontumor-bearing controls. Analysis of DNA fragmentation in skeletal muscle clearly showed enhanced laddering in the skeletal muscle of tumor-bearing animals, suggesting an apoptotic phenomenon. Interestingly, the degree of laddering (total DNA fragmented) increased with tumor burden. These results suggest that DNA fragmentation may be a primary event in cancer-associated cachexia. (C) 2000 Academic Press. C1 Univ Barcelona, Dept Bioquim & Biol Mol, Barcelona, Spain. VA Puget Sound Hlth Care Syst, Amer Lake Div, Ctr Geriatr Res Educ & Clin, Tacoma, WA 98493 USA. RP van Royen, M (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, Barcelona, Spain. NR 37 TC 77 Z9 80 U1 0 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD APR 13 PY 2000 VL 270 IS 2 BP 533 EP 537 DI 10.1006/bbrc.2000.2462 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 305DY UT WOS:000086525200034 PM 10753659 ER PT J AU Stadtmauer, EA O'Neill, A Goldstein, LJ Crilley, PA Mangan, KF Ingle, JN Brodsky, I Martino, S Lazarus, HM Erban, JK Sickles, C Glick, JH AF Stadtmauer, EA O'Neill, A Goldstein, LJ Crilley, PA Mangan, KF Ingle, JN Brodsky, I Martino, S Lazarus, HM Erban, JK Sickles, C Glick, JH CA Philadelphia Bone Marrow Transplan TI Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANTATION; CONSOLIDATION THERAPY; FOLLOW-UP; SUPPORT; RESCUE; CYCLOPHOSPHAMIDE; CARBOPLATIN; REMISSION; SELECTION; THIOTEPA AB Background: We conducted a randomized trial in which we compared high-dose chemotherapy plus hematopoietic stem-cell rescue with a prolonged course of monthly conventional-dose chemotherapy in women with metastatic breast cancer. Methods: Women 18 to 60 years of age who had metastatic breast cancer received four to six cycles of standard combination chemotherapy. Patients who had a complete or partial response to induction chemotherapy were then randomly assigned to receive either a single course of high doses of carboplatin, thiotepa, and cyclophosphamide plus transplantation of autologous hematopoietic stem cells or up to 24 cycles of cyclophosphamide, methotrexate, and fluorouracil in conventional doses. The primary end point was survival. Results: The median follow-up was 37 months. Of 553 patients who enrolled in the study, 58 had a complete response to induction chemotherapy and 252 had a partial response. Of these, 110 patients were assigned to receive high-dose chemotherapy plus hematopoietic stem cells and 89 were assigned to receive conventional-dose chemotherapy. In an intention-to-treat analysis, we found no significant difference in survival overall at three years between the two treatment groups (32 percent in the transplantation group and 38 percent in the conventional-chemotherapy group). There was no significant difference between the two treatments in the median time to progression of the disease (9.6 months for high-dose chemotherapy plus hematopoietic stem cells and 9.0 months for conventional-dose chemotherapy). Conclusions: As compared with maintenance chemotherapy in conventional doses, high-dose chemotherapy plus autologous stem-cell transplantation soon after the induction of a complete or partial remission with conventional-dose chemotherapy does not improve survival in women with metastatic breast cancer. (N Engl J Med 2000;342:1069-76.) (C) 2000, Massachusetts Medical Society. C1 Univ Penn, Ctr Canc, Bone Marrow & Stem Cell Transplant Program, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Hahnemann Univ, Philadelphia, PA USA. Temple Univ, Philadelphia, PA 19122 USA. Mayo Clin, Rochester, MN USA. John Wayne Canc Inst, Santa Monica, CA USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. RP Stadtmauer, EA (reprint author), Univ Penn, Ctr Canc, Bone Marrow & Stem Cell Transplant Program, 16 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. FU NCI NIH HHS [CA16520, CA15488, CA23318] NR 18 TC 308 Z9 311 U1 0 U2 6 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 APR 13 PY 2000 VL 342 IS 15 BP 1069 EP 1076 DI 10.1056/NEJM200004133421501 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 303DZ UT WOS:000086406700001 PM 10760307 ER PT J AU Growdin, JH Gonzalez, RG Greenberg, SM Perakis, CR Primavera, JM AF Growdin, JH Gonzalez, RG Greenberg, SM Perakis, CR Primavera, JM TI Case 11-2000: A 74-year-old man with memory loss, language impairment, and personality changes. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID QUANTITATIVE NEUROPATHOLOGIC ANALYSIS; PICKS-DISEASE; ALZHEIMERS-DISEASE; FRONTOTEMPORAL DEMENTIA; BODIES; TAU; CONSORTIUM C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Growdin, JH (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 34 TC 2 Z9 2 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 APR 13 PY 2000 VL 342 IS 15 BP 1110 EP 1117 DI 10.1056/NEJM200004133421507 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 303DZ UT WOS:000086406700007 ER PT J AU Price, BH Richardson, EP AF Price, BH Richardson, EP TI The neurologic illness of Eugene O'Neill - A clinicopathological report. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID TREMOR; ATAXIA C1 McLean Hosp, Dept Neurol, Belmont, MA 02478 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Price, BH (reprint author), McLean Hosp, Dept Neurol, 115 Mill St, Belmont, MA 02478 USA. NR 28 TC 4 Z9 5 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 APR 13 PY 2000 VL 342 IS 15 BP 1126 EP 1133 DI 10.1056/NEJM200004133421511 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 303DZ UT WOS:000086406700011 PM 10760316 ER PT J AU Pandey, P Farber, R Nakazawa, A Kumar, S Bharti, A Nalin, C Weichselbaum, R Kufe, D Kharbanda, S AF Pandey, P Farber, R Nakazawa, A Kumar, S Bharti, A Nalin, C Weichselbaum, R Kufe, D Kharbanda, S TI Hsp27 functions as a negative regulator of cytochrome c-dependent activation of procaspase-3 SO ONCOGENE LA English DT Article DE Hsp27; cytochrome c; caspase-3; apoptosis ID HEAT-SHOCK PROTEIN; PROGRAMMED CELL-DEATH; EMBRYONIC STEM-CELLS; ALPHA-B-CRYSTALLIN; CAENORHABDITIS-ELEGANS; PROTEOLYTIC ACTIVATION; ICE/CED-3 PROTEASE; INDUCED APOPTOSIS; CARCINOMA-CELLS; DNA-DAMAGE AB The release of mitochondrial cytochrome c by genotoxic stress induces the formation of a cytosolic complex with Apaf-1 (mammalian CED4 homolog) and thereby the activation of procaspase-3 (cas-3) and procaspase-9 (cas-9). Here we demonstrate that heat-shock protein 27 (Hsp27) inhibits cytochrome c (cyt c)-dependent activation of cas-3. Hsp27 had no effect on cyt c release, Apaf-1 and cas-9 activation. By contrast, our results show that Hsp27 associates with cas-3, but not Apaf-1 or cas-9, and inhibits activation of cas-3 by cas-9-mediated proteolysis, Furthermore, the present results demonstrate that immunodepletion of Hsp27 depletes cas-3, Importantly, treatment of cells with DNA damaging agents dissociates the Hsp27/cas-3 complex and relieves inhibition of cas-3 activation. These findings define a novel function for Hsp27 and provide the first evidence that a heat shock protein represses cas-3 activation. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Novartis Pharmaceut Corp, E Hanover, NJ 07936 USA. Univ Chicago, Dept Radiat & Cellular Oncol, Chicago, IL 60637 USA. RP Kharbanda, S (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA29431, CA75216] NR 46 TC 201 Z9 211 U1 1 U2 2 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 13 PY 2000 VL 19 IS 16 BP 1975 EP 1981 DI 10.1038/sj.onc.1203531 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 306TT UT WOS:000086613200001 PM 10803458 ER PT J AU Yeh, JJ Lunetta, KL van Orsouw, NJ Moore, FD Mutter, GL Vijg, J Dahia, PLM Eng, C AF Yeh, JJ Lunetta, KL van Orsouw, NJ Moore, FD Mutter, GL Vijg, J Dahia, PLM Eng, C TI Somatic mitochondrial DNA (mtDNA) mutations in papillary thyroid carcinomas and differential mtDNA sequence variants in cases with thyroid tumours SO ONCOGENE LA English DT Article DE mitochondria; thyroid tumours; sequence variants; mutations ID TUMORS; APOPTOSIS; CANCER AB Somatic mutations in mtDNA have recently been identified in colorectal tumours, Studies of oncocytic tumours have led to hypotheses which propose that defects in oxidative phosphorylation may result in a compensatory increase in mitochondrial replication and/or gene expression. Mutational analysis of mtDNA in thyroid neoplasia, which is characterised by increased numbers of mitochondria and is also one of the most common sites of oncocytic tumours, has been limited to date. Using the recently developed technique of two-dimensional gene scanning, me have successfully examined 21 cases of thyroid tumours, six cases of nonneoplastic thyroid pathology, 30 population controls, nine foetal thyroid tissues and nine foetal tissues of nonthyroid origin, either kidney or liver. We have identified three different somatic mutations (23%) in papillary thyroid carcinomas. In addition, we have found significant differential distributions of mtDNA sequence variants between thyroid carcinomas and controls. Interestingly, these variants appear to be more frequent in the genes which encode complex I of the mitochondrial electron transport chain compared to normal population controls, These findings suggest first, that somatic mtDNA mutations may be involved in thyroid tumorigenesis and second, that the accumulation of certain non-somatic variants may be related to tumour progression in the thyroid. C1 Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet & Human Canc Genet Program, Med Res Facil 690C, Columbus, OH 43210 USA. Dana Farber Canc Inst, Charles A Dana Human Canc Genet Unit, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. San Antonio Canc Inst, Inst Drug Dev, San Antonio, TX USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Eng, C (reprint author), Ohio State Univ, Ctr Comprehens Canc, Clin Canc Genet & Human Canc Genet Program, Med Res Facil 690C, 420 W 12th Ave, Columbus, OH 43210 USA. RI Mutter, George/C-5819-2009; OI Eng, Charis/0000-0002-3693-5145 FU NCI NIH HHS [P30CA16058] NR 22 TC 128 Z9 137 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 13 PY 2000 VL 19 IS 16 BP 2060 EP 2066 DI 10.1038/sj.onc.1203537 PG 7 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 306TT UT WOS:000086613200010 PM 10803467 ER PT J AU Marshall, MN Shekelle, PG Leatherman, S Brook, RH AF Marshall, MN Shekelle, PG Leatherman, S Brook, RH TI The public release of performance data - What do we expect to gain? A review of the evidence SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID NEW-YORK-STATE; BYPASS GRAFT-SURGERY; CARDIAC-SURGERY; QUALITY IMPROVEMENT; OUTCOMES DATA; HEALTH-CARE; MORTALITY; INFORMATION; INDICATORS; CONSUMERS AB Context information about the performance of hospitals, health professionals, and health care organizations has been made public in the United States for more than a decade. The expected gains of public disclosure have not been made clear, and both the benefits and potential risks have received minimal empirical investigation. Objective To summarize the empirical evidence concerning public disclosure of performance data, relate the results to the potential gains, and identify areas requiring further research. Data Sources A literature search was conducted on MEDLINE and EMBASE databases for articles published between January 1986 and October 1999 in peer-reviewed journals. Review of citations, public documents, and expert advice was conducted to identify studies not found in the electronic databases. Study Selection Descriptive, observational, or experimental evaluations of CIS reporting systems were selected for inclusion. Data Extraction Included studies were organized based on use of public data by consumers, purchasers, physicians, and hospitals; impact on quality of care outcomes; and costs. Data Synthesis Seven US reporting systems have been the subject of published empirical evaluations. Descriptive and observational methods predominate, Consumers and purchasers rarely search out the information and do not understand or trust it; it has a small, although increasing, impact on their decision making. Physicians are skeptical about such data and only a small proportion makes use of it, Hospitals appear to be most responsive to the data. In a limited number of studies, the publication of performance data has been associated with an improvement in health outcomes. Conclusions There are several potential gains from the public disclosure of performance data, but use of the information by provider organizations for quality improvement may be the most productive area for further research. C1 Univ Exeter, Sch Postgrad Med & Hlth Sci, Exeter, Devon, England. RAND Hlth Program, Santa Monica, CA USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Ctr Hlth Care Policy & Evaluat, United Hlth Grp, Minnetonka, MN USA. Univ Cambridge, Judge Inst Management, Cambridge, England. Univ Calif Los Angeles, Ctr Hlth Serv, Los Angeles, CA USA. RP Marshall, MN (reprint author), Univ Manchester, Natl Primary Care Res & Dev Ctr, 5th Floor,Williamson Bldg,Oxford Rd, Manchester M13 9PL, Lancs, England. NR 50 TC 491 Z9 493 U1 2 U2 28 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 12 PY 2000 VL 283 IS 14 BP 1866 EP 1874 DI 10.1001/jama.283.14.1866 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 300HY UT WOS:000086248600033 PM 10770149 ER PT J AU Hajjar, RJ Schwinger, RHG Schmidt, U Kim, CS Lebeche, D Doye, AA Gwathmey, JK AF Hajjar, RJ Schwinger, RHG Schmidt, U Kim, CS Lebeche, D Doye, AA Gwathmey, JK TI Myofilament calcium regulation in human myocardium SO CIRCULATION LA English DT Article DE myocardium; heart failure; calcium; cGMP; myocytes ID STAGE HEART-FAILURE; HUMAN VENTRICULAR MYOCARDIUM; CROSS-BRIDGE KINETICS; TROPONIN-T ISOFORMS; FAILING HUMAN-HEART; SARCOPLASMIC-RETICULUM; DILATED CARDIOMYOPATHY; PROTEIN-KINASE; CA-2+ SENSITIVITY; ATPASE ACTIVITY AB Background-We investigated whether decreased myofilament calcium contractile activation may, in part, contribute to heart failure. Methods and Results-Calcium concentration required for 50% activation and Hill coefficient for fibers from nonfailing and failing human hearts at pH 7.1 were not different. Maximum calcium-activated force (F-max) was also not different. However, at pH 6.8 and 6.9, differences were seen in myofilament calcium activation between nonfailing and failing hearts. At lower pH, failing myocardium was shifted left on the calcium axis compared with nonfailing myocardium, which suggested an increase in myofilament calcium responsiveness. Increased inorganic phosphate concentration decreased maximal force development by 56% in nonfailing and 36% in failing myocardium and shifted the calcium-force relationship by 2.01+/-0.22 versus 0.86+/-0.13 mu mol/L, respectively (P<0.05), Addition of cAMP resulted in a 0.56 mu mol/L, shift toward higher intracellular calcium concentrations in nonfailing myocardium and a 1.04 mu mol/L shift in failing myocardium. Protein kinase A in the presence of cAMP resulted in a further rightward shift in nonfailing human myocardium but did not further shift the calcium-force relationship in fibers from failing hearts. cGMP also resulted in a greater decrease in myofilament calcium sensitivity in fibers from failing hearts. Conclusions-We propose that changes at the level of the thin myofilaments result in differential responses to changes in the intracellular milieu in nonfailing versus failing myocardium. C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Gwathmey Inc, Cambridge, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Univ Cologne, Clin Internal Med 3, Lab Muscle Res & Mol Cardiol, D-5000 Cologne 41, Germany. RP 763 Concord Ave,Bldg E, Cambridge, MA 02138 USA. EM gwathmey@earthlink.net FU NHLBI NIH HHS [R01 HL049574-05S1, R01 HL049574-06, 2RO1-HL-49574, R01 HL049574-08, R01 HL049574-06S1, R01 HL049574-05, R44-HL-52249, KO8-HL-03561, R01 HL049574-07] NR 41 TC 36 Z9 37 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD APR 11 PY 2000 VL 101 IS 14 BP 1679 EP 1685 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 302MB UT WOS:000086367900020 PM 10758050 ER PT J AU Martin, KJ Pardee, AB AF Martin, KJ Pardee, AB TI Identifying expressed genes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID DIFFERENTIAL DISPLAY; MESSENGER-RNA; CLONING; DNA C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. RP Martin, KJ (reprint author), Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. NR 20 TC 32 Z9 34 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 APR 11 PY 2000 VL 97 IS 8 BP 3789 EP 3791 DI 10.1073/pnas.97.8.3789 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 304AV UT WOS:000086461100003 PM 10760250 ER PT J AU Falvo, JV Brinkman, BMN Tsytsykova, AV Tsai, EY Yao, TP Kung, AL Goldfeld, AE AF Falvo, JV Brinkman, BMN Tsytsykova, AV Tsai, EY Yao, TP Kung, AL Goldfeld, AE TI A stimulus-specific role for CREB-binding protein (CBP) in T cell receptor-activated tumor necrosis factor alpha gene expression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RUBINSTEIN-TAYBI SYNDROME; FACTOR-DEFICIENT MICE; HUMAN B-CELLS; TRANSCRIPTION FACTORS; COACTIVATORS P300; INTERFERON-BETA; NUCLEAR FACTOR; RETINOIC-ACID; FAMILY; VIRUS AB The cAMP response element binding protein (CREB)-binding protein (CBP)/p300 family of coactivator proteins regulates gene transcription through the integration of multiple signal transduction pathways. Here, we show that induction of tumor necrosis factor alpha (TNF-alpha) gene expression in T cells stimulated by engagement of the T cell receptor (TCR) or by virus infection requires CBP/p300. Strikingly, in mice lacking one copy of the CBP gene, TNF-cu gene induction by TCR activation is inhibited, whereas virus induction of the TNF-alpha gene is not affected. Consistent with these findings, the transcriptional activity of CBP is strongly potentiated by TCR activation but not by virus infection of T cells. Thus, CBP gene dosage and transcriptional activity are critical in TCR-dependent TNF-alpha gene expression, demonstrating a stimulus-specific requirement for CBP in the regulation of a specific gene. C1 Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goldfeld, AE (reprint author), Ctr Blood Res, 800 Huntington Ave, Boston, MA 02115 USA. RI Brinkman, Brigitta/C-1100-2009 FU NIGMS NIH HHS [GM-56492, R01 GM056492] NR 41 TC 45 Z9 45 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 APR 11 PY 2000 VL 97 IS 8 BP 3925 EP 3929 DI 10.1073/pnas.97.8.3925 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 304AV UT WOS:000086461100028 PM 10760264 ER PT J AU Shoichet, SA Malik, TH Rothman, JH Shivdasani, RA AF Shoichet, SA Malik, TH Rothman, JH Shivdasani, RA TI Action of the Caenorhabditis elegans GATA factor END-1 in Xenopus suggests that similar mechanisms initiate endoderm development in ecdysozoa and vertebrates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID DNA-BINDING PROTEINS; TRANSCRIPTION FACTOR GATA-1; HEART TUBE FORMATION; VENTRAL MORPHOGENESIS; MESODERM FORMATION; VISCERAL ENDODERM; GENE; DROSOPHILA; DIFFERENTIATION; EXPRESSION AB In ecdysozoan protostomes, including arthropods and nematodes, transcription factors of the GATA family specify the endoderm: Drosophila dGATAb (ABF/Serpent) and Caenorhabditis elegans END-1 play important roles in generating this primary germ layer. end-1 is the earliest expressed endoderm-specific gene known in C. elegans and appears to initiate the program of gene expression required for endoderm differentiation, including a cascade of GATA factors required for development and maintenance of the intestine. Among vertebrate GATA proteins, the GATA-4/5/6 subfamily regulates aspects of late endoderm development, but a role for GATA factors in establishing the endoderm is unknown. We show here that END-1 binds to the canonical target DNA sequence WGATAR with specificity similar to that of vertebrate GATA-1 and GATA-4, and that it functions as a transcriptional activator. We exploited this activity of END-1 to demonstrate that establishment of the vertebrate endoderm, like that of invertebrate species, also appears to involve GATA transcriptional activity. Like the known vertebrate endoderm regulators Mixer and Sox17, END-1 is a potent activator of endoderm differentiation in isolated Xenopus ectoderm. Moreover, a dominant inhibitory GATA-binding fusion protein abrogates endoderm differentiation in intact embryos, By examining these effects in conjunction with those of Mixer- and Sox17 beta-activating and dominant inhibitory constructs, we further establish the likely relationships between GATA activity and these regulators in early development of the vertebrate endoderm. These results suggest that GATA factors may function sequentially to regulate endoderm differentiation in both protostomes and deuterostomes. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 54 TC 41 Z9 43 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 11 PY 2000 VL 97 IS 8 BP 4076 EP 4081 DI 10.1073/pnas.97.8.4076 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 304AV UT WOS:000086461100054 PM 10760276 ER PT J AU Liu, XD Constantinescu, SN Sun, Y Bogan, JS Hirsch, D Weinberg, RA Lodish, HF AF Liu, XD Constantinescu, SN Sun, Y Bogan, JS Hirsch, D Weinberg, RA Lodish, HF TI Generation of mammalian cells stably expressing multiple genes at predetermined levels SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID 5' NONTRANSLATED REGION; RIBOSOME ENTRY SITE; RETROVIRAL VECTORS; HIGH-TITER; RAPID PRODUCTION; INTERNAL ENTRY; HELPER-FREE; SYSTEM; COEXPRESSION; TRANSLATION AB Expression of cloned genes at desired levels in cultured mammalian cells is essential for studying protein function. Controlled levels of expression have been difficult to achieve, especially for cell lines with low transfection efficiency or when expression of multiple genes is required. An internal ribosomal entry site (IRES) has been incorporated into many types of expression vectors to allow simultaneous expression of two genes. However, there has been no systematic quantitative analysis of expression levels in individual cells of genes linked by an IRES, and thus the broad use of these vectors in functional analysis has been limited. We constructed a set of retroviral expression vectors containing an IRES followed by a quantitative selectable marker such as green fluorescent protein (GFP) or truncated cell surface proteins CD2 or CD4. The gene of interest is placed in a multiple cloning site 5' of the IRES sequence under the control of the retroviral long terminal repeat (LTR) promoter. These vectors exploit the similar to 100-fold differences in levels of expression of a retrovirus vector depending on its site of insertion in the host chromosome. We show that the level of expression of the gene downstream of the IRES and the expression level and functional activity of the gene cloned upstream of the IRES are highly correlated in stably infected target cells. This feature makes our vectors extremely useful for the rapid generation of stably transfected cell populations or clonal cell lines expressing specific amounts of a desired protein simply by fluorescent activated cell sorting (FACS) based on the level of expression of the gene downstream of the IRES. We show how these vectors can be used to generate cells expressing high levels of the erythropoietin receptor (EpoR) or a dominant negative Smad3 protein and to generate cells expressing two different cloned proteins, Ski and Smad4. Correlation of a biologic effect with the level of expression of the protein downstream of the IRES provides strong evidence for the function of the protein placed upstream of the IRES. (C) 2000 Academic Press. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lodish, HF (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. RI Bogan, Jonathan/A-1575-2010; Constantinescu, Stefan /E-5277-2012 OI Bogan, Jonathan/0000-0001-6463-8466; FU NCI NIH HHS [CA-63260]; NHLBI NIH HHS [HL41484, HL 32262] NR 25 TC 111 Z9 115 U1 0 U2 11 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD APR 10 PY 2000 VL 280 IS 1 BP 20 EP 28 DI 10.1006/abio.2000.4478 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 304MQ UT WOS:000086488400003 PM 10805516 ER PT J AU Heydari, AR You, SH Takahashi, R Gutsmann-Conrad, A Sarge, KD Richardson, A AF Heydari, AR You, SH Takahashi, R Gutsmann-Conrad, A Sarge, KD Richardson, A TI Age-related alterations in the activation of heat shock transcription factor 1 in rat hepatocytes SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID PROTEIN-70 MESSENGER-RNA; DECREASED EXPRESSION; DIPLOID FIBROBLASTS; GENE-TRANSCRIPTION; STRESS; CELLS; HSP70; LIVER; OLIGOMERIZATION; PHOSPHORYLATION AB The induction of hsp70 transcription by heat shock is significantly reduced in hepatocytes isolated from old rats compared to hepatocytes isolated from young! adult rats, and the decline in hsp70 transcription is correlated with a decrease in the induction of heat shock transcription factor 1 (HSF1) binding to the heat shock element. However, the decreased HSF1 binding activity to DNA is not due to reduced levels of HSF1 that are available for activation by heat shock. In fact, the levels of HSF1 are two- to threefold higher in hepatocytes from old rats, and the age-related increase in the levels of HSF1 protein in hepatocytes appears to arise from a decrease in the degradation of the HSF1 because HSF1 mRNA levels do not change and the synthesis of HSF1 decreases approximately 50% with age. No evidence was found for an impairment in HSF1 oligomerization in hepatocytes from old rats, e.g., the level of HSF1 trimers, the nuclear translocation of HSF1, and the phosphorylation of HSF1 after heat shock are similar in hepatocytes isolated from young/adult and old rats. However, the thermostability of the DNA binding activity of HSF1 was significantly reduced with age in a cell-free system as well as in isolated hepatocytes. (C) 2000 Academic Press. C1 S Texas Vet Hlth Care Syst, Audie L Murphy Div, GRECC 182, San Antonio, TX 78284 USA. Wayne State Univ, Dept Nutr & Food Sci, Detroit, MI 48202 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Univ Kentucky, Dept Biochem, Lexington, KY 40536 USA. RP Richardson, A (reprint author), S Texas Vet Hlth Care Syst, Audie L Murphy Div, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG01188, AG01548] NR 52 TC 79 Z9 84 U1 0 U2 7 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 10 PY 2000 VL 256 IS 1 BP 83 EP 93 DI 10.1006/excr.2000.4808 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 304HB UT WOS:000086476700011 PM 10739655 ER PT J AU Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Wiseman, E Bridge, P AF Bartzokis, G Beckson, M Lu, PH Edwards, N Rapoport, R Wiseman, E Bridge, P TI Age-related brain volume reductions in amphetamine and cocaine addicts and normal controls: implications for addiction research SO PSYCHIATRY RESEARCH-NEUROIMAGING LA English DT Article DE aging; psychostimulant addiction; gray matter; white matter; frontal lobe; temporal lobe ID MAGNETIC-RESONANCE; GRAY-MATTER; IN-VIVO; MRI; ABUSERS; LOBE; HIPPOCAMPUS; DEPENDENCE; METABOLISM; ACTIVATION AB The study evaluated the relationship between age and frontal and temporal lobe volumes in young cohorts of cocaine-dependent (CD), amphetamine-dependent (Am), and normal control subjects. Ten CD, nine Am, and 16 age- and gender-matched control subjects underwent magnetic resonance imaging (MRI). The volume of the frontal and temporal lobes was measured from an identically positioned slab of seven contiguous 3-mm-thick coronal images. Follow-up measures of the gray and white matter subcomponents of these volumes were also obtained. Both CD and Am groups had a significantly smaller temporal lobe volumes, but only the CD group demonstrated a significantly greater decline in temporal lobe volume with age (intracranial volume, education, and race were controlled for in all statistical analyses). Segmenting the brain regions into gray and white matter revealed that the negative correlation between age and temporal lobe volume of CD patients was mostly due to a significant age-related decline in the gray matter subcomponent. Negative trends between age and gray matter volumes were also observed in the Am and normal groups. In the frontal lobes, age was negatively correlated with gray matter volume in the control, CD, and Am groups. Unlike the consistent decreases in gray matter volumes, white matter showed non-significant increases in volume with age. The data suggest that CD patients may have an accelerated age-related decline in temporal lobe gray matter volume and a smaller temporal lobe volume compared to normal controls. In the frontal lobe, age-related gray matter volume reductions occur in all three groups. These age-related cortical gray matter volume reductions may be a biological marker for the risk of addictive behavior, which also decreases with age. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Dept Psychiat, Little Rock, AR 72205 USA. Greater Los Angeles VA Healthcare Syst, W Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90074 USA. NIDA, Medicat Dev Div, Rockville, MD 20857 USA. RP Bartzokis, G (reprint author), Cent Arkansas Vet Healthcare Syst, Mental Hlth Serv Line, 2200 Ft Roots Dr,Bldg 170 116A-NLR, N Little Rock, AR 72114 USA. RI Bartzokis, George/K-2409-2013 FU NIDA NIH HHS [1YO1 DA 50038] NR 32 TC 77 Z9 81 U1 2 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0925-4927 J9 PSYCHIAT RES-NEUROIM JI Psychiatry Res. Neuroimaging PD APR 10 PY 2000 VL 98 IS 2 BP 93 EP 102 DI 10.1016/S0925-4927(99)00052-9 PG 10 WC Clinical Neurology; Neuroimaging; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 310BN UT WOS:000086806800002 PM 10762735 ER PT J AU Foo, NC Yen, TSB AF Foo, NC Yen, TSB TI Activation of promoters for cellular lipogenic genes by hepatitis B virus large surface protein SO VIROLOGY LA English DT Article DE hepatitis B virus; large surface protein; ground glass cells; farnesyl diphosphate synthase; fatty acid synthase; NF-Y ID ENDOPLASMIC-RETICULUM; NF-Y; TRANSCRIPTION FACTOR; REGULATORY ELEMENT; SYNTHASE PROMOTER; RESPONSE PATHWAY; EXPRESSION; STRESS; SECRETION; ANTIGEN AB Hepatitis B virus large surface protein has the unusual property of accumulating in a particulate form within a preGolgi compartment, leading to marked proliferation of intracellular membranes. We show here that large surface protein activates the promoters for two lipogenic genes that code for farnesyl diphosphate synthase and fatty acid synthase. This activation is transduced, in part, by the transcription factor NF-Y. Although NF-Y Is also necessary for the transcriptional induction of chaperone proteins residing in the endoplasmic reticulum by unfolded proteins, other inducers of chaperone synthesis do not activate the promoters for farnesyl diphosphate synthase and fatty acid synthase. Our results suggest the presence of a novel signaling pathway from the endoplasmic reticulum to the nucleus that causes the intracellular membrane proliferation seen in the hepatocytes of persons with accumulated large surface protein particles. (C) 2000 Academic Press. C1 Univ Calif San Francisco, Dept Pathol, Pathol Serv 113B, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Pathol Serv, San Francisco, CA 94121 USA. RP Yen, TSB (reprint author), Univ Calif San Francisco, Dept Pathol, Pathol Serv 113B, 4150 Clement St, San Francisco, CA 94143 USA. FU NCI NIH HHS [R01-CA-55578] NR 32 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD APR 10 PY 2000 VL 269 IS 2 BP 420 EP 425 DI 10.1006/viro.1999.0148 PG 6 WC Virology SC Virology GA 304MK UT WOS:000086487800019 PM 10753720 ER PT J AU Tsang, YM Chiong, F Kuznetsov, D Kasarskis, E Geula, C AF Tsang, YM Chiong, F Kuznetsov, D Kasarskis, E Geula, C TI Motor neurons are rich in non-phosphorylated neurofilaments: cross-species comparison and alterations in ALS SO BRAIN RESEARCH LA English DT Article DE brainstem; cholinergic; choline acetyltransferase; motor cortex; phosphorylated neurofilament; spinal cord ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRANSGENIC MICE; SELECTIVE VULNERABILITY; SPINAL-CORD; IN-VITRO; SUBUNIT; PROTEIN; DISEASE; EXPRESSION; GENE AB The localization and distribution of non-phosphorylated neurofilaments (NP-NF) in the upper and lower motor neurons was investigated in the rat, the common marmoset, the rhesus monkey and man using the SMI-32 antibody. Within the spinal cord of all species studied, the most intense NP-NF immunoreactivity was observed within the ventral horn alpha-motor neurons. Concurrent staining for the cholinergic marker choline acetyltransferase (ChAT) demonstrated that virtually all of the ChAT-positive alpha-motor neurons contain NP-NF immunoreactivity. Although NP-NF staining was also observed in other neurons within the ventral and intermediate horns, these neurons were loosely scattered and contained a considerably lower staining intensity. The only other prominent NP-NF staining in the spinal cord occurred within the neurons of the dorsal nucleus of Clark and the intermediolateral cell column. Phosphorylated neurofilament (P-NF) immunoreactivity was found primarily in neuronal processes. Occasionally, a solitary motor neuron contained weak P-NF immunoreactivity. Within the brainstem, neurons in all cranial nerve motor nuclei contained intense NP-NF immunoreactivity. The distribution and apparent density of NP-NF immunoreactive neurons in these nuclei was virtually identical to that observed for neurons immunoreactive for ChAT. NP-NF immunoreactive neurons of relatively lower intensity were found in many other regions of the brainstem. All of the giant Betz cells of layer (L) V in the motor cortex contained dark NP-NF immunoreactivity. Within the spinal cord of amyotrophic lateral sclerosis (ALS) patients, both Nissl and NP-NF staining demonstrated the dramatic loss of alpha-motor neurons characteristic of this disorder. Some of the remaining motor neurons contained intense P-NF immunoreactivity. These observations suggest that NP-NF immunoreactivity is a good marker for motor neurons in health and disease and may be a useful tool for studies of motor neuron degeneration (MND). (C) 2000 Elsevier Science B.V. All rights reserved. C1 Harvard Univ, Sch Med, Dept Med, Lab Neurodegenerat & Aging Res, Boston, MA 02215 USA. Beth Israel Deacness Med Ctr, Sect Gerontol, Boston, MA 02215 USA. Univ Kentucky, Sch Med, Dept Neurol, Lexington, KY 40536 USA. RP Geula, C (reprint author), Harvard Univ, Sch Med, Dept Med, Lab Neurodegenerat & Aging Res, 21-27 Burlington Ave,POB 15709, Boston, MA 02215 USA. NR 40 TC 73 Z9 74 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD APR 7 PY 2000 VL 861 IS 1 BP 45 EP 58 DI 10.1016/S0006-8993(00)01954-5 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 302DJ UT WOS:000086349900006 PM 10751564 ER PT J AU Winnay, JN Bruning, JC Burks, DJ Kahn, CR AF Winnay, JN Bruning, JC Burks, DJ Kahn, CR TI Gab-1-mediated IGF-1 signaling in IRS-1-deficient 3T3 fibroblasts SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INSULIN-RECEPTOR SUBSTRATE-1; FACTOR-I-RECEPTOR; PLECKSTRIN HOMOLOGY DOMAINS; GRB2 BINDING-SITE; GROWTH-FACTOR; PHOSPHATIDYLINOSITOL 3-KINASE; PHOSPHOTYROSINE PROTEIN; DOCKING PROTEIN; TYROSINE KINASE; SH2 DOMAIN AB The insulin receptor substrate (IRS) family of proteins mediate a variety of intracellular signaling events by serving as signaling platforms downstream of several receptor tyrosine kinases including the insulin and insulin-like growth factor-1 (IGF-1) receptors. Recently, several new members of this family have been identified including IRS-3, IRS-4, and growth factor receptor-binding protein a-associated binder-1 (Gab-l). 3T3 cell lines derived from IRS-l-deficient embryos exhibit a 70-80% reduction in IGF-l-stimulated S-phase entry and a parallel decrease in the induction of the immediate-early genes c-fos and egr-1 but unaltered activation of the mitogen-activated protein kinases extracellular signal-regulated kinase-l and extracellular signal-regulated kinase-2. Reconstitution of IRS-1 expression in IRS-1-deficient fibroblasts by retroviral mediated gene transduction is capable of restoring these defects. Overexpression of Gab-l in IRS-l-deficient fibroblasts also results in the restoration of egr-1 induction to levels similar to those achieved by IRS-1 reconstitution and markedly increases IGF-l-stimulated S-phase progression. Gab-l is capable of regulating these biological end points despite the absence of IGF-1 stimulated tyrosine phosphorylation. These data provide evidence that Gab-l may serve as a unique signaling intermediate in insulin/IGF-1 signaling for induction of early gene expression and stimulation of mitogenesis without direct tyrosine phosphorylation. C1 Joslin Diabet Ctr, Div Cellular & Mol Physiol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Kahn, CR (reprint author), Joslin Diabet Ctr, Div Cellular & Mol Physiol, Boston, MA 02215 USA. FU NIDDK NIH HHS [DK36836, DK33201] NR 40 TC 36 Z9 36 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 APR 7 PY 2000 VL 275 IS 14 BP 10545 EP 10550 DI 10.1074/jbc.275.14.10545 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 302BT UT WOS:000086345600089 PM 10744748 ER PT J AU Lowell, BB Spiegelman, BM AF Lowell, BB Spiegelman, BM TI Towards a molecular understanding of adaptive thermogenesis SO NATURE LA English DT Article ID BROWN ADIPOSE-TISSUE; MITOCHONDRIAL UNCOUPLING PROTEIN; RESTING ENERGY-EXPENDITURE; THYROID-HORMONE; METABOLIC-RATE; BODY-WEIGHT; OXIDATIVE-PHOSPHORYLATION; TARGETED DISRUPTION; GENE-EXPRESSION; TRANSGENIC MICE AB Obesity results when energy In lake exceeds energy expenditure. Naturally occurring genetic mutations, as well as ablative lesions, have shown that the brain regulates both aspects of energy balance and that abnormalities in energy expenditure contribute to the development of obesity. Energy can be expended by performing work or producing heat (thermogenesis). Adaptive thermogenesis, or the regulated production of heat, is influenced by environmental temperature and diet. Mitochondria, the organelles that convert food to carbon dioxide, water and ATP are fundamental in mediating effects on energy dissipation. Recently there have been significant advances in understanding the molecular regulation of energy expenditure in mitochondria and the mechanisms of transcriptional control of mitochondrial genes. Here we explore these developments in relation to classical physiological views of adaptive thermogenesis. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Lowell, BB (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, 99 Brookline Ave, Boston, MA 02215 USA. NR 93 TC 830 Z9 852 U1 13 U2 86 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 6 PY 2000 VL 404 IS 6778 BP 652 EP 660 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303BC UT WOS:000086400100065 PM 10766252 ER PT J AU Schwartz, MW Woods, SC Porte, D Seeley, RJ Baskin, DG AF Schwartz, MW Woods, SC Porte, D Seeley, RJ Baskin, DG TI Central nervous system control of food intake SO NATURE LA English DT Review ID PROOPIOMELANOCORTIN MESSENGER-RNA; HYPOTHALAMIC NEUROPEPTIDE-Y; AGOUTI-RELATED PROTEIN; LEPTIN RECEPTOR; BODY-WEIGHT; MELANOCORTIN RECEPTORS; GENE-EXPRESSION; OB/OB MICE; IN-VIVO; PARAVENTRICULAR NUCLEUS AB New information regarding neuronal circuits that control food intake and their hormonal regulation has extended our understanding of energy homeostasis, the process whereby energy intake is matched to energy expenditure over time. The profound obesity that results in rodents (and in the rare human case as well) from mutation of key signalling molecules involved in this regulatory system highlights its Importance to human health, Although each new signalling pathway discovered in the hypothalamus is a potential target for drug development in the treatment of obesity the growing number of such signalling molecules indicates that food intake is controlled by a highly complex process. Se better understand how energy homeostasis can be achieved, we describe a model that delineates the roles of individual hormonal and neuropeptide signalling pathways in the control of food Intake and the means by which obesity can arise from Inherited or acquired defects in their function. C1 Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. Univ Washington, Harborview Med Ctr, Dept Biol Struct, Seattle, WA 98104 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98104 USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45267 USA. RP Schwartz, MW (reprint author), Univ Washington, Harborview Med Ctr, Dept Med, Seattle, WA 98104 USA. RI sheng, jian/E-9474-2012; Schwartz, Michael/H-9950-2012 NR 121 TC 3443 Z9 3531 U1 33 U2 349 PU MACMILLAN MAGAZINES LTD PI LONDON PA PORTERS SOUTH, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD APR 6 PY 2000 VL 404 IS 6778 BP 661 EP 671 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 303BC UT WOS:000086400100066 PM 10766253 ER PT J AU Arico, M Valsecchi, MG Camitta, B Schrappe, M Chessells, J Baruchel, A Gaynon, P Silverman, 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 Silverman, L Janka-Schaub, G Kamps, W Pui, CH Masera, G TI Outcome of treatment in children with philadelphia chromosome-positive acute lymphoblastic leukemia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID BONE-MARROW TRANSPLANTATION; PEDIATRIC-ONCOLOGY-GROUP; CLINICAL-SIGNIFICANCE; POOR-PROGNOSIS; PROSPECTIVE METAANALYSIS; INTENSIVE CHEMOTHERAPY; INTERIM ANALYSIS; CANCER GROUP; CHILDHOOD; THERAPY AB Background: Children with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL) have a poor prognosis, and there is no consensus on the optimal treatment for this variant of ALL. Methods: We reviewed the medical records of patients with Ph-positive ALL who were treated with intensive chemotherapy, with or without bone marrow transplantation, by 10 study groups or large single institutions from 1986 to 1996. Data on 326 children and young adults, who ranged in age from 0.4 to 19.9 years (median, 8.1), were analyzed to determine the rate of complete remission and the probability of event-free, disease-free, and overall survival according to standard prognostic factors and type of treatment. Results: The 267 patients who had a complete remission after induction chemotherapy (82 percent) were stratified into three subgroups according to the age and leukocyte count at the time of diagnosis: those with the best prognosis (a leukocyte count of less than 50,000 per cubic millimeter and an age of less than 10 years; 95 patients); those with an intermediate prognosis (intermediate-risk features; 92 patients); and those with the worst prognosis (a leukocyte count of more than 100,000 per cubic millimeter; 80 patients). The estimates of disease-free survival at five years (+/-SE) were 49+/-5 percent (for patients with the best prognosis), 30+/-5 percent (for those with an intermediate prognosis), and 20+/-5 percent (for those with the worst prognosis) (P<0.001 for the overall comparison). We also found that transplantation of bone marrow from an HLA-matched related donor offered significantly greater benefit than intensive chemotherapy alone in terms of protecting patients from relapse or other adverse events (relative risk, 0.3; 95 percent confidence interval, 0.2 to 0.5; P<0.001). This finding was consistent in all three subgroups. Conclusions: Unlike the usual type of ALL, Ph-positive ALL is associated with a poor prognosis. Nevertheless, in some patients with favorable prognostic features, the disease can be controlled by intensive chemotherapy. Transplantation of bone marrow from an HLA-matched related donor is superior to other types of transplantation and to intensive chemotherapy alone in prolonging initial complete remissions. (N Engl J Med 2000;342:998-1006.) (C) 2000, Massachusetts Medical Society. C1 Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy. Univ Verona, Dept Publ Hlth, I-37100 Verona, Italy. Med Coll Wisconsin, Midw Childrens Canc Ctr, Dept Pediat, Milwaukee, WI 53226 USA. Med Hsch Hannover, Dept Pediat Hematol Oncol, Hannover, Germany. Inst Child Hlth, Leukemia Res Fund, London, England. Hop St Louis, Serv Pediat Hematol, Paris, France. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Univ So Calif, Los Angeles, CA USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Hamburg, Dept Pediat Hematol & Oncol, Hamburg, Germany. Beatrix Children Hosp, Dept Pediat Oncol, Groningen, Netherlands. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Tennessee, Coll Med, Memphis, TN USA. Univ Milan, Dept Pediat, Monza, Italy. Osped San Gerardo, Monza, Italy. RP Arico, M (reprint author), Policlin San Matteo, IRCCS, Pediat Clin, Dept Pediat, I-27100 Pavia, Italy. RI SESM, SESM/C-1440-2008; Schrappe, Martin/A-8109-2010 FU NCI NIH HHS [CA 36401, CA 51001, CA21765]; Telethon [E.0755] NR 42 TC 357 Z9 374 U1 0 U2 3 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 APR 6 PY 2000 VL 342 IS 14 BP 998 EP 1006 DI 10.1056/NEJM200004063421402 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 300JB UT WOS:000086248900002 PM 10749961 ER PT J AU Peabody, JW Luck, J Glassman, P Dresselhaus, TR Lee, M AF Peabody, JW Luck, J Glassman, P Dresselhaus, TR Lee, M TI Comparison of vignettes, standardized patients, and chart abstraction - A prospective validation study of 3 methods for measuring quality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CLINICAL DECISION-MAKING; SIMULATED PATIENTS; GENERAL-PRACTICE; PHYSICIAN JUDGMENTS; CONTROLLED TRIAL; CARE; PERFORMANCE; OUTCOMES; CONSULTATION; ASSOCIATION AB Context Better health care quality is a universal goal, yet measuring quality has proven to be difficult and problematic. A central problem has been isolating physician practices from other effects of the health care system, Objective To validate clinical vignettes as a method for measuring the competence of physicians and the quality of their actual practice. Design Prospective trial conducted in 1997 comparing 3 methods for measuring the quality of care for 4 common outpatient conditions: (1) structured reports by standardized patients (SPs), trained actors who presented unannounced to physicians' clinics (the gold standard); (2) abstraction of medical records for those same visits; and (3) physicians' responses to clinical vignettes that exactly corresponded to the SPs' presentations. Setting Outpatient primary care clinics at 2 Veterans Affairs medical centers. Participants Ninety-eight (97%) of 101 general internal medicine staff physicians, faculty, and second- and third-year residents consented to be randomized for the study. From this group, 10 physicians at each site were randomly selected for inclusion. Main Outcome Measures A total of 160 quality scores (8 cases x 20 physicians) were generated for each method using identical explicit criteria based on national guidelines and local expert panels, Scores were defined as the percentage of process criteria correctly met and were compared among the 3 methods. Results The quality of care, as measured by all 3 methods, ranged from 76.2% (SPs) to 71.0% (vignettes) to 65.6% (chart abstraction). Measuring quality using vignettes consistently produced scores closer to the gold standard of SP scores than using chart abstraction, This pattern was robust when the scores were disaggregated by the 4 conditions (P<.001 to <.05), by case complexity (P<.001), by site (P<.001), and by level of physician training (P values from <.001 to <.05). The pattern persisted, although less dominantly, when we assessed the component domains of the clinical encounter-history, physical examination, diagnosis, and treatment, Vignettes were responsive to expected directions of variation in quality between sites and levels of training. The vignette responses did not appear to be sensitive to physicians' having seen an SP presenting with the same case. Conclusions Our data indicate that quality of health care can be measured in an outpatient setting by using clinical vignettes. Vignettes appear to be a valid and comprehensive method that directly focuses on the process of care provided in actual clinical practice. Vignettes show promise as an inexpensive case-mix adjusted method for measuring the quality of care provided by a group of physicians. C1 Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Inst Global Hlth, San Francisco, CA 94105 USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Univ Calif San Diego, San Diego Vet Affairs Med Ctr, Sch Med, La Jolla, CA 92093 USA. RP Peabody, JW (reprint author), Univ Calif San Francisco, San Francisco Vet Affairs Med Ctr, Inst Global Hlth, Suite 508,74 New Montgomery St, San Francisco, CA 94105 USA. NR 61 TC 597 Z9 598 U1 3 U2 32 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 5 PY 2000 VL 283 IS 13 BP 1715 EP 1722 DI 10.1001/jama.283.13.1715 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 298BK UT WOS:000086119300032 PM 10755498 ER PT J AU Fihn, SD AF Fihn, SD TI The quest to quantify quality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 Vet Affairs Puget Sound Healthcare Syst, Seattle, WA 98108 USA. Univ Washington, Dept Med, Seattle, WA USA. RP Fihn, SD (reprint author), Vet Affairs Puget Sound Healthcare Syst, 1660 S Columbian Way,HSR&D 152, Seattle, WA 98108 USA. NR 21 TC 17 Z9 17 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 5 PY 2000 VL 283 IS 13 BP 1740 EP 1742 DI 10.1001/jama.283.13.1740 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 298BK UT WOS:000086119300036 PM 10755502 ER PT J AU Widlund, HR Vitolo, JM Thiriet, C Hayes, JJ AF Widlund, HR Vitolo, JM Thiriet, C Hayes, JJ TI DNA sequence-dependent contributions of core histone tails to nucleosome stability: Differential effects of acetylation and proteolytic tail removal SO BIOCHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR-BINDING; RIBOSOMAL-RNA GENE; POSITIONING SEQUENCES; CHROMATIN; RECONSTITUTION; MECHANISMS; OCTAMER; INVITRO; STABILIZATION; TETRAHYMENA AB Modulation of nucleosome stability in chromatin plays an important role in eukaryotic gene expression. The core histone N-terminal tail domains are believed to modulate the stability of wrapping nucleosomal DNA and the stability of the chromatin filament. We analyzed the contribution of the tail domains to the stability of nucleosomes containing selected DNA sequences that are intrinsically straight, curved, flexible, or inflexible. We find that the presence of the histone tail domains stabilizes nucleosomes containing DNA sequences that are intrinsically straight or curved. However, the tails do not significantly contribute to the free energy of nucleosome formation with flexible DNA. Interestingly, hyperacetylation of the core histone tail domains does not recapitulate the effect of tail removal by limited proteolysis with regard to nucleosome stability. We find that acetylation of the tails has the same minor effect on nucleosome stability for all the selected DNA sequences. A comparison of histone partitioning between long donor chromatin, acceptor DNA, and free histones in solution shows that the core histone tails mediate internucleosomal interactions within an H1-depleted chromatin fiber amounting to an average free energy of about 1 kcal/mol. Thus, such interactions would be significant with regard to the free energies of sequence-dependent nucleosome positioning. Last, we analyzed the contribution of the H2A/H2B dimers to nucleosome stability. We find that the intact nucleosome is stabilized by 900 cal/mol by the presence of the dimers regardless of sequence. The biological implications of these observations are discussed. C1 Univ Rochester, Med Ctr, Dept Biochem & Biophys, Rochester, NY 14642 USA. Chalmers Univ Technol, Lundberg Inst, Dept Biochem & Biophys, SE-41390 Gothenburg, Sweden. RP Widlund, HR (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM52426] NR 61 TC 44 Z9 45 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 4 PY 2000 VL 39 IS 13 BP 3835 EP 3841 DI 10.1021/bi991957l PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299JF UT WOS:000086194800036 PM 10736184 ER PT J AU Pahlavani, MA Vargas, DM Guo, ZM Richardson, A AF Pahlavani, MA Vargas, DM Guo, ZM Richardson, A TI Normal immune function in young and old DNA polymerase-beta deficient mice SO IMMUNOLOGY LETTERS LA English DT Article DE DNA polymerase-beta; DNA repair; knockout mice; immune function; aging ID BASE-EXCISION-REPAIR; DAMAGE; CELLS AB The effect of the DNA polymerase-beta (beta-pol) deficiency on mitogenic response and cytokine production was studied in spleen lymphocytes from 4-5- and 20-22-month-old beta-pol(-/+) mice and their age-matched wild-type littermates. The proliferative response of lymphocytes to Concanavalin A (Con A) and lipopolysaccharide (LPS) was measured by [H-3]thymidine incorporation. and the induction of cytokine production (interleukin (IL)-2, IL-4, and interferon necrosis factor (IFN)-gamma) was assessed by enzyme-linked immunosorbent assay. There was no significant difference in Con A- or LPS-induced proliferation or cytokine production in young beta-pol(-/+) mice compared with young wild-type littermates or in old beta-pol(-/+) mice compared with old wild-type littermates. However, mitogen-induced proliferation and cytokine production changed significantly with age. The proliferative response to Con A and to LPS, and the IL-2 production was significantly lower, and IL-4 and IFN-gamma levels were significantly higher in lymphocytes from old beta-pol(-/+) mice and old wild-type mice than in lymphocytes from young beta-pol(-/+) mice and young wild-type littermates. In addition, flow cytometric analysis showed no significant differences between young beta-pol(-/+) mice and young wild-type littermates or between old beta-pol(-/+) mice and old wild-type littermates in the proportion of B- and T-cell populations, and T-cell subsets. However, the number of lymphocytes expressing CD4(+) phenotype slightly decreased and the proportion of lymphocytes expressing CD44/Pgp-1 (memory) phenotype increased with age. Thus, we found no evidence for alteration in immune function in DNA polymerase-beta deficient mice, although they exhibit a decline in immunologic function with age. (C) 2000 Published by Elsevier Science S.A. All rights reserved. C1 Audie L Murphy Mem Vet Hosp, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. RP Pahlavani, MA (reprint author), Audie L Murphy Mem Vet Hosp, S Texas Vet Hlth Care Syst, 7400 Merton Minter Blvd, San Antonio, TX 78284 USA. FU NIA NIH HHS [AG00677, AG14088, P01-AG14674] NR 22 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD APR 3 PY 2000 VL 72 IS 1 BP 17 EP 21 DI 10.1016/S0165-2478(00)00159-0 PG 5 WC Immunology SC Immunology GA 304QP UT WOS:000086495200003 PM 10789676 ER PT J AU Gomez-Tortosa, E Newell, K Irizarry, MC Sanders, JL Hyman, BT AF Gomez-Tortosa, E Newell, K Irizarry, MC Sanders, JL Hyman, BT TI alpha-Synuclein immunoreactivity in dementia with Lewy bodies: morphological staging and comparison with ubiquitin immunostaining SO ACTA NEUROPATHOLOGICA LA English DT Article DE Lewy bodies; alpha-synuclein; ubiquitin; dementia; Parkinson's disease ID MULTIPLE SYSTEM ATROPHY; PARKINSONS-DISEASE; BODY DISEASE; NACP/ALPHA-SYNUCLEIN; NEUROFILAMENT; ACCUMULATION; AGGREGATION; CONSORTIUM; PROTEINS; MUTATION AB alpha-Synuclein is a presynaptic protein recently identified as a specific component of Lewy bodies (LB) and Lewy neurites. The aim of this study was to assess the morphology and distribution of alpha-synuclein immunoreactivity in cases of dementia with LB (DLB), and to compare alpha-synuclein with ubiquitin immunostaining. We examined substantia nigra, paralimbic regions (entorhinal cortex, cingulate gyrus, insula and hippocampus), and neocortex (frontal and occipital association cortices) with double alpha-synuclein and ubiquitin immunostaining in 25 cases meeting neuropathological criteria for DLB. alpha-Synuclein immunostaining was more specific than ubiquitin immunostaining in that it differentiated LB from globose tangles. It was also slightly more sensitive, staining 4-5% more intracytoplasmic structures, especially diffuse alpha-synuclein deposits that were ubiquitin negative. In addition to LB, alpha-synuclein staining showed filiform and globose neurites in the substantia nigra, CA2-3 regions of the hippocampus, and entorhinal cortex. A spectrum of alpha-synuclein staining was seen in substantia nigra: from diffuse "cloud-like" inclusions to aggregated intracytoplasmic inclusions with variable ubiquitin staining to classic LB. We hypothesize that these represent different stages in LB formation. C1 Massachusetts Gen Hosp East, Alzheimers Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. RP Hyman, BT (reprint author), Massachusetts Gen Hosp East, Alzheimers Res Unit, 149 13th St,Room 6405, Charlestown, MA 02129 USA. FU NIA NIH HHS [AGO8487, P5O-AGO5134] NR 29 TC 101 Z9 104 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD APR PY 2000 VL 99 IS 4 BP 352 EP 357 PG 6 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 304NF UT WOS:000086489800003 PM 10787032 ER PT J AU Podolsky, DK AF Podolsky, DK TI Review article: healing after inflammatory injury - coordination of a regulatory peptide network SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 8th Taisho International Symposium on Gastroenterology CY APR 16-17, 1999 CL SHIMODA, JAPAN ID GROWTH-FACTOR-BETA; EPITHELIAL-CELL PROLIFERATION; INTESTINAL TREFOIL FACTOR; SPASMOLYTIC POLYPEPTIDE; FACTOR RECEPTOR-3; BARRIER FUNCTION; PRIMARY CULTURE; MIGRATION; RESTITUTION; FAMILY AB Intestinal epithelial cells are capable of producing a variety of cytokines and other regulatory factors that can affect functional regulation of the epithelium itself, through autocrine and paracrine mechanisms, as well as functional integration with lamina propria populations. The bi-directional nature of this cytokine network is now apparent, with the demonstration that both rat and human intestinal epithelium-derived cell lines possess a much greater array of cytokine receptors than previously anticipated. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Study Inflammatory Bowel Dis,Dept Med, Boston, MA 02114 USA. RP Podolsky, DK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 32 Fruit St, Boston, MA 02114 USA. FU NIDDK NIH HHS [DK 41557, DK 46906, DK 53304] NR 54 TC 17 Z9 17 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD APR PY 2000 VL 14 SU 1 BP 87 EP 93 DI 10.1046/j.1365-2036.2000.014s1087.x PG 7 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 308NJ UT WOS:000086719200015 PM 10807409 ER PT J AU Rex, DK Johnson, DA Lieberman, DA Burt, RW Sonnenberg, A AF Rex, DK Johnson, DA Lieberman, DA Burt, RW Sonnenberg, A TI Colorectal cancer prevention 2000: Screening recommendations of the American College of Gastroenterology SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Review ID FECAL-OCCULT-BLOOD; CONTRAST BARIUM ENEMA; FLEXIBLE FIBEROPTIC SIGMOIDOSCOPY; AVERAGE-RISK PERSONS; ADENOMA FOLLOW-UP; ASYMPTOMATIC PATIENTS; FAMILY HISTORY; COLON-CANCER; COST-EFFECTIVENESS; TRANSPARENT CAP AB In conjunction with ACG Consumer Brochure: "ACG Recommendations on Colorectal Cancer Screening for Average and Higher Risk Patients in Clinical Practice". C1 Indiana Univ Hosp, Indianapolis, IN 46202 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Portland VA Med Ctr, Portland, OR USA. Univ Utah, Salt Lake City, UT USA. VA Med Ctr, Albuquerque, NM USA. RP Rex, DK (reprint author), Indiana Univ Hosp, Suite 2300,550 N Univ Blvd, Indianapolis, IN 46202 USA. NR 142 TC 408 Z9 417 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2000 VL 95 IS 4 BP 868 EP 877 DI 10.1111/j.1572-0241.2000.02059.x PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 301HU UT WOS:000086305400005 PM 10763931 ER PT J AU El-Zimaity, HMT Graham, DY Genta, RM Lechago, J AF El-Zimaity, HMT Graham, DY Genta, RM Lechago, J TI Sustained increase in gastric antral epithelial cell proliferation despite cure of Helicobacter pylori infection SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID ANTIGASTRIC AUTOANTIBODIES; NUCLEAR ANTIGEN; MUCOSA; ERADICATION; ANTIBODIES; MIMICRY; CANCER; CAGA AB OBJECTIVE: Studies of the effect of Helicobacter pylori treatment on gastric mucosa proliferation have yielded inconsistent results. We compared gastric mucosa cell proliferation posttherapy and in uninfected controls. METHODS: Biopsies were obtained from patients with H. pylori infection before treatment and at intervals for up to 33 months. Epithelial cell proliferation was determined using Ki-67 immunostaining. The labeling index (LI) is the proportion of positively labeled cells with respect to the total number of cells. The proliferative index was calculated by multiplying the labeling index (LI) and the proliferation zone PZ (PZ = length of the area between the uppermost and lowest labeled cells). RESULTS: The study included 27 patients with H. pylori gastritis and 35 controls. Epithelial cell proliferation (LI) was greater with H. pylori infection than without in both the antrum and corpus (65 +/- 5 vs 91 +/- 8 in the antrum and 44 +/- 3 vs 72 +/- 8 in the corpus, for uninfected controls vs H. pylori gastritis, respectively) (p = 0.0001). In the antrum there was no significant decrease in epithelial cell proliferation after cure of the H. pylori infection despite follow-up for >2 yr (labeling index = 83 +/- 10). In contrast, epithelial cell proliferation decreased in the corpus and became similar to that in controls after 7-13 months. CONCLUSIONS: Patients with H, pylori infection have sustained high epithelial cell proliferation in the antrum compared to that in uninfected subjects. A continued increase in proliferation in the antrum after cure of H. pylori infection suggests continuing damage. (C) 2000 by Am. Cell. of Gastroenterology. C1 Methodist Hosp, Vet Affairs Med Ctr, Dept Pathol, Houston, TX 77030 USA. Methodist Hosp, Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP El-Zimaity, HMT (reprint author), VA Med Ctr, Gastrointestinal Mucosa Pathol Lab, Dept Pathol, Rm 3A352,111-D,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 31 TC 9 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2000 VL 95 IS 4 BP 930 EP 935 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 301HU UT WOS:000086305400014 PM 10763940 ER PT J AU Tham, TCK Lichtenstein, DR Vandervoort, J Wong, RCK Slivka, A Banks, PA Yim, HB Carr-Locke, DL AF Tham, TCK Lichtenstein, DR Vandervoort, J Wong, RCK Slivka, A Banks, PA Yim, HB Carr-Locke, DL TI Pancreatic duct stents for "obstructive type" pain in pancreatic malignancy SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CANCER PAIN; CARCINOMA AB OBJECTIVE: Obstruction of the main pancreatic duct from malignancy with secondary ductal hypertension may be an important contributor to pain. The aim of our study was to determine the efficacy and safety of pancreatic stent placement for patients with "obstructive" pain due to pancreatic malignancy. METHODS: Pancreatic duct stents were placed in 10 consecutive patients with malignant pancreatic duct obstruction and abdominal pain. Seven patients had "obstructive" type pain and three had chronic unremitting pain. Nine had primary pancreatic ductal adenocarcinoma and one had metastatic melanoma. There were eight women and two men. Mean age was 61 yr (range, 47-80 yr). All patients had dominant main pancreatic duct strictures with proximal dilation. Tumors were unresectable. All patients took potent analgesics before endoscopic stent therapy. Polyethylene pancreatic stents, 5- and 7-French, were successfully placed in seven patients, and self-expanding metallic stents were successfully placed in three patients. RESULTS: There were no procedure-related complications. One patient required a single repeat examination to replace a migrated stent. Seven patients (75%) experienced a reduction in pain. Analgesia was no longer required in five (50%). Three patients who did not improve had chronic pain rather than "obstructive" pain. CONCLUSIONS: Pancreatic stent placement for patients with "obstructive" pain secondary to a malignant pancreatic duct stricture appears to be safe and effective. It should be considered as a therapeutic option in these patients. It does not seem to be effective for chronic unremitting pain. (C) 2000 by Am. Cell. of Gastroenterology. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Gastroenterol, Boston, MA USA. RP Tham, TCK (reprint author), Ulster Hosp, Belfast BT16 0RH, Antrim, North Ireland. NR 8 TC 33 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD APR PY 2000 VL 95 IS 4 BP 956 EP 960 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 301HU UT WOS:000086305400018 PM 10763944 ER PT J AU Goodfriend, TL AF Goodfriend, TL TI Angiotensin receptors: History and mysteries SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article; Proceedings Paper CT Symposium to Commemorate the 100th Anniversary of the Discovery of Renin CY APR 24, 1998 CL HELSINKI, FINLAND DE angiotensin; receptors; hypertension; cardiovascular diseases ID II TYPE-1 RECEPTOR; ESSENTIAL-HYPERTENSION; BLOOD-PRESSURE; RAT-BRAIN; EXPRESSION; ANTAGONISTS; MODULATION; ESTROGEN; MEDIATE; CLONING AB Angiotensin receptors became relatively easy to study when radioactive derivatives of the peptide were synthesized for radioimmunoassays. Binding assays in vitro led to the discovery of receptors in many tissues different from those involved in the classic actions of angiotensin. The physiologic significance of receptors in sites such as the gonads, other endocrine organs, peripheral blood cells, and many regions of the brain is still uncertain. Kinetics of the binding reaction are susceptible to intracellular guanine nucleotides, and extracellular cations, fatty acids, steroids, and eicosanoids. Synthesis of receptors is under equally complex control. Receptor binding assays simplified screening for angiotensin antagonists. Nonpeptide antagonists proved so specific they revealed the existence of receptor subtypes. The two principal subtypes are found in different tissues and trigger different postreceptor cascades. Studies of receptors, the genes that code for them, and the drugs that block them have led to a growing awareness of angiotensin's effects on the structure of the heart, vessels, and kidneys, some of which are pathologic. The existence of receptor subtypes, the different signal transduction cascades they stimulate, the widespread location of receptors, and the range of effects they mediate suggest that the angiotensins are of broad relevance in biology and pathology. This multidimensional matrix also indicates that receptor antagonists may have effects not yet described. (C) 2000 American Journal of Hypertension, Ltd. C1 William S Middleton Mem Vet Hosp, Med Res Serv, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI USA. Univ Wisconsin, Dept Pharmacol, Madison, WI 53706 USA. RP Goodfriend, TL (reprint author), William S Middleton Mem Vet Hosp, Med Res Serv, Room C-3127,2500 Overlook Terr, Madison, WI 53705 USA. NR 56 TC 15 Z9 15 U1 1 U2 2 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 APR PY 2000 VL 13 IS 4 BP 442 EP 449 DI 10.1016/S0895-7061(99)00212-5 PN 1 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 312QR UT WOS:000086954400021 PM 10821350 ER PT J AU Woodin, MA Liu, YC Neuberg, D Hauser, R Smith, TJ Christiani, DC AF Woodin, MA Liu, YC Neuberg, D Hauser, R Smith, TJ Christiani, DC TI Acute respiratory symptoms in workers exposed to vanadium-rich fuel-oil ash SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE vanadium; PM10; occupational epidemiology; occupational lung disease; boilermakers; industrial hygiene ID PULMONARY-FUNCTION; FIREFIGHTERS AB Background Occupational exposure to fuel-oil ash, with its high vanadium content, may cause respiratory illness. It is unclear, however, what early acute health effects may occur on the pathway from normal to compromised respiratory function. Methods Using a repeated measures design, we studied prospectively 18 boilermakers overhauling an oil-fired boiler and 11 utility worker controls. Subjects completed a respiratory symptom diary five times per day by using a 0-3 scale where 0 = symptom not present, 1 = mild symptom, 2 = moderate symptom, and 3 = severe symptom. Daily symptom severity was calculated by using the highest reported score each day for upper and lower respiratory symptoms. Daily symptom frequency was calculated by summing all upper or lower airway symptom reports, then dividing by number of reporting times. Respiratory symptom frequency and severity were analyzed for dose-response relationships with estimated vanadium and PM10 doses to the lung and upper airway by using robust regression. Results During the overhaul, 72% of boilermakers reported lower airway symptoms, and 67% reported upper airway symptoms. These percentages were 27 and 36 for controls. Boilermakers had more frequent and more severe upper and lower respiratory symptoms compared to utility workers, and this difference was greatest during interior boiler work. A statistically significant dose-response pattern for frequency and severity of both upper and lower respiratory symptoms was seen with vanadium and PM10 in the three lower exposure quartiles. However, there was a reversal in the dose-response trend in the highest exposure quartile, reflecting a possible healthy worker effect. Conclusions Boilermakers experience more frequent and more sever respiratory symptoms than utility workers. This is most statistically significant during boiler work and is associated with increasing dose estimates of lung and nasal vanadium and PM10. Am. J. Ind. Med. 37:353-363, 2000. (C) 2000 Wiley-Liss, Inc. 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, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med,Pulm & Crit Care Unit, Boston, MA 02114 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 [ES05947, ES07069, ES00002] NR 31 TC 34 Z9 36 U1 0 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD APR PY 2000 VL 37 IS 4 BP 353 EP 363 DI 10.1002/(SICI)1097-0274(200004)37:4<353::AID-AJIM5>3.0.CO;2-L PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 289NT UT WOS:000085629400005 PM 10706747 ER PT J AU Steinman, TI AF Steinman, TI TI Pain management in polycystic kidney disease SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Editorial Material ID RENAL-DISEASE C1 BIDMC, Dialysis Unit, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Steinman, TI (reprint author), BIDMC, Dialysis Unit, Boston, MA USA. NR 14 TC 6 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2000 VL 35 IS 4 BP 770 EP 772 DI 10.1016/S0272-6386(00)70029-1 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 299XL UT WOS:000086223700030 PM 10739803 ER PT J AU Muther, R Nissenson, AR Dickmeyer, J Steinman, T Mattern, W Parker, T Emmott, B AF Muther, R Nissenson, AR Dickmeyer, J Steinman, T Mattern, W Parker, T Emmott, B CA Medical Advisory Board of RMS TI Disease management (DM) improves vascular access (VA) in hemodialysis patients (HD PTS). SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. Renal Management DM, McGaw Pk, IL USA. Beth Israel Deac Med Ctr, Boston, MA USA. Univ N Carolina, Chapel Hill, NC USA. Kidney Associates, Kansas City, MO USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2000 VL 35 IS 4 MA 51 BP A21 EP A21 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 299XL UT WOS:000086223700085 ER PT J AU Nissenson, AR Parker, T Nielsen, J AF Nissenson, AR Parker, T Nielsen, J TI Disease management (DM) improves outcomes in ESRD patients. SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Beth Israel Deac Med Ctr, Boston, MA USA. RMS DM, McGaw Pk, IL USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD APR PY 2000 VL 35 IS 4 MA 53 BP A22 EP A22 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 299XL UT WOS:000086223700087 ER PT J AU Hashizume, H Baluk, P Morikawa, S McLean, JW Thurston, G Roberge, S Jain, RK McDonald, DM AF Hashizume, H Baluk, P Morikawa, S McLean, JW Thurston, G Roberge, S Jain, RK McDonald, DM TI Openings between defective endothelial cells explain tumor vessel leakiness SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID VASCULAR-PERMEABILITY FACTOR; BLOOD-VESSELS; GROWTH-FACTOR; MICROVASCULAR ARCHITECTURE; XENOTRANSPLANTED TUMORS; NEOPLASTIC TISSUES; SCANNING ELECTRON; TRANSGENIC MICE; FINE-STRUCTURE; ANGIOGENESIS AB Leakiness of blood vessels in tumors may contribute to disease progression and is key to certain forms of cancer therapy, but the structural basis of the leakiness is unclear. We sought to determine whether endothelial gaps or transcellular holes, similar to those found in leaky vessels in inflammation, could explain the leakiness of tumor vessels. Blood vessels in MCa-IV mouse mammary carcinomas, which are known to be unusually leaky (functional pore size 1.2-2 mu m), were compared to vessels in three less leaky tumors and normal mammary glands. Vessels were identified by their binding of intravascularly injected fluorescent cationic liposomes and Lycopersicon esculentum lectin and by CD31 (PECAM) immunoreactivity, The luminal surface of vessels in all four tumors had a defective endothelial monolayer as revealed by scanning electron microscopy, In MCa-IV tumors, 14% of the vessel surface was lined by poorly connected, overlapping cells. The most superficial lining cells, like endothelial cells, had CD31 immunoreactivity and fenestrae with diaphragms, but they had a branched phenotype with cytoplasmic projections as long as 50 mu m. Some branched cells were separated by intercellular openings (mean diameter 1.7 mu m; range, 0.3-4.7 mu m). Transcellular holes (mean diameter 0.6 mu m) were also present but mere only 8% as numerous as intercellular openings. Some CD31-positive cells protruded into the vessel lumen; others sprouted into perivascular tumor tissue. Tumors in RIP-Tag2 mice had, in addition, tumor cell-lined lakes of extravasated erythrocytes. We conclude that some tumor vessels have a defective cellular lining composed of disorganized, loosely connected, branched, overlapping or sprouting endothelial cells. Openings between these cells contribute to tumor vessel leakiness and may permit access of macromolecular therapeutic agents to tumor cells. C1 Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Edwin L Steele Lab, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP McDonald, DM (reprint author), Univ Calif San Francisco, Cardiovasc Res Inst, 513 Parnassus Ave, San Francisco, CA 94143 USA. FU NCI NIH HHS [R35-CA-56591]; NHLBI NIH HHS [P01 HL024136, HL-24136, HL-59157, R01 HL059157] NR 85 TC 833 Z9 857 U1 4 U2 66 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2000 VL 156 IS 4 BP 1363 EP 1380 DI 10.1016/S0002-9440(10)65006-7 PG 18 WC Pathology SC Pathology GA 303GJ UT WOS:000086413900028 PM 10751361 ER PT J AU Faccio, L Chen, A Fusco, C Martinotti, S Bonventre, JV Zervos, AS AF Faccio, L Chen, A Fusco, C Martinotti, S Bonventre, JV Zervos, AS TI Mxi2, a splice variant of p38 stress-activated kinase, is a distal nephron protein regulated with kidney ischemia SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE Mxi2 kinase; stress signaling; p38 kinase; distal tubule; Mxi2/p38 genomic locus ID TUBULE BRUSH-BORDER; MAP KINASE; C-JUN; SUBSTRATE-SPECIFICITY; CELLULAR STRESSES; MOLECULAR-CLONING; TERMINAL KINASES; PHOSPHORYLATION; CELLS; CYTOKINES AB Mxi2 is one of three known alternative spliced forms of the stress-activated mitogen-activated protein kinase p38 (CSBP). Mxi2 was originally identified as a Max-interacting protein and is the smallest member of the family of stress-activated kinases isolated to date. Mxi2 lacks most of the XI domain found in p38 and instead has a distinct COOH-terminal sequence of 17 amino acids. Here we present the genomic structure of the Mxi2/p38 locus on human chromosome 6q21.2/21.3 and establish the origin of the three spliced forms of p38. Using Mxi2-specific antibodies in mouse organs, we found the Mxi2 protein to be present exclusively in the kidney. Mxi2 is present predominantly in the distal tubule of the nephron and the level of the protein decreased during kidney ischemia-reperfusion. Stress signals or other known activators of the p38 pathway including MAP kinase-kinase 3 and MAP kinase-kinase 6 did not induce the kinase activity of Mxi2 using ATF-2 as a substrate. With the use of hybrid proteins encoding different portions of Mxi2 and p38 polypeptides, the different properties of Mxi2 can be assigned to its unique COOH terminus. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Med Serv, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Charlestown, MA 02129 USA. Univ Aquila, Dept Expt Med, I-67100 Laquila, Italy. RP Zervos, AS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [R01DK55734] NR 51 TC 16 Z9 18 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2000 VL 278 IS 4 BP C781 EP C790 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 301TG UT WOS:000086325900018 PM 10751326 ER PT J AU Stevens, AL Breton, S Gustafson, CE Bouley, R Nelson, RD Kohan, DE Brown, D AF Stevens, AL Breton, S Gustafson, CE Bouley, R Nelson, RD Kohan, DE Brown, D TI Aquaporin 2 is a vasopressin-independent, constitutive apical membrane protein in rat vas deferens SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE water channels; indirect immunofluorescence; cell polarity; endocytosis; male reproductive tract ID MALE REPRODUCTIVE-TRACT; KIDNEY COLLECTING DUCT; CHIP28 WATER CHANNEL; MICROTUBULE DISRUPTION; CAUDA-EPIDIDYMIDIS; PLASMA-MEMBRANE; N-GLYCOSYLATION; CELLS; TRAFFICKING; LOCALIZATION AB Aquaporin 2 (AQP2), the vasopressin-regulated water channel, was originally identified in renal collecting duct principal cells. However, our recent description of AQP2 in the vas deferens indicated that this water channel may have extrarenal functions, possibly related to sperm concentration in the male reproductive tract. In this study, we have examined the regulation and membrane insertion pathway of AQP2 in the vas deferens. The amino acid sequence of vas deferens AQP2 showed 100% identity to the renal protein. AQP2 was highly expressed in the distal portion (ampulla) of the vas deferens, but not in the proximal portion nearest the epididymis. It was concentrated on the apical plasma membrane of vas deferens principal cells, and very little was detected on intracellular vesicles. Protein expression levels and cellular localization patterns were similar in normal rats and vasopressin-deficient Brattleboro homozygous rats, and were not changed after 36 h of dehydration, or after 3 days of vasopressin infusion into Brattleboro rats. AQP2 was not found in apical endosomes (labeled with Texas Red-dextran) in vas deferens principal cells, indicating that it is not rapidly recycling in this tissue. Finally, vasopressin receptors were not detectable on vas deferens epithelial cell membranes using a [H-3]vasopressin binding assay. These data indicate that AQP2 is a constitutive apical membrane protein in the vas deferens, and that it is not vasopressin-regulated in this tissue. Thus AQP2 contains targeting information that can be interpreted in a cell-type-specific fashion in vivo. C1 Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02114 USA. Univ Utah, Hlth Sci Ctr, Div Nephrol, Salt Lake City, UT 84132 USA. RP Brown, D (reprint author), MGH East, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. FU NIDDK NIH HHS [DK38452, DK52043, K08DK02132] NR 56 TC 46 Z9 47 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD APR PY 2000 VL 278 IS 4 BP C791 EP C802 PG 12 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 301TG UT WOS:000086325900019 PM 10751327 ER PT J AU Pawlik, TM Lohmann, R Souba, WW Bode, BP AF Pawlik, TM Lohmann, R Souba, WW Bode, BP TI Hepatic glutamine transporter activation in burn injury: role of amino acids and phosphatidylinositol-3-kinase SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE liver; glucagon; cell volume; signal transduction ID PERFUSED-RAT-LIVER; THERMAL-INJURY; NITROGEN-METABOLISM; CELL-VOLUME; PRIMARY CULTURES; HEPATOCYTES; SYSTEM; MUSCLE; STIMULATION; RESPONSES AB Burn injury elicits a marked, sustained hypermetabolic state in patients characterized by accelerated hepatic amino acid metabolism and negative nitrogen balance. The transport of glutamine, a hey substrate in gluconeogenesis and ureagenesis, was examined in hepatocytes isolated from the livers of rats after a 20% total burn surface area full-thickness scald injury. A latent and profound two- to threefold increase in glutamine transporter system N activity was first observed after 48 h in hepatocytes from injured rats compared with controls, persisted for 9 days, and waned toward control values after 18 Bays, corresponding with convalescence. Further studies showed that the profound increase was fully attributable to rapid posttranslational transporter activation by amino acid-induced cell swelling and that this form of regulation may be elicited in part by glucagon. The phosphatidylinositol-3-kinase (PI3K) inhibitors wortmannin and LY-294002 each significantly attenuated transporter stimulation by amino acids. The data suggest that PI3K-dependent system N activation by amino acids may play an important role in fueling accelerated hepatic nitrogen metabolism after burn injury. C1 Massachusetts Gen Hosp, Dept Surg, Surg Oncol Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Bode, BP (reprint author), St Louis Univ, Dept Biol, 8507 Laclede Ave, St Louis, MO 63103 USA. FU NIGMS NIH HHS [5P50 GM-21700-23] NR 46 TC 8 Z9 9 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 APR PY 2000 VL 278 IS 4 BP G532 EP G541 PG 10 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 303ZL UT WOS:000086458000005 PM 10762606 ER PT J AU Greene, EL Houghton, O Collinsworth, G Garnovskaya, MN Nagai, T Sajjad, T Bheemanathini V Grewal, JS Paul, RV Raymond Jr AF Greene, EL Houghton, O Collinsworth, G Garnovskaya, MN Nagai, T Sajjad, T Bheemanathini, V Grewal, JS Paul, RV Raymond, JR TI 5-HT(2A) receptors stimulate mitogen-activated protein kinase via H(2)O(2) generation in rat renal mesangial cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE serotonin receptor; kidney; signal transduction; reactive oxygen species; NADP(H) oxidase ID ANGIOTENSIN-II; SIGNAL-TRANSDUCTION; OXIDASE ACTIVATION; HYDROGEN-PEROXIDE; ENDOTHELIAL-CELLS; NADPH OXIDASE; SEROTONIN; SUPEROXIDE; PATHWAY; INHIBITION AB Serotonin (5-HT) stimulates mitogenesis in rat renal mesangial cells through a G protein-coupled 5-HT(2A) receptor. We tested the hypothesis that oxidants might be involved in the signal transduction pathway Linking the receptor to extracellular signal-regulated protein kinase (ERK). 5-HT rapidly increased the activity and phosphorylation of ERK. These effects were blocked by the 5-HT(2A) receptor antagonist ketanserin. The peak effect was noted at 5-10 min, and half-maximal stimulation was achieved at 10-30 nM 5-HT. Chemical inhibitor and activator studies supported the involvement of phospholipase CI protein kinase C (PKC), and reactive oxygen species (ROS, i.e., H(2)O(2) and superoxide) generated by an NAD(P)H oxidase-like enzyme in the ERK activation cascade. Mapping studies supported a location for the NAD(P)H oxidase enzyme and the ROS downstream from PKC. Our studies are most consistent with an ERK activation pathway as follows: 5-HT(2A) receptor --> G protein --> phospholipase C --> diacylglycerol - classical PKC - NAD(P)H oxidase - superoxide --> superoxide dismutase -->, H(2)O(2) --> mitogen-activated extracellular signal-regulated kinase - ERK. These studies demonstrate a role for the 5-HT(2A) receptor in rapid, potent, and efficacious activation of ERK in rat renal mesangial cells. They support a role for oxidants in cont eying the stimulatory signal from 5-HT. because I) chemical antioxidants attenuate the 5-HT signal, 2) oxidants and 5-HT selectively activate ERK to a similar degree, 3) 5-HT produces superoxide and H(2)O(2) in these cells, and 4) a specific enzyme [NAD(P)H oxidase] has been implicated as the source of the ROS, which react selectively downstream of classical PKC. C1 Med Univ S Carolina, Dept Internal Med, Div Nephrol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Greene, EL (reprint author), Med Univ S Carolina, Dept Internal Med, Div Nephrol, Rm 829C CSB,171 Ashley Ave, Charleston, SC 29425 USA. EM greeneel@musc.edu FU NHLBI NIH HHS [HL-03710]; NIDDK NIH HHS [DK-52448] NR 43 TC 64 Z9 68 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2000 VL 278 IS 4 BP F650 EP F658 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 303ZJ UT WOS:000086457800017 PM 10751227 ER PT J AU Huang, MS Adebanjo, OA Awumey, E Biswas, G Koval, A Sodam, BR Sun, L Moonga, BS Epstein, J Goldstein, S Lai, FA Lipschitz, D Zaidi, M AF Huang, MS Adebanjo, OA Awumey, E Biswas, G Koval, A Sodam, BR Sun, L Moonga, BS Epstein, J Goldstein, S Lai, FA Lipschitz, D Zaidi, M TI IP(3), IP(3) receptor, and cellular senescence SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE inositol 1,4,5-trisphosphate; fibroblasts; cytosolic calcium; growth factors ID CALCIUM-BINDING PROTEIN; CYTOSOLIC-FREE CALCIUM; GROWTH-FACTOR BINDING; HUMAN-FIBROBLASTS; INOSITOL TRISPHOSPHATE; INTRACELLULAR CALCIUM; ALZHEIMER DONORS; BRADYKININ STIMULATION; REPLICATIVE SENESCENCE; SIGNAL-TRANSDUCTION AB Herein we demonstrate that replicative cellular senescence in vitro results in sharply reduced inositol 1,4,5-trisphosphate (IP(3)) receptor levels, reduced mitogen-evoked IP(3) formation and Ca(2+) release, and Ca(2+) store depletion. Human diploid fibroblasts (HDFs) underwent either 30 mean population doublings [mean population doublings (hTPDs) thymidine labeling index (TI) >92% ("young" or between 53 and 58 MPDs (TI < 28); "senescent")]. We found that the cytosolic Ca(2+) release triggered by either ionomycin or by several IP(3)-generating mitogens, namely bradykinin, thrombin, platelet-derived growth factor PDGF, and epidermal growth factor (EGF), was attenuated markedly in senescent HDFs. Notably, the triggered cytosolic Ca(2+) transients were of a smaller magnitude in senescent HDFs. However, the response latency seen with both PDGF and EGF was greater for senescent cells. Finally a smaller proportion of senescent HDFs showed oscillations. In parallel, IP(3) formation in response to bradykinin or EGF was also attenuated in senescent HDFs. Furthermore, senescent HDFs displayed a sharply diminished Ca(2+) release response to intracellularly applied IP(3) Finally to compare IP(3) receptor protein levels directly in young and senescent HDFs, their microsomal membranes were probed in Western blots with a highly specific anti-IP(3) receptor antiserum, Ab(40). A similar to 260-kDa band corresponding to the IP(3) receptor protein was noted; its intensity was reduced by similar to 50% in senescent cells. Thus, we suggest that reduced IP3 receptor expression, lowered IP(3) formation, and Ca(2+) release, as well as Ca(2+) store depletion, all contribute to the deficient Ca(2+) signaling seen in HDFs undergoing replicative senescence. C1 CUNY Mt Sinai Sch Med, Dept Med, Div Endocrinol, New York, NY 10029 USA. Vet Affairs Geriatr Res Educ & Clin Ctr, Little Rock, AR 72205 USA. Vet Affairs Med Ctr, Ctr Skeletal Aging, Philadelphia, PA 19104 USA. Coll Med, Sch Med, Dept Med, Philadelphia, PA 19104 USA. CUNY Mt Sinai Sch Med, Dept Geriatr, New York, NY 10029 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Bronx Vet Affairs Geriatr Res Educ & Clin Ctr, New York, NY 10029 USA. Univ Penn, Sch Vet, Biochem Labs, Philadelphia, PA 19104 USA. Univ Wales Coll Cardiff, Dept Med, Cardiff CF4 4XN, S Glam, Wales. RP Zaidi, M (reprint author), CUNY Mt Sinai Sch Med, Dept Med, Div Endocrinol, Annenberg 5,POB 1050,1 Gustave Levy Pl, New York, NY 10029 USA. FU NIA NIH HHS [R01-AG 14702] NR 34 TC 12 Z9 13 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2000 VL 278 IS 4 BP F576 EP F584 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 303ZJ UT WOS:000086457800008 PM 10751218 ER PT J AU Shayakul, C Smith, CP Mackenzie, HS Lee, WS Brown, D Hediger, MA AF Shayakul, C Smith, CP Mackenzie, HS Lee, WS Brown, D Hediger, MA TI Long-term regulation of urea transporter expression by vasopressin in Brattleboro rats SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE water restriction; urinary concentration; descending thin limb; inner medullary collecting duct ID MEDULLARY COLLECTING DUCT; WATER PERMEABILITY; KIDNEY; CLONING; OXYTOCIN; CHANNEL AB Regulation of urea concentration in the renal medullary interstitium is important for maintenance of hypertonicity and therefore the osmotic driving force for water reabsorption. Studies in Sprague-Dawley rats showed that restriction of water intake for 3 days results in upregulation of urea transporter (UT) mRNA in the inner stripe of outer medulla of the kidney (2.9-kb UT2) but not in the inner medulla (4.0-kb UT1). The present study was performed to investigate the role of vasopressin in long-term regulation of UT1 and UT2 in neurogenic diabetes insipidus (Brattleboro) rats treated with a 7-day continuous infusion of [,Arg(8)]-vasopressin (AVP)I [deamino-Cys(1), D-Arg(8)]-vasopressin (dDAVP) or vehicle. Northern analysis showed that water restriction alone had no effect on the level of UT2 mRNA in vehicle-treated Brattleboro rats but UT2 mRNA markedly Increased and UT1 mRNA modestly decreased after treatment with dDAVP. In situ hybridization further demonstrated that the UT2 signal is upregulated and spread along the descending thin limbs of loops of Henle and that UTI signal is downregulated in the inner medullary collecting ducts in vasopressin-treated rats, with a greater response for dDAVP compared with the AVP-treated group. Immunocyto-chemistry studies revealed that the UT1 and UT2 proteins are also modified in the same pattern as the transcript changes. Our studies reveal the role of vasopressin in longterm regulation of UT1 and UT2 expression during water restriction. C1 Harvard Univ, Sch Med, Inst Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Membrane Biol Program, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. RP Hediger, MA (reprint author), Harvard Univ, Sch Med, Inst Med, Rm 570,77 Ave Louis Pastuer, Boston, MA 02115 USA. EM mhediger@rics.bwh.harvard.edu RI chen, xuanlan/H-4158-2011 FU NIDDK NIH HHS [R01-DK 42956] NR 34 TC 32 Z9 33 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD APR PY 2000 VL 278 IS 4 BP F620 EP F627 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 303ZJ UT WOS:000086457800013 PM 10751223 ER PT J AU Ganzini, L Leong, GB Fenn, DS Silva, JA Weinstock, R AF Ganzini, L Leong, GB Fenn, DS Silva, JA Weinstock, R TI Evaluation of competence to consent to assisted suicide: Views of forensic psychiatrists SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID WASHINGTON-STATE; UNITED-STATES; EUTHANASIA; PHYSICIANS; ATTITUDES; OREGON AB Objective: Mental health evaluation of competence to consent has been proposed as an important safeguard for patients requesting assisted suicide, yet mental health professionals have not developed guidelines or standards to aid in such evaluations. The authors surveyed a national sample of forensic psychiatrists in the United States regarding the process, thresholds, and standards that should be used to determine competence to consent to assisted suicide. Method: An anonymous questionnaire was sent to board-certified forensic psychiatrists between August and October 1997. Results: Of the 456 forensic psychiatrists who were sent the questionnaire, 290 (64%) responded. Sixty-six percent believed that assisted suicide was ethical in at least some circumstances, and 63% thought that it should be legalized for some competent persons. Twenty-four percent indicated that it was unethical for psychiatrists to determine competence; however, 61% thought such an evaluation should be required in some or all cases. Seventy-eight percent recommended a very stringent standard of competence. Seventy-three percent believed that at least two independent examiners were needed to determine competence, and 44% favored requiring judicial review of a decision. Fifty-eight percent believed that the presence of major depressive disorder should result in an automatic finding of incompetence. Psychiatrists with ethical objections to assisted suicide advocated a higher threshold for competence and more extensive review of a decision. Conclusions: The ethical views of psychiatrists may influence their clinical opinions regarding patient competence to consent to assisted suicide. The extensive evaluation recommended by forensic psychiatrists would likely both minimize this bias and assure that only competent patients have access to assisted suicide, but the process might burden terminally ill patients. C1 Portland Vet Affairs Med Ctr, Mental Hlth Div P7 1DMH, Portland, OR 97207 USA. Oregon Hlth Sci Univ, Dept Psychiat, Ctr Eth Hlth Care, Portland, OR 97201 USA. Western State Hosp, Ctr Forens Serv, Tacoma, WA USA. Vet Affairs Outpatient Clin, San Jose, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. RP Ganzini, L (reprint author), Portland Vet Affairs Med Ctr, Mental Hlth Div P7 1DMH, POB 1034, Portland, OR 97207 USA. NR 14 TC 39 Z9 39 U1 2 U2 5 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 APR PY 2000 VL 157 IS 4 BP 595 EP 600 DI 10.1176/appi.ajp.157.4.595 PG 6 WC Psychiatry SC Psychiatry GA 300BE UT WOS:000086232300015 PM 10739419 ER PT J AU Sorensen, G Stoddard, AM Youngstrom, R Emmons, K Barbeau, E Khorasanizadeh, F Levenstein, C AF Sorensen, G Stoddard, AM Youngstrom, R Emmons, K Barbeau, E Khorasanizadeh, F Levenstein, C TI Local labor unions' positions on worksite tobacco control SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID SMOKING AB Objectives. This report describes local unions' positions on tobacco control initiatives and factors related to these positions., Methods. A national random-sample of local union leaders was surveyed by telephone. Results. Forty-eight percent of local unions supported worksite smoking bans or restrictions, and only 8% opposed both a ban and a restriction. Conclusions. Support for tobacco control initiatives among local unions was higher than might be expected on the basis of previous evidence. Engaging unions in smoking policy formation is likely to contribute to the larger public health goal of reducing smoking and exposure to secondhand smoke among workers. C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Dept Biostat & Epidemiol, Amherst, MA 01003 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Univ Lowell, Dept Work Environm, Lowell, MA 01854 USA. RP Sorensen, G (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 19 Z9 19 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 2000 VL 90 IS 4 BP 618 EP 620 DI 10.2105/AJPH.90.4.618 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 297WW UT WOS:000086106500018 PM 10754979 ER PT J AU Arozullah, AM Yarnold, PR Weinstein, RA Nwadiaro, N McIlraith, TB Chmiel, JS Sipler, AM Chan, CL Goetz, MB Schwartz, DN Bennett, CL AF Arozullah, AM Yarnold, PR Weinstein, RA Nwadiaro, N McIlraith, TB Chmiel, JS Sipler, AM Chan, CL Goetz, MB Schwartz, DN Bennett, CL TI A new preadmission staging system for predicting inpatient mortality from HIV-associated Pneumocystis carinii pneumonia in the early highly active antiretroviral therapy (HAART) era SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; IN-HOSPITAL MORTALITY; CLASSIFICATION TREE ANALYSIS; SERUM LACTATE-DEHYDROGENASE; AIDS PATIENTS; EXAMPLE; LONDON; CARE; PCP AB A common severe complication of human immunodeficiency virus (HIV) infection has been Pneumocystis carinii pneumonia (PCP). Recently, with increasing use of PCP prophylaxis and multidrug antiretroviral therapy, the clinical manifestations of HIV infection have changed dramatically and the predictors of inpatient mortality for PCP may have also changed. We developed a new staging system for predicting inpatient mortality for patients with HIV-associated PCP admitted between 1995 and 1997. Trained abstractors per formed chart reviews of 1,660 patients hospitalized with HIV-associated PCP between 1995 and 1997 at 78 hospitals in seven metropolitan areas in the United States. The overall inpatient mortality rate was 11.3%. Hierarchically optimal classification tree analysis identified an ordered five-category staging system based on three predictors: wasting, alveolar-arterial oxygen gradient (AaPo(2)), and serum albumin level. The mortality rate increased with stage: 3.7% for Stage 1, 8.5% for Stage 2, 16.1% for Stage 3, 23.3% for Stage 4, and 49.1% for Stage 5. This new staging system may be useful for severity of illness adjustment in the current era while exploring current variation in HIV-associated PCP inpatient mortality rates among hospitals and across cities. C1 VA Chicago Hlth Care Syst, Lakeside Div, Chicago, IL 60611 USA. Brockton W Roxbury Vet Affairs Med Ctr, W Roxbury, MA USA. Edward Hines Vet Adm Med Ctr, Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. Univ Illinois, Coll Med, Dept Med, Chicago, IL USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Prevent Med, Chicago, IL USA. Univ Illinois, Dept Psychol, Chicago, IL 60680 USA. Cook Cty Hosp, Chicago, IL 60612 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Bennett, CL (reprint author), VA Chicago Hlth Care Syst, Lakeside Div, 400 E Ontario St, Chicago, IL 60611 USA. RI Bennett, Charles/C-2050-2008; OI Goetz, Matthew/0000-0003-4542-992X FU NIDA NIH HHS [5R01DA10628-02] NR 23 TC 35 Z9 35 U1 0 U2 0 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 2000 VL 161 IS 4 BP 1081 EP 1086 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 306AF UT WOS:000086573400005 PM 10764294 ER PT J AU Littner, MR Ilowite, JS Tashkin, DP Friedman, M Serby, CW Menjoge, SS Witek, TJ AF Littner, MR Ilowite, JS Tashkin, DP Friedman, M Serby, CW Menjoge, SS Witek, TJ TI Long-acting bronchodilation with once-daily dosing of tiotropium (Spiriva) in stable chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID ANTIMUSCARINIC BRONCHODILATOR; COPD; MANAGEMENT; BA-679-BR; BROMIDE AB Tiotropium (Spiriva; Ba679BR) is a new-generation, long-acting anticholinergic bronchodilator that has muscarinic M-1 and M-3 receptor subtype selectivity. A multicenter, randomized, double-blind, parallel group, placebo-controlled study was conducted to evaluate the dose-response characteristics of tiotropium inhalation powder given once daily to stable patients with chronic obstructive pulmonary disease (COPD). Patients (mean FEV1 = 1.08 L [42% predicted]) were randomized to receive 0, 4.5, 9, 18, or 36 mu g tiotropium once daily at noon for 4 wk, with spirometry done before and hourly for 6 h after dosing. Patients measured and recorded their peak expiratory flow rates (PEFRs) three times each day. Significant dose-related improvement in FEV1 and significant improvement in FVC occurred within 1 h after the first dose of tiotropium as compared with placebo. Over the 29 d of the study, all doses of tiotropium produced significant increases over placebo in trough (i.e, as measured spirometrically at 20 to 24 h after the previous dose and just before the next dose of tiotropium), peak, and 6-h postdose average FEV1 and FVC, and in PEFR, without a significant difference among the different doses investigated. PEFR gradually returned to pretreatment baseline levels over a 3-wk evaluation period following the discontinuation of tiotropium. The overall safety profile far the tiotropium doses was, similar to that for placebo. In summary, tiotropium was shown to be safe and effective in doses ranging from 4.5 to 36 mu g delivered once daily. The improvements in spirometry with once-daily dosing confirm the long duration of action of tiotropium reported in single-dose studies, and its sustained improvement of spirometric measures over the 1 mo of testing in the study points to utility of tiotropium as a maintenance bronchodilator for patients with COPD. On the basis of the comparable bronchodilator response at doses from 9 to 36 mu g, and advantages suggested by the safely profile at doses below 36 mu g In this study, a dose of 18 mu g once daily was selected for use in long-term studies of the safety and efficacy of tiotropium. C1 Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care & Nursing Home, Sepulveda, CA USA. Univ Calif Los Angeles, Sch Med, Div Pulm, Los Angeles, CA USA. Winthrop Univ Hosp, Div Pulm, Mineola, NY 11501 USA. Tulane Univ, Med Ctr, Sect Pulm Dis Crit Care & Environm Med, New Orleans, LA USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. RP Littner, MR (reprint author), Vet Adm Med Ctr, 111P,16111 Plummer St, Sepulveda, CA 91343 USA. NR 18 TC 146 Z9 159 U1 0 U2 4 PU AMER LUNG ASSOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD APR PY 2000 VL 161 IS 4 BP 1136 EP 1142 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 306AF UT WOS:000086573400013 PM 10764302 ER PT J AU Forman, HP Kamin, DS Covey, AM Sunshine, JH AF Forman, HP Kamin, DS Covey, AM Sunshine, JH TI Changes in the market for diagnostic radiologists as measured through a help wanted index SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ONCOLOGY TRAINING-PROGRAMS; PHYSICIAN WORKFORCE; EMPLOYMENT EXPERIENCE; MANAGED CARE AB OBJECTIVE. We sought to create and validate a help wanted index for tracking changes in the radiology job market. SUBJECTS AND METHODS. All jobs advertised in Radiology and the American Journal of Roentgenology from January 1991 through December 1998 were tracked according to three separate parameters: academic versus private practice, subspecialty, and region. Statistical comparison was made between the first and second 48-month subperiods to identify changes. RESULTS. Thirteen thousand seven hundred one advertised positions were coded. A dramatic decrease in job advertisements was noted after December 1991, with advertisements falling to one eighth of their late 1991 peak. A recovery has occurred, with advertising now approaching peak levels. Shifts were seen toward more private practice, midwestern location, vascular and interventional, and mammography positions. Declines occurred in the share of positions in California, the Southwest, and several radiology subspecialties. Other trends were noted but were statistically less significant. A strong correlation (R = 0.98) was found between the annual number of positions advertised and radiologists' median incomes relative to those of all physicians. CONCLUSION. The job market in radiology, much as in other fields, can be tracked in a coincident manner with the use of a help wanted index. Changes in the makeup of radiology practice are important and are identified in a well-constructed index. These findings have validity and can be useful as an adjunct to other information for policy and planning purposes. C1 Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02115 USA. Amer Coll Radiol, Dept Res, Reston, VA 20191 USA. RP Forman, HP (reprint author), Yale Univ, Sch Med, Dept Diagnost Radiol, 333 Cedar St,SP2-332, New Haven, CT 06520 USA. NR 33 TC 21 Z9 21 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2000 VL 174 IS 4 BP 933 EP 938 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296HN UT WOS:000086019100006 PM 10749225 ER PT J AU Boland, GWL Slater, G Lu, DSK Eisenberg, P Lee, MJ Mueller, PR AF Boland, GWL Slater, G Lu, DSK Eisenberg, P Lee, MJ Mueller, PR TI Prevalence and significance of gallbladder abnormalities seen on sonography in intensive care unit patients SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID CRITICALLY ILL PATIENTS; PERCUTANEOUS CHOLECYSTOSTOMY; ACUTE CHOLECYSTITIS; DIAGNOSIS AB OBJECTIVE. We evaluated sonographic abnormalities of the gallbladder other than acalculous cholecystitis across a broad range of intensive care unit (ICU) patients. SUBJECTS AND METHODS. Fifty-five consecutive patients (age range, 18-94 years old; mean age, 56 years; 33 men, 22 women), who were admitted to the ICU with a variety of diagnoses, underwent sonography of the gallbladder twice a week. Patients with gallbladder calculi were excluded from the study. The gallbladder was examined for the recognized sonographic features of acalculous cholecystitis: gallbladder wall thickening, gallbladder distention, intramural gallbladder lucencies (striated gallbladder wall), pericholecystic fluid, gallbladder sludge, and Murphy's sign. These findings were correlated with clinical and laboratory parameters that are associated with acalculous cholecystitis: fever, WBC, liver function rests, levels of serum bilirubin, mechanical ventilation status, and administration of parenteral nutrition, narcotic analgesics, antibiotics, and presser agents. RESULTS. Eleven of the 55 patients were found to have gallbladder calculi and were excluded from the study. Thirty-seven (84%) of the remaining 44 patients had at least one sonographic abnormality while in the ICU. Twenty-five (57%) of the 44 patients had as many as three abnormalities found on sonography, and six (14%) of 44 patients had four or five sonographic findings of gallbladder abnormalities while in the ICU. No statistically significant correlation was found among any of these sonographic abnormalities and the clinical and laboratory parameters. CONCLUSION. Gallbladder abnormalities are frequently seen on sonography in ICU patients. even if these patients are not suspected of having acalculous cholecystitis; therefore, sonography appears to be of limited value in diagnosing acalculous cholecystitis in ICU patients. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. NR 12 TC 38 Z9 39 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2000 VL 174 IS 4 BP 973 EP 977 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296HN UT WOS:000086019100013 PM 10749232 ER PT J AU Sahani, D Saini, S Fatuga, GA Halpern, EF Lanser, ME Zimmerman, JB Fischman, AJ AF Sahani, D Saini, S Fatuga, GA Halpern, EF Lanser, ME Zimmerman, JB Fischman, AJ TI Quantitative measurements of medical images for pharmaceutical clinical trials: Comparison between on-site and off-site assessments SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PET IMAGING PROBE; DOPAMINE TRANSPORTER; PRIMATE BRAIN; SPECT; ALTROPANE; BINDING; NEURONS; MONKEYS AB OBJECTIVE, In pharmaceutical clinical trials, quantitative measurements on medical images are often conducted to confirm drug efficacy. This study aims to compare the quantitative image analysis performance of an off-site core laboratory with the performance of investigators from multiple clinical sites. MATERIALS AND METHODS, In a phase I clinical trial, 25 healthy subjects underwent dynamic brain single-photon emission computed tomography (SPECT) scintigraphy with I-123-Altropane, a cocaine analogue with high affinity and selectivity for dopamine transporter sites in the striatum, In 20 patients examined on-site and off-site, a total of 80 measurements were made to calculate the drug's binding potential. A trained technologist off-site at a central core laboratory and on-site investigators at different clinical sites performed the image analysis. These results were compared with measurements made by a subspecialty radiologist whose assessments were the reference standard. Statistical analysis was performed using multiple regression analysis. RESULTS. Measurements from the central core laboratory (off-site) highly correlated (r = 0.95) with measurements of the reference standard. Measurements from the clinical sites (on-site) grouped together had lower correlation (r = 0.84) with the reference standard. This difference was statistically significant (p < 0.05), CONCLUSION. Training and experience in the specific type of image analysis are critical in obtaining consistent data. Quantitative analysis by dedicated personnel at a core laboratory provides highly reproducible results. The findings support off-site assessment of medical images in pharmaceutical clinical trials. C1 Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. World Care Inc, Cambridge Ctr 1, Cambridge, MA 02142 USA. Boston Life Sci Inc, Boston, MA 02116 USA. RP Saini, S (reprint author), Harvard Univ, Sch Med, Dept Radiol, 32 Fruit St, Boston, MA 02114 USA. NR 13 TC 6 Z9 6 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2000 VL 174 IS 4 BP 1159 EP 1162 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 296HN UT WOS:000086019100050 PM 10749269 ER PT J AU Cubilla, AL Velazques, EF Reuter, VE Oliva, E Mihm, MC Young, RH AF Cubilla, AL Velazques, EF Reuter, VE Oliva, E Mihm, MC Young, RH TI Warty (condylomatous) squamous cell carcinoma of the penis - A report of 11 cases and proposed classification of 'verruciform' penile tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE penis; warty carcinoma; condyloma acuminatum ID HUMAN PAPILLOMAVIRUS; VERRUCOUS CARCINOMA AB Within the spectrum of penile squamous cell carcinomas, those that we descriptively refer to collectively as the "verruciform" lesions are particularly difficult to subclassify, In a review of 50 such tumors, we found 11 distinctive neoplasms with condylomatous features conforming to the appearance of so-called "warty (condylomatous) carcinoma." The average patient age was 55 years and the average duration of disease was 19 months. The primary tumor involved multiple anatomic sites (glans, coronal sulcus, and foreskin) in seven cases and a single site (glans or foreskin) in four cases. Grossly, white to gray cauliflower-like tumors typically measuring approximately 5 cm were noted. Histologically the tumors were mainly papillomatous with acanthosis and hyperkeratosis. The papillae had prominent fibrovascular cores. The most conspicuous microscopic findings were striking nuclear atypia of koilocytotic type and clear cytoplasm. The interface between tumor and stroma was irregular in the majority of cases; deep invasion df corpus cavernosum was noted in five cases. The differential diagnosis included verrucous carcinoma, low-grade papillary squamous cell carcinoma, not otherwise specified, and giant condyloma acuminatum. Among other differences, the first two lesions show no koilocytotic changes and the last lacks malignant features and irregular stromal invasion. Metastatic spread occurred in two patients; both are alive with evidence of recurrent disease 12 and 72 months after initial diagnosis. A third patient was alive with recurrent disease 12 months after diagnosis. Five patients were free of disease 8, 12, 24, 52, and 108 months after diagnosis. Three patients were lost to follow up. Warty (condylomatous) carcinomas of the penis are morphologically distinctive verruciform neoplasms with features of human papillomavirus-related lesions and should be distinguished from other verruciform tumors so that differences in behavior, if any, between these tumors will become established. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. Inst Patol & Investigac, Asuncion, Paraguay. Fac Ciencias Med, Asuncion, Paraguay. NYU, Dept Pathol, New York, NY 10016 USA. Cornell Univ, Coll Med, Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. RP Young, RH (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. NR 33 TC 78 Z9 80 U1 0 U2 1 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 APR PY 2000 VL 24 IS 4 BP 505 EP 512 DI 10.1097/00000478-200004000-00004 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 299RM UT WOS:000086211700004 PM 10757397 ER PT J AU Yantiss, RK Clement, PB Young, RH AF Yantiss, RK Clement, PB Young, RH TI Neoplastic and pre-neoplastic changes in gastrointestinal endometriosis - A study of 17 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE gastrointestinal tract; endometriosis; neoplasms; premalignant changes ID EXTRAOVARIAN ENDOMETRIOSIS; CELL-CARCINOMA; STROMAL TUMORS; LARGE-BOWEL; COLON; PERFORATION; APPENDIX AB The clinicopathologic features of neoplasms arising in gastrointestinal endometriosis have not been well characterized. In this series, we report 17 cases of gastrointestinal endometriosis complicated by neoplasms (14 cases) or precancerous changes (three cases). Four patients, one of whom also had hypermenorrhea, presented with chronic abdominal pain and five had obstructive symptoms; one of these also had rectal bleeding. One patient presented with an acute abdomen and fecal peritonitis, one had vaginal bleeding, and one had a progressive change in bowel habits. Nine patients had a long history of endometriosis, II patients had had hysterectomies, and eight of these had also received unopposed estrogen therapy. The lesions involved the rectum (6), sigmoid (6), colon, unspecified (2), and small intestine (3), and comprised 8 endometrioid adenocarcinomas (EA), 4 mullerian adenosarcomas (MAS), 1 endometrioid stromal sarcoma (ESS), 1 endometrioid adenofibroma of borderline malignancy (EBA) with carcinoma in situ, 2 atypical hyperplasias (AH), and one endometrioid adenocarcinoma in situ (ACIS). The tumors ranged in size from 2 to 15 cm and all involved the serosa and muscularis propria. Two tumors extended into the mucosa, with mucosal ulceration in one. Follow-up was available in 11 cases. One patient with EA was dead of disease at 1 year, one had two recurrences at 1 and 2 years, and three were alive with no evidence of disease (ANED) at 9 months to 13 years (mean, 68 mos). The patient with the EBA was ANED at 3 months. Two patients with MAS were ANED at 2 and 3 years. The patient with ESS had a recurrence at 3 years and was ANED 6 years after her original diagnosis. One woman with AH was ANED at 60 months and the patient with ACIS was ANED at 16 months. One of the carcinomas was originally misdiagnosed as a primary intestinal adenocarcinoma. The pathologist should be aware of the possibility of a tumor of genital tract type when evaluating intestinal neoplasms in females, particularly if they have a history of endometriosis and have received unopposed estrogen therapy. C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ British Columbia, Dept Pathol, Vancouver, BC, Canada. Vancouver Gen Hosp, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Young, RH (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 45 TC 94 Z9 101 U1 0 U2 1 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 APR PY 2000 VL 24 IS 4 BP 513 EP 524 DI 10.1097/00000478-200004000-00005 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 299RM UT WOS:000086211700005 PM 10757398 ER PT J AU Ulbright, TM Srigley, JR Reuter, VE Wojno, K Roth, LM Young, RH AF Ulbright, TM Srigley, JR Reuter, VE Wojno, K Roth, LM Young, RH TI Sex cord-stromal tumors of the testis with entrapped germ cells - A lesion mimicking unclassified mixed germ cell sex cord-stromal tumors SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 88th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 20-26, 1999 CL SAN FRANCISCO, CALIFORNIA SP US & Canadian Acad Pathol DE sex cord-stromal tumor; mixed germ cell sex cord-stromal tumor; entrapped germ cells; testicular neoplasms ID PLACENTAL ALKALINE-PHOSPHATASE; GONADOBLASTOMA; NEOPLASMS; PLOIDY; OVARY; EXPRESSION AB The authors describe 10 sex cord-stromal tumors of the testis that incorporated germ cells, thereby mimicking the unclassified type of mixed germ cell sex cord-stromal tumor (MGCSCST). These neoplasms occurred in patients from 3 to 48 years old (mean age, 26 years) who presented with testicular masses. On microscopic examination, nine tumors had a combination of tubular and cord-like arrangements of sex cord cells with transition to spindle-shaped tumor cells. They were diagnosed as either unclassified sex cord-stromal tumors (n = 5) or Sertoli-stromal cell tumors (n = 4). One tumor was a pure Sertoli cell tumor. The admired germ cells were usually at the periphery and in clusters, but occasionally were in the center or more diffuse. In nine patients the germ cells resembled spermatogonia, having round nuclei with uniform, dusty chromatin and inconspicuous or small nucleoli, None of these cells stained with a variety of markers used for neoplastic germ cells, and in one case in which the non-neoplastic Sertoli cells were strongly reactive for inhibin but the neoplastic Sertoli cells were not, all the germ cells within the tumor occurred adjacent to inhibin-positive Sertoli cells. With static cytophotometry, a diploid deoxyribonucleic acid content was found in these germ cells in the two investigated cases. In one case the germ cells had the morphologic appearance of seminoma cells and they stained positively for the markers of neoplastic germ cells. This case was interpreted as a "collision" tumor between a Sertoli cell tumor and a seminoma. The authors conclude that sex cord-stromal tumors with entrapped germ cells of the testis are more common than unclassified MGCSCSTs-a bona fide testicular example of which has not been seen by any of the authors. C1 Indiana Univ, Med Ctr, Dept Pathol & Lab Med, Indianapolis, IN USA. Credit Valley Hosp, Dept Lab Med, Mississauga, ON, Canada. McMaster Univ, Hamilton, ON, Canada. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. St John Hosp, Dept Pathol, Detroit, MI USA. Med Ctr, Dept Pathol, Detroit, MI USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Ulbright, TM (reprint author), Indiana Univ Hosp, Dept Pathol, Room 3465,550 N Univ Blvd, Indianapolis, IN 46202 USA. NR 23 TC 28 Z9 28 U1 1 U2 3 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 APR PY 2000 VL 24 IS 4 BP 535 EP 542 DI 10.1097/00000478-200004000-00007 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 299RM UT WOS:000086211700007 PM 10757400 ER PT J AU Fitzgerald, DW Behets, F Caliendo, A Roberfroid, D Lucet, C Fitzgerald, JW Kuykens, L AF Fitzgerald, DW Behets, F Caliendo, A Roberfroid, D Lucet, C Fitzgerald, JW Kuykens, L TI Economic hardship and sexually transmitted diseases in Haiti's rural Artibonite Valley SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID CHLAMYDIA-TRACHOMATIS INFECTION; NEISSERIA-GONORRHOEAE; HEALTH; WOMEN; MORTALITY; SURVEILLANCE; CERVICITIS; REDUCTION; AIDS AB A study was conducted to determine the prevalence rate and risk factors for sexually transmitted diseases (STDs) in Haiti's rural Artibonite Valley. Women attending antenatal services at Hospital Albert Schweitzer from October to December 1996 were tested for gonorrhea, chlamydia, trichomonas, syphilis, and human immunodeficiency virus (HIV). Of the 476 women tested, 121 (25.4%) had trichomonas, 11/475 (2.3%) had gonorrhea, 51/475 (10.7%) had chlamydia, 32/474 (6.8%) were seropositive for syphilis, 20/469 (4.3%) were seropositive for HIV, and 191 (40.1%) had at least one STD. Nearly 30% of the women reported having entered a sexual relationship out of economic necessity and had increased odds of HIV infection, Odds Ratio (OR) 6.3 (P < 0.001). We postulate that due to recent economic hardship in rural Haiti, women are entering into sexual relationships out of economic necessity and that this trend is contributing to the growing HIV epidemic. We recommend STD prevention and development programs that target young people and economically disadvantaged women. C1 Hosp Albert Schweitzer, Deschapelles, Haiti. Cornell Univ, Coll Med, Div Int Med & Infect Dis, New York, NY USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02124 USA. RP Fitzgerald, DW (reprint author), Lynx Air, POB 407139, Ft Lauderdale, FL 33340 USA. FU FIC NIH HHS [TW00002] NR 41 TC 23 Z9 24 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD APR PY 2000 VL 62 IS 4 BP 496 EP 501 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 401TX UT WOS:000166945300013 PM 11220766 ER PT J AU Muth, CM Shank, ES Larsen, B AF Muth, CM Shank, ES Larsen, B TI Severe diving accidents: pathophysiology, symptomatology therapy SO ANAESTHESIST LA German DT Article DE diving accident; decompression illness; decompression sickness; arterial gas embolism; hyperbaric oxygen therapy ID ARTERIAL GAS EMBOLISM; AIR-EMBOLISM; DECOMPRESSION-SICKNESS; VASCULAR-PERMEABILITY; PULMONARY BAROTRAUMA; BLOOD-FLOW; ILLNESS; BUBBLES; OXYGEN; ACTIVATION AB Decompression injuries are potentially life-threatening incidents, generated by a rapid decline in ambient pressure. Although typically seen in divers,they may be observed in compressed air workers and others exposed to hyperbaric environments. Decompression illness (DCl) results from liberation of gas bubbles in the blood and tissues. DCl may be classified as decompression sickness (DCS) or arterial gas embolism (AGE), depending on where the gas bubbles lodge. DCS occurs after longer exposures to a hyperbaric environment with correspondingly larger up-take of inert gas. DCS may be classified into type 1 with cutaneous symptoms and musculoskeletal pain only or type 2 with neurologic and/or pulmonary symptoms as well. AGE usually results from a pulmonary barotrauma, and with cerebral arterial involvement, the symptoms are similar to a stroke. The most important therapy, in the field, is oxygen resuscitation with the highest possible concentration and volume delivered. The definitive treatment is rapid recompression with hyperbaric oxygen therapy. Additional therapeutic measures are discussed. C1 Univ Saarlandes Kliniken, Druckkammerzentrum Homburg Gelande, D-66424 Homburg, Germany. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Div Hyperbar Med, Boston, MA 02114 USA. Univ Saarlandes Kliniken, Klin Anaesthesiol & Intens Med, D-66424 Homburg, Germany. RP Muth, CM (reprint author), Univ Saarlandes Kliniken, Druckkammerzentrum Homburg Gelande, Gebaude 10, D-66424 Homburg, Germany. NR 51 TC 25 Z9 25 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0003-2417 J9 ANAESTHESIST JI Anaesthesist PD APR PY 2000 VL 49 IS 4 BP 302 EP 316 DI 10.1007/s001010050832 PG 15 WC Anesthesiology SC Anesthesiology GA 314RX UT WOS:000087072300008 PM 10840540 ER PT J AU Talke, P Chen, R Thomas, B Aggarwall, A Gottlieb, A Thorborg, P Heard, S Cheung, A Son, SL Kallio, A AF Talke, P Chen, R Thomas, B Aggarwall, A Gottlieb, A Thorborg, P Heard, S Cheung, A Son, SL Kallio, A TI The hemodynamic and adrenergic effects of perioperative dexmedetomidine infusion after vascular surgery SO ANESTHESIA AND ANALGESIA LA English DT Article ID SELECTIVE ALPHA-2-ADRENOCEPTOR AGONIST; ADMINISTERED DEXMEDETOMIDINE; INTRAVENOUS DEXMEDETOMIDINE; ISOFLURANE REQUIREMENTS; ABDOMINAL HYSTERECTOMY; BYPASS-SURGERY; CLONIDINE; ANESTHESIA; MEDETOMIDINE; HUMANS AB We tested dexmedetomidine, an alpha(2) agonist that decreases heart rate, brood pressure, and plasma norepinephrine concentration, for its ability to attenuate stress responses during emergence from anesthesia after major vascular operations. Patients scheduled for vascular surgery received either dexmedetomidine (n = 22) or placebo (n = 19) IV beginning 20 min before the induction of anesthesia and continuing until 48 h after the end of surgery. All patients received standardized anesthesia. Heart rate and arterial blood pressure were kept within predetermined limits by varying anesthetic level and using vasoactive medications. Heart rate, arterial blood pressure, and inhaled anesthetic concentration were monitored continuously; additional measurements included plasma and urine catecholamines. During emergence from anesthesia, heart rate was slower with dexmedetomidine (73 +/- 11 bpm) than placebo (83 +/- 20 bpm) (P = 0.006), and the percentage of time the heart rate was within the predetermined hemodynamic limits was more frequent with dexmedetomidine (P < 0.05). Plasma norepinephrine levels increased only in the placebo group and were significantly lower for the dexmedetomidine group during the immediate postoperative period (P = 0.0002). We conclude that dexmedetomidine attenuates increases in heart rate and plasma norepinephrine concentrations during emergence hum anesthesia. Implications: The alpha(2) agonist, dexmedetomidine, attenuates increases in heart rate and plasma norepinephrine concentrations during emergence from anesthesia in vascular surgery patients. C1 Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90073 USA. Piedmont Anesthesia Associates, Atlanta, GA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Univ Massachusetts, Med Ctr, Worcester, MA USA. Univ Penn, Philadelphia, PA 19104 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Talke, P (reprint author), Univ Calif San Francisco, Dept Anesthesia, San Francisco, CA 94143 USA. NR 15 TC 120 Z9 172 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2000 VL 90 IS 4 BP 834 EP 839 PG 6 WC Anesthesiology SC Anesthesiology GA 299GZ UT WOS:000086191800011 PM 10735784 ER PT J AU Wallace, AW Tom, WL AF Wallace, AW Tom, WL TI Interaction of L-arginine and phosphodiesterase inhibitors in vasodilation of the porcine internal mammary artery SO ANESTHESIA AND ANALGESIA LA English DT Article ID MYOCARDIAL-ISCHEMIA; ENDOTHELIAL DYSFUNCTION; CORONARY-ARTERIES; NITRIC-OXIDE; RABBIT AORTA; IN-VITRO; RELAXATION; NITROGLYCERIN; REPERFUSION; RESISTANCE AB We tested the hypothesis that L-arginine (the substrate for nitric oxide production)-combined with amrinone, milrinone (Type III phosphodiesterase [PDE] inhibitors), zaprinast, or sildenafil (Type V PDE inhibitors)-would vasodilate synergistically. Internal mammary artery segments were excised from anesthetized swine, divided into rings, and suspended in a tissue bath at 37 degrees C. Force of contraction was measured during dose-response testing of combinations of L-arginine and amrinone, milrinone, zaprinast, or sildenafil. Amrinone and milrinone were additive to L-arginine. N-G-methyl-L-arginine (L-NMA) inhibited the effects of milrinone but not amrinone. The effective concentration of amrinone eliciting 50% relaxation (EC50) was 3.8E-05M (n = 6) when given alone and 4.4E-05M (n = 6) with L-NMA. Milrinone had EC50 = 6.0E-06M alone(n = 6) and 2.8E-05M(n = 6) with L-NMA. Zaprinast (EC50 = 6.5E-05M, n = 6) and sildenafil (EC30 = 1.8E-05M, n = 6) were synergistic with L-arginine. L-NMA blocked their effects, increasing the EC50 for zaprinast to 9.9E-03M and the EC30 for sildenafil to 6.1E + 02M. In conclusion, L-arginine is additive to the vasodilation of the type III PDE inhibitors, amrinone and milrinone, but synergistic with the type V PDE inhibitors, zaprinast and sildenafil. Implications: Amrinone and milrinone, Type III cAMP-dependent phosphodiesterase inhibitors, are additive to L-arginine-dependent vasodilation. Zaprinast and sildenafil, Type V cGMP-dependent phosphodiesterase inhibitors, are synergistic with L-arginine. C1 San Francisco Vet Adm Med Ctr, Dept Anesthesiol, San Francisco, CA USA. Univ Calif San Francisco, Dept Anesthesiol, San Francisco, CA 94143 USA. RP Wallace, AW (reprint author), VAMC Anesthesia 129, 4150 Clement St, San Francisco, CA 94121 USA. NR 35 TC 7 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2000 VL 90 IS 4 BP 840 EP 846 PG 7 WC Anesthesiology SC Anesthesiology GA 299GZ UT WOS:000086191800012 PM 10735785 ER PT J AU Denman, WT Swanson, EL Rosow, D Ezbicki, K Connors, PD Rosow, CE AF Denman, WT Swanson, EL Rosow, D Ezbicki, K Connors, PD Rosow, CE TI Pediatric evaluation of the bispectral index (BIS) monitor and correlation of BIS with end-tidal sevoflurane concentration in infants and children SO ANESTHESIA AND ANALGESIA LA English DT Article ID EEG; ANESTHESIA; PROPOFOL; SEDATION; ELECTROENCEPHALOGRAM; RECOVERY; ISOFLURANE; ALFENTANIL; MIDAZOLAM; PREDICTS AB The bispectral index: (BLS) has been det eloped in adults and correlates well with clinical hypnotic effects of anesthetics. We investigated whether BIS reflects clinical markers of hypnosis and demonstrates agent dose-responsiveness in infants and children. Sn an observational arm of this study, BIS values in children undergoing general anesthesia were observed and compared with similar data collected previously in a study of adults. In a second arm of the study, a range of steady-state end-tidal concentrations of sevoflurane was administered and corresponding BIS documented. Data were examined for differences between infants (0-2 vr) and children (2-12 yr). No difference was seen in BIS values in children before induction, during maintenance, and on emergence compared with adult values. There was no difference in BIS between infants and children at similar clinical levels of anesthesia. In children and infants, BIS was inversely proportional to the end-tidal concentration of sevoflurane. The sevoflurane concentration for a BIS = 50 (95% confidence interval) was significantly different: 1.55% (1.40-1.70) for infants versus 1.25% (1.12-1.37) for children. Although validation with specific behavioral end points was not possible, BIS correlated with clinical indicators of anesthesia in children as it did in adults: as depth of anesthesia increased, BIS diminished. BIS correlated with sevoflurane concentration in infants and children. The concentration-response difference between infants and children was consistent with data showing that minimum alveolar concentration is higher in children less than 1 yr of age. Implications: The use of bispectral index (sis) during general anesthesia improves the titration of anesthetics in adults. The data from this study suggest that the same equipment and method of electroencephalogram analysis may he applied to infants and children. C1 Massachusetts Gen Hosp, Clin 3, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Denman, WT (reprint author), Massachusetts Gen Hosp, Clin 3, Dept Anesthesia & Crit Care, 32 Fruit St, Boston, MA 02114 USA. NR 17 TC 135 Z9 160 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD APR PY 2000 VL 90 IS 4 BP 872 EP 877 PG 6 WC Anesthesiology SC Anesthesiology GA 299GZ UT WOS:000086191800018 PM 10735791 ER PT J AU Yasuda, M Takamatsu, J D'Souza, I Crowther, RA Kawamata, T Hasegawa, M Hasegawa, H Spillantini, MG Tanimukai, S Poorkaj, P Varani, L Varani, G Iwatsubo, T Goedert, M Schellenberg, GD Tanaka, C AF Yasuda, M Takamatsu, J D'Souza, I Crowther, RA Kawamata, T Hasegawa, M Hasegawa, H Spillantini, MG Tanimukai, S Poorkaj, P Varani, L Varani, G Iwatsubo, T Goedert, M Schellenberg, GD Tanaka, C TI A novel mutation at position+12 in the intron following exon 10 of the tau gene in familial frontotemporal dementia (FTD-Kumamoto) SO ANNALS OF NEUROLOGY LA English DT Article; Proceedings Paper CT International Symposium on Dementia CY SEP 11-13, 1999 CL KOBE, JAPAN ID PAIRED HELICAL FILAMENTS; MULTIPLE SYSTEM TAUOPATHY; PRESENILE-DEMENTIA; PROTEIN-TAU; MONOCLONAL-ANTIBODY; MICROTUBULE-BINDING; ALZHEIMERS-DISEASE; ISOFORMS; PHOSPHORYLATION; EXPRESSION AB Exonic and intronic mutations in the tau gene cause familiar frontotemporal dementia and parkinsonism linked to chromosome 17. Here, we describe a new mutation, consisting of a C-to-T transition at position +12 of the intron following exon 10 of the tau gene in the Kumamoto pedigree, showing frontotemporal dementia. The mutation caused a marked reduction in melting temperature of the tau exon 10-splicing regulatory element RNA and a targe increase in exon 10-containing transcripts. Brain tissue from affected individuals showed an abnormal preponderance of exon 10-containing transcripts that was reflected at the protein level by an overproduction of tau isoforms with four microtubule-binding repeats. Immunostaining revealed the presence of tau aggregates in degenerating neurons and glial cells. isolated tau filaments had a twisted ribbon-like morphology and were made of hyperphosphorylated four-repeat tau isoforms. The additional mutation located close to the splice-donor site of the intron following exon 10 of the tau gene supports the view that intronic mutations exercize their pathogenic effect by destabilizing RNA secondary structure. C1 Inst Aging Brain & Cognit Disorders, Himeji, Hyogo 6700981, Japan. Kikuchi Natl Hosp, Div Clin Res, Kumamoto, Japan. Univ Tokyo, Grad Sch Pharmaceut Sci, Dept Neuropathol & Neurosci, Tokyo, Japan. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ Clin Ctr, Seattle, WA USA. Univ Washington, Dept Med, Div Gerontol & Geriatr Med, Seattle, WA 98195 USA. Univ Washington, Dept Pharmacol & Neurol, Seattle, WA USA. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. Univ Cambridge, Dept Neurol, Cambridge, England. RP Yasuda, M (reprint author), Inst Aging Brain & Cognit Disorders, 520 Saisho Ko, Himeji, Hyogo 6700981, Japan. OI varani, luca/0000-0002-0963-0987 FU NIA NIH HHS [R01 AG11762] NR 46 TC 72 Z9 73 U1 1 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 APR PY 2000 VL 47 IS 4 BP 422 EP 429 DI 10.1002/1531-8249(200004)47:4<422::AID-ANA4>3.0.CO;2-G PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 300XF UT WOS:000086278500004 PM 10762152 ER PT J AU Killiany, RJ Gomez-Isla, T Moss, M Kikinis, R Sandor, T Jolesz, F Tanzi, R Jones, K Hyman, BT Albert, MS AF Killiany, RJ Gomez-Isla, T Moss, M Kikinis, R Sandor, T Jolesz, F Tanzi, R Jones, K Hyman, BT Albert, MS TI Use of structural magnetic resonance imaging to predict who will get Alzheimer's disease SO ANNALS OF NEUROLOGY LA English DT Article ID CINGULATE CORTEX; HIPPOCAMPAL; DEMENTIA; MEMORY; DIAGNOSIS; ATROPHY; IMPAIRMENT; SEVERITY; NEURONS; SCANS AB We used magnetic resonance imaging (MRI) measurements to determine whether persons in the prodromal phase of Alzheimer's disease (AD) could be accurately identified before they developed clinically diagnosed dementia. Normal subjects (n = 24) and those with mild memory difficulty (n = 79) received an MRI scan at baseline and were then followed annually for 3 pears to determine which individuals subsequently met clinical criteria for AD. Patients with mild AD at baseline were also evaluated (n = 16). Nineteen of the 79 subjects with mild memory difficulty "converted" to a diagnosis of probable AD after 3 years of follow-up. Baseline MRI measures of the entorhinal cortex, the banks of the superior temporal sulcus, and the anterior cingulate were most useful in discriminating the status of the subjects on follow-up examination. The accuracy of discrimination was related to the clinical similarity between groups. One hundred percent (100%) of normal subjects and patients with mild AD could be discriminated from one another based on these MRT measures. When the normals were compared with the individuals with memory impairments who ultimately developed AD (the converters), the accuracy of discrimination was 93%, based on the MRI measures at baseline (sensitivity = 0.95; specificity = 0.90). The discrimination of the normal subjects and the individuals with mild memory problems who did not progress to the point where they met clinical criteria for probable AD over the 3 years of follow-up (the "questionables") was 85% and the discrimination of the questionables and converters was 75%. The apolipoprotein E genotype did not improve the accuracy of discrimination. The specific regions selected for each of these discriminations provides information concerning the hierarchical fashion in which the pathology of AD may affect the brain during its prodromal phase. C1 Boston Univ, Dept Anat & Neurobiol, Boston, MA 02215 USA. Brandeis Univ, Heller Sch Social Policy, Waltham, MA 02254 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. RP Albert, MS (reprint author), Massachusetts Gen Hosp, Psychiat Gerontol 149-9124,149 13th St, Charlestown, MA 02129 USA. FU NCI NIH HHS [P01-CA67165]; NIA NIH HHS [P01-AG04953, R01-AG08487] NR 40 TC 424 Z9 446 U1 1 U2 16 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 APR PY 2000 VL 47 IS 4 BP 430 EP 439 DI 10.1002/1531-8249(200004)47:4<430::AID-ANA5>3.0.CO;2-I PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 300XF UT WOS:000086278500005 PM 10762153 ER PT J AU Andreassen, OA Ferrante, RJ Klivenyi, P Klein, AM Shinobu, LA Epstein, CJ Beal, MF AF Andreassen, OA Ferrante, RJ Klivenyi, P Klein, AM Shinobu, LA Epstein, CJ Beal, MF TI Partial deficiency of manganese superoxide dismutase exacerbates a transgenic mouse model of amyotrophic lateral sclerosis SO ANNALS OF NEUROLOGY LA English DT Article ID INCREASED OXIDATIVE DAMAGE; NITRIC-OXIDE SYNTHASE; HYDROGEN-PEROXIDE; MUTANT MICE; NEURODEGENERATIVE DISEASES; MOTOR-NEURONS; ANIMAL-MODEL; K-M; DEGENERATION; ALS AB The pathogenesis of neuronal cell death as a consequence of mutations in copper/zinc superoxide dismutase (SOD1) associated with familial amyotrophic lateral sclerosis may involve oxidative damage and mitochondrial dysfunction. We examined whether crossing transgenic mice with the G93A SOD1 mutation with transgenic mice with a partial depletion of manganese superoxide dismutase (SOD2) mould affect the disease phenotype. Compared with G93A mice alone, the mice with partial deficiency of SOD2 and the G93A SOD1 mutation showed a significant decrease in survival and an exacerbation of motor deficits detected by rotorod testing. There was a significant exacerbation of loss of motor neurons and substantia nigra dopaminergic neurons in the G93A mice with a partial deficiency of SOD2 compared with G93A mice at 110 days. Microvesiculation of large motor neurons was more prominent in the G93A mice with a partial deficiency of SOD2 compared with G93A mice at 90 days. These findings provide further evidence that both oxidative damage and mitochondrial dysfunction may play a role in the pathogenesis of motor neuron death associated with mutations in SOD1. C1 Cornell Univ, Med Ctr, New York Hosp, Dept Neurol, New York, NY 10021 USA. Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Dept Vet Affairs, Bedford, MA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biophys, San Francisco, CA 94143 USA. Cornell Univ, Med Ctr, New York Hosp, Dept Neurol, New York, NY 10021 USA. RP Beal, MF (reprint author), Cornell Univ, Med Ctr, New York Hosp, Dept Neurol, 525 E 68th St, New York, NY 10021 USA. FU NIA NIH HHS [P01 AG12992]; NINDS NIH HHS [NS35255, NS38180] NR 54 TC 58 Z9 59 U1 0 U2 1 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 APR PY 2000 VL 47 IS 4 BP 447 EP 455 DI 10.1002/1531-8249(200004)47:4<447::AID-ANA7>3.0.CO;2-R PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 300XF UT WOS:000086278500007 PM 10762155 ER PT J AU Desloge, RB Zeitels, SM AF Desloge, RB Zeitels, SM TI Endolaryngeal microsurgery at the anterior glottal commissure: Controversies and observations SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE anterior commissure; atypia; cancer; dysplasia; glottis; laryngoscopy; larynx; microlaryngoscopy; papilloma; phonosurgery; Reinke's edema; vocal cord; vocal fold ID LASER-SURGERY; VOCAL CORD; CARCINOMA; EXPOSURE; CANCER; CORDECTOMY; EXPERIENCE; LARYNX AB There are a number of tenets regarding endolaryngeal microsurgical management of disease that involves and/or encroaches upon the anterior glottal commissure (AGC). They include avoidance of 1) bilateral epithelial incisions near the AGC, 2) removal of papillomatosis in the AGC, and 3) resection of bilateral keratosis with atypia or carcinoma at the AGC. During the last 6 years, 115 patients underwent microsurgical management of disease at the AGC: carcinoma in 20 (T1 in 15 and T2 in 5), keratosis in 41, papillomatosis in 20, and polypoid corditis (Reinke's edema) in 34. No patients with polypoid corditis developed a synechia or web. All cancers were successfully resected en bloc; 1 of the 20 patients developed a microscopic local failure that was successfully reresected endoscopically. Eleven of the 20 cancers required excision of part of the supraglottis to establish adequate exposure for the glottic cancer resection. Eight of 15 patients with bilateral keratosis underwent staged resections. Fourteen of 15 patients with bilateral papillomatosis required staged resections. Twelve of the total 1 15 patients presented with a web secondary to prior microsurgery, and 3 developed a new, clinically insignificant web. The complications of management of disease in or near the AGC described by other authors were not noted in this series. This success was primarily the result of improved exposure in the AGC, which was achieved by use of larger and better-designed laryngoscopes and by resection of supraglottic tissue as necessary. Positioning these prototype laryngoscopes was facilitated by the use of elevated-vector suspension and external counterpressure. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Zeitels, SM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Div Laryngol, 243 Charles St, Boston, MA 02114 USA. NR 51 TC 38 Z9 41 U1 0 U2 2 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD APR PY 2000 VL 109 IS 4 BP 385 EP 392 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 303JN UT WOS:000086418900009 PM 10778894 ER PT J AU McLean-Muse, A Montgomery, WW Hillman, RE Varvares, M Bunting, G Doyle, P Eng, J AF McLean-Muse, A Montgomery, WW Hillman, RE Varvares, M Bunting, G Doyle, P Eng, J TI Montgomery (R) thyroplasty implant for vocal fold immobility: Phonatory outcomes SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Speech-Language-Hearing-Association CY NOV 23, 1997 CL BOSTON, MASSACHUSETTS SP Amer Speech Language Hearing Assoc DE laryngoplasty; Montgomery (R) Thyroplasty Implant System; thyroplasty; unilateral vocal fold paralysis; vocal fold immobility; vocal fold medialization; voice ID SPEAKING FUNDAMENTAL-FREQUENCY; LARYNGEAL FRAMEWORK SURGERY; I THYROPLASTY; ARYTENOID ADDUCTION; PARALYSIS; MEDIALIZATION; LARYNGOPLASTY; VOICE AB Forty-three patients with a diagnosis of unilateral vocal fold immobility underwent thyroplasty type I with the Montgomery(R) Thyroplasty Implant System. Preoperative and postoperative evaluations were completed by means of videostroboscopic, acoustic, and aerodynamic measures. Clinicians' perceptions of vocal quality and patients' satisfaction with the surgery and vocal quality were determined. Improvements after surgery were observed for glottal closure, vocal fold amplitude, mucosal wave activity, average intensity, maximum intensity range, maximum phonation time, glottal airflow, average sound pressure, and subglottal pressure. Average postsurgical fundamental frequency values fell within normal limits and did not display significant changes relative to presurgical values. The clinicians' perceptual evaluations indicated an improvement in voice quality for most patients. A majority of patients expressed satisfaction with the surgery and resulting voice quality. The results of the present study, in combination with the surgical advantages that have been described for the Montgomery(R) Thyroplasty Implant System, support the view that this approach offers an attractive alternative for treating unilateral vocal fold immobility. C1 Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. RP McLean-Muse, A (reprint author), Emerson Coll, Sch Commun Sci & Disorders, 100 Beacon St, Boston, MA 02116 USA. FU NIDCD NIH HHS [DC00266, DC02085] NR 27 TC 21 Z9 21 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD APR PY 2000 VL 109 IS 4 BP 393 EP 400 PG 8 WC Otorhinolaryngology SC Otorhinolaryngology GA 303JN UT WOS:000086418900010 PM 10778895 ER PT J AU Brophy, VH Vasquez, J Nelson, RG Forney, JR Rosowsky, A Sibley, CH AF Brophy, VH Vasquez, J Nelson, RG Forney, JR Rosowsky, A Sibley, CH TI Identification of Cryptosporidium parvum dihydrofolate reductase inhibitors by complementation in Saccharomyces cerevisiae SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID THYMIDYLATE SYNTHASE GENE; PNEUMOCYSTIS-CARINII; TOXOPLASMA-GONDII; PLASMODIUM-FALCIPARUM; ANTIFOLATE ACTIVITY; ESCHERICHIA-COLI; YEAST; EXPRESSION; DNA; TRANSMISSION AB There is a pressing need for drugs effective against the opportunistic protozoan pathogen Cryptosporidium parvum. Folate metabolic enzymes and enzymes of the thymidylate cycle, particularly dihydrofolate reductase (DHFR), have been widely exploited as chemotherapeutic targets. Although many DHFR inhibitors have been synthesized, only a few have been tested against C. parvum. To expedite and facilitate the discovery of effective anti-Cryptosporidium antifolates, we have developed a rapid and facile method to screen potential inhibitors of C. parvum DHFR using the model eukaryote, Saccharomyces cerevisiae. We expressed the DHFR genes of C. parvum, Plasmodium falciparum, Toxoplasma gondii, Pneumocystis carinii, and humans in the same DHFR-deficient yeast strain and observed that each heterologous enzyme complemented the yeast DHFR deficiency. In this work we describe our use of the complementation system to screen known DHFR inhibitors and our discovery of several compounds that inhibited the growth of yeast reliant on the C. parvum enzyme. These same compounds were also potent or selective inhibitors of the purified recombinant C. parvum DHFR enzyme. Six novel lipophilic DHFR inhibitors potently inhibited the growth of yeast expressing C. parvum DHFR However, the inhibition was nonselective, as these compounds also strongly inhibited the growth of yeast dependent on the human enzyme. Conversely, the antibacterial DHFR inhibitor trimethoprim and two close structural analogs were highly selective, but weak, inhibitors of yeast complemented by the C. parvum enzyme. Future chemical refinement of the potent and selective lead compounds identified in this study may allow the design of an efficacious antifolate drug for the treatment of cryptosporidiosis. C1 Univ Washington, Dept Genet, Seattle, WA 98195 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, Div Infect Dis, San Francisco, CA 94143 USA. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Div Expt Therapeut, Washington, DC 20307 USA. 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 Sibley, CH (reprint author), Univ Washington, Dept Genet, Box 357360, Seattle, WA 98195 USA. FU NIAID NIH HHS [R01 AI029904, AI42321, U01 AI40319, AI29904] NR 65 TC 30 Z9 31 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD APR PY 2000 VL 44 IS 4 BP 1019 EP 1028 DI 10.1128/AAC.44.4.1019-1028.2000 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 295YX UT WOS:000085997200033 PM 10722506 ER PT J AU Wrone, DA Tanabe, KK Cosimi, AB Gadd, MA Souba, WW Sober, AJ AF Wrone, DA Tanabe, KK Cosimi, AB Gadd, MA Souba, WW Sober, AJ TI Lymphedema after sentinel lymph node biopsy for cutaneous melanoma - A report of 5 cases SO ARCHIVES OF DERMATOLOGY LA English DT Article ID EARLY-STAGE MELANOMA; MALIGNANT-MELANOMA; GROIN DISSECTION; LYMPHADENECTOMY; FIBROMYALGIA; MORBIDITY; TRIAL AB Background: Sentinel lymph node (SLN) biopsy has rapidly become the procedure of choice for assessing the lymph node status of patients with 1992 American Joint Coimmittee on Cancer stages I and II melanoma. The procedure was designed to be less invasive and, therefore, less likely to cause complications than a complete lymph node dissection. To our knowledge, this is the first report in the literature documenting extremity Lymphedema following SLN biopsy. Observation: We report 5 cases of lymphedema after SLN biopsy in patients being routinely followed up after melanoma surgery at the Massachusetts General Hospital Melanoma Center, Boston. Three cases were mild, and 2 were moderate. Potential contributing causes of lymphedema were present in 4 patients and included the transient formation of hematomas and seromas, obesity, the possibility of occult metastatic melanoma, and the proximal extremity location of the primary melanoma excision. Four of the patients underwent an SLN biopsy at our institution. We used the total number of SLN procedures (N = 235) that we have performed to calculate a 1.7% baseline incidence of lymphedema after SLN biopsy. Conclusions: Sentinel lymph node biopsy can be complicated by mild and moderate degrees of lymphedema, with an incidence of at least 1.7%. Some patients may have contributing causes for lymphedema other than the SLN biopsy, but many of these causes are difficult to modify or avoid. C1 Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Melanoma Ctr, Boston, MA 02114 USA. RP Sober, AJ (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Bartlett 622, Boston, MA 02114 USA. NR 20 TC 36 Z9 40 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD APR PY 2000 VL 136 IS 4 BP 511 EP 514 DI 10.1001/archderm.136.4.511 PG 4 WC Dermatology SC Dermatology GA 303GF UT WOS:000086413600008 PM 10768650 ER PT J AU Lessell, S AF Lessell, S TI What can we expect in neuro-ophthalmology in the next century? SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article AB Since it is quite unlikely that the advances made in neuro-ophthalmology could have been foreseen 100 years ago, it would be hubris to predict what lies ahead in the next 100 years. It is safer to confine myself to what I hope will and will not happen. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02118 USA. RP Lessell, S (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02118 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD APR PY 2000 VL 118 IS 4 BP 553 EP 554 PG 2 WC Ophthalmology SC Ophthalmology GA 302ZZ UT WOS:000086397500016 PM 10766142 ER PT J AU Finkelstein, JA Metlay, JP Davis, RL Rifas-Shiman, SL Dowell, SF Platt, R AF Finkelstein, JA Metlay, JP Davis, RL Rifas-Shiman, SL Dowell, SF Platt, R TI Antimicrobial use in defined populations of infants and young children SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; RESPIRATORY-TRACT INFECTIONS; ACUTE OTITIS-MEDIA; ANTIBIOTIC-RESISTANCE; PENICILLIN; PREVALENCE; CARE; PNEUMOCOCCI; STRATEGY; COLDS AB Background: Antimicrobial overprescribing contributes to bacterial resistance, but data on use in infants and young children are limited. Objectives: To assess antimicrobial use in a defined population of infants and young children and to determine diagnosis-specific prescribing rates for common infections. Design and Setting: Retrospective cohort study of children served by 44 practices affiliated with 2 managed care organizations. Patients: Children aged 3 months to 72 months enrolled in either health plan between September 1, 1994, and August 31, 1996. Analysis: Rates of antimicrobial use were calculated as the number of pharmacy dispensings divided by the number of person-years of observation contributed to the cohort in 2 age groups (3 to <36 months and 36 to <72 months). Other outcomes included the distribution of diagnoses associated with antimicrobial dispensing and population-based rates of diagnosis of common acute respiratory tract illnesses. Results: A total of 46 477 children contributed 59 710 person-years of observation across the 2 health plans. Rates of antimicrobial dispensing for children aged 3 to 36 months were 3.2 and 2.1 dispensings per person-year in the 2 populations. A substantial fraction of younger children (35% in population A and 23% in population B) received 4 or more antimicrobial prescriptions in a single year. For children aged 36 to 72 months, the dispensing rates for the 2 populations were 2.0 and 1.5 antimicrobials per person-year. We found significant differences in rates between the populations studied and a decrease in use at all sites from 1995 to 1996. The diagnosis of otitis media accounted for 56% of antimicrobial drugs dispensed to children aged 3 to 36 months and 40% of those dispensed to children aged 36 to 72 months. Antimicrobial prescribing for colds and upper respiratory tract infections, bronchitis, and sinusitis was less frequent than previously reported but accounted for 10% to 14% of antimicrobial drugs dispensed. Conclusions: In these populations, otitis media accounted for the largest number of antimicrobial agents dispensed to children younger than 6 years. Clearly inappropriate indications such as cold, upper respiratory tract infection, and bronchitis accounted for smaller fractions of antimicrobial use but may be most amenable to change. However, interventions that encourage use of strict criteria for diagnosis and treatment of otitis media will likely have the greatest impact on overall antimicrobial exposure. Monitoring defined populations longitudinally will allow assessment of the effectiveness of such national and local initiatives. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Resp Dis Branch, Atlanta, GA USA. RP Finkelstein, JA (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 126 Brookline Ave,Suite 200, Boston, MA 02215 USA. NR 25 TC 98 Z9 99 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD APR PY 2000 VL 154 IS 4 BP 395 EP 400 PG 6 WC Pediatrics SC Pediatrics GA 302LK UT WOS:000086366400014 PM 10768680 ER PT J AU Garber, SL Rintala, DH Hart, KA Fuhrer, MJ AF Garber, SL Rintala, DH Hart, KA Fuhrer, MJ TI Pressure ulcer risk in spinal cord injury: Predictors of ulcer status over 3 years SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT 73rd Annual Meeting of the American-Congress-of-Rehabilitation-Medicine CY OCT 15, 1996 CL CHICAGO, ILLINOIS SP Amer Congress Rehabil Med DE pressure ulcers; spinal cord injury ID SORES; COMMUNITY; MANAGEMENT AB Objective: To identify predictors of pressure ulcers in men with spinal cord injury over a 3-year period. Design: Longitudinal, two-panel, cohort. Setting: Community. Participants: One hundred eighteen men with spinal cord injury. Measures: Interviews, questionnaires, and physical examinations were completed in two phases, 3 years apart. Information obtained included demographic and spinal cord injury characteristics; ulcer history; health beliefs and practices; measures of impairment, disability, and handicap; and skin integrity. Results: Thirty-one percent of the participants reported having a pressure ulcer in the 12 months before Phase 2. Some Phase 1 predictors of self-reported ulcers in the year before Phase 2 were a younger age at onset of spinal cord injury, previous pressure ulcer surgery, and the presence of a pressure ulcer in the year before Phase 1. On examination at Phase 2, 59% presented with an ulcer. Phase 1 predictors of ulcer presence at Phase 2 examination were similar to predictors for self-reported ulcers. Conclusion: Individuals with the identified predictive characteristics are at greater risk for developing pressure ulcers. These individuals should receive additional interventions to reduce that risk. Potential interventions include more systematic and frequent follow-up, frequent review of pressure ulcer prevention and management strategies, and provision of needed personal assistance and relevant equipment. C1 Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Inst Rehabil & Res, Houston, TX USA. Vet Affairs Med Ctr, Ctr Excellence Hlth Aging Disabil, Houston, TX 77030 USA. NIH, Bethesda, MD 20892 USA. RP Garber, SL (reprint author), Houston VA Med Ctr, 580-128,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 36 TC 68 Z9 69 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2000 VL 81 IS 4 BP 465 EP 471 DI 10.1053/mr.2000.3889 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 300WW UT WOS:000086277600014 PM 10768537 ER PT J AU DiGiovine, MM Cooper, RA Boninger, ML Lawrence, BM VanSickle, DP Rentschler, AJ AF DiGiovine, MM Cooper, RA Boninger, ML Lawrence, BM VanSickle, DP Rentschler, AJ TI User assessment of manual wheelchair ride comfort and ergonomics SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE wheelchair; ride comfort; ergonomics; pain ID WHOLE-BODY VIBRATION; DISCOMFORT; SEAT AB Objective: To examine wheelchair-user perceived ride comfort during propulsion and to compare the ride comfort of ultralight and lightweight manual wheelchairs, An ultralight wheelchair is defined as having a high degree of adjustability, whereas a lightweight wheelchair has minimal adjustability. Design and Participants: Repeated measures design of a sample of 30 community-dwelling manual wheelchair users evaluating 7 different manual wheelchairs over an activities of daily living course. Setting: A rehabilitation engineering center. Main Outcome Measures: Subject ratings of perceived ride comfort and basic ergonomics while propelling over the activities of daily Living course. Ratings were recorded for each wheelchair on individual tasks and for the course overall. Results: The Invacare Action XT wheelchair was ranked best for both ride comfort and basic ergonomics. The ride-comfort scores (p <.05) and wheelchair ergonomics ratings (p <.05) for the ultralight wheelchair group were significantly different from those for lightweight wheelchair group. Conclusion: There are differences in perceived ride comfort and basic ergonomics between the designs of the wheelchairs (lightweight vs ultralight). Subjects perceived that ultralight wheelchairs were more comfortable and had better basic ergonomics than lightweight wheelchairs. C1 VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, Pittsburgh, PA 15206 USA. Univ Pittsburgh, Dept Rehabil Sci & Technol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Orthopaed Surg, Div Phys Med & Rehabil, Pittsburgh, PA 15260 USA. UPMC Hlth Syst, Pittsburgh, PA USA. RP Cooper, RA (reprint author), VA Pittsburgh Healthcare Syst, Human Engn Res Labs 151 R1, 7180 Highland Dr, Pittsburgh, PA 15206 USA. OI Boninger, Michael/0000-0001-6966-919X NR 13 TC 39 Z9 40 U1 2 U2 8 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD APR PY 2000 VL 81 IS 4 BP 490 EP 494 DI 10.1053/mr.2000.3845 PG 5 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 300WW UT WOS:000086277600018 PM 10768541 ER PT J AU Deluzio, KJ Banks, SA Costigan, PA Ladouceur, D O'Flynn, H Wyss, UP Jasty, M Rubash, H Harris, WH AF Deluzio, KJ Banks, SA Costigan, PA Ladouceur, D O'Flynn, H Wyss, UP Jasty, M Rubash, H Harris, WH TI Kinematics and kinetics of total knee replacement patients; fluoroscopy, motion analysis, and forceplate data SO ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY LA English DT Article; Proceedings Paper CT XXVth Congress of the Societe-de-Biomecanique and XIth Congress of the Societe-Canadienne-de-Biomecanique CY AUG 23-26, 2000 CL MONTREAL, CANADA SP Soc Biomecan, Soc Canadienne Biomecan C1 Clin Mech Grp, Kingston, ON, Canada. Good Samaritan Med Ctr, W Palm Beach, FL USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Deluzio, KJ (reprint author), Clin Mech Grp, Kingston, ON, Canada. RI Banks, Scott/B-6345-2008 OI Banks, Scott/0000-0003-0404-6826 NR 6 TC 0 Z9 0 U1 0 U2 0 PU SWETS ZEITLINGER PUBLISHERS PI LISSE PA P O BOX 825, 2160 SZ LISSE, NETHERLANDS SN 1381-3455 J9 ARCH PHYSIOL BIOCHEM JI Arch. Physiol. Biochem. PD APR PY 2000 VL 108 IS 1-2 BP 3 EP 3 PG 1 WC Biochemistry & Molecular Biology; Biophysics; Endocrinology & Metabolism; Physiology SC Biochemistry & Molecular Biology; Biophysics; Endocrinology & Metabolism; Physiology GA 364FX UT WOS:000089882600003 ER PT J AU Jimenez, RE Warshaw, AL Rattner, DW Willett, CG McGrath, D Fernandez-del Castillo, C AF Jimenez, RE Warshaw, AL Rattner, DW Willett, CG McGrath, D Fernandez-del Castillo, C TI Impact of laparoscopic staging in the treatment of pancreatic cancer SO ARCHIVES OF SURGERY LA English DT Article; Proceedings Paper CT 80th Annual Meeting of the New-England-Surgical-Society CY SEP 24-26, 1999 CL NEWPORT, RHODE ISLAND SP New England Surg Soc ID PERITONEAL CYTOLOGY; COMPUTED-TOMOGRAPHY; PROGNOSTIC VALUE; CARCINOMA; HEAD; ADENOCARCINOMA; PANCREATICODUODENECTOMY; ULTRASONOGRAPHY; RESECTABILITY; PALLIATION AB Hypothesis: Staging laparoscopy in patients with pancreatic cancer identifies unsuspected metastases, allows treatment selection, and helps predict survival. Design: Inception cohort. Setting: Tertiary referral center. Patients: A total of 125 consecutive patients with radiographic stage II to III pancreatic ductal adenocarcinoma who underwent staging laparoscopy with peritoneal cytologic examination between July 1994 and November 1998. Seventy-eight proximal tumors and 47 distal rumors were localized. Interventions: Based on the findings of spiral computed tomography (CT) and laparoscopy, patients were stratified into 3 groups. Group 1 patients had unsuspected metastases found at laparoscopy and were palliated without further operation. Group 2 patients had no demonstrable metastases, but CT indicated unresectability due to vessel invasion. This group underwent external beam radiation with fluorouracil chemotherapy followed in selected cases by intraoperative radiation. Patients in group 3 had no metastases or definitive vessel invasion and were resection candidates. Results: Staging laparoscopy revealed unsuspected metastases in 39 patients (31.2%), with 9 having positive cytologic test results as the only evidence of metastatic disease (group 1). Fifty-five patients (44.0%) had localized but unresectable carcinoma (group 2), of whom 2 (3.6%) did not tolerate treatment, 20 (36.4%) developed metastatic disease during treatment, and 21 (38.2%) received intraoperative radiation. Of 31 patients with potentially resectable tumors (group 3), resection for cure was performed in 23 (resectability rate, 74.2%). Median survival was 7.5 months for patients with metastatic disease, 10.5 months for those receiving chemoradiation, and 14.5 months for those who underwent tumor resection (P = .01 for group 2 vs group 1; P < .001 for group 3 vs group 1). Conclusions: Staging laparoscopy, combined with spiral CT, allowed stratification of patients into 3 treatment groups that correlated with treatment opportunity and subsequent survival. Among the 125 patients, laparoscopy obviated 39 unnecessary operations and irradiation in patients with metastatic disease not detectable by CT. Laparoscopic staging can help focus aggressive treatment on patients with pancreatic cancer who might benefit. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Fernandez-del Castillo, C (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,WACC 336, Boston, MA 02114 USA. NR 32 TC 120 Z9 129 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0004-0010 J9 ARCH SURG-CHICAGO JI Arch. Surg. PD APR PY 2000 VL 135 IS 4 BP 409 EP 414 DI 10.1001/archsurg.135.4.409 PG 6 WC Surgery SC Surgery GA 301ZJ UT WOS:000086340200003 PM 10768705 ER PT J AU Harte, RA Hulten, LM Lindmark, H Reue, K Schotz, MC Khoo, J Rosenfeld, ME AF Harte, RA Hulten, LM Lindmark, H Reue, K Schotz, MC Khoo, J Rosenfeld, ME TI Low level expression of hormone-sensitive lipase in arterial macrophage-derived foam cells: potential explanation for low rates of cholesteryl ester hydrolysis SO ATHEROSCLEROSIS LA English DT Article DE atherosclerosis; hormone-sensitive lipase; macrophage-derived foam cells; neutral cholesteryl ester hydrolase ID DEPENDENT PROTEIN-KINASE; LOW-DENSITY-LIPOPROTEIN; MESSENGER-RNA; PHOSPHORYLATION; MOBILIZATION; DIFFERENCE; HYDROLASE; EFFLUX; HDL AB Conversion of arterial macrophages into foam cells is a key process involved in both the initiation and progression of atherosclerotic lesions. Foam cell formation involves the progressive accumulation and storage of lipoprotein-derived cholesteryl esters. The resulting imbalance in cholesterol metabolism in arterial foam cells may be due in part to an inadequately low level of cytoplasmic neutral cholesteryl ester hydrolase (NCEH) activity. In this study, we have demonstrated that hormone-sensitive lipase (HSL) mRNA is expressed at very low levels in macrophage-derived foam cells, using the unique approach of extracting mRNA from macrophage-derived foam cells purified from human and rabbit atherosclerotic plaques coupled with reverse transcriptase polymerase chain reaction (RT-PCR). We also demonstrate that macrophage-derived foam cells isolated from rabbit atherosclerotic lesions exhibit a resistance to high density lipoprotein (HDL)-mediated cholesterol efflux along with reduced levels of NCEH activity compared to lipid-loaded mouse peritoneal macrophages. Thus, low level expression of HSL may partially account for the reduced NCEH activity observed in arterial foam cells isolated from atherosclerosis-susceptible species. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. Univ Washington, Interdisciplinary Program Nutr Sci, Seattle, WA 98195 USA. Sahlgrenska Univ Hosp, Wallenberg Lab Cardiovasc Res, Gothenburg, Sweden. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. W Los Angeles VA Med Ctr, Lipid Res Lab, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. RP Rosenfeld, ME (reprint author), Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. FU NIDDK NIH HHS [DK35816] NR 29 TC 16 Z9 17 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD APR PY 2000 VL 149 IS 2 BP 343 EP 350 DI 10.1016/S0021-9150(99)00345-7 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 302BK UT WOS:000086344900010 PM 10729384 ER PT J AU Safren, SA Gonzalez, RE Horner, KJ Leung, AW Heimberg, RG Juster, HR AF Safren, SA Gonzalez, RE Horner, KJ Leung, AW Heimberg, RG Juster, HR TI Anxiety in ethnic minority youth - Methodological and conceptual issues and review of the literature SO BEHAVIOR MODIFICATION LA English DT Review ID AMERICAN CHILDREN AFRAID; AFRICAN-AMERICAN; MIDDLE-CLASS; DISORDERS; ADOLESCENTS; FEARS; PREVALENCE; COMMUNITY; STRESS; WHITE AB Although current research has documented a relatively high prevalence of anxiety disorders in American youth, this research has been conducted mainly with nonminority samples. Fair treatment and increasing numbers of ethnic minority persons in the United States require that more should be known about minority youth. However, research with majority youth cannot be safely generalized to minority youth for several reasons, such as potential differences in the manifestation of anxiety, differences in style of response to assessment devices, and different life circumstances. This review is presented in two major sections. First, the authors address definition of terms and fully examine the significance of studying anxiety in ethnic minority youth. Also considered are methodological issues such as sampling and participation biases. Second, the authors review anxiety in ethnic minority children and adolescents in the United States including studies addressing fears, worries, trait anxiety, test anxiety, and anxiety disorders. C1 Temple Univ, Dept Psychol, Philadelphia, PA 19122 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Fenway Community Hlth, Cambridge, MA 02138 USA. SUNY Albany, Albany, NY 12222 USA. RP Heimberg, RG (reprint author), Temple Univ, Dept Psychol, Weiss Hall,1701 N 13th St, Philadelphia, PA 19122 USA. FU PHS HHS [44119] NR 103 TC 21 Z9 21 U1 6 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 J9 BEHAV MODIF JI Behav. Modificat. PD APR PY 2000 VL 24 IS 2 BP 147 EP 183 DI 10.1177/0145445500242001 PG 37 WC Psychology, Clinical SC Psychology GA 302LW UT WOS:000086367400001 PM 10804678 ER PT J AU Heaton, JT Brauth, SE AF Heaton, JT Brauth, SE TI Telencephalic nuclei control late but not early nestling calls in the budgerigar SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE archistriatum; birdsong; budgerigar; foodbegging; lesion; nestling; parrot; vocal development ID VOCAL CONTROL PATHWAYS; MELOPSITTACUS-UNDULATUS; FUNCTIONAL-ANATOMY; AUDITORY PATHWAYS; BENGALESE FINCHES; CONTACT CALLS; CONNECTIONS; FOREBRAIN; VOCALIZATIONS; PLASTICITY AB Bilateral lesions targeting the central nucleus of the anterior archistriatum (AAc) were placed in nestling budgerigars (Melopsittacus undulatus) aged 5, 9, 13, 22, 26, and 33 days post-hatch in order to evaluate the role of the telencephalon in producing nestling vocalizations in this species. In budgerigars, AAc is the final common pathway from telencephalic vocal control nuclei to brainstem respiratory and syringeal motorneuron pools. The results show that lesions destroying AAc bilaterally in addition to surrounding archistriatum and neostriatum do not alter the production of early simple patterned foodbegging calls but do prevent both the normal transition at 3-4 weeks post-hatch to more complex begging calls as well as the emergence of individually-distinctive contact calls around the time of fledging. These vocal results are strikingly similar to those obtained in previous studies in which early deafening of nestlings (Heaton and Brauth, 1999) and early lesioning of auditory areas in the anterior telencephalon (Hall WS, Brauth SE, Heaton JT. Comparison of the effects of lesions in nucleus basalis and field 'L' on vocal control learning and performance in the budgerigar (M. undulatus), Brain Behav. Evol., 1994;44:133-148) did not affect call production until 3-4 weeks post-hatch. These data combined support the idea that neither auditory feedback nor telencephalic sensorimotor circuits are necessary for the production of nestling calls before 3 weeks post-hatch. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Eye & Ear Infirm, Voice & Speech Lab, Boston, MA 02114 USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. RP Brauth, SE (reprint author), Massachusetts Eye & Ear Infirm, Voice & Speech Lab, 243 Charles St, Boston, MA 02114 USA. FU NIMH NIH HHS [MH40698, MH10417] NR 28 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD APR PY 2000 VL 109 IS 1 BP 129 EP 135 DI 10.1016/S0166-4328(99)00157-6 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 298GF UT WOS:000086130400013 PM 10699664 ER PT J AU Mukhin, YV Garnovskaya, MN Collinsworth, G Pendergrass, D Magai, T Pinckney, S Greene, EL Raymond, JR AF Mukhin, YV Garnovskaya, MN Collinsworth, G Pendergrass, D Magai, T Pinckney, S Greene, EL Raymond, JR TI 5-Hydroxytryptamine(1A) receptor/G(i)beta gamma stimulates mitogen-activated protein kinase via NAD(P)H oxidase and reactive oxygen species upstream of Src in Chinese hamster ovary fibroblasts SO BIOCHEMICAL JOURNAL LA English DT Article DE G protein; phosphorylation; proliferation; serotonin receptor; tyrosine kinase ID SMOOTH-MUSCLE CELLS; TYROSINE-PHOSPHATASE CATALYSIS; HYDROGEN-PEROXIDE; 5-HT1A RECEPTOR; MESANGIAL CELLS; NADPH OXIDASE; REDOX REGULATION; ANGIOTENSIN-II; C-JUN; DIFFERENTIAL ACTIVATION AB The hypothesis of this work is that the 'serotonin' or 5-hydroxytryptamine (5-HT)(1A) receptor, which activates the extracellular signal-regulated kinase (ERK) through a G(1)beta gamma-mediated pathway, does so through the intermediate actions of reactive oxygen species (ROS). Five criteria were shown to support a key role for ROS in the activation of ERK by the 5-HT1A receptor. (1) Antioxidants inhibit activation of ERK by 5-HT. (2) Application of cysteine-reactive oxidant molecules activates ERK. (3) The 5-HT1A receptor alters cellular redox properties, and generates both superoxide and hydrogen peroxide. (4) A specific ROS-producing enzyme [NAD(P)H oxidase] is involved in the activation of ERK. (5) There is specificity both in the effects of various chemical oxidizers, and in the putative location of the ROS in the ERK activation pathway. We propose that NAD(P)H oxidase is located in the ERK activation pathway stimulated by the transfected 5-HT1A receptor in Chinese hamster ovary (CHO) cells downstream of G(1)beta gamma subunits and upstream of or at the level of the non-receptor tyrosine kinase, Src. Moreover, these experiments provide cofirmation that the transfected human 5-HT1A receptor induces the production of ROS (superoxide and hydrogen peroxide) in CHO cells, and support the possibility that an NAD(P)H oxidase-like enzyme might be involved in the 5-HT-mediated generation of both superoxide and hydrogen peroxide. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. RP Raymond, JR (reprint author), Med Univ S Carolina, Dept Med, 96 Jonathan Lucas St, Charleston, SC 29425 USA. FU NHLBI NIH HHS [HL03710]; NIDDK NIH HHS [DK52448] NR 51 TC 49 Z9 53 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD APR 1 PY 2000 VL 347 BP 61 EP 67 DI 10.1042/0264-6021:3470061 PN 1 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 309WQ UT WOS:000086792600008 PM 10727402 ER PT J AU Lewandrowski, KU Gresser, JD Wise, DL Trantolo, DJ AF Lewandrowski, KU Gresser, JD Wise, DL Trantolo, DJ TI Bioresorbable bone graft substitutes of different osteoconductivities: a histologic evaluation of osteointegration of poly(propylene glycol-co-fumaric acid)-based cement implants in rats SO BIOMATERIALS LA English DT Article DE bioresorbable; bone graft substitute; osteoconductivity; biocompatibility ID FOREIGN-BODY REACTIONS; BIODEGRADABLE POLYMERS; FUMARATE); OSTEOLYSIS; FIXATION; LESIONS; SCREWS AB Bioresorbable bone graft substitutes may significantly reduce the disadvantages associated with autografts, allografts and other synthetic materials currently used in bone graft procedures. We investigated the biocompatibility and osteointegration of a bioresorbable bone graft substitute made from the unsaturated polyester poly(propylene-glycol-co-fumaric acid), or simply poly(propylene fumarate), PPF, which is crosslinked in the presence of soluble and insoluble calcium filler salts. Four sets of animals each having three groups of 8 were evaluated by grouting bone graft substitutes of varying compositions into 3-mm holes that were made into the anteromedial tibial metaphysis of rats. Four different formulations varying as to the type of soluble salt filler employed were used: set 1-calcium acetate, set 2-calcium gluconate, set 3-calcium propionate, and set 4-control with hydroxapatite, HA, only. Animals of each of the three sets were sacrificed in groups of 8 at postoperative week 1, 3, and 7. Histologic analysis revealed that in vivo biocompatibility and osteointegration of bone graft substitutes was optimal when calcium acetate was employed as a soluble salt filler. Other formulations demonstrated implant surface erosion and disintegration which was ultimately accompanied by an inflammatory response. This study suggested that PPF-based bone graft substitutes can be designed to provide an osteoconductive pathway by which bone will grow in faster because of its capacity to develop controlled porosities in vivo. Immediate applicability of this bone graft substitute, the porosity of which can be tailored for the reconstruction of defects of varying size and quality of the recipient bed, is to defects caused by surgical debridement of infections, previous surgery, tumor removal, trauma, implant revisions and joint fusion. Clinical implications of the relation between developing porosity, resulting osteoconduction, and bone repair in vivo are discussed. (C) 2000 Published by Elsevier Science Ltd. All rights reserved. C1 Cambridge Sci Inc, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Orthopaed Res Labs, Boston, MA 02114 USA. RP Trantolo, DJ (reprint author), Cambridge Sci Inc, 180 Fawcett St, Cambridge, MA 02138 USA. FU NIAMS NIH HHS [AR 45062]; NIDCR NIH HHS [1 R43 DE 12290-01A1] NR 30 TC 84 Z9 87 U1 4 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD APR PY 2000 VL 21 IS 8 BP 757 EP 764 DI 10.1016/S0142-9612(99)00179-9 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 289XY UT WOS:000085648300001 PM 10721744 ER PT J AU McGlave, PB Shu, XO Wen, WQ Anasetti, C Nadermanee, A Champlin, R Antin, JH Kernan, NA King, R Weisdorf, DJ AF McGlave, PB Shu, XO Wen, WQ Anasetti, C Nadermanee, A Champlin, R Antin, JH Kernan, NA King, R Weisdorf, DJ TI Unrelated donor marrow transplantation for chronic myelogenous leukemia: 9 years' experience of the National Marrow Donor Program SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; VERSUS-HOST DISEASE; TOTAL-BODY IRRADIATION; T-CELL DEPLETION; HLA CLASS-I; BONE-MARROW; CHRONIC PHASE; HEMATOLOGIC MALIGNANCIES; ALLOGENEIC MARROW; INTERFERON-ALPHA AB Over a period of 8.5 years (February 1988 to October 1996), 1423 patients with chronic myelogenous leukemia (CML) underwent unrelated donor (URD) bone marrow transplants (BMTs) facilitated by the National Marrow Donor Program (NMDP) at 85 transplant centers. One hundred thirty-seven evaluable (9.9%) patients failed to engraft, and an additional 83 (6.6%) evaluable patients experienced late graft failure, Grade III/IV acute graft-versus-host disease (GVHD) developed in 33% of patients (95% confidence interval [CI], 30%-36%), The incidence of extensive chronic GVHD was 60% (95% CI, 56%-63%) at 2 years. Only 5.7% of patients (95% CI, 3.6%-7.8%) transplanted in chronic phase developed hematologic relapse at 3 years. Several factors were independently associated with improved disease-free survival (DFS), including transplant in chronic phase, transplant within 1 year of diagnosis, younger recipient age, a cytomegalovirus seronegative recipient, and development of no or mild acute GVHD. The combined effect of these factors on outcome is manifest in a subset (n = 157) of young (less than 35 years), chronic phase patients transplanted within 1 year of diagnosis using HLA-matched donors who had 63% (95% CI, 53%-73%) DFS at 3 years. URD BMT therapy for CML is both feasible and effective with more frequent and more rapid identification of suitable donors. Early URD transplant during chronic phase yields good results and should be considered in CML patients otherwise eligible for transplant but without a suitable related donor,(Blood, 2000;95:2219-2225) (C) 2000 by The American Society of Hematology. C1 Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Natl Marrow Donor Program, Minneapolis, MN USA. Univ S Carolina, Columbia, SC 29208 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Dana Farber Partners Canc Care, Boston, MA USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP McGlave, PB (reprint author), Univ Minnesota, Sch Med, Box 480,420 Delaware St SE, Minneapolis, MN 55455 USA. FU NCI NIH HHS [CA33572, CA30206, CA65493] NR 49 TC 164 Z9 171 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 APR 1 PY 2000 VL 95 IS 7 BP 2219 EP 2225 PG 7 WC Hematology SC Hematology GA 298GC UT WOS:000086130100008 PM 10733488 ER PT J AU Stock, W Tsai, T Golden, C Rankin, C Sher, D Slovak, ML Pallavicini, MG Radich, JP Boldt, DH AF Stock, W Tsai, T Golden, C Rankin, C Sher, D Slovak, ML Pallavicini, MG Radich, JP Boldt, DH TI Cell cycle regulatory gene abnormalities are important determinants of leukemogenesis and disease biology in adult acute lymphoblastic leukemia SO BLOOD LA English DT Article ID SOUTHWEST-ONCOLOGY-GROUP; CYTOGENETICALLY ABERRANT CELLS; HEMATOPOIETIC PROGENITOR CELLS; CLINICAL-SIGNIFICANCE; GROUP EXPERIENCE; STEM-CELLS; MARROW; P53; COMPARTMENT; EXPRESSION AB To test the hypothesis that cell cycle regulatory gene abnormalities are determinants of clinical outcome in adult acute lymphoblastic leukemia (ALL), we screened lymphoblasts from patients on a Southwest Oncology Group protocol for abnormalities of the genes, retinoblastoma (Rb), p53, p15(INK4B), and p16(INK4A), Aberrant expression occurred in 33 (85%) patients in the following frequencies: Rb, 51%; p16(INK4A), 41%; p53, 26%, Thirteen patients (33%) had abnormalities in 2 or more genes. Outcomes were compared in patients with 0 to 1 abnormality versus patients with multiple abnormalities. The 2 groups did not differ in a large number of clinical and laboratory characteristics. The CR rates for patients with 0 to 1 and multiple abnormalities were similar (69% and 54%, respectively). Patients with 0 to 1 abnormality had a median survival time of 25 months(n = 26; 95% CI, 13-46 months) versus 8 months (n = 13; 95% CI, 4-12 months) for those with multiple abnormalities (P <.01). Stem cells (CD34+lin-) were isolated from adult ALL bone marrows and tested for p16(INK4A) expression by immunocytochemistry, In 3 of 5 patients lymphoblasts and sorted stem cells lacked p16(INK4A) expression. In 2 other patients only 50% of sorted stem cells expressed p16(INK4A), By contrast, pig expression was present in the CD34+lin- compartment In 95% (median) of 9 patients whose lymphoblasts expressed p16(INK4A), Therefore, cell cycle regulatory gene abnormalities are frequently present in adult ALL lymphoblasts, and they may be important determinants of disease outcome. The presence of these abnormalities In the stem compartment suggests that they contribute to leukemogenesis. Eradication of the stem cell subset harboring these abnormalities may be important to achieve cure, (Blood, 2000;95:2364-2371) (C) 2000 by The American Society of Hematology. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, San Antonio, TX 78229 USA. Univ Illinois, Dept Med, Chicago, IL USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. SW Oncol Grp, Leukemia Biol Program, San Antonio, TX USA. SW Oncol Grp, Cytogenet Program, San Antonio, TX USA. Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA. Childrens Hosp, Dept Hematol Oncol, Oakland, CA 94609 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Genet Program, Seattle, WA 98104 USA. City Hope Natl Med Ctr, Dept Cytogenet, Duarte, CA 91010 USA. RP Boldt, DH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Hematol, Mail Code 7880,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. FU NCI NIH HHS [CA6032, CA32102, CA3333572] NR 37 TC 22 Z9 23 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 APR 1 PY 2000 VL 95 IS 7 BP 2364 EP 2371 PG 8 WC Hematology SC Hematology GA 298GC UT WOS:000086130100028 PM 10733508 ER PT J AU Kikuchi, T Kimura, RS Paul, DL Takasaka, T Adams, JC AF Kikuchi, T Kimura, RS Paul, DL Takasaka, T Adams, JC TI Gap junction systems in the mammalian cochlea SO BRAIN RESEARCH REVIEWS LA English DT Article; Proceedings Paper CT Workshop on Gap Junctions in the Nervous and Cardiovascular Systems: Clinical Implications CY JUN 06-11, 1998 CL RIO JANEIRO, BRAZIL DE connexin 26; K+; ion transport ID ULTRASTRUCTURAL ANALYSIS; SENSORINEURAL DEAFNESS; CONNEXIN-26 MUTATIONS; INNER-EAR AB Recent findings that a high proportion of non-syndromic hereditary sensorineural hearing loss is due to mutations in the gene for connexin 26 indicate the crucial role that the gene product plays for normal functioning of the cochlea. Excluding sensory cells, most cells in the cochlea are connected via gap junctions and these gap junctions appear to play critical roles in cochlear ion homeostasis. Connexin 26 occurs in gap junctions connecting all cell classes in the cochlea, There are two independent systems of cells, which are defined by interconnecting gap junctions. The first system, the epithelial cell gap junction system, is mainly composed of all organ of Corti supporting cells, and also includes interdental cells in the spiral limbus and root cells within the spiral ligament. The second system, the connective tissue cell gap junction system, consists of strial intermediate cells, strial basal cells, fibrocytes in the spiral ligament, mesenchymal cells lining the bony otic capsule facing the scala vestibuli, mesenchymal dark cells in the supralimbal zone, and fibrocytes in the spiral limbus, One function of these gap junctional systems is the recirculation of K+ ions from hair cells to the strial marginal cells. Interruption of this recirculation, which may be caused by the mutation in connexin 26 gene, would deprive the stria vascularis of K+ and result in hearing loss. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Tohoku Univ, Sch Med, Dept Otolaryngol, Aoba Ku, Sendai, Miyagi 9808574, Japan. Harvard Univ, Sch Med, Dept Otolaryngol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. RP Kikuchi, T (reprint author), Tohoku Univ, Sch Med, Dept Otolaryngol, Aoba Ku, 1-1 Seiryo Machi, Sendai, Miyagi 9808574, Japan. NR 8 TC 151 Z9 176 U1 0 U2 1 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 APR PY 2000 VL 32 IS 1 SI SI BP 163 EP 166 DI 10.1016/S0165-0173(99)00076-4 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 315UK UT WOS:000087131200019 PM 10751665 ER PT J AU Takeshita, H Kusuzaki, K Murata, H Suginoshita, T Hirata, M Hashiguchi, S Ashihara, T Gebhardt, MC Mankin, HJ Hirasawa, Y AF Takeshita, H Kusuzaki, K Murata, H Suginoshita, T Hirata, M Hashiguchi, S Ashihara, T Gebhardt, MC Mankin, HJ Hirasawa, Y TI Osteoblastic differentiation and P-glycoprotein multidrug resistance in a murine osteosarcoma model SO BRITISH JOURNAL OF CANCER LA English DT Article DE P-glycoprotein; multidrug resistance; differentiation; malignancy; osteosarcoma ID MDR1B MESSENGER-RNA; TUMOR PROGRESSION; RAT-LIVER; EXPRESSION; CELLS; GENE; MODULATION AB A recent study of multidrug resistance (MDR) 1 gene transfected osteosarcoma cells found a cause-effect relationship between increased expression of P-glycoprotein (P-gp) and a low aggressive phenotype, However, several experimental and clinical studies have observed contradictory findings in that P-gp expression has been associated with tumour progression. In the present study, we characterized P-gp-positive and P-gp-negative single-cell clones of a murine osteosarcoma, to further investigate the relationship between P-gp expression and changes in cell phenotype, Although these clones were all selected by doxorubicin (DOX) exposure, they were heterogeneous with respect to MDR1 gene expression. The P-gp-positive clones revealed MDR phenotype, whereas the P-gp-negative clones showed no resistance to drugs. Morphological and functional analysis showed that both the P-gp-positive and P-gp-negative clones were more differentiated than the parent cells in terms of enhanced activity of cellular alkaline phosphatase, an increase in well-organized actin stress fibres and enhanced osteogenic activity. Moreover, these subclones all displayed a decrease in malignant potential such as oncogenic activity, tumour growth rate and metastatic ability, regardless of their P-gp status. These results indicate that the observed osteoblastic differentiation and less aggressive phenotype in DOX-selected osteosarcoma cells may not only be explained by the direct effect of P-gp, and accordingly, consideration of the effect of DOX, as well as P-gp, appears to be important. (C) 2000 Cancer Research Campaign. C1 Kyoto Prefectural Univ Med, Dept Orthopaed Surg, Kyoto 602, Japan. Kyoto Prefectural Univ Med, Dept Pathol 1, Kyoto 602, Japan. Otsu Municipal Hosp, Dept Orthopaed Surg, Otsu, Shiga 520, Japan. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Takeshita, H (reprint author), Kyoto Prefectural Univ Med, Dept Orthopaed Surg, Kyoto 602, Japan. NR 25 TC 6 Z9 6 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 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD APR PY 2000 VL 82 IS 7 BP 1327 EP 1331 DI 10.1054/bjoc.1999.1099 PG 5 WC Oncology SC Oncology GA 294NR UT WOS:000085917800015 PM 10755409 ER PT J AU Fonseca, R Trendle, MC Leong, T Kyle, RA Oken, MM Kay, NE Van Ness, B Greipp, PR AF Fonseca, R Trendle, MC Leong, T Kyle, RA Oken, MM Kay, NE Van Ness, B Greipp, PR TI Prognostic value of serum markers of bone metabolism in untreated multiple myeloma patients SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myeloma; bone; prognosis; telopeptide ID TRIAL E9486; TELOPEPTIDE AB Bone involvement is a central feature of multiple myeloma (MM). We investigated whether serum markers of osteoblastic and osteoclastic activity correlate with the presence of bone disease and survival in 313 MM patients enrolled in a phase III trial (E9486). Five markers were measured, including osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), bone alkaline phosphatase (BAP), carboxy-terminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). We analysed the relationship between serum levels of these markers and the presence of bone manifestations, and survival. Serum levels of ICTP and BAP correlated significantly with bone pain, lesions and fractures. Serum level of ICTP was also higher in stage II-III compared with stage I disease. The serum level of ICTP was significantly associated with shortened survival in the univariate analysis. The median survival times were 4.1 and 3.5 years for low and high ICTP respectively (P = 0.02). There was a strong relationship between ICTP and beta-2-microgolobulin (B2M). ICTP stands out as a significant marker of bone disease. Incorporation of these markers into clinical trials assessing the use of bisphosphonates in MM is needed to determine whether they might serve as indicators of effectiveness of these agents. C1 Mayo Clin, Dept Pathol & Lab Med, Rochester, MN 55905 USA. Mayo Clin, Dept Hematol & Internal Med, Rochester, MN 55905 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Virginia Piper Canc Inst, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. RP Greipp, PR (reprint author), Mayo Clin, Dept Pathol & Lab Med, Hilton 930, Rochester, MN 55905 USA. OI Fonseca, Rafael/0000-0002-5938-3769 FU NCI NIH HHS [CA 13650, CA 15947, CA 23318] NR 15 TC 60 Z9 63 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD APR PY 2000 VL 109 IS 1 BP 24 EP 29 DI 10.1046/j.1365-2141.2000.01960.x PG 6 WC Hematology SC Hematology GA 323FH UT WOS:000087554100003 PM 10848778 ER PT J AU Michelson, D Fava, M Amsterdam, J Apter, J Londborg, P Tamura, R Tepner, RG AF Michelson, D Fava, M Amsterdam, J Apter, J Londborg, P Tamura, R Tepner, RG TI Interruption of selective serotonin reuptake inhibitor treatment - Double-blind, placebo-controlled trial SO BRITISH JOURNAL OF PSYCHIATRY LA English DT Article ID DISCONTINUATION; MULTICENTER; FLUOXETINE; DEPRESSION; SAFETY AB Background Abrupt interruption of therapy with selective serotonin reuptake inhibitors (SSRIs) has been associated with somatic and psychological symptoms. Aims Systematically to assess symptoms and effects on daily functioning related to interruption of SSRI therapy. Method Patients treated with fluoxetine, setraline or paroxetine underwent identical five-day periods of treatment interruption and continued active treatment under double-blind order-randomised conditions, with regular assessment of new symptoms. Results Placebo substitution for paroxetine was associated with increases in the number and severity of adverse events following the second missed dose, and increases in functional impairment at five days. Placebo substitution for sertraline resulted in less pronounced changes, while interruption of fluoxetine was not associated with any significant increase in symptomatology. Conclusions Abrupt interruption of SSRI treatment can result in a syndrome characterised by specific physical and psychological symptoms. Incidence, timing and severity of symptoms vary among SSRIs in a fashion that appears to be related to plasma elimination characteristics. Declaration of interest This work was sponsored by Eli Lilly and Company. C1 Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. Princeton Biomed Res, Princeton, NJ USA. Seattle Clin Res Ctr, Seattle, WA USA. RP Michelson, D (reprint author), Lilly Corp Ctr, Lilly Res Labs, Drop Code 2423, Indianapolis, IN 46285 USA. NR 18 TC 122 Z9 124 U1 1 U2 6 PU ROYAL COLLEGE OF PSYCHIATRISTS PI LONDON PA BRITISH JOURNAL OF PSYCHIATRY 17 BELGRAVE SQUARE, LONDON SW1X 8PG, ENGLAND SN 0007-1250 J9 BRIT J PSYCHIAT JI Br. J. Psychiatry PD APR PY 2000 VL 176 BP 363 EP 368 DI 10.1192/bjp.176.4.363 PG 6 WC Psychiatry SC Psychiatry GA 302PN UT WOS:000086374300010 PM 10827885 ER PT J AU Compton, C Fenoglio-Preiser, CM Pettigrew, N Fielding, LP AF Compton, C Fenoglio-Preiser, CM Pettigrew, N Fielding, LP TI American Joint Committee on Cancer prognostic factors consensus conference - Colorectal working group SO CANCER LA English DT Review DE colorectal carcinoma; prognostic factor; predictive factor; staging; staging systems; molecular marker; oncogenes; host response; survival ID CELL NUCLEAR ANTIGEN; NUCLEOLAR ORGANIZER REGIONS; NEGATIVE COLON-CANCER; LONG-TERM SURVIVAL; K-RAS MUTATION; LYMPH-NODE MICROMETASTASES; DNA PLOIDY PATTERN; LARGE BOWEL-CANCER; WILD-TYPE P53; RECTAL-CANCER AB BACKGROUND. The American Joint Committee on Cancer (AJCC), which regularly reviews TNM staging systems, established a working party to develop recommendations for colorectal carcinoma. METHODS. A multidisciplinary consensus conference using published literature developed an arbitrary classification system of prognostic marker value (Category I, IIA, IIB, III, and IV), which forms the framework for this report. RESULTS. The working party concluded that several T categories should be subdivided: pTis into intraepithelial carcinoma (pTie) and intramucosal carcinoma (pTim); pT1 into pT1a and pT1b corresponding to the absence or presence of blood or lymphatic vessel invasion, respectively; and pT4 into pT4a and pT4b according to the absence or presence of tumor involving the surface of the specimen, respectively. The working party also recommended that TNM groups be stratified based on the presence or absence of elevated serum levels of carcinoembryonic antigen (CEA) (greater than or equal to 5 ng/mL) on preoperative clinical examination. In addition, the working party also concluded that carcinoma of the appendix should be excluded from the colorectal carcinoma staging system because of fundamental differences in natural history. CONCLUSIONS. The TNM categories and stage groupings for colorectal carcinoma published in the current AJCC manual have clinical and academic value. However, a few categories require subdivision to provide increasing discrimination for individual patients. The serum marker CEA should be added to the staging system, whereas multiple other factors should be recorded as part of good good clinical practice. Although many molecular and oncogenic markers show promise to supplement or modify the current staging systems eventually, to the authors' knowledge none have yet been evaluated sufficiently to recommend their inclusion in the TNM system. (C) 2000 American Cancer Society. C1 York Hosp, York Hlth Syst, Dept Surg, York, PA 17405 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Univ Manitoba, Winnipeg, MB R3T 2N2, Canada. RP Fielding, LP (reprint author), York Hosp, York Hlth Syst, Dept Surg, 1001 S George St, York, PA 17405 USA. NR 175 TC 356 Z9 374 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD APR 1 PY 2000 VL 88 IS 7 BP 1739 EP 1757 DI 10.1002/(SICI)1097-0142(20000401)88:7<1739::AID-CNCR30>3.0.CO;2-T PG 19 WC Oncology SC Oncology GA 299RU UT WOS:000086212300030 PM 10738234 ER PT J AU Tsao, H Zhang, X Fowlkes, K Haluska, FG AF Tsao, H Zhang, X Fowlkes, K Haluska, FG TI Relative reciprocity of NRAS and PTEN/MMAC1 alterations in cutaneous melanoma cell lines SO CANCER RESEARCH LA English DT Article ID POLYMERASE CHAIN-REACTION; HUMAN-COLON CARCINOMA; RAS GENE-MUTATIONS; TUMOR-SUPPRESSOR; MALIGNANT-MELANOMA; POINT MUTATIONS; PTEN; ONCOGENE; IDENTIFICATION; DELETION AB Both inactivation of the tumor suppressor gene, PTEN/MMAC1. and oncogenic activation of RAS have been described in human cutaneous melanoma, In mice, activation of a RAS-containing pathway is a necessary step in the pathogenesis of murine melanomas, Because PTEN negatively regulates on the downstream effects of phosphatidylinositol-3-kinase (P13-K), we hypothesized that the loss of PTEN/MMAC1 and the activation of RAS may be largely equivalent because RAS is a known positive upstream regulator of P13-K, We expanded our previous survey of PTEN/MMAC1 mutations and analyzed the RAS status of 53 cutaneous melanoma cell lines, 18 glioma cell lines, and 17 uncultured cutaneous melanoma metastasis, Overall, 51% of the cell lines had alterations in either PTEN/MMAC1 or RAS, We found 16 cell lines (30%) with alterations in PTEN/MMAC1 and 11 cell lines (21%) with activating NRAS mutations; only 1 cell line had concurrent alterations in both genes. Moreover, glioma cell lines with a high frequency of PTEN/MMAC1 inactivation had no identifiable RAS alterations. Ectopic expression of PTEN in several cutaneous melanoma cell lines suppressed colony formation irrespective of PTEN/MMAC1 status; furthermore, PTEN expression in cell lines carrying activated RAS also suppressed colony formation. The relative reciprocity of PTEN/MMAC1 abrogation and NRAS activation suggests that the two genetic changes, in a subset of cutaneous melanomas, are functionally overlapping. C1 Massachusetts Gen Hosp, Dept Dermatol, Div Hematol Oncol, Boston, MA 02114 USA. Dana Farber Partners CancCare, Boston, MA 02114 USA. China Med Univ, Dept Med Genet, Shenyang, Peoples R China. RP Haluska, FG (reprint author), Massachusetts Gen Hosp, Dept Dermatol, Div Hematol Oncol, Boston, MA 02114 USA. NR 48 TC 156 Z9 160 U1 0 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 APR 1 PY 2000 VL 60 IS 7 BP 1800 EP 1804 PG 5 WC Oncology SC Oncology GA 301YK UT WOS:000086338000005 PM 10766161 ER PT J AU Browder, T Butterfield, CE Kraling, BM Shi, B Marshall, B O'Reilly, MS Folkman, J AF Browder, T Butterfield, CE Kraling, BM Shi, B Marshall, B O'Reilly, MS Folkman, J TI Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer SO CANCER RESEARCH LA English DT Article ID STERICALLY STABILIZED LIPOSOMES; METASTATIC BREAST-CANCER; ENDOTHELIAL-CELLS; ORAL ETOPOSIDE; TUMOR ANGIOGENESIS; MITOMYCIN-C; THERAPY; AGENTS; PACLITAXEL; GROWTH AB To reveal the antiangiogenic capability of cancer chemotherapy, we developed an alternative antiangiogenic schedule for administration of cyclophosphamide. We show here that this antiangiogenic schedule avoided drug resistance and eradicated Lewis lung carcinoma and L1210 leukemia, an outcome not possible with the conventional schedule. When Lewis lung carcinoma and EMT-6 breast cancer were made drug resistant before therapy, the antiangiogenic schedule suppressed tumor growth 3-fold more effectively than the conventional schedule. When another angiogenesis inhibitor, TNP-470, was added to the antiangiogenic schedule of cyclophosphamide, drug-resistant Lewis lung carcinomas were eradicated. Each dose of the antiangiogenic schedule of fyclophosphamide induced the apoptosis of endothelial cells within tumors, and endothelial cell apoptosis preceded the apoptosis of drug-resistant tumor tells. This antiangiogenic effect was more pronounced in p53-null mice in which the apoptosis of p53-null endothelial cells induced by cyclophosphamide was so vigorous that drug-resistant tumors comprising 4.5% of body weight were eradicated. Thus, by using a dosing schedule of cyclophosphamide that provided more sustained apoptosis of endothelial cells within the vascular bed of a tumor, we show that a chemotherapeutic agent can more effectively control tumor growth in mice, regardless of whether the tumor cells are drug resistant. C1 Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Folkman, J (reprint author), Childrens Hosp, Surg Res Lab, Hunnewell 103,300 Longwood Ave, Boston, MA 02115 USA. RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X FU NCI NIH HHS [P01 CA45548] NR 60 TC 1051 Z9 1100 U1 3 U2 48 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2000 VL 60 IS 7 BP 1878 EP 1886 PG 9 WC Oncology SC Oncology GA 301YK UT WOS:000086338000019 PM 10766175 ER PT J AU Volloch, V Gabai, VL Rits, S Force, T Sherman, MY AF Volloch, V Gabai, VL Rits, S Force, T Sherman, MY TI HSP72 can protect cells from heat-induced apoptosis by accelerating the inactivation of stress kinase JNK SO CELL STRESS & CHAPERONES LA English DT Article ID N-TERMINAL KINASE; FAS LIGAND EXPRESSION; NECROSIS-FACTOR-ALPHA; RAT MESANGIAL CELLS; ATP-BINDING DOMAIN; C-JUN; MAMMALIAN-CELLS; PATHWAY; THERMOTOLERANCE; ACTIVATION AB The major heat shock protein Hsp72 prevents heat-induced apoptosis. We have previously demonstrated that transiently expressed Hsp72 exerts its anti-apoptotic effect by suppressing the activity of stress-kinase JNK, an early component of the apoptotic pathway initiated by heat shock. On the other hand, constitutive expression of Hsp72 does not lead to suppression of heat-induced JNK activation, yet still efficiently prevents apoptosis. To address this apparent contradiction, we studied the effects of constitutively expressed Hsp72 on activation of JNK and apoptosis in Rat-1 fibroblasts. We found that the level of heat-induced apoptosis directly correlated with the duration rather than the magnitude of JNK activity following heat shock. Constitutively expressed Hsp72 strongly reduced the duration of JNK while it did not suppress initial JNK activation. These effects were due to Hsp72-mediated acceleration of JNK dephosphorylation. Addition of vanadate to inhibit JNK phosphatase activity completely prevented the anti-apoptotic action of Hsp72. Therefore, suppression of heat-induced apoptosis by Hsp72 could be fully accounted for by its effects on JNK activity. C1 Tufts Univ, Ctr Biotechnol, Medford, MA 02155 USA. Boston Biomed Res Inst, Watertown, MA 02472 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Volloch, V (reprint author), Tufts Univ, Ctr Biotechnol, 4 Colby St, Medford, MA 02155 USA. RI Gabai, Vladimir/I-1650-2013; OI Force, Thomas/0000-0002-0450-8659 NR 34 TC 44 Z9 47 U1 0 U2 2 PU CELL STRESS SOC INTERNATIONAL PI STORRS PA UNIV CONNECTICUT, DEPT M C B, 75 NORTH EAGLEVILLE RD, U-44, STORRS, CT 06269-3044 USA SN 1355-8145 J9 CELL STRESS CHAPERON JI Cell Stress Chaperones PD APR PY 2000 VL 5 IS 2 BP 139 EP 147 DI 10.1379/1466-1268(2000)005<0139:HCPCFH>2.0.CO;2 PG 9 WC Cell Biology SC Cell Biology GA 356KL UT WOS:000089442400008 PM 11147965 ER PT J AU Prochazka, AV AF Prochazka, AV TI New developments in smoking cessation SO CHEST LA English DT Article; Proceedings Paper CT Symposium on the Multimodality Approach to Lung Cancer - Update CY FEB, 1998 CL UNIV COLORADO, CTR CANC, VAIL, COLORADO SP Univ Colorado, Ctr Canc, Univ Colorado, Sch Med, Off Continuning Educ HO UNIV COLORADO, CTR CANC DE bupropion; drug therapy; nicotine; smoking cessation; therapy; tobacco ID DOUBLE-BLIND TRIAL; NICOTINE NASAL SPRAY; TRANSDERMAL NICOTINE; COST-EFFECTIVENESS; RANDOMIZED TRIAL; GENERAL-PRACTICE; PATCH; INTERVENTIONS; REPLACEMENT; WITHDRAWAL AB Research on smoking has increased in the past several years, and many new therapeutic modalities have been developed. Primary intervention for smoking cessation begins with systematic identification of smokers and a formal diagnosis of nicotine dependence. Providing self-help brochures without clinical advice has marginal efficacy, but these can be useful as an adjunct to clinician intervention. Several large studies have shown that physician advice alone can lead to quit rates of up to 10%, and follow-up for patients trying to quit can double cessation rates. Behavioral therapy alone has demonstrated cessation rates of approximately 20% for those willing to participate. Drug therapy remains the most attractive method of smoking cessation for many patients. The standard approach has been nicotine substitution using one of the four forms of nicotine replacement (gum, patches, nasal spray, inhaler) currently available. The efficacy of nicotine replacement products is similar, with each agent providing a doubling of the cessation rate. Thus, the choice of agent depends on patient factors and preference. Bupropion is the first nonnicotine-containing agent approved for smoking cessation, with cessation rates ranging from 10.5 to 24.4%, depending on dose. One-year follow-up suggests a continued benefit with this agent, The combination of bupropion and transdermal nicotine has also been shown to be effective for smoking cessation in clinical trials. Effective approaches to smoking cessation should combine identification of smokers, provision of advice at each visit, and widespread availability of treatment. C1 Denver VA Med Ctr, Ambulatory Care Sect, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Gen Internal Med, Denver, CO 80262 USA. RP Prochazka, AV (reprint author), Denver VA Med Ctr, Ambulatory Care Sect, 1055 Clermont, Denver, CO 80220 USA. NR 52 TC 26 Z9 26 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD APR PY 2000 VL 117 IS 4 SU 1 BP 169S EP 175S DI 10.1378/chest.117.4_suppl_1.169S PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 308CA UT WOS:000086690000018 PM 10777474 ER PT J AU Tambouret, R Geisinger, KR Powers, CN Khurana, KK Silverman, JF Bardales, R Pitman, MB AF Tambouret, R Geisinger, KR Powers, CN Khurana, KK Silverman, JF Bardales, R Pitman, MB TI The clinical application and cost analysis of fine-needle aspiration biopsy in the diagnosis of mass lesions in sarcoidosis SO CHEST LA English DT Article DE cytology; fine-needle aspiration biopsy; sarcoidosis ID WEGENERS GRANULOMATOSIS; HODGKINS-DISEASE; WHIPPLES DISEASE; SPECIAL STAINS; LYMPH-NODES; CYTOLOGY; LUNG; TUBERCULOSIS; MEDIASTINUM; FEATURES AB Background: Sarcoidosis is a prevalent disease of unknown cause characterized by granulomatous inflammation that often creates deep and/or superficial mass lesions. Tissue samples ale considered the "gold standard" ill diagnosis; however, it is a medically treated disease. We analyzed the utility and relative cost-effectiveness of fine-needle aspiration biopsy (FNAB) in the clinical investigation of patients with both suspected and unsuspected sarcoidosis. Methods: All FNAB cases with sarcoidosis either as the cytologic diagnosis or mentioned as part of the differential diagnosis were retrospectively reviewed for clinical history, follow-up, cytologic features, and surgical pathology findings. Comparative anal? sis of cost of FNAB and excisional biopsy were also made. Results: Thirty-two FNABs in 28 patients included 17 women and 11 men, Anatomic sites included lymph node (n = 17), lung (n = 5), salivary gland (n = 8), and liver (n = 2), Sarcoidosis had already been diagnosed or was a clinical consideration prior to FNAB ill 14 cases. Chest radiograph showed abnormal findings in 19 cases. Angiotensin-converting enzyme (ACE) wits measured in seven patients and was elevated in four. All aspirates showed granulomatous inflammation; in 22 patients, special stains or cultures for microorganisms n ere negative, Simultaneous or subsequent excisional biopsies confirmed the FNAB findings in 17 patients. Institutional ratios of excisional biopsy to FNAB in the diagnosis of sarcoidosis ranged from 4 to 19:1, The cost of FNAB was only 12.5 to 50% that of tissue biopsy, Conclusions: FNAB appears to be underutilized in the diagnosis of sarcoidosis. When used in conjunction with radiologic and laboratory data, FNAB may be a reliable and cost-effective method of diagnosis, especially in patients with an established diagnosis of sarcoidosis. C1 Harvard Univ, Sch Med, James Wright Labs, Gen Hosp, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pathol, Richmond, VA 23298 USA. SUNY Hlth Sci Ctr, Dept Pathol, Syracuse, NY 13210 USA. Allegheny Univ Hlth Sci, Allegheny Gen Hosp, Dept Pathol, Pittsburgh, PA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. RP Tambouret, R (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 43 TC 28 Z9 30 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 APR PY 2000 VL 117 IS 4 BP 1004 EP 1011 DI 10.1378/chest.117.4.1004 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 307AK UT WOS:000086631100016 PM 10767231 ER PT J AU Pereira, N Parisi, A Dec, GW Choo, J Hajjar, R Gordon, PC AF Pereira, N Parisi, A Dec, GW Choo, J Hajjar, R Gordon, PC TI Myocardial stunning in hyperthyroidism SO CLINICAL CARDIOLOGY LA English DT Article DE hyperthyroidism; left ventricular dysfunction; myocardial stunning ID REVERSIBLE CARDIOMYOPATHY; CORONARY VASOSPASM; HEART-FAILURE; THYROTOXICOSIS; SPASM; STATE AB The cases of two patients with hyperthyroidism and acute left ventricular (LV) dysfunction with segmental wall motion abnormalities resulting in heart failure are reported. Both had electrocardiographic changes mimicking ischemic coronary artery disease. Treatment with antithyroid medications, beta blockers, and angiotensin-converting enzyme inhibitors rapidly restored LV function. The rapid reversibility suggests a role for myocardial stunning, an important entity to recognize in hyperthyroidism since this form of LV dysfunction can be reversed with appropriate treatment. C1 Brown Univ, Miriam Hosp, Sch Med, Providence, RI 02906 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Heart Failure Cardiac Transplant Serv, Boston, MA 02114 USA. RP Gordon, PC (reprint author), Brown Univ, Miriam Hosp, Sch Med, 164 Summit Ave, Providence, RI 02906 USA. NR 13 TC 9 Z9 13 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD APR PY 2000 VL 23 IS 4 BP 298 EP 300 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 299CZ UT WOS:000086179400017 PM 10763082 ER PT J AU Carroll, MC AF Carroll, MC TI A protective role for innate immunity in autoimmune disease SO CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT 1st Annual Forum on Immunologic Science - A View of the Cutting Edge CY JUN 25-27, 1999 CL DALLAS, TEXAS DE complement receptors; follicular dendritic cells; systemic lupus erythematosus; natural antibody ID SYSTEMIC LUPUS-ERYTHEMATOSUS; REACTIVE LYMPHOCYTES-B; ANTIGEN-RECEPTOR; COMPLEMENT RECEPTOR-1; AUTOANTIBODY PRODUCTION; MONOCLONAL-ANTIBODIES; PERIPHERAL TOLERANCE; NEGATIVE SELECTION; ACQUIRED-IMMUNITY; CELL REPERTOIRE AB Systemic lupus erythematosus is an incurable autoimmune disease characterized by autoantibodies directed against highly conserved nuclear proteins and DNA. While the cause of lupus is not known, B-lymphocytes are essential for disease. Most striking is that deficiency in components of the innate immune system such as complement is a major risk factor in disease. One explanation for the involvement of complement and innate immunity is that they are important in the induction and maintenance of B cell tolerance to lupus antigens. (C) 2000 Academic Press. C1 Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Carroll, MC (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, 200 Longwood Ave, Boston, MA 02115 USA. NR 69 TC 22 Z9 23 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2000 VL 95 IS 1 SU S BP S30 EP S38 DI 10.1006/clim.1999.4813 PN 2 PG 9 WC Immunology SC Immunology GA 303EQ UT WOS:000086408700006 PM 10729235 ER PT J AU Sachs, DH AF Sachs, DH TI Mixed chimerism as an approach to transplantation tolerance SO CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT 1st Annual Forum on Immunologic Science - A View of the Cutting Edge CY JUN 25-27, 1999 CL DALLAS, TEXAS DE chimerism; tolerance; transplantation; xenotransplantation ID NONLETHAL PREPARATIVE REGIMEN; BONE-MARROW TRANSPLANTATION; DONOR-SPECIFIC TOLERANCE; ALLOGENEIC CHIMERISM; CYNOMOLGUS MONKEYS; NUDE-MICE; PIG; XENOGRAFTS; REJECTION; INDUCTION AB The induction of tolerance to transplanted organs could make transplantation safer and more uniformly successful. One of the most promising approaches currently being investigated involves the induction of deletional tolerance through the establishment of "mixed chimerism." In this laboratory, we first studied mixed chimerism as an approach to transplantation tolerance in mice, using a nonmyeloablative preparative regimen consisting of 300 R whole-body irradiation, 700 R thymic irradiation, and treatment with monoclonal antibodies to CD4 and CD8. This approach has subsequently been extended successfully to the induction of tolerance to renal transplants in fully mismatched cynomolgus monkeys. In addition, the same approach, with minor modifications, has been found effective in producing mixed chimerism and transplantation tolerance in the concordant xenogeneic baboon to cynomolgus monkey species combination. Because pigs have many advantages as a potential xenograft donor for humans, we are also trying to extend our nonmyeloablative regimen for production of mixed chimerism to the discordant pig --> primate combination. We have used absorption of natural antibodies to prevent hyperacute rejection and then proceeded with a mixed chimerism approach. Administration of pig hematopoietic stem cells along with pig recombinant cytokines (SCF and IL-3) to primates has enabled the pig bone marrow to survive in these xenogeneic hosts for over 6 months. This chimerism has apparently been sufficient to markedly diminish T cell immunity and the induction of new T-cell-dependent responses. However, to date we have not succeeded in preventing the return of natural antibodies, which appear to be the cause of eventual loss of organ transplants and are the subject of further intensive investigations. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02129 USA. RP Sachs, DH (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02129 USA. FU NHLBI NIH HHS [2PO1 HL18646]; NIAID NIH HHS [2RO1 AI31046, 5RO1 AI37692] NR 36 TC 41 Z9 43 U1 0 U2 1 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD APR PY 2000 VL 95 IS 1 SU S BP S63 EP S68 DI 10.1006/clim.1999.4814 PN 2 PG 6 WC Immunology SC Immunology GA 303EQ UT WOS:000086408700009 PM 10729238 ER PT J AU Gross, PA Asch, S Kitahata, MM Freedberg, KA Barr, D Melnick, DA Bozette, SA AF Gross, PA Asch, S Kitahata, MM Freedberg, KA Barr, D Melnick, DA Bozette, SA TI Performance measures for guidelines on preventing opportunistic infections in patients infected with human immunodeficiency virus SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID PNEUMOCYSTIS-CARINII PNEUMONIA; ACTIVE ANTIRETROVIRAL THERAPY; SOCIETY USA PANEL; HIV-INFECTION; UPDATED RECOMMENDATIONS; UNITED-STATES; AIDS; DISCONTINUATION; PROPHYLAXIS; MANAGEMENT AB This article serves as a complement to the 1999 US Public Health Service/Infectious Diseases Society of America guidelines on the prevention of opportunistic infections in persons infected with HIV, published in this issue of Clinical Infectious Diseases [1], A number of performance measures to assess compliance with the guidelines and to aid in their implementation are proposed. C1 Hackensack Univ, Med Ctr, Dept Internal Med, Hackensack, NJ 07601 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Vet Adm Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Vet Adm San Diego Healthcare Syst, San Diego, CA USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Rand Hlth, Santa Monica, CA USA. Univ Washington, Ctr AIDS & STD, Harborview Med Ctr, Seattle, WA 98195 USA. Boston Univ, Harvard Boston Med Ctr, Boston, MA 02215 USA. George Washington Univ, Ctr Hlth Policy Res, Forum Collaborat HIV Res, Washington, DC USA. Kaiser Permanente, Springfield, VA USA. RP Gross, PA (reprint author), Hackensack Univ, Med Ctr, Dept Internal Med, 30 Prospect Ave, Hackensack, NJ 07601 USA. FU NIAID NIH HHS [R01 AI058736] NR 32 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5720 SOUTH WOODLAWN AVE, CHICAGO, IL 60637-1603 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD APR PY 2000 VL 30 SU 1 BP S85 EP S93 DI 10.1086/313845 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 314QQ UT WOS:000087067600008 PM 10770917 ER PT J AU Hornicek, FJ Gebhardt, MC Wolfe, MW Kharrazi, D Takeshita, H Parekh, SG Zurakowski, D Mankin, HJ AF Hornicek, FJ Gebhardt, MC Wolfe, MW Kharrazi, D Takeshita, H Parekh, SG Zurakowski, D Mankin, HJ TI P-glycoprotein levels predict poor outcome in patients with osteosarcoma SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 4th Combined Meeting of the American-and-European-Musculoskeletal-Tumor-Societies CY MAY 06-10, 1998 CL WASHINGTON, D.C. SP Amer & European Musculoskeletal Tumor Soc ID MULTIDRUG-RESISTANCE GENE; SOFT-TISSUE; EXPRESSION; EFFLUX AB To evaluate the relationship between the expression of P-glycoprotein by osteosarcomas and the rate of metastasis and death, a retrospective review of 172 patients who were diagnosed with osteosarcoma between 1987 and 1992 was performed. Forty patients had P-glycoprotein levels available. The majority of the osteosarcomas were Stage II-B (33 patients), with the remaining seven being Stage III. Tumor sites included 25 femurs, seven humeri, five tibias, and one each of pelvis, radius, and fibula. The patients with Stage III disease at presentation were treated differently from the time of diagnosis and therefore, these seven patients with Stage III osteosarcoma were excluded from additional analyses. The expression of P-glycoprotein by cultured tumor cells from biopsy specimens was determined using immunofluorescent microscopy. In the 33 patients with Stage IIB osteosarcoma with detectable P-glycoprotein, 67% (10 of 15) had metastases develop as compared with 28% (five of 18) of patients with undetectable P-glycoprotein, Similarly, 53% (eight of 15) of patients with tumors expressing P-glycoprotein died of disease compared with 11% (two of 18) with no detectable P-glycoprotein. Expression of P-glycoprotein by tumor cells seems to be associated with an estimated ninefold increase in the odds of death and a fivefold increase in the odds of metastases in patients,vith Stage IIB osteosarcoma, Kaplan-Meier survivorship analysis revealed that patients with detectable glycoprotein fared worse in terms of survival time and metastasis-free survival. Adjusting for covariates in the Cox proportional hazards model, expression of P-glycoprotein and its level were significantly predictive of time to death in patients with Stage IIB osteosarcoma. C1 Massachusetts Gen Hosp, Orthopaed Oncol Unit, Boston, MA 02114 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. RP Hornicek, FJ (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Unit, GRB 606,55 Fruit St, Boston, MA 02114 USA. NR 18 TC 27 Z9 31 U1 0 U2 1 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 APR PY 2000 IS 373 BP 11 EP 17 DI 10.1097/00003086-200004000-00003 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 303RJ UT WOS:000086437400004 PM 10810457 ER PT J AU DeGroot, H Mankin, H AF DeGroot, H Mankin, H TI Total knee arthroplasty in patients who have massive osteoarticular allografts SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT 4th Combined Meeting of the American-and-European-Musculoskeletal-Tumor-Societies CY MAY 06-10, 1998 CL WASHINGTON, D.C. SP Amer & European Musculoskeletal Tumor Soc ID TUMORS; BONE AB The authors treated 24 patients with total knee arthroplasty who had a massive allograft used to reconstruct the knee and who later bad instability, degeneration, or a fracture near the articular surface of the graft develop. Patients then were followed up for a minimum of 2 years and a mean of 8.2 years, Overall, 96% of the patients retained a functional limb, although 46% underwent revision surgery, and an additional 12% had some other major complication. Statistical analysis showed a significant negative effect of chemotherapy on revision-free survival of the prosthesis. Patients with high-grade tumors were at significantly greater risk of fracture of the allograft-prosthesis composite. Certain technical factors were identified that seemed to predispose the allograft-prosthesis reconstructions to early failure. Total knee arthroplasty can be used to treat patients with complications of massive osteoarticular allografts and may prolong the functional life of an otherwise successful Limb salvage reconstruction. C1 Univ Massachusetts, Dept Orthoped & Phys Rehabil, Worcester, MA 01605 USA. Massachusetts Gen Hosp, Orthopaed Oncol Unit, Boston, MA 02114 USA. RP DeGroot, H (reprint author), Univ Massachusetts, Dept Orthoped, 55 Lake Ave N, Worcester, MA 01655 USA. NR 18 TC 5 Z9 5 U1 0 U2 1 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 APR PY 2000 IS 373 BP 62 EP 72 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 303RJ UT WOS:000086437400010 PM 10810463 ER PT J AU Temple, HT Scully, SP O'Keefe, RJ Katapurum, S Mankin, HJ AF Temple, HT Scully, SP O'Keefe, RJ Katapurum, S Mankin, HJ TI Clinical outcome of 38 patients with juxtacortical osteosarcoma SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID PAROSTEAL OSTEOGENIC-SARCOMA AB Thirty-eight patients presented with previously untreated, predominantly low-grade juxtacortical osteosarcoma, There were 12 (32%) men and 26 (68%) women with a mean age of 28.9 years. The most common sites of tumor were the distal femur (n = 28) and proximal tibia (n = 5), Twenty-five patients presented with Stage LB tumors. Twelve had Stage IIB, which although it was predominantly low-grade, had an area of high grade tumor, so the tumors were considered dedifferentiated. One patient had Stage III tumor, All patients were alive at 6.75 years' average followup, Negative but close margins were achieved in all but two patients (range, 1-80 mm), Intramedullary extension was seen in 17 (44.7%) patients, and the adjacent cortex was invoiced in 27 (71.1%) patients, There was no statistically significant difference between tumor size, site, radiographic appearance, cortical or intramedullary extension, grade, resection margin, or pretreatment duration of symptoms and local recurrence. Intramedullary extension of tumor does not seem to increase the risk of metastatic disease, Dedifferentiation of predominantly low-grade juxtacortical osteosarcoma in not previously treated tumors is uncommon, Based on these data, close but negative margins may be adequate in achieving local disease control and preventing metastases in these patients. C1 Univ Miami, Sch Med, Dept Orthopaed & Rehabil, Miami, FL USA. Univ Rochester, Sch Med & Dent, Dept Orthopaed Surg, Rochester, NY USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed, Boston, MA USA. RP Scully, SP (reprint author), Duke Univ, Med Ctr, Dept Surg Orthopaed, Box 3312, Durham, NC 27710 USA. NR 25 TC 9 Z9 10 U1 0 U2 0 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 APR PY 2000 IS 373 BP 208 EP 217 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 303RJ UT WOS:000086437400026 PM 10810479 ER PT J AU Chin, KR Altman, DT Altman, GT Mitchell, TM Tomford, WW Lhowe, DW AF Chin, KR Altman, DT Altman, GT Mitchell, TM Tomford, WW Lhowe, DW TI Retrograde nailing of femur fractures in patients with myelopathy and who are nonambulatory SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID FEMORAL-SHAFT; FIXATION; PLATE; KNEE AB The authors studied 10 consecutive patients with closed femoral shaft or supracondylar fractures who mere nonambulatory and who mere treated by reamed retrograde intramedullary nailing,ia an intercondylar notch approach. The study consisted of five women and five men with an average age of 60.7 years (range, 40-89 gears). Sis patients had spinal cord lesions, one had a brain injury, one had cerebral palsy, one had multiple sclerosis, and one had progressive myelopathy. Three fractures were supracondylar, and seven fractures involved the mid-distal diaphysis. The average time of surgery was 110 minutes (range, 70-225 minutes) with an average estimated blood loss of 288 mt (range, 150-400 mt). There were two postoperative deaths (at 15 days and 2 months, respectively) after the procedure that were attributable to pneumonia. The remaining eight patients were observed for an average of 13 months (range, 6-30 months) after surgery. All fractures healed as evaluated radiographically. Retrograde intramedullary nailing is a simple, safe, and effective alternative to nonoperative treatment for femoral shaft or supracondylar fractures in patients who are nonambulatory. Stabilization by this method allows fracture healing and rapid return of patients to their previous level of function. There mere no nonunions, malunions, significant shortening, implant failure, or mound infections. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Mercy Hosp, Dept Orthopaed Surg, Pittsburgh, PA USA. Beth Israel Deaconess Med Ctr, Dept Orthopaed Surg, Boston, MA USA. RP Chin, KR (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, GRB 606, Boston, MA 02114 USA. NR 28 TC 5 Z9 5 U1 0 U2 1 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 APR PY 2000 IS 373 BP 218 EP 226 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 303RJ UT WOS:000086437400027 PM 10810480 ER PT J AU Ryan, JM Dupuy, DE Pitman, M Boland, GW Hahn, PF Mueller, PR AF Ryan, JM Dupuy, DE Pitman, M Boland, GW Hahn, PF Mueller, PR TI Metastases to the liver from extraskeletal myxoid chondrosarcoma and successful treatment with percutaneous ethanol injection SO CLINICAL RADIOLOGY LA English DT Article ID MESENCHYMAL CHONDROSARCOMA; THERAPY C1 Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Musculoskeletal Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cytol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ryan, JM (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Abdominal & Intervent Radiol, White 220,55 Fruit St, Boston, MA 02114 USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 13 TC 4 Z9 5 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0009-9260 J9 CLIN RADIOL JI Clin. Radiol. PD APR PY 2000 VL 55 IS 4 BP 314 EP 317 DI 10.1053/crad.1999.0076 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 351BA UT WOS:000089135100012 PM 10767194 ER PT J AU Bodennec, J Brichon, G Koul, O Portoukalian, J Zwingelstein, G AF Bodennec, J Brichon, G Koul, O Portoukalian, J Zwingelstein, G TI Differential labelling of sphingolipids by [H-3]serine and ([H-3]methyl)-methionine in fish leukocytes SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE phytosphingosine; sphingosine; neutral glycosphingolipids; ceramide; sphingomyelin; fish leukocytes; serine; methionine ID THIN-LAYER CHROMATOGRAPHY; SACCHAROMYCES-CEREVISIAE; SPHINGOMYELIN METABOLISM; SIMULTANEOUS SEPARATION; BICINCHONINIC ACID; BIOSYNTHESIS; CELLS; DIACYLGLYCEROL; TEMPERATURE; GLYCINE AB Long chain bases are constituents of all sphingolipids and their biosynthesis is presumed to occur via the initial condensation of serine with palmitoyl-CoA. The biosynthesis of phytosphingosine, a long chain base containing three hydroxyl groups, has been less studied than sphingosine but is assumed to occur by hydroxylation of sphinganine. We report in this paper that the label from ([H-3]methyl)-methionine is preferentially incorporated into phytosphingosine bases of neutral glycosphingolipids, whereas the label from [H-3]serine is mainly incorporated into the sphingoid base of sphingomyelin. These results show that in fish leukocytes the biosynthesis of individual sphingoid bases and their downstream sphingolipid products follow different pathways of metabolism. Our observations suggest that in fish leukocytes the synthesis of the constitutive long chain bases of sphingomyelin and complex glycosphingolipids is coordinately regulated and may be localized in separate compartments. (C) 2000 Elsevier Science Inc. All rights reserved. C1 Univ Lyon Sud, Fac Med, Lab Tumor Glycobiol, F-69921 Oullins, France. Univ Lyon 1, Inst Michel Pacha, F-83500 La Seyne Sur Mer, France. Eunice Kennedy Shriver Ctr Mental Retardat Inc, Waltham, MA 02452 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. RP Portoukalian, J (reprint author), Univ Lyon Sud, Fac Med, Lab Tumor Glycobiol, Lyon Sud BP 12, F-69921 Oullins, France. FU NICHD NIH HHS [HD 13021] NR 36 TC 0 Z9 2 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0305-0491 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD APR PY 2000 VL 125 IS 4 BP 523 EP 531 DI 10.1016/S0305-0491(00)00153-X PG 9 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 322YU UT WOS:000087537800009 PM 10904865 ER PT J AU Erwin, BA Newman, E McMackin, RA Morrissey, C Kaloupek, DG AF Erwin, BA Newman, E McMackin, RA Morrissey, C Kaloupek, DG TI PTSD, malevolent environment, and criminality among criminally involved male adolescents SO CRIMINAL JUSTICE AND BEHAVIOR LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; SEXUAL ABUSE; PREVALENCE; CONSEQUENCES; OFFENDERS; VIOLENCE; IMPAIRMENTS; COMMUNITY; EXPOSURE; VICTIMS AB Post-traumatic stress disorder (PTSD) is a chronic and impairing disorder that is pervasive but often overlooked in the assessment and treatment of adolescents involved in the juvenile justice system. The present study examined the occurrence of malevolent environment factors (e.g., poverty, hunger), substance use, trauma exposure, and PTSD among 51 male adolescent offenders recruited from juvenile treatment facilities representing the highest level of security in Massachusetts. Participants completed self-report instruments and semistructured interviews. Much of the information gathered was verified with records kept by the Department of Youth Services. The results of the current study suggest that among male adolescent offenders, exposure to malevolent environmental factors and traumatic life events is common and rates of PTSD are high. We conclude that PTSD and lifetime exposure to potentially traumatic events should be assessed routinely in rehabilitative settings. C1 Boston VA Med Ctr, Natl Ctr PTSD, Boston, MA 02130 USA. Massachusetts Dept Publ Hlth, Boston, MA 02111 USA. Boston VA Med Ctr, Natl Ctr PTSD, Boston, MA 02130 USA. RP Erwin, BA (reprint author), Temple Univ, Dept Psychol, Adult Anziety Clin Temple, Weiss Hall, Philadelphia, PA 19122 USA. OI Kaloupek, Danny/0000-0002-0795-593X NR 48 TC 36 Z9 36 U1 4 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0093-8548 J9 CRIM JUSTICE BEHAV JI Crim. Justice Behav. PD APR PY 2000 VL 27 IS 2 BP 196 EP 215 DI 10.1177/0093854800027002004 PG 20 WC Psychology, Clinical; Criminology & Penology SC Psychology; Criminology & Penology GA 297VA UT WOS:000086102300004 ER PT J AU Medoff, BD Harris, RS Kesselman, H Venegas, J Amato, MBP Hess, D AF Medoff, BD Harris, RS Kesselman, H Venegas, J Amato, MBP Hess, D TI Use of recruitment maneuvers and high positive end-expiratory pressure in a patient with acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; mechanical ventilation; positive end-expiratory pressure; recruitment; lung injury ID INDUCED LUNG INJURY; VOLUME CURVE; MECHANICAL VENTILATION; TIDAL VOLUME; FAILURE; PEEP; MANAGEMENT; INFLATION; STRATEGY; SYSTEM AB Objective: To present the use of a novel high-pressure recruitment maneuver followed by high levels of positive end-expiratory pressure in a patient with the acute respiratory distress syndrome (ARDS), Design: Observations in one patient. Setting: The medical intensive care unit at a tertiary care university teaching hospital. Patient: A 32-yr-old woman with severe ARDS secondary to streptococcal sepsis, Interventions: The patient had severe gas exchange abnormalities because of acute lung injury and marked lung collapse. Attempts to optimize recruitment based on the inflation pressure-volume (:PV) curve were not sufficient to avoid dependent lung collapse. We used a recruitment maneuver using 40 cm H2O of positive end-expiratory pressure (PEEP) and 20 cm H2O of pressure controlled ventilation above PEEP for 2 mins to successfully recruit the lung. The recruitment was maintained with 25 cm H2O of PEEP, which was much higher than the PEEP predicted by the lower inflection point (P-Flex) of the PV curve. Measurements and Main Results: Recruitment was assessed by improvements in oxygenation and by computed tomography of the chest, With the recruitment maneuvers, the patient had a dramatic improvement in gas exchange and we were able to demonstrate nearly complete recruitment of the lung by computed tomography, A PV curve was measured that demonstrated a P-Flex of 16-18 cm H2O. Conclusion: Accumulating data suggest that the maximization and maintenance of lung recruitment may reduce lung parenchymal injury from positive pressure ventilation in ARDS, We demonstrate that in this case PEEP atone was not adequate to recruit the injured lung and that a high-pressure recruitment maneuver was required, After recruitment, high-level PEEP was needed to prevent derecruitment and this level of PEEP was not adequately predicted by the P-Flex of the PV curve. C1 Massachusetts Gen Hosp, Resp Care Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia Biomed Engn, Boston, MA 02114 USA. Univ Sao Paulo, Hosp Clin, Div Pulm, Resp Intens Care Unit, Sao Paulo, Brazil. RP Hess, D (reprint author), Massachusetts Gen Hosp, Resp Care Serv, Ellison 401,55 Fruit St, Boston, MA 02114 USA. NR 33 TC 73 Z9 79 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2000 VL 28 IS 4 BP 1210 EP 1216 DI 10.1097/00003246-200004000-00051 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 311AV UT WOS:000086862800051 PM 10809308 ER PT J AU Quezado, ZMN Eichacker, PQ AF Quezado, ZMN Eichacker, PQ TI Inhaled nitric oxide: Move than a selective pulmonary vasodilator SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE inhaled nitric oxide; vasodilator; systemic effects; sepsis; leukocyte; inflammation ID RESPIRATORY-DISTRESS SYNDROME; ACUTE LUNG INJURY; HYPERTENSION; THERAPY; SEPSIS; NO C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. RP Quezado, ZMN (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Quezado, Zenaide/O-4860-2016 OI Quezado, Zenaide/0000-0001-9793-4368 NR 16 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2000 VL 28 IS 4 BP 1235 EP 1236 DI 10.1097/00003246-200004000-00063 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 311AV UT WOS:000086862800063 PM 10809320 ER PT J AU von Boehmer, H Rajewsky, K AF von Boehmer, H Rajewsky, K TI Lymphocyte development - Commitment, selection and switching - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cologne, Genet Inst, D-50931 Cologne, Germany. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2000 VL 12 IS 2 BP 141 EP 143 DI 10.1016/S0952-7915(99)00063-1 PG 3 WC Immunology SC Immunology GA 292GQ UT WOS:000085786300001 ER PT J AU Klein, L Kyewski, B AF Klein, L Kyewski, B TI Self-antigen presentation by thymic stromal cells: a subtle division of labor SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID SINGLE MHC/PEPTIDE LIGAND; T-CELLS; CLASS-II; POSITIVE SELECTION; NEGATIVE SELECTION; TOLERANCE INDUCTION; EPITHELIAL-CELLS; INTRATHYMIC EXPRESSION; PRESENTATION PATHWAY; PRESENTING CELLS AB Self-antigen-MHC complexes expressed by thymic stromal cells serve as ligands for TCR-mediated positive and negative selection, resulting in a self-M HC-restricted, self-tolerant T cell repertoire. It has recently become apparent that thymic stromal cells differ in their accessibility to antigen as well as their ability to process and present antigen, These differences result in the sampling by thymic stromal cells of largely nonoverlapping self-antigen pools and the display of self-peptide profiles specific for each cell type. In conjunction with single or serial cell-cell interactions between thymocytes and stromal cells, such differences in self-antigen display allow for maximal (re)presentation of 'self' in the thymus and optimize the efficacy of positive and negative selection. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. German Canc Res Ctr, Tumor Immunol Program, D-69120 Heidelberg, Germany. RP Klein, L (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. RI Klein, Ludger/G-8785-2011 NR 76 TC 104 Z9 105 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD APR PY 2000 VL 12 IS 2 BP 179 EP 186 DI 10.1016/S0952-7915(99)00069-2 PG 8 WC Immunology SC Immunology GA 292GQ UT WOS:000085786300007 PM 10712940 ER PT J AU Kuperberg, G Heckers, S AF Kuperberg, G Heckers, S TI Schizophrenia and cognitive function SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Review ID WORKING-MEMORY; THOUGHT-DISORDER; DEFICITS; WORD; DYSFUNCTION; ABNORMALITIES; TASK AB Schizophrenia is often associated with cognitive deficits, particularly within the domains of memory and language. Specific cognitive deficits have recently been linked to psychotic phenomena, including verbal hallucinations and disorganized speech. Impairments of working and semantic memory are primarily due to dysfunction of the frontal cortex, temporal cortex, and hippocampus. Cognitive skills in schizophrenia predict social functioning and may serve as outcome measures in the development of effective treatment strategies. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. RP Kuperberg, G (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CNY-9,Bldg 149,13th St, Charlestown, MA 02129 USA. RI Heckers, Stephan/F-3051-2010 OI Heckers, Stephan/0000-0003-3601-9910 NR 46 TC 154 Z9 160 U1 5 U2 9 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD APR PY 2000 VL 10 IS 2 BP 205 EP 210 DI 10.1016/S0959-4388(00)00068-4 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 306JP UT WOS:000086593800007 PM 10753790 ER PT J AU McKee, GT AF McKee, GT TI The cervical (Pap) smear-personal experience on both sides of the Atlantic SO CYTOPATHOLOGY LA English DT Review ID LABORATORY-ACCREDITATION PROGRAM; OF-AMERICAN-PATHOLOGISTS; PAPANICOLAOU SMEAR; LIABILITY ISSUES; CYTOLOGY; CYTOPATHOLOGY; REGULATIONS; PERSPECTIVE; QUALITY C1 Massachusetts Gen Hosp, Dept Cytopathol, Boston, MA 02114 USA. RP McKee, GT (reprint author), Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. NR 31 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0956-5507 J9 CYTOPATHOLOGY JI Cytopathology PD APR PY 2000 VL 11 IS 2 BP 82 EP 90 DI 10.1046/j.1365-2303.2000.00221.x PG 9 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 308NM UT WOS:000086719500002 PM 10772007 ER PT J AU Hayashi, T Hirshman, MF Fujii, N Habinowski, SA Witters, LA Goodyear, LJ AF Hayashi, T Hirshman, MF Fujii, N Habinowski, SA Witters, LA Goodyear, LJ TI Metabolic stress and altered glucose transport - Activation of AMP-activated protein kinase as a unifying coupling mechanism SO DIABETES LA English DT Article ID RAT SKELETAL-MUSCLE; TISSUE DISTRIBUTION; BETA-SUBUNIT; INSULIN; CONTRACTION; CELL; TRANSLOCATION; STIMULATION; ADIPOCYTES; WORTMANNIN AB 5' AMP-activated protein kinase (AMPK) can be activated in response to cellular fuel depletion and leads to switching off ATP-consuming pathways and switching on ATP-regenerating pathways in many cell types. We have hypothesized that AMPK is a central mediator of insulin-independent glucose transport, which enables fuel-depleted muscle cells to take up glucose for ATP regeneration under conditions of metabolic stress. To test this hypothesis, rat epitrochlearis muscles were isolated and incubated in vitro under several conditions that evoke metabolic stress accompanied by intracellular fuel depletion, Rates of glucose transport in the isolated muscles were increased by all of these conditions, including contraction (5-fold above basal), hypoxia (8-fold), 2,4-dinotrophenol (11-fold), rotenone (7-fold), and hyperosmolarity (8-fold). All of these stimuli simultaneously increased both alpha 1 and alpha 2 isoform-specific AMPK activity. There was close correlation between alpha 1 (r(2) = 0.72) and alpha 2 (r(2) = 0.67) AMPK activities and the rate of glucose transport, irrespective of the metabolic stress used, all of which compromised muscle fuel status as judged by ATP, phosphocreatine, and glycogen content, 5-Aminoimidazole-4-carboxamide ribonucleoside, a pharmacological AMPK activator that is metabolized to an AMP-mimetic ZMP, also increased both glucose transport and AMPK activity but did not change fuel status, Insulin stimulated glucose transport by 6.5-fold above basal but did not affect AMPK activity, These results suggest that the activation of AMPK may be a common mechanism leading to insulin-independent glucose transport in skeletal muscle under conditions of metabolic stress. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dartmouth Coll Sch Med, Dept Med & Biochem, Endocrine Metab Div, Hanover, NH USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR42238, AR45670]; NIDDK NIH HHS [DK375712] NR 38 TC 315 Z9 319 U1 2 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2000 VL 49 IS 4 BP 527 EP 531 DI 10.2337/diabetes.49.4.527 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 300YR UT WOS:000086281800001 PM 10871188 ER PT J AU Abraham, RS Kudva, YC Wilson, SB Strominger, JL David, CS AF Abraham, RS Kudva, YC Wilson, SB Strominger, JL David, CS TI Co-expression of HLA DR3 and DQ8 results in the development of spontaneous insulitis and loss of tolerance to GAD65 in transgenic mice SO DIABETES LA English DT Article ID DEPENDENT DIABETES-MELLITUS; COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; T-CELL; PRONE MICE; SUSCEPTIBILITY; IDDM; RESISTANCE; MOLECULES; ALPHA AB Specific HLA DQ and DR alleles have been associated with susceptibility to type 1 diabetes. HLA DQ8 and DQ2 have been shown to strongly predispose to disease and to be in Linkage disequilibrium with at-risk DR4 and DR3 alleles, respectively. Inheritance of a mixed DR3/DR4 haplotype confers the greatest risk. A double transgenic mouse expressing both DR3 and DQ8 was generated to investigate potential major histocompatibility complex class II interactions. The DR3/DQ8 transgenic mice developed a spontaneous loss of tolerance to GAD65, in which the T-cell response to GAD65 was restricted by HLA DR. Although the mice also showed spontaneous insulitis, they did not progress to overt diabetes, Mice expressing either transgene (DQ8 or DR3) alone showed mild infiltration of their islets, which disappeared when DQ8 or DR3 was co-expressed with a resistant DR2 allele or the neutral DQ6 allele. Therefore, in a fashion analogous to human diabetes, the murine model demonstrated a requirement for a combination of at-risk DR and DQ allotypes for the initiation of spontaneous autoimmunity. C1 Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Endocrinol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA USA. Harvard Univ, Dept Mol & Cellular Immunol, Cambridge, MA 02138 USA. RP David, CS (reprint author), Mayo Clin & Mayo Fdn, Dept Immunol, 200 1st St SW, Rochester, MN 55905 USA. FU NIAID NIH HHS [AI-14764] NR 47 TC 41 Z9 41 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0012-1797 J9 DIABETES JI Diabetes PD APR PY 2000 VL 49 IS 4 BP 548 EP 554 DI 10.2337/diabetes.49.4.548 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 300YR UT WOS:000086281800004 PM 10871191 ER PT J AU Boyko, EJ Fujimoto, WY Leonetti, DL Newell-Morris, L AF Boyko, EJ Fujimoto, WY Leonetti, DL Newell-Morris, L TI Visceral adiposity and risk of type 2 diabetes - A prospective study among Japanese Americans SO DIABETES CARE LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; BODY-FAT DISTRIBUTION; FASTING PLASMA-INSULIN; ANTHROPOMETRIC MEASUREMENTS; ABDOMINAL OBESITY; COMPUTED-TOMOGRAPHY; TISSUE DISTRIBUTION; MASS INDEX; FOLLOW-UP; MEN AB OBJECTIVE - We conducted a prospective study among Japanese Americans of diabetes incidence in relation to visceral and regional adiposity, fasting insulin and C-peptide, and a measure of insulin secretion, because little prospective data exist on these associations. RESEARCH DESIGN AND METHODS - Baseline variables included plasma glucose, C-peptide, and insulin measured after an overnight fast and 30 and 120 min after a 75-g oral glucose tolerance test; abdominal, thoracic, and thigh fat areas by computed tomography (CT); BMI (kg/m(2)); and insulin secretion (incremental insulin response [IIR]). RESULTS - Study subjects included 290 second-generation (nisei) and 230 third-generation (sansei) Japanese Americans without diabetes, of whom 65 and 13, respectively, developed diabetes. Among nisei, significant predictors of diabetes risk for a 1 SD increase in continuous variables included intra-abdominal fat area (IAFA) (odds ratio, 95% CI) (1.6, 1.1-2.3), fasting plasma C-peptide (1.4, 1.1-1.8), and the IIR (0.5, 0.3-0.9) after adjusting for age, sex, impaired glucose tolerance, family diabetes history, and CT-measured fat areas other than intraabdominal. Intra-abdominal fat area remained a significant predictor of diabetes incidence even after adjustment for BMI, total body fat area, and subcutaneous fat area, although no measure of regional or total adiposity was related to development of diabetes. Among sansei, all adiposity measures were related to diabetes incidence, but, in adjusted models, only IAFA remained significantly associated with higher risk (2.7, 1.4-5.4, BMI-adjusted). CONCLUSIONS - Greater visceral adiposity precedes the development of type 2 diabetes in Japanese Americans and demonstrates an effect independent of fasting insulin, insulin secretion, glycemia, total and regional adiposity, and family history of diabetes. C1 Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. RP Boyko, EJ (reprint author), Vet Affairs Puget Sound, Epidemiol Res & Informat Ctr, 1660 S Columbian Way,S111GIMC, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL-49293]; NIDDK NIH HHS [DK-17047, DK-31170] NR 45 TC 319 Z9 326 U1 0 U2 8 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2000 VL 23 IS 4 BP 465 EP 471 DI 10.2337/diacare.23.4.465 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 298YG UT WOS:000086167900007 PM 10857936 ER PT J AU Stellato, RK Feldman, HA Hamdy, O Horton, ES McKinlay, JB AF Stellato, RK Feldman, HA Hamdy, O Horton, ES McKinlay, JB TI Testosterone, sex hormone-binding globulin, and the development of type 2 diabetes in middle-aged men - Prospective results from the Massachusetts Male Aging Study SO DIABETES CARE LA English DT Article ID INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; ANDROGEN LEVELS; ELDERLY MEN; ADULT MEN; MELLITUS; HYPERINSULINEMIA; WOMEN; OBESE; DYSLIPIDEMIA AB OBJECTIVE - The objective was to examine prospectively the association between low testosterone and sex hormone-binding globulin (SHBG) levels and the subsequent development of type 2 diabetes in men. RESEARCH DESIGN AND METHODS - Analyses were conducted on the cohort of the Massachusetts Male Aging Study, a population-based random sample of men aged 40-70. Of the 1,709 men enrolled in 1987-1989 (T-1), 1,156 were followed up 7-10 years later (T-2). Testosterone and SHBG levels at T-1 were used to predict new cases of diabetes between T-1 and T-2. RESULTS - After controlling for potential confounders, diabetes at follow-up was predicted jointly and independently by lower baseline levels of free testosterone and SHBG. The odds ratio for future diabetes was 1.58 for a decrease of ISD in free testosterone (4 ng/dl) and 1.89 for a 1SD decrease in SHBG (16 nmol/l), both significant at P < 0.02. CONCLUSIONS - Our prospective findings are consistent with previous, mainly cross-sectional reports, suggesting that low levels of testosterone and SHBG play some role in the development of insulin resistance and subsequent type 2 diabetes. C1 New England Res Inst, Watertown, MA 02172 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA USA. RP McKinlay, JB (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02172 USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIA NIH HHS [AG-04673]; NIDDK NIH HHS [DK-44995, DK-51345] NR 40 TC 345 Z9 365 U1 0 U2 5 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2000 VL 23 IS 4 BP 490 EP 494 DI 10.2337/diacare.23.4.490 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 298YG UT WOS:000086167900011 PM 10857940 ER PT J AU Moreno, MJ Clayburne, G Schumacher, HR AF Moreno, MJ Clayburne, G Schumacher, HR TI Processing of noninflammatory synovial fluids with hyaluronidase for cytospin preparations improves the accuracy of differential counts SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article DE neutrophils; monocytes; joint fluid; crystals AB Differential leukocyte counts on noninflammatory synovial fluids (NISF) are not widely reported or used in research, apparently dire to technical, difficulties related to either high viscosity or low numbers of cells. We describe an evaluation of a technique using hyaluronidase and cytospin preparations to study NISF: Twenty-three consecutive synovial fluids (SF) with less than 2,000 white blood cells (WBC)/mm(3) were studied either by the usual smear of a single drop or by adding two drops of hyaluronidase (150 USP units/ml) to 0.25 cc of SF and cytocentrifuging at 800 rpm for 10 min. Both preparations were stained with Wright's stain. Cytospin preparations gave better morphology, and in 22/23 specimens we could count 100 cells on one slide. Smeared preparations gave dark cells and required 2-3 slides to count 100 cells. Differential counts on the cytospin preparations consistently showed higher percentages of monocytes, suggesting that these cells wt l-e underdetected and misinterpreted as lymphocytes on the routine smears. Polymorphonuclear leukocytes (PMN) were significantly less frequent (P 0.005) in osteoarthritis (OA) fluids than in the other diseases with NISF Relatively more PMN may suggest consideration of a diagnosis other than OA. Cytospin preparations of hyaluronicdase-treated NISF may open up an important area for investigation of the role of SF cells in less inflammatory diseases. Published 2000 Wiley-Liss, Inc. C1 Dept Vet Affairs Med Ctr, Arthrit & Immunol Ctr, Philadelphia, PA 19104 USA. RP Schumacher, HR (reprint author), Vet Affairs Med Ctr, Arthrit Immunol Ctr, 151K,Univ & Woodland Ave, Philadelphia, PA 19104 USA. NR 13 TC 13 Z9 14 U1 0 U2 4 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 APR PY 2000 VL 22 IS 4 BP 256 EP 258 DI 10.1002/(SICI)1097-0339(200004)22:4<256::AID-DC13>3.0.CO;2-G PG 3 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 299HP UT WOS:000086193200013 PM 10787150 ER PT J AU Bonetti, M Vitale, RA AF Bonetti, M Vitale, RA TI Asymptotic behavior of a set-statistic SO DISCRETE & COMPUTATIONAL GEOMETRY LA English DT Article ID CONVEX AB The existence theorem of Minkowski for a polytope with given facet normals and areas is adapted to a data-analytic context. More precisely, we show that a centered, random point sample arising from an absolutely continuous distribution in R-d can be uniquely mapped into such a polytope almost surely. With increasing sample size, the sequence of (scaled) polytopes converges almost surely to a limiting convex body that is associated with the underlying distribution. An accompanying central limit theorem is proved using methods from the theory of empirical processes. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Bonetti, M (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 655 Huntington Ave, Boston, MA 02115 USA. OI Bonetti, Marco/0000-0003-2304-4180 NR 21 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0179-5376 J9 DISCRETE COMPUT GEOM JI Discret. Comput. Geom. PD APR PY 2000 VL 23 IS 3 BP 333 EP 341 DI 10.1007/PL00009504 PG 9 WC Computer Science, Theory & Methods; Mathematics SC Computer Science; Mathematics GA 286WE UT WOS:000085471200003 ER PT J AU Greist, JH Osgood-Hynes, DJ Baer, L Marks, IM AF Greist, JH Osgood-Hynes, DJ Baer, L Marks, IM TI Technology-based advances in the management of depression - Focus on the COPE (TM) program SO DISEASE MANAGEMENT & HEALTH OUTCOMES LA English DT Article ID MAJOR DEPRESSION; COMPUTER REMINDERS; PSYCHOTHERAPY; CARE AB Depression remains under-recognised and under-treated despite it being more disabling than any other medical disorder and the availability of effective protocol-based psychotherapy and pharmacotherapy treatments. Prevailing psycho therapy seldom employs evidence-based treatments, continuing instead the use of idiosyncratic psychotherapies of dubious value. Computer interview programs have been developed and evaluated that have the potential to make protocol-based psychotherapy of proven efficacy available over the Internet. Interactive voice response (IVR) makes these programs even more accessible through any touch-tone telephone. COPE(TM) is a self-help program for patients with depression that combines a series of booklets, videotapes and IVR telephone calls. One trial reported significant reductions in Hamilton Depression Rating Scale scores in patients with depression who completed a 12-week COPE(TM) program. Impediments to dissemination of these computer tools that complement, supplement and reinforce best practice values include developer's limited knowledge of business practices and the slow change of practice paradigms. C1 Healthcare Technol Syst LLC, Madison, WI 53717 USA. Massachusetts Gen Hosp, Dept Psychiat, Charleston, MA USA. Inst Psychiat, Dept Expt Psychopathol, London, England. RP Greist, JH (reprint author), Healthcare Technol Syst LLC, 7617 Mineral Point Rd,Suite 300, Madison, WI 53717 USA. NR 34 TC 10 Z9 10 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1173-8790 J9 DIS MANAG HEALTH OUT JI Dis. Manag. Health Outcomes PD APR PY 2000 VL 7 IS 4 BP 193 EP 200 DI 10.2165/00115677-200007040-00003 PG 8 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 306AJ UT WOS:000086573700003 ER PT J AU Dickey, C Ziegner, U Agadjanyan, MG Srikantan, V Refaeli, Y Prabhu, A Sato, A Wiliiams, WV Weiner, DB Ugen, KE AF Dickey, C Ziegner, U Agadjanyan, MG Srikantan, V Refaeli, Y Prabhu, A Sato, A Wiliiams, WV Weiner, DB Ugen, KE TI Murine monoclonal antibodies biologically active against the amino region of HIV-1 gp120: Isolation and characterization SO DNA AND CELL BIOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DEPENDENT CELLULAR CYTOTOXICITY; ENVELOPE GLYCOPROTEIN; T4 MOLECULE; NEUTRALIZING EPITOPE; SEQUENCE DIVERSITY; IMMUNE-RESPONSE; GP160 EPITOPES; VIRAL-PROTEIN; HTLV-III/LAV AB The human immunodeficiency virus (HIV)-1 envelope glycoprotein is synthesized as a precursor (gp160) and subsequently cleaved to generate the external gp120 and transmembrane gp41 glycoproteins, Both gp120 and gp41 have been demonstrated to mediate critical functions of HIV, including viral attachment and fusion with the cell membrane. The antigenic variability of the HIV-1 envelope glycoprotein has presented a significant problem in the design of appropriate and successful vaccines and offers one explanation for the ability of HIV to evade immune surveillance. Therefore, the development and characterization of functional antibodies against conserved regions of the envelope glycoprotein is needed. Because of this need, we generated a panel of murine monoclonal antibodies (MuMabs) against the HIV-1 envelope glycoprotein, To accomplish this, we immunized Balb/C mice with a recombinant glycoprotein 160 (gp160) that was synthesized in a baculovirus expression system. From the growth-positive hybridomas, three MuMabs were generated that demonstrated significant reactivity with recombinant gp120 but failed to show reactivity against HIV-1 gp41, as determined by enzyme-linked immunosorbent assay (ELISA). Using vaccinia constructs that synthesize variant truncated subunits of gp160, we were able to map reactivity of all three of the Mabs (ID6, AC4, and AD3) to the first 204 residues of gp120 (i.e., the N terminus of gp120) via Western blot analysis. Elucidation of the epitopes for these Mabs may have important implications for inhibition of infection by HIV-1. Our initial attempts to map these Mabs with linear epitopes have not elucidated a specific antigenic determinant; however, several physical characteristics have been determined that suggest a continuous surface epitope, Although these antibodies failed to neutralize cell-free or cell-associated infection by HIV-1, they did mediate significant antibody-dependent cellular cytotoxity (ADCC) activity, indicating potential therapeutic utility. In summary, these data suggest the identification of a potentially novel site in the first 200 aa of gp120 that mediates ADCC. C1 Univ S Florida, Coll Med, Dept Med Microbiol & Immunol, Tampa, FL 33612 USA. Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Bethesda, MD 20814 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Cambridge, MA 02138 USA. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pediat, Philadelphia, PA 19107 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. RP Ugen, KE (reprint author), Univ S Florida, Coll Med, Dept Med Microbiol & Immunol, MDC 10,12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. RI Ugen, Kenneth/H-6544-2011; Weiner, David/H-8579-2014 FU NHLBI NIH HHS [HL59818] NR 73 TC 9 Z9 9 U1 1 U2 3 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1044-5498 J9 DNA CELL BIOL JI DNA Cell Biol. PD APR PY 2000 VL 19 IS 4 BP 243 EP 252 DI 10.1089/104454900314519 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Cell Biology; Genetics & Heredity GA 306QJ UT WOS:000086607300006 PM 10798448 ER PT J AU Robbins, SJ Ehrman, RN Childress, AR Cornish, JW O'Brien, CP AF Robbins, SJ Ehrman, RN Childress, AR Cornish, JW O'Brien, CP TI Mood state and recent cocaine use are not associated with levels of cocaine cue reactivity SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE cue reactivity; cocaine dependence; mood state; craving; cocaine use ID ABUSE PATIENTS; SMOKING URGES; ABSTINENCE; HUMANS; RESPONSES; ALCOHOL; IMAGERY; AVAILABILITY; INPATIENT; SMOKERS AB Eighty-one cocaine-dependent outpatients were assessed for their reactions to cocaine-related cues in a laboratory setting. All subjects contributed a urine sample prior to the session. Compared with non-drug control cues, the cocaine stimuli produced increases in physiological arousal, self-reports of high, craving, and withdrawal, and self-reports of negative mood. Subjects who tested cocaine-positive on the day of testing differed only in skin resistance responding from those who tested cocaine-negative. Changes in cue-induced physiological and self-report measures were also not associated with between-subject variations in mood as measured by the Profile of Mood States (POMS) questionnaire administered prior to cue assessment. Thus, variations in baseline mood and recent cocaine use history do not introduce an additional source of variability in cue reactivity measurements. However, negative mood states at the start of a session were associated with higher levels of self-reported craving, high, and withdrawal both before and after cue exposure. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Beaver Coll, Dept Psychol, Glenside, PA 19038 USA. Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Robbins, SJ (reprint author), Beaver Coll, Dept Psychol, 450 S Easton Rd, Glenside, PA 19038 USA. FU NIDA NIH HHS [P50DA09252-02, DA03008] NR 49 TC 25 Z9 25 U1 4 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD APR 1 PY 2000 VL 59 IS 1 BP 33 EP 42 DI 10.1016/S0376-8716(99)00103-9 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 294VQ UT WOS:000085931400003 PM 10706973 ER PT J AU Sanchez, CP Kuizon, BD Abdella, PA Juppner, H Salusky, IB Goodman, WG AF Sanchez, CP Kuizon, BD Abdella, PA Juppner, H Salusky, IB Goodman, WG TI Impaired growth, delayed ossification, and reduced osteoclastic activity in the growth plate of calcium-supplemented rats with renal failure SO ENDOCRINOLOGY LA English DT Article ID INTERMITTENT CALCITRIOL THERAPY; HORMONE-RELATED PEPTIDE; BONE-FORMATION; SECONDARY HYPERPARATHYROIDISM; APLASTIC OSTEODYSTROPHY; PEDIATRIC-PATIENTS; RISK-FACTORS; IN-VIVO; EXPRESSION; ANGIOGENESIS AB Linear growth is reduced in prepubertal children with adynamic renal osteodystrophy, suggesting that the proliferation and/or differentiation of epiphyseal growth plate chondrocytes is abnormal in this disorder. To examine this issue, in situ hybridization and histochemistry were used to measure selected markers of endochondral bone formation and bone resorption in the proximal tibia of subtotally nephrectomized rats fed a high calcium diet to induce biochemical changes consistent with adynamic osteodystrophy. Blood ionized calcium concentrations were higher and serum PTH levels were lower in nephrectomized, calcium-supplemented rats than in either intact or nephrectomized control animals. Linear growth and tibial length were reduced, but messenger RNA levels for type II collagen, type X collagen, and the PTH/PTHrP receptor did not differ from control values in nephrectomized rats given supplemental calcium. In contrast, both the width of epiphyseal cartilage and the height of the zone of hypertrophic chondrocytes were greater in calcium-supplemented nepkrectomized rats. These morphological changes were associated with decreases in histochemical staining for tartrate-resistant acid phosphatase and lower levels of messenger RNA expression for the matrix metalloproteinase MMP-9/gelatinase B immediately adjacent to the epiphyseal growth plate. Diminished chondroclastic/osteoclastic activity alters growth plate morphology and adversely affects linear bone growth in calcium-supplemented, nephrectomized rats. C1 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. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Goodman, WG (reprint author), Univ Calif Los Angeles, Ctr Med, Div Nephrol, 7-155 Factor Bldg,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM wgoodman@ucla.edu NR 33 TC 34 Z9 35 U1 4 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 EI 1945-7170 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2000 VL 141 IS 4 BP 1536 EP 1544 DI 10.1210/en.141.4.1536 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WJ UT WOS:000088385800032 PM 10746661 ER PT J AU Yildiran, ST Saracli, MA Fothergill, AW Rinaldi, MG AF Yildiran, ST Saracli, MA Fothergill, AW Rinaldi, MG TI In vitro susceptibility of environmental Cryptococcus neoformans variety neoformans isolates from Turkey to six antifungal agents, including SCH56592 and voriconazole SO EUROPEAN JOURNAL OF CLINICAL MICROBIOLOGY & INFECTIOUS DISEASES LA English DT Article ID IN-VITRO; PIGEON DROPPINGS; VAR. NEOFORMANS; SEROTYPE-A; ITRACONAZOLE; FLUCONAZOLE; YEASTS AB The in vitro antifungal susceptibility of 27 environmental (pigeon droppings) isolates of Cryptococcus neoformans var. neoformans, isolated from throughout Turkey, to six antifungal agents (amphotericin B, flucytosine, fluconazole, voriconazole, itraconazole, and SCH56592) was studied. Voriconazole, itraconazole, and SCH56592 all showed comparable activity and were more active than the remaining three antifungal agents tested. Overall, SCH56592 was the most active agent (MIC90, 0.015 mu g/ml, at both 48 and 72 h), followed by itraconazole (MIC90, 0.03 mu g/ml, at both 48 and 72 h) and voriconazole (MIC90, 0.25 mu g/ml, at both 48 and 72 h), respectively. Antifungal susceptibility data for environmental isolates may reflect patterns for the clinical isolates recovered from patients from the same geographic area. C1 Gulhane Mil Med Acad & Sch Med, Dept Microbiol & Clin Microbiol, Div Med Mycol, TR-06018 Ankara, Turkey. Univ Texas, Hlth Sci Ctr, Dept Pathol, Fungus Testing Lab, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX 78284 USA. RP Yildiran, ST (reprint author), Gulhane Mil Med Acad & Sch Med, Dept Microbiol & Clin Microbiol, Div Med Mycol, TR-06018 Ankara, Turkey. NR 18 TC 13 Z9 13 U1 0 U2 3 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0934-9723 J9 EUR J CLIN MICROBIOL JI Eur. J. Clin. Microbiol. Infect. Dis. PD APR PY 2000 VL 19 IS 4 BP 317 EP 319 DI 10.1007/s100960050484 PG 3 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 316WC UT WOS:000087190200015 PM 10834825 ER PT J AU Walter, U Frantzke, A Sarukhan, A Zober, C von Boehmer, H Buer, J Lechner, O AF Walter, U Frantzke, A Sarukhan, A Zober, C von Boehmer, H Buer, J Lechner, O TI Monitoring gene expression of TNFR family members by beta-cells during development of autoimmune diabetes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE TNF receptor family; beta-cell; diabetes; TCR-HA x INS-HA mouse; NOD mouse ID CD8 T-CELLS; TRANSGENIC MICE; NOD MICE; INTERFERON-GAMMA; SCID MOUSE; MELLITUS; ANTIGEN; REQUIREMENT; DISEASE; MODEL AB Autoimmune diabetes results from destruction of pancreatic beta-cells by islet-infiltrating leukocytes. Different molecular mechanisms seem to be involved in this destruction but the results from many studies have not provided a clear picture so far. Therefore, we have developed a multiplex single-cell reverse transcription polymerase chain reaction to analyze the expression of genes of the tumor necrosis factor receptor (TNFR) family in pancreatic beta-cells during the development of autoimmune diabetes in a TCR-HA x INS-HA double transgenic as well as a non-obese diabetic (NOD) animal model. To this end we have followed the expression of cell surface receptors of the TNFR family in NOD mice as well as in double transgenic mice that express in their T cells class II MHC-restricted TCR specific for peptide 111-119 from influenza hemagglutinin (TCR-HA) as well as hemagglutinin under the control of the rat insulin promoter (INS-HA). Both types of mice develop insulitis and diabetes spontaneously. The data show a significant increase in the expression of Fas and TNFR2 (p75) during the development of insulitis, whereas TNFR1 (p55) is already expressed in beta-cells before the onset of insulitis. As ligands for these receptors are already expressed at high levels during the phase of insulitis, it is possible that beta-cell death is regulated by intracellular inhibitors of apoptosis pathways. C1 Inst Necker, INSERM, U373, Paris, France. Hannover Med Sch, Dept Hematol & Oncol, D-3000 Hannover, Germany. German Ctr Biotechnol, Mucosal Immun Grp, Braunschweig, Germany. Hannover Med Sch, Inst Med Microbiol, D-3000 Hannover, Germany. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 48 TC 25 Z9 27 U1 0 U2 0 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 APR PY 2000 VL 30 IS 4 BP 1224 EP 1232 DI 10.1002/1521-4141(200004)30:4<1224::AID-IMMU1224>3.0.CO;2-B PG 9 WC Immunology SC Immunology GA 305MK UT WOS:000086543700029 PM 10760812 ER PT J AU Podesta, M Zocchi, E Pitto, A Usai, C Franco, L Bruzzone, S Guida, L Bacigalupo, A Scadden, DT Walseth, TF De Flora, A Daga, A AF Podesta, M Zocchi, E Pitto, A Usai, C Franco, L Bruzzone, S Guida, L Bacigalupo, A Scadden, DT Walseth, TF De Flora, A Daga, A TI Extracellular cyclic ADP-ribose increases intracellular free calcium concentration and stimulates proliferation of human hemopoietic progenitors SO FASEB JOURNAL LA English DT Article DE bone marrow cells; intracellular calcium homeostasis; cytokine-like activity of cyclic ADP-ribose; expansion of hemopoietic progenitors ID HEMATOPOIETIC STEM-CELLS; INOSITOL TRISPHOSPHATE; CYCLASE ACTIVITY; RYANODINE RECEPTORS; ENDOGENOUS LEVELS; MICE LACKING; HUMAN CD38; RADIOIMMUNOASSAY; DIFFERENTIATION; GLYCOPROTEIN AB Cyclic ADP-ribose (cADPR) is a universal second messenger that regulates many calcium-related cellular events by releasing calcium from intracellular stores. Since these events include enhanced cell proliferation and since the bone marrow harbors both ectoenzymes that generate cADPR from NAD(+) (CD38 and BST-1), we investigated the effects of extracellular cADPR on human hemopoietic progenitors (HP). Exposure of HE to 100 mu M cADPR for 24 h induced a significant increase in colony output (P<0.01) and colony size (P<0.003). A horizontal expansion of HP, as demonstrated by a markedly increased replating efficiency in semisolid medium (up to 700 times compared to controls), was also observed, indicating that cADPR priming can affect cell growth for multiple generations over several weeks after exposure. Influx of extracellular cADPR into the cells was demonstrated, and a causal relationship between the functional effects and the increase of intracellular free calcium concentration induced by cADPR on HP was established through the use of specific antagonists. Similar effects on HP were produced by nanomolar concentrations of the nonhydrolyzable cADPR analog 3-deaza-cADPR, These data demonstrate that extracellular cADPR behaves as a cytokine enhancing the proliferation of human HP, a finding that may have biomedical applications for the ex vivo expansion of hemopoietic cells.-Podesta, M., Zocchi, E., Pitto, A, Usai, C., Franco, L., Bruzzone, S., Guida, L., Bacigalupo, A., Scadden, D. T., Walseth, T. F., De Flora, A., Daga, A Extracellular cyclic ADP-ribose increases intracellular free calcium concentration and stimulates proliferation of human hemopoietic progenitors. C1 Univ Genoa, Dept Expt Med, Biochem Sect, I-16132 Genoa, Italy. S Martino Hosp, Dept Hematol, Genoa, Italy. Natl Res Council, Inst Cybernet & Biophys, Genoa, Italy. Harvard Univ, Sch Med, Dept Expt Hematol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Minnesota, Dept Pharmacol, Minneapolis, MN 55455 USA. Natl Inst Canc Res, IST, Genoa, Italy. RP De Flora, A (reprint author), Univ Genoa, Dept Expt Med, Biochem Sect, Viale Benedetto XV-1, I-16132 Genoa, Italy. RI Daga, Antonio/C-3041-2008; Bruzzone, Santina/A-4264-2015 OI Bruzzone, Santina/0000-0003-2034-3716 FU NIDA NIH HHS [P50 DA011806] NR 37 TC 60 Z9 63 U1 1 U2 19 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 APR PY 2000 VL 14 IS 5 BP 680 EP 690 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 301DH UT WOS:000086292700006 PM 10744625 ER PT J AU Foitzik, K Lindner, G Mueller-Roever, S Maurer, M Botchkareva, N Botchkarev, V Handjiski, B Metz, M Hibino, T Soma, T Dotto, GP Paus, R AF Foitzik, K Lindner, G Mueller-Roever, S Maurer, M Botchkareva, N Botchkarev, V Handjiski, B Metz, M Hibino, T Soma, T Dotto, GP Paus, R TI Control of murine hair follicle regression (catagen) by TGF-beta 1 in vivo SO FASEB JOURNAL LA English DT Article DE in vivo; apoptosis; TGF-beta receptor ID GROWTH-FACTOR-BETA; TGF-BETA; IN-VIVO; TRANSFORMING GROWTH-FACTOR-BETA-1; DEPENDENT CHANGES; TRANSGENIC MICE; MAST-CELLS; SKIN; EXPRESSION; APOPTOSIS AB The regression phase of the hair cycle (catagen) is an apoptosis-driven process accompanied by terminal differentiation, proteolysis, and matrix remodeling. As an inhibitor of keratinocyte proliferation and inductor of keratinocyte apoptosis, transforming growth factor beta 1 (TGF-beta 1) has been proposed to play an important role in catagen regulation. This is suggested, for example, by maximal expression of TGF-beta 1 and its receptors during late anagen and the onset of catagen of the hair cycle. We examined the potential involvement of TGF-beta 1 in catagen control. We compared the first spontaneous entry of hair follicles into catagen between TGF-beta 1 null mice and age-matched wild-type littermates, and assessed the effects of TGF-beta 1 injection on murine anagen hair follicles in vivo. At day 18 p.p., hair follicles in TGF-beta 1 -/- mice were still in early catagen, whereas hair follicles of +/+ littermates had already entered the subsequent resting phase (telogen). TGF-beta 1 -/- mice displayed more Ki-67-positive cells and fewer apoptotic cells than comparable catagen follicles from +/+ mice. In contrast, injection of TGF-beta 1 into the back skin of mice induced premature catagen development. In addition, the number of proliferating follicle keratinocytes was reduced and the number of TUNEL + cells was increased in the TGF-beta 1-treated mice compared to controls. Double visualization of TGF-beta type II receptor (TGFRII) and TUNEL reactivity revealed colocalization of apoptotic nuclei and TGFRII in catagen follicles. These data strongly support that TGF-beta 1 ranks among the elusive endogenous regulators of catagen induction in vivo, possibly via the inhibition of keratinocyte proliferation and induction of apoptosis. Thus, TCF-beta RII agonists and antagonists may provide useful therapeutic tools for human hair growth disorders based on premature or retarded catagen development (effluvium, alopecia, hirsutism). C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Humboldt Univ, Dept Dermatol, Berlin, Germany. Univ London Queen Mary Coll, Ctr Cutaneous Res, London E1 4NS, England. Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. Boston Univ, Dept Dermatol, Boston, MA 02118 USA. Shiseido Res Ctr, Yokohama, Kanagawa, Japan. RP Paus, R (reprint author), Univ Hamburg, Dept Dermatol, UKE, Martinistr 52, D-20246 Hamburg, Germany. RI Metz, Martin/B-8799-2009; Hendrix, Sven/F-4059-2010; Metz, Martin/M-5237-2013 OI Metz, Martin/0000-0002-4070-9976; Hendrix, Sven/0000-0003-2344-7369; Metz, Martin/0000-0002-4070-9976 FU NCI NIH HHS [CA 16038, CA73796]; NIAMS NIH HHS [AR39190] NR 46 TC 171 Z9 182 U1 0 U2 5 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 APR PY 2000 VL 14 IS 5 BP 752 EP 760 PG 9 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 301DH UT WOS:000086292700012 PM 10744631 ER PT J AU Lew, EA Pisegna, JR Starr, JA Soffer, EF Forsmark, C Modlin, IM Walsh, JH Beg, M Bochenek, W Metz, DC AF Lew, EA Pisegna, JR Starr, JA Soffer, EF Forsmark, C Modlin, IM Walsh, JH Beg, M Bochenek, W Metz, DC TI Intravenous pantoprazole rapidly controls gastric acid hypersecretion in patients with Zollinger-Ellison syndrome SO GASTROENTEROLOGY LA English DT Article ID PROTON PUMP INHIBITORS; SUBSTITUTED BENZIMIDAZOLES; OMEPRAZOLE; PHARMACOKINETICS; MANAGEMENT; SECRETION; EFFICACY; SURGERY; SAFETY AB Background Be Aims: Parenteral control of gastric acid hypersecretion in conditions such as Zollinger-Ellison syndrome (ZES) or idiopathic gastric acid hypersecretion is necessary perioperatively or when oral medications cannot be taken for other reasons (e.g., during chemotherapy, acute upper gastrointestinal bleeding, or in intensive care unit settings). Methods: We evaluated the efficacy and safety of 15-minute infusions of the proton pump inhibitor pantoprazole (80-120 mg every 8-12 hours) in controlling acid output for up to 7 days. Effective control was defined as acid output > 10 milliequivalents per hour (mEq/h) (<5 mEq/h in patients with prior acid-reducing surgery) for 24 hours. Results: The 21 patients enrolled had a mean age of 51.9 years (range, 29-75) and a mean disease duration of 8.1 years (range, <0.5-21); 13 were male, 7 had multiple endocrine neoplasia syndrome type 1, 4 had undergone acid-reducing surgery, 2 had received chemotherapy, and 13 had undergone gastrinoma resections without cure. Basal acid output (mean +/- SD) was 40.2 +/- 27.9 mEq/h (range, 11.2-117.9), In all patients, acid output was controlled within the first hour (mean onset of effective control, 41 minutes) after an initial 80-mg intravenous pantoprazole dose. Pantoprazole, 80 mg every 12 hours, was effective in 17 of 21 patients (81%) for up to 7 days. Four patients required upward dose titration, 2 required 120 mg pantoprazole every 12 hours, and 2 required 80 mg every 8 hours. At study end, acid output remained controlled for 6 hours beyond the next expected dose in 71% of patients (n = 15); mean acid output increased to 4.0 mEq/h (range, 0-9.7), No serious or unexpected adverse events were observed. Conclusions: Intravenous pantoprazole, 160-240 mg/day administered in divided doses by 15-minute infusion, rapidly and effectively controlled acid output within 1 hour and maintained control for up to 7 days in all ZES patients. C1 Univ Penn, Med Ctr, Dept Med, Div Gastroenterol,GI Physiol Lab, Philadelphia, PA 19104 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Div Digest Dis, CURE UCLA Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Florida, Dept Gastroenterol, Gainesville, FL USA. Yale Univ, Sch Med, GI Surg Pathol Res Grp, New Haven, CT USA. Wyeth Ayerst Res, Clin Res & Dev, Radnor, PA USA. RP Metz, DC (reprint author), Univ Penn, Med Ctr, Dept Med, Div Gastroenterol,GI Physiol Lab, 3 Ravdin,3400 Spruce St, Philadelphia, PA 19104 USA. FU NCRR NIH HHS [MO1-RR00040, MO1-RR00082, MO1-RR09758] NR 35 TC 52 Z9 55 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 BP 696 EP 704 DI 10.1016/S0016-5085(00)70139-9 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 298BH UT WOS:000086119100010 PM 10734021 ER PT J AU Abreu, MT Palladino, AA Arnold, ET Kwon, RS McRoberts, JA AF Abreu, MT Palladino, AA Arnold, ET Kwon, RS McRoberts, JA TI Resiliency of a model human intestinal epithelium to Fas-mediated apoptotic injury, evidence for junctional restructuring in its repair. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4264 BP A802 EP A803 PN 1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703277 ER PT J AU Ambra, G Doria, A Kim, HT Weber, HC AF Ambra, G Doria, A Kim, HT Weber, HC TI Investigation of the human bombesin receptor subtype-3 gene for the presence of mutations in obese individuals: A pilot study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Boston Univ, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4761 BP A852 EP A852 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703475 ER PT J AU Andres, PG Beck, PL Mizoguchi, E Mitzoguchi, A Bhan, AK Dawson, T Kuziel, WA Maeda, N MacDermott, RP Podolsky, DK Reinecker, HC AF Andres, PG Beck, PL Mizoguchi, E Mitzoguchi, A Bhan, AK Dawson, T Kuziel, WA Maeda, N MacDermott, RP Podolsky, DK Reinecker, HC TI Mice with a selective deletion of the chemokine receptors CCR5 or CCR2 are protected from DSS-mediated colitis: Lack of CCR5 expression results in Th2 type immune response in the intestine. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, GI Unit,CSIBD, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. Univ Texas, Dept Mol Genet & Microbiol, Austin, TX 78712 USA. Albany Med Coll, Div Gastroenterol, Albany, NY 12208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3766 BP A686 EP A686 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702803 ER PT J AU Beck, PL Xavier, RJ Rosenberg, IR Podolsky, DK AF Beck, PL Xavier, RJ Rosenberg, IR Podolsky, DK TI Intestinal epithelial cell expression of TGFB dominant negative receptor II (DNRII) results in decreased wound healing in vitro and increased susceptibility to colonic injury in vivo. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. HMS, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4843 BP A872 EP A872 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703553 ER PT J AU Beck, PL Xavier, RJ Kosaka, T Dangler, CA Wang, TC Fox, JG AF Beck, PL Xavier, RJ Kosaka, T Dangler, CA Wang, TC Fox, JG CA GI Research Group TI Defining the roles of lymphocytes and sialyl-Lewis-x (sLe(x)) in Helicobacter in induced gastric injury. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calgary, GI Res Grp, Calgary, AB, Canada. Massachusetts Gen Hosp, Ctr Study IBD, Boston, MA 02114 USA. MIT, Div Comparat Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3995 BP A737 EP A737 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703008 ER PT J AU Beck, PL Xavier, RJ Ezedi, I Mizoguchi, A Mizoguchi, E Bhan, AK Podolsky, DK AF Beck, PL Xavier, RJ Ezedi, I Mizoguchi, A Mizoguchi, E Bhan, AK Podolsky, DK TI Targeted disruption of fucosyltransferase VII (FTVII) significantly attenuates dextran sodium sulfate (DSS)-induced colitis in intestinal trefoil (ITF) deficient mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. HMS, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1210 BP A189 EP A189 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700760 ER PT J AU Boushey, RP Tavares, W Yusta, B Koh, TJ Wang, TC Drucker, DJ AF Boushey, RP Tavares, W Yusta, B Koh, TJ Wang, TC Drucker, DJ TI Essential roles of the gastrin and glucagon genes in the response to experimental murine colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Toronto, UHN, TGH, Toronto, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4338 BP A821 EP A821 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703351 ER PT J AU Brand, SA Wang, TD Schomacker, KT Poneros, JM Compton, CC Pedrosa, MC Nishioka, NS AF Brand, SA Wang, TD Schomacker, KT Poneros, JM Compton, CC Pedrosa, MC Nishioka, NS TI Detection of high-grade dysplasia in Barrett's esophagus by 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) fluorescence spectroscopy. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02215 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1225 BP A193 EP A193 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700775 ER PT J AU Burke, C Arber, N Phillips, RK Hultcrantz, R Bjork, J Syngal, S Rodriquez, M Luchtefeld, M Botomon, VA Wruble, L Kuwada, S AF Burke, C Arber, N Phillips, RK Hultcrantz, R Bjork, J Syngal, S Rodriquez, M Luchtefeld, M Botomon, VA Wruble, L Kuwada, S TI Exisulind continues to prevent colonic adenoma formation in familial adenomatous polyposis (FAP) patients treated for 18 months. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. St Marks Hosp, Harrow, Middx, England. Karolinska Inst, Stockholm, Sweden. Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Ferguson Blodgett Res Fdn, Grand Rapids, MI USA. Cleveland Clin Fdn, Ft Lauderdale, FL USA. Mid S Clin Res Inst, Memphis, TN USA. Univ Utah, Salt Lake City, UT 84112 USA. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3605 BP A657 EP A657 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702693 ER PT J AU Burke, C van Stolk, R Arber, N Hultcrantz, R Bjork, J Syngal, S Rodriquez, M Luchtefeld, M Botomon, VA Wruble, L Kuwada, S Phillips, RK AF Burke, C van Stolk, R Arber, N Hultcrantz, R Bjork, J Syngal, S Rodriquez, M Luchtefeld, M Botomon, VA Wruble, L Kuwada, S Phillips, RK TI Exisulind prevents adenoma formation in familial adenomatous polyposis(FAP). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. Karolinska Inst, Stockholm, Sweden. Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Ferguson Blodgett Res Fdn, Grand Rapids, MI USA. Cleveland Clin Fdn, Ft Lauderdale, FL USA. Med S Clin Res Inst, Memphis, TN USA. Univ Utah, Salt Lake City, UT 84112 USA. St Marks Hosp, Harrow, Middx, England. NR 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3604 BP A657 EP A657 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702692 ER PT J AU Cario, E Brown, D McKee, M Podolsky, DK AF Cario, E Brown, D McKee, M Podolsky, DK TI Polarized intestinal epithelial cells express Toll-like receptors on the apical pole in vitro. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Gastrointestinal Unit, CSIBD, Boston, MA 02114 USA. Massachusetts Gen Hosp, Program Membrane Biol, CSIBD, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4309 BP A814 EP A814 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703322 ER PT J AU Colucci, R Del Tacca, M Fleming, J Wang, TC AF Colucci, R Del Tacca, M Fleming, J Wang, TC TI Overexpression of histidine decarboxylase decreases its own transcription through down-regulation of ERK activity. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Pisa, Dept Oncol, Div Pharmacol, Pisa, Italy. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3060 BP A590 EP A590 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702424 ER PT J AU Deavall, DG Raychowdhury, R Dockray, GJ Dimaline, R AF Deavall, DG Raychowdhury, R Dockray, GJ Dimaline, R TI Control of cholecystokinin gene transcription by PACAP in STC-1 cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Liverpool, Liverpool L69 3BX, Merseyside, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 603 BP A83 EP A83 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700337 ER PT J AU Di Bisceglie, AM Bonkovsky, HL Dienstag, JL Everson, GT Lindsay, KL Gretch, DR Hoefs, JC Lee, WH Lok, AS Tralka, TS Shiffman, ML Wright, EC AF Di Bisceglie, AM Bonkovsky, HL Dienstag, JL Everson, GT Lindsay, KL Gretch, DR Hoefs, JC Lee, WH Lok, AS Tralka, TS Shiffman, ML Wright, EC TI Design of the halt-c trial (hepatitis C antiviral long-term treatment to prevent cirrhosis). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 St Louis Univ, Sch Med, St Louis, MO USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. USC, Sch Med, Los Angeles, CA USA. Univ Washington, Seattle, WA 98195 USA. Univ Calif Irvine, Med Ctr, Orange, CA USA. Univ Texas, Dallas, TX 75230 USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. NIDDK, NIH, Bethesda, MD USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. New England Res Inst, Waltham, MA USA. RI Lok, Anna /B-8292-2009 NR 0 TC 3 Z9 3 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 APR PY 2000 VL 118 IS 4 SU 2 MA 6515 BP A1435 EP A1435 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784101588 ER PT J AU Dominitz, JA Koepsell, TD Boyko, EJ AF Dominitz, JA Koepsell, TD Boyko, EJ TI Association between analgesic use and inflammatory bowel disease (IBD) flares: A retrospective cohort study. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3024 BP A581 EP A581 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702388 ER PT J AU El-Serag, HB Mason, AC AF El-Serag, HB Mason, AC TI Risk factors for the rising rates of hepatocellular carcinoma in the United States. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3792 BP A693 EP A693 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702829 ER PT J AU El-Serag, HB Everhart, JE AF El-Serag, HB Everhart, JE TI Improved survival following esophageal variceal hemorrhage in the department of veterans affairs (VA). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Houston VAMC, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1220 BP A192 EP A192 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700770 ER PT J AU Farrell, JJ Lester, J Gazelle, GS Kelsey, PB AF Farrell, JJ Lester, J Gazelle, GS Kelsey, PB TI Cost analysis of inpatient colonic diverticular bleeding. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. HMS, Boston, MA USA. Massachusetts Gen Hosp, DATA Grp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5021 BP A1083 EP A1083 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100086 ER PT J AU Farrell, JJ Xavier, R Taylor, N Fox, JG Wang, TC AF Farrell, JJ Xavier, R Taylor, N Fox, JG Wang, TC TI Secretory phospholipase A2 promoter regulation by gastrin and Helicobacter pylori, using cell culture and a green fluorescent protein transgenic mouse model. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. HMS, Boston, MA USA. MIT, Div Comparat Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4005 BP A740 EP A740 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703018 ER PT J AU Farrell, JJ Kelsey, PB Graeme-Cook, F Chung, RT AF Farrell, JJ Kelsey, PB Graeme-Cook, F Chung, RT TI Sclerosing pancreatocholangitis: A reversible variant of PSC. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. HMS, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2172 BP A420 EP A420 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701720 ER PT J AU Fleming, JV Sussman, JS Colucci, R Bulitta, CJ Wang, TC AF Fleming, JV Sussman, JS Colucci, R Bulitta, CJ Wang, TC TI Gastrin preferentially stabilizes L-histidine carboxylase (HDC) isoforms that have been processed at both the amino-and carboxy-terminal ends. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2882 BP A547 EP A547 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702246 ER PT J AU Fox, JG Handt, LK Xu, SL Dewhirst, FE Dangler, CA Motzel, S Klein, HJ AF Fox, JG Handt, LK Xu, SL Dewhirst, FE Dangler, CA Motzel, S Klein, HJ TI Two novel Helicobacter spp isolated from colonic tissue of macaques with chronic idiopathic colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Merck Res Lab, W Point, PA USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4315 BP A815 EP A815 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703328 ER PT J AU Fox, JG Harper, CM Xu, SL Dewhirst, FE Paster, BJ AF Fox, JG Harper, CM Xu, SL Dewhirst, FE Paster, BJ TI Isolation and characterization of urease positive novel Helicobacter spp isolated from gastric mucosa of white sided dolphins (Lagenorhynchus acutus). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Forsyth Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2568 BP A473 EP A473 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701935 ER PT J AU Fox, JG Chien, CC Dewhirst, FE Shen, Z Melito, PL Woodward, DL Rodgers, FG AF Fox, JG Chien, CC Dewhirst, FE Shen, Z Melito, PL Woodward, DL Rodgers, FG TI A novel Helicobacter sp isolated from humans with diarrhea: An example of an emerging pathogen. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Div Comparat Med, Cambridge, MA 02139 USA. Forsyth Inst, Boston, MA USA. Natl Lab Enter Pathogens, Winnipeg, MB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1992 BP A376 EP A376 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701540 ER PT J AU Fox, JG Dangler, CA Beck, PL Wang, TC Whary, MT Shi, HN Nagler-Anderson, CN AF Fox, JG Dangler, CA Beck, PL Wang, TC Whary, MT Shi, HN Nagler-Anderson, CN TI Intestinal helminth infection modulates inflammation and reduces gastric atrophy in a mouse model of Helicobacter infection. SO GASTROENTEROLOGY 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 W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1226 BP A194 EP A194 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700776 ER PT J AU Furuta, GT Turner, JR Black, ED Podolsky, DK Colgan, SP AF Furuta, GT Turner, JR Black, ED Podolsky, DK Colgan, SP TI Intestinal epithelial barrier function is uniquely resistant to changes elicited by hypoxia; Critical role for hypoxia inducible factor-1 (HIF-1)-dependent induction of intestinal trefoil factor (ITF). SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Wayne State Univ, Detroit, MI USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3676 BP A671 EP A671 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702746 ER PT J AU Gaspard, JP Warshaw, AL Jensen, RT Chung, DC AF Gaspard, JP Warshaw, AL Jensen, RT Chung, DC TI Mapping of a novel pancreatic endocrine tumor suppressor gene locus to a 0.5 cm region on chromosome 3p. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3274 BP A643 EP A643 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702638 ER PT J AU Gopal, DV Rabkin, J Berk, BS Corless, CL Olyaei, A Orloff, SL Rosen, HR AF Gopal, DV Rabkin, J Berk, BS Corless, CL Olyaei, A Orloff, SL Rosen, HR TI Treatment of progressive HCV recurrence post liver transplantation with combination interferon plus ribavirin. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1157 BP A996 EP A996 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783704054 ER PT J AU Gukovskaya, AS Mouria, M Jung, Y Zaninovic, V Pandol, SJ AF Gukovskaya, AS Mouria, M Jung, Y Zaninovic, V Pandol, SJ TI Intracellular mechanisms of CCK-induced apoptosis in pancreatic acinar cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 898 BP A156 EP A156 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700630 ER PT J AU Gukovsky, I Blinman, TA Mouria, M Zaninovic, V Livingston, E Pandol, SJ Gukovskaya, AS AF Gukovsky, I Blinman, TA Mouria, M Zaninovic, V Livingston, E Pandol, SJ Gukovskaya, AS TI p38 map kinase is a key regulator of cytokine and chemokine expression in pancreatic acinar cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 899 BP A157 EP A157 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700631 ER PT J AU Hartwig, W Jimenez, RE Bozena, AA Warshaw, ALL Fernandez-del Castillo, C AF Hartwig, W Jimenez, RE Bozena, AA Warshaw, ALL Fernandez-del Castillo, C TI Trypsin induces the expression of Mac-1 and ICAM-1 and contributes to neutrophil migration in acute pancreatitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 940 BP A166 EP A166 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700672 ER PT J AU Hoecker, M Wessler, S Cramer, T Wang, T Rosewicz, S Wiedenmann, B Naumann, M AF Hoecker, M Wessler, S Cramer, T Wang, T Rosewicz, S Wiedenmann, B Naumann, M TI Helicobacter pylori regulates the human histidine decarboxylase (HDC) promoter through cagA-independent transactivation of a proximal cis-regulatory element. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Charite, Berlin, Germany. MPI Infekt Biol, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RI Cramer, Thorsten/S-2479-2016 OI Cramer, Thorsten/0000-0002-6462-239X NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4012 BP A741 EP A741 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703025 ER PT J AU Iwakiri, D Podolsky, DK AF Iwakiri, D Podolsky, DK TI Keratinocyte growth factor regulates expression of the intestinal trefoil factor gene through a cis-regulatory element regulating goblet cell-specific transcription. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2380 BP A436 EP A436 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701783 ER PT J AU Jacobson, BC Ferris, TG Shea, TL Greenbarg, P Wang, TC AF Jacobson, BC Ferris, TG Shea, TL Greenbarg, P Wang, TC TI Who ts using chronic acid-suppression therapy and why? SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Partners Community HealthCare Inc, Boston, MA USA. Merck Medco Managed Care LLC, Franklin Lakes, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2514 BP A460 EP A460 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701881 ER PT J AU Jensen, DM Ho, S Hamamah, S Frankl, H Faigel, D DeMarco, D Chitayat, R Jensen, ME Alofaituli, G Fontana, L Cheng, S Lam, F AF Jensen, DM Ho, S Hamamah, S Frankl, H Faigel, D DeMarco, D Chitayat, R Jensen, ME Alofaituli, G Fontana, L Cheng, S Lam, F TI A randomized study of omeprazole compared to misoprostol for prevention of recurrent ulcers and ulcer hemorrhage in high risk patients ingesting aspirin or NSAIDs. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Med Ctr, Minneapolis, MN USA. Kaiser Permanente, Panorama City, CA USA. Kaiser Permanente, Los Angeles, CA USA. VA Med Ctr, Portland, OR USA. Baylor Univ, Med Ctr, Dallas, TX USA. Columbia W Hills Med Ctr, W Hills, CA USA. Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4931 BP A892 EP A892 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703627 ER PT J AU Kamal, M Wakelin, D Smith, A Ouellette, A Podolsky, DK Mahida, YR AF Kamal, M Wakelin, D Smith, A Ouellette, A Podolsky, DK Mahida, YR TI Paneth, intermediate and goblet cell hyperplasia in T-spiralis-infected mice is mediated, by a unique population of T cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Nottingham, Div Gastroenterol, Nottingham NG7 2RD, England. Univ Nottingham, Sch Biomed Sci, Nottingham NG7 2RD, England. IAH Compton, Compton, Berks, England. Univ Calif Irvine, Irvine, CA 92717 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1917 BP A358 EP A358 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701465 ER PT J AU Kearney, DJ Brousal, A AF Kearney, DJ Brousal, A TI Retreatment of Helicobacter pylori non-responders. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5745 BP A1255 EP A1255 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100819 ER PT J AU Kinoshita, KK Podolsky, DK AF Kinoshita, KK Podolsky, DK TI Intestinal trefoil factor induces immune and iinflammatory response: Upregulation of IL-8 and IL-1b in epithelial and monocytic cells via NFKB. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4231 BP A794 EP A794 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703244 ER PT J AU Kinugasa, T Gu, XB Yang, H Reinecker, HC AF Kinugasa, T Gu, XB Yang, H Reinecker, HC TI Extracellular regulated mitogen activated kinase activity is required for the regulation of the intestinal epithelial cell barrier function by IL-17 SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, CSIBD, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2891 BP A549 EP A549 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702255 ER PT J AU Kinugasa, T Gu, XB Reinecker, HC AF Kinugasa, T Gu, XB Reinecker, HC TI The claudin family of tight junction associated proteins regulates the intestinal paracellular barrier under the control of inflammatory mediators. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, CSIBD, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2890 BP A549 EP A549 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702254 ER PT J AU Klopcic, CE Psendorfer, P Fernandez, I Chen, J Walker, WA Nanthakumar, NN AF Klopcic, CE Psendorfer, P Fernandez, I Chen, J Walker, WA Nanthakumar, NN TI Characterization of the developing human jejunal and ileal xenograft in vivo using disaccharidases as markers. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1625 BP A290 EP A290 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701173 ER PT J AU Kuldau, JG Corless, C Wildes, JW Magilner, M Lieberman, DA Fennerty, MB Faigel, DO AF Kuldau, JG Corless, C Wildes, JW Magilner, M Lieberman, DA Fennerty, MB Faigel, DO TI Comparison of gastritis grading scales for the diagnosis of Helicobacter pylori (HP) infection. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. OHSU, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3825 BP A698 EP A698 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702849 ER PT J AU Kuratani, K Tache, Y AF Kuratani, K Tache, Y TI Vagal stimulation of gastric secretion by intracisternal RX77368: Modulation by central NMDA or AMPA/kainate receptors in anesthetized rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Greater LA Heathcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, DDRC, CURE, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2360 BP A431 EP A431 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701763 ER PT J AU Lee, CA Silva, M Kelly, AJ McCormick, BA AF Lee, CA Silva, M Kelly, AJ McCormick, BA TI Intestinal epithelial orchestration of neutrophil mlovement in response to S-typhimurium (S.t.) is mediated by a S.t. secreted protein, SipA SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3813 BP A695 EP A695 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702837 ER PT J AU Lembo, T Robson, K Zaman, MS Gralnek, IM AF Lembo, T Robson, K Zaman, MS Gralnek, IM TI The long-term clinical outcome and impact of nonspecific esophageal motility disorders. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Beth Israel Med Ctr, Boston, MA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5448 BP A1185 EP A1185 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100522 ER PT J AU Ling, Y Fuller, CR Pete, G DaCosta, CM D'Ercole, AJ Kahn, CR Lund, PK AF Ling, Y Fuller, CR Pete, G DaCosta, CM D'Ercole, AJ Kahn, CR Lund, PK TI Partial dependence on IRS-1 for normal and IGF-I induced small bowel growth in vivo. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ N Carolina, Chapel Hill, NC USA. Howard Univ, Washington, DC 20059 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4968 BP A1070 EP A1070 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100033 ER PT J AU Ling, Y Fuller, CR Pete, G DaCosta, CM D'Ercole, AJ Kahn, CR Lund, PK AF Ling, Y Fuller, CR Pete, G DaCosta, CM D'Ercole, AJ Kahn, CR Lund, PK TI Partial dependence on IRS-1 for normal and IGF-I mediated small bowel growth in vivo. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Dept Cellular & Mol Physiol, Chapel Hill, NC USA. Dept Pediat, Chapel Hill, NC USA. Howard Univ, Washington, DC 20059 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Dept Cell & Mol Physiol & Pediat, Chapel Hill, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3777 BP A689 EP A689 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702814 ER PT J AU Luedtke-Heckenkamp, K Golden, HM Podolsky, DK Reinecker, HC AF Luedtke-Heckenkamp, K Golden, HM Podolsky, DK Reinecker, HC TI The mouse IL-17 receptor promoter is under autocrine control and regulated by two inhibitor/enhancer elements in intestinal epithelial cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3065 BP A591 EP A591 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702429 ER PT J AU McDonald, MJ Longnecker, DS Moonka, R Robinson, L Bell, RH AF McDonald, MJ Longnecker, DS Moonka, R Robinson, L Bell, RH TI Hypergastrinemia induced by proton pump inhibitor (PPI) causes pancreatic growth but does not promote pancreatic carcinogenesis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Madigan Army Med Ctr, Tacoma, WA 98431 USA. Dartmouth Med Sch, Lebanon, NH USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2296 BP A1042 EP A1042 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783704240 ER PT J AU Mizoguchi, A Mizoguchi, E Saubermann, LJ Higaki, K Blumberg, RS Bhan, AK AF Mizoguchi, A Mizoguchi, E Saubermann, LJ Higaki, K Blumberg, RS Bhan, AK TI Clonal expansion and survival of the colonic CD4(+) VB8.2(+) T cells characterized by a specific CDR3 motif in the TCRA KO mice with colitis. SO GASTROENTEROLOGY 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 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3768 BP A687 EP A687 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702805 ER PT J AU Mizoguchi, E Mizoguchi, A Preffer, FI Bhan, AK AF Mizoguchi, E Mizoguchi, A Preffer, FI Bhan, AK TI Regulatory role of mature B cells in a murine model of inflammatory bowel disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3770 BP A687 EP A687 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702807 ER PT J AU Mouria, M Gukovskaya, AS Pandol, SJ AF Mouria, M Gukovskaya, AS Pandol, SJ TI Mechanisms of the effects of food polyphenolic compounds on apoptosis in pancreatic cancer cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2843 BP A538 EP A538 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702207 ER PT J AU Muehlhoefer, A Saubermann, LJ Gu, XB Luedtke-Heckenkamp, K Xavier, R Blumberg, RS Podolsky, DK MacDermott, RP Reinecker, HC AF Muehlhoefer, A Saubermann, LJ Gu, XB Luedtke-Heckenkamp, K Xavier, R Blumberg, RS Podolsky, DK MacDermott, RP Reinecker, HC TI Fractalkine is an epithelial and endothelial cell derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, CSIBD, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA. Albany Med Coll, Div Gastroenterol, Albany, NY 12208 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 719 BP A111 EP A111 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700453 ER PT J AU Napadow, VJ Wedeen, VJ Reese, T Gilbert, RJ AF Napadow, VJ Wedeen, VJ Reese, T Gilbert, RJ TI Creating a virtual anatomic atlas of the musculature of the in vivo human tongue with diffusion tensor magnetic resonance imaging. SO GASTROENTEROLOGY 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 W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4767 BP A854 EP A854 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703481 ER PT J AU Napadow, VJ Wedeen, VJ Chen, Q Mai, V So, PP Gilbert, RJ AF Napadow, VJ Wedeen, VJ Chen, Q Mai, V So, PP Gilbert, RJ TI Quantification of microscopic lingual myofiber orientation by diffusion tensor MR imaging and 3D resolved two-photon microscopy. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Hosp, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2123 BP A408 EP A409 PN 1 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701671 ER PT J AU Nguyen, DD Mizoguchi, A Mizoguchi, E Liu, CH Breck, P Bhan, AK Podolsky, DK Snapper, SB AF Nguyen, DD Mizoguchi, A Mizoguchi, E Liu, CH Breck, P Bhan, AK Podolsky, DK Snapper, SB TI Altered chemokine and cytokine profiles in WASP-KO mice yield potential insights into the pathogenesis of the associated chronic colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calgary, Calgary, AB, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4842 BP A872 EP A872 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703552 ER PT J AU Oh, K Ueki, T Fujimoto, J Kaneda, Y Nakamura, T Takahashi, H AF Oh, K Ueki, T Fujimoto, J Kaneda, Y Nakamura, T Takahashi, H TI Therapeutic effect of hepatocyte growth factor in TNBS induced colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Hyogo Coll Med, Nishinomiya, Hyogo, Japan. Osaka Univ, Sch Med, Osaka, Japan. Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4806 BP A864 EP A864 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703520 ER PT J AU Okolo, CN Bronner, MP Nguyen, TD AF Okolo, CN Bronner, MP Nguyen, TD TI Mast cell recruitment in chronic pancreatitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3312 BP A652 EP A652 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702675 ER PT J AU Okumura, A Takahashi, H AF Okumura, A Takahashi, H TI Role of secretory and nonsecretory pathways in antibody-dependent cell-mediated cytotoxicity (ADCC) to human hepatoma cells. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 114 BP A921 EP A921 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703746 ER PT J AU Ooi, CJ Rosenberg, IM Reinecker, HC Podolsky, DK AF Ooi, CJ Rosenberg, IM Reinecker, HC Podolsky, DK TI Regulation of tight junction proteins in human subjects with inflammatory bowel disease. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4235 BP A795 EP A795 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703248 ER PT J AU Opitz, OG Suliman, Y Rhoades, B Sharpless, NE Rustgi, AK AF Opitz, OG Suliman, Y Rhoades, B Sharpless, NE Rustgi, AK TI The combination of cyclin D1 overexpression and p53 inactivation is critical for oral-esophageal-carcinogenesis in transgenic mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4121 BP A768 EP A768 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703134 ER PT J AU Provenzale, D Gralnek, I Ofman, J Rabeneck, L Koff, R AF Provenzale, D Gralnek, I Ofman, J Rabeneck, L Koff, R TI Gastroenterologist specialist care is effective and cost-effective compared to care provided by generalists. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Duke Univ, Med Ctr, Durham VA Med Ctr, Durham, NC USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. ZYNX Hlth Inc, Beverly Hills, CA USA. VA Med Ctr, Houston, TX USA. Columbia Metrowest Med Ctr, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5061 BP A1093 EP A1093 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100126 ER PT J AU Rabeneck, L Wristers, K Campbell, CJ Souchek, J Menke, T Wray, N AF Rabeneck, L Wristers, K Campbell, CJ Souchek, J Menke, T Wray, N TI Dyspepsia patients are not all the same: Differences between VA and private practice settings. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3919 BP A719 EP A719 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702932 ER PT J AU Raychowdhury, R Mclaughlin, J Wang, TC AF Raychowdhury, R Mclaughlin, J Wang, TC TI Identification and characterization of a new gastrin response element (GAS-RE3) in the human histidine decarboxylase gene promoter. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1020 BP A181 EP A181 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700727 ER PT J AU Sampliner, RE Faigel, DO Lieberman, DA Fennerty, MB Ippoliti, AF Lewin, KJ Weinstein, WM AF Sampliner, RE Faigel, DO Lieberman, DA Fennerty, MB Ippoliti, AF Lewin, KJ Weinstein, WM TI Reversal of Barrett's esophagus with high dose omeprazole and electrocoagulation 6 month follow-up. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 So Arizona VA Hlth Care Syst, Tucson, AZ USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Univ Calif Los Angeles, Ctr Hlth Sci, Los Angeles, CA 90024 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1370 BP A228 EP A228 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700918 ER PT J AU Sarkar, S Hobson, A Aziz, Q Woolf, CJ Thompson, DG AF Sarkar, S Hobson, A Aziz, Q Woolf, CJ Thompson, DG TI Central sensitisation contributes to oesophageal hypersensitivity in non-cardiac chest pain. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Hope Hosp, Salford M6 8HD, Lancs, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1190 BP A184 EP A184 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700740 ER PT J AU Saubermann, LJ Beck, P de Jong, YP Pitman, RS Terhorst, C Exley, M Snapper, SB Balk, SP Hagen, SJ Podolsky, DK Koezuka, Y Blumberg, RS AF Saubermann, LJ Beck, P de Jong, YP Pitman, RS Terhorst, C Exley, M Snapper, SB Balk, SP Hagen, SJ Podolsky, DK Koezuka, Y Blumberg, RS TI Natural killer (NK)-T cell activation by a-galactosylceramide in the presence of CD1d provides protection against colitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. Kirin Pharm Res Lab, Gunma, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1211 BP A189 EP A189 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700761 ER PT J AU Shields, HM Nishioka, NS Rosenberg, SJ Puricelli, WP Ransil, BJ Zwas, FR Upton, MP AF Shields, HM Nishioka, NS Rosenberg, SJ Puricelli, WP Ransil, BJ Zwas, FR Upton, MP TI Barrett's epithelium, dysplasia, and multilayered epithelium: Is there a relationship? SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Yale Univ, Greenwich Hosp, Sch Med, Greenwich, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5962 BP A1306 EP A1306 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784101036 ER PT J AU Takahashi, H Yamamoto, H AF Takahashi, H Yamamoto, H TI Bacterial flora, but not LPS, induced colonic intestinal epithelial cell injuries in TH1-activated mice. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5243 BP A1138 EP A1138 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100317 ER PT J AU Takehara, T Friedman, SL Takahashi, H AF Takehara, T Friedman, SL Takahashi, H TI Inhibition of p53-mediated apoptosis by Bcl-xL endogenously expressed in human hepatocellular carcinoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Mt Sinai Med Ctr, New York, NY 10029 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 123 BP A923 EP A923 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703755 ER PT J AU Takehara, T Takahashi, H AF Takehara, T Takahashi, H TI Asparagine deamidation as a novel posttranslational modification of Bcl-xL. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2433 BP A443 EP A443 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701811 ER PT J AU Takeshima, F Alt, FW Liu, CH Hartwig, J Rosen, FS Goldberg, M Southwick, F Snapper, SB AF Takeshima, F Alt, FW Liu, CH Hartwig, J Rosen, FS Goldberg, M Southwick, F Snapper, SB TI The actin-based motility of Shigella flexneri requires N-WASP. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Gainesville, Gainesville, FL 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Ctr Blood Res, Boston, MA USA. MA Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2371 BP A434 EP A434 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701774 ER PT J AU Tamori, K Yuan, PQ Yang, H Miampamba, M Kuratani, K Tache, Y AF Tamori, K Yuan, PQ Yang, H Miampamba, M Kuratani, K Tache, Y TI Peripheral CRF inhibits cold restraint-induced activation of Fos expression in the gastric duodenal myenteric plexus in rats. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, DDRC, CURE, Los Angeles, CA USA. VA Greater LA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 598 BP A81 EP A81 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700332 ER PT J AU Targownik, L Gralnek, IM Dulai, GS Oei, T Chang, D Alofaituli, G Bernstein, CN AF Targownik, L Gralnek, IM Dulai, GS Oei, T Chang, D Alofaituli, G Bernstein, CN TI Do persons with acute, non-variceal upper gi hem hemorrhage (UGIH) require admission to an icu/monitored bed? Comparison of a Canadian and US center. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Manitoba, Winnipeg, MB, Canada. VA Greater Los Angeles Healthcare Syst, 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 W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4935 BP A893 EP A893 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703631 ER PT J AU Taupin, D Farrell, JJ Koh, T Podolsky, DK Wang, TC MacCallum, P AF Taupin, D Farrell, JJ Koh, T Podolsky, DK Wang, TC MacCallum, P TI Generation and charaterization of a spasmolytic polypeptide (TFF2) knockout mouse. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Peter MacCallum Canc Inst, Melbourne, MA USA. Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. HMS, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 4348 BP A823 EP A823 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783703361 ER PT J AU Tavakkolizadeh, A Berger, UV Rhoads, DB Shen, R Levitsky, LL Zinner, MJ Ashley, SW Whang, EE Zinner, J AF Tavakkolizadeh, A Berger, UV Rhoads, DB Shen, R Levitsky, LL Zinner, MJ Ashley, SW Whang, EE Zinner, J TI Diurnal variation in SGLT1 induction and function. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3142 BP A610 EP A610 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702506 ER PT J AU Taylor, NS Chien, CC Knox, KA Young, VB Schauer, DB Fox, JG AF Taylor, NS Chien, CC Knox, KA Young, VB Schauer, DB Fox, JG TI Evidence of cytolethal distending toxin in multiple strains of H-pullorum isolated from humans with diarrhea. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 1779 BP A327 EP A327 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783701327 ER PT J AU Tsao, H Gaspard, JP Haluska, FG Chung, DC AF Tsao, H Gaspard, JP Haluska, FG Chung, DC TI Mutational analysis of the CDK-4 gene in human pancreatic endocrine tumors. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 5325 BP A1157 EP A1157 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784100399 ER PT J AU Tsuzuki, Y Fukumura, D Koike, C Jain, RK AF Tsuzuki, Y Fukumura, D Koike, C Jain, RK TI The orthotopic microenvironment promotes tumor growth and VEGF121 expression in human pancreatic adenocarcinoma. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 EI 1528-0012 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 6426 BP A1415 EP A1415 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RY UT WOS:000086784101499 ER PT J AU Vaquero, E Gukovsky, I Zaninovic, V Gukovskaya, AS Pandol, SJ AF Vaquero, E Gukovsky, I Zaninovic, V Gukovskaya, AS Pandol, SJ TI Upregulation of transcription factors and cytokine mRNA expression in taurocholate-induced pancreatitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 3316 BP A653 EP A653 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783702679 ER PT J AU Vaquero, E Gukovskaya, AS Brennan, ML Lusis, AJ Holland, SM Pandol, SJ AF Vaquero, E Gukovskaya, AS Brennan, ML Lusis, AJ Holland, SM Pandol, SJ TI Leukocyte NADPH oxidase but not myeloperoxidase regulates pancreatic trypsin activation in cerulein induced pancreatitis. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 956 BP A170 EP A170 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783700688 ER PT J AU Yen, TW Zhou, W Bell, RH AF Yen, TW Zhou, W Bell, RH TI The gastrin receptor promotes pancreatic growth: Initial studies in a novel transgenic mouse. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2000 VL 118 IS 4 SU 2 MA 2386 BP A1053 EP A1053 PN 1 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 309RU UT WOS:000086783704284 ER PT J AU Bouma, BE Tearney, GJ Compton, CC Nishioka, NS AF Bouma, BE Tearney, GJ Compton, CC Nishioka, NS TI High-resolution imaging of the human esophagus and stomach in vivo using optical coherence tomography SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROINTESTINAL-TRACT; ENDOSCOPIC ULTRASOUND; BARRETT-ESOPHAGUS; BIOPSY; ULTRASONOGRAPHY; REFLECTOMETRY; SURVEILLANCE; TISSUES AB Background: Optical coherence tomography is a new, high spatial-resolution, cross-sectional imaging technique. We investigated the ability of optical coherence tomography to provide detailed images of subsurface structures in the upper gastrointestinal (GI) tract. Methods: Optical coherence tomography was performed during routine upper GI endoscopy on 32 patients including 20 patients with Barrett's esophagus. An endoscopic mucosal biopsy was obtained immediately after imaging and was used for histopathologic correlation. Results: Optical coherence tomography provided clear delineation of layers of the normal human esophagus extending from the epithelium to the longitudinal muscularis propria. Gastric mucosa was differentiated from esophageal mucosa, Barrett's esophagus was differentiated from normal esophageal mucosa, and esophageal adenocarcinoma was distinguished from normal esophagus and Barrett's esophagus. Conclusions: Optical coherence tomography allows visualization of the subsurface architectural morphology of the upper GI tract. The diagnostic information provided by this new imaging modality suggests that it may be a useful adjunct to endoscopy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Labs Photomed, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Bouma, BE (reprint author), MGH BAR 703,50 Blossom St, Boston, MA 02114 USA. NR 21 TC 200 Z9 206 U1 2 U2 10 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 BP 467 EP 474 DI 10.1016/S0016-5107(00)70449-4 PN 1 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 301DN UT WOS:000086293300021 PM 10744824 ER PT J AU Ayub, K Qureshi, W Brown, R Cole, RA Graham, DY AF Ayub, K Qureshi, W Brown, R Cole, RA Graham, DY TI Pulsed irrigation evacuation: A better technique for colon cleansing? SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 VA Med Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 2 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 3423 BP AB88 EP AB88 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300117 ER PT J AU Bjorkman, DJ Zaman, A Fennerty, MB Lieberman, DA DiSario, JA AF Bjorkman, DJ Zaman, A Fennerty, MB Lieberman, DA DiSario, JA TI Preliminary results of a multicenter randomized trial of urgent vs. elective endoscopy in acute nonvariceal upper GI bleeding (UGIB). SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Utah, Salt Lake City, UT USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 3571 BP AB129 EP AB129 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300265 ER PT J AU Bounds, BC Pitman, MB Brugge, WR AF Bounds, BC Pitman, MB Brugge, WR TI Yield of EUS-guided fine needle aspiration cytology of pancreatic juice for diagnosis of pancreatic malignancy. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 4570 BP AB171 EP AB171 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300411 ER PT J AU Brand, SA Bouma, BE Tearney, GJ Poneros, JM Nishioka, NS AF Brand, SA Bouma, BE Tearney, GJ Poneros, JM Nishioka, NS TI Immediate effects of photodynamic therapy on dysplastic Barrett's epithelium as measured by optical coherence tomography. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 7118 BP AB271 EP AB271 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300783 ER PT J AU Chang, KJ Angelov, FA Coleman, JA Wiersema, MJ Gress, FG Faigel, DO Das, A Kochman, ML Catalano, MF Gerdes, H Bhutani, MS Carrougher, JG AF Chang, KJ Angelov, FA Coleman, JA Wiersema, MJ Gress, FG Faigel, DO Das, A Kochman, ML Catalano, MF Gerdes, H Bhutani, MS Carrougher, JG TI A prospective, multi-center comparison between the relative work of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) - An American endosonography committee study. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Calif Irvine, Med Ctr, Orange, CA USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Winthrop Univ Hosp, Mineola, NY 11501 USA. Portland VA Med Ctr, Portland, OR USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Univ Penn, Hlth Syst, Philadelphia, PA 19104 USA. St Lukes Med Ctr, Milwaukee, WI USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Florida, Gainesville, FL USA. Tacoma Digest Dis Ctr, Tacoma, WA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 4592 BP AB177 EP AB177 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300433 ER PT J AU Dulai, GS T, OT Dong, C Alofaituli, G Gralnek, IM AF Dulai, GS T, OT Dong, C Alofaituli, G Gralnek, IM TI Over utilization of healthcare resources for low-risk patients with acute, non-variceal upper GI hemorrhage (UGIH): A retrospective cohort study. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 3572 BP AB129 EP AB129 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300266 ER PT J AU Faigel, DO Lieberman, DA Weinstein, WM Fanning, S Sampliner, RE Fennerty, MB AF Faigel, DO Lieberman, DA Weinstein, WM Fanning, S Sampliner, RE Fennerty, MB TI Squamous overgrowth of Barrett's metaplasia after multipolar electrocoagulation (MPEC) is not a widespread phenomenon: An endoscopic ultrasound study. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. Univ Calif Los Angeles, Hlth Sci Ctr, Los Angeles, CA USA. Univ Arizona, Tucson, AZ USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 6947 BP AB227 EP AB227 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300612 ER PT J AU Farrell, JJ Kelsey, PB AF Farrell, JJ Kelsey, PB TI Duodenoscope-assisted cholangiopancreatoscopy (DACP) achieves technical aims and impacts on biliary and pancreatic disease management. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. HMS, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 7157 BP AB281 EP AB281 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300822 ER PT J AU Fleischer, DE Wang, GQ Wang, GQ Nishioka, NS Bouma, B Farahvash, M Liu, BN Tse, T Dong, Z Dawsey, SM AF Fleischer, DE Wang, GQ Wang, GQ Nishioka, NS Bouma, B Farahvash, M Liu, BN Tse, T Dong, Z Dawsey, SM TI Endoscopic mucosal resection using a cap method (EMR-C) provides safe and effective treatment for early esophageal cancer. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Washington, DC 20007 USA. CICAMS, Inst Canc, Beijing, Peoples R China. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Boston, MA 02115 USA. Univ Tehran, Tehran 14174, Iran. VAMC, Washington, DC USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 7046 BP AB253 EP AB253 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300711 ER PT J AU Gopal, DV Faigel, DO de Garmo, P AF Gopal, DV Faigel, DO de Garmo, P TI Physician resource utilization for endoscopic ultrasound vs. ERCP. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Oregon Hlth Sci Univ, Cori Res Grp, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR 97201 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 4577 BP AB172 EP AB172 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300418 ER PT J AU Jensen, DM Kovacs, TO Jutabha, R Machicado, GA Gralnek, IM Savides, TJ Smith, J Lam, F Fontana, L Cheng, S Jensen, ME Alofaituli, G AF Jensen, DM Kovacs, TO Jutabha, R Machicado, GA Gralnek, IM Savides, TJ Smith, J Lam, F Fontana, L Cheng, S Jensen, ME Alofaituli, G TI Randomized, controlled trial of medical therapy compared with endoscopic therapy for prevention of recurrent ulcer hemorrhage in patients with non-bleeding adherent clots. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Oschner Fdn, New Orleans, LA USA. RI smith, james/C-9922-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 4461 BP AB141 EP AB141 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300302 ER PT J AU Jensen, DM Kovacs, TO Jutabha, P Gralnek, IM Machicado, GA Savides, TJ Smith, J Cheng, S Fontana, L Lam, F Jensen, ME Gornbein, J AF Jensen, DM Kovacs, TO Jutabha, P Gralnek, IM Machicado, GA Savides, TJ Smith, J Cheng, S Fontana, L Lam, F Jensen, ME Gornbein, J TI Randomized, prospective study of bipolar coagulation alone compared to combination epinephrine injection and bipolar coagulation for prevention of rebleeding from ulcers with non-bleeding visible vessels. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. USCD Med Ctr, San Diego, CA USA. Oschner Clin, New Orleans, LA USA. Univ Calif Los Angeles, Hlth Sci Ctr, Los Angeles, CA USA. RI smith, james/C-9922-2016 NR 0 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 3576 BP AB130 EP AB130 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300270 ER PT J AU Machicado, GA Jensen, DM Hirabayashi, K AF Machicado, GA Jensen, DM Hirabayashi, K TI Randomized double blind study of efficacy and safety of ethanolamine-alcohol mixtures or morrhuate for hemostasis of bleeding canine gastric varices. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 3544 BP AB122 EP AB122 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300238 ER PT J AU Poneros, JM Brand, S Bouma, BE Tearney, GJ Nishioka, NS AF Poneros, JM Brand, S Bouma, BE Tearney, GJ Nishioka, NS TI Diagnosis of specialized intestinal metaplasia by optical coherence tomography. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Wellman Lab Photomed, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 4918 BP AB226 EP AB226 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300609 ER PT J AU Poneros, JM Kelsey, PB AF Poneros, JM Kelsey, PB TI Endoscopic siphon drainage of massive traumatic biliary and pancreatic fistulas. SO GASTROINTESTINAL ENDOSCOPY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD APR PY 2000 VL 51 IS 4 MA 4672 BP AB199 EP AB199 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 313PD UT WOS:000087007300513 ER PT J AU Kaufman, KM Farris, AD Gross, JK Kirby, MY Harley, JB AF Kaufman, KM Farris, AD Gross, JK Kirby, MY Harley, JB TI Characterization and genomic sequence of the murine 60 kD Ro gene SO GENES AND IMMUNITY LA English DT Article DE 60 kD Ro; lupus; SSA; Sjogren's syndrome; chromosome 1; mapping; chromosomal assignment ID SYSTEMIC LUPUS-ERYTHEMATOSUS; 60-KDA RO; SS-A/RO; MICE; AUTOIMMUNITY; MOUSE; AUTOANTIGEN; SPECIFICITY; LOCI; DNA AB Autoantibodies binding 60 kD Ro (or SS-A) are commonly found in patients with systemic lupus erythematosus and Sjogren's syndrome. While many studies have examined the autoimmune response directed against this RNA-protein, its function is still uncertain. As part of a broad effort to better understand animal models of anti-Ro autoimmunity we have characterized the murine 60 kD Ro gene. Southern blot analysis of mouse genomic DNA suggests that the 60 kD Ro gene is a single copy gene. The complete sequence of the gene was determined from three overlapping genomic lambda phage clones (GenBank accession number AF065398). The murine 60 kD Ro gene spans similar to 23 kb and consists of 8 or 9 exons. DNA sequence analysis revealed the presence of multiple B1 repetitive units. It maps in synteny with the human 60 kD Ro gene. Therefore, the isolation and characterization of the 60 kD Ro gene will be instrumental for future studies on protein function and the role this protein plays in the development of autoimmune responses. C1 Oklahoma Med Res Fdn, Arthrit & Immunol Program, Oklahoma City, OK 73104 USA. US Dept Vet Affairs, Med Ctr, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA. RP Kaufman, KM (reprint author), Oklahoma Med Res Fdn, Arthrit & Immunol Program, 825 NE 13th St, Oklahoma City, OK 73104 USA. FU NIAID NIH HHS [AI31584, AI24717]; NIAMS NIH HHS [AR42460, AR42474]; NIGMS NIH HHS [GM08237] NR 28 TC 2 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD APR PY 2000 VL 1 IS 4 BP 265 EP 270 DI 10.1038/sj.gene.6363675 PG 6 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 342UA UT WOS:000088662500004 PM 11196703 ER PT J AU Cook, S Penson, R Duska, L Nikrui, N Goodman, A Fuller, A Seiden, M AF Cook, S Penson, R Duska, L Nikrui, N Goodman, A Fuller, A Seiden, M TI Efficacy and hematologic toxicity of salvage chemotherapy following stem cell-supported high-dose chemotherapy in women with recurrent ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; peripheral blood stem cell transplantation; recurrent disease ID STAGE-III; CARCINOMA; CISPLATIN; TRANSPLANTATION; THERAPY; CA-125 AB Objective. The objective of this study was to determine the efficacy and hematologic toxicity of salvage chemotherapy in patients with recurrent ovarian cancer following high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT), Methods. A retrospective analysis of 19 Massachusetts General Hospital case records of women with relapsed ovarian cancer following PBSCT was conducted. Results. Between February 1996 and September 1998, 24 women with ovarian cancer were treated with PBSCT. Nine patients were treated with an upfront PBSCT regimen to consolidate first-line chemotherapy and 15 patients were treated with PBSCT after a median of two lines (range: 1-3) of prior chemotherapy. Sixteen patients presented with relapsed disease at a median of 230 days post-PBSCT and 3 patients had persistent disease through high-dose chemotherapy. Each of these 19 patients has been treated with salvage chemotherapy following PBSCT, Patients received one of six different first-line salvage chemotherapy regimens, Sixteen of nineteen patients are alive a median of 383 days (range: 156-868) after relapse following PBSCT. Three patients died of progressive disease at a median of 284 days (range: 224-648) after post-PBSCT relapse. Six patients achieved a complete response, four patients had a partial response, three patients had stable disease, and six patients had progressive disease in response to first-line salvage chemotherapy, Seven patients experienced grade III/IV neutropenia, and three patients experienced grade III/IV thrombocytopenia, Conclusions. We conclude that in a patient population selected for chemotherapy sensitive and low-volume disease prior to PBSCT, patients with recurrent tumor appear to respond to salvage chemotherapy, and associated hematologic toxicity is acceptable and manageable. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. RP Seiden, M (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St, Boston, MA 02114 USA. NR 17 TC 4 Z9 4 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 APR PY 2000 VL 77 IS 1 BP 48 EP 54 DI 10.1006/gyno.1999.5710 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 304NW UT WOS:000086491200008 PM 10739690 ER PT J AU Garrett, AP Ng, SW Muto, MG Welch, WR Bell, DA Berkowitz, RS Mok, SC AF Garrett, AP Ng, SW Muto, MG Welch, WR Bell, DA Berkowitz, RS Mok, SC TI ras gene activation and infrequent mutation in papillary serous carcinoma of the peritoneum SO GYNECOLOGIC ONCOLOGY LA English DT Article DE K-ras; peritoneal carcinoma; ovarian carcinoma; multifocality; oncogene ID OVARIAN EPITHELIAL TUMORS; C-RAS; CANCER; EXTRAOVARIAN; EXPRESSION; ONCOGENE; PROTEIN; ADENOCARCINOMA; KINASE; WOMEN AB Objective. The ras genes are a well-studied family of protooncogenes whose involvement in many cancers has been delineated. However, K-ras mutations have not previously been examined in papillary serous carcinoma of the peritoneum (PSCP), a tumor which resembles serous epithelial ovarian carcinoma (SEOC) both in histology and epidemiology. In this study we examine the role of the K-ras oncogene in PSCP compared to SEOC. Methods. Using single-strand conformational polymorphism analysis and cycle sequencing protocols, we evaluated our collection of 51 cases of PSCP for K-ras mutations and compared these findings with the experience in SEOC. We then examined 5 cases of PSCP for activation of ras proteins and MAP kinase to evaluate the potential involvement of the ras pathway in PSCP tumorigenesis. Results. We found only one K-ras mutation in our 51 cases (2%) of PSCP compared to three mutations in 46 cases (6.5%) of high-grade, late-stage SEOC. This was not significantly different (P > 0.10), In the single PSCP case with a K-ras mutation, the mutation was found in only one of five tumor sites tested. All four mutations involved a single nucleotide alteration in codon 12 (GGT to GTT, Gly to Val), To evaluate the ras pathway in PSCP, we used the known activated ras binding domain on Raf-1 to perform an assay to test for activated ras, We identified ras activation in 4 of 5 PSCP cases tested and, to confirm that the activation was functional, we tested and found similar activation of MAP kinase, a downstream mediator for EL-ras expression. Conclusions, K-ras mutations occur at low rates in both PSCP and high-grade, late-stage SEOC, and therefore K-ras mutations are not involved in the development of these two diseases. Finding the mutation in only one of multiple tumor sites in the PSCP case supports growing evidence for a multifocal origin of PSCP. Our findings of ras activation in four of five cases of PSCP suggest that ras activation by mechanisms other than genetic mutation is important for PSCP tumorigenesis, (C) 2000 Academic Press. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Lab Gynecol Oncol, Dept Obstet & Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp,Div Gynecol Oncol, Dept Obstet & Gynecol & Reprod Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02114 USA. RP Mok, SC (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Lab Gynecol Oncol, Dept Obstet & Gynecol & Reprod Biol, RFB-472,221 Longwood Ave, Boston, MA 02115 USA. FU NCI NIH HHS [R01CA69291, R01CA63381, R01CA69453] NR 34 TC 3 Z9 4 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 APR PY 2000 VL 77 IS 1 BP 105 EP 111 DI 10.1006/gyno.2000.5747 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 304NW UT WOS:000086491200016 PM 10739698 ER PT J AU Hunt, MK Lederman, R Potter, S Stoddard, A Sorensen, G AF Hunt, MK Lederman, R Potter, S Stoddard, A Sorensen, G TI Results of employee involvement in planning and implementing the Treatwell 5-a-Day work-site study SO HEALTH EDUCATION & BEHAVIOR LA English DT Article ID VEGETABLE INTAKE; HEALTH-PROGRAM; COMMUNITY; STATES; FRUIT AB When work-site health promotion programs incorporate theories of community organization, it is likely that employee ownership and participation are enhanced. This article reports quantitative indicators of involvement of Employee Advisory Board(EAB)members in the Treatwell 5-a-Day work-site study and examines relationships between EAB member time spent on project activities and work-site size, with indicators of the extent of implementation and variables associated with behavior change and work-site support. The results reported here indicate that a greater number of EAB member hours spent on program activities was associated with a greater number of events implemented. Smaller work-site size was associated with greater employee awareness of the program and greater participation in project activities as reported on the employee survey. These results suggest that the number of hours employee representatives devote to project activities might be an important consideration in planning employee involvement in work-site health promotion programming. C1 Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA. Dana Farber Canc Inst, Div Canc Epidemiol & Control, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP Hunt, MK (reprint author), Dana Farber Canc Inst, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [5 R01 CA59728] NR 21 TC 21 Z9 21 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 2000 VL 27 IS 2 BP 223 EP 231 DI 10.1177/109019810002700208 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 298WK UT WOS:000086162300007 PM 10768803 ER PT J AU Kerr, EA Mittman, BS Hays, RD Zemencuk, JK Pitts, J Brook, RH AF Kerr, EA Mittman, BS Hays, RD Zemencuk, JK Pitts, J Brook, RH TI Associations between primary care physician satisfaction and self-reported aspects of utilization management SO HEALTH SERVICES RESEARCH LA English DT Article; Proceedings Paper CT 16th Annual Meeting of the Association-for-Health-Services-Research CY JUN 27-29, 1999 CL CHICAGO, ILLINOIS SP Assoc Hltht Serv Res DE utilization management; utilization review; physician satisfaction; capitation ID QUALITY AB Objective. To evaluate the association between physician-reported utilization management (UM) techniques in capitated physician groups and physician satisfaction with capitated care. Study Setting. 1,138 primary care physicians from 89 California capitated physician groups in 1995. Study Design. Eighty percent of physicians (N = 910) responded to a mail survey regarding the UM policies in their groups and their satisfaction with the care they deliver. Physician-reported UM strategies measured included group-mandated preauthorization (number of referrals requiring preauthorization, referral denial rate, and referral turnaround time), group-provided explicit practice guidelines, and group-delivered educational programs regarding capitated care. We also measured two key dimensions of satisfaction with capitated care (multi- item scales): (1) satisfaction with capitated care autonomy and quality, and (2) satisfaction with administrative burden for capitated patients. Extraction Methods. We constructed two multivariate linear regression models to examine associations between physician-reported UM strategies and physician satisfaction, controlling for demographic and practice characteristics and adjusting for clustering. Principal Findings. Physician-reported denial rate and turnaround time were significantly negatively associated with capitated care satisfaction. Physicians who reported that their groups provided more guidelines were more satisfied on both dimensions, while physicians who reported that their groups sponsored more educational programs were more satisfied with administrative burden. The number of clinical decisions requiring preauthorization was not significantly associated with either dimension of satisfaction. Conclusions. Physicians who reported that their groups used UM methods that directly affected their autonomy (high denial rates and long turnaround times) were less satisfied with care for capitated patients. However, a preauthorization policy for referrals or tests was not, in and of itself, associated with satisfaction. Indirect control mechanisms such as guidelines and education were positively associated with satisfaction. C1 VA Ctr Practice Management & Outcomes Res, Ann Arbor, MI 48113 USA. Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. VA Greater Los Angeles Healthcare Syst, VA Ctr Hlth Care Provider Behav, Sepulveda, CA USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Pfizer Hlth Solut, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. RP Kerr, EA (reprint author), VA Ctr Practice Management & Outcomes Res, POB 130170, Ann Arbor, MI 48113 USA. RI Hays, Ronald/D-5629-2013 NR 23 TC 17 Z9 17 U1 0 U2 3 PU HEALTH ADMINISTRATION PRESS PI MELROSE PARK PA C/O FOUNDATION AMER COLL HEALTHCARE EXECUTIVES 1951 CORNELL AVE, MELROSE PARK, IL 60160 USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD APR PY 2000 VL 35 IS 1 BP 333 EP 349 PN 2 PG 17 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 302RC UT WOS:000086378200013 PM 10778819 ER PT J AU Kiani, A Rao, A Aramburu, J AF Kiani, A Rao, A Aramburu, J TI Manipulating immune responses with immunosuppressive agents that target NFAT SO IMMUNITY LA English DT Review ID ACTIVATED T-CELLS; TRANSCRIPTION FACTOR NFAT1; SEVERE COMBINED IMMUNODEFICIENCY; SMOOTH-MUSCLE CELLS; ATP-DEFICIENT MICE; CYCLOSPORINE-A; NUCLEAR FACTOR; GENE-EXPRESSION; KAPPA-B; GROWTH-FACTOR C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Tech Univ Dresden, Med Klin 1, Klinikum Carl Gustav Carus, D-01307 Dresden, Germany. Ctr Blood Res, Boston, MA 02115 USA. RP Rao, A (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RI Aramburu, J/G-8991-2014 OI Aramburu, J/0000-0001-9279-9523 NR 117 TC 210 Z9 217 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD APR PY 2000 VL 12 IS 4 BP 359 EP 372 DI 10.1016/S1074-7613(00)80188-0 PG 14 WC Immunology SC Immunology GA 309FH UT WOS:000086757300001 PM 10795734 ER PT J AU Young, VB Dangler, CA Fox, JG Schauer, DB AF Young, VB Dangler, CA Fox, JG Schauer, DB TI Chronic atrophic gastritis in SCID mice experimentally infected with Campylobacter fetus SO INFECTION AND IMMUNITY LA English DT Article ID HELICOBACTER-PYLORI INFECTION; EUTHYMIC GERMFREE-MICE; MOUSE MODEL; FELIS INFECTION; JEJUNI; COLONIZATION; PATHOGENESIS; IMMUNOGENICITY; VACCINE; STRAINS AB Campylobacter fetus is a cause of enteritis and invasive extraintestinal disease in humans. In order to develop an animal model of C.fetus infection, outbred ICR SCID mice sere orally challenged with a clinical isolate of C.fetus. The stomachs of SCID mice were heavily colonized with C. fetus, and colonization was associated with the development of chronic atrophic gastritis. This lesion was characterized by an inflammatory infiltrate of granulocytes and macrophages that over time resulted in a loss of specialized parietal and chief cells in the corpus and the appearance of a metaplastic mucous epithelium. This lesion bears similarity to that encountered during experimental murine infection with Helicobacter pylori or Helicobacter felis. Despite colonization of the cecum and colon tissues by C.fetus in SCID mice, no lesions were noted in these tissues. A follow-up study confirmed these findings for SCID mice and also demonstrated that C.fetus could also infect the gastric mucose of wild-type, outbred ICR mice. However, in ICR mice, the anatomic extent of colonization was more limited and the severity of inflammation and epithelial alterations was significantly less than that observed in infected SCID mice. The stomach may represent an unrecognized environmental niche for Campylobacter species. C1 MIT, Div Bioengn & Environm Hlth, Cambridge, MA 02139 USA. MIT, Div Comparat Med, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Med, Infect Dis Unit, Boston, MA 02114 USA. RP Schauer, DB (reprint author), MIT, Div Bioengn & Environm Hlth, Room 56-787, Cambridge, MA 02139 USA. RI Young, Vincent/B-3179-2009 OI Young, Vincent/0000-0003-3687-2364 FU NIAID NIH HHS [R01 AI037750, AI37750, AI01398]; NIDDK NIH HHS [R56 DK052413, R01 DK052413, DK52413] NR 34 TC 17 Z9 18 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2000 VL 68 IS 4 BP 2110 EP 2118 DI 10.1128/IAI.68.4.2110-2118.2000 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300049 PM 10722608 ER PT J AU Angelakopoulos, H Hohmann, EL AF Angelakopoulos, H Hohmann, EL TI Pilot study of phoP/phoQ-deleted Salmonella enterica serovar Typhimurium expressing Helicobacter pylori urease in adult volunteers SO INFECTION AND IMMUNITY LA English DT Article ID TYPHI VACCINE STRAIN; IMMUNE-RESPONSE; IMMUNIZATION; SAFETY; HUMANS; IMMUNOGENICITY; INFECTION; BLOOD; FEVER; MICE AB Attenuated Salmonella enterica serovar Typhi has been studied as an oral vaccine vector. Despite success with attenuated S. enterica serovar Typhimurium vectors in animals, early clinical trials of S. enterica serovar Typhi expressing heterologous antigens have shown that few subjects have detectable immune responses to vectored antigens. A previous clinical study of phoP/phoQ-deleted S. enterica serovar Typhi expressing Helicobacter pylori urease from a multicopy plasmid showed that none of eight subjects had detectable immune responses to the vectored antigen. In an attempt to further define the variables important for engendering immune responses to vectored antigens in humans, six volunteers were inoculated,vith 5 x 10(7) to 8 x 10(7) CFU of phoP/phoQ-deleted S. enterica serovar Typhimurium expressing the same antigen. Two of the six volunteers had fever; none had diarrhea, bacteremia, or other serious side effects. The volunteers were more durably colonized than in previous studies of phoP/phoQ-deleted S. enterica serovar Typhi. Five of the six volunteers seroconverted to S. enter ica serovar Typhimurium antigens and had strong evidence of anti-Salmonella mucosal immune responses by enzyme-linked immunospot studies. Three of six: (three of five who seroconverted to Salmonella) had immune responses in the most sensitive assay of urease-specific immunoglobulin production by blood mononuclear cells in vitro. One of these had a fourfold or greater increase in end-point immunoglobulin titer in serum versus urease. Attenuated S. enterica serovar Typhimurium appears to be more effective than S. enterica serovar Typhi for engendering immune responses to urease, Data suggest that this may be related to a greater stability of antigen-expressing plasmid in S. enterica serovar Typhimurium and/or prolonged intestinal colonization. Specific factors unique to nontyphoidal salmonellae may also be important for stimulation of the gastrointestinal immune system. C1 Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. RP Hohmann, EL (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Gray Jackson 504, Boston, MA 02114 USA. FU NCRR NIH HHS [M01 RR001066, MO1 RR01066-21]; NIAID NIH HHS [R01AI45137] NR 31 TC 112 Z9 124 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2000 VL 68 IS 4 BP 2135 EP 2141 DI 10.1128/IAI.68.4.2135-2141.2000 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300052 PM 10722611 ER PT J AU Haake, DA Chao, G Zuerner, RL Barnett, JK Barnett, D Mazel, M Matsunaga, J Levett, PN Bolin, CA AF Haake, DA Chao, G Zuerner, RL Barnett, JK Barnett, D Mazel, M Matsunaga, J Levett, PN Bolin, CA TI The leptospiral major outer membrane protein LipL32 is a lipoprotein expressed during mammalian infection SO INFECTION AND IMMUNITY LA English DT Article ID INTERROGANS SEROVAR HARDJO; TREPONEMA-PALLIDUM; SEQUENCE-ANALYSIS; PATHOGENIC LEPTOSPIRA; MOLECULAR-CLONING; BOVIS INFECTION; BORRELIA-BURGDORFERI; GENE; VACCINATION; IMMUNOGEN AB We report the cloning of the gene encoding the 32-kDa lipoprotein, designated LipL32, the most prominent protein in the leptospiral protein profile. We obtained the N-terminal amino acid sequence of a staphylococcal V8 proteolytic-digest fragment to design an oligonucleotide probe. A Lambda-Zap II library containing EcoRI fragments of Leptospira kirschneri DNA was screened, and a 5.0-kb DNA fragment which contained the entire structural lipL32 gene was identified. Several lines of evidence indicate that LipL32 is lipid modified in a manner similar to that of other procaryotic lipoproteins. The deduced amino acid sequence of LipL32 would encode a 272-amino-acid poly-peptide with a 19-amino-acid signal peptide, followed by a lipoprotein signal peptidase cleavage site. LipL32 is intrinsically labeled during incubation of L. kirschneri in media containing [H-3]palmitate. The linkage of palmitate and the amino-terminal cysteine of LipL32 is acid labile, LipL32 is completely solubilized by Triton X-114 extraction of L. kirschneri; phase separation results in partitioning of LipL32 exclusively into the hydrophobic, detergent phase, indicating that it is a component of the leptospiral outer membrane. CaCl2 (20 mM) must be present during phase separation for recovery of LipL32. LipL32 is expressed not only during cultivation but also during mammalian infection. Immunohistochemistry demonstrated intense LipL32 reactivity with L. kirshneri infecting proximal tubules of hamster kidneys. LipL32 is also a prominent immunogen during human leptospirosis. The sequence and expression of LipL32 is highly conserved among pathogenic Leptospira species. These findings indicate that LipL32 my be important in the pathogenesis, diagnosis, and prevention of Leptospirosis. C1 VA Greater LA Healthcare Syst, Div Infect Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90095 USA. ARS, Natl Anim Dis Ctr, USDA, Ames, IA 50010 USA. Univ So Indiana, Dept Biol, Evansville, IN 47712 USA. Univ W Indies, Sch Clin Med & Res, Bridgetown, Barbados. RP VA Greater LA Healthcare Syst, Div Infect Dis, 111F, Los Angeles, CA 90073 USA. EM dhaake@ucla.edu FU NIAID NIH HHS [R29 AI034431, AI-34431, R01 AI034431, R21 AI034431, R29 AI034431-04] NR 42 TC 257 Z9 320 U1 2 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2000 VL 68 IS 4 BP 2276 EP 2285 DI 10.1128/IAI.68.4.2276-2285.2000 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 296EP UT WOS:000086010300071 PM 10722630 ER PT J AU Lee, CH Ko, YC Goggins, W Huang, JJ Huang, MS Kao, EL Wang, HZ AF Lee, CH Ko, YC Goggins, W Huang, JJ Huang, MS Kao, EL Wang, HZ TI Lifetime environmental exposure to tobacco smoke and primary lung cancer of non-smoking Taiwanese women SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE lung cancer; environmental tobacco smoke; case-control studies; epidemiology; effect modification ID MULTIPLE RISK-FACTORS; NONSMOKING WOMEN; PASSIVE SMOKING; MULTICENTER; RELIABILITY; HISTORIES AB Background For a female population with a high lung cancer mortality rate, such as Taiwanese women, who smoke relatively rarely, but live in an environment with high male smoking prevalence, the risk and population burden of lung cancer due to environmental tobacco smoke (ETS) are relatively important. Methods An age-matched case-control study was designed to investigate the effects of cumulative environmental exposure to tobacco smoke during childhood and adult life on lung cancer risk among non-smoking women in Taiwan. Information on passive smoking from all possible sources and life periods were obtained from interviews with 268 and 445 lifetime non-smoking cases and controls. Conditional logistic regression and synergism 'S' index were applied to the data to assess the independent and joint effects of passive smoking in different life stages while controlling for possible confounding variables. Results Risks of contracting lung cancer among women near-distantly exposed to the highest level of ETS in childhood (>20 smoker-years) and in adult life (>40 smoker-years) were 1.8-fold (95% CI: 1.2-2.9) and 2.2-fold (95% CI: 1.4-3.7) higher than that among women being never exposed to ETS, and the two variables accounted for about 37% of tumours in this non-smoking female population. Children were found to be more susceptible to ETS than adults and such early exposure was found to modify the effect of subsequent tobacco smoke exposure in adult life based on an additive interaction model. Conclusions Environmental tobacco smoke exposure occurring in childhood potentiates the effect of high doses of exposure in adult life in determining the development of lung cancer. Smoking prohibition would be expected to protect about 37% of non-smoking Taiwanese women against lung cancer. C1 Kaohsiung Med Univ, Sch Publ Hlth, Kaohsiung 807, Taiwan. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02115 USA. Kaohsiung Med Univ, Grad Sch Med, Kaohsiung 807, Taiwan. Kaohsiung Med Univ, Dept Internal Med, Kaohsiung 807, Taiwan. Kaohsiung Med Univ, Dept Surg Med, Kaohsiung 807, Taiwan. Kaohsiung Med Univ, Dept Ophthalmol, Kaohsiung 807, Taiwan. RP Ko, YC (reprint author), Kaohsiung Med Univ, Sch Publ Hlth, 100 Shih Chuan 1st Rd, Kaohsiung 807, Taiwan. RI Kao, Eing-Long/D-5157-2009; Ko, Ying-Chin/C-2084-2009; Lee, Chien-Hung/D-4437-2009 OI Lee, Chien-Hung/0000-0002-0988-264X NR 26 TC 64 Z9 67 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2000 VL 29 IS 2 BP 224 EP 231 DI 10.1093/ije/29.2.224 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 323XE UT WOS:000087589600004 PM 10817117 ER PT J AU Tsai, EC Boyko, EJ Leonetti, DL Fujimoto, WY AF Tsai, EC Boyko, EJ Leonetti, DL Fujimoto, WY TI Low serum testosterone level as a predictor of increased visceral fat in Japanese-American men SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE testosterone; visceral adiposity; body fat distribution; diabetes mellitus; insulin resistance; Japanese Americans; computed tomography ID HORMONE-BINDING-GLOBULIN; DEPENDENT DIABETES-MELLITUS; FASTING PLASMA-INSULIN; C-PEPTIDE LEVELS; ADIPOSE-TISSUE; OBESE MEN; COMPUTED-TOMOGRAPHY; GLUCOSE-TOLERANCE; SEX-HORMONES; RISK-FACTORS AB OBJECTIVE: To examine the association between baseline testosterone levels and changes in visceral adiposity in Japanese-American men. DESIGN: Prospective observational study. SUBJECTS: Second-generation Japanese-American males enrolled in a community-based population study. MEASUREMENTS: At baseline, 110 men received a 75 g oral glucose tolerance test (OGTT), and an assessment of body mass index (BMI); visceral adiposity measured as intra-abdominal fat area (IAF) using computed tomography (CT); fasting insulin and C-peptide levels; and total testosterone levels. IAF was re-measured after 7.5 y. Subcutaneous fat areas were also measured by CT in the abdomen, thorax and thigh. The total fat (TF) was calculated as the sum of IAF and total subcutanous fat areas (SCF). RESULTS: After 7.5 y, IAF increased by a mean of 8.0 cm(2) (95% CI: 0.8, 15.3). Baseline total testosterone was significantly correlated with change in IAF (r = -0.26, P = 0.006), but not to any appreciable degree with change in BMI, TF, or SCF. In a linear regression model with change in IAF as the dependent variable, baseline testosterone was significantly related to this outcome while adjusting for baseline IAF, SCF:, BMI, age, diabetes mellitus status (OGTT by the WHO diagnostic criteria) and fasting C-peptide (regression coefficient for baseline testosterone [nmol/l] = -107.13, P = 0.003). CONCLUSIONS: In this Japanese-American male cohort, lower baseline total testosterone independently predicts an increase in IAF. This would suggest that by predisposing to an increase in visceral adiposity, low levels of testosterone may increase the risk of type 2 diabetes mellitus. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Anthropol, Seattle, WA 98195 USA. Seattle Epidemiol Res & Informat Ctr, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA USA. RP Tsai, EC (reprint author), VAMC, HSR&D 152,1660 S Columbian Way, Seattle, WA 98108 USA. FU NCRR NIH HHS [RR 00037]; NHLBI NIH HHS [HL 49293]; NIDDK NIH HHS [DK 31170] NR 51 TC 106 Z9 126 U1 0 U2 6 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 2000 VL 24 IS 4 BP 485 EP 491 DI 10.1038/sj.ijo.0801183 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 300RR UT WOS:000086266400013 PM 10805506 ER PT J AU Trotti, A Byhardt, R Stetz, J Gwede, C Corn, B Fu, K Gunderson, L McCormick, B Morris, M Rich, T Shipley, W Curran, W AF Trotti, A Byhardt, R Stetz, J Gwede, C Corn, B Fu, K Gunderson, L McCormick, B Morris, M Rich, T Shipley, W Curran, W CA Radiation Therapy Oncology Grp TI Common toxicity criteria: Version 2.0. an improved reference for grading the acute effects of cancer treatment: Impact on radiotherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Review DE toxicity; acute effects; side effects; adverse events; morbidity; complications; normal tissue effects; radiation; chemotherapy; chemoradiation; combined modality AB In 1997, the National Cancer Institute (NCI) led an effort to revise and expand the Common Toxicity Criteria (CTC) with the goal of integrating systemic agent, radiation, and surgical criteria into a comprehensive and standardized system. Representatives from the Radiation Therapy Oncology Group (RTOG) participated in this process in an effort to improve acute radiation related criteria and to achieve better clarity and consistency among modalities. CTC v, 2.0 replaces the previous NCI CTC and the RTOG Acute Radiation Morbidity Scoring Criteria and includes more than 260 individual adverse events with more than 100 of these applicable to acute radiation effects. One of the advantages of the revised criteria for radiation oncology is the opportunity to grade acute radiation effects not adequately captured under the previous RTOG system, A pilot study conducted by the RTOG indicated the new criteria are indeed more comprehensive and were preferred by research associates. CTC v, 2.0 represents an improvement in the evaluation and grading of acute toxicity for all modalities. (C) 2000 Elsevier Science Inc. C1 Univ S Florida, H Lee Moffitt Canc Ctr, Div Radiat Oncol, Tampa, FL 33612 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. RTOG Headquarters, Philadelphia, PA USA. Thomas Jefferson Univ Hosp, Bodine Canc Treatment Ctr, Philadelphia, PA 19107 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Mayo Clin, Sch Med, Rochester, MN USA. Cornell Univ Med Coll, Mem Sloan Kettering Canc Ctr, New York, NY USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Virginia, Ctr Sci, Charlottesville, VA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Trotti, A (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, Div Radiat Oncol, 12902 Magnolia Dr, Tampa, FL 33612 USA. RI huang, hongqi/N-1473-2014 NR 5 TC 513 Z9 557 U1 3 U2 16 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 APR 1 PY 2000 VL 47 IS 1 BP 13 EP 47 DI 10.1016/S0360-3016(99)00559-3 PG 35 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 303MW UT WOS:000086426500002 PM 10758303 ER PT J AU Young, RH AF Young, RH TI Meigs' syndrome: Dr. Richard Cabot's hidden first American case SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE Meigs' syndrome; Dr. Joe V. Meigs; Dr. Richard C. Cabot AB The syndrome known most widely as "Meigs' syndrome" is so named as a result of the description of it by Dr. Joe V. Meigs (a gynecologist with a strong interest in pathology) and Dr. John W. Cass (an internist with a major interest in pulmonary disease) in 1937. In his final writings on the topic 17 years later, Dr. Meigs reviewed the literature prior to his first report in more detail than he had initially and credited appropriately those who had noted the association of ovarian fibromatous tumors, ascites and pleural effusion in earlier times. He did not, however, record the description of the association by the great physician, Dr. Richard C. Cabot in 1912 even though they worked in the same hospital and the case in question was one of those that formed the basis of the report of Meigs and Cass. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Young, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, 32 Fruit St,WRN 219, Boston, MA 02114 USA. NR 21 TC 3 Z9 3 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD APR PY 2000 VL 8 IS 2 BP 165 EP 168 DI 10.1177/106689690000800213 PG 4 WC Pathology; Surgery SC Pathology; Surgery GA 326AU UT WOS:000087710300010 PM 11493983 ER PT J AU Freeman, EE Grosskreutz, CL AF Freeman, EE Grosskreutz, CL TI The effects of FK506 on retinal ganglion cells after optic nerve crush SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CEREBRAL-ISCHEMIA; NEURONS; BRAIN; IMMUNOPHILINS; SURVIVAL; NEUROTOXICITY; CALCINEURIN; INCREASES; PROTECTS; NUMBER AB PURPOSE. The purpose of this study was twofold: to determine whether immunophilins were present in the rat retina and to determine the physiologic consequence of their presence. METHODS. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were performed on rat retinal tissue, and the immunophilin FKBP12 was found to be present in retina. Immunohistochemical studies showed the presence of FKBP12 in retinal ganglion cells (RGCs). In rats, optic nerve crush was performed on one side and a sham operation on the other side. By gavage, animals were given 5 mg/kg per day of the FKBP12 ligand FK506 in sterile phosphate-buffered saline (PBS) or in PBS alone. Eight days after nerve crush, the total number of back-labeled RGCs was estimated from retinal wholemounts. RESULTS. In control eyes, the number of labeled ganglion cells was 74,104 +/- 4,166 (mean +/- SEM) in rats receiving vehicle and 74,993 +/- 3,098 in animals receiving FK506 daily. Eight days after optic nerve crush, 27,775 +/- 3,332 labeled ganglion cells were counted in retinas of animals receiving vehicle (n = 11), whereas 33% more ganglion cells (37,118 +/- 2,475) were counted in animals receiving FK506 daily (n = 11). This difference was statistically significant (P < 0.05). CONCLUSIONS. The data presented demonstrate that the immunophilin FKBP12 is present in retina and specifically in RGCs. In addition, the FKBP12 ligand FK506 confers neuroprotection on RGCs after optic nerve crush. This neuroprotection may occur as a result of FK506's ability to interfere with apoptotic mechanisms after optic nerve crush. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Consultat Serv, Boston, MA 02114 USA. RP Grosskreutz, CL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol,Glaucoma Consultat Serv, 243 Charles St, Boston, MA 02114 USA. OI Freeman, Ellen/0000-0002-1403-8427 FU NEI NIH HHS [K11EY00342] NR 21 TC 36 Z9 38 U1 0 U2 1 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 APR PY 2000 VL 41 IS 5 BP 1111 EP 1115 PG 5 WC Ophthalmology SC Ophthalmology GA 299LA UT WOS:000086199000022 PM 10752948 ER PT J AU Barouch, FC Miyamoto, K Allport, JR Fujita, K Bursell, SE Aiello, LP Luscinskas, FW Adamis, AP AF Barouch, FC Miyamoto, K Allport, JR Fujita, K Bursell, SE Aiello, LP Luscinskas, FW Adamis, AP TI Integrin-mediated neutrophil adhesion and retinal leukostasis in diabetes SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID CELL-SURFACE RECEPTORS; LEUKOCYTE DYNAMICS; IN-VITRO; MICROCIRCULATION; ENDOTHELIUM; MOLECULE-1; MONOCYTES; SELECTIN; MAC-1; RATS AB PURPOSE. A critical early event in the pathogenesis of diabetic retinopathy is leukocyte adhesion to the diabetic retinal vasculature. The process is mediated, in part, by intercellular adhesion molecule-1 (ICAM-1) and results in blood-retinal barrier breakdown and capillary nonperfusion. This study evaluated the expression and function of the corresponding ICAM-1-binding leukocyte beta(2)-integrins in experimental diabetes. METHODS. Diabetes was induced in Long Evans rats with streptozotocin. The expression of the surface integrin subunits CD11a, CD11b, and CD18 on rat neutrophils isolated from peripheral blood was quantitated with flow cytometry. In vitro neutrophil adhesion was studied using quantitative endothelial cell-neutrophil adhesion assays. The adhesive role of the integrin subunits CD11a, CD11b, and CD18 was tested using specific neutralizing monoclonal antibodies. CD18 bioactivity was blocked in vivo with anti-CD18 F(ab')(2) fragments, and the effect on retinal leukocyte adhesion was quantitated with acridine orange leukocyte fluorography. RESULTS. Neutrophil CD11a, CD11b, and CD18 surface integrin levels were 62% (n = 5, P = 0.006), 54% (n = 5, p = 0.045), and 38% (n = 5, P = 0.009) greater in diabetic versus nondiabetic animals, respectively. Seventy-five percent more neutrophils from diabetic versus nondiabetic animals adhered to rat endothelial cell monolayers (n = 6, P = 0.02). Pretreatment of leukocytes with either anti-CD 11b or anti-CD 18 antibodies lowered the proportion of adherent diabetic neutrophils by 41% (n = 6, P = 0.01 for each treatment), whereas anti-CD11a antibodies had no significant effect (n = 6, P = 0.5). In vivo, systemic administration of anti-CD18 F(ab'), fragments decreased diabetic retinal leukostasis by 62% (n = 5, P = 0.001). CONCLUSIONS. Neutrophils from diabetic animals exhibit higher levels of surface integrin expression and integrin-mediated adhesion. In vivo, CD18 blockade significantly decreases leukostasis in the diabetic retinal microvasculature. Integrin adhesion molecules may serve as therapeutic targets for the treatment and/or prevention of early diabetic retinopathy. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Childrens Hosp, Surg Res Lab, Boston, MA 02115 USA. Kyoto Univ, Grad Sch Med, Dept Ophthalmol & Visual Sci, Kyoto, Japan. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Vasc Res Div, Boston, MA USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Ophthalmol, Boston, MA 02115 USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. FU NEI NIH HHS [EY 12611]; NHLBI NIH HHS [HL 36028, HL 53993] NR 22 TC 142 Z9 156 U1 0 U2 4 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 APR PY 2000 VL 41 IS 5 BP 1153 EP 1158 PG 6 WC Ophthalmology SC Ophthalmology GA 299LA UT WOS:000086199000028 PM 10752954 ER PT J AU Ambati, J Canakis, CS Miller, JW Gragoudas, ES Edwards, A Weissgold, DJ Kim, I Delori, FC Adamis, AP AF Ambati, J Canakis, CS Miller, JW Gragoudas, ES Edwards, A Weissgold, DJ Kim, I Delori, FC Adamis, AP TI Diffusion of high molecular weight compounds through sclera SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 09-14, 1999 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol, Natl Hlth Public Serv Award, Childern Hosp Res Fdn ID RETINAL GANGLION-CELLS; DRUG-DELIVERY; GROWTH-FACTOR; IN-VIVO; MACROMOLECULES; NEOVASCULARIZATION; DEGENERATION; PERMEABILITY; INHIBITION; EYE AB PURPOSE. To determine the in vitro permeability of the sclera to high molecular weight compounds and the relationship between scleral permeability and molecular size. METHODS. Fresh rabbit sclera was mounted in a two-chamber diffusion apparatus, and its permeability to sodium fluorescein, fluorescein isothiocyanate (FITC)- conjugated bovine serum albumin, FITC-IgG, and FITC dextrans ranging in molecular weight from 4 to 150 kDa was determined by fluorescence spectrophotometry. Electron microscopy was used to assess the impact of the experimental design on scleral ultrastructural integrity. The effect of the diffusion apparatus on scleral hydration was examined. Rabbit scleral permeability was compared with previously reported data for human and bovine sclera. RESULTS. Scleral permeability decreased with increasing molecular weight and molecular radius, consistent with previous human and bovine data. Molecular radius was a better predictor of scleral permeability than molecular weight. The sclera was more permeable to globular proteins than to linear dextrans of similar molecular weight. The experimental apparatus did not alter scleral ultrastructure. Permeability of rabbit sclera was similar to human sclera but greater than bovine sclera. CONCLUSIONS. Large molecules, such as IgG, diffuse across sclera in a manner consistent with porous diffusion through a fiber matric. Transscleral delivery of immunoglobulins and other large com pounds to the choroid and retina may be feasible. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Tufts Univ, Dept Chem Engn, Medford, MA 02155 USA. Univ Vermont, Dept Ophthalmol, Burlington, VT USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Childrens Hosp, Surg Res Lab, Boston, MA USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 31 TC 210 Z9 218 U1 0 U2 11 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 APR PY 2000 VL 41 IS 5 BP 1181 EP 1185 PG 5 WC Ophthalmology SC Ophthalmology GA 299LA UT WOS:000086199000032 PM 10752958 ER PT J AU Ambati, J Gragoudas, ES Miller, JW You, TT Miyamoto, K Delori, FC Adamis, AP AF Ambati, J Gragoudas, ES Miller, JW You, TT Miyamoto, K Delori, FC Adamis, AP TI Transscleral delivery of bioactive protein to the choroid and retina SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 09-14, 1999 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol, Natl Hlth Public Serv Award, Childern Hosp Res Fdn ID ENDOTHELIAL GROWTH-FACTOR; DRUG-DELIVERY; IN-VIVO; RETROBULBAR INJECTION; GANGLION-CELLS; NEOVASCULARIZATION; DEGENERATION; SCLERA; SUBCONJUNCTIVAL; INHIBITION AB PURPOSE. To investigate the feasibility of transscleral drug delivery to the choroid and retina. METHODS. An osmotic pump was used to deliver IgG across the sclera of pigmented rabbits, and levels were measured in the choroid, retina, vitreous humor, aqueous humor, orbit, and plasma over 28 days. This method was then used to deliver an anti-intercellular adhesion molecule-1 (ICAM-1) monoclonal antibody (mAb), and its effect on inhibiting vascular endothelial growth factor (VEGF)-induced leukostasis in the choroid and retina was determined by measuring tissue myeloperoxidase (MPO) activity. RESULTS. Levels of retinal and choroidal IgG were significantly higher than baseline at all points up to 28 days (P less than or equal to 0.01). IgG levels in the orbit, vitreous humor, aqueous humor, and plasma were negligible (P > 0.05). MPO activity in the choroid of eyes treated with anti-ICAM-1 mAb was 80% less (P = 0.01) than in eyes receiving an equal rate of delivery of an isotype control antibody. Inhibition of MPO activity in the retina was 70% (P = 0.01). The plasma concentration of anti-ICAM-1 mAb was 31,000-fold less than the concentration in the osmotic pump. CONCLUSIONS. Minimally invasive transscleral delivery can be used to deliver therapeutic levels of bioactive drugs to the choroid and retina with negligible systemic absorption. This method of ocular drug delivery may be used in the treatment of a variety of chorioretinal disorders. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Childrens Hosp, Surg Res Lab, Boston, MA USA. Harvard Univ, Sch Med, Schepens Eye Res Inst, Boston, MA USA. RP Adamis, AP (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. NR 39 TC 125 Z9 127 U1 0 U2 6 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 APR PY 2000 VL 41 IS 5 BP 1186 EP 1191 PG 6 WC Ophthalmology SC Ophthalmology GA 299LA UT WOS:000086199000033 PM 10752959 ER PT J AU Altfeld, M Addo, MM Kreuzer, KA Rockstroh, JK Dumoulin, FL Schliefer, K Leifeld, L Sauerbruch, T Spengler, U AF Altfeld, M Addo, MM Kreuzer, KA Rockstroh, JK Dumoulin, FL Schliefer, K Leifeld, L Sauerbruch, T Spengler, U TI T(H)1 to T(H)2 shift of cytokines in peripheral blood of HIV-infected patients is detectable by reverse transcriptase polymerase chain reaction but not by enzyme-linked immunosorbent assay under nonstimulated conditions SO JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE cytokines; RT-PCR; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; NECROSIS-FACTOR-ALPHA; MONONUCLEAR-CELLS; IMMUNOPATHOGENIC MECHANISMS; SEMIQUANTITATIVE ANALYSIS; TYPE-2 CYTOKINES; POLARIZED TYPE-1; GENE-EXPRESSION; AIDS; ACTIVATION AB Background: Dysregulation of cytokines has been implicated in the pathogenesis of HIV infection. Therefore, we determined tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), IL-4, IL-10, and interferon-gamma (IFN-gamma) mRNA and serum levels in HIV-infected patients under nonstimulated conditions. Material and Methods: Blood samples of 32 HIV-infected patients and 10 healthy HIV-negative controls were analyzed. Cytokine serum levels were quantified by enzyme-linked immunosorbent assay (ELISA). Cytokine mRNA levels were determined semiquantitatively by competitive reverse transcriptase polymerase chain reaction (RT-PCR) and expressed as ratios relative to those of beta-actin. Results: Competitive RT-PCR was shown to be more sensitive than protein ELISA in analyzing cytokine production. We found a significant correlation between steady-state mRNA ratios and serum protein levels for TNF-alpha. Significantly higher cytokine mRNA ratios were found in those patients with IL-10 and IFN-gamma levels detectable by ELISA. Steady-state mRNA ratios of TNF-alpha, IL-4, and IL-10 were significantly increased in patients with highly replicative HIV-infection. Furthermore, elevated IL-4:IFN-gamma ratios were related to both high viral load and loss of CD4 cells. Discussion: Determination of steady-state mRNA ratios by semiquantitative RT-PCR represents a sensitive method to analyze cytokines in peripheral blood of HIV-infected patients under nonstimulated conditions. The data obtained with this technique provide further evidence for a T(H)1 to T(H)2 cytokine shift with progressive HIV disease. C1 Univ Bonn, Dept Internal Med 1, D-5300 Bonn, Germany. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, AIDS Res Ctr, 149 13th St,5th Floor, Charlestown, MA 02129 USA. NR 30 TC 34 Z9 38 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 J ACQ IMMUN DEF SYND JI J. Acquir. Immune Defic. Syndr. PD APR 1 PY 2000 VL 23 IS 4 BP 287 EP 294 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 313PQ UT WOS:000087008400001 PM 10836750 ER PT J AU Venegas, JG Galletti, GG AF Venegas, JG Galletti, GG TI Low-pass filtering, a new method of fractal analysis: application to PET images of pulmonary blood flow SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE coefficient of variation; digital filtering; fractal dimension; functional imaging; spatial heterogeneity ID HETEROGENEITY; LUNGS AB The pattern of a spatial structure that repeats itself independently of the scale of magnification or resolution is often characterized by a fractal dimension (D). Two-dimensional low-pass filtering, which may serve as a method to assess D, was applied to functional images of pulmonary perfusion measured by positron emission tomography. The corner frequency of a low-pass filter is inversely proportional to the resolution scale. The method was applied to three types of images: random noise images, synthetic fractal images, and positron emission tomographic images of pulmonary perfusion. images were processed with two-dimensional lowpass filters of decreasing corner frequencies, and a spatial heterogeneity index, the coefficient of variation, was calculated for each low-pass-filtered image. The natural logarithm of the coefficient of variation scaled linearly with the natural logarithm of the resolution scale for the PET images studied (average R-2 = 0.99). D ranged-from 1.25 to 1.36 for the residual distribution of pulmonary perfusion after vertical gradients were removed by linear regression. D of the same data without removal of vertical gradients ranged from 1.11 to 1.14, but the fractal plots had systematic deviations from linearity and a lower linear correlation coefficient (R-2 = 0.96). The method includes all data in the lung field and is insensitive to the effects of misregistration. We conclude that low-pass filtering offers new insights into the interpretation of D of two-dimensional functional images as a measure of the frequency content of spatial heterogeneity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biomed Engn,Anesthesiol Serv,Clin 2, Boston, MA 02114 USA. RP Venegas, JG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biomed Engn,Anesthesiol Serv,Clin 2, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL-38267] NR 24 TC 23 Z9 23 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 APR PY 2000 VL 88 IS 4 BP 1365 EP 1373 PG 9 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 301MA UT WOS:000086312900030 PM 10749831 ER PT J AU Nguyen, T Shrager, J Kaiser, L Mei, LJ Daood, M Watchko, J Rubinstein, N Levine, S AF Nguyen, T Shrager, J Kaiser, L Mei, LJ Daood, M Watchko, J Rubinstein, N Levine, S TI Developmental myosin heavy chains in the adult human diaphragm: coexpression patterns and effect of COPD SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE human diaphragmatic muscle; embryonic myosin heavy chain; neonatal myosin heavy chain; fiber types; immunocytochemistry ID RAT SKELETAL-MUSCLE; OBSTRUCTIVE PULMONARY-DISEASE; HUMAN MASSETER MUSCLE; ELECTROPHORETIC SEPARATION; CONTRACTILE PROPERTIES; CELLULAR ADAPTATIONS; RESPIRATORY MUSCLES; NORMAL MEN; FATIGUE; ISOFORMS AB In preliminary experiments we noted developmental (i.e., embryonic and neonatal) myosin heavy chains (MHCs) in the diaphragms of patients with severe chronic obstructive pulmonary disease (COPD). We hypothesized that this finding represented new fiber formation secondary to injury associated with the mechanical stress of COPD or previously undescribed MHCs in the human diaphragm. To distinguish between these possibilities, me analyzed diaphragmatic biopsies obtained from 9 patients with severe COPD (forced expiratory volume in 1 s = 21 +/- 2% predicted, residual volume = 283 +/- 22% predicted) and 10 age-matched controls. First, using immunocytochemistry with specific monoclonal antibodies, we noted that control diaphragms had greater proportions of fibers expressing embryonic (50 +/- 2 vs. 28 +/- 3%, P < 0.0001) and neonatal (52 +/- 2 vs. 32 +/- 3%, P < 0.001) MHCs than COPD diaphragms. Second, SDS-PAGE demonstrated that these developmental MHCs represented only a very small fraction of the diaphragmatic MHC content. Third, the RT-PCR demonstrated mRNA coding for embryonic and neonatal MHCs in COPD and control diaphragms. Last, COPD and control diaphragms exhibited normal histology on light microscopy. We conclude that the presence of developmental MHC isoforms does not indicate new fiber formation in diaphragms of patients with severe COPD. Although these results represent the first systematic description of embryonic and neonatal MHCs in normal adult human diaphragms, their function remains to be elucidated. C1 Philadelphia Vet Affairs Med Ctr, Med Serv, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Univ Pittsburgh, Sch Med, Magee Womens Res Inst, Dept Pediat, Pittsburgh, PA 15213 USA. Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Res Serv, Philadelphia, PA 19104 USA. RP Levine, S (reprint author), VA Med Ctr, Pulm & Crit Care Sect 111P, Univ & Woodland Ave, Philadelphia, PA 19004 USA. NR 53 TC 26 Z9 28 U1 0 U2 1 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 APR PY 2000 VL 88 IS 4 BP 1446 EP 1456 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 301MA UT WOS:000086312900040 PM 10749841 ER PT J AU Smith, SE Estok, DM Harris, WH AF Smith, SE Estok, DM Harris, WH TI 20-year experience with cemented primary and conversion total hip arthroplasty using so-called second-generation cementing techniques in patients aged 50 years or younger SO JOURNAL OF ARTHROPLASTY LA English DT Article DE cemented; primary total hip arthroplasty; age <= 50 years; revision; lysis ID REPLACEMENT AB We present the 20-year experience of 47 hips in 40 patients aged 50 years or younger with cemented primary total hip arthroplasty using second-generation femoral cementing techniques. Average follow-up duration in the 23 patients living at least 17 years was 18.2 years. Overall, 18 hips (38%) had components revised or removed for any reason, at an average duration of 12.6 years. Every revision or reoperation involved removing the acetabular component. Of these 18 acetabular components, 15 (32%) were revised for aseptic loosening. Eleven additional acetabular components were loose by radiographic criteria at final follow-up, yielding prevalence of aseptic acetabular loosening (55%). Four femoral components (8%) were revised for osteolysis without loosening, and 3 (6%) were revised for aseptic loosening. Femoral osteolysis, with or without component loosening, led to revision in 5 (11%) hips compared with 6% for aseptic loosening alone. Osteolysis was the primary problem leading to acetabular and femoral component revision in this series of people less than or equal to 50 years old over the first 20 years after the index operation. C1 Massachusetts Gen Hosp, Orthopaed Biomech Lab, Boston, MA 02114 USA. RP Massachusetts Gen Hosp, Orthopaed Biomech Lab, GrJ 1126,55 Fruit St, Boston, MA 02114 USA. NR 29 TC 47 Z9 50 U1 0 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 EI 1532-8406 J9 J ARTHROPLASTY JI J. Arthroplast. PD APR PY 2000 VL 15 IS 3 BP 263 EP 273 DI 10.1016/S0883-5403(00)90463-7 PG 11 WC Orthopedics SC Orthopedics GA 303ZW UT WOS:000086458900001 PM 10794220 ER PT J AU Rogers, MB Sexton, JA DeCastro, GJ Calderwood, SB AF Rogers, MB Sexton, JA DeCastro, GJ Calderwood, SB TI Identification of an operon required for ferrichrome iron utilization in Vibrio cholerae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TRANSCRIPTIONAL REGULATION; ESCHERICHIA-COLI; FUR GENE; VIRULENCE; TRANSPORT; RECEPTOR; PROTEINS; CLONING; FHUA; FAMILY AB Mutagenesis of Vibrio cholerae with TnphoA, followed by screening for fusions that were activated under low-iron conditions, led to the identification of seven independent fusion strains, each of which was deficient in the ability to utilize ferrichrome as a sole iron source for growth in a plate bioassay and had an insertion in genes encoding products homologous to Escherichia coli FhuA or FhuD. Expression of the gene fusions was independent of IrgB but regulated by Fur. We report here a map of the operon and the predicted amino acid sequence of FhuA, based on the nucleotide sequence. Unlike those of the E. coli fhu operon, the V. cholerac ferrichrome utilization genes are located adjacent and opposite in orientation to a gene encoding an ATP-binding cassette transporter homolog, but this gene, if disrupted, does not affect the utilization of ferrichrome in vitro. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP Calderwood, SB (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Jackson 504,55 Fruit St, Boston, MA 02114 USA. FU NIAID NIH HHS [R01AI34968]; NIDDK NIH HHS [F32 DK009651, F32DK09651] NR 21 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2000 VL 182 IS 8 BP 2350 EP 2353 DI 10.1128/JB.182.8.2350-2353.2000 PG 4 WC Microbiology SC Microbiology GA 299NU UT WOS:000086205400041 PM 10735886 ER PT J AU Stover, EP Siegel, LC Body, SC Levin, J Parks, P Maddi, R D'Ambra, MN Mangano, DT Spiess, BD AF Stover, EP Siegel, LC Body, SC Levin, J Parks, P Maddi, R D'Ambra, MN Mangano, DT Spiess, BD CA Institutions MultiCenter Study Per TI Institutional variability in red blood cell conservation practices for coronary artery bypass graft surgery SO JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA LA English DT Article DE transfusion; blood; blood products; packed red blood cells; blood conservation; cardiac surgery; coronary artery bypass graft surgery; red cell salvage; cell-saver; shed mediastinal blood; normovolemic hemodilution; autologous blood ID CARDIAC-SURGERY; CARDIOPULMONARY BYPASS; TRANSFUSION PRACTICE; AUTOLOGOUS BLOOD; AUTO-TRANSFUSION; DOUBLE-BLIND; OPERATIONS; PLASMAPHERESIS; MULTICENTER; ACID AB Objective:To assess whether substantial institutional variability exists in red blood cell conservation practices associated with coronary artery bypass graft (CABG) surgery. Design: Prospective, randomized patient enrollment and data collection. Setting: Twenty-four U.S. academic institutions participating in the Multicenter Study of Perioperative Ischemia. Participants: A well-defined subset of primary CABG surgery patients (n = 713) expected to be at low risk for bleeding and exposure to allogeneic transfusion. Interventions: None (observational study). Measurements and Main Results: Frequency of use of red blood cell conservation techniques was determined among institutions. Correlation was determined between use of each technique and transfusion of allogeneic red blood cells and between use of each technique and median institutional blood loss. Significant variability (p < 0.01) was detected in institutional transfusion practice with respect to the use of predonated autologous whole blood, normovolemic hemodilution, red cell salvage, and reinfusion of shed mediastinal blood. The frequency of institutional use of these techniques was not associated with allogeneic transfusion (r(2) < 0.15) or blood loss (r(2) < 0.10) in the low-risk population of patients examined. Conclusions: Institutions vary significantly in perioperative blood conservation practices for CABG surgery. Further study to determine the appropriate use of these techniques is warranted. Copyright (C) 2000 by W.B. Saunders Company. C1 Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. Univ Calif San Francisco, Sch Med, Dept Lab Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Anesthesia, San Francisco, CA 94143 USA. Ischemia Res & Educ Fdn, San Francisco, CA USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Anesthesia, Richmond, VA 23298 USA. RP Stover, EP (reprint author), Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA. OI Siegel, Lawrence/0000-0002-8456-7551 NR 32 TC 25 Z9 24 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-0770 J9 J CARDIOTHOR VASC AN JI J. Cardiothorac. Vasc. Anesth. PD APR PY 2000 VL 14 IS 2 BP 171 EP 176 PG 6 WC Anesthesiology; Cardiac & Cardiovascular Systems; Respiratory System; Peripheral Vascular Disease SC Anesthesiology; Cardiovascular System & Cardiology; Respiratory System GA 305GJ UT WOS:000086530800014 PM 10794337 ER PT J AU Hood, JK Casolari, JM Silver, PA AF Hood, JK Casolari, JM Silver, PA TI Nup2p is located on the nuclear side of the nuclear pore complex and coordinates Srp1p/importin-alpha export SO JOURNAL OF CELL SCIENCE LA English DT Article DE Nup2p; Srp1p; Cse1p; nucleoporin; yeast; nuclear export ID PROTEIN IMPORT; SACCHAROMYCES-CEREVISIAE; MOLECULAR ARCHITECTURE; YEAST NUCLEOPORIN; TARGETING COMPLEX; TRANSPORT FACTORS; RAN; BINDING; ALPHA; BETA AB Proteins bearing canonical nuclear localization sequences are imported into the nucleus by the importin/karyopherin-alpha/beta heterodimer, Recycling of the importin-alpha subunit to the cytoplasm requires the action of Gas, a member of the importin-beta superfamily. In the yeast Saccharomyces ceresivisiae, the essential gene CSE1 encodes a Cas homologue that exports the yeast importin-alpha protein Srp1p/Kap60p from the nucleus. In this report, we describe a role for the FXFG nucleoporin Nup2p, and possibly the related Nup1p, in the Cse1p-mediated nuclear export pathway. Yeast cells lacking Nup2p or containing a particular temperature-sensitive mutation in NUP1 accumulate Srp1p in the nucleus. Similarly, Cse1p is displaced from the nuclear rim to the nuclear interior in Delta nup2 cells. We do not observe any biochemical interaction between Cse1p and Nup2p. Instead, we find that Nup2p binds directly to Srp1p, We have localized Nup2p to the interior face of the nuclear pore complex, and have shown that its N terminus is sufficient for targeting Nup2p to the pore, as well as for binding to Srp1p, Taken together, these data suggest that Nup2p is an important NPC docking site in the Srp1p export pathway. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 44 Binney St, Boston, MA 02115 USA. NR 45 TC 43 Z9 44 U1 2 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR PY 2000 VL 113 IS 8 BP 1471 EP 1480 PG 10 WC Cell Biology SC Cell Biology GA 310XQ UT WOS:000086855200015 PM 10725229 ER PT J AU Yamada, M Huang, ZH Dalkara, T Endres, M Laufs, U Waeber, C Huang, PL Liao, JK Moskowitz, MA AF Yamada, M Huang, ZH Dalkara, T Endres, M Laufs, U Waeber, C Huang, PL Liao, JK Moskowitz, MA TI Endothelial nitric oxide synthase-dependent cerebral blood flow augmentation by L-arginine after chronic statin treatment SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE HMG-CoA reductase inhibitor; type III nitric oxide synthase; nitric oxide; endothelium; hyperemia ID COA REDUCTASE INHIBITORS; VASODILATION; HUMANS; ISCHEMIA; INSULIN; STROKE; MICE; PARADOX; GERBIL; RAT AB Nitric oxide, a product of nitric oxide synthase activity, relaxes vascular smooth muscle and elevates brain blood flow. We evaluated the importance of eNOS to cerebral blood flow augmentation after L-arginine infusion and increases in flow after eNOS upregulation in SV-129 mice. Blood flow was measured by laser-Doppler flowmetry before and after L-arginine infusion (450 mg/kg during a 15-minute period) or measured by C-14-iodoamphetamine indicator fractionation or C-14-iodoantipyrine tissue equilibration techniques. rCBF increased by 26% (laser Doppler flowmetry) after L-arginine infusion but did not change in mutant mice deficient in eNOS expression. After eNOS upregulation by chronic simvastatin treatment (2 mg/kg subcutaneously, daily for 14 days), L-arginine amplified and sustained the hyperemia (38%) and increased absolute brain blood flow from 86 +/- 7 to 119 +/- 10 mL/100 g per minute. Furthermore, pretreatment with simvastatin enhanced blood flow within ischemic brain tissue after middle cerebral artery occlusion. Together, these findings suggest that eNOS activity is critical for blood flow augmentation during acute L-arginine infusion, and chronic eNOS upregulation combined with L-arginine administration provides a novel strategy to elevate cerebral blood flow in the normal and ischemic brain. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Vasc Med & Atherosclerosis Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Hacettepe Univ Hosp, Dept Neurol, Ankara, Turkey. RP Moskowitz, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, 149th St,Room 6403, Charlestown, MA 02129 USA. RI Moskowitz, Michael/D-9916-2011; Waeber, Christian/A-8333-2009 OI Waeber, Christian/0000-0001-6078-0027 FU NHLBI NIH HHS [1R01 HL6202]; NINDS NIH HHS [5P50 NS10828] NR 41 TC 99 Z9 102 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2000 VL 20 IS 4 BP 709 EP 717 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 304CW UT WOS:000086466000008 PM 10779015 ER PT J AU Clemmons, DR Moses, AC McKay, MJ Sommer, A Rosen, DM Ruckle, J AF Clemmons, DR Moses, AC McKay, MJ Sommer, A Rosen, DM Ruckle, J TI The combination of insulin-like growth factor I and insulin-like growth factor-binding protein-3 reduces insulin requirements in insulin-dependent type 1 diabetes: Evidence for in vivo biological activity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID IGF-I; RHIGF-I; GLYCEMIC CONTROL; HORMONE; ADULTS; MELLITUS; RESISTANCE; IMPROVES; GLUCOSE; ENHANCEMENT AB Insulin-Like growth factor-I (TGF-I) enhances insulin action in normal subjects and in patients with both type 1 and 2 diabetes; however, its administration is associated with significant side effects in a high percentage of patients. The coadministration of IGF binding protein-3 (IGFBP-3, the predominant IGF binding protein in serum) with IGF-I limits IGF-I inducible side effects, but it does not attenuate the ability of IGF-I to enhance protein synthesis and bone accretion; therefore, we determined whether IGF-I/IGFBP-3 would retain biological activity in type I DM and limit side effects associated with free IGF-I administration. Twelve patients received recombinant human IGF-I plus IGFBP-3 (2 mg/kg day) by continuous sc infusion for 2 weeks. Each subject served as his own control; and, during a paired 2-week period, each received a placebo infusion. The order of the treatments was randomized. Subjects were placed on a constant caloric intake but mere allowed to adjust insulin doses to maintain appropriate levels of glycemic control. Subjects measured blood glucose four times per day at home and kept a log of their insulin use. Frequent sampling for glucose, insulin, and GH was conducted during four inpatient study periods, one at the beginning and one at the end of each a-week study interval. During IGF-I/IGFBP-3, insulin doses were reduced by 49%, and mean serum glucose was reduced by 23%. Free insulin levels obtained during frequent sampling in hospital fell 47% on IGF-I/IGFBP-3, compared with control, but showed no change with placebo. Concomitant glucose measurements did not differ in the two treatment groups. There was no change in body weight. Fructosamine levels decreased by 12%, but this was not significant (P < 0.1). Fasting triglyceride was unchanged, but cholesterol declined from 110 +/- 24 to 149 +/- 31 mg/dL (P < 0.05). IGFBP-2 (an IGF-I-dependent responsive variable) rose from 141 +/- 56 to 251 +/- 98 ng/mL (P < 0.01) on IGF-I/IGFBP-3. To analyze the mechanism by which IGF-I/IGFBP-3 might reduce insulin requirements, the change in serum GH was quantified. Mean GH levels were reduced by 72%, from 2.48 to 0.55 ng/mL (P < 0.001). An equal number (40%) of drug- and placebo treated subjects had minor hypoglycemic episodes at home that required adjustment of insulin doses. No episode was classified as severe. In contrast to previous studies with free IGF-I, there were no cases of edema, headache, jaw pain, retinal edema, or Bell's palsy. No subject withdrew because of drug complications. These findings indicate that IGF-I/IGFBP-5 is biologically active on carbohydrate metabolism, as measured by a decrease in insulin requirements in patients with type 1 diabetes. Further studies will be required to determine the long-term safety and efficacy of this combination in patients with insulin resistance and diabetes. C1 Univ N Carolina, Div Endocrinol, Dept Med, Chapel Hill, NC 27599 USA. Celtrix Pharmaceut Inc, San Jose, CA USA. NW Kinet, Tacoma, WA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA USA. RP Clemmons, DR (reprint author), Univ N Carolina, Div Endocrinol, Dept Med, CB 7170, Chapel Hill, NC 27599 USA. EM endo@med.unc.edu FU NCRR NIH HHS [RR-000046]; NIA NIH HHS [AG02331] NR 37 TC 94 Z9 110 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 APR PY 2000 VL 85 IS 4 BP 1518 EP 1524 DI 10.1210/jc.85.4.1518 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WY UT WOS:000088387200027 PM 10770191 ER PT J AU Rasmussen, SK Lautier, C Hansen, L Echwald, SM Hansen, T Ekstrom, CT Urhammer, SA Borch-Johnsen, K Grigorescu, F Smith, RJ Pedersen, O AF Rasmussen, SK Lautier, C Hansen, L Echwald, SM Hansen, T Ekstrom, CT Urhammer, SA Borch-Johnsen, K Grigorescu, F Smith, RJ Pedersen, O TI Studies of the variability of the genes encoding the insulin-like growth factor I receptor and its ligand in relation to type 2 diabetes mellitus SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BIRTH-WEIGHT; INTRAUTERINE GROWTH; HUMAN-FETUS; SENSITIVITY; RESISTANCE; MUTATIONS; FAMILIES; DELETION; GLUCOSE; LIFE AB Insulin-Like growth factor I (IGF-I) is an important regulator of many aspects of growth, differentiation, and development, and as low birth weight has been associated with impaired glucose tolerance and overt type 2 diabetes in adult Life, we considered the genes encoding the IGF-I and the IGF-I receptor (IGF-IR) as candidates for low birth weight, insulin resistance, and type 2 diabetes. Here we report the mutational analysis of the coding regions of the IGF-I and IGF-IR performed on genomic DNA from probands of 82 Danish type 2 diabetic families. No mutations predicting changes in the amino acid sequences of the IGF-I or IGF-IR genes were detected, but several silent and intronic polymorphisms were found. The impact of the most prevalent polymorphism, GAG1013GAA of the IGF-IR, was evaluated in a population-based sample of 349 young healthy subjects, where the variant had an allele frequency of 0.44 (95% confidence interval, 0.40-0.48). No significant relationships between this variant and birth weight, birth length, or insulin sensitivity index were detected. In addition, we did not observe any significant differences in allelic frequencies of the codon 1013 variant between 395 type 2 diabetic patients (allele frequency, 0.52; 95% confidence interval, 0.49-0.55) and 238 matched glucose-tolerant control subjects (allelic frequency, 0.47; 95% confidence interval, 0.43-0.50). In conclusion, variability in the coding regions of IGF-I and the IGF-IR does not associate with reduced birth weight, insulin sensitivity index, or type 2 diabetes in the Danish population. C1 Steno Diabet Ctr, DK-2820 Gentofte, Denmark. Hagedorn Res Inst, DK-2820 Gentofte, Denmark. Inst Univ Rech Clin, Mol Endocrinol Lab, F-34093 Montpellier, France. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Glostrup Univ Hosp, Ctr Prevent Med, DK-2820 Gentofte, Denmark. RP Rasmussen, SK (reprint author), Steno Diabet Ctr, Niels Steensens Vej 2-6, DK-2820 Gentofte, Denmark. OI Ekstrom, Claus Thorn/0000-0003-1191-373X NR 22 TC 44 Z9 45 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2000 VL 85 IS 4 BP 1606 EP 1610 DI 10.1210/jc.85.4.1606 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 337WY UT WOS:000088387200041 PM 10770205 ER PT J AU Hammond, CS Wasson, JH Walker-Corkery, ES Fowler, FJ Barry, MJ AF Hammond, CS Wasson, JH Walker-Corkery, ES Fowler, FJ Barry, MJ TI An educational intervention does not improve outcomes of prostate-related problems in primary care SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Meeting Abstract C1 Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Massachusetts, Boston, MA 02125 USA. RP Hammond, CS (reprint author), Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Hanover, NH 03756 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 2000 VL 53 IS 4 BP 438 EP 438 PG 1 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 309UP UT WOS:000086787900015 ER PT J AU Martuza, RL AF Martuza, RL TI Conditionally replicating herpes vectors for cancer therapy SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID SIMPLEX VIRUS; RIBONUCLEOTIDE REDUCTASE; ANTITUMOR-ACTIVITY; MALIGNANT GLIOMAS; GENE-TRANSFER; MUTANT; TUMORS; GROWTH; MODEL C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Martuza, RL (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, WHT502 55 Fruit St, Boston, MA 02114 USA. FU NINDS NIH HHS [NS32677, R01 NS032677] NR 30 TC 92 Z9 93 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 APR PY 2000 VL 105 IS 7 BP 841 EP 846 DI 10.1172/JCI9744 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 300XW UT WOS:000086279900002 PM 10749560 ER PT J AU Attorri, S Dunbar, S Clarridge, JE AF Attorri, S Dunbar, S Clarridge, JE TI Assessment of morphology for rapid presumptive identification of Mycobacterium tuberculosis and Mycobacterium kansasii SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CORD FORMATION; COMPLEX; CULTURES; PROBES AB Mycobacterium tuberculosis often exhibits serpentine cording when grown in liquid medium, whereas Mycobacterium kansasii can be larger and cross-barred, We assessed the use of these morphologic characteristics as a cost-effective method for rapid presumptive identification of isolates from BACTEC bottles. Without specific training, using the Kinyoun acid-fast stain, definitive cording was found in 237 of 373 specimens positive for M. tuberculosis (64%) and cross-barring was recognized within 63 of 76 (83%) of the specimens positive for M. kansasii, giving sensitivities specificities, positive predictive values, and negative predictive values of 63.5, 96, 92, and 79%, respectively, for M. tuberculosis and 83, 95, 59, and 98%, respectively, for M kansasii. With training and experience, these results improved to 74.5, 98, 96, and 84% and 93, 98, 79, and 98%, respectively. The major improvements were in distinguishing the pseudocording or loose aggregation of Mycobacterium avium complex from M. tubereculosis and the long bended forms of Mycobacterium gordonae from M. kansasii. Mycobacterium asiaticum and Mycobacterium szulgai, which rarely occur, are genetically related to M kansasii and morphologically difficult to distinguish. In defined circumstances, serpentine cording and cross-barring can be used for rapid presumptive identification of M. tuberculosis and M. kansasii, respectively, and as guides for initial probe selection to reduce costs. C1 VA Med Ctr, Pathol & Lab Med Serv 113, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Microbiol & Immunol, Houston, TX 77030 USA. RP Clarridge, JE (reprint author), VA Med Ctr, Pathol & Lab Med Serv 113, 2002 Holcombe Blvd, Houston, TX 77030 USA. NR 8 TC 17 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2000 VL 38 IS 4 BP 1426 EP 1429 PG 4 WC Microbiology SC Microbiology GA 301GN UT WOS:000086302500020 PM 10747119 ER PT J AU Crivellari, D Bonetti, M Castiglione-Gertsch, M Gelber, RD Rudenstam, CM Thurlimann, B Price, KN Coates, AS Hurny, C Bernhard, J Lindtner, J Collins, J Senn, HJ Cavalli, F Forbes, J Gudgeon, A Simoncini, E Cortes-Funes, H Veronesi, A Fey, M Goldhirsch, A AF Crivellari, D Bonetti, M Castiglione-Gertsch, M Gelber, RD Rudenstam, CM Thurlimann, B Price, KN Coates, AS Hurny, C Bernhard, J Lindtner, J Collins, J Senn, HJ Cavalli, F Forbes, J Gudgeon, A Simoncini, E Cortes-Funes, H Veronesi, A Fey, M Goldhirsch, A CA Int Breast Canc Study Grp TI Burdens and benefits of adjuvant cyclophosphamide, methotrexate, and fluorouracil and tamoxifen for elderly patients with breast cancer: The International Breast Cancer Study Group Trial VII SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID COOPERATIVE ONCOLOGY GROUP; QUALITY-OF-LIFE; CHEMOTHERAPY; THERAPY; WOMEN; POSTMENOPAUSAL; EXPERIENCE; MORTALITY; TOXICITY; SURVIVAL AB Purpose: Information on the tolerability and efficacy of adjuvant chemoendocrine therapy for older women is limited. We studied these issues using the data collected as part of the International Breast Cancer Study Group Trial VII. Patients and Methods: Postmenopausal women with operable, node-positive breast cancer were randomized to receive either tamoxifen atone for 5 years (306 patients) or tamoxifen plus three consecutive cycles of classical cyclophosphamide (100 mg/m(2) orally days 1 to 14), methotrexate (40 mg/m(2) intravenous days 1 and 8), and fluorouracil (600 mg/m(2) intravenous days 1 and 8) every 28 days (CMF; 302 patients). The median follow-up was 8.0 years. Results: Among the 299 patients who received at least one dose of CMF, women 65 years of age or older (n = 76) had higher grades of toxicity compared with women less than 65 years old (n = 223) (P = .004), More women in the older age group compared with the younger women experienced grade 3 toxicity of any type (17% v 7%, respectively), grade 3 hematologic toxicity (9% v 5%, respectively), and grade 3 mucosal toxicity (4% v 1%, respectively), Older patients also received less than their expected CMF dose compared with younger postmenopausal women (P = .0008). The subjective burdens of treatment, however, were similar for younger and older patients based on quality-of-life measurer (performance status, coping, physical wellbeing, mood, and appetite), Far older patients, the 5-year disease-free survival (DFS) rates were 63% for CMF plus tamoxifen and 61% for tamoxifen alone (hazards ratio [HR], 1.00; 95% confidence interval [Cl], 0.65 to 1.52; P = .99). For younger patients, the corresponding 5-year DFS rates were 61% and 53% (HR, 0.70; 95% Cl, 0.53 to 0.91; P = .008), hut the test for heterogeneity of CMF effect according to age group was not statistically significant, The reduced effectiveness of CMF among older women could not be attributed to doss reductions according to dose received. Conclusion: CMF tolerability and effectiveness were both reduced for older patients compared with younger postmenopausal node-positive breast cancer patients who received tamoxifen for 5 years. The development and evaluation of less toxic and more effective chemotherapy regimens are required for high-risk elderly patients. (C) 2000 by American Society of Clinical Oncology. C1 Ctr Riferimento Oncol Aviano, Aviano, Italy. Osped Civile, Brescia, Italy. Fdn Beretta, Brescia, Italy. Ist Europeo Oncol, Milan, Italy. Dana Farber Canc Inst, Int Breast Canc Study Grp, Ctr Stat, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Int Breast Canc Study Grp, Coordinating Ctr, Bern, Switzerland. Inselspital Bern, Swiss Grp Clin Canc Res, CH-3010 Bern, Switzerland. Kantonsspital, St Gallen, Switzerland. Burgerspital, St Gallen, Switzerland. Ctr Tumor Detect & Prevent, St Gallen, Switzerland. Osped San Giovanni, Swiss Grp Clin Canc Res, Bellinzona, Italy. Osped Civico, Lugano, Switzerland. Sahlgrens Univ Hosp, W Swedish Breast Canc Study Grp, S-41345 Gothenburg, Sweden. Univ Sydney, Sydney, NSW 2006, Australia. Australian Canc Soc, Sydney, NSW, Australia. Anticanc Council Victoria, Melbourne, Vic, Australia. Univ Newcastle, Waratah, Australia. Inst Oncol, Ljubljana, Slovenia. Groote Schuur Hosp, ZA-7925 Cape Town, South Africa. Madrid Breast Canc Grp, Madrid, Spain. RP Crivellari, D (reprint author), Ctr Riferimento Oncol Aviano, Via Pedemontana Occidentale 12, Aviano, Italy. OI Bonetti, Marco/0000-0003-2304-4180 FU NCI NIH HHS [CA-06516, CA-75362] NR 28 TC 195 Z9 199 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 2000 VL 18 IS 7 BP 1412 EP 1422 PG 11 WC Oncology SC Oncology GA 300RG UT WOS:000086265500002 PM 10735888 ER PT J AU Spitler, LE Grossbard, ML Ernstoff, MS Silver, G Jacobs, M Hayes, FA Soong, SJ AF Spitler, LE Grossbard, ML Ernstoff, MS Silver, G Jacobs, M Hayes, FA Soong, SJ TI Adjuvant therapy of stage III and IV malignant melanoma using granulocyte-macrophage colony-stimulating factor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACTIVE SPECIFIC IMMUNOTHERAPY; NECROSIS-FACTOR-ALPHA; C-KIT-LIGAND; METASTATIC MELANOMA; PROGNOSTIC FACTORS; MULTIFACTORIAL ANALYSIS; CUTANEOUS MELANOMA; SURGICAL-TREATMENT; IMPROVED SURVIVAL; RANDOMIZED TRIAL AB Purpose: To evaluate granulocyte-macrophage colany-stimulating factor (GM-CSF) as surgical adjuvant therapy in patients with malignant melanoma who are at high risk of recurrence. Patients and Methods: Forty-eight assessable patients with stage III or IV melanoma were treated in a phase II trial with long-term, chronic, intermittent GM-CSF after surgical resection of disease. Patients with stage III disease were required to have more than four positive nodes or a more than 3-cm mass, All patients were rendered clinically disease-free by surgery before enrollment. The GM-CSF wets administered subcutaneously in 28-day cycles, such that a dose of 125 mu g/m(2) was delivered daily for 14 days followed by 14 days of rest. Treatment cycles continued for 1 year or until disease recurrence. Patients were evaluated for toxicity and disease-free and overall survival. Results: Overall and disease-free survival were significantly prolonged in patients who received GM-CSF compared with matched historical controls. The median survival duration was 57.5 months in the study patients versus 12.2 months in the matched controls (P < .001). GM-CSF wets well tolerated; only one subject discontinued drug due to an adverse event (grade 2 injection site reaction). Conclusion: GM-CSF may provide an antitumor effect that prolongs survival and disease-free survival in patients with stage III and IV melanoma who are clinically disease-free. These results support institution of a prospective, randomized clinical trial to definitively determine the value of surgical adjuvant therapy with GM-CSF in such patients, J Clin Oncol 18:1614-1621. (C) 2000 by American Society of Clinical Oncology. C1 No Calif Melanoma Ctr, San Francisco, CA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. Norris Cotton Canc Ctr, Lebanon, NH USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. RP Spitler, LE (reprint author), St Francis Mem Hosp, No Calif Med Ctr, 900 Hyde St, San Francisco, CA 94109 USA. NR 41 TC 148 Z9 152 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 2000 VL 18 IS 8 BP 1614 EP 1621 PG 8 WC Oncology SC Oncology GA 307LV UT WOS:000086655500003 PM 10764421 ER PT J AU Park, CC Mitsumori, M Nixon, A Recht, A Connolly, J Gelman, R Silver, B Hetelekidis, S Abner, A Harris, JR Schnitt, SJ AF Park, CC Mitsumori, M Nixon, A Recht, A Connolly, J Gelman, R Silver, B Hetelekidis, S Abner, A Harris, JR Schnitt, SJ TI Outcome at 8 years after breast-conserving surgery and radiation therapy for invasive breast cancer: Influence of margin status and systemic therapy on local recurrence SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 21st Annual San Antonio Breast Cancer Symposium CY DEC 12-15, 1998 CL SAN ANTONIO, TEXAS ID EXCISION; RISK; LUMPECTOMY; CARCINOMA; TRIAL; CONSERVATION; IRRADIATION; TAMOXIFEN; TUMORS AB Purpose: To examine the relationship between pathologic margin status and outcome at 8 years after breast-conserving surgery and radiation therapy, Patients and Methods: The study population comprised 533 patients with international Union Against Cancer/American Joint Committee on Cancer clinical stage I or II breast cancer who had assessable margins, who received at least 60 Gy to the primary tumor bed, and who had more than 8 years of potential follow-up. Each margin was scored (according to the presence of inversive or in situ disease that touched the inked surgical margin) as one of the following: negative, close, focally positive, or extensively positive. Outcome at 8 years was calculated using crude rates of first site of failure. A polychotomous logistic regression analysis was performed, Median follow-vp time was 127 months. Results: At 8 years, patients with close margins and those with negative margins both held a rate of local recurrence (LR) of: 7%, patients with extensively positive margins had an LR rate of 27%, whereas patients with focally positive margins had an intermediate rate of LR of 14%, In the polychotomous logistic regression model, margin status and the use of systemic therapy were the only two variables that had significant effects on the risk ratio of LR to remaining alive and free of disease, Among the 45 patients with focally positive margins who received systemic therapy, the crude LR rate was 7% at 8 years (95% confidence interval, 1% to 20%), Conclusion: Pathologic margin status and the use of adjuvant systemic therapy are the most important factors associated with LR among patients treated with breast-conserving surgery and radiation therapy. J Clin Oncol 88:1668-1675, (C) 2000 by American Society of Clinical Oncology. C1 Joint Ctr Radiat Therapy, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Div Biostat, Boston, MA 02115 USA. RP Park, CC (reprint author), Joint Ctr Radiat Therapy, 330 Brookline Ave, Boston, MA 02215 USA. NR 23 TC 324 Z9 338 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR PY 2000 VL 18 IS 8 BP 1668 EP 1675 PG 8 WC Oncology SC Oncology GA 307LV UT WOS:000086655500009 PM 10764427 ER PT J AU Caroff, SN Mann, SC Keck, PE Francis, A AF Caroff, SN Mann, SC Keck, PE Francis, A TI Residual catatonic state following neuroleptic malignant syndrome SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article AB Neuroleptic malignant syndrome (NMS) is usually a self-limited disorder, with most cases resolving within 2 weeks after antipsychotic drug discontinuation. However, the course of NMS may not always be short-lived. In this report, the authors describe five patients who developed a residual catatonic state that persisted after acute hyperthermic symptoms of NMS had subsided and compare them with 27 similar cases in the literature. Two of our patients recovered gradually with supportive treatment. Three patients were treated with electroconvulsive therapy (ECT). Of these, two showed a positive response, although one died later of intercurrent pneumonia. A third patient did not respond to ECT, but recovered gradually thereafter. Although dopamine agonists or benzodiazepines have been advocated for the treatment of residual symptoms in previous case reports, ECT was the treatment most often associated with a. rapid response and no mortality, even in patients refractory to pharmacotherapy. In conclusion, catatonic and parkinsonian symptoms of NMS may persist as a residual state lasting for weeks to months after more fulminant acute symptoms abate. These residual symptoms may be more Likely to develop in patients with preexisting structural brain disorders. Although patients may improve gradually with supportive care or pharmacotherapy, ECT can often be highly effective in treating the residual catatonic state that follows NMS. C1 Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Cincinnati, Coll Med, Dept Psychiat, Biol Psychiat Program, Cincinnati, OH USA. SUNY Stony Brook, Sch Med, Dept Psychiat, Stony Brook, NY 11794 USA. RP Caroff, SN (reprint author), Dept Vet Affairs Med Ctr, 116A Univ Ave, Philadelphia, PA 19104 USA. NR 26 TC 39 Z9 40 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD APR PY 2000 VL 20 IS 2 BP 257 EP 259 DI 10.1097/00004714-200004000-00021 PG 3 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 301GR UT WOS:000086302800021 PM 10770467 ER PT J AU Braaten, EB Rosen, LA AF Braaten, EB Rosen, LA TI Self-regulation of affect in attention deficit-hyperactivity disorder (ADHD) and non-ADHD boys: Differences in empathic responding SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY LA English DT Article ID EMOTIONAL EXPRESSIVENESS; COMORBID DISORDERS; NORMATIVE DATA; FOLLOW-UP; BEHAVIOR; CHILDREN; SYMPTOMS; CRITERIA; CONDUCT; RATINGS AB This study examined differences in empathy and other emotions between buys with and without attention deficit-hyperactivity disorder (ADHD). Empathy was measured by an empathy response task (ERT) and through self- and parent reports of emotion. On the ERT, children responded verbally to 8 fictitious stories. Results from the ERT revealed that boys with ADHD were less empathic than boys without ADHD. Boys with ADHD less frequently matched the emotion they identified in the character with the one identified in themselves and gave fewer character-centered interpretations in their descriptions of the character's emotion. Parent-report data revealed that boys with ADHD exhibited more behavioral manifestations of sadness, anger, and guilt than did boys without ADHD. No differences were found, however, on measures of emotional intensity or emotional reactions to external contingencies. The results are discussed with respect to current theories of ADHD. C1 Massachusetts Gen Hosp, Dept Psychiat, Wang Ambulatory Care Ctr 805, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. RP Braaten, EB (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Wang Ambulatory Care Ctr 805, 15 Parkman St, Boston, MA 02114 USA. NR 46 TC 87 Z9 89 U1 3 U2 27 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-006X J9 J CONSULT CLIN PSYCH JI J. Consult. Clin. Psychol. PD APR PY 2000 VL 68 IS 2 BP 313 EP 321 DI 10.1037//0022-006X.68.2.313 PG 9 WC Psychology, Clinical SC Psychology GA 321ZM UT WOS:000087485300014 PM 10780132 ER PT J AU Antisdel, JE Chrisler, JC AF Antisdel, JE Chrisler, JC TI Comparison of eating attitudes and behaviors among adolescent and young women with type 1 diabetes mellitus and phenylketonuria SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article; Proceedings Paper CT 102nd Annual Conference of the American-Psychological-Association CY AUG 11-16, 1994 CL LOS ANGELES, CALIFORNIA SP Amer Psychol Assoc DE type 1 diabetes mellitus; phenylketonuria; eating problems ID ANOREXIA-NERVOSA; MATERNAL PHENYLKETONURIA; METABOLIC CONTROL; INSULIN OMISSION; WEIGHT-CONTROL; DISORDERS; IDDM; ADHERENCE; INTELLIGENCE; PREVALENCE AB The purpose of this study was to assess the eating attitudes and behaviors associated with two chronic diseases that have strong dietary treatment components: type 1 diabetes mellitus and phenylketonuria (PKU). Participants consisted of female campers and staff members who were attending one of two summer camps that specialize in the care of females with type 1 diabetes mellitus (N = 54) and PKU (N = 30). Eating attitudes and behaviors, psychological adjustment, and disease-specific knowledge were assessed using standardized and nonstandardized self-report questionnaires. There was no overall difference in the presence of disordered eating symptomatology between those with diabetes and those with PKU. However, differences in patterns of eating attitudes and behaviors were observed. The data suggest that living with chronic diseases which are treated with dietary management may adversely affect eating attitudes and behaviors and may Increase susceptibility to the development of eating disturbances. C1 Connecticut Coll, Dept Psychol, New London, CT 06320 USA. Joslin Diabet Ctr, Sect Behav & Mental Hlth Res, Boston, MA USA. RP Chrisler, JC (reprint author), Connecticut Coll, Dept Psychol, New London, CT 06320 USA. FU NIDDK NIH HHS [T32DK07260] NR 46 TC 13 Z9 13 U1 3 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 2000 VL 21 IS 2 BP 81 EP 86 DI 10.1097/00004703-200004000-00001 PG 6 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 305KC UT WOS:000086537900001 PM 10791475 ER PT J AU Griffey, RT Brown, DFM Nadel, ES AF Griffey, RT Brown, DFM Nadel, ES TI Cyanosis SO JOURNAL OF EMERGENCY MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Harvard Affiliated Emergency Med Residency, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Emergency Med, Boston, MA 02115 USA. RP Brown, DFM (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St, Boston, MA 02114 USA. NR 5 TC 9 Z9 9 U1 0 U2 1 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 APR PY 2000 VL 18 IS 3 BP 369 EP 371 DI 10.1016/S0736-4679(99)00229-2 PG 3 WC Emergency Medicine SC Emergency Medicine GA 295PR UT WOS:000085977500014 PM 10729678 ER PT J AU Clever, SL Edwards, KA Feudtner, C Braddock, CH AF Clever, SL Edwards, KA Feudtner, C Braddock, CH TI Defining the "hidden curriculum": Does medical students' ethical experience on clinical rotations vary by specialty? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, RWJ Clin Scholars, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Ctr Excellence Hlth Serv Res & Dev, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 28 EP 28 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400022 ER PT J AU Lehmann, LS Weeks, JC Cook, EF Meehan, B AF Lehmann, LS Weeks, JC Cook, EF Meehan, B TI Pelvic exams on anesthetized women for practice: A national survey of fourth year medical students. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 37 EP 38 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400064 ER PT J AU Simon, SR Hamann, C Fletcher, SW AF Simon, SR Hamann, C Fletcher, SW TI Are OSCEs worth the effort? Faculty and student perceptions of an objective structured clinical examination. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Pilgrim Hlth Care, Boston, MA USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 44 EP 44 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400091 ER PT J AU Taneda, K Boyko, EJ Martin, DC Fihn, SD Itoh, H Ohbu, S Fukui, T Matsui, Y AF Taneda, K Boyko, EJ Martin, DC Fihn, SD Itoh, H Ohbu, S Fukui, T Matsui, Y TI The impact of autopsies on clinical education of residents. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Kyoto Univ Hosp, Kyoto 606, Japan. St Lukes Int Hosp, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 46 EP 46 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400102 ER PT J AU Barton, MB Moore, S Allen, JD Emmons, KE Fletcher, SW AF Barton, MB Moore, S Allen, JD Emmons, KE Fletcher, SW TI Is perception of breast cancer risk related to health and psychological status? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 53 EP 53 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400131 ER PT J AU Burman, ML McDonell, MB Fihn, SD Bradley, KA AF Burman, ML McDonell, MB Fihn, SD Bradley, KA TI Determinants of alcohol advice or treatment among at-risk drinkers in the outpatient setting. Results from the ACQUIP study. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Ctr Excellence, HSR&D, Seattle, WA USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 56 EP 56 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400143 ER PT J AU Herndon, B Kilbourne, AM Wang, M Lee, M Asch, S Andersen, R Gelberg, L AF Herndon, B Kilbourne, AM Wang, M Lee, M Asch, S Andersen, R Gelberg, L TI HIV testing among high-risk homeless women - Good news from Los Angeles County. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Greater Los Angeles VA Healthcare Syst, Los Angeles, CA USA. VA Pittsburgh Healthcare Syst, Dept Med, Pittsburgh, PA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Family Med, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 70 EP 70 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400203 ER PT J AU Huang, ES Melgs, JB Singer, DE AF Huang, ES Melgs, JB Singer, DE TI The magnitude and timing of effect of preventive strategies in type 2 diabetes mellitus. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 72 EP 72 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400212 ER PT J AU Kolbusz, KM Elicler, IA Kaur, J Mak, EB Collins, D AF Kolbusz, KM Elicler, IA Kaur, J Mak, EB Collins, D TI Effectiveness of exercise demonstration for arthritis patients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 LUMC, Maywood, IL USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 77 EP 78 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400234 ER PT J AU Lawrence, VA Hilsenbeck, SG Noveck, H Poses, RM Carson, JL AF Lawrence, VA Hilsenbeck, SG Noveck, H Poses, RM Carson, JL TI Medical complications after hip fracture repair. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. Brown Univ, Providence, RI 02912 USA. Vet Adm Med Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 79 EP 79 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400241 ER PT J AU Messersmith, WA Brown, DFM Barry, MJ AF Messersmith, WA Brown, DFM Barry, MJ TI The prevalence and implications of incidental findings on emergency department abdominal CT scans. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 83 EP 83 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400259 ER PT J AU Micek, MA Braddock, CH Bradley, KA Martin, D McDonell, MB Fihn, SD AF Micek, MA Braddock, CH Bradley, KA Martin, D McDonell, MB Fihn, SD TI The relationship between patient satisfaction and health related beliefs. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Dept Med, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Ctr Excellence, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 83 EP 84 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400260 ER PT J AU Mortensen, EM Obrosky, DS Coley, CM Singer, DE Marrie, TJ Kapoor, WN Fine, MJ AF Mortensen, EM Obrosky, DS Coley, CM Singer, DE Marrie, TJ Kapoor, WN Fine, MJ TI Predictors of pneumonia-related and non-pneumonia-related mortality in community-acquired pneumonia. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Univ Alberta, Edmonton, AB, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 85 EP 85 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400265 ER PT J AU Natarajan, S Bradford, WD Kleckley, TV Silverstein, MD AF Natarajan, S Bradford, WD Kleckley, TV Silverstein, MD TI Independent effects of cardiovascular disease and diabetes on acute health care utilization and health status. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Ralph H Johnson VAMC, Charleston, SC USA. Med Univ S Carolina, Div Gen Internal Med, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 87 EP 87 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400275 ER PT J AU Natarajan, S Nietert, PJ Kleckley, TV Silverstein, MD AF Natarajan, S Nietert, PJ Kleckley, TV Silverstein, MD TI Impact of multiple cardiovascular risk factors on acute health care utilization and health status. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Ralph H Johnson VAMC, Charleston, SC USA. Med Univ S Carolina, Div Gen Internal Med, Charleston, SC 29425 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 87 EP 87 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400276 ER PT J AU Rigotti, NA Thorndike, AN Durcan, MJ White, JD Johnston, JA Niaura, R Gonzales, D Sachs, DPL Hayes, JT Hurt, RD AF Rigotti, NA Thorndike, AN Durcan, MJ White, JD Johnston, JA Niaura, R Gonzales, D Sachs, DPL Hayes, JT Hurt, RD TI Smokers taking bupropion gain less weight after smoking cessation: A gender-related effect. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Palo Alto Ctr Pulm Dis Prevent, Palo Alto, CA USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Brown Univ, Providence, RI 02912 USA. Glaxo Wellcome Res & Dev Ltd, Res Triangle Pk, NC USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 93 EP 93 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400300 ER PT J AU Rigotti, NA Wechsler, H AF Rigotti, NA Wechsler, H TI Cigar smoking by US college students. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 93 EP 93 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400301 ER PT J AU Atlas, SJ Dedier, JJ Singer, DE AF Atlas, SJ Dedier, JJ Singer, DE TI Variation in processes of care for patients with community-acquired pneumonia at US academic hospitals. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 99 EP 99 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400324 ER PT J AU Badgett, RG Mulrow, CD Levy, LS Arterburn, J AF Badgett, RG Mulrow, CD Levy, LS Arterburn, J TI Observations on how clincians use SUMsearch. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Audie L Murphy Mem Vet Hosp, San Antonio, TX 78284 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 99 EP 99 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400327 ER PT J AU Braddock, CH Edwards, KA Micek, M Levinson, W AF Braddock, CH Edwards, KA Micek, M Levinson, W TI What factors predict physician involvement of patients in clinical decisions? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Dept Med, Seattle, WA USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. Univ Chicago, Gen Internal Med Sect, Chicago, IL 60637 USA. VA Puget Sound, Ctr Excellence Hlth Serv Res & Dev, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 104 EP 104 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400345 ER PT J AU Dedier, JJ Atlas, SJ Singer, DE AF Dedier, JJ Atlas, SJ Singer, DE TI The relationship between quality care process markers, Severity of illness, and outcomes in patients hospitalized with community-acquired pneumonia at US academic institutions. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 108 EP 108 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400364 ER PT J AU Delichatsios, HK Lobb, R Hunt, MK Emmons, K Gillman, MW AF Delichatsios, HK Lobb, R Hunt, MK Emmons, K Gillman, MW TI Eat smarti efficacy of a low intensity clinician centered dietary intervention. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 109 EP 109 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400367 ER PT J AU Geraci, JM Johnson, ML Gordon, HS Petersen, NJ Daley, J Hur, K Henderson, WG Khurl, SF Wray, NP AF Geraci, JM Johnson, ML Gordon, HS Petersen, NJ Daley, J Hur, K Henderson, WG Khurl, SF Wray, NP TI Mortality after non-cardiac surgery: Prediction from administrative versus clinical data. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Houston VA Med Ctr, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. MGH Partners HealthCare Syst, Inst Hlth Policy, Boston, MA USA. Hines VA Med Ctr, VA Cooperat Studies Program, Hines, IL USA. W Roxbury VA Med Ctr, Surg Serv, W Roxbury, MA USA. RI Gordon, Howard/E-4420-2010 OI Gordon, Howard/0000-0002-6712-5954 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 116 EP 116 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400399 ER PT J AU Groeneveld, PW AF Groeneveld, PW TI A cost-effectiveness comparison of the cyclooxygenase-1-sparing agents celecoxib and rofecoxib with three other strategies for high-dose nonsteroidal anti-inflammatory drug therapy. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Div Gen Internal Med, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 120 EP 120 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400413 ER PT J AU Holm, EA Fine, MJ Singer, DE Kapoor, WN Marrie, TJ Siu, AL AF Holm, EA Fine, MJ Singer, DE Kapoor, WN Marrie, TJ Siu, AL TI Adverse outcomes of instability on hospital discharge in patients with pneumonia. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Mt Sinai Hosp, New York, NY 10029 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Victoria Gen Hosp, Halifax, NS B3H 2Y9, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 120 EP 121 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400416 ER PT J AU Hickam, DH Joos, SK AF Hickam, DH Joos, SK TI Effect of a primary care delivery model on satisfaction with medical care among young adult patients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Portland VA Med Ctr, HSR&D Program, Portland, OR USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 121 EP 121 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400419 ER PT J AU Huang, ES Singer, DE Hooper, DC AF Huang, ES Singer, DE Hooper, DC TI Trends in fluoroquinolone use and resistance at an academic medical center from 1993-1999. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 122 EP 122 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400422 ER PT J AU Jacobs, BP Lee, M Patterson, M Avins, A AF Jacobs, BP Lee, M Patterson, M Avins, A TI Personal use and prescribing patterns of complementary and alternative medicine among university physicians. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 San Francisco Vet Affairs Med Ctr, Gen Internal Med Sect, San Francisco, CA USA. Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 123 EP 123 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400427 ER PT J AU Jacobs, BP Lee, M Patterson, M Avins, A AF Jacobs, BP Lee, M Patterson, M Avins, A TI Personal use and prescribing patterns of alternative medicine among university physicians. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 123 EP 123 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400426 ER PT J AU Keating, NL Weeks, JC Landrum, MB Guadagnoli, E AF Keating, NL Weeks, JC Landrum, MB Guadagnoli, E TI Treatment of early stage breast cancer - Does seeing a medical oncologist prior to surgery influence type of surgery and satisfaction? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 127 EP 127 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400441 ER PT J AU Misra, B Stafford, RS AF Misra, B Stafford, RS TI Patterns and variations of hypertension treatment in a capitated insurance plan. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Howard Univ, Coll Med, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 136 EP 136 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400480 ER PT J AU Misra, B Stafford, RS AF Misra, B Stafford, RS TI Examination of antihypertensive polypharmacy predictors from claims data. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Howard Univ, Coll Med, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 136 EP 136 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400479 ER PT J AU Redinbaugh, EM Block, SD Seltzer, DL Gadmer, N Mitchell, A Arnold, R AF Redinbaugh, EM Block, SD Seltzer, DL Gadmer, N Mitchell, A Arnold, R TI Experience makes a difference in physicians' grief reactions to their patient deaths. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 141 EP 141 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400500 ER PT J AU Schinpper, JL Stafford, RS AF Schinpper, JL Stafford, RS TI Secondary prevention of coronary artery disease at a large teaching hospital. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 144 EP 145 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400514 ER PT J AU Weisbord, S Whittle, J Brooks, R AF Weisbord, S Whittle, J Brooks, R TI Why don't patients with atrial fibrillation receive warfarin? SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 154 EP 154 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400552 ER PT J AU Winterbottom, LM Noel, GL Jackson, JA Borrego, C Snodgrass, LS Smith, DC AF Winterbottom, LM Noel, GL Jackson, JA Borrego, C Snodgrass, LS Smith, DC TI Evaluation of employee attitudes on budget-driven medical service reductions. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 155 EP 155 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400556 ER PT J AU Gadmer, NM Ruopp, PG Arnold, RM Redinbaugh, EM McDonald, MC Selzer, DL Good, MDV Block, SD AF Gadmer, NM Ruopp, PG Arnold, RM Redinbaugh, EM McDonald, MC Selzer, DL Good, MDV Block, SD TI Grief, gratitude, and chaos: Strangers at the death bed. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Educ, Boston, MA 02115 USA. Univ Pittsburgh, Pittsburgh, PA USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 161 EP 162 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400584 ER PT J AU Rosenfeld, KE Steckart, J Patterson, R AF Rosenfeld, KE Steckart, J Patterson, R TI Conceptualizing spiritual well-being: A focus group study of older adults with chronic illness. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 167 EP 167 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400608 ER PT J AU Haidet, P El Farra, R AF Haidet, P El Farra, R TI The lure of the unifying diagnosis. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston VAMC, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 181 EP 181 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400666 ER PT J AU Lu, HD Haidet, P AF Lu, HD Haidet, P TI Conjunctivitis as a manifestation of gonococcal infection. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston VAMC, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 189 EP 190 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400703 ER PT J AU Sutton, PR Johnson, TJ AF Sutton, PR Johnson, TJ TI Fever and delirium in a hospitalized man with Diffuse Lewy Body Dementia. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Dept Med, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 200 EP 200 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400749 ER PT J AU Vidrih, JA Walensky, RP Freedberg, KA AF Vidrih, JA Walensky, RP Freedberg, KA TI Acute HIV-1 syndrome presenting with a false-positive monospot. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Boston Med Ctr, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 203 EP 203 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400761 ER PT J AU Edwards, KA Braddock, CH Back, A Marshall, S AF Edwards, KA Braddock, CH Back, A Marshall, S TI Ward ethics: Building survival skills for third-year students. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Univ Washington, Sch Med, Deans Off, Seattle, WA USA. VA Puget Sound, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 211 EP 211 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400796 ER PT J AU Haidet, P Pierrel, S Moran, B Yeoman, L AF Haidet, P Pierrel, S Moran, B Yeoman, L TI Faculty development for problem-based learning tutors through peer observation and feedback. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Baylor Coll Med, Houston, TX 77030 USA. Houston Vet Affairs Med Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 213 EP 213 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400806 ER PT J AU Jackson, VA Hallward, A Worthen, HG Pels, RJ Bor, DH Conant, L AF Jackson, VA Hallward, A Worthen, HG Pels, RJ Bor, DH Conant, L TI A safe place to grieve-a group for residents to discuss suffering and dying patients. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Boston VA Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Med, Cambridge Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 215 EP 215 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400814 ER PT J AU Meigs, JB Stafford, RS AF Meigs, JB Stafford, RS TI Cardiovascular disease prevention practices by US physicians for patients with diabetes SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE cardiovascular disease; type 2 diabetes; prevention ID CORONARY HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; AVERAGE CHOLESTEROL LEVELS; RISK-FACTORS; GLUCOSE-TOLERANCE; RANDOMIZED TRIAL; BETA-BLOCKERS; MORTALITY; HYPERTENSION; INSULIN AB OBJECTIVE: Cardiovascular diseases account for the majority of morbidity and mortality In patients with type 2 diabetes mellitus. We describe patterns of cardiovascular disease primary prevention practices used for patients with diabetes by U.S. office-based physicians. MEASUREMENTS AND MAIN RESULTS: We analyzed a representative sample of 14,038 visits from the 1995 and 1996 National Ambulatory Medical Care Surveys (NAMCS), including 1,489 visits by patients with diabetes. Physicians completed visit forms describing diagnoses, demographics, services provided, and current medications. Diabetes was defined by diagnostic codes; patients with ischemic heart disease or younger than 30 years were excluded. We estimated national visit volumes by extrapolation using NAMCS sampling weights. Independent determinants of prevention practices were evaluated using multiple logistic regression. Actual visits sampled translated into an estimated 407 million office visits in 1995 and 1996, of which 44.8 million (11%) were by patients with diabetes. Overall, patients with diabetes received more cardiovascular disease prevention services than patients without diabetes, including cholesterol reduction (8% vs 5%, P < .001) and exercise counseling (22% vs 13%, P < .001), blood pressure measurement (82% vs 72%, P < .001), and aspirin prescription (5% vs 2%, P < .001). Patients with diabetes and hyperlipidemia were more likely to receive lipid-lowering medications than patients without these diagnoses (67% vs 51%, P = .007), but those who had diabetes and hypertension or who smoked were no more likely than those without to receive antihypertensive medications or smoking cessation counseling, respectively. These effects persisted in multiple logistic regression analyses controlling for potential confounders. CONCLUSIONS: Patients with diabetes visiting U.S. physicians in 1995 and 1996 received somewhat more cardiovascular disease prevention services than patients without diabetes. Absolute rates of services, however, remained lower than desired based on national recommendations. Current evidence suggests that wider implementation of these recommendations can be expected to reduce the burden of cardiovascular disease in patients with diabetes. C1 Massachusetts Gen Hosp, Div Gen Med, Med Serv, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, Med Serv, 50 Staniford St,9th Floor, Boston, MA 02114 USA. FU NHLBI NIH HHS [K08HL03548] NR 76 TC 51 Z9 51 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 IS 4 BP 220 EP 228 DI 10.1111/j.1525-1497.2000.03079.x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 307AM UT WOS:000086631300002 PM 10759996 ER PT J AU Wade, BJ Garcia, D AF Wade, BJ Garcia, D TI Should generalists biopsy? Preliminary evaluation of a flexible sigmoidoscopy screening program. SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Los Angeles VA Hlth Care Syst, Sepulveda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2000 VL 15 SU 1 BP 232 EP 233 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 308CE UT WOS:000086690400885 ER PT J AU Pins, GD Collins-Pavao, ME Van De Water, L Yarmush, ML Morgan, JR AF Pins, GD Collins-Pavao, ME Van De Water, L Yarmush, ML Morgan, JR TI Plasmin triggers rapid contraction and degradation of fibroblast-populated collagen lattices SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE matrix metalloproteinases; serine proteinases; wound healing ID MATRIX-DEGRADING METALLOPROTEINASES; ENDOTHELIAL GROWTH-FACTOR; HUMAN-SKIN FIBROBLASTS; UROKINASE RECEPTOR; TISSUE INHIBITOR; GENE-EXPRESSION; CELLS; ACTIVATOR; INVITRO; GELS AB We examined the role of the serine proteinase plasmin in regulating fibroblast-mediated tissue remodeling during wound healing. As an in vitro model system, collagen lattices were seeded with human dermal fibroblasts, and various concentrations of plasmin were added to the medium of the contracting lattices. Within 16 h, fibroblast-populated collagen lattices treated with plasmin rapidly contracted from approximately 20 mm to less than 2 mm in diameter. Measurements of collagen lattices with radiolabeled collagen indicated that, when these lattices included either fibroblasts or conditioned medium derived from fibroblast-populated collagen lattices, exogenous plasmin induced collagen degradation and rapid lattice contraction. Western blot analyses of conditioned medium demonstrated that fibroblasts in collagen lattices secreted the latent matrix metalloproteinase, MMP-1, which was subsequently cleaved by plasmin. Additionally, rapidlattice contraction and collagen degradation were blocked when collagen lattices were treated simultaneously with plasmin and aprotinin or a tissue inhibitor of metalloproteinases, TIMP-1. These results provide strong evidence that plasmin regulates rapid contraction of collagen lattices by activating fibroblast-secreted MMP-1 that triggers collagen degradation. The findings from this study suggest that fibroblast-populated collagen lattices can be used as an in vitro model system to investigate the mechanisms by which plasmin and cell-secreted plasminogen activators control MMP-1 mediated extracellular lattice degradation and remodeling during wound healing. C1 Shriners Hosp Children, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg Serv, Boston, MA 02114 USA. RP Morgan, JR (reprint author), Shriners Hosp Children, 51 Blossom St, Boston, MA 02114 USA. OI Morgan, Jeffrey/0000-0002-7546-3443 NR 54 TC 37 Z9 37 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2000 VL 114 IS 4 BP 647 EP 653 DI 10.1046/j.1523-1747.2000.00858.x PG 7 WC Dermatology SC Dermatology GA 302CA UT WOS:000086346300008 PM 10733668 ER PT J AU Rattner, DW AF Rattner, DW TI Physicians' choice for their own hernia repairs SO JOURNAL OF LAPAROENDOSCOPIC & ADVANCED SURGICAL TECHNIQUES-PART A LA English DT Article ID INGUINAL HERNIORRHAPHY; TRIAL AB Background and Purpose: While the optimal method of inguinal herniorrhaphy is controversial, there is growing acceptance that laparoscopic hernia repair is a legitimate alternative to conventional techniques. This study sought to determine if physicians as patients had different preferences for their own hernia repairs than nonphysician patients. Patients and Methods: Total endoscopic preperitoneal (TEP) herniorrhaphy was introduced into the author's practice in 1995. Open herniorrhaphies (OH) were performed under local anesthesia and were almost all tension-free repairs. Patients were given the option of surgical technique after a discussion with the author, although patients with primary unilateral hernias were encouraged to undergo a tension-free OH. A prospective database was kept and subsequently analyzed. Results: In the 3 years from June 1, 1995, to June 1, 1998, a total of 138 OH and 77 TEP repairs were performed. There were 19 physicians among the 215 patients. During the 3-year period, the annual percentage of laparoscopic herniorrhaphies increased from 27% (21/79) to 46% (32/70) (P = 0.024). The shift in physician preference for TEP from 16% (1/6) in 1995 to 75% (6/8) in 1997 was more dramatic than the shift in the population at large: 22% (20/73) to 42% (26/62). All patients undergoing TEP repair for recurrent hernias stated their recovery was easier than after their original OH. Four of seven physicians with recurrent hernias also had bilateral hernias. None required hospitalization. The median time to return to work was 4 days in the TEP physician group and 7 days in the physician OH group. The median time to return to work was 10 days in the TEP nonphysician group and 16 days in the OH nonphysician group. Conclusions: Physicians cared for by the author are increasingly choosing a laparoscopic approach for their hernia repairs even when they have primary unilateral hernias. Patients return to work more rapidly after TEP repairs than after OH. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Rattner, DW (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 8 TC 6 Z9 6 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1092-6429 J9 J LAPAROENDOSC ADV A JI J. Laparoendosc. Adv. Part A PD APR PY 2000 VL 10 IS 2 BP 75 EP 77 DI 10.1089/lap.2000.10.75 PG 3 WC Surgery SC Surgery GA 306NN UT WOS:000086602900002 PM 10794210 ER PT J AU Hamner, MB Frueh, BC Ulmer, HG Huber, MG Twomey, TJ Tyson, C Arana, GW AF Hamner, MB Frueh, BC Ulmer, HG Huber, MG Twomey, TJ Tyson, C Arana, GW TI Psychotic features in chronic posttraumatic stress disorder and schizophrenia - Comparative severity SO JOURNAL OF NERVOUS AND MENTAL DISEASE LA English DT Article; Proceedings Paper CT Annual Meeting of the Anxiety-Disorders-Association-of-America CY MAR, 1999 CL SAN DIEGO, CALIFORNIA SP Anixety Disorders Assoc Amer ID AUDITORY HALLUCINATIONS; NEGATIVE SYMPTOMS; DEPRESSION; SUBTYPES AB Psychotic features are frequent in combat veterans with chronic posttraumatic stress disorder (PTSD), may correlate with severity of PTSD symptoms,;and may reflect a distinct subtype of the disorder. These psychotic features include auditory and visual hallucinations and delusional thinking that is usually paranoid in nature. Psychotic features may be under-recognized in chronic PTSD because patients are reluctant to report these symptoms and because they may not have overt changes in affect or bizarre delusions characteristic of other psychoses, e.g., schizophrenia. To further assess these phenomena, we compared clinical ratings on the Positive and Negative Syndrome Scale (PANSS) and other assessments, including the Clinical Global Impression Scale and the Structured Clinical Interview with Psychotic Screen, in veterans meeting DSM-nt criteria for chronic PTSD with well-defined comorbid psychotic features (N = 40) or chronic sckizophrenia (N = 40). The patients with schizophrenia had modestly higher composite PANSS scores and positive symptom scores although average scores in both groups were moderate to severe in intensity. Negative symptom and general psychopathology subscale scores were comparable in both groups. Regarding specific positive symptoms, hallucinations were comparable between groups in severity; however, schizophrenia patients had slightly more intense delusions and conceptual disorganization. These data further validate the occurrence of positive as well as negative symptoms of psychosis in chronic PTSD in a range of severity that may approach that of patients with schizophrenia. Although meeting DSM-IV criteria for two different major psychiatric disorders, these two patient populations were remarkably similar with respect to not only positive but also negative symptoms. C1 Ralph H Johnson VA Med Ctr, Mental Hlth Serv, Charleston, SC 29401 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. RP Hamner, MB (reprint author), Ralph H Johnson VA Med Ctr, Mental Hlth Serv, 116 Mental Hlth,109 Bee St, Charleston, SC 29401 USA. NR 26 TC 56 Z9 58 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-3018 J9 J NERV MENT DIS JI J. Nerv. Ment. Dis. PD APR PY 2000 VL 188 IS 4 BP 217 EP 221 DI 10.1097/00005053-200004000-00004 PG 5 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 304DQ UT WOS:000086467900004 PM 10789998 ER PT J AU Gilbert, M O'Neill, A Grossman, S Grunnet, M Mehta, M Jubelirer, S Hellman, R AF Gilbert, M O'Neill, A Grossman, S Grunnet, M Mehta, M Jubelirer, S Hellman, R TI A phase II study of preradiation chemotherapy followed by external beam radiotherapy for the treatment of patients with newly diagnosed glioblastoma multiforme: an Eastern Cooperative Oncology Group Study (E2393) SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE glioblastoma multiforme; chemotherapy; radiotherapy; phase II trial ID MALIGNANT GLIOMAS; BRAIN-TUMORS; RADIATION; TRIAL; IRRADIATION; ASTROCYTOMA; THERAPY; TABLES; ADULTS AB Recent publications support the use of preradiation chemotherapy in the treatment of selected primary brain tumors. In the pediatric population, this treatment strategy often delays radiotherapy and may improve the outcome in patients. This manuscript describes the use of a preradiation chemotherapy approach for adult patients with newly diagnosed glioblastoma multiforme. The main objective of this trial was to determine the feasibility of delivering up to 3 monthly cycles of a 72 h continuous simultaneous intravenous infusion of BCNU (40 mg/m(2)/day) and cisplatin (40 mg/m(2)/day). Patients were evaluated for tumor response or progression after each cycle. Following the completion of the chemotherapy treatments or evidence of tumor progression, patients underwent external beam radiotherapy. A dose of 45 Gy was delivered to the pretreatment tumor volume plus surrounding edema and a margin of 3.0 cm. An additional 14.4 Gy was delivered to the preoperative volume plus a 2 cm margin. Fifty patients were enrolled, 47 were eligible and analyzable. Overall, 79% of patients were able to complete at least 2 cycles of treatment, exceeding the predefined measure of feasibility. One patient achieved a complete response, 10 patients a partial response and 18 patients had stable disease at completion of the chemotherapy treatments. Twenty-four patients experienced grade 4 toxicity, mostly hematologic. All patients were able to undergo radiotherapy following chemotherapy. These results indicate that a preradiation strategy is feasible. Although responses to the chemotherapy were seen, a phase III trial is needed to determine whether this approach provides an advantage over standard treatment; such a phase III trial has been undertaken by ECOG. C1 Emory Univ, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Oncol Ctr, Baltimore, MD USA. Univ Connecticut, Farmington, CT USA. Univ Wisconsin, Madison, WI USA. Charleston Area Med Ctr, Charleston, WV USA. Lawrence Mem Hosp, New London, CT USA. RP Gilbert, M (reprint author), Emory Univ, 1365 Clifton Rd, Atlanta, GA 30322 USA. OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA73590, CA21076, CA23318] NR 25 TC 30 Z9 31 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD APR PY 2000 VL 47 IS 2 BP 145 EP 152 DI 10.1023/A:1006402123397 PG 8 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 350NX UT WOS:000089109000010 PM 10982156 ER PT J AU Schmahmann, JD AF Schmahmann, JD TI The role of the cerebellum in affect and psychosis SO JOURNAL OF NEUROLINGUISTICS LA English DT Review DE fastigial nucleus; limbic system; cognition; emotion; schizophrenia; dysmetria of thought ID FASTIGIAL NUCLEUS PROJECTIONS; POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW ABNORMALITIES; RHESUS-MONKEY; EFFERENT CONNECTIONS; COGNITIVE DYSMETRIA; HUMAN BRAIN; HORSERADISH-PEROXIDASE; ELECTRICAL-STIMULATION; AFFECTIVE-DISORDER AB Anatomical, clinical, find functional imaging studies suggest that the cerebellum is an essential component of the distributed neural circuitry subserving cognition. This paper addresses the experimental and clinical data pointing to the role of the cerebellum in the modulation of affect and emotion as well as of thought. There are cerebellar connections with the reticular system (arousal), hypothalamus (autonomic function and emotional expression), limbic system (experience and expression of emotion), and paralimbic and neocortical association areas (cognitive dimensions of affect). Clinical studies point to cerebellar modulation of aggression and mood, including the cerebellar cognitive affective syndrome in adults and children, the posterior fossa syndrome of transient mutism and behavioral change following surgery that involves the vermis, and behavioral modification by cerebellar neurosurgical manipulation. Functional imaging studies reveal cerebellar involvement in nociception, in autonomic behaviors such as hunger and thirst, and in affective experiences. These observations provide support for the hypothesis that the cerebellum is an essential node in the distributed neural circuitry subserving cognitive and affective functions, and that there is a topographic organization of behaviors in the cerebellum The hypothesis that the phylogenetically older fastigial nucleus, vermis and flocculonodular robe constitute the "limbic cerebellum" is further developed to suggest that these cerebellar structures should be considered an extension of the Papez circuit. The concept is proposed that there is a universal cerebellar transform (UCT), possibly error detection, prevention, and correction utilizing an internal model, the disruption of which leads to dysmetria, the universal cerebellar impairment (UCI). Dysmetria of movement, or ataxia, is matched by dysmetria of thought, including the cerebellar cognitive affective syndrome, abnormalities of affect, and psychotic thinking. (C) 2000 published by Elsevier Science Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, Burnham 823,Fruit St, Boston, MA 02114 USA. NR 140 TC 137 Z9 141 U1 7 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0911-6044 J9 J NEUROLINGUIST JI J. Neurolinguist. PD APR-JUL PY 2000 VL 13 IS 2-3 BP 189 EP 214 DI 10.1016/S0911-6044(00)00011-7 PG 26 WC Linguistics; Neurosciences; Psychology, Experimental SC Linguistics; Neurosciences & Neurology; Psychology GA 318JD UT WOS:000087279500007 ER PT J AU Euler, T Masland, RH AF Euler, T Masland, RH TI Light-evoked responses of bipolar cells in a mammalian retina SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID INNER PLEXIFORM LAYER; TRANSMITTER-GATED CURRENTS; RECEPTOR RHO-SUBUNITS; RAT RETINA; CAT RETINA; GABA(C) RECEPTORS; SLICE PREPARATION; RABBIT RETINA; ON-CENTER; GANGLION-CELLS AB We recorded light-evoked responses from rod and cone bipolar cells using parch-clamp techniques in a slice preparation of the rat retina. Rod bipolar cells responded to light with a sustained depolarization (ON response) followed at light offset by a slight hyperpolarization. ON and OFF cone bipolar cells were encountered, both with diverse temporal properties. The responses of rod bipolar cells were composed primarily of two components, a nonspecific cation current and a chloride current. The chloride current was reduced greatly in axotomized cells and could be suppressed by coapplication of the GABA, antagonist bicuculline and the GABA(C) antagonist (1,2,5,6-tetrahydropyridine-4-yl) methylphosphinic acid. This suggests that it largely reflects feedback from GABAergic amacrine cells. The response latency of intact rod bipolar cells was shorter than that of the axotomized cells, and the sensitivity curve covered more than twice the dynamic range. Application of the GABA receptor antagonists partially mimicked the effects of axotomy. These findings suggest that functional properties of the axon terminal system-notably synaptic feedback from amacrine cells-play an important role in defining the response properties of mammalian bipolar cells. C1 Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Wellman 429,Fruit St, Boston, MA 02114 USA. OI Euler, Thomas/0000-0002-4567-6966 NR 94 TC 155 Z9 157 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD APR PY 2000 VL 83 IS 4 BP 1817 EP 1829 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 306LV UT WOS:000086598900005 PM 10758094 ER PT J AU Brand, JG AF Brand, JG TI Receptor and transduction processes for umami taste SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT International Symposium on Glutamate CY OCT 12-14, 1998 CL BERGAMO, ITALY SP Baylor Coll Med, Univ Pittsburgh Sch Med, Ctr Nutrit, Int Glutamate Tech Comm, Monell Chem Senses Ctr, Int Union Food Sci & Technol, Mario Negri Inst Pharmacol Res DE umami; glutamate; taste; nucleotides; calcium imaging; glutamate receptor ID BEHAVIORAL DISCRIMINATION; MONOSODIUM GLUTAMATE; AMINO-ACIDS; SUBSTANCES; MICE; RESPONSES; CELLS AB The unique taste of umami argues for a specific receptor at the taste cell level. The taste synergism between monosodium glutamate (MSG) and certain 5'-ribonucleotides provides a pharmacologic test for hypothetical mechanisms of umami taste. Early neurophysiologic and biochemical studies demonstrated specific recognition of L-glutamate by taste tissue and suggested that the synergism found with certain 5'-ribonucleotides was due to a peripheral event. The search fdr a receptor for umami relies at present on the data in the literature on central nervous system (CNS) glutamate receptors. These data distinguish several classes of receptors on the bases of pharmacologic properties and mode of action. Two hypotheses now seek to explain umami taste transduction. One states that umami is transduced by an N-methyl-D-aspartate (NMDA)-type glutamate ion channel receptor, the other that this taste is transduced via a metabotropic-type glutamate receptor. Evidence for the first hypothesis derives from earlier reconstitution studies, revealing a glutamate-stimulated ion channel conductance whose kinetics were affected by 5'-ribonucleotides. Additional evidence is provided from more recent calcium-imaging and patch-clamp studies, both showing that an ionotropic-type receptor on rodent taste cells mediates glutamate-induced depolarization. Evidence for the second mechanism derives from studies that located the message for an metabotropic-type (mGluR4) receptor to rat taste buds, and from whole-cell patch-clamp recordings that revealed sustained cellular conductances to glutamate and an mGluR4 agonist. It appears likely that both mechanisms are involved in umami taste transduction, suggesting the possibility that reception and transduction of the umami signal constitute a collective property of a number of cells within the taste bud. C1 Univ Penn, Sch Dent Med, Dept Biochem, Monell Chem Senses Ctr,Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Brand, JG (reprint author), Univ Penn, Sch Dent Med, Dept Biochem, Monell Chem Senses Ctr,Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. FU NIDCD NIH HHS [DC-00356] NR 27 TC 25 Z9 26 U1 0 U2 4 PU AMER SOC NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 2000 VL 130 IS 4 SU S BP 942S EP 945S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 300VQ UT WOS:000086274200010 PM 10736357 ER PT J AU Leffler, CT Gozani, SN Cros, D AF Leffler, CT Gozani, SN Cros, D TI Median neuropathy at the wrist: Diagnostic utility of clinical findings and an automated electrodiagnostic device SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CARPAL-TUNNEL-SYNDROME; HAND SYMPTOM DIAGRAM; CONDUCTION; NERVE; TEMPERATURE; DISABILITY; EFFICACY; ACCURACY; WORKERS; TESTS AB Clinical findings have limited value in predicting electrophysiologically confirmed median neuropathy at the wrist (MNW). To determine the value of clinical findings and an automated electrophysiologic neurodiagnostic device (AEND) in diagnosing MNW, we studied two groups of 75 consecutive patients (an initial group and a validation group, 150 total) referred to an academic electrophysiology laboratory for upper extremity complaints The definitive standard for MNW was the neurologist's diagnosis after formal clinical and electrodiagnostic evaluation. The neurologist was blinded to the results of the AEND (NC-Stat(TM), NeuroMetrix, Inc). In the validation group, the AEND yielded a distal motor latency (DML) in 97% of hands with a conventional motor response, and the correlation of the AEND DML with the conventional DML was 0.94 (P < 0.001). Of 248 symptomatic hands, the neurologist diagnosed 117 (47%) with MNW: At 90% specificity, the AEND DML, had a sensitivity of 86% fm MNW: Age, body mass index, sensory symptoms in digits I to 3, and nocturnal awakening were independent clinical predictors of MNW. Each I-msec increase in the adjusted AEND DML was independently associated with an OR of 298 (95% confidence interval, 40 to 2233) for MNW: Each I-msec increase in the F-wave latency was independently associated with an OR of 2.6 (95% confidence interval 1.3 to 4.9) for MNW. Compared with a model based solely on clinical variables, an algorithm including symptom variables plus the AEND DML had an odds ratio for correct diagnostic classification of 6.3 (95% confidence interval, 3.8 to 12.3). The sensitivity at 90% specificity improved fi om 40% for the clinical model to 86% for the model with DML. A practical method for integrating clinical and electrophysiologic findings to assess the risk of MNW was proposed. This method correctly stratified 79% of control and MNW patients into very low and high-risk groups, respectively. We concluded that MNW diagnosis is significantly improved with an AEND. C1 NeuroMetrix, Cambridge, MA 02142 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Leffler, CT (reprint author), NeuroMetrix, 1 Mem Dr, Cambridge, MA 02142 USA. NR 48 TC 36 Z9 36 U1 1 U2 3 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 APR PY 2000 VL 42 IS 4 BP 398 EP 409 DI 10.1097/00043764-200004000-00015 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 306EM UT WOS:000086584400009 PM 10774509 ER PT J AU Lee, JT Dodson, TB AF Lee, JT Dodson, TB TI The effect of mandibular third molar presence and position on the risk of an angle fracture SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID 3RD MOLARS AB Purpose: This study assessed the relationship between the presence and position of mandibular third molars (M3) and angle fractures. Patients and Methods: A retrospective cohort study design and a sample composed of patients admitted for treatment of mandible fractures between January 1993 and April 1998 were used. Data sources were the patients' medical records and radiographs. The predictor variables were the presence and position of M3. M3 position was grouped into 9 categories based on the Pell and Gregory classification. The outcome variable was the presence of an angle fracture. Other study variables included age, sex, race, mechanism of injury, and fracture location. Results: The eligible sample was composed of 437 patients, of whom 367 had data available for analysis. Patients with M3 present had a 1.9 times (95% confidence interval = 1.2 to 2.9) greater chance of an angle fracture than patients without M3s (P = .003). There was a statistically significant variation in the risk for an angle fracture, depending on M3 position (P = .049). Conclusion: The study results confirm other reports that patients with M3 present have an increased risk for angle fractures. Furthermore, it also showed that the risk for an angle fracture varied depending on M3 position. C1 Emory Univ, Sch Med, Dept Surg, Div Oral & Maxillofacial Surg, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. RP Lee, JT (reprint author), Emory Clin, 1365B Clifton Rd,Suite B2300, Atlanta, GA 30322 USA. NR 18 TC 35 Z9 38 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 APR PY 2000 VL 58 IS 4 BP 394 EP 398 DI 10.1016/S0278-2391(00)90921-2 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 299RX UT WOS:000086212600012 PM 10759119 ER PT J AU Cwikla, SJ Tsuji, T McBride, J Wong, DTW Todd, R AF Cwikla, SJ Tsuji, T McBride, J Wong, DTW Todd, R TI doc-1-mediated apoptosis in malignant hamster oral keratinocytes SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID PROGRAMMED CELL-DEATH; TUMOR-SUPPRESSOR GENE; CANCER; PHOSPHATIDYLSERINE; IDENTIFICATION; EXPRESSION; THERAPY; DOC-1 AB Purpose: Cell cycle mediators involved in inducing apoptosis are frequently deregulated during carcinogenesis. Deleted in oral cancer-1 (doc-1) is an S-phase regulator that is inactivated during oral carcinogenesis. Transfection of doc-1 into malignant oral keratinocytes lends to increased cell loss. It is hypothesized that ectopic expression of doc-1 in hamster oral cancer cells induces apoptosis. Materials and Methods: Malignant hamster oral keratinocytes (wt-HCPC-1), which lack measurable doc-1 mRNA and protein, were previously transfected with either a CMV-doc-1 expression vector construct (doc-HCPC-1) or the parental control vector pcDNA3 (cv-HCPC-1). A trypan blue exclusion assay was performed to examine cell death in the parental or wild-type HCPC-1 keratinocytes, HCPC-1 transfected with the parental pcDNA3 vector, and the doc-1 transfected HCPC-1 cells. To examine whether ectopic expression of doc-l mediates gross cellular changes consistent with apoptosis, toluidine blue-safranin differential staining and the quantitative fluorescent microscopy assays were performed. To identify early apoptotic cytochemical changes observed in the cell membrane and nucleus, annexin V/propidium iodide (PI) fluorescence-activated cell sorter (FACS) analysis and the terminal deoxytransferase-mediated dUTP nick-end labeling (TUNEL) assay were performed. Results: Doc-HCPC-1 showed elevated numbers of dead cells over wt-HCPC-1 and cv-HCPC-1 in the trypan blue exclusion assay. Toluidine blue-safranin staining and quantitative fluorescent microscopy showed significant morphologic changes in the doc-1 transfectants consistent with apoptosis (P < .05). TUNEL assays (P < .05) and annexin V/PI FAGS analysis (P < .05) also showed early cytochemical changes in the doc-HCPC-1 transfectants, confirming that ectopic expression of doc-1 induces apoptosis. Conclusions: These data suggest that doc-1 induces apoptosis in malignant hamster oral keratinocytes. It is hypothesized that doc-1 is a mediator of apoptosis that is inactivated during hamster oral carcinogenesis. C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Dept Oral Med & Diagnost Sci, Div Oral Pathol, Boston, MA USA. Massachusetts Gen Hosp, Dept Oral & Maxillofacial Surg, Boston, MA 02114 USA. RP Todd, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, 188 Longwood Ave, Boston, MA 02115 USA. FU NIDCR NIH HHS [R29 DE11983, P01 DE12467] NR 32 TC 19 Z9 21 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 2000 VL 58 IS 4 BP 406 EP 414 DI 10.1016/S0278-2391(00)90924-8 PG 9 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 299RX UT WOS:000086212600015 PM 10759121 ER PT J AU Rochon, E Waters, GS Caplan, D AF Rochon, E Waters, GS Caplan, D TI The relationship between measures of working memory and sentence comprehension in patients with Alzheimer's disease SO JOURNAL OF SPEECH LANGUAGE AND HEARING RESEARCH LA English DT Article DE dementia of the Alzheimer's type; working memory; sentence comprehension ID SHORT-TERM-MEMORY; MINI-MENTAL STATE; INDIVIDUAL-DIFFERENCES; SYNTACTIC COMPREHENSION; ARTICULATORY REHEARSAL; APHASIC PATIENTS; SENILE DEMENTIA; CAPACITY THEORY; LANGUAGE; IMPAIRMENTS AB Patients with dementia of the Alzheimer's type (DAT) and age- and education-matched older volunteers were tested on a battery of working memory tests, as well as on two tests of sentence comprehension. Patients had reduced spans and impaired central executive processes in working memory but showed normal effects of phonological and articulatory variables on span. On the sentence comprehension tasks, DAT patients showed effects of the number of propositions in a sentence but not of syntactic complexity. Impairment in the central executive processes of working memory in DAT patients was correlated with the effect of the number of propositions in a sentence on the sentence comprehension tasks. The results suggest that patients with DAT have working memory impairments that ore related to their ability to map the meanings of sentences onto depictions of events in the world. C1 McGill Univ, Montreal, PQ, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Rochon, E (reprint author), Univ Toronto, Dept Speech Language Pathol, Tanz Neurosci Bldg,6 Queens Pk Crescent W, Toronto, ON M5S 3H2, Canada. EM elizabeth.rochon@toronto.ca OI Rochon, Elizabeth/0000-0001-5521-0513 FU NIA NIH HHS [AG09661] NR 72 TC 39 Z9 42 U1 1 U2 9 PU AMER SPEECH-LANGUAGE-HEARING ASSOC PI ROCKVILLE PA 10801 ROCKVILLE PIKE, ROCKVILLE, MD 20852-3279 USA SN 1092-4388 J9 J SPEECH LANG HEAR R JI J. Speech Lang. Hear. Res. PD APR PY 2000 VL 43 IS 2 BP 395 EP 413 PG 19 WC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation SC Audiology & Speech-Language Pathology; Linguistics; Rehabilitation GA 297EQ UT WOS:000086069300008 PM 10757692 ER PT J AU Semrud-Clikeman, M Steingard, RJ Filipek, P Biederman, J Bekken, K Renshaw, PF AF Semrud-Clikeman, M Steingard, RJ Filipek, P Biederman, J Bekken, K Renshaw, PF TI Using MRI to examine brain-behavior relationships in males with attention deficit disorder with hyperactivity SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE magnetic resonance imaging; attention-deficit hyperactivity disorder; neuropsychology; assessment ID QUANTITATIVE MORPHOLOGY; CAUDATE-NUCLEUS; CHILDREN; ORGANIZATION; DYSFUNCTION; ASYMMETRY; ADHD AB Objective: The relationship between neuropsychological measures of inhibition and sustained attention and structural brain differences in the regions of the caudate and the frontal region was examined in males with attention deficit disorder with hyperactivity (ADD/H). Method: Ten males with ADD/H (aged 8-17) and 11 male controls (aged 9-18) participated in a neuropsychological evaluation and had a magnetic resonance imaging scan. Results: As had been reported previously by these authors, the children with ADD/H were found to have reversed asymmetry of the head of the caudate, smaller volume of the left caudate head. and smaller volume of the white matter of the right frontal lobe. Children with ADD/H were found to score more poorly on measures of inhibition and sustained attention but not on measures of IQ, achievement, or motor speed. Comparison of neuropsychological measures and brain structure measures indicated a significant relationship between reversed caudate asymmetry and measures of inhibition and externalizing behavior; i.e., children with reversed caudate asymmetry performed more poorly on measures of inhibition regardless of group membership. Poorer performance on sustained attention tasks was related to smaller volume of the right-hemispheric white matter. Conclusions: There is emerging evidence that compromised brain morphology of selected regions is related to behavioral measures of inhibition and attention. C1 Univ Texas, Dept Educ Psychol, Austin, TX 78712 USA. Harvard Univ, Sch Med, Cambridge Hosp, Cambridge, MA 02138 USA. Univ Calif Irvine, Med Ctr, Dept Pediat, Irvine, CA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. McLean Hosp, Dept Neurol & Radiol, Boston, MA USA. RP Semrud-Clikeman, M (reprint author), Univ Texas, Dept Educ Psychol, SZB 504, Austin, TX 78712 USA. NR 42 TC 136 Z9 143 U1 3 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2000 VL 39 IS 4 BP 477 EP 484 DI 10.1097/00004583-200004000-00017 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 299GG UT WOS:000086190000017 PM 10761350 ER PT J AU Asawanonda, P Anderson, RR Taylor, CR AF Asawanonda, P Anderson, RR Taylor, CR TI Pendulaser carbon dioxide resurfacing laser versus electrodesiccation with curettage in the treatment of isolated, recalcitrant psoriatic plaques SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID PULSED DYE-LASER; KOEBNER; CRYOTHERAPY AB Background: Treatment of recalcitrant psoriatic plaques located on certain areas of the body remains problematic despite the many therapeutic options available. Objective: This study was conducted to determine the efficacy of Pendulaser carbon dioxide (CO2) resurfacing laser to that of electrodesiccation with curettage in the treatment of recalcitrant psoriatic plaques. Methods:A single psoriatic plaque was divided into thirds, one parr treated with CO2 resurfacing laser, another with electrodesiccation and curettage, and the third left untreated. The psoriatic epidermis and papillary dermis were removed by the two treatment modalities. Results: CO2 resurfacing laser and electrodesiccation with curettage produced similar therapeutic effects in terms of improvement of psoriasis and were significantly better than the control 4 months later, but flat at 6 months. Conclusion: For limited recalcitrant psoriatic plaques, CO2 resurfacing laser and electrodesiccation with curettage may provide an alternative short-term treatment; however, caution must be exercised and cite moderately high risk of scarring carefully weighed against; the potential benefits. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Dermatol, Cambridge, MA 02138 USA. RP Asawanonda, P (reprint author), King Chulalongkorn Mem Hosp, Dept Med, Div Dermatol, Bangkok, Thailand. NR 22 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2000 VL 42 IS 4 BP 660 EP 666 DI 10.1016/S0190-9622(00)90181-6 PG 7 WC Dermatology SC Dermatology GA 300RH UT WOS:000086265600016 PM 10727314 ER PT J AU Hung, J Landzberg, MJ Jenkins, KJ King, MEE Lock, JE Palacios, IF Lang, P AF Hung, J Landzberg, MJ Jenkins, KJ King, MEE Lock, JE Palacios, IF Lang, P TI Closure of patent foramen ovale for paradoxical emboli: Intermediate-term risk of recurrent neurological events following transcatheter device placement SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ATRIAL SEPTAL ANEURYSM; CRYPTOGENIC STROKE; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; CEREBROVASCULAR EVENTS; SURGICAL CLOSURE; PREVENTION; DEFECT; ULTRASOUND; PREVALENCE; AGE AB OBJECTIVES We report the largest and the longest follow-up to date of patients who underwent transcatheter patent foramen ovale (PFO) closure for paradoxical embolism. BACKGROUND Closure of a PFO has been proposed as an alternative to anticoagulation in patients with presumed paradoxical emboli. METHODS Data were collected for patients following PFO closure with the Clamshell, CardioSEAL or Buttoned Devices at two institutions. There were 63 patients (46 +/- 18 years) with a follow-up of 2.6 +/- 2.4 years. Fifty-four (86%) had effective closure of the foramen ovale (trivial or no residual shunt by echocardiography) while seven (11%) had mild and two (3%) had moderate residual shunting. RESULTS There were four deaths (leukemia, pulmonary embolism, sepsis following a hip fracture and lung cancer). There were four recurrent embolic neurological events following device placement: one stroke and three transient events. The stroke occurred in a 56-year-old patient six months following device placement. A follow-up transesophageal echocardiogram showed a well seated device without residual shunting. Two of the four events were associated with suboptimal device performance tone patient had a significant residual shunt and a second patient had a "friction lesion" in the left atrial wall associated with a displaced fractured device arm). The risk of recurrent stroke or transient neurological evens following device placement was 3.2% per year for all patients. CONCLUSION Transcatheter closure of PFO is an alternative therapy for paradoxical emboli in selected patients. Improved device performance may reduce the risk of recurrent neurological events. Further studies are needed to identify patients most likely to benefit from this intervention. CT Am Coil Cardiol 2000;35:1311-6) (C) 2000 by the American College of Cardiology. C1 Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Lang, P (reprint author), Childrens Hosp, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. NR 35 TC 140 Z9 148 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD APR PY 2000 VL 35 IS 5 BP 1311 EP 1316 DI 10.1016/S0735-1097(00)00514-3 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 300RL UT WOS:000086265900027 PM 10758974 ER PT J AU Oslin, DW Streim, J Katz, IR Edell, WS TenHave, T AF Oslin, DW Streim, J Katz, IR Edell, WS TenHave, T TI Change in disability follows inpatient treatment for late life depression SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE depression; disability; geriatrics ID FUNCTIONAL STATUS; PRIMARY-CARE; MORTALITY; PERFORMANCE; OUTCOMES; SYMPTOMS; IMPACT; TESTS AB OBJECTIVES: The objective of this study was to examine the relationship between functional disability and improvement in late life depression after acute inpatient treatment. DESIGN: The study was a longitudinal assessment of depression and disability. Patients were assessed during an initial inpatient hospitalization and then 3 months postdischarge. SETTING: All patients were evaluated initially after admission to one of 71 inpatient psychiatric treatment facilities. PARTICIPANTS: The study comprised of 2572 patients older than age 60 who were relatively cognitively intact and experiencing significant depressive symptoms. MEASUREMENTS: Depressive symptoms were measured using the Geriatric Depression Scale. Disability was measured using the Instrumental Activities of Daily Living Scale and the Medical Outcomes SF-36. RESULTS: Depressive symptoms improved in the majority of patients. Moreover, improvement in depressive symptomatology was significantly related to improvement in instrumental activities of daily living (IADLs) and to health-related quality of life as measured by the SF-36. This relationship was strongest among those who initially presented with some disability in IADLs. CONCLUSIONS: This work underscores further the disabling nature of depression. Moreover, findings from this study suggest that treatment focused on depression can lead to significant improvements in both depressive symptoms and functional abilities. However, the results also suggest that the relationship between depression and disability is complex and that the effect of treating depression is not the only factor in the reversal of disability. C1 Univ Penn, Sect Geriat Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Study Addict, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. Mental Hlth Outcomes, Lewisville, TX USA. Univ Penn, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. RP Oslin, DW (reprint author), Univ Penn, Sect Geriat Psychiat, 3600 Market St,Room 790, Philadelphia, PA 19104 USA. FU NIMH NIH HHS [2P30 MH 52129-05] NR 24 TC 34 Z9 37 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2000 VL 48 IS 4 BP 357 EP 362 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 302LJ UT WOS:000086366300001 PM 10798459 ER PT J AU Sloss, EM Solomon, DH Shekelle, PG Young, RT Saliba, D MacLean, CH Rubenstein, LZ Schnelle, JF Kamberg, CJ Wenger, NS AF Sloss, EM Solomon, DH Shekelle, PG Young, RT Saliba, D MacLean, CH Rubenstein, LZ Schnelle, JF Kamberg, CJ Wenger, NS TI Selecting target conditions for quality of care improvement in vulnerable older adults SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE vulnerable elders; quality of care; quality improvement ID RESIDENT ASSESSMENT INSTRUMENT; NURSING-HOME; HEALTH-CARE; POPULATION; SERVICES; DISEASE; IMPACT; FALLS; PAIN AB OBJECTIVE: To identify a set of geriatric conditions as optimal targets for quality improvement to be used in a quality measurement system for vulnerable older adults. DESIGN: Discussion and two rounds of ranking of conditions by a panel of geriatric clinical experts informed by literature reviews. METHODS: A list of 78 conditions common among vulnerable older people was reduced to 35 on the basis of their (1) prevalence, (2) impact on health and quality of life, (3) effectiveness of interventions in improving mortality and quality of life, (4) disparity in the quality of care across providers and geographic areas, and (5) feasibility of obtaining the data needed to test compliance with quality indicators. A panel of 12 experts in geriatric care discussed and then ranked the 35 conditions on the basis of the same five criteria. We then selected 21 conditions, based on panelists' iterative rankings. Using available national data, we compiled information about prevalence of the selected conditions for community-dwelling older people and older nursing home residents and estimated the proportion of inpatient and outpatient care attributable to the selected conditions. RESULTS: The 21 conditions selected as targets for quality improvement among vulnerable older adults include (in rank order): pharmacologic management; depression; dementia; heart failure; stroke (and atrial fibrillation); hospitalization and surgery; falls and mobility disorders; diabetes mellitus; end-of-life care; ischemic heart disease; hypertension; pressure ulcers; osteoporosis; urinary incontinence; pain management; preventive services; hearing impairment; pneumonia and influenza; vision impairment; malnutrition; and osteoarthritis. The selected conditions had mean rank scores from 1.2 to 3.8, and those excluded from 4.6 to 6.9, on a scale from 1 (highest ranking) to 7 (lowest ranking). Prevalence of the selected conditions ranges from 10 to 50% among community-dwelling older adults and from 25 to 80% in nursing home residents for the six most common selected conditions. The 21 target conditions account for at least 43% of all acute hospital discharges and 33% of physician office visits among persons 65 years of age and older. Actual figures must be higher because several of the selected conditions (e.g., end-of-life care) are not recorded as diagnoses. CONCLUSIONS: Twenty-one conditions were selected as targets for quality improvement in vulnerable older people for use in a quality measurement system. The 21 geriatric conditions selected are highly prevalent in this group and likely account for more than half of the care provided to this group in hospital and ambulatory settings. C1 RAND, Washington, DC 20005 USA. RAND, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Vet Affairs Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. RP Sloss, EM (reprint author), RAND, 1333 H St NW,Suite 800, Washington, DC 20005 USA. NR 38 TC 64 Z9 65 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2000 VL 48 IS 4 BP 363 EP 369 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 302LJ UT WOS:000086366300002 PM 10798460 ER PT J AU Liao, S Ferrell, BA AF Liao, S Ferrell, BA TI Fatigue in an older population SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE fatigue; long-term care; quality of life ID SYSTEMIC LUPUS-ERYTHEMATOSUS; RHEUMATOID-ARTHRITIS; PRIMARY-CARE; HEALTHY-INDIVIDUALS; COMMUNITY ONCOLOGY; CANCER; CHEMOTHERAPY; PREVALENCE; EPIDEMIOLOGY; THERAPY AB OBJECTIVES: Fatigue is a common symptom that has not been studied well in the older populations. The purpose of this pilot study was to ex-amine the epidemiology of fatigue symptoms in relation to demographic and medical characteristics of older patients in a long-term care setting. DESIGN: A cross-sectional interviewer-assisted survey. PARTICIPANTS/SETTING: A total of 199 ambulatory older residents of a single residential care facility. MEASUREMENTS: Along with medical and demographic characteristics, the survey included mental status (Folstein), activities of daily living (Katz and Lawton), depression (Yesavage GDS), a 3-minute walk, a 7-item pain scale, and the modified Piper Fatigue Scale. RESULTS: One-hundred ninety-nine (65%) of 308 potential subjects completed the study (mean age 88 pears, 82% female). Of these 199 subjects, 195 (98%) reported some fatigue symptoms (median duration 44 weeks). Significant (P < .0005) relationships were found between fatigue and GDS (r = 0.57), S-minute walk (r = -0.29), Lawton IADLs (r = 0.31), pain (r = 0.36), and number of medications (r = 0.26). No significant relationships were found between fatigue and age, sex, Folstein score, or number of medical diagnoses. Multivariate regression analysis identified GDS, pain, number of medications and 3-minute walk as significant predictors of fatigue intensity (multiple R = 0.68, r(2) = 0.46, P < .02). CONCLUSIONS: Fatigue is a symptom often found among older residents of a residential facility and has important implications fur quality of life. Fatigue is poorly recognized and probably undertreated in older people. C1 Univ California, Med Ctr,Irvine Sch Med, Primary Care Med Grp, Dept Internal Med, Orange, CA 92868 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, VA Multicampus Program Geriatr Med & Gerontol, Los Angeles, CA USA. Ctr Geriatr Res Educ & Clin, Vet Affairs Greater Los Angeles Hlth Care Syst, Sepulveda, CA USA. RP Liao, S (reprint author), Univ California, Med Ctr,Irvine Sch Med, Primary Care Med Grp, Dept Internal Med, 101 City Dr S,Pavil 3,2nd Floor, Orange, CA 92868 USA. NR 49 TC 80 Z9 82 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2000 VL 48 IS 4 BP 426 EP 430 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 302LJ UT WOS:000086366300013 PM 10798471 ER PT J AU Flachskampf, FA Chandra, S Gaddipatti, A Levine, RA Weyman, AE Ameling, W Hanrath, P Thomas, JD AF Flachskampf, FA Chandra, S Gaddipatti, A Levine, RA Weyman, AE Ameling, W Hanrath, P Thomas, JD TI Analysis of shape and motion of the mitral annulus in subjects with and without cardiomyopathy by echocardiographic 3-dimensional reconstruction SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY LA English DT Article ID VALVE PROLAPSE; DIAGNOSIS; DYNAMICS; RINGS; SIZE AB The shape and dynamics of the mitral annulus of 10 patients without heart disease (controls), 3 patients with dilated cardiomyopathy, and 5 patients with hypertrophic obstructive cardiomyopathy and normal systolic function were analyzed by transesophageal echocardiography and 3-dimensional reconstruction. Mitral annular orifice area, apico-basal motion of the annulus, and nonplanarity were calculated over time. Annular area was largest in end diastole and smallest in end systole. Mean areas were 11.8 +/- 2.5 cm(2) (controls), 15.2 +/- 4.2 cm(2) (dilated cardiomyopathy), and 10.2 +/- 2.4 cm(2) (hypertrophic cardiomyopathy) (P = not significant). After correction for body surface, annuli. from patients with normal left ventricular function were smaller than annuli from patients with dilated cardiomyopathy (5.9 +/- 1.2 cm(2)/m(2) vs 7.7 +/- 1.0 cm(2)/m(2); P < .02). The change in area during the cardiac cycle showed significant differences: 23.8% +/- 5.1% (controls), 13.2% +/- 2.3% (dilated cardiomyopathy), and 32.4% +/- 7.6% (hypertrophic cardiomyopathy) (P < .001). Apico-basal motion was highest in controls, followed by those with hypertrophic obstructive and dilated cardiomyopathy (1.0 +/- 0.3 cm, 0.8 +/- 0.2 cm, 0.3 +/- 0.2 cm, respectively; P < .01). Visual inspection and Fourier analysis showed a consistent pattern of anteroseptal and posterolateral elevations of the annulus toward the left atrium. In conclusion, although area changes and apico-basal motion of the mitral annulus strongly depend on left ventricular systolic function, nonplanarity is a structural feature preserved throughout the cardiac cycle in all three groups. C1 Rhein Westfal TH Aachen, Med Klin 1, Aachen, Germany. Cleveland Clin Fdn, Dept Cardiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Ultrasound Lab, Boston, MA 02114 USA. Rhein Westfal TH Aachen, Rogowski Inst Elect Engn & Data Proc, Aachen, Germany. RP Flachskampf, FA (reprint author), Med Klin 2, Ostl Stadtmauerstr 29, D-91054 Erlangen, Germany. NR 15 TC 94 Z9 100 U1 0 U2 6 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0894-7317 J9 J AM SOC ECHOCARDIOG JI J. Am. Soc. Echocardiogr. PD APR PY 2000 VL 13 IS 4 BP 277 EP 287 DI 10.1067/mje.2000.103878 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 305JN UT WOS:000086536500005 PM 10756245 ER PT J AU Yamada, K Mawulawde, K Menard, MT Shimizu, A Aretz, HT Choo, JK Allison, KS Slisz, JK Sachs, DH Madsen, JC AF Yamada, K Mawulawde, K Menard, MT Shimizu, A Aretz, HT Choo, JK Allison, KS Slisz, JK Sachs, DH Madsen, JC TI Mechanisms of tolerance induction and prevention of cardiac allograft vasculopathy in miniature swine: The effect of augmentation of donor antigen load SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; RENAL-ALLOGRAFTS; CLASS-I; TRANSPLANTATION TOLERANCE; GRAFT ARTERIOSCLEROSIS; INTERNATIONAL-SOCIETY; HEART-TRANSPLANTATION; IMMUNE-MECHANISMS; TIME-COURSE; MODEL AB Objective: Cotransplantation of a donor kidney along with a heart allograft can induce tolerance to both organs and prevent cardiac allograft vasculopathy in miniature swine. To determine whether the tolerogenic effect of donor kidney cotransplantation was due to an effect specific to the kidney graft or to an increase in donor antigen load, we compared heart-kidney recipients with recipients receiving two class I disparate hearts or with recipients receiving donor peripheral mononuclear cells at the time of isolated heart transplantation. Methods: Recipients of major histocompatibility complex class I disparate allografts received 12 days of cyclosporine (INN: ciclosporin; 10-13 mg/kg administered intravenously on days 0-11). Group 1 animals received a heart alone (n = 5). Group 2 animals received heart and kidney allografts (n = 4). Group 3 animals received two major histocompatibility complex-matched heart allografts (n = 4), Two double-heart recipients were thymectomized 21 days before transplantation. Group 4 animals received a heart allograft and an infusion of high-dose donor peripheral blood leukocytes (2.5 x 10(9) cells/kg, n = 2). Results: Vasculopathy developed in group I recipients and the allografts were rejected within 55 days. Group 2 recipients accepted their heart and kidney allografts indefinitely without vasculopathy, Euthymic recipients from group 3 accepted their hearts long-term (>190 and >197 days), but vascular lesions developed. In thymectomized recipients from group 3, the hearts were rejected in 63 and 96 days with severe vasculopathy. Group 4 recipients demonstrated transient macrochimerism but their hearts were rejected within 47 and 63 days. Conclusions: The beneficial effects of donor kidney cotransplantation on cardiac allograft survival and prevention of cardiac allograft vasculopathy are likely to involve both an increase in donor antigen load and an effect specific to the kidney allograft. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. RP Madsen, JC (reprint author), Massachusetts Gen Hosp, Dept Surg, EDR 105, Boston, MA 02114 USA. FU NHLBI NIH HHS [R01-HL54211] NR 30 TC 19 Z9 19 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2000 VL 119 IS 4 BP 709 EP 719 DI 10.1016/S0022-5223(00)70005-5 PN 1 PG 11 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 305GG UT WOS:000086530600011 PM 10733759 ER PT J AU Cohn, LH AF Cohn, LH TI Becoming a surgical leader SO JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY LA English DT Article; Proceedings Paper CT 79th Annual Meeting of the American-Association-for-Thoracic-Surgery CY APR 18-21, 1999 CL NEW ORLEANS, LOUISIANA SP Amer Assoc Thorac Surg C1 Brigham & Womens Hosp, Div Cardiac Surg, Boston, MA 02115 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA. RP Cohn, LH (reprint author), Brigham & Womens Hosp, Div Cardiac Surg, 75 Francis St, Boston, MA 02115 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-5223 J9 J THORAC CARDIOV SUR JI J. Thorac. Cardiovasc. Surg. PD APR PY 2000 VL 119 IS 4 SU S BP S42 EP S44 DI 10.1067/mtc.2000.104726 PN 2 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 306CT UT WOS:000086579600008 PM 10727962 ER PT J AU Benacerraf, BR Shipp, TD Bromley, B AF Benacerraf, BR Shipp, TD Bromley, B TI Is a full bladder still necessary for pelvic sonography? SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE bladder, sonography; pelvis, sonography; transvaginal sonography ID TRANS-VAGINAL SONOGRAPHY AB The objective was to determine whether a full bladder is routinely necessary for a complete sonographic evaluation of the female pelvis. Over the course of 1 month, all women having a gynecologic sonogram were scanned initially transabdominally through a full bladder by the sonographer (standard images taken). A physician then joined the sonographer and scanned the patient transvaginally without prior knowledge of the findings seen transvesically. The physician finished the examination transabdominally, with the bladder empty. The physician and sonographer then determined (1) whether the scan was sufficient transvaginally only, (2) whether the scan was sufficient transvaginally and transabdominally with an empty bladder, or (3) or whether a full bladder was necessary. Two hundred and six consecutive patients were scanned prospectively. The transvaginal scan alone was sufficient to demonstrate all findings for 172 (83.5%) patients. The transvaginal and transabdominal scans through an empty bladder were needed for 31 (15.1%) patients. Three patients (1.5%) required a full bladder in addition to the other two techniques to visualize one normal ovary each. In conclusion, transvaginal scanning with an adjunctive transabdominal empty bladder approach can replace the full bladder technique for routine pelvic sonography. The transabdominal scan with an empty bladder is necessary, particularly for patients with enlarged uteri. It is no longer reasonable, however, to subject all patients undergoing pelvic sonography to bladder distention. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 7 TC 12 Z9 12 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2000 VL 19 IS 4 BP 237 EP 241 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 415ZV UT WOS:000167754200002 PM 10759346 ER PT J AU Andreadis, S Lavery, T Davis, HE Le Doux, JM Yarmush, ML Morgan, JR AF Andreadis, S Lavery, T Davis, HE Le Doux, JM Yarmush, ML Morgan, JR TI Toward a more accurate quantitation of the activity of recombinant retroviruses: Alternatives to titer and multiplicity of infection (vol 74, pg 1258, 2000) SO JOURNAL OF VIROLOGY LA English DT Correction ID MEDIATED GENE-TRANSFER; HALF-LIFE; TRANSDUCTION; VECTOR; CELLS; TIME; EFFICIENCY; KINETICS; RANGE; LINES AB In this paper, we present a mathematical model with experimental support of how several key parameters govern the adsorption of active retrovirus particles onto the surface of adherent cells. These parameters, including time of adsorption, volume of virus, and the number, size, and type of target cells, as well as the intrinsic properties of the virus, diffusion coefficient, and half-life (t(1/2)), have been incorporated into a mathematical expression that describes the rate at which active virus particles adsorb to the cell surface. From this expression, we have obtained estimates of C-vo, the starting concentration of active retrovirus particles, In contrast to titer, C-vo is independent of the specific conditions of the assay, The relatively slow diffusion (D = 2 x 10(-8) cm(2)/s) and rapid decay (t(1/2) = 6 to 7 h) of retrovirus particles explain why C-vo values are significantly higher than titer values. Values of C-vo also indicate that the number of defective particles in a retrovirus stock is much lower than previously thought, which has implications especially for the use of retroviruses for in vivo gene therapy. With this expression, we have also computed AVC (active viruses/cell), the number of active retrovirus particles that would adsorb per cell during a given adsorption time. In contrast to multiplicity of infection, which is based on titer and is subject to the same inaccuracies, AVC is based on the physicochemical parameters of the transduction assay and so is a more reliable alternative. C1 Shriners Hosp Crippled Children, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Ctr Engn Med, Surg Serv, Boston, MA 02114 USA. RP Morgan, JR (reprint author), Shriners Hosp Crippled Children, 51 Blossom St, Boston, MA 02114 USA. FU NICHD NIH HHS [HD-28528] NR 25 TC 41 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2000 VL 74 IS 7 BP 3431 EP 3439 DI 10.1128/JVI.74.7.3431-3431.2000 PG 9 WC Virology SC Virology GA 295NH UT WOS:000085974400056 PM 10755888 ER PT J AU Gundlach, BR Lewis, MG Sopper, S Schnell, T Sodroski, J Stahl-Hennig, C Uberla, K AF Gundlach, BR Lewis, MG Sopper, S Schnell, T Sodroski, J Stahl-Hennig, C Uberla, K TI Evidence for recombination of live, attenuated immunodeficiency virus vaccine with challenge virus to a more virulent strain SO JOURNAL OF VIROLOGY LA English DT Article ID RHESUS-MONKEYS; DELETION MUTANT; NEF DELETION; HIV TYPE-1; PROTECTION; MACAQUES; AIDS; RESISTANCE; SIV; SURVIVAL AB Live, attenuated immunodeficiency virus vaccines, such as nef deletion mutants, are the most effective vaccines tested in the simian immunodeficiency virus (SIV) macaque model. In two independent studies designed to determine the breadth of protection induced by live, attenuated SN vaccines, we noticed that three of the vaccinated macaques developed higher set point viral load levels than unvaccinated control monkeys, Two of these vaccinated monkeys developed AIDS, while the control monkeys infected in parallel remained asymptomatic. Concomitant with an increase in viral load, a recombinant of the vaccine virus and the challenge virus could be detected. Therefore, the emergence of more-virulent recombinants of live, attenuated immunodeficiency viruses and less-aggressive wild-type viruses seems to be an additional risk of live, attenuated immunodeficiency virus vaccines. C1 Univ Leipzig, Inst Virol, D-04103 Leipzig, Germany. Univ Erlangen Nurnberg, Inst Virol, Erlangen, Germany. Univ Wurzburg, Inst Virol & Immunobiol, D-8700 Wurzburg, Germany. Deutsch Primatenzentrum, Gottingen, Germany. Henry M Jackson Fdn, Rockville, MD USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Uberla, K (reprint author), Univ Leipzig, Inst Virol, Liebigstr 24, D-04103 Leipzig, Germany. RI Uberla, Klaus/C-5676-2008 NR 32 TC 57 Z9 57 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2000 VL 74 IS 8 BP 3537 EP 3542 DI 10.1128/JVI.74.8.3537-3542.2000 PG 6 WC Virology SC Virology GA 296VT UT WOS:000086048000012 PM 10729127 ER PT J AU Yan, G Schoenfeld, D Penney, C Hurxthal, K Taylor, AE Faustman, D AF Yan, G Schoenfeld, D Penney, C Hurxthal, K Taylor, AE Faustman, D TI Identification of premature ovarian failure patients with underlying autoimmunity SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I EXPRESSION; HYPERGONADOTROPIC AMENORRHEA; OVULATION INDUCTION; CONTROLLED TRIAL; OOPHORITIS; ASSOCIATION; THERAPY; WOMEN AB Although known causes of premature ovarian failure (POF) include X chromosome deletions, radiation and chemotherapy, and genetic defects of the gonadotropin hormones or receptors, at least one third to one half of cases remain idiopathic. A significant proportion of patients with apparently idiopathic POF have some evidence for an autoimmune etiology. However, the only gold standard for detecting autoimmune causes of immune ovarian destruction has been invasive ovarian biopsy. Serum antibodies to ovarian and other self-tissue have been described in up to one third of women with POF, but the tests are not well standardized, not well correlated with ovarian histology, and highly variable. Recently, specific defects of expression of cell surface markers on peripheral blood lymphocytes have been shown to identify, in population-based studies, individuals destined to develop autoimmune pancreatic destruction and type I diabetes mellitus, even before any other evidence of autoimmunity. We, therefore, sought to test the ability of cell surface marker expression in women with POF to identify autoimmune defects. Seventeen women with POF, 11 of whom had positive antibody titers to ovary, thyroid, or antinuclear antibody, were studied on at least two occasions and compared in blinded fashion with normal controls and patients with autoimmune type I diabetes mellitus. The most useful marker for identifying autoimmunity was the surface density of conformationally correct HLA class I molecules on macrophages, a structure essential for T cell education. Using this marker, 7 of the 9 patients with autoantibodies and 3 of the 8 patients without autoantibodies were identified as having evidence of a defect in self-antigen presentation similar to that of type I diabetics (chi-square, p = 0.03). Subsequent testing identified antismooth muscle antibodies in 1 of the women with a defect of HLA class I molecules but no previously identified autoimmunity. In addition, there were increased numbers of CD8 T cells in both autoimmune POF and insulin-dependent diabetes mellitus (IDDM) patients. Exclusive to POF patients was a statistically significant increase in CD8 density on T cells. This was most prominent in POF patients with an underlying autoimmune etiology. These data further support a role for autoimmunity in POF patients and suggest that the further development of cell surface markers in combination with other diagnostic tests could result in diagnosis before the development of complete ovarian failure. The possibility for disease-specific therapy to prevent further autoimmune ovarian damage in selected POF patients is also envisioned. C1 Massachusetts Gen Hosp E, Immunobiol Lab, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. RP Faustman, D (reprint author), Bldg 149,13th St,CNY-3601, Charlestown, MA 02129 USA. FU NICHD NIH HHS [R01-HD32460-02, U54-HD]; NIDDK NIH HHS [P30 DK40561] NR 28 TC 28 Z9 30 U1 0 U2 2 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 APR PY 2000 VL 9 IS 3 BP 275 EP 287 DI 10.1089/152460900318461 PG 13 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 306PK UT WOS:000086604900006 PM 10787223 ER PT J AU Zhu, WH Guo, XD Villaschi, S Nicosia, RF AF Zhu, WH Guo, XD Villaschi, S Nicosia, RF TI Regulation of vascular growth and regression by matrix metalloproteinases in the rat aorta model of angiogenesis SO LABORATORY INVESTIGATION LA English DT Article ID MICROVASCULAR ENDOTHELIAL-CELLS; IN-VITRO; EXPRESSION; INVITRO; LOCALIZATION; PROLIFERATION; ORGANIZATION; MICROVESSELS; PROGRESSION; COLLAGENASE AB Matrix metalloproteinases (MMPs) have been implicated in the formation of microvessels during angiogenesis, but their role in vascular regression is poorly understood. The rat aorta model of angiogenesis was used to study the function of MMPs at different stages of the angiogenic process. Gelatin zymography and Western analysis demonstrated production of MMP-2 and MMP-9 by aortic outgrowths in serum-free collagen gel culture. MMP-2 was found in both culture medium and collagen gel, whereas MMP-9 was predominantly associated with the gel. MMP expression increased gradually during the angiogenic growth phase and stayed high when vessels regressed and collagen lysed around the aortic rings. The MMP inhibitors, batimastat and marimastat, blocked formation of microvessels when added to the culture medium at the beginning of the experiment. They, however, stabilized the microvessels and prevented vascular regression after the angiogenic growth phase. This effect was observed also under conditions of angiogenic stimulation by basic fibroblast growth factor. MMP inhibitor-mediated stabilization of microvessels was associated with inhibition of collagen lysis and accumulation of collagen fibrils in the subendothelial space. This study demonstrates that MMPs promote microvessel formation during the early stages of angiogenesis, but also contribute to the reabsorption of the neovasculature in the later stages of this process. The time-dependent divergent effects of MMPs on microvessel growth and survival may influence the in vivo activity of MMP inhibitors used to treat angiogenesis-dependent disorders. C1 VA Puget Sound Hlth Care Syst, Pathol & Lab Med S113 Lab, Seattle, WA 98108 USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. NCI, Dept Pathol, Bethesda, MD 20892 USA. Univ Roma Tor Vergata, Dipartimento Biopatol, Rome, Italy. RP Nicosia, RF (reprint author), VA Puget Sound Hlth Care Syst, Pathol & Lab Med S113 Lab, 1660 S Columbian Way, Seattle, WA 98108 USA. FU NHLBI NIH HHS [HL52585] NR 41 TC 78 Z9 83 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 2000 VL 80 IS 4 BP 545 EP 555 PG 11 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 307DP UT WOS:000086638200011 PM 10780671 ER PT J AU Batchelor, T AF Batchelor, T TI Temozolomide for malignant brain tumours SO LANCET LA English DT Editorial Material ID GLIOMA; TRIAL C1 Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. RP Batchelor, T (reprint author), Massachusetts Gen Hosp, Brain Tumor Ctr, Boston, MA 02114 USA. NR 11 TC 13 Z9 14 U1 0 U2 1 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 1 PY 2000 VL 355 IS 9210 BP 1115 EP 1116 DI 10.1016/S0140-6736(00)02055-9 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 302TC UT WOS:000086380900004 PM 10791369 ER PT J AU Rauch, SD AF Rauch, SD TI Transferrin microheterogeneity in human perilymph SO LARYNGOSCOPE LA English DT Article DE transferrin; perilymph; fistula ID CEREBROSPINAL-FLUID; GEL-ELECTROPHORESIS; BETA-2 TRANSFERRIN; GUINEA-PIG; FISTULA; BETA-2-TRANSFERRIN; IDENTIFICATION; FLUORESCEIN; DIAGNOSIS; PROFILES AB Objectives/Hypothesis: Assay for beta(2)-(asialo-) transferrin has been advocated for use in diagnosis of cerebrospinal fluid (CSF) leak or perilymphatic fistula based on the fact that it is present in these fluids but not in serum. Quantitation of the sensitivity of transferrin assays has not been reported previously. The present study was undertaken to quantify the sensitivity of a microelectrophoretic assay of beta(2)-transferrin and assess its potential applicability to clinical diagnosis of perilymphatic fistula. Study Design: The initial part of the study was a prospective bench biochemistry assessment of assay sensitivity and reliability. Subsequent application of the assay was a blinded prospective clinical trial. Methods: Transferrin is a ubiquitous monomeric glycoprotein consisting of 679 amino acids, two iron-binding sites, and two N-Linked complex glycan chains. The N-glycan chains branch in variable degree, carrying from zero to eight sialic acid residues. This variation in sialylation has been termed "microheterogeneity." When both iron-binding: sites are saturated, the microheterogeneity of sialic acid content results in isoelectric points ranging from pH 5 to pH 6. Thus these nine transferrin variants can be distinguished by isoelectric focusing. Samples of transferrin solution or body fluids (serum, CSF, and perilymph) were incubated in iron-loading buffer to saturate both iron-binding sites and then subjected to isoelectric focusing (IEF). The separated proteins were immunoprecipitated in the IEF gel and silver stained for visualization. Serial dilutions of pure transferrin solution were used to determine assay sensitivity. Neuraminidase was used to digest sialic acid side chains from pure transferrin in solution, and the reaction product was used as a reference standard for comparison to assay of unknown fluids. Patient inner ear fluid samples obtained during stapedectomy or cochlear implantation were used to assess clinical applicability of the assay. Results: This microelectrophoretic technique, using only 0.3 mu L of iron-loaded sample, was able to consistently detect less than 250 pg of transferrin in solution and separate the different sialylation variants based on their isoelectric points. Assay of patient serum samples clearly demonstrated transferrin microheterogeneity. Assay of CSF consistently showed the predicted beta(2)-(asialo-) transferrin band. Assay of inner ear fluid samples also demonstrated transferrin microheterogeneity. However, no inner ear fluid samples had detectable levels of beta(2)-transferrin. presumably, perilymph sample dilution during iron loading and by admixture with serum, local anesthetic, or middle ear secretions lowered the beta(2)-transferrin concentration below the detection Limen of the assay. Conclusions: Microelectrophoretic assay of iron-loaded transferrin can detect as little as 250 pg of protein and can identify microheterogeneity in serum, CSF, and perilymph. However, dilutional effects of sample handling and preparation can lower the beta(2)-transferrin concentration of inner ear fluid samples below the detection limen of the assay. Thus, depending on the relative amounts of serum and perilymph (or CSF) in a mixed sample, electrophoretic separation of transferrin variants may not be diagnostic. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. RP Rauch, SD (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC01654] NR 30 TC 9 Z9 9 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2000 VL 110 IS 4 BP 545 EP 552 DI 10.1097/00005537-200004000-00006 PG 8 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 301UF UT WOS:000086328100006 PM 10763998 ER PT J AU Lee, NJ Wang, SJ Durairaj, KK Srivatsan, ES Wang, MB AF Lee, NJ Wang, SJ Durairaj, KK Srivatsan, ES Wang, MB TI Increased expression of transforming growth factor-beta 1, acidic fibroblast growth factor, and basic fibroblast growth factor in fetal versus adult fibroblast cell lines SO LARYNGOSCOPE LA English DT Article; Proceedings Paper CT Meeting of the Western Section of the American-Laryngological-Rhinological-and-Otological-Society CY JAN 08-09, 2000 CL SAN FRANCISCO, CALIFORNIA SP Amer Laryngol Rhinol & Otolog Soc, Western Sect DE fibroblasts; fetal; wound-healing; growth factors; Western blot ID SKIN WOUNDS AB Objectives: Fetal wound healing occurs without scar tissue formation. Differences in growth factor expression between fetal and adult fibroblasts have been explored. Recently we used RNA expression studies to demonstrate that transforming growth fan tor (TGF)-beta 1, acidic fibroblast growth factor (alpha-FGF), and basic fibroblast growth factor (beta-FGF) could be detected in both fetal and adult fibroblast cell lines. In addition, adult fibroblasts showed greater relative expression of these growth factors than fetal fibroblasts. The aim of this study was to identify the level of protein expression in fetal and adult fibroblasts. Study Design/Methods: Fetal. and adult fibroblasts were grown in culture using standard and serum-free media. After protein extraction, Western blot studies were performed to detect the presence and amount of TGF beta-1, alpha-FGF, and beta-FGF growth factor proteins. beta-Tubulin was used as a control Results: TGF beta-1, alpha-FGF, and beta-FGF proteins were detected in fetal and adult fibroblasts grown in standard and serum-free media The fetal fibroblasts showed higher levels of all three growth factor proteins compared with the adult fibroblasts. Conclusions: Western blot studies suggest higher levels of TGF beta-1, alpha-FGF, and beta-FGF expression in fetal fibroblasts. It is clear that significant differences exist in the expression/production of these growth factors and it seems likely that further study. of these differences will help elucidate the unique healing capabilities of fetal fibroblasts. C1 Univ Calif Los Angeles, Div Head & Neck Surg, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Vet Adm Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA 90024 USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, Div Head & Neck Surg, Sch Med, 10833 Le Conte Ave,CHS 62-132, Los Angeles, CA 90095 USA. NR 14 TC 4 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0023-852X J9 LARYNGOSCOPE JI Laryngoscope PD APR PY 2000 VL 110 IS 4 BP 616 EP 619 DI 10.1097/00005537-200004000-00015 PG 4 WC Medicine, Research & Experimental; Otorhinolaryngology SC Research & Experimental Medicine; Otorhinolaryngology GA 301UF UT WOS:000086328100015 PM 10764007 ER PT J AU Kelly, K AF Kelly, K TI Spinal cord injury: A guide for living. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. RP Kelly, K (reprint author), Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU BOWKER MAGAZINE GROUP CAHNERS MAGAZINE DIVISION PI NEW YORK PA 249 W 17TH ST, NEW YORK, NY 10011 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD APR 1 PY 2000 VL 125 IS 6 BP 123 EP 124 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 297KB UT WOS:000086080800185 ER PT J AU Perry, MC Ihde, DC Herndon, JE Grossbard, ML Grethein, SJ Atkins, JN Vokes, EE Green, MR AF Perry, MC Ihde, DC Herndon, JE Grossbard, ML Grethein, SJ Atkins, JN Vokes, EE Green, MR TI Paclitaxel/ifosfamide or navelbine/ifosfamide chemotherapy for advanced non-small cell lung cancer: CALGB 9532 SO LUNG CANCER LA English DT Article DE non-small cell lung cancer; non-cisplatin containing regimens; paclitaxel/ifosfamide; vinorelbine/ifosfamide ID PHASE-I; IFOSFAMIDE AB In order to explore non-cisplatin containing regimens for advanced non-small cell lung cancer, Cancer and Leukemia Group B conducted a randomized Phase-II study of two novel combinations, paclitaxel/ifosfamide and vinorelbine/ifosfamide, Both regimens were active with a 38% response rate (95% CI: 24%, 53%) and 31% (95% CI: 18%, 47%), respectively, Median survivals were 8.5 and 7.4 months. Toxicity, mostly neutropenia, was acceptable. These two combinations establish a 'proof of principle' that non-cisplatin containing regimens also have activity in this setting. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved. C1 Univ Missouri, Ellis Fischel Canc Ctr, Div Hematol Oncol, Columbia, MO 65201 USA. Washington Univ, Jewish Hosp St Louis, St Louis, MO 63110 USA. CALGB, Ctr Stat, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Hlth Sci Ctr, Syracuse, NY 13210 USA. Wake Forest Univ, Sch Med, Winston Salem, NC USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Perry, MC (reprint author), Univ Missouri, Ellis Fischel Canc Ctr, Div Hematol Oncol, Room 524,115 Business Loop 70 W, Columbia, MO 65201 USA. FU NCI NIH HHS [CA31946] NR 5 TC 19 Z9 20 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD APR PY 2000 VL 28 IS 1 BP 63 EP 68 DI 10.1016/S0169-5002(99)00129-4 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 300TE UT WOS:000086267600009 PM 10704711 ER PT J AU Ubel, PA Baron, J Nash, B Asch, DA AF Ubel, PA Baron, J Nash, B Asch, DA TI Are preferences for equity over efficiency in health care allocation "all or nothing"? SO MEDICAL CARE LA English DT Article DE ethics; allocation; rationing; cost-effectiveness analysis; physician survey; general public survey ID COST-EFFECTIVENESS ANALYSIS; LIVERS AB BACKGROUND. In a previous study we showed that within a budget constraint, most people would rather offer a less effective screening test to 100% of a Medicaid population, thereby saving 1,000 lives, than a more effective test to 50% of the population, thereby saving 1,100 lives. We present here a study exploring whether this preference for equity over efficiency persists when neither test can be offered to the entire population. METHODS. Members of Physicians' Online and prospective jurors at the Philadelphia County Courthouse randomly received I of 3 questionnaires (41, 42, or 43) describing a limited budget to screen Medicaid enrollees for colon cancer, In all questionnaires, test I was said to save 1,000 lives, and test 2, a more effective and more expensive test, was said to save 1;100. In 41,test I was offered to 100% and test:! to 50% of the population In 42, the 2 tests could be offered to 50% and 25%, respectively; in 43,to 90% and 40%, respectively. Respondents indicated which test they recommended and provided justification. RESULTS. The majority of physicians (59%) and the general public (56%) receiving Q1 favored the less effective screening test However, of those receiving Q2,only 26% of physicians and 27% of the general public recommended the less effective screening test And of: those receiving Q3, only 38% of physicians and 28% of the general public recommended the less effective test. Justifications for these recommendations were based largely on concerns for equality of: treatment among those who chose the less effective test and concerns for saving the most lives among those who preferred the more effective test. CONCLUSIONS, Although most: respondents show a preference for equity over efficiency when equity means that 100% of a population can receive a service, many fewer;respondents maintain this preference when equity is no longer absolute. This result suggests that the preference for equity is sometimes "all or none." C1 Univ Penn, Div Gen Internal Med, Sch Med, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. Univ Penn, Sch Med, Ctr Bioeth, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychol, Philadelphia, PA 19104 USA. Physicians Online, Tarrytown, NY USA. RP Ubel, PA (reprint author), Univ Penn, Div Gen Internal Med, Sch Med, 1223 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. FU NCI NIH HHS [R01 CA78052-01] NR 20 TC 30 Z9 30 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2000 VL 38 IS 4 BP 366 EP 373 DI 10.1097/00005650-200004000-00003 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 296XN UT WOS:000086052200003 PM 10752968 ER PT J AU Orlander, JD Gupta, M Fincke, BG Manning, ME Hershman, W AF Orlander, JD Gupta, M Fincke, BG Manning, ME Hershman, W TI Co-teaching: a faculty development strategy SO MEDICAL EDUCATION LA English DT Article DE education, medical, graduate, management, methods; internal medicine, education; hospitals, teaching; medical staff, hospital; mentors; teaching ID EDUCATION AB It has been stated that faculty development programmes which are closely linked to particular teaching contexts are most likely to be effective. Over the past 10 years we have developed a model of 'co-teaching' for faculty development which is based upon this premise and which can be applied to any clinical rotation. In this paper we describe our model, in which paired physicians focus on developing their teaching skills while sharing the clinical supervision of residents and medical students. Through iterative phases of teaching, debriefing and planning, co-teachers gain experience in analysing teaching encounters and develop skills in self-evaluation. Teaching occurs in the usual clinical settings such as attending (consultant) teaching rounds, clinic precepting, and case conferences. We discuss our model in the context of educational theory and related literature. We support our positive assessment of the co-teaching model through the precepts of collaborative inquiry and case study methodology. Vignettes, taken from the experiences of the authors, are used to demonstrate how the model is used to develop effective solutions to problems and to help in the maturation of one's skill as an educator. Successful implementation of the model is predicated on the development of a truly collaborative process between co-teachers. We share lessons we have learned from our experience of implementing the model in different clinical venues, such as the contrast between teaching on a hospital ward or in the clinic. This collaborative process has been well received by junior and senior faculty participants in our institution for more than a decade. C1 Boston Univ, Sch Med, VA Boston Healthcare Syst, Gen Internal Med Sect,Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Gen Internal Med Sect,Evans Dept Med, Boston, MA 02118 USA. RP Orlander, JD (reprint author), Boston VAMC 111, 150 S Huntington Ave, Boston, MA 02130 USA. NR 28 TC 18 Z9 18 U1 2 U2 8 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0308-0110 J9 MED EDUC JI Med. Educ. PD APR PY 2000 VL 34 IS 4 BP 257 EP 265 DI 10.1046/j.1365-2923.2000.00494.x PG 9 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 301YC UT WOS:000086337300006 PM 10733721 ER PT J AU Chen, T Dong, H Yong, R Duncan, MJ AF Chen, T Dong, H Yong, R Duncan, MJ TI Pleiotropic pigmentation mutants of Porphyromonas gingivalis SO MICROBIAL PATHOGENESIS LA English DT Article DE Porphyromonas gingivalis; pigmentation mutants ID PROTEINASE LYS-GINGIPAIN; CYSTEINE PROTEINASE; ARG-GINGIPAIN; EPITHELIAL-CELLS; ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; SHIGELLA-FLEXNERI; MATRIX PROTEINS; ORAL-SURFACES; O-ANTIGEN AB Porphyromonas gingivalis is a Gram-negative, black pigmented oral anaerobe associated with adult periodontitis. The adherence of the bacterium to junctional epithelial cells is the first step in infection and colonization. The molecular mechanisms and genetics of colonization are, as yet, not well understood, although it has been demonstrated that P. gingivalis fimbriae are involved in adhesion. In addition, cell surface cysteine proteinases may play a role either directly as adhesins or indirectly through their involvement in the biogenesis of fimbriae. A link has been established between cysteine proteinase-hemagglutinating activity and colongy pigmentation on blood agar. in this study a P. gingivalis ATCC 33277 transposon library was screened for white mutants. Pleiotropic mutants were identified with altered pigmentation, proteinase, hemagglutinin and haemolytic activities. Although the mutants fell into two classes based on the above phenotypes, by electron microscopy both classes showed increased fimbriation and decreased vesicle formation. Sequencing of genomic DNA flanking the transposon insertions revealed that one class of mutants carried disruptions in the gene encoding Lys-gingipain (kgp) and the other in a gene homologous to a glycosyl transferase. Potential roles for these genes in pigmentation, fimbriation, vesicle formation and attachment to epithelial cells are discussed. (C) 2000 Academic Press. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. RP Duncan, MJ (reprint author), Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. FU NIDCR NIH HHS [R01 DE 10510, R01 DE 12082] NR 44 TC 26 Z9 30 U1 0 U2 2 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD APR PY 2000 VL 28 IS 4 BP 235 EP 247 DI 10.1006/mpat.1999.0338 PG 13 WC Immunology; Microbiology SC Immunology; Microbiology GA 306BK UT WOS:000086576100006 PM 10764615 ER PT J AU De la Serna, IL Carlson, KA Hill, DA Guidi, CJ Stephenson, RO Sif, S Kingston, RE Imbalzano, AN AF De la Serna, IL Carlson, KA Hill, DA Guidi, CJ Stephenson, RO Sif, S Kingston, RE Imbalzano, AN TI Mammalian SWI-SNF complexes contribute to activation of the hsp70 gene SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HEAT-SHOCK FACTOR; NUCLEOSOME REMODELING FACTOR; METALLOTHIONEIN-I GENE; SACCHAROMYCES-CEREVISIAE; TRANSCRIPTIONAL ACTIVATION; GLUCOCORTICOID RECEPTOR; BINDING PROTEIN; MESSENGER-RNA; DNA-BINDING; RETINOBLASTOMA PROTEIN AB ATP-dependent chromatin-remodeling complexes are conserved among all eukaryotes and function by altering nucleosome structure to allow cellular regulatory factors access to the DNA. Mammalian SWI-SNF complexes contain either of two highly conserved ATPase subunits: BRG1 or BRM. To identify cellular genes that require mammalian SWI-SNF complexes for the activation of gene expression, we have generated cell lines that inducibly express mutant forms of the BRG1 or BRM ATPases that are unable to bind and hydrolyze ATP. The mutant subunits physically associate with at least two endogenous members of mammalian SWI-SNF complexes, suggesting that nonfunctional, dominant negative complexes may be formed. We determined that expression of the mutant BRG1 or BRM proteins impaired the ability of cells to activate the endogenous stress response gene hsp70 in response to arsenite, a metabolic inhibitor, or cadmium, a heavy metal. Activation of hsp70 by heat stress, however, was unaffected. Activation of the heme oxygenase 1 promoter by arsenite or cadmium and activation of the cadmium-inducible metallothionein promoter also were unaffected by the expression of mutant SWI-SNF components. Analysis of a subset of constitutively expressed genes revealed no or minimal effects on transcript levels. We propose that the requirement for mammalian SWI-SNF complexes in gene activation events will be specific to individual genes and signaling pathways. C1 Univ Massachusetts, Sch Med, Dept Cell Biol, Worcester, MA 01655 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Imbalzano, AN (reprint author), Univ Massachusetts, Sch Med, Dept Cell Biol, 55 Lake Ave N, Worcester, MA 01655 USA. FU NIGMS NIH HHS [R01 GM048405, R01 GM056244, R01 GM48405, R01 GM56244] NR 93 TC 122 Z9 123 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 APR PY 2000 VL 20 IS 8 BP 2839 EP 2851 DI 10.1128/MCB.20.8.2839-2851.2000 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 299VJ UT WOS:000086218300023 PM 10733587 ER PT J AU Amaya, F Decosterd, I Samad, TA Plumpton, C Tate, S Mannion, RJ Costigan, M Woolf, CJ AF Amaya, F Decosterd, I Samad, TA Plumpton, C Tate, S Mannion, RJ Costigan, M Woolf, CJ TI Diversity of expression of the sensory neuron-specific TTX-resistant voltage-gated sodium ion channels SNS and SNS2 SO MOLECULAR AND CELLULAR NEUROSCIENCE LA English DT Article ID RAT DORSAL-ROOT; GANGLION NEURONS; CAPSAICIN-RECEPTOR; DOWN-REGULATION; SPINAL-CORD; NA+-CHANNEL; SMALL-CELLS; PAIN; CURRENTS; HYPERSENSITIVITY AB The differential distribution of two tetrodotoxin resistant (TTXr) voltage-gated sodium channels SNS (PN3) and SNS2 (NaN) in rat primary sensory neurons has been investigated. Both channels are sensory neuron specific with SNS2 restricted entirely to those small dorsal root ganglion (DRG) cells with unmyelinated axons (C-fibers). SNS, in contrast, is expressed both in small C-fiber DRG cells and in 10% of cells with myelinated axons (A-fibers). All SNS expressing A-fiber cells are Trk-A positive and many express the vanilloid-like receptor VRL1. About half of C-fiber DRG neurons express either SNS or SNS2, and in most, the channels are colocalized. SNS and SNS2 are found both in NGF-responsive and GDNF-responsive C-fibers and many of these cells also express the capsaicin receptor VR1. A very small proportion of small DRG cells express either only SNS or only SNS2. At least four different classes of A- and C-fiber one neurons exist, therefore, with respect to expression of these sodium channels. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Glaxo Wellcome Res & Dev Ltd, Stevenage SG1 2NY, Herts, England. RP Costigan, M (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 149 13th St,Room 4309, Charlestown, MA 02129 USA. FU NINDS NIH HHS [NS38253-01] NR 38 TC 181 Z9 185 U1 5 U2 19 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1044-7431 J9 MOL CELL NEUROSCI JI Mol. Cell Neurosci. PD APR PY 2000 VL 15 IS 4 BP 331 EP 342 DI 10.1006/mcne.1999.0828 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 309NV UT WOS:000086775100001 PM 10845770 ER PT J AU Slack, FJ Basson, M Liu, ZC Ambros, V Horvitz, HR Ruvkun, G AF Slack, FJ Basson, M Liu, ZC Ambros, V Horvitz, HR Ruvkun, G TI The lin-41 RBCC gene acts in the C-elegans heterochronic pathway between the let-7 regulatory RNA and the LIN-29 transcription factor SO MOLECULAR CELL LA English DT Article ID NEMATODE CAENORHABDITIS-ELEGANS; POSTEMBRYONIC DEVELOPMENTAL EVENTS; TEMPORAL PATTERN-FORMATION; RING FINGER; ZINC-FINGER; RAR-ALPHA; PROTEIN; ENCODES; DOMAIN; REGION AB Null mutations in the C. elegans heterochronic gene lin-41 cause precocious expression of adult fates at larval stages. Increased lin-41 activity causes the opposite phenotype, reiteration of larval fates. let-7 mutations cause similar reiterated heterochronic phenotypes that are suppressed by lin-41 mutations, showing that lin-41 is negatively regulated by let-7. lin-41 negatively regulates the timing of LIN-29 adult specification transcription factor expression. lin-41 encodes an RBCC protein, and two elements in the lin-41 3'UTR are complementary to the 21 nucleotide let-7 regulatory RNA. A lin-41::GFP fusion gene is downregulated in the tissues affected by lin-41 at the time that the let-7 regulatory RNA is upregulated. We suggest that late larval activation of let-7 RNA expression downregulates LIN-41 to relieve inhibition of lin-29. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Dartmouth Coll, Dept Sci Biol, Hanover, NH 03755 USA. RP Ruvkun, G (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. OI Slack, Frank/0000-0001-8263-0409 FU NIGMS NIH HHS [GM44619, F32 GM018663, GM18663, R01 GM24663] NR 40 TC 455 Z9 487 U1 5 U2 24 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell. PD APR PY 2000 VL 5 IS 4 BP 659 EP 669 DI 10.1016/S1097-2765(00)80245-2 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 309VM UT WOS:000086790000007 PM 10882102 ER PT J AU Rektorschek, M Buhmann, A Weeks, D Schwan, D Bensch, KW Eskandari, S Scott, D Sachs, G Melchers, K AF Rektorschek, M Buhmann, A Weeks, D Schwan, D Bensch, KW Eskandari, S Scott, D Sachs, G Melchers, K TI Acid resistance of Helicobacter pylori depends on the UreI membrane protein and an inner membrane proton barrier SO MOLECULAR MICROBIOLOGY LA English DT Article ID ALLELIC EXCHANGE; UREASE ACTIVITY; METABOLISM; PH; LOCALIZATION; TRANSPORTER; GASTRITIS; SURVIVAL; STRAINS; BIOLOGY AB ureI encodes an inner membrane protein of Helicobacter pylori. The role of the bacterial inner membrane and UreI in acid protection and regulation of cytoplasmic urease activity in the gastric microorganism was studied. The irreversible inhibition of urease when the organism was exposed to a protonophore (3,3',4',5-tetrachlorsalicylanide; TCS) at acidic pH showed that the inner membrane protected urease from acid. Isogenic ureI knockout mutants of several H. pylori strains were constructed by replacing the ureI gene of the urease gene cluster with a promoterless kanamycin resistance marker gene (kan(R)). Mutants carrying the modified ureAB-kan(R)-EFGH operon all showed wild-type levels of urease activity at neutral pH in vitro. The mutants resisted media of pH > 4.0 but not of pH < 4.0. Whereas wild-type bacteria showed high levels of urease activity below pH 4.0, this ability was not retained in the ureI mutants, resulting in inhibition of metabolism and cell death. Gene complementation experiments with plasmid-derived H. pylori ureI restored wild-type properties. The activation of urease activity found in structurally intact but permeabilized bacteria treated with 0.01% detergent (polyoxy-ethylene-8-laurylether; C12E8), suggested a membrane-limited access of urea to internal urease at neutral pH. Measurement of C-14-urea uptake into Xenopus oocytes injected with ureI cRNA showed acid activation of uptake only in injected oocytes. Acceleration of urea uptake by UreI therefore mediates the increase of intracellular urease activity seen under acidic conditions. This increase of urea permeability is essential for H. pylori survival in environments below pH 4.0. ureI-independent urease activity may be sufficient for maintenance of bacterial viability above pH 4.0. C1 Byk Gulden Pharmaceut Konstanz, Dept Biol Mol, Constance, Germany. W LA Healthcare Ctr, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Physiol, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. RP Melchers, K (reprint author), Byk Gulden Pharmaceut Konstanz, Dept Biol Mol, Constance, Germany. NR 41 TC 51 Z9 56 U1 0 U2 5 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 APR PY 2000 VL 36 IS 1 BP 141 EP 152 DI 10.1046/j.1365-2958.2000.01835.x PG 12 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 301YM UT WOS:000086338200014 PM 10760171 ER PT J AU Chmura, SJ Nodzenski, E Kharbanda, S Pandey, P Quintas, J Kufe, DW Weichselbaum, RR AF Chmura, SJ Nodzenski, E Kharbanda, S Pandey, P Quintas, J Kufe, DW Weichselbaum, RR TI Down-regulation of ceramide production abrogates ionizing radiation-induced cytochrome c release and apoptosis SO MOLECULAR PHARMACOLOGY LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; SIGNAL-TRANSDUCTION; CONFERS RESISTANCE; SPHINGOMYELIN; CELLS; BCL-X(L); DISRUPTION; INHIBITORS; ACTIVATION; WEHI-231 AB Previous work has demonstrated that down-regulation of ceramide production after selection of cells with N-oleoylethanolamine (OE), an inhibitor of ceramidase, results in resistance to DNA damage-induced apoptosis. We report here that acute exposure of WEHI-231 cells (murine B-cell lymphoma) to OE activates neutral sphingomyelinase, induces ceramide production and increases intracellular reactive oxygen species. OE exposure also induces mitochondrial permeability, cytochrome c release, and apoptosis. Cells selected for resistance to OE exhibit little if any change in reactive oxygen species and cytochrome c release when exposed either to OE or to toxic doses of ceramide. Importantly, the OE resistant cells are also resistant to ionizing radiation-induced cytochrome c release and apoptosis. These findings demonstrate that down-regulation of neutral sphingomyelinase activity is associated with decreased DNA-damage-induced apoptosis. In addition, the data suggests that agents that modify extranuclear targets responsible for ceramide production select for cells resistant to ionizing radiation-induced apoptosis through alterations in mitochondrial function. C1 Univ Chicago, Dept Radiat & Cellular Oncol, Div Biol Sci, Chicago, IL 60637 USA. Univ Chicago, Pritzker Sch Med, Chicago, IL 60637 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weichselbaum, RR (reprint author), Univ Chicago Hosp, Dept Radiat Oncol, 5841 S Maryland Ave,MC 1105, Chicago, IL 60637 USA. FU NCI NIH HHS [5R01CA41608]; NIGMS NIH HHS [GM07183] NR 29 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2000 VL 57 IS 4 BP 792 EP 796 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 297DM UT WOS:000086066500020 PM 10727527 ER PT J AU Herrlinger, U Woiciechowski, C Sena-Esteves, M Aboody, KS Jacobs, AH Rainov, NG Snyder, EY Breakefield, XO AF Herrlinger, U Woiciechowski, C Sena-Esteves, M Aboody, KS Jacobs, AH Rainov, NG Snyder, EY Breakefield, XO TI Neural precursor cells for delivery of replication-conditional HSV-1 vectors to intracerebral gliomas SO MOLECULAR THERAPY LA English DT Article DE HSV-1; gene therapy; virus vector; glioma; DNA replication; neural precursor cells; migration ID HERPES-SIMPLEX VIRUS; EXPERIMENTAL BRAIN-TUMORS; VIRAL-DNA SYNTHESIS; NERVE GROWTH-FACTOR; GENE-EXPRESSION; THYMIDINE KINASE; RIBONUCLEOTIDE REDUCTASE; AMPLICON VECTORS; TYPE-1; LATENCY AB Cellular delivery of a replication-conditional herpes simplex virus type 1 (HSV-1) vector provides a means for gene therapy of invasive tumor cells. LacZ-bearing neural precursor cells, which can migrate and differentiate in the brain, were infected with a ribonucleotide reductase-deficient HSV-1 mutant virus (rRp450) that replicates only in dividing cells. Replication of rRp450 in neural precursor cells was blocked prior to implantation into the tumor by growth arrest in late G(1) phase through treatment with mimosine. Viral titers in the medium of mimosine-treated, rRp450-infected neural precursor cells were below detection levels 3 days after infection. In culture, after removal of mimosine and passaging, cells resumed growth and replication of rRp450 so that, 7 days later, virus was present in the medium and cell death was evident. Mimosine-treated neural precursor cells injected into established intracerebral CNS-1 gliomas in nude mice migrated extensively throughout the tumor and into the surrounding parenchyma beyond the tumor over 3 days. Mimosine-treated neural precursor cells, infected with rRp450 and injected into intracerebral CNS-1 tumors, also migrated within the tumor with the appearance of foci of HSV-thymidine kinase-positive (TK+) cells, presumably including tumor cells, distributed throughout the tumor and in the surrounding parenchyma over a similar period. This migratory cell delivery method has the potential to expand the range of delivery of HSV-1 vectors to tumor cells in the brain. C1 Massachusetts Gen Hosp, Serv Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neurosurg Serv, Mol Neurogenet Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Tubingen, Dept Neurol, D-7400 Tubingen, Germany. Humboldt Univ, Dept Neurosurg, Berlin, Germany. Univ Cologne, Dept Neurol, Cologne, Germany. Univ Halle Wittenberg, Dept Neurosurg, Halle, Germany. RP Breakefield, XO (reprint author), Massachusetts Gen Hosp E, Dept Mol Neurogenet, 13th St,Bldg 149,6th Floor, Charlestown, MA 02129 USA. FU NCI NIH HHS [CA69246]; NINDS NIH HHS [NS24279, NS34247] NR 65 TC 104 Z9 111 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2000 VL 1 IS 4 BP 347 EP 357 DI 10.1006/mthe.2000.0046 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 366RV UT WOS:000090019100008 PM 10933953 ER PT J AU Lewin, M Carlesso, N Tung, CH Tang, XW Cory, D Scadden, DT Weissleder, R AF Lewin, M Carlesso, N Tung, CH Tang, XW Cory, D Scadden, DT Weissleder, R TI Tat peptide-derivatized magnetic nanoparticles allow in vivo tracking and recovery of progenitor cells SO NATURE BIOTECHNOLOGY LA English DT Article DE stem cells; CD34; neural progenitor cells; magnetic resonance; iron oxide; homing ID HEMATOPOIETIC STEM-CELLS; IRON-OXIDE; BONE-MARROW; LYMPH-NODES; IN-VIVO; MICROSCOPY; PROTEIN; SUSCEPTIBILITY; MIGRATION; DELIVERY AB The ability to track the distribution and differentiation of progenitor and stem cells by high-resolution in vivo imaging techniques would have significant clinical and research implications. We have developed a cell labeling approach using short HIV-Tat peptides to derivatize superparamagnetic nanoparticles. The particles are efficiently internalized into hematopoietic and neural progenitor cells in quantities up to 10-30 pg of superparamagnetic iron per cell. Iron incorporation did not affect cell viability, differentiation, or proliferation of CD34(+) cells. Following intravenous injection into immunodeficient mice, 4% of magnetically CD34(+) cells homed to bone marrow per gram of tissue, and single cells could be detected by magnetic resonance (MR) imaging in tissue samples. In addition, magnetically labeled cells that had homed to bone marrow could be recovered by magnetic separation columns. Localization and retrieval of cell populations in vivo enable detailed analysis of specific stem cell and organ interactions critical for advancing the therapeutic use of stem cells. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. MIT, Dept Nucl Engn, NMR Facil, Cambridge, MA 02139 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [R01 CA46973, R01 CA59649]; NIAID NIH HHS [R01 AI/CA 46973] NR 38 TC 1306 Z9 1378 U1 21 U2 231 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2000 VL 18 IS 4 BP 410 EP 414 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 303UY UT WOS:000086444300023 PM 10748521 ER PT J AU Lindblad-Toh, K Winchester, E Daly, MJ Wang, DG Hirschhorn, JN Laviolette, JP Ardlie, K Reich, DE Robinson, E Sklar, P Shah, N Thomas, D Fan, JB Gingeras, T Warrington, J Patil, N Hudson, TJ Lander, ES AF Lindblad-Toh, K Winchester, E Daly, MJ Wang, DG Hirschhorn, JN Laviolette, JP Ardlie, K Reich, DE Robinson, E Sklar, P Shah, N Thomas, D Fan, JB Gingeras, T Warrington, J Patil, N Hudson, TJ Lander, ES TI Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse SO NATURE GENETICS LA English DT Article ID GENOME AB Single-nucleotide polymorphisms (SNPs) have been the focus of much attention in human genetics because they are extremely abundant and well-suited for automated large-scale genotyping, Human SNPs, however, are less informative than other types of genetic markers (such as simple-sequence length polymorphisms or microsatellites) and thus more loci are required for mapping traits. SNPs offer similar advantages for experimental genetic organisms such as the mouse, but they entail no loss of informativeness because bi-allelic markers are fully informative in analysing crosses between inbred strains. Here we report a large-scale analysis of SNPs in the mouse genome. We characterized the rate of nucleotide polymorphism in eight mouse strains and identified a collection of 2,848 SNPs located in 1,755 sequence-tagged sites (STSs) using high-density oligonucleotide arrays. Three-quarters of these SNPs have been mapped on the mouse genome, providing a first-generation SNP map of the mouse. We have also developed a multiplex genotyping procedure by which a genome scan can be performed with only six genotyping reactions per animal. C1 MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. Bristol Myers Squibb, Princeton, NJ USA. Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Affymetrix Inc, Santa Clara, CA USA. McGill Univ, Ctr Hlth, Montreal Genome Ctr, Montreal, PQ H3A 2T5, Canada. MIT, Dept Biol, Cambridge, MA 02139 USA. RP Lindblad-Toh, K (reprint author), MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. OI Gingeras, Thomas/0000-0001-9106-3573 FU NHGRI NIH HHS [HG01806] NR 11 TC 302 Z9 323 U1 3 U2 22 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2000 VL 24 IS 4 BP 381 EP 386 DI 10.1038/74215 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 299HK UT WOS:000086192800017 PM 10742102 ER PT J AU Aiello, LP AF Aiello, LP TI Keeping in touch with angiogenesis SO NATURE MEDICINE LA English DT Editorial Material ID ENDOTHELIAL GROWTH-FACTOR; PHVEGF(165); ISCHEMIA; FLUID AB Isthemic peripheral neuropathy is a frequent, severe and irreversible complication of critical limb ischemia. Therapeutic angiogenesis may ameliorate vascular insufficiency and may also provide direct beneficial effects on neural integrity, indicating a new paradigm for the treatment of neuronal disorders (pages 405-413). C1 Harvard Univ, Sch Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. RP Aiello, LP (reprint author), Harvard Univ, Sch Med, 1 Joslin Pl, Boston, MA 02215 USA. NR 11 TC 11 Z9 11 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2000 VL 6 IS 4 BP 379 EP 381 DI 10.1038/74633 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 376UA UT WOS:000165474100022 PM 10742139 ER PT J AU Asea, A Kraeft, SK Kurt-Jones, EA Stevenson, MA Chen, LB Finberg, RW Koo, GC Calderwood, SK AF Asea, A Kraeft, SK Kurt-Jones, EA Stevenson, MA Chen, LB Finberg, RW Koo, GC Calderwood, SK TI HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine SO NATURE MEDICINE LA English DT Article ID HEAT-SHOCK-PROTEIN; NF-KAPPA-B; HUMAN MONOCYTES; BACTERIAL LIPOPOLYSACCHARIDE; ANTIINFLAMMATORY DRUGS; INTRACELLULAR CALCIUM; LYMPHOCYTES-T; CUTTING EDGE; INDUCE HSP70; NK CELLS AB Here, we demonstrate a previously unknown function for the 70-kDa heat-shock protein (HSP70) as a cytokine. HSP70 bound with high affinity to the plasma membrane, elicited a rapid intracellular calcium flux, activated nuclear factor (NF)-kappaB and upregulated the expression of pro-inflammatory cytokines tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta and IL-6 in human monocytes. Furthermore, two different signal transduction pathways were activated by exogenous HSP70: one dependent on CD14 and intracellular calcium, which resulted in increased IL-1 beta, IL-6 and TNF-alpha; and the other independent of CD14 but dependent on intracellular calcium, which resulted in an increase in TNF-alpha but not IL-1 beta or IL-6. These findings indicate that CD14 is a co-receptor for HSP70-mediated signaling in human monocytes and are indicative of an previously unrecognized function for HSP70 as an extracellular protein with regulatory effects on human monocytes, having a dual role as chaperone and cytokine. 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 Canc Biol, Boston, MA 02115 USA. Merck Res Labs, Dept Immunol Res, Rahway, NJ 07065 USA. RP Calderwood, SK (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. RI Finberg, Robert/E-3323-2010; Ain, Kenneth/A-5179-2012; Asea, Alexzander/I-4112-2013 OI Ain, Kenneth/0000-0002-2668-934X; Asea, Alexzander/0000-0003-3592-3481 FU NCI NIH HHS [CA31303, CA47407, CA50642] NR 44 TC 1009 Z9 1073 U1 6 U2 41 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2000 VL 6 IS 4 BP 435 EP 442 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 376UA UT WOS:000165474100038 PM 10742151 ER PT J AU Werkele, T Kurtz, J Ito, H Ronquillo, JV Dong, V Zhao, GL Shaffer, J Sayegh, MH Sykes, M AF Werkele, T Kurtz, J Ito, H Ronquillo, JV Dong, V Zhao, GL Shaffer, J Sayegh, MH Sykes, M TI Allogeneic bone marrow transplantation with co-stimulatory blockade induces macrochimerism and tolerance without cytoreductive host treatment SO NATURE MEDICINE LA English DT Article ID NONLETHAL PREPARATIVE REGIMEN; RENAL-ALLOGRAFT REJECTION; T-CELLS; CLONAL DELETION; CHIMERISM; MICE; ENGRAFTMENT; INDUCTION; ACCEPTANCE; RECONSTITUTION AB Allogeneic bone marrow transplantation tin immunocompetent adults) has always required cytoreductive treatment of recipients with irradiation or cytotoxic drugs to achieve lasting engraftment at levels detectable by non-PCR-based techniques ('macrochimerism' or 'mixed chimerism')(1-11). Only syngeneic marrow engraftment at such levels has been achieved in unconditioned hosts(12,13). This requirement for potentially toxic myelosuppressive host pre-conditioning has precluded the clinical use of allogeneic bone marrow transplantation for many indications other than malignancies, including tolerance induction. We demonstrate here that treatment of naive mice with a high dose of fully major histocompatibility complex-mismatched allogeneic bone marrow, followed by one injection each of monoclonal antibody against CD154 and cytotoxic T-lymphocyte antigen 4 immunoglobulin, resulted in multi-lineage hematopoietic macrochimerism (of about 15%) that persisted for up to 34 weeks. Long-term chimeras developed donor-specific tolerance (donor skin graft survival of more than 145 days) and demonstrated ongoing intrathymic deletion of donor-reactive T cells. A protocol of high-dose bone marrow transplantation and co-stimulatory blockade can thus achieve allogeneic bone marrow engraftment without cytoreduction or T-cell depletion of the host, and eliminates a principal barrier to the more widespread use of allogeneic bone marrow transplantation(14-18). Although efforts have been made to minimize host pre-treatment for allogeneic bone marrow transplantation for tolerance induction, so far none have succeeded in eliminating pre-treatment completely. Our demonstration that this can be achieved provides the rationale for a safe approach for inducing robust transplantation tolerance in large animals and humans. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,BMT Sect, Boston, MA 02129 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Lab Immunogenet & Transplantat, Boston, MA 02115 USA. RP Sykes, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,BMT Sect, MGH E,Bldg 149-5102,13th St, Boston, MA 02129 USA. OI Wekerle, Thomas/0000-0001-5159-2796 NR 35 TC 3 Z9 4 U1 0 U2 1 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2000 VL 6 IS 4 BP 464 EP 469 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 376UA UT WOS:000165474100044 ER PT J AU Blaustein, RO Cole, PA Williams, C Miller, C AF Blaustein, RO Cole, PA Williams, C Miller, C TI Tethered blockers as molecular 'tape measures' for a voltage-gated K+ channel SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID POTASSIUM CHANNELS; BINDING-SITE; CHARYBDOTOXIN; TETRAETHYLAMMONIUM; PERMEATION; BLOCKADE; ION AB The propagation of electrical signals in excitable cells is orchestrated by a molecular family of voltage-dependent ion channel proteins. These K+, Na+, and Ca++ channels are all composed of four identical or similar units, each containing six transmembrane segments (S1-S6) in a roughly four-fold symmetric structure. The S5-S6 sequences fold into a central pore unit, which is surrounded by a voltage-gating module composed of S1-S4. The recent structure of KcsA, a two-transmembrane bacterial K+ channel, illuminates the physical character of the pore unit, but little is known about the arrangement of the surrounding S1-S4 sequences. To locate regions of this gating module in space, we synthesized a series of compounds of varying length that function as molecular 'tape measures': quaternary ammonium (QA) pore blockers that can be tethered to specific test residues. We show that in a Shaker K+ channel, the extracellular ends of st and S3 are similar to 30 Angstrom from the tetraethylammonium (TEA) blocking site at the external opening of the pore. A portion of the S3-S4 loop is, at 17-18 Angstrom, considerably closer. C1 Brandeis Univ, Howard Hughes Med Inst, Dept Biochem, Waltham, MA 02454 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Rockefeller Univ, Bioorgan Chem Lab, New York, NY 10021 USA. RP Miller, C (reprint author), Brandeis Univ, Howard Hughes Med Inst, Dept Biochem, Waltham, MA 02454 USA. NR 22 TC 77 Z9 79 U1 2 U2 7 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 2000 VL 7 IS 4 BP 309 EP 311 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 300ME UT WOS:000086256100016 PM 10742176 ER PT J AU Cheng, LL Anthony, DC Comite, AR Black, PM Tzika, AA Gonzalez, RG AF Cheng, LL Anthony, DC Comite, AR Black, PM Tzika, AA Gonzalez, RG TI Quantification of microheterogeneity in glioblastoma multiforme with ex vivo high-resolution magic-angle spinning (HRMAS) proton magnetic resonance spectroscopy SO NEURO-ONCOLOGY LA English DT Article ID HUMAN BRAIN-TUMORS; MOBILE LIPID-ACCUMULATION; HIGH-GRADE ASTROCYTOMAS; H-1 MR SPECTROSCOPY; IN-VITRO; H-1-NMR SPECTROSCOPY; NMR-SPECTRA; NECROTIC TISSUE; CLASSIFICATION; NEOPLASMS AB Microheterogeneity is a routinely observed neuropathologic characteristic in brain tumor pathology, Although microheterogeneity is readily documented by routine histologic techniques, these techniques only measure tumor status at the time of biopsy or surgery and do not indicate likely tumor progression. A biochemical screening technique calibrated against pathologic standards would greatly assist in predicting tumor progression from its biological activity. Here we demonstrate for the first time that proton magnetic resonance spectroscopy (H-1 MRS) with high-resolution magic-angle spinning (HRMAS), a technique introduced in 1997, can presence tissue histopathologic features while producing well-resolved spectra of cellular metabolites in the identical intact tissue specimens. Observed biochemical alterations and tumor histopathologic characteristics can thus be correlated for the same surgical specimen, obviating the problems caused by tumor microheterogeneity. We analyzed multiple specimens of a single human glioblastoma multiforme surgically removed from a 44-year-old patient. Each specimen was first measured with HRMAS H-1 MRS to determine tumor metabolites, then evaluated by quantitative histopathology, The concentrations of lactate and mobile lipids measured with HRMAS linearly reflected the percentage of tumor necrosis, Moreover, metabolic ratios of phosphorylcholine to choline correlated linearly with the percentage of the highly cellular malignant glioma, The quantification of tumor metabolic changes with HRMAS H-1 MRS, in conjunction with subsequent histopathology of the same tumor specimen, has the potential to further our knowledge of the biochemistry of tumor heterogeneity during development, and thus ultimately to improve our accuracy in diagnosing, characterizing, and evaluating tumor progression. C1 Massachusetts Gen Hosp, NMR Ctr, Dept Pathol, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Div Neuroradiol, Boston, MA 02129 USA. Childrens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Cheng, LL (reprint author), MGH CNY-7,149 13th St, Charlestown, MA 02129 USA. OI Anthony, Douglas/0000-0002-3815-2240 FU NCI NIH HHS [CA77727]; NCRR NIH HHS [RR13213]; NINDS NIH HHS [NS34626] NR 54 TC 91 Z9 100 U1 0 U2 12 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2000 VL 2 IS 2 BP 87 EP 95 DI 10.1215/15228517-2-2-87 PG 9 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 366TA UT WOS:000090019600003 PM 11303625 ER PT J AU Ferrigno, P Silver, PA AF Ferrigno, P Silver, PA TI Polyglutamine expansions: Proteolysis, chaperones, and the dangers of promiscuity SO NEURON LA English DT Review ID INTRANUCLEAR INCLUSIONS; NUCLEAR-LOCALIZATION; HUNTINGTONS-DISEASE; TRANSGENIC MICE; GENE; AGGREGATION; REPEATS; MODEL; DEATH C1 Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. 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 Silver, PA (reprint author), Harvard Univ, Sch Med, Dept Canc Biol, Boston, MA 02115 USA. NR 19 TC 46 Z9 48 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 2000 VL 26 IS 1 BP 9 EP 12 DI 10.1016/S0896-6273(00)81132-0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 309MA UT WOS:000086770500004 PM 10798387 ER PT J AU Dale, AM Liu, AK Fischl, BR Buckner, RL Belliveau, JW Lewine, JD Halgren, E AF Dale, AM Liu, AK Fischl, BR Buckner, RL Belliveau, JW Lewine, JD Halgren, E TI Dynamic statistical parametric mapping: Combining fMRI and MEG for high-resolution imaging of cortical activity SO NEURON LA English DT Article ID MEDIAL TEMPORAL-LOBE; DEPTH-RECORDED POTENTIALS; SURFACE-BASED ANALYSIS; HUMAN BRAIN ACTIVITY; CEREBRAL BLOOD-FLOW; HUMAN VISUAL-CORTEX; INTRACEREBRAL POTENTIALS; FIELD POTENTIALS; FUNCTIONAL MRI; RARE TARGET AB Functional magnetic resonance imaging (fMRI) can provide maps of brain activation with millimeter spatial resolution but is limited in its temporal resolution to the order of seconds. Here, we describe a technique that combines structural and functional MRI with magnetoencephalography (MEG) to obtain spatiotemporal maps of human brain activity with millisecond temporal resolution. This new technique was used to obtain dynamic statistical parametric maps of cortical activity during semantic processing of visually presented words. An initial wave of activity was found to spread rapidly from occipital visual cortex to temporal, parietal, and frontal areas within 185 ms, with a high degree of temporal overlap between different areas. Repetition effects were observed in many of the same areas following this initial wave of activation, providing evidence for the involvement of feedback mechanisms in repetition priming. C1 Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. Univ Utah, Dept Radiol, Salt Lake City, UT 84108 USA. INSERM, F-13258 Marseille, France. Washington Univ, Dept Psychol Anat & Neurobiol & Radiol, St Louis, MO 63130 USA. RP Dale, AM (reprint author), Massachusetts Gen Hosp, Nucl Magnet Resonance Ctr, Charlestown, MA 02129 USA. RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [R01-RR13609]; NINDS NIH HHS [R01 NS018741, R01-NS18741] NR 79 TC 704 Z9 710 U1 4 U2 33 PU CELL PRESS PI CAMBRIDGE PA 1050 MASSACHUSETTES AVE, CIRCULATION DEPT, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD APR PY 2000 VL 26 IS 1 BP 55 EP 67 DI 10.1016/S0896-6273(00)81138-1 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 309MA UT WOS:000086770500008 PM 10798392 ER PT J AU Harwood, DG Sultzer, DL Wheatley, MV AF Harwood, DG Sultzer, DL Wheatley, MV TI Impaired insight in Alzheimer disease: Association with cognitive deficits, psychiatric symptoms, and behavioral disturbances SO NEUROPSYCHIATRY NEUROPSYCHOLOGY AND BEHAVIORAL NEUROLOGY LA English DT Article ID NEUROBEHAVIORAL RATING-SCALE; MINI-MENTAL-STATE; MEMORY DEFICIT; DEPRESSION; ANOSOGNOSIA; DEMENTIA; UNAWARENESS; AWARENESS; PREVALENCE; CLINICIAN AB Objective: The purpose of this study was to evaluate symptoms associated with impaired insight in patients with Alzheimer disease (AD). Background: Although unawareness of deficits is common in AD. the relation of awareness to psychiatric and behavioral disturbances has not been extensively studied. Method: We conducted a cross-sectional investigation of 91 patients with probable AD according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. Awareness of cognitive and functional deficits was measured with the Inaccurate Insight item from the Neurobehavioral Rating Scale. Psychiatric and behavioral symptoms were measured using factor scores and individual items from the Neurobehavioral Rating Scale. Global cognitive deficits were measured using the Mini-Mental State Examination (MMSE). Results: Stepwise regression analysis showed that insight was associated with MMSE score, depression/anxiety factor score, and agitation/disinhibition factor score. Variables not associated with awareness of deficits included patient age, behavioral retardation factor score, verbal output disturbance factor score, and psychosis factor score. Post hoc analyses showed a positive relation (i,e., greater insight. more symptomatology) between deficit awareness and symptoms of depressed mood and anxiety. There was a negative relation (i.e.. greater insight, less symptomatology) between insight and symptoms of hostility, agitation, inattention, and tension. In a follow-up stepwise regression analysis, increased deficit awareness was associated with a higher MMSE score, greater depressed mood, and decreased agitation. Conclusions: These findings suggest that patients with AD may experience symptoms of depressed mood in relation to increased awareness of decrements in functioning. The data also indicate that patients with poor insight demonstrate greater agitated behavior. Consistent with previous research, impaired insight was higher in the later stages of the illness. C1 Univ Calif Los Angeles, Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. Vet Affairs Med Ctr Greater Los Angeles Healthcar, Mental Hlth Serv, Los Angeles, CA USA. RP Sultzer, DL (reprint author), W Los Angeles Vet Affairs Med Ctr, 3 South,116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIMH NIH HHS [MH00910, MH56031] NR 42 TC 91 Z9 95 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-878X J9 NEUROPSY NEUROPSY BE JI Neuropsychiatr. Neuropsychol. Behav. Neurol. PD APR PY 2000 VL 13 IS 2 BP 83 EP 88 PG 6 WC Clinical Neurology; Psychiatry; Psychology SC Neurosciences & Neurology; Psychiatry; Psychology GA 408AL UT WOS:000167304300002 PM 10780626 ER PT J AU Stiver, SI Ogilvy, CS AF Stiver, SI Ogilvy, CS TI Micro-arteriovenous malformations: Significant hemorrhage from small arteriovenous shunts SO NEUROSURGERY LA English DT Article DE arteriovenous malformation; clinical outcome; hemorrhage; seizures; stereotactic surgery ID NATURAL-HISTORY; EPILEPSY; BRAIN; SIZE AB OBJECTIVE: Micro-arteriovenous malformations (AVMs) represent approximately 8 to 10% of surgically treated brain AVMs. We examined the clinical presentations, radiological features, principles of surgical resection, and factors affecting outcomes for micro-AVM lesions. METHODS: Twelve patients with micro-AVMs that had been treated by surgical resection were retrospectively analyzed. The mean follow-up monitoring period was 35 months (range, 2-76 mo). Outcomes, as assessed in follow-up visits and telephone interviews (using a questionnaire), were classified according to the Glasgow Outcome Scale. RESULTS: All 12 patients presented with intracranial hemorrhage, which was intraparenchymal and superficially situated in 10 patients (83%) and intraventricular in 2 patients (17%). Hemorrhages were large (mean volume, 23 ml(3); range, 1-58 ml(3)) and were associated with neurological deficits for 10 of 12 patients (83%). The identification of an arterialized draining vein during surgery and stereotactic angiography greatly facilitated surgical localization of the lesions. One patient (8%) developed a mild permanent deficit as a result of surgery. Although Glasgow Outcome Scale scores were excellent for all except one patient, nine patients (75%) experienced long-term neurological problems. CONCLUSION: Micro-AVMs typically present with large hemorrhages and are associated with significant neurological deficits. If a superficial clot is present, surgical resection of the lesion is strongly advocated. The ultimate clinical outcomes are determined primarily by deficits present after the initial hemorrhaging episodes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurosurg Serv, Boston, MA USA. RP Stiver, SI (reprint author), Beth Israel Deaconess Med Ctr, Res N,Room 287,330 Brookline Ave, Boston, MA 02215 USA. NR 30 TC 9 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-396X J9 NEUROSURGERY JI Neurosurgery PD APR PY 2000 VL 46 IS 4 BP 811 EP 818 DI 10.1097/00006123-200004000-00008 PG 8 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 302HR UT WOS:000086360100017 PM 10764253 ER PT J AU Picard, C AF Picard, C TI Pattern of expanding consciousness in midlife women: Creative movement and the narrative as modes of expression SO NURSING SCIENCE QUARTERLY LA English DT Article DE creative movement; health as expanding consciousness; narrative; Newman's theory; pattern; women ID BREAST-CANCER; HEALTH; MUSIC AB This study is based on Newman's theory of expanding consciousness; it expands Newman's method to include creative movement as a mode of expression. The researcher engaged in two in-depth interviews and one creative movement group experience with each of 17 midlife women. Results demonstrate expanding consciousness at midlife, with patterns of meaning identified in relationships with others, self and spirit as well as challenges of loss, illness, and threats to relationships. Activities of consciousness were choosing, balancing, accepting, and letting go. Concepts of flow, turbulence, and a movement dialectic were identified in study findings. Creative movement supported self-awareness. C1 Massachusetts Gen Hosp, Inst Hlth Profess, Grad Nursing Program, Boston, MA 02114 USA. RP Picard, C (reprint author), Massachusetts Gen Hosp, Inst Hlth Profess, Grad Nursing Program, Boston, MA 02114 USA. NR 36 TC 21 Z9 21 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0894-3184 J9 NURS SCI QUART JI Nurs. Sci. Q. PD APR PY 2000 VL 13 IS 2 BP 150 EP 157 DI 10.1177/08943180022107438 PG 8 WC Nursing SC Nursing GA 394NJ UT WOS:000166529900013 PM 11847700 ER PT J AU Tomford, WW AF Tomford, WW TI Chondroprotective agents in the treatment of articular cartilage degeneration SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE LA English DT Article DE chondroprotection; glucosamine; chondroitin sulfate; hyaluronic acid; articular cartilage; osteoarthritis ID DOUBLE-BLIND; INTRAARTICULAR INJECTIONS; OSTEOARTHRITIS; HYALURONAN; GLUCOSAMINE; TRIAL; KNEE AB Glucosamine, chondroitin. sulfate, and hyaluronic acid provide new and exciting treatments for osteoarthritis. Although the use of these drugs is still controversial, they have gained popularity among the lay public, suggesting that they may have beneficial effects. Studies are now being performed to test the effectiveness of these medicines and, in particular, whether they function simply as placebos. Knowledge of these treatments is important for orthopedists treating young patients with articular cartilage damage. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Tomford, WW (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. NR 10 TC 2 Z9 2 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 1060-1872 J9 OPER TECHN SPORT MED JI Oper. Tech. Sports Med. PD APR PY 2000 VL 8 IS 2 BP 120 EP 121 DI 10.1053/otsm.2000.6578 PG 2 WC Sport Sciences; Surgery SC Sport Sciences; Surgery GA 339VG UT WOS:000088498100006 ER PT J AU Gill, TJ AF Gill, TJ TI The role of the microfracture technique in the treatment of full-thickness chondral injuries SO OPERATIVE TECHNIQUES IN SPORTS MEDICINE LA English DT Article DE microfracture; cartilage; treatment; indications; results AB Microfracture is indicated for both traumatic and degenerative full-thickness chondral defects. The technique is useful for both unipolar and "kissing" (bipolar) lesions in both the primary treatment and revision settings. There are no contraindications to the technique based on the size or location of the lesion, although smaller (<400 mm(2)), acute (<12 weeks from injury) femoral and trochlear lesions have the most predictable results. Relative contraindications to microfracture include chondral defects greater than 5 to 10 mm deep and the presence of a malaligned limb. Clinical studies have shown significant (P<.05) improvement in all functional parameters studied following the use of microfracture for the treatment of full-thickness, traumatic chondral defects. Of note, improvement in symptoms of pain and swelling continue to be seen until 2 years after surgery following microfracture. The microfacture tfchnique is a cost-effective, technically feasible, highly efficacious procedure available to all surgeons who perform arthroscopy of the knee. It is a reasonable first approach to the treatment of chondral defects, because it does not burn any bridges with regard to future procedures such as a mosaic-plasty or autologous chondrocyte transplantation if the microfracture should fail. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Gill, TJ (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, 15 Parkman St, Boston, MA 02114 USA. NR 4 TC 11 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1060-1872 J9 OPER TECHN SPORT MED JI Oper. Tech. Sports Med. PD APR PY 2000 VL 8 IS 2 BP 138 EP 140 DI 10.1053/otsm.2000.6583 PG 3 WC Sport Sciences; Surgery SC Sport Sciences; Surgery GA 339VG UT WOS:000088498100010 ER PT J AU Johansson, I Bratt, P Hay, DI Schluckebier, S Stromberg, N AF Johansson, I Bratt, P Hay, DI Schluckebier, S Stromberg, N TI Adhesion of Candida albicans, but not Candida krusei, to salivary statherin and mimicking host molecules SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE Candida albicans; Candida krusei; saliva; proline-rich proteins; statherin ID PROLINE-RICH PROTEINS; CALCIUM-PHOSPHATE PRECIPITATION; EPITHELIAL-CELL RECEPTORS; HUMAN-PAROTID SALIVA; APATITIC SURFACES; ADHERENCE; BINDING; INHIBITION; IDENTIFICATION; ACTINOMYCES AB The aim of the present study was to identify salivary molecules affecting adhesion of Candida albicans and Candida krusei to salivary pellicles and epithelial cells. Strains of C. albicans (GDH18, GDH3339, CA1957, ATCC 28366 and ATCC 10321), but not C. krusei (strains ATCC 14243 and Ck9), bound to saliva-coated hydroxyapatite and buccal epithelial cells. Parotid saliva fractions containing statherin, glycosylated proline-rich proteins (PRP) and as yet unidentified components mediated adhesion of strain GDH18; Fuc alpha 1-2Gal beta 1-4Glc partly inhibited the adhesion to those fractions not containing statherin. Pure statherin, but not PRP-1, mediated dose-dependent adhesion of C, albicans strain GDH18 to hydroxyapatite beads. Candida isolates (GDH18, GDH3339 and CA1957) bound somewhat more avidly to statherin/saliva relative to ATCC strains 28366 and 10321, while the opposite was true for adhesion to buccal epithelial cells. Adhesion of C, albicans strain GDH18 to saliva-coated hydroxyapatite and buccal epithelial cells was completely (93%) and partly (43%) blocked by statherin-specific immunoglobulin G (IgG) antibodies, respectively. Control IgG antibodies did not block Candida adhesion. Blockage of Candida adhesion to epithelial cells also occurred with Fuc alpha 1-2Gal beta 1-4Glc (49%) and N-acetylglucosamine (38%), while statherin specific IgG antibodies in combination with Fuc alpha 1-2Gal beta 1-4Glc almost completely eliminated Candida adhesion (79%). In addition, statherin in solution blocked the adhesion of strain GDH18 to epithelial cells by inducing aggregation of Candida cells. C1 Umea Univ, Dept Cariol, SE-90187 Umea, Sweden. Forsyth Dent Ctr, Boston, MA 02115 USA. RP Johansson, I (reprint author), Umea Univ, Dept Cariol, SE-90187 Umea, Sweden. FU NIDCR NIH HHS [DE 8601, DE7009] NR 49 TC 27 Z9 28 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD APR PY 2000 VL 15 IS 2 BP 112 EP 118 DI 10.1034/j.1399-302x.2000.150207.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 292UJ UT WOS:000085813200007 PM 11155174 ER PT J AU Smith, DJ Trantolo, DJ King, WF Gusek, EJ Fackler, PH Gresser, JD De Souza, VL Wise, DL AF Smith, DJ Trantolo, DJ King, WF Gusek, EJ Fackler, PH Gresser, JD De Souza, VL Wise, DL TI Induction of secretory immunity with bioadhesive poly (D,L-lactide-co-glycolide) microparticles containing Streptococcus sobrinus glucosyltransferase SO ORAL MICROBIOLOGY AND IMMUNOLOGY LA English DT Article DE PLGA; microparticles; glucosyltransferase; Streptococcus sobrinus; saliva; IgA ID TOXIN-B-SUBUNIT; BIODEGRADABLE MICROSPHERES; PROTEIN ANTIGEN; MUTANS; IMMUNIZATION; RESPONSES; MATRICES; RELEASE AB The effect of mucosal delivery of Streptococcus sobrinus glucosyltransferase (GTF) in bioadhesive poly (D,L-lactide-co-glycolide) (PLGA) microparticles on induction of salivary IgA and serum IgG antibody responses was measured in Sprague-Dawley rats. Preparations of GTF/PLGA/gelatin microparticles, or PLGA/gelatin microparticles or GTF in alum, were administered four times at weekly intervals by intranasal or intragastric routes. Two subcutaneous injections of GTF in PLGA/gelatin microparticles or in alum were given to separate groups of rats. Significant elevations in salivary IgA antibody levels to S. sobrinus GTF were observed only in the groups immunized intranasally 28 days after immunizations were begun. Five of six rats given the GTF microparticles intranasally had positive salivary IgA antibody responses to GTF, and the mean salivary IgA antibody level of this group was 30-fold higher than any other mucosally or systemically immunized group. Salivary IgA responses in the GTF-microparticle group remained significantly higher than all other mucosally immunized groups for at least 10 weeks after the primary immunization. All rats in this group demonstrated aspects of anamnesis following a more limited secondary course of intranasal administration. Intranasal administration of GTF in microparticles also induced a serum IgG response to GTF in some rats. After secondary intranasal GTF microparticle administration, several rats had sustained serum IBG antibody levels that were within the range of sera from rats subcutaneously injected with GTF in microparticles or in alum. Thus intranasal delivery of GTF-containing bioadhesive microparticles induced the highest and longest lasting salivary immune response of any mucosal or systemic route or vehicle tested and could be expected to be a useful method for induction of mucosal immunity. C1 Forsyth Dent Ctr, Dept Immunol, Boston, MA 02115 USA. Cambridge Sci Inc, Belmont, MA USA. RP Smith, DJ (reprint author), Forsyth Dent Ctr, Dept Immunol, 140 Fenway, Boston, MA 02115 USA. FU NIDCR NIH HHS [DE-12434, DE-06153] NR 21 TC 14 Z9 16 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0902-0055 J9 ORAL MICROBIOL IMMUN JI Oral Microbiol. Immunol. PD APR PY 2000 VL 15 IS 2 BP 124 EP 130 DI 10.1034/j.1399-302x.2000.150209.x PG 7 WC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology SC Dentistry, Oral Surgery & Medicine; Immunology; Microbiology GA 292UJ UT WOS:000085813200009 PM 11155176 ER PT J AU Friedlander, AH Maeder, LA AF Friedlander, AH Maeder, LA TI The prevalence of calcified carotid artery atheromas on the panoramic radiographs of patients with type 2 diabetes mellitus SO ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY ORAL RADIOLOGY AND ENDODONTICS LA English DT Article ID RISK-FACTORS; COMPLICATIONS; STROKE; LIPOPROTEIN; PREDICTORS; MORTALITY; DISEASE AB Objective. Type 2 diabetes mellitus, which afflicts 15 million Americans, is associated with accelerated cervical carotid artery atherosclerosis and a heightened risk of stroke. This study attempted to determine the prevalence of calcified atherosclerotic lesions in a group of patients with type 2 diabetes mellitus. Study design. The panoramic radiographs of 49 men (age range, 55 to 81; mean age, 66.2 years) receiving routine dental treatment and insulin for diabetes at a Department of Affairs Veterans clinic were evaluated for calcified atheromas. Age-match controls, free of diabetes, were assessed in a like manner. Statistical comparison of the atheroma prevalence rates was by means of the Fisher exact test and statistical comparison of atherogenic risk factors was by means of t test with Bonferroni adjustment and, where necessary, the Mann-Whitney U test. Results. The radiographs of the diabetics (mean age, 66.9 years) revealed that 20.4% had atheromas whereas those of the controls (mean age, 68.1 years) demonstrated that 4% had atheromas (a statistically significant difference; P = .0275). Also statistically significant was the prevalence of atherogenic risk factors (plasma glucose, low density lipoproteins, and serum triglycerides) identified in the diabetic group. The radiographic appearance of the atheromas manifested by both groups of individuals, however was similar, with the lesions located 1.5-2.5 cm inferior-posterior to angle of the mandible. Conclusions. People with type 2 diabetes have a greater prevalence of calcified atheromas on their panoramic radiographs than do nondiabetics. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Med Ctr, Hosp Dent Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90094 USA. Univ So Calif, Sch Dent, Los Angeles, CA 90089 USA. RP Friedlander, AH (reprint author), VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90024 USA. NR 25 TC 29 Z9 30 U1 0 U2 1 PU MOSBY-YEAR BOOK INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1079-2104 J9 ORAL SURG ORAL MED O JI Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod. PD APR PY 2000 VL 89 IS 4 BP 420 EP 424 DI 10.1016/S1079-2104(00)70122-3 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 306CD UT WOS:000086577900008 PM 10760724 ER PT J AU Leffert, RD AF Leffert, RD TI Nerve lesions about the shoulder SO ORTHOPEDIC CLINICS OF NORTH AMERICA LA English DT Article ID THORACIC-OUTLET SYNDROME; NEUROPATHY AB The shoulder is the most mobile joint in the body. Because it serves as a way station for the nerves supplying the upper limb, it creates a potential for nerve lesions that may be caused or significantly influenced by the complex dynamics of the shoulder girdle. This article presents the most commonly encountered lesions as well as an algorithm for their diagnosis and treatment. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Leffert, RD (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St, Boston, MA 02114 USA. NR 58 TC 4 Z9 4 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0030-5898 J9 ORTHOP CLIN N AM JI Orthop. Clin. North Am. PD APR PY 2000 VL 31 IS 2 BP 331 EP + DI 10.1016/S0030-5898(05)70151-6 PG 16 WC Orthopedics SC Orthopedics GA 307XP UT WOS:000086679700015 PM 10736400 ER PT J AU Gliklich, RE Taghizadeh, F Winkelman, JW AF Gliklich, RE Taghizadeh, F Winkelman, JW TI Health status in patients with disturbed sleep and obstructive sleep apnea SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article; Proceedings Paper CT 102nd Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 13-16, 1998 CL SAN ANTONIO, TEXAS SP Amer Acad Otolaryngol Head & Neck Surg ID RISK FACTOR; INFARCTION; MEN AB The health status of 435 consecutive patients with sleep disturbances necessitating polysomnography was investigated. Patients underwent overnight polysomnography and health status assessment, including the Medical Outcomes Study SF-36 Health Survey and the Pittsburgh Sleep Qualify Index. Based on a respiratory distress index (RDI) greater than 10 to define apnea, patients with apnea were significantly (P < 0.05) more likely to be male, be older, and have higher body mass index and tower oxygen saturation levers than patients without apnea. Multiple domains of the SF-36 Health Survey and the Pittsburgh Steep Quality Index were-significantly worse (P < 0.05) for this population when normative data were compared. Although few differences were observed between the apneic and nonapneic patients when a cutoff point for apnea was defined as an RDI greater than 10 or 20, increasing RDI was significantly associated with worsening physical functioning scores. Overall, decrements in health status measures were more strongly correlated with the number of oxygen desaturations below 85% than with increasing RDI. We conclude that patients with sleep disturbances demonstrate significant decrements in general and sleep-specific health status, but these decrements are more closely associated with oxygen desaturation than RDI. C1 Massachusetts Eye & Ear Infirm, Clin Outcomes Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Penn State Univ, Coll Med, Hershey, PA USA. Brigham & Womens Hosp, Sleep Disroders Lab, Boston, MA 02115 USA. RP Gliklich, RE (reprint author), Massachusetts Eye & Ear Infirm, Clin Outcomes Res Unit, 243 Charles St, Boston, MA 02114 USA. NR 13 TC 14 Z9 15 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 APR PY 2000 VL 122 IS 4 BP 542 EP 546 DI 10.1016/S0194-5998(00)70098-2 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 303KG UT WOS:000086420600013 PM 10740175 ER PT J AU Busch, B Cohen, L Biederman, L Spencer, T Wilens, T Sayer, J Mounteaux, M Mick, E Faraone, S AF Busch, B Cohen, L Biederman, L Spencer, T Wilens, T Sayer, J Mounteaux, M Mick, E Faraone, S TI ADHD in children: Does the ascertainment site predict the clinical correlates and degree of functional impairment? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Tufts Med Sch, Dept Pediat, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 137 BP 24A EP 24A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300138 ER PT J AU Chen, FH Sun, W Ding, SL Wetzel, GT Sarma, JSM Singh, BN Klitzner, TS AF Chen, FH Sun, W Ding, SL Wetzel, GT Sarma, JSM Singh, BN Klitzner, TS TI Dronedarone alters calcium current kinetics in isolated mouse ventricular myocytes SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Cardiovasc Res Labs, Los Angeles, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 227 BP 39A EP 39A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300228 ER PT J AU Levy, H Schonberger, J Somkiat, S Fatkin, D MacRae, E Halpin, C Eavey, R Philbin, E Seidman, JG Seidman, C AF Levy, H Schonberger, J Somkiat, S Fatkin, D MacRae, E Halpin, C Eavey, R Philbin, E Seidman, JG Seidman, C TI Dilated cardiomyopathy and sensorineural hearing loss: A heritable syndrome that maps to 6q23-24 SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 269 BP 46A EP 46A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300270 ER PT J AU Ingelfinger, JR Rasch, R Shih, S Woods, LL AF Ingelfinger, JR Rasch, R Shih, S Woods, LL TI Sexual dimorphism in perinatal programming: Effect of maternal protein restriction on the renin-angiotensin system and renal development SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Boston, MA USA. Oregon Hlth Sci Univ, Div Nephrol, Portland, OR 97201 USA. Univ Aarhus, Dept Cell Biol, Aarhus, Denmark. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 415 BP 71A EP 71A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300416 ER PT J AU Kenney, AM Rowitch, DH AF Kenney, AM Rowitch, DH TI Sonic hedgehog: A G1-phase regulator of neuronal precursor cell cycle progression SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 421 BP 72A EP 72A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300422 ER PT J AU Levitsky, LL Rhoads, DB Sudati, J Yang, F Agulian, T Osathanondh, R AF Levitsky, LL Rhoads, DB Sudati, J Yang, F Agulian, T Osathanondh, R TI Differential expression of genes in the developing human liver SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 429 BP 73A EP 73A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300430 ER PT J AU Lu, R Yok, DI Alberta, JA Stiles, CD Rowitch, DH AF Lu, R Yok, DI Alberta, JA Stiles, CD Rowitch, DH TI Sonic hedgehog-regulated oligodendrocyte lineage genes encoding bHLH proteins in the mammalian central nervous system SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 433 BP 74A EP 74A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300434 ER PT J AU Holmes, LB Adams, J Coull, B Harvey, EA AF Holmes, LB Adams, J Coull, B Harvey, EA TI Anticonvulsant face: Association with cognitive dysfunction SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 479 BP 82A EP 82A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300480 ER PT J AU Gidwani, PP Ferris, TG Gokhale, M Campbell, EG Perrin, JM AF Gidwani, PP Ferris, TG Gokhale, M Campbell, EG Perrin, JM TI Are pediatric residents prepared to address psychosocial conditions? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 518 BP 88A EP 88A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300519 ER PT J AU Insoft, RM Carew, A AF Insoft, RM Carew, A TI A novel pediatric residency transport rotation curriculum: Meeting the RRC requirements and beyond SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Pediat Transport Program, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 531 BP 91A EP 91A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300532 ER PT J AU Dolan, MA Lee, C Sedik, H Boudreaux, ED Singh, AK Camargo, CA AF Dolan, MA Lee, C Sedik, H Boudreaux, ED Singh, AK Camargo, CA TI Environmental tobacco smoke exposure among children presenting to the emergency department with acute asthma SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Karl K Long Mem Hosp, Baton Rouge, LA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 623 BP 106A EP 106A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300624 ER PT J AU Sedik, H Barr, RG Clark, S Camargo, CA AF Sedik, H Barr, RG Clark, S Camargo, CA TI Prospective study of sudden-onset asthma exacerbations in children SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Henry Ford Hosp, Div Pediat Emergency Med, Detroit, MI 48202 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Accid & Emergency, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 697 BP 118A EP 118A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300698 ER PT J AU Gensure, RC Jueppner, H AF Gensure, RC Jueppner, H TI PTHrP binds to different regions in human PTH/PTHrP receptor and PTH-2 receptor based on photoaffinity crosslinking SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 757 BP 129A EP 129A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300758 ER PT J AU Hirschhorn, JN Altshuler, D Lindgren, C Lane, CR Nemesh, J Bolk, S Sklar, P Groop, L Lander, ES AF Hirschhorn, JN Altshuler, D Lindgren, C Lane, CR Nemesh, J Bolk, S Sklar, P Groop, L Lander, ES TI Large-scale, family-based, candidate gene association study of type 2 diabetes mellitus and abdominal obesity SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. MIT, Whitehead Inst, Ctr Genome Res, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Lund, Malmo, Sweden. RI Altshuler, David/A-4476-2009 OI Altshuler, David/0000-0002-7250-4107 NR 0 TC 0 Z9 0 U1 1 U2 5 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 774 BP 131A EP 131A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300775 ER PT J AU Palmert, MR Mansfield, MJ Crigler, JF Crowley, WF Boepple, PA AF Palmert, MR Mansfield, MJ Crigler, JF Crowley, WF Boepple, PA TI Adrenarche dues not correlate with changes in growth and body composition: A longitudinal study during gonadal suppression SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 804 BP 136A EP 136A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300805 ER PT J AU Jean, W Perrin, JM AF Jean, W Perrin, JM TI Evaluation of children by insurance and chronic conditions SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Univ Missouri, Sch Med, Kansas City, MO 64108 USA. Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 879 BP 149A EP 149A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155300880 ER PT J AU Beal, AC Kuhlthau, KA Perrin, JM AF Beal, AC Kuhlthau, KA Perrin, JM TI Physician and WIC breastfeeding advice for African American and white women SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Child & Adolescent Hlth Policy Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1021 BP 174A EP 174A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301022 ER PT J AU Kaushal, R Bates, DW Landrigan, C Federico, F Clapp, MD McKenna, KJ Goldman, DA AF Kaushal, R Bates, DW Landrigan, C Federico, F Clapp, MD McKenna, KJ Goldman, DA TI Medication errors and adverse drug events in hospitalized children SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Quality Improvement & Risk Management, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1182 BP 201A EP 201A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301182 ER PT J AU Kuhlthau, KA Perrin, JM AF Kuhlthau, KA Perrin, JM TI Ancillary therapy use by children with and without chronic conditions SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Ctr Child & Adolescent Hlth Policy, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1202 BP 204A EP 204A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301202 ER PT J AU Smith, SR Kublthau, KA Perrin, JM AF Smith, SR Kublthau, KA Perrin, JM TI The hearing-impaired community's knowledge of HIV/AIDS SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Div Gen Pediat, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1338 BP 227A EP 227A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301337 ER PT J AU Albers, S Marsden, D Quackenbush, E Lee, JS Stark, AR Irons, M AF Albers, S Marsden, D Quackenbush, E Lee, JS Stark, AR Irons, M TI Early detection of neonatal CPT II deficiency by tandem mass spectrometry SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Hosp, Div Genet & Metab, Boston, MA 02115 USA. State Lab Inst, New England Newborn Screening Program, Jamaica, NY USA. Childrens Hosp, Div Newborn Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1399 BP 237A EP 237A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301398 ER PT J AU Ficicioglu, CH Mandell, R Shih, VE AF Ficicioglu, CH Mandell, R Shih, VE TI Argininosuccinate lyase deficiency: Longterm outcome of 12 patients detected by newborn screening SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1413 BP 240A EP 240A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301412 ER PT J AU Stoler, JM Ryan, L Holmes, LB AF Stoler, JM Ryan, L Holmes, LB TI Alcohol dehydrogenase genotypes and relation to infant outcome SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Dana Farber Canc Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1445 BP 245A EP 245A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301444 ER PT J AU Fitzgerald, C Wang, S Johnston, KA Schmidt, EV AF Fitzgerald, C Wang, S Johnston, KA Schmidt, EV TI Genetic interactions between c-myc and translation initiation factor eIF4E: Activated 4EBP1 blocks transformation SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 MassGen Hosp Children, Serv Pediat, Boston, MA USA. Harvard Univ, Sch Med, MGH Canc Ctr, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1465 BP 248A EP 248A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301463 ER PT J AU Galardy, PJ McMahon, LE Grabowski, EF AF Galardy, PJ McMahon, LE Grabowski, EF TI Adherent sickle erythrocytes induce increased endothelial cell tissue factor activity SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1466 BP 249A EP 249A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301464 ER PT J AU Grabowski, EF Shih, S Ingelfinger, JR Petteruti, PG AF Grabowski, EF Shih, S Ingelfinger, JR Petteruti, PG TI Shigatoxin augments the expression of functional tissue factor by activated human glomerular endothelial cells SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1467 BP 249A EP 249A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301465 ER PT J AU Tetteh, NA Yamashita, T Garcia-Higuera, I Futaki, M Yagasaki, H D'Andrea, AD AF Tetteh, NA Yamashita, T Garcia-Higuera, I Futaki, M Yagasaki, H D'Andrea, AD TI Phosphorylation and the Fanconi Anemia pathway SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 1495 BP 253A EP 253A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155301493 ER PT J AU Hagerty, JJ Krauss, B Insoft, RM AF Hagerty, JJ Krauss, B Insoft, RM TI Characterization of capnograms in healthy newborns SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Boston Childrens Hosp, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2126 BP 360A EP 360A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302125 ER PT J AU Argani, S Ingelfinger, JR Alexander, SI AF Argani, S Ingelfinger, JR Alexander, SI TI Kimura's syndrome. A Th2 disease? SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2620 BP 443A EP 443A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302619 ER PT J AU Umezu, M Chan, JSD Tang, SS Ingelfinger, JR AF Umezu, M Chan, JSD Tang, SS Ingelfinger, JR TI Angiotensinogen-transfected rat proximal tubule cells as a model for study of angiotensinogen expression SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Hop Maison Neuve Rosemont, Res Ctr, Montreal, PQ H1T 2M4, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2685 BP 454A EP 454A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302684 ER PT J AU Welch, TR Frenzke, M Witte, DP Davis, AE AF Welch, TR Frenzke, M Witte, DP Davis, AE TI Attentuated interstitial lesion in an immune complex glomerulonephritis in C5a receptor knock out mice SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Ctr Blood Res, Boston, MA 02115 USA. Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2687 BP 454A EP 454A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302686 ER PT J AU Grant, PE Zourabia, A Krishnamoorthy, K Insoft, RM Boas, DA AF Grant, PE Zourabia, A Krishnamoorthy, K Insoft, RM Boas, DA TI Spatially resolved near infrared spectroscopy of the human newborn brain SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Tufts Univ, Boston, MA 02111 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 SU S MA 2712 BP 459A EP 459A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 298TM UT WOS:000086155302711 ER PT J AU Duerinckx, AJ Takahashi, M AF Duerinckx, AJ Takahashi, M TI Coronary magnetic resonance angiography in patients with Kawasaki disease. SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 W Los Angeles Vet Affairs Med Ctr, Dept Radiol, Los Angeles, CA 90073 USA. Childrens Hosp, Cardiol Sect, Los Angeles, CA 90027 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2000 VL 47 IS 4 MA 38 BP 555 EP 555 PN 1 PG 1 WC Pediatrics SC Pediatrics GA 298QQ UT WOS:000086151000063 ER PT J AU Joffe, S Lieu, TA Escobar, GJ AF Joffe, S Lieu, TA Escobar, GJ TI The critical role of population-based epidemiology in cost-effectiveness research SO PEDIATRICS LA English DT Editorial Material ID INFANTS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Pilgrim Hlth Care, Div Ambulatory Care & Prevent, Boston, MA 02115 USA. Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94611 USA. RP Joffe, S (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. OI Joffe, Steven/0000-0002-0667-7384 NR 11 TC 2 Z9 2 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2000 VL 105 IS 4 BP 862 EP 863 DI 10.1542/peds.105.4.862 PG 3 WC Pediatrics SC Pediatrics GA 299GC UT WOS:000086189400039 PM 10742335 ER PT J AU Berkey, CS Rockett, HRH Field, AE Gillman, MW Frazier, AL Camargo, CA Colditz, GA AF Berkey, CS Rockett, HRH Field, AE Gillman, MW Frazier, AL Camargo, CA Colditz, GA TI Activity, dietary intake, and weight changes in a longitudinal study of preadolescent and adolescent boys and girls SO PEDIATRICS LA English DT Article DE physical activity; gym class; inactivity; television; videos; video/computer games; energy intake; dietary fat; dietary fiber; body mass index; adiposity; obesity; weight change; preadolescence; adolescence; longitudinal ID BODY-MASS INDEX; FOOD FREQUENCY QUESTIONNAIRE; PHYSICAL-ACTIVITY; PRESCHOOL-CHILDREN; ENERGY-EXPENDITURE; CHILDHOOD OBESITY; FAT DISTRIBUTION; YOUNG ADULTHOOD; HEIGHT INDEXES; UNITED-STATES AB Objective. To examine the role of physical activity, inactivity, and dietary patterns on annual weight changes among preadolescents and adolescents, taking growth and development into account. Study Design. We studied a cohort of 6149 girls and 4620 boys from all over the United States who were 9 to 14 years old in 1996. All returned questionnaires in the fall of 1996 and a year later in 1997. Each child provided his or her current height and weight and a detailed assessment of typical past-year dietary intakes, physical activities, and recreational inactivities (TV, videos/VCR, and video/computer games). Methods. Our hypotheses were that physical activity and dietary fiber intake are negatively correlated with annual changes in adiposity and that recreational inactivity (TV/videos/games), caloric intake, and dietary fat intake are positively correlated with annual changes in adiposity. Separately for boys and girls, we performed regression analysis of 1-year change in body mass index (BMI; kg/m(2)). All hypothesized factors were in the model simultaneously with several adjustment factors. Results. Larger increases in BMI from 1996 to 1997 were among girls who reported higher caloric intakes (.0061 +/- .0026 kg/m(2) per 100 kcal/day; beta +/- standard error), less physical activity (-.0284 +/-.0142 kg/m(2)/hour/day) and more time with TV/videos/games (.0372 +/-.0106 kg/ m(2)/hour/day) during the year between the 2 BMI assessments. Larger BMI increases were among boys who reported more time with TV/videos/games (.0384 +/-.0101) during the year. For both boys and girls, a larger rise in caloric intake from 1996 to 1997 predicted larger BMI increases (girls:.0059 +/-.0027 kg/m(2) per increase of 100 kcal/day; boys:.0082 +/-.0030). No significant associations were noted for energy-adjusted dietary fat or fiber. Conclusions. For both boys and girls, a 1-year increase in BMI was larger in those who reported more time with TV/videos/games during the year between the 2 BMI measurements, and in those who reported that their caloric intakes increased more from 1 year to the next. Larger year-to-year increases in BMI were also seen among girls who reported higher caloric intakes and less physical activity during the year between the 2 BMI measurements. Although the magnitudes of these estimated effects were small, their cumulative effects, year after year during adolescence, would produce substantial gains in body weight. Strategies to prevent excessive caloric intakes, to decrease time with TV/videos/games, and to increase physical activity would be promising as a means to prevent obesity. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Berkey, CS (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NIDDK NIH HHS [DK46834] NR 78 TC 200 Z9 208 U1 3 U2 32 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2000 VL 105 IS 4 AR e56 DI 10.1542/peds.105.4.e56 PG 6 WC Pediatrics SC Pediatrics GA 299GC UT WOS:000086189400014 PM 10742377 ER PT J AU Sabolic, I Herak-Kramberger, CM Blanusa, M Brown, D AF Sabolic, I Herak-Kramberger, CM Blanusa, M Brown, D TI Loss of brush-border proteins in cadmium-induced nephrotoxicity in rat SO PERIODICUM BIOLOGORUM LA English DT Article DE brush-border; cadmium; carbonic anhydrase; cell adhesion molecule; dipeptidyl peptidase; heavy metals; kidney; nephrotoxicity ID MEMBRANE-VESICLES; INTOXICATED RATS; PLASMA-MEMBRANE; TREATED RATS; ECTO-ATPASE; KIDNEY; LOCALIZATION; TRANSPORT; METALLOTHIONEIN; ENZYMES AB Background and purpose: Nephropathy due to chronic cadmium (Cd) exposure in man and experimental animals is manifested by defects of reabsorptive and secretory functions in the renal proximal tubule (PT). Previous studies have indicated that, in vivo, Cd causes loss of brush-border membrane (BBM) and impaired function (lower Vmax) of some BBM transporters, whereas in vitro, Cd directly inhibits the activity of several BBM transporters. Our recent studies in Cd-intoxicated ra ts showed that the lower Vmax of some BBM transporters may be related to the loss of specific proteins from the membrane. In this paper we provide evidence that the loss of BBM proteins in Cd-nephrotordcity affects not only specific transporters but also other types of membrane proteins, such as ectoenzymes and cell adhesion molecules. Materials and methods: To induce Cd-nephrotoxicity, rats were treated with CdCl2 (2 mg Cd/kg b.m., s.c.) daily for two weeks. Nephrotoxicity was confirmed by the symptoms of reabsorptive defects in the urine and by measuring Cd in the tissue. Specific polyclonal and monoclonal antibodies were used to study the abundance of membrane proteins by indirect immunofluorescence and immunoblotting in cryosections of kidney tissue and isolated renal cortical BBM, respectively. Results: Nephrotoxicity was manifested by phosphaturia, proteinuria, polyuria, and accumulation of Cd in the renal tissue. Immunocytochemical studies in tissue sections from Cd-treated ra Is sh owed a drama tic loss of some BBM ecto-proteins, such as carbonic anhydrase IV, dipepdidylpeptidase IV and cell adhesion molecule CAM-105. These data were supported by decreased density of the corresponding protein bands in immunoblots of isolated BBM. Conclusion: In addition to the loss of reabsorptive surface due to shortening and focal loss of microvilli, the loss of various BBM proteins may contribute to the impairment of PT functions in Cd-nephrotoxicity. C1 Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Zagreb 10001, Croatia. Inst Med Res & Occupat Hlth, Mineral Metab Unit, Zagreb 10001, Croatia. Massachusetts Gen Hosp, Renal Unit, Boston, MA 02129 USA. Massachusetts Gen Hosp, Program Membrane Biol, Boston, MA 02129 USA. RP Sabolic, I (reprint author), Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Ksaverska Cesta 2,POB 291, Zagreb 10001, Croatia. NR 31 TC 5 Z9 5 U1 0 U2 0 PU PERIODICUM BIOLOGORUM PI ZAGREB PA HRVATSKO PRIRODOSLOVNO DRUSTVO ILICA 16/111, 41000 ZAGREB, CROATIA SN 0031-5362 J9 PERIOD BIOL JI Period. Biol. PD APR PY 2000 VL 102 IS 1 BP 33 EP 41 PG 9 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 319KG UT WOS:000087339600007 ER PT J AU Mirela, B Mila, MP Brown, D Ivan, S AF Mirela, B Mila, MP Brown, D Ivan, S TI In colchicine-treated rats, cellular distribution of AQP-1 in convoluted and straight proximal tubule segments is differently affected (vol 439, pg 321, 2000) SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Correction C1 Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Zagreb 10001, Croatia. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA 02119 USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA 02119 USA. RP Ivan, S (reprint author), Inst Med Res & Occupat Hlth, Unit Mol Toxicol, Ksaverska Cesta 2, Zagreb 10001, Croatia. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD APR PY 2000 VL 439 IS 6 BP 853 EP 853 DI 10.1007/s004240000267 PG 1 WC Physiology SC Physiology GA 304AM UT WOS:000086460400023 ER PT J AU Soukos, NS Socransky, SS Mulholland, SE Lee, S Doukas, AG AF Soukos, NS Socransky, SS Mulholland, SE Lee, S Doukas, AG TI Photomechanical drug delivery into bacterial biofilms SO PHARMACEUTICAL RESEARCH LA English DT Article DE photomechanical wave; biofilm; A. viscosus; methylene blue; confocal scanning laser microscopy ID PSEUDOMONAS-AERUGINOSA BIOFILMS; STRESS WAVES; MICROBIAL BIOFILMS; METHYLENE-BLUE; IN-VITRO; ANTIBIOTICS; GRADIENT; CELLS AB Purpose. To investigate whether photomechanical waves generated by lasers can increase the permeability of a biofilm of the oral pathogen Actinomyces viscosus. Methods. Biofilms of Actinomyces viscosus were formed on bovine enamel surfaces. The photomechanical wave was generated by ablation of a target with a a-switched ruby laser and launched into the biofilm in the presence of 50 mu g/ml methylene blue. The penetration depth of methylene blue was measured by confocal scanning laser microscopy. Also, the exposed biofilms were irradiated with light at 666 nm. After illumination, adherent bacteria were scraped and spread over the surfaces of blood agar plates. Survival fractions were calculated by counting bacterial colonies. Results. Confocal scanning laser microscopy revealed that a single photomechanical wave was sufficient to induce a 75% increase in the penetration depth of methylene blue into the biofilm. This significantly increased the concentration of methylene blue in the biofilm enabling its photodestruction. Conclusions. Photomechanical waves provide a potentially powerful tool for drug delivery that might be utilized for treatment of microbial infections. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, Boston, MA 02114 USA. Forsyth Inst, Dept Periodontol, Boston, MA 02115 USA. RP Soukos, NS (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Dermatol,Wellman Labs Photomed, 50 Blossom St WEL 224, Boston, MA 02114 USA. NR 30 TC 41 Z9 42 U1 1 U2 1 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 APR PY 2000 VL 17 IS 4 BP 405 EP 409 DI 10.1023/A:1007568702118 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 322NT UT WOS:000087516200006 PM 10870983 ER PT J AU Ellis, SL Billups, SJ Malone, DC Carter, BL Covey, D Mason, B Jue, S Carmichael, J Guthrie, K Sintek, CD Dombrowski, R Geraets, DR Amato, M AF Ellis, SL Billups, SJ Malone, DC Carter, BL Covey, D Mason, B Jue, S Carmichael, J Guthrie, K Sintek, CD Dombrowski, R Geraets, DR Amato, M TI Types of interventions made by clinical pharmacists in the IMPROVE study SO PHARMACOTHERAPY LA English DT Article ID ELDERLY OUTPATIENTS; VETERANS-AFFAIRS; CONTROLLED TRIAL; CARE CLINICS; MANAGEMENT; SERVICES AB The purpose of this study was to describe and evaluate the activities and interventions provided by ambulatory care clinical pharmacists during the IMPROVE (Impact of Managed Pharmaceutical Care on Resource Utilization and Outcomes in Veterans Affairs Medical Centers) study. A total of 523 patients were randomized into the intervention arm at nine Veterans Affairs medical centers if they were considered to be at high risk for drug-related problems. Patients randomized to the control group had no interventions and they are not reported. Using a standard form, pharmacists were asked to document the length of visit, method of contact, medical conditions addressed, and drug-related problems addressed and resolved during each contact. Seventy-eight ambulatory care clinical pharmacists documented 1855 contacts over 12 months, an average of 3.54 +/- 2.31/patient. The length of visits was 15 minutes or more for 73% of contacts. In-person contacts accounted for 1421 visits (76.6%), with the remainder being telephone contacts. During each contact the average number of drug-related problems addressed and resolved were 1.64 +/- 1.16 and 1.14 +/- 0.98, respectively. More drug-related problems were addressed and resolved when visits were 15 minutes or longer (p=0.001) and when the contact was in person (p=0.001). These data may provide information to clinical pharmacists developing pharmacy-managed clinics for patients at high risk for drug-related problems. The information may be a benchmark for types of interventions that can be made, as well as the time commitments required to make them. C1 Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharm Practice, Denver, CO 80262 USA. Kaiser Permanente, Denver, CO USA. Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. James A Haley Vet Hosp, Tampa Bay, FL USA. Boise VAMC, Boise, ID USA. Reno Vet Affairs Med Ctr, Reno, NV USA. John L McClellan Mem Vet Hosp, Little Rock, AR USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Baltimore VAMC, Baltimore, MD USA. Iowa City Vet Affairs Med Ctr, Iowa City, IA USA. STVHCS, Audie Murphy Div, San Antonio, TX USA. RP Carter, BL (reprint author), Univ Colorado, Hlth Sci Ctr, Sch Pharm, Dept Pharm Practice, 4200 E 9th Ave,C238, Denver, CO 80262 USA. NR 25 TC 38 Z9 39 U1 0 U2 6 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER BOX 806 171 HARRISON AVE, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD APR PY 2000 VL 20 IS 4 BP 429 EP 435 DI 10.1592/phco.20.5.429.35055 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 300XE UT WOS:000086278400010 PM 10772374 ER PT J AU Kanofsky, JR Sima, PD AF Kanofsky, JR Sima, PD TI Structural and environmental requirements for quenching of singlet oxygen by cyanine dyes SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article; Proceedings Paper CT 26th Meeting of the American-Society-for-Photobiology CY JUL 11-15, 1998 CL SNOWBIRD, UTAH SP Amer Soc Photobiol ID MOLECULAR-OXYGEN; SOLVENT; PHOTOSENSITIZATION; PHENOLS; AMINES; PI AB Singlet-oxygen quenching constants were measured for 19 cyanine dyes in acetonitrile, The most efficient quenchers were 1-butyl-2-[2-[3-[(1-butyl-6-chlorobenz[cd]indol-2(1H)-ylidene)ethylidene]-2-chloro-1-cyclohexen-1-yl]ethenyl]-6-chlorobenz[cd]indolium and 6-chloro-2-[2-[3-(6-chloro-1-ethylbenz[cd]indol-2(1H)-ylidene)ethylidene]-2-phenyl-1-cyclopenten-1-yl]ethenyl]-1-ethyl-benz[cd]indolium, having quenching constants with diffusion-controlled values of 2.0 +/- 0.1 x 10(10) and 1.5 +/- 0.1 x 10(10) M-1 s(-1), respectively. There was a trend toward increased quenching constants for cyanine dyes with the absorption band maxima at longer wavelengths. However, the quenching constants correlated better with the oxidation potentials of the cyanine dyes, suggesting that quenching proceeds by charge transfer rather than energy transfer. The quenching constants for 1,1',3,3,3',3'-hexamethylindotricarbocyanine perchlorate and 1,1'-diethyl-4,4'-carbocyanine iodide were measured in several solvents as well as in aqueous solutions of detergent micelles. In different solvents, the quenching constants varied by as much as a factor of 50, The quenching constants were largest in solvents with the highest values on the pi* scale of Kamlet, Abboud, Abraham and Taft, This was consistent with quenching occurring by charge transfer. Within cells, cyanine dyes concentrate in membrane-bound organelles. The quenching constants were substantial within detergent micelles, To the extent that micelles are models for biological membranes, cyanine dyes may be effective biological singlet-oxygen quenchers. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Med Serv, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Med, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA. RP Kanofsky, JR (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Med Serv, POB 278, Hines, IL 60141 USA. NR 25 TC 27 Z9 29 U1 3 U2 9 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 2000 VL 71 IS 4 BP 361 EP 368 DI 10.1562/0031-8655(2000)071<0361:SAERFQ>2.0.CO;2 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 305LA UT WOS:000086540500002 ER PT J AU Sima, PD Kanofsky, JR AF Sima, PD Kanofsky, JR TI Cyanine dyes as protectors of K562 cells from photosensitized cell damage SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article; Proceedings Paper CT 26th Meeting of the American-Society-for-Photobiology CY JUL 11-15, 1998 CL SNOWBIRD, UTAH SP Amer Soc Photobiol ID SINGLET OXYGEN; LEUKEMIA-CELLS; INACTIVATION; MECHANISM; INVITRO AB Several cyanine dyes were found to protect K562 leukemia cells against toxicity mediated by cis -di(4-sulfonatophenyl)diphenylporphine (TPPS2) and light. Most cyanine dyes derived from dimethylindole were better photoprotectors than cyanine dyes with other structures. This correlated with the fact that cyanine dyes derived from dimethylindole were predominately monomeric at millimolar concentrations within K562 cells, while other cyanine dyes formed aggregates. For cyanine dyes that are derived from dimethylindole and have absorption band wavelengths greater than 700 nm, fluorescence-energy transfer from TPPS2 to the cyanine dye was the most important mechanism for photoprotection, There was no spectroscopic evidence for complex formation between the cyanine dyes and TPPS2, The dimethylindole derivative, 1,1',3,3,3',3'-hexamethylindodicarbocyanine, was an excellent photoprotector, but a poor quencher of TPPS2 fluorescence and a relatively poor singlet-oxygen quencher. This cyanine dye may act by quenching excited triplet TPPS2. Singlet-oxygen quenching may contribute to the photoprotection provided by cyanine dyes not derived from dimethylindole. Differences in the subcellular distribution of the various cyanine dyes studied may have contributed to the different apparent mechanisms of photoprotection. C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, Hines, IL 60141 USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Med Serv, Hines, IL 60141 USA. Loyola Univ, Stritch Sch Med, Dept Med, Maywood, IL 60153 USA. Loyola Univ, Stritch Sch Med, Dept Mol & Cellular Biochem, Maywood, IL 60153 USA. RP Kanofsky, JR (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Res Serv, POB 278, Hines, IL 60141 USA. NR 21 TC 21 Z9 22 U1 0 U2 5 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD APR PY 2000 VL 71 IS 4 BP 413 EP 421 DI 10.1562/0031-8655(2000)071<0413:CDAPOK>2.0.CO;2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 305LA UT WOS:000086540500008 PM 10824591 ER PT J AU Silverman, RP Bonasser, L Passaretti, D Randolph, MA Yaremchuk, MJ AF Silverman, RP Bonasser, L Passaretti, D Randolph, MA Yaremchuk, MJ TI Adhesion of tissue-engineered cartilage to native cartilage SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID PERIOSTEAL GRAFTS; ARTICULAR-CARTILAGE; DEFECTS; RECONSTRUCTION; REPAIR; KNEE AB Reconstruction of cartilaginous defects to correct both craniofacial deformities and joint surface irregularities remains a challenging and controversial clinical problem. It has been shown that tissue-engineered cartilage can be produced in a nude mouse model. Before tissue-engineered cartilage is used clinically to fill in joint defects or to reconstruct auricular or nasal cartilaginous defects, it is important to determine whether it will integrate with or adhere to the adjacent native cartilage at the recipient site. The purpose of this study was to determine whether tissue-engineered cartilage would adhere to adjacent cartilage in vivo. Tissue-engineered cartilage was produced using a fibrin glue polymer (80 mg/cc purified porcine fibrinogen polymerized with 50 U/cc bovine thrombin) mixed with fresh swine articular chondrocytes. The polymer/chondrocyte mixture was sandwiched between two 6-mm-diameter discs of fresh articular cartilage. These constructs were surgically inserted into a subcutaneous pocket on the backs of nude mice (n = 15). The constructs were harvested 6 weeks later and assessed histologically, biomechanically, and by electron microscopy. Control samples consisted of cartilage discs held together by fibrin glue alone (no chondrocytes) (n = 10). Histologic evaluation of the experimental constructs revealed a layer of neocartilage between the two native cartilage discs. The neocartilage appeared to fill all irregularities along the surface of the cartilage discs. Safranin-O and toluidine blue staining indicated the presence of glycosaminoglycans and collagen, respectively. Control samples showed no evidence of neocartilage formation. Electron microscopy of the neocartilage revealed the formation of collagen fibers similar in appearance to the normal cartilage matrix in the adjacent native cartilage discs. The interface between the neocartilage and the native cartilage demonstrated neocartilage matrix directly adjacent to the normal cartilage matrix without any gaps or intervening capsule. The mechanical properties of the experimental constructs, as calculated from stress-strain curves, differed significantly from those of the control samples. The mean modulus for the experimental group was 0.74 +/- 0.22 MPa, which was 3.5 times greater than that of the control group (p < 0.0002). The mean tensile strength of the experimental group was 0.064 +/- 0.024 MPa, which was 62.6 times greater than that of the control group (p < 0.0002). The mean failure strain of the experimental group was 0.16 +/- 0.061 percent, which was 4.3 times greater than that of the control group (p < 0.0002). Finally, the mean fracture energy of the experimental group was 0.00049 +/- 0.00032 J, which was 15.6 times greater than that of the control group. Failure occurred in all cases at the interface between neocartilage and native cartilage. This study demonstrated that tissue-engineered cartilage produced using a fibrin-based polymer does adhere to adjacent native cartilage and can be used to join two separate pieces of cartilage in the nude mouse model. Cartilage pieces joined in this way can withstand forces significantly greater than those tolerated by cartilage samples joined only by fibrin glue. C1 Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Div Plast Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Massachusetts, Med Ctr, Dept Anesthesiol, Worcester, MA USA. RP Yaremchuk, MJ (reprint author), Massachusetts Gen Hosp, Wang Ambulatory Care Ctr, Div Plast Surg, Suite 453,25 Fruit St, Boston, MA 02114 USA. RI Bonassar, Lawrence/C-2103-2016 OI Bonassar, Lawrence/0000-0003-1094-6433 FU NIADDK NIH HHS [R03 AM45059] NR 15 TC 52 Z9 55 U1 1 U2 4 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 APR PY 2000 VL 105 IS 4 BP 1393 EP 1398 DI 10.1097/00006534-200004040-00019 PG 6 WC Surgery SC Surgery GA 295YD UT WOS:000085995500019 PM 10744230 ER PT J AU Netscher, DT Meade, RA Goodman, CM Alford, EL Stewart, MG AF Netscher, DT Meade, RA Goodman, CM Alford, EL Stewart, MG TI Quality of life and disease-specific functional status following microvascular reconstruction for advanced (T3 and T4) oropharyngeal cancers SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID SQUAMOUS-CELL CARCINOMA; OF-LIFE; NECK-CANCER; OROMANDIBULAR RECONSTRUCTION; PERFORMANCE STATUS; RADIATION-THERAPY; LARYNGEAL-CANCER; ORAL-CANCER; HEAD; RADIOTHERAPY AB In an effort to evaluate quality-of-life benefits of ablative head and neck cancer surgery and microvascular reconstruction, a longitudinal study was under-taken in which patients with T3 or T4 oropharyngeal cancers without systemic metastases at presentation were administered both general and disease-specific quality-of-life instruments preoperatively and postoperatively. In an initial prospective pilot study, 17 cancer patients were evaluated both preoperatively and postoperatively using the Medical Outcomes Short-Form Wealth Survey questionnaire (SF-36) and the Performance Status Scale Tor Head and Neck Cancer Patients. In the second part of the study, the need was recognized for a different disease-specific measure, for more frequent intervals of longitudinal follow-up (rather than be limited by a single data collection point), and for a noncancer control group. Since then, 17 more cancer patients were evaluated in the second part of the study and were compared with patients who had similar reconstructions after suffering head and neck trauma and also with age-matched controls. Instead of the performance status scale, the University of Washington Head and Neck Quality of Life questionnaire was substituted. Interval assessments were done at 1, 3, 6, and 12 months and preoperatively. Whereas many of the general and disease-specific quality of life subclasses initially worsened following extensive surgery and radiation therapy, most returned to the preoperative baseline by 6 months following conclusion of treatment and surpassed pretreatment values at 1 year. It can be concluded, based on this study, that large resections and reconstructions for head and neck cancer patients are justified in terms of outcome; the resection controls the local disease, and the microvascular reconstruction restores quality of life and functional status. C1 Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. Baylor Coll Med, Dept Otolaryngol & Commun Sci, Houston, TX 77030 USA. Dept Vet Affairs Med Ctr, Houston, TX USA. RP Netscher, DT (reprint author), Suite 800,6560 Fannin, Houston, TX 77030 USA. NR 30 TC 34 Z9 35 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 APR PY 2000 VL 105 IS 5 BP 1628 EP 1634 DI 10.1097/00006534-200004050-00005 PG 7 WC Surgery SC Surgery GA 299QF UT WOS:000086208800005 PM 10809090 ER PT J AU Tanabe, YN Randolph, MA Shimizu, A Lee, WPA AF Tanabe, YN Randolph, MA Shimizu, A Lee, WPA TI Prolonged survival of musculoskeletal xenografts with combined cyclosporine and 15-deoxyspergualin SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID LONG-TERM SURVIVAL; HAMSTER HEART XENOGRAFTS; CARDIAC XENOGRAFTS; GRAFT-REJECTION; RAT-HEART; RETRANSPLANTATION; TRANSPLANTATION; ALLOGRAFTS; XENOTRANSPLANTATION; DEOXYSPERGUALIN AB This study was undertaken to evaluate the feasibility of performing vascularized musculoskeletal xenografts between mice and rats using immunosuppression. Vascularized musculoskeletal grafts were harvested from the hind limb of C57BL/6J (B6) mice, transplanted heterotopically into Lewis rats, and revascularized by microanastomoses of the graft artery and the recipient femoral artery and the graft vein to the recipient femoral vein. Recipient rats were divided into four groups. Group 1 received no immunosuppression (n = 10), group 2 was treated with cyclosporine (10 mg/kg/day; n = 10), group 3 was treated with 15-deoxyspergualin (5 mg/kg/day; n = 10), and group 4 received both cyclosporine and 15-deoxyspergualin (n = 10). Graft survival was directly examined on postoperative days 4, 7, and 14. In vitro assays were performed using mixed lymphocyte reactions and anti-donor cytotoxic antibody assays to assess the recipient's immune response. Grafts were examined by histology and immunohistochemistry. All grafts in group 1 were rejected by day 4. In groups 2 and 3, all grafts were rejected by day 7. In group 4, however, 8 of 10 recipients had viable grafts on day 14. Data from mixed lymphocyte reactions showed that cell-mediated immune responses were uniformly suppressed in groups 2, 3, and 4 compared with group 1. However, anti-donor antibody production was only partly suppressed in groups 2 and 3, suggesting that graft rejection was primarily caused by circulating cytotoxic anti-donor antibodies in groups 1, 2, and 3. Histologic observations in groups 1, 2, and 3 confirmed the important role of the humoral mechanism in xenograft rejection. Furthermore, immunohistochemical results demonstrated that the small vessels in the rejected grafts showed anti-rat immunoglobulin and complement depositions. Only a combination therapy of cyclosporine and 15-deoxyspergualin attenuated the rejection of xenografts. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, Boston, MA 02114 USA. RP Randolph, MA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg, WACC 453, Boston, MA 02114 USA. NR 21 TC 1 Z9 1 U1 0 U2 0 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 APR PY 2000 VL 105 IS 5 BP 1695 EP 1703 DI 10.1097/00006534-200004050-00015 PG 9 WC Surgery SC Surgery GA 299QF UT WOS:000086208800015 PM 10809100 ER PT J AU Sowers, JR Williams, M Epstein, M Bakris, G AF Sowers, JR Williams, M Epstein, M Bakris, G TI Hypertension in patients with diabetes - Strategies for drug therapy to reduce complications SO POSTGRADUATE MEDICINE LA English DT Article ID CALCIUM-CHANNEL; RENAL-FUNCTION; NEPHROPATHY; PROGRESSION; COMBINATION; BLOCKER AB Hypertension in diabetic patients must be treated aggressively if patients are to benefit from reduced risk of morbidity and mortality, Diabetes itself:must be diagnosed promptly, particularly in at-risk patients, so appropriate lifestyle modifications can be made at the earliest opportunity, Although this may reduce or delay onset of hypertension, antihypertensive drug treatment should be initiated in the diabetic patient with even high-normal blood pressure; Traditional approaches to management of hypertension are in appropriate for most patients with. diabetes, While ACE inhibitors, calcium antagonists, angiotensin II receptor blockers, beta blockers, and low-dose diuretics, alone or in combination, all currently have roles in hypertension management, the outcomes of studies now under way may clarify some st-ill unanswered questions about the dangerous combination of:high blood pressure and diabetes. C1 Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, Chicago, IL 60612 USA. SUNY Hlth Sci Ctr, Coll Med, Brooklyn, NY 11203 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Beth Israel Deaconess Med Ctr, Dialysis Unit, Boston, MA USA. Univ Miami, Sch Med, Div Nephrol, Coral Gables, FL 33124 USA. RP Bakris, G (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Prevent Med, 1700 W Van Burren St,Suite 470, Chicago, IL 60612 USA. NR 19 TC 12 Z9 13 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD APR PY 2000 VL 107 IS 4 BP 47 EP + PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 302ZR UT WOS:000086396800011 PM 10778410 ER PT J AU Ecker, JL Shipp, TD Bromley, B Benacerraf, B AF Ecker, JL Shipp, TD Bromley, B Benacerraf, B TI The sonographic diagnosis of Dandy-Walker and Dandy-Walker variant: associated findings and outcomes SO PRENATAL DIAGNOSIS LA English DT Article DE Dandy-Walker; Dandy-Walker variant; obstetric ultrasound ID CLINICAL-SIGNIFICANCE; MALFORMATION; ABNORMALITIES; FEATURES AB Outcomes of pregnancies with sonographically diagnosed Dandy-Walker (DW) or Dandy-Walker variant (DWV) syndromes vary widely. We examined our own experience with these diagnoses in an effort to identify those sonographic features that best predicted neonatal outcome. We identified 50 fetuses with DW and 49 with DWV diagnosed sonographically. Eighty-six per cent of fetuses with DW and 85% of fetuses with DWV had other sonographically identifiable anomalies, the most common being ventriculomegaly (DW: 32%; DWV: 27%) and cardiac defects (DW:38%; DWV: 41%). Forty-six per cent and 36% of available karyotypes in cases of DW and DWV, respectively, were abnormal. 50 out of 99 women in our series elected pregnancy termination. Only three pregnancies with DW resulted in a living infant, and only one of these had a normal paediatric examination at six-week follow-up. Thirteen out of 49 infants with DWV survived the neonatal period and 7 of 13 were reported initially as normal infants, including six with an isolated finding of DWV. We conclude that overall, the prognosis for these posterior fossa defects is grim but not uniformly fatal. The presence of other anomalies is associated with the worst prognosis. Isolated Dandy-Walker variant has the highest chance of leading to a normal neonate. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Obstet Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Vincent Obstet Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Ecker, JL (reprint author), Massachusetts Gen Hosp, Dept Obstet & Gynecol, Vincent Obstet Serv, Founders 431,33 Fruit St, Boston, MA 02114 USA. NR 13 TC 64 Z9 78 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD APR PY 2000 VL 20 IS 4 BP 328 EP 332 DI 10.1002/(SICI)1097-0223(200004)20:4<328::AID-PD806>3.3.CO;2-F PG 5 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 308HE UT WOS:000086703800009 PM 10740206 ER PT J AU Bromley, B Krishnamoorthy, KS Benacerraf, BR AF Bromley, B Krishnamoorthy, KS Benacerraf, BR TI Aicardi syndrome: prenatal sonographic findings. A report of two cases SO PRENATAL DIAGNOSIS LA English DT Article DE prenatal sonography; brain cyst; agenesis of the corpus callosum; aicardi syndrome ID CORPUS-CALLOSUM; FETAL AGENESIS AB The prenatal sonographic findings in two children with Aicardi syndrome are reported. Copyright (C) 2000 John Wiley & Sons, Ltd. C1 Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. RP Bromley, B (reprint author), Diag Ultrasound Associates, 333 Longwood Ave,Suite 400, Boston, MA 02115 USA. NR 10 TC 1 Z9 2 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0197-3851 J9 PRENATAL DIAG JI Prenat. Diagn. PD APR PY 2000 VL 20 IS 4 BP 344 EP 346 DI 10.1002/(SICI)1097-0223(200004)20:4<344::AID-PD807>3.3.CO;2-A PG 3 WC Genetics & Heredity; Obstetrics & Gynecology SC Genetics & Heredity; Obstetrics & Gynecology GA 308HE UT WOS:000086703800013 PM 10740210 ER PT J AU Braaten, EB Viney, W AF Braaten, EB Viney, W TI Some late nineteenth century perspectives on sex and emotional expression SO PSYCHOLOGICAL REPORTS LA English DT Article ID FEMINIST PSYCHOLOGY; POLITICS; WOMEN; ESSENTIALISM; GENDER AB A review of nineteenth century popular literature indicates a deep and sustained public interest in sex differences in emotional expression. The conclusions advanced by popular writers included a catalog of perceived sex differences, reinforced by an essentialist philosophy that provided justification for the separation of sexual spheres and restrictions on political, educational, and vocational opportunities for women. Current scientific research on sex differences appears in popular media and is often presented in the context of an essentialist philosophy comparable with that which was dominant in the nineteenth century. Unfortunately, the subtleties and complexities of sex differences are not always communicated to the public and there is thus a potential for misinterpretation or even misuse. C1 Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. RP Viney, W (reprint author), Colorado State Univ, Dept Psychol, Ft Collins, CO 80523 USA. NR 59 TC 1 Z9 1 U1 0 U2 0 PU PSYCHOLOGICAL REPORTS PI MISSOULA PA P O BOX 9229, MISSOULA, MT 59807 USA SN 0033-2941 J9 PSYCHOL REP JI Psychol. Rep. PD APR PY 2000 VL 86 IS 2 BP 575 EP 585 DI 10.2466/PR0.86.2.575-585 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 316AX UT WOS:000087146100037 PM 10840915 ER PT J AU Reiner, BI Siegel, EL Flagle, C Hooper, FJ Cox, RE Scanlon, M AF Reiner, BI Siegel, EL Flagle, C Hooper, FJ Cox, RE Scanlon, M TI Effect of filmless imaging on the utilization of radiologic services SO RADIOLOGY LA English DT Article DE economics, medical; picture archiving and communication system (PACS); radiology and radiologists, socioeconomic issues ID COST; SYSTEMS; TRENDS AB PURPOSE: To determine the effect of a large-scale picture archiving and communication system (PACS) on in- and outpatient utilization of radiologic services. MATERIALS AND METHODS: Data were collected at the Baltimore Veterans Affairs (VA) Medical Center (BVAMC) before and after implementation of an enterprise-wide PACS; the numbers and types of imaging examinations performed for fiscal years 1993 and 1996 were evaluated. These data were compared with those from a similar academic medical center, the Philadelphia VA Medical Center (PVAMC), and with aggregate data obtained nationally for all VA hospitals over comparable periods. RESULTS: Inpatient utilization, defined as the number of examinations per inpatient day, increased by 82% (from 0.265 to 0.483 examinations per patient day) after a transition to filmless operation at BVAMC. This is substantially greater than the increases of 38% (from 0.263 to 0.362 examinations per patient day) and 11%(from 0.190 to 0.211 examinations per patient day) at the film-based PVAMC and nationally, respectively. Outpatient utilization, defined as the number of examinations per visit, increased by 21% (from 0.108 to 0.131 examinations per visit) at BVAMC, compared with a 1% increase (from 0.087 to 0.088 examinations per visit) at PVAMC and a net decrease of 19% (from 0.148 to 0.120 examinations per visit) nationally. CONCLUSION: The transition to filmless operation was associated with increases in inpatient and outpatient utilization of radiologic services, which substantially exceeded changes at PVAMC and nationally over the same interval. C1 Vet Affairs Maryland Hlth Care Syst, Dept Radiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Radiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Amer Radiol Serv, Baltimore, MD USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Philadelphia Vet Affairs Med Ctr, Dept Radiol, Philadelphia, PA USA. RP Siegel, EL (reprint author), Vet Affairs Maryland Hlth Care Syst, Dept Radiol, 10 N Greene St, Baltimore, MD 21201 USA. NR 13 TC 59 Z9 62 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMER PI EASTON PA 20TH AND NORTHAMPTON STS, EASTON, PA 18042 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2000 VL 215 IS 1 BP 163 EP 167 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 298UC UT WOS:000086156700024 PM 10751482 ER PT J AU Sato, N Sze, G Awad, IA Putman, CM Shibazaki, T Endo, K AF Sato, N Sze, G Awad, IA Putman, CM Shibazaki, T Endo, K TI Parenchymal perianeurysmal cystic changes in the brain: Report of five cases SO RADIOLOGY LA English DT Article DE aneurysm, cerebral; aneurysm, CT; aneurysm, MR; cyst, perianeurysmal ID VASCULAR-PERMEABILITY FACTOR; ENDOTHELIAL GROWTH-FACTOR; ARACHNOID CYST; TUMOR-TISSUE; ANGIOGENESIS; EXPRESSION; ANEURYSM; PROTEINS; EDEMA AB PURPOSE: To describe parenchymal perianeurysmal cystic changes in the brain. MATERIALS AND METHODS: Among 247 patients with cerebral aneurysms described in the medical or radiologic records in three institutions, five had perianeurysmal cystic changes. These were evaluated with computed tomography or magnetic resonance (MR) imaging and were categorized according to size, appearance, and the presence of hemosiderin deposit. Confirmation at stereotactic needle biopsy was available in one case. RESULTS: Perianeurysmal cysts comprised multiple clustered cysts in three cases and a unilocular cyst in two, and diameters were 1.5-3.5 cm. Hemosiderin was depicted at MR imaging in one unilocular cyst. Associated aneurysms had diameters of 0.7-4.0 cm, and prominent aneurysmal thrombosis and calcifications were seen in two cases. Findings at stereotactic needle biopsy were of mild reactive gliosis, At long-term follow-up in two patients, the cystic regions were stable. CONCLUSION: Parenchymal perianeurysmal cysts are rare and may display various morphologic characteristics from unilocular to multilocular. Since there may or may not be evidence of previous hemorrhage, other mechanisms such as abnormal angiogenesis factors may play a role. C1 Yale Univ, Sch Med, Dept Diagnost Radiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA. Gunma Univ, Sch Med, Dept Diagnost Radiol, Maebashi, Gumma 371, Japan. Gunma Univ, Sch Med, Dept Neurosurg, Maebashi, Gumma 371, Japan. Gunma Univ, Sch Med, Dept Nucl Med, Maebashi, Gumma 371, Japan. Massachusetts Gen Hosp, Dept Intervent Neuroradiol, Boston, MA 02114 USA. RP Sze, G (reprint author), Yale Univ, Sch Med, Dept Diagnost Radiol, 333 Cedar St,POB 208042, New Haven, CT 06520 USA. NR 19 TC 7 Z9 8 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 APR PY 2000 VL 215 IS 1 BP 229 EP 233 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 298UC UT WOS:000086156700033 PM 10751491 ER PT J AU Demetri, GD AF Demetri, GD TI Pharmacologic treatment options in patients with thrombocytopenia SO SEMINARS IN HEMATOLOGY LA English DT Article ID COLONY-STIMULATING FACTOR; RECOMBINANT HUMAN INTERLEUKIN-11; PHASE-I TRIAL; BONE-MARROW TRANSPLANTATION; C-MPL LIGAND; CHEMOTHERAPY-INDUCED ANEMIA; HUMAN MEGAKARYOCYTE GROWTH; FUSION PROTEIN PIXY321; HIGH-DOSE CARBOPLATIN; OVARIAN-CANCER C1 Dana Farber Canc Inst, Sarcoma Ctr, Ctr Sarcoma & Bone Oncol, Boston, MA 02115 USA. RP Demetri, GD (reprint author), Dana Farber Canc Inst, Sarcoma Ctr, Ctr Sarcoma & Bone Oncol, 44 Binney St, Boston, MA 02115 USA. NR 79 TC 8 Z9 10 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2000 VL 37 IS 2 SU 4 BP 11 EP 18 PG 8 WC Hematology SC Hematology GA 314QK UT WOS:000087066900003 PM 10831284 ER PT J AU Kuter, DJ AF Kuter, DJ TI Future directions with platelet growth factors SO SEMINARS IN HEMATOLOGY LA English DT Article ID HUMAN MEGAKARYOCYTE GROWTH; RECOMBINANT HUMAN THROMBOPOIETIN; HUMAN-IMMUNODEFICIENCY-VIRUS; HEMATOPOIETIC STEM-CELLS; FACTOR PEG-RHUMGDF; BODY IRRADIATION; ADVANCED CANCER; C-MPL; THROMBOCYTOPENIA; LIVER C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hematol Oncol Unit, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hematol Oncol Unit, 100 Blossom St, Boston, MA 02114 USA. FU NHLBI NIH HHS [HL54838, HL61222] NR 47 TC 19 Z9 26 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2000 VL 37 IS 2 SU 4 BP 41 EP 49 DI 10.1053/shem.2000.7390 PG 9 WC Hematology SC Hematology GA 314QK UT WOS:000087066900007 PM 10831288 ER PT J AU Iliopoulos, O Eng, C AF Iliopoulos, O Eng, C TI Genetic and clinical aspects of familial renal neoplasms SO SEMINARS IN ONCOLOGY LA English DT Review ID TUMOR-SUPPRESSOR GENE; HIPPEL-LINDAU-DISEASE; ENDOTHELIAL GROWTH-FACTOR; TUBEROUS-SCLEROSIS-2 TSC2 GENE; HUMAN MET PROTOONCOGENE; CENTRAL-NERVOUS-SYSTEM; RNA-POLYMERASE-II; CELL CARCINOMA; TUBEROUS SCLEROSIS; VHL GENE C1 Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Ohio State Univ, Human Canc Genet Program, Columbus, OH 43210 USA. RP Iliopoulos, O (reprint author), Dana Farber Canc Inst, Dept Adult Oncol, 44 Binney St, Boston, MA 02115 USA. OI Eng, Charis/0000-0002-3693-5145 NR 126 TC 38 Z9 38 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 0093-7754 EI 1532-8708 J9 SEMIN ONCOL JI Semin. Oncol. PD APR PY 2000 VL 27 IS 2 BP 138 EP 149 PG 12 WC Oncology SC Oncology GA 301ZP UT WOS:000086340700004 PM 10768593 ER PT J AU Krieger, JN AF Krieger, JN TI Consider diagnosis and treatment of trichomoniasis in men SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID SEXUALLY-TRANSMITTED DISEASES; VAGINALIS; PROSTATITIS; POPULATION; URETHRITIS C1 Univ Washington, Sch Med, Dept Urol, Seattle, WA 98195 USA. RP Krieger, JN (reprint author), VA Puget Sound Hlth Care Syst, Dept Urol, 112UR,1660 S Columbian Way, Seattle, WA 98109 USA. NR 16 TC 13 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD APR PY 2000 VL 27 IS 4 BP 241 EP 242 DI 10.1097/00007435-200004000-00011 PG 2 WC Infectious Diseases SC Infectious Diseases GA 303CY UT WOS:000086404300011 PM 10782748 ER PT J AU Bellamy, SL Gibberd, R Hancock, L Howley, P Kennedy, B Klar, N Lipsitz, S Ryan, L AF Bellamy, SL Gibberd, R Hancock, L Howley, P Kennedy, B Klar, N Lipsitz, S Ryan, L TI Analysis of dichotomous outcome data for community intervention studies SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID LINEAR MIXED MODELS; SMOKING CESSATION COMMIT; STATISTICAL DESIGN; TRIAL AB Community intervention trials are becoming increasingly popular as a tool for evaluating the effectiveness of health education and intervention strategies. Typically, units such as households, schools, towns, counties, are randomized to receive either intervention or control, then outcomes are measured on individuals within each of the units of randomization. It is well recognized that the design and analysis of such studies must account for the clustering of subjects within the units of randomization. Furthermore, there are usually both subject level and cluster level covariates that must be considered in the modelling process. While suitable methods are available for continuous outcomes, data analysis is more complicated when dichotomous outcomes are measured on each subject. This paper will compare and contrast several of the available methods that can be applied in such settings, including random effects models, generalized estimating equations and methods based on the calculation of `design effects', as implemented in the computer package SUDAAN. For completeness, the paper will also compare these methods of analysis with more simplistic approaches based on the summary statistics. All the methods will be applied to a case study based on an adolescent anti-smoking intervention in Australia. The paper concludes with some general discussion and recommendations for routine design and analysis. C1 Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Newcastle, Hlth Serv Res Grp, Newcastle, NSW 2308, Australia. Hunter Ctr Hlth Advancement, Newcastle, NSW, Australia. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. Med Univ S Carolina, Dept Biometry & Epidemiol, Charleston, SC 29425 USA. RP Bellamy, SL (reprint author), Dana Farber Canc Inst, Dept Biostat, 44 Binney St, Boston, MA 02115 USA. RI Ryan, Louise/A-4562-2009; parkinson, lynne/C-1949-2008; OI Ryan, Louise/0000-0001-5957-2490; Parkinson, Lynne/0000-0001-9433-9555 NR 16 TC 36 Z9 37 U1 0 U2 3 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD APR PY 2000 VL 9 IS 2 BP 135 EP 159 DI 10.1191/096228000672549488 PG 25 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 333RL UT WOS:000088144500005 PM 10946431 ER PT J AU Nguyen, TV Brownell, AL Chen, YCI Livni, E Coyle, JT Rosen, BR Cavagna, F Jenkins, BG AF Nguyen, TV Brownell, AL Chen, YCI Livni, E Coyle, JT Rosen, BR Cavagna, F Jenkins, BG TI Detection of the effects of dopamine receptor supersensitivity using pharmacological MRI and correlations with PET SO SYNAPSE LA English DT Article DE supersensitivity; apomorphine; amphetamine; fMRI; CBV; PET; 6-OHDA; dopamine; raclopride; CFT ID C-14 2-DEOXYGLUCOSE AUTORADIOGRAPHY; BASAL GANGLIA; RAT STRIATUM; C-FOS; GLUCOSE-UTILIZATION; SUPER-SENSITIVITY; TIME COURSE; SCHIZOPHRENIA; BINDING; NEURONS AB Receptor supersensitivity is an important concept for understanding neurotransmitter and receptor dynamics. Traditionally, detection of receptor supersensitivity has been performed using autoradiography or positron emission tomography (PET). We show that use of magnetic resonance imaging (MRI) not only enables one to detect dopaminergic supersensitivity, but that the hemodynamic time course reflective of this fact is different in different brain regions. In rats unilaterally lesioned with intranigral 6-hydroxydopamine, apomorphine injections lead to a large increase in hemodynamic response (cerebral blood volume, CBV) in the striato-thalamo-cortico circuit on the lesioned side but had little effect on the intact side. Amphetamine injections lead to increases in hemodynamic responses on the intact side and little on the lesioned side in the same animals. The time course for the increase in CBV after either amphetamine or apomorphine administration was longer in striatum and thalamus than in frontal cortex. C-11-PET studies of ligands which bind to the dopamine transporter (2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane 1,5-naphthalnendisulfonate, WIN 35, 428 or CFT) and D2 receptors (raclopride) confirm that there is a loss of presynaptic dopamine terminals as well as upregulation of D2 receptors in striatum in these same animals. Pharmacologic MRI should become a sensitive tool to measure functional supersensitivity in humans, providing a complementary picture to that generated using PET studies of direct receptor binding. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, MGH NMR Ctr, Dept Radiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, PET Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Bracco SPA, Milan, Italy. RP Jenkins, BG (reprint author), MGH NMR Ctr, Bldg 149 13th St, Charlestown, MA USA. FU NIDA NIH HHS [P01DA09467]; NIMH NIH HHS [MH19126] NR 51 TC 68 Z9 70 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 2000 VL 36 IS 1 BP 57 EP 65 DI 10.1002/(SICI)1098-2396(200004)36:1<57::AID-SYN6>3.0.CO;2-K PG 9 WC Neurosciences SC Neurosciences & Neurology GA 290CV UT WOS:000085659400006 PM 10700026 ER PT J AU Lu, MCK Sammel, MD Cleveland, RH Ryan, LM Holmes, LB AF Lu, MCK Sammel, MD Cleveland, RH Ryan, LM Holmes, LB TI Digit effects produced by prenatal exposure to antiepileptic drugs SO TERATOLOGY LA English DT Article ID FETAL-HYDANTOIN SYNDROME; PHALANGEAL HYPOPLASIA; ANTICONVULSANT DRUGS; IN-UTERO; PHENYTOIN; CHILDREN; TERATOGENESIS; MONOTHERAPY; INFANTS; NEWBORN AB The hypothesis tested was that digit anomalies among individuals exposed in utero to antiepileptic drugs (AED) are best identified by a systematic search, including radiographs and dermatoglyphics, rather than relying only on visual inspection, A systematic search was made for five types of digit abnormalities in 46 AED-exposed individuals ages 5-29 years in comparison with controls: visible anomalies, size of fingernails, dermal ridge patterns, length of metacarpals and phalanges, and qualitative changes in the distal phalanges. Among the AED-exposed, nail size was not decreased. However, there was a 10.8% frequency of digit anomalies, a 12% frequency of three or more arch patterns, and significant shortening and qualitative changes in the distal phalanges, all of which are consistent with the fetal effects of AED. Among the 42 individuals who underwent all evaluations, 14.3% had two or more of these abnormalities, most of which would not be identified by clinical inspection. This frequency is much higher in these AED-exposed individuals than in the general population. Radiographs in 13 individuals over a period of several years showed that the changes in the phalanges and metacarpals persisted. (C) 2000 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. RP Holmes, LB (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Serv Pediat, Warren 801,55 Fruit St, Boston, MA 02114 USA. RI Ryan, Louise/A-4562-2009 OI Ryan, Louise/0000-0001-5957-2490 NR 28 TC 20 Z9 20 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0040-3709 J9 TERATOLOGY JI Teratology PD APR PY 2000 VL 61 IS 4 BP 277 EP 283 DI 10.1002/(SICI)1096-9926(200004)61:4<277::AID-TERA6>3.0.CO;2-W PG 7 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 296CL UT WOS:000086005400006 PM 10716746 ER PT J AU Ross, DS AF Ross, DS TI Worm-eaten bones SO THYROID LA English DT Editorial Material ID HYPOTHYROIDISM; REPLACEMENT; FRACTURES; THERAPY; DENSITY; WOMEN C1 Massachusetts Gen Hosp, Dept Med, Thyroid Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ross, DS (reprint author), Massachusetts Gen Hosp, Dept Med, Thyroid Unit, ACC-730, Boston, MA 02114 USA. NR 14 TC 3 Z9 3 U1 1 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2000 VL 10 IS 4 BP 331 EP 333 DI 10.1089/thy.2000.10.331 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 310FZ UT WOS:000086817000007 PM 10807061 ER PT J AU Kaihara, S Borenstein, J Koka, R Lalan, S Ochoa, ER Ravens, M Pien, H Cunningham, B Vacanti, JP AF Kaihara, S Borenstein, J Koka, R Lalan, S Ochoa, ER Ravens, M Pien, H Cunningham, B Vacanti, JP TI Silicon micromachining to tissue engineer branched vascular channels for liver fabrication SO TISSUE ENGINEERING LA English DT Article ID IN-VITRO; SKIN; HEPATOCYTES AB To date, many approaches to engineering new tissue have emerged and they have all relied on vascularization from the host to provide permanent engraftment and mass transfer of oxygen and nutrients. Although this approach has been useful in many tissues, it has not been as successful in thick, complex tissues, particularly those comprising the large vital organs such as the liver, kidney, and heart. In this study, we report preliminary results using micromachining technologies on silicon and Pyrex surfaces to generate complete vascular systems that may be integrated with engineered tissue before implantation. Using standard photolithography techniques, trench patterns reminiscent of branched architecture of vascular and capillary networks were etched onto silicon and Pyrex surfaces to serve as templates. Hepatocytes and endothelial cells were cultured and subsequently lifted as single-cell monolayers from these two-dimensional molds. Both cell types were viable and proliferative on these surfaces. In addition, hepatocytes maintained albumin production. The lifted monolayers were then folded into compact three-dimensional tissues. Thus, with the use microfabrication technology in tissue engineering, it now seems feasible to consider lifting endothelial cells as branched vascular networks from two-dimensional templates that mag ultimately be combined with layers of parenchymal tissue, such as hepatocytes, to form three-dimensional conformations of living vascularized tissue for implantation. C1 Harvard Univ, Sch Med, Dept Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Charles Stark Draper Lab Inc, Cambridge, MA 02139 USA. Ctr Innovat Minimally Invas Therapy, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Vacanti, JP (reprint author), Harvard Univ, Sch Med, Dept Surg, 55 Fruit St, Boston, MA 02114 USA. NR 33 TC 213 Z9 217 U1 3 U2 38 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD APR PY 2000 VL 6 IS 2 BP 105 EP 117 DI 10.1089/107632700320739 PG 13 WC Cell & Tissue Engineering SC Cell Biology GA 311AQ UT WOS:000086862400002 PM 10941206 ER PT J AU Hadlock, T Sundback, C Hunter, D Cheney, M Vacanti, JP AF Hadlock, T Sundback, C Hunter, D Cheney, M Vacanti, JP TI A polymer foam conduit seeded with Schwann cells promotes guided peripheral nerve regeneration SO TISSUE ENGINEERING LA English DT Article ID SCIATIC-NERVE; GUIDANCE CHANNELS; SILICONE CHAMBER; RAT; REPAIR; GROWTH; INCREASES; DELIVERY; GRAFTS; ACID AB Alternatives to autografts have long been sought for use in bridging neural gaps. Many entubulation materials have been studied, although with generally disappointing results in comparison with autografts. The purpose of this study was to design a more effective neural guidance conduit, to introduce Schwann cells into the conduit, and to determine regenerative capability through it fn an in vivo model. A novel, fully biodegradable polymer conduit was designed and fabricated for use in peripheral nerve repair, which approximates the macro- and microarchitecture of native peripheral nerves. It comprised a series of longitudinally aligned channels, with diameters ranging from 60 to 550 microns. The lumenal surfaces promoted the adherence of Schwann cells, whose presence is known to play a key role in nerve regeneration. This unique channel architecture increased the surface area available for Schwann cell adherence up to five-fold over that available through a simple hollow conduit. The conduit was composed of a high-molecular-weight copolymer of lactic and glycolic acids (PLGA) (MW 130,000) in an 85:15 monomer ratio. A novel foam-processing technique, employing low-pressure injection molding, was used to create highly porous conduits (approximately 90% pore volume) with continuous longitudinal channels. Using this technique, conduits were constructed containing 1, 5, 16, 45, or more longitudinally aligned channels. Prior to cellular seeding of these conduits, the foams were prewet with 50% ethanol, flushed with physiologic saline, and coated with laminin solution (10 mu g/mL). A Schwann cell suspension was dynamically introduced into these processed foams at a concentration of 5 X 10(5) cells/mL, using a simple bioreactor flow loop. In vivo regeneration studies were carried out in which cell-laden five-channel polymer conduits (individual channel ID 500 mu m, total conduit OD 2.3 mm) were implanted across a 7-mm gap in the rat sciatic nerve (n = 4), and midgraft axonal regeneration compared with autografts (n = 6). At 6 weeks, axonal regeneration was observed in the midconduit region of all five channels in each experimental animal, The cross-sectional area comprising axons relative to the open conduit cross sectional area (mean 26.3%, SD 10.1%) compared favorably with autografts (mean 23.8%, SD 3.6%). Our methodology can be used to create polymer foam conduits containing longitudinally aligned channels, to introduce Schwann cells into them, and to implant them into surgically created neural defects. These conduits provide an environment permissive to axonal regeneration. Furthermore, this polymer foam-processing method and unique channeled architecture allows the introduction of neurotrophic factors into the conduit in a controlled fashion. Deposition of different factors into distinct regions within the conduit may be possible to promote more precisely guided neural regeneration. C1 Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Lab Tissue Engn & Organ Fabricat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Washington Univ, Dept Plast Surg, St Louis, MO USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [T32DC00020] NR 40 TC 227 Z9 257 U1 4 U2 52 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD APR PY 2000 VL 6 IS 2 BP 119 EP 127 DI 10.1089/107632700320748 PG 9 WC Cell & Tissue Engineering SC Cell Biology GA 311AQ UT WOS:000086862400003 PM 10941207 ER PT J AU Sodian, R Sperling, JS Martin, DP Egozy, A Stock, U Mayer, JE Vacanti, JP AF Sodian, R Sperling, JS Martin, DP Egozy, A Stock, U Mayer, JE Vacanti, JP TI Fabrication of a trileaflet heart valve scaffold from a polyhydroxyalkanoate biopolyester for use in tissue engineering SO TISSUE ENGINEERING LA English DT Article; Proceedings Paper CT 2nd Bi-Annual Meeting of the Tissue-Engineering-Society CY DEC 04-06, 1998 CL ORLANDO, FLORIDA SP Tissue Engn Soc AB Previously, we reported the implantation of a single tissue engineered leaflet in the posterior position of the pulmonary valve in a lamb model. The major problems with this leaflet replacement were the scaffold's inherent stiffness, thickness, and nonpliability. We have now created a scaffold for a trileaflet heart valve using a thermoplastic polyester. In this experiment, we show the suitability of this material in the production of a biodegradable, biocompatible scaffold for tissue engineered heart valves. A heart valve scaffold was constructed from a thermoplastic elastomer. The elastomer belongs to a class of biodegradable, biocompatible polyesters known as polyhydroxyalkanoates (PHAs) and is produced by fermentation (Metabolix Inc., Cambridge, MA). It was modified by a salt leaching technique to create a porous, three-dimensional structure, suitable for tissue engineering. The trileaflet heart valve scaffold consisted of a cylindrical stent (1 mm x 15 mm x 20 mm I.D.) containing three valve leaflets. The leaflets were formed from a single piece of PHA (0.3 mm thick), and were attached to the outside of the stent by thermal processing techniques, which required no suturing. After fabrication, the heart valve construct was allowed to crystallize (4 degrees C for 24 h), and salt particles mere leached into doubly distilled water over a period of 5 days to yield pore sizes ranging from 80 to 200 microns. Ten heart valve scaffolds were fabricated and seeded with vascular cells from an ovine carotid artery. After 4 days of incubation, the constructs were examined by scanning electron microscopy. The heart valve scaffold was tested in a pulsatile flow bioreactor and it was noted that the leaflets opened and closed. Cells attached to the polymer and formed a confluent layer after incubation. One advantage of this material is the ability to mold a complete trileaflet heart valve scaffold without the need for suturing leaflets to the conduit. Second advantage is the use of only one polymer material (PHA) as opposed to hybridized polymer scaffolds. Furthermore, the mechanical properties of PHA, such as elasticity and mechanical strength, exceed those of the previously utilized material. This experiment shows that PHAs can be used to fabricate a three-dimensional, biodegradable heart valve scaffold. C1 Harvard Univ, Childrens Hosp, Sch Med, Dept Surg Res, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Cardiac Res, Boston, MA 02115 USA. Metabolix Inc, Cambridge, MA USA. RP Vacanti, JP (reprint author), Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 15 TC 125 Z9 139 U1 3 U2 25 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD APR PY 2000 VL 6 IS 2 BP 183 EP 188 DI 10.1089/107632700320793 PG 6 WC Cell & Tissue Engineering SC Cell Biology GA 311AQ UT WOS:000086862400008 PM 10941212 ER PT J AU Alyea, E AF Alyea, E TI Adoptive immunotherapy: insights from donor lymphocyte infusions SO TRANSFUSION LA English DT Editorial Material ID BONE-MARROW TRANSPLANTATION; GRAFT-VERSUS-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; RELAPSE; TRANSFUSIONS C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Alyea, E (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 10 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2000 VL 40 IS 4 BP 393 EP 395 DI 10.1046/j.1537-2995.2000.40040393.x PG 3 WC Hematology SC Hematology GA 307FP UT WOS:000086643000001 PM 10773047 ER PT J AU Garratty, G Dzik, W Issitt, PD Lublin, DM Reid, ME Zelinski, T AF Garratty, G Dzik, W Issitt, PD Lublin, DM Reid, ME Zelinski, T TI Terminology for blood group antigens and genes - historical origins and guidelines in the new millennium SO TRANSFUSION LA English DT Article ID CELL SURFACE-ANTIGENS; ISBT WORKING PARTY; NOMENCLATURE; SYSTEM C1 Amer Red Cross, Blood Serv, Los Angeles, CA 90006 USA. Massachusetts Gen Hosp, Blood Transfus Serv, Boston, MA 02114 USA. Duke Univ, Med Ctr, Transfus Serv, Durham, NC USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10021 USA. Univ Manitoba, Rh Lab, Winnipeg, MB, Canada. RP Garratty, G (reprint author), Amer Red Cross, Blood Serv, 1130 S Vermont Ave, Los Angeles, CA 90006 USA. NR 43 TC 28 Z9 28 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2000 VL 40 IS 4 BP 477 EP 489 DI 10.1046/j.1537-2995.2000.40040477.x PG 13 WC Hematology SC Hematology GA 307FP UT WOS:000086643000016 PM 10773062 ER PT J AU Sachs, RK Hlatky, LR Trask, BJ AF Sachs, RK Hlatky, LR Trask, BJ TI Radiation-produced chromosome aberrations - colourful clues SO TRENDS IN GENETICS LA English DT Article ID IN-SITU HYBRIDIZATION; INTERPHASE CHROMOSOMES; CHROMATIN; ORGANIZATION; PARTICLES; REPAIR; MODEL; LOOPS AB Ionizing radiation produces many chromosome aberrations. A rich variety of aberration types can now be seen with the technique of chromosome painting. Apart from being important in medicine and public health, radiation-produced aberrations act as colourful molecular clues to damage-processing mechanisms and, because juxtaposition of different parts of the genome is involved, to interphase nuclear organization. Recent studies using chromosome painting have helped to identify DNA double-strand-break repair and misrepair pathways, to determine the extent of chromosome territories and motions, and to characterize different aberration patterns left behind by different kinds of radiation. C1 Univ Calif Berkeley, Dept Math, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Dept Adult Oncol, Boston, MA 02115 USA. Univ Washington, Dept Mol Biotechnol, Seattle, WA 98195 USA. RP Sachs, RK (reprint author), Univ Calif Berkeley, Dept Math, Evans Hall,MC 3840, Berkeley, CA 94720 USA. RI huang, hongqi/N-1473-2014 NR 30 TC 39 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD APR PY 2000 VL 16 IS 4 BP 143 EP 146 DI 10.1016/S0168-9525(99)01960-5 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 299FL UT WOS:000086185900001 PM 10729825 ER PT J AU Chin, L DePinho, RA AF Chin, L DePinho, RA TI Flipping the oncogene switch - illumination of tumor maintenance and regression SO TRENDS IN GENETICS LA English DT Article ID TELOMERE MAINTENANCE; TRANSGENIC MICE; IN-VIVO; CELLS; ANGIOGENESIS; APOPTOSIS; RAS; CANCER; GROWTH AB The genetic construction of cancer-prone mice, combined with the capacity to control transgene expression in vivo, provides new opportunities to study the role of oncogenes in the maintenance of fully formed tumors. These inducible cancer models provide a means to dissect how specific oncogenic signals influence host-tumor symbiosis, to validate the importance of a given oncogenic lesion in established advanced tumors, and to predict the biological response and adaptations to therapies targeted to that cancer-causing genetic alteration. C1 Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst,Dept Dermatol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP Chin, L (reprint author), Harvard Univ, Sch Med, Dept Adult Oncol, Dana Farber Canc Inst,Dept Dermatol, 44 Binney St, Boston, MA 02115 USA. NR 22 TC 24 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0168-9525 J9 TRENDS GENET JI Trends Genet. PD APR PY 2000 VL 16 IS 4 BP 147 EP 150 DI 10.1016/S0168-9525(99)01968-X PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 299FL UT WOS:000086185900002 PM 10729826 ER PT J AU D'Amico, AV Whittington, R Malkowicz, SB Wu, YH Chen, MH Art, M Tomaszewski, JE Wein, A AF D'Amico, AV Whittington, R Malkowicz, SB Wu, YH Chen, MH Art, M Tomaszewski, JE Wein, A TI Combination of the preoperative PSA level, biopsy Gleason score, percentage of positive biopsies, and MRI T-stage to predict early PSA failure in men with clinically localized prostate cancer SO UROLOGY LA English DT Article ID BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; PATHOLOGICAL STAGE; ANTIGEN FAILURE; SURVIVAL AB Objectives. Early (2 years or less) prostate-specific antigen (PSA) failure has been shown to predict for distant failure, The independent clinical predictors of time to postoperative PSA failure were used to identify prostate cancer patients at high risk for early PSA failure. Methods. A Cox regression multivariable analysis was used to determine whether additional predictive information was provided by the endorectal coil magnetic resonance imaging (erMRI) T-stage when controlling for the established prognostic factors in predicting the time to postoperative PSA failure in 977 men with palpable (T2) or PSA-detected (T1c) prostate cancer. Results. Preoperative PSA (P = 0.0001), percentage of positive prostate biopsies (P = 0.0001), erMRI T-stage (P = 0.0001), biopsy Gleason score (P = 0.0015), and clinical stage T2c disease (P = 0.004) were independent predictors of time to postoperative PSA failure. Two-year PSA failure rates derived from the Cox regression model and bootstrap estimates of the 95% confidence intervals are presented in nomogram format stratified by the preoperative PSA, percentage of positive prostate biopsies, erMRI T-stage, and the biopsy Gleason score. Conclusions, Patients at high risk for early PSA failure and subsequent distant progression include men with erMRI T3 disease and 3 or more of 6 cores positive for a Gleason score 6 or higher disease when the PSA is more than 10 but not more than 20 ng/mL and any Gleason score when the PSA is more than 20 ng/mL. Men with erMRI T2 disease and 3 or more of 6 cores positive for a Gleason score 8 or higher disease and who have a PSA more than 20 ng/mL are also at high risk. Neoadjuvant therapy trials in these select patients may be justified, UROLOGY 55: 572-577, 2000. (C) 2000, Elsevier Science Inc. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Hosp Univ Penn, Dept Radiat Oncol, Philadelphia, PA 19104 USA. Hosp Univ Penn, Dept Urol, Philadelphia, PA 19104 USA. Worcester Polytech Inst, Dept Math Sci, Worcester, MA 01609 USA. Hosp Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP D'Amico, AV (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol, L-2 Level,75 Francis St, Boston, MA 02115 USA. NR 18 TC 76 Z9 80 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD APR PY 2000 VL 55 IS 4 BP 572 EP 577 DI 10.1016/S0090-4295(99)00479-3 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 298VY UT WOS:000086161200025 PM 10736506 ER PT J AU Munshi, HG Montgomery, RB AF Munshi, HG Montgomery, RB TI Severe neutropenia: a diagnostic approach SO WESTERN JOURNAL OF MEDICINE LA English DT Review ID COLONY-STIMULATING FACTOR; DRUG-INDUCED AGRANULOCYTOSIS; AUTOIMMUNE NEUTROPENIA; GRANULOCYTE; SARCOIDOSIS; PATIENT C1 Univ Washington, Sch Med, Div Oncol,Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Montgomery, RB (reprint author), Univ Washington, Sch Med, Div Oncol,Dept Med, Vet Affairs Puget Sound Hlth Care Syst, 111-ONC,1660 S Columbian Way, Seattle, WA 98108 USA. NR 35 TC 11 Z9 15 U1 0 U2 1 PU B M J PUBLISHING INC PI SAN FRANCISCO PA 221 MAIN ST, PO BOX 7690, SAN FRANCISCO, CA 94120-7690 USA SN 0093-0415 J9 WESTERN J MED JI West. J. Med. PD APR PY 2000 VL 172 IS 4 BP 248 EP 252 DI 10.1136/ewjm.172.4.248 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 301AW UT WOS:000086286800025 PM 10778379 ER PT J AU Malcon, C Kaddurah-Daouk, R Beal, MF AF Malcon, C Kaddurah-Daouk, R Beal, MF TI Neuroprotective effects of creatine administration against NMDA and malonate toxicity SO BRAIN RESEARCH LA English DT Article DE excitotoxicity; free radical; mitochondria; malonate; N-methyl-D-aspartate; creatine; nicotine ID NMR MAGNETIZATION-TRANSFER; METHYL-D-ASPARTATE; INTRACELLULAR CA2+; SPINAL NEURONS; MITOCHONDRIAL; KINASE; BRAIN; NEUROTOXICITY; DEATH; DYSFUNCTION AB We examined whether creatine administration could exert neuroprotective effects against excitotoxicity mediated by N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainic acid. Oral administration of 1% creatine significantly attenuated striatal excitotoxic lesions produced by NMDA, but had no effect on lesions produced by AMPA or kainic acid. Both creatine and nicotinamide can exert significant protective effects against malonate-induced striatal lesions. We, therefore, examined whether nicotinamide could exert additive neuroprotective effects with creatine against malonate-induced lesions. Nicotinamide with creatine produced significantly better neuroprotection than creatine alone against malonate-induced lesions. Creatine can, therefore, produce significant neuroprotective effects against NMDA mediated excitotoxic lesions in vivo and the combination of nicotinamide with creatine exerts additive neuroprotective effects. (C) 2000 Elsevier Science B.V. All rights reserved. C1 Massachusetts Gen Hosp, Neurol Serv, Neurochem Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Avicena Grp, Cambridge, MA USA. New York Hosp, Cornell Med Ctr, Dept Neurol, New York, NY 10021 USA. RP Beal, MF (reprint author), Cornell Univ, Weill Med Coll, Dept Neurol, 525 E 68th St, New York, NY 10021 USA. FU NINDS NIH HHS [NS32365, NS39258] NR 28 TC 52 Z9 55 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 31 PY 2000 VL 860 IS 1-2 BP 195 EP 198 DI 10.1016/S0006-8993(00)02038-2 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 297KD UT WOS:000086081000026 PM 10727643 ER PT J AU Hajjar, RJ del Monte, F Matsui, T Rosenzweig, A AF Hajjar, RJ del Monte, F Matsui, T Rosenzweig, A TI Prospects for gene therapy for heart failure SO CIRCULATION RESEARCH LA English DT Review DE gene therapy; heart failure; Ca2+ cycling; excitation-contraction coupling ID ADRENERGIC SIGNAL-TRANSDUCTION; PRESSURE-OVERLOAD HYPERTROPHY; HUMAN VENTRICULAR MYOCARDIUM; IN-VIVO; DIASTOLIC DYSFUNCTION; CALCIUM MOBILIZATION; GROWTH-FACTOR; APOPTOSIS; MYOCYTES; RAT AB Heart failure represents an enormous clinical challenge in need of effective therapeutic approaches, The possibility of gene therapy for heart failure merits consideration at this time because of improvements in vector technology; cardiac gene delivery; and, most importantly, our understanding of the molecular pathogenesis of heart Failure. We will first review recent advances in cardiac gene delivery in animal models and then examine several targets being considered for therapeutic intervention. In this context, gene transfer provides not only a potential therapeutic modality but also an important tool to help validate specific targets. Several interventions, particularly those enhancing sarcoplasmic calcium transport, show promise in animal models of heart failure and in myopathic cardiomyocytes derived from patients. However, bridging the gap between these basic investigative studies and clinical gene therapy remains a formidable task. Early experiments in rodents will need to be extended to large-animal models with clinical-grade vectors and delivery systems to assess both efficacy and safety. On the basis of a foundation of rigorous science and a growing understanding of heart failure pathogenesis, there is reason for cautious optimism for the future. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Cardiovasc Gene Therapy,Cardiovasc Res Ct, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP Rosenzweig, A (reprint author), Massachusetts Gen Hosp E, Cardiovasc Res Ctr, 149 13th St,4th Floor,Room 4214, Charlestown, MA 02129 USA. FU NHLBI NIH HHS [HL50361, HL57623, HL59521] NR 62 TC 95 Z9 100 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 31 PY 2000 VL 86 IS 6 BP 616 EP 621 PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 302LZ UT WOS:000086367700004 PM 10746995 ER PT J AU Yauch, RL Kazarov, AR Desai, B Lee, RT Hemler, ME AF Yauch, RL Kazarov, AR Desai, B Lee, RT Hemler, ME TI Direct extracellular contact between integrin alpha(3)beta(1) and TM4SF protein CD151 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LEUKEMIA-VIRUS TYPE-1; MHC CLASS-II; TRANSMEMBRANE-4 SUPERFAMILY; MONOCLONAL-ANTIBODIES; T-CELLS; ELECTRON-MICROSCOPY; SIGNAL-TRANSDUCTION; SYNCYTIUM FORMATION; C33 ANTIGEN; ASSOCIATION AB Previously we established that the alpha(3)beta(1) integrin shows stable, specific, and stoichiometric association with the TM4SF (tetraspannin) protein CD151. Here we used a membrane impermeable cross-linking agent to show a direct association between extracellular domains of alpha(3)beta(1) and CD151. The alpha(3)beta(1)-CD151 association site was then mapped using chimeric alpha(6)/alpha(3) integrins and CD151/NAG2 TM4SF proteins. Complex formation required an extracellular alpha(3) Site (amino acids (aa) 570-705) not previously known to be involved in specific integrin contacts with other proteins and a region (aa 186-217) within the large extracellular loop of CD151. Notably, the anti-CD151 monoclonal antibody TS151r binding epitope, previously implicated in alpha(3) integrin association, was mapped to the same region of CD151 (aa 186-217). Finally, we demonstrated that both NH2- and COOH-terminal domains of CD151 are located on the inside of the plasma membrane, thus confirming a long suspected model of TM4SF protein topology. C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Rm D-1430,44 Binney St, Boston, MA 02115 USA. FU NCI NIH HHS [CA86712]; NIGMS NIH HHS [GM38903] NR 51 TC 138 Z9 142 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 31 PY 2000 VL 275 IS 13 BP 9230 EP 9238 DI 10.1074/jbc.275.13.9230 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299PF UT WOS:000086206500024 PM 10734060 ER PT J AU Singh, IS Viscardi, RM Kalvakolanu, I Calderwood, S Hasday, JD AF Singh, IS Viscardi, RM Kalvakolanu, I Calderwood, S Hasday, JD TI Inhibition of tumor necrosis factor-alpha transcription in macrophages exposed to febrile range temperature - A possible role for heat shock factor-1 as a negative transcriptional regulator SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR GENE-EXPRESSION; HUMAN-MONOCYTES; BINDING ACTIVITY; PROTECTS MICE; CELL-LINE; LIPOPOLYSACCHARIDE; ACTIVATION; CACHECTIN; ENDOTOXIN; TNF AB We previously reported that expression of tumor necrosis factor-alpha (TNF alpha) was attenuated in macrophages exposed to febrile range temperatures. In this study, we analyzed the influence of temperature on TNF alpha transcription in the Raw 264.7 macrophage cell line during incubation at 37 and 39.5 degrees C, The initial activation of TNF alpha transcription in response to endotoxin (LPS) was comparable in the 37 and 39.5 degrees C cell cultures, peaking within 10 min of LPS stimulation. However, the duration of transcriptional activation was markedly reduced in the 39.5 degrees C cells (30-60 min) compared with the 37 degrees C cells (2-4 h), Deletion mapping of the TNF alpha gene revealed that the proximal 85-nucleotide promoter sequence and the 5'-untranslated region were sufficient for temperature sensitivity. This sequence contains six heat shock response element (HRE) half-sites but no complete HREs, Electrophoretic mobility shift and immunoblot assays demonstrated that nuclear transclocation of heat shock factor (HSF) and its activation to a DNA-binding form occurred in the 39.5 degrees C cells in the absence of heat shock protein-70 gene activation. The proximal TNF alpha promoter/5'-untranslated region sequence competed for HSF binding to a classic HRE. Overexpression of HSF-1 reduced activity of the TNF alpha promoter. These data suggest that partial activation of HSF-I during exposure to febrile, sub-heat shock temperatures may block TNF alpha transcription by binding to its proximal promoter or 5'-untranslated region. C1 Baltimore VA Med Ctr, Med & Res Serv, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Med, Div Pulm & Crit Care Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pediat, Div Neonatol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. Univ Maryland, Baltimore Cytoking Core Lab, Baltimore, MD 21201 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joint Ctr Radiat Therapy, Boston, MA 02115 USA. RP Hasday, JD (reprint author), Baltimore VA Med Ctr, Med & Res Serv, Rm 3D127,10 N Greene St, Baltimore, MD 21201 USA. NR 43 TC 97 Z9 104 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 MAR 31 PY 2000 VL 275 IS 13 BP 9841 EP 9848 DI 10.1074/jbc.275.13.9841 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 299PF UT WOS:000086206500103 PM 10734139 ER PT J AU Kaur, A Rosenzweig, M Johnson, RP AF Kaur, A Rosenzweig, M Johnson, RP TI Immunological memory and acquired immunodeficiency syndrome pathogenesis SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES B-BIOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Synposium on Immunological Memory CY MAR 10-11, 1999 CL LONDON, ENGLAND SP Royal Soc London DE human immunodeficiency virus; simian immunodeficiency virus; T-cell turnover; cytomegalovirus; bromodeoxyuridine ID CD4(+) T-CELLS; INFECTED RHESUS MACAQUES; CHRONIC VIRAL-INFECTION; HIV-1 INFECTION; VIRUS TYPE-1; PERIPHERAL-BLOOD; HOMOSEXUAL MEN; RAPID TURNOVER; LIFE-SPAN; IN-VITRO AB Infection with the human immunodeficiency virus results in profound perturbations in immunological memory, ultimately resulting in increased susceptibility to opportunistic infections and acquired immunodeficiency syndrome (AIDS). We have used rhesus macaques infected with the simian immunodeficiency virus (SIV) as a model to understand better the effects of AIDS virus infection on immunological memory. Acute infection with SIV resulted in significant deficits in CD4(+) helper responses to cytomegalovirus (CMV) as well as CMV-specific cytotoxic T-lymphocyte and neutralizing antibody responses. Reactivation of CMV was associated with high levels of SIV replication and suppression of both T-helper and cytotoxic responses to CMV. We have also studied the effects of SIV infection on T-cell turnover in non-human primates. T-cell turnover was evaluated using the nucleoside analogue bromodeoxyuridine (BrdU) in combination with five-colour flow cytometric analysis. T cells in normal animals turned over at relatively rapid rates, with memory cells turning over more quickly than naive cells. In SIV-infected animals, the labelling and elimination rates of both CD4(+) and CD8(+) BrdU-labelled cells were increased by two- to threefold compared with normal controls. Further analysis of immunological memory in nonhuman primates should offer the opportunity to extend immunological insights from murine models to the pathogenesis and prevention of AIDS. C1 Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, Southborough, MA 01772 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Infect Dis Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. RP Johnson, RP (reprint author), Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Div Immunol, 1 Pine Hill Dr, Southborough, MA 01772 USA. FU NCRR NIH HHS [RR00168]; NIAID NIH HHS [AI36550, AI43890] NR 59 TC 10 Z9 10 U1 0 U2 0 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T ROY SOC B JI Philos. Trans. R. Soc. Lond. Ser. B-Biol. Sci. PD MAR 29 PY 2000 VL 355 IS 1395 BP 381 EP 390 PG 10 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 303FB UT WOS:000086410400012 PM 10794059 ER PT J AU Guo, Z Cupples, LA Kurz, A Auerbach, SH Volicer, L Chui, H Green, RC Sadovnick, AD Duara, R DeCarli, C Johnson, K Go, RC Growdon, JH Haines, JL Kukull, WA Farrer, LA AF Guo, Z Cupples, LA Kurz, A Auerbach, SH Volicer, L Chui, H Green, RC Sadovnick, AD Duara, R DeCarli, C Johnson, K Go, RC Growdon, JH Haines, JL Kukull, WA Farrer, LA TI Head injury and the risk of AD in the MIRAGE study SO NEUROLOGY LA English DT Article DE AD; head injury; APOE genotype ID APOLIPOPROTEIN-E GENOTYPE; ALZHEIMERS-DISEASE; 1ST-DEGREE RELATIVES; BRAIN INJURY; DEMENTIA; ONSET; TRAUMA; AGE; DEPOSITION; DIAGNOSIS AB Objectives: It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE-is an element of 4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study. Subjects: A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study. Methods: Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with unaffected spouses using conditional logistic regression analysis. To account for the unique biologic relationship between probands and their parents and siblings, odds of AD were computed using a generalized estimating equation (GEE) Poisson regression approach. GEE logistic regression was used to examine the joint effects of APOE genotype and head injury on the odds of AD in probands and a control group comprised of unaffected siblings and spouses. Results: Comparison of probands with their unaffected spouses yielded odds ratios for AD of 9.9 (95% CI, 6.5 to 15.1) for head injury with loss of consciousness and 3.1 (2.3 to 4.0) for head injury without loss of consciousness. The corresponding odds derived from the comparison of probands with their parents and sibs were 4.0 (2.9 to 5.5) for head injury with loss of consciousness and 2.0 (1.5 to 2.7) for head injury without loss of consciousness. Head injury without loss of consciousness did not significantly increase the risk of AD in spouses (OR = 1.3; 95% CI, 0.4 to 4.1). The joint effects of head injury and APOE genotype were evaluated in a subsample of 942 probands and 327 controls (spouses and siblings). Head injury increased the odds of AD to a greater extent among those lacking is an element of 4 (OR = 3.3) than among is an element of 4 heterozygotes (OR = 1.8) or homozygotes (OR = 1.3). Conclusion: Head injury is a risk factor for AD. The magnitude of the risk is proportional to severity and heightened among first-degree relatives of AD patients. The influence of head injury on the risk of AD appears to be greater among persons lacking APOE-is an element of 4 compared with those having one or two is an element of 4 alleles, suggesting that these risk factors may have a common biologic underpinning. C1 Boston Univ, Sch Med, Dept Med, Genet Program, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Epidemiol & Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA. Tech Univ Munich, Psychiat Klin, D-8000 Munich, Germany. Edith Nourse Rogers Mem Vet Adm Hosp, Ctr Geriatr Res Educ & Clin, Bedford, MA 01730 USA. Univ So Calif, Rancho Los Amigos Med Ctr, Geriatr Neurobehav & Alzheimers Ctr, Downey, CA 90242 USA. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. Univ Miami, Sch Med, Mt Sinai Med Ctr, Wien Ctr Alzheimers Dis & Memory Disorders, Miami, FL USA. Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66103 USA. Mayo Clin, Rochester, MN USA. Univ Alabama, Dept Epidemiol, Birmingham, AL USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Vanderbilt Univ, Sch Med, Program Human Genet, Nashville, TN 37212 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. RP Farrer, LA (reprint author), Boston Univ, Sch Med, Dept Med, Genet Program, L320,715 Albany St, Boston, MA 02118 USA. RI DeCarli, Charles/B-5541-2009; Haines, Jonathan/C-3374-2012; OI Farrer, Lindsay/0000-0001-5533-4225; Kukull, Walter/0000-0001-8761-9014 FU NIA NIH HHS [R01-AG09029] NR 45 TC 245 Z9 253 U1 2 U2 13 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 28 PY 2000 VL 54 IS 6 BP 1316 EP 1323 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 297XY UT WOS:000086109300021 PM 10746604 ER PT J AU Moll, J de Oliveira-Souza, R Passman, LJ Cunha, FC Souza-Lima, F Andreiuolo, PA AF Moll, J de Oliveira-Souza, R Passman, LJ Cunha, FC Souza-Lima, F Andreiuolo, PA TI Functional MRI correlates of real and imagined tool-use pantomimes SO NEUROLOGY LA English DT Article DE tool-use pantomimes; hemispheric specialization; functional MRI ID CONCEPTUAL APRAXIA; FMRI; ACTIVATION; AREAS AB Objective: To study the pattern of cerebral activation related to the performance of tool-use pantomimes with functional MRI (fMRI) using a task-subtraction design. Background: Tool use comprises a particular category of transitive actions. Inability to pantomime the use of tools has been classically associated with retrorolandic dominant hemisphere damage. However, where in the left hemisphere these transitive representations are generated is unclear. Methods: Echoplanar images were acquired in eight alternating task and control periods. Sixteen right-handed normal adults pantomimed the use of common tools and utensils with each hand. The control condition consisted of a sequence of nonsymbolic complex movements of forearm, hand, and fingers at a self-paced rate. Eight individuals also imagined the execution of the real task and control actions. A repeated measures ANOVA compared activations in five regions of interest in each hemisphere. Results: Regardless of which hand was used, the left hemisphere was more active than the right in both real (p < 0.02) and imagined (p < 0.04) tasks. Activations clustered in the left intraparietal cortex and posterior dorsolateral frontal cortex. Conclusions: Pantomiming the use of tools is associated with activation of the left intraparietal cortex and dorsolateral frontal cortex. The left intraparietal cortex may store the representations of tool-use formulae, whereas the dorsolateral frontal cortex activation may reflect the switching between innervatory motor programs. C1 Hosp Barra Or & LABS, Funct MRI Ctr, Neuroimaging Div, Rio De Janeiro, Brazil. Univ Fed Rio de Janeiro, Hosp Gaffree & Guinle, Rio De Janeiro, Brazil. Philippe Pinel Inst, Rio De Janeiro, Brazil. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. RP Moll, J (reprint author), Rua Pinheiro Guimaraes,22-5 Andar, BR-22281080 Rio De Janeiro, Brazil. RI Moll, Jorge/B-2654-2013 NR 27 TC 119 Z9 120 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 28 PY 2000 VL 54 IS 6 BP 1331 EP 1336 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 297XY UT WOS:000086109300023 PM 10746606 ER PT J AU Jones, AL Quimby, BB Hood, JK Ferrigno, P Keshava, PH Silver, PA Corbett, AH AF Jones, AL Quimby, BB Hood, JK Ferrigno, P Keshava, PH Silver, PA Corbett, AH TI SAC3 may link nuclear protein export to cell cycle progression SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; PORE COMPLEX PROTEIN; SPINDLE POLE BODY; BUDDING YEAST; GENE ENCODES; LOCALIZATION; PROTEOLYSIS; TRANSPORT; MUTATIONS; MITOSIS AB Selective movement of proteins between the nucleus and the cytoplasm is a regulatory mechanism exploited extensively by the eukaryotic cell. We have identified the evolutionarily conserved Sac3 protein, which was implicated previously in the regulation of mitosis [Bauer, A. & Kolling. R, (1996) J. cell Sci. 109, 1575-1583] as a novel mediator of nuclear protein export We show that Sac3p is localized to the nuclear pore, where it interacts with nucleoporins, Loss of SAC3 function results in a block in nuclear export of a nuclear export signal-containing reporter protein. Our results also demonstrate that SAC3 interacts genetically with the nuclear protein export factors Crm1p/Xpo1p and Yrb2p, Taken together, these data indicate a link between nuclear protein export and transition through the cell cycle. C1 Emory Univ, Rollins Res Ctr 4117, Dept Biochem, Atlanta, GA 30322 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Corbett, AH (reprint author), Emory Univ, Rollins Res Ctr 4117, Dept Biochem, 1510 Clifton Rd NE, Atlanta, GA 30322 USA. NR 56 TC 34 Z9 34 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3224 EP 3229 DI 10.1073/pnas.050432997 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200049 PM 10716708 ER PT J AU Coller, HA Grandori, C Tamayo, P Colbert, T Lander, ES Eisenman, RN Golub, TR AF Coller, HA Grandori, C Tamayo, P Colbert, T Lander, ES Eisenman, RN Golub, TR TI Expression analysis with oligonucleotide microarrays reveals that MYC regulates genes involved in growth, cell cycle, signaling, and adhesion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID C-MYC; SACCHAROMYCES-CEREVISIAE; FK506-BINDING PROTEIN; TRANSFORMATION; TROPOMYOSIN-1; TRANSCRIPTION; RECEPTOR; ONCOGENE; ENCODES; ALPHA AB MYC affects normal and neoplastic cell proliferation by altering gene expression, but the precise pathways remain unclear. We used oligonucleotide microarray analysis of 6,416 genes and expressed sequence tags to determine changes in gene expression caused by activation of c-MYC in primary human fibroblasts. In these experiments, 27 genes were consistently induced, and 9 genes were repressed. The identity of the genes revealed that MYC may affect many aspects of cell physiology altered in transformed cells: cell growth, cell cycle, adhesion, and cytoskeletal organization. Identified targets possibly linked to MYC's effects on cell growth include the nucleolar proteins nucleolin and fibrillarin, as well as the eukaryotic initiation factor 5A. Among the cell cycle genes identified as targets, the G1 cyclin D2 and the cyclin-dependent kinase binding protein CksHs2 were induced whereas the cyclin-dependent kinase inhibitor p21(Cip1) was repressed. A role for MYC in regulating cell adhesion and structure is suggested by repression of genes encoding the extracellular matrix proteins fibronectin and collagen, and the cytoskeletal protein tropomyosin. A possible mechanism far MYC-mediated apoptosis was revealed by identification of the tumor necrosis factor receptor associated protein TRAP1 as a MYC target. Finally, two immunophilins, peptidyl-prolyl cis-trans isomerase F and FKBP52, the latter of which plays a role in cell division in Arabidopsis, were up-regulated by MYC We also explored pattern-matching methods as an alternative approach for identifying MYC target genes. The genes that displayed an expression profile most similar to endogenous Myc in microarray-based expression profiling of myeloid differentiation models were highly enriched for MYC target genes. C1 MIT, Whitehead Inst Biomed Res, Ctr Genome Res, Cambridge, MA 02139 USA. Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Coller, HA (reprint author), Fred Hutchinson Canc Res Ctr A3 100, 100 Fairview Ave N, Seattle, WA 98109 USA. FU NCI NIH HHS [R01 CA020525, CA20525, CA75125, R37 CA020525] NR 38 TC 600 Z9 613 U1 0 U2 22 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3260 EP 3265 DI 10.1073/pnas.97.7.3260 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200055 PM 10737792 ER PT J AU Borghesani, PR Alt, FW Bottaro, A Davidson, L Aksoy, S Rathbun, GA Roberts, TM Swat, W Segal, RA Gu, YS AF Borghesani, PR Alt, FW Bottaro, A Davidson, L Aksoy, S Rathbun, GA Roberts, TM Swat, W Segal, RA Gu, YS TI Abnormal development of Purkinje cells and lymphocytes in Atm mutant mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ATAXIA-TELANGIECTASIA GENE; IONIZING-RADIATION; CEREBELLAR NEURONS; DEFICIENT MICE; NERVOUS-SYSTEM; BRITISH-ISLES; DNA-DAMAGE; C-ABL; PROTEIN; PRODUCT AB Motor incoordination. immune deficiencies, and an increased risk of cancer are the characteristic features of the hereditary disease ataxia-telangiectasia (A-T), which is caused by mutations in the ATM gene, Through gene targeting, we have generated a line of Atm mutant mice, Atm(y/y) mice. In contrast to other Atm mutant mice, Atm(y/y) mice show a lower incidence of thymic lymphoma and survive beyond a few months of age. Atm(y/y) mice exhibit deficits in motor learning indicative of cerebellar dysfunction. Even though we found no gross cerebellar degeneration in older Atm(y/y) animals, ectopic and abnormally differentiated Purkinje cells were apparent in mutant mice of ail ages. These findings establish that some neuropathological abnormalities seen in A-T patients also are present in Atm mutant mice. In addition, we report a previously unrecognized effect of Atm deficiency on development or maintenance of CD4(+)8(+) thymocytes. We discuss these findings in the context of the hypothesis that abnormal development of Purkinje cells and lymphocytes contributes to the pathogenesis of A-T. C1 Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Cellular & Mol Biol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Howard Hughes Med Inst, Boston, MA 02115 USA. FU NCI NIH HHS [T32 CA09642, T32 CA009642]; NIAID NIH HHS [AI35714, P01 AI035714]; NINDS NIH HHS [R01 NS037757, NS37757] NR 47 TC 128 Z9 129 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3336 EP 3341 DI 10.1073/pnas.050584897 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200069 PM 10716718 ER PT J AU Hong, DH Pawlyk, BS Shang, JZ Sandberg, MA Berson, EL Li, TS AF Hong, DH Pawlyk, BS Shang, JZ Sandberg, MA Berson, EL Li, TS TI A retinitis pigmentosa GTPase regulator (RPGR)-deficient mouse model for X-linked retinitis pigmentosa (RP3) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID NUCLEOTIDE-EXCHANGE FACTOR; RPGR GENE; A-WAVE; EXPRESSION; PHOTOTRANSDUCTION; LOCALIZATION; FAMILIES; MUTATION; HOMOLOGY; RCC1 AB The X-linked RP3 locus codes for retinitis pigmentosa GTPase regulator (RPGR), a protein of unknown function with sequence homology to the guanine nucleotide exchange factor for Ran GTPase. We created an RPGR-deficient murine model by gene knockout. In the mutant mice, cone photoreceptors exhibit ectopic: localization of cone opsins in the cell body and synapses and rod photoreceptors have a reduced level of rhodopsin, Subsequently, both cone and rod photoreceptors degenerate, RPGR was found normally localized to the connecting cilia of rod and cone photoreceptors. These data point to a role for RPGR in maintaining the polarized protein distribution across the connecting cilium by facilitating directional transport or restricting redistribution. The function of RPGR is essential for the long-term maintenance of photoreceptor viability. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 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 [EY10309, R01 EY010309] NR 32 TC 161 Z9 162 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 28 PY 2000 VL 97 IS 7 BP 3649 EP 3654 DI 10.1073/pnas.060037497 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 299JK UT WOS:000086195200123 PM 10725384 ER PT J AU Drezek, R Dunn, A Richards-Kortum, R AF Drezek, R Dunn, A Richards-Kortum, R TI A pulsed finite-difference time-domain (FDTD) method for calculating light scattering from biological cells over broad wavelength ranges SO OPTICS EXPRESS LA English DT Article ID ABSORPTION AB We combine the finite-difference time-domain method with pulse response techniques in order to calculate the light scattering properties of biological cells over a range of wavelengths simultaneously. The method we describe can be used to compute the scattering patterns of cells containing multiple heterogeneous organelles, providing greater geometric flexibility than Mie theory solutions. Using a desktop computer, we calculate the scattering patterns for common homogeneous models of biological cells and also for more complex representations of cellular morphology. We find that the geometry chosen significantly impacts scattering properties, emphasizing the need for careful consideration of appropriate theoretical models of cellular scattering and for accurate microscopic determination of optical properties. (C)2000 Optical Society of America. C1 Univ Texas, Biomed Engn Program, Austin, TX 78712 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charleston, MA 02129 USA. RP Drezek, R (reprint author), Univ Texas, Biomed Engn Program, Austin, TX 78712 USA. RI Drezek, Rebekah/A-5101-2012; Dunn, Andrew/I-9527-2014; Richards-Kortum, Rebecca/P-4074-2014 OI Richards-Kortum, Rebecca/0000-0003-2347-9467 NR 28 TC 83 Z9 85 U1 1 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD MAR 27 PY 2000 VL 6 IS 7 BP 147 EP 157 PG 11 WC Optics SC Optics GA 299FZ UT WOS:000086187600002 PM 19404346 ER PT J AU Fraley, AW Vaish, NK Szostak, JW McLaughlin, LW AF Fraley, AW Vaish, NK Szostak, JW McLaughlin, LW TI Broadening the scope of RNA selection assays: Synthesis, polymerization activity, and use of functionalized uridine nucleotide triphosphates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Boston Coll, Dept Chem, Chestnut Hill, MA 02467 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 147-ORGN BP U116 EP U117 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 317UW UT WOS:000087246200632 ER PT J AU Jayaraman, A Yarmush, ML Roth, CM AF Jayaraman, A Yarmush, ML Roth, CM TI Dynamics of stress response mRNA and protein expression in rat hepatocytes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Childrens Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 163-BIOT BP U185 EP U186 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246100891 ER PT J AU Marton, D Kang, YH Berthiaume, F AF Marton, D Kang, YH Berthiaume, F TI Chronic exposure to cytokines suppresses liver-specific functions of cultured hepatocytes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Yeshiva Univ, Stern Coll Women, Dept Biol, New York, NY 10016 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 737-CHED BP U404 EP U404 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246102128 ER PT J AU Roth, CM Roy, P Margolies, MN Yarmush, ML AF Roth, CM Roy, P Margolies, MN Yarmush, ML TI Effect of pressure on the complex between digoxigenin and antibody 26-10. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 340-BIOT BP U224 EP U224 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101064 ER PT J AU Walton, SP Jayaraman, A Roth, CM Stephanopoulos, GN Yarmush, ML AF Walton, SP Jayaraman, A Roth, CM Stephanopoulos, GN Yarmush, ML TI Prediction of antisense oligonucleotide binding affinity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. RI Walton, S. Patrick/A-7007-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 26 PY 2000 VL 219 MA 300-BIOT BP U217 EP U218 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 317UV UT WOS:000087246101024 ER PT J AU Scully, RE AF Scully, RE TI Influence of origin of ovarian cancer on efficacy of screening SO LANCET LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Scully, RE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, James Homer Wright Pathol Labs, Boston, MA 02114 USA. NR 11 TC 28 Z9 28 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 MAR 25 PY 2000 VL 355 IS 9209 BP 1028 EP 1029 DI 10.1016/S0140-6736(00)02026-2 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 302TB UT WOS:000086380800002 PM 10744081 ER PT J AU Sheng, SH Li, JQ McNulty, KA Avery, D Kleyman, TR AF Sheng, SH Li, JQ McNulty, KA Avery, D Kleyman, TR TI Characterization of the selectivity filter of the epithelial sodium channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN SECONDARY STRUCTURE; SENSITIVE NA+ CHANNEL; CATION-PI INTERACTIONS; TOAD URINARY-BLADDER; POTASSIUM CHANNEL; ION SELECTIVITY; STRUCTURE PREDICTION; K+ CHANNEL; MEMBRANE TOPOLOGY; WEAVER MUTATION AB The epithelial sodium channel (ENaC) is composed of three homologous subunits termed alpha, beta, and gamma. Previous studies suggest that selected residues within a hydrophobic region immediately preceding the second membrane-spanning domain of each subunit contribute to the conducting pore of ENaC. We probed the pore of mouse ENaC by systematically mutating all 24 amino acids within this putative pore region of the alpha-subunit to cysteine and co-expressing these mutants with wild type beta- and gamma-subunits of mouse ENaC in Xenopus laevis oocytes, Functional characteristics of these mutants were examined by two-electrode voltage clamp and single channel recording techniques. Two distinct domains were identified based on the functional changes associated with point mutations. An amino-terminal domain (alpha-Val(569)-alpha-Gly(579)) showed minimal changes in cation selectivity or amiloride sensitivity following cysteine substitution. In contrast, cysteine substitutions within the carboxyl-terminal domain (alpha-Ser(580)-alpha-Ser(592)) resulted in significant changes in cation selectivity and moderately altered amiloride sensitivity. The mutant channels containing alpha G587C or alpha S589C were permeable to K+, and mutation of a GSS tract (positions alpha 587-alpha 589) to GYG resulted in a moderately K+-selective channel. Our results suggest that the C-terminal portion of the pore region within the alpha-subunit contributes to the selectivity filter of ENaC. C1 Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Kleyman, TR (reprint author), Div Renal, 700 Clin Res Bldg,415 Curie Blvd, Philadelphia, PA 19104 USA. OI Sheng, Shaohu/0000-0002-7198-1702 FU NIDDK NIH HHS [DK54354] NR 51 TC 68 Z9 70 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 MAR 24 PY 2000 VL 275 IS 12 BP 8572 EP 8581 DI 10.1074/jbc.275.12.8572 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WU UT WOS:000086507700046 PM 10722696 ER PT J AU Aguirre, V Uchida, T Yenush, L Davis, R White, MF AF Aguirre, V Uchida, T Yenush, L Davis, R White, MF TI The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAY; PLECKSTRIN HOMOLOGY DOMAIN; TYROSINE PHOSPHORYLATION; PHOSPHATIDYLINOSITOL 3-KINASE; JUXTAMEMBRANE REGION; 3T3-L1 ADIPOCYTES; BRAIN INJURY; IN-VIVO AB Tumor necrosis factor alpha (TNF alpha) inhibits insulin action, in part, through serine phosphorylation of IRS proteins; however, the phosphorylation sites that mediate the inhibition are unknown. TNF alpha promotes multipotential signal transduction cascades, including the activation of the Jun NH2-terminal kinase (JNK), Endogenous JNK associates with IRS-1 in Chinese hamster ovary cells. Anisomycin, a strong activator of JNK in these cells, stimulates the activity of JNK bound to IRS-1 and inhibits the insulin-stimulated tyrosine phosphorylation of IRS-I, Serine 307 is a major site of JNK phosphorylation in IRS-1, Mutation of serine 307 to alanine eliminates phosphorylation of IRS-1 by JNK and abrogates the inhibitory effect of TNF alpha on insulin-stimulated tyrosine phosphorylation of IRS-I. These results suggest that phosphorylation of serine 307 might mediate, at least partially, the inhibitory effect of proinflammatory cytokines like TNF alpha on IRS-I function. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, Boston, MA 02215 USA. Univ Massachusetts, Howard Hughes Med Inst, Dept Mol Med, Worcester, MA 01605 USA. RP White, MF (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Howard Hughes Med Inst, 1 Joslin Pl, Boston, MA 02215 USA. RI Yenush, Lynne/J-8815-2014 OI Yenush, Lynne/0000-0001-8589-7002 FU NIDDK NIH HHS [DK38712] NR 66 TC 835 Z9 875 U1 6 U2 40 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 24 PY 2000 VL 275 IS 12 BP 9047 EP 9054 DI 10.1074/jbc.275.12.9047 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 304WU UT WOS:000086507700105 PM 10722755 ER PT J AU Cho, G Keefe, AD Liu, RH Wilson, DS Szostak, JW AF Cho, G Keefe, AD Liu, RH Wilson, DS Szostak, JW TI Constructing high complexity synthetic libraries of long ORFs using in vitro selection SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE in vitro selection; mRNA display; mRNA-protein fusions; synthetic library; TIM barrel ID INDOLE-3-GLYCEROL PHOSPHATE SYNTHASE; ARCHAEON SULFOLOBUS-SOLFATARICUS; NONPOLAR AMINO-ACIDS; DISPLAY; PROTEINS; PERIODICITY; STABILITY; PEPTIDES; SEQUENCE; SURFACE AB We present a method that can significantly increase the complexity of protein libraries used for in vitro or in vivo protein selection experiments. Protein libraries are often encoded by chemically synthesized DNA, in which part of the open reading frame is randomized. There are, however, major obstacles associated with the chemical synthesis of long open reading frames, especially those containing random segments. Insertions and deletions that occur during chemical synthesis cause frameshifts, and stop codons in the random region will cause premature termination. These problems can together greatly reduce the number of full-length synthetic genes in the library. We describe a strategy in which smaller segments of the synthetic open reading frame are selected in vitro using mRNA display for the absence of frameshifts and stop codons. These smaller segments are then ligated together to form combinatorial libraries of long uninterrupted open reading frames. This process can increase the number of full-length open reading frames in libraries by up to two orders of magnitude, resulting in protein libraries with complexities of greater than 10(13). We have used this methodology to generate three types of displayed protein library: a completely random sequence library, a library of concatemerized oligopeptide cassettes with a propensity for forming amphipathic cc-helical or P-strand structures, and a library based on one of the most common enzymatic scaffolds, the alpha/beta (TIM) barrel. (C) 2000 Academic Press. C1 Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Szostak, JW (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Howard Hughes Med Inst, Boston, MA 02114 USA. NR 26 TC 84 Z9 87 U1 2 U2 11 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 24 PY 2000 VL 297 IS 2 BP 309 EP 319 DI 10.1006/jmbi.2000.3571 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 297YY UT WOS:000086112000004 PM 10715203 ER PT J AU Rubin, GM Yandell, MD Wortman, JR Miklos, GLG Nelson, CR Hariharan, IK Fortini, ME Li, PW Apweiler, R Fleischmann, W Cherry, JM Henikoff, S Skupski, MP Misra, S Ashburner, M Birney, E Boguski, MS Brody, T Brokstein, P Celniker, SE Chervitz, SA Coates, D Cravchik, A Gabrielian, A Galle, RF Gelbart, WM George, RA Goldstein, LSB Gong, FC Guan, P Harris, NL Hay, BA Hoskins, RA Li, JY Li, ZY Hynes, RO Jones, SJM Kuehl, PM Lemaitre, B Littleton, JT Morrison, DK Mungall, C O'Farrell, PH Pickeral, OK Shue, C Vosshall, LB Zhang, J Zhao, Q Zheng, XQH Zhong, F Zhong, WY Gibbs, R Venter, JC Adams, MD Lewis, S AF Rubin, GM Yandell, MD Wortman, JR Miklos, GLG Nelson, CR Hariharan, IK Fortini, ME Li, PW Apweiler, R Fleischmann, W Cherry, JM Henikoff, S Skupski, MP Misra, S Ashburner, M Birney, E Boguski, MS Brody, T Brokstein, P Celniker, SE Chervitz, SA Coates, D Cravchik, A Gabrielian, A Galle, RF Gelbart, WM George, RA Goldstein, LSB Gong, FC Guan, P Harris, NL Hay, BA Hoskins, RA Li, JY Li, ZY Hynes, RO Jones, SJM Kuehl, PM Lemaitre, B Littleton, JT Morrison, DK Mungall, C O'Farrell, PH Pickeral, OK Shue, C Vosshall, LB Zhang, J Zhao, Q Zheng, XQH Zhong, F Zhong, WY Gibbs, R Venter, JC Adams, MD Lewis, S TI Comparative genomics of the eukaryotes SO SCIENCE LA English DT Review ID DROSOPHILA-MELANOGASTER; INNATE IMMUNITY; CAENORHABDITIS-ELEGANS; MOLECULAR-CLONING; RECEPTOR FAMILY; CYTOCHROME-C; PROTEIN; GENE; BINDING; GASTRULATION AB A comparative analysis of the genomes of Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae-and the proteins they are predicted to encode-was undertaken in the context of cellular, developmental, and evolutionary processes. The nonredundant protein sets of flies and worms are similar in size and are only twice that of yeast, but different gene families are expanded in each genome, and the multidomain proteins and signaling pathways of the fly and worm are far more complex than those of yeast. The fly has orthologs to 177 of the 289 human disease genes examined and provides the foundation for rapid analysis of some of the basic processes involved in human disease. C1 Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley Drosophila Genome Project, Berkeley, CA 94720 USA. Celera Genom, Rockville, MD 20850 USA. Genetixxpress, Sydney, NSW 2108, Australia. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. EMBL, EBI, Cambridge CB10 1SD, England. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Fred Hutchinson Canc Res Ctr, Howard Hughes Med Inst, Seattle, WA 98109 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. NINDS, Neurogenet Unit, Neurochem Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley Drosophila Genome Project, Berkeley, CA 94720 USA. Neomorphic, Berkeley, CA 94710 USA. Univ Leeds, Sch Biol, Leeds LS2 9JT, W Yorkshire, England. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. Univ Calif San Diego, Howard Hughes Med Inst, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Howard Hughes Med Inst, Dept Pharmacol, La Jolla, CA 92093 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. BC Canc Res Ctr, Genome Sequence Ctr, Vancouver, BC V52 4E6, Canada. Univ Maryland, Cell & Mol Biol Program, Baltimore, MD 21201 USA. CNRS, Ctr Genet Mol, F-91198 Gif Sur Yvette, France. MIT, Ctr Learning & Memory, Cambridge, MA 02139 USA. NCI, Regulat Cell Growth Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr,NIH, Ft Detrick, MD 21702 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Rubin, GM (reprint author), Univ Calif Berkeley, Howard Hughes Med Inst, Berkeley, CA 94720 USA. RI Jones, Steven/C-3621-2009; OI Lewis, Suzanna/0000-0002-8343-612X; O'Farrell, Patrick/0000-0003-0011-2734; Rubin, Gerald/0000-0001-8762-8703 FU NHGRI NIH HHS [P4IHG00739, P50HG00750]; NIGMS NIH HHS [R01 GM037193, R01 GM037193-14, R01 GM037193-15, R01 GM060988, R01 GM060988-01]; NINDS NIH HHS [R01 NS040296, R01 NS040296-01] NR 84 TC 1120 Z9 1153 U1 9 U2 106 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 24 PY 2000 VL 287 IS 5461 BP 2204 EP 2215 DI 10.1126/science.287.5461.2204 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296WE UT WOS:000086049100035 PM 10731134 ER PT J AU Lee, L Tirnauer, JS Li, JJ Schuyler, SC Liu, JY Pellman, D AF Lee, L Tirnauer, JS Li, JJ Schuyler, SC Liu, JY Pellman, D TI Positioning of the mitotic spindle by a cortical-microtubule capture mechanism SO SCIENCE LA English DT Article ID SACCHAROMYCES-CEREVISIAE; ACTIN CYTOSKELETON; NUCLEAR MIGRATION; BINDING PROTEIN; YEAST; ORIENTATION; DYNEIN; SITES; BNI1P; EB1 AB Correct positioning of the mitotic spindle is critical for cell division and development. Spindle positioning involves a search-and-capture mechanism whereby dynamic microtubules find and then interact with specific sites on the submembrane cortex. Genetic, biochemical, and imaging experiments suggest a mechanism for cortical-microtubule capture. Bim1p, Located at microtubule distal ends, bound Kar9p, a protein associated with the daughter cell cortex. Bim1p is the yeast ortholog of human EB1, a binding partner for the adenomatous polyposis coli tumor suppressor. EB1 family proteins may have a general role in linking the microtubule cytoskeleton to cortical polarity determinants. C1 Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, Boston, MA 02115 USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Hematol, Boston, MA 02115 USA. RP Pellman, D (reprint author), Harvard Univ, Childrens Hosp, Sch Med, Dana Farber Canc Inst,Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM daivd_pellman@dfci.harvard.edu FU NIDDK NIH HHS [KO8 DK02578]; NIGMS NIH HHS [GM55772] NR 34 TC 215 Z9 217 U1 0 U2 2 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 24 PY 2000 VL 287 IS 5461 BP 2260 EP 2262 DI 10.1126/science.287.5461.2260 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 296WE UT WOS:000086049100050 PM 10731147 ER EF